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7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Arrhythmia-induced cardiomyopathy : Cynthia M Tracy, MD : William J McKenna, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 24, 2022. INTRODUCTION Cardiomyopathies are diseases of the heart muscle, inclusive of a variety of myocardial disorders that manifest with various structural and functional phenotypes and are frequently genetic. Although some have defined cardiomyopathy to include myocardial disease caused by known cardiovascular causes (such as hypertension, ischemic heart disease, or valvular disease), current major society definitions of cardiomyopathy exclude heart disease secondary to such cardiovascular disorders [1,2]. (See "Definition and classification of the cardiomyopathies" and "Causes of dilated cardiomyopathy".) The prognosis in patients with dilated cardiomyopathy is variable and dependent on the cause; importantly, there are some etiologies that may improve or resolve following treatment. One such cause is an arrhythmia-induced cardiomyopathy (also known as tachycardia-induced cardiomyopathy, tachycardia-mediated cardiomyopathy, and tachymyopathy), a relatively rare though well-recognized entity caused by long-standing tachycardia, which in most instances is readily treatable with a good prognosis [3]. Arrhythmia-induced cardiomyopathy has been reported with nearly all types of tachyarrhythmias and frequent ectopy, both supraventricular and ventricular [4]. A common clinical problem is determining whether the tachycardia is the primary cause of the patient's cardiomyopathy, or if the tachycardia is secondary to a cardiomyopathy of different etiology. This topic will discuss arrhythmia-induced cardiomyopathy as a primary cause of cardiomyopathy. Arrhythmias occurring in the setting of a specific cardiomyopathy are discussed separately. (See "Hypertrophic cardiomyopathy in adults: Supraventricular https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 1/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death" and "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations", section on 'Ventricular arrhythmias'.) EPIDEMIOLOGY While the exact incidence of arrhythmia-induced cardiomyopathy remains unclear, an association between tachycardia and cardiomyopathy has been recognized for some time [5-8]. Virtually every form of supraventricular tachyarrhythmia, including ectopic atrial tachycardia (AT), nonparoxysmal junctional tachycardia, and atrial fibrillation (AF), has been associated with reversible left ventricular (LV) dysfunction or "cardiomyopathy." The development of a cardiomyopathy has also been documented with ventricular tachyarrhythmias and frequent ectopic beats [9-11]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm" and 'Frequent ectopic beats' below.) Some insight into the prevalence of arrhythmia-induced cardiomyopathy can be derived from cohort studies of patients undergoing catheter ablation for symptomatic arrhythmias. As examples: Among a cohort of 331 patients who were referred for catheter ablation of incessant AT, myocardial dysfunction was present in 9 percent of patients [12]. Patients with an arrhythmia-induced cardiomyopathy were younger (mean age 39 versus 51 years), more frequently male (60 versus 38 percent), and had incessant or very frequent paroxysmal tachycardia (100 versus 20 percent). Among a cohort of 625 patients undergoing catheter ablation for a variety of tachyarrhythmias, a tachycardia-induced cardiomyopathy was present in 2.7 percent (17 of 625 patients) [13]. Among a cohort of 1269 patients undergoing ablation for atrial flutter, 184 had reduced LV ejection fraction (LVEF; <40 percent) at baseline [14]. PATHOPHYSIOLOGY Chronic tachycardia ultimately produces significant cardiac structural changes, including LV dilation and cellular morphologic changes [15-19]. However, the exact mechanism by which tachycardia produces these changes is not well defined. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 2/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate Animal models, initially developed in the general investigation of heart failure (HF), have been studied extensively in the evaluation of arrhythmia-induced cardiomyopathy. Rapid pacing produces changes in animals that are similar to those observed in humans, including a marked depression of LVEF, elevated filling pressures, depressed cardiac output, and increased systemic vascular resistance [16-18,20-24]. These changes are generally reversible with cessation of the tachycardia, although in some cases LVEF may not return to baseline [24,25]. Similar findings have been reported in an animal model following the delivery of premature ventricular complexes/contractions (PVCs; also referred to as premature ventricular beats or premature ventricular depolarizations) in a bigeminal pattern for 12 weeks, which resulted in LV dilation and reduction in LVEF [26]. The morphologic and biochemical changes that result from an arrhythmia-induced cardiomyopathy also may produce electrophysiologic abnormalities. In a canine model, chronic tachycardia was associated with ventricular arrhythmias (including polymorphic ventricular tachycardia [VT] and sudden death) that result from a prolongation in repolarization [27]. Many alterations in neurohumoral and cellular activation have been described, and several factors probably contribute to the development of rate-related myocardial dysfunction. Although data supporting certain potential mechanisms are compelling, it remains unclear whether they play an etiologic role or if they arise as a consequence of tachycardia. Depletion of myocardial energy stores and myocardial ischemia Studies in animal models have shown that persistent tachycardia depletes high-energy stores as evidenced by reduced myocardial levels of creatine, phosphocreatine, and adenosine triphosphate (ATP), and diminished activity of the Na-K-ATPase pump [28-30]. These changes are probably due to alterations in cellular metabolism with mitochondrial injury and increased activity of Krebs cycle oxidative enzymes [15,20]. Myocardial ischemia may play a role in the development of arrhythmia-induced cardiomyopathy. Similar depletions in high-energy stores are seen in ischemic models following vessel occlusion, situations where high-energy stores are rapidly depleted and LV dysfunction occurs [31,32]. High-energy stores return to normal within days after the ischemic insults. Tachycardia-induced depletion of high-energy stores, which may be mediated in part by ischemia, is reversible and may explain the reversibility of this cardiomyopathy. Abnormalities in subendocardial to subepicardial flow ratios and impaired coronary flow have been found in arrhythmia-induced cardiomyopathy [33-36]. The impaired coronary https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 3/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate blood flow occurs in association with elevation in cardiac filling pressures and impaired LV diastolic function [25,37,38]. Abnormal calcium handling and beta adrenergic responsiveness Abnormalities in both calcium channel activity and sarcoplasmic reticulum calcium transport may contribute to the myocardial dysfunction in arrhythmia-induced cardiomyopathy [20,35]. Diminished beta-adrenergic responsiveness has also been described and may be due to reduced myocyte beta-1 receptor density (downregulation) [37,39,40]. The reduction in beta receptor density and responsiveness is independent of hemodynamic and neurohumoral factors [41]. Oxidative stress and injury In patients with AF and atrial dysfunction, there is histologic evidence of oxidative stress and injury in the atrial myocardium [42]. This results in peroxynitrite formation, which modifies myofibrillar proteins, contributes to loss of fibrillar protein function, and alters myofibrillar energetics. Support for the role of oxidative stress comes from one animal study which found that the administration of the antioxidant vitamins E, C, and beta-carotene attenuated the cardiac dysfunction and prevented beta receptor downregulation produced by rapid cardiac pacing [43]. Genetic basis and ACE gene polymorphism An association has been reported between a gene polymorphism and arrhythmia-induced cardiomyopathy. Levels of angiotensin converting enzyme (ACE) are associated with a 287 base pair insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene. The DD genotype is associated with increased serum ACE levels and a higher incidence of both ischemic and idiopathic dilated cardiomyopathy. In a study comparing 20 patients with arrhythmia-induced cardiomyopathy, 20 controls with persistent tachycardia but normal LV function, and 24 normal volunteers, the DD genotype was significantly more common in the patients with arrhythmia-induced cardiomyopathy [44]. Histopathologic and immunologic findings Among a cohort of 189 patients with new onset HF and reduced LVEF not related to valvular or ischemic heart disease, 19 patients met criteria for tachycardia-induced cardiomyopathy. Endomyocardial biopsies in the tachycardia-induced cardiomyopathy patients showed a stronger myocardial expression of + major histocompatibility complex class II molecule and enhanced infiltration of CD68 macrophages compared with patients with idiopathic dilated cardiomyopathy. Compared to patients with ischemic cardiomyopathy, those with tachycardia induced cardiomyopathy had fewer T cells and macrophages. Fibrosis was also less prominent in the tachycardia https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 4/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate induced cardiomyopathy patients. However, electron microscopy in these patients showed abnormal mitochondrial distribution and enhanced myocyte size. RNA expression analysis showed alterations in metabolic pathways [45]. ARRHYTHMIAS ASSOCIATED WITH ARRHYTHMIA-INDUCED CARDIOMYOPATHY A number of tachyarrhythmias have been associated with arrhythmia-induced cardiomyopathy, including AF, atrial flutter, atrial tachycardia (AT), reentrant supraventricular tachycardias, and VT [11,46-60]. In addition, very frequent ectopic beats, both atrial and ventricular, have been associated with arrhythmia-induced cardiomyopathy. Regardless of the arrhythmia, therapy to restore normal sinus rhythm or to slow the ventricular rate (or eliminate ectopy) appears to result in an improvement in LV function ( table 1). However, most descriptive series include only a small number of patients. Supraventricular arrhythmias Atrial fibrillation and atrial flutter Epidemiologic studies have shown that patients with AF are at increased risk for HF [61]. In some patients, restoration of sinus rhythm or control of the rapid ventricular rate markedly improves or even normalizes the LVEF, indicating that the LV dysfunction was primarily due to the rapid AF rather than another etiology. Improvement in LV function is seen with both rhythm and rate control, although it may be more likely with rhythm control. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm".) There is an association between HF and AF, and it is often not possible to determine which is causative. Nevertheless, an estimated 25 to 50 percent of patients with LV dysfunction and AF have some component of arrhythmia-induced cardiomyopathy [4,62-64]. There are less data on the frequency and predictors of arrhythmia-induced cardiomyopathy in patients with atrial flutter. In one study of patients undergoing ablation for atrial flutter, 25 percent had evidence for cardiomyopathy prior to ablation [65]. Of these, 57 percent had significant improvement in their LVEF postablation. The only predictor of reversibility of cardiomyopathy in this study was average heart rate. Similarly, in a cohort of 1269 patients undergoing ablation for atrial flutter, 184 had reduced LVEF (<40 percent) at baseline. Of these patients with reduced LVEF, 103 patients (56 percent) had marked improvement in LVEF at six months. Those who experienced improvement in the LVEF had similar survival to patients who https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 5/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate did not have baseline depressed LVEF. Those whose LVEF failed to improve had a three-fold higher mortality [14]. Atrial tachycardia Incessant AT, an infrequent cause of symptomatic supraventricular tachyarrhythmia, can cause myocardial dysfunction in approximately 10 percent of patients [12]. Children are more likely than adults to present with arrhythmia-induced cardiomyopathy due to incessant AT. When AT is seen in adults, it is more commonly associated with another cardiac problem, and distinguishing the effect of tachycardia from that of the underlying cardiac disease may be difficult. (See "Focal atrial tachycardia", section on 'Incessant AT resulting in cardiomyopathy' and "Atrial tachyarrhythmias in children", section on 'Atrial ectopic tachycardia and focal atrial tachycardia'.) Incessant AT and ectopic AT have been associated with the development of cardiomyopathy that can be reversed with restoration of sinus rhythm [46-52]. Improved techniques for catheter ablation frequently permit definitive therapy for AT, which can lead to the resolution of myocardial dysfunction with a high degree of success [12,46,52]. (See "Focal atrial tachycardia", section on 'Treatment of incessant AT'.) Reentrant supraventricular tachycardias Reentrant supraventricular tachycardias, including atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reciprocating tachycardia (AVRT), are more commonly paroxysmal but can cause a persistent tachycardia. Cases of arrhythmia-induced cardiomyopathy have been described with persistent junctional reciprocating tachycardia, accessory pathway mediated tachycardia (ie, AVRT) and AVNRT [50,54- 57]. In the absence of other factors, the cardiomyopathy related to an incessant reentrant supraventricular tachycardia is reversible following catheter ablation [55]. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway" and "Atrioventricular nodal reentrant tachycardia".) Ventricular arrhythmias Only rare reports have described reversible cardiomyopathy related to VT, since this arrhythmia is usually associated with some form of underlying structural heart disease. However, idiopathic LV tachycardia or right ventricular outflow tract VT can arise in structurally normal hearts [9,10,54]. In rare cases, these arrhythmias are persistent or repetitive enough to result in a cardiomyopathy. In one study of patients with repetitive monomorphic VT and/or premature ventricular complexes/contractions (PVCs), an arrhythmia-induced cardiomyopathy was seen in 9 percent, all of which improved with treatment [66]. Similar to supraventricular arrhythmias, the myopathy usually reverses following ablation of the arrhythmia [58]. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 6/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate Unlike monomorphic VT, which can be present and hemodynamically stable for extended periods of time, polymorphic VT, which is generally an unstable rhythm, and ventricular fibrillation, a non-perfusing rhythm, are not associated with arrhythmia-induced cardiomyopathy. Frequent ectopic beats Frequent ventricular ectopy Very frequent ventricular ectopy in the form of PVCs has been associated with a reversible cardiomyopathy, even in the absence of sustained ventricular arrhythmias [11,59,66-74]. While most earlier studies defined "frequent" as greater than 10 percent of overall heartbeats, in contemporary practice a cutoff of >15 percent of all heartbeats is more commonly used. Although some patients with similarly high PVC burdens can maintain normal cardiac function, PVC-induced cardiomyopathy has also been reported in patients with PVC burdens as low as 4 to 5 percent. In a prospective observational cohort study of 80 patients (59 percent male, mean age 53 years) with frequent PVCs (mean PVC burden 22 percent) and reduced LVEF ( 50 percent) who underwent catheter ablation, 53 patients (66 percent) had successful long-term elimination of PVCs, with significant improvement in LVEF and New York Heart Association (NYHA) functional class [70]. In a 2014 systematic review and meta-analysis of radiofrequency ablation for the treatment of idiopathic PVCs originating from the right ventricular outflow tract, catheter ablation was associated with a significant improvement in LVEF, though the meta-analysis was limited by significant heterogeneity among the studies [75]. (See "Premature ventricular complexes: Treatment and prognosis".) In addition to the overall frequency of PVCs, QRS duration, epicardial site of origin of PVCs, and resulting dyssynchrony all appear to play a role in the development of cardiomyopathy and are associated with outcomes following catheter ablation. Greater dyssynchrony increases the risk of cardiomyopathy, wider QRS complexes appear more likely to result in cardiomyopathy with a lower overall burden of PVCs while also being associated with longer times to normalization of LV systolic function following ablation, and epicardial PVC origin also appears to predict delayed LV function recovery [74,76-80]. Frequent atrial ectopy Premature atrial complexes (PACs; also referred to as premature atrial beats, premature supraventricular complexes, or premature supraventricular beats) are usually benign, but a high burden of PACs has been associated with a reversible cardiomyopathy [81,82]. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 7/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate CLINICAL PRESENTATION The clinical presentation of arrhythmia-induced cardiomyopathy is variable but usually involves signs and/or symptoms related to the tachyarrhythmia (eg, palpitations, dyspnea, chest discomfort, etc), HF (eg, dyspnea, edema, weight gain, orthopnea, etc), or both. In our experience, HF symptoms are more common since patients with symptomatic tachyarrhythmias will frequently seek medical attention earlier in the course of their care and prior to the development of a cardiomyopathy. The approach to the patient with suspected arrhythmia- induced cardiomyopathy includes a thorough history and physical examination, with appropriately selected tests to establish the diagnosis and assess acuity, severity, and etiology. Several professional societies have issued recommendations for the evaluation of patients with suspected HF or cardiomyopathy [83-86]. Signs and symptoms The clinical presentation of arrhythmia-induced cardiomyopathy is variable but usually involves symptoms of palpitations or HF. Patients may present with palpitations or other symptom (eg, dyspnea, chest discomfort) related to the rapidity or irregularity of their arrhythmia. However, those with more rapid heart rates typically present with symptoms related to the inappropriate heart rate before enough time has elapsed to result in a cardiomyopathy. In contrast, patients with tachycardia but a relatively slower heart rate and no obvious symptoms may have little or no awareness of the arrhythmia. While such patients without palpitations are occasionally discovered during a routine medical exam for other reasons, typically they present with fatigue, decreased exercise tolerance, or symptomatic HF. Given that patients with more rapid heart rates often present earlier with symptoms related to the tachycardia, some investigators have hypothesized that patients with atrial arrhythmias who subsequently develop arrhythmia-induced cardiomyopathy have slower overall heart rates than patients who do not develop arrhythmia-induced cardiomyopathy. Published reports in both adult and pediatric populations support this hypothesis: In a retrospective cohort study of 331 patients who had undergone ablation for atrial tachycardia (AT), among whom 9 percent presented with evidence of arrhythmia-induced cardiomyopathy, those with arrhythmia-induced cardiomyopathy had slower ventricular heart rates during tachycardia compared with patients who did not have arrhythmia- induced cardiomyopathy (120 versus 149 beats per minute) [12]. (See "Focal atrial tachycardia", section on 'Incessant AT resulting in cardiomyopathy'.) In a retrospective cohort study of 16 pediatric patients with focal AT, those with AT arising from the atrial appendages were more likely to be asymptomatic at presentation, more https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 8/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate likely to have a ventricular heart rate less than 120 beats per minute, and more commonly presented with arrhythmia-induced cardiomyopathy [87]. ECG findings All patients should have an electrocardiogram (ECG) to document the cardiac rhythm and ventricular heart rate. Whenever possible, obtaining prior ECGs can be extremely helpful to determine whether ambiguous P wave morphologies are related to the sinus node (as seen on prior tracings) versus an ectopic atrial focus. There are no specific ECG findings that distinguish patients with and without arrhythmia-induced cardiomyopathy, and the ECG findings will vary depending upon the underlying tachyarrhythmia. However, by definition, all patients with an arrhythmia-induced cardiomyopathy should have a heart rate greater than 100 beats per minute. APPROACH TO THE DIAGNOSIS Arrhythmia-induced cardiomyopathy is defined by the presence of a sustained tachycardia (or frequent episodes of tachycardia or very frequent ectopy) which results in LV systolic dysfunction. Determining which of the pathologies (the arrhythmia or the cardiomyopathy) is the primary pathologic process is key to establishing the diagnosis. Usually the diagnosis of arrhythmia-induced cardiomyopathy can only be made following a successful trial of therapy to slow the ventricular rate or to restore sinus rhythm along with the exclusion of other potential causes of cardiomyopathy. Patients in whom arrhythmia-induced cardiomyopathy is suspected should undergo continuous cardiac monitoring for 24 to 48 hours and have non-invasive imaging to assess cardiac structure and function. For most patients, a transthoracic echocardiogram is the preferred test for assessing cardiac structure and function due to its widespread availability and ease of performance; however, cardiovascular magnetic resonance (CMR) imaging is a reasonable alternative approach in centers with expertise in this modality. DIAGNOSTIC TESTING Once arrhythmia-induced cardiomyopathy is suspected, appropriately selected tests can help to establish the diagnosis. All of the following are performed as part of the initial evaluation. Cardiac monitoring Heart rate over time should be continuously measured for 24 to 48 hours using inpatient telemetry or ambulatory (Holter) monitoring to document the average heart rate and, in some cases, provide additional information on the underlying rhythm [88]. A sustained heart rate greater than 100 beats per minute, and particularly greater than 120 beats https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 9/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate per minutes, is consistent with arrhythmia-induced cardiomyopathy. Because of the potential reversible nature of arrhythmia-induced cardiomyopathy, if uncertainty persists regarding the cardiac rhythm, full invasive electrophysiologic studies may be necessary to establish the underlying cardiac rhythm and guide the optimal therapy. (See 'Treatment' below and "Invasive diagnostic cardiac electrophysiology studies".) Assessment of cardiac structure and function All patients with suspected arrhythmia- induced cardiomyopathy should undergo an assessment of cardiac structure and function to document LV size and function, in particular LVEF. Transthoracic echocardiography is the most common and widespread test for documenting cardiac structure and function, but CMR imaging is an alternative approach. While there are no absolute echocardiographic parameters that can distinguish arrhythmia-induced cardiomyopathy from other forms of dilated cardiomyopathy, in general, the LV end-diastolic dimension tends to be smaller in patients with arrhythmia-induced cardiomyopathy [4,89]. In patients with improved LVEF after treatment of an arrhythmia, CMR may be useful for the evaluation of cardiac structure and function. Patients who have a CMR that demonstrates a low LVEF or late gadolinium enhancement have incomplete resolution of cardiac injury [90]. Alternatively, in assessing the underlying cause of arrhythmia-induced cardiomyopathy, patients in one study with frequent premature ventricular complexes/contractions (PVCs) who failed to improve LVEF after treatment were found to have late gadolinium enhancement on CMR, and likely the cause of the cardiomyopathy was not purely tachycardia mediated [91]. Studies have suggested the use of two-dimensional strain echocardiography as a tool to predict recovery from arrhythmia induced cardiomyopathy [92]. In a study of 71 patients with presumed tachycardia-induced cardiomyopathy, a lower LVEF at baseline and higher relative apical longitudinal strain ratio (RALSR) were associated with no recovery in LVEF during follow-up. However, by multivariate analysis the RALSR was found to be a significant predictor of functional recovery after the arrhythmia was treated. Excluding other causes of cardiomyopathy Patients with newly diagnosed HF and/or cardiomyopathy require an assessment for genetic and other causes of LV dysfunction and exclusion of significant underlying coronary heart disease (CHD). Decisions on the initial use of stress testing or coronary angiography should be made based on the presence or absence of symptoms suggestive of CHD and the individual patient's likelihood of CHD. The differential diagnosis of dilated cardiomyopathy, and the approach to excluding CHD, are discussed in greater detail separately. While patients with HF and cardiomyopathies of other etiologies may exhibit rapid heart rates (eg, persistent sinus tachycardia), this can usually be distinguished from an arrhythmia-induced cardiomyopathy by comparison of ECG findings over time (eg, sinus P https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 10/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate wave morphology) and response to treatment. An important part of the evaluation is a careful review of the family history, and when the phenotype is clear, genetic testing should be recommended. Several of the genetically determined arrhythmogenic cardiomyopathies can present with frequent ectopy (PVCs, nonsustained VT, and/or AF in association with LV dilation and/or impaired function, eg, desmoplakin, filamin C, lamin AC, desmin) [93,94]. (See "Causes of dilated cardiomyopathy" and "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Detection of coronary artery disease'.) TREATMENT The initial treatments for a patient with HF and suspected arrhythmia-induced cardiomyopathy are the same as those used in most other patients with HF with reduced ejection fraction (eg, angiotensin converting enzyme [ACE] inhibitors or angiotensin II receptor blockers [ARBs], beta blockers, diuretics) and tachyarrhythmias (eg, rate-control medications, consideration of antiarrhythmic drugs and/or cardioversion). However, because of the potentially reversible nature of arrhythmia-induced cardiomyopathy, efforts should be made to achieve adequate ventricular heart rate control or to restore sinus rhythm [4]. Additionally, given the potentially reversible nature of this condition, an adequate trial of therapy is required prior to assessment of the need for cardiac resynchronization therapy or an implantable cardioverter-defibrillator. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Overview of the management of heart failure with reduced ejection fraction in adults", section on 'Pharmacologic therapy'.) Patients with atrial fibrillation or flutter For patients in whom AF or atrial flutter is the suspected cause of cardiomyopathy, the initial approach to management is similar to other patients with HF and includes prompt rate control with AV nodal blockers and appropriate anticoagulation. (See "The management of atrial fibrillation in patients with heart failure".) Beyond these initial steps, controversy still exists as to whether rate control or rhythm control is the optimal therapy for AF- or atrial flutter-induced cardiomyopathy. Our strategy for management is as follows: For minimally symptomatic patients with AF in whom adequate rate control is achieved, we continue medical therapy. In patients with a cardiomyopathy whose origin is suspected to be AF or atrial flutter, heart rate control through either rate control or rhythm control can be effective at improving cardiac function [95-98]. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 11/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate For patients with AF who remain significantly symptomatic or in whom adequate rate control is not achieved with medical therapy alone, we pursue a rhythm control strategy. For patients with atrial flutter, rapid ventricular rates, and newly recognized LV systolic function, rate control may be difficult to achieve with medication; in these patients, we perform early electrical cardioversion. Management of AF and/or atrial flutter is geared towards avoidance of thromboembolic events, reduction of symptoms, and avoidance of arrhythmia-induced cardiomyopathy. Control of heart rate can be met through either a rate control strategy with atrioventricular (AV) nodal blocking agents (or ablation and pacer implant in cases of multiple drug failures) or through maintenance of sinus rhythm (rhythm control strategy). Strategies for rate control versus rhythm control are discussed elsewhere, and choices of agents are dictated by cardiac structure, underlying pathology, and function. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Restoration of sinus rhythm in atrial flutter", section on 'Indications' and "Management of atrial fibrillation: Rhythm control versus rate control".) At initial presentation of the patient with rapid ventricular rates and newly recognized depressed EF, the concern exists that at least some component is related to arrhythmia-induced cardiomyopathy. This is particularly suspected in younger patients with severe symptoms from the AF. A trial of early cardioversion is warranted in these patients with subsequent monitoring for improvement in cardiac function [99]. Patients with another SVT For supraventricular tachyarrhythmias (SVTs) other than AF or atrial flutter that result in arrhythmia-induced cardiomyopathy, restoration of sinus rhythm is the usual goal. Options for the restoration of sinus rhythm include electrical cardioversion, antiarrhythmic drugs, and catheter ablation of the arrhythmia. The initial choice of modality will vary depending upon the underlying SVT as well as the local expertise and availability of options (ie, some centers do not perform catheter ablation) but should be made in conjunction with an electrophysiologist experienced in the treatment of sustained tachyarrhythmias. Certain SVTs are more amenable to electrical cardioversion (eg, atrioventricular nodal reentrant tachycardia), while others are often refractory or recurrent following cardioversion (eg, atrial tachycardia). Often, atrial arrhythmias can be refractory to antiarrhythmics, and AV nodal blocking agents may be required in high doses to achieve appropriate heart rates. In patients with depressed LVEF, it is important to avoid agents that have a higher likelihood of proarrhythmia (eg, flecainide) or that could further depress LVEF (eg, disopyramide). If an ablation is performed, close follow-up is required even after successful ablation because of the tendency for cardiomyopathy to recur if tachycardia recurs. (See "Focal atrial tachycardia", https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 12/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate section on 'Catheter ablation' and "Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome", section on 'Catheter ablation' and "Atrial tachyarrhythmias in children", section on 'Management' and "Atrioventricular nodal reentrant tachycardia", section on 'Catheter ablation'.) Patients with frequent ectopy For patients presenting with a high burden of premature ventricular complexes/contractions (PVCs) and newly recognized cardiomyopathy, initial management is to look for underlying causes (such as CAD, valvular heart disease, arrhythmogenic right ventricular dysplasia [ARVD], etc) and initiation of guideline-based optimal medical therapy for HF [100]. Correction of electrolytes and initiation of beta blockers are typical first therapies. (See "Overview of the management of heart failure with reduced ejection fraction in adults".) Given the possibility of arrhythmia-induced cardiomyopathy in patients with a high PVC burden (eg, >15 to 20 percent of total beats on a 24-hour ambulatory monitor) and associated with LV dysfunction, we generally pursue radiofrequency catheter ablation [100-102]. Catheter ablation of high-frequency PVCs has emerged as a safe and effective therapy and may be considered if medical management is ineffective or poorly tolerated and depending on patient preference [59,74,103-105]. While it is not possible to specify an exact percentage (PVC burden) for which a patient might benefit from ablation of frequent PVCs as studies have had a wide range in their inclusion criteria, consideration may be given with a burden of above 10 percent, but our approach is typically to offer ablation at a higher burden (eg, >15 to 20 percent PVCs). The approach to catheter ablation in patients with a high PVC burden is discussed in greater detail separately. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy" and "Premature ventricular complexes: Treatment and prognosis", section on 'Catheter ablation'.) Patients with refractory tachyarrhythmias In the event that a supraventricular arrhythmia is likely the cause of cardiomyopathy and cannot be primarily ablated, AV node ablation with either biventricular pacing or conduction system pacing is a reasonable approach to management. While there are no studies that specifically address the strategy of AV nodal ablation and biventricular pacemaker placement in patients with arrhythmia-induced cardiomyopathy, there is indirect evidence to support this approach. In a trial that included patients with HF, a narrow QRS, and permanent AF but who did not explicitly have arrhythmia-induced cardiomyopathy, patients assigned to medical rate control had a higher risk of death or rehospitalization due to HF or worsening of HF when compared with patients assigned to AV node ablation and cardiac https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 13/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate resynchronization therapy (38 versus 10 percent; hazard ratio 0.28, 95% CI 0.11-0.72) [106]. The effect of this approach on recovery of LVEF was not reported. Other trials and studies of patients with preexisting AV node block, HF, and various causes of LV systolic dysfunction are discussed elsewhere. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) FOLLOW-UP Whereas the initial cardiomyopathy may have taken months to develop, recurrent tachycardia can lead to an abrupt decline in LVEF. Diastolic dysfunction can persist even after systolic function has normalized and can lead to decreased coronary flow reserve. In patients who develop a recurrence of the arrhythmia, the increased myocardial oxygen demand in the face of the decreased reserve can lead to redevelopment of cardiomyopathy [107,108]. As such, close ongoing monitoring with clinic visits, ambulatory (Holter) monitoring, and echocardiography are essential. Although there are minimal data and no society guidelines regarding the frequency of monitoring in these patients, we follow up with patients using a combination of clinic visits, echocardiography, and ambulatory monitoring every three to six months for one to two years following the initial clinical improvement. The following is a typical follow-up schedule: Four to six weeks after initial presentation Clinical follow-up, ECG. Three months after initial presentation Clinical follow-up, ECG, echocardiogram, outpatient ambulatory monitor. Six months after initial presentation Clinical follow-up, ECG. Twelve months after initial presentation Clinical follow-up, ECG, echocardiogram, ECG, outpatient ambulatory monitor if symptoms suggest recurrence. Eighteen to 24 months after initial presentation Clinical follow-up, ECG. If complete recovery of EF is noted and angiotensin converting enzyme (ACE) inhibitors and beta blockers are tapered off, additional monitoring is required to be sure that EF remains normal [4]. PROGNOSIS https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 14/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate Following the restoration of sinus rhythm or ventricular rate control of the presenting tachycardia, most patients will have significant improvement and/or normalization of LVEF over a period of months. As such, patients who have not experienced sudden cardiac arrest or a sustained ventricular arrhythmia, and whose LVEF has improved to 40 percent or greater, usually do not require implantation of an implantable cardioverter-defibrillator (ICD). (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) In some patients whose LVEF has normalized, the LV chamber may remain somewhat enlarged. Despite the apparent normalization of cardiac function when a tachycardia has been terminated or rate controlled, ultrastructural abnormalities of the myocardium may persist [60]. 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EF, the concern exists that at least some component is related to arrhythmia-induced cardiomyopathy. This is particularly suspected in younger patients with severe symptoms from the AF. A trial of early cardioversion is warranted in these patients with subsequent monitoring for improvement in cardiac function [99]. Patients with another SVT For supraventricular tachyarrhythmias (SVTs) other than AF or atrial flutter that result in arrhythmia-induced cardiomyopathy, restoration of sinus rhythm is the usual goal. Options for the restoration of sinus rhythm include electrical cardioversion, antiarrhythmic drugs, and catheter ablation of the arrhythmia. The initial choice of modality will vary depending upon the underlying SVT as well as the local expertise and availability of options (ie, some centers do not perform catheter ablation) but should be made in conjunction with an electrophysiologist experienced in the treatment of sustained tachyarrhythmias. Certain SVTs are more amenable to electrical cardioversion (eg, atrioventricular nodal reentrant tachycardia), while others are often refractory or recurrent following cardioversion (eg, atrial tachycardia). Often, atrial arrhythmias can be refractory to antiarrhythmics, and AV nodal blocking agents may be required in high doses to achieve appropriate heart rates. In patients with depressed LVEF, it is important to avoid agents that have a higher likelihood of proarrhythmia (eg, flecainide) or that could further depress LVEF (eg, disopyramide). If an ablation is performed, close follow-up is required even after successful ablation because of the tendency for cardiomyopathy to recur if tachycardia recurs. (See "Focal atrial tachycardia", https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 12/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate section on 'Catheter ablation' and "Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome", section on 'Catheter ablation' and "Atrial tachyarrhythmias in children", section on 'Management' and "Atrioventricular nodal reentrant tachycardia", section on 'Catheter ablation'.) Patients with frequent ectopy For patients presenting with a high burden of premature ventricular complexes/contractions (PVCs) and newly recognized cardiomyopathy, initial management is to look for underlying causes (such as CAD, valvular heart disease, arrhythmogenic right ventricular dysplasia [ARVD], etc) and initiation of guideline-based optimal medical therapy for HF [100]. Correction of electrolytes and initiation of beta blockers are typical first therapies. (See "Overview of the management of heart failure with reduced ejection fraction in adults".) Given the possibility of arrhythmia-induced cardiomyopathy in patients with a high PVC burden (eg, >15 to 20 percent of total beats on a 24-hour ambulatory monitor) and associated with LV dysfunction, we generally pursue radiofrequency catheter ablation [100-102]. Catheter ablation of high-frequency PVCs has emerged as a safe and effective therapy and may be considered if medical management is ineffective or poorly tolerated and depending on patient preference [59,74,103-105]. While it is not possible to specify an exact percentage (PVC burden) for which a patient might benefit from ablation of frequent PVCs as studies have had a wide range in their inclusion criteria, consideration may be given with a burden of above 10 percent, but our approach is typically to offer ablation at a higher burden (eg, >15 to 20 percent PVCs). The approach to catheter ablation in patients with a high PVC burden is discussed in greater detail separately. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy" and "Premature ventricular complexes: Treatment and prognosis", section on 'Catheter ablation'.) Patients with refractory tachyarrhythmias In the event that a supraventricular arrhythmia is likely the cause of cardiomyopathy and cannot be primarily ablated, AV node ablation with either biventricular pacing or conduction system pacing is a reasonable approach to management. While there are no studies that specifically address the strategy of AV nodal ablation and biventricular pacemaker placement in patients with arrhythmia-induced cardiomyopathy, there is indirect evidence to support this approach. In a trial that included patients with HF, a narrow QRS, and permanent AF but who did not explicitly have arrhythmia-induced cardiomyopathy, patients assigned to medical rate control had a higher risk of death or rehospitalization due to HF or worsening of HF when compared with patients assigned to AV node ablation and cardiac https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 13/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate resynchronization therapy (38 versus 10 percent; hazard ratio 0.28, 95% CI 0.11-0.72) [106]. The effect of this approach on recovery of LVEF was not reported. Other trials and studies of patients with preexisting AV node block, HF, and various causes of LV systolic dysfunction are discussed elsewhere. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) FOLLOW-UP Whereas the initial cardiomyopathy may have taken months to develop, recurrent tachycardia can lead to an abrupt decline in LVEF. Diastolic dysfunction can persist even after systolic function has normalized and can lead to decreased coronary flow reserve. In patients who develop a recurrence of the arrhythmia, the increased myocardial oxygen demand in the face of the decreased reserve can lead to redevelopment of cardiomyopathy [107,108]. As such, close ongoing monitoring with clinic visits, ambulatory (Holter) monitoring, and echocardiography are essential. Although there are minimal data and no society guidelines regarding the frequency of monitoring in these patients, we follow up with patients using a combination of clinic visits, echocardiography, and ambulatory monitoring every three to six months for one to two years following the initial clinical improvement. The following is a typical follow-up schedule: Four to six weeks after initial presentation Clinical follow-up, ECG. Three months after initial presentation Clinical follow-up, ECG, echocardiogram, outpatient ambulatory monitor. Six months after initial presentation Clinical follow-up, ECG. Twelve months after initial presentation Clinical follow-up, ECG, echocardiogram, ECG, outpatient ambulatory monitor if symptoms suggest recurrence. Eighteen to 24 months after initial presentation Clinical follow-up, ECG. If complete recovery of EF is noted and angiotensin converting enzyme (ACE) inhibitors and beta blockers are tapered off, additional monitoring is required to be sure that EF remains normal [4]. PROGNOSIS https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 14/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate Following the restoration of sinus rhythm or ventricular rate control of the presenting tachycardia, most patients will have significant improvement and/or normalization of LVEF over a period of months. As such, patients who have not experienced sudden cardiac arrest or a sustained ventricular arrhythmia, and whose LVEF has improved to 40 percent or greater, usually do not require implantation of an implantable cardioverter-defibrillator (ICD). (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) In some patients whose LVEF has normalized, the LV chamber may remain somewhat enlarged. Despite the apparent normalization of cardiac function when a tachycardia has been terminated or rate controlled, ultrastructural abnormalities of the myocardium may persist [60]. Additional evidence for persistent myocardial abnormality despite normalization of systolic function was seen in a study of successfully ablated patients with atrial tachycardia. These patients demonstrated LV structure and function changes including diffuse fibrosis on contrast-enhanced CMR imaging long after successful ablation (64 36 months) [90]. As noted previously, late- gadolinium enhancement on CMR suggests the presence of fibrosis and identifies irreversible structural changes that may predict incomplete recovery of LV function. For any patient whose LVEF fails to normalize with correction of the tachyarrhythmia, other underlying pathology should be considered including permanent structural changes [90,109]. If arrhythmia-induced cardiomyopathy recurs, these patients are at substantial risk for sudden death, and ICD implantation should be contemplated [107]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 15/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Beyond the Basics topics (see "Patient education: Atrial fibrillation (Beyond the Basics)" and "Patient education: Catheter ablation for abnormal heartbeats (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definition Arrhythmia-induced cardiomyopathy is a relatively rare cause of a dilated cardiomyopathy resulting from prolonged periods of rapid ventricular heart rates. Arrhythmia-induced cardiomyopathy often improves or resolves following treatment and is associated with a good prognosis in most patients. (See 'Introduction' above.) Pathophysiology Chronic tachycardia ultimately produces significant structural changes in the heart, with impressive left ventricular (LV) dilation and cellular morphologic changes leading to a cardiomyopathy. The precise mechanism(s) by which a chronic tachycardia produces these changes remain incompletely described. (See 'Pathophysiology' above.) Association with specific arrhythmias Virtually all tachyarrhythmias have been reported to cause arrhythmia-induced cardiomyopathy, and frequent ectopic beats have also been associated with this condition. In most cases, the myocardial dysfunction improves or normalizes following therapy to control the ventricular heart rate or to restore normal sinus rhythm. (See 'Arrhythmias associated with arrhythmia-induced cardiomyopathy' above.) Clinical presentation The clinical presentation of arrhythmia-induced cardiomyopathy is variable but usually involves signs and/or symptoms related to the tachyarrhythmia (eg, palpitations, dyspnea, chest discomfort, etc), heart failure (HF; eg, dyspnea, edema, weight gain, orthopnea, etc), or both. In our experience, HF symptoms are more common since patients with symptomatic tachyarrhythmias will frequently seek medical attention earlier in the course of their care and prior to the development of a cardiomyopathy. (See 'Clinical presentation' above.) ECG findings All patients should have an ECG to document the cardiac rhythm and ventricular heart rate, with comparison to prior ECGs when available. There are no specific https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 16/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate ECG findings that distinguish patients with and without arrhythmia-induced cardiomyopathy, and the ECG findings will vary depending upon the underlying tachyarrhythmia. (See 'ECG findings' above.) Approach to diagnosis Arrhythmia-induced cardiomyopathy is defined by the presence of a sustained tachycardia (or frequent episodes of tachycardia or very frequent ectopy) that results in with LV systolic dysfunction. Usually the diagnosis of arrhythmia-induced cardiomyopathy can only be made following a successful trial of therapy to slow the ventricular rate or to restore sinus rhythm along with the exclusion of other potential causes of cardiomyopathy. Patients in whom arrhythmia-induced cardiomyopathy is suspected should undergo continuous cardiac monitoring for 24 to 48 hours and have non- invasive imaging to assess cardiac structure and function. For most patients, a transthoracic echocardiogram is the preferred test for assessing cardiac structure and function, although cardiovascular magnetic resonance (CMR) imaging is a reasonable alternative. (See 'Approach to the diagnosis' above and 'Diagnostic testing' above.) Treatment The initial treatments for a patient with HF and suspected arrhythmia-induced cardiomyopathy are the same as those used in most other patients with HF (eg, angiotensin converting enzyme [ACE] inhibitors or angiotensin II receptor blockers [ARBs], beta blockers, diuretics) and tachyarrhythmias (eg, rate-control medications, consideration of antiarrhythmic drugs and/or cardioversion). However, because of the potential reversible nature of arrhythmia-induced cardiomyopathy, aggressive efforts should be made to achieve excellent ventricular heart rate control or to restore sinus rhythm. (See 'Treatment' above.) For minimally symptomatic patients with atrial fibrillation (AF) in whom adequate rate control is achieved, we continue medical therapy. For patients with AF who remain significantly symptomatic, or patients in whom adequate rate control is not achieved with medical therapy alone, we pursue a rhythm control strategy. (See "Management of atrial fibrillation: Rhythm control versus rate control" and "Atrial fibrillation: Cardioversion".) For patients with atrial flutter, rapid ventricular rates, and newly recognized depressed LV ejection fraction (LVEF), rate control may be difficult to achieve with medication. Because of this, we perform early electrical cardioversion in these patients. (See "Restoration of sinus rhythm in atrial flutter".) For supraventricular tachyarrhythmias (SVTs) other than AF or atrial flutter that result in arrhythmia-induced cardiomyopathy, restoration of sinus rhythm is the usual goal. The https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 17/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate initial choice of modality (ie, electrical cardioversion, antiarrhythmic drugs, or catheter ablation of the arrhythmia) will vary depending upon the underlying SVT as well as the local expertise and availability of options. For patients presenting with a high burden of premature ventricular complexes/contractions (PVCs) and associated with LV dysfunction, we generally pursue radiofrequency catheter ablation. On rare occasions when all efforts at ventricular rate control, restoration of sinus rhythm, and catheter ablation of the arrhythmia have been unsuccessful for the treatment of SVTs, ablation of the AV node with insertion of a permanent pacemaker may be considered. Long-term monitoring Close ongoing monitoring with clinic visits, ambulatory (Holter) monitoring, and echocardiography is essential to assess for any recurrence. We follow up with patients using a combination of clinic visits, echocardiography, and ambulatory monitoring every three to six months for one to two years following the initial clinical improvement. (See 'Follow-up' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Westphal JG, Rigopoulos AG, Bakogiannis C, et al. The MOGE(S) classification for cardiomyopathies: current status and future outlook. Heart Fail Rev 2017; 22:743. 2. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail 2017; 23:628. 3. Shinbane JS, Wood MA, Jensen DN, et al. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J Am Coll Cardiol 1997; 29:709. 4. Gopinathannair R, Etheridge SP, Marchlinski FE, et al. Arrhythmia-Induced Cardiomyopathies: Mechanisms, Recognition, and Management. J Am Coll Cardiol 2015; 66:1714. 5. Kasper EK, Agema WR, Hutchins GM, et al. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol 1994; 23:586. 6. SHACHNOW N, SPELLMAN S, RUBIN I. Persistent supraventricular tachycardia; case report with review of literature. Circulation 1954; 10:232. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 18/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 7. Engel TR, Bush CA, Schaal SF. Tachycardia-aggravated heart disease. Ann Intern Med 1974; 80:384. 8. Coleman HN 3rd, Taylor RR, Pool PE, et al. Congestive heart failure following chronic tachycardia. Am Heart J 1971; 81:790. 9. Vijgen J, Hill P, Biblo LA, Carlson MD. Tachycardia-induced cardiomyopathy secondary to right ventricular outflow tract ventricular tachycardia: improvement of left ventricular systolic function after radiofrequency catheter ablation of the arrhythmia. J Cardiovasc Electrophysiol 1997; 8:445. 10. Singh B, Kaul U, Talwar KK, Wasir HS. Reversibility of "tachycardia induced cardiomyopathy" following the cure of idiopathic left ventricular tachycardia using radiofrequency energy. Pacing Clin Electrophysiol 1996; 19:1391. 11. Baman TS, Lange DC, Ilg KJ, et al. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm 2010; 7:865. 12. Medi C, Kalman JM, Haqqani H, et al. Tachycardia-mediated cardiomyopathy secondary to focal atrial tachycardia: long-term outcome after catheter ablation. J Am Coll Cardiol 2009; 53:1791. 13. Donghua Z, Jian P, Zhongbo X, et al. Reversal of cardiomyopathy in patients with congestive heart failure secondary to tachycardia. J Interv Card Electrophysiol 2013; 36:27. 14. Brembilla-Perrot B, Ferreira JP, Manenti V, et al. Predictors and prognostic significance of tachycardiomyopathy: insights from a cohort of 1269 patients undergoing atrial flutter ablation. Eur J Heart Fail 2016; 18:394. 15. Spinale FG, Hendrick DA, Crawford FA, et al. Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine. Am J Physiol 1990; 259:H218. 16. Howard RJ, Stopps TP, Moe GW, et al. Recovery from heart failure: structural and functional analysis in a canine model. Can J Physiol Pharmacol 1988; 66:1505. 17. Morgan DE, Tomlinson CW, Qayumi AK, et al. Evaluation of ventricular contractility indexes in the dog with left ventricular dysfunction induced by rapid atrial pacing. J Am Coll Cardiol 1989; 14:489. 18. Spinale FG, Tomita M, Zellner JL, et al. Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia. Am J Physiol 1991; 261:H308. 19. Kajstura J, Zhang X, Liu Y, et al. The cellular basis of pacing-induced dilated cardiomyopathy. Myocyte cell loss and myocyte cellular reactive hypertrophy. Circulation 1995; 92:2306. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 19/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 20. O'Brien PJ, Ianuzzo CD, Moe GW, et al. Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies. Can J Physiol Pharmacol 1990; 68:34. 21. Ohno M, Cheng CP, Little WC. Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure. Circulation 1994; 89:2241. 22. Armstrong PW, Stopps TP, Ford SE, de Bold AJ. Rapid ventricular pacing in the dog: pathophysiologic studies of heart failure. Circulation 1986; 74:1075. 23. Wilson JR, Douglas P, Hickey WF, et al. Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects. Circulation 1987; 75:857. 24. Damiano RJ Jr, Tripp HF Jr, Asano T, et al. Left ventricular dysfunction and dilatation resulting from chronic supraventricular tachycardia. J Thorac Cardiovasc Surg 1987; 94:135. 25. Yamamoto K, Burnett JC Jr, Meyer LM, et al. Ventricular remodeling during development and recovery from modified tachycardia-induced cardiomyopathy model. Am J Physiol 1996; 271:R1529. 26. Huizar JF, Kaszala K, Potfay J, et al. Left ventricular systolic dysfunction induced by ventricular ectopy: a novel model for premature ventricular contraction-induced cardiomyopathy. Circ Arrhythm Electrophysiol 2011; 4:543. 27. Pak PH, Nuss HB, Tunin RS, et al. Repolarization abnormalities, arrhythmia and sudden death in canine tachycardia-induced cardiomyopathy. J Am Coll Cardiol 1997; 30:576. 28. Moe GW, Montgomery C, Howard RJ, et al. Left ventricular myocardial blood flow, metabolism, and effects of treatment with enalapril: further insights into the mechanisms of canine experimental pacing-induced heart failure. J Lab Clin Med 1993; 121:294. 29. Spinale FG, Holzgrefe HH, Mukherjee R, et al. LV and myocyte structure and function after early recovery from tachycardia-induced cardiomyopathy. Am J Physiol 1995; 268:H836. 30. Spinale FG, Clayton C, Tanaka R, et al. Myocardial Na+,K(+)-ATPase in tachycardia induced cardiomyopathy. J Mol Cell Cardiol 1992; 24:277. 31. Kloner RA, DeBoer LW, Darsee JR, et al. Recovery from prolonged abnormalities of canine myocardium salvaged from ischemic necrosis by coronary reperfusion. Proc Natl Acad Sci U S A 1981; 78:7152. 32. Reimer KA, Hill ML, Jennings RB. Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. J Mol Cell Cardiol 1981; 13:229. 33. Spinale FG, Tanaka R, Crawford FA, Zile MR. Changes in myocardial blood flow during development of and recovery from tachycardia-induced cardiomyopathy. Circulation 1992; 85:717. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 20/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 34. Shannon RP, Komamura K, Shen YT, et al. Impaired regional subendocardial coronary flow reserve in conscious dogs with pacing-induced heart failure. Am J Physiol 1993; 265:H801. 35. Perreault CL, Shannon RP, Komamura K, et al. Abnormalities in intracellular calcium regulation and contractile function in myocardium from dogs with pacing-induced heart failure. J Clin Invest 1992; 89:932. 36. Tanaka R, Fulbright BM, Mukherjee R, et al. The cellular basis for the blunted response to beta-adrenergic stimulation in supraventricular tachycardia-induced cardiomyopathy. J Mol Cell Cardiol 1993; 25:1215. 37. Sasayama S, Asanoi H, Ishizaka S. Continuous measurement of the pressure-volume relationship in experimental heart failure produced by rapid ventricular pacing in conscious dogs. Eur Heart J 1992; 13 Suppl E:47. 38. Selby DE, Palmer BM, LeWinter MM, Meyer M. Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction. J Am Coll Cardiol 2011; 58:147. 39. Marzo KP, Frey MJ, Wilson JR, et al. Beta-adrenergic receptor-G protein-adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing. Circ Res 1991; 69:1546. 40. Wakili R, Yeh YH, Yan Qi X, et al. Multiple potential molecular contributors to atrial hypocontractility caused by atrial tachycardia remodeling in dogs. Circ Arrhythm Electrophysiol 2010; 3:530. 41. Yonemochi H, Yasunaga S, Teshima Y, et al. Rapid electrical stimulation of contraction reduces the density of beta-adrenergic receptors and responsiveness of cultured neonatal rat cardiomyocytes. Possible involvement of microtubule disassembly secondary to mechanical stress. Circulation 2000; 101:2625. 42. Mihm MJ, Yu F, Carnes CA, et al. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 2001; 104:174. 43. Shite J, Qin F, Mao W, et al. Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction in tachycardia-induced cardiomyopathy. J Am Coll Cardiol 2001; 38:1734. 44. Deshmukh PM, Krishnamani R, Romanyshyn M, et al. Association of angiotensin converting enzyme gene polymorphism with tachycardia cardiomyopathy. Int J Mol Med 2004; 13:455. 45. Mueller KAL, Heinzmann D, Klingel K, et al. Reply: Histopathological and Immunological Characteristics of Tachycardia-Induced Cardiomyopathy. J Am Coll Cardiol 2017; 70:1687. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 21/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 46. Chiladakis JA, Vassilikos VP, Maounis TN, et al. Successful radiofrequency catheter ablation of automatic atrial tachycardia with regression of the cardiomyopathy picture. Pacing Clin Electrophysiol 1997; 20:953. 47. Gillette PC, Smith RT, Garson A Jr, et al. Chronic supraventricular tachycardia. A curable cause of congestive cardiomyopathy. JAMA 1985; 253:391. 48. Gallagher JJ. Tachycardia and cardiomyopathy: the chicken-egg dilemma revisited. J Am Coll Cardiol 1985; 6:1172. 49. Bertil Olsson S, Blomstr m P, Sabel KG, William-Olsson G. Incessant ectopic atrial tachycardia: successful surgical treatment with regression of dilated cardiomyopathy picture. Am J Cardiol 1984; 53:1465. 50. Packer DL, Bardy GH, Worley SJ, et al. Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction. Am J Cardiol 1986; 57:563. 51. Rao PS, Najjar HN. Congestive cardiomyopathy due to chronic tachycardia: resolution of cardiomyopathy with antiarrhythmic drugs. Int J Cardiol 1987; 17:216. 52. Gillette PC, Wampler DG, Garson A Jr, et al. Treatment of atrial automatic tachycardia by ablation procedures. J Am Coll Cardiol 1985; 6:405. 53. Sanders P, Morton JB, Kistler PM, et al. Reversal of atrial mechanical dysfunction after cardioversion of atrial fibrillation: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy. Circulation 2003; 108:1976. 54. Fishberger SB, Colan SD, Saul JP, et al. Myocardial mechanics before and after ablation of chronic tachycardia. Pacing Clin Electrophysiol 1996; 19:42. 55. Aguinaga L, Primo J, Anguera I, et al. Long-term follow-up in patients with the permanent form of junctional reciprocating tachycardia treated with radiofrequency ablation. Pacing Clin Electrophysiol 1998; 21:2073. 56. Leman RB, Gillette PC, Zinner AJ. Resolution of congestive cardiomyopathy caused by supraventricular tachycardia using amiodarone. Am Heart J 1986; 112:622. 57. Corey WA, Markel ML, Hoit BD, Walsh RA. Regression of a dilated cardiomyopathy after radiofrequency ablation of incessant supraventricular tachycardia. Am Heart J 1993; 126:1469. 58. Grimm W, Menz V, Hoffmann J, Maisch B. Reversal of tachycardia induced cardiomyopathy following ablation of repetitive monomorphic right ventricular outflow tract tachycardia. Pacing Clin Electrophysiol 2001; 24:166. 59. Yarlagadda RK, Iwai S, Stein KM, et al. Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 22/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate Circulation 2005; 112:1092. 60. Nerheim P, Birger-Botkin S, Piracha L, Olshansky B. Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia. Circulation 2004; 110:247. 61. Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med 2002; 113:359. 62. Luchsinger JA, Steinberg JS. Resolution of cardiomyopathy after ablation of atrial flutter. J Am Coll Cardiol 1998; 32:205. 63. Redfield MM, Kay GN, Jenkins LS, et al. Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Mayo Clin Proc 2000; 75:790. 64. Edner M, Caidahl K, Bergfeldt L, et al. Prospective study of left ventricular function after radiofrequency ablation of atrioventricular junction in patients with atrial fibrillation. Br Heart J 1995; 74:261. 65. Pizzale S, Lemery R, Green MS, et al. Frequency and predictors of tachycardia-induced cardiomyopathy in patients with persistent atrial flutter. Can J Cardiol 2009; 25:469. 66. Hasdemir C, Ulucan C, Yavuzgil O, et al. Tachycardia-induced cardiomyopathy in patients with idiopathic ventricular arrhythmias: the incidence, clinical and electrophysiologic characteristics, and the predictors. J Cardiovasc Electrophysiol 2011; 22:663. 67. Bogun F, Crawford T, Reich S, et al. Radiofrequency ablation of frequent, idiopathic premature ventricular complexes: comparison with a control group without intervention. Heart Rhythm 2007; 4:863. 68. Yokokawa M, Kim HM, Good E, et al. Relation of symptoms and symptom duration to premature ventricular complex-induced cardiomyopathy. Heart Rhythm 2012; 9:92. 69. Mountantonakis SE, Frankel DS, Gerstenfeld EP, et al. Reversal of outflow tract ventricular premature depolarization-induced cardiomyopathy with ablation: effect of residual arrhythmia burden and preexisting cardiomyopathy on outcome. Heart Rhythm 2011; 8:1608. 70. Penela D, Van Huls Van Taxis C, Aguinaga L, et al. Neurohormonal, structural, and functional recovery pattern after premature ventricular complex ablation is independent of structural heart disease status in patients with depressed left ventricular ejection fraction: a prospective multicenter study. J Am Coll Cardiol 2013; 62:1195. 71. El Kadri M, Yokokawa M, Labounty T, et al. Effect of ablation of frequent premature ventricular complexes on left ventricular function in patients with nonischemic https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 23/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate cardiomyopathy. Heart Rhythm 2015; 12:706. 72. Baser K, Bas HD, LaBounty T, et al. Recurrence of PVCs in patients with PVC-induced cardiomyopathy. Heart Rhythm 2015; 12:1519. 73. Penela D, Acosta J, Aguinaga L, et al. Ablation of frequent PVC in patients meeting criteria for primary prevention ICD implant: Safety of withholding the implant. Heart Rhythm 2015; 12:2434. 74. Laplante L, Benzaquen BS. A Review of the Potential Pathogenicity and Management of Frequent Premature Ventricular Contractions. Pacing Clin Electrophysiol 2016; 39:723. 75. Lamba J, Redfearn DP, Michael KA, et al. Radiofrequency catheter ablation for the treatment of idiopathic premature ventricular contractions originating from the right ventricular outflow tract: a systematic review and meta-analysis. Pacing Clin Electrophysiol 2014; 37:73. 76. Yokokawa M, Kim HM, Good E, et al. Impact of QRS duration of frequent premature ventricular complexes on the development of cardiomyopathy. Heart Rhythm 2012; 9:1460. 77. Carballeira Pol L, Deyell MW, Frankel DS, et al. Ventricular premature depolarization QRS duration as a new marker of risk for the development of ventricular premature depolarization-induced cardiomyopathy. Heart Rhythm 2014; 11:299. 78. Deyell MW, Park KM, Han Y, et al. Predictors of recovery of left ventricular dysfunction after ablation of frequent ventricular premature depolarizations. Heart Rhythm 2012; 9:1465. 79. Yokokawa M, Good E, Crawford T, et al. Recovery from left ventricular dysfunction after ablation of frequent premature ventricular complexes. Heart Rhythm 2013; 10:172. 80. Walters TE, Rahmutula D, Szilagyi J, et al. Left Ventricular Dyssynchrony Predicts the Cardiomyopathy Associated With Premature Ventricular Contractions. J Am Coll Cardiol 2018; 72:2870. 81. Pacchia CF, Akoum NW, Wasmund S, Hamdan MH. Atrial bigeminy results in decreased left ventricular function: an insight into the mechanism of PVC-induced cardiomyopathy. Pacing Clin Electrophysiol 2012; 35:1232. 82. Hasdemir C, Simsek E, Yuksel A. Premature atrial contraction-induced cardiomyopathy. Europace 2013; 15:1790. 83. Arnold JM, Liu P, Demers C, et al. Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: diagnosis and management. Can J Cardiol 2006; 22:23. 84. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42:3599. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 24/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 85. Heart Failure Society of America, Lindenfeld J, Albert NM, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010; 16:e1. 86. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136:e137. 87. Sakaguchi H, Miyazaki A, Yamamoto M, et al. Clinical characteristics of focal atrial tachycardias arising from the atrial appendages during childhood. Pacing Clin Electrophysiol 2011; 34:177. 88. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 89. Jeong YH, Choi KJ, Song JM, et al. Diagnostic approach and treatment strategy in tachycardia-induced cardiomyopathy. Clin Cardiol 2008; 31:172. 90. Ling LH, Kalman JM, Ellims AH, et al. Diffuse ventricular fibrosis is a late outcome of tachycardia-mediated cardiomyopathy after successful ablation. Circ Arrhythm Electrophysiol 2013; 6:697. 91. Hasdemir C, Yuksel A, Camli D, et al. Late gadolinium enhancement CMR in patients with tachycardia-induced cardiomyopathy caused by idiopathic ventricular arrhythmias. Pacing Clin Electrophysiol 2012; 35:465. 92. Kusunose K, Torii Y, Yamada H, et al. Clinical Utility of Longitudinal Strain to Predict Functional Recovery in Patients With Tachyarrhythmia and Reduced LVEF. JACC Cardiovasc Imaging 2017; 10:118. 93. Ortiz-Genga M, Garc a-Hern ndez S, Monserrat-Iglesias L, McKenna WJ. Preventing Sudden Death in Arrhythmogenic Cardiomyopathy: Careful Family and Genetic Evaluation Key to Appropriate Diagnosis and Management. Can J Cardiol 2021; 37:819. 94. Ortiz-Genga MF, Cuenca S, Dal Ferro M, et al. Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies. J Am Coll Cardiol 2016; 68:2440. 95. Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol 1992; 69:1570. 96. Gentlesk PJ, Sauer WH, Gerstenfeld EP, et al. Reversal of left ventricular dysfunction following ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2007; 18:9. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 25/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 97. Manolis AG, Katsivas AG, Lazaris EE, et al. Ventricular performance and quality of life in patients who underwent radiofrequency AV junction ablation and permanent pacemaker implantation due to medically refractory atrial tachyarrhythmias. J Interv Card Electrophysiol 1998; 2:71. 98. Prabhu S, Taylor AJ, Costello BT, et al. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. J Am Coll Cardiol 2017; 70:1949. 99. Anter E, Jessup M, Callans DJ. Atrial fibrillation and heart failure: treatment considerations for a dual epidemic. Circulation 2009; 119:2516. 100. Latchamsetty R, Bogun F. Premature Ventricular Complex-Induced Cardiomyopathy. JACC Clin Electrophysiol 2019; 5:537. 101. Eugenio PL. Frequent Premature Ventricular Contractions: An Electrical Link to Cardiomyopathy. Cardiol Rev 2015; 23:168. 102. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 103. Takemoto M, Yoshimura H, Ohba Y, et al. Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease. J Am Coll Cardiol 2005; 45:1259. 104. Zhong L, Lee YH, Huang XM, et al. Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: a single-center retrospective study. Heart Rhythm 2014; 11:187. 105. Berruezo A, Penela D, J uregui B, et al. Mortality and morbidity reduction after frequent premature ventricular complexes ablation in patients with left ventricular systolic dysfunction. Europace 2019; 21:1079. 106. Brignole M, Pokushalov E, Pentimalli F, et al. A randomized controlled trial of atrioventricular junction ablation and cardiac resynchronization therapy in patients with permanent atrial fibrillation and narrow QRS. Eur Heart J 2018; 39:3999. 107. Dandamudi G, Rampurwala AY, Mahenthiran J, et al. Persistent left ventricular dilatation in tachycardia-induced cardiomyopathy patients after appropriate treatment and normalization of ejection fraction. Heart Rhythm 2008; 5:1111. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 26/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 108. Moe GW, Armstrong P. Pacing-induced heart failure: a model to study the mechanism of disease progression and novel therapy in heart failure. Cardiovasc Res 1999; 42:591. 109. Ling LH, Taylor AJ, Ellims AH, et al. Sinus rhythm restores ventricular function in patients with cardiomyopathy and no late gadolinium enhancement on cardiac magnetic resonance imaging who undergo catheter ablation for atrial fibrillation. Heart Rhythm 2013; 10:1334. Topic 1062 Version 48.0 https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 27/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate GRAPHICS |
of idiopathic premature ventricular contractions originating from the right ventricular outflow tract: a systematic review and meta-analysis. Pacing Clin Electrophysiol 2014; 37:73. 76. Yokokawa M, Kim HM, Good E, et al. Impact of QRS duration of frequent premature ventricular complexes on the development of cardiomyopathy. Heart Rhythm 2012; 9:1460. 77. Carballeira Pol L, Deyell MW, Frankel DS, et al. Ventricular premature depolarization QRS duration as a new marker of risk for the development of ventricular premature depolarization-induced cardiomyopathy. Heart Rhythm 2014; 11:299. 78. Deyell MW, Park KM, Han Y, et al. Predictors of recovery of left ventricular dysfunction after ablation of frequent ventricular premature depolarizations. Heart Rhythm 2012; 9:1465. 79. Yokokawa M, Good E, Crawford T, et al. Recovery from left ventricular dysfunction after ablation of frequent premature ventricular complexes. Heart Rhythm 2013; 10:172. 80. Walters TE, Rahmutula D, Szilagyi J, et al. Left Ventricular Dyssynchrony Predicts the Cardiomyopathy Associated With Premature Ventricular Contractions. J Am Coll Cardiol 2018; 72:2870. 81. Pacchia CF, Akoum NW, Wasmund S, Hamdan MH. Atrial bigeminy results in decreased left ventricular function: an insight into the mechanism of PVC-induced cardiomyopathy. Pacing Clin Electrophysiol 2012; 35:1232. 82. Hasdemir C, Simsek E, Yuksel A. Premature atrial contraction-induced cardiomyopathy. Europace 2013; 15:1790. 83. Arnold JM, Liu P, Demers C, et al. Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: diagnosis and management. Can J Cardiol 2006; 22:23. 84. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42:3599. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 24/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 85. Heart Failure Society of America, Lindenfeld J, Albert NM, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010; 16:e1. 86. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136:e137. 87. Sakaguchi H, Miyazaki A, Yamamoto M, et al. Clinical characteristics of focal atrial tachycardias arising from the atrial appendages during childhood. Pacing Clin Electrophysiol 2011; 34:177. 88. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 89. Jeong YH, Choi KJ, Song JM, et al. Diagnostic approach and treatment strategy in tachycardia-induced cardiomyopathy. Clin Cardiol 2008; 31:172. 90. Ling LH, Kalman JM, Ellims AH, et al. Diffuse ventricular fibrosis is a late outcome of tachycardia-mediated cardiomyopathy after successful ablation. Circ Arrhythm Electrophysiol 2013; 6:697. 91. Hasdemir C, Yuksel A, Camli D, et al. Late gadolinium enhancement CMR in patients with tachycardia-induced cardiomyopathy caused by idiopathic ventricular arrhythmias. Pacing Clin Electrophysiol 2012; 35:465. 92. Kusunose K, Torii Y, Yamada H, et al. Clinical Utility of Longitudinal Strain to Predict Functional Recovery in Patients With Tachyarrhythmia and Reduced LVEF. JACC Cardiovasc Imaging 2017; 10:118. 93. Ortiz-Genga M, Garc a-Hern ndez S, Monserrat-Iglesias L, McKenna WJ. Preventing Sudden Death in Arrhythmogenic Cardiomyopathy: Careful Family and Genetic Evaluation Key to Appropriate Diagnosis and Management. Can J Cardiol 2021; 37:819. 94. Ortiz-Genga MF, Cuenca S, Dal Ferro M, et al. Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies. J Am Coll Cardiol 2016; 68:2440. 95. Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol 1992; 69:1570. 96. Gentlesk PJ, Sauer WH, Gerstenfeld EP, et al. Reversal of left ventricular dysfunction following ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2007; 18:9. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 25/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 97. Manolis AG, Katsivas AG, Lazaris EE, et al. Ventricular performance and quality of life in patients who underwent radiofrequency AV junction ablation and permanent pacemaker implantation due to medically refractory atrial tachyarrhythmias. J Interv Card Electrophysiol 1998; 2:71. 98. Prabhu S, Taylor AJ, Costello BT, et al. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. J Am Coll Cardiol 2017; 70:1949. 99. Anter E, Jessup M, Callans DJ. Atrial fibrillation and heart failure: treatment considerations for a dual epidemic. Circulation 2009; 119:2516. 100. Latchamsetty R, Bogun F. Premature Ventricular Complex-Induced Cardiomyopathy. JACC Clin Electrophysiol 2019; 5:537. 101. Eugenio PL. Frequent Premature Ventricular Contractions: An Electrical Link to Cardiomyopathy. Cardiol Rev 2015; 23:168. 102. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 103. Takemoto M, Yoshimura H, Ohba Y, et al. Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease. J Am Coll Cardiol 2005; 45:1259. 104. Zhong L, Lee YH, Huang XM, et al. Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: a single-center retrospective study. Heart Rhythm 2014; 11:187. 105. Berruezo A, Penela D, J uregui B, et al. Mortality and morbidity reduction after frequent premature ventricular complexes ablation in patients with left ventricular systolic dysfunction. Europace 2019; 21:1079. 106. Brignole M, Pokushalov E, Pentimalli F, et al. A randomized controlled trial of atrioventricular junction ablation and cardiac resynchronization therapy in patients with permanent atrial fibrillation and narrow QRS. Eur Heart J 2018; 39:3999. 107. Dandamudi G, Rampurwala AY, Mahenthiran J, et al. Persistent left ventricular dilatation in tachycardia-induced cardiomyopathy patients after appropriate treatment and normalization of ejection fraction. Heart Rhythm 2008; 5:1111. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 26/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate 108. Moe GW, Armstrong P. Pacing-induced heart failure: a model to study the mechanism of disease progression and novel therapy in heart failure. Cardiovasc Res 1999; 42:591. 109. Ling LH, Taylor AJ, Ellims AH, et al. Sinus rhythm restores ventricular function in patients with cardiomyopathy and no late gadolinium enhancement on cardiac magnetic resonance imaging who undergo catheter ablation for atrial fibrillation. Heart Rhythm 2013; 10:1334. Topic 1062 Version 48.0 https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 27/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate GRAPHICS Tachycardia-mediated cardiomyopathy: Improvement with treatment Associated arrhythmia Number of patients Evidence for improvement Treatment Atrial fibrillation 14 AV node ablation and pacer Increased EF Atrial fibrillation 12 Cardioversion Increased EF Atrial fibrillation 10 Rate control or Increased EF conversion Ectopic atrial 10 Surgical ablation Increased EF tachycardia AVRT 4 Medications Increased EF RVOT VT 1 Ablation Increased EF LV VT 1 Ablation Increased EF AVRT: atrioventricular reentrant tachycardia mediated by an accessory pathway; EF: ejection fraction; RVOT VT: right ventricular outflow tract ventricular tachycardia; LV VT: idiopathic left ventricular tachycardia. Graphic 59233 Version 1.0 https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 28/29 7/6/23, 11:10 AM Arrhythmia-induced cardiomyopathy - UpToDate Contributor Disclosures Cynthia M Tracy, MD No relevant financial relationship(s) with ineligible companies to disclose. William J McKenna, MD Consultant/Advisory Boards: Bristol Meyers Squibb [Novel pharmacological treatments for HCM]; Cytokinetics [Novel pharmacological treatments for HCM]; Health in Code [Genetic testing in inherited cardiac disease]; Tenaya Therapeutics [Gene therapy in cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy/print 29/29 |
7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome : Bradley P Knight, MD, FACC : Peter J Zimetbaum, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 06, 2021. INTRODUCTION Conduction from the atria to the ventricles normally occurs via the atrioventricular (AV) node/His-Purkinje system. Patients with a preexcitation syndrome have an additional or alternative pathway, known as an accessory pathway, which directly connects the atria and ventricle and bypasses the AV node. AV conduction through an accessory pathway (most commonly a direct AV connection) results in the earlier activation of the ventricles than if the impulse had traveled through the AV node; hence the term preexcitation. Accessory pathway is a generic term which may indicate either a "tract" which bypasses the AV node but inserts into the specialized conduction system (eg, the bundle of His, right or left bundles, or one of the fascicles), or a "connection" which bypasses the AV node and terminates directly within the myocardium. Other names that may be used include anomalous AV pathway, connection, or tract; accessory AV bypass pathway, connection, or tract; or simply AV bypass, tract, or pathway. (See "General principles of asynchronous activation and preexcitation".) At other times, the specific sites of origin and termination are used. Examples include accessory AV connection, atrio-Hisian pathway or connection, or atriofascicular pathway or connection ( table 1). Preexcitation through an AV bypass tract, the bundle of Kent, during sinus rhythm produces the electrocardiographic (ECG) pattern described by Wolff, Parkinson, and White in 1930 [1]. The terms preexcitation and Wolff-Parkinson-White (WPW) pattern are often used interchangeably. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 1/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate The ECG pattern of WPW should be differentiated from the "WPW syndrome," since patients with the latter have both the ECG pattern of preexcitation and paroxysmal tachyarrhythmias [2]. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) This topic will review the anatomy and electrophysiologic properties of the accessory pathways. These accessory pathways are clinically important because they can serve as one limb of a reentrant circuit during AV reentrant tachycardia, either orthodromic and antidromic, or can allow for frequent rapid conduction to the ventricles during atrial fibrillation leading to ventricular fibrillation and cardiac arrest. The related issue of asynchronous activation, the arrhythmias associated with WPW, and the pharmacologic and nonpharmacologic treatments of patients with this syndrome are discussed separately. A detailed discussion of electrophysiologic mapping techniques is found elsewhere. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis" and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome" and "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) ANATOMIC CONSIDERATIONS There are several types of accessory pathways ( table 1 and figure 1) [3,4]: The classic accessory pathway is the AV bypass tract or bundle of Kent in patients with Wolff-Parkinson-White pattern. This pathway directly connects atrial and ventricular myocardium, bypassing the AV node/His-Purkinje system. James fibers, atrionodal tracts, connect the atrium to the distal or compact AV node. (See "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction".) Atrio-Hisian tracts connect the atrium to His bundle. Various types of Hisian-fascicular tracts, also known as Mahaim fibers, connect the atrium (atriofascicular pathways), AV node (nodofascicular pathways) or His bundle (fasciculoventricular) to distal Purkinje fibers or ventricular myocardium. (See "Atriofascicular ("Mahaim") pathway tachycardia".) The gross anatomy of AV accessory pathways should be considered in two planes that run transversely at the level of and parallel to the AV groove and longitudinally perpendicular to the AV groove [5]. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 2/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Transverse plane In the transverse plane, bypass tracts can cross the AV groove anywhere except between the left and right fibrous trigones where the atrial myocardium is not in direct juxtaposition with ventricular myocardium. The remainder of the transverse plane can then be divided into quadrants consisting of the left free wall, posteroseptal, right free wall, and anteroseptal spaces ( figure 2) [5,6]. The distribution of accessory pathways within these regions is not homogeneous [7,8]: 46 to 60 percent of accessory pathways are found within the left free wall space 25 percent are within the posteroseptal space 13 to 21 percent of pathways are within the right free wall space 2 percent are within the anteroseptal space The left and right free wall spaces can be subdivided into anterior, anterolateral, lateral, posterolateral, and posterior zones. Distinctive 12-lead ECG patterns of fully preexcited QRS morphology have been validated during surgical mapping and ablation of accessory pathways within each of these subdivisions [9-13] Detailed knowledge of accessory pathway location within the free wall regions is of critical importance to the interventional electrophysiologist performing catheter ablation procedures [14]. Longitudinal plane Accessory pathway anatomy in the longitudinal plane can be most easily understood by studying a longitudinal section of the left free wall region ( figure 3). AV accessory pathways exist only between the annulus fibrosus and the epicardial reflection off the atrial and ventricular walls, confined within the AV groove subepicardial fat of the right and left free walls, the anteroseptal space, and the posteroseptal space. Accessory pathways insert directly into the atrial and basal ventricular myocardium, although they may course through the AV groove at a variable depth from subepicardial to subendocardial [5]. There are also vascular structures located in these regions. These include the circumflex coronary artery and coronary sinus in the left free wall space; the coronary sinus, middle cardiac vein, and posterior descending artery in the posteroseptal space; and the right coronary artery in the anteroseptal and right free wall spaces. AV accessory pathways may run in an oblique course rather than perpendicular to the transverse plane of the AV groove. As a result, the fibers may have an atrial insertion point that is transversely several centimeters removed from the point of ventricular attachment [15]. Finally, bypass tracts may occasionally exist as broad bands of tissue rather than discrete hair- like structures [5]. Associated structural cardiac abnormalities Accessory pathways are associated with structural heart abnormalities. Patients with hypertrophic cardiomyopathy appear to have a https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 3/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate higher incidence of accessory pathways than the normal population. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation".) In one study, familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome was mapped to a locus on chromosome 7q3 [16]. Patients with Ebstein anomaly can have right sided accessory pathways associated with the abnormal tricuspid valve and often have multiple accessory pathways. (See "Clinical manifestations and diagnosis of Ebstein anomaly".) There is an association with a dilated cardiomyopathy and ventricular preexcitation that can have a genetic basis. In addition, there are patients with a dilated cardiomyopathy felt to be caused by the ventricular dyssynchrony introduced by the ventricular preexcitation. This can resolve after ablation of the accessory pathway analogous to the improvements in ventricular function seen after cardiac resynchronization pacing therapy in patients with left bundle branch block and ventricular dysfunction [17,18]. Posteroseptal accessory pathways may involve more than just the atrial and ventricular musculature, and include the musculature surrounding the coronary sinus [19]. In a study of 480 patients with posteroseptal or left posterior accessory pathways, 171 were found to involve the coronary sinus musculature [20]. The delta wave was negative in lead II in 70 percent of these patients. A coronary sinus diverticulum was found in 21 percent of these patients at this tertiary referral center, but in only 2 percent of the patients who had not had a prior ablation attempt. For this reason, it is important to perform venography of the proximal coronary sinus during an ablation procedure in a patient with a posteroseptal accessory pathway when elimination of the pathway proves to be difficult. ELECTROPHYSIOLOGY OF PREEXCITATION The normal temporal and spatial sequence of atrial and ventricular activation is altered in the Wolff-Parkinson-White (WPW) type of preexcitation because conduction between the atria and ventricles involves both an accessory pathway and the normal AV node-His Purkinje system. The vast majority of accessory pathways generate a fast action potential due to the rapid inward sodium current, similar to normal His-Purkinje tissue and atrial and ventricular myocardium (see "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs"). As a result, they have constant antegrade and retrograde conduction at all rates until the refractory period is reached, at which time conduction is completely blocked (nondecremental conduction). In contrast, the AV node, which depends on the slow inward calcium current for generation and propagation of its action potential, exhibits decremental conduction in which the conduction https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 4/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate time of the impulse propagating through the AV node increases as the cycle length shortens (heart rate increased) [21]. Thus, AV conduction is more rapid through the accessory pathway than through the AV node, a difference that is increased at fast heart rates. This difference has potentially great clinical importance. The progressive prolongation of AV nodal conduction time at faster atrial rates has a protective role, limiting the ventricular response to rapid atrial rates in atrial fibrillation or atrial flutter. This decreasing speed of conduction until some but not all beats are transmitted through the AV nodal tissue is called decremental conduction. Accessory pathways are dependent on the rapid inward sodium current for depolarization and characteristically do not demonstrate decremental conduction. As a result, arrhythmias that utilize accessory pathways can conduct frequently and rapidly, leading to very fast ventricular rates during atrial fibrillation that may degenerate into ventricular fibrillation. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Mahaim fibers may have somewhat different properties in that they may show slow and decremental anterograde conduction, proximal AV nodal-like electrophysiologic properties and distal bundle branch-like properties, conduction block in response to adenosine, and heat- induced automaticity during radiofrequency catheter ablation. Spontaneous automaticity may arise in Mahaim fibers, particularly during ablation procedures of the atrial insertion, and this may trigger antidromic circus movement tachycardias [22]. Accessory pathways that directly connect the atrium to the ventricle can occasionally show slow and decremental conduction in the retrograde direction. When these slowly conducting pathways serve as the retrograde limb during orthodromic AV reentrant tachycardia, the RP interval is usually longer than the PR interval. These accessory pathways can lead to the permanent form of junctional reciprocating tachycardia and are usually located in the posteroseptal space [23]. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Permanent junctional reciprocating tachycardia'.) Rarely, accessory pathways that directly connect the atrium to the ventricle can also show decremental conduction in the antegrade direction. In these patients, preexcitation is not evident during sinus rhythm because conduction over the AV node is faster than over the accessory pathway, but the pathway can serve as the antegrade limb during antidromic AV reentrant tachycardia and give rise to a wide QRS tachycardia. These pathways are also usually in the posteroseptal location [24]. Ventricular activation Since an AV accessory pathway usually bypasses and conducts faster than the AV node, the onset of ventricular activation is earlier than expected if depolarization https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 5/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate occurred via the AV node. Since the accessory pathway usually exhibits nondecremental conduction, early activation remains constant at all heart rates. Preexcited intraventricular conduction in WPW spreads from the insertion point of the AV bypass tract in the ventricular myocardium via direct muscle fiber-to-muscle fiber conduction. This process is inherently slower than ventricular depolarization resulting from rapid His-Purkinje system conduction. Thus, the net effect is earlier initial excitation of the ventricles (via the accessory pathway) but slower activation of the ventricular myocardium than occurs normally. The net effect is that the QRS complex consists of fusion between early ventricular activation caused by preexcitation with the later ventricular activation resulting from transmission through the AV node and the infranodal conduction system to the ventricles. The initial part of ventricular activation is slowed and the upstroke of the QRS complex is slurred because of slow muscle fiber-to-muscle fiber conduction; this is termed a delta wave ( figure 4A-B). The sooner conduction occurs over the accessory pathway in relation to the AV node, the greater the amount of myocardium depolarized via the accessory pathway, resulting in a more prominent or wider delta wave, and increasing prolongation of the QRS complex ( figure 5). Minimal preexcitation in WPW Preexcitation and delta waves may not be apparent in sinus rhythm in patients with WPW who have a left-lateral bypass tract as the antegrade route for conduction; in this setting, the time for the atrial impulse to travel from the sinus node to reach the atrial insertion of the accessory pathway is longer than the time to reach the AV node. The presence of a septal Q wave in lead V6 of the surface ECG is useful to exclude minimal preexcitation with a high degree of reliability [25]. When there is uncertainty regarding the presence of ventricular preexcitation, vagal maneuvers can be performed or intravenous adenosine can be administered to cause transient AV nodal blockade. The P wave signal-averaged ECG may also be of help in identifying a concealed left-sided accessory pathway. In one series, such a bypass tract was associated with a more prolonged filtered P wave duration (132 versus 119 milliseconds in controls or patients with an AV nodal reentrant tachycardia) [26]. In addition, delta waves are not seen with non-WPW forms of preexcitation, such as Mahaim or James fibers, since these pathways terminate in the conducting system or in the ventricular myocardium close to the conducting system. Most Mahaim tachycardias, for example, are due to atriofascicular pathways. (See "Atriofascicular ("Mahaim") pathway tachycardia".) PR interval Since the impulse bypasses the AV node, the preexcited PR interval is often shorter than what would be considered normal; however, it may not be abnormally short in the https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 6/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate absolute sense [27]. The degree of PR interval shortening and the amount of QRS interval widening depend upon several factors: The balance between the antegrade conduction time and refractory period of the accessory pathway and those of the normal AV node/His-Purkinje system; the conduction properties of both are variably influenced by the autonomic nervous system. The atrial insertion point of the AV bypass tract. The site of atrial impulse origin. Interatrial conduction time. Atrial refractoriness. Because of these factors, preexcitation may be less apparent during sinus tachycardia when AV node conduction time is short due to elevated sympathetic tone and decreased vagal tone. In addition, as mentioned above, an AV bypass tract that crosses the AV groove in the left lateral region may result in inapparent preexcitation and minimal PR interval shortening in sinus rhythm because of the greater interatrial distance required for impulse propagation from the sinus node to the left atrial insertion of the bypass tract. Intermittent preexcitation Intermittent preexcitation should be distinguished from day-to- day variability in preexcitation which results from changes in AV nodal conduction in relation to those of the accessory pathway usually due to changes in autonomic tone. True intermittent preexcitation is characterized by abrupt loss of the delta wave, normalization of the QRS duration, and an increase in the PR interval during a continuous ECG recording in the absence of any significant change in heart rate. This finding is generally a reliable sign that the AV bypass tract has a relatively long antegrade refractory period and is not capable of frequent impulse conduction, thus placing the patient at low risk for ventricular arrhythmias [27]. Preexcitation alternans In preexcitation alternans, a QRS complex manifesting a delta wave alternates with a normal QRS complex. This is also a marker for an accessory pathway with a relatively long antegrade refractory period. Concertina effect The amount of fusion of the QRS complex varies with the electrophysiologic properties of the accessory pathway, which are influenced by sympathetic and parasympathetic tone and their effect on the AV node. As a result, the appearance and width of the QRS complex depends upon the balance between preexcitation and normal excitation via the AV node. If AV nodal conduction is fast, the amount of myocardium activated via the accessory pathway is less, and hence there is a longer PR interval, less prominent delta https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 7/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate wave, and narrower QRS complex. If AV nodal conduction is slow, more myocardium is activated via the accessory pathway, resulting in a shorter PR interval, more prominent delta wave, and wider QRS complex. Changing degrees of AV nodal conduction and hence fusion in some patients may cause the QRS duration and the PR interval to periodically wax and wane, resulting in an appearance referred to as the "concertina effect" of preexcitation ( waveform 1 and waveform 2). In this phenomenon, PR intervals and QRS complex durations show a cyclic pattern, eg, preexcitation becomes progressively more prominent over a number of QRS complex cycles followed by a gradual diminution in the degree of preexcitation over several QRS cycles despite a fairly constant heart rate [28,29]. Accessory pathways exhibiting decremental conduction Approximately 10 percent of patients have accessory pathways in which conduction slows at faster rates of stimulation (decremental conduction), similar to the situation with the AV node. As noted above, the progressive prolongation of AV nodal conduction time at faster atrial rates has a protective role, limiting the ventricular response to rapid atrial rates in atrial fibrillation or atrial flutter. Accessory pathways which display decremental conduction in one direction may exhibit varied electrophysiologic properties in the other. As an example, one study examined the characteristics of the accessory pathway in 74 patients with decremental accessory pathways [30]. Among 64 patients with retrograde decremental conduction, anterograde conduction was not present in 64 percent, was intermittent in 8 percent, and was nondecremental in 28 percent. Five patients had anterograde but not retrograde conduction, and five had conduction in both directions. Another study examined 384 symptomatic patients with a single accessory pathway and found that retrograde decremental conduction over the accessory pathway was present in the posteroseptal (17 percent) and left free wall (3 percent), but absent in the other locations. Anterograde decremental conduction was only seen in the right free wall location (12 percent) [24]. Concealed accessory pathways Although AV accessory pathways usually conduct antegradely and retrogradely, some AV bypass tracts are capable of propagating impulses in only one direction [8,12,14,29-31]. Bypass tracts that conduct only in an antegrade direction are uncommon. They often cross the right AV groove, and frequently possess decremental conduction properties [8,27,31-33]. Bypass tracts that conduct only in the retrograde direction occur more frequently with an incidence reported as high as 16 percent [34]. Because they do not preexcite the ventricles, the surface ECG during sinus rhythm appears normal and therefore these pathways are called https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 8/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate "concealed." Some concealed pathways may be able to conduct anterograde, but have such long refractory periods that they do not conduct during sinus rhythm and are concealed. Preexcitation can sometimes be seen in patients with this type of a concealed accessory pathway after a long sinus pause, such as immediately after termination of AV reciprocating tachycardia. Most concealed AV bypass tracts exhibit nondecremental conduction and, because they serve as conduit for retrograde ventriculoatrial conduction, they are associated with reentrant arrhythmias [34,35]. Concealed accessory pathways that have decremental properties are usually located in the posteroseptal region. However, these pathways also occur in nonseptal locations with an incidence as high as 25 percent in one series [36]. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Prevalence of concealed accessory pathways'.) RELATIONSHIP BETWEEN ACCESSORY PATHWAY SITE AND THE ELECTROCARDIOGRAPHIC PATTERN Many articles have attempted to correlate the site of the accessory pathway with the ECG pattern [13,37-41]. However, the ECG appearance of activation depends upon the extent of preexcitation and fusion; as a result, the same pathway may not always produce the identical ECG pattern. Furthermore, as many as 13 percent of individuals with preexcitation have more than one accessory pathway. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Accessory pathway location'.) The surface ECG does, however, provide important clues for the cardiologist to direct invasive mapping. It also serves as a guide for the electrophysiologist to anticipate the morbidity of the particular procedural approach required to treat a particular accessory pathway (eg, ablation of pathways near the AV node and bundle of His has a higher inherent risk of inducing AV block and requiring a permanent pacemaker). This information related to pathway location is helpful when counseling patients about the risks of ablation. The optimal time to use the surface ECG to estimate the location of the accessory pathway is in the electrophysiology laboratory during atrial pacing at a rate that results in maximal preexcitation. Localizing the accessory AV connection site based upon the ECG A useful approach to map the location of the common form of accessory pathway, the accessory AV connection (AAVC), combines the algorithms of Milstein ( figure 2 and algorithm 1) and Arruda ( figure 2 and algorithm 2) [13,39,41,42]. The Milstein approach accurately localizes the AAVC to general regions along the AV rings; the Arruda approach is more precise, as has been confirmed by https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 9/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate endocardial mapping, and is helpful in further discriminating the septal areas of the AV rings. Distinctly classifying the posteroseptal/midseptal/anteroseptal areas also helps the clinician prepare the patient for different treatment options, including radiofrequency ablation, medical therapy, or monitoring. (See "Treatment of arrhythmias associated with the Wolff-Parkinson- White syndrome".) Vector of the delta wave The first step is to assess the vector of the delta wave: Is the delta wave vector directed away from or isoelectric to the leftward leads I, aVL, or V6? In other words, is the delta wave a Q wave or isoelectric in I, aVL, or V6? If yes and a left bundle branch block (LBBB)-type pattern is also present, (QRS 0.09 sec in lead I with an rS pattern in V1 or V2), a right anteroseptal pathway is suggested ( waveform 3). This connection initiates a generally rightward activation of the right ventricle (RV) in one of the leftward leads (leading to negative delta waves in aVL and/or V6). The asynchronous activation of the right and then the left ventricle (LV) produces the LBBB-like ECG pattern. The QRS axis is greater than +30 which helps distinguish the right anteroseptal from a right lateral pathway. If yes and a LBBB-type configuration is not present, a left lateral pathway is suggested ( waveform 4 and waveform 5). Preexcitation begins in the lateral portion of the left ventricle; as a result, initial activation is to the right as reflected by a negative delta wave in one or more of the leftward leads (ECG 2 shows isoelectric to negative polarity in I and aVL while ECG 3 shows a negative delta wave in aVL). The pattern may then resemble an atypical right bundle branch block, because preexcitation begins in the left ventricle. If the delta waves in leads I, aVL and V6 are other than a Q wave or isoelectric, examine the vector first in the frontal plane and then in the horizontal plane. Specifically, see if the delta wave vector in the frontal plane forms a Q wave or is isoelectric in two of leads II, III, or aVF. If yes, examine the horizontal plane. If there is an Rs or RS in V1, V2, or V3, a posteroseptal pathway is suggested ( waveform 6A-D). Preexcitation therefore begins in the posterior portion of the septum and sweeps anteriorly, giving the initial positive R complex in the anterior precordial leads. Further discrimination is discussed in the legends to the ECGs. If yes, and the pattern is other than an Rs or RS in V1, V2, or V3, a right lateral pathway is suggested ( waveform 7). Preexcitation begins in the lateral portion of the right ventricle, which is anatomically anterior and to the right; as a result, activation is posteriorly and to the left. A LBBB-type pattern results because the RV is activated before the LV. The axis is https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 10/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate less than +30 (ECG 5 has a negative delta wave in III and is isoelectric in aVF), which distinguishes the right lateral from the anteroseptal pathway. If the pattern in leads II, III or aVF is not a Q or isoelectric delta wave, then: A left bundle branch type of pattern (QRS equal to or greater than 90 msec in I and rS in V1 or V2) with a QRS axis of more than +30 suggests a right anteroseptal pathway ( waveform 3). A left bundle branch type of pattern (QRS equal to or greater than 90 msec in I and rS in V1 or V2) with an axis that is +30 or less suggests a right lateral pathway ( waveform 7). An Rs or RS in V1 or V2, but a pattern not that of a left bundle branch type as defined above, suggests a left lateral pathway ( waveform 4 and waveform 5). If other than an Rs or RS, the pathway may be difficult to localize and probably represents a left anterior lateral pathway ( waveform 8). Another algorithm is based upon a stepwise discriminant analysis of 18 variables in patients who had undergone successful catheter ablation [13]: Right-sided pathways were distinguished from left-sided pathways by the QRS transition in V1 to V3. Anterior-posterior, septal, and lateral pathways were localized by an analysis of delta wave and QRS polarities. The algorithm was quite successful in identifying right- and left-sided accessory pathways, right free wall from right septal, right anterolateral from posterolateral, and anteroseptal from other right septal pathways ( waveform 9). Left anterolateral pathways were also distinguished from left posterior pathways, and right posterolateral pathways were distinguished from left posteroseptal pathways. The reader who wishes to pursue the ECG patterns further should consult the sophisticated and complex scheme based upon delta wave polarity, which has been described in detail elsewhere [9]. Mahaim fibers may be suggested by a narrow QRS with an rS pattern in lead III. During tachycardia, these individuals usually have a LBBB-like QRS complex with left axis deviation [43]. A more detailed discussion for the specialist is available elsewhere [44]. SUMMARY https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 11/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Patients with a preexcitation syndrome have an additional or alternative pathway, known as an accessory pathway, which directly connects the atria and ventricle and bypasses the atrioventricular (AV) node. During sinus rhythm, AV conduction through an accessory pathway (most commonly a direct AV connection) results in the earlier activation of the ventricles than if the impulse had traveled through the AV node, resulting in ventricular preexcitation. (See 'Introduction' above.) Some accessory pathways are associated with structural heart abnormalities. (See 'Anatomic considerations' above.) The classic accessory pathway is the AV bypass tract in patients with the Wolff-Parkinson- White (WPW) pattern. This pathway directly connects atrial and ventricular myocardium, bypassing the AV node/His-Purkinje system. (See 'Anatomic considerations' above.) Delta waves may not be apparent in sinus rhythm in patients with WPW who have a left- lateral bypass tract as the antegrade route for conduction. (See 'Minimal preexcitation in WPW' above.) Although AV accessory pathways usually conduct antegrade and retrograde, some AV bypass tracts are capable of propagating impulses in only one direction. (See 'Concealed accessory pathways' above.) The electrocardiographic (ECG) appearance of activation depends upon the extent of preexcitation and fusion; as a result, the same pathway may not always produce the identical ECG pattern. (See 'Relationship between accessory pathway site and the electrocardiographic pattern' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wolff, L, Parkinson, et al. Bundle branch block with a short P-R interval in healthy young people prone to paroxysmal tachycardia. Am Heart J 1930; 5:685. 2. Definition of terms related to cardiac rhythm. Am Heart J 1978; 95:796. 3. Waller BF. Clinicopathological correlations of the human cardiac conduction system. In: Card iac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadelphia 1990. p.249. 4. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 12/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 5. Ferguson TB, Cox JL. Surgical treatment for the Wolff-Parkinson-White syndrome: the endoc ardial approach. In: Cardiac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadel phia 1990. p.897. 6. Cox JL, Gallagher JJ, Cain ME. Experience with 118 consecutive patients undergoing operation for the Wolff-Parkinson-White syndrome. J Thorac Cardiovasc Surg 1985; 90:490. 7. Cain ME, Cox JL. Surgical treatment of supraventricular arrhythmias. In: Management of car diac arrhythmias: the nonpharmacologic approach, Platia E (Ed), JB Lippincott, Philadelphia 1987. p.304. 8. Gallagher JJ, Sealy WC, Kasell J. Intraoperative mapping studies in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1979; 2:523. 9. Gallagher JJ, Pritchett EL, Sealy WC, et al. The preexcitation syndromes. Prog Cardiovasc Dis 1978; 20:285. 10. Reddy GV, Schamroth L. The localization of bypass tracts in the Wolff-Parkinson-White syndrome from the surface electrocardiogram. Am Heart J 1987; 113:984. 11. Fananapazir L, German LD, Gallagher JJ, et al. Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways. Circulation 1990; 81:578. 12. Lindsay BD, Crossen KJ, Cain ME. Concordance of distinguishing electrocardiographic features during sinus rhythm with the location of accessory pathways in the Wolff- Parkinson-White syndrome. Am J Cardiol 1987; 59:1093. 13. Milstein S, Sharma AD, Guiraudon GM, Klein GJ. An algorithm for the electrocardiographic localization of accessory pathways in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1987; 10:555. 14. Cain ME, Luke RA, Lindsay BD. Diagnosis and localization of accessory pathways. Pacing Clin Electrophysiol 1992; 15:801. 15. Otomo K, Gonzalez MD, Beckman KJ, et al. Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation. Circulation 2001; 104:550. 16. MacRae CA, Ghaisas N, Kass S, et al. Familial Hypertrophic cardiomyopathy with Wolff- Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 1995; 96:1216. 17. Dai CC, Guo BJ, Li WX, et al. Dyssynchronous ventricular contraction in Wolff-Parkinson- White syndrome: a risk factor for the development of dilated cardiomyopathy. Eur J Pediatr 2013; 172:1491. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 13/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 18. Chiu SN, Chang CW, Lu CW, Wu MH. Restored cardiac function after successful resynchronization by right anterior and anteroseptal accessory pathway ablation in Wolff- Parkinson-White syndrome associated dilated cardiomyopathy. Int J Cardiol 2013; 163:e19. 19. Chauvin M, Shah DC, Ha ssaguerre M, et al. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation 2000; 101:647. 20. Sun Y, Arruda M, Otomo K, et al. Coronary sinus-ventricular accessory connections producing posteroseptal and left posterior accessory pathways: incidence and electrophysiological identification. Circulation 2002; 106:1362. 21. Prystowsky EN, Page RL. Electrophysiology and autonomic influences of the human atrioven tricular node. In: Electrophysiology of the Sinoatrial and Atrioventricular Nodes, Mazgalev T, Dreifus L, Michelson EL (Eds). 22. Sternick EB, Timmermans C, Sosa E, et al. The electrocardiogram during sinus rhythm and tachycardia in patients with Mahaim fibers: the importance of an "rS" pattern in lead III. J Am Coll Cardiol 2004; 44:1626. 23. Gaita F, Haissaguerre M, Giustetto C, et al. Catheter ablation of permanent junctional reciprocating tachycardia with radiofrequency current. J Am Coll Cardiol 1995; 25:648. 24. de Chillou C, Rodriguez LM, Schl pfer J, et al. Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location. J Am Coll Cardiol 1992; 20:666. 25. Bogun F, Kalusche D, Li YG, et al. Septal Q waves in surface electrocardiographic lead V6 exclude minimal ventricular preexcitation. Am J Cardiol 1999; 84:101. 26. Yoshida T, Ikeda H, Hiraki T, et al. Detection of concealed left sided accessory atrioventricular pathway by P wave signal averaged electrocardiogram. J Am Coll Cardiol 1999; 33:55. 27. Josephson ME. Preexcitation Syndromes. In: Clinical Cardiac Electrophysiology, Lea & Febige r, Philadelphia 1993. p.311. 28. German LD, Gallagher JJ. Functional properties of accessory atrioventricular pathways in Wolff-Parkinson-White syndrome. Clinical implications. Am J Med 1984; 76:1079. 29. Nalos, PC, Deng, et al. Intermittent preexcitation: Clinical recognition and management. Pract Cardiol 1985; 11:49. 30. Chen SA, Tai CT, Chiang CE, et al. Electrophysiologic characteristics, electropharmacologic responses and radiofrequency ablation in patients with decremental accessory pathway. J Am Coll Cardiol 1996; 28:732. |
SUMMARY https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 11/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Patients with a preexcitation syndrome have an additional or alternative pathway, known as an accessory pathway, which directly connects the atria and ventricle and bypasses the atrioventricular (AV) node. During sinus rhythm, AV conduction through an accessory pathway (most commonly a direct AV connection) results in the earlier activation of the ventricles than if the impulse had traveled through the AV node, resulting in ventricular preexcitation. (See 'Introduction' above.) Some accessory pathways are associated with structural heart abnormalities. (See 'Anatomic considerations' above.) The classic accessory pathway is the AV bypass tract in patients with the Wolff-Parkinson- White (WPW) pattern. This pathway directly connects atrial and ventricular myocardium, bypassing the AV node/His-Purkinje system. (See 'Anatomic considerations' above.) Delta waves may not be apparent in sinus rhythm in patients with WPW who have a left- lateral bypass tract as the antegrade route for conduction. (See 'Minimal preexcitation in WPW' above.) Although AV accessory pathways usually conduct antegrade and retrograde, some AV bypass tracts are capable of propagating impulses in only one direction. (See 'Concealed accessory pathways' above.) The electrocardiographic (ECG) appearance of activation depends upon the extent of preexcitation and fusion; as a result, the same pathway may not always produce the identical ECG pattern. (See 'Relationship between accessory pathway site and the electrocardiographic pattern' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wolff, L, Parkinson, et al. Bundle branch block with a short P-R interval in healthy young people prone to paroxysmal tachycardia. Am Heart J 1930; 5:685. 2. Definition of terms related to cardiac rhythm. Am Heart J 1978; 95:796. 3. Waller BF. Clinicopathological correlations of the human cardiac conduction system. In: Card iac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadelphia 1990. p.249. 4. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 12/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 5. Ferguson TB, Cox JL. Surgical treatment for the Wolff-Parkinson-White syndrome: the endoc ardial approach. In: Cardiac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadel phia 1990. p.897. 6. Cox JL, Gallagher JJ, Cain ME. Experience with 118 consecutive patients undergoing operation for the Wolff-Parkinson-White syndrome. J Thorac Cardiovasc Surg 1985; 90:490. 7. Cain ME, Cox JL. Surgical treatment of supraventricular arrhythmias. In: Management of car diac arrhythmias: the nonpharmacologic approach, Platia E (Ed), JB Lippincott, Philadelphia 1987. p.304. 8. Gallagher JJ, Sealy WC, Kasell J. Intraoperative mapping studies in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1979; 2:523. 9. Gallagher JJ, Pritchett EL, Sealy WC, et al. The preexcitation syndromes. Prog Cardiovasc Dis 1978; 20:285. 10. Reddy GV, Schamroth L. The localization of bypass tracts in the Wolff-Parkinson-White syndrome from the surface electrocardiogram. Am Heart J 1987; 113:984. 11. Fananapazir L, German LD, Gallagher JJ, et al. Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways. Circulation 1990; 81:578. 12. Lindsay BD, Crossen KJ, Cain ME. Concordance of distinguishing electrocardiographic features during sinus rhythm with the location of accessory pathways in the Wolff- Parkinson-White syndrome. Am J Cardiol 1987; 59:1093. 13. Milstein S, Sharma AD, Guiraudon GM, Klein GJ. An algorithm for the electrocardiographic localization of accessory pathways in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1987; 10:555. 14. Cain ME, Luke RA, Lindsay BD. Diagnosis and localization of accessory pathways. Pacing Clin Electrophysiol 1992; 15:801. 15. Otomo K, Gonzalez MD, Beckman KJ, et al. Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation. Circulation 2001; 104:550. 16. MacRae CA, Ghaisas N, Kass S, et al. Familial Hypertrophic cardiomyopathy with Wolff- Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 1995; 96:1216. 17. Dai CC, Guo BJ, Li WX, et al. Dyssynchronous ventricular contraction in Wolff-Parkinson- White syndrome: a risk factor for the development of dilated cardiomyopathy. Eur J Pediatr 2013; 172:1491. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 13/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 18. Chiu SN, Chang CW, Lu CW, Wu MH. Restored cardiac function after successful resynchronization by right anterior and anteroseptal accessory pathway ablation in Wolff- Parkinson-White syndrome associated dilated cardiomyopathy. Int J Cardiol 2013; 163:e19. 19. Chauvin M, Shah DC, Ha ssaguerre M, et al. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation 2000; 101:647. 20. Sun Y, Arruda M, Otomo K, et al. Coronary sinus-ventricular accessory connections producing posteroseptal and left posterior accessory pathways: incidence and electrophysiological identification. Circulation 2002; 106:1362. 21. Prystowsky EN, Page RL. Electrophysiology and autonomic influences of the human atrioven tricular node. In: Electrophysiology of the Sinoatrial and Atrioventricular Nodes, Mazgalev T, Dreifus L, Michelson EL (Eds). 22. Sternick EB, Timmermans C, Sosa E, et al. The electrocardiogram during sinus rhythm and tachycardia in patients with Mahaim fibers: the importance of an "rS" pattern in lead III. J Am Coll Cardiol 2004; 44:1626. 23. Gaita F, Haissaguerre M, Giustetto C, et al. Catheter ablation of permanent junctional reciprocating tachycardia with radiofrequency current. J Am Coll Cardiol 1995; 25:648. 24. de Chillou C, Rodriguez LM, Schl pfer J, et al. Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location. J Am Coll Cardiol 1992; 20:666. 25. Bogun F, Kalusche D, Li YG, et al. Septal Q waves in surface electrocardiographic lead V6 exclude minimal ventricular preexcitation. Am J Cardiol 1999; 84:101. 26. Yoshida T, Ikeda H, Hiraki T, et al. Detection of concealed left sided accessory atrioventricular pathway by P wave signal averaged electrocardiogram. J Am Coll Cardiol 1999; 33:55. 27. Josephson ME. Preexcitation Syndromes. In: Clinical Cardiac Electrophysiology, Lea & Febige r, Philadelphia 1993. p.311. 28. German LD, Gallagher JJ. Functional properties of accessory atrioventricular pathways in Wolff-Parkinson-White syndrome. Clinical implications. Am J Med 1984; 76:1079. 29. Nalos, PC, Deng, et al. Intermittent preexcitation: Clinical recognition and management. Pract Cardiol 1985; 11:49. 30. Chen SA, Tai CT, Chiang CE, et al. Electrophysiologic characteristics, electropharmacologic responses and radiofrequency ablation in patients with decremental accessory pathway. J Am Coll Cardiol 1996; 28:732. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 14/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 31. Murdock CJ, Leitch JW, Teo WS, et al. Characteristics of accessory pathways exhibiting decremental conduction. Am J Cardiol 1991; 67:506. 32. Tchou P, Lehmann MH, Jazayeri M, Akhtar M. Atriofascicular connection or a nodoventricular Mahaim fiber? Electrophysiologic elucidation of the pathway and associated reentrant circuit. Circulation 1988; 77:837. 33. Gillette PC, Garson A Jr, Cooley DA, McNamara DG. Prolonged and decremental antegrade conduction properties in right anterior accessory connections: Wide QRS antidromic tachycardia of left bundle branch block pattern without Wolff-Parkinson-White configuration in sinus rhythm. Am Heart J 1982; 103:66. 34. Ross DL, Uther JB. Diagnosis of concealed accessory pathways in supraventricular tachycardia. Pacing Clin Electrophysiol 1984; 7:1069. 35. Gillette PC. Concealed anomalous cardiac conduction pathways: a frequent cause of supraventricular tachycardia. Am J Cardiol 1977; 40:848. 36. Meiltz A, Weber R, Halimi F, et al. Permanent form of junctional reciprocating tachycardia in adults: peculiar features and results of radiofrequency catheter ablation. Europace 2006; 8:21. 37. Fitzpatrick AP, Gonzales RP, Lesh MD, et al. New algorithm for the localization of accessory atrioventricular connections using a baseline electrocardiogram. J Am Coll Cardiol 1994; 23:107. 38. Gallagher JJ, Sealy WC, Kasell J, Wallace AG. Multiple accessory pathways in patients with the pre-excitation syndrome. Circulation 1976; 54:571. 39. Arruda, M, Wang, et al. ECG algorithm for predicting sites of successful radiofrequency ablation of accessory pathways (abstract). Pacing Clin Electrophysiol 1993; 16(Pt 2):865. 40. Epstein AE, Kirklin JK, Holman WL, et al. Intermediate septal accessory pathways: electrocardiographic characteristics, electrophysiologic observations and their surgical implications. J Am Coll Cardiol 1991; 17:1570. 41. Arruda MS, McClelland JH, Wang X, et al. Development and validation of an ECG algorithm for identifying accessory pathway ablation site in Wolff-Parkinson-White syndrome. J Cardiovasc Electrophysiol 1998; 9:2. 42. Moss JD, Gerstenfeld EP, Deo R, et al. ECG criteria for accurate localization of left anterolateral and posterolateral accessory pathways. Pacing Clin Electrophysiol 2012; 35:1444. 43. Sternick EB, Sosa EA, Timmermans C, et al. Automaticity in Mahaim fibers. J Cardiovasc Electrophysiol 2004; 15:738. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 15/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 44. Sternick EB, Gerken LM. The 12-lead ECG in patients with Mahaim fibers. Ann Noninvasive Electrocardiol 2006; 11:63. Topic 953 Version 28.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 16/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate GRAPHICS Terminology and anatomic connections of preexcitation pathways Old Proposed or commonly used Anatomic connections terminology terminology Kent bundle* Accessory AV connection or AV bypass Atrium to ventricle tract James fiber Atrionodal bypass tract Atrium to low AV node Atriofascicular bypass tract Atrium to bundle of His Mahaim fiber Atriofascicular bypass tract Atrium to bundle branch Nodofascicular bypass tract AV node to bundle branch Nodoventricular bypass tract AV node to ventricular tissue Fasciculoventricular bypass tract Bundle branch to ventricular tissue AV: atrioventricular. These bypass tracts result in delta waves and the Wolff-Parkinson-White syndrome. These bypass tracts result in the Lown-Ganong-Levine syndrome and enhanced AV nodal conduction. Graphic 53343 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 17/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Types of accessory pathways Diagram of 4 types of abnormal conduction pathways: classic accessory atrioventricular pathway (red), atriofascicular pathway (green), fasciculoventricular pathway (light blue), and nodoventricular pathway (dark blue). The atrioventricular node and His-Purkinje system are represented in yellow. Atrioventricular, atriofascicular, and nodoventricular pathways are capable of supporting atrioventricular reciprocating tachycardias. In contrast, an isolated fasciculoventricular pathway can cause subtle preexcitation but does not support clinical tachycardia. Graphic 138850 Version 1.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 18/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Schematic showing anatomic locations of accessory pathways as they cross the AV junction The atrioventricular (AV) valve plane of the heart is viewed from the cardiac apex. The tricuspid valve is on the left in this figure and the mitral valve on the right; the coronary sinus, which provides the venous drainage of the heart, passes posterior to the mitral valve and empties into the right atrium above the tricuspid valve. All AV bypass tracts cross the AV valve plane; their locations are named with respect to this orientation (eg, an anteroseptal bypass tract crosses the AV valve plane from atrium to ventricle in the region marked "anteroseptal" in the figure, at approximately 10 to 11 o'clock with respect to the mitral valve ring). Reproduced with permission from: Cosio FG, Anderson RH, Becker A, et al. Living anatomy of the atrioventricular junctions. A guide to electrophysiological Statement from the Cardiac Nomenclature Study Group, Working Group of Arrythmias, European Society of Cardiology, and the Task Force on Cardiac Nomenclature from NASPE. North American Society of Pacing and Electrophysiology. Eur Heart J 1999; 20:1068. Copyright 1999 European Society of Cardiology. Graphic 77941 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 19/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Schematic showing anatomic locations of accessory pathways in the left ventricular (LV) free wall Longitudinal cross section of the free wall of the left ventricle at the level of the atrioventricular (AV) groove. The accessory pathways are present in the AV groove fat pad at variable depths in relation to the mitral annulus and the epicardium overlying the AV groove. Graphic 76316 Version 2.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 20/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate AV conduction with a concealed accessory pathway Schematic representation of AV conduction. The normal pacemaker is in the sinoatrial (SA) node at the junction of the superior vena cava and the right atrium. The SA node activates the right and left atria (shown in green). In the absence of an accessory pathway (AP) or, as in this case, if the AP is concealed, ventricular activation results from the impulse traversing the AV node, the specialized infranodal conducting system (His bundle, bundle branches, and fascicular branches, shown in red), thereby activating the ventricular myocardium (shown in yellow). The ECG shows a normal PR interval and a narrow QRS complex. The inset on the right shows the timing of SA node (SAN), right (RA) and left atrial (LA), His bundle (H), and the beginning of normal ventricular activation (V ). All of ventricular activation (shown in yellow) is due to normal AV nodal and infranodal conduction. N AV: atrioventricular; ECG: electrocardiogram. Graphic 73740 Version 5.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 21/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate AV conduction through an overt accessory pathway Compared with normal conduction in the preceding diagram, the accessory pathway (AP) is now overt. As a result, ventricular activation results from both early activation (pre-excitation) of the free wall of the left ventricle (shown in blue) and from normal activation (shown in yellow). The degree of unopposed pre-excitation depends upon the time required to conduct through the right and left atria, the AP, and the ventricular myocardium as compared with conduction through the normal pathways. The inset on the right shows the ECG timing of these events. The net effect is a QRS complex that is a fusion of ventricular pre-excitation (blue) and normal excitation (yellow). Early activation throughout the AP (V ) P occurs at about the same time as His bundle depolarization (H). This leads to a shorter PR interval, a small delta wave (arrow), and some prolongation of the QRS duration. AV: atrioventricular. Graphic 53773 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 22/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Conduction through an accessory pathway with AV nodal delay Compared with conduction through an AP with normal AV node conduction, delayed conduction through the AV node allows more of the ventricular myocardium to be activated by pre-excitation (shown in blue). The inset on the right shows the ECG timing of these events. The atrial to His interval is increased due to the AV nodal delay (RA to H); His activation is so delayed that it follows activation caused by the AP (V ). The PR interval is short due to the pre- excitation, the delta wave (arrow) is more pronounced due to the greater and unopposed early forces (blue), and the QRS duration is P prolonged due to the later than normal ventricular activation caused by the AV nodal delay (yellow). AV: atrioventricular; ECG: electrocardiogram. Graphic 62454 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 23/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) showing concertina effect in Wolff-Parkinson-White syndrome The 12-lead ECG and rhythm strip during sinus rhythm show a short PR interval and QRS complex which is aberrated and has a delta wave. After the fifth complex on the rhythm strip, there is a sinus pause after which the QRS compex is still aberrated but the PR interval is somewhat longer. Subsequently, the PR interval becomes progressively shorter. This variability in the PR interval during sinus rhythm is known as the "concertina effect." Graphic 53508 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 24/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Single-lead electrocardiogram (ECG) strip showing concertina effect in Wolff-Parkinson-White syndrome Single channel rhythm strip from a patient with the Wolff-Parkinson- White syndrome shows progressive shortening of the PR interval with the development of a widened QRS complex due to a delta wave. The P wave appears to merge with the QRS complex (arrows). The last two QRS complexes again show a normal PR interval and a narrow QRS complex. Graphic 65293 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 25/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Algorithm (Milstein) to localize accessory pathway in preexcitation syndrome Mapping algorithm for localization of accessory pathway in the preexcitation syndrome using the morphology of the delta wave on the electrocardiogram. LBBB: left bundle branch block; RAS: right anteroseptal; LL: left lateral; PS: posteroseptal; RL: right lateral. + QRS 90 msec in L1 and rS in V1 and V2. Reproduced with permission from Milstein S, Sharma AD, Guiraudon GM, et al. Pacing Clin Electrophysiol 1987; 10:555. Copyright 1987 Futura Publishing Company. Graphic 70648 Version 5.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 26/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Algorithm (Arruda) to localize accessory pathway in preexcitation syndrome https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 27/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 28/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Mapping algorithm for localization of accessory pathway in the preexcitation syndrome using the morphology of the delta wave on the electrocardiogram. R/S: R-S wave ratio; PPV: positive predictive value; LL: left lateral; LAL: left anterolateral; LP: left posterior; LPL: left posterolateral; CS/MCV: coronary sinus/middle cardiac vein; AS: right anteroseptal; MS: midseptal; LPS: left posteroseptal; RPS: right posteroseptal; RA: right anterior; RAP: right anterior paraseptal; RAL: right anterolateral; RL: right lateral; RP: right posterior; RPL: right posterolateral. Data from Arruda M, Wang X, McClelland J, et al, Pacing Clin Electrophysiol 1993; 16:865. Graphic 57692 Version 5.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 29/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right anterior septal accessory AV pathway Electrocardiogram from a patient with Wolff-Parkinson-White syndrome during sinus tachycardia shows a maximally preexcited QRS complex which has a left bundle branch block pattern and is markedly positive in the inferior leads. The delta wave is isoelectric in leads aVL and V6. These features localize the accessory pathway to the right anterior septum. Graphic 50415 Version 4.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 30/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left lateral accessory AV pathway Electrocardiogram in sinus rhythm from a patient with the Wolff-Parkinson- White syndrome shows a maximally preexcited QRS. The PR is short, the QRS has a right bundle branch block morphology, there is a prominent RS complex in V1, the QRS is negative, and the delta wave is isoelectric in leads I and aVL, localizing the accessory pathway to the left lateral annulus. Graphic 74370 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 31/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left lateral accessory AV pathway Electrocardiogram in sinus rhythm from a patient with Wolff-Parkinson- White syndrome shows a widened QRS complex which is not maximally preexcited. Although the delta wave and QRS are positive in lead I, the negative delta wave in lead aVL and the right bundle branch block morphology localize the accessory pathway to the left lateral mitral annulus. Graphic 50322 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 32/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right posteroseptal accessory AV pathway Electrocardiogram in sinus rhythm from a patient with Wolff-Parkinson-White syndrome shows a maximally preexcited QRS complex. There is early transition across the precordial leads, with R/S ratio of 1 occurring in lead V2. The delta waves are positive in the lateral leads I, aVL, and V6, and negative in leads III and aVF, localizing the pathway to the posteroseptal area. The positive delta wave in lead II and in the lateral leads localize the pathway to the right side. Graphic 69988 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 33/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right posteroseptal accessory AV pathway Electrocardiogram during rapid atrial pacing from a patient with Wolff- Parkinson-White syndrome. The QRS complex is maximally excited; the PR interval is short, and there is a left bundle branch morphology, left axis deviation, and early transition across the anterior precordial leads. The delta waves are positive in the lateral leads I, aVL, and V6 and negative in the inferior leads, localizing the pathway to the posteroseptal region. The negative delta wave in lead II places the pathway on the right, in the area between the coronary sinus os and middle cardiac vein. Graphic 57211 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 34/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right posteroseptal accessory AV pathway The 12 lead ECG during rapid atrial pacing shows QRS complexes that are maximally preexcited; the complexes have a pattern suggesting an AV accessory pathway located in the right posteroseptal area. At the time of ablation, the pathway was localized to the midseptal region. Graphic 59055 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 35/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left posteroseptal accessory AV pathway Electrocardiogram during right atrial pacing in a patient with Wolff- Parkinson-White syndrome shows a long stimulus to the P wave with a short PR interval, the appearance of both right and left bundle branch block morphologies, and a negative QRS morphology and delta wave in the inferior leads. This localizes the pathway to the posteroseptal area. The presence of a positive delta wave in lead I, RS ratio in lead V1 of approximately 1, and a negative delta wave in lead II places the pathway on the left side, inside the coronary sinus os or along the middle cardiac vein. This type of accessory pathway may be related to cardiac venous anomalies and aneurysms. Graphic 71868 Version 4.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 36/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right lateral accessory AV pathway Electrocardiogram in sinus rhythm from a patient with Wolff-Parkinson-White syndrome shows classic preexcitation with a short PR interval, delta wave, and widened QRS complex with a left bundle branch block morphology. The delta wave is positive in the lateral leads 1, aVL, and V6, it is negative in lead III and isoelectric in lead aVF. The QRS axis of <30L distinguishes this pathway from an anteroseptal accessory AV pathway. Courtesy of Morton F Arnsdorf, MD. Graphic 77218 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 37/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left anterior lateral accessory pathway Electrocardiogram during atrial pacing in a patient with the Wolff- Parkinson-White syndrome shows QRS complexes that are maximally preexcited. The PR interval is short, there is a right bundle branch morphology, and the axis is rightward. The delta wave is positive in the lateral leads I, avL, and V6, localizing the pathway to the left anterior lateral region. Courtesy of Morton F Arnsdorf, MD. Graphic 69928 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 38/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a midseptal accessory AV pathway Electrocardiogram from a patient with Wolff-Parkinson-White syndrome. The ECG criteria for a midseptal pathway are intermediate between those for posteroseptal and anteroseptal connections within the triangle of Koch. These pathways have been difficult to predict from the surface ECG and have usually been grouped as septal pathways. The ECG shows positive delta waves in the lateral leads I, aVL, and V6, with early transition and a tall R wave in lead V2. The delta wave is positive in leads II and aVF and negative in lead III, and the QRS axis is <0 , localizing the pathway in the midseptum. Graphic 51236 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 39/40 7/6/23, 11:11 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Contributor Disclosures Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 40/40 |
7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Atriofascicular ("Mahaim") pathway tachycardia : Luigi Di Biase, MD, PhD, FHRS, FACC, Edward P Walsh, MD : Brian Olshansky, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 23, 2022. INTRODUCTION th The term preexcitation was originally used in the first half of the 20 century to describe premature activation of the ventricles in patients with the Wolff-Parkinson-White (WPW) syndrome [1]. This term has since been broadened to include other less common conditions in which antegrade ventricular activation occurs partially or totally via an abnormal conduction pathway. This topic will discuss the anatomy, clinical manifestations, diagnosis, and treatment of patients with atriofascicular ("Mahaim") pathway tachycardias. Additional details regarding WPW syndrome and other syndromes with accessory conductions pathways are presented separately. (See "General principles of asynchronous activation and preexcitation" and "Wolff-Parkinson- White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis" and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome" and "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction".) NOMENCLATURE, ANATOMY, AND PHYSIOLOGY Nomenclature and anatomy Several types of abnormal conduction pathways have been identified ( figure 1), although firm histopathologic correlation with clinical arrhythmias has not been established for all [2]. Accessory atrioventricular (AV) pathways Classic Wolff-Parkinson-White (WPW) syndrome is caused by a small band of myocytes running between atrial and ventricular muscle that bridges the normal fibrous insulation along the AV junction, resulting in a https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 1/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate pattern of short PR interval and a delta wave on the electrocardiogram (ECG). These connections, formerly referred to as bundles of Kent, are now designated by the more accurate label of "accessory AV pathways" [3]. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) Accessory atrio-Hisian pathways Accessory atrio-Hisian pathways (also referred to as James fibers) have been implicated as the potential cause of the Lown-Ganong-Levine syndrome. In the initial report (authored by James) of these pathways, a potential microscopic conduction fiber pathway was seen linking atrial myocardium directly to the bundle of His, thereby bypassing the AV node and resulting in an ECG appearance of a short PR interval, but with a normal QRS and no delta wave [4]. What remains uncertain, however, is whether this is a true clinical entity or simply conventional AV nodal reentry in a patient who happens to have enhanced conduction in their AV nodal fast pathway. (See "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction".) Atriofascicular pathways Atriofascicular tachycardia is now understood to involve a specialized conduction pathway arising from the lateral right atrium that extends far down into the body of the right ventricle (RV) and is quite distinct from the AV node and bundle of His. Although nodoventricular fibers might still be involved in some rare cases of atypical supraventricular tachycardia [5-7], atriofascicular tachycardia is now known to be caused by a reentry circuit that is critically dependent on an atriofascicular pathway or a long AV fiber with unique conduction properties. The term "Mahaim" fiber is still retained by some as a shorthand synonym for an atriofascicular pathway, although it is universally understood that the label is imprecise. Clarification of the true mechanism for atriofascicular pathway tachycardia came about in the 1980s as a result of careful intracardiac electrophysiologic studies and fortuitous observations during arrhythmia surgery. Initial observations suggested the possibility of an unusual type of pathway along the right AV groove possessing decremental conduction properties [8]. These observations were further supported by the elimination of presumptive "Mahaim" fiber tachycardia; this was done by surgically interrupting atriofascicular pathways in two patients along the anterolateral tricuspid valve, proving that the culprit conduction pathway was truly remote from the AV node [9]. Electrophysiology Atriofascicular pathways exhibit structural and functional features that can almost be likened to a secondary AV conduction system. The atrial end is comprised of cells with AV nodal-like properties situated along the right AV groove in the lateral or anterolateral position. Conduction at the atrial end exhibits clear decrement in response to premature beats, and a Wenckebach-type of periodicity in response to trains of rapid atrial pacing, very similar to https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 2/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate behavior of the normal AV node. There is even histologic evidence of cells resembling AV nodal tissue at this site [10]. Traveling away from the atrial end is a long fiber that crosses the AV groove and descends into the body of the RV along the endocardium of the anterior free wall. The fiber is electrically insulated along its length similar to the His bundle or bundle branches, such that the site of earliest ventricular activation is not at the AV groove as seen with conventional accessory AV pathways in WPW syndrome, but much further towards the apex of the RV in the region where the moderator band attaches to the free wall. Because a major extension of the normal right bundle branch also runs along the moderator band towards the free wall, the terminal portion of an atriofascicular pathway is closely approximated or even attached to normal conduction tissues. Conceptually, one can envision three potential models for the terminal portion of an atriofascicular fiber [11-13]: Termination far down on the RV free wall but not attached to the right bundle branch (which would most accurately be described as a "long AV fiber") [14]. Termination within the muscle of the moderator band, close to, but not in direct contact with, the distal right bundle branch (intermediate between "AV" and "atriofascicular"). Fused in direct electrical continuity with the distal right bundle branch (true "atriofascicular"). All three models can account for the clinical behavior of this particular pathway, but based on detailed analysis of conduction patterns during electrophysiologic testing [15], the vast majority of cases seem to involve the fusion model of direct continuity. Occasionally, cases are reported with subtle electrophysiologic findings that suggest a long fiber with decremental conduction that does not quite make contact with right bundle tissue [16], but the distinction is usually not critical from a treatment point of view, nor is it always easy to make the distinction. Hence, the label "atriofascicular" is applied unless there is very convincing evidence to the contrary. CLINICAL FEATURES Many patients with atriofascicular pathways have minimal ECG changes in sinus rhythm, though a subtle delta wave with a normal PR interval may be seen in some cases. Patients typically have a structurally and functionally normal heart and do not come to medical attention until they experience a tachycardia event. The lone exception is patients with Ebstein anomaly of the https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 3/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate tricuspid valve, a situation which is strongly associated with atriofascicular pathways (as well as WPW syndrome) [17,18]. (See "Clinical manifestations and diagnosis of Ebstein anomaly" and "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Anatomy'.) Arrhythmias and symptoms Antidromic reentry (antegrade conduction over the accessory pathway with retrograde conduction via the AV node) is the most common tachycardia seen with atriofascicular pathways ( waveform 1). Less frequently, the retrograde limb involves a second conventional accessory AV pathway, or retrograde conduction may shift between the AV node and one of these secondary accessory AV pathways [13,17,19,20]. Other tachycardia substrates often coexist with an atriofascicular fiber. Approximately 40 percent of patients with a proven atriofascicular fiber have other accessory AV pathways and/or dual AV nodal physiology [17,19,21-23]. Often, a conventional Wolff-Parkinson-White pathway can mask the presence of an atriofascicular pathway, which only becomes apparent after surgical or catheter ablation of the primary accessory pathway [21]. Atriofascicular pathways can also function as a bystander and conduct anterograde impulses during AV nodal reentrant tachycardia, atrial flutter, or any other sort of atrial tachycardia ( figure 2) [19,22]. The two most distinctive functional characteristics of an atriofascicular pathway include its decremental properties and the fact that it is only capable of antegrade conduction [24]. Therefore, when actively involved as part of a reentrant tachycardia, it will only support antidromic reentry. Passive antegrade conduction may also occur over an atriofascicular pathway during sinus rhythm or any other type of supraventricular tachycardia. Some atriofascicular pathways are known to exhibit intrinsic automaticity, which can present as single premature beats or brief salvos that appear to be of ventricular origin [25,26]. ECG findings Resting ECG The resting ECG in patients with an atriofascicular fiber is often normal [17,19,21,24]. This is due to preferential ventricular activation via the AV node at normal resting heart rates. There are several conditions under which conduction via the atriofascicular pathway occurs: Enhanced vagal tone, rapid pacing, or a premature beat may slow AV nodal conduction and favor conduction partially or exclusively over the atriofascicular pathway [17]. The relative refractoriness of the AV node and fiber may change with time, resulting in a variable degree of preexcitation during sinus rhythm. https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 4/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Premature atrial complexes (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) or an ectopic rhythm arising near the atrial insertion can preferentially engage the atriofascicular pathway. Whenever some or all conduction proceeds over an atriofascicular pathway, the PR interval still falls into the normal range, but the QRS is variably distorted by early RV activation, resulting in a pattern of partial or complete left bundle branch block. The absence of a sharp septal Q wave due to relative delay in left bundle activation results in a somewhat slurred QRS upstroke, but whether the initial portion of the QRS should be referred to as a true delta wave is a matter of semantics. Regardless, conduction over an atriofascicular pathway does indeed satisfy the strict definition of preexcitation in that a ventricular site is activated ahead of the normal His-Purkinje system. One study of sinus rhythm ECGs of patients with atriofascicular pathways identified a narrow QRS complex with an rS pattern in lead III in 20 of 33 cases (61 percent) [16]. In contrast, among 200 young adults with a history of palpitations but no structural heart disease, a narrow QRS with an rS in III was found in only 6 percent. More recently, terminal notching and slurring in the non-preexcited QRS has been described as a common finding in patients with atriofascicular pathways that resolves once the involved fibers are successfully eliminated with catheter ablation [27]. ECG with antidromic reentrant tachycardia Antidromic reentry involving an atriofascicular pathway has a regular rate and abrupt onset. Several ECG features that have been suggested as characteristic of antidromic reentry involving an atriofascicular pathway include ( waveform 1) [21,28]: QRS axis between 0 and minus 75 QRS duration of 0.15 seconds or less R-wave in lead 1 rS complex in lead V1 Precordial transition in lead V4 or later Cycle length between 220 and 450 ms (heart rates of 130 to 270) Although these surface ECG markers can be a useful starting point in the acute setting to raise suspicion about an atriofascicular mechanism, they are not diagnostic, and invasive electrophysiology studies are usually required for an accurate diagnosis. (See 'Evaluation' below.) EVALUATION https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 5/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Patients with suspected atriofascicular ("Mahaim" fiber) tachycardia should all have had an ECG as part of the initial presentation. Additional testing for such patients also typically includes: Transthoracic echocardiography to assess for any structural cardiac abnormalities (especially Ebstein anomaly). Invasive electrophysiology studies (EPS) for confirmation of the diagnosis and, in many cases, therapeutic catheter ablation of the abnormal pathway. When invasive EPS is performed, baseline sinus rhythm intervals are often normal or show only slightly shortened HV intervals ( waveform 2). Atrial pacing maneuvers should uncover the antegrade conduction abnormalities [29]. The AH interval and the A-V time will prolong in the expected fashion as progressively premature atrial extrastimuli are delivered, but at some point there will be a shift (often subtle at first) in antegrade conduction away from the AV node and towards the atriofascicular pathway. This manifests itself as a progressively shortened HV interval and a more preexcited-appearing QRS with left bundle branch block features and earliest ventricular timing towards the RV apical region. Coaxing conduction antegrade down the atriofascicular pathway can be highly dependent on the site of atrial stimulation. The closer the stimulation site is to the atrial end of the fiber, the more obvious and dramatic the preexcitation. Thus, atrial stimulation from the right atrial appendage or lateral right atrium along the AV groove is the preferred technique for uncovering these fibers. Stimulation from the coronary sinus or some other left atrial site will often fail completely to engage an atriofascicular pathway since the AV node has a chance to conduct long before the atrial activation wavefront ever reaches the right lateral region. As atrial extrastimuli are delivered more prematurely, conduction begins to approach maximal preexcitation where the His signal becomes obscured by the preexcited QRS. Even at this point, the A-QRS interval may continue to prolong because of decremental conduction within the pathway. Eventually, a critical coupling interval can be reached where the normal AV node is refractory and antegrade conduction occurs exclusively over the atriofascicular pathway. This is the point at which antidromic reentry can develop, since conduction may now return to the atrium in a retrograde fashion via the His bundle and AV node to complete the circuit. Tachycardia can also be induced with rapid atrial pacing that achieves the same critical shift towards exclusive antegrade conduction in the atriofascicular pathway. During induced antidromic tachycardia involving an atriofascicular pathway, the QRS will have a pattern of complete left bundle branch block with no preceding His bundle potential. Instead, the His potential will be observed after the QRS, and on close inspection of the His bundle electrogram, the His-Purkinje system can usually be confirmed to be activated in a retrograde https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 6/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate manner from distal-to-proximal as opposed to the normal proximal-to-distal pattern seen in sinus rhythm [29,30]. When the RV is mapped carefully, the earliest ventricular activation will be localized to the anterior free wall near the insertion of the moderator band [31]. Unless another retrograde AV bypass tract or a retrograde AV nodal slow-pathway is present, earliest retrograde atrial timing during antidromic tachycardia will usually be recorded on the His bundle catheter. Premature atrial extrastimuli delivered during preexcited tachycardia not altering the atrial activation at the septal level, but resulting in advancement of the next ventricular and atrial complexes (ie, tachycardia reset) definitely indicate that the atriofascicular pathway is an integral part of the reentrant circuit (ie, the tachycardia is sustained by antidromic reentry) [30,32]. DIAGNOSIS In some instances, the presence of an atriofascicular pathway may be suspected based on the surface ECG, on which the PR interval remains normal but the QRS is variably distorted by early RV activation, resulting in a pattern of partial or complete left bundle branch block. However, given that the ECG findings may be subtle or entirely absent at rest, intracardiac electrophysiologic study is usually required to make a firm diagnosis of an atriofascicular pathway. Baseline sinus rhythm intervals can be normal or may show a slightly short HV interval with RV activation occurring a bit earlier than expected. However, when atrial pacing maneuvers are performed, the antegrade conduction abnormalities become more apparent [29]. (See 'Evaluation' above.) TREATMENT Acute management In the acute setting at initial presentation of sustained antidromic tachycardia involving an atriofascicular pathway, the wide-QRS pattern on ECG may be hard to distinguish from several other tachycardia mechanisms, including ventricular tachycardia. It is therefore best to approach acute treatment according to the standard algorithm for any wide- QRS complex tachycardia. (See "Wide QRS complex tachycardias: Approach to management".) For patients with a known established diagnosis of atriofascicular pathway tachycardia (ie, a supraventricular tachycardia [SVT] rather than ventricular tachycardia or wide-QRS complex tachycardia of unknown origin), the approach to acute therapy is similar to other SVTs. Since antidromic atriofascicular reentry is regular and monomorphic, this means that a cautious trial of adenosine is a reasonable first step if the patient is hemodynamically stable. Adenosine is nearly always effective in this setting. (See "Overview of the acute management of tachyarrhythmias", section on 'Narrow QRS complex tachyarrhythmias'.) https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 7/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Chronic management For chronic treatment of atriofascicular pathway tachycardia, most patients are suitable candidates for catheter ablation, but the techniques used for mapping differ somewhat from those used for a conventional Wolff-Parkinson-White pathway. In rare circumstances, pharmacologic therapy can be used in an effort to suppress arrhythmias. Catheter ablation The atrial end of the atriofascicular pathway is the most productive and reliable site for ablation [29,33], but because atriofascicular pathways are capable only of antegrade conduction, the atrial insertion cannot be easily mapped with simple analysis of retrograde atrial activation patterns. Instead, electrophysiologists must rely on one or more of the following techniques: Stimulus to "delta-wave" mapping (aimed to disclose the atrial pacing site along the tricuspid annulus associated with the shortest "stimulus-to-delta" interval) [33]. Premature right atrial stimulation during antidromic tachycardia (to identify the site from which the latest coupled atrial extrastimulus advances the next ventricular electrogram) [30]. Direct recording of a discrete potential from the fiber near the tricuspid annulus [29,31,34]. Identification of a site with a discrete potential has become the most widely used and dependable technique for mapping atriofascicular fibers ( waveform 2). Promising sites will register a sharp signal that is very similar in frequency and amplitude to a His bundle potential, with timing midway between the atrial and ventricular electrograms during antidromic tachycardia or preexcited atrial pacing [29,31,34-37]. These potentials can be recorded on the atrial side of the tricuspid valve at the AV groove, as well as on the ventricular side just below the valve. The combination of its long ventricular endocardial course, arborization of its distal segments, and potential fusion with the right bundle branch, all make identification of the true ventricular insertion of these fibers difficult [31]. Fortunately, precise location of the ventricular end is usually not critical since ablation is never performed at this site. Once thorough mapping has been performed and a high-quality atriofascicular potential has been localized, radiofrequency (RF) ablation can be performed using standard techniques. A brief period of accelerated automaticity from the atriofascicular fiber often occurs as the tissue is heated (similar to ablation near the normal AV node and His bundle) and is usually a promising sign. This automaticity should resolve within the first few seconds of the RF application if the catheter tip is in good position. The reported permanent success rate for RF ablation in this condition is excellent, in the range of 87 to 100 percent [29,38]. https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 8/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Pharmacologic therapy Pharmacologic therapy can be used as an alternative to catheter ablation if necessary. Prior to the development of ablation techniques, empiric drug therapy was the preferred treatment of "Mahaim" fiber tachycardia. Since this is a relatively rare condition, there have been no large-scale comparative trials of different classes of drugs. The published data are limited to case reports and small studies demonstrating sensitivity to various classes of antiarrhythmic agents. Because drug therapy is so uncommonly used (and studied) in this condition, and since for most patients catheter ablation is by far the preferred option, it is not possible to make a recommendation for any one agent. Antegrade conduction in atriofascicular pathways appears to be acutely sensitive to adenosine but not necessarily to other agents that predominately affect the AV node, such as calcium blockers and beta blockers [39]. In some cases, however, the AV nodal blocking agents may be effective in preventing tachycardia by affecting AV nodal conduction in the retrograde limb of the tachycardia. Both class IA and IC agents, as well as class III agents, also may slow or prevent tachycardia in patients with antidromic tachycardia related to atriofascicular pathways [40]. SUMMARY AND RECOMMENDATIONS Cardiac preexcitation describes premature activation of the ventricles over an abnormal pathway distinct from the normal cardiac conduction system. (See 'Nomenclature, anatomy, and physiology' above.) The classic form of cardiac preexcitation occurs in Wolff-Parkinson-White (WPW) syndrome, involving a short connection along the atrioventricular (AV) groove, referred to as an "accessory AV pathway." Atriofascicular pathways, formerly referred to as "Mahaim" fibers, are now understood to involve a specialized conduction pathway arising from the lateral right atrium that extends far down into the body of the right ventricle and is quite distinct from the AV node and bundle of His. Atriofascicular pathways exhibit structural and functional features that can almost be likened to a secondary AV conduction system. (See 'Electrophysiology' above.) Many patients with atriofascicular pathways have minimal ECG changes, but in some cases a subtle delta wave with a normal PR interval can be seen. The most common tachycardia in this condition is antidromic reentry using the atriofascicular pathway as the antegrade limb and the AV node as the retrograde limb (See 'Clinical features' above.) https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 9/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Patients with suspected atriofascicular ("Mahaim" fiber) tachycardia should all have had an ECG as part of the initial presentation. Additional testing for such patients also includes transthoracic echocardiography and, frequently, invasive electrophysiology studies for confirmation of the diagnosis and, in many cases, therapeutic catheter ablation of the abnormal pathway. (See 'Evaluation' above and 'Diagnosis' above.) Most patients are suitable candidates for transcatheter ablation, but the techniques used for mapping differ somewhat from those used for a conventional WPW pathway. In rare circumstances, pharmacologic therapy can be used in an effort to suppress arrhythmias. (See 'Treatment' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Ohnell, RF. Pre-Excitation: A Cardiac Abnormality, Norstedt and Soner, Stockholm 1944. 2. Hoffmayer KS, Han FT, Singh D, Scheinman MM. Variants of accessory pathways. Pacing Clin Electrophysiol 2020; 43:21. 3. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. 4. JAMES TN. Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J 1961; 62:756. 5. Hamdan MH, Kalman JM, Lesh MD, et al. Narrow complex tachycardia with VA block: diagnostic and therapeutic implications. Pacing Clin Electrophysiol 1998; 21:1196. 6. Morady F, Scheinman MM, Gonzalez R, Hess D. His-ventricular dissociation in a patient with reciprocating tachycardia and a nodoventricular bypass tract. Circulation 1981; 64:839. 7. Wu DL, Yeh SJ, Yamamoto T, et al. Participation of a concealed nodoventricular fiber in the genesis of paroxysmal tachycardias. Am Heart J 1990; 119:583. 8. Gillette PC, Garson A Jr, Cooley DA, McNamara DG. Prolonged and decremental antegrade conduction properties in right anterior accessory connections: Wide QRS antidromic tachycardia of left bundle branch block pattern without Wolff-Parkinson-White configuration in sinus rhythm. Am Heart J 1982; 103:66. 9. Klein GJ, Guiraudon GM, Kerr CR, et al. "Nodoventricular" accessory pathway: evidence for a distinct accessory atrioventricular pathway with atrioventricular node-like properties. J Am Coll Cardiol 1988; 11:1035. https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 10/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate 10. Becker AE, Anderson RH, Durrer D, Wellens HJ. The anatomical substrates of wolff- parkinson-white syndrome. A clinicopathologic correlation in seven patients. Circulation 1978; 57:870. 11. Klein LS, Hackett FK, Zipes DP, Miles WM. Radiofrequency catheter ablation of Mahaim fibers at the tricuspid annulus. Circulation 1993; 87:738. 12. Jongbloed MR, Wijffels MC, Schalij MJ, et al. Development of the right ventricular inflow tract and moderator band: a possible morphological and functional explanation for Mahaim tachycardia. Circ Res 2005; 96:776. 13. Haissaguerre M, Warin JF, Le Metayer P, et al. Catheter ablation of Mahaim fibers with preservation of atrioventricular nodal conduction. Circulation 1990; 82:418. 14. Yang JD, Zhou GB, Sun Q, et al. Electrocardiographic and electrophysiologic differentiation between atriofascicular, long atrioventricular, and short atrioventricular decrementally conducting accessory pathways. Europace 2018; 20:1666. 15. Gandhavadi M, Sternick EB, Jackman WM, et al. Characterization of the distal insertion of atriofascicular accessory pathways and mechanisms of QRS patterns in atriofascicular antidromic tachycardia. Heart Rhythm 2013; 10:1385. 16. Sternick EB, Timmermans C, Rodriguez LM, Wellens HJ. Mahaim fiber: an atriofascicular or a long atrioventricular pathway? Heart Rhythm 2004; 1:724. 17. Ellenbogen KA, Ramirez NM, Packer DL, et al. Accessory nodoventricular (Mahaim) fibers: a clinical review. Pacing Clin Electrophysiol 1986; 9:868. 18. Walsh EP. Ebstein's Anomaly of the Tricuspid Valve: A Natural Laboratory for Re-Entrant Tachycardias. JACC Clin Electrophysiol 2018; 4:1271. 19. Gallagher JJ, Smith WM, Kasell JH, et al. Role of Mahaim fibers in cardiac arrhythmias in man. Circulation 1981; 64:176. 20. Bardy GH, German LD, Packer DL, et al. Mechanism of tachycardia using a nodofascicular Mahaim fiber. Am J Cardiol 1984; 54:1140. 21. Bardy GH, Fedor JM, German LD, et al. Surface electrocardiographic clues suggesting presence of a nodofascicular Mahaim fiber. J Am Coll Cardiol 1984; 3:1161. 22. Sung RJ, Styperek JL. Electrophysiologic identification of dual atrioventricular nodal pathway conduction in patients with reciprocating tachycardia using anomalous bypass tracts. Circulation 1979; 60:1464. 23. Abbott JA, Scheinman MM, Morady F, et al. Coexistent Mahaim and Kent accessory connections: diagnostic and therapeutic implications. J Am Coll Cardiol 1987; 10:364. https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 11/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate 24. Arias MA, Pach n M, Mart n-Sierra C. Spontaneous Wide QRS Complex Rhythm in a Patient With Wide QRS Complex Tachycardia. Circulation 2020; 141:1498. 25. Venier S, Khairy P, Thibault B, Rivard L. Ablation of a symptomatic spontaneous automatic focus arising from an atriofascicular fiber. HeartRhythm Case Rep 2016; 2:379. 26. Strohmer B, Schernthaner C, Hwang C. Spontaneous automaticity arising from a successfully ablated Mahaim fiber. J Interv Card Electrophysiol 2007; 20:25. 27. Liao Z, Ma J, Hu J, et al. New observation of electrocardiogram during sinus rhythm on the atriofascicular and decremental atrioventricular pathways/clinical perspective: [corrected] terminal QRS [corrected] complex slurring or notching. Circ Arrhythm Electrophysiol 2011; 4:897. 28. Sternick EB, Lokhandwala Y, Bohora S, et al. Is the 12-lead electrocardiogram during antidromic circus movement tachycardia helpful in predicting the ablation site in atriofascicular pathways? Europace 2014; 16:1610. 29. McClelland JH, Wang X, Beckman KJ, et al. Radiofrequency catheter ablation of right atriofascicular (Mahaim) accessory pathways guided by accessory pathway activation potentials. Circulation 1994; 89:2655. 30. Tchou P, Lehmann MH, Jazayeri M, Akhtar M. Atriofascicular connection or a nodoventricular Mahaim fiber? Electrophysiologic elucidation of the pathway and associated reentrant circuit. Circulation 1988; 77:837. 31. Ha ssaguerre M, Cauchemez B, Marcus F, et al. Characteristics of the ventricular insertion sites of accessory pathways with anterograde decremental conduction properties. Circulation 1995; 91:1077. 32. Sherwin ED, Walsh EP, Abrams DJ. Variable QRS morphologies in Ebstein's anomaly: what is the mechanism? Heart Rhythm 2013; 10:933. 33. Okishige K, Strickberger SA, Walsh EP. Catheter ablation of the atrial origin of a decrementally conducting atriofascicular accessory pathway by radiofrequency current. J Cardiovasc Electrophysiol 1991; 2:465. 34. Heald SC, Davies DW, Ward DE, et al. Radiofrequency catheter ablation of Mahaim tachycardia by targeting Mahaim potentials at the tricuspid annulus. Br Heart J 1995; 73:250. 35. Brugada J, Mart nez-S nchez J, Kuzmicic B, et al. Radiofrequency catheter ablation of atriofascicular accessory pathways guided by discrete electrical potentials recorded at the tricuspid annulus. Pacing Clin Electrophysiol 1995; 18:1388. https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 12/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate 36. Cardona-Guarache R, Han FT, Nguyen DT, et al. Ablation of Supraventricular Tachycardias From Concealed Left-Sided Nodoventricular and Nodofascicular Accessory Pathways. Circ Arrhythm Electrophysiol 2020; 13:e007853. 37. Jackman WM. Recording the Accessory His Bundle Potential from a Right Atriofascicular Accessory Pathway. Card Electrophysiol Clin 2016; 8:765. 38. M nnig G, Wasmer K, Milberg P, et al. Predictors of long-term success after catheter ablation of atriofascicular accessory pathways. Heart Rhythm 2012; 9:704. 39. Ellenbogen KA, Rogers R, Old W. Pharmacological characterization of conduction over a Mahaim fiber: evidence for adenosine sensitive conduction. Pacing Clin Electrophysiol 1989; 12:1396. 40. Strasberg B, Coelho A, Palileo E, et al. Pharmacological observations in patients with nodoventricular pathways. Br Heart J 1984; 51:84. Topic 1001 Version 24.0 https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 13/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate GRAPHICS Types of accessory pathways Diagram of 4 types of abnormal conduction pathways: classic accessory atrioventricular pathway (red), atriofascicular pathway (green), fasciculoventricular pathway (light blue), and nodoventricular pathway (dark blue). The atrioventricular node and His-Purkinje system are represented in yellow. Atrioventricular, atriofascicular, and nodoventricular pathways are capable of supporting atrioventricular reciprocating tachycardias. In contrast, an isolated fasciculoventricular pathway can cause subtle preexcitation but does not support clinical tachycardia. Graphic 138850 Version 1.0 https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 14/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate 12-lead electrocardiogram (ECG) consistent with Mahaim fiber tachycardia Electrocardiogram from a patient with an atrioventricular reentrant tachycardia due to a Mahaim accessory pathway. The QRS complexes are wide with a left bundle branch block morphology and left axis deviation; these changes are characteristic of a Mahaim fiber tachycardia. Graphic 56384 Version 3.0 https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 15/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Anatomy of an atriofascicular pathway Schematic showing the normal conduction system (yellow) as well as an atriofascicular pathway (green) connecting the atria directly to the conduction system fascicles, bypassing the AV node. AV: atrioventricular; LA: left atrium; LV: left ventricle; RA: right atrium; RV: right ventricle. Graphic 128531 Version 2.0 https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 16/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Intracardiac electrogram during ablation of Mahaim fiber tachycardia Top panel shows surface leads I and V1 and intracardiac recordings from the right ventricular apex (RVA), His-bundle (HBE), and a mapping catheter (MaP) located at the tricuspid annulus. A Mahaim potential (M) is seen in the MaP recording, located between the atrial (A) and ventricular (V) electrogram. In bottom panel, radiofrequency current is applied at the site of the M potential, resulting in loss of Mahaim conduction and termination of the tachycardia. Graphic 79320 Version 4.0 https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 17/18 7/6/23, 11:11 AM Atriofascicular ("Mahaim") pathway tachycardia - UpToDate Contributor Disclosures Luigi Di Biase, MD, PhD, FHRS, FACC Consultant/Advisory Boards: Abbott [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Baylis Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Biosense Webster [Ablation products]; Biotronik [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Boston Scientific [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Medtronic [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Stereotaxis [Ablation products]; Zoll Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]. All of the relevant financial relationships listed have been mitigated. Edward P Walsh, MD No relevant financial relationship(s) with ineligible companies to disclose. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atriofascicular-mahaim-pathway-tachycardia/print 18/18 |
7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway : Luigi Di Biase, MD, PhD, FHRS, FACC, Edward P Walsh, MD : Samuel L vy, MD, Bradley P Knight, MD, FACC : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 26, 2022. INTRODUCTION In 1930, Louis Wolff, Sir John Parkinson, and Paul Dudley White published a seminal article describing 11 patients who suffered from attacks of tachycardia associated with a sinus rhythm electrocardiographic (ECG) pattern of bundle branch block with a short PR interval [1]. This was subsequently termed the Wolff-Parkinson-White (WPW) syndrome, although earlier isolated case reports describing similar findings had already been published. In 1943, the ECG features of preexcitation were correlated with anatomic evidence for the existence of anomalous bundles of conducting tissue that bypassed all or part of the normal atrioventricular (AV) conduction system ( figure 1). AV reentrant (or reciprocating) tachycardia (AVRT) is a reentrant tachycardia with an anatomically defined circuit that consists of two distinct pathways, the normal AV conduction system and an AV accessory pathway, linked by common proximal (the atria) and distal (the ventricles) tissues. While other arrhythmias can utilize the accessory pathway for conduction from the anatomic site of tachycardia origin to other regions of the heart (eg, atrial fibrillation and atrial flutter) ( figure 2), AVRT is a specific reentrant tachycardia in which the accessory pathway is necessary for initiation and maintenance of the tachycardia [2]. The different types of AVRT, along with their ECG findings, will be discussed here. The approach to treatment of arrhythmias associated with an accessory pathway is presented in detail https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 1/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate separately. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome".) NORMAL AV CONDUCTION VERSUS ACCESSORY AV PATHWAY CONDUCTION Normal AV conduction occurs through the AV node. However, in the presence of an accessory pathway, conduction from the atria to the ventricles may occur in a variety of ways (exclusively via the AV node, exclusively via the accessory pathway, or a combination of both). Normal and accessory AV conduction are discussed in detail elsewhere. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Normal AV conduction versus accessory AV pathway conduction'.) TACHYCARDIAS REQUIRING AN AV ACCESSORY PATHWAY FOR INITIATION AND MAINTENANCE AVRT is a reentrant tachycardia with an anatomically defined circuit that consists of two distinct pathways, the normal AV conduction system and an AV accessory pathway, linked by common proximal (the atria) and distal (the ventricles) tissues. If sufficient differences in conduction time and refractoriness exist between the normal conduction system and the accessory pathway, a properly timed premature impulse of atrial, junctional, or ventricular origin can initiate reentry. (See "Reentry and the development of cardiac arrhythmias".) The two major types of this arrhythmia in persons with an AV accessory pathway are narrow complex (orthodromic) and wide complex (antidromic) AVRT. The width of the QRS complex can usually distinguish between these paroxysmal arrhythmias: Narrow QRS complex (orthodromic AVRT) If the tachycardia has a narrow QRS complex, the antegrade limb (ie, the pathway that conducts the supraventricular impulse to the ventricle) is the AV node/His-Purkinje system. In this setting, any preexcitation (manifest as a delta wave on the surface ECG) seen during sinus rhythm is lost since antegrade conduction is not occurring via the accessory pathway (ie, the ventricle is not preexcited) ( figure 3 and waveform 1 and waveform 2). (See 'Narrow complex AVRT' below.) Wide QRS complex (antidromic AVRT) If the tachycardia has a wide QRS complex, the possibilities include AVRT with antegrade conduction over the accessory pathway (antidromic AVRT) or orthodromic AVRT with aberrant QRS conduction resulting in a wide QRS complex ( figure 4 and waveform 3 and waveform 4). (See 'Wide complex https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 2/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate AVRT' below and "Left bundle branch block", section on 'Functional LBBB' and "Wide QRS complex tachycardias: Approach to the diagnosis".) A third type of arrhythmia, permanent junctional reciprocating tachycardia, is a type of orthodromic AVRT that is typically seen in childhood. (See 'Permanent junctional reciprocating tachycardia' below.) Narrow complex AVRT Narrow complex (orthodromic) AVRT composes 90 to 95 percent of the reentrant tachycardias associated with the Wolff-Parkinson-White (WPW) syndrome [2,3]. Orthodromic AVRT can be initiated by atrial or ventricular premature beats (APBs or VPBs) ( figure 3) [2]. APBs initiating orthodromic AVRT are blocked in the accessory pathway but conduct antegrade to the ventricles over the AV node/His-Purkinje system. After conduction through the ventricles, the impulse then travels back to the atria in a retrograde fashion via the AV accessory pathway to complete the first reentrant loop. VPBs initiating orthodromic AVRT are blocked in the AV node/His-Purkinje system but conduct retrograde to the atria over the accessory pathway. After conduction through the atria, the impulse then travels back to the ventricles in an antegrade fashion via the normal AV conduction system to complete the reentrant circuit [2,4]. ECG findings in orthodromic AVRT The ECG during orthodromic AVRT ( waveform 1 and waveform 2) typically shows the following: Ventricular rate ranging from 150 to 250 (or greater) beats per minute and usually regular. Narrow QRS complexes (in the absence of underlying conduction system disease or in the absence of aberrancy). Inverted P waves with an RP interval that is usually less than one-half the tachycardia RR interval. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'RP relationship'.) Constant RP interval regardless of the tachycardia cycle length [5]. Beat-to-beat oscillation in QRS amplitude (QRS alternans) sometimes occurs during orthodromic AVRT and is most commonly seen when the rate is very rapid [6,7]. The mechanism for QRS alternans is not clear but may in part result from oscillations in the relative refractory period of the AV node-His-Purkinje system [8,9]. https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 3/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Ischemic-appearing ST segment depression also can occur during orthodromic AVRT, even in young individuals who are unlikely to have coronary artery disease [10]. Several factors may contribute to the ST segment depression in these arrhythmias, including changes in autonomic nervous system tone, intraventricular conduction disturbances, a longer ventriculoatrial interval, and a retrograde P wave of longer duration that overlaps into the ST segment [11]. The location of the ST segment changes may vary with the location of the accessory pathway [12,13]. Wide complex AVRT Wide complex (antidromic) AVRT is the least common arrhythmia associated with WPW syndrome, occurring in less than 10 percent of patients [2]. In a retrospective observational study of 807 patients (age range 5 to 85 years) with preexcitation on a surface ECG who also underwent invasive electrophysiologic studies (EPS), 63 patients (8 percent) were found to have inducible antidromic AVRT during EPS (compared with 55 percent rate of inducible orthodromic AVRT in the same population) [14]. In another retrospective study of 1147 pediatric patients (age less than 21 years) who underwent invasive EPS, antidromic AVRT was identified in only 30 patients (3 percent), with the accessory pathways in these patients having rapid anterograde conduction characteristics [15]. As with orthodromic AVRT, antidromic AVRT can be initiated by atrial or ventricular premature beats (APBs or VPBs) ( figure 4) [2]. APBs initiating antidromic AVRT are blocked in the AV node/His-Purkinje system but conduct antegrade to the ventricles over the accessory pathway. After conduction through the ventricles, the impulse then travels back to the atria in a retrograde fashion via the AV node/His-Purkinje system to complete the first reentrant loop. VPBs initiating antidromic AVRT are blocked in the accessory pathway but conduct retrograde to the atria over the AV node/His-Purkinje system. After conduction through the atria, the impulse then travels back to the ventricles in an antegrade fashion via the accessory pathway to complete the reentrant circuit. An unusual type of antidromic reentry can also occur in patients with an atriofascicular fiber (sometimes referred to as a Mahaim fiber) that can be difficult to distinguish from antidromic reentry using a conventional AV accessory pathway reentry in the acute setting. (See "Atriofascicular ("Mahaim") pathway tachycardia".) ECG findings in antidromic AVRT The ECG during antidromic AVRT ( figure 4 and waveform 3 and waveform 4) typically shows the following: Ventricular rate ranging from 150 to 250 (or greater) beats per minute and usually regular. Wide QRS complexes which are fully preexcited. https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 4/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Inverted P waves with an RP interval that is usually more than one-half the tachycardia RR interval and a short PR interval. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'RP relationship'.) Constant RP interval regardless of the tachycardia cycle length [5]. Susceptibility to antidromic AVRT also appears to be dependent upon a transverse distance of at least 4 cm between the bypass tract and the normal AV conduction system. Consequently, most antidromic AVRTs use a left-sided accessory pathway as the antegrade route for conduction [2,5]. In some patients with antidromic AVRT and a left-sided accessory pathway, preexcitation may not be apparent in sinus rhythm because the time for the atrial impulse to reach the atrial insertion of the accessory pathway is longer than the time to reach the AV node ( waveform 5). A rare variant of antidromic AVRT can occur in patients with multiple accessory pathways when anterograde conduction occurs over one accessory pathways and retrograde conduction returns to the atrium via a second accessory pathway. In such cases, the AV node is not necessary for maintenance of reentry. The ECG during pathway-pathway tachycardia is indistinguishable from conventional antidromic AVRT, and confirmation of the precise circuit usually requires mapping at electrophysiology study. Approximately 10 percent of patients undergoing catheter ablation can be found to have multiple accessory pathways [16]. Permanent junctional reciprocating tachycardia Permanent or incessant junctional reciprocating (or reentrant) tachycardia (PJRT) is a type of orthodromic AVRT that most often occurs in early childhood, although clinically asymptomatic patients presenting later in life are not uncommon. In the older patient, PJRT tends to be less incessant, perhaps due to variable autonomic tone, and has a somewhat slower ventricular rate, felt to be the result of a prolongation of retrograde conduction through the accessory pathway [17]. The heart rate is usually between 120 and 200 beats/minute, and the QRS duration is generally normal ( waveform 6). Chronic suppression of PJRT is usually not possible with drugs, and ablation of the accessory pathway is often necessary to achieve arrhythmia control [3,18-20]. The incessant nature of PJRT may result in dilated cardiomyopathy and heart failure; these changes are potentially reversible if the accessory pathway can be successfully ablated [3,17,18,21]. (See "Clinical features and diagnosis of supraventricular tachycardia (SVT) in children", section on 'Permanent junctional reciprocating tachycardia' and "Arrhythmia-induced cardiomyopathy" and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Catheter ablation'.) https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 5/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate ECG findings in PJRT PJRT is an orthodromic AVRT mediated by a concealed, retrogradely conducting AV accessory pathway that has slow and decremental conduction properties [19,22,23]. Because of this, PJRT has similar ECG findings as seen in typical orthodromic AVRT. (See 'ECG findings in orthodromic AVRT' above.) Nevertheless, one major ECG difference is seen between PJRT and typical orthodromic AVRT. The retrograde conduction properties of the accessory pathway in PJRT are slower compared with both the anterograde conduction properties of the AV node and the usual "fast" accessory pathways found in patients with AVRT [17]. Therefore, slow retrograde conduction over the accessory pathway causes the RP interval during PJRT to be long, usually more than one-half the tachycardia RR interval. The accessory pathway in patients with PJRT is most often located within the posteroseptal region, although other portions of the AV groove may also harbor this unique pathway [19,20,23,24]. P waves resulting from retrograde conduction are easily seen on the ECG and are inverted in leads 2, 3, aVF, and V3 to V6. CLINICAL MANIFESTATIONS OF AVRT AND PJRT The response to a rapid heart rate can be quite variable depending on how fast the heart is beating, resultant blood pressure and tissue perfusion, underlying comorbidities, and the sensitivity of the individual patient to the symptoms. Patients with AV reentrant (or reciprocating) tachycardia (AVRT) or permanent junctional reciprocating (or reentrant) tachycardia (PJRT) can present with a variety of symptoms, including: Palpitations Syncope or presyncope Lightheadedness or dizziness Diaphoresis Chest pain Shortness of breath Most commonly, patients with AVRT present with palpitations, the sensation of a rapid or irregular heart beat felt in the anterior chest or neck. Because of the persistent nature and the rapid ventricular heart rate associated with PJRT, some patients with PJRT may present with findings of impaired left ventricular function compatible with a tachycardia-mediated cardiomyopathy. The presenting symptoms of tachycardias and tachycardia-mediated cardiomyopathy are discussed in greater detail separately. (See "Evaluation of palpitations in https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 6/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate adults" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Clinical manifestations' and "Arrhythmia-induced cardiomyopathy".) DIAGNOSIS OF AVRT AND PJRT The diagnosis of AV reentrant (or reciprocating) tachycardia (AVRT) or permanent junctional reciprocating (or reentrant) tachycardia (PJRT) typically requires only a surface electrocardiogram (ECG) which shows a heart rate greater than 100 beats per minute along with regularly occurring QRS complexes. An old ECG performed when the patient is not having a tachycardia can be helpful for identifying the presence of a delta wave suggesting preexcitation and an accessory pathway. Once a QRS complex width has been identified, further scrutiny of the ECG is required to identify the specific arrhythmia in a particular patient, as diagnostic evaluation and therapy will differ depending on the underlying arrhythmia ( algorithm 1). (See 'ECG findings in orthodromic AVRT' above and 'ECG findings in antidromic AVRT' above and 'ECG findings in PJRT' above and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Evaluation'.) Invasive electrophysiology testing is usually not required to broadly make the diagnosis of AVRT or PJRT, but on rare occasions it is needed to diagnose (and potentially treat with catheter ablation) the specific arrhythmia. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Electrophysiologic testing'.) DIFFERENTIAL DIAGNOSIS The differential diagnosis for patients with orthodromic AV reentrant (or reciprocating) tachycardia (AVRT) or permanent junctional reciprocating (or reentrant) tachycardia (PJRT) and a narrow QRS complex (<120 msec duration) includes other supraventricular tachyarrhythmias with regularly occurring, narrow QRS complexes ( algorithm 1). This differential diagnosis is discussed in greater detail separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia' and "Atrioventricular nodal reentrant tachycardia".) For patients with a wide QRS complex tachycardia (ie, those with antidromic AVRT; or those with orthodromic AVRT or PJRT and underlying conduction system disease), ventricular tachycardia should be a part of the differential diagnosis along with aberrantly conducted supraventricular tachyarrhythmias (eg, focal atrial tachycardia and AV nodal reentry tachycardia). This differential https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 7/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate diagnosis is discussed in greater detail separately. (See "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Differential diagnosis of WCT'.) TREATMENT OF AVRT AND PJRT The approaches to both acute and chronic treatment of AV reentrant (or reciprocating) tachycardia or permanent junctional reciprocating (or reentrant) tachycardia are discussed separately. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome" and "Overview of the acute management of tachyarrhythmias", section on 'Regular narrow QRS complex tachyarrhythmias'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Catheter ablation of arrhythmias" and "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is a reentrant tachycardia with an anatomically defined circuit that consists of two distinct pathways, the normal AV conduction system and an AV accessory pathway ( figure 1), linked by common proximal (the atria) and distal (the ventricles) tissues. (See 'Introduction' above.) The two major types of this arrhythmia in persons with an AV accessory pathway are orthodromic AVRT (including permanent junctional reciprocating tachycardia [PJRT]) and antidromic AVRT. Narrow complex (orthodromic) AVRT composes 90 to 95 percent of the reentrant tachycardias associated with the Wolff-Parkinson-White (WPW) syndrome. The ECG during orthodromic AVRT ( waveform 1 and waveform 2) typically shows a regular ventricular rate ranging from 150 to 250 (or greater) beats per minute, narrow QRS complexes, inverted P waves with an RP interval that is usually less than one-half the tachycardia RR interval, and a constant RP interval. (See 'Narrow complex AVRT' above and 'ECG findings in orthodromic AVRT' above.) https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 8/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Wide complex (antidromic) AVRT is the least common arrhythmia associated with WPW syndrome, occurring in only 5 to 10 percent of patients. The ECG during antidromic AVRT ( figure 4 and waveform 3 and waveform 4) typically shows a regular ventricular rate ranging from 150 to 250 (or greater) beats per minute, wide QRS complexes, inverted P waves with an RP interval that is usually more than one-half the tachycardia RR interval, and a constant RP interval. (See 'Wide complex AVRT' above and 'ECG findings in antidromic AVRT' above.) PJRT is a narrow complex (orthodromic) AVRT most often occurring in early childhood. PJRT has similar ECG findings as seen in typical orthodromic AVRT with one major difference; slow retrograde conduction over the accessory pathway causes the RP interval during PJRT to be long, usually more than one-half the tachycardia RR interval. (See 'Permanent junctional reciprocating tachycardia' above and 'ECG findings in PJRT' above.) Most commonly, patients with AVRT present with palpitations, the sensation of a rapid or irregular heart beat felt in the anterior chest or neck. Because of the persistent nature and the rapid ventricular heart rate associated with PJRT, some patients with PJRT may present with findings of impaired left ventricular function compatible with a tachycardia-mediated cardiomyopathy. (See 'Clinical manifestations of AVRT and PJRT' above.) The diagnosis of AVRT or PJRT typically requires only a surface electrocardiogram (ECG) which shows a heart rate greater than 100 beats per minute along with regularly occurring QRS complexes. An old ECG performed when the patient is not having a tachycardia can be helpful for identifying the presence of a delta wave suggesting preexcitation and an accessory pathway. Once a narrow QRS complex tachycardia has been identified, further scrutiny of the ECG is required to identify the specific arrhythmia in a particular patient. (See 'Diagnosis of AVRT and PJRT' above.) The differential diagnosis and approach to treatment for AVRT and PJRT are discussed in greater detail separately. (See "Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia'.) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 9/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 1. Wolff L, Parkinson J, White PD. Bundle-branch block with short P-R interval in healthy young people prone to paroxysmal tachycardia. 1930. Ann Noninvasive Electrocardiol 2006; 11:340. 2. Josephson ME. Preexcitation syndromes. In: Clinical Cardiac Electrophysiology, 4th, Lippinco t Williams & Wilkins, Philadelphia 2008. p.339. 3. Chugh A, Morady F. Atrioventricular reentry and variants. In: Cardiac electrophysiology from cell to bedside, 5th edition, Zipes DP, Jalife J (Eds), Saunders/Elsevier, Philadelphia 2009. p.60 5-614. 4. Akhtar M, Lehmann MH, Denker ST, et al. Electrophysiologic mechanisms of orthodromic tachycardia initiation during ventricular pacing in the Wolff-Parkinson-White syndrome. J Am Coll Cardiol 1987; 9:89. 5. Cain ME, Luke RA, Lindsay BD. Diagnosis and localization of accessory pathways. Pacing Clin Electrophysiol 1992; 15:801. 6. Green M, Heddle B, Dassen W, et al. Value of QRS alteration in determining the site of origin of narrow QRS supraventricular tachycardia. Circulation 1983; 68:368. 7. Kay GN, Pressley JC, Packer DL, et al. Value of the 12-lead electrocardiogram in discriminating atrioventricular nodal reciprocating tachycardia from circus movement atrioventricular tachycardia utilizing a retrograde accessory pathway. Am J Cardiol 1987; 59:296. 8. Tchou PJ, Lehmann MH, Dongas J, et al. Effect of sudden rate acceleration on the human His-Purkinje system: adaptation of refractoriness in a dampened oscillatory pattern. Circulation 1986; 73:920. 9. Gallagher JJ, Sealy WC, Kasell J, Wallace AG. Multiple accessory pathways in patients with the pre-excitation syndrome. Circulation 1976; 54:571. 10. Man KC, Brinkman K, Bogun F, et al. 2:1 atrioventricular block during atrioventricular node reentrant tachycardia. J Am Coll Cardiol 1996; 28:1770. 11. Nelson SD, Kou WH, Annesley T, et al. Significance of ST segment depression during paroxysmal supraventricular tachycardia. J Am Coll Cardiol 1988; 12:383. 12. Riva SI, Della Bella P, Fassini G, et al. Value of analysis of ST segment changes during tachycardia in determining type of narrow QRS complex tachycardia. J Am Coll Cardiol 1996; 27:1480. 13. Scheinman MM, Wang YS, Van Hare GF, Lesh MD. Electrocardiographic and electrophysiologic characteristics of anterior, midseptal and right anterior free wall accessory pathways. J Am Coll Cardiol 1992; 20:1220. https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 10/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 14. Brembilla-Perrot B, Pauriah M, Sellal JM, et al. Incidence and prognostic significance of spontaneous and inducible antidromic tachycardia. Europace 2013; 15:871. 15. Ceresnak SR, Tanel RE, Pass RH, et al. Clinical and electrophysiologic characteristics of antidromic tachycardia in children with Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 2012; 35:480. 16. Zachariah JP, Walsh EP, Triedman JK, et al. Multiple accessory pathways in the young: the impact of structural heart disease. Am Heart J 2013; 165:87. 17. Dorostkar PC, Silka MJ, Morady F, Dick M 2nd. Clinical course of persistent junctional reciprocating tachycardia. J Am Coll Cardiol 1999; 33:366. 18. Aguinaga L, Primo J, Anguera I, et al. Long-term follow-up in patients with the permanent form of junctional reciprocating tachycardia treated with radiofrequency ablation. Pacing Clin Electrophysiol 1998; 21:2073. 19. Guarnieri T, Sealy WC, Kasell JH, et al. The nonpharmacologic management of the permanent form of junctional reciprocating tachycardia. Circulation 1984; 69:269. 20. Ticho BS, Saul JP, Hulse JE, et al. Variable location of accessory pathways associated with the permanent form of junctional reciprocating tachycardia and confirmation with radiofrequency ablation. Am J Cardiol 1992; 70:1559. 21. Packer DL, Bardy GH, Worley SJ, et al. Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction. Am J Cardiol 1986; 57:563. 22. Brugada P, Vanagt EJ, Bar FW, Wellens HJ. Incessant reciprocating atrioventricular tachycardia. Factors playing a role in the mechanism of the arrhythmia. Pacing Clin Electrophysiol 1980; 3:670. 23. Critelli G, Gallagher JJ, Monda V, et al. Anatomic and electrophysiologic substrate of the permanent form of junctional reciprocating tachycardia. J Am Coll Cardiol 1984; 4:601. 24. Okumura K, Henthorn RW, Epstein AE, et al. "Incessant" atrioventricular (AV) reciprocating tachycardia utilizing left lateral AV bypass pathway with a long retrograde conduction time. Pacing Clin Electrophysiol 1986; 9:332. Topic 976 Version 28.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 11/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate GRAPHICS Types of accessory pathways Diagram of 4 types of abnormal conduction pathways: classic accessory atrioventricular pathway (red), atriofascicular pathway (green), fasciculoventricular pathway (light blue), and nodoventricular pathway (dark blue). The atrioventricular node and His-Purkinje system are represented in yellow. Atrioventricular, atriofascicular, and nodoventricular pathways are capable of supporting atrioventricular reciprocating tachycardias. In contrast, an isolated fasciculoventricular pathway can cause subtle preexcitation but does not support clinical tachycardia. Graphic 138850 Version 1.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 12/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 13/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Orthodromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows an atrial premature beat (APB,*) that is blocked in the accessory pathway (AP), which has a long refractory period but is conducted antegradely through the atrioventricular node (N) and the His-Purkinje system, resulting in a normal PR interval and a narrow and normal QRS complex, as seen on the rhythm strip. After normal myocardial activation, the impulse is conducted retrogradely along the AP, activating the atrium in a retrograde fashion (panel B), which results in a negative P wave. If this activation sequence repeats itself (panel C), an orthodromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 71302 Version 7.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 14/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Electrocardiogram (ECG) showing orthodromic atrioventricular reentrant tachycardia (AVRT) Atrioventricular reentrant tachycardia (AVRT) is a supraventricular tachycardia associated with an accessory pathway connection between the atria and ventricles. The pathway may conduct antegrade only, retrograde only, or both antegrade and retrograde. AVRT is usually initiated by an atrial premature beat (arrow). The most common type of AVRT, termed orthodromic AVRT, uses the AV node and His Purkinje system (which has a relatively short refractory period) for antegrade conduction to the ventricles and the accessory AV pathway (which in these patients has a relatively long antegrade refractory period when compared to the node) for retrograde conduction. During orthodromic AVRT, QRS complexes are narrow. During sinus rhythm, however, wide and bizarre QRS complexes (indicative of the WPW pattern) are caused by conduction over both the accessory and normal pathways, resulting in a fusion beat. Since there is 1:1 retrograde activation of the atrium, a negative P wave may be present following the QRS complex. Graphic 54720 Version 5.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 15/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Graphic 69872 Version 2.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 16/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 12-lead electrocardiogram (ECG) showing orthodromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG from a patient with Wolff-Parkinson-White shows a regular tachycardia. However, in contrast to the QRS pattern during sinus rhythm, the QRS complexes are narrow, without evidence of a delta wave or pre-excitation; this is due to the fact that antegrade ventricular activation occurs via the normal atrioventricular node-His Purkinje pathway, while retrograde atrial activation is via the accessory pathway. Therefore, this is called an orthodromic atrioventricular reentrant tachycardia (OAVRT). Courtesy of Martin Burke, DO. Graphic 68804 Version 5.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 17/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 18/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Antidromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows the activation sequence with an atrial premature beat (APB,*). The impulse reaches the atrioventricular node (N) before it has repolarized and hence is blocked in this structure. However, the accessory pathway (AP), which has a short refractory period, is able to conduct the impulse antegradely, resulting in an APB with a widened QRS morphology similar to the sinus beat. As seen in panel B, following myocardial activation, the impulse is conducted retrogradely along the His-Purkinje system and AV node, resulting in retrograde atrial activation, seen on the rhythm strip as an inverted P wave. If this activation sequence repeats itself (panel C), a wide QRS complex antidromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 50433 Version 4.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 19/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 12-lead electrocardiogram (ECG) showing antidromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG of a patient with Wolff-Parkinson-White shows a regular tachycardia. The QRS complexes are widened and are identical to the QRS complexes seen in sinus rhythm; the antegrade conduction to the ventricle is via the accessory pathway and retrograde conduction is via the normal His- atrioventricular node pathway. This is, therefore, an antidromic atrioventricular reentrant tachycardia (AVRT). Courtesy of Martin Burke, DO. Graphic 54484 Version 20.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 20/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 21/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 12-lead electrocardiogram (ECG) showing antidromic atrioventricular reentrant tachycardia (AVRT) The 12-lead ECG shows a wide complex tachycardia in a patient with Wolff- Parkinson-White syndrome and a left lateral accessory pathway. The QRS complexes are wide and have a morphology that is similar to that during sinus rhythm, confirming that this is an antidromic atrioventricular reentrant tachycardia. Graphic 71410 Version 5.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 22/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate WPW syndrome with a left posterior accessory pathway The 12 lead ECG from a patient with Wolff-Parkinson-White syndrome (WPW) shows a short PR interval and a delta wave which results in a widened QRS complex. The delta wave is positive in leads I, avL, and V1 to V6 and negative in leads II, III, and avF, compatible with a left posterior accessory pathway. Graphic 80663 Version 2.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 23/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Permanent form of junctional tachycardia 12-lead ECG and lead II rhythm strip obtained from a patient with |
Graphic 71302 Version 7.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 14/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Electrocardiogram (ECG) showing orthodromic atrioventricular reentrant tachycardia (AVRT) Atrioventricular reentrant tachycardia (AVRT) is a supraventricular tachycardia associated with an accessory pathway connection between the atria and ventricles. The pathway may conduct antegrade only, retrograde only, or both antegrade and retrograde. AVRT is usually initiated by an atrial premature beat (arrow). The most common type of AVRT, termed orthodromic AVRT, uses the AV node and His Purkinje system (which has a relatively short refractory period) for antegrade conduction to the ventricles and the accessory AV pathway (which in these patients has a relatively long antegrade refractory period when compared to the node) for retrograde conduction. During orthodromic AVRT, QRS complexes are narrow. During sinus rhythm, however, wide and bizarre QRS complexes (indicative of the WPW pattern) are caused by conduction over both the accessory and normal pathways, resulting in a fusion beat. Since there is 1:1 retrograde activation of the atrium, a negative P wave may be present following the QRS complex. Graphic 54720 Version 5.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 15/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Graphic 69872 Version 2.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 16/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 12-lead electrocardiogram (ECG) showing orthodromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG from a patient with Wolff-Parkinson-White shows a regular tachycardia. However, in contrast to the QRS pattern during sinus rhythm, the QRS complexes are narrow, without evidence of a delta wave or pre-excitation; this is due to the fact that antegrade ventricular activation occurs via the normal atrioventricular node-His Purkinje pathway, while retrograde atrial activation is via the accessory pathway. Therefore, this is called an orthodromic atrioventricular reentrant tachycardia (OAVRT). Courtesy of Martin Burke, DO. Graphic 68804 Version 5.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 17/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 18/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Antidromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows the activation sequence with an atrial premature beat (APB,*). The impulse reaches the atrioventricular node (N) before it has repolarized and hence is blocked in this structure. However, the accessory pathway (AP), which has a short refractory period, is able to conduct the impulse antegradely, resulting in an APB with a widened QRS morphology similar to the sinus beat. As seen in panel B, following myocardial activation, the impulse is conducted retrogradely along the His-Purkinje system and AV node, resulting in retrograde atrial activation, seen on the rhythm strip as an inverted P wave. If this activation sequence repeats itself (panel C), a wide QRS complex antidromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 50433 Version 4.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 19/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 12-lead electrocardiogram (ECG) showing antidromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG of a patient with Wolff-Parkinson-White shows a regular tachycardia. The QRS complexes are widened and are identical to the QRS complexes seen in sinus rhythm; the antegrade conduction to the ventricle is via the accessory pathway and retrograde conduction is via the normal His- atrioventricular node pathway. This is, therefore, an antidromic atrioventricular reentrant tachycardia (AVRT). Courtesy of Martin Burke, DO. Graphic 54484 Version 20.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 20/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 21/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate 12-lead electrocardiogram (ECG) showing antidromic atrioventricular reentrant tachycardia (AVRT) The 12-lead ECG shows a wide complex tachycardia in a patient with Wolff- Parkinson-White syndrome and a left lateral accessory pathway. The QRS complexes are wide and have a morphology that is similar to that during sinus rhythm, confirming that this is an antidromic atrioventricular reentrant tachycardia. Graphic 71410 Version 5.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 22/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate WPW syndrome with a left posterior accessory pathway The 12 lead ECG from a patient with Wolff-Parkinson-White syndrome (WPW) shows a short PR interval and a delta wave which results in a widened QRS complex. The delta wave is positive in leads I, avL, and V1 to V6 and negative in leads II, III, and avF, compatible with a left posterior accessory pathway. Graphic 80663 Version 2.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 23/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Permanent form of junctional tachycardia 12-lead ECG and lead II rhythm strip obtained from a patient with junctional tachycardia at a rate of 165 beats/min. The QRS complex is narrow and there are negative P waves with a long RP interval due to slow retrograde conduction via an accessory pathway. The tachycardia tends to terminate spontaneously and recur, as seen in the rhythm strip. Termination is due to retrograde block in the accessory pathway with absence of the retrograde P wave (arrow). An atrial premature beat (*) reinitiates the tachycardia. Graphic 67767 Version 4.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 24/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 25/26 7/6/23, 11:12 AM Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway - UpToDate Contributor Disclosures Luigi Di Biase, MD, PhD, FHRS, FACC Consultant/Advisory Boards: Abbott [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Baylis Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Biosense Webster [Ablation products]; Biotronik [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Boston Scientific [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Medtronic [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Stereotaxis [Ablation products]; Zoll Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]. All of the relevant financial relationships listed have been mitigated. Edward P Walsh, MD No relevant financial relationship(s) with ineligible companies to disclose. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atrioventricular-reentrant-tachycardia-avrt-associated-with-an-accessory-pathway/print 26/26 |
7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. General principles of asynchronous activation and preexcitation : Bradley P Knight, MD, FACC : Peter J Zimetbaum, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 25, 2021. INTRODUCTION Normal electrical activation of the right and left ventricles during the cardiac cycle follows a precisely defined pattern. After an impulse emerges from the atrioventricular (AV) node, it traverses the His bundle, and propagates down the bundle branches and the fascicles of the bundle branches to the terminal Purkinje fibers and ultimately the ventricular myocardium. Conduction abnormalities result in asynchronous electrical activation causing asynchronous mechanical activation of the ventricles. This problem can be induced by one of two mechanisms: delayed activation of an area of the ventricles or early activation (preexcitation) of an area of the ventricles. This topic will present an overview of asynchronous activation and preexcitation. The clinical manifestations of abnormal activation or preexcitation are discussed in detail separately. (See "Right bundle branch block" and "Left bundle branch block" and "Left anterior fascicular block" and "Left posterior fascicular block" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) DELAYED ACTIVATION Delayed activation causes asynchronous activation and may be a result of anatomic abnormalities or of physiologic properties of the cardiac tissues. Activation delay may occur https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 1/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate between the ventricles or portions of the ventricles (interventricular delay), within the terminal Purkinje fibers and/or ventricular myocardium (intraventricular delay) or between layers of the heart (intramural delay) [1]. Clinically, conduction delay causing ventricular electrical dyssynchrony is manifest as an abnormal QRS complex on the electrocardiogram (ECG). Specific ECG patterns that are clinically distinguished include right bundle branch block (RBBB), left bundle branch block (LBBB), a prolonged QRS complex without specific features of LBBB or RBBB (usually called "intraventricular conduction delay" or IVCD), left anterior hemiblock, and left posterior hemiblock. While all of these conduction patterns are sometimes referred to collectively as forms of intraventricular conduction delay, the precise location of the conduction disturbance cannot be reliably determined from the surface ECG. In the case of RBBB and LBBB, it is probably more accurate to refer to these entities as forms of "interventricular conduction delay." Interventricular conduction delay Delayed or blocked conduction in the bundles or their fascicles results in asynchronous activation and repolarization of the right and left ventricles. This, in turn, gives rise to characteristic ECG patterns. The classic examples of interventricular conduction delay are RBBB and LBBB. Fascicular block is not strictly an interventricular conduction delay, but results from a conduction disturbance in the left anterior or posterior fascicle. It is important to recognize that a bundle branch pattern on an ECG can be due to conduction delay rather than complete block, because delay in the other bundle branch can cause equal delay to the ventricles resulting in apparent resolution of the bundle branch block pattern. (See "Right bundle branch block" and "Left bundle branch block".) Intraventricular and intramural conduction delay Intraventricular conduction delay is a delay within the myocardium itself. This occurs commonly in cardiomyopathies, resulting in regional differences in the time to peak systolic contraction. Intramural or transmural delay is a delay in activation between the endocardium and myocardium, also commonly noted in cardiomyopathies. Both intraventricular and intramural conduction delays occur together with interventricular left bundle branch block. The term parietal block has been used to describe conduction delays in the terminal Purkinje conduction system. This phenomenon may result in a QRS duration in ECG leads V1 to V3 that significantly exceeds the QRS duration in leads V4 to V6 (right ventricular parietal block) or vice versa (left ventricular parietal block). Right ventricular parietal block is seen in some patients with arrhythmogenic right ventricular cardiomyopathy. Genesis of ECG pattern Two factors, magnitude and duration, determine the ECG changes seen with a given type of block. https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 2/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate Magnitude The magnitude (or amplitude) of the extracellular signal generated by the wavefront of unopposed dipoles can be affected by a number of factors. Examples include: A gain of force as with ventricular enlargement A loss of force as with myocardial infarction A change in cancellation due to asynchrony that can increase or decrease unopposed dipoles With regard to cancellation, the term "activation" is used to describe those unopposed boundaries that result in an electrocardiographically recorded potential. Many other wavefronts exist, however, and "cancel" each other. Normal synchronous ventricular depolarization results in a predictable sequence of opposed and unopposed wavefronts that result in the normal ECG [2,3]. Asynchronous activation generally reduces the amount of signal cancellation, resulting in a larger extracellularly recorded electrogram. With left bundle block, for example, left ventricular activation is delayed, occurring later than activation of the right bundle. As a result, the left ventricular signal is not partially canceled by that from the right ventricle, leading to an increase in amplitude of the QRS complex. This is the reason that standard voltage criteria for ventricular enlargement are invalid in bundle branch blocks. Duration Asynchronous activation can also affect the duration of the recorded potential. The time of initiation of activation is unchanged in this setting, but termination is delayed due to slower conduction to the blocked ventricle. The net effect is increased duration of the P wave or QRS complex, depending upon the site of disease. PREEXCITATION Ventricular preexcitation can occur when there is a premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) or when ventricular pacing occurs before the expected timing of ventricular activation through the atrioventricular (AV) node. Ventricular pacing causes asynchronous activation due to preexcitation of either ventricle. Right ventricular pacing preexcites the right ventricle and causes a pattern that has some of the electrocardiographic (ECG) features of left bundle branch block (LBBB); left ventricular pacing preexcites the left ventricle and has some of the ECG features of a right bundle branch block. Preexciting the ventricles with pacing is used in patients with congestive heart failure and ventricular mechanical dyssynchrony caused by an LBBB to resynchronize the ventricles and improve mechanical synchrony. (See "Cardiac resynchronization therapy in heart failure: System implantation and programming".) https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 3/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate Preexciting the right ventricle with right ventricular pacing can be used to intentionally induce mechanical dyssynchrony. This has been used to reduce the outflow tract gradient in patients with hypertrophic cardiomyopathy and an outflow tract obstruction. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Therapies of limited benefit'.) However, the term "ventricular preexcitation" is usually used to refer to preexcitation of the ventricle caused by AV conduction over an accessory pathway. The preexcitation syndromes are conditions in which atrial activation of the ventricles occurs earlier than would be expected if atrioventricular conduction occurred normally through the AV node. General anatomic considerations A number of conducting pathways have been described ( table 1). These include: Accessory atrioventricular connections, often called Kent bundles in the older literature, which directly connect the atria and ventricles [4-6]. These connections are typically located at one of the atrioventricular valves. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) James fibers, which connect the atria with the low AV node (atrionodal accessory pathway) or the bundle of His (atriofascicular accessory pathway) [7]. (See "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction", section on 'Lown-Ganong- Levine pattern'.) So-called Mahaim fibers of several types that arise from the atrium and insert into a bundle branch (atriofascicular), arise from the AV node and insert into a bundle branch (nodofascicular), arise from the AV node and insert into ventricular tissue (nodoventricular accessory pathways). An accessory pathway can also arise from the His-bundle or one of the bundle branches and insert into ventricular tissue (fasciculoventricular accessory pathway) [8-11]. Terminology based upon anatomic connections is gradually replacing the venerable eponyms and some attempt has been made at standardization [8]. The European Study Group for Preexcitation suggests that the term "connection" should be used to describe pathways that insert into ventricular myocardium while "tracts" should be applied to pathways that insert into specialized conduction tissue [5]. However, the terms are often used interchangeably and tract is increasingly replacing connection ( table 1) [12]. Atrioventricular accessory pathways (connections) Ninety-five percent of atrioventricular accessory pathways conduct rapidly and have the characteristics of INa (sodium) dependent https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 4/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate phase 0 action potentials that occur in normal "fast response" myocardium. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) Five percent show decremental conduction, the mechanism of which is uncertain. Possible explanations include geometric factors, partial inactivation of the sodium channel, or perhaps dependence on a calcium channel. The fast response pathways often conduct rapidly, have short refractory periods, and can conduct frequently. This poses a particular problem during rapid supraventricular tachycardias such as atrial flutter, which may conduct 1:1, and atrial fibrillation, which may produce ventricular flutter and fibrillation. In preexcitation syndromes in which the accessory pathway inserts eccentrically, the resultant ventricular depolarization represents a fusion between ventricular activation initiated by the fast response, rapidly conducting bypass pathway and that initiated by the slow response, slowly conducting atrioventricular node. This is the pattern characteristic of patients with the Wolff- Parkinson-White syndrome. The principles of this fusion are illustrated in the figure ( figure 1A-C). The PR interval is shortened due to the preexcitation The eccentric ventricular activation results in a slurred upstroke of the QRS or delta wave The QRS duration is increased due to the asynchronous activation between the preexcited and normally excited portions of the ventricular myocardium How the ECG can be used to identify the location of the accessory pathway is discussed elsewhere. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) James fibers (intranodal or atrionodal bypass tract) Lown-Ganong-Levine syndrome The Lown-Ganong-Levine syndrome is characterized by palpitations in patients with an ECG that shows a short PR interval and a normal QRS duration [13]. For many years, this disorder was thought to be due to tracts that connected the atrium with the low AV node or the His bundle (via James fibers) [7]. (See "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction".) The current concept, however, is that the short PR interval with a normal QRS pattern results, in most cases, from enhanced or accelerated AV nodal conduction and less often from an accessory pathway [12,14-16]. A short PR interval appears to be more frequent in patients with concealed accessory pathways, but has also been associated with dual pathway physiology and AV nodal reentrant tachycardia [15]. However, only patients with symptomatic tachyarrhythmias https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 5/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate are studied electrophysiologically. As a result, it is uncertain whether all individuals with a short PR interval and normal QRS complex have enhanced AV nodal conduction or accessory pathways near the AV node. Reentrant SVT A case of incessant supraventricular tachycardia (SVT), which continued despite AV block, has been reported [17]. An atrial tachycardia, AV nodal reentrant tachycardia, and an orthodromic tachycardia using a concealed accessory AV pathway were excluded as causes. The earliest retrograde atrial activation was at the posterolateral tricuspid annulus, and the tachycardia was eliminated by ablation at this site. These observations strongly suggest a concealed atrionodal pathway as the cause. Role of Mahaim fibers Mahaim pathways arise from the atria, AV node, fascicle, or one of the bundle branches and insert into fascicle or ventricular tissue. The precise characteristics of Mahaim fibers have been debated [10]. It was presumed that certain of these pathways, in which the AV node was normally traversed, could explain the situation in which the PR interval was normal but the QRS was widened (presumably due to eccentric activation of the ventricles) [18]. Some patients also had a prolonged PR interval with eccentric ventricular activation. This could be explained by slowed AV nodal conduction and anomalous connections at the level of or below the AV node. However, surgical and catheter ablation studies suggest that electrophysiologic characteristics attributed to nodoventricular Mahaim fibers are due to atriofascicular accessory connections with decremental conduction [19-24]. One report, for example, suggests the presence of an atrioventricular connection in the tricuspid ring [21]. This connection has slow and rate- dependent conduction, blocks with adenosine, has intrinsic automaticity, and links to a rapidly conducting insulated pathway that generates a "His-like" potential. Despite these observations, some experts still believe that nodofascicular tracts exist and are functional [12]. An orthodromic AVRT with atrioventricular dissociation has been presented as evidence for a nodoventricular type of Mahaim fiber [25]. Fasciculoventricular pathways can be demonstrated in 1 to 2 percent of adults who show ventricular preexcitation and are referred for electrophysiologic investigation [11,26]. These pathways can be thought of as a loss of insulation around the His-Purkinje system resulting in a direct connection to the local ventricular myocardium causing ventricular preexcitation. These pathways do not participate in reentrant rhythms and must be recognized during an EP study, mostly so that ablation is not attempted unnecessarily. Enhanced AV nodal conduction with a short AH interval is common, but normal AH interval lengthening may occur during incremental atrial pacing [11,26]. The administration of https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 6/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate adenosine may help to reveal the relationship between the fasciculoventricular pathway and its connection to the AV node and the infranodal conduction system. With AV nodal connections, a high degree of AV block or even complete AV block may occur with preexcited conducted beats. Familial Mahaim syndrome has been reported and suggests possible genetic transmission in some patients [27]. Classification of arrhythmias associated with accessory pathways The accessory pathways have two effects, which facilitate the development of certain supraventricular tachyarrhythmias: they can provide a pathway for reentry; and they can produce preexcitation, which results in a wide complex tachycardia. The atrioventricular reentrant tachycardias (AVRT) can utilize both the AV node and an accessory pathway in the reentrant circuit. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Orthodromic AVRT, the most common form, uses a circuit consisting of antegrade conduction through the AV node and retrograde conduction through the accessory pathway. In the absence of preexisting or functional bundle branch block, this produces a narrow QRS tachycardia in which the P wave follows the QRS complex ( figure 2). The less common, or antidromic, form of AVRT conducts antegrade through the accessory pathway and retrograde through the AV node, producing a wide QRS complex with a delta wave and a P wave that follows the QRS complex. This would be a reentrant form of a "preexcited tachycardia" that uses the AV node (see below) ( figure 3). The permanent form of junctional reciprocating tachycardia (PJRT) is a clinical syndrome of a nearly incessant supraventricular tachycardia. It is typically seen in young patients who can present with a tachycardia-mediated cardiomyopathy. The term PJRT is often used interchangeably with a nearly incessant AVRT using a slowly conducting concealed accessory pathway [28]. However, some patients with an atrial tachycardia or atypical AV nodal reentry can also present with a nearly incessant SVT. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Permanent junctional reciprocating tachycardia'.) As discussed above, the so-called James and Mahaim fibers may also be involved in reentrant arrhythmias. Preexcited tachycardias Preexcited tachycardias, such as the WPW syndrome, are wide complex tachycardias that conduct antegrade over the accessory pathway. They are induced by supraventricular tachycardias, including atrial fibrillation, atrial flutter, and the family of atrial https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 7/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate tachycardias including the antidromic form of AVRT. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) SUMMARY Delayed activation causes asynchronous electrical and mechanical activation and may be a result of anatomic abnormalities or of physiologic properties of the cardiac tissues. Clinically, conduction delay causing asynchronous ventricular activation is usually manifest as an abnormal QRS complex on the electrocardiogram (ECG). Specific ECG patterns that are clinically distinguished include right bundle branch block (RBBB), left bundle branch block (LBBB), a prolonged QRS complex without specific features of LBBB or RBBB (usually called "intraventricular conduction delay" or IVCD), left anterior hemiblock, and left posterior hemiblock. (See 'Delayed activation' above.) Two factors, magnitude and duration, determine the ECG changes seen with a given type of block. Normal synchronous ventricular depolarization results in a predictable sequence of opposed and unopposed wavefronts that results in the normal ECG. Asynchronous activation generally reduces the amount of signal cancellation, resulting in a larger extracellularly recorded electrogram. The time of initiation of activation is unchanged in the setting of asynchronous activation, but termination is delayed due to slower conduction to the blocked ventricle. The net effect is an increased duration of the QRS complex. (See 'Genesis of ECG pattern' above.) Ventricular preexcitation can occur when there is a PVC or when ventricular pacing occurs before the expected timing of ventricular activation through the atrioventricular (AV) node. However, the term "ventricular preexcitation" is usually used to refer to preexcitation of the ventricle caused by AV conduction over an accessory pathway. The preexcitation syndromes are conditions in which atrial activation of the ventricles occurs earlier than would be expected if atrioventricular conduction occurred normally through the AV node. (See 'Preexcitation' above.) A number of conducting pathways have been described, including those connecting the atria with the ventricles, the atria with the AV node, the atria with the His-Purkinje system, and the AV node with the ventricles ( table 1). (See 'General anatomic considerations' above.) The accessory pathways have two effects which facilitate the development of certain supraventricular tachyarrhythmias: they can provide a pathway for reentry, either https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 8/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate orthodromically or antidromically; and they can produce preexcitation, which, during tachycardia and anterograde conduction over the pathway, either as part of the circuit or as a bystander, results in a wide QRS complex tachycardia. (See 'Classification of arrhythmias associated with accessory pathways' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Auricchio A, Fantoni C, Regoli F, et al. Characterization of left ventricular activation in patients with heart failure and left bundle-branch block. Circulation 2004; 109:1133. 2. Durrer D, van Dam RT, Freud GE, et al. Total excitation of the isolated human heart. Circulation 1970; 41:899. 3. Van Dam RT, Janse MJ. Activation of the Heart. In: Comprehensive Electrocardiology: Theory and Practice in Health and Disease, MacFarlane P, Veitch Lawrie TD (Eds), Pergamon Press, New York 1980. p.101. 4. Kent, AF . Researches on the structure and function of the mammalian heart. J Physiol 1893; 14:233. 5. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. 6. Boineau JP, Moore EN. Evidence for propagation of activation across an accessory atrioventricular connection in types A and B pre-excitation. Circulation 1970; 41:375. 7. JAMES TN. Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J 1961; 62:756. 8. MAHAIM I. Kent's fibers and the A-V paraspecific conduction through the upper connections of the bundle of His-Tawara. Am Heart J 1947; 33:651. 9. Lev M, Fox SM 3rd, Bharati S, et al. Mahaim and James fibers as a basis for a unique variety of ventricular preexcitation. Am J Cardiol 1975; 36:880. 10. Klein GJ, Guiraudon G, Guiraudon C, Yee R. The nodoventricular Mahaim pathway: an endangered concept? Circulation 1994; 90:636. 11. Sternick EB, Gerken LM, Vrandecic MO, Wellens HJ. Fasciculoventricular pathways: clinical and electrophysiologic characteristics of a variant of preexcitation. J Cardiovasc Electrophysiol 2003; 14:1057. 12. Josephson ME. Clinical Cardiac Electrophysiology: Techniques and Interpretations, 2d ed, Le a & Febiger, Philadelphia 1993. https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 9/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate 13. LOWN B, GANONG WF, LEVINE SA. The syndrome of short P-R interval, normal QRS complex and paroxysmal rapid heart action. Circulation 1952; 5:693. 14. Denes P, Wu D, Amat-y-Leon F, et al. The determinants of atrioventricular nodal re-entrance with premature atrial stimulation in patients with dual A-V nodal pathways. Circulation 1977; 56:253. 15. Benditt DG, Pritchett LC, Smith WM, et al. Characteristics of atrioventricular conduction and the spectrum of arrhythmias in lown-ganong-levine syndrome. Circulation 1978; 57:454. 16. Bauernfeind RA, Swiryn S, Strasberg B, et al. Analysis of anterograde and retrograde fast pathway properties in patients with dual atrioventricular nodal pathways: observations regarding the pathophysiology of the Lown-Ganong-Levine syndrome. Am J Cardiol 1982; 49:283. 17. Zivin A, Morady F. Incessant tachycardia using a concealed atrionodal bypass tract. J Cardiovasc Electrophysiol 1998; 9:191. 18. Wellens HJJ. The preexcitation syndrome. In: Electrical Stimulation of the Heart, Wellens HJJ (Ed), University Park Press, Baltimore 1971. p.97. 19. Gillette PC, Garson A Jr, Cooley DA, McNamara DG. Prolonged and decremental antegrade conduction properties in right anterior accessory connections: Wide QRS antidromic tachycardia of left bundle branch block pattern without Wolff-Parkinson-White configuration in sinus rhythm. Am Heart J 1982; 103:66. 20. Klein GJ, Guiraudon GM, Kerr CR, et al. "Nodoventricular" accessory pathway: evidence for a distinct accessory atrioventricular pathway with atrioventricular node-like properties. J Am Coll Cardiol 1988; 11:1035. 21. McClelland JH, Wang X, Beckman KJ, et al. Radiofrequency catheter ablation of right atriofascicular (Mahaim) accessory pathways guided by accessory pathway activation potentials. Circulation 1994; 89:2655. 22. Cappato R, Schl ter M, Mont L, Kuck KH. Anatomic, electrical, and mechanical factors affecting bipolar endocardial electrograms. Impact on catheter ablation of manifest left free-wall accessory pathways. Circulation 1994; 90:884. 23. Grogin HR, Lee RJ, Kwasman M, et al. Radiofrequency catheter ablation of atriofascicular and nodoventricular Mahaim tracts. Circulation 1994; 90:272. 24. Li HG, Klein GJ, Thakur RK, Yee R. Radiofrequency ablation of decremental accessory pathways mimicking "nodoventricular" conduction. Am J Cardiol 1994; 74:829. 25. Mantovan R, Verlato R, Corrado D, et al. Orthodromic tachycardia with atrioventricular dissociation: evidence for a nodoventricular (Mahaim) fiber. Pacing Clin Electrophysiol 2000; https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 10/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate 23:276. 26. Gallagher JJ, Smith WM, Kasell JH, et al. Role of Mahaim fibers in cardiac arrhythmias in man. Circulation 1981; 64:176. 27. Ott P, Marcus FI. Familial Mahaim syndrome. Ann Noninvasive Electrocardiol 2001; 6:272. 28. Shih HT, Miles WM, Klein LS, et al. Multiple accessory pathways in the permanent form of junctional reciprocating tachycardia. Am J Cardiol 1994; 73:361. Topic 898 Version 20.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 11/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate GRAPHICS Terminology and anatomic connections of preexcitation pathways Old terminology Proposed or commonly used terminology Anatomic connections Kent bundle* Accessory AV connection or AV bypass tract Atrium to ventricle James fiber Atrionodal bypass tract Atrium to low AV node Atriofascicular bypass tract Atrium to bundle of His Mahaim fiber Atriofascicular bypass tract Atrium to bundle branch Nodofascicular bypass tract AV node to bundle branch Nodoventricular bypass tract AV node to ventricular tissue Fasciculoventricular bypass tract Bundle branch to ventricular tissue AV: atrioventricular. These bypass tracts result in delta waves and the Wolff-Parkinson-White syndrome. These bypass tracts result in the Lown-Ganong-Levine syndrome and enhanced AV nodal conduction. Graphic 53343 Version 6.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 12/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate AV conduction with a concealed accessory pathway Schematic representation of AV conduction. The normal pacemaker is in the sinoatrial (SA) node at the junction of the superior vena cava and the right atrium. The SA node activates the right and left atria (shown in green). In the absence of an accessory pathway (AP) or, as in this case, if the AP is concealed, ventricular activation results from the impulse traversing the AV node, the specialized infranodal conducting system (His bundle, bundle branches, and fascicular branches, shown in red), thereby activating the ventricular myocardium (shown in yellow). The ECG shows a normal PR interval and a narrow QRS complex. The inset on the right shows the timing of SA node (SAN), right (RA) and left atrial (LA), His bundle (H), and the beginning of normal ventricular activation (V ). All of ventricular activation (shown in yellow) is due to normal AV nodal and infranodal conduction. N AV: atrioventricular; ECG: electrocardiogram. Graphic 73740 Version 5.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 13/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate AV conduction through an overt accessory pathway Compared with normal conduction in the preceding diagram, the accessory pathway (AP) is now overt. As a result, ventricular activation results from both early activation (pre-excitation) of the free wall of the left ventricle (shown in blue) and from normal activation (shown in yellow). The degree of unopposed pre-excitation depends upon the time required to conduct through the right and left atria, the AP, and the ventricular myocardium as compared with conduction through the normal pathways. The inset on the right shows the ECG timing of these events. The net effect is a QRS complex that is a fusion of ventricular pre-excitation (blue) and normal excitation (yellow). Early activation throughout the AP (V ) P occurs at about the same time as His bundle depolarization (H). This leads to a shorter PR interval, a small delta wave (arrow), and some prolongation of the QRS duration. AV: atrioventricular. Graphic 53773 Version 6.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 14/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate Conduction through an accessory pathway with AV nodal delay Compared with conduction through an AP with normal AV node conduction, delayed conduction through the AV node allows more of the ventricular myocardium to be activated by pre-excitation (shown in blue). The inset on the right shows the ECG timing of these events. The atrial to His interval is increased due to the AV nodal delay (RA to H); His activation is so delayed that it follows activation caused by the AP (V ). The PR interval is short due to the pre- excitation, the delta wave (arrow) is more pronounced due to the greater and unopposed early forces (blue), and the QRS duration is prolonged due to the later than normal ventricular activation caused by the AV nodal delay (yellow). P AV: atrioventricular; ECG: electrocardiogram. Graphic 62454 Version 6.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 15/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate Orthodromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows an atrial premature beat (APB,*) that is blocked in the accessory pathway (AP), which has a long refractory period but is conducted antegradely through the atrioventricular node (N) and the His-Purkinje system, resulting in a normal PR interval and a narrow and normal QRS complex, as seen on the rhythm strip. After normal myocardial activation, the impulse is conducted retrogradely along the AP, activating the atrium in a retrograde fashion (panel B), which results in a negative P wave. If this activation sequence repeats itself (panel C), an orthodromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 71302 Version 7.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 16/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate Antidromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows the activation sequence with an atrial premature beat (APB,*). The impulse reaches the atrioventricular node (N) before it has repolarized and hence is blocked in this structure. However, the accessory pathway (AP), which has a short refractory period, is able to conduct the impulse antegradely, resulting in an APB with a widened QRS morphology similar to the sinus beat. As seen in panel B, following myocardial activation, the impulse is conducted retrogradely along the His-Purkinje system and AV node, resulting in retrograde atrial activation, seen on the rhythm strip as an inverted P wave. If this activation sequence repeats itself (panel C), a wide QRS complex antidromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 50433 Version 4.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 17/18 7/6/23, 11:13 AM General principles of asynchronous activation and preexcitation - UpToDate Contributor Disclosures Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 18/18 |
7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction : Philip J Podrid, MD, FACC : Peter J Zimetbaum, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 02, 2022. INTRODUCTION The term cardiac preexcitation was originally used to describe premature activation of the ventricle prior to activation via the normal atrioventricular (AV) node His-Purkinje system in patients with the Wolff-Parkinson-White syndrome (WPW). This term has been broadened to include all conditions in which antegrade ventricular activation or retrograde atrial activation occurs partially or totally via an anomalous (or accessory) pathway distinct from the normal cardiac conduction system. The classic form of cardiac preexcitation remains the WPW pattern, which is characterized by a short PR interval (less than 120 milliseconds) and a broad QRS complex due to a delta wave resulting from direct myocardial activation that is slower than activation via the normal conduction system and hence the delta wave. The anatomic substrate for WPW pattern is a band of myocytes (which has similar electrophysiologic properties as the His-Purkinje system), also known as the bundle of Kent, which bridges the fibrous AV junction (ie, a direct atrial-ventricular accessory pathway that bypasses the AV node and normal His-Purkinje system). The electrocardiographic (ECG) features are a result of premature and direct ventricular myocardial activation due to conduction over the accessory pathway that directly innervates the ventricular myocardium. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome" and "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 1/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Several other pathways have been postulated to result in cardiac preexcitation. However, most lack the histopathologic correlation that has been demonstrated for the WPW syndrome. The Lown-Ganong-Levine (LGL) pattern and enhanced AV nodal conduction (EAVNC) share some common features and have often been considered to have a similar etiology. The mechanisms proposed to account for these conditions include more rapid conduction within the AV node ("slick AV node") or as a result of a bypass of the normal AV nodal tissue ( figure 1). The LGL syndrome and EAVNC will be discussed in detail here. Mahaim fiber tachycardia, another non- WPW form of preexcitation, is discussed separately. (See "Atriofascicular ("Mahaim") pathway tachycardia".) LOWN-GANONG-LEVINE PATTERN The Lown-Ganong-Levine (LGL) pattern is characterized by the presence of a short PR interval (120 milliseconds) and normal QRS complex on the surface ECG. This finding may represent a perinodal accessory pathway or enhanced AV nodal conduction ( waveform 1). This bypass tract or accessory pathway is known as a bundle of James. This pathway links the atrial myocardium with the bundle of His. Thus, there is a short PR interval but a normal QRS complex as ventricular activation is still via the normal His-Purkinje system. Patients with palpitations who had a short PR interval but normal QRS complex on the resting ECG (ie, LGL syndrome) were first described in 1938 and then further evaluated by Lown, Ganong, and Levine in 1952 [1,2]. The latter report consisted of a retrospective examination of 13,500 consecutive ECGs at a single tertiary care center. 200 subjects were identified with a short PR interval, most of whom had a normal QRS complex [2]. The incidence of paroxysmal supraventricular tachycardia was significantly higher in these patients when compared with a control group with a normal PR interval (11 versus 0.5 percent). Electrophysiologic properties The electrophysiologic mechanism for the short PR interval in the LGL pattern is abnormal (fast) AV conduction with normal His-Purkinje fiber conduction. There is a bypass of the AV node with a tissue pathway, known as a bundle of James, that enters the bundle of His. This accounts for a short PR interval with normal QRS complexes. The following abnormalities have been found in patients with LGL pattern [3-7]: Abbreviated AH intervals at rest. Shortened AV nodal refractory times. Abnormal responses to rapid atrial pacing (ie, AH intervals remain constant as the rate of atrial pacing increases until there is failure of conduction, ie, block). This is due to the fact https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 2/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate that unlike the AV node, the accessory pathway (similar to the His-Purkinje system) manifests all-or-none conduction (ie, the pathway either conducts or does not conduct, and there is no change in the velocity of conduction when heart rate increases). The first two represent abnormal AV nodal function while the third can also represent an accessory pathway ( figure 1). Enhanced atrioventricular nodal conduction Since the description of the LGL pattern, it has been recognized that some of these patients have enhanced AV nodal conduction (EAVNC) [8]. Although both LGL and EAVNC refer to a presumed abnormality in or bypass of normal AV nodal function, diagnosis of the LGL pattern is based upon clinical and ECG findings while diagnosis of EAVNC requires the following specific electrophysiologic criteria [8]: AH interval in sinus rhythm of less than or equal to 60 milliseconds (normal 80 to 120 milliseconds in most subjects) 1:1 conduction between atrium and His bundle maintained during right atrial pacing at cycle lengths below 300 milliseconds AH prolongation 100 milliseconds at the shortest 1:1 conduction when compared with the sinus rhythm value The definition of EAVNC was subsequently broadened by including patients who had increase in AH interval of not more than 100 milliseconds during pacing at a cycle length of 300 milliseconds compared with the value measured during sinus rhythm. In one study, the individual criteria for EAVNC were fulfilled in 20 to 50 percent of patients undergoing electrophysiologic study for the evaluation of cardiac arrhythmia or syncope; however, only 11 percent fulfilled all three criteria for EAVNC [9]. Caution with sympathomimetic agents Drugs that can increase the heart rate or cause atrial tachyarrhythmias (eg, sympathomimetic agents like dextroamphetamine) should be used with caution in patients with LGL or EAVNC. While there are no data about the risk of any sympathomimetic agent and developing arrhythmias with LGL, there would seem to be similar pathophysiologic considerations as are seen in patients with the Wolff-Parkinson-White (WPW) syndrome. Sympathomimetic agents would enhance conduction through the AV node (making an AVRT more likely), as well as change refractoriness of the atrial myocardium (making atrial arrhythmias more likely and hence conducted more rapidly to the ventricle as a result of the bypass tract). Electrophysiology of EAVNC By definition, patients with EAVNC have an abnormally short AH interval and an abnormal magnitude and pattern of response to decremental or rapid atrial pacing. (See "Invasive diagnostic cardiac electrophysiology studies".) https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 3/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate With a progressive increase in the rate of atrial pacing, the normal AV node demonstrates a progressive physiologic conduction delay (decremental conduction) as manifested by increases in the PR and AH intervals (AV nodal Wenckebach) until complete AV block occurs. The progressive prolongation of AV nodal conduction time or AH interval with rapid atrial pacing has a protective role, limiting the ventricular response to rapid atrial rates in atrial fibrillation or atrial flutter. In patients with EAVNC and LGL, different patterns of AH response to decremental atrial pacing (ie, increasing pacing rates) have been elicited ( figure 2) [3-5,10,11]: The response to pacing may be similar to that of normal subjects, but the initial AH interval and magnitude of prolongation is less (type 1 response). There may be an initial increase in the AH interval followed by a plateau phase and then a further increase in the AH interval at faster pacing rates (type 2 response). Approximately 10 percent of subjects have little or no increase in the AH interval with incremental atrial pacing (type 3 response); this is the most abnormal response and is what is typically seen with LGL as a result of stable conduction velocity through the accessory pathway or bundle of James. There may be an initial flat AH response until very short pacing cycle lengths when marked AH prolongation occurs (type 4 response). The patterns of nodal refractoriness also differ. Most subjects with LGL pattern and EAVNC exhibit shorter AV nodal effective and functional refractory periods than control subjects but similar atrial refractoriness [3,4,7,12]. The criteria for EAVNC are empirically derived, raising a question as to whether this represents a discrete electrophysiologic entity. In one study of electrophysiologic evaluation in 160 consecutive patients, 11 percent fulfilled all criteria for EAVNC; however, there was a unimodal and continuous frequency distribution for the three criteria for EAVNC and all of the criteria fell within the lower end of their calculated normal distribution curves [9]. No factor reliably distinguished the subgroup of patients with abnormally rapid AV nodal conduction. This suggests that the criteria used to define EAVNC represent one end of the normal spectrum of AV nodal function rather than identifying a distinct group of individuals with an abnormality of the AV node. RELATIONSHIP BETWEEN LGL PATTERN AND EAVNC https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 4/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate While there is significant overlap between these two conditions, they are diagnostically distinct. Since the patients in the original description of LGL were not studied electrophysiologically, the basis for the short PR interval and incidence of EAVNC in this group is unknown. Few studies have examined EAVNC in patients with LGL pattern, and most published data on the LGL pattern do not allow an incidence to be accurately estimated. In one study, the incidence of EAVNC (defined as the presence of all three of the above criteria) in a group of subjects with LGL was found to be 58 percent [3], but other reports found an incidence of less than 30 percent [4-6]. A short PR interval is not always found in patients with EAVNC since AV nodal conduction is only one component of the PR interval; in addition, conduction velocity does not necessarily correlate with AV refractoriness which is the limiting factor in the ability of the AV node to conduct 1:1. However, LGL and EAVNC share some common features and have often been considered to have a similar etiology. The mechanisms proposed to account for these conditions include more rapid conduction within or bypass of the normal AV nodal tissue. ANATOMIC-PHYSIOLOGIC CORRELATION Little progress has been made in correlating observed physiologic responses with anatomic abnormalities in these syndromes. LGL and EAVNC probably represent one end of the normal spectrum of AV nodal conduction properties. This hypothesis is supported by the unimodal and near normal distribution of the PR interval and AV nodal conduction properties [9,13]. Nevertheless, it is impossible to exclude a distinct AV nodal bypass tract or an abnormality in conduction characteristics as the cause in some cases. The proposed explanations fall into two main groups, anatomic and physiologic. Anatomic theories One anatomic explanation centers around the proposed existence of a bypass tract or accessory pathway arising from within the atria and inserting into the low portion of the AV node or proximal portion of the His bundle. Such a pathway would bypass the transitional portion of the AV node which is largely responsible for conduction delay and AV nodal decremental properties ( figure 1) [4,14-18]: James fibers The existence of tracts of atrial tissue running from the atria and inserting into the low AV node (James fibers) has been well established [14]. These tracts are, however, present in all hearts and probably represent a normal part of the complex anatomy of the AV node. Their functional significance has not been established, but these fibers have been felt to be the anatomic basis responsible for LGL and abnormal AV conduction. https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 5/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Brechenmacher fibers Brechenmacher fibers (atrio-Hisian tracts) could theoretically be present in the patients with EAVNC who show no decremental conduction during decremental atrial pacing (type 3 response) [15]; however there has not been clinicopathologic support for such tracts as the cause of the LGL pattern or EAVNC. The reported frequency of these tracts is 0.03 percent which is considerably lower than the expected incidence if they were to account for a significant proportion of individuals with abnormal AV nodal conduction. Intranodal bypass tracts The existence of intranodal bypass tracts would permit rapid conduction through the AV node, avoiding the usual decremental pathways. The fact that most patients with EAVNC show some degree of decrementation with incremental atrial pacing makes complete bypass of the AV node unlikely but does not exclude partial bypass. The normal AV node demonstrates decremental conduction in which adjacent cells are unable to fully excite subsequent cells in the conduction pathway. This property is enhanced by a short coupling interval (ie, increased rate) between successive electrical stimuli. Decremental conduction within the AV node is clinically manifest as a progressive prolongation in AV conduction time with increased atrial rates, ultimately resulting in Wenckebach block. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)".) Decremental conduction is diminished in patients with EAVNC. This could be explained by abnormal tissue in the region of the AV node, such as functional myocardial fibers rather than AV nodal tissue. Alternatively, the usual arrangement of the cellular fibers and the relatively poor intercellular excitation coupling, which are responsible for decremental conduction, may be abnormal [18]. Decremental conduction is absent in patients with LGL as there is tissue which bypasses the AV node and the bypass tract does not demonstrate decremental conduction. Another possible cause for the enhanced AV nodal conduction is an underdeveloped or anatomically small node [4,8,19-21]. The conduction properties of the AV node change with aging; infants and children are generally able to sustain more rapid conduction than adults [22,23]. The basis of this may not be anatomic but related to autonomic tone. Accurate premortem measurement of AV nodal size is not possible, so correlations between AV nodal conduction properties and AV nodal size have not been performed in humans. However, the lack of influence of size on the conduction properties of the AV node in other species suggests that this factor alone is not sufficient to account for the variation seen among individuals [24]. Physiologic theories The physiologic theories suggest that there is either an abnormality of the intrinsic conduction characteristics of the AV node or disturbed autonomic tone https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 6/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate [3,4,8,20,21,25]. Supporting a physiologic basis is the observation that most patients with EAVNC do show some degree of AH prolongation with decremental atrial pacing, a feature not usually seen with AV bypass tracts. In addition, many of these patients respond to a pharmacologic challenge in a manner similar to those with normal AV nodes [21,26-29]. Another theory is EAVNC represents conduction primarily over the fast pathway in patients with dual AV nodal physiology, thereby masking slow pathway conduction. However, the incidence of AV nodal reentry in patients with LGL or EAVNC is not appreciably higher than in subjects with normal AV nodal conduction [3,10,30,31]. Furthermore, in patients with EAVNC and dual pathways, both the fast and the slow pathways demonstrate enhanced conduction when compared with control subjects with dual AV nodal pathways but no evidence of EAVNC [7]. This finding suggests that a generalized abnormality of AV nodal conduction exists in patients with EAVNC. There is limited information concerning the role of the autonomic nervous system in patients with EAVNC. Although autonomic blockade may partially reverse the conduction abnormalities in these patients, rapid conduction is usually still present, suggesting that increased sympathetic and/or reduced vagal tone is not the sole factor responsible for this condition [20,27]. ARRHYTHMIAS ASSOCIATED WITH LGL SYNDROME AND EAVNC It is uncertain if an abnormality in AV nodal conduction is associated with arrhythmia. Although the LGL syndrome implies recurrent palpitations, it has not been conclusively established whether this is due to an increased incidence of tachyarrhythmias or symptoms resulting from a more rapid heart rate during sinus tachycardia. The incidence of EAVNC in the general population is difficult to establish since the diagnosis requires formal electrophysiologic testing. Thus, the reports of arrhythmias associated with EAVNC are based upon a very select group of individuals who are undergoing electrophysiologic testing. Etiology of arrhythmia EAVNC has been shown to coexist with dual AV nodal pathways and both overt and concealed accessory AV pathways [3,7,8,10,26,28,32,33]. Although the presence of overt preexcitation (ie, Wolff-Parkinson-White [WPW] pattern) precludes a diagnosis of LGL, this has been found in association with dual AV nodal pathways and concealed accessory AV connections. LGL The most common mechanism for arrhythmia in patients with the LGL syndrome, accounting for more than 50 percent of cases, is an orthodromic AV reentry tachycardia https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 7/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate (AVRT) using an accessory AV connection (ie, fast conduction to the ventricles via the accessory pathway [bundle of James] and retrograde activation of the atria via the AV node) [3,10,30]. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) EAVNC In patients with EAVNC, the most common mechanism is AV nodal reentry tachycardia (AVNRT) if there are dual AV nodal pathways present. Although the relative incidence of these arrhythmias varies in different studies, it does not seem different from that reported in patients without LGL or EAVNC [34,35]. (See "Atrioventricular nodal reentrant tachycardia".) The presence of rapid conduction over the AV node is unlikely to increase the frequency of tachycardia in patients with AVNRT or AVRT since both result from slow conduction or complete block within the AV node. Thus, enhanced conduction in EAVNC should not favor initiation of these arrhythmias. Atrial fibrillation, atrial flutter, and ventricular tachycardia have also been described in patients with the LGL syndrome and EAVNC ( figure 3) [2,3,27,36,37]. A rapid ventricular response is possible with atrial fibrillation or atrial flutter. The most likely mechanism by which EAVNC may predispose to ventricular arrhythmias is the degeneration of rapid ventricular response to atrial arrhythmia into ventricular tachycardia and fibrillation. This occurrence has been reported in patients with and without underlying cardiac disease but is uncommon [3,36,38]. It is also a complication of atrial fibrillation in the WPW syndrome. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) Influence of EAVNC on the tachycardia rate The contribution of EAVNC to the ventricular rate during a tachycardia is dependent upon the type of tachycardia. Some studies have suggested that EAVNC is associated with a more rapid heart rate during AVRT and atrial fibrillation or flutter [3,8,27,33]. AVRT The rate of an AVRT is limited by the conduction through the weakest limb of the circuit, which in orthodromic AVRT is conduction over the AV node. In this situation, the presence of EAVNC may result in more rapid heart rates as AV conduction is enhanced [10,14]. In LGL, the antegrade conduction to the ventricles during orthodromic AVRT is via the accessory pathway, which conducts rapidly while retrograde conduction back to the atria is via the AV node, which conducts slower. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 8/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate AVNRT In patients with the typical form of AVNRT, the slow pathway within the AV node is the weak limb. Since the rate of the tachycardia is not critically dependent upon the conduction characteristics of the fast AV nodal pathway, the limb presumed to be abnormal in EAVNC, the presence of EAVNC does not alter the rate of a typical AVNRT [10,29]. Atrial fibrillation or atrial flutter The ventricular response during atrial fibrillation or flutter is significantly faster in patients with EAVNC or LGL than in control subjects [3,27,36,38]. Cases of 1:1 AV conduction in excess of 300 beats/min have been documented in patients with EAVNC or LGL [27]. Similar to the situation with the Wolff-Parkinson-White syndrome, the propensity for rapid ventricular responses to atrial fibrillation and atrial flutter makes the aggressive treatment of these arrhythmias necessary, particularly in patients who have underlying ischemic heart disease or cardiomyopathy who not are likely to tolerate rapid ventricular rates. ANTIARRHYTHMIC DRUGS The effects of various classes of antiarrhythmic drugs in patients with EAVNC compared with controls have not been extensively studied. This is complicated by the fact that the LGL syndrome and EAVNC probably have multiple causes. Digitalis Digitalis and other cardiac glycosides exert their major effect in supraventricular tachycardia by enhancement of vagal tone at the level of the AV node. It has been postulated that patients with EAVNC have reduced parasympathetic tone and an attenuated AV nodal response to acetylcholine [21]. In one series of eight patients with EAVNC and medically refractory AVRT, digitalis produced little or no slowing of antegrade AV nodal conduction or prolongation of AV nodal refractoriness [33]. Digitalis does not have any effect on the accessory pathway in LGL, although it may be of benefit because of slowing conduction via the AV node. The change in retrograde AV nodal conduction and refractoriness may prevent AVRT in these patients. Beta blockers The effects of beta blockers in patients with EAVNC has varied widely. In some studies, beta blockers are equally effective in slowing AV nodal conduction and the tachycardia rate in patients with and without EAVNC [11,26]. However, other reports have found no effect in EAVNC [33,39]. Beta blockers have no direct effect on the accessory pathway in LGL but like digitalis may slow conduction through the AV node and may be of benefit, similar to what can be seen with digitalis. https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 9/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Calcium channel blockers The effects of calcium blockers, in particular verapamil, are variable in LGL and EAVNC. In one study, verapamil had little effect on AV nodal conduction characteristics or refractory periods in the subjects with a short PR interval in contrast to significant depressant effects seen in a control group [40]. In contrast, another report found that verapamil substantially affected both AV conduction time and refractoriness of the AV node in patients with EAVNC or LGL [41]. Similar to digitalis and beta blockers, there is no direct effect on the accessory pathway properties. The ability of oral verapamil to prevent tachycardia in patients with a short PR interval has not been evaluated in a controlled trial. In one series, verapamil was ineffective or only marginally effective in six of nine patients with recurrent supraventricular tachycardia and EAVNC [30]. (See "Calcium channel blockers in the treatment of cardiac arrhythmias".) Class I and III antiarrhythmic drugs There is even less information about the effectiveness of class I and III antiarrhythmic drugs in patients with the LGL syndrome or EAVNC. It has been proposed that AV nodal conduction in these patients is less calcium channel-dependent and less influenced by parasympathetic tone [11]. Thus, drugs with predominant sodium channel- blocking activity may have more of an effect on AV conduction than in normal individuals. As the accessory pathway in LGL (bundle of James) is similar to His-Purkinje tissue, these antiarrhythmic drugs may slow conduction or prolong refractoriness in this pathway and hence may prevent AVRT. Agents such as sotalol or amiodarone which have multiple effects may be particularly effective, but this remains to be confirmed. RADIOFREQUENCY CATHETER ABLATION In recent years, catheter ablation has become the preferred therapy for various supraventricular tachycardias and for tachyarrhythmias in the Wolff-Parkinson-White (WPW) syndrome. The majority of patients with a short PR interval or EAVNC who have reentrant tachycardias are suitable for ablation directed at an accessory pathway (if documented) or one limb of the AV node (if dual AV nodal pathways are present). In patients who have rapid ventricular responses to atrial fibrillation or atrial flutter, an effective treatment is the creation of complete heart block using radiofrequency ablation followed by implantation of a permanent pacemaker [42]. SUMMARY AND RECOMMENDATIONS Definitions The Lown-Ganong-Levine (LGL) pattern is characterized by the presence of a short PR interval and normal QRS complex on the surface ECG, a finding which may https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 10/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate represent a perinodal accessory pathway or enhanced atrioventricular nodal conduction (EAVNC). Although both LGL and EAVNC refer to a presumed abnormality in or bypass of normal AV nodal function, diagnosis of the LGL pattern versus EAVNC is based upon clinical and ECG findings as well as specific electrophysiologic criteria measured during invasive electrophysiology studies. (See 'Lown-Ganong-Levine pattern' above.) Pathophysiology Despite evidence to partially support numerous theories, the precise mechanisms for the LGL pattern and EAVNC, as well as the anatomic and physiologic correlation, remain undetermined. (See 'Anatomic-physiologic correlation' above.) Arrhythmias (See 'Arrhythmias associated with LGL syndrome and EAVNC' above.) LGL The most common mechanism for arrhythmia in patients with the LGL syndrome, accounting for more than 50 percent of cases, is an orthodromic AV reentry tachycardia (AVRT) using an accessory AV connection (the bundle of James). Paroxysmal supraventricular tachycardia (particularly AVRT) occurs much more frequently in patients with LGL syndrome when compared with persons with a normal PR interval. (See 'Lown-Ganong-Levine pattern' above.) EAVNC In EAVNC, the mechanism for arrhythmia is most likely AV nodal reentry tachycardia (AVNRT) due to dual AV nodal pathways. Atrial fibrillation, atrial flutter, and ventricular tachycardia have also been described. Management The optimal treatment of arrhythmias in the LGL syndrome and EAVNC is unclear, but radiofrequency catheter ablation appears to be a suitable and effective option for such patients. (See 'Antiarrhythmic drugs' above and 'Radiofrequency catheter ablation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Clerc, A, Robert-Levy, et al. A propos du raccourcissement permanent de l'espace P-R del'electrocardiogramme sans deformation du complexe ventriculaire. Arch Mal Coeur 1938; 31:569. 2. LOWN B, GANONG WF, LEVINE SA. The syndrome of short P-R interval, normal QRS complex and paroxysmal rapid heart action. Circulation 1952; 5:693. 3. Benditt DG, Pritchett LC, Smith WM, et al. Characteristics of atrioventricular conduction and the spectrum of arrhythmias in lown-ganong-levine syndrome. Circulation 1978; 57:454. https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 11/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate 4. Caracta AR, Damato AN, Gallagher JJ, et al. Electrophysiologic studies in the syndrome of short P-R interval, normal QRS complex. Am J Cardiol 1973; 31:245. 5. Iannone LA. Electrophysiology of atrial pacing in patients with short PR interval, normal QRS complex. Am Heart J 1975; 89:74. 6. Bissett JK, Thompson AJ, DeSoyza N, Murphy ML. Atrioventricular conduction in patients with short PR intervals and normal QRS complexes. Br Heart J 1973; 35:123. 7. Ward DE, Bexton R, Camm AJ. Characteristics of atrio-His conduction in the short PR interval, normal QRS complex syndrome. Evidence for enhanced slow-pathway conduction. Eur Heart J 1983; 4:882. 8. Gallagher JJ, Sealy WC, Kasell J, Wallace AG. Multiple accessory pathways in patients with the pre-excitation syndrome. Circulation 1976; 54:571. 9. Jackman WM, Prystowsky EN, Naccarelli GV, et al. Reevaluation of enhanced atrioventricular nodal conduction: evidence to suggest a continuum of normal atrioventricular nodal physiology. Circulation 1983; 67:441. 10. Benditt, DG, Epstein, et al. Enhanced atrioventricular conduction in patients without preexcitation syndrome: relationship to heart rate in paroxysmal reciprocating tachycardia. Circulation 1974; 65:1982. 11. Benditt DG, Dunbar D, Almquist A, et al. AV node bypass tracts and enhanced AV conductio n: Relation to ventricular preexcitation. In: Cardiac Pre-excitation Syndromes, Benditt DG, Be nson D, Woodrow DW Jr (Eds), Martinus Nijhoff, Boston 1986. p.225. 12. Bissett JK, de Soyza N, Kane JJ, Murphy ML. Altered refractory periods in patients with short P-R intervals and normal QRS complex. Am J Cardiol 1975; 35:487. 13. Lepehkin, E . The P-Q-R-S-T-U complex. In: Modern Electrocardiography, Williams & Wilkins, Baltimore, 1951; 1:237. 14. JAMES TN. Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J 1961; 62:756. 15. Brechenmacher C. Atrio-His bundle tracts. Br Heart J 1975; 37:853. 16. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. 17. Anderson RH, Becker AE, Brechenmacher C, et al. The human atrioventricular junctional area. A morphological study of the A-V node and bundle. Eur J Cardiol 1975; 3:11. 18. Bharati S, Bauernfiend R, Scheinman M, et al. Congenital abnormalities of the conduction system in two patients with tachyarrhythmias. Circulation 1979; 59:593. https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 12/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate 19. Childers R. The AV node: normal and abnormal physiology. Prog Cardiovasc Dis 1977; 19:361. 20. Prystowsky EN, Pritchett LC, Smith WM, et al. Electrophysiologic assessment of the atrioventricular conduction system after surgical correction of ventricular preexcitation. Circulation 1979; 59:789. 21. Benditt DG, Klein GJ, Kriett JM, et al. Enhanced atrioventricular nodal conduction in man: electrophysiologic effects of pharmacologic autonomic blockade. Circulation 1984; 69:1088. 22. Abella JB, Teixeira OH, Misra KP, Hastreiter AR. Changes of atrioventricular conduction with age in infants and children. Am J Cardiol 1972; 30:876. 23. DuBrow W, Fisher EA, Amaty-Leon G, et al. Comparison of cardiac refractory periods in children and adults. Circulation 1975; 51:485. 24. Meijler FL. Atrioventricular conduction versus heart size from mouse to whale. J Am Coll Cardiol 1985; 5:363. 25. Moro C, Cos o FG. Electrophysiologic study of patients with short P-R interval and normal QRS complex. Eur J Cardiol 1980; 11:81. 26. Josephson ME, Kastor JA. Supraventricular tachycardia in Lown-Ganong-Levine syndrome: atrionodal versus intranodal reentry. Am J Cardiol 1977; 40:521. 27. Moleiro F, Mendoza IJ, Medina-Ravell V, et al. One to one atrioventricular conduction during atrial pacing at rates of 300/minute in absence of Wolff-Parkinson-White Syndrome. Am J Cardiol 1981; 48:789. 28. Denes, P, Wu, et al. Demonstration of dual AV pathways in a patient with the Lown-Ganong- Levine syndrome. Chest 1974; 64:343. 29. Bauernfeind RA, Ayres BF, Wyndham CC, et al. Cycle length in atrioventricular nodal reentrant paroxysmal tachycardia with observations on the Lown-Ganong-Levine syndrome. Am J Cardiol 1980; 45:1148. 30. Ward DE, Camm J. Mechanisms of junctional tachycardias in the Lown-Ganong-Levine syndrome. Am Heart J 1983; 105:169. 31. Gallagher JJ, Pritchett EL, Sealy WC, et al. The preexcitation syndromes. Prog Cardiovasc Dis 1978; 20:285. 32. Wiener I. Syndromes of Lown-Ganong-Levine and enhanced atrioventricular nodal conduction. Am J Cardiol 1983; 52:637. 33. Holmes DR Jr, Hartzler GO, Maloney JD. Concealed retrograde bypass tracts and enhanced atrioventricular nodal conduction. An unusual subset of patients with refractory paroxysmal supraventricular tachycardia. Am J Cardiol 1980; 45:1053. https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 13/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate 34. Fisher JD. Role of electrophysiologic testing in the diagnosis and treatment of patients with known and suspected bradycardias and tachycardias. Prog Cardiovasc Dis 1981; 24:25. 35. Josephson ME. Paroxysmal supraventricular tachycardia: an electrophysiologic approach. Am J Cardiol 1978; 41:1123. 36. Myerburg RJ, Sung RJ, Castellanos A. Ventricular tachycardia and ventricular fibrillation in patients with short P-R intervals and narrow QRS complexes. Pacing Clin Electrophysiol 1979; 2:568. 37. Blanc, JJ, Fontaliran, et al. Electrophysiologic and histopathologic correlation (abstract). Pacing Clin Electrophysiol 1981; 4:A. 38. Castellanos A, Vagueiro MC, Befeler B, Myerburg RJ. Syndrome of short P-R, narrow QRS and repetitive supraventricular tachyarrhythmias: the possible occurrence of the R-on-T phenomenon and the limits of this syndrome. Eur J Cardiol 1975; 2:337. 39. Prystowsky EN, Greer S, Packer DL, et al. Beta-blocker therapy for the Wolff-Parkinson-White syndrome. Am J Cardiol 1987; 60:46D. 40. Seipel L, Breithardt G, Both A. Atrioventricular (AV) and ventriculoatrial (VA) conduction patte rn in patients with short P-R interval and normal QRS complex. In: Cardiac pacing, Luderitz B (Ed), Springer-Verlag, Berlin 1976. p.52. 41. Moro, C, Cosio, FG . Electrophysiological study of patients with short P-R interval and normal QRS complex. Eur J Cardiol 1980; II:81. 42. Yeung-Lai-Wah JA, Alison JF, Lonergan L, et al. High success rate of atrioventricular node ablation with radiofrequency energy. J Am Coll Cardiol 1991; 18:1753. Topic 1000 Version 17.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 14/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate GRAPHICS Types of accessory pathways Diagram of 4 types of abnormal conduction pathways: classic accessory atrioventricular pathway (red), atriofascicular pathway (green), fasciculoventricular pathway (light blue), and nodoventricular pathway (dark blue). The atrioventricular node and His-Purkinje system are represented in yellow. Atrioventricular, atriofascicular, and nodoventricular pathways are capable of supporting atrioventricular reciprocating tachycardias. In contrast, an isolated fasciculoventricular pathway can cause subtle preexcitation but does not support clinical tachycardia. Graphic 138850 Version 1.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 15/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Lown-Ganong-Levine syndrome The 12 lead ECG of a patient with the Lown-Ganong-Levine syndrome shows a short PR interval of 0.10 second and a normal QRS complex. Graphic 74221 Version 2.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. Graphic 69872 Version 2.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 16/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Patterns of AV nodal conduction in EAVNC |
physiology. Circulation 1983; 67:441. 10. Benditt, DG, Epstein, et al. Enhanced atrioventricular conduction in patients without preexcitation syndrome: relationship to heart rate in paroxysmal reciprocating tachycardia. Circulation 1974; 65:1982. 11. Benditt DG, Dunbar D, Almquist A, et al. AV node bypass tracts and enhanced AV conductio n: Relation to ventricular preexcitation. In: Cardiac Pre-excitation Syndromes, Benditt DG, Be nson D, Woodrow DW Jr (Eds), Martinus Nijhoff, Boston 1986. p.225. 12. Bissett JK, de Soyza N, Kane JJ, Murphy ML. Altered refractory periods in patients with short P-R intervals and normal QRS complex. Am J Cardiol 1975; 35:487. 13. Lepehkin, E . The P-Q-R-S-T-U complex. In: Modern Electrocardiography, Williams & Wilkins, Baltimore, 1951; 1:237. 14. JAMES TN. Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J 1961; 62:756. 15. Brechenmacher C. Atrio-His bundle tracts. Br Heart J 1975; 37:853. 16. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. 17. Anderson RH, Becker AE, Brechenmacher C, et al. The human atrioventricular junctional area. A morphological study of the A-V node and bundle. Eur J Cardiol 1975; 3:11. 18. Bharati S, Bauernfiend R, Scheinman M, et al. Congenital abnormalities of the conduction system in two patients with tachyarrhythmias. Circulation 1979; 59:593. https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 12/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate 19. Childers R. The AV node: normal and abnormal physiology. Prog Cardiovasc Dis 1977; 19:361. 20. Prystowsky EN, Pritchett LC, Smith WM, et al. Electrophysiologic assessment of the atrioventricular conduction system after surgical correction of ventricular preexcitation. Circulation 1979; 59:789. 21. Benditt DG, Klein GJ, Kriett JM, et al. Enhanced atrioventricular nodal conduction in man: electrophysiologic effects of pharmacologic autonomic blockade. Circulation 1984; 69:1088. 22. Abella JB, Teixeira OH, Misra KP, Hastreiter AR. Changes of atrioventricular conduction with age in infants and children. Am J Cardiol 1972; 30:876. 23. DuBrow W, Fisher EA, Amaty-Leon G, et al. Comparison of cardiac refractory periods in children and adults. Circulation 1975; 51:485. 24. Meijler FL. Atrioventricular conduction versus heart size from mouse to whale. J Am Coll Cardiol 1985; 5:363. 25. Moro C, Cos o FG. Electrophysiologic study of patients with short P-R interval and normal QRS complex. Eur J Cardiol 1980; 11:81. 26. Josephson ME, Kastor JA. Supraventricular tachycardia in Lown-Ganong-Levine syndrome: atrionodal versus intranodal reentry. Am J Cardiol 1977; 40:521. 27. Moleiro F, Mendoza IJ, Medina-Ravell V, et al. One to one atrioventricular conduction during atrial pacing at rates of 300/minute in absence of Wolff-Parkinson-White Syndrome. Am J Cardiol 1981; 48:789. 28. Denes, P, Wu, et al. Demonstration of dual AV pathways in a patient with the Lown-Ganong- Levine syndrome. Chest 1974; 64:343. 29. Bauernfeind RA, Ayres BF, Wyndham CC, et al. Cycle length in atrioventricular nodal reentrant paroxysmal tachycardia with observations on the Lown-Ganong-Levine syndrome. Am J Cardiol 1980; 45:1148. 30. Ward DE, Camm J. Mechanisms of junctional tachycardias in the Lown-Ganong-Levine syndrome. Am Heart J 1983; 105:169. 31. Gallagher JJ, Pritchett EL, Sealy WC, et al. The preexcitation syndromes. Prog Cardiovasc Dis 1978; 20:285. 32. Wiener I. Syndromes of Lown-Ganong-Levine and enhanced atrioventricular nodal conduction. Am J Cardiol 1983; 52:637. 33. Holmes DR Jr, Hartzler GO, Maloney JD. Concealed retrograde bypass tracts and enhanced atrioventricular nodal conduction. An unusual subset of patients with refractory paroxysmal supraventricular tachycardia. Am J Cardiol 1980; 45:1053. https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 13/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate 34. Fisher JD. Role of electrophysiologic testing in the diagnosis and treatment of patients with known and suspected bradycardias and tachycardias. Prog Cardiovasc Dis 1981; 24:25. 35. Josephson ME. Paroxysmal supraventricular tachycardia: an electrophysiologic approach. Am J Cardiol 1978; 41:1123. 36. Myerburg RJ, Sung RJ, Castellanos A. Ventricular tachycardia and ventricular fibrillation in patients with short P-R intervals and narrow QRS complexes. Pacing Clin Electrophysiol 1979; 2:568. 37. Blanc, JJ, Fontaliran, et al. Electrophysiologic and histopathologic correlation (abstract). Pacing Clin Electrophysiol 1981; 4:A. 38. Castellanos A, Vagueiro MC, Befeler B, Myerburg RJ. Syndrome of short P-R, narrow QRS and repetitive supraventricular tachyarrhythmias: the possible occurrence of the R-on-T phenomenon and the limits of this syndrome. Eur J Cardiol 1975; 2:337. 39. Prystowsky EN, Greer S, Packer DL, et al. Beta-blocker therapy for the Wolff-Parkinson-White syndrome. Am J Cardiol 1987; 60:46D. 40. Seipel L, Breithardt G, Both A. Atrioventricular (AV) and ventriculoatrial (VA) conduction patte rn in patients with short P-R interval and normal QRS complex. In: Cardiac pacing, Luderitz B (Ed), Springer-Verlag, Berlin 1976. p.52. 41. Moro, C, Cosio, FG . Electrophysiological study of patients with short P-R interval and normal QRS complex. Eur J Cardiol 1980; II:81. 42. Yeung-Lai-Wah JA, Alison JF, Lonergan L, et al. High success rate of atrioventricular node ablation with radiofrequency energy. J Am Coll Cardiol 1991; 18:1753. Topic 1000 Version 17.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 14/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate GRAPHICS Types of accessory pathways Diagram of 4 types of abnormal conduction pathways: classic accessory atrioventricular pathway (red), atriofascicular pathway (green), fasciculoventricular pathway (light blue), and nodoventricular pathway (dark blue). The atrioventricular node and His-Purkinje system are represented in yellow. Atrioventricular, atriofascicular, and nodoventricular pathways are capable of supporting atrioventricular reciprocating tachycardias. In contrast, an isolated fasciculoventricular pathway can cause subtle preexcitation but does not support clinical tachycardia. Graphic 138850 Version 1.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 15/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Lown-Ganong-Levine syndrome The 12 lead ECG of a patient with the Lown-Ganong-Levine syndrome shows a short PR interval of 0.10 second and a normal QRS complex. Graphic 74221 Version 2.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. Graphic 69872 Version 2.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 16/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Patterns of AV nodal conduction in EAVNC The atrial to His (A-H) interval, which represents atrioventricular (AV) nodal conduction time, is plotted against the pacing cycle length or A1-A2 interval. The normal response is a progressive lengthening of the AH interval with a shorter pacing cycle length (ie, faster heart rate), a phenomenon known as decremental conduction. In patients with enhanced AV nodal conduction (EAVNC), four patterns of response are seen. Type I represents reduced AH interval prolongation in response to atrial pacing; type II shows an initial increase in the AH interval followed by a plateau and then a further increase in the AH interval with faster pacing rates; type III reveals no change in AH interval in response to increasing atrial pacing rates; type IV represents no change in AH interval until the pacing cycle lengths are very short, thereby resulting in marked AH prolongation. Graphic 63880 Version 1.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 17/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate AF in EAVNC The 12 lead ECG during sinus rhythm (panel A) in a patient with enhanced atrioventricular nodal conduction (EAVNC). The ECG shows a normal PR interval and QRS complex without evidence of preexcitation. During atrial fibrillation (AF) (panel B), there is a rapid ventricular response of up to 270 beats/min, a result of EAVNC and a short AV nodal refractory period. Graphic 81361 Version 1.0 https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 18/19 7/6/23, 11:14 AM Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/lown-ganong-levine-syndrome-and-enhanced-atrioventricular-nodal-conduction/print 19/19 |
7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome : Luigi Di Biase, MD, PhD, FHRS, FACC, Edward P Walsh, MD : Samuel L vy, MD, Bradley P Knight, MD, FACC : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 30, 2023. INTRODUCTION Conduction from the atria to the ventricles normally occurs via the atrioventricular node (AV)- His-Purkinje system. Patients with a preexcitation syndrome have an additional pathway, known as an accessory pathway, which directly connects the atria and ventricles, bypassing the AV node. Normal conduction through the AV node is slower than conduction over the accessory pathway. Thus, when there is conduction over an accessory pathway, the ventricles are activated earlier than if the impulse had traveled through the AV node. This early activation, referred to as preexcitation, is responsible for the classic electrocardiographic (ECG) findings of a shortened PR interval and, in most patients, a delta wave ( waveform 1). Symptoms, ranging from mild palpitations to syncope and, rarely, even sudden cardiac death, are the result of tachycardia, usually due to a macroreentrant circuit involving the AV node, the ventricles, the accessory pathway, and the atria. This classic supraventricular tachycardia associated with WPW syndrome is called AV reentrant or reciprocating tachycardia (AVRT). However, preexcited atrial fibrillation (AF) or atrial flutter with a rapid ventricular response may also result in symptoms. Fortunately, the incidence of sudden death in patients with the WPW syndrome is quite low, ranging from 0 to 0.39 percent annually in several large case series, with the lowest risk seen in asymptomatic patients. Patients with the WPW syndrome are usually treated because of symptomatic arrhythmias. Treatment may sometimes be extended to asymptomatic patients with a WPW pattern if certain https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 1/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate "high-risk" features are present. However, most asymptomatic patients with the WPW electrocardiographic pattern are not treated. Treatment options for persons with arrhythmias and the WPW syndrome include nonpharmacologic therapies (ie, catheter ablation of the accessory pathway) as well as pharmacologic therapy (to slow ventricular heart rates or to prevent arrhythmias). The choice of the optimal therapy depends on the acuity of the arrhythmia(s) and the risk of sudden cardiac death, with pharmacologic agents being the treatment of choice for most acute arrhythmias, while catheter ablation is nearly always preferred for the long-term prevention of recurrent arrhythmias involving the accessory pathway. This topic will review the available therapeutic options for the treatment of arrhythmias in the WPW syndrome. The clinical manifestations, approach to diagnosis, and the types of arrhythmias which can occur in persons with an accessory pathway and the WPW pattern are discussed separately. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) ACUTE TREATMENT OF SYMPTOMATIC ARRHYTHMIAS While the preferred long-term treatment approach for patients with an accessory pathway, preexcitation, and symptomatic arrhythmias is catheter-based radiofrequency ablation, patients who present with an acute arrhythmia often require initial pharmacologic therapy for ventricular rate control or restoration of sinus rhythm. However, because of the electrophysiologic differences between AV nodal tissue and tissue comprising an accessory pathway, standard therapy for heart rate control may actually worsen symptoms and lead to clinical deterioration in patients with a tachycardia involving an accessory pathway. Knowledge of the presence of an accessory pathway is critical in choosing the correct initial pharmacologic therapy. (See 'Treatment to prevent recurrent arrhythmias' below and "Overview of the acute management of tachyarrhythmias".) Initial assessment of hemodynamic stability As with any patient presenting with a symptomatic tachyarrhythmia, patients with a tachycardia suspected to involve an accessory pathway should undergo an initial assessment of hemodynamic status. Patients who are hemodynamically stable can be evaluated and treated according to the type of suspected arrhythmia. However, patients with hemodynamic instability or compromise related to an ongoing tachycardia should undergo urgent electrical cardioversion [1,2]. The technique for urgent https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 2/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate electrical cardioversion is discussed elsewhere. (See "Cardioversion for specific arrhythmias".) Orthodromic AVRT In patients with orthodromic atrioventricular reciprocating tachycardia (AVRT), antegrade conduction occurs via the AV node with retrograde conduction via an accessory pathway. In such patients, antegrade conduction across the AV node is typically the "weak link" of the reentrant circuit. Thus, the approach to patients with orthodromic AVRT is similar to patients with other types of paroxysmal supraventricular tachycardia, where relatively specific therapies that lengthen AV nodal refractoriness and depress its conduction can block the impulse within the AV node and terminate and prevent the tachycardia. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Narrow complex AVRT' and "Overview of the acute management of tachyarrhythmias", section on 'Regular narrow QRS complex tachyarrhythmias'.) We employ a step-wise approach to termination of orthodromic AVRT ( table 1). We recommend initial treatment of acute symptomatic orthodromic AVRT with one or more vagal maneuvers (such as the Valsalva maneuver and carotid sinus massage) [1,2]. These may be sufficient to cause AV node block and tachycardia termination in many patients [3]. (See "Vagal maneuvers".) If vagal maneuvers are ineffective, pharmacologic therapy with an AV nodal blocking agent (ie, adenosine, verapamil, beta blockers) should be instituted: We suggest intravenous adenosine rather than intravenous verapamil as the initial choice based on its efficacy and short half-life. Intravenous adenosine is effective for acute termination of orthodromic AVRT in 80 to 90 percent of patients [4-6]. Its ultrashort duration of action makes it a preferred agent before resorting to emergent DC cardioversion in the patient whose hemodynamic state is more tenuous. The protocol for intravenous adenosine administration is described in the algorithm ( algorithm 1). Prior to adenosine administration, the patient should be advised of the possibility of feeling lightheaded, dizzy, or near syncopal during the injection. On rare occasions, adenosine has been reported to transiently increase atrial vulnerability to AF, a potentially serious proarrhythmic effect, and cause atrial ectopy that can reinitiate orthodromic AVRT after acute tachycardia termination [4,7-9]. If adenosine is ineffective, we proceed with intravenous verapamil as the second line agent. Intravenous verapamil, given as 5 mg boluses in a full-grown patient (0.1 mg/kg in children to a maximum dose of 5 mg; contraindicated in children less than 12 months of age) every https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 3/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate two to three minutes (up to a cumulative initial dose of up to 15 mg), is as effective as adenosine for acutely terminating orthodromic AVRT, provided that the patient is not profoundly hypotensive or suffering from heart failure associated with severely depressed ventricular systolic function rather than the rapid heart rate ( table 1) [10,11]. (See "Calcium channel blockers in the treatment of cardiac arrhythmias".) If vagal maneuvers, adenosine, and verapamil are all ineffective in terminating orthodromic AVRT, second line therapy choices include intravenous procainamide and beta blockers approved for intravenous administration (propranolol, metoprolol, and esmolol) ( table 1) [12-14]. Procainamide (20 to 50 mg/minute given intravenously while monitoring the blood pressure closely every 5 to 10 minutes until the arrhythmia terminates, hypotension ensues, the QRS is prolonged by more than 50 percent, or a total of 17 mg/kg [1.2 g for a 70 kg patient] has been given) slows conduction and prolongs refractoriness in atrial and ventricular myocardium, accessory pathways, and the His-Purkinje system, while having no effect or causing slight shortening of AV nodal refractory period [15,16]. For young children, the dose for procainamide is a bolus given over 15 to 30 minutes (7 to 10 mg/kg bolus for infants <12 months of age compared with 10 to 15 mg/kg bolus for children older than 12 months), followed by an infusion of 20 to 50 micrograms/kg/minute. Procainamide is the preferred drug if the orthodromic AVRT presents as a wide QRS complex tachycardia due to functional or preexisting chronic bundle branch block or if the diagnosis of orthodromic AVRT is in doubt. (See "Wide QRS complex tachycardias: Approach to management".) Metoprolol 2.5 to 5 mg IV bolus over two to five minutes; if no response, an additional 2.5 to 5 mg IV bolus may be administered every 10 minutes to a total dose of 15 mg. Permanent junctional reciprocating tachycardia Permanent junctional reciprocating tachycardia (PJRT) is a persistent tachycardia (with a long RP interval on the surface electrocardiogram) that most often occurs in early childhood and is usually caused by a rare type of orthodromic AVRT involving a slowly conducting concealed accessory pathway, which is usually posteroseptal in location. As implied by the name, PJRT is incessant. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Permanent junctional reciprocating tachycardia'.) Ablation of the accessory pathway is the preferred treatment for PJRT caused by a slowly conducting accessory pathway since this arrhythmia is often refractory to medical therapy. In a cohort of 194 patients (median age at diagnosis 3.2 months, 57 percent less than one year of age) from 11 institutions treated for PJRT between 2000 and 2010, initial medical management https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 4/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate (attempted in 76 percent of patients) led to complete control of the arrhythmia in only 23 percent of patients [17]. An additional 47 percent of patients had clinical improvement with slower and/or less sustained tachycardia, but perfect pharmacologic control is less common. However, in patients presenting with acute symptomatic PJRT, the choice of initial medical therapy is similar to conventional orthodromic AVRT [18]. Adenosine and verapamil can be tried but usually only interrupt PJRT for a few beats. Intravenous procainamide will occasionally result in a longer-lasting interruption of PJRT, but it rarely results in perfect control. As a temporizing measure prior to ablation, effective medical control of PJRT can often be achieved with oral flecainide. (See 'Orthodromic AVRT' above and 'Catheter ablation' below.) Antidromic AVRT In patients with antidromic atrioventricular reciprocating tachycardia (AVRT), antegrade conduction occurs via the accessory pathway with retrograde conduction usually via the AV node (or sometimes via a second accessory pathway if multiple pathways are present). Even though retrograde AV node conduction may be a "weak link" during antidromic AVRT, in the acute setting it is difficult to exclude the possibility of a second accessory pathway as the retrograde limb without formal electrophysiologic testing, and treatment must be done cautiously. Assuming the tachycardia is strictly regular and monomorphic, a trial of a short- acting AV node-specific blocking drug such as adenosine ( algorithm 1) can still be attempted, but failure to convert the tachycardia should make one suspicious of a second accessory pathway participating in the circuit, at which point an alternate agent such as procainamide should be considered. Practically speaking, verification of an antidromic AVRT is difficult outside the electrophysiology laboratory, so the intravenous drug of choice for acute treatment to terminate known or suspected antidromic AVRT is procainamide [2]. Procainamide is typically infused intravenously at 20 to 50 mg/minute given while monitoring the blood pressure closely every 5 to 10 minutes until the arrhythmia terminates, hypotension ensues, the QRS is prolonged by more than 50 percent, or a total of 17 mg/kg (1.2 g for a 70 kg patient) has been given. Even if it does not result in tachycardia termination, intravenous procainamide will usually slow the tachycardia rate and improve the hemodynamic state ( table 1). If the diagnosis is not certain, the patient should be considered to have an undiagnosed wide QRS tachycardia; of particular concern is ventricular tachycardia, which can become hemodynamically unstable or even degenerate into ventricular fibrillation following administration of one of these drugs. If uncertainty ever exists about the exact tachycardia mechanism, a presumptive diagnosis of ventricular tachycardia should be made, and the patient https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 5/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate treated accordingly. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Wide complex AVRT' and "Wide QRS complex tachycardias: Approach to the diagnosis" and "Wide QRS complex tachycardias: Approach to management".) Atrial fibrillation with preexcitation In patients with an accessory pathway capable of antegrade conduction who develop AF, conduction to the ventricle often occurs through a combination of the normal conduction pathway (via the AV node) and the accessory pathway. However, because most accessory pathways have a shorter refractory period than the AV node, the ventricular rate can be more rapid if AV conduction occurs preferentially via the accessory pathway. As such, AV nodal blocking drugs (adenosine, verapamil, beta blockers, and digoxin) should be avoided in patients with preexcited AF since blocking the AV node will promote conduction down the accessory pathway and may sometimes directly enhance the rate of conduction over the accessory pathway. (See 'When to avoid AV nodal blockers' below.) The goals of acute drug therapy for preexcited AF are prompt control of the ventricular response and, ideally, termination of AF. If the patient is unstable because of a rapid ventricular response, electrical cardioversion should be performed. For more stable patients, trials of intravenous medications can be performed cautiously. Treatment of preexcited AF requires a parenteral drug with rapid onset of action that lengthens antegrade refractoriness and slows conduction in both the AV node/His-Purkinje system and the accessory pathway. The following is our approach to the acute treatment of patients with preexcited AF, which is consistent with published professional society guidelines [1,2,19]: For patients who are hemodynamically unstable, we recommend urgent electrical cardioversion [1,2,19]. (See "Cardioversion for specific arrhythmias", section on 'External cardioversion/defibrillation'.) For patients who are hemodynamically stable, we suggest initial medical therapy for rhythm control versus rate control. This is based on the greater ease of controlling the ventricular rate in sinus rhythm. While there is no clear first-line medication for rhythm control, options include procainamide and ibutilide [1,2]. Intravenous procainamide is effective for acute therapy of preexcited AF because of its effects on atrial and ventricular myocardium without any AV nodal blocking effect. Because of its effect on atrial myocardium, procainamide may terminate AF; however, if AF persists, the ventricular rate usually slows due to effects on refractoriness and conduction in the accessory pathway. The pediatric experience with ibutilide is very limited, so procainamide is usually the preferred intravenous drug option for preexcited AF in the younger population. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 6/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Procainamide is typically infused intravenously at 20 to 50 mg/minute given while monitoring the blood pressure closely every 5 to 10 minutes until the arrhythmia terminates, hypotension ensues, the QRS is prolonged by more than 50 percent, or a total of 17 mg/kg (1.2 g for a 70 kg patient) has been given. Even if it does not result in tachycardia termination, intravenous procainamide will usually slow the tachycardia rate and improve the hemodynamic state ( table 1). This is often followed by an infusion of 1 to 4 mg/minute. For young children, the dose for procainamide is a bolus given over 15 to 30 minutes (7 to 10 mg/kg bolus for infants <12 months of age compared with 10 to 15 mg/kg bolus for children older than 12 months), followed by an infusion of 20 to 50 micrograms/kg/minute. Ibutilide, a class III antiarrhythmic drug that prolongs the refractoriness of the AV node, His-Purkinje system, and accessory pathway, is useful for acute termination of AF and atrial flutter. In one series of 22 patients with WPW and AF during an electrophysiologic study, ibutilide prolonged the shortest preexcited RR interval and terminated the arrhythmia in 95 percent [20]. (See "Therapeutic use of ibutilide".) For all patients with preexcited AF, we recommend not using standard AV nodal blocking medications (ie, beta blockers, non-dihydropyridine calcium channel blockers [verapamil and diltiazem], digoxin, adenosine, and amiodarone). Blocking the AV node may result in increased conduction of atrial impulses to the ventricle by way of the accessory pathway, increasing the ventricular rate and potentially resulting in hemodynamic instability. (See 'When to avoid AV nodal blockers' below.) The class IC antiarrhythmic drugs flecainide and propafenone and the class III agent dofetilide are effective when used in this setting, but the parenteral formulations of these drugs are not approved for use in some countries, including the United States [21-24]. When to avoid AV nodal blockers AV node-specific antiarrhythmic drugs that are normally used to control the ventricular rate during AF are contraindicated ( table 1) for patients with preexcited AF: Verapamil is perhaps the most dangerous AV nodal blocker to administer to patients with preexcited AF [25-27]. Intravenous verapamil lengthens AV node refractoriness, decreases concealed conduction into the accessory pathway, and has no direct effect on the accessory pathway. Myocardial contractility and systemic vascular resistance are also reduced; these effects may cause a reflex increase in already elevated sympathetic tone that further shortens accessory pathway refractoriness. Precipitation of cardiac arrest by https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 7/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate degeneration of preexcited AF to ventricular fibrillation has been reported after intravenous verapamil administration [27]. Adenosine causes an effect similar to verapamil and also can precipitate ventricular fibrillation. Adenosine will not convert AF and has only a transient effect on the AV node. Its use is contraindicated in AF. Beta blockers, when used alone, do not increase accessory pathway refractoriness. Additionally, inhibition of AV node conduction may enhance the preexcited ventricular rate response by decreasing the degree of concealed retrograde conduction into the accessory pathway. An accessory pathway with a short intrinsic antegrade refractory period that was initially competing with the AV node could then become the dominant route for rapid, antegrade conduction. Amiodarone, which may slow conduction in an accessory pathway during chronic oral administration, is not known to slow accessory pathway conduction with acute IV administration [28,29]. Because amiodarone also has beta blocking properties, it may increase conduction via the accessory pathway, leading to a faster ventricular rate and the potential for ventricular fibrillation [19]. Amiodarone should generally not be used in patients with AF and accessory pathway. Digoxin is also contraindicated because of blockade of AV nodal conduction and its unpredictable effect on accessory pathway refractoriness [30]. The vagomimetic action of digoxin lengthens AV node refractoriness and reduces concealed retrograde conduction into the accessory pathway. TREATMENT TO PREVENT RECURRENT ARRHYTHMIAS Once patients with the Wolff-Parkinson-White syndrome have been stabilized following an acute episode of symptomatic tachyarrhythmia, patients should be evaluated for additional therapy aimed at preventing recurrent symptomatic arrhythmias. The preferred long-term treatment approach for nearly all patients with an accessory pathway, preexcitation, and a symptomatic arrhythmia is catheter ablation of the accessory pathway. However, for patients who are not candidates for ablation procedures, or for very select patients with rare, well-tolerated arrhythmias, antiarrhythmic therapy is an alternative. When antiarrhythmic drugs are used, the choice of agent is determined by the etiology of the arrhythmia and its electrophysiologic properties ( table 1). https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 8/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Catheter ablation For patients with an accessory pathway and symptomatic arrhythmias including orthodromic AVRT, antidromic AVRT, and preexcited AF or atrial flutter, we recommend catheter ablation rather than pharmacologic therapy [1]. Initial case-series demonstrated both the safety and efficacy of this approach, data which have been replicated in numerous studies [31-37]. The standard energy source used to ablate accessory pathways is radiofrequency current, although cryoenergy can be used as an alternative to radiofrequency energy to ablate accessory pathways that are in close proximity to the AV node or bundle of His [38]. (See "Overview of catheter ablation of cardiac arrhythmias".) Indications for ablation Patients with an accessory pathway are candidates for ablation in the following settings: Symptomatic tachyarrhythmias. Occupations in which the development of symptoms would put themselves or others at risk (eg, truck drivers or airline pilots, some athletes). Selected asymptomatic patients. (See 'Asymptomatic patients' below.) Symptomatic patients Symptom control is the most common indication for ablation. The 2015 ACC/AHA/HRS guidelines on the management of supraventricular arrhythmias recommended catheter ablation as a first-line therapy for patients who have had symptomatic AVRT or preexcited AF [1]. Asymptomatic patients The optimal approach is controversial in asymptomatic patients who are coincidentally found to have evidence of an accessory pathway on an ECG (ie, WPW pattern) [39-41]. The risk of sudden cardiac death (SCD) is low, and the risk of developing symptoms also appears to be low, although a wide range of incidences have been reported [42,43]. Among those with a WPW ECG pattern, the likelihood of developing symptoms varies with age. Children are at the highest risk, while those who remain asymptomatic over age 35 years are unlikely to develop symptoms [40]. In a prospective study of 550 asymptomatic patients with WPW ECG pattern who were followed for a median of 22 months, 13 patients (2.4 percent) developed ventricular fibrillation (VF) [44], most of whom (11 of 13) were children. Fortunately, all of the patients developed warning symptoms (usually presyncope or dizziness) and sought medical attention, and none died from the VF episode. The 2015 ACC/AHA/HRS guidelines state that observation of patients with WPW pattern alone is reasonable; however, the guidelines also state that catheter ablation is reasonable in asymptomatic patients [1]. Additionally, in a 2012 consensus statement on the management of asymptomatic young patients with the WPW pattern, ablation is recommended for patients felt https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 9/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate to be at higher risk of SCD based on the results of electrophysiologic testing [45]. (See "Wolff- Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrophysiology studies (EPS)'.) For most asymptomatic patients with preexcitation, particularly those over age 35 to 40 years, we suggest observation. However, in some asymptomatic patients, particularly children, who are felt to be at higher risk of an arrhythmia or SCD, we suggest risk stratification to identify individuals who may benefit from treatment ( algorithm 2). Localizing the accessory pathway The location of most accessory pathways can be estimated using the preexcitation pattern on the surface electrocardiogram. However, more precise localization of the accessory pathway during catheter-based mapping prior to catheter ablation utilizes several parameters [34]. To determine the atrial insertion site, the earliest site of retrograde atrial activation during orthodromic atrioventricular (AV) reciprocating tachycardia (AVRT) or ventricular pacing must be identified [46,47]. The assumption is that the local retrograde ventriculoatrial (VA) interval on the recording electrode will be shortest at the atrial insertion site. Compared with pacing at sites more remote from the accessory pathway, atrial pacing near the atrial insertion of the accessory pathway will create a greater degree of preexcitation with a shorter delay between the stimulus and the onset of the delta wave [48]. More precise localization of the ventricular insertion site is obtained by mapping along the AV groove in sinus rhythm to determine the site of earliest ventricular activation during preexcited beats. Local ventricular activation at the ventricular insertion site frequently precedes the onset of the delta wave on the surface ECG by 10 to 40 milliseconds ( waveform 2) [49,50]. If preexcitation is minimal in sinus rhythm, then atrial pacing can be performed to facilitate ventricular preexcitation by delaying AV nodal conduction. Efficacy The acute success rate with catheter-based ablation is approximately 85 to 95 percent but can approach 100 percent depending upon the location of the accessory pathway and the precision of pathway localization [34-37,44]. Success rates are lower (84 to 89 percent) for septal accessory pathways ( waveform 3 and waveform 4) [31,32,35,36,51-55]. Additionally, long-term success rates may be closer to 80 percent at five years post-ablation [56]. As examples of the efficacy of ablation: In a meta-analysis that included data from 64 studies, including 3495 patients undergoing radiofrequency catheter ablation (RFA) and 749 patients undergoing cryoablation of septal accessory pathways, acute procedural success was similar with either approach (89 versus https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 10/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 86 percent with RFA versus cryoablation, respectively) [55]. Long-term success rates were higher with RFA (88 versus 76 percent with cryoablation), although cryoablation resulted in lower risk of persistent AV block (0 versus 3 percent with RFA). In a study of 519 patients from a single, large volume center who underwent EP study and radiofrequency ablation of accessory pathways in the late 1990s and were followed for an average of 22 months, accessory pathway conduction was abolished in 92 percent of patients, although one or two additional ablation procedures were required in 6 percent [54]. In a single-center, prospective observational study of 1168 patients who underwent RFA between May 2005 and May 2010 and were followed for a median of eight years, there were no episodes of ventricular fibrillation or sudden cardiac death [44]. In addition to location (ie, septal, lateral, etc) of the accessory pathway, the efficacy of catheter ablation can be affected by the presence of multiple accessory pathways and the depth of the accessory pathway within the myocardial (ie, epicardial versus endocardial). Multiple accessory pathways Multiple accessory pathways are found in as many as 13 percent of patients with WPW syndrome. Ablation of multiple accessory pathways is possible, but it requires a longer procedure time and is associated with a higher rate of recurrence [35,57,58]. As an example, in one study of 858 patients undergoing EP study and ablation for WPW syndrome in which multiple accessory pathways were identified in 8.5 percent of patients, procedural success was similar for single and multiple pathways, but the rate of recurrent arrhythmias over a mean follow-up of 43 months was significantly higher in persons with multiple accessory pathways (9.5 versus 2.5 percent) [58]. Epicardial accessory pathway location One reason that catheter ablation may fail is with an accessory pathway that is located closer to the epicardial surface. In such patients, the usual ablation procedure via transvenous catheters at the endocardial surface may not affect the critical tissue. Although not widely done, percutaneous epicardial ablation is possible via subxiphoid access of the pericardial space. The feasibility of this approach was demonstrated in a report of 48 patients with a variety of arrhythmias (10 with WPW syndrome) who had failed endocardial ablation [59]. Via subxiphoid instrumentation, 5 of the 10 patients had accessory pathways localized to the epicardial surface, and three were successfully ablated. Catheter ablation is also effective in the treatment of PJRT. From a cohort of 194 patients (median age at diagnosis 3.2 months, 57 percent less than one year of age) from 11 institutions treated for PJRT between 2000 and 2010, 140 patients underwent a total of 175 catheter ablation https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 11/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate procedures [17]. PJRT was successfully eliminated in 90 percent of patients, with minor complications reported in only 9 percent of patients, and no major complications. Arrhythmia recurrence Recurrent arrhythmias involving an accessory pathway, manifested by return of delta waves on the electrocardiogram or spontaneous paroxysmal supraventricular tachycardia, have been reported in 5 to 12 percent of patients [36,51,52,58,60]. The recurrence rate is higher with ablation of multiple pathways or right free wall or septal accessory pathways [53,58,60]. Approximately one-half of recurrences occur in the first 12 hours after the procedure [60]. Repeat ablation usually leads to permanent cure in patients who experience a recurrence [60]. To unmask any residual conduction via an accessory pathway prior to ending the ablation procedure, intravenous adenosine can be administered to transiently block the AV node. We primarily use adenosine when there is difficulty determining if the pathway has been successfully ablated. AF can recur following accessory pathway ablation; however, the ability for AF to be preexcited with conduction via an accessory pathway should be reduced or eliminated following ablation. In a series of 91 patients with documented paroxysmal AF prior to successful ablation of an accessory pathways, 18 (20 percent) had recurrent episodes of AF at two-year follow-up, although advancing age was the only independent predictor of recurrent AF on multivariate analysis [61]. Complications Data on complication rates come from both case series and a voluntary national registry. The reported incidence of nonfatal complications is on the order of 2 to 4 percent, which is similar to rates seen with ablation procedures for other arrhythmias [35,36,45]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) The incidence and nature of complications in general clinical practice was illustrated in a report from a voluntary national registry in the United States of 3357 patients undergoing EP study and ablation for a variety of indications [36]. Among the 654 patients treated for WPW syndrome, major procedural complications occurred in 2 percent, most commonly cardiac tamponade. Specific complications may occur that are related to the anatomic site of ablation, including complete AV block resulting from ablation of a septal accessory pathway near the AV node, acute interatrial shunting related to transseptal catheterization for ablation of left-sided accessory pathways (although there are usually no adverse long-term sequelae), and inappropriate sinus tachycardia may be present following ablation of a posteroseptal accessory pathway, suggesting disruption of the parasympathetic and/or sympathetic innervation of the sinus and AV nodes [62-68]. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 12/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Surgical ablation Prior to the advent of catheter-mediated radiofrequency ablation, surgical ablation of accessory pathways was the standard technique in patients with drug-refractory WPW syndrome. The long-term success rate for WPW surgery is now almost 100 percent with an operative mortality rate of less than 1 percent [69-71]. Despite these excellent outcomes, catheter-mediated radiofrequency ablation has emerged as the preferred therapy for treatment of accessory pathways. However, surgical ablation remains an effective treatment strategy in patients suffering from highly symptomatic and hemodynamically unstable, drug-refractory arrhythmias in whom radiofrequency energy catheter ablation has failed, when performed at centers with a proven track record of success in performing the procedure [72]. Medical therapy for arrhythmia prevention For patients with an accessory pathway and symptomatic arrhythmias (including orthodromic AVRT, antidromic AVRT, and preexcited AF or atrial flutter) who are not candidates for or who refuse ablation of the accessory pathway, we suggest pharmacologic therapy aimed at preventing further arrhythmias and/or slowing the ventricular response rate [1]. Chronic therapy with verapamil or digoxin should be avoided in all patients with WPW syndrome. For recurrent orthodromic AVRT The efficacy of an antiarrhythmic drug in preventing orthodromic atrioventricular reciprocating tachycardia (AVRT) is related to its ability to alter the electrophysiologic properties of the circuit, rendering it incapable of sustaining reentry. Antiectopic activity to decrease the number of arrhythmia triggers (eg, premature atrial complex [PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat] and ventricular premature beats) is another desirable effect. The class IC antiarrhythmic drugs flecainide and propafenone ( table 2) possess the most favorable benefit/risk ratio and are the drugs of choice for prevention of recurrent orthodromic AVRT [73-76]. An important exception is the presence of known coronary disease, a setting in which class IC drugs can increase mortality due to proarrhythmia [77]. Both flecainide and propafenone have been approved for prevention of paroxysmal supraventricular tachyarrhythmias, including orthodromic AVRT. Propafenone has a potential advantage since it also has mild beta blocking activity [75,76]. Beta blockers are still occasionally used as second-line therapy for chronic suppression of orthodromic AVRT in patients with "low-risk" WPW accessory pathways (eg, only intermittently manifest or know to have a long effective refractory period), but they are not advised for patients who have developed or may develop preexcited AF. Chronic therapy with verapamil or digoxin should be avoided in all patients with WPW syndrome. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 13/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate The class IA antiarrhythmic drugs ( table 2) lengthen antegrade and retrograde refractoriness and slow conduction in the accessory pathway. However, these drugs are less potent than the class IC drugs, they only minimally lengthen AV node refractoriness, and they have a substantial risk of intolerable noncardiac adverse effects. Amiodarone has multiple electrophysiologic effects that make it effective in suppressing orthodromic AVRT, including beta blocking activity, class III effects to prolong action potential repolarization, blockade of the fast sodium and slow calcium inward currents, and suppression of ectopic beats [78-80] (see "Amiodarone: Clinical uses"). These effects result in slowing of impulse conduction and lengthening of refractoriness in both the bypass tract and the AV node/His-Purkinje system. However, it has a number of common adverse effects, including pulmonary, thyroid, and hepatic toxicity, which is a concern for patients with WPW who are often young and may require many years of therapy. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) For recurrent antidromic AVRT Ablation of the accessory pathway is the preferred therapy |
successfully ablated. Catheter ablation is also effective in the treatment of PJRT. From a cohort of 194 patients (median age at diagnosis 3.2 months, 57 percent less than one year of age) from 11 institutions treated for PJRT between 2000 and 2010, 140 patients underwent a total of 175 catheter ablation https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 11/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate procedures [17]. PJRT was successfully eliminated in 90 percent of patients, with minor complications reported in only 9 percent of patients, and no major complications. Arrhythmia recurrence Recurrent arrhythmias involving an accessory pathway, manifested by return of delta waves on the electrocardiogram or spontaneous paroxysmal supraventricular tachycardia, have been reported in 5 to 12 percent of patients [36,51,52,58,60]. The recurrence rate is higher with ablation of multiple pathways or right free wall or septal accessory pathways [53,58,60]. Approximately one-half of recurrences occur in the first 12 hours after the procedure [60]. Repeat ablation usually leads to permanent cure in patients who experience a recurrence [60]. To unmask any residual conduction via an accessory pathway prior to ending the ablation procedure, intravenous adenosine can be administered to transiently block the AV node. We primarily use adenosine when there is difficulty determining if the pathway has been successfully ablated. AF can recur following accessory pathway ablation; however, the ability for AF to be preexcited with conduction via an accessory pathway should be reduced or eliminated following ablation. In a series of 91 patients with documented paroxysmal AF prior to successful ablation of an accessory pathways, 18 (20 percent) had recurrent episodes of AF at two-year follow-up, although advancing age was the only independent predictor of recurrent AF on multivariate analysis [61]. Complications Data on complication rates come from both case series and a voluntary national registry. The reported incidence of nonfatal complications is on the order of 2 to 4 percent, which is similar to rates seen with ablation procedures for other arrhythmias [35,36,45]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) The incidence and nature of complications in general clinical practice was illustrated in a report from a voluntary national registry in the United States of 3357 patients undergoing EP study and ablation for a variety of indications [36]. Among the 654 patients treated for WPW syndrome, major procedural complications occurred in 2 percent, most commonly cardiac tamponade. Specific complications may occur that are related to the anatomic site of ablation, including complete AV block resulting from ablation of a septal accessory pathway near the AV node, acute interatrial shunting related to transseptal catheterization for ablation of left-sided accessory pathways (although there are usually no adverse long-term sequelae), and inappropriate sinus tachycardia may be present following ablation of a posteroseptal accessory pathway, suggesting disruption of the parasympathetic and/or sympathetic innervation of the sinus and AV nodes [62-68]. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 12/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Surgical ablation Prior to the advent of catheter-mediated radiofrequency ablation, surgical ablation of accessory pathways was the standard technique in patients with drug-refractory WPW syndrome. The long-term success rate for WPW surgery is now almost 100 percent with an operative mortality rate of less than 1 percent [69-71]. Despite these excellent outcomes, catheter-mediated radiofrequency ablation has emerged as the preferred therapy for treatment of accessory pathways. However, surgical ablation remains an effective treatment strategy in patients suffering from highly symptomatic and hemodynamically unstable, drug-refractory arrhythmias in whom radiofrequency energy catheter ablation has failed, when performed at centers with a proven track record of success in performing the procedure [72]. Medical therapy for arrhythmia prevention For patients with an accessory pathway and symptomatic arrhythmias (including orthodromic AVRT, antidromic AVRT, and preexcited AF or atrial flutter) who are not candidates for or who refuse ablation of the accessory pathway, we suggest pharmacologic therapy aimed at preventing further arrhythmias and/or slowing the ventricular response rate [1]. Chronic therapy with verapamil or digoxin should be avoided in all patients with WPW syndrome. For recurrent orthodromic AVRT The efficacy of an antiarrhythmic drug in preventing orthodromic atrioventricular reciprocating tachycardia (AVRT) is related to its ability to alter the electrophysiologic properties of the circuit, rendering it incapable of sustaining reentry. Antiectopic activity to decrease the number of arrhythmia triggers (eg, premature atrial complex [PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat] and ventricular premature beats) is another desirable effect. The class IC antiarrhythmic drugs flecainide and propafenone ( table 2) possess the most favorable benefit/risk ratio and are the drugs of choice for prevention of recurrent orthodromic AVRT [73-76]. An important exception is the presence of known coronary disease, a setting in which class IC drugs can increase mortality due to proarrhythmia [77]. Both flecainide and propafenone have been approved for prevention of paroxysmal supraventricular tachyarrhythmias, including orthodromic AVRT. Propafenone has a potential advantage since it also has mild beta blocking activity [75,76]. Beta blockers are still occasionally used as second-line therapy for chronic suppression of orthodromic AVRT in patients with "low-risk" WPW accessory pathways (eg, only intermittently manifest or know to have a long effective refractory period), but they are not advised for patients who have developed or may develop preexcited AF. Chronic therapy with verapamil or digoxin should be avoided in all patients with WPW syndrome. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 13/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate The class IA antiarrhythmic drugs ( table 2) lengthen antegrade and retrograde refractoriness and slow conduction in the accessory pathway. However, these drugs are less potent than the class IC drugs, they only minimally lengthen AV node refractoriness, and they have a substantial risk of intolerable noncardiac adverse effects. Amiodarone has multiple electrophysiologic effects that make it effective in suppressing orthodromic AVRT, including beta blocking activity, class III effects to prolong action potential repolarization, blockade of the fast sodium and slow calcium inward currents, and suppression of ectopic beats [78-80] (see "Amiodarone: Clinical uses"). These effects result in slowing of impulse conduction and lengthening of refractoriness in both the bypass tract and the AV node/His-Purkinje system. However, it has a number of common adverse effects, including pulmonary, thyroid, and hepatic toxicity, which is a concern for patients with WPW who are often young and may require many years of therapy. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) For recurrent antidromic AVRT Ablation of the accessory pathway is the preferred therapy for chronic prevention of antidromic AVRT. An important concern about long-term medical therapy of this arrhythmia is the potential for very rapid ventricular rates should AF develop, given that the accessory pathway is capable of antegrade preexcited conduction during AF. We suggest drug therapy for the prevention of recurrent antidromic AVRT only in patients who are not candidates for or who refuse ablation of the accessory pathway. (See 'Catheter ablation' above.) The selection of an effective antiarrhythmic drug should be based upon the effect of the drug on the electrophysiologic properties of the various parts of the reentrant circuit and on the ability to suppress the arrhythmia. The AV nodal blocking agents (beta blockers, calcium channel blockers, and digoxin) are contraindicated because of the possible occurrence of AF with accelerated conduction down the accessory pathway. (See 'When to avoid AV nodal blockers' above.) The class IC drugs flecainide and propafenone ( table 2) are the agents of choice in the absence of other contraindications such as underlying structural heart disease or myocardial ischemia ( table 1). These drugs may increase mortality in patients with known coronary disease due to proarrhythmia [77]. Class IA drugs and amiodarone are also effective but are less desirable because of side effects. For recurrent preexcited atrial fibrillation Ablation of the accessory pathway is the preferred therapy for the prevention of recurrent preexcited AF. While ablation of the accessory pathway will not directly impact the development of AF, it should prevent the possibility of very rapid ventricular rates due to antegrade conduction via the accessory pathway. We suggest https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 14/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate medical therapy for the prevention of recurrent preexcited AF only in patients who are not candidates for, or refuse, ablation of the accessory pathway. (See 'Catheter ablation' above.) The drug selected for prevention of intermittent AF in the WPW syndrome should possess antifibrillatory activity on the atrial myocardium, antiectopic activity to suppress both PACs and ventricular premature beats that can induce AF, and should prevent AVRT since the latter can subsequently degenerate into AF. The drug must also lengthen refractoriness in both the accessory pathway and the AV node and His-Purkinje system to provide adequate background protection against a rapid ventricular response should AF intermittently occur. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations" and "Atrial fibrillation in adults: Use of oral anticoagulants".) The class IC drugs flecainide and propafenone ( table 2) possess the best electrophysiologic profile for achieving these goals if no cardiac contraindications exist [81,82]. Class IA drugs are less potent and have more noncardiac adverse effects as previously noted. Amiodarone may be useful for the prevention of recurrent AF when class IC and IA drugs are ineffective and/or not tolerated and when ablation therapy is inappropriate or has failed [83,84]. Amiodarone should not be used in the acute management of AF. (See 'When to avoid AV nodal blockers' above.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Catheter ablation of arrhythmias" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 15/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Wolff-Parkinson-White syndrome (The Basics)") Beyond the Basics topic (see "Patient education: Wolff-Parkinson-White syndrome (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Patients requiring treatment Symptomatic patients Patients with the Wolff-Parkinson-White (WPW) syndrome with symptomatic arrhythmia are generally treated to manage the symptoms caused by the arrhythmia and reduce the risk of a life-threatening arrhythmia. (See 'Acute treatment of symptomatic arrhythmias' above and 'Treatment to prevent recurrent arrhythmias' above.) Asymptomatic patients For most asymptomatic patients with preexcitation, particularly those over age 35 to 40, we suggest observation rather than ablation or pharmacotherapy (Grade 2C). However, risk stratification is performed in certain asymptomatic patients who are felt to be at higher risk of an arrhythmia or sudden cardiac death (SCD; particularly children, individuals with congenital heart disease, and those with cardiomyopathy) to identify those who may benefit from treatment ( algorithm 2). (See 'Asymptomatic patients' above.) Treatment options These include nonpharmacologic therapies (ie, catheter ablation of the accessory pathway) as well as pharmacologic therapy (to slow ventricular heart rates or to prevent arrhythmias). The choice of the optimal therapy depends on the acuity of the arrhythmia(s) and the risk of sudden cardiac death. (See 'Acute treatment of symptomatic arrhythmias' above and 'Treatment to prevent recurrent arrhythmias' above.) Hemodynamic instability All patients with any arrhythmia (ie, orthodromic atrioventricular reciprocating tachycardia [AVRT], antidromic AVRT, atrial fibrillation/flutter) involving an accessory pathway should undergo prompt initial assessment of hemodynamic status. Patients who are felt to be hemodynamically unstable related to their arrhythmia should undergo urgent electrical cardioversion. (See 'Initial assessment of hemodynamic stability' above and "Cardioversion for specific arrhythmias".) https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 16/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Acute orthodromic AVRT For patients with acute symptomatic orthodromic AVRT who are hemodynamically stable, our approach is as follows ( table 1) (see 'Orthodromic AVRT' above): Initial therapy We recommend initial treatment with one or more vagal maneuvers rather than pharmacologic therapy (Grade 1B). Pharmacologic therapy If vagal maneuvers are ineffective, pharmacologic therapy with an AV nodal blocking agent (ie, adenosine, verapamil, beta blockers) should be instituted. We suggest intravenous adenosine rather than intravenous verapamil as the initial choice based on its efficacy and short half-life (Grade 2B). If adenosine is ineffective, we proceed with intravenous verapamil as the second line agent. If orthodromic AVRT persists, intravenous procainamide and beta blockers approved for intravenous administration (eg, propranolol, metoprolol, and esmolol) are additional therapeutic options. Acute antidromic AVRT For patients with acute symptomatic antidromic AVRT who are hemodynamically stable, we treat with intravenous procainamide in an effort to terminate the tachycardia or, if the tachycardia persists, slow the ventricular response. (See 'Antidromic AVRT' above.) Acute atrial fibrillation For patients with acute symptomatic preexcited atrial fibrillation (AF) who are hemodynamically stable, our approach is as follows (see 'Atrial fibrillation with preexcitation' above): Recommended therapy We suggest initial medical therapy for rhythm control versus rate control (Grade 2C). This is based on the greater ease of controlling the ventricular rate in sinus rhythm. While there is no clear first-line medication for rhythm control, options include procainamide and ibutilide. Drugs to avoid For all patients with preexcited AF, we recommend against using standard AV nodal blocking medications (ie, beta blockers, non-dihydropyridine calcium channel blockers [verapamil and diltiazem], digoxin, adenosine, and amiodarone) (Grade 1A). Blocking the AV node may result in increased conduction of atrial impulses to the ventricle by way of the accessory pathway, increasing the ventricular rate and potentially resulting in hemodynamic instability. (See 'When to avoid AV nodal blockers' above.) Prevention of recurrent arrhythmias https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 17/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate First-line therapy For patients with an accessory pathway and symptomatic arrhythmias including orthodromic AVRT, antidromic AVRT, and preexcited AF or atrial flutter, we recommend catheter ablation (Grade 1A). (See 'Catheter ablation' above.) Alternate therapy For patients with an accessory pathway and symptomatic arrhythmias (including orthodromic AVRT, antidromic AVRT, and preexcited AF or atrial flutter) who are not candidates for, or refuse, ablation of the accessory pathway, we suggest pharmacologic therapy (Grade 2C). (See 'Medical therapy for arrhythmia prevention' above.) For prevention of recurrent orthodromic AVRT in the absence of underlying structural heart disease, class IC antiarrhythmic drugs (eg, flecainide, propafenone) are the drugs of choice, although beta blockers, class IA antiarrhythmic drugs, and amiodarone may also be considered. For prevention of recurrent antidromic AVRT and preexcited AF in the absence of underlying structural heart disease, class IC antiarrhythmic drugs (eg, flecainide, propafenone) are also the drugs of choice. However, the AV nodal blocking agents (beta blockers, calcium channel blockers, and digoxin) are contraindicated in these patients, so class IA antiarrhythmic drugs and amiodarone should be considered in patients with concurrent structural heart disease. Failed catheter ablation For patients with preexcitation and symptomatic arrhythmias or AF or atrial flutter who have failed catheter ablation of the accessory pathway, we typically perform a repeat attempt at catheter ablation or consider proceeding with surgical ablation. (See 'Catheter ablation' above and 'Surgical ablation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. 2. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 18/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 3. Walker S, Cutting P. Impact of a modified Valsalva manoeuvre in the termination of paroxysmal supraventricular tachycardia. Emerg Med J 2010; 27:287. 4. Belardinelli L, Linden J, Berne RM. The cardiac effects of adenosine. Prog Cardiovasc Dis 1989; 32:73. 5. diMarco JP, Sellers TD, Lerman BB, et al. Diagnostic and therapeutic use of adenosine in patients with supraventricular tachyarrhythmias. J Am Coll Cardiol 1985; 6:417. 6. DiMarco JP, Sellers TD, Berne RM, et al. Adenosine: electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983; 68:1254. 7. Exner DV, Muzyka T, Gillis AM. Proarrhythmia in patients with the Wolff-Parkinson-White syndrome after standard doses of intravenous adenosine. Ann Intern Med 1995; 122:351. 8. Dougherty AH, Gilman JK, Wiggins S, et al. Provocation of atrioventricular reentry tachycardia: a paradoxical effect of adenosine. Pacing Clin Electrophysiol 1993; 16:8. 9. DiMarco JP, Miles W, Akhtar M, et al. Adenosine for paroxysmal supraventricular tachycardia: dose ranging and comparison with verapamil. Assessment in placebo-controlled, multicenter trials. The Adenosine for PSVT Study Group. Ann Intern Med 1990; 113:104. 10. Rinkenberger RL, Prystowsky EN, Heger JJ, et al. Effects of intravenous and chronic oral verapamil administration in patients with supraventricular tachyarrhythmias. Circulation 1980; 62:996. 11. Sung RJ, Elser B, McAllister RG Jr. Intravenous verapamil for termination of re-entrant supraventricular tachycardias: intracardiac studies correlated with plasma verapamil concentrations. Ann Intern Med 1980; 93:682. 12. Jackman WM, Friday KJ, Fitzgerald DM, et al. Use of intracardiac recordings to determine the site of drug action in paroxysmal supraventricular tachycardia. Am J Cardiol 1988; 62:8L. 13. Kowey PR, Friehling TD, Marinchak RA. Electrophysiology of beta blockers in supraventricular arrhythmias. Am J Cardiol 1987; 60:32D. 14. Anderson S, Blanski L, Byrd RC, et al. Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group. Am Heart J 1986; 111:42. 15. Mandel WJ, Laks MM, Obayashi K, et al. The Wolff-Parkinson-White syndrome: pharmacologic effects of procaine amide. Am Heart J 1975; 90:744. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 19/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 16. Wellens HJ. The wide QRS tachycardia. Ann Intern Med 1986; 104:879. 17. Kang KT, Potts JE, Radbill AE, et al. Permanent junctional reciprocating tachycardia in children: a multicenter experience. Heart Rhythm 2014; 11:1426. 18. Dorostkar PC, Silka MJ, Morady F, Dick M 2nd. Clinical course of persistent junctional reciprocating tachycardia. J Am Coll Cardiol 1999; 33:366. 19. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:2071. 20. Glatter KA, Dorostkar PC, Yang Y, et al. Electrophysiological effects of ibutilide in patients with accessory pathways. Circulation 2001; 104:1933. 21. Bianconi L, Boccadamo R, Pappalardo A, et al. Effectiveness of intravenous propafenone for conversion of atrial fibrillation and flutter of recent onset. Am J Cardiol 1989; 64:335. 22. Suttorp MJ, Kingma JH, Jessurun ER, et al. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. J Am Coll Cardiol 1990; 16:1722. 23. Suttorp MJ, Kingma JH, Lie-A-Huen L, Mast EG. Intravenous flecainide versus verapamil for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. Am J Cardiol 1989; 63:693. 24. Krahn AD, Klein GJ, Yee R. A randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of intravenously administered dofetilide in patients with Wolff- Parkinson-White syndrome. Pacing Clin Electrophysiol 2001; 24:1258. 25. Garratt C, Antoniou A, Ward D, Camm AJ. Misuse of verapamil in pre-excited atrial fibrillation. Lancet 1989; 1:367. 26. Gulamhusein S, Ko P, Carruthers SG, Klein GJ. Acceleration of the ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome after verapamil. Circulation 1982; 65:348. 27. McGovern B, Garan H, Ruskin JN. Precipitation of cardiac arrest by verapamil in patients with Wolff-Parkinson-White syndrome. Ann Intern Med 1986; 104:791. 28. Boriani G, Biffi M, Frabetti L, et al. Ventricular fibrillation after intravenous amiodarone in Wolff-Parkinson-White syndrome with atrial fibrillation. Am Heart J 1996; 131:1214. 29. Simonian SM, Lotfipour S, Wall C, Langdorf MI. Challenging the superiority of amiodarone for rate control in Wolff-Parkinson-White and atrial fibrillation. Intern Emerg Med 2010; 5:421. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 20/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 30. Sellers TD Jr, Bashore TM, Gallagher JJ. Digitalis in the pre-excitation syndrome. Analysis during atrial fibrillation. Circulation 1977; 56:260. 31. Jackman WM, Wang XZ, Friday KJ, et al. Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N Engl J Med 1991; 324:1605. 32. Kuck KH, Schl ter M, Geiger M, et al. Radiofrequency current catheter ablation of accessory atrioventricular pathways. Lancet 1991; 337:1557. 33. Calkins H, Sousa J, el-Atassi R, et al. Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test. N Engl J Med 1991; 324:1612. 34. Chen SA, Tai CT. Ablation of atrioventricular accessory pathways: current technique-state of the art. Pacing Clin Electrophysiol 2001; 24:1795. 35. Calkins H, Langberg J, Sousa J, et al. Radiofrequency catheter ablation of accessory atrioventricular connections in 250 patients. Abbreviated therapeutic approach to Wolff- Parkinson-White syndrome. Circulation 1992; 85:1337. 36. Scheinman MM, Huang S. The 1998 NASPE prospective catheter ablation registry. Pacing Clin Electrophysiol 2000; 23:1020. 37. Aguinaga L, Primo J, Anguera I, et al. Long-term follow-up in patients with the permanent form of junctional reciprocating tachycardia treated with radiofrequency ablation. Pacing Clin Electrophysiol 1998; 21:2073. 38. Rodriguez LM, Geller JC, Tse HF, et al. Acute results of transvenous cryoablation of supraventricular tachycardia (atrial fibrillation, atrial flutter, Wolff-Parkinson-White syndrome, atrioventricular nodal reentry tachycardia). J Cardiovasc Electrophysiol 2002; 13:1082. 39. Wellens HJ. Should catheter ablation be performed in asymptomatic patients with Wolff- Parkinson-White syndrome? When to perform catheter ablation in asymptomatic patients with a Wolff-Parkinson-White electrocardiogram. Circulation 2005; 112:2201. 40. Pappone C, Santinelli V. Should catheter ablation be performed in asymptomatic patients with Wolff-Parkinson-White syndrome? Catheter ablation should be performed in asymptomatic patients with Wolff-Parkinson-White syndrome. Circulation 2005; 112:2207. 41. Chevalier P, Cadi F, Scridon A, et al. Prophylactic radiofrequency ablation in asymptomatic patients with Wolff-Parkinson-White is not yet a good strategy: a decision analysis. Circ Arrhythm Electrophysiol 2013; 6:185. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 21/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 42. Todd DM, Klein GJ, Krahn AD, et al. Asymptomatic Wolff-Parkinson-White syndrome: is it time to revisit guidelines? J Am Coll Cardiol 2003; 41:245. 43. Etheridge SP, Escudero CA, Blaufox AD, et al. Life-threatening event risk in children with Wolff-Parkinson-White syndrome: a multicenter international study. J Am Coll Cardiol EP 2018; 4:433. 44. Pappone C, Vicedomini G, Manguso F, et al. Wolff-Parkinson-White syndrome in the era of catheter ablation: insights from a registry study of 2169 patients. Circulation 2014; 130:811. 45. Pediatric and Congenital Electrophysiology Society (PACES), Heart Rhythm Society (HRS), American College of Cardiology Foundation (ACCF), et al. PACES/HRS expert consensus statement on the management of the asymptomatic young patient with a Wolff-Parkinson- White (WPW, ventricular preexcitation) electrocardiographic pattern: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the Canadian Heart Rhythm Society (CHRS). Heart Rhythm 2012; 9:1006. 46. Crossen KJ, Lindsay BD, Cain ME. Reliability of retrograde atrial activation patterns during ventricular pacing for localizing accessory pathways. J Am Coll Cardiol 1987; 9:1279. 47. Jackman WM, Friday KJ, Yeung-Lai-Wah JA, et al. New catheter technique for recording left free-wall accessory atrioventricular pathway activation. Identification of pathway fiber orientation. Circulation 1988; 78:598. 48. Denes P, Wyndham CR, Amat-y-Leon F, et al. Atrial pacing at multiple sites in the Wolff- Parkinson-White syndrome. Br Heart J 1977; 39:506. 49. Mitchell LB, Mason JW, Scheinman MM, et al. Recordings of basal ventricular preexcitation from electrode catheters in patients with accessory atrioventricular connections. Circulation 1984; 69:233. 50. Chen X, Borggrefe M, Shenasa M, et al. Characteristics of local electrogram predicting successful transcatheter radiofrequency ablation of left-sided accessory pathways. J Am Coll Cardiol 1992; 20:656. 51. Scheinman MM. Catheter ablation for cardiac arrhythmias, personnel, and facilities. North American Society of Pacing and Electrophysiology Ad Hoc Committee on Catheter Ablation. Pacing Clin Electrophysiol 1992; 15:715. 52. Kay GN, Epstein AE, Dailey SM, Plumb VJ. Role of radiofrequency ablation in the management of supraventricular arrhythmias: experience in 760 consecutive patients. J Cardiovasc Electrophysiol 1993; 4:371. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 22/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 53. Calkins H, Yong P, Miller JM, et al. Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group. Circulation 1999; 99:262. 54. Dagres N, Clague JR, Kottkamp H, et al. Radiofrequency catheter ablation of accessory pathways. Outcome and use of antiarrhythmic drugs during follow-up. Eur Heart J 1999; 20:1826. 55. Bravo L, Atienza F, Eidelman G, et al. Safety and efficacy of cryoablation vs. radiofrequency ablation of septal accessory pathways: systematic review of the literature and meta- analyses. Europace 2018; 20:1334. 56. Backhoff D, Klehs S, Muller MJ, et al. Long-term follow-up after radiofrequency catheter ablation of accessory atrioventricular pathways in children. J Am Coll Cardiol EP 2018; 4:448. 57. Chen SA, Hsia CP, Chiang CE, et al. Reappraisal of radiofrequency ablation of multiple accessory pathways. Am Heart J 1993; 125:760. 58. Huang JL, Chen SA, Tai CT, et al. Long-term results of radiofrequency catheter ablation in patients with multiple accessory pathways. Am J Cardiol 1996; 78:1375. 59. Schweikert RA, Saliba WI, Tomassoni G, et al. Percutaneous pericardial instrumentation for endo-epicardial mapping of previously failed ablations. Circulation 2003; 108:1329. 60. Langberg JJ, Calkins H, Kim YN, et al. Recurrence of conduction in accessory atrioventricular connections after initially successful radiofrequency catheter ablation. J Am Coll Cardiol 1992; 19:1588. 61. Dagres N, Clague JR, Lottkamp H, et al. Impact of radiofrequency catheter ablation of accessory pathways on the frequency of atrial fibrillation during long-term follow-up; high recurrence rate of atrial fibrillation in patients older than 50 years of age. Eur Heart J 2001; 22:423. 62. Liu J, Dole LR. Late complete atrioventricular block complicating radiofrequency catheter ablation of a left posteroseptal accessory pathway. Pacing Clin Electrophysiol 1998; 21:2136. 63. Seidl K, Hauer B, Zahn R, Senges J. Unexpected complete AV block following transcatheter ablation of a left posteroseptal accessory pathway. Pacing Clin Electrophysiol 1998; 21:2139. 64. Kessler DJ, Pirwitz MJ, Horton RP, et al. Intracardiac shunts resulting from transseptal catheterization for ablation of accessory pathways in otherwise normal hearts. Am J Cardiol 1998; 82:391. 65. Fitchet A, Turkie W, Fitzpatrick AP. Transeptal approach to ablation of left-sided arrhythmias does not lead to persisting interatrial shunt: a transesophageal echocardiographic study. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 23/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Pacing Clin Electrophysiol 1998; 21:2070. 66. Kocovic DZ, Harada T, Shea JB, et al. Alterations of heart rate and of heart rate variability after radiofrequency catheter ablation of supraventricular tachycardia. Delineation of parasympathetic pathways in the human heart. Circulation 1993; 88:1671. 67. Psychari SN, Theodorakis GN, Koutelou M, et al. Cardiac denervation after radiofrequency ablation of supraventricular tachycardias. Am J Cardiol 1998; 81:725. 68. Hamdan MH, Page RL, Wasmund SL, et al. Selective parasympathetic denervation following posteroseptal ablation for either atrioventricular nodal reentrant tachycardia or accessory pathways. Am J Cardiol 2000; 85:875. 69. Cox JL, Gallagher JJ, Cain ME. Experience with 118 consecutive patients undergoing operation for the Wolff-Parkinson-White syndrome. J Thorac Cardiovasc Surg 1985; 90:490. 70. Lawrie GM, Lin HT, Wyndham CR, DeBakey ME. Surgical treatment of supraventricular arrhythmias. Results in 67 patients. Ann Surg 1987; 205:700. 71. Johnson DC, Nunn GR, Richards DA, et al. Surgical therapy for supraventricular tachycardia, a potentially curable disorder. J Thorac Cardiovasc Surg 1987; 93:913. 72. Holman WL, Kay GN, Plumb VJ, Epstein AE. Operative results after unsuccessful radiofrequency ablation for Wolff-Parkinson-White syndrome. Am J Cardiol 1992; 70:1490. 73. Kim SS, Lal R, Ruffy R. Treatment of paroxysmal reentrant supraventricular tachycardia with flecainide acetate. Am J Cardiol 1986; 58:80. 74. Ward DE, Jones S, Shinebourne EA. Use of flecainide acetate for refractory junctional tachycardias in children with the Wolff-Parkinson-White syndrome. Am J Cardiol 1986; 57:787. 75. Ludmer PL, McGowan NE, Antman EM, Friedman PL. Efficacy of propafenone in Wolff- Parkinson-White syndrome: electrophysiologic findings and long-term follow-up. J Am Coll Cardiol 1987; 9:1357. 76. Musto B, D'Onofrio A, Cavallaro C, Musto A. Electrophysiological effects and clinical efficacy of propafenone in children with recurrent paroxysmal supraventricular tachycardia. Circulation 1988; 78:863. 77. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781. 78. Rosenbaum MB, Chiale PA, Ryba D, Elizari MV. Control of tachyarrhythmias associated with Wolff-Parkinson-White syndrome by amiodarone hydrochloride. Am J Cardiol 1974; 34:215. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 24/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 79. Wellens HJ, Lie KI, B r FW, et al. Effect of amiodarone in the Wolff-Parkinson-White syndrome. Am J Cardiol 1976; 38:189. 80. Feld GK, Nademanee K, Weiss J, et al. Electrophysiologic basis for the suppression by amiodarone of orthodromic supraventricular tachycardias complicating pre-excitation syndromes. J Am Coll Cardiol 1984; 3:1298. 81. Chouty F, Coumel P. Oral flecainide for prophylaxis of paroxysmal atrial fibrillation. Am J Cardiol 1988; 62:35D. 82. Antman EM, Beamer AD, Cantillon C, et al. Long-term oral propafenone therapy for suppression of refractory symptomatic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1988; 12:1005. 83. Kappenberger LJ, Fromer MA, Steinbrunn W, Shenasa M. Efficacy of amiodarone in the Wolff-Parkinson-White syndrome with rapid ventricular response via accessory pathway during atrial fibrillation. Am J Cardiol 1984; 54:330. 84. Feld GK, Nademanee K, Stevenson W, et al. Clinical and electrophysiologic effects of amiodarone in patients with atrial fibrillation complicating the Wolff-Parkinson-White syndrome. Am Heart J 1988; 115:102. Topic 996 Version 48.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 25/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate GRAPHICS ECG in Wolff-Parkinson-White The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 Normal ECG https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 26/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 27/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible |
20:1826. 55. Bravo L, Atienza F, Eidelman G, et al. Safety and efficacy of cryoablation vs. radiofrequency ablation of septal accessory pathways: systematic review of the literature and meta- analyses. Europace 2018; 20:1334. 56. Backhoff D, Klehs S, Muller MJ, et al. Long-term follow-up after radiofrequency catheter ablation of accessory atrioventricular pathways in children. J Am Coll Cardiol EP 2018; 4:448. 57. Chen SA, Hsia CP, Chiang CE, et al. Reappraisal of radiofrequency ablation of multiple accessory pathways. Am Heart J 1993; 125:760. 58. Huang JL, Chen SA, Tai CT, et al. Long-term results of radiofrequency catheter ablation in patients with multiple accessory pathways. Am J Cardiol 1996; 78:1375. 59. Schweikert RA, Saliba WI, Tomassoni G, et al. Percutaneous pericardial instrumentation for endo-epicardial mapping of previously failed ablations. Circulation 2003; 108:1329. 60. Langberg JJ, Calkins H, Kim YN, et al. Recurrence of conduction in accessory atrioventricular connections after initially successful radiofrequency catheter ablation. J Am Coll Cardiol 1992; 19:1588. 61. Dagres N, Clague JR, Lottkamp H, et al. Impact of radiofrequency catheter ablation of accessory pathways on the frequency of atrial fibrillation during long-term follow-up; high recurrence rate of atrial fibrillation in patients older than 50 years of age. Eur Heart J 2001; 22:423. 62. Liu J, Dole LR. Late complete atrioventricular block complicating radiofrequency catheter ablation of a left posteroseptal accessory pathway. Pacing Clin Electrophysiol 1998; 21:2136. 63. Seidl K, Hauer B, Zahn R, Senges J. Unexpected complete AV block following transcatheter ablation of a left posteroseptal accessory pathway. Pacing Clin Electrophysiol 1998; 21:2139. 64. Kessler DJ, Pirwitz MJ, Horton RP, et al. Intracardiac shunts resulting from transseptal catheterization for ablation of accessory pathways in otherwise normal hearts. Am J Cardiol 1998; 82:391. 65. Fitchet A, Turkie W, Fitzpatrick AP. Transeptal approach to ablation of left-sided arrhythmias does not lead to persisting interatrial shunt: a transesophageal echocardiographic study. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 23/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Pacing Clin Electrophysiol 1998; 21:2070. 66. Kocovic DZ, Harada T, Shea JB, et al. Alterations of heart rate and of heart rate variability after radiofrequency catheter ablation of supraventricular tachycardia. Delineation of parasympathetic pathways in the human heart. Circulation 1993; 88:1671. 67. Psychari SN, Theodorakis GN, Koutelou M, et al. Cardiac denervation after radiofrequency ablation of supraventricular tachycardias. Am J Cardiol 1998; 81:725. 68. Hamdan MH, Page RL, Wasmund SL, et al. Selective parasympathetic denervation following posteroseptal ablation for either atrioventricular nodal reentrant tachycardia or accessory pathways. Am J Cardiol 2000; 85:875. 69. Cox JL, Gallagher JJ, Cain ME. Experience with 118 consecutive patients undergoing operation for the Wolff-Parkinson-White syndrome. J Thorac Cardiovasc Surg 1985; 90:490. 70. Lawrie GM, Lin HT, Wyndham CR, DeBakey ME. Surgical treatment of supraventricular arrhythmias. Results in 67 patients. Ann Surg 1987; 205:700. 71. Johnson DC, Nunn GR, Richards DA, et al. Surgical therapy for supraventricular tachycardia, a potentially curable disorder. J Thorac Cardiovasc Surg 1987; 93:913. 72. Holman WL, Kay GN, Plumb VJ, Epstein AE. Operative results after unsuccessful radiofrequency ablation for Wolff-Parkinson-White syndrome. Am J Cardiol 1992; 70:1490. 73. Kim SS, Lal R, Ruffy R. Treatment of paroxysmal reentrant supraventricular tachycardia with flecainide acetate. Am J Cardiol 1986; 58:80. 74. Ward DE, Jones S, Shinebourne EA. Use of flecainide acetate for refractory junctional tachycardias in children with the Wolff-Parkinson-White syndrome. Am J Cardiol 1986; 57:787. 75. Ludmer PL, McGowan NE, Antman EM, Friedman PL. Efficacy of propafenone in Wolff- Parkinson-White syndrome: electrophysiologic findings and long-term follow-up. J Am Coll Cardiol 1987; 9:1357. 76. Musto B, D'Onofrio A, Cavallaro C, Musto A. Electrophysiological effects and clinical efficacy of propafenone in children with recurrent paroxysmal supraventricular tachycardia. Circulation 1988; 78:863. 77. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781. 78. Rosenbaum MB, Chiale PA, Ryba D, Elizari MV. Control of tachyarrhythmias associated with Wolff-Parkinson-White syndrome by amiodarone hydrochloride. Am J Cardiol 1974; 34:215. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 24/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 79. Wellens HJ, Lie KI, B r FW, et al. Effect of amiodarone in the Wolff-Parkinson-White syndrome. Am J Cardiol 1976; 38:189. 80. Feld GK, Nademanee K, Weiss J, et al. Electrophysiologic basis for the suppression by amiodarone of orthodromic supraventricular tachycardias complicating pre-excitation syndromes. J Am Coll Cardiol 1984; 3:1298. 81. Chouty F, Coumel P. Oral flecainide for prophylaxis of paroxysmal atrial fibrillation. Am J Cardiol 1988; 62:35D. 82. Antman EM, Beamer AD, Cantillon C, et al. Long-term oral propafenone therapy for suppression of refractory symptomatic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1988; 12:1005. 83. Kappenberger LJ, Fromer MA, Steinbrunn W, Shenasa M. Efficacy of amiodarone in the Wolff-Parkinson-White syndrome with rapid ventricular response via accessory pathway during atrial fibrillation. Am J Cardiol 1984; 54:330. 84. Feld GK, Nademanee K, Stevenson W, et al. Clinical and electrophysiologic effects of amiodarone in patients with atrial fibrillation complicating the Wolff-Parkinson-White syndrome. Am Heart J 1988; 115:102. Topic 996 Version 48.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 25/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate GRAPHICS ECG in Wolff-Parkinson-White The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 Normal ECG https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 26/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 27/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone Antidromic AV reentrant tachycardia Acute termination* Unstable patients: Adenosine, verapamil, diltiazem, Synchronized cardioversion beta blockers, digoxin should all be avoided if NOT certain of diagnosis Stable patients (if CERTAIN of the diagnosis): Same progression of therapies as acute termination of orthodromic AVRT Stable patients (if NOT certain of the diagnosis): IV procainamide, synchronized cardioversion if procainamide is ineffective or not available https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 28/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Chronic prevention First line: Catheter ablation of the accessory pathway Digoxin Beta blockers Second line: Oral flecainide or propafenone in the absence of Verapamil, diltiazem structural or ischemic heart disease Other therapies: Oral IA antiarrhythmic agent OR oral amiodarone Pre-excited atrial fibrillation Acute termination* Unstable patients: Amiodarone Synchronized cardioversion Stable patients: Digoxin Beta blockers First line: IV ibutilide or IV procainamide Adenosine Other therapies: IC antiarrhythmic agent or dofetilide; synchronized cardioversion if other therapies are ineffective or not available Verapamil, diltiazem Chronic prevention First line: Catheter ablation or the accessory pathway Oral digoxin Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone AVRT: atrioventricular reciprocating tachycardia; IV: intravenous; class IC: flecainide, propafenone; class IA: quinidine, procainamide, disopyramide. Cardioversion is indicated if hemodynamically unstable or drugs are ineffective. Ablation of the accessory pathway is generally preferred to cure the arrhythmia. Procainamide is the intravenous drug of choice for acute termination of suspected antidromic AVRT. If the tachycardia is definitely known to be antidromic AVRT, and it has been verified that the AV node (rather than a second accessory pathway) is acting as the retrograde limb of the circuit, one could consider treatment with an agent such as adenosine similar to therapy for orthodromic AVRT, https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 29/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate but it is rare to have all of the necessary data in the acute setting to justify use of AV nodal blocking agents. Graphic 62762 Version 7.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 30/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 31/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 32/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Algorithmic approach to risk stratification of asymptomatic patients with Wolff-Parkinson-White ECG pattern ECG: electrocardiogram; EPS: electrophysiology studies; AVRT: atrioventricular reciprocating tachycardia; AF: atrial fibrillation; WPW: Wolff-Parkinson-White. Preexcitation on the surface ECG is identified by a short PR interval (less than 120 milliseconds) leading into QRS, which is widened with a slurred upstroke (delta wave). Preexcitation is defined as intermittent when an ECG at any point in time shows the loss of preexcitation. In patients who are unable to perform exercise testing (eg, very young patients), ambulatory ECG monitoring or, rarely, sodium channel blocker challenge with procainamide is an alternative to assess for persistent or intermittent preexcitation. All approaches to risk stratification in patients with ventricular preexcitation are imperfect and can be associated with false positives as well as false negatives. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 33/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Options for invasive EPS include the standard transvenous intracardiac EPS or a transesophageal atrial EPS. Refer to the UpToDate topic on treatment of symptomatic arrhythmias in patients with WPW. For most asymptomatic patients with preexcitation and no high- risk features identified on EPS, particularly those over age 35 to 40 years, we suggest observation. However, in some asymptomatic patients, particularly children, some electrophysiologists discuss and/or proceed with catheter ablation as a therapeutic option even in the absence of high risk features. Refer to UpToDate content on treatment of WPW for additional information. Graphic 119379 Version 3.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 34/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Intracardiac and surface electrocardiogram (ECG) recordings during electrophysiologic (EP) study in Wolff-Parkinson-White syndrome Shown are five surface ECG leads (I, aVF, V1, V3, V6) and intracardiac recordings from the high right atrium (HRA), lateral mitral annulus (HBE1-2 and HBE3-4), coronary sinus (proximal to distal, CS9-10, CS7-8, CS5-6, CS3-4, and CS1-2), and the right ventricular apex (RVA3-4). During the diagnostic electrophysiology study, orthodromic atrioventricular reentrant tachycardia was induced. Recordings from the CS demonstrated that the earliest site of ventricular activation was at CS7-8, indicating a left lateral location of the accessory pathway (arrow). The mapping catheter (HBE1-2,3-4) was advanced through a patent foramen ovale to the lateral mitral annulus. Activation mapping was used to select the ablation site; during sinus rhythm, the ablation catheter was maneuvered to the site along the mitral annulus, which recorded earliest ventricular activity (HBE1-2) (ie, the atrial [A] and ventricular [V] electrograms recorded from the ablation catheter tip were continuous and the local ventricular activity preceded the onset of the delta wave on the surface ECG). Graphic 72398 Version 5.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 35/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Radiofrequency ablation for WPW syndrome Surface ECG and intracardiac electrograms from a patient with Wolff- Parkinson-White syndrome (WPW) and a right lateral accessory pathway are simultaneously recorded. The patient is initially being paced from the high right atrium (HRA) at a cycle length of 500 milliseconds to maximize preexcitation. The accessory pathway is localized to an area of the tricuspid annulus (Ta), and radiofrequency (RF) current is delivered via a deflectable tip ablation catheter. Preexcitation disappears (*) within 1.2 seconds. Graphic 51546 Version 4.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 36/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Intracardiac and surface ECG recordings during electrophysiologic study post-radiofrequency ablation of accessory pathway in Wolff- Parkinson-White Shown are five surface leads (I, AVF, V1, V3, and V6) and intracardiac recording from the high right atrium (HRA), lateral mitral annulus (HBE1-2 and HBE3-4), coronary sinus proximal to distal (CS9-10, 7-8, 5-6, 3-4, 1-2), and right ventricular apex (RVA3-4). The tip of the mapping catheter is positioned at the site along the mitral annulus recording the earliest ventricular activity (HBE1-2) (ie, the location of the accessory pathway). Within a few beats after the application of radiofrequency energy (RF on), the delta wave on the ECG disappeared (arrow) and the PR interval normalized. Prior to ablation, the recordings from the CS catheter show continuous atrial (A) and ventricular (V) electrograms; after ablation, there is a normal interval between A and V. Graphic 78363 Version 5.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 37/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 38/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 39/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Contributor Disclosures Luigi Di Biase, MD, PhD, FHRS, FACC Consultant/Advisory Boards: Abbott [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Baylis Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Biosense Webster [Ablation products]; Biotronik [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Boston Scientific [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Medtronic [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Stereotaxis [Ablation products]; Zoll Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]. All of the relevant financial relationships listed have been mitigated. Edward P Walsh, MD No relevant financial relationship(s) with ineligible companies to disclose. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 40/40 |
7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis : Luigi Di Biase, MD, PhD, FHRS, FACC, Edward P Walsh, MD : Samuel L vy, MD, Bradley P Knight, MD, FACC : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 29, 2022. INTRODUCTION In 1930, Louis Wolff, Sir John Parkinson, and Paul Dudley White published a seminal article describing 11 patients who suffered from attacks of tachycardia associated with a sinus rhythm electrocardiographic (ECG) pattern of bundle branch block with a short PR interval [1]. This was subsequently termed Wolff-Parkinson-White (WPW) syndrome, although earlier isolated case reports describing similar patients had been published. In 1943, the ECG features of preexcitation were correlated with anatomic evidence for the existence of anomalous bundles of conducting tissue that bypassed all or part of the normal atrioventricular (AV) conduction system. This topic will discuss the definitions, anatomy, epidemiology, clinical manifestations, and diagnosis of WPW syndrome as well as the approach to risk stratification of asymptomatic patients. The treatment options for patients with tachyarrhythmias and WPW syndrome are discussed separately. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome".) DEFINITIONS Normal AV conduction versus accessory AV pathway conduction In the normal heart, the atria and the ventricles are electrically isolated, with conduction of electrical impulses from the atria to the ventricles normally occurring via the AV node and the His-Purkinje system. Patients https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 1/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate with a preexcitation syndrome have an additional pathway, known as an accessory pathway (also called bundle of Kent), which directly connects the atria and ventricles, thereby allowing electrical activity to bypass the AV node, leading to "preexcitation" or earlier than usual activation of the His-Purkinje system ( table 1). Tissue in the accessory pathways, which are congenital in origin and result from failure of resorption of the myocardial syncytium at the annulus fibrosis of the AV valves during fetal development, typically conducts electrical impulses more quickly than the AV node, resulting in the shorter PR interval seen on the surface ECG. (See 'Electrocardiographic findings' below and "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction" and "Atriofascicular ("Mahaim") pathway tachycardia".) It has been estimated that most accessory pathways (60 to 75 percent) are capable of bidirectional conduction (antegrade and retrograde) between the atrium and ventricle. However, some accessory pathways (17 to 37 percent) are only capable of conduction in a retrograde fashion from ventricle to atrium [2]. When accessory pathways conduct exclusively in the retrograde direction (so-called "concealed" accessory pathways), they do not generate a delta wave (ie, slurred upstroke of the QRS complex) and the WPW pattern on the surface ECG but are still capable of supporting reentrant tachycardia. Retrograde conduction can occur following ventricular pacing or premature beats, and it can form the retrograde arm of an orthodromic AV reentrant tachycardia (AVRT) circuit. The vast majority of concealed accessory pathways are left- sided [3]. (See 'Electrocardiographic findings' below and 'Anatomy' below and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Narrow complex AVRT'.) Less commonly (5 to 27 percent), an accessory pathway is only capable of conduction in the antegrade direction; in such cases, the ECG does show a delta wave and the WPW pattern on the surface ECG, and the pathway can form the antegrade arm of an antidromic AVRT circuit. The mechanism responsible for unidirectional conduction along an accessory pathway (antegrade only or retrograde only) remains undetermined. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Wide complex AVRT'.) Accessory pathways that appear to be concealed may be capable of antegrade conduction in some situations: If AV nodal conduction is enhanced and/or the accessory pathway is left lateral (ie, far from the sinus node), conduction may proceed over the normal AV node-His Purkinje system more quickly than over the accessory pathway. In these cases, antegrade accessory pathway conduction occurs, but is not manifest on the surface ECG. Transient blockade of AV nodal conduction with adenosine may expose the "concealed" pathway. https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 2/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate In some patients with left free wall accessory pathways, pacing the left atrium via the coronary sinus, in an area closer to the accessory pathway, may be necessary to bring out antegrade accessory pathway conduction and overt preexcitation. Some accessory pathways (in any location) may have limited antegrade conduction potential due to a long refractory period and only become manifest at slower heart rates. WPW pattern versus WPW syndrome Two terms, distinguished by the presence or absence of arrhythmias, have been used to describe patients with AV accessory pathways: The WPW pattern is applied to the patient with preexcitation manifest on an ECG in the absence of symptomatic arrhythmias. WPW syndrome is applied to the patient with both preexcitation manifest on an ECG and symptomatic arrhythmias involving the accessory pathway. Persons with either the WPW pattern or WPW syndrome can have identical findings on the surface ECG. In either situation, antegrade conduction through the accessory pathway results in earlier activation, or preexcitation, of part of the ventricles. The classic WPW ECG pattern ( waveform 1 and waveform 2) has two major features: a shortened PR interval and a widened QRS complex due to a delta wave. The ECG findings are discussed in greater detail elsewhere. (See 'Electrocardiographic findings' below.) ANATOMY Accessory pathway location Electrophysiologic studies and mapping have shown that accessory AV pathways may be located anywhere along the AV ring (groove) or in the septum. The most frequent locations are left lateral (50 percent), posteroseptal (30 percent), right anteroseptal (10 percent), and right lateral (10 percent). (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) Many studies have attempted to correlate the site of the accessory pathway with the ECG pattern [4-7]. However, the ECG appearance of activation depends upon the extent of preexcitation and, as a result, the same pathway may not always produce the same ECG pattern. Furthermore, up to 13 percent of individuals with preexcitation have more than one accessory pathway [8,9]. The probability is increased in subjects with a family history of preexcitation, as well in as patients with Ebstein malformation of the tricuspid valve and certain forms of cardiomyopathy [9,10]. (See 'Familial WPW' below.) https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 3/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Associated cardiac abnormalities Most patients with AV accessory pathways do not have coexisting structural cardiac abnormalities [11]. Associated congenital heart disease, when present, is more likely to be right-sided than left-sided in location [12,13]. Ebstein anomaly is the congenital lesion most strongly associated with WPW syndrome. As many as 10 to 20 percent of such patients have one or more accessory pathways; the majority of these are located in the right free wall and right posteroseptal spaces [14-16]. (See "Clinical manifestations and diagnosis of Ebstein anomaly".) An association between mitral valve prolapse and left-sided accessory pathways has also been reported. However, this association may simply reflect the random coexistence of two relatively common conditions [17,18]. In addition, a familial form of WPW syndrome is associated with hypertrophic cardiomyopathy (HCM). (See 'Familial WPW' below.) EPIDEMIOLOGY When discussing the prevalence of WPW, it is important to distinguish between the WPW pattern (ie, ECG abnormalities in asymptomatic patients) and WPW syndrome. Both are fairly infrequent, occurring in less than 1 percent of the general population, with the WPW pattern between 10 and 100 times more common than WPW syndrome. Prevalence of WPW pattern The prevalence of a WPW pattern on the surface ECG is estimated at 0.13 to 0.25 percent in the general population [11,19,20]. The prevalence appears higher (up to 0.55 percent) among first-degree relatives of persons with the WPW pattern, suggesting a familial component. (See 'Familial WPW' below.) The WPW pattern on the ECG may be intermittent and may even disappear permanently over time [19,21-24]. In several large cohorts, the frequency of intermittent preexcitation appears to range between 10 and 40 percent [21,23,24]. In one cohort study, 22 percent of individuals who eventually manifested the WPW pattern on an ECG initially had a normal tracing, and in 40 percent of these patients, the WPW pattern disappeared on subsequent ECGs [21]. In a cohort of 328 patients with preexcitation (mean age 13 years), 41 patients (13 percent) were noted to have intermittent preexcitation [23]. In a single-center cohort of 295 patients with preexcitation (mean age 12 years at presentation), 39 patients (13 percent) had intermittent preexcitation, and another 30 (10 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 4/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate percent) had loss of preexcitation on ambulatory monitoring or exercise testing [24]. Intermittent and/or persistent loss of preexcitation may indicate that the accessory pathway has a relatively longer baseline refractory period, which makes it more susceptible to age-related degenerative changes and variations in autonomic tone [21,22,25]. Compared with patients with a persistent WPW pattern, those in whom antegrade conduction via the accessory pathway disappeared were older (50 versus 39 years) and had a longer refractory period of the accessory pathway at initial electrophysiologic study ([EPS]; 414 versus 295 milliseconds) [22]. (See 'Risk stratification of asymptomatic patients with WPW pattern' below.) Prevalence of WPW syndrome The prevalence of WPW syndrome is substantially lower than that of the WPW pattern alone. The exact value has varied in different studies, depending in part upon the duration of follow-up: In a review of 22,500 healthy aviation personnel, the WPW pattern on an ECG was seen in 0.25 percent, and only 1.8 percent of these patients had documented arrhythmia [26]. In a report of 228 subjects with the WPW pattern by ECG who were followed for 22 years, the overall incidence of arrhythmia resulting in WPW syndrome was 1 percent per year [27]. In a study of 432,166 children, ages 6 to 20 years, the prevalence of WPW syndrome was 0.07 percent [28]. Different types of supraventricular arrhythmias occur in WPW syndrome. AV reentrant tachycardia (AVRT): up to 80 percent Atrial fibrillation (AF): 15 to 30 percent Atrial flutter: 5 percent or less The incidence of sudden cardiac death (SCD) in asymptomatic persons is quite low, with a meta- analysis of 20 studies (1869 patients), estimating the risk at 0.13 percent per year [29]. The occurrence of arrhythmia is related to the age at the time preexcitation was discovered [21,30]. In one cohort study of 113 persons with the WPW pattern, one-third of asymptomatic individuals less than 40 years of age at the time the WPW pattern was identified eventually had symptomatic arrhythmias, compared with none of those who were 40 years of age or older at diagnosis [21]. As noted above, the WPW pattern may disappear in asymptomatic patients; a similar course can occur in patients with WPW syndrome [19,21,22]. In one cohort of 113 patients with WPW https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 5/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate syndrome or AV nodal reentrant tachycardia who were followed for nine years, 23 percent lost antegrade conduction and ventricular preexcitation, 8 percent lost retrograde conduction in the accessory pathway, and 10 percent had disappearance of their arrhythmias [31]. (See 'Prevalence of WPW pattern' above.) Prevalence of concealed accessory pathways The true prevalence of concealed accessory pathways is unknown. Since the presence of a concealed accessory pathway is only identified during an arrhythmia (eg, AVRT), such a pathway cannot be identified during sinus rhythm using an ECG alone. Thus, only patients with symptomatic arrhythmias who undergo diagnostic EPS ever have concealed accessory pathways diagnosed. Among patients with symptomatic supraventricular tachycardias (SVTs) presenting for catheter ablation, the prevalence of concealed accessory pathways is approximately 15 percent [32-34]. Familial WPW Among patients with WPW syndrome, 3.4 percent have first-degree relatives with a preexcitation syndrome [35]. A familial form of WPW syndrome has infrequently been reported and is usually inherited as an autosomal dominant trait [10,36,37]. Two studies of three families with affected subjects who had an early onset of conduction disease and frequent episodes of AF mapped the gene responsible for WPW syndrome to chromosome 7q34-q36 [36]. Missense mutations were identified in the PRKAG2 gene, which encodes the gamma-2 regulatory subunit of AMP-activated protein kinase [36,37]. An inherited form of WPW syndrome associated with familial HCM has been described and may be due to either mutations in the PRKAG2 gene, as with isolated familial WPW syndrome, or in the LAMP2 gene, which is responsible for glycogen storage disease IIb (Danon disease). (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing", section on 'PRKAG2 and LAMP2 genes'.) CLINICAL MANIFESTATIONS As noted above, the majority of patients with the WPW pattern on their ECG remains asymptomatic. However, a small percentage of patients with the WPW pattern develop arrhythmias (eg, AV reentrant [or reciprocating] tachycardia [AVRT], atrial fibrillation [AF] with rapid ventricular response, etc) as a part of WPW syndrome. Most patients who develop an arrhythmia will present with one or more of the following symptoms: Palpitations Lightheadedness and/or dizziness Syncope or presyncope Chest pain https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 6/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Sudden cardiac arrest Arrhythmias associated with WPW Tachycardias associated with WPW syndrome can be classified into those in which the accessory pathway is necessary for initiation and maintenance of the tachycardia, and those in which the bypass tract acts as a "bystander," providing a route of conduction from the anatomic site of tachycardia origin to other regions of the heart ( figure 1). Tachycardias requiring an accessory pathway for initiation and maintenance AVRT is a reentrant tachycardia with an anatomically defined circuit that consists of two distinct pathways, the normal AV conduction system and an AV accessory pathway, linked by common proximal (the atria) and distal (the ventricles) tissues. If sufficient differences in conduction time and refractoriness exist between the normal conduction system and the bypass tract, a properly timed premature impulse can initiate reentry. (See "Reentry and the development of cardiac arrhythmias".) The two major forms of this type of arrhythmia in WPW syndrome are orthodromic AVRT (ie, antegrade conduction via the AV node and retrograde conduction via the accessory pathway) and antidromic AVRT (ie, antegrade conduction via the accessory pathway and retrograde conduction via the AV node). The width of the QRS complex can usually distinguish between these paroxysmal arrhythmias. A full discussion of AVRT is presented separately. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Tachycardias not requiring an accessory pathway for initiation and maintenance Atrial tachyarrhythmias, junctional tachycardias including AV nodal reentrant tachycardia (AVNRT), ventricular tachycardia (VT), and ventricular fibrillation (VF) can all occur in patients with an accessory pathway ( waveform 3). In these settings, the accessory pathway may serve as a route for ventricular or atrial activation, but is generally not involved in the initiation of the arrhythmia and is not required for perpetuation of the arrhythmia. Atrioventricular nodal reentrant tachycardia AVNRT can use the bystander accessory pathway to transmit impulses between the atrium and the ventricle ( waveform 3). When AVNRT occurs in WPW syndrome, the arrhythmia cannot be distinguished from either antidromic or orthodromic AVRT without electrophysiologic studies (EPS). (See "Atrioventricular nodal reentrant tachycardia".) Atrial fibrillation AF occurs in 10 to 30 percent of persons with WPW syndrome ( waveform 4) [38,39]. AF generally originates within the atria or pulmonary veins, independent of the accessory pathway, but the accessory pathway functions as another route for the conduction of atrial impulses to the ventricles. However, the 10 to 30 percent frequency https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 7/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate with which intermittent AF occurs in patients with WPW syndrome is striking because of the low prevalence of coexisting structural heart disease, which is a major predisposing factor for AF in subjects without an accessory pathway. This observation suggests that the AV accessory pathway itself may be related to the genesis of AF, perhaps due to retrograde conduction to the atrium at a time when it is vulnerable to the development of AF. Characteristic findings on the ECG in patients with AF and an accessory pathway include an irregularly irregular rhythm with QRS morphology changes from beat to beat, which may be associated with rapid AV transmission ( waveform 4). A sustained ventricular rate greater than 180 to 200 beats per minute can create "pseudo-regularized" RR intervals when the ECG is recorded at standard speed (25 mm per second). When atrial impulses are transmitted along the accessory pathway in AF, ventricular rates may exceed 300 beats per minute and can degenerate into VF. (See "The electrocardiogram in atrial fibrillation" and 'Ventricular fibrillation and sudden death' below.) The QRS morphology and rate of impulse conduction during AF along the accessory pathway is dependent upon several factors, including: The shorter the refractory period of the accessory pathway, the more rapid is the antegrade impulse conduction and, because of more preexcitation, the QRS complexes are wider. Patients with very short refractory periods and rapid AF represent the group at greatest risk for degeneration to VF. (See 'Ventricular fibrillation and sudden death' below.) The degree to which the AV node/His-Purkinje system competes with the accessory pathway for ventricular activation. The presence of multiple accessory pathways. Retrograde activation of the accessory pathway. AF is often preceded by AVRT in individuals with WPW syndrome, with one report suggesting that as many as 35 percent of episodes of AF were preceded by AVRT [38,40,41]. However, the mechanisms by which AVRT precipitates AF are not well understood, but increased stretching due to increased atrial pressure and conduction disturbances in atrial myocardium due to reduced refractoriness could play a role. Atrial flutter Atrial flutter is due to a reentrant circuit (usually within the right atrium) which is not AV node dependent and therefore exists independently of the accessory pathway. Atrial flutter can, like AF, conduct antegrade via an accessory pathway causing a preexcited tachycardia ( waveform 5). Depending upon the various refractory periods of the normal and pathologic AV accessory pathways, atrial flutter potentially could conduct 1:1 to the ventricles https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 8/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate during a preexcited tachycardia, making the arrhythmia difficult to distinguish from VT. When atrial flutter is transmitted antegrade along the accessory pathway, ventricular rates may exceed 300 beats per minute and can degenerate into VF. (See 'Ventricular fibrillation and sudden death' below.) Ventricular tachycardia Coexisting VT is uncommon because patients with WPW syndrome infrequently have structural heart disease [12,18]. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) Ventricular fibrillation and sudden death In most cases, VF occurring in patients with WPW syndrome results from the rapid ventricular response during AF that has persisted and ultimately deteriorated into VF. Although the frequency with which AF with rapid AV conduction via an accessory pathway degenerates into VF is unknown, VF as the initial manifestation of WPW syndrome appears to be quite rare, occurring in only 8 of 690 patients with WPW syndrome in one single-center cohort [42]. Additionally, it is reassuring to note that the incidence of sudden death in patients with WPW syndrome is quite low. (See 'Prevalence of WPW syndrome' above.) Patients with the WPW pattern who appear to be at increased risk for VF include those with [11,30,43-46]: A history of AVRT and/or AF A very short antegrade refractory period (<250 milliseconds) of the accessory pathway noted during EPS Short RR intervals (<250 milliseconds) during an induced or spontaneous episode of AF In contrast, intermittent preexcitation, characterized by the intermittent loss of the delta wave, suggests that the bypass tract has a long refractory period, making the development of VF unlikely [11,46]. However, preexcitation and arrhythmias have been previously undiagnosed in up to 25 percent of individuals with VF or sudden death [43,45,47]. (See 'Electrophysiology studies (EPS)' below.) Some medications, primarily AV nodal blockers (eg, verapamil, adenosine, digoxin), have been associated with an increased risk of VF in patients with preexcitation and AF due to preferential conduction via the accessory pathway. This is discussed in greater detail elsewhere. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome".) DIAGNOSIS https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 9/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate The diagnosis of the WPW pattern, which usually requires only a surface ECG, is typically prompted by an incidental finding on an ECG obtained for another clinical indication. Identification of a short PR interval and a delta wave is usually adequate to confirm the diagnosis of the WPW pattern. In some rare circumstances, invasive electrophysiology testing can be helpful in confirming the diagnosis of an accessory pathway or detecting patients with short effective refractory periods (<250 milliseconds), for example in competitive athletes. (See 'Electrocardiographic findings' below.) The diagnosis of WPW syndrome is typically made in a patient with a preexisting WPW pattern on an ECG who develops an arrhythmia that involves the accessory pathway, although some patients initially present with an arrhythmia and no known history of the WPW pattern. This diagnosis should be suspected in persons with an arrhythmia and a very rapid ventricular heart rate, particularly when a delta wave can be identified and particularly in children or young adults presenting with a paroxysmal arrhythmia. EVALUATION Electrocardiographic findings The hallmark of AV accessory pathway function during sinus rhythm is preexcitation in which depolarization of all or part of the ventricles occurs via an accessory pathway (ie, by direct myocardial activation) that is separate from the normal AV conduction system and that occurs earlier than expected after atrial depolarization. This results in shortening of the PR interval, a delta wave, and widening of the QRS complex. (See "General principles of asynchronous activation and preexcitation".) WPW pattern on ECG The classic ECG pattern of preexcitation in sinus rhythm is characterized by a fusion between conduction via the accessory pathway and the normal AV node/His-Purkinje system. The classic ECG pattern of preexcitation in sinus rhythm in persons with either the WPW pattern or WPW syndrome ( waveform 1 and waveform 2) has two major features: The PR interval is short (less than 0.12 seconds) due to rapid AV conduction through the accessory pathway and bypass of the AV node. The QRS complex consists of fusion between early and direct ventricular myocardial activation caused by preexcitation and the later ventricular activation resulting from transmission through the AV node and the infranodal conduction system to the ventricles. While beginning earlier than expected, the initial part of ventricular activation is slowed, and the upstroke of the QRS complex is slurred because of slow muscle-fiber-to-muscle- fiber conduction. This is termed a delta wave. The more rapid the conduction along the https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 10/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate accessory pathway, the greater the amount of myocardium depolarized via the accessory pathway, resulting in a more prominent or wider delta wave, and increasing prolongation of the QRS complex. Some accessory pathways do not conduct antegrade to the ventricles, but instead are able to conduct retrograde from the ventricle to the atrium. Because there is no antegrade conduction over the accessory pathway, the characteristic ECG findings of the WPW pattern are absent. The diagnosis in patients with a concealed accessory pathway can only be made following ventricular ectopy or ventricular pacing or during electrophysiologic testing. (See 'Normal AV conduction versus accessory AV pathway conduction' above and 'Electrophysiology studies (EPS)' below.) Preexcitation and delta waves may not be apparent in sinus rhythm in patients with WPW syndrome who have a left-lateral bypass tract as the antegrade route for conduction. In this setting, the time for the atrial impulse to reach the atrial insertion of the accessory pathway is longer than the time to reach the AV node ( waveform 6), thereby minimizing preexcitation. Delta waves can occasionally be seen in patients with some atypical conduction pathways that do not connect in the usual AV fashion. One such pathway, sometimes referred to as a "Mahaim fiber," is now better understood to be an atriofascicular pathway. These pathways are found along the right lateral AV groove and run as a long conduction fiber along the right ventricular free-wall to approximately (or possibly connect to) the distal portion of the right bundle branch. Atriofascicular pathways only conduct in the antegrade direction but can participate in antidromic tachycardia using the normal conduction tissues as the retrograde limb of a circuit. Clinical features of atypical conduction pathways are discussed separately. (See "Atriofascicular ("Mahaim") pathway tachycardia".) Exercise uncommonly causes an abrupt loss of preexcitation as the sinus rate increases ( waveform 7). This is a reassuring but not absolute indicator that the accessory pathway is unlikely to conduct atrial fibrillation (AF) with a rapid ventricular response. More often, preexcitation becomes inapparent because increasing sympathetic and decreasing vagal tone enhances AV nodal conduction. (See 'Risk stratification of asymptomatic patients with WPW pattern' below.) WPW pattern and ECG interpretation for other disorders The abnormal sequence of activation that occurs with electrical conduction via the accessory pathway gives rise to an abnormal sequence of repolarization, resulting in ST-T wave abnormalities. The vectors or direction of the secondary ST-T wave changes are usually directed opposite to the vectors of the delta wave and the QRS complex. As a result of the abnormal activation sequence, abnormalities https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 11/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate affecting the ventricles, such as ischemia, infarction, hypertrophy, and pericarditis, may not always be reliably diagnosed in the presence of a WPW pattern. Electrophysiology studies (EPS) Invasive EPS is used in asymptomatic patients with the WPW pattern as a risk-stratification tool, with ablation added if that risk is deemed to be high [11]. Before proceeding with EPS for this purpose, it may be possible to estimate risk in some cases by less-invasive means. (See 'Risk stratification of asymptomatic patients with WPW pattern' below.) The indications for EPS in patients with known or suspected WPW syndrome are still evolving. In most instances, EPS is not required to make the diagnosis of the WPW pattern or syndrome, but EPS is sometimes combined with mapping and transcatheter ablation of the accessory pathway for both diagnostic and therapeutic purposes during the same session. We proceed with EPS in the following situations (see 'Risk stratification of asymptomatic patients with WPW pattern' below): When the diagnosis is uncertain based on the surface ECG and other noninvasive testing. For risk stratification purposes when a higher risk would alter the approach to therapy. (See 'Risk stratification of asymptomatic patients with WPW pattern' below.) As part of a therapeutic catheter ablation procedure. In certain asymptomatic patients with a WPW pattern when there is a coexistent cardiac comorbidity (eg, cardiomyopathy, coronary artery disease, significant valvular disease, congenital heart defects, etc) and catheter ablation is being considered. The more difficult decision involves otherwise healthy patients with preexcitation on their ECG but no symptoms (ie, the WPW pattern) and no cardiac comorbidities. In such cases, the principle reasons for EPS are: To confirm the diagnosis if doubt exists. To determine if the accessory pathway is capable of supporting reentrant tachycardia. To measure the conduction characteristics of the accessory pathway in an effort to estimate the patient's risk for rapid conduction if an episode of AF were to develop in the future. DIFFERENTIAL DIAGNOSIS https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 12/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Differential diagnosis of ECG findings The ECG findings in persons with the WPW pattern can be similar to ECG findings seen in other cardiac conditions [48]: Myocardial infarction (MI) A negative delta wave (presenting as a Q wave) may mimic an MI pattern. Conversely, a positive delta wave may mask the presence of a previous MI. (See "ECG tutorial: Myocardial ischemia and infarction".) Ventricular premature beats (VPBs) or idioventricular rhythm Intermittent WPW may be mistaken for frequent VPBs. The WPW pattern is occasionally seen on alternate beats and may suggest ventricular bigeminy. If the WPW pattern persists for several beats, the rhythm may be misdiagnosed as an accelerated idioventricular rhythm. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation" and "ECG tutorial: Ventricular arrhythmias", section on 'Accelerated idioventricular rhythm'.) Bundle branch block The QRS duration is equal to or greater than 0.12 seconds because of preexcitation (ie, the delta wave). Preexcited beats are sometimes confused with left or right bundle branch block as a result. However, the terminal portion of the QRS is usually normal, due to normal conduction through the AV node and ventricular activation via the Purkinje system. This is in contrast to intraventricular conduction defects such as right or left bundle branch block in which the conduction delay occurs in either the terminal portion of or throughout the QRS complex. (See "Right bundle branch block", section on 'ECG findings and diagnosis' and "Left bundle branch block", section on 'ECG findings and diagnosis'.) Some patients with cardiomyopathy and certain congenital heart defects (eg, single ventricle) may have atrial enlargement combined with abnormal ventricular activation that can result in a pattern of "pseudo-preexcitation." Some cases of HCM may mimic a WPW pattern as the PR is often short and the QRS widened because of hypertrophy [49]. Differential diagnosis of supraventricular tachycardia The differential diagnosis for SVT is fairly extensive and is discussed in detail separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia'.) RISK STRATIFICATION OF ASYMPTOMATIC PATIENTS WITH WPW PATTERN Patients who initially present with the WPW pattern on a surface ECG but without a symptomatic arrhythmia represent a significant clinical challenge with regard to risk stratification and management. While the majority of such asymptomatic WPW patients (who are often young and https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 13/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate otherwise healthy) will remain asymptomatic [50], reported rates of symptomatic arrhythmia development have been as high as 20 percent over three years [30]. One approach to asymptomatic patients with WPW pattern is risk stratification using noninvasive tests and/or an electrophysiologic study (EPS) to identify those patients at greatest risk [11,46]. Mechanism of and risk factors for SCD in WPW The mechanism of SCD in patients with WPW syndrome is ventricular fibrillation (VF), which generally occurs during an episode of atrial fibrillation (AF) in which there is rapid conduction to the ventricle, leading to an excessively rapid ventricular response that degenerates into VF. Identifying asymptomatic patients at the greatest risk for VF would provide a rationale for more aggressive therapy (eg, catheter ablation). There is conflicting evidence as to which findings predict the development of symptoms and/or SCD. Some of the findings that have been suggested to predict a higher likelihood of symptoms include [11,46,50-52]: Short refractory period of the accessory pathway Short preexcited RR interval during AF Younger age Male gender Inducible AV reentrant (or reciprocating) tachycardia (AVRT) or AF during EPS Multiple accessory pathways Short preexcited RR interval during rapid atrial pacing Ebstein malformation The refractory period refers to the amount of time required after one conducted impulse for the accessory pathway (or any cardiac tissue) to "reset" and be able to conduct a subsequent impulse. This characteristic often defines how frequently an accessory pathway can conduct to the ventricle. The refractory period is usually similar to the shortest preexcited RR interval during AF, though the correlation is far from perfect. Approach to risk stratification In general, patients with asymptomatic ventricular preexcitation are at low risk of a cardiac arrest. Those patients who have had a cardiac arrest almost always experience symptoms of tachycardia first. Therefore, most patients who truly have no symptoms can simply be reassured and advised to notify their clinician immediately if they experience any rapid palpitation or syncope. At times however, patients seek further reassurance and can be evaluated further with additional risk stratification. Risk stratification of asymptomatic patients with the WPW pattern ( algorithm 1) can be performed noninvasively or via invasive EPS, though it must be emphasized that all risk-stratification schemes are imperfect and can be associated with false https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 14/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate positives as well as false negatives, especially in young patients [50]. Our approach to risk stratification is as follows: Begin with noninvasive evaluation Although the refractory period of an accessory pathway is usually measured during an EPS, patients with an accessory pathway that has a long refractory period can often be identified noninvasively. Intermittent loss of preexcitation (as detected by loss of delta wave on an ECG) suggests that the accessory pathway has a long refractory period and will not be able to conduct frequently enough during AF to produce VF. Intermittent preexcitation or loss of preexcitation may be seen in the following settings: Resting ECG At increased heart rates during exercise Ambulatory ECG monitoring for 24 to 48 hours Following intravenous administration of a sodium channel blocker, such as procainamide We proceed with risk stratification as follows ( |
For risk stratification purposes when a higher risk would alter the approach to therapy. (See 'Risk stratification of asymptomatic patients with WPW pattern' below.) As part of a therapeutic catheter ablation procedure. In certain asymptomatic patients with a WPW pattern when there is a coexistent cardiac comorbidity (eg, cardiomyopathy, coronary artery disease, significant valvular disease, congenital heart defects, etc) and catheter ablation is being considered. The more difficult decision involves otherwise healthy patients with preexcitation on their ECG but no symptoms (ie, the WPW pattern) and no cardiac comorbidities. In such cases, the principle reasons for EPS are: To confirm the diagnosis if doubt exists. To determine if the accessory pathway is capable of supporting reentrant tachycardia. To measure the conduction characteristics of the accessory pathway in an effort to estimate the patient's risk for rapid conduction if an episode of AF were to develop in the future. DIFFERENTIAL DIAGNOSIS https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 12/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Differential diagnosis of ECG findings The ECG findings in persons with the WPW pattern can be similar to ECG findings seen in other cardiac conditions [48]: Myocardial infarction (MI) A negative delta wave (presenting as a Q wave) may mimic an MI pattern. Conversely, a positive delta wave may mask the presence of a previous MI. (See "ECG tutorial: Myocardial ischemia and infarction".) Ventricular premature beats (VPBs) or idioventricular rhythm Intermittent WPW may be mistaken for frequent VPBs. The WPW pattern is occasionally seen on alternate beats and may suggest ventricular bigeminy. If the WPW pattern persists for several beats, the rhythm may be misdiagnosed as an accelerated idioventricular rhythm. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation" and "ECG tutorial: Ventricular arrhythmias", section on 'Accelerated idioventricular rhythm'.) Bundle branch block The QRS duration is equal to or greater than 0.12 seconds because of preexcitation (ie, the delta wave). Preexcited beats are sometimes confused with left or right bundle branch block as a result. However, the terminal portion of the QRS is usually normal, due to normal conduction through the AV node and ventricular activation via the Purkinje system. This is in contrast to intraventricular conduction defects such as right or left bundle branch block in which the conduction delay occurs in either the terminal portion of or throughout the QRS complex. (See "Right bundle branch block", section on 'ECG findings and diagnosis' and "Left bundle branch block", section on 'ECG findings and diagnosis'.) Some patients with cardiomyopathy and certain congenital heart defects (eg, single ventricle) may have atrial enlargement combined with abnormal ventricular activation that can result in a pattern of "pseudo-preexcitation." Some cases of HCM may mimic a WPW pattern as the PR is often short and the QRS widened because of hypertrophy [49]. Differential diagnosis of supraventricular tachycardia The differential diagnosis for SVT is fairly extensive and is discussed in detail separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia'.) RISK STRATIFICATION OF ASYMPTOMATIC PATIENTS WITH WPW PATTERN Patients who initially present with the WPW pattern on a surface ECG but without a symptomatic arrhythmia represent a significant clinical challenge with regard to risk stratification and management. While the majority of such asymptomatic WPW patients (who are often young and https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 13/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate otherwise healthy) will remain asymptomatic [50], reported rates of symptomatic arrhythmia development have been as high as 20 percent over three years [30]. One approach to asymptomatic patients with WPW pattern is risk stratification using noninvasive tests and/or an electrophysiologic study (EPS) to identify those patients at greatest risk [11,46]. Mechanism of and risk factors for SCD in WPW The mechanism of SCD in patients with WPW syndrome is ventricular fibrillation (VF), which generally occurs during an episode of atrial fibrillation (AF) in which there is rapid conduction to the ventricle, leading to an excessively rapid ventricular response that degenerates into VF. Identifying asymptomatic patients at the greatest risk for VF would provide a rationale for more aggressive therapy (eg, catheter ablation). There is conflicting evidence as to which findings predict the development of symptoms and/or SCD. Some of the findings that have been suggested to predict a higher likelihood of symptoms include [11,46,50-52]: Short refractory period of the accessory pathway Short preexcited RR interval during AF Younger age Male gender Inducible AV reentrant (or reciprocating) tachycardia (AVRT) or AF during EPS Multiple accessory pathways Short preexcited RR interval during rapid atrial pacing Ebstein malformation The refractory period refers to the amount of time required after one conducted impulse for the accessory pathway (or any cardiac tissue) to "reset" and be able to conduct a subsequent impulse. This characteristic often defines how frequently an accessory pathway can conduct to the ventricle. The refractory period is usually similar to the shortest preexcited RR interval during AF, though the correlation is far from perfect. Approach to risk stratification In general, patients with asymptomatic ventricular preexcitation are at low risk of a cardiac arrest. Those patients who have had a cardiac arrest almost always experience symptoms of tachycardia first. Therefore, most patients who truly have no symptoms can simply be reassured and advised to notify their clinician immediately if they experience any rapid palpitation or syncope. At times however, patients seek further reassurance and can be evaluated further with additional risk stratification. Risk stratification of asymptomatic patients with the WPW pattern ( algorithm 1) can be performed noninvasively or via invasive EPS, though it must be emphasized that all risk-stratification schemes are imperfect and can be associated with false https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 14/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate positives as well as false negatives, especially in young patients [50]. Our approach to risk stratification is as follows: Begin with noninvasive evaluation Although the refractory period of an accessory pathway is usually measured during an EPS, patients with an accessory pathway that has a long refractory period can often be identified noninvasively. Intermittent loss of preexcitation (as detected by loss of delta wave on an ECG) suggests that the accessory pathway has a long refractory period and will not be able to conduct frequently enough during AF to produce VF. Intermittent preexcitation or loss of preexcitation may be seen in the following settings: Resting ECG At increased heart rates during exercise Ambulatory ECG monitoring for 24 to 48 hours Following intravenous administration of a sodium channel blocker, such as procainamide We proceed with risk stratification as follows ( algorithm 1): We perform a resting 12-lead ECG in everyone. Unless there is intermittent preexcitation at rest, an exercise ECG test should be performed in all patients who are able to exercise on a treadmill. We perform ambulatory ECG monitoring only in patients who are unable to perform treadmill exercise (eg, young children). Only rarely do we perform sodium channel blocker challenge. The observation of an abrupt and unambiguous loss of preexcitation at faster sinus rates on an ECG, exercise testing, ambulatory ECG monitoring, or sodium channel blocker challenge is generally considered a sufficient sign that the accessory pathway has limited antegrade conduction potential and is unlikely to result in life-threatening ventricular rates during AF. Expert consensus is that these "low-risk" patients can usually be followed without invasive testing as long as they remain asymptomatic. If preexcitation persists at maximum heart rates during exercise testing, or is persistent during the entire period of ambulatory monitoring or sodium channel blocker challenge, it does not necessarily mean that the patient is "high-risk," but rather that the risk cannot be determined by noninvasive means. A decision to proceed to EPS in these indeterminate https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 15/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate cases for better resolution of accessory pathway profile must be made on a case-by-case basis with careful discussion between clinician and patient. Follow-up if needed with invasive EPS In patients whose noninvasive testing reveals persistent preexcitation, or for patients in whom noninvasive testing is not feasible or nondiagnostic, we proceed with invasive EPS. An alternative approach to risk stratification is to proceed directly to EPS as an initial means of risk stratification in all patients with an asymptomatic WPW ECG pattern [46]. Options for invasive EPS include the standard transvenous intracardiac EPS or, less commonly, a transesophageal atrial EPS. Among a cohort of 224 asymptomatic patients with ventricular preexcitation, 76 patients aged 35 years or less were found to have inducible AVRT or AF during EPS and were randomly assigned to catheter ablation (37 patients, median follow-up 27 months) of the accessory pathway or no therapy (35 patients, median follow-up 21 months) [53]. In the ablation group, only two patients (5 percent) had arrhythmic events, both due to a mechanism that was unrelated to the ablated accessory pathway (AV nodal reentrant tachycardia), while in the control group, 21 patients (60 percent) had arrhythmic events (VF in one patient, SVT in 15 patients, and AF in five patients). The five-year estimated incidence of arrhythmic events was significantly lower for patients treated with ablation than for controls (7 versus 77 percent). A 2015 systematic review of asymptomatic patients with the WPW pattern, which included patients from six studies (one randomized trial of ablation versus no ablation in 76 patients, and five prospective cohorts that included 883 patients who did not undergo ablation), reported the likelihood of arrhythmic events over a range of follow-up as long as eight years [54]. Among the 76 patients randomized to ablation or no ablation, the five-year Kaplan-Meier estimate of arrhythmic events was 7 percent in the ablation group compared with 77 percent in the group who did not undergo ablation. Among the 883 patients in the cohort studies who did not undergo ablation, most patients had an uneventful course, but up to 9 percent developed malignant AF (RR interval 250 milliseconds), and up to 2 percent experienced VF. In summary, initial risk-stratification with EPS successfully identified those with a higher likelihood of developing symptoms, and treatment of these high-risk patients with ablation reduced arrhythmic events [11]. However, life-threatening arrhythmias were rare in the absence of ablation and serious complications developed in 2 percent of patients undergoing risk stratification. Thus, it remains unknown whether initial risk stratification with EPS produces a net reduction in morbidity or mortality. A full discussion of the approach to accessory pathway ablation in asymptomatic patients is presented separately. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Catheter ablation'.) https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 16/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Wolff-Parkinson-White syndrome (The Basics)") Beyond the Basics topic (see "Patient education: Wolff-Parkinson-White syndrome (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definition Wolff-Parkinson-White (WPW) syndrome is a condition resulting from conduction via one or more accessory pathways that directly connects the atria and ventricles and bypasses the atrioventricular (AV) node. Individuals with this condition have a short PR interval and a widened QRS complex on their ECG and paroxysmal tachycardia. (See 'Introduction' above.) Manifest versus concealed pathways Most accessory pathways are capable of antegrade conduction (exhibiting either antegrade conduction alone or bidirectional conduction) from atrium to ventricle and thus manifest as WPW pattern. However, some https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 17/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate accessory pathways conduct only in a retrograde fashion from ventricle to atrium. When there is no antegrade conduction through the accessory pathway (ie, no preexcitation), the characteristic WPW ECG pattern is absent, and the pathway is described as "concealed." (See 'Normal AV conduction versus accessory AV pathway conduction' above.) Anatomy The accessory pathway may be located anywhere along the AV ring (groove) or in the septum. The most frequent locations are left lateral (50 percent), posteroseptal (30 percent), right anteroseptal (10 percent), and right lateral (10 percent). Up to 13 percent of individuals with preexcitation have more than one accessory pathway. (See 'Anatomy' above.) Prevalence The prevalence of a WPW pattern on the surface ECG is estimated at 0.13 to 0.25 percent in the general population. The WPW pattern on the ECG may be intermittent and may even disappear permanently over time, depending on the conduction properties of the accessory pathway. The prevalence of WPW syndrome (the WPW pattern plus tachyarrhythmia) is substantially lower than that of the WPW pattern alone, perhaps as low as 2 percent of patients with the WPW pattern on the surface ECG. (See 'Prevalence of WPW pattern' above and 'Prevalence of WPW syndrome' above.) ECG features The classic ECG pattern of preexcitation in sinus rhythm is characterized by a fusion between conduction via the accessory pathway and the normal AV node/His- Purkinje system, resulting in the following ECG characteristics (see 'Electrocardiographic findings' above): The PR interval is short (less than 0.12 seconds) due to rapid AV conduction through the accessory pathway and bypass of the AV node. The initial part of ventricular activation is slowed, and the upstroke of the QRS complex is slurred because of slow muscle-fiber-to-muscle-fiber conduction; this is termed a delta wave. The QRS complex is widened and consists of fusion between early ventricular activation caused by preexcitation with the later ventricular activation resulting from transmission through the AV node and the infranodal conduction system to the ventricles. WPW pattern versus syndrome The majority of patients with the WPW pattern on their ECG remain asymptomatic, although a small percentage of patients with the WPW pattern develop arrhythmias as a part of WPW syndrome. Most patients who develop an arrhythmia will present with palpitations, with syncope or SCD occurring much less frequently. (See 'Clinical manifestations' above.) https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 18/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Tachycardias Tachycardias associated with WPW syndrome can be classified into those in which the accessory pathway is necessary for initiation and maintenance of the tachycardia, and those in which the bypass tract acts as a "bystander," providing a route of conduction from the anatomic site of tachycardia origin to other regions of the heart (see 'Arrhythmias associated with WPW' above): AV reentrant (or reciprocating) tachycardia (AVRT) This is a reentrant tachycardia with an anatomically defined circuit that consists of two distinct pathways, the normal AV conduction system, and an AV accessory pathway, linked by common proximal (the atria) and distal (the ventricles) tissues. The two major forms of AVRT are orthodromic and antidromic AVRT, defined by the direction of conduction through the AV node and the accessory pathway. (See 'Tachycardias requiring an accessory pathway for initiation and maintenance' above and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Atrial fibrillation (AF) This arrhythmia occurs in 10 to 30 percent of persons with WPW syndrome, somewhat higher than might be expected given the low prevalence of coexisting structural heart disease. When atrial impulses are transmitted along the accessory pathway in AF, ventricular rates may exceed 300 beats per minute and can degenerate into ventricular fibrillation (VF). (See 'Atrial fibrillation' above.) Ventricular fibrillation In most cases, VF occurring in patients with WPW syndrome results from the rapid ventricular response during AF that has persisted and ultimately deteriorated into VF. Although the frequency with which AF with rapid AV conduction via an accessory pathway degenerates into VF is unknown, the incidence of sudden death in patients with WPW syndrome is quite low. (See 'Ventricular fibrillation and sudden death' above.) Diagnosis The diagnosis of the WPW pattern can nearly always be made by reviewing the surface ECG. In addition, in some rare circumstances invasive electrophysiology testing can be helpful in confirming the diagnosis of an accessory pathway. WPW syndrome is diagnosed following the development of an arrhythmia in a patient with a preexisting WPW pattern on an ECG. (See 'Diagnosis' above.) Differential diagnosis The ECG findings in persons with the WPW pattern can be similar to ECG findings seen in other cardiac conditions, including prior myocardial infarction, ventricular premature beats, idioventricular rhythm, and bundle branch block. (See 'Differential diagnosis of ECG findings' above.) https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 19/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Risk stratification for asymptomatic patients Our approach to risk stratification of asymptomatic patients with the WPW pattern is as follows ( algorithm 1) (see 'Approach to risk stratification' above): Initial noninvasive evaluation, including a resting 12-lead ECG in everyone and, unless there is intermittent preexcitation at rest, an exercise ECG test in all patients who are able to exercise on a treadmill. If patients are unable to exercise, ambulatory ECG monitoring and/or sodium channel blocker challenge are additional noninvasive risk stratification options. The observation of an abrupt and unambiguous loss of preexcitation at faster heart rates is generally considered a sufficient sign that the accessory pathway has limited antegrade conduction potential and the patient is considered "low-risk" for life-threatening ventricular rates. If preexcitation persists at maximum heart rates during exercise testing, or is persistent during the entire period of ambulatory monitoring or sodium channel blocker challenge, it does not necessarily mean that the patient is "high-risk," but rather that the risk cannot be determined by noninvasive means. A decision to proceed to electrophysiology study in these indeterminate cases for better resolution of accessory pathway profile must be made on a case-by-case basis with careful discussion between clinician and patient. (See 'Risk stratification of asymptomatic patients with WPW pattern' above and "Treatment of arrhythmias associated with the Wolff-Parkinson- White syndrome", section on 'Asymptomatic patients'.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wolff L, Parkinson J, White PD. Bundle-branch block with short P-R interval in healthy young people prone to paroxysmal tachycardia. 1930. Ann Noninvasive Electrocardiol 2006; 11:340. 2. Miller JM. Therapy of Wolff-Parkinson-White syndrome and concealed bypass tracts: Part I. J Cardiovasc Electrophysiol 1996; 7:85. 3. Kuck KH, Friday KJ, Kunze KP, et al. Sites of conduction block in accessory atrioventricular pathways. Basis for concealed accessory pathways. Circulation 1990; 82:407. 4. Milstein S, Sharma AD, Guiraudon GM, Klein GJ. An algorithm for the electrocardiographic localization of accessory pathways in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1987; 10:555. 5. Fitzpatrick AP, Gonzales RP, Lesh MD, et al. New algorithm for the localization of accessory atrioventricular connections using a baseline electrocardiogram. J Am Coll Cardiol 1994; https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 20/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 23:107. 6. Reddy GV, Schamroth L. The localization of bypass tracts in the Wolff-Parkinson-White syndrome from the surface electrocardiogram. Am Heart J 1987; 113:984. 7. Epstein AE, Kirklin JK, Holman WL, et al. Intermediate septal accessory pathways: electrocardiographic characteristics, electrophysiologic observations and their surgical implications. J Am Coll Cardiol 1991; 17:1570. 8. Colavita PG, Packer DL, Pressley JC, et al. Frequency, diagnosis and clinical characteristics of patients with multiple accessory atrioventricular pathways. Am J Cardiol 1987; 59:601. 9. Zachariah JP, Walsh EP, Triedman JK, et al. Multiple accessory pathways in the young: the impact of structural heart disease. Am Heart J 2013; 165:87. 10. Vidaillet HJ Jr, Pressley JC, Henke E, et al. Familial occurrence of accessory atrioventricular pathways (preexcitation syndrome). N Engl J Med 1987; 317:65. 11. Pediatric and Congenital Electrophysiology Society (PACES), Heart Rhythm Society (HRS), American College of Cardiology Foundation (ACCF), et al. PACES/HRS expert consensus statement on the management of the asymptomatic young patient with a Wolff-Parkinson- White (WPW, ventricular preexcitation) electrocardiographic pattern: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the Canadian Heart Rhythm Society (CHRS). Heart Rhythm 2012; 9:1006. 12. Deal BJ, Keane JF, Gillette PC, Garson A Jr. Wolff-Parkinson-White syndrome and supraventricular tachycardia during infancy: management and follow-up. J Am Coll Cardiol 1985; 5:130. 13. SCHIEBLER GL, ADAMS P Jr, ANDERSON RC. The Wolff-Parkinson-White syndrome in infants and children. A review and a report of 28 cases. Pediatrics 1959; 24:585. 14. LEV M, GIBSON S, MILLER RA. Ebstein's disease with Wolff-Parkinson-White syndrome; report of a case with a histopathologic study of possible conduction pathways. Am Heart J 1955; 49:724. 15. Cappato R, Schl ter M, Weiss C, et al. Radiofrequency current catheter ablation of accessory atrioventricular pathways in Ebstein's anomaly. Circulation 1996; 94:376. 16. Attenhofer Jost CH, Connolly HM, O'Leary PW, et al. Left heart lesions in patients with Ebstein anomaly. Mayo Clin Proc 2005; 80:361. 17. Gallagher JJ, Pritchett EL, Sealy WC, et al. The preexcitation syndromes. Prog Cardiovasc Dis https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 21/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 1978; 20:285. 18. Josephson ME. Preexcitation syndromes. In: Clinical Cardiac Electrophysiology, 4th, Lippinco t Williams & Wilkins, Philadelphia 2008. p.339. 19. Krahn AD, Manfreda J, Tate RB, et al. The natural history of electrocardiographic preexcitation in men. The Manitoba Follow-up Study. Ann Intern Med 1992; 116:456. 20. Kobza R, Toggweiler S, Dillier R, et al. Prevalence of preexcitation in a young population of male Swiss conscripts. Pacing Clin Electrophysiol 2011; 34:949. 21. Munger TM, Packer DL, Hammill SC, et al. A population study of the natural history of Wolff- Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989. Circulation 1993; 87:866. 22. Klein GJ, Yee R, Sharma AD. Longitudinal electrophysiologic assessment of asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. N Engl J Med 1989; 320:1229. 23. Mah DY, Sherwin ED, Alexander ME, et al. The electrophysiological characteristics of accessory pathways in pediatric patients with intermittent preexcitation. Pacing Clin Electrophysiol 2013; 36:1117. 24. Kiger ME, McCanta AC, Tong S, et al. Intermittent versus Persistent Wolff-Parkinson-White Syndrome in Children: Electrophysiologic Properties and Clinical Outcomes. Pacing Clin Electrophysiol 2016; 39:14. 25. Klein GJ, Gulamhusein SS. Intermittent preexcitation in the Wolff-Parkinson-White syndrome. Am J Cardiol 1983; 52:292. 26. SMITH RF. THE WOLFF-PARKINSON-WHITE SYNDROME AS AN AVIATION RISK. Circulation 1964; 29:672. 27. Fitzsimmons PJ, McWhirter PD, Peterson DW, Kruyer WB. The natural history of Wolff- Parkinson-White syndrome in 228 military aviators: a long-term follow-up of 22 years. Am Heart J 2001; 142:530. 28. Chiu SN, Wang JK, Wu MH, et al. Cardiac conduction disturbance detected in a pediatric population. J Pediatr 2008; 152:85. 29. Obeyesekere MN, Leong-Sit P, Massel D, et al. Risk of arrhythmia and sudden death in patients with asymptomatic preexcitation: a meta-analysis. Circulation 2012; 125:2308. 30. Pappone C, Santinelli V, Rosanio S, et al. Usefulness of invasive electrophysiologic testing to stratify the risk of arrhythmic events in asymptomatic patients with Wolff-Parkinson-White pattern: results from a large prospective long-term follow-up study. J Am Coll Cardiol 2003; 41:239. https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 22/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 31. Chen SA, Chiang CE, Tai CT, et al. Longitudinal clinical and electrophysiological assessment of patients with symptomatic Wolff-Parkinson-White syndrome and atrioventricular node reentrant tachycardia. Circulation 1996; 93:2023. 32. Calkins H, Sousa J, el-Atassi R, et al. Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test. N Engl J Med 1991; 324:1612. 33. Kay GN, Epstein AE, Dailey SM, Plumb VJ. Role of radiofrequency ablation in the management of supraventricular arrhythmias: experience in 760 consecutive patients. J Cardiovasc Electrophysiol 1993; 4:371. 34. Farshidi A, Josephson ME, Horowitz LN. Electrophysiologic characteristics of concealed bypass tracts: clinical and electrocardiographic correlates. Am J Cardiol 1978; 41:1052. 35. Massumi, RA . Familial Wolff-Parkinson-White syndrome with cardiomyopathy. Am J Med 1967; 43:931. 36. Gollob MH, Green MS, Tang AS, et al. Identification of a gene responsible for familial Wolff- Parkinson-White syndrome. N Engl J Med 2001; 344:1823. 37. Gollob MH, Seger JJ, Gollob TN, et al. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 2001; 104:3030. 38. Campbell RW, Smith RA, Gallagher JJ, et al. Atrial fibrillation in the preexcitation syndrome. Am J Cardiol 1977; 40:514. 39. Sharma AD, Klein GJ, Guiraudon GM, Milstein S. Atrial fibrillation in patients with Wolff- Parkinson-White syndrome: incidence after surgical ablation of the accessory pathway. Circulation 1985; 72:161. 40. Sung RJ, Castellanos A, Mallon SM, et al. Mechanisms of spontaneous alternation between reciprocating tachycardia and atrial flutter-fibrillation in the Wolff-Parkinson-White syndrome. Circulation 1977; 56:409. 41. Fujimura O, Klein GJ, Yee R, Sharma AD. Mode of onset of atrial fibrillation in the Wolff- Parkinson-White syndrome: how important is the accessory pathway? J Am Coll Cardiol 1990; 15:1082. 42. Timmermans C, Smeets JL, Rodriguez LM, et al. Aborted sudden death in the Wolff- Parkinson-White syndrome. Am J Cardiol 1995; 76:492. 43. Klein GJ, Bashore TM, Sellers TD, et al. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. N Engl J Med 1979; 301:1080. https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 23/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 44. Oren JW 4th, Beckman KJ, McClelland JH, et al. A functional approach to the preexcitation syndromes. Cardiol Clin 1993; 11:121. 45. Montoya PT, Brugada P, Smeets J, et al. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. Eur Heart J 1991; 12:144. 46. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. 47. Yee, R, Klein, et al. Tachycardia associated with accessory atrioventricular pathways. In: Card iac Electrophysiology, Zipes, DP, Jalife, J (Eds), WB Saunders, Philadelphia 1990. p.463. 48. Wang K, Asinger R, Hodges M. Electrocardiograms of Wolff-Parkinson-White syndrome simulating other conditions. Am Heart J 1996; 132:152. 49. Sternick EB. Familial pseudo-WPW syndrome. J Cardiovasc Electrophysiol 2009; 20:E62; author reply E63. 50. Etheridge SP, Escudero CA, Blaufox AD, et al. Life-Threatening Event Risk in Children With Wolff-Parkinson-White Syndrome: A Multicenter International Study. JACC Clin Electrophysiol 2018; 4:433. 51. Wellens HJ. Should catheter ablation be performed in asymptomatic patients with Wolff- Parkinson-White syndrome? When to perform catheter ablation in asymptomatic patients with a Wolff-Parkinson-White electrocardiogram. Circulation 2005; 112:2201. 52. Pappone C, Santinelli V. Should catheter ablation be performed in asymptomatic patients with Wolff-Parkinson-White syndrome? Catheter ablation should be performed in asymptomatic patients with Wolff-Parkinson-White syndrome. Circulation 2005; 112:2207. 53. Pappone C, Santinelli V, Manguso F, et al. A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-White syndrome. N Engl J Med 2003; 349:1803. 54. Al-Khatib SM, Arshad A, Balk EM, et al. Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e575. Topic 962 Version 41.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 24/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate GRAPHICS Terminology and anatomic connections of preexcitation pathways Old Proposed or commonly used Anatomic connections terminology terminology Kent bundle* Accessory AV connection or AV bypass Atrium to ventricle tract James fiber Atrionodal bypass tract Atrium to low AV node Atriofascicular bypass tract Atrium to bundle of His Mahaim fiber Atriofascicular bypass tract Atrium to bundle branch Nodofascicular bypass tract AV node to bundle branch Nodoventricular bypass tract AV node to ventricular tissue Fasciculoventricular bypass tract Bundle branch to ventricular tissue AV: atrioventricular. These bypass tracts result in delta waves and the Wolff-Parkinson-White syndrome. These bypass tracts result in the Lown-Ganong-Levine syndrome and enhanced AV nodal conduction. Graphic 53343 Version 6.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 25/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 12-lead electrocardiogram showing the Wolff-Parkinson- White pattern The 2 main electrocardiographic features of Wolff-Parkinson-White pattern include a short PR interval (<0.12 seconds) and a delta wave (arrows). The QRS complex is wide (>0.12 seconds) and represents a fusion beat; the initial portion (delta wave) results from rapid ventricular activation via the accessory pathway (preexcitation), while the termination of ventricular activation is via the normal conduction system, leading to a fairly normal terminal portion of the QRS. Graphic 75578 Version 10.0 ECG of sinus rhythm to Normal electrocardiogram (ECG) Normal sinus rhythm at a rate of 71 beats/minute, a P wave axis of 45 , and a PR interval of 0.15 seconds. https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 26/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate ECG: electrocardiogram. Courtesy of Morton Arnsdorf, MD. Graphic 58149 Version 5.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 27/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 12-lead electrocardiogram of a patient in sinus rhythm with Wolff-Parkinson-White pattern Nearly full preexcitation is manifest in normal sinus rhythm on the 12-lead electrocardiogram in this patient with a short accessory pathway refractory period. The ventricular complex in preexcitation is a fusion of the impulse that preexcites the ventricles due to rapid conduction through an accessory pathway and of the impulse that takes the usual route through the atrioventricular node; this fusion creates the delta wave that is characteristic of Wolff-Parkinson-White electrocardiogram pattern. Courtesy of Morton F Arnsdorf, MD. Graphic 76226 Version 9.0 ECG of sinus rhythm to Normal electrocardiogram (ECG) https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 28/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Normal sinus rhythm at a rate of 71 beats/minute, a P wave axis of 45 , and a PR interval of 0.15 seconds. ECG: electrocardiogram. Courtesy of Morton Arnsdorf, MD. Graphic 58149 Version 5.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 29/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 30/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Electrophysiology study (EPS) tracings of surface and intracardiac electrograms showing degeneration of orthodromic atrioventricular reciprocating tachycardia (AVRT) into atrial tachycardia Surface ECG leads I, AVF, and VI and intracardiac electrograms are simultaneously recorded. The first three QRS complexes represent an orthodromic atrioventricular reentrant tachycardia (AVRT). The |
syndromes. Cardiol Clin 1993; 11:121. 45. Montoya PT, Brugada P, Smeets J, et al. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. Eur Heart J 1991; 12:144. 46. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. 47. Yee, R, Klein, et al. Tachycardia associated with accessory atrioventricular pathways. In: Card iac Electrophysiology, Zipes, DP, Jalife, J (Eds), WB Saunders, Philadelphia 1990. p.463. 48. Wang K, Asinger R, Hodges M. Electrocardiograms of Wolff-Parkinson-White syndrome simulating other conditions. Am Heart J 1996; 132:152. 49. Sternick EB. Familial pseudo-WPW syndrome. J Cardiovasc Electrophysiol 2009; 20:E62; author reply E63. 50. Etheridge SP, Escudero CA, Blaufox AD, et al. Life-Threatening Event Risk in Children With Wolff-Parkinson-White Syndrome: A Multicenter International Study. JACC Clin Electrophysiol 2018; 4:433. 51. Wellens HJ. Should catheter ablation be performed in asymptomatic patients with Wolff- Parkinson-White syndrome? When to perform catheter ablation in asymptomatic patients with a Wolff-Parkinson-White electrocardiogram. Circulation 2005; 112:2201. 52. Pappone C, Santinelli V. Should catheter ablation be performed in asymptomatic patients with Wolff-Parkinson-White syndrome? Catheter ablation should be performed in asymptomatic patients with Wolff-Parkinson-White syndrome. Circulation 2005; 112:2207. 53. Pappone C, Santinelli V, Manguso F, et al. A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-White syndrome. N Engl J Med 2003; 349:1803. 54. Al-Khatib SM, Arshad A, Balk EM, et al. Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e575. Topic 962 Version 41.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 24/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate GRAPHICS Terminology and anatomic connections of preexcitation pathways Old Proposed or commonly used Anatomic connections terminology terminology Kent bundle* Accessory AV connection or AV bypass Atrium to ventricle tract James fiber Atrionodal bypass tract Atrium to low AV node Atriofascicular bypass tract Atrium to bundle of His Mahaim fiber Atriofascicular bypass tract Atrium to bundle branch Nodofascicular bypass tract AV node to bundle branch Nodoventricular bypass tract AV node to ventricular tissue Fasciculoventricular bypass tract Bundle branch to ventricular tissue AV: atrioventricular. These bypass tracts result in delta waves and the Wolff-Parkinson-White syndrome. These bypass tracts result in the Lown-Ganong-Levine syndrome and enhanced AV nodal conduction. Graphic 53343 Version 6.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 25/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 12-lead electrocardiogram showing the Wolff-Parkinson- White pattern The 2 main electrocardiographic features of Wolff-Parkinson-White pattern include a short PR interval (<0.12 seconds) and a delta wave (arrows). The QRS complex is wide (>0.12 seconds) and represents a fusion beat; the initial portion (delta wave) results from rapid ventricular activation via the accessory pathway (preexcitation), while the termination of ventricular activation is via the normal conduction system, leading to a fairly normal terminal portion of the QRS. Graphic 75578 Version 10.0 ECG of sinus rhythm to Normal electrocardiogram (ECG) Normal sinus rhythm at a rate of 71 beats/minute, a P wave axis of 45 , and a PR interval of 0.15 seconds. https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 26/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate ECG: electrocardiogram. Courtesy of Morton Arnsdorf, MD. Graphic 58149 Version 5.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 27/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 12-lead electrocardiogram of a patient in sinus rhythm with Wolff-Parkinson-White pattern Nearly full preexcitation is manifest in normal sinus rhythm on the 12-lead electrocardiogram in this patient with a short accessory pathway refractory period. The ventricular complex in preexcitation is a fusion of the impulse that preexcites the ventricles due to rapid conduction through an accessory pathway and of the impulse that takes the usual route through the atrioventricular node; this fusion creates the delta wave that is characteristic of Wolff-Parkinson-White electrocardiogram pattern. Courtesy of Morton F Arnsdorf, MD. Graphic 76226 Version 9.0 ECG of sinus rhythm to Normal electrocardiogram (ECG) https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 28/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Normal sinus rhythm at a rate of 71 beats/minute, a P wave axis of 45 , and a PR interval of 0.15 seconds. ECG: electrocardiogram. Courtesy of Morton Arnsdorf, MD. Graphic 58149 Version 5.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 29/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 30/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Electrophysiology study (EPS) tracings of surface and intracardiac electrograms showing degeneration of orthodromic atrioventricular reciprocating tachycardia (AVRT) into atrial tachycardia Surface ECG leads I, AVF, and VI and intracardiac electrograms are simultaneously recorded. The first three QRS complexes represent an orthodromic atrioventricular reentrant tachycardia (AVRT). The QRS complexes are narrow and there is retrograde activation of the atrium (P) which, based upon timing with the vertical line after the second QRS complex, begins at the distal coronary sinus (DCS) which is the site of earliest atrial activation and is consistent with a left lateral accessory pathway. After the third complex, the vertical line indicates atrial activation at the proximal coronary sinus (PCS) which is premature and has a different morphology (A'). This atrial premature beat initiates a rapid atrial tachycardia (*) and atrial activity now precedes the QRS complex. The atrial tachycardia has a wide complex because of antegrade conduction via the accessory pathway. HRA: high right atrium; HBEP: proximal His Bundle electrogram; HBED: distal His Bundle electrogram; MCS: mid coronary sinus; RVA: right ventricular apex. Graphic 65336 Version 3.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 31/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate ECG pre-excited atrial fibrillation 12-lead ECG showing atrial fibrillation in a patient with antegrade conduction through both the AV node and accessory pathway. The occasional narrow QRS complexes reflect conduction through the AV node, while the QRS complexes, with instantaneous rates close to 300 beats per minute, are due to antegrade conduction via accessory pathway (probably postero-septal based on the QRS morphology). AV: atrioventricular; ECG: electrocardiogram. Reproduced with permission from: Nathanson LA, McClennen S, Safran C, Goldberger AL. ECG Wave-Maven: Self-Assessment Program f Students and Clinicians. http://ecg.bidmc.harvard.edu. Graphic 117553 Version 1.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 32/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 12-lead electrocardiogram showing atrial flutter in preexcitation syndrome Atrial flutter is generated within the right atrium and the atrial impulses in this case are conducted to the ventricle by an accessory pathway. There is 1:1 conduction with a ventricular rate of 300 beats/min. The QRS complexes are widened or aberrant and have a bundle branch block morphology and a left axis deviation, suggesting the presence of an atriofascicular (Mahaim) accessory pathway. Courtesy of Morton Arnsdorf, MD. Graphic 78602 Version 4.0 Normal ECG https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 33/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 34/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate 12-lead electrocardiogram (ECG) showing a left lateral atrioventricular accessory pathway in a patient with Wolff-Parkinson-White (WPW) syndrome Electrocardiogram during sinus rhythm from a patient with a left lateral accessory pathway. Panel A: Normal PR interval and a fairly normal QRS complex. Panel B: With pacing from the coronary sinus at a site close to the accessory pathway, the QRS complexes are maximally preexcited. Graphic 59047 Version 5.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 35/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Electrocardiogram (ECG) strips showing loss of preexcitation with exercise in person with the Wolff-Parkinson-White (WPW) pattern Leads aVF, V1, and V5 from the surface ECG of a patient with Wolff- Parkinson-White pattern and a right anterior accessory pathway. Prior to exercise, the resting ECG shows preexcitation with a short PR interval, delta wave, and prolonged QRS interval. With exercise and a heart rate of 130 beats per minute, there is abrupt loss of preexcitation: the PR interval lengthens, the delta wave disappears, and the QRS complex morphology normalizes. Adapted from: Strasberg B, Ashley WW, Wyndham CR, et al. Am J Cardiol 1980; 45:745. Graphic 76833 Version 4.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 36/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Algorithmic approach to risk stratification of asymptomatic patients with Wolff-Parkinson-White ECG pattern ECG: electrocardiogram; EPS: electrophysiology studies; AVRT: atrioventricular reciprocating tachycardia; AF: atrial fibrillation; WPW: Wolff-Parkinson-White. Preexcitation on the surface ECG is identified by a short PR interval (less than 120 milliseconds) leading into QRS, which is widened with a slurred upstroke (delta wave). Preexcitation is defined as intermittent when an ECG at any point in time shows the loss of preexcitation. In patients who are unable to perform exercise testing (eg, very young patients), ambulatory ECG monitoring or, rarely, sodium channel blocker challenge with procainamide is an alternative to assess for persistent or intermittent preexcitation. All approaches to risk stratification in patients with ventricular preexcitation are imperfect and can be associated with false positives as well as false negatives. https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 37/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Options for invasive EPS include the standard transvenous intracardiac EPS or a transesophageal atrial EPS. Refer to the UpToDate topic on treatment of symptomatic arrhythmias in patients with WPW. For most asymptomatic patients with preexcitation and no high- risk features identified on EPS, particularly those over age 35 to 40 years, we suggest observation. However, in some asymptomatic patients, particularly children, some electrophysiologists discuss and/or proceed with catheter ablation as a therapeutic option even in the absence of high risk features. Refer to UpToDate content on treatment of WPW for additional information. Graphic 119379 Version 3.0 https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 38/39 7/6/23, 11:15 AM Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis - UpToDate Contributor Disclosures Luigi Di Biase, MD, PhD, FHRS, FACC Consultant/Advisory Boards: Abbott [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Baylis Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Biosense Webster [Ablation products]; Biotronik [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Boston Scientific [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Medtronic [Ablation products and cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]; Stereotaxis [Ablation products]; Zoll Medical [Cardiac devices, defibrillators, or pacemakers of left atrial appendage closure]. All of the relevant financial relationships listed have been mitigated. Edward P Walsh, MD No relevant financial relationship(s) with ineligible companies to disclose. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/wolff-parkinson-white-syndrome-anatomy-epidemiology-clinical-manifestations-and-diagnosis/print 39/39 |
7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Normal sinus rhythm and sinus arrhythmia : William H Sauer, MD : Brian Olshansky, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 10, 2022. INTRODUCTION Normal sinus rhythm (NSR) is the rhythm that originates from the sinus node and describes the characteristic rhythm of the healthy human heart. The rate in NSR is generally regular but will vary depending on autonomic inputs into the sinus node. When there is irregularity in the sinus rate, it is termed "sinus arrhythmia." A sinus rhythm faster than the normal range is called a sinus tachycardia, while a slower rate is called a sinus bradycardia. (See "Sinus tachycardia: Evaluation and management" and "Sinus bradycardia".) The sinoatrial (SA) node, due to its small mass, does not have a visible manifestation on the electrocardiogram (ECG). The behavior of the SA node, therefore, must be inferred from the atrial response. The upper right atrium is depolarized first, followed by the simultaneous depolarization of the remainder of the right and some of the left atrium, and finally by depolarization of the left atrial appendage. The blood supply and anatomy of the SA node along with the ECG characteristics of NSR and sinus arrhythmia will be discussed here. Abnormalities of SA nodal function are considered elsewhere. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Sinoatrial nodal pause, arrest, and exit block".) NORMAL SINUS HEART RATE The normal heart rate has been considered to be between 60 and 100 beats per minute, although there is some disagreement with regard to the normal rate in adults. The range th (defined by 1st and 99 percentiles) is between 43 and 102 beats per minute in men and https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 1/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate between 47 and 103 beats per minute in women ( table 1) [1-3]. There is also important variability in age in young children. The normal heart rate is 110 to 150 beats per minute in infants, with gradual slowing over the first six years of life. A variety of pharmacologic agents and physiologic conditions can result in changes to the normal sinus heart rate. These conditions are discussed in greater detail separately. (See "Sinus tachycardia: Evaluation and management", section on 'Etiology and clinical syndromes' and "Sinus bradycardia", section on 'Etiology'.) The normal heart rate increases with exertion and decreases following the cessation of activity. The rate at which the heart rate returns to baseline following exercise can have prognostic importance, a concept which is discussed in greater detail elsewhere. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Heart rate response to exercise' and "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Heart rate recovery after exercise'.) ANATOMY The sinoatrial (SA) node is located high (superiorly) in the right atrium at the junction of the crista terminalis (a thick band of atrial muscle at the border of the atrial appendage) and the superior vena cava. The SA node is located beneath the epicardial surface of the crista terminalis; there is a layer of atrial muscle between the SA node and the endocardium so that it does not occupy the entire thickness of the atrial myocardium. Human histologic studies have demonstrated that the SA node has a crescent-like shape with an average length of 13.5 mm [4]. A characteristic feature of the SA node is extensive connective tissue, mainly collagen and fibroblasts, enmeshed with specialized cells capable of pacemaking activity. All of these cells within the SA node are capable of pacemaker activity, and depending on autonomic activation, the origin of the electrical activity can shift from one area of the SA node to another (superiorly during predominant sympathetic activation and more inferiorly during predominant parasympathetic activation). Studies have described a collection of cells, known as the paranodal cells, which are electrically and histologically distinct from the SA node [5]. These cells are thought to facilitate electrical conduction from the SA node to the rest of the atrium and have been hypothesized as a source of some of the more common atrial tachycardias originating from the cristae terminalis area. (See "Focal atrial tachycardia", section on 'Sites of origin'.) While it may appear that the electrical signals from the SA node to the atrial periphery can exit randomly, there appear to be preferential pathways of conduction from the sinus pacemaker cells to the atrium [6]. Whether these are functional or anatomical exit paths remains unclear. https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 2/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate The conduction velocity within the SA node is very slow compared with non-nodal atrial tissue. This is a result of poor electrical coupling arising from the relative paucity of gap junctions in the center of the node compared with the periphery [7]. SA nodal dysfunction may result from abnormalities in impulse generation or in conduction across the paranodal cells. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Sinoatrial nodal pause, arrest, and exit block".) BLOOD SUPPLY Historically, studies had suggested that over 90 percent of hearts have only one arterial branch to the SA node, and common wisdom was that the right coronary artery supplied the SA node in approximately 55 percent of hearts [8]. More recent data, however, suggest that the SA nodal artery may take one of six different routes, and two or more branches to the node may be present in approximately 54 percent of hearts [8]. This suggests that collateral blood supplies are common and perhaps explains the rarity of infarction involving the SA node. However, sinus node injury may be seen as a complication of left atrial ablation depending on the course of the SA nodal artery relative to the atrial tissue targeted with ablation [9,10]. ELECTROCARDIOGRAPHIC CHARACTERISTICS OF NSR P wave duration and amplitude The P wave is normally less than 120 milliseconds in duration and under 0.15 or 0.20 mV (or in some texts 0.25 mV) in height in standard lead II, with the permissible maximum varying according to the lead [11]. The terminal component in lead V1 should be less than 0.04 seconds long and 0.1 mV (1 mm) deep. Atrial repolarization usually is not seen on the electrocardiogram. (See "ECG tutorial: Basic principles of ECG analysis", section on 'P wave'.) P wave axis and morphology A normal P wave axis (0 to +90 ) and morphology help define normal sinus rhythm on the ECG. The normal axis results in the following P wave characteristics on the ECG ( waveform 1): Upright in leads I, II and usually aVF Inverted in aVR Upright, biphasic or inverted in III and aVL The right to left activation results in P waves that are upright or biphasic in V1 and V2, and upright in V3 through V6 https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 3/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate The P wave duration and morphology may be abnormal during NSR, usually reflecting atrial disease or atrial electrical conduction abnormality. A brief description follows with a more comprehensive discussion presented separately. (See "ECG tutorial: Chamber enlargement and hypertrophy".) Left atrial enlargement The ECG pattern of "left atrial enlargement" (LAE) lacks precision since it can arise from dilatation, hypertrophy, or an electrical conduction defect. The left atrium is a leftward and posterior structure, so LAE increases the leftward and posterior vectors and, when there is an associated intraatrial conduction delay, prolongs the duration of the P wave. The ECG criteria for LAE reflect these events ( waveform 2): The P wave is wide in lead II ( 120 milliseconds) and is usually notched in I and II. The P duration/PR segment duration is greater than 1.6 [12]. The terminal P wave in lead V1 is deep and delayed with the negative deflection being greater than 40 milliseconds in duration and/or 0.1 mV (1 mm) in height. The Morris index of the P terminal force is the product of the amplitude and duration of the terminal portion of the P wave in V1, and a value of 40 mV-millisecond suggests left atrial enlargement [13]. A negative P duration in V1 divided by the PR segment that is 1.0 has also been suggested as a criterion for LAE [14]. The axis of the late component is often to the left (40 or less). Right atrial enlargement Similar to LAE, the ECG pattern of right atrial enlargement (RAE) lacks precision as RAE may arise from dilatation, hypertrophy, or a conduction defect. The right atrium is a rightward and anterior structure, so RAE results in an increase in the anterior, rightward, and inferior forces of early atrial activation (which, as noted above, begins in the right atrium). This leads to the following pattern of right atrial enlargement ( waveform 2): Prominent P waves (0.2 mV [2 mm] or greater in height) in the limb leads, particularly II and aVF, and in an anterior lead such as V1. The initial P force in lead V1 is often 60 mV-millisecond. The P wave duration is 110 milliseconds or less with an axis of 65 or more. Biatrial enlargement Biatrial enlargement has characteristics of both right atrial and left atrial abnormalities. The right atrial abnormality increases the P wave amplitude in the appropriate leads, and the left atrial abnormality will broaden and notch the P waves and may increase the terminal force of the P waves in V1 ( waveform 2). https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 4/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate The PR interval The normal PR interval is 120 to 200 milliseconds. The PR interval tends to shorten as the heart rate increases due to rate-related shortening of action potentials and perhaps the effects of the autonomic nervous system on the atrioventricular (AV) node. Although there is some difference between small and large adults, the maximum PR interval is: 170 milliseconds for sinus rates over 130 beats per minute 180 to 190 milliseconds for rates between 100 and 130 beats per minute 200 milliseconds for rates between 70 and 100 beats per minute 210 milliseconds for rates slower than 70 beats per minute Children have shorter upper limits of normal for PR intervals; 0.14 seconds is a useful figure to remember under age 14, although the PR interval may be somewhat longer at slow rates and somewhat shorter at fast rates. The PR interval is independent of whether or not sinus rhythm is present. Normal sinus rhythm can be present even in the presence of complete heart block. (See "Third-degree (complete) atrioventricular block".) SINUS ARRHYTHMIA Sinus arrhythmia is defined as an irregularity in the rate of normal sinus rhythm. Sinus arrhythmia is considered present when there is a variation in the P-P interval by 0.12 seconds (120 milliseconds) or more but atrial activation appears to be occurring via the sinus node. Occasionally, there can be irregularity in the sinus rate, but the P-wave morphology varies and this can be consistent with "wandering atrial pacemaker" discussed elsewhere. There are three types of sinus arrhythmia: Respiratory, or phasic Nonrespiratory, or nonphasic Nonrespiratory, ventriculophasic sinus arrhythmia Respiratory type Respiratory sinus arrhythmia is a common, benign, and usually normal phenomenon that is related mechanistically to alternations in autonomic input directly and due to changes in cardiac filling during respiration. Respiratory sinus arrhythmia has been associated with obesity, diabetes mellitus, and hypertension. Some studies suggest that respiratory sinus arrhythmia is the result of these conditions, while others have documented a reduced respiratory sinus arrhythmia among individuals prior to the onset of disease. While severe respiratory sinus arrhythmia has been associated with several systemic conditions, for https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 5/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate the most part, respiratory sinus arrhythmia is benign and does not require additional cardiac evaluation. During the respiratory cycle, inspiration reflexively inhibits vagal tone, thereby increasing the sinus rate, while with expiration vagal tone rises to its previous state, and the rate declines ( waveform 3) [15]. This type of sinus arrhythmia disappears with breath holding. However, stimulation of the carotid baroreceptors by neck suction during breath holding will restore sinus arrhythmia, suggesting that the autonomic changes responsible for sinus arrhythmia can also be due to baroreflex stimulation. Baroreceptor stimulation may result from cyclic alterations in arterial blood pressure induced by the respiratory effect on venous return [16]. Respiratory sinus arrhythmia also appears to be less prominent as people age. As an example, in a study of 24 healthy volunteers without evidence of cardiovascular disease or risk factors for cardiovascular disease, respiratory sinus arrhythmia in older subjects (age 59 to 71 years, n = 15) was less than 20 percent of that in younger subjects (<31 years of age, n = 9) [17]. A possible reason for this observation is an age-related decrease in carotid distensibility and baroreflex sensitivity, without a change in resting vagal tone. Other factors may contribute to respiratory sinus arrhythmia. These include sympathetic mechanisms, elevations in arterial PCO2 that increase the magnitude of respiratory sinus arrhythmia, probably via a direct effect on the medulla, and drugs that increase vagal tone, such as morphine or digitalis [18-21]. By contrast, hypocapnia caused by voluntary hyperventilation reduces sinus arrhythmia [19]. Sinus arrhythmia is also reduced in diabetes mellitus, perhaps reflecting autonomic dysfunction [22]. In some subjects, autonomic changes during respiration cause the activation within the SA node to change, leading to subtle changes in P wave morphology and the PR interval. If depression of the SA node is sufficient, ectopic atrial pacemakers may occur; in this setting, prominently different P waves may be seen. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Wandering atrial pacemaker' and "Multifocal atrial tachycardia", section on 'Definition, pathogenesis, and prevalence'.) Nonrespiratory type Nonrespiratory sinus arrhythmia differs in that the acceleration and deceleration of the SA node is not related to the respiratory cycle. This form of sinus arrhythmia can occur in the normal heart, in the diseased heart, or after digitalis intoxication. Ventriculophasic type A ventriculophasic sinus arrhythmia occurs most often in patients with third-degree AV block, but it can also be seen after a compensatory pause induced by a premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations). This arrhythmia is characterized by intermittent https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 6/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate differences in the PP intervals based upon their relationship to the QRS complex. The two P waves surrounding a QRS complex have a shortened interval (ie, they occur at a faster rate) when compared with two P waves that occur sequentially without an intervening QRS complex ( waveform 4). The cause is not fully understood but seems to be related to increased filling during the long cycle; this is followed by a forceful systole and increased stroke volume which, in turn, trigger a baroreceptor response. In orthotopic cardiac transplantation, ventriculophasic arrhythmia is absent despite intact vagal innervation to the atrial remnant, which suggests that the lack of pulsatile blood flow in the SA node may contribute to the absence of the ventriculophasic arrhythmias [23]. Heart rate turbulence (HRT) is based on the evaluation of ventriculophasic arrhythmia following a PVC and describes the short-term fluctuation in sinus cycle length that follows such a beat. This is discussed in greater detail separately. (See "Evaluation of heart rate variability", section on 'Heart rate turbulence'.) SUMMARY AND RECOMMENDATIONS Normal sinus rhythm (NSR) is the characteristic rhythm of the healthy human heart. NSR is considered to be present if the heart rate is in the normal range, the P waves are normal on the ECG, and the rate does not vary significantly. (See 'Introduction' above.) The sinus node is located high (superiorly) in the right atrium at the junction of the crista terminalis, a thick band of atrial muscle at the border of the atrial appendage, and the superior vena cava. Human histologic studies have demonstrated that the sinus node has a crescent-like shape with an average length of 13.5 mm. A collection of cells known as the paranodal cells, which are electrically and histologically distinct from the sinus node, are thought to facilitate electrical conduction from the sinus node to the rest of the atrium. (See 'Anatomy' above.) The blood supply to the sinoatrial (SA) node is complex as the SA nodal artery may take one of six different routes, and two or more branches to the node may be present in more than 50 percent of the population. This suggests that collateral blood supplies are common and perhaps explains the rarity of infarction of the SA node. (See 'Blood supply' above.) The P wave is normally less than 0.12 seconds in duration and under 0.15 or 0.20 mV (or in some texts 0.25 mV) in standard lead II, with the permissible maximum varying according to the lead. The terminal component in lead V1 should be less than 0.04 seconds long and 1 mm deep. (See 'P wave duration and amplitude' above.) https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 7/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate A normal P wave axis (0 to +90 ) and morphology help define the normal sinus mechanism on the ECG. (See 'P wave axis and morphology' above.) The normal PR interval is 120 to 200 milliseconds. The PR interval tends to shorten as the heart rate increases due to rate-related shortening of action potentials and perhaps the effects of the autonomic nervous system on the AV node. (See 'The PR interval' above.) If the heart rate is in the normal range and the P waves are normal on the ECG but the R-R interval is variable, the rhythm is called sinus arrhythmia. The formal definition of sinus arrhythmia is a variation in the P-P interval by 0.12 seconds (120 milliseconds) or more in the presence of normal P waves and the usual PR interval. (See 'Sinus arrhythmia' above.) There are three types of sinus arrhythmia: respiratory, or phasic; and nonrespiratory, or nonphasic. Respiratory sinus arrhythmia is common, usually normal, and decreases with age. Respiratory sinus arrhythmia results from changes in autonomic tone during the respiratory cycle. Inspiration reflexively inhibits vagal tone, thereby increasing the sinus rate. With expiration, vagal tone rises to its previous state, and the rate declines ( waveform 3). In some subjects, autonomic change during respiration causes the pacemaker to change location within the SA node, leading to subtle changes in P wave morphology and the PR interval. If depression of the SA node is sufficient, ectopic atrial pacemakers may occur. (See 'Respiratory type' above.) Nonrespiratory sinus arrhythmia differs in that the acceleration and deceleration of the SA node is not related to the respiratory cycle. This form of sinus arrhythmia can occur in the normal heart, in the diseased heart, or after digitalis intoxication. Ventriculophasic sinus arrhythmia occurs in patients with third-degree atrioventricular (AV) block but can also be seen after a compensatory pause induced by a PVC. This arrhythmia is characterized by intermittent differences in the PP intervals based upon their relationship to the QRS complex. The two P waves surrounding a QRS complex have a shortened interval (ie, they occur at a faster rate) when compared with two P waves that occur sequentially without an intervening QRS complex ( waveform 4). (See 'Nonrespiratory type' above.) Respiratory sinus arrhythmia by itself does not require any specific cardiac evaluation. (See 'Sinus arrhythmia' above.) Use of UpToDate is subject to the Terms of Use. https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 8/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate REFERENCES 1. Spodick DH. Normal sinus heart rate: sinus tachycardia and sinus bradycardia redefined. Am Heart J 1992; 124:1119. 2. Spodick DH, Raju P, Bishop RL, Rifkin RD. Operational definition of normal sinus heart rate. Am J Cardiol 1992; 69:1245. 3. Mason JW, Ramseth DJ, Chanter DO, et al. Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 2007; 40:228. 4. S nchez-Quintana D, Cabrera JA, Farr J, et al. Sinus node revisited in the era of electroanatomical mapping and catheter ablation. Heart 2005; 91:189. 5. Chandler NJ, Greener ID, Tellez JO, et al. Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation 2009; 119:1562. 6. Stiles MK, Brooks AG, Roberts-Thomson KC, et al. High-density mapping of the sinus node in humans: role of preferential pathways and the effect of remodeling. J Cardiovasc Electrophysiol 2010; 21:532. 7. Boyett MR, Honjo H, Kodama I. The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res 2000; 47:658. 8. Kawashima T, Sasaki H. The morphological significance of the human sinuatrial nodal branch (artery). Heart Vessels 2003; 18:213. 9. Hai JJ, Mulpuru SK, Williamson EE, et al. Sinus nodal dysfunction after left atrial flutter ablation: a preventable complication. Circ Arrhythm Electrophysiol 2014; 7:360. 10. Killu AM, Fender EA, Deshmukh AJ, et al. Acute Sinus Node Dysfunction after Atrial Ablation: Incidence, Risk Factors, and Management. Pacing Clin Electrophysiol 2016; 39:1116. 11. Hancock EW, Deal BJ, Mirvis DM, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009; 53:992. 12. MACRUZ R, PERLOFF JK, CASE RB. A method for the electrocardiographic recognition of atrial enlargement. Circulation 1958; 17:882. 13. MORRIS JJ Jr, ESTES EH Jr, WHALEN RE, et al. P-WAVE ANALYSIS IN VALVULAR HEART DISEASE. Circulation 1964; 29:242. https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 9/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate 14. Waggoner AD, Adyanthaya AV, Quinones MA, Alexander JK. Left atrial enlargement. Echocardiographic assessment of electrocardiographic criteria. Circulation 1976; 54:553. 15. Coker R, Koziell A, Oliver C, Smith SE. Does the sympathetic nervous system influence sinus arrhythmia in man? Evidence from combined autonomic blockade. J Physiol 1984; 356:459. 16. Piepoli M, Sleight P, Leuzzi S, et al. Origin of respiratory sinus arrhythmia in conscious humans. An important role for arterial carotid baroreceptors. Circulation 1997; 95:1813. 17. Kaushal P, Taylor JA. Inter-relations among declines in arterial distensibility, baroreflex function and respiratory sinus arrhythmia. J Am Coll Cardiol 2002; 39:1524. 18. Taylor JA, Myers CW, Halliwill JR, et al. Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans. Am J Physiol Heart Circ Physiol 2001; 280:H2804. 19. Sasano N, Vesely AE, Hayano J, et al. Direct effect of Pa(CO2) on respiratory sinus arrhythmia in conscious humans. Am J Physiol Heart Circ Physiol 2002; 282:H973. 20. Al-Ani M, Forkins AS, Townend JN, Coote JH. Respiratory sinus arrhythmia and central respiratory drive in humans. Clin Sci (Lond) 1996; 90:235. 21. Hrushesky WJ, Fader D, Schmitt O, Gilbertsen V. The respiratory sinus arrhythmia: a measure of cardiac age. Science 1984; 224:1001. 22. Smith SA. Reduced sinus arrhythmia in diabetic autonomic neuropathy: diagnostic value of an age-related normal range. Br Med J (Clin Res Ed) 1982; 285:1599. 23. de Marchena E, Colvin-Adams M, Esnard J, et al. Ventriculophasic sinus arrhythmia in the orthotopic transplanted heart: mechanism of disease revisited. Int J Cardiol 2003; 91:71. Topic 1073 Version 27.0 https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 10/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate GRAPHICS Normal heart rates in adults based on age and sex HR (beats per minute) Age All Male Female (years) N Mean 1%-99% N Mean 1%-99% N Mean 1%-99% 20-29 6086 67 43-98 3127 64 42-99 2959 69 46-99 30-39 9569 69 46-100 4605 67 44-99 4964 70 48-100 40-49 15,392 69 46-101 7104 68 45-101 8288 70 48-102 50-59 18,578 68 46-102 9936 68 45-102 8642 69 47-102 60-69 16,585 67 44-102 9457 65 42-102 7128 68 46-101 70-79 8432 65 43-101 4509 64 42-102 3923 67 44-101 80-89 2259 65 44-101 1001 63 41-98 1258 67 46-102 90-99 119 70 43-146 58 64 43-95 81 72 44-147 Normal heart rate values (with range from 1st to 99th percentile) for heart rate (beats/minute) in 77,276 healthy adults according to age and gender. %: percent; HR: heart rate. Data from: Mason JW, Ramseth DJ, Chanter DO, et al. Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 2007; 40:228. Graphic 77746 Version 4.0 https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 11/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate Normal ECG Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 12/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate Electrocardiograms showing atrial enlargement P wave morphology with atrial enlargement in leads I, II, and V1. The P waves in left atrial enlargement (left panel) are wide (>0.12 seconds) and notched in leads I and II, and the terminal segment has a negative deflection that is deep and delayed in V1. In right atrial enlargement (middle panel), the P wave amplitude is increased (0.28 mV) in lead II. Biatrial enlargement (right panel) has characteristics of both atrial abnormalities: the P wave amplitude (0.22 mV) and duration (0.12 seconds) are increased in lead II, and there is deep terminal negativity in V1. Courtesy of Morton Arnsdorf, MD. Graphic 64928 Version 5.0 https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 13/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate Electrocardiogram (ECG) rhythm strip demonstrating respiratory sinus arrhythmia Lead II showing normal sinus rhythm with sinus arrhythmia in a healthy 26 year-old woman. Note the marked variation in the P-P intervals induced by respiration. Courtesy of Morton Arnsdorf, MD. Graphic 65949 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 14/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate Electrocardiographic (ECG) rhythm strip demonstrating ventriculophasic sinus arrhythmia Complete AV block is seen as evidenced by the AV dissociation. A junctional escape rhythm sets the ventricular rate at 45 bpm. The PP intervals vary because of ventriculophasic sinus arrhythmia; this is defined when the PP interval that includes a QRS is shorter than a PP interval that excludes a QRS. The QRS generates a strong enough pulse to activate the carotid sinus mechanism, which slows the subsequent PP interval. AV: atrioventricular. With permission of Dr. Frank Yanowitz, University of Utah, from the Alan E. Lindsay ECG Learning Center in Cyberspace. Graphic 54964 Version 6.0 https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 15/16 7/6/23, 11:16 AM Normal sinus rhythm and sinus arrhythmia - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/normal-sinus-rhythm-and-sinus-arrhythmia/print 16/16 |
7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinoatrial nodal pause, arrest, and exit block : Munther K Homoud, MD : Brian Olshansky, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 21, 2022. INTRODUCTION The sinoatrial (SA) node represents the integrated activity of pacemaker cells, sometimes called P cells, in a compact region at the junction of the high right atrium and the superior vena cava. Perinodal cells, sometimes called transitional or (T) cells, transmit the electrical impulse from the SA node to the right atrium. Each of these cell types has distinct expression profiles of ion channels and gap junctions. Given the architecture of the SA node, SA nodal dysfunction typically results from either abnormalities in impulse generation by the P cells or abnormalities in conduction across the T cells. SA nodal dysfunction is more commonly an acquired condition, but in some patients it can be inherited, with gene mutations having been described in some forms of inherited SA nodal dysfunction [1]. Patients with SA nodal dysfunction may be asymptomatic or highly symptomatic as in cases of sinus node dysfunction (SND). Sinoatrial nodal pauses, arrest, and exit block will be discussed here. Additional details regarding the anatomy and electrophysiology of the SA node, as well as a discussion of the SND, are presented separately. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history".) ETIOLOGY Sinus pause, arrest, and exit block may arise from hyperkalemia; excessive vagal tone; ischemic, inflammatory, or infiltrative or fibrotic disease of the SA node; sleep apnea; certain drugs (eg, https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 1/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate digitalis). The causes of SND are discussed in detail elsewhere. (See "Clinical manifestations of hyperkalemia in adults" and "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Etiology' and "Obstructive sleep apnea and cardiovascular disease in adults", section on 'Other arrhythmias' and "Cardiac arrhythmias due to digoxin toxicity", section on 'Sinus bradycardia, tachycardia, block, and arrest'.) In patients receiving one or more agents that depress SA node and atrioventricular (AV) node function, a syndrome of bradycardia, renal failure, AV block, shock, and hyperkalemia (BRASH), has been described [2,3]. Patients with BRASH are generally taking therapeutic doses of SA and AV node blocking medications, and the level of hyperkalemia may be mild. However, the severity of bradycardia (caused by sinus arrest and/or AV block) is generally greater than expected for either the dose/level of SA and AV node blocker or the level of hyperkalemia. TYPES OF SA NODAL DYSFUNCTION Sinus pause or arrest A sinus pause or arrest is defined as the transient absence of sinus P waves on the electrocardiogram (ECG) that may last from two seconds to several minutes ( waveform 1). This abnormality is an alteration in discharge by the SA pacemaker; as a result, the duration of the pause has no arithmetical relationship to the basic sinus rate (ie, the cycle length of the pause is not a multiple of the basic sinus cycle length as would occur with 2:1 or 3:1 SA nodal block). The pause or arrest often allows escape beats or rhythms to occur, but lower pacemakers may be sluggish or even absent in SND. A pause that is two seconds and perhaps somewhat longer does not necessarily indicate disease, since it can occur in the normal heart [4,5]. Longer episodes of sinus arrest can produce symptoms of dizziness, presyncope, syncope, and, rarely, death. SA nodal exit block SA nodal exit block occurs as a result of interference with the delivery of impulses from the SA node to its neighboring atrial tissue. This results in the absence of a P wave on the surface ECG since the P wave is the only manifestation of SA nodal activity. Following the convention for AV nodal block, SA nodal exit block can be classified as first, second, or third degree. This problem is most easily conceptualized as having three components: A relatively constant input The input is from the SA nodal pacemaker, which is not seen on the surface ECG. The behavior of the SA nodal pacemaker is, as noted above, inferred from the P waves of atrial activation. The rate or cycle length of the input can be presumed from portions on the ECG where normal P-P cycles are observed. https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 2/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate An area across which block occurs Exit block is thought to involve the perinodal T cells. The type of exit block in the perinodal tissues must be inferred from the output or response, that is, from the P waves. An output The P wave abnormalities reflect the type of exit block which is present. First degree SA nodal exit block reflects a slowing of impulse exit but there is still 1:1 conduction. This abnormality cannot be recognized on the ECG recorded from the body surface. Second degree SA nodal exit block has two types: Type I (Wenckebach type) is characterized by progressively decreasing P-P intervals prior to a pause caused by a dropped P wave; the pause has a duration that is less than two P-P cycles ( waveform 2). The mechanisms of Wenckebach conduction are considered elsewhere. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)".) In type II exit block, the P-P output is an integer multiple of the presumed sinus pacemaker input (eg, 2:1, 3:1, 4:1). Therefore the P-P cycle length surrounding the pause is a multiple of the normal P-P interval ( waveform 3). Third degree SA nodal exit block prevents sinus node pacemaker impulses from reaching the right atrium. This disorder cannot be distinguished from sinus arrest because the P-wave recorded on the surface ECG is not a direct measure of sinus node activity, only of atrial depolarization (which will be absent). Variants of SA nodal dysfunction Sinus arrhythmia Sinus arrhythmia is a term that describes small changes in the sinus cycle length. The formal definition of sinus arrhythmia is a variation in the P-P interval by 0.12 sec (120 msec) or more in the presence of normal P waves and the usual PR interval ( waveform 4), or a difference of 10 percent or greater between the longest and shortest P-P intervals. Sinus arrhythmia is more common in the young and also in those exposed to digoxin or morphine, while it is less frequently seen in older patients and those with diabetes. Typically, the P wave morphology remains relatively constant, but small variations in the PR interval may be seen. There are two predominant types of sinus arrhythmia, one occurring as a result of normal respiration and another in the presence of digoxin toxicity. Sinus arrhythmia (except when due to digoxin toxicity) is not considered abnormal and rarely causes symptoms; therefore, no treatment is typically recommended. (See "Normal sinus rhythm and sinus arrhythmia", section on 'Sinus arrhythmia'.) https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 3/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Wandering atrial pacemaker Wandering atrial pacemaker refers to a change in the dominant pacemaker focus from the sinus node. A wandering atrial pacemaker is present when there are three or more ectopic foci within the atrial myocardium that serve as the dominant pacemaker ( waveform 5). Because the location of the pacemaker changes, the PR interval can vary as well depending on its proximity to the AV node. Wandering pacemaker is not considered pathologic and can often be seen in young, healthy individuals (eg, athletes). Rarely is this symptomatic; therefore, no treatment is typically indicated. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Wandering atrial pacemaker'.) ELECTROPHYSIOLOGIC AND ELECTROCARDIOGRAPHIC FEATURES Electrocardiographic features The mass of the crescent-shaped SA node is too small to create an electrical signal that can be routinely recorded on the surface electrocardiogram (ECG). As a result, we generally infer SA nodal activity from the ECG appearance of the response to that activity (ie, P waves). Although signal-averaged ECGs focusing on the P wave can identify sinus nodal dysfunction, this is not a commonly used clinical tool due in large measure to problems in registration, particularly during a sinus arrhythmia, and because many of the conduction events are transient and are missed by this technique [6]. Hence, common signs of SA nodal dysfunction on the surface ECG include marked sinus bradycardia that is disproportionate to an individual's metabolic or conditioned state and periods of absent P waves ( waveform 6 and waveform 7 and waveform 8). In order to more clearly delineate the mechanism underlying periods of SA nodal dysfunction, electrophysiology studies can be attempted, but these are not commonly performed because understanding the precise mechanism for SA nodal dysfunction very infrequently changes patient management decisions. Patients with BRASH syndrome have ECG findings of sinus arrest, AV block, and may or may not have other signs of hyperkalemia including peaked T waves and QRS prolongation [2,3]. (See 'Etiology' above.) Electrophysiologic features SA nodal activity can be recorded using an intracardiac electrode catheter [7-12]. The following observations were noted in a study of 38 patients with severe symptomatic sinus node dysfunction (SND) in whom intracardiac SA nodal electrograms could be recorded [12]: Nine had complete SA block, unidirectional in seven and bidirectional in two. 13 had normal 1:1 SA conduction. Nine had second degree SA exit block. https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 4/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Seven patients had no recordable sinus nodal electrogram, which could result from technical failure or from SA nodal quiescence. Electrophysiologic techniques utilizing both pacing at different rates and extra stimuli can be used to assess several characteristics of SA nodal function, including postpacing escape times, SA nodal recovery time, SA nodal conduction time, SA nodal refractoriness, and the assessment of the "intrinsic" heart rate and other parameters following pharmacologic and autonomic intervention. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Electrocardiographic and electrophysiologic recordings'.) SND can coexist with AV node conduction disturbances. This has been termed binodal disease. Electrophysiologic studies suggest that individuals with binodal disease also commonly have intra-atrial conduction disturbances [13]. (See "ECG tutorial: Atrioventricular block".) TREATMENT Therapy begins by establishing whether the patient is experiencing symptoms as a result of sinus node dysfunction. Asymptomatic patients with SA nodal pauses, arrest, or exit block often do not require treatment. Patients with symptoms are often treated by discontinuing possible offending drugs and/or with a permanent pacemaker. (See "Sinus bradycardia", section on 'Management' and "Sinus node dysfunction: Treatment".) Patients with BRASH syndrome require prompt therapy to interrupt the vicious cycle of worsening bradycardia causing worsening renal function and worsening hyperkalemia. Management includes treatment of hyperkalemia, management of bradycardia (including withdrawal of drugs inhibiting sinus node and AV node function), and if needed, fluid resuscitation [2,3]. (See "Treatment and prevention of hyperkalemia in adults" and "Beta blocker poisoning" and "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock".) SUMMARY AND RECOMMENDATIONS A sinus pause or arrest is the transient absence of sinus P waves on the electrocardiogram (ECG) that may last from two seconds to several minutes. This abnormality is an alteration in discharge by the SA pacemaker; as a result, the duration of the pause has no arithmetical relationship to the basic sinus rate. The pause or arrest often allows escape beats or rhythms to occur. (See 'Sinus pause or arrest' above.) https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 5/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate SA nodal exit block occurs as a result of interference with the delivery of impulses from the SA node to its neighboring atrial tissue. This results in the absence of a P wave on the surface ECG since the P wave is the only manifestation of SA nodal activity. Following the convention for atrioventricular nodal block, SA nodal exit block can be classified as first, second, or third degree. (See 'SA nodal exit block' above.) Other variations of SA nodal dysfunction which are generally non-pathologic include sinus arrhythmia and wandering atrial pacemaker. (See 'Variants of SA nodal dysfunction' above.) Asymptomatic patients with SA nodal pauses, arrest, or exit block often do not require treatment. Patients with symptoms are often treated by discontinuing possible offending drugs and/or with a permanent pacemaker. (See 'Treatment' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Alan Cheng, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Park DS, Fishman GI. The cardiac conduction system. Circulation 2011; 123:904. 2. Farkas JD, Long B, Koyfman A, Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia. J Emerg Med 2020; 59:216. 3. Arif AW, Khan MS, Masri A, et al. BRASH Syndrome with Hyperkalemia: An Under-Recognized Clinical Condition. Methodist Debakey Cardiovasc J 2020; 16:241. 4. Hilgard J, Ezri MD, Denes P. Significance of ventricular pauses of three seconds or more detected on twenty-four-hour Holter recordings. Am J Cardiol 1985; 55:1005. 5. Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977; 39:390. 6. Yamada T, Fukunami M, Shimonagata T, et al. Identification of sinus node dysfunction by use of P-wave signal-averaged electrocardiograms in paroxysmal atrial fibrillation: a prospective study. Am Heart J 2001; 142:286. 7. Hombach V, Gil-Sanchez D, Zanker R, et al. An approach to direct detection of sinus nodal activity in man. J Electrocardiol 1979; 12:343. https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 6/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate 8. Hariman RJ, Krongrad E, Boxer RA, et al. Method for recording electrical activity of the sinoatrial node and automatic atrial foci during cardiac catheterization in human subjects. Am J Cardiol 1980; 45:775. 9. Reiffel JA, Gang E, Gliklich J, et al. The human sinus node electrogram: a transvenous catheter technique and a comparison of directly measured and indirectly estimated sinoatrial conduction time in adults. Circulation 1980; 62:1324. 10. Asseman P, Berzin B, Desry D, et al. Persistent sinus nodal electrograms during abnormally prolonged postpacing atrial pauses in sick sinus syndrome in humans: sinoatrial block vs overdrive suppression. Circulation 1983; 68:33. 11. Gomes JA, Hariman RI, Chowdry IA. New application of direct sinus node recordings in man: assessment of sinus node recovery time. Circulation 1984; 70:663. 12. Wu DL, Yeh SJ, Lin FC, et al. Sinus automaticity and sinoatrial conduction in severe symptomatic sick sinus syndrome. J Am Coll Cardiol 1992; 19:355. 13. Sakai Y, Imai S, Sato Y, et al. Clinical and electrophysiological characteristics of binodal disease. Circ J 2006; 70:1580. Topic 894 Version 23.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 7/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate GRAPHICS Sinus pause Sinus pause is the result of intermittent failure of sinus node impulse generation. This is manifest as a long RR cycle length (in this tracing P to P interval) which is longer than the RR interval of the underlying sinus rhythm. There is no relationship between the cycle length of the pause and that of the intrinsic sinus rhythm. The P-P interval for the beats before and after the pause are less than two times the underlying sinus P-P interval. Graphic 75018 Version 2.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. Graphic 69872 Version 2.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 8/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Single-lead electrocardiogram (ECG) showing lead V1 in type I (Wenckebach type) sinoatrial block There is a 3:2 SA block, resulting in group beating of pairs of sinus beats. The P-P interval during the pause has a duration (1040 msec) that is less than two P-P cycles (1360 msec); this finding distinguishes this arrhythmia from type II SA block in which the pause duration is the same as that of two P-P cycles. Courtesy of Morton Arnsdorf, MD. Graphic 68081 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 9/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Single-lead electrocardiogram (ECG) showing lead V5 in type II sinoatrial block There is a 3:2 SA block, resulting in group beating of pairs of sinus beats. The P-P interval during the pause has a duration (1840 msec) that is approximately equal to two P-P cycles (920 msec); this finding distinguishes this arrhythmia from type I SA block in which the pause duration is less than that of two P-P cycles. There may be some sinus variability, as in this case, due to sinus arrhythmia and possibly to baroreceptor responses to varying diastolic filling intervals. Courtesy of Morton Arnsdorf, MD. Graphic 54936 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 10/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Sinus arrhythmia Sinus arrhythmia is present when there is a sinus rhythm with variability in the cycle lengths between successive P waves. This rhythm strip reveals a gradual increase and decrease in the heart rate with the respiratory cycle; the heart rate increases with inspiration and decreases with expiration. Graphic 73688 Version 2.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. Graphic 69872 Version 2.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 11/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Wandering atrial pacemaker A wandering atrial pacemaker is present when there are multiple ectopic foci within the atrial myocardium that serve as dominant pacemakers. There is a changing vector of atrial activation which causes a changing P wave morphology and PR interval duration. The QRS intervals have very variable cycle lengths since the ectopic foci have differences of automaticity and rates of impulse generation. The rhythm is therefore irregularly irregular. QRS morphology is not altered from that seen during sinus rhythm, since activation of the ventricular myocardium occurs normally via the His-Purkinje system. Graphic 54943 Version 2.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. Graphic 69872 Version 2.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 12/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Single lead electrocardiogram (ECG) showing sick sinus syndrome and atrial fibrillation Rhythm strip showing sick sinus syndrome. The initial part (left) of the tracing reveals coarse atrial fibrillation with irregular ventricular response in the absence of drugs that slow AV nodal conduction. The atrial fibrillation terminates and is followed by a sinus beat with a prolonged sinus node recovery time of nearly four seconds. Courtesy of Ary Goldberger, MD. Graphic 51193 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 13/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Single-lead electrocardiogram (ECG) showing manifestations of sick sinus syndrome (SSS) with sinus arrest Example of sick sinus syndrome (SSS). In this example, sinus arrest is seen with a junctional escape beat, a premature atrial complex, and eventual resumption of sinus activity. Courtesy of Alan Cheng, MD, FACC, FAHA, FHRS. Graphic 91605 Version 1.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 14/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Single lead electrocardiogram (ECG) showing sick sinus syndrome (SSS) with ectopic atrial and junctional beats Example of sick sinus syndrome (SSS). In this example, sinus rhythm abruptly pauses, followed by two ectopic atrial beats, a junctional escape beat, and resumption of sinus activity. Courtesy of Alan Cheng, MD, FACC, FAHA, FHRS. Graphic 91606 Version 1.0 https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 15/16 7/6/23, 11:16 AM Sinoatrial nodal pause, arrest, and exit block - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinoatrial-nodal-pause-arrest-and-exit-block/print 16/16 |
7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinoatrial nodal reentrant tachycardia (SANRT) : Munther K Homoud, MD : Samuel L vy, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 18, 2021. INTRODUCTION Atrial tachycardias have traditionally been characterized as automatic, triggered, or reentrant. However, the European Society of Cardiology and the North American Society of Pacing and Electrophysiology in 2001 proposed a classification that takes into consideration both anatomic features and electrophysiologic mechanisms [1]. In 2015, the joint American College of Cardiology, American Heart Association, and Heart Rhythm Society guidelines further defined sinus node reentrant tachycardia as "a specific type of focal atrial tachycardia that is due to microreentry arising from the sinus node complex, characterized by abrupt onset and termination, resulting in a P-wave morphology that is indistinguishable from sinus rhythm" [2]. Atrial tachycardia is the overriding term that includes two major categories: Focal atrial tachycardia due to an automatic, triggered, or microreentrant mechanism Macroreentrant atrial tachycardia, including typical atrial flutter and other well- characterized macroreentrant circuits in the right and left atrium Sinoatrial nodal reentrant tachycardia (SANRT), also called sinus node reentry or sinus node reentrant tachycardia, falls into the latter group of reentrant arrhythmias. This topic will discuss the mechanisms, clinical manifestations, and treatment of SANRT. Discussions of other specific atrial arrhythmias are presented separately. (See "Focal atrial tachycardia" and "Intraatrial reentrant tachycardia" and "Overview of atrial flutter".) DEFINITION AND MECHANISMS https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 1/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Initially described in the 1940s [3], SANRT has often been considered a form of atrial tachycardia. However, SANRT has an activation sequence similar to that of normal sinus rhythm so that the P waves on the surface ECG appear to be normal. In comparison, intraatrial reentry has a different activation sequence of atrial depolarization, leading to a P wave morphology that differs from that of normal sinus rhythm. (See "Intraatrial reentrant tachycardia".) Some of the electrophysiologic features that distinguish SA nodal reentrant tachycardia and other reentrant atrial rhythms ( figure 1) from automatic and triggered atrial tachycardias are summarized ( table 1). The exact mechanism of SA nodal reentry is not known; however, three possibilities have been suggested [4] (see "Reentry and the development of cardiac arrhythmias"): Reentry occurring entirely within the SA node, based primarily on one animal study in which the reentrant pathway was localized within the SA node [5]. Reentry involving the SA node and perinodal tissue, based on a number of studies that have suggested the reentrant loop involves more than the SA node [4,6-8]. What we call the SA node is actually the integrated activity of pacemaker cells in the compact region of the SA node [9]. These several thousand cells depolarize and produce action potentials almost synchronously and seem to influence each other through cell-to-cell coupling, a process that has been called "mutual entrainment" [10,11]. Reentry using the SA node as the refractory center around which reentry occurs, although there is limited evidence for this potential mechanism [4]. Using high resolution optical mapping, both micro- and macro- reentry have been demonstrated as mechanisms of SANRT in a post-myocardial infarction model. Additionally, SANRT was not seen in structurally normal hearts, as it required functional and/or structural abnormalities to support reentry [12]. Reentry with the SA node only or the SA node and perinodal tissue is the most likely mechanism of SANRT [13,14]. INCIDENCE SANRT, an uncommon arrhythmia that rarely causes symptoms, occurs most commonly in adults and children who have structural heart disease [15-18]. In patients with supraventricular tachycardia referred for electrophysiologic study, estimates of the frequency of SANRT have ranged from 2 to 17 percent [16,19]. However, approximately 10 to 15 percent of patients who https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 2/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate undergo electrophysiologic studies for symptomatic atrial tachycardia have sinus nodal echoes (single or multiple reentrant beats that utilize the SA node), indicating the presence of a substrate for SA nodal tachycardia [16,19]. In addition, the actual incidence of this arrhythmia may be higher than appreciated since many patients are asymptomatic and do not come to electrophysiologic study. CLINICAL MANIFESTATIONS In most cases, the clinical manifestations and significance of SANRT are minimal. Most patients are asymptomatic, while others have symptoms that range from palpitations and lightheadedness to, in rare cases, syncope. Symptoms, when present, tend to start and stop abruptly. If a patient is examined during an episode of arrhythmia, he or she will have a regular heart rate greater than 100 beats per minute. Most episodes of SANRT do not precipitate hemodynamic compromise or limiting symptoms. However, on rare occasions, SANRT can be sufficiently recurrent, rapid, and/or sustained to be symptomatic. Higher ventricular rates associated with SANRT in a patient with underlying advanced cardiac or pulmonary disease can sometimes exacerbate their disease, leading to signs and symptoms of angina, heart failure, or worsening systemic oxygenation. In the face of persistently elevated ventricular rates (eg, for weeks to months), particularly if baseline ventricular dysfunction exists, heart failure (tachycardia-mediated cardiomyopathy) may ensue [20,21]. (See "Arrhythmia-induced cardiomyopathy".) DIAGNOSIS The diagnosis of SANRT should be considered in the presence of a regular but rapid pulse and heartbeat on physical examination. The electrocardiogram (ECG) will show P waves with a rate between 100 and 150 beats per minute. Given that the P waves are virtually identical to those observed in sinus rhythm, patients may often be thought to have inappropriate sinus tachycardia. In most cases, the diagnosis of SANRT cannot be confirmed without invasive electrophysiologic studies. Vagal maneuvers and adenosine can sometimes help as either will slow the tachycardia before the arrhythmia is abruptly terminated. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia'.) While pursuing invasive testing to make the diagnosis is not generally necessary, when symptoms are present clinically or the arrhythmia appears incessant, it is important to distinguish SANRT from other supraventricular tachycardias (SVT). In a patient with sustained https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 3/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate tachycardia and reduced left ventricular function in whom tachycardia-mediated cardiomyopathy is a consideration, we would suggest more aggressive efforts at confirming or excluding SANRT as the diagnosis. (See "Arrhythmia-induced cardiomyopathy".) Electrocardiographic findings As mentioned above, SANRT has an activation sequence similar to that of normal sinus rhythm (see 'Definition and mechanisms' above). Thus, the surface ECG has P waves that are virtually identical to those observed in sinus rhythm and often will be interpreted as a sinus tachycardia. The abrupt onset and termination of the arrhythmias can aid clinically in differentiating SANRT from sinus tachycardia. Conduction through the AV node, the specialized infranodal conduction system (His bundle, fascicles and bundle branches, terminal Purkinje fibers), and the ventricles also should be similar to normal AV conduction unless the rapid rate causes some type of functional conduction disturbance (ie, rate-related bundle branch block). The rate in SANRT is usually between 100 and 150 beats per minute. Episodes vary in length, lasting anywhere from seconds to hours. The response to vagal maneuvers can aid in differentiating sinus tachycardia (gradual slowing in response to vagal stimulus) from SANRT (abrupt termination of the arrhythmia). Patients should undergo continuous ECG monitoring during the vagal maneuvers. (See 'Autonomic maneuvers' below.) Electrophysiologic features Clinically, when symptoms are present or the arrhythmia appears incessant, it is important to distinguish SANRT from other supraventricular tachycardias (SVT), particularly focal atrial tachycardia. Since the surface electrocardiogram alone is not reliable in distinguishing SANRT from other types of SVT, invasive electrophysiological studies (EPS) can be employed to help make this distinction. Since macroreentrant atrial arrhythmias, including SANRT, are reentrant, they can be entrained during EPS with manifest and concealed fusion, and upon cessation of atrial pacing, the post pacing interval should be within 30 milliseconds of the tachycardia cycle length if pacing is performed within the reentrant pathway. The use of newer mapping techniques such as electroanatomical mapping further helps to make this distinction where focal mechanisms display centrifugal activation patterns, reentry displays an "early meets late," and the entire cycle length of the tachycardia can be mapped to the chamber containing the tachycardia. The initiation with premature atrial complexes (PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) independent of intraatrial or AV nodal conduction delays or, better yet, in the presence of AV block, helps confirm the diagnosis. The P wave morphology is identical to sinus node P wave morphology. (See "Invasive diagnostic cardiac electrophysiology studies".) https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 4/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate SA nodal reentrant tachycardia can be initiated by PACs, atrial pacing, and, unlike intraatrial reentry, by premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) and ventricular pacing with retrograde VA conduction. The rarity of induction of intraatrial reentry by a PVC is due to the delay in retrograde VA conduction which limits the prematurity with which the premature beat can depolarize the atrium. Neither the AV node nor a bypass tract is a necessary part of the circuit. The reentrant circuit can be penetrated and reentry aborted by premature atrial depolarizations or atrial pacing. Differential diagnosis The differential diagnosis for sinoatrial nodal reentrant tachycardia (SANRT) is similar to that for other narrow QRS complex tachycardias (assuming there is normal AV conduction without bundle branch block) and includes: Atrial flutter Atrioventricular reciprocating tachycardia Focal atrial tachycardia Intraatrial reentrant tachycardia Sinus tachycardia, including inappropriate sinus tachycardia Atrioventricular nodal reentrant tachycardia Only the abrupt onset and termination of the arrhythmia aids clinically in differentiating SANRT from sinus tachycardia, which is not a paroxysmal condition but manifests a gradual increase and decrease in rate ( waveform 1). Other arrhythmias included in the differential diagnosis, however, typically have a P wave morphology that is different from normal, although the difference may be subtle. In addition, other reentrant tachycardias are usually, but not always, more rapid than SANRT (rate up to 240 beats per minute versus 100 to 150 beats per minute). A more in-depth discussion of the differential diagnosis of narrow QRS complex tachycardias is presented separately. TREATMENT Most episodes of SA nodal reentrant tachycardia require no specific therapy since the usual rates (100 to 150 beats/min) rarely produce symptoms or hemodynamic compromise. However, persistent and/or symptomatic SANRT requires treatment to relieve symptoms and to prevent long-term sequelae such as tachycardia-mediated cardiomyopathy [22]. (See "Arrhythmia- induced cardiomyopathy".) https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 5/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Efforts to acutely terminate SANRT should begin with vagal maneuvers. If vagal maneuvers are unsuccessful, intravenous adenosine can be administered for the acute termination of SANRT. Chronic suppressive therapy, when necessary, is usually with verapamil, although digoxin and amiodarone have been tried with some success. Catheter ablation of SANRT is generally the treatment of choice for chronic management of this arrhythmia given its efficacy. Autonomic maneuvers For the acute termination of symptomatic SANRT, we suggest carotid sinus massage or another vagal maneuver as the initial therapy. (See "Vagal maneuvers".) The SA node has extensive autonomic innervation. As a result, carotid sinus massage and other vagal maneuvers (such as the Valsalva maneuver) generally terminate SA nodal reentrant arrhythmias abruptly [13,19,21]. This is in contrast to the effect of vagal maneuvers on sinus tachycardia and reentrant intraatrial rhythms. The response to sinus tachycardia is characterized by gradual slowing and then gradual acceleration upon cessation of the maneuver. The atria are less well innervated than the sinus node. As a result, vagal stimulation has a variable and often negligible effect on reentrant intraatrial rhythms. Enhancement of vagal tone may, however, result in AV nodal blockade, which will result in a reduction in the ventricular rate without altering the atrial rate. Pharmacologic therapy There are no large studies of pharmacologic therapy in SA nodal reentrant tachycardia because of the rarity of the arrhythmia and its general lack of clinical consequence. Several drugs have been evaluated for both acute termination and chronic suppression of SANRT in small nonrandomized studies: Adenosine acutely terminated SANRT in six of six patients in a single-center cohort [23]. Verapamil (two of two) and amiodarone (four of four) effectively prevented induction of SANRT during electrophysiologic testing in a single-center cohort [21]. Beta blockers have not been extensively studied but failed to prevent induction of SANRT in two of two patients during electrophysiologic testing in a single-center cohort [21]. Ouabain, an analog of digoxin, successfully prevented induction of SANRT during electrophysiologic testing in a single-center cohort. In addition, digoxin has been reported to successfully suppress recurrent SANRT for 18 months in an infant [21,24]. Radiofrequency catheter ablation SANRT is on occasion sufficiently symptomatic or persistent to warrant specific intervention. Increasing experience is being gained with https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 6/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate radiofrequency ablation of a portion of the reentrant circuit [16,20,25-28]. Of approximately 45 patients in these reports, the arrhythmia recurred in only one patient who then underwent a second successful ablation. Evaluation in a larger number of patients with longer follow-up is required to more accurately determine the role of ablation in this disorder. However, we feel that catheter ablation should be considered as first-line therapy for symptomatic patients or in patients with persistent tachycardia who are at risk for or who have developed tachycardia- mediated cardiomyopathy. (See "Arrhythmia-induced cardiomyopathy".) Our approach to treatment Based on the limited available evidence, we take the following approach to treatment: For acute termination of symptomatic SANRT that persists despite the use of vagal maneuvers, we suggest intravenous adenosine. Synchronized cardioversion can be used in an unstable patient. For chronic suppression of recurrent SANRT, we suggest catheter ablation rather than pharmacologic therapy. This choice is based upon the high success rates of catheter ablation in conjunction with fewer potential long-term medication side effects. For chronic therapy of SANRT when ablation is not an option or has been unsuccessful in preventing recurrent SANRT, we suggest verapamil or beta adrenergic receptor blockers as the first choice, followed by the combination of both if SANRT recurs. If SANRT recurs despite the combination of verapamil and beta adrenergic receptor blockers, amiodarone can be considered. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Sinoatrial nodal reentrant tachycardia (SANRT), also called "sinus node reentry" or "sinus node reentrant tachycardia," is a reentrant tachyarrhythmias involving the SA node and/or perinodal tissue. (See 'Definition and mechanisms' above.) SANRT occurs most commonly in adults and children who have structural heart disease and is estimated to be responsible for anywhere from 2 to 17 percent of supraventricular https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 7/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate tachycardias. (See 'Incidence' above.) In most cases, the clinical manifestations and significance of SANRT are minimal. Most patients are asymptomatic, while others have symptoms that range from palpitations and lightheadedness to, in rare cases, syncope. (See 'Clinical manifestations' above.) The diagnosis of SANRT should be considered in the presence of a regular but rapid pulse and heartbeat on physical examination. The electrocardiogram (ECG) will show P waves with a rate between 100 and 150 beats per minute. Given that the P waves are virtually identical to those observed in sinus rhythm, in most cases the diagnosis cannot be confirmed without invasive electrophysiologic studies. (See 'Diagnosis' above.) The differential diagnosis for SANRT is similar to that for other narrow QRS complex tachycardias (assuming there is normal AV conduction without bundle branch block). Only the abrupt onset and termination of the arrhythmia aids clinically in differentiating SANRT from sinus tachycardia, which is not a paroxysmal condition but manifests a gradual increase and decrease in rate. (See 'Differential diagnosis' above.) While SANRT is most often transient and asymptomatic, persistent and/or symptomatic SANRT requires treatment to relieve symptoms and to prevent long-term sequelae such as tachycardia-mediated cardiomyopathy. We take the following approach to treatment (see 'Our approach to treatment' above): For acute termination of symptomatic SANRT that persists despite the use of vagal maneuvers, we suggest intravenous adenosine (Grade 2C). For chronic suppression of recurrent SANRT, we suggest catheter ablation rather than pharmacologic therapy (Grade 2C). This choice is based upon the high success rates of catheter ablation in conjunction with fewer potential long-term medication side effects. For chronic therapy of SANRT when ablation is not an option or has been unsuccessful in preventing recurrent SANRT, we suggest verapamil or beta adrenergic receptor blockers as the first choice (Grade 2C), followed by the combination of both if SANRT recurs. If SANRT recurs despite the combination of verapamil and beta adrenergic receptor blockers, amiodarone is another option. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 8/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate 1. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2016; 13:e136. 3. Barker PS, Wilson FN, Johnson FD. The mechanism of auricular paroxysmal tachycardia. Am Heart J 1943; 26:435. 4. Kirchhoff CJ, Bonke FI, Allessie MA. Sinus node reentry: Fact or fiction?. In: Cardiac Arrhythmi as: Where to Go from Here?, Brugade P, Wellens HJ (Eds), Martinus Nijhoff, The Hague 1987. p.53. 5. Allessie MA, Bonke FI. Direct demonstration of sinus node reentry in the rabbit heart. Circ Res 1979; 44:557. 6. Childers RW, Arnsdorf MF, De la Fuente DJ, et al. Sinus nodal echoes. Clinical case report and canine studies. Am J Cardiol 1973; 31:220. 7. Paulay KL, Varghese PJ, Damato AN. Sinus node reentry. An in vivo demonstration in the dog. Circ Res 1973; 32:455. 8. Strauss HC, Bigger JT Jr. Electrophysiological properties of the rabbit sinoatrial perinodal fibers. Circ Res 1972; 31:490. 9. Bleeker WK, Mackaay AJ, Masson-P vet M, et al. Functional and morphological organization of the rabbit sinus node. Circ Res 1980; 46:11. 10. Jalife J. Mutual entrainment and electrical coupling as mechanisms for synchronous firing of rabbit sino-atrial pace-maker cells. J Physiol 1984; 356:221. 11. Jalife J. Synchronization of pacemaker cells in the sinus node. In: Atrial Arrhythmias: Current Concepts and Management, Touboul P, Waldo AL (Eds), Mosby Year Book, St. Louis 1990. p.6 9. 12. Glukhov AV, Hage LT, Hansen BJ, et al. Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness. Circ Arrhythm Electrophysiol 2013; 6:984. 13. Coss SF, Steinberg JS. Supraventricular tachyarrhythmias involving the sinus node: clinical and electrophysiologic characteristics. Prog Cardiovasc Dis 1998; 41:51. https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 9/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate 14. Narula OS. Sinus node re-entry: a mechanism for supraventricular tachycardia. Circulation 1974; 50:1114. 15. Pahlajani DB, Miller RA, Serratto M. Sinus node re-entry and sinus node tachycardia. Am Heart J 1975; 90:305. 16. Gomes JA, Mehta D, Langan MN. Sinus node reentrant tachycardia. Pacing Clin Electrophysiol 1995; 18:1045. 17. Garson A Jr, Gillette PC. Electrophysiologic studies of supraventricular tachycardia in children. I. Clinical-electrophysiologic correlations. Am Heart J 1981; 102:233. 18. Blaufox AD, Numan M, Knick BJ, Saul JP. Sinoatrial node reentrant tachycardia in infants with congenital heart disease. Am J Cardiol 2001; 88:1050. 19. Josephson ME. Supraventricular Tachycardias. In: Clinical Cardiac Electrophysiology: Techniq ues and Interpretations, 4th, Lippincott, Williams, and Wilkins, Philadelphia 2008. 20. Kay GN, Chong F, Epstein AE, et al. Radiofrequency ablation for treatment of primary atrial tachycardias. J Am Coll Cardiol 1993; 21:901. 21. Gomes JA, Hariman RJ, Kang PS, Chowdry IH. Sustained symptomatic sinus node reentrant tachycardia: incidence, clinical significance, electrophysiologic observations and the effects of antiarrhythmic agents. J Am Coll Cardiol 1985; 5:45. 22. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 23. Engelstein ED, Lippman N, Stein KM, Lerman BB. Mechanism-specific effects of adenosine on atrial tachycardia. Circulation 1994; 89:2645. 24. Ozer S, Schaffer M. Sinus node reentrant tachycardia in a neonate. Pacing Clin Electrophysiol 2001; 24:1038. 25. Lesh MD, Van Hare GF, Epstein LM, et al. Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms. Circulation 1994; 89:1074. 26. Sanders WE Jr, Sorrentino RA, Greenfield RA, et al. Catheter ablation of sinoatrial node reentrant tachycardia. J Am Coll Cardiol 1994; 23:926. 27. Ivanov MY, Evdokimov VP, Vlasenco VV. Predictors of successful radiofrequency catheter ablation of sinoatrial tachycardia. Pacing Clin Electrophysiol 1998; 21:311. 28. Goya M, Iesaka Y, Takahashi A, et al. Radiofrequency catheter ablation for sinoatrial node reentrant tachycardia: electrophysiologic features of ablation sites. Jpn Circ J 1999; 63:177. https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 10/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Topic 918 Version 29.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 11/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate GRAPHICS Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 12/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Electrophysiologic characteristics of the different types of supraventricular tachycardia (SVT) Characteristic Reentrant Triggered Automatic Initiation by extrastimuli and/or continuous pacing Yes Yes No Initiation by continuous pacing depends upon the rate and number of stimuli No Yes No Termination by extrastimuli Yes No No Termination by continuous pacing (overdrive) Yes Yes No Overdrive suppression of tachycardia No No Yes Overdrive enhancement of tachycardia Yes Yes No Entrainment possible Yes No No First P wave identical to P waves in arrhythmia No Sometimes Yes Warm-up or acceleration of pacemaker after onset No Sometimes Yes Graphic 53347 Version 2.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 13/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Single-lead electrocardiogram (ECG) showing sinoatrial (SA) nodal reentrant tachycardia Electrocardiogram showing SA nodal reentrant tachycardia. The first three beats are normal sinus beats at a rate of about 107 beats/min; the fourth beat is an atrial premature beat that is followed by a return to sinus rhythm. The eighth beat (arrow) represents the sudden onset of SA nodal reentrant tachycardia at a rate of about 145 beats/min. Since the P waves are similar to the sinus beats, the diagnosis is suggested only by the abrupt onset of the tachycardia. Courtesy of Morton F Arnsdorf, MD. Graphic 76364 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 14/15 7/6/23, 11:16 AM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 15/15 |
7/6/23, 11:17 AM Sinus bradycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinus bradycardia : Munther K Homoud, MD : Jonathan Piccini, MD, MHS, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 25, 2022. INTRODUCTION Sinus bradycardia is a rhythm in which the rate of impulses arising from the sinoatrial (SA) node is lower than expected. The normal adult heart rate, arising from the SA node, has been considered historically to range from 60 to 100 beats per minute, with sinus bradycardia being defined as a sinus rhythm with a rate below 60 beats per minute. The heart rate reflects a complex interplay between the sympathetic and parasympathetic nervous systems. It is affected by numerous factors, including age and physical conditioning ( table 1) [1,2]. Sinus arrhythmia, the fluctuation in sinus rate with respiratory cycles, often accompanies sinus bradycardia. (See "Normal sinus rhythm and sinus arrhythmia".) The etiology, clinical presentation, evaluation, and management of sinus bradycardia will be reviewed here. Primary sinus node dysfunction (ie, sinus node dysfunction) is discussed in detail separately. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation" and "Sinus node dysfunction: Treatment".) DEFINITION AND ECG FEATURES Normal sinus rhythm (NSR) is the characteristic rhythm of the healthy heart. NSR is considered to be present in adults if the heart rate is between 60 and 100 beats per minute, the P wave vector on the electrocardiogram (ECG) is normal (ie, consistent with SA nodal impulse origin), https://www.uptodate.com/contents/sinus-bradycardia/print 1/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate and the rate is largely regular ( waveform 1). The normal sinus P wave demonstrates right atrial followed by left atrial depolarization and high to low atrial activation giving rise to an upright P wave in leads I, II, and aVL, and a negative P wave in lead aVR. By conventional definition, bradycardia indicates a heart rate less than 60 beats per minute with a normal P wave vector on the surface ECG. As such, sinus bradycardia is typically thought of as sinus rhythm occurring at a rate of less than 60 beats per minute, although one professional society has advocated a rate of less than 50 beats per minute ( waveform 2) [3]. A rate less than 50 beats per minute may be a more pragmatic definition, as most patients with sinus rates in the 50s are asymptomatic. It is important to note that the rate at which a patient is labeled as having bradycardia is somewhat age dependent. ETIOLOGY Sinus bradycardia occurs in healthy patients as an adaptive response, particularly in well- conditioned persons or while sleeping, but it can also occur as a pathologic response in a variety of conditions. It is very important to recognize that in normal healthy children and adults, sinus bradycardia is a frequent and normal finding, particularly during sleep when rates may transiently drop as low as 30 beats per minute, and pauses of up to two seconds are not uncommon [4-7]. Sinus bradycardia may also be seen in the absence of heart disease in the following settings: Well-conditioned athletes, particularly in endurance athletic activities, where bradycardia is generally attributed to increased vagal tone induced by exercise conditioning [8-12]. Some older adult patients, although this may represent an early manifestation of sinus node dysfunction (SND) [13]. Sinus bradycardia may represent a manifestation of rare familial forms of SND that have been described. Mutations in two genes, HCN4 and SCN5A, have been associated with sinoatrial (SA) node dysfunction as well as other hereditary arrhythmic disorders such as the Brugada syndrome, atrial fibrillation, and progressive cardiac conduction disease [14- 16]. Sinus bradycardia can be seen in a variety of pathophysiologic settings ( table 2), including: Sinus node dysfunction Sinus bradycardia may be the first manifestation of SA node dysfunction [17,18]. Primary disease of the SA node is discussed in detail separately. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation".) https://www.uptodate.com/contents/sinus-bradycardia/print 2/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate Medications A number of drugs can depress the SA node and slow the heart rate as either an expected response to or side effect of therapy, or as a toxicity related to overdose. These include: Parasympathomimetic agents (eg, acetylcholine, carbachol, acetylcholinesterase inhibitors) Sympatholytic drugs (eg, beta blockers, methyldopa, clonidine) Opioids and sedatives Cimetidine Digitalis Non-dihydropyridine calcium channel blockers (diltiazem and verapamil) Ivabradine Amiodarone and other antiarrhythmic drugs The chronic hepatitis C drugs sofosbuvir and daclatasvir in patients receiving amiodarone [19] Lithium Chemotherapeutic agents (eg, thalidomide, lenalidomide, paclitaxel) Organophosphate compounds [20] A 2020 scientific statement from the American Heart Association details drugs associated with bradycardia [21]. Acute myocardial infarction Sinus bradycardia occurs in 15 to 25 percent of patients with acute myocardial infarction, particularly those involving the right coronary artery as it supplies the SA node in approximately 60 percent of people. Increased vagal activity is primarily responsible, and the bradycardia is typically transient. If treatment is necessary because of hemodynamic compromise or ischemia, sinus bradycardia usually responds well to intravenous atropine (0.6 to 1.0 mg in the majority of cases). (See "Supraventricular arrhythmias after myocardial infarction", section on 'Sinus bradycardia'.) Obstructive sleep apnea Individuals with obstructive sleep apnea frequently have sinus bradycardia that may be severe (<30 beats per minute) during apneic episodes [22]. Therapies to improve the apnea frequently alleviate the bradycardia [23]. (See "Obstructive sleep apnea and cardiovascular disease in adults", section on 'Other arrhythmias'.) Exaggerated vagal activity Vasovagal responses may be associated with a profound bradycardia due to heightened parasympathetic activity and sympathetic withdrawal on the SA node. There are a variety of stimuli for vagal activation, including carotid sinus stimulation, vomiting, coughing, and Valsalva maneuver. The combination of the slow https://www.uptodate.com/contents/sinus-bradycardia/print 3/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate heart rate and an associated decline in peripheral vascular resistance is often sufficient to produce presyncope or syncope. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".) Increased intracranial pressure and other central nervous system conditions Increased intracranial pressure should be excluded when sinus bradycardia occurs in a patient with neurologic dysfunction. Stroke is another neurological condition that can display sinus bradycardia. Sinus bradycardia is also seen with trauma to the cervical or thoracic spine where sympathetic denervation of the heart leaves an unopposed parasympathetic tone [24]. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Clinical manifestations'.) Infectious causes Infectious agents associated with relative sinus bradycardia include Lyme disease, Chagas disease, legionella, psittacosis, Q fever, typhoid fever, typhus, babesiosis, malaria, leptospirosis, yellow fever, dengue fever, viral hemorrhagic fevers, trichinosis, and Rocky Mountain Spotted fever [25,26]. Other causes Other causes of sinus bradycardia include hypothyroidism, anorexia nervosa, hypothermia, and severe prolonged hypoxia. Sinus bradycardia is also seen in the long QT syndrome and in the catecholaminergic polymorphic ventricular tachycardia syndrome, two forms of genetic channelopathies. CLINICAL PRESENTATION In the vast majority of patients, sinus bradycardia itself does not directly cause symptoms, although a patient with comorbid conditions that might be exacerbated by reduced cardiac output (eg, angina, heart failure) may present with worsening symptoms related to the comorbidity. Symptoms related to the slow heart rate itself can occur, including lightheadedness, presyncope or syncope, worsening of angina pectoris or heart failure, cognitive slowing, and exercise intolerance. Symptoms may be subtle, with many patients noting only fatigue, which is frequently ascribed to aging rather than bradycardia. There is no specific heart rate below which all patients develop symptoms, as cardiac output will vary depending upon the ability to increase stroke volume related to underlying conditioning or comorbidities. Sinus bradycardia associated with pathology of the sinoatrial node is part of the sinus node dysfunction (SND). SND often does not respond appropriately to exercise (chronotropic incompetence), and fatigue or dyspnea on exertion may be the presenting feature. SND and https://www.uptodate.com/contents/sinus-bradycardia/print 4/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate chronotropic incompetence are discussed in detail separately. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Heart rate response to exercise'.) EVALUATION Confirm sinus bradycardia Sinus bradycardia is generally confirmed by ECG after a slow pulse is identified on physical examination, with the diagnosis usually being easy to establish from the surface ECG. An upright P wave in leads I, II, and aVL, and a negative P wave in lead aVR, indicates a sinus origin of the bradycardia. It is vital to exclude other causes of bradyarrhythmias such as atrioventricular (AV) block. Differential diagnosis Sinus bradycardia should be distinguished from other bradyarrhythmias ( table 3) resulting in a reduced heart rate (ie, second- or third-degree AV block, junctional escape rhythm, ventricular escape rhythm). This is easily done by establishing the 1:1 relationship between P waves and QRS complexes on the surface ECG. Patients with more than one P wave for every QRS complex have second- or third-degree AV block, while patients with no discernible P waves will have an escape rhythm (either junctional or ventricular in origin). The heart rate is often clinically assessed by detection of the pulse with a plethysmograph system, and conditions other than sinus bradycardia can cause a reduction in measured pulse rate (for example, ventricular bigeminy, in which the premature ventricular complex beats result in diminished pulse pressure, which may not be detected). In such cases of ineffective bigeminy, a falsely low heart rate can be recorded. Thus, it is important to always obtain an ECG when new or unexpected bradycardia is identified. Further evaluation For the majority of patients with sinus bradycardia, the underlying cause can usually be determined from history and physical examination alone. In addition to the measurement of a full set of vital signs, including temperature and pulse oximetry, important features to elicit in a history and examination include: Quantity of exercise performed and level of fitness Exposure to medications and toxins Signs of infectious exposure (eg, tick or insect bites) or other systemic conditions (eg, eating disorders, hypothyroidism) The evaluation of a patient who presents with sinus bradycardia requires a comprehensive evaluation where the history is probably the most important component of the evaluation https://www.uptodate.com/contents/sinus-bradycardia/print 5/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate ( algorithm 1). The aim of the initial evaluation is to establish the presence or absence of symptoms, and any evidence of hemodynamic compromise as a result of the bradycardia. This may include hypotension, chest discomfort, altered mental status, or shortness of breath. The presence of hemodynamic compromise demands immediate attention to the cause of the bradycardia and its amelioration. Once hemodynamic compromise has been excluded, the clinician will have to exclude diseases, cardiovascular or other, associated with sinus bradycardia and, most importantly, drugs associated with sinus bradycardia ( algorithm 1). The list of medications, cardiovascular and otherwise, that suppress the sinus node is extensive. Symptoms may be subtle such as lightheadedness, unexplained falls, or exertional dyspnea due to chronotropic incompetence, or they may be pronounced such as syncope. These symptoms point to underlying sinus node disease, which may or may not be exacerbated by drugs that suppress the sinus node. Sinus bradycardia in a healthy, athletic individual requires no further evaluation or intervention. On the other hand, sinus bradycardia in an older individual may indicate sinus node dysfunction (SND) [27]. Sinus bradycardia may be associated with ischemic heart disease if the blood supply to the sinus node (right coronary artery or, in some patients, the left circumflex artery) is compromised. Patients with congestive heart failure have slower heart rates than their healthy counterparts [28]. Sinus bradycardia in an individual with a history of atrial fibrillation and/or conduction disease, especially if associated with a family history of sinoatrial node dysfunction, should raise the possibility of a hereditary form of SND [15]. MANAGEMENT For asymptomatic patients with sinus bradycardia, treatment is neither indicated nor required. The following approach should be followed when symptoms occur ( algorithm 1): For patients with symptoms who have evidence of hemodynamic instability, we administer atropine (1.0 mg intravenous [IV] push, which can be repeated every three to five minutes, if needed, to a total dose of 3 mg) [29-31]. If symptoms do not improve following atropine, proceed with temporary cardiac pacing and/or IV dopamine or epinephrine infusion [29-31]. (See "Temporary cardiac pacing" and "Advanced cardiac life support (ACLS) in adults", section on 'Bradycardia'.) If beta adrenergic or calcium channel blocker overdose is suspected, administer IV glucagon. The glucagon dose is 3 to 10 mg IV bolus given over three to five minutes; the bolus may repeat once if no response (increase in heart rate). If there is a response to https://www.uptodate.com/contents/sinus-bradycardia/print 6/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate bolus glucagon therapy, start a continuous infusion at 3 to 5 mg per hour titrated according to response [30]. If symptoms improve, the patient should be monitored with continuous cardiac telemetry. For patients who are hemodynamically stable, the following should be considered: Patients with signs or symptoms of acute myocardial ischemia or infarction should be treated accordingly. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the acute management of ST-elevation myocardial infarction".) Patients with evidence of another systemic condition associated with sinus bradycardia (eg, hypothyroidism, infection, etc) should be treated accordingly. (See "Treatment of primary hypothyroidism in adults" and "Lyme carditis".) Patients in whom a medication is suspected to be causing the symptomatic bradycardia should have the medication withheld. If the medication is mandatory for the treatment of a comorbid condition (eg, beta blockers for severe angina), a permanent pacemaker may be required [30]. If the symptoms resolve and heart rate improves following the withdrawal of the suspected offending agent, no additional immediate treatment is required. Patients with no other evidence of a potential cause should be evaluated for SND. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation".) PROGNOSIS There is no adverse prognostic significance to sinus bradycardia in otherwise healthy subjects. In subjects over the age of 40, for example, there is no adverse effect on longevity [32]. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more https://www.uptodate.com/contents/sinus-bradycardia/print 7/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Bradycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Definition Sinus bradycardia, most commonly defined as sinus rhythm with a rate below 60 beats per minute ( waveform 2), occurs in normal children and adults, particularly during sleep or at rest, in well-conditioned athletes, and in some older adult patients. Sinus bradycardia can also be seen in a variety of pathophysiologic settings, most commonly due to medication effects/toxicities or primary sinoatrial disease ( table 2). (See 'Definition and ECG features' above and 'Etiology' above.) Symptoms In the vast majority of patients, sinus bradycardia itself does not cause symptoms. However, a slow heart rate can cause symptoms such as fatigue, lightheadedness, and presyncope or syncope. Patients with comorbid conditions that might be exacerbated by reduced cardiac output (eg, angina, heart failure) may present with worsening symptoms related to the comorbidity. (See 'Clinical presentation' above.) Evaluation The aim of the initial evaluation is to establish the presence or absence of symptoms, and any evidence of hemodynamic compromise as a result of the bradycardia ( algorithm 1). Once hemodynamic compromise has been excluded, the clinician will have to exclude diseases, cardiovascular or other, associated with sinus bradycardia and, most importantly, drugs associated with sinus bradycardia. (See 'Further evaluation' above.) Management For asymptomatic patients with sinus bradycardia, treatment is neither indicated nor required. The approach to the treatment of patients with symptomatic sinus bradycardia is presented within the text and the adjoining algorithm ( algorithm 1). (See 'Management' above.) Prognosis There is no adverse prognostic significance to asymptomatic sinus bradycardia in otherwise healthy subjects. (See 'Prognosis' above.) https://www.uptodate.com/contents/sinus-bradycardia/print 8/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Spodick DH. Normal sinus heart rate: sinus tachycardia and sinus bradycardia redefined. Am Heart J 1992; 124:1119. 2. Spodick DH, Raju P, Bishop RL, Rifkin RD. Operational definition of normal sinus heart rate. Am J Cardiol 1992; 69:1245. 3. Kadish AH, Buxton AE, Kennedy HL, et al. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography. A report of the ACC/AHA/ACP- ASIM Task Force on Clinical Competence (ACC/AHA Committee to Develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography). J Am Coll Cardiol 2001; 38:2091. 4. Scott O, Williams GJ, Fiddler GI. Results of 24 hour ambulatory monitoring of electrocardiogram in 131 healthy boys aged 10 to 13 years. Br Heart J 1980; 44:304. 5. Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977; 39:390. 6. Bjerregaard P. Mean 24 hour heart rate, minimal heart rate and pauses in healthy subjects 40-79 years of age. Eur Heart J 1983; 4:44. 7. Hilgard J, Ezri MD, Denes P. Significance of ventricular pauses of three seconds or more detected on twenty-four-hour Holter recordings. Am J Cardiol 1985; 55:1005. 8. Talan DA, Bauernfeind RA, Ashley WW, et al. Twenty-four hour continuous ECG recordings in long-distance runners. Chest 1982; 82:19. 9. Abdon NJ, Landin K, Johansson BW. Athlete's bradycardia as an embolising disorder? Symptomatic arrhythmias in patients aged less than 50 years. Br Heart J 1984; 52:660. 10. Balady GJ, Cadigan JB, Ryan TJ. Electrocardiogram of the athlete: an analysis of 289 professional football players. Am J Cardiol 1984; 53:1339. 11. Northcote RJ, Canning GP, Ballantyne D. Electrocardiographic findings in male veteran endurance athletes. Br Heart J 1989; 61:155. https://www.uptodate.com/contents/sinus-bradycardia/print 9/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate 12. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998; 339:364. 13. Agruss NS, Rosin EY, Adolph RJ, Fowler NO. Significance of chronic sinus bradycardia in elderly people. Circulation 1972; 46:924. 14. Milanesi R, Baruscotti M, Gnecchi-Ruscone T, DiFrancesco D. Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. N Engl J Med 2006; 354:151. 15. Ruan Y, Liu N, Priori SG. Sodium channel mutations and arrhythmias. Nat Rev Cardiol 2009; 6:337. 16. Hao X, Zhang Y, Zhang X, et al. TGF- 1-mediated fibrosis and ion channel remodeling are key mechanisms in producing the sinus node dysfunction associated with SCN5A deficiency and aging. Circ Arrhythm Electrophysiol 2011; 4:397. 17. Alpert MA, Flaker GC. Arrhythmias associated with sinus node dysfunction. Pathogenesis, recognition, and management. JAMA 1983; 250:2160. 18. Eraut D, Shaw DB. Sinus bradycardia. Br Heart J 1971; 33:742. 19. Renet S, Chaumais MC, Antonini T, et al. Extreme bradycardia after first doses of sofosbuvir and daclatasvir in patients receiving amiodarone: 2 cases including a rechallenge. Gastroenterology 2015; 149:1378. 20. Ludomirsky A, Klein HO, Sarelli P, et al. Q-T prolongation and polymorphous ("torsade de pointes") ventricular arrhythmias associated with organophosphorus insecticide poisoning. Am J Cardiol 1982; 49:1654. 21. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 22. Caples SM, Rosen CL, Shen WK, et al. The scoring of cardiac events during sleep. J Clin Sleep Med 2007; 3:147. 23. Becker H, Brandenburg U, Peter JH, Von Wichert P. Reversal of sinus arrest and atrioventricular conduction block in patients with sleep apnea during nasal continuous positive airway pressure. Am J Respir Crit Care Med 1995; 151:215. 24. Gilson GJ, Miller AC, Clevenger FW, Curet LB. Acute spinal cord injury and neurogenic shock in pregnancy. Obstet Gynecol Surv 1995; 50:556. 25. Cunha BA. The diagnostic significance of relative bradycardia in infectious disease. Clin Microbiol Infect 2000; 6:633. 26. Puljiz I, Beus A, Kuzman I, Seiwerth S. Electrocardiographic changes and myocarditis in trichinellosis: a retrospective study of 154 patients. Ann Trop Med Parasitol 2005; 99:403. https://www.uptodate.com/contents/sinus-bradycardia/print 10/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate 27. Dobrzynski H, Boyett MR, Anderson RH. New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation 2007; 115:1921. 28. Sanders P, Kistler PM, Morton JB, et al. Remodeling of sinus node function in patients with congestive heart failure: reduction in sinus node reserve. Circulation 2004; 110:897. 29. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S729. 30. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 31. https://cpr.heart.org/-/media/CPR-Files/CPR-Guidelines-Files/Algorithms/AlgorithmACLS_Bra dycardia_200612.pdf (Accessed on January 06, 2022). 32. Tresch DD, Fleg JL. Unexplained sinus bradycardia: clinical significance and long-term prognosis in apparently healthy persons older than 40 years. Am J Cardiol 1986; 58:1009. Topic 1075 Version 31.0 https://www.uptodate.com/contents/sinus-bradycardia/print 11/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate GRAPHICS Normal heart rates in adults based on age and sex HR (beats per minute) Age All Male Female (years) N Mean 1%-99% N Mean 1%-99% N Mean 1%-99% 20-29 6086 67 43-98 3127 64 42-99 2959 69 46-99 30-39 9569 69 46-100 4605 67 44-99 4964 70 48-100 40-49 15,392 69 46-101 7104 68 45-101 8288 70 48-102 50-59 18,578 68 46-102 9936 68 45-102 8642 69 47-102 60-69 16,585 67 44-102 9457 65 42-102 7128 68 46-101 70-79 8432 65 43-101 4509 64 42-102 3923 67 44-101 80-89 2259 65 44-101 1001 63 41-98 1258 67 46-102 90-99 119 70 43-146 58 64 43-95 81 72 44-147 Normal heart rate values (with range from 1st to 99th percentile) for heart rate (beats/minute) in 77,276 healthy adults according to age and gender. %: percent; HR: heart rate. Data from: Mason JW, Ramseth DJ, Chanter DO, et al. Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 2007; 40:228. Graphic 77746 Version 4.0 https://www.uptodate.com/contents/sinus-bradycardia/print 12/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate ECG of sinus rhythm to Normal electrocardiogram (ECG) Normal sinus rhythm at a rate of 71 beats/minute, a P wave axis of 45 , and a PR interval of 0.15 seconds. ECG: electrocardiogram. Courtesy of Morton Arnsdorf, MD. Graphic 58149 Version 5.0 https://www.uptodate.com/contents/sinus-bradycardia/print 13/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate Single lead electrocardiogram (ECG) showing sinus bradycardia Marked sinus bradycardia at a rate of 25 to 30 beats/min. The normal P waves (upright in lead II) and PR interval are consistent with a sinus mechanism with normal atrioventricular (AV) conduction. Courtesy of Ary Goldberger, MD. Graphic 52675 Version 4.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinus-bradycardia/print 14/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate Causes of bradycardia Intrinsic Extrinsic Idiopathic degenerative disorder Drugs Ischemic heart disease Antiarrhythmic agents Chronic ischemia Class IA - quinidine, procainamide Acute myocardial infarction Class IC - propafenone, flecainide Hypertensive heart disease Class II - -blockers Cardiomyopathy Class III - sotalol, amiodarone, dronedarone Trauma Class IV - diltiazem, verapamil Surgery for congenital heart disease Cardiac glycosides Heart transplant Antihypertensive agents Inflammation Clonidine, reserpine, methyldopa Collagen vascular disease Antipsychotic agents Rheumatic fever Lithium, phenothiazines, amitriptyline Pericarditis Autonomically mediated Infection Vasovagal syncope (cardioinhibitory) Viral myocarditis Carotid sinus hypersensitivity Lyme disease (Borrelia burgdorfer I) Hypothyroidism Neuromuscular disorder Intracranial hypertension Friedreich ataxia Hypothermia X-linked muscular dystrophy Hyperkalemia Familial disorder Hypoxia Anorexia nervosa Reproduced with permission from: Fuster V, Walsh R, Harrington R. Hurst's the Heart, 13th ed, McGraw-Hill Professional, New York 2010. Copyright 2010 The McGraw-Hill Companies, Inc. Graphic 65521 Version 11.0 https://www.uptodate.com/contents/sinus-bradycardia/print 15/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate Major etiologies of bradyarrhythmias Sinus bradycardia and its variants - including sinoatrial block Atrioventricular heart block or dissociation - can occur with sinus rhythm or atrial fibrillation or flutter Second or third degree AV block Isorhythmic AV dissociation and related variants Wandering atrial pacemaker Junctional (AV nodal) escape rhythms - can occur with sinus rhythm or atrial fibrillation or flutter Ventricular escape (idioventricular) rhythms Graphic 50037 Version 1.0 https://www.uptodate.com/contents/sinus-bradycardia/print 16/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate Algorithm for the diagnosis and management of sinus bradycardia https://www.uptodate.com/contents/sinus-bradycardia/print 17/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate https://www.uptodate.com/contents/sinus-bradycardia/print 18/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate ECG: electrocardiogram; ETT: exercise tolerance test; TSH: thyroid stimulating hormone; IV: intravenous; MI: myocardial infarction; HR: heart rate; ILR: implantable loop recorder; SSS: sick sinus syndrome; PPM: permanent pacemaker. If atropine is ineffective, IV infusion of dopamine (5 to 20 mcg/kg/minute) or epinephrine (2 to 10 mcg/minute) may also be considered prior to temporary pacing. Graphic 103718 Version 2.0 https://www.uptodate.com/contents/sinus-bradycardia/print 19/20 7/6/23, 11:17 AM Sinus bradycardia - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Jonathan Piccini, MD, MHS, FACC, FAHA, FHRS Grant/Research/Clinical Trial Support: Abbott [Atrial fibrillation, catheter ablation]; AHA [Atrial fibrillation, cardiovascular disease]; Bayer [Atrial fibrillation]; Boston Scientific [Cardiac mapping, pacemaker/ICD, atrial fibrillation care]; iRhythm [Atrial fibrillation]; NIA [Atrial fibrillation]; Philips [Lead management]. Consultant/Advisory Boards: Abbott [Atrial fibrillation, catheter ablation]; Abbvie [Atrial fibrillation]; Bayer [Atrial fibrillation]; Boston Scientific [Cardiac mapping, atrial fibrillation, pacemaker/ICD]; ElectroPhysiology Frontiers [Atrial fibrillation, catheter ablation]; Element Science [DSMB]; Medtronic [Atrial fibrillation, pacemaker/ICDs]; Milestone [Supraventricular tachycardia]; Pacira [Atrial fibrillation]; Philips [Lead extraction]; ReCor [Cardiac arrhythmias]; Sanofi [Atrial fibrillation]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinus-bradycardia/print 20/20 |
7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation : Munther K Homoud, MD : Samuel L vy, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 30, 2022. INTRODUCTION Sinus node dysfunction (SND), also historically referred to as sick sinus syndrome (SSS) is characterized by dysfunction of the sinoatrial (SA) node that is often secondary to senescence of the SA node and surrounding atrial myocardium. Patients with SND are typically symptomatic with fatigue, lightheadedness, palpitations, presyncope, and/or syncope, although the occasional patient may be identified during electrocardiography (ECG) or ambulatory ECG monitoring performed for another indication. The clinical manifestations, evaluation, and approach to diagnosis of SND will be reviewed here. The causes, natural history, and management of SND, along with the appropriate timing of referral to a specialist, are discussed in detail separately. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Sinus node dysfunction: Treatment" and "Arrhythmia management for the primary care clinician", section on 'Referral to a specialist'.) DEFINITION SND is a clinical syndrome characterized by chronic sinoatrial (SA) node dysfunction, a sluggish or absent SA nodal pacemaker after electrical cardioversion, and/or depressed escape pacemakers in the presence or absence of atrioventricular (AV) nodal conduction disturbances [1-3]. SND may also manifest as chronotropic incompetence with inappropriate heart rate responses to physiological demands during activity. SND can also be accompanied by AV nodal https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 1/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate conduction disturbances and by atrial tachyarrhythmias as part of the tachycardia-bradycardia syndrome. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Definition'.) CLINICAL PRESENTATION SND is defined by electrocardiogram (ECG) abnormalities (eg, bradycardia, sinus pauses, sinus arrest) that occur in association with clinical signs and symptoms. Most patients with SND present with one or more of the following nonspecific symptoms: fatigue, lightheadedness, palpitations, presyncope, syncope, dyspnea on exertion, or chest discomfort. Symptoms are frequently intermittent with gradual progression in frequency and severity, although some patients may present with profound, persistent symptoms at the initial visit. Rarely, SND may be asymptomatic and identified on routine ECG or ambulatory ECG monitoring. Symptoms Patients with symptomatic SND are primarily older and frequently have comorbid diseases. Patients with SND often seek medical attention with symptoms of lightheadedness, presyncope, syncope, and, in patients with alternating periods of bradycardia and tachycardia, palpitations and/or other symptoms associated with a rapid heart rate. Patients with coexisting cardiac pathology may notice increasing dyspnea on exertion or worsening chest discomfort related to lower heart rate and the resulting reduction in cardiac output. Because symptoms may be variable in nature, nonspecific, and frequently transient, it may be challenging at times to establish this symptom-rhythm relationship. Prior to any testing beyond an ECG, a thorough evaluation should be performed for potentially reversible causes, which include medication use (eg, beta blockers, calcium channel blockers, digoxin, antiarrhythmics), myocardial ischemia, systemic illness (eg, hypothyroidism), and autonomic imbalance. (See 'Approach to the diagnosis' below.) SND is defined by ECG abnormalities (eg, bradycardia, sinus pauses, sinus arrest) that occur in association with clinical signs and symptoms. Of note, ECG abnormalities alone, in particular sinus bradycardia, do not always denote the presence of SND. As an example, highly conditioned athletes often have a pronounced increase in vagal tone at rest with heart rates well below 60 beats per minute in the absence of symptoms. ECG findings The diagnosis of SND in persons with suggestive symptoms is often made from the surface ECG. ECG manifestations can include: Periods of inappropriate, and often severe (less than 50 beats per minutes), bradycardia [1,3]. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 2/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Sinus pauses, arrest, and sinoatrial (SA) exit block with, and often without, appropriate atrial and junctional escape rhythms. The failure of escape pacemakers may lead to symptoms including syncope [1,3]. (See "Sinoatrial nodal pause, arrest, and exit block".) Alternating bradycardia and atrial tachyarrhythmias in over 50 percent of cases [1,4-9]. Atrial fibrillation is most common, but atrial flutter and paroxysmal supraventricular tachycardias (ie, due to atrial tachycardia) may also occur. Atrial arrhythmias seem to develop slowly over time, possibly the result of a progressive pathological process that affects the SA node and the atrium [10-12]. Various examples of the ECG findings that may be seen are shown in the accompanying figures ( waveform 1 and waveform 2 and waveform 3). APPROACH TO THE DIAGNOSIS There are no standardized criteria for establishing a diagnosis of SND, and the initial clues to the diagnosis of SND are most often gleaned from the patient s history. However, the symptoms of SND are nonspecific and the electrocardiogram (ECG) findings may not be diagnostic. Hence, the key to making a diagnosis of SND is to establish a correlation between the patient's symptoms and the underlying rhythm at the time of the symptoms. Patients may present with symptoms of fatigue, lightheadedness, presyncope, syncope, dyspnea on exertion, chest discomfort, and/or palpitations. A routine ECG and/or ambulatory ECG monitoring may confirm the diagnosis if typical ECG findings (eg, one or more of sinus bradycardia; sinus pauses, arrest, and sinoatrial [SA] exit block; or alternating bradycardia and atrial tachyarrhythmias) can be correlated with symptoms. In some patients, however, additional diagnostic testing may be required, and SND should not be diagnosed until any potentially reversible causes have been identified and treated. Our approach is as follows ( algorithm 1): Comprehensive history and physical examination, resting 12-lead ECG, review of prior records and ECG tracings, and exercise stress testing The key to making a diagnosis of SND is establishing a symptom-rhythm correlation. Hence, a good history and ECG findings during symptoms are often sufficient to diagnose SND. Careful review of prior records, in particular previous ECG tracings, can provide subtle clues to changes in the ECG over time. For patients with clinically suspected SND in whom the diagnosis remains uncertain following the initial ECG, we perform exercise stress testing. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 3/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Exercise stress testing can aid in identifying abnormal sinus node function, excluding myocardial ischemia, and can help guide device programming for patients who ultimately receive a permanent pacemaker (eg, rate responsiveness). A subnormal increase in heart rate after exercise (ie, chronotropic incompetence) can help identify individuals with abnormal sinus node function who may benefit from a pacemaker implantation [13,14]. While there are various definitions on what is considered subnormal, most clinicians diagnose chronotropic incompetence as the inability of achieving at least 80 percent of the maximum predicted heart rate with exercise testing [15]. The sensitivity and specificity of this latter approach, however, are uncertain, and the results obtained may not be reproducible [16]. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".) Careful review for potentially reversible causes and medication use should be performed to exclude remediable causes for apparent SND [15]. In patients with medication use (eg, beta blockers, calcium channel blockers, digoxin, antiarrhythmics, and acetylcholine esterase inhibitors) suspected to result in symptomatic bradycardia, the patient should remain on an ECG monitor while the medications are withdrawn. If symptoms and ECG abnormalities persist following the withdrawal of the medications (ie, after three to five half-lives), then SND can be diagnosed. Similarly, patients with symptomatic bradycardia suspected to be due to myocardial ischemia, hypothyroidism, or another condition should receive treatment directed at that condition while ECG monitoring continues. If SND cannot be definitively diagnosed following history, physical, and initial 12-lead ECG, ambulatory ECG monitoring (with a continuous monitor [Holter] for 1 to 14 days and/or event monitor for up to four weeks) should be performed to identify symptomatic episodes of arrhythmias and average heart rates over extended periods of surveillance [15]. (See "Ambulatory ECG monitoring".) In patients with suspected SND but without a confirmed diagnosis following ambulatory ECG monitoring, additional testing may include: Extended ambulatory ECG monitoring with an insertable cardiac monitor (also sometimes called an implantable cardiac monitor or an implantable loop recorder). (See 'Ambulatory ECG monitoring and event recording' below.) Electrophysiology studies (EPS) have historically been used, but the very limited sensitivity of EPS in detecting evidence of SND has limited the usefulness of EPS. In symptomatic patients with suspected SND but no ECG documentation, EPS may be considered. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 4/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Referral to a cardiac electrophysiologist should be considered at any point in the diagnostic approach, but is most helpful if SND is suspected but not confirmed following the initial period of ambulatory ECG monitoring (up to four weeks). Once SND is confirmed, treatment typically involves referral for implantation of a pacemaker. Management of SND is discussed in detail separately. (See "Sinus node dysfunction: Treatment".) DIAGNOSTIC TESTING For patients in whom SND is clinically suspected but not confirmed by electrocardiogram (ECG) and/or exercise stress test findings, a number of different modalities may be helpful. In most patients, ambulatory ECG monitoring for an extended period of time (typically two to four weeks but potentially longer) has the greatest yield and allows for correlation with symptoms. In select patients where the diagnosis remains uncertain, other diagnostic testing options include adenosine administration, carotid sinus massage, and invasive electrophysiology studies. Ambulatory ECG monitoring and event recording For patients with clinically suspected SND in whom the initial ECG and monitoring are non-diagnostic, we perform additional ambulatory ECG monitoring [15]. We most frequently use an ambulatory event monitor for two to four weeks to try to capture the ECG during a symptomatic episode. Rare patients with frequent symptoms may be successfully diagnosed with an ambulatory Holter monitor worn for 24 to 48 hours, while patients with less frequent symptoms may require extended monitoring for months to years with an implantable cardiac monitor. The introduction of the insertable cardiac monitor into the diagnostic armamentarium has enhanced the diagnostic yield of the clinical evaluation [17]. The challenge of evaluating patients with SND remains the nonspecificity of symptoms, apart from syncope, and the inconsistency of electrocardiographic clues. Management requires correlation between symptoms and electrocardiographic findings. The insertable cardiac monitor is uniquely suited to achieve this goal and is becoming more frequently and earlier in the cascade of diagnostic tools. (See "Ambulatory ECG monitoring".) Ambulatory ECG monitoring with a 24-hour Holter monitor may provide important clues in 50 to 70 percent of patients with suspected SND [18-20]. However, the sensitivity and specificity of a 24-hour continuous monitor is relatively low due to the variable nature of symptoms and short duration of monitoring [21]. The use of cardiac event monitors, ambulatory ECG monitors which are typically worn for two to four weeks, has been shown to be more effective than 24-hour continuous monitors in establishing a diagnosis [22,23]. In some instances where the symptoms are very infrequent, the use of implantable event monitors have been used that allow for monitoring periods of greater than one year [24]. Variable patient compliance and sensitivity to https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 5/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate the adhesive electrode patches further limits the utility of two- to four-week week monitoring. The enhanced diagnostic utility of insertable cardiac monitoring has significantly reduced the role of pharmacological challenge, determining the intrinsic heart rate and invasive electrophysiological studies. The latter tests are of limited diagnostic yield lacking both sensitivity and specificity. Pharmacologic challenge A number of drugs have been used in aiding the diagnosis of SND, but none are used in routine clinical practice. Atropine and isoproterenol Atropine (1 or 2 mg) and isoproterenol (2 to 3 mcg/minute) may be useful, since both agents normally increase the sinus rate [25,26]. A suggested abnormal response is an increase in the sinus rate of less than 25 percent, or to a rate below 90 beats per minute. Since in most cases the diagnosis of SND can be achieved by establishing a symptom-rhythm correlation with the use of ambulatory monitor and a comprehensive history and physical exam, testing with these agents is rarely necessary. Adenosine Adenosine has been proposed as an alternative to invasive electrophysiology studies, but its routine use is not yet established [27-29]. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Electrocardiographic and electrophysiologic recordings'.) Calculating the intrinsic heart rate The intrinsic heart rate (IHR) is the heart rate in the presence of complete pharmacological denervation of the sinus node [30]. This is achieved with the simultaneous use of beta blockers and atropine. The calculation of the IHR following simultaneous administration of beta blockers and atropine is largely of historical interest and is rarely performed in the modern evaluation of patients with suspected SND. Electrophysiologic testing Invasive electrophysiologic studies (EPS) are rarely used for the evaluation of SND (eg, symptomatic patient who has no electrocardiographic findings suggestive of SND but no other evident cause for the symptoms) because of their limited sensitivity in eliciting bradyarrhythmic abnormalities as well as the widespread availability of diagnostic options for long-term monitoring. However, EPS may be helpful in patients with suspected SND who also describe sustained episodes of tachyarrhythmias in an effort to identify a tachycardia (eg, atrial tachycardia) that would be potentially curable with ablation [15]. The 2018 ACC/AHA/HRS guidelines do not support performing invasive EP studies for the sole purpose of establishing a diagnosis of SND [15]. The function of the sinus node can be evaluated invasively (ie, EP studies) within the context of evaluating a patient with other conditions such as a life-threatening arrhythmia that may warrant an implantable cardioverter defibrillator. Establishing a diagnosis of SND under such circumstances may lead the operator to consider https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 6/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate implanting an ICD with atrial pacing capabilities. These guidelines have conferred a Class IIb indication for invasive EP studies for establishing the diagnosis of SND. The salient aspects of electrophysiology studies that aid in eliciting a bradyarrhythmic abnormality include assessment of the SA node recovery time, SA conduction time, and the sinus node and atrial tissue refractory periods. A more detailed discuss of invasive EPS is presented separately. (See "Invasive diagnostic cardiac electrophysiology studies".) DIFFERENTIAL DIAGNOSIS While SND is common, other conditions should also be considered in the differential diagnosis, including carotid sinus hypersensitivity, neurocardiogenic syncope with a predominant cardioinhibitory component, and physiologically normal bradycardia especially among highly conditioned athletes. Carotid sinus massage is typically not employed in diagnosing SND but is often used to establish the presence of carotid sinus hypersensitivity that may elucidate a cause for syncope. Some have advocated for its use in the assessment of SND due to previous reports describing an association between carotid sinus hypersensitivity and SND [31]. With carotid sinus massage, a pause longer than three seconds and/or a symptomatic drop in blood pressure are indicative of carotid sinus hypersensitivity. This study has limited specificity in establishing a diagnosis of carotid sinus hypersensitivity as the reason for syncope. Occasionally, otherwise asymptomatic older adult individuals may exhibit sinus pauses greater than three seconds in duration. Hence, interpretation of the results of carotid sinus massage must be made in the proper clinical context. The technique for performing this test and contraindications are discussed in detail elsewhere. (See "Vagal maneuvers", section on 'Carotid sinus massage'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Syncope" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 7/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Sinus node dysfunction (The Basics)") SUMMARY AND RECOMMENDATIONS Definition Sinus node dysfunction (SND) is characterized by dysfunction of the sinoatrial (SA) node that is often secondary to senescence of the SA node and surrounding atrial myocardium. SND is characterized by chronic sinoatrial (SA) node dysfunction, a sluggish or absent SA nodal pacemaker after electrical cardioversion, and/or depressed escape pacemakers in the presence or absence of atrioventricular (AV) nodal conduction disturbances. SND may also manifest as chronotropic incompetence with inappropriate heart rate responses to physiological demands during activity. (See 'Definition' above.) Clinical presentation SND is defined by ECG abnormalities that occur in association with clinical signs and symptoms. Most patients with SND with present with one or more of the following nonspecific symptoms: fatigue, lightheadedness, palpitations, presyncope, syncope, dyspnea on exertion, or angina. Symptoms are frequently intermittent with gradual progression in frequency and severity. (See 'Clinical presentation' above.) ECG findings Typical ECG findings in patients with SND include one or more of sinus bradycardia; sinus pauses, arrest, and SA exit block; and alternating bradycardia and atrial tachyarrhythmias ( waveform 1 and waveform 2 and waveform 3). (See 'ECG findings' above.) Diagnosis There are no standardized criteria for making a diagnosis of SND, and the key is to establish a symptom-rhythm correlation. The initial clues to the diagnosis of SND are most often gleaned from the patient s history. However, the symptoms of SND are https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 8/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate nonspecific and the ECG findings may not be diagnostic. Hence, the key to making a diagnosis of SND is to establish a correlation between the patient's symptoms and the underlying rhythm at the time of the symptoms. Our approach to the diagnosis of SND is summarized in the text ( algorithm 1). (See 'Approach to the diagnosis' above.) Role of ambulatory monitoring Patients with clinically suspected SND in whom the initial ECG and monitoring are non-diagnostic should undergo ambulatory ECG monitoring. We most frequently use an ambulatory event monitor for two to four weeks to try to capture the ECG during a symptomatic episode. (See 'Ambulatory ECG monitoring and event recording' above.) Role of additional evaluation For patients in whom the diagnosis remains uncertain following ambulatory ECG monitoring, additional diagnostic options include the insertion of an insertable cardiac monitor that may last as long as three years. Pharmacologic challenge and invasive electrophysiology testing are rarely employed. Referral to a cardiac electrophysiologist should be considered. (See 'Diagnostic testing' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Alan Cheng, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Ferrer MI. The sick sinus syndrome in atrial disease. JAMA 1968; 206:645. 2. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967; 29:469. 3. Ferrer MI. The Sick Sinus Syndrome, Futura Press, New York 1974. 4. SHORT DS. The syndrome of alternating bradycardia and tachycardia. Br Heart J 1954; 16:208. 5. BIRCHFIELD RI, MENEFEE EE, BRYANT GD. Disease of the sinoatrial node associated with bradycardia, asystole, syncope, and paroxysmal atrial fibrillation. Circulation 1957; 16:20. 6. Rubenstein JJ, Schulman CL, Yurchak PM, DeSanctis RW. Clinical spectrum of the sick sinus syndrome. Circulation 1972; 46:5. 7. Kaplan BM, Langendorf R, Lev M, Pick A. Tachycardia-bradycardia syndrome (so-called "sick sinus syndrome"). Pathology, mechanisms and treatment. Am J Cardiol 1973; 31:497. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 9/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate 8. Gomes JA, Kang PS, Matheson M, et al. Coexistence of sick sinus rhythm and atrial flutter- fibrillation. Circulation 1981; 63:80. 9. Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus- node dysfunction. N Engl J Med 2002; 346:1854. 10. Ferrer MI. The etiology and natural history of sinus node disorders. Arch Intern Med 1982; 142:371. 11. Simonsen E, Nielsen JS, Nielsen BL. Sinus node dysfunction in 128 patients. A retrospective study with follow-up. Acta Med Scand 1980; 208:343. 12. Thery C, Gosselin B, Lekieffre J, Warembourg H. Pathology of sinoatrial node. Correlations with electrocardiographic findings in 111 patients. Am Heart J 1977; 93:735. 13. Eraut D, Shaw DB. Sinus bradycardia. Br Heart J 1971; 33:742. 14. Kay GN. Quantitation of chronotropic response: comparison of methods for rate- modulating permanent pacemakers. J Am Coll Cardiol 1992; 20:1533. 15. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 16. Josephson, ME. Sinus Node Function. In: Clinical Cardiac Electrophysiology: Techniques and I nterpretations, 4th, Lippincott, Williams, & Wilkins, Philadelphia 2008. p.69-92. 17. Furukawa T, Maggi R, Bertolone C, et al. Additional diagnostic value of very prolonged observation by implantable loop recorder in patients with unexplained syncope. J Cardiovasc Electrophysiol 2012; 23:67. 18. Lipski J, Cohen L, Espinoza J, et al. Value of Holter monitoring in assessing cardiac arrhythmias in symptomatic patients. Am J Cardiol 1976; 37:102. 19. Reiffel JA, Bigger JT Jr, Cramer M, Reid DS. Ability of Holter electrocardiographic recording and atrial stimulation to detect sinus nodal dysfunction in symptomatic and asymptomatic patients with sinus bradycardia. Am J Cardiol 1977; 40:189. 20. Gibson TC, Heitzman MR. Diagnostic efficacy of 24-hour electrocardiographic monitoring for syncope. Am J Cardiol 1984; 53:1013. 21. Kerr CR, Strauss HC. The measurement of sinus node refractoriness in man. Circulation 1983; 68:1231. 22. Kinlay S, Leitch JW, Neil A, et al. Cardiac event recorders yield more diagnoses and are more cost-effective than 48-hour Holter monitoring in patients with palpitations. A controlled https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 10/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate clinical trial. Ann Intern Med 1996; 124:16. 23. Zimetbaum PJ, Josephson ME. The evolving role of ambulatory arrhythmia monitoring in general clinical practice. Ann Intern Med 1999; 130:848. 24. Vavetsi S, Nikolaou N, Tsarouhas K, et al. Consecutive administration of atropine and isoproterenol for the evaluation of asymptomatic sinus bradycardia. Europace 2008; 10:1176. 25. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al. Electrophysiologic effects of atropine on sinus node and atrium in patients with sinus nodal dysfunction. Am J Cardiol 1976; 38:848. 26. Talano JV, Euler D, Randall WC, et al. Sinus node dysfunction. An overview with emphasis on autonomic and pharmacologic consideration. Am J Med 1978; 64:773. 27. Burnett D, Abi-Samra F, Vacek JL. Use of intravenous adenosine as a noninvasive diagnostic test for sick sinus syndrome. Am Heart J 1999; 137:435. 28. Fragakis N, Iliadis I, Sidopoulos E, et al. The value of adenosine test in the diagnosis of sick sinus syndrome: susceptibility of sinus and atrioventricular node to adenosine in patients with sick sinus syndrome and unexplained syncope. Europace 2007; 9:559. 29. Viskin S, Justo D, Halkin A. Should the 'adenosine-challenge test' be part of the routine work- up for syncope? Europace 2007; 9:557. 30. Opthof T. The normal range and determinants of the intrinsic heart rate in man. Cardiovasc Res 2000; 45:177. 31. Thormann J, Schwarz F, Ensslen R, Sesto M. Vagal tone, significance of electrophysiologic findings and clinical course in symptomatic sinus node dysfunction. Am Heart J 1978; 95:725. Topic 896 Version 35.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 11/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate GRAPHICS Single lead electrocardiogram (ECG) showing sick sinus syndrome and atrial fibrillation Rhythm strip showing sick sinus syndrome. The initial part (left) of the tracing reveals coarse atrial fibrillation with irregular ventricular response in the absence of drugs that slow AV nodal conduction. The atrial fibrillation terminates and is followed by a sinus beat with a prolonged sinus node recovery time of nearly four seconds. Courtesy of Ary Goldberger, MD. Graphic 51193 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 12/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram (ECG) showing manifestations of sick sinus syndrome (SSS) with sinus arrest Example of sick sinus syndrome (SSS). In this example, sinus arrest is seen with a junctional escape beat, a premature atrial complex, and eventual resumption of sinus activity. Courtesy of Alan Cheng, MD, FACC, FAHA, FHRS. Graphic 91605 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 13/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Single lead electrocardiogram (ECG) showing sick sinus syndrome (SSS) with ectopic atrial and junctional beats Example of sick sinus syndrome (SSS). In this example, sinus rhythm abruptly pauses, followed by two ectopic atrial beats, a junctional escape beat, and resumption of sinus activity. Courtesy of Alan Cheng, MD, FACC, FAHA, FHRS. Graphic 91606 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 14/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Algorithm for evaluation of the patient with suspected sick sinus syndrome (SSS) H&P: history and physical; ECG: electrocardiogram; ETT: exercise treadmill test; PPM: permanent pacemaker; SSS: sick sinus syndrome. Graphic 103295 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 15/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 16/16 |
7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinus node dysfunction: Treatment : Munther K Homoud, MD : N A Mark Estes, III, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 16, 2022. INTRODUCTION Sinus node dysfunction (SND), also historically referred to as sick sinus syndrome, is characterized by dysfunction of the sinoatrial (SA) node that is often secondary to senescence of the SA node and surrounding atrial myocardium. The initial clues to the diagnosis of SND are often derived from taking the history and obtaining a routine electrocardiogram (ECG), though the symptoms (eg, fatigue, lightheadedness, palpitations, presyncope, and/or syncope) and ECG findings are frequently vague and nonspecific. The occasional patient may be identified during a standard ECG or ambulatory ECG monitoring performed for another indication. Different forms of SND exist electrophysiologically from inappropriate sinus bradycardia, chronotropic incompetence, sinus pauses, SA exit block and the tachycardia-bradycardia syndrome. Treatment of SND is directed at symptoms and typically involves the implantation of a permanent pacemaker. (See "Permanent cardiac pacing: Overview of devices and indications".) The treatment of SND will be reviewed here. The etiologies, clinical manifestations, diagnosis, evaluation, and natural history are discussed in detail separately. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation" and "Arrhythmia management for the primary care clinician", section on 'Referral to a specialist'.) DEFINITION https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 1/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate SND is a clinical syndrome characterized by chronic sinoatrial (SA) node dysfunction, a sluggish or absent SA nodal pacemaker after electrical cardioversion, and/or depressed escape pacemakers in the presence or absence of atrioventricular (AV) nodal conduction disturbances [1-3]. SND may also manifest as chronotropic incompetence with inappropriate heart rate responses to physiologic demands during activity. SND can also be accompanied by AV nodal conduction disturbances and by atrial tachyarrhythmias as part of the tachycardia-bradycardia syndrome. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Definition'.) TREATMENT Treatment of SND is directed at ameliorating symptoms, which may include lightheadedness, presyncope, syncope, and, less often, dyspnea on exertion or worsening angina. In addition, patients with tachycardia-bradycardia syndrome may present with palpitations and other symptoms associated with a rapid heart rate. While some individuals present with frank syncope, patients more commonly report progressive development of symptoms and often equate this with natural aging. Specific treatment for the control of symptomatic SND usually involves the implantation of a pacemaker. There is a limited role for pharmacologic intervention in symptomatic and/or hemodynamically unstable sinoatrial (SA) node dysfunction. Definitive therapy of irreversible SA node dysfunction requires the implantation of a permanent pacemaker. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and 'Long-term management' below.) It is important to recognize that there may be an "extrinsic" component to SND compounding the "intrinsic" component inherent to the dysfunctional SA node. The most common of these extrinsic agents are pharmacologic agents. The higher prevalence of hypertension, coronary artery disease, and atrial fibrillation (AF) in the same group of patients with SND would make it more likely that the pharmacologic regimen of such patients may include beta adrenergic blockers, non-dihydropyridine calcium channel blockers, and antiarrhythmic agents, all of which would potentially exacerbate any underlying SA node dysfunction. Initial management The initial management of the patient with symptomatic SND depends on the presence and severity of any signs and symptoms (eg, lightheadedness, presyncope, syncope, dyspnea on exertion or worsening angina) related to the ventricular rate. Unstable patients require immediate pharmacologic therapy and, in most instances, should also receive temporary pacing to increase heart rate and cardiac output. Once the patient is hemodynamically stable, assessment and treatment for any potentially reversible causes should https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 2/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate occur, followed by placement of a permanent pacemaker for patients without an identifiable reversible etiology. The evaluation and management of patients with symptomatic SND should include a review of the patient's medical regimen. Identifying pharmacologic agents with the potential to exacerbate SND (extrinsic component) is critical. If possible, discontinuing or modifying the dose of the implicated agent may help stave off the need for permanent pacing. (See 'Stable patients' below.) In order to treat patients with apparent SND appropriately, it is important to try to correlate symptoms with bradycardia or, less commonly, the associated tachycardia. Some patients have episodic symptoms suggestive of an arrhythmia (eg, lightheadedness or palpitations) but are found to have a relatively normal heart rhythm during an episode. Due to the intermittent nature of symptomatic arrhythmias, ambulatory monitoring or an event recorder is often required to establish this correlation. Bradyarrhythmias and pauses during sleep are not taken into consideration when deciding on implantation of a pacemaker. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation".) Unstable patients Patients with SND are rarely hemodynamically unstable for a prolonged period; however, those who are should be urgently treated ( algorithm 1) using the Advanced Cardiac Life Support (ACLS) protocol with atropine, dopamine, or epinephrine as well as temporary cardiac pacing (either with transcutaneous or, if immediately available, transvenous pacing) [4]. (See "Advanced cardiac life support (ACLS) in adults", section on 'Bradycardia'.) The most important clinical determination in a patient presenting with SND is whether or not the patient is hemodynamically stable or not due to the resulting bradycardia and the ensuing reduced cardiac output. Signs and symptoms of hemodynamic instability include hypotension, altered mental status, signs of shock, ongoing ischemic chest pain, and evidence of acute pulmonary edema. Such patients should be treated according to the ACLS protocol for patients with symptomatic bradycardia ( algorithm 2) [4]: Except in a transplanted (ie, denervated) heart, the first line of therapy in symptomatic bradycardia is atropine. Atropine should be promptly administered if intravenous (IV) access is available, but treatment with atropine should not delay treatment with transcutaneous pacing or a chronotropic agent. The initial dose of atropine is 0.5 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg. If the patient remains unstable, temporary cardiac pacing should be provided, although the need for this is rare in this patient population. The duration of temporary cardiac pacing https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 3/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate should be as brief as possible, with discontinuation following treatment of reversible causes or implantation of a permanent pacemaker if no reversible cause is identified. In the absence of central venous access, the most immediate way to provide temporary cardiac pacing is via transcutaneous pacing. Transcutaneous pacing is uncomfortable for the patient and may have variable efficacy depending on how well the impulses are transmitted to the myocardium; as such, transcutaneous pacing should be viewed as a temporizing measure until temporary transvenous pacing can be provided. (See "Temporary cardiac pacing".) In patients with hypotension associated with SND following atropine therapy, we administer dopamine, epinephrine, or isoproterenol via IV infusion for heart rate and blood pressure augmentation. If dopamine is chosen, we begin at a dose of 2 mcg/kg/minute and titrate up to 20 mcg/kg/minute if needed. If epinephrine is chosen, we begin at a dose of 2 mcg/minute and titrate up to 10 mcg/minute if needed. If isoproterenol is chosen, we begin at a dose of 2 mcg/minute and titrate up to 10 mcg/minute if needed. Once a hemodynamically unstable patient has been stabilized, the approach to further management is the same as for patients who were initially stable. (See 'Stable patients' below.) Stable patients Patients with SND who are hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing ( algorithm 1). However, many patients can have recurrent prolonged pauses or periods of bradycardia, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration. While stable patients are being monitored, evaluation and treatment should focus on a search for reversible causes of SA nodal depression, such as drugs (eg, beta blockers, calcium channel blockers, digoxin), ischemia, and autonomic imbalance. Not infrequently, a symptomatic bradyarrhythmia is induced by medications. The management of patients with suspected beta blocker or calcium channel blocker toxicity/overdose (either accidental or intentional) is discussed in detail separately. (See "Beta blocker poisoning" and "Calcium channel blocker poisoning".) In patients taking a beta blocker or calcium channel blocker for certain indications (ie, hypertension), there are alternative medications that can be equally effective without slowing https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 4/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate the heart rate. However, for adequate medical treatment of atrial or ventricular tachyarrhythmias, or angina related to coronary artery disease, beta blockers or calcium channel blockers may be required. Patients with SND felt to be medication-induced should be observed while the offending agent or agents are withdrawn, if clinically feasible. Such patients will often have improvement or resolution of symptoms following removal of the medication(s). For patients with drug-induced bradycardia in whom the risk/benefit ratio favors the continuation of the offending agent, pacemaker insertion is indicated. (See 'Long-term management' below.) A discussion of possible reversible causes and the approach to evaluation is presented separately. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation", section on 'Approach to the diagnosis'.) Long-term management The long-term management of the patient with symptomatic SND depends on the extent of symptoms and conduction abnormalities ( algorithm 1), as well as the likelihood of recurrence or progression leading to subsequent problems (eg, syncope, cardiac arrest, etc). Asymptomatic patients Persons with bradycardia and no symptoms attributable to the bradycardia do not require placement of a permanent pacemaker. Instead, these patients may be followed with intermittent examinations and deferral of pacemaker placement. Professional society guidelines do not generally recommend implanting a pacemaker in asymptomatic individuals with bradycardia or pauses [5]. (See "Permanent cardiac pacing: Overview of devices and indications", section on 'Class III: Pacing not indicated'.) Symptomatic patients For patients with symptomatic SND and documented symptomatic bradycardia, we recommend implantation of a permanent pacemaker rather than medical therapy or observation alone [5]. Pacemaker placement is indicated in patients with SND and a documented correlation between symptoms and sinus bradycardia or sinus pauses [5]. Symptoms of syncope and lightheadedness are reversed in virtually all patients following pacemaker placement, but there does not appear to be a survival benefit [6-10]. Temporary pacing Due to the complications associated with the use of temporary pacing wires, this therapy should be reserved for patients who fail to respond to medical therapy and for the shortest amount of time possible [11]. The use of externalized permanent pacemakers utilizing active fixation leads allows the patient greater mobility and fewer complications if the interval until the insertion of a permanent pacemaker is prolonged [12]. (See "Temporary cardiac pacing".) https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 5/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Permanent pacing Selection of the type of pacemaker and appropriate programming for a specific patient depends upon the presence or absence of atrioventricular (AV) conduction abnormalities, the presence or absence of atrial arrhythmias, the desire to maintain AV synchrony, and the need for rate-responsiveness ( algorithm 3). (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation".) Pacing within the atrium (utilizing either AAI or DDD) is required. Single chamber atrial- based pacing (AAI) can be used in selected cases when AV conduction is considered to be normal and when the expectation of developing impaired AV conduction is minimal [5,13]. While there is an advantage in minimizing the number of leads used in a pacemaker (AAI versus DDD), the fear of the future development and progression of atrioventricular conduction disease has led to the widespread adoption of dual chamber (DDD) versus single chamber (AAI) pacing. The guidelines recommend DDD for symptomatic SND with extension of the AV interval to minimize ventricular pacing [5,13]. When it is anticipated that the patient will require frequent pacing, physiologic pacing is preferred. Physiologic pacing refers to pacing modes that most closely approximate normal cardiac behavior by maintaining AV synchrony (ie, AAI or DDD systems, in contrast to VVI systems). Promoting intrinsic AV conduction and minimizing right ventricular pacing has been shown to reduce the likelihood of developing AF, heart failure, hospitalization, and pacemaker syndrome. (See "Modes of cardiac pacing: Nomenclature and selection", section on 'Physiologic pacing' and "Modes of cardiac pacing: Nomenclature and selection", section on 'Pacemaker syndrome'.) Given that patients with SND will often have chronotropic incompetence, programming rate response should be considered. This allows the pacemaker's lower rate to increase commensurate with the patient's physical activity. Several randomized trials and a subsequent 2006 meta-analysis have compared physiologic (DDD) and nonphysiologic (VVI) pacing in various settings [14-18]. While some trials were limited to patients with SND, others included patients with both SND and AV block. Among the more than 7000 patients included in the meta-analysis, some clinical benefits were seen with physiologic pacing, primarily a reduction in the development of AF and stroke, but there was no significant difference in all-cause mortality with physiologic pacing when compared with VVI pacing. Approximately one-half of patients in the meta-analysis had SND, and a subgroup analysis demonstrated a greater benefit from physiologic pacing in patients with SND compared with those with AV block, including a possible reduction in the combined endpoint of https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 6/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate cardiovascular death and stroke [14]. (See "Modes of cardiac pacing: Nomenclature and selection", section on 'Potential advantages'.) For patients without a baseline bundle branch block, the incidence of high-grade AV block requiring ventricular pacing has been estimated to be between 0.6 and 1.8 percent per year [19- 22]. However, the risk of high-grade AV block is greater in patients with a complete bundle branch block or bifascicular block at presentation (7 percent per year) [22]. This observation suggests that AAI pacing may be safe in patients with SND who do not have baseline AV conduction abnormalities or bundle branch block. The largest randomized trial evaluating AAI pacing and DDD pacing in patients with SND is the DANPACE trial, a multicenter, randomized study of 1415 patients with SND and apparently normal AV conduction (baseline PR 0.22 seconds or less, baseline QRS less than 0.12 seconds) who were followed for a mean 5.4 years after initial pacemaker insertion [23]. There was no significant difference in the primary outcome of death from any cause in the AAI group versus the DDD group (hazard ratio [HR] 1.06, 95% CI 0.88- 1.29). Among the prespecified secondary outcomes, patients with an AAI pacemaker were significantly more likely to undergo pacemaker reoperation (22 versus 12 percent in the DDD group), although less than half of the AAI patients undergoing pacemaker reoperation did so because of a need for DDD pacing (9.3 percent). The annualized rate of developing the need for DDD pacing was 1.7 percent, which is consistent with the previously published rates. A more detailed discussion of various pacemaker modalities and functions is presented separately. (See "Modes of cardiac pacing: Nomenclature and selection".) Pharmacologic therapy There are no recommended pharmacologic therapies for patients with symptomatic SND; however, withdrawal of pharmacologic agents with the potential to exacerbate SND is frequently beneficial. Many patients with SND have an SA node that is unresponsive or has a blunted response to pharmacologic agents. In a trial of 107 patients with symptomatic SND who were randomly assigned to no therapy, a rate-responsive pacemaker, or oral theophylline (which can increase heart rate by stimulation of the sympathetic nervous system) and followed for an average of 19 months, patients assigned to pacemaker therapy had a significantly lower incidence of syncope compared with those assigned to no therapy (6 versus 23 percent respectively) and a trend towards less syncope when compared with those receiving theophylline (6 versus 17 percent) [24]. Implantation of a pacemaker and theophylline had an equivalent benefit on the incidence of heart failure compared with controls (3 versus 17 percent). Anticoagulation Patients with SND who require pacemaker therapy have a high incidence of AF [25]. A known history of AF prior to pacemaker implantation as well as the duration of time since pacemaker implantation are the two most important determinants of the https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 7/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate development of AF [25]. Thromboembolism may occur in patients with SND, particularly those with the tachycardia-bradycardia syndrome and associated AF [18,26,27]. Tachycardia- bradycardia syndrome, with periods of alternating atrial tachyarrhythmias and bradycardia, occurs in over 50 percent of cases of SND, with AF being the most common tachyarrhythmia [15,28]. Thromboembolism is most likely related to the associated AF. Thus, decisions surrounding anticoagulation of patients with tachycardia-bradycardia SND with documented episodes of AF should be guided by a discussion of the potential benefits and risks of anticoagulation ( table 1 and table 2) [29]. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Patients with pacemakers may be less likely to be aware of the development of AF, particularly if AV conduction abnormalities prevent a rapid ventricular response [30]. Due to the thromboembolic risks associated with unrecognized AF, patients with pacemakers should be closely observed, by means of routine pacemaker interrogation, for the development of AF. Contemporary pacemakers are able to detect and record brief episodes of AF, which may be clinically significant [31]. Nevertheless, determining the duration of atrial tachyarrhythmias that should mandate consideration of systemic anticoagulation remains a topic of controversy and investigation with no clear guidelines [29,32]. Unless there are contraindications, patients with AF should be risk stratified on their need for anticoagulant therapy ( table 1). Most patients with SND are older adults, and older adult patients have both increased sensitivity to warfarin and an increased risk of bleeding complications ( table 2). Thus, careful monitoring is required. Other newer anticoagulants are now available and may be considered in select patients who require anticoagulation. These issues are discussed in detail separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Catheter ablation Patients with symptomatic sinus node dysfunction and paroxysmal AF can have significant post-conversion pauses that would mandate the implantation of a permanent pacemaker (PPM). PPMs allow for antiarrhythmic agents and/or more aggressive rate control with higher doses of rate-controlling agents without exacerbating the pauses that ensue upon reversion to sinus rhythm. In a select group of patients, implantation of a pacemaker can be averted by eliminating AF through catheter ablation [33]. The clinician should be mindful that, following ablation, AF may continue for three to six months before the full effect of the ablation is realized or that the long-term result of the ablation is not the complete but rather the partial elimination of AF, leaving them vulnerable to the consequences of post- conversion pauses/bradyarrhythmias. In rare instances, patients may be symptomatic due to profound sinus bradycardia alone, without evidence of AF or other tachyarrhythmias. In a pilot study involving 62 patients (40 patients <50 years of age, 22 patients 50 years of age) with symptomatic sinus bradycardia, https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 8/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate catheter ablation of the atrial ganglionated plexus, thereby modifying autonomic input to the sinus node, resulted in significantly increased resting heart rate and attenuation of symptoms in all patients, although the effect was greater in patients <50 years of age (19.3 versus 10.8 beats per minute) and was attenuated at one year in patients 50 years of age [34]. Though thought- provoking as a means of improving symptoms without implantation of a permanent pacemaker, these data should be replicated in additional studies with longer-term follow-up to determine if the benefit is sustained or attenuated with time. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Syncope" and "Society guideline links: Atrial fibrillation" and "Society guideline links: Cardiac implantable electronic devices".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Sinus node dysfunction (The Basics)" and "Patient education: Pacemakers (The Basics)" and "Patient education: Bradycardia (The Basics)") Beyond the Basics topic (see "Patient education: Pacemakers (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 9/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Definition and clinical presentation Sinus node dysfunction (SND) is a clinical syndrome characterized by sinoatrial (SA) node dysfunction (not due to a reversible cause), a sluggish or absent SA nodal pacemaker after electrical cardioversion, and/or depressed escape pacemakers. These abnormalities can result in profound sinus bradycardia, sinus pauses, sinus arrest, SA nodal exit block, and inappropriate responses to physiologic demands during exercise or stress. (See 'Definition' above.) Initial management The initial management of the patient with symptomatic SND depends on the presence and severity of any signs and symptoms (eg, lightheadedness, presyncope, syncope, dyspnea on exertion or worsening angina) related to the ventricular rate ( algorithm 1). Unstable patients Patients with SND are rarely hemodynamically unstable for a prolonged period; however, those who are should be urgently treated using the Advanced Cardiac Life Support protocol with atropine, dopamine, or epinephrine as well as temporary cardiac pacing (either with transcutaneous or, if immediately available, transvenous pacing) ( algorithm 2). (See 'Unstable patients' above and "Advanced cardiac life support (ACLS) in adults", section on 'Bradycardia'.) Stable patients Monitor Patients with SND who are hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing. However, many patients can have recurrent prolonged pauses or periods of bradycardia, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration. (See 'Stable patients' above.) Avoid drugs exacerbating SND The evaluation and management of patients with symptomatic SND should include a review of the patient's medical regimen. Identifying pharmacologic agents with the potential to exacerbate SND (extrinsic component) is critical. If possible, discontinuing or modifying the dose of the implicated agent may help stave off the need for permanent pacing. Long-term management The long-term management of the patient with symptomatic SND depends on the extent of symptoms and conduction abnormalities ( algorithm 1), as well as the likelihood of recurrence or progression leading to subsequent problems (eg, syncope, cardiac arrest, etc). Asymptomatic patients Persons with bradycardia and no symptoms attributable to the bradycardia do not require placement of a permanent pacemaker. Instead, these https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 10/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate patients may be followed with intermittent examinations and deferral of pacemaker placement. (See 'Asymptomatic patients' above.) Symptomatic patients For patients with symptomatic SND and documented symptomatic bradycardia, we recommend implantation of a permanent pacemaker rather than medical therapy or observation alone (Grade 1A). Selection of the type of pacemaker and appropriate programming for a specific patient depends upon the presence or absence of atrioventricular (AV) conduction abnormalities, the presence or absence of atrial arrhythmias, the desire to maintain AV synchrony, and the need for rate-responsiveness ( algorithm 3). (See 'Symptomatic patients' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Alan Cheng, MD, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Ferrer MI. The sick sinus syndrome in atrial disease. JAMA 1968; 206:645. 2. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967; 29:469. 3. Ferrer MI. The Sick Sinus Syndrome, Futura Press, New York 1974. 4. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S444. 5. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 6. H rtel G, Talvensaari T. Treatment of sinoatrial syndrome with permanent cardiac pacing in 90 patients. Acta Med Scand 1975; 198:341. 7. Albin G, Hayes DL, Holmes DR Jr. Sinus node dysfunction in pediatric and young adult patients: treatment by implantation of a permanent pacemaker in 39 cases. Mayo Clin Proc 1985; 60:667. https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 11/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate 8. Skagen K, Fischer Hansen J. The long-term prognosis for patients with sinoatrial block treated with permanent pacemaker. Acta Med Scand 1976; 199:13. 9. Lichstein E, Aithal H, Jonas S, et al. Natural history of severe sinus bradycardia discovered by 24 hour Holter monitoring. Pacing Clin Electrophysiol 1982; 5:185. 10. Flaker G, Greenspon A, Tardiff B, et al. Death in patients with permanent pacemakers for sick sinus syndrome. Am Heart J 2003; 146:887. 11. Murphy JJ. Current practice and complications of temporary transvenous cardiac pacing. BMJ 1996; 312:1134. 12. Braun MU, Rauwolf T, Bock M, et al. Percutaneous lead implantation connected to an external device in stimulation-dependent patients with systemic infection a prospective and controlled study. Pacing Clin Electrophysiol 2006; 29:875. 13. Gillis AM, Russo AM, Ellenbogen KA, et al. HRS/ACCF expert consensus statement on pacemaker device and mode selection. Developed in partnership between the Heart Rhythm Society (HRS) and the American College of Cardiology Foundation (ACCF) and in collaboration with the Society of Thoracic Surgeons. Heart Rhythm 2012; 9:1344. 14. Healey JS, Toff WD, Lamas GA, et al. Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data. Circulation 2006; 114:11. 15. Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus- node dysfunction. N Engl J Med 2002; 346:1854. 16. Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med 2000; 342:1385. 17. Kerr CR, Connolly SJ, Abdollah H, et al. Canadian Trial of Physiological Pacing: Effects of physiological pacing during long-term follow-up. Circulation 2004; 109:357. 18. Andersen HR, Thuesen L, Bagger JP, et al. Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. Lancet 1994; 344:1523. 19. Rosenqvist M, Obel IW. Atrial pacing and the risk for AV block: is there a time for change in attitude? Pacing Clin Electrophysiol 1989; 12:97. 20. Andersen HR, Nielsen JC, Thomsen PE, et al. Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome. Circulation 1998; 98:1315. 21. Kristensen L, Nielsen JC, Pedersen AK, et al. AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker. Pacing Clin Electrophysiol 2001; 24:358. https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 12/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate 22. Brandt J, Anderson H, F hraeus T, Sch ller H. Natural history of sinus node disease treated with atrial pacing in 213 patients: implications for selection of stimulation mode. J Am Coll Cardiol 1992; 20:633. 23. Nielsen JC, Thomsen PE, H jberg S, et al. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Eur Heart J 2011; 32:686. 24. Alboni P, Menozzi C, Brignole M, et al. Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the THEOPACE study: a randomized controlled trial. Circulation 1997; 96:260. 25. Gillis AM, Morck M. Atrial fibrillation after DDDR pacemaker implantation. J Cardiovasc Electrophysiol 2002; 13:542. 26. Andersen HR, Nielsen JC, Thomsen PE, et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997; 350:1210. 27. Rubenstein JJ, Schulman CL, Yurchak PM, DeSanctis RW. Clinical spectrum of the sick sinus syndrome. Circulation 1972; 46:5. 28. Hocini M, Sanders P, Deisenhofer I, et al. Reverse remodeling of sinus node function after catheter ablation of atrial fibrillation in patients with prolonged sinus pauses. Circulation 2003; 108:1172. 29. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. 30. Corea F, Tambasco N. Cardiac pacing: atrial fibrillation may go unrecognised. Lancet Neurol 2005; 4:265. 31. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012; 366:120. 32. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373. 33. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2017; 14:e275. https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 13/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate 34. Qin M, Zhang Y, Liu X, et al. Atrial Ganglionated Plexus Modification: A Novel Approach to Treat Symptomatic Sinus Bradycardia. JACC Clin Electrophysiol 2017; 3:950. Topic 1072 Version 35.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 14/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate GRAPHICS Algorithm for treatment of patients with sick sinus syndrome ECG: electrocardiogram; BP: blood pressure; IV: intravenous; PPM: permanent pacemaker; SSS: sick sinus syndrome. The initial dose of atropine is 0.5 mg IV push. This dose may be repeated every three to five minutes to a total dose of 3 mg. https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 15/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate While transcutaneous pacing may be initially successful in stabilizing the patient, it may not be consistently reliable and is frequently uncomfortable for the patient. Prepare for urgent transvenous pacing (if required) and obtain central venous access (preferably right internal jugular vein access). Dopamine IV infusion typically begins at a dose of 2 mcg/kg/minute and can be titrated up to 20 mcg/kg/minute if needed for heart rate and blood pressure augmentation. Epinephrine IV infusion typically begins at a dose of 2 mcg/minute and can be titrated up to 20 mcg/minute if needed for heart rate and blood pressure augmentation. Isoproterenol IV infusion typically begins at a dose of 2 mcg/minute and can be titrated up to 10 mcg/minute if needed for heart rate and blood pressure augmentation. Reversible causes of SSS may include drugs (eg, beta blockers, calcium channel blockers, digoxin), ischemia, and autonomic imbalance. Graphic 113726 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 16/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Adult bradycardia algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130748 Version 10.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 17/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Selection of pacemaker systems for patients with sinus node dysfunction Decisions are illustrated by diamonds. Shaded boxes indicate type of pacemaker. AV: atrioventricular. Reproduced with permission from: Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008; 51(21):e1-e62. Illustration used with permission of Elsevier Inc. All rights reserved. Copyright 2008 Elsevier Inc. Graphic 77929 Version 5.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 18/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Comparison of the CHADS and CHA DS -VASc risk stratification scores for 2 patients with nonvalvular AF 2 2 Definition and scores for CHADS and Stroke risk stratification with the 2 CHA DS -VASc CHADS and CHA DS -VASc scores 2 2 2 2 2 Unadjusted [1] CHADS acronym Score CHADS acronym ischemic stroke rate (% per year) 2 2 Congestive HF 1 0 0.6 Hypertension 1 1 3.0 Age 75 years 1 2 4.2 Diabetes mellitus 1 3 7.1 Stroke/TIA/TE 2 4 11.1 Maximum score 6 5 12.5 6 13.0 Unadjusted ischemic stroke rate CHA DS -VASc acronym 2 2 [2] CHA DS -VASc acronym Score 2 2 (% per year) Congestive HF 1 0 0.2 Hypertension 1 1 0.6 Age 75 years 2 2 2.2 Diabetes mellitus 1 3 3.2 Stroke/TIA/TE 2 4 4.8 Vascular disease (prior MI, PAD, or aortic plaque) 1 5 7.2 Age 65 to 74 years 1 6 9.7 Sex category (ie, female sex) 1 7 11.2 Maximum score 9 8 10.8 9 12.2 |
patient data. Circulation 2006; 114:11. 15. Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus- node dysfunction. N Engl J Med 2002; 346:1854. 16. Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med 2000; 342:1385. 17. Kerr CR, Connolly SJ, Abdollah H, et al. Canadian Trial of Physiological Pacing: Effects of physiological pacing during long-term follow-up. Circulation 2004; 109:357. 18. Andersen HR, Thuesen L, Bagger JP, et al. Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. Lancet 1994; 344:1523. 19. Rosenqvist M, Obel IW. Atrial pacing and the risk for AV block: is there a time for change in attitude? Pacing Clin Electrophysiol 1989; 12:97. 20. Andersen HR, Nielsen JC, Thomsen PE, et al. Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome. Circulation 1998; 98:1315. 21. Kristensen L, Nielsen JC, Pedersen AK, et al. AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker. Pacing Clin Electrophysiol 2001; 24:358. https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 12/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate 22. Brandt J, Anderson H, F hraeus T, Sch ller H. Natural history of sinus node disease treated with atrial pacing in 213 patients: implications for selection of stimulation mode. J Am Coll Cardiol 1992; 20:633. 23. Nielsen JC, Thomsen PE, H jberg S, et al. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Eur Heart J 2011; 32:686. 24. Alboni P, Menozzi C, Brignole M, et al. Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the THEOPACE study: a randomized controlled trial. Circulation 1997; 96:260. 25. Gillis AM, Morck M. Atrial fibrillation after DDDR pacemaker implantation. J Cardiovasc Electrophysiol 2002; 13:542. 26. Andersen HR, Nielsen JC, Thomsen PE, et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997; 350:1210. 27. Rubenstein JJ, Schulman CL, Yurchak PM, DeSanctis RW. Clinical spectrum of the sick sinus syndrome. Circulation 1972; 46:5. 28. Hocini M, Sanders P, Deisenhofer I, et al. Reverse remodeling of sinus node function after catheter ablation of atrial fibrillation in patients with prolonged sinus pauses. Circulation 2003; 108:1172. 29. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. 30. Corea F, Tambasco N. Cardiac pacing: atrial fibrillation may go unrecognised. Lancet Neurol 2005; 4:265. 31. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012; 366:120. 32. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373. 33. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2017; 14:e275. https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 13/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate 34. Qin M, Zhang Y, Liu X, et al. Atrial Ganglionated Plexus Modification: A Novel Approach to Treat Symptomatic Sinus Bradycardia. JACC Clin Electrophysiol 2017; 3:950. Topic 1072 Version 35.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 14/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate GRAPHICS Algorithm for treatment of patients with sick sinus syndrome ECG: electrocardiogram; BP: blood pressure; IV: intravenous; PPM: permanent pacemaker; SSS: sick sinus syndrome. The initial dose of atropine is 0.5 mg IV push. This dose may be repeated every three to five minutes to a total dose of 3 mg. https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 15/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate While transcutaneous pacing may be initially successful in stabilizing the patient, it may not be consistently reliable and is frequently uncomfortable for the patient. Prepare for urgent transvenous pacing (if required) and obtain central venous access (preferably right internal jugular vein access). Dopamine IV infusion typically begins at a dose of 2 mcg/kg/minute and can be titrated up to 20 mcg/kg/minute if needed for heart rate and blood pressure augmentation. Epinephrine IV infusion typically begins at a dose of 2 mcg/minute and can be titrated up to 20 mcg/minute if needed for heart rate and blood pressure augmentation. Isoproterenol IV infusion typically begins at a dose of 2 mcg/minute and can be titrated up to 10 mcg/minute if needed for heart rate and blood pressure augmentation. Reversible causes of SSS may include drugs (eg, beta blockers, calcium channel blockers, digoxin), ischemia, and autonomic imbalance. Graphic 113726 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 16/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Adult bradycardia algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130748 Version 10.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 17/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Selection of pacemaker systems for patients with sinus node dysfunction Decisions are illustrated by diamonds. Shaded boxes indicate type of pacemaker. AV: atrioventricular. Reproduced with permission from: Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008; 51(21):e1-e62. Illustration used with permission of Elsevier Inc. All rights reserved. Copyright 2008 Elsevier Inc. Graphic 77929 Version 5.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 18/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Comparison of the CHADS and CHA DS -VASc risk stratification scores for 2 patients with nonvalvular AF 2 2 Definition and scores for CHADS and Stroke risk stratification with the 2 CHA DS -VASc CHADS and CHA DS -VASc scores 2 2 2 2 2 Unadjusted [1] CHADS acronym Score CHADS acronym ischemic stroke rate (% per year) 2 2 Congestive HF 1 0 0.6 Hypertension 1 1 3.0 Age 75 years 1 2 4.2 Diabetes mellitus 1 3 7.1 Stroke/TIA/TE 2 4 11.1 Maximum score 6 5 12.5 6 13.0 Unadjusted ischemic stroke rate CHA DS -VASc acronym 2 2 [2] CHA DS -VASc acronym Score 2 2 (% per year) Congestive HF 1 0 0.2 Hypertension 1 1 0.6 Age 75 years 2 2 2.2 Diabetes mellitus 1 3 3.2 Stroke/TIA/TE 2 4 4.8 Vascular disease (prior MI, PAD, or aortic plaque) 1 5 7.2 Age 65 to 74 years 1 6 9.7 Sex category (ie, female sex) 1 7 11.2 Maximum score 9 8 10.8 9 12.2 AF: atrial fibrillation; CHADS : Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism (doubled); CHA DS -VASc: Congestive heart failure, Hypertension, Age 75 years (doubled), Diabetes mellitus, prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age 65 to 74 years, Sex category; HF: heart failure; TIA: transient ischemic attack; TE: thromboembolism; MI: myocardial infarction; PAD: peripheral artery disease. 2 2 2 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 19/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate [3] These unadjusted (not adjusted for possible use of aspirin) stroke rates were published in 2012 Actual rates of stroke in contemporary cohorts might vary from these estimates. . References: 1. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classi cation schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285:2864. 2. Lip GYH, Nieuwlaat R, Pisters R, et al. Re ning clinical risk strati cation for predicting stroke and thromboembolism in atrial brillation using a novel risk factor-based approach: the euro heart survey on atrial brillation. Chest 2010; 137:263. 3. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk strati cation schemes for ischaemic stroke and bleeding in 182 678 patients with atrial brillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33:1500. Original table and unadjusted ischemic stroke rates, as noted above, have been modi ed for this publication. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 94752 Version 14.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 20/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Clinical characteristics comprising the HAS-BLED bleeding risk score Letter Clinical characteristic* Points H Hypertension (ie, uncontrolled blood pressure) 1 A Abnormal renal and liver function (1 point each) 1 or 2 S Stroke 1 B Bleeding tendency or predisposition 1 L Labile INRs (for patients taking warfarin) 1 E Elderly (age greater than 65 years) 1 D Drugs (concomitant aspirin or NSAIDs) or excess alcohol use (1 point each) 1 or 2 Maximum 9 points HAS-BLED Bleeds per 100 patient-years score (total points) 0 1.13 1 1.02 2 1.88 3 3.74 4 8.70 5 to 9 Insufficient data The HAS-BLED bleeding risk score has only been validated in patients with atrial fibrillation receiving warfarin. Refer to UpToDate topics on anticoagulation in patients with atrial fibrillation and on specific anticoagulants for further information and other bleeding risk scores and their performance relative to clinical judgment. INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs. Hypertension is defined as systolic blood pressure >160 mmHg. Abnormal renal function is defined as the presence of chronic dialysis, renal transplantation, or serum creatinine 200 micromol/L. Abnormal liver function is defined as chronic hepatic disease (eg, cirrhosis) or biochemical evidence of significant hepatic derangement (eg, bilirubin more than 2 times the upper limit of normal, plus 1 or more of aspartate transaminase, alanine transaminase, and/or alkaline phosphatase more than 3 times the upper limit of normal). Bleeding predisposition includes chronic bleeding disorder or https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 21/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate previous bleeding requiring hospitalization or transfusion. Labile INRs for a patient on warfarin include unstable INRs, excessively high INRs, or <60% time in therapeutic range. Based on initial validation cohort from Pisters R. A novel-user-friendly score (HAS-BLED) to assess 1- year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093. Actual rates of bleeding in contemporary cohorts may vary from these estimates. Original gure modi ed for this publication. Lip GY. Implications of the CHA2DS2-VASc and HAS-BLED Scores for thromboprophylaxis in atrial brillation. Am J Med 2011; 124:111. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 75259 Version 16.0 https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 22/23 7/6/23, 11:22 AM Sinus node dysfunction: Treatment - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinus-node-dysfunction-treatment/print 23/23 |
7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinus tachycardia: Evaluation and management : Munther K Homoud, MD : Jonathan Piccini, MD, MHS, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 25, 2022. INTRODUCTION Sinus tachycardia is a rhythm in which the rate of impulses arising from the sinoatrial (SA) node is elevated. Sinus tachycardia is most often a normal and physiologic response, for example during exercise. However, sinus tachycardia can in some instances be inappropriate or pathologic. It is one of the most commonly encountered (and often overlooked) heart rhythms that may portend an adverse prognosis, particularly in patients with cardiovascular disease. The etiology, clinical presentation, evaluation, and management of sinus tachycardia, including inappropriate sinus tachycardia, will be reviewed here. Other supraventricular tachycardias, including sinoatrial reentry supraventricular tachycardia (which involves tissue from the SA node), are discussed elsewhere. (See "Overview of the acute management of tachyarrhythmias", section on 'Narrow QRS complex tachyarrhythmias' and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation" and "Sinoatrial nodal reentrant tachycardia (SANRT)".) DEFINITION AND ECG FEATURES Normal sinus rhythm (NSR) is the characteristic rhythm of the healthy human heart. NSR is considered to be present in adults if the heart rate is between 60 and 100 beats per minute, the P wave vector on the electrocardiogram (ECG) is normal, and the rate is largely regular ( waveform 1). Inspection of the P-wave vector is often overlooked but is important. The https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 1/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate normal sinus P wave demonstrates right followed by left atrial depolarization giving rise to an upright P wave in leads I, II and aVL, and a negative P wave in lead aVR. By conventional definition, a tachycardia requires the heart rate to be greater than 100 beats per minute. As such, sinus tachycardia can be thought of as a sinus-driven rhythm (normal- appearing P wave axis on the surface ECG) which is occurring at a rate of greater than 100 beats per minute ( waveform 2). However, the "normal" heart rate is, in part, the result of the complex interplay between the sympathetic and parasympathetic nervous systems. It is affected by numerous factors and varies in part with age ( table 1) [1-3]. The heart rate is usually between 110 and 150 beats per minute in infants, with gradual slowing over the next six years. The resting sinus rate in older children and adults is approximately 65 to 85 beats per minute, with slowing in older age [4-6]. There is also considerable variation based upon level of fitness and underlying medical comorbidities. (See "Normal sinus rhythm and sinus arrhythmia".) ETIOLOGY AND CLINICAL SYNDROMES Sinus tachycardia as a physiologic response In the majority of patients, sinus tachycardia is a physiologic response to a demand for greater cardiac output, increased sympathomimetic state, or vagal/parasympathetic withdrawal. Sinus tachycardia is an important mechanism for increasing cardiac output in the setting of infection or volume depletion or other stressors/illnesses. Sinus tachycardia is a normal physiologic response to exercise and conditions in which catecholamine release is physiologically enhanced or, less commonly, in situations where the parasympathetic nervous system is withdrawn. A long list of other factors may be responsible in selected cases, including: Fever Volume depletion Hypotension and shock Sepsis Anemia Hypoxia Pulmonary embolism Acute coronary ischemia and myocardial infarction Pain Anxiety https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 2/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate Sleep deprivation Pheochromocytoma Hyperthyroidism Decompensated heart failure Chronic pulmonary disease Exposure to stimulants (nicotine, caffeine, amphetamines), anticholinergic drugs, beta blocker withdrawal, or illicit drugs Abrupt withdrawal of medications such as beta blockers Postural orthostatic tachycardia syndrome Postural orthostatic tachycardia syndrome (POTS) is a condition that occurs predominantly in young women in the absence of structural heart disease. Characteristically, patients develop symptoms upon assuming the standing position. Symptoms may include palpitations, fatigue, lightheadedness, or exercise intolerance. The 2015 Heart Rhythm Consensus statement defined POTS as a heart rate rise of 30 beats per minute ( 40 beats per minute in individuals 12 to 19 years of age) in the absence of orthostatic hypotension ( 20 mmHg systolic blood pressure drop) [7]. Sinus tachycardia is only one component of this condition, which is a disorder of autonomic dysregulation [8]. (See "Postural tachycardia syndrome".) Inappropriate sinus tachycardia Inappropriate sinus tachycardia, also called chronic nonparoxysmal sinus tachycardia, is an unusual condition that occurs in individuals without apparent heart disease or other cause for sinus tachycardia, such as hyperthyroidism or fever, and is generally considered a diagnosis of exclusion [9-12]. Inappropriate sinus tachycardia is defined as a resting heart rate >100 beats per minute (with a mean heart rate >90 beats per minute over 24 hours) associated with highly symptomatic palpitations [7,13]. Commonly used criteria to define inappropriate sinus tachycardia include [14]: P wave axis and morphology similar or identical to sinus rhythm. Resting heart rate of 100 beats per minute or greater (with a mean heart rate >90 beats per minute over 24 hours) or with activity heart rates of 100 beats per minute or greater but in excess of what one would expect for the amount of exertion. Additionally, patients with inappropriate sinus tachycardia classically experience a drop in heart rate during sleep. Palpitations, presyncope, or both related to the tachycardia. Very rarely do patients experience syncope. Exclusion of identifiable causes of sinus tachycardia. Exclusion of atrial tachycardia. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 3/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate Most of these patients are young and female. Among a single-center cohort of 305 patients with inappropriate sinus tachycardia seen between 1998 and 2018, 92 percent were female, with an average age of 33 years [15]. Affected patients have an elevated resting heart rate and/or an exaggerated heart rate response to exercise that is out of proportion to the body's physiological needs; many patients have both. Patients are invariably symptomatic; the presence of symptoms is an essential component of the definition. In contrast to sinus tachycardia occurring as a physiologic response, inappropriate sinus tachycardia can continue for months or years and may produce troublesome symptoms, most commonly with palpitations, but other common symptoms include chest discomfort, fatigue, dizziness/presyncope/syncope, and shortness of breath [15]. Most patients have resting heart rates of greater than 100 beats per minute and average heart rates on a 24-hour Holter greater than 90 beats per minute with no clear physiologic, pathologic, or pharmacologic trigger [12]. Characteristic of this disorder, the mean heart rate drops during sleep. Absence of nocturnal abatement of tachycardia should prompt consideration of a diagnosis other than inappropriate sinus tachycardia. The diurnal variations in heart rate seen in inappropriate sinus tachycardia may explain the low incidence of developing tachycardia-associated cardiomyopathy in this disease [12,16]. However, patients may rarely develop cardiomyopathy secondary to a sustained rapid heart rate. (See "Arrhythmia-induced cardiomyopathy".) The pathophysiologic mechanism behind this disease is poorly understood and is thought to consist of intrinsic sinus node hyperactivity coupled with autonomic perturbations modulated by neurohormonal influences [12]. One study suggested that this tachycardia is related to a primary sinus node abnormality, characterized by a high intrinsic heart rate, depressed efferent cardiovagal reflex, and beta-adrenergic hypersensitivity [10,17]. Both isoproterenol and enhanced vagal tone shift the pacemaker site along the crista terminalis, while adenosine slows the rate but has little effect on the pacemaker focus and on activation sequence [18,19]. The shifting site of the SA pacemaker within the large epicardial SA nodal complex can be problematic when ablation is considered as a therapy [18]. CLINICAL PRESENTATION Most patients with physiologic sinus tachycardia do not have symptoms directly attributable to the tachycardia itself but present with signs or symptoms related to the associated condition (eg, pain, fever, shortness of breath, etc). However, a patient with a greater awareness of his or her heartbeat may report palpitations (subjective awareness of a rapid or forceful heartbeat). https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 4/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate In contrast, patients with postural orthostatic tachycardia syndrome or inappropriate sinus tachycardia are commonly symptomatic, as discussed above. (See 'Postural orthostatic tachycardia syndrome' above and 'Inappropriate sinus tachycardia' above.) As with any tachycardia, sinus tachycardia can indirectly lead to symptoms due to the impact of the tachycardia in the presence of underlying heart disease. Tachycardia may result in: Decreased cardiac output due to shortened ventricular filling time Increased myocardial oxygen consumption Reduced coronary blood flow The above physiologic changes induced by tachycardia may result in symptoms of angina or dyspnea, the severity of which will depend upon how rapidly the heart is beating and the extent of the underlying cardiac comorbidities. In rare cases, sustained inappropriate sinus tachycardia can lead to tachycardia-induced cardiomyopathy [20,21]. (See "Arrhythmia-induced cardiomyopathy".) Examination of precordial pulsation and the arterial pulse as means of assessing heart rate and rhythm is discussed separately. (See "Examination of the precordial pulsation" and "Examination of the arterial pulse".) DIAGNOSTIC EVALUATION Confirm sinus tachycardia Sinus tachycardia is generally confirmed by ECG after a rapid pulse is identified on physical examination, with the diagnosis usually being easy to establish from the surface ECG. An upright P wave in leads I and II indicates a sinus origin of the tachycardia [1]. However, the P waves may be difficult to identify at heart rates above 140 beats per minute, since they are often superimposed on the preceding T wave ( waveform 2). As a result, sinus tachycardia can be confused with another supraventricular tachycardia. Vagal maneuvers (eg, carotid sinus massage, Valsalva maneuver) or intravenous AV nodal blocking agents (eg, adenosine, verapamil) may help in the differentiation of sinus tachycardia from another supraventricular tachycardia by inducing one or more of the following (see "Vagal maneuvers"): Slowing the sinus rate to allow definitive identification of the sinus P waves. Causing transient AV nodal block to make atrial flutter with 2:1 block ( waveform 3) or atrial tachycardia apparent. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 5/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate Termination of a paroxysmal supraventricular tachycardia (atrioventricular nodal reentrant tachycardia or atrioventricular reentrant tachycardia). (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) Differential diagnosis Sinus tachycardia should be distinguished from atrial tachycardias, which may appear similar on the ECG. Focal atrial tachycardia is a regular atrial rhythm at a constant rate of >100 beats per minute originating outside of the sinus node. If the focus of the atrial tachycardia is close to the sinoatrial (SA) node, such as in the case of atrial tachycardia emanating from the superior crista terminalis, the P wave may be similar in appearance to a sinus P wave, giving the impression of a sinus tachycardia. The sudden and inappropriate onset of tachycardia on an ECG monitor can help differentiate one from the other. Sinus tachycardia also must be distinguished from sinoatrial nodal reentrant tachycardia. Sinus node reentrant tachycardia is a reentrant arrhythmia that is paroxysmal with a discrete onset and offset (unlike sinus tachycardia) [1]. Distinguishing focal atrial tachycardia or sinoatrial nodal reentrant tachycardia from sinus tachycardia can often only be accomplished in the EP laboratory. (See "Focal atrial tachycardia" and "Sinoatrial nodal reentrant tachycardia (SANRT)".) The primary distinction between sinus tachycardia and an atrial tachycardia is made based on the clinical situation and the onset and termination of the tachycardia. Sinus tachycardia is an appropriate response to a physiologic, pathologic, or pharmacologic trigger. Its onset and resolution are gradual. In contrast, atrial tachycardias are paroxysmal in nature with abrupt onset and termination. Atrial tachycardias can generally be distinguished by their abrupt onset and termination, in contrast to the slow ramping up and slowing down of the heart rate in sinus tachycardia [22]. Further evaluation For the majority of patients with sinus tachycardia, the underlying cause is determined from history and physical examination. Important features to elicit in a history and examination include exposure to stimulants and drugs, pain, and anxiety; and measurement of a full set of vital signs, including temperature and pulse oximetry [13]. Clues derived from the history and physical examination will direct subsequent evaluation, which can range from simple reassurance to admission and extensive testing depending on the situation. As examples: Patients with pain or anxiety will often require only simple reassurance, with return of the sinus rate to the normal range. Patients with a fever or other signs of infection should have a complete blood count drawn along with workup focused at the source of infection. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 6/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate Patients with signs or symptoms of volume depletion should be rehydrated; if the suspected cause of the volume depletion is anemia, a complete blood count should be performed. Patients with signs of symptoms of hyperthyroidism (TSH), pheochromocytoma (24-hour urinary catecholamines and metanephrines), or another systemic illness should have an evaluation focused on the suspected disorder. The most important component of evaluation in sinus tachycardia is determining if the sinus tachycardia is due to a physiologic insult such as infection, pulmonary embolus, or blood loss. Patients with sinus tachycardia who have hypotension or signs of shock related to suspected volume depletion, signs of sepsis related to infection, or acute clinical deterioration related to another suspected medical condition (eg, hypoxia, myocardial ischemia, heart failure, etc) should be admitted for evaluation and treatment. The postural orthostatic tachycardia syndrome, of which sinus tachycardia is one component, is diagnosed using a set of diagnostic criteria that incorporates exaggerated postural changes in heart rate elicited by standing, in the absence of orthostatic hypotension. The diagnosis of inappropriate sinus tachycardia is challenging and is typically made in a patient with persistent tachycardia in whom other clinical entities have been excluded. (See 'Inappropriate sinus tachycardia' above.) MANAGEMENT Treat the underlying cause In most settings, sinus tachycardia will improve or resolve following treatment directed at the underlying etiology. Rarely, patients with sinus tachycardia who have hypotension or signs of shock related to suspected volume depletion, signs of sepsis related to infection, or acute clinical deterioration related to another suspected medical condition (eg, hypoxia, myocardial ischemia, heart failure, etc) should be admitted for evaluation and treatment. Management is generally driven by the underlying causation, as therapy that is indicated for sinus tachycardia in certain conditions (eg, beta blockers for acute myocardial ischemia) may be contraindicated in other conditions (eg, hypovolemia or sepsis). Management in patients with acute coronary syndrome Sinus tachycardia occurs in one- third or more of patients with acute coronary syndromes [23,24]. The reasons for sinus tachycardia in acute coronary syndromes can vary significantly from a reaction to pain, associated anxiety, hypoxia, or even impending cardiogenic shock. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 7/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate The heart rate usually declines over time to a level that reflects the degree of activation of the sympathetic nervous system. Patients with persistent sinus tachycardia usually have larger infarcts that are more often anterior and a marked impairment in left ventricular function, which is associated with substantial morbidity and increased early and 30-day mortality [24-27]. In addition, sinus tachycardia may increase the size of ischemic injury and infarction due to increased myocardial oxygen demand. In view of the prognostic importance of sinus tachycardia, it is important to exclude other causes of this arrhythmia. These include fear, anxiety, fever, pericarditis, and medications. Heart failure, hypoxia, recurrent ischemia, and hypotension should be aggressively treated. In the absence of identifiable triggers, sinus tachycardia in acute myocardial infarction can be treated with cautious beta blockade. However, most patients will receive such therapy independent of the tachycardia since early beta blocker administration is part of routine management of acute myocardial infarction. (See "Acute myocardial infarction: Role of beta blocker therapy".) Inappropriate sinus tachycardia Treatment of symptomatic inappropriate sinus tachycardia is frequently challenging, often with suboptimal results [7,13,28]. Prior to beginning treatment, it is important to exclude other etiologies of sinus tachycardia, notably postural orthostatic tachycardia syndrome (POTS), and continue withdrawing any medications that may be contributing to tachycardia (eg, stimulants). (See 'Catheter ablation' below.) The pharmacologic management of inappropriate sinus tachycardia continues to evolve as new treatments are being developed. Once other etiologies of sinus tachycardia have been excluded, our approach to therapy is as follows: For patients with symptomatic inappropriate sinus tachycardia, we suggest a trial of beta blockade as the initial medical therapy. For patients with persistently symptomatic inappropriate sinus tachycardia after a trial of beta blockers, we suggest using ivabradine (5 mg to 7.5 mg twice daily). Radiofrequency catheter ablation to modify the sinus node may be a treatment of last resort for patients with refractory symptoms. However, symptomatic recurrence after sinus node modification is frequent, and repeated procedures often result in pacemaker implantation. Beta blockers While usually considered a first line of treatment, beta blockers have been poorly tolerated (usually due to the higher doses required for adequate heart rate control) and/or minimally effective for patients with inappropriate sinus tachycardia [13,28]. When attempting beta blocker therapy, we typically start long-acting metoprolol 50 mg daily, with https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 8/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate upward titration for adequate heart rate and symptom control. The results with beta blockers are often disappointing, however, since even if ventricular rates can be controlled, the symptoms will often persist [12,13]. Beta blocker therapy may be effective if the cause of inappropriate sinus tachycardia is overactivity of the sympathetic nervous system [29]. However, control of the heart rate is difficult if the sinus tachycardia results from depressed vagal activity. Ivabradine For patients with persistently symptomatic inappropriate sinus tachycardia, we suggest using ivabradine (5 mg to 7.5 mg twice daily) with or without a beta adrenergic receptor blocker. Although ivabradine is not available in all countries, and its use for inappropriate sinus tachycardia would be considered an off-label use in the United States, various professional society guidelines for the treatment of supraventricular tachycardia both support the use of ivabradine alone or, preferably, in conjunction with beta blockers for inappropriate sinus tachycardia [7,13,28]. Ivabradine is labeled by the FDA for use in patients with systolic heart failure (ejection fraction <35 percent) with a resting heart rate above 70 beats per minute. It is a selective blocker of the sodium channel I , one of the channels that regulates sinus node automaticity [30-32]. f Ivabradine decreases the depolarizing I current in the sinoatrial node, thereby decreasing the f heart rate [32,33]. A large randomized study of ivabradine versus placebo in patients with coronary artery disease and left ventricular dysfunction supports the safety and efficacy of ivabradine for lowering heart rates, although these patients did not have inappropriate sinus tachycardia and there are limited data on long-term safety and efficacy [34]. Additionally, ivabradine appears to be an effective treatment option for patients with inappropriate sinus tachycardia [35-38]. In a systematic review and pooled analysis that included 145 patients (70 percent female) from nine studies (one randomized trial and eight observational studies), all studies reported a reduction in heart rate following ivabradine (averaging between 10 and 20 percent reduction in mean resting heart rate) [39]. The majority of patients also reported improvement in symptoms following ivabradine. In a double-blind study of 21 patients with inappropriate sinus tachycardia, patients received either ivabradine (5 mg twice daily) or placebo for six weeks, followed by a washout period and cross over to the other treatment for six additional weeks [36]. Symptom evaluation and heart rate assessment using supine, standing, and exercise electrocardiography were performed at the beginning and end of each phase of the study. Ivabradine use resulted in the following outcomes: https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 9/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate Improvement in symptoms in all patients, with 14 patients (67 percent) reporting elimination of >70 percent of symptoms and 9 patients (43 percent) reporting complete resolution of symptoms while on ivabradine. Significant reductions in resting heart rate (from 88 to 76 beats per minute), standing heart rate (from 108 to 92 beats per minute), and heart rate during effort (176 to 158 beats per minute). Significant increases in exercise time (7.2 to 8.9 minutes). The long-term safety and efficacy of ivabradine is unknown. In early studies, it was shown to increase the risk for atrial fibrillation and development of phosphenes (enhanced visual brightness). Patients who develop atrial fibrillation should stop the medication. Continued use of ivabradine in the presence of phosphenes is reasonable [34]. (See "Approach to the patient with visual hallucinations".) Catheter ablation For patients with persistent symptomatic inappropriate sinus tachycardia despite optimal pharmacologic therapy, radiofrequency catheter ablation can be attempted, although ablation is performed very rarely and only after all other therapeutic options have been exhausted. The results of catheter ablation of the sinus node have been mixed. The goal is to modify the sinus node without ablating it completely to avoid the need for permanent pacemaker implantation. However, if the tachycardia is a reflex response related to POTS, ablation may lead to worsening symptoms; hence the importance of excluding POTS before attempting ablation of the sinus node. In fact, the 2015 consensus statement relegates catheter ablation/modification of the sinus node for inappropriate sinus tachycardia and for POTS as ineffective and probably harmful (class III) [7]. (See "Postural tachycardia syndrome", section on 'Management'.) Total sinus node ablation and sinus node modification have been attempted in small numbers of patients with inappropriate sinus tachycardia; both are technically difficult because the sinus node is a sizable (and largely epicardial) complex of cells lying along the lateral right atrial wall, not a tiny discrete focus [40]. Total sinus node ablation leaves the patient with a junctional rhythm, which usually necessitates permanent pacemaker implantation. Sinus node modification involves an initial ablation at the superior aspect of the sinoatrial nodal complex. Ablation then proceeds inferiorly until the resting heart rate and the heart rate in response to isoproterenol infusion decrease markedly. In patients who do not respond adequately to medical therapy or endocardial ablation, an alternative approach utilizing epicardial (via the pericardial space) ablation has been described [41,42]. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 10/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate Although studies are limited, both in number and in duration of follow-up, ablation for inappropriate sinus tachycardia may be modestly effective in highly selected patients with expert electrophysiologists performing the procedure. A 2017 systematic review of the literature identified 153 patients (mean age 35 years, 91 percent female, mean heart rate 105 beats per minute by 24-hour ambulatory recording) who underwent catheter ablation after failing to adequately respond to maximal medical therapy (mean 3.5 drugs) for inappropriate sinus tachycardia [40]. Acute procedural success (not uniformly defined) was reported in 89 percent of patients, with 86 percent of patients having a successful outcome at mean follow-up of 28 months, although 20 percent of patients reported recurrent symptoms. Severe procedure complications (eg, pericardial tamponade, superior vena cava syndrome, phrenic nerve paralysis) occurred in 13 patients (9 percent), and 15 patients (10 percent) required permanent pacemaker implantation. In a prospective registry of patients undergoing catheter ablation, 40 patients underwent ablation for inappropriate sinus tachycardia; acute success was achieved in 71.4 percent, but 10 percent had recurrent symptoms [43]. Other data suggest a much higher overall recurrence rate between 27 and 45 percent, in addition to the risks of right phrenic nerve injury, the future need for a pacemaker, and the risk of superior vena cava syndrome as a result of occlusion/thrombosis [13]. Sinus node ablation, however, is not effective in patients with inappropriate sinus tachycardia who have features of POTS; although the sinus rate is effectively slowed, there is no significant improvement in clinical symptoms [44]. In fact, ablation of the sinus node in POTS could lead to significant exacerbation of symptoms [12]. Given the young age of patients with inappropriate sinus tachycardia, the potential need for a pacemaker, the possible complications of the procedure (eg, phrenic nerve paralysis, superior vena cava syndrome), mixed results, and high recurrence rates, professional society guidelines do not support routine treatment with catheter ablation or modification of the sinus node for inappropriate sinus tachycardia, although it may be useful in very specific patients [7,13,28]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Supraventricular arrhythmias".) https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 11/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Definition Sinus tachycardia is a rhythm in which the rate of impulses arising from the sinoatrial (SA) node is elevated. The normal heart rate has been considered historically to range from 60 to 100 beats per minute, with sinus tachycardia being defined as a sinus rhythm with a rate exceeding 100 beats per minute. However, the "normal" heart rate varies in part with age as well as level of fitness and underlying medical comorbidities ( table 1). (See 'Definition and ECG features' above.) Causes and syndromes The most common cause of sinus tachycardia is a physiologic response to exercise and other conditions with catecholamine release, such as fever, volume depletion, hypoxia, pain, and anxiety. Other clinical syndromes associated with sinus tachycardia include autonomic dysregulation (eg, postural orthostatic tachycardia syndrome [POTS]) and inappropriate sinus tachycardia (cause unknown). (See 'Etiology and clinical syndromes' above.) Symptoms In the vast majority of patients, physiologic sinus tachycardia itself does not directly cause symptoms, although a patient with a greater awareness of his or her heartbeat may report palpitations (manifest as the sensation of a rapid heartbeat). However, as with any tachycardia, sinus tachycardia can indirectly lead to other symptoms https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 12/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate due to the impact of the tachycardia in the presence of underlying heart disease. (See 'Clinical presentation' above.) In contrast, patients with POTS or inappropriate sinus tachycardia are generally symptomatic. (See 'Postural orthostatic tachycardia syndrome' above and 'Inappropriate sinus tachycardia' above.) Diagnosis Sinus tachycardia is generally confirmed by ECG after a rapid pulse is identified on physical examination, with the diagnosis usually being easy to establish from the surface ECG. Since the tachycardia arises from the SA node, the P waves should have a normal or near-normal appearance on ECG and should occur in a regular fashion ( waveform 2). (See 'Confirm sinus tachycardia' above.) Management For physiologic sinus tachycardia In most settings, sinus tachycardia will improve or resolve following treatment directed at the underlying etiology. Patients with sinus tachycardia who have hypotension or signs of shock related to suspected volume depletion, signs of sepsis, or acute clinical deterioration related to another suspected medical condition (eg, hypoxia, myocardial ischemia, heart failure, etc) require admission for evaluation and treatment. (See 'Management' above.) For acute coronary syndrome Because persistent tachycardia in a patient with acute coronary syndrome can result in larger infarcts and a more marked impairment in left ventricular function, treatment of sinus tachycardia with beta blockers is appropriate in most patients. (See 'Management in patients with acute coronary syndrome' above and "Acute myocardial infarction: Role of beta blocker therapy".) For inappropriate sinus tachycardia Treatment of symptomatic inappropriate sinus tachycardia is challenging, often with suboptimal results. Before embarking on treatment, exclusion of secondary causes of sinus tachycardia is imperative. For patients with symptomatic inappropriate sinus tachycardia, we suggest a trial of beta blockade as the initial medical therapy (Grade 2C). We typically start long-acting metoprolol 25 to 50 mg daily, with upward titration for adequate heart rate and symptom control. Results are often disappointing. (See 'Beta blockers' above.) For patients with persistently symptomatic inappropriate sinus tachycardia, we suggest using ivabradine (5 mg to 7.5 mg twice daily) (Grade 2C). If symptomatic sinus tachycardia persists or the response is suboptimal, we will then add a beta blocker. Ivabradine is not available in all countries and its use for inappropriate sinus https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 13/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate tachycardia would be considered an off-label use in the United States. (See 'Ivabradine' above.) For patients with persistent symptomatic inappropriate sinus tachycardia despite optimal pharmacologic therapy, radiofrequency catheter ablation may be attempted. Postural orthostatic tachycardia syndrome must be excluded first, since ablation may worsen symptoms in these patients. (See 'Catheter ablation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD and Brian Olshansky, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Yusuf S, Camm AJ. The sinus tachycardias. Nat Clin Pract Cardiovasc Med 2005; 2:44. 2. Palatini P. Heart rate as a cardiovascular risk factor: do women differ from men? Ann Med 2001; 33:213. 3. Fox K, Borer JS, Camm AJ, et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol 2007; 50:823. 4. Scott O, Williams GJ, Fiddler GI. Results of 24 hour ambulatory monitoring of electrocardiogram in 131 healthy boys aged 10 to 13 years. Br Heart J 1980; 44:304. 5. Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977; 39:390. 6. Bjerregaard P. Mean 24 hour heart rate, minimal heart rate and pauses in healthy subjects 40-79 years of age. Eur Heart J 1983; 4:44. 7. Sheldon RS, Grubb BP 2nd, Olshansky B, et al. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm 2015; 12:e41. 8. Low PA, Sandroni P, Joyner M, Shen WK. Postural tachycardia syndrome (POTS). J Cardiovasc Electrophysiol 2009; 20:352. 9. Bauernfeind RA, Amat-Y-Leon F, Dhingra RC, et al. Chronic nonparoxysmal sinus tachycardia in otherwise healthy persons. Ann Intern Med 1979; 91:702. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 14/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate 10. Morillo CA, Klein GJ, Thakur RK, et al. Mechanism of 'inappropriate' sinus tachycardia. Role of sympathovagal balance. Circulation 1994; 90:873. 11. Krahn AD, Yee R, Klein GJ, Morillo C. Inappropriate sinus tachycardia: evaluation and therapy. J Cardiovasc Electrophysiol 1995; 6:1124. 12. Olshansky B, Sullivan RM. Inappropriate sinus tachycardia. J Am Coll Cardiol 2013; 61:793. 13. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. 14. Lee RJ, Shinbane JS. Inappropriate sinus tachycardia. Diagnosis and treatment. Cardiol Clin 1997; 15:599. 15. Shabtaie SA, Witt CM, Asirvatham SJ. Natural history and clinical outcomes of inappropriate sinus tachycardia. J Cardiovasc Electrophysiol 2020; 31:137. 16. Rubenstein JC, Freher M, Kadish A, Goldberger JJ. Diurnal heart rate patterns in inappropriate sinus tachycardia. Pacing Clin Electrophysiol 2010; 33:911. 17. Olshansky B. What's So Inappropriate About Sinus Tachycardia? J Cardiovasc Electrophysiol 2008; 19:977. 18. Glatter KA, Cheng J, Dorostkar P, et al. Electrophysiologic effects of adenosine in patients with supraventricular tachycardia. Circulation 1999; 99:1034. 19. Lee RJ, Kalman JM, Fitzpatrick AP, et al. Radiofrequency catheter modification of the sinus node for "inappropriate" sinus tachycardia. Circulation 1995; 92:2919. 20. Romeo E, Grimaldi N, Sarubbi B, et al. A pediatric case of cardiomyopathy induced by inappropriate sinus tachycardia: efficacy of ivabradine. Pediatr Cardiol 2011; 32:842. 21. Winum PF, Cayla G, Rubini M, et al. A case of cardiomyopathy induced by inappropriate sinus tachycardia and cured by ivabradine. Pacing Clin Electrophysiol 2009; 32:942. 22. Coss SF, Steinberg JS. Supraventricular tachyarrhythmias involving the sinus node: clinical and electrophysiologic characteristics. Prog Cardiovasc Dis 1998; 41:51. 23. DeSanctis RW, Block P, Hutter AM Jr. Tachyarrhythmias in myocardial infarction. Circulation 1972; 45:681. 24. Crimm A, Severance HW Jr, Coffey K, et al. Prognostic significance of isolated sinus tachycardia during first three days of acute myocardial infarction. Am J Med 1984; 76:983. 25. Severance HW Jr, Morris KG, Wagner GS. Criteria for early discharge after acute myocardial infarction: validation in a community hospital. Arch Intern Med 1982; 142:39. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 15/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate 26. McNeer JF, Wallace AG, Wagner GS, et al. The course of acute myocardial infarction. Feasibility of early discharge of the uncomplicated patient. Circulation 1975; 51:410. |
ERROR: type should be string, got "https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 12/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate due to the impact of the tachycardia in the presence of underlying heart disease. (See 'Clinical presentation' above.) In contrast, patients with POTS or inappropriate sinus tachycardia are generally symptomatic. (See 'Postural orthostatic tachycardia syndrome' above and 'Inappropriate sinus tachycardia' above.) Diagnosis Sinus tachycardia is generally confirmed by ECG after a rapid pulse is identified on physical examination, with the diagnosis usually being easy to establish from the surface ECG. Since the tachycardia arises from the SA node, the P waves should have a normal or near-normal appearance on ECG and should occur in a regular fashion ( waveform 2). (See 'Confirm sinus tachycardia' above.) Management For physiologic sinus tachycardia In most settings, sinus tachycardia will improve or resolve following treatment directed at the underlying etiology. Patients with sinus tachycardia who have hypotension or signs of shock related to suspected volume depletion, signs of sepsis, or acute clinical deterioration related to another suspected medical condition (eg, hypoxia, myocardial ischemia, heart failure, etc) require admission for evaluation and treatment. (See 'Management' above.) For acute coronary syndrome Because persistent tachycardia in a patient with acute coronary syndrome can result in larger infarcts and a more marked impairment in left ventricular function, treatment of sinus tachycardia with beta blockers is appropriate in most patients. (See 'Management in patients with acute coronary syndrome' above and \"Acute myocardial infarction: Role of beta blocker therapy\".) For inappropriate sinus tachycardia Treatment of symptomatic inappropriate sinus tachycardia is challenging, often with suboptimal results. Before embarking on treatment, exclusion of secondary causes of sinus tachycardia is imperative. For patients with symptomatic inappropriate sinus tachycardia, we suggest a trial of beta blockade as the initial medical therapy (Grade 2C). We typically start long-acting metoprolol 25 to 50 mg daily, with upward titration for adequate heart rate and symptom control. Results are often disappointing. (See 'Beta blockers' above.) For patients with persistently symptomatic inappropriate sinus tachycardia, we suggest using ivabradine (5 mg to 7.5 mg twice daily) (Grade 2C). If symptomatic sinus tachycardia persists or the response is suboptimal, we will then add a beta blocker. Ivabradine is not available in all countries and its use for inappropriate sinus https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 13/22 7/6/23, 11:22 AM Sinus tachycardia: Evaluation and management - UpToDate tachycardia would be considered an off-label use in the United States. (See 'Ivabradine' above.) For patients with persistent symptomatic inappropriate sinus tachycardia despite optimal pharmacologic therapy, radiofrequency catheter ablation may be attempted. Postural orthostatic tachycardia syndrome must be excluded first, since ablation may worsen symptoms in these patients. (See 'Catheter ablation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD and Brian Olshansky, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Yusuf S, Camm AJ. The sinus tachycardias. Nat Clin Pract Cardiovasc Med 2005; 2:44. 2. Palatini P. Heart rate as a cardiovascular risk factor: do women differ from men? Ann Med 2001; 33:213. 3. Fox K, Borer JS, Camm AJ, et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol 2007; 50:823. 4. Scott O, Williams GJ, Fiddler GI. Results of 24 hour ambulatory monitoring of electrocardiogram in 131 healthy boys aged 10 to 13 years. Br Heart J 1980; 44:304. 5. Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977; 39:390. 6. Bjerregaard P. Mean 24 hour heart rate, minimal heart rate and pauses in healthy subjects 40-79 years of age. Eur Heart J 1983; 4:44. 7. Sheldon RS, Grubb BP 2nd, Olshansky B, et al. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm 2015; 12:e41. 8. Low PA, Sandroni P, Joyner M, Shen WK. Postural tachycardia syndrome (POTS). J Cardiovasc Electrophysiol 2009; 20:352. 9. Bauernfeind RA, Amat-Y-Leon F, Dhingra RC, et al. Chronic nonparoxysmal sinus tachycardia in otherwise healthy persons. Ann Intern Med 1979; 91:702. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 14/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate 10. Morillo CA, Klein GJ, Thakur RK, et al. Mechanism of 'inappropriate' sinus tachycardia. Role of sympathovagal balance. Circulation 1994; 90:873. 11. Krahn AD, Yee R, Klein GJ, Morillo C. Inappropriate sinus tachycardia: evaluation and therapy. J Cardiovasc Electrophysiol 1995; 6:1124. 12. Olshansky B, Sullivan RM. Inappropriate sinus tachycardia. J Am Coll Cardiol 2013; 61:793. 13. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. 14. Lee RJ, Shinbane JS. Inappropriate sinus tachycardia. Diagnosis and treatment. Cardiol Clin 1997; 15:599. 15. Shabtaie SA, Witt CM, Asirvatham SJ. Natural history and clinical outcomes of inappropriate sinus tachycardia. J Cardiovasc Electrophysiol 2020; 31:137. 16. Rubenstein JC, Freher M, Kadish A, Goldberger JJ. Diurnal heart rate patterns in inappropriate sinus tachycardia. Pacing Clin Electrophysiol 2010; 33:911. 17. Olshansky B. What's So Inappropriate About Sinus Tachycardia? J Cardiovasc Electrophysiol 2008; 19:977. 18. Glatter KA, Cheng J, Dorostkar P, et al. Electrophysiologic effects of adenosine in patients with supraventricular tachycardia. Circulation 1999; 99:1034. 19. Lee RJ, Kalman JM, Fitzpatrick AP, et al. Radiofrequency catheter modification of the sinus node for \"inappropriate\" sinus tachycardia. Circulation 1995; 92:2919. 20. Romeo E, Grimaldi N, Sarubbi B, et al. A pediatric case of cardiomyopathy induced by inappropriate sinus tachycardia: efficacy of ivabradine. Pediatr Cardiol 2011; 32:842. 21. Winum PF, Cayla G, Rubini M, et al. A case of cardiomyopathy induced by inappropriate sinus tachycardia and cured by ivabradine. Pacing Clin Electrophysiol 2009; 32:942. 22. Coss SF, Steinberg JS. Supraventricular tachyarrhythmias involving the sinus node: clinical and electrophysiologic characteristics. Prog Cardiovasc Dis 1998; 41:51. 23. DeSanctis RW, Block P, Hutter AM Jr. Tachyarrhythmias in myocardial infarction. Circulation 1972; 45:681. 24. Crimm A, Severance HW Jr, Coffey K, et al. Prognostic significance of isolated sinus tachycardia during first three days of acute myocardial infarction. Am J Med 1984; 76:983. 25. Severance HW Jr, Morris KG, Wagner GS. Criteria for early discharge after acute myocardial infarction: validation in a community hospital. Arch Intern Med 1982; 142:39. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 15/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate 26. McNeer JF, Wallace AG, Wagner GS, et al. The course of acute myocardial infarction. Feasibility of early discharge of the uncomplicated patient. Circulation 1975; 51:410. 27. Becker RC, Burns M, Gore JM, et al. Early assessment and in-hospital management of patients with acute myocardial infarction at increased risk for adverse outcomes: a nationwide perspective of current clinical practice. The National Registry of Myocardial Infarction (NRMI-2) Participants. Am Heart J 1998; 135:786. 28. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 29. Femen a F, Baranchuk A, Morillo CA. Inappropriate sinus tachycardia: current therapeutic options. Cardiol Rev 2012; 20:8. 30. DiFrancesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res 2006; 53:399. 31. DiFrancesco D, Noble D. The funny current has a major pacemaking role in the sinus node. Heart Rhythm 2012; 9:299. 32. Koruth JS, Lala A, Pinney S, et al. The Clinical Use of Ivabradine. J Am Coll Cardiol 2017; 70:1777. 33. DiFrancesco D, Camm JA. Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs 2004; 64:1757. 34. Tendera M, Talajic M, Robertson M, et al. Safety of ivabradine in patients with coronary artery disease and left ventricular systolic dysfunction (from the BEAUTIFUL Holter Substudy). Am J Cardiol 2011; 107:805. 35. Cal L, Rebecchi M, Sette A, et al. Efficacy of ivabradine administration in patients affected by inappropriate sinus tachycardia. Heart Rhythm 2010; 7:1318. 36. Cappato R, Castelvecchio S, Ricci C, et al. Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double- blind, crossover evaluation. J Am Coll Cardiol 2012; 60:1323. 37. Ptaszynski P, Kaczmarek K, Ruta J, et al. Metoprolol succinate vs. ivabradine in the treatment of inappropriate sinus tachycardia in patients unresponsive to previous pharmacological therapy. Europace 2013; 15:116. 38. Benezet-Mazuecos J, Rubio JM, Farr J, et al. Long-term outcomes of ivabradine in inappropriate sinus tachycardia patients: appropriate efficacy or inappropriate patients. https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 16/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate Pacing Clin Electrophysiol 2013; 36:830. 39. Mathew ST, Po SS, Thadani U. Inappropriate sinus tachycardia-symptom and heart rate reduction with ivabradine: A pooled analysis of prospective studies. Heart Rhythm 2018; 15:240. 40. Rodr guez-Ma ero M, Kreidieh B, Al Rifai M, et al. Ablation of Inappropriate Sinus Tachycardia: A Systematic Review of the Literature. JACC Clin Electrophysiol 2017; 3:253. 41. Schweikert RA, Saliba WI, Tomassoni G, et al. Percutaneous pericardial instrumentation for endo-epicardial mapping of previously failed ablations. Circulation 2003; 108:1329. 42. Koplan BA, Parkash R, Couper G, Stevenson WG. Combined epicardial-endocardial approach to ablation of inappropriate sinus tachycardia. J Cardiovasc Electrophysiol 2004; 15:237. 43. Scheinman MM, Huang S. The 1998 NASPE prospective catheter ablation registry. Pacing Clin Electrophysiol 2000; 23:1020. 44. Shen WK, Low PA, Jahangir A, et al. Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome? Pacing Clin Electrophysiol 2001; 24:217. Topic 1074 Version 40.0 https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 17/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate GRAPHICS ECG of sinus rhythm to Normal electrocardiogram (ECG) Normal sinus rhythm at a rate of 71 beats/minute, a P wave axis of 45 , and a PR interval of 0.15 seconds. ECG: electrocardiogram. Courtesy of Morton Arnsdorf, MD. Graphic 58149 Version 5.0 https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 18/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate Electrocardiogram (ECG) showing sinus tachycardia at a rate of 150 beats/min Note the difficulty in separating the P waves from the T waves in the standard leads. The P waves are most evident in lead V1 (arrow) where the terminal negativity suggests left atrial enlargement. Courtesy of Morton Arnsdorf, MD. Graphic 78938 Version 3.0 https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 19/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate Normal heart rates in adults based on age and sex HR (beats per minute) Age All Male Female (years) N Mean 1%-99% N Mean 1%-99% N Mean 1%-99% 20-29 6086 67 43-98 3127 64 42-99 2959 69 46-99 30-39 9569 69 46-100 4605 67 44-99 4964 70 48-100 40-49 15,392 69 46-101 7104 68 45-101 8288 70 48-102 50-59 18,578 68 46-102 9936 68 45-102 8642 69 47-102 60-69 16,585 67 44-102 9457 65 42-102 7128 68 46-101 70-79 8432 65 43-101 4509 64 42-102 3923 67 44-101 80-89 2259 65 44-101 1001 63 41-98 1258 67 46-102 90-99 119 70 43-146 58 64 43-95 81 72 44-147 Normal heart rate values (with range from 1st to 99th percentile) for heart rate (beats/minute) in 77,276 healthy adults according to age and gender. %: percent; HR: heart rate. Data from: Mason JW, Ramseth DJ, Chanter DO, et al. Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 2007; 40:228. Graphic 77746 Version 4.0 https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 20/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate Atrial flutter at a rate of 250 beats/minute with 2:1 AV conduction in the presence of left bundle branch block Although every other flutter wave can be seen at the end of the T wave in the first part of the tracing (arrows), a sinus mechanism cannot be excluded. The flutter waves become clearly apparent after carotid sinus massage is applied to slow conduction through the AV node, thereby increasing the degree of AV block. AV: atrioventricular Courtesy of Morton Arnsdorf, MD. Graphic 76876 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 21/22 7/6/23, 11:23 AM Sinus tachycardia: Evaluation and management - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Jonathan Piccini, MD, MHS, FACC, FAHA, FHRS Grant/Research/Clinical Trial Support: Abbott [Atrial fibrillation, catheter ablation]; AHA [Atrial fibrillation, cardiovascular disease]; Bayer [Atrial fibrillation]; Boston Scientific [Cardiac mapping, pacemaker/ICD, atrial fibrillation care]; iRhythm [Atrial fibrillation]; NIA [Atrial fibrillation]; Philips [Lead management]. Consultant/Advisory Boards: Abbott [Atrial fibrillation, catheter ablation]; Abbvie [Atrial fibrillation]; Bayer [Atrial fibrillation]; Boston Scientific [Cardiac mapping, atrial fibrillation, pacemaker/ICD]; ElectroPhysiology Frontiers [Atrial fibrillation, catheter ablation]; Element Science [DSMB]; Medtronic [Atrial fibrillation, pacemaker/ICDs]; Milestone [Supraventricular tachycardia]; Pacira [Atrial fibrillation]; Philips [Lead extraction]; ReCor [Cardiac arrhythmias]; Sanofi [Atrial fibrillation]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinus-tachycardia-evaluation-and-management/print 22/22" |
7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Advanced cardiac life support (ACLS) in adults : Jonathan Elmer, MD, MS, FNCS : Ron M Walls, MD, FRCPC, FAAEM, Richard L Page, MD : Jonathan Grayzel, MD, FAAEM All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 27, 2023. INTRODUCTION The field of resuscitation has advanced over more than two centuries [1]. The Paris Academy of Science recommended mouth-to-mouth ventilation for drowning victims in 1740 [2]. In 1891, Dr. Friedrich Maass performed the first documented chest compressions on humans [3]. The American Heart Association (AHA) formally endorsed cardiopulmonary resuscitation (CPR) in 1963, and by 1966 they had adopted standardized CPR guidelines for instruction to lay rescuers [2]. Advanced cardiac life support (ACLS) guidelines have evolved over the past several decades based on a combination of scientific evidence of variable strength and expert consensus. The AHA and European Resuscitation Council developed the most recent ACLS Guidelines in 2020 and 2021, respectively, using the comprehensive review of resuscitation literature performed by the International Liaison Committee on Resuscitation (ILCOR) [4-6]. Guidelines are reviewed continually, with formal updates published periodically in the journals Circulation and Resuscitation. This topic will discuss the management of cardiac arrhythmias in adults as generally described in the most recent iteration of the ACLS Guidelines. Where our suggestions differ or expand upon the published guidelines, we state this explicitly. The evidence supporting the published guidelines is presented separately, as are issues related to basic life support (BLS), airway management, post-cardiac arrest management, pediatric resuscitation, and controversial treatments for cardiac arrest patients. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 1/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Basic resuscitation (see "Adult basic life support (BLS) for health care providers" and "Basic airway management in adults") Airway management (see "Overview of advanced airway management in adults for emergency medicine and critical care" and "Extraglottic devices for emergency airway management in adults" and "Rapid sequence intubation in adults for emergency medicine and critical care" and "Emergency cricothyrotomy (cricothyroidotomy)") Post-resuscitation care (see "Initial assessment and management of the adult post-cardiac arrest patient" and "Intensive care unit management of the intubated post-cardiac arrest adult patient") Resuscitation in specific settings (see "Accidental hypothermia in adults" and "Drowning (submersion injuries)" and "Electrical injuries and lightning strikes: Evaluation and management" and "Initial management of the critically ill adult with an unknown overdose" and "Anaphylaxis: Emergency treatment") Pediatric resuscitation (see "Pediatric basic life support (BLS) for health care providers" and "Pediatric advanced life support (PALS)" and "Basic airway management in children") Evidence and non-standard treatments (see "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest" and "Therapies of uncertain benefit in basic and advanced cardiac life support") RESUSCITATION OF PATIENTS WITH COVID-19 Interim guidance for the performance of cardiopulmonary resuscitation (CPR) in patients with suspected or confirmed coronavirus disease 2019 (COVID-19)-related illness was first published by the American Heart Association (AHA) in 2020 and updated in 2021 [7,8]. This guidance and associated algorithms for basic life support (BLS) and ACLS can be accessed using the following graphic and reference ( algorithm 1) [8]. Original and updated guidance emphasizes several key points: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) offers significant protection to health care providers, including those involved in resuscitation of patients with suspected or confirmed COVID-19. Don personal protective equipment (PPE) according to local guidelines and availability. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 2/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Providers must follow local guidelines for use of PPE to protect against SARS-CoV-2 infection. We prefer rescuers use an N95 mask or its equivalent and eye protection because of the risk of aerosolization of virus from chest compressions, positive-pressure ventilation, and intubation. Because providers with surgical or procedural masks may initiate chest compressions, these providers should be relieved as soon as possible by personnel with higher-level PPE. Airway management, including bag-valve-mask (BVM) ventilation, should be delayed until all providers have donned appropriate PPE [9]. Minimize the number of clinicians performing resuscitation; use a negative-pressure room whenever possible; keep the door to the resuscitation room closed if possible. May use a mechanical device, if resources and expertise are available, to perform chest compressions on adults and on adolescents who meet minimum height and weight requirements. Use a high-efficiency particulate air (HEPA) filter for BVM and mechanical ventilation as soon as it is available. A single responder can perform defibrillation or initiate chest compressions while a patient is prone. Provided the patient is intubated, chest compressions can be accomplished by pushing on the chest wall behind the heart with the hands centered over the T7-T10 vertebral bodies. This approach is likely to be less effective than chest compressions in a supine patient with a compression board in place. We recommend patients be repositioned in a supine position and placed on a compression board as soon as sufficient personnel with appropriate PPE are available. EVIDENCE-BASED GUIDELINES Because of the nature of resuscitation research, few randomized controlled trials have been completed in humans. Many of the recommendations in the Guidelines for ACLS and subsequent updates published jointly by the American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR), hereafter referred to as the ACLS Guidelines, are made based upon observational studies, animal studies, and expert consensus [4-6]. Guideline recommendations are classified according to the GRADE system [10]. The evidence supporting the ACLS Guidelines is reviewed in detail separately. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest".) PRINCIPLES OF MANAGEMENT https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 3/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Excellent basic life support and its importance Excellent cardiopulmonary resuscitation (CPR) and early defibrillation for appropriately shockable arrhythmias remain the cornerstones of basic life support (BLS) and ACLS [4,5,11-14]. Although iterative updates for the ACLS Guidelines have suggested a number of revisions, including medications and monitoring, the emphasis on timely, excellent CPR and its critical role in resuscitative efforts remains unchanged ( algorithm 2 and algorithm 3) [15,16]. The most recent versions of the ACLS algorithms can be accessed online here. We emphasize the term "excellent CPR" because anything short of this standard does not achieve adequate cerebral and coronary perfusion, thereby compromising a patient's chances for neurologically intact survival. CPR is discussed in detail separately; key principles in the performance of ACLS are summarized in the following table ( table 1). (See "Adult basic life support (BLS) for health care providers".) Studies in both the in-hospital and prehospital settings demonstrate that chest compressions are often performed incorrectly, inconsistently, and with excessive interruption [17-21]. To be effective, chest compressions must be of sufficient depth (5 to 6 cm, or 2 to 2.5 inches) and rate (between 100 and 120 per minute) and must allow for complete recoil of the chest between compressions. Chest compression fraction, the proportion of total CPR time during which chest compressions are delivered, should be above 80 percent. In the past, clinicians frequently interrupted CPR to check for pulses, perform tracheal intubation, or obtain venous access. Current ACLS Guidelines strongly recommend that every effort be made not to interrupt CPR; interventions that have not been shown to improve outcomes, including tracheal intubation, venous access, and administration of medications to treat arrhythmias are carried out while CPR is performed. If the airway is obstructed, immediate management must be initiated and may necessitate interruption of compressions. (See "Airway foreign bodies in adults", section on 'Life-threatening asphyxiation' and "Emergency cricothyrotomy (cricothyroidotomy)".) A single biphasic defibrillation shock remains the recommended treatment for ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). CPR should be performed until the defibrillator is charged and resumed immediately after the shock is given, without pausing to recheck a pulse [22,23]. Assessment of waveform end-tidal carbon dioxide (EtCO ) may be used 2 as an adjunct to pulse checks if the patient is intubated (receiving asynchronous ventilation); however, further study of its reliability is needed. Interruptions in CPR (eg, for subsequent attempts at defibrillation) should occur no more frequently than every two minutes and for the shortest possible duration. Compressions are paused briefly for ventilation when using a bag- https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 4/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate valve-mask (BVM) ventilation device at a ratio of 30:2. (See "Carbon dioxide monitoring (capnography)", section on 'Effectiveness of CPR'.) There is a delay between the return of an organized electrical rhythm and effective myocardial contractions [24]. Thus, post-defibrillation pulse and rhythm checks are performed after two minutes of additional CPR or potentially in the brief pause while ventilations are being administered. Key elements in the performance of manual defibrillation are described in the following table ( table 2). Patients are often overventilated during resuscitation, resulting in excessive intrathoracic pressure, which can compromise venous return and result in reduced cardiac output and inadequate cerebral and cardiac perfusion. Delivery of 30 compressions followed by two rescue breaths is recommended in patients without an advanced airway in place. ACLS Guidelines advise asynchronous ventilations at 8 to 10 per minute if an endotracheal tube or extraglottic airway is in place, while continuous chest compressions are performed simultaneously [25]. In contrast to ACLS, we believe 6 to 8 appropriate tidal volume ventilations per minute by bag with supplemental oxygen are likely sufficient in the low-flow state of cardiac arrest and prevent excessive intrathoracic pressure [26]. Resuscitation team management A growing body of literature demonstrates that employing the principles of Crisis Resource Management (CRM), adapted from the aviation industry and introduced into medical care by anesthesiologists, decreases disorganization during resuscitation and improves patient care [27-30]. A primary goal of CRM is to access the collective knowledge and experience of the team in order to provide the best care possible and to compensate for oversights or other challenges that any individual is likely to experience during such stressful events. Training in these principles to improve the quality of ACLS performed by health care clinicians is feasible and recommended [31,32]. Two principles provide the foundation for CRM: leadership and communication [29]. Resuscitations usually involve health care providers from different disciplines, sometimes from different areas of an institution, who may not have worked together previously. Under these circumstances, role clarity can be difficult to establish. In CRM, it is imperative that one person assumes the role of team leader [29]. This person is responsible for the global management of the resuscitation, including ensuring that all required tasks are carried out competently, assigning specific team members their responsibilities, incorporating new information and coordinating communication among all team members, developing and implementing management strategies that will maximize patient outcome, and reassessing performance throughout the resuscitation. Many clinical systems pre-determine the leader for hospital resuscitation ( code ) teams. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 5/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate The team leader must avoid performing technical procedures, as performance of a task inevitably shifts attention from the primary leadership responsibilities. In circumstances where staff expertise is limited, the team leader may be required to perform certain critical procedures. In these situations, leadership is specifically transferred to another clinician, if possible, or the team leader may be forced temporarily to perform both roles, although this compromises the ability to provide proficient leadership and assimilate new information. In CRM, communication is organized to provide effective and efficient care. All pertinent communication goes through the team leader, and the team leader shares important information with the team. When the team leader determines the need to perform a task, the request is directed to a specific team member, ideally by name. That team member verbally acknowledges the request and performs the task or, if unable to do so, informs the team leader that someone else should be assigned. Team members must be comfortable providing such feedback to the team leader. Specific emphasis is placed on the assigned team member repeating back medication doses and defibrillator energy settings to the team leader. This "closed-loop" communication leads to a more orderly transfer of information and is the appropriate standard for all communication during resuscitations. Though most decisions emanate from the team leader, a good team leader enlists the collective wisdom and experience of the entire team as needed. Team members must be encouraged to speak up if they have an observation, concern, or a feasible suggestion. Efforts should be made to overcome the tendency to withhold potentially lifesaving suggestions due to the fear of being incorrect or the nature of hierarchies that exist in many health care institutions. Extraneous personnel not directly involved with patient care are asked to leave to reduce noise and to ensure that orders from the leader and feedback from the resuscitation team can be heard clearly, and all non-critical verbalization must stop to ensure team harmony and clear communication. INITIAL MANAGEMENT AND ECG INTERPRETATION In the 2010 ACLS Guidelines, circulation assumed a more prominent role in the initial management of cardiac arrest, and this approach continues in subsequent iterations and updates. The "mantra" remains: circulation, airway, breathing (C-A-B). Once unresponsiveness is recognized, resuscitation begins by addressing circulation (excellent chest compressions), followed by airway opening, and then rescue breathing. In parallel, additional resources are mobilized by calling for help. Identifying a specific individual to call for help is more effective than a vague, general instruction for someone to do so. The ACLS Guidelines emphasize the importance of excellent, uninterrupted chest compressions and early defibrillation. Rescue https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 6/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate breathing is performed after the initiation of excellent chest compressions. Advanced airway management may be delayed if there is adequate rescue breathing without an advanced airway in place. (See 'Excellent basic life support and its importance' above and "Adult basic life support (BLS) for health care providers", section on 'Recognition of cardiac arrest'.) In the non-cardiac arrest situation, the other initial interventions for ACLS include administering oxygen (if the patient's oxygen saturation is measurable and below 94 percent), establishing vascular access, placing the patient on a cardiac and oxygen saturation monitor, and obtaining an electrocardiogram (ECG) [15,16,33]. Unstable patients must receive immediate care, even when data are incomplete or presumptive ( algorithm 2 and algorithm 3). The most recent versions of the ACLS algorithms can be accessed online here. Patients with ST elevation myocardial infarction (STEMI) on ECG should be prepared for rapid transfer to the catheterization laboratory, receive a thrombolytic (if not contraindicated), or be transferred to a center with percutaneous coronary intervention (PCI) capabilities. These decisions are made based on local resources and protocols. Stable patients require an assessment of their ECG to provide appropriate treatment consistent with ACLS Guidelines. Although it is best to make a definitive interpretation of the ECG prior to making management decisions, the settings in which ACLS Guidelines are commonly employed require a modified, empirical approach. Such an approach is guided by the following questions: Is the rhythm fast or slow? Are the QRS complexes wide or narrow? Is the rhythm regular or irregular? The answers to these questions often enable the clinician to make a provisional diagnosis and initiate appropriate therapy. AIRWAY MANAGEMENT In the minutes following sudden cardiac arrest, oxygen delivery is limited primarily by reduced blood flow, leading to the recommendation that excellent chest compressions take priority over ventilation during the initial resuscitation [4,6,11]. (See 'Principles of management' above.) Suggested approach to airway management while performing ACLS ACLS Guidelines support the use of a bag-valve-mask (BVM) device or placement of a supraglottic airway for ventilation during the initial management of sudden cardiac arrest unless one cannot ventilate the patient by these means or there is high certainty of rapid, successful placement of the https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 7/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate tracheal tube without interruption of chest compressions [34]. Generally, endotracheal intubation can be deferred until after return of spontaneous circulation (ROSC). The performance of BVM ventilation is described in detail separately. (See "Basic airway management in adults".) The ventilation rate is determined by whether the patient is intubated. If the patient is not intubated but ventilated using a BVM, the compression to ventilation ratio is 30:2. Although rescuers may be tempted to deliver non-synchronized BVM ventilations during cardiopulmonary resuscitation (CPR) to minimize interruptions in compressions, the mechanics of mask ventilations make it impossible to deliver adequate tidal volume during an active compression. If the patient is intubated, we suggest performing no more than 6 to 8 non-synchronized ventilations per minute (the ACLS Guidelines recommend 10 breaths per minute with an advanced airway in place; we believe fewer breaths are adequate). Tidal volumes of approximately 600 mL delivered in a controlled fashion such that chest rise occurs over no more than one second is recommended in the ACLS Guidelines. (See "Adult basic life support (BLS) for health care providers", section on 'Ventilations'.) Overzealous ventilation (excess volume and/or frequency) elevates intrathoracic pressure, thereby decreasing venous return, ventricular filling, and stroke volume with compressions; all of which result in inadequate cerebral perfusion. In addition, overventilation can cause gastric inflation, which increases the risk of regurgitation and aspiration. As a standard bag-valve-mask for adults has a volume of 1000 to 1500 mL, even if some air is lost to the environment, a full squeeze of the bag during ventilation is unnecessary to deliver 600 mL. Techniques and technical considerations A blindly inserted extraglottic airway (eg, laryngeal mask airway, laryngeal tube, Combitube) can be placed without interrupting excellent chest compressions, provides adequate ventilation in most cases, and may reduce the risk of aspiration compared with BVM ventilation [35]. We believe that this is a reasonable approach, equal or superior to BVM ventilation. Extraglottic airways can be placed by basic providers, and are considered alternatives to BVM ventilation, whereas tracheal intubation is an advanced technique for providers with the requisite training. Extraglottic airways and tracheal intubation are discussed separately. (See "Extraglottic devices for emergency airway management in adults", section on 'Extraglottic airway devices' and "Direct laryngoscopy and endotracheal intubation in adults".) https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 8/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate If intubation is to be performed during cardiac arrest, it must be done by a trained provider, ideally require less than 10 seconds to complete, be performed without interruption of chest compressions, and occur only after all other essential resuscitative maneuvers have been initiated. Once performed, rescuers must avoid hyperventilation. If ventilation is inadequate using a BVM or an extraglottic airway (eg, upper airway obstruction), intubation can be attempted during ongoing chest compressions or deferred to the two-minute interval (after a complete cycle of CPR) when the resuscitator is already committed to stopping CPR for a rhythm check and possible defibrillation. If ventilation cannot be provided by BVM or an extraglottic airway because of apparent obstruction, the clinician must determine immediately whether arrest is due to upper airway obstruction and intervene as necessary. The ACLS Guidelines include the following additional recommendations about airway management during the performance of ACLS [36]: It is reasonable to provide 100 percent oxygen during CPR. In patients with ROSC, oxygen concentration is adjusted to maintain oxygen saturation above 94 percent. Hyperoxia may be harmful to patients and should be avoided. (See "Initial assessment and management of the adult post-cardiac arrest patient", section on 'Mechanical ventilation' and "Overview of the acute management of ST-elevation myocardial infarction", section on 'Therapies of unclear benefit'.) Cricoid pressure should not be applied during intubation. It may be useful for preventing gastric insufflation during BVM ventilation. These issues are discussed separately. (See "Rapid sequence intubation in adults for emergency medicine and critical care", section on 'Positioning and protection'.) Oropharyngeal and nasopharyngeal airways can improve the quality of BVM ventilation and should be used whenever possible. (See "Basic airway management in adults", section on 'Airway adjuncts'.) Continuous waveform capnography (performed in addition to clinical assessment) is recommended for both confirming and monitoring correct tracheal tube placement and for monitoring the quality of CPR and ROSC. If waveform capnography is not available, a non-waveform carbon dioxide (CO ) detector may be used in addition to clinical 2 assessment. (See "Carbon dioxide monitoring (capnography)", section on 'Clinical applications for intubated patients'.) Evidence concerning airway management https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 9/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Randomized trials The optimal approach to airway management for victims of sudden cardiac arrest remains uncertain, but it is likely BVM ventilation or an extraglottic airway, which are equally effective as tracheal intubation, more rapidly placed, and require less training. In a randomized trial of BVM ventilation (1020 patients) versus tracheal intubation (1023 patients) for pre-hospital management of out-of-hospital cardiac arrest in France or Belgium between 2015 and 2017, the primary outcome (survival with favorable neurologic outcome at 28 days) was similar in the two groups (4.3 percent for BVM compared with 4.2 percent for tracheal intubation) [37]. The trial failed to meet the prespecified criteria for noninferiority. Ambulance teams in these countries include physicians with training in intubation, which is not common in many countries. In a multicenter cluster randomized trial of a supraglottic airway device (4886 patients) versus tracheal intubation (4410 patients) for pre-hospital airway management of out-of- hospital cardiac arrest in England between 2015 and 2017, the primary outcome (favorable neurologic outcome at hospital discharge or 30 days, or at three- or six-month follow-up) was similar between the two groups [38,39]. There were no differences in survival at 72 hours or at 30 days. However, initial ventilation success occurred more commonly in the supraglottic airway group (87 versus 79 percent). In a multicenter cluster-crossover trial of a laryngeal tube (1505 patients) versus tracheal intubation (1499 patients) for pre-hospital airway management of out-of-hospital cardiac arrest in the United States between 2015 and 2017, the primary outcome (72-hour survival) occurred significantly more often in patients randomized to receive the laryngeal tube (18 versus 15 percent) [40]. Survival to discharge and functionally favorable survival were also greater in the laryngeal tube group. In a network meta-analysis of eight randomized and three quasi-randomized trials involving just under 16,000 patients, no difference in survival or neurologic outcome was found among the three approaches to prehospital airway management: supraglottic airway, BVM ventilation, and tracheal intubation [35]. Supraglottic airway placement was associated with a higher rate of ROSC. Until additional data are available suggesting a clear improvement in patient-important outcomes from a particular ventilatory technique, BVM ventilation or placement of a supraglottic device (with close attention to avoiding overventilation) remains the preferred approach to airway management for cardiac arrest patients. (See 'Suggested approach to airway management while performing ACLS' above.) https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 10/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Observational studies The results of two large observational studies suggest that endotracheal intubation is not the best approach for managing patients with sudden cardiac arrest: In a prospective nationwide Japanese study involving 649,359 patients with sudden out-of- hospital cardiac arrest, the rate of survival with a favorable neurologic outcome was significantly lower among those managed with advanced airway techniques compared with BVM (1.1 versus 2.9 percent; odds ratio [OR] 0.38, 95% CI 0.36-0.39) [41]. Higher rates of survival with a favorable neurologic outcome when using BVM persisted across all analyzed subgroups, including adjustments for initial rhythm, ROSC, bystander CPR, and additional treatments. A study drawing on data collected between 2000 and 2014 from the Get With the Guidelines - Resuscitation multicenter registry used a propensity-matched cohort to compare outcomes among intubated and non-intubated patients who sustained in- hospital cardiac arrest [42]. In this study, each of 43,314 patients intubated during the first 15 minutes of presentation following sudden cardiac arrest were matched with patients not intubated in the same minute. Rates of ROSC (57.8 versus 59.3 percent), survival (16.3 versus 19.4 percent), and survival with good functional outcome (10.6 versus 13.6 percent) were all lower among intubated patients, and this held true across all prespecified subgroup analyses. Although both of these studies have limitations due to their observational nature and may not be generalizable to all settings, their size and consistent findings across all subgroup analyses support their conclusions. MEDICATIONS USED DURING CPR Epinephrine Epinephrine is the only medication indicated in sudden cardiac arrest regardless of arrest rhythm. Epinephrine is a sympathomimetic catecholamine that binds alpha-1, alpha-2, beta-1, and beta-2 receptors. During cardiopulmonary resuscitation (CPR), epinephrine is administered to increase systemic vasomotor tone via alpha-1 agonism, thereby increasing diastolic blood pressure and coronary perfusion pressure. The ACLS Guidelines recommend epinephrine (1 mg intravenous [IV] or intraosseous [IO] every three to five minutes) be administered after two minutes of CPR in shockable rhythms after the first rescue shock is delivered. Some study results have raised doubts about the benefit of epinephrine [43-45]. In a randomized trial of 8014 patients who suffered out-of-hospital cardiac arrest, IV epinephrine https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 11/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate increased the rate of return of spontaneous circulation (ROSC) compared with placebo (36 versus 12 percent) but did not improve survival at 30 days (3.2 versus 2.4 percent) [43]. This trial did not standardize or measure post-arrest care, potentially attenuating the benefit from improved ROSC in the epinephrine group. Pending formal change to ACLS protocols, we suggest giving epinephrine in accordance with existing guidelines. Atropine Atropine is not recommended for the treatment of asystole or pulseless electrical activity. For symptomatic bradycardia, the initial dose of atropine is 1 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg. (See 'Approach to bradycardia' below.). Amiodarone and lidocaine Evidence suggests that antiarrhythmic drugs provide little survival benefit in refractory ventricular tachycardia (VT) or ventricular fibrillation (VF) [4-6]. A randomized trial of 3026 patients with out-of-hospital VT/VF refractory to initial defibrillation compared IV or IO amiodarone, lidocaine, and placebo and found no differences in survival to hospital discharge or functionally favorable survival in the overall study population [46]. In patients with witnessed collapse, amiodarone or lidocaine resulted in improved survival compared with placebo (28 versus 28 versus 23 percent). The ACLS Guidelines state that antiarrhythmic drugs may be used in certain situations, but the recommended timing of administration is not specified. We suggest that antiarrhythmic drugs may be administered after a second unsuccessful defibrillation attempt in anticipation of a third shock, particularly among patients with witnessed arrest in whom time to administration may be shorter [47]. (See 'Refractory pulseless ventricular tachycardia or ventricular fibrillation' below.) When used, amiodarone (300 mg IV/IO bolus with a repeat dose of 150 mg IV as indicated) or lidocaine (1 to 1.5 mg/kg IV/IO bolus, then 0.5 to 0.75 mg/kg every 5 to 10 minutes) may be administered in VT/VF unresponsive to defibrillation, CPR, and epinephrine. Magnesium Magnesium sulfate (2 to 4 g IV/IO bolus followed by a maintenance infusion) is used to treat polymorphic VT consistent with torsade de pointes but is not recommended for routine use in adult cardiac arrest patients. (See 'Irregular wide complex' below and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management", section on 'Initial management'.) Other medications Vasopressin Outcomes of patients who receive vasopressin during CPR are not superior to those who receive epinephrine alone, so vasopressin administration is not recommended in the ACLS Guidelines [48]. Among patients who have suffered in-hospital https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 12/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate cardiac arrest, three randomized controlled trials support administration of vasopressin (20 IU IV with each dose of epinephrine) together with glucocorticoids (methylprednisolone 40 mg IV once) as an adjunct to standard CPR [49-51]. Across trials, addition of vasopressin and glucocorticoid to standard care increased the rate of ROSC but did not consistently result in improved survival or functionally favorable recovery. Vasopressin and glucocorticoid administration are not currently recommended by ACLS Guidelines but may be reasonable during resuscitation of in-hospital cardiac arrest. Calcium Calcium chloride has both vasopressor and inotropic effects but has not shown benefit when used to treat cardiac arrest. A randomized trial of calcium chloride versus placebo during resuscitation of out-of-hospital cardiac arrest was terminated early because of a trend towards reduced rates of ROSC in patients receiving calcium [52]. Calcium chloride (1g IV) should not be routinely administered during CPR but may be indicated in some special circumstances (eg, hyperkalemia, calcium-channel blocker toxicity). (See "Treatment and prevention of hyperkalemia in adults" and "Calcium channel blocker poisoning".) Sodium bicarbonate Sodium bicarbonate can mitigate acidosis and hyperkalemia that may incite or worsen during cardiac arrest. However, according to a meta-analysis of four randomized trials and 10 observational studies, routine sodium bicarbonate administration during CPR did not provide a benefit [53]. Selective use of sodium bicarbonate (50 to 100 mEq IV) may be reasonable when there is clinical suspicion or laboratory evidence of significant pre-existing metabolic acidosis or hyperkalemia. (See "Approach to the adult with metabolic acidosis", section on 'Overview of therapy' and "Bicarbonate therapy in lactic acidosis".) MANAGEMENT OF SPECIFIC ARRHYTHMIAS Immediate patient management is algorithmic and does not depend on cardiac rhythm, as detailed above. (See 'Initial management and ECG interpretation' above.) The potential sudden cardiac arrest victim is assessed for responsiveness, breathing, and presence of a pulse. For patients with effective respiration and a palpable pulse, treatment is determined by the ventricular rate (tachycardiac or bradycardia) and clinical assessment of overall stability. (See 'Arrhythmias with a pulse' below.) Pulseless patients are managed initially with cardiopulmonary resuscitation. Patients with pulseless ventricular tachycardia (VT) and ventricular fibrillation (VF) are defibrillated as https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 13/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate rapidly as possible. Additional clinical considerations are discussed in greater detail below. (See 'Pulseless patient in sudden cardiac arrest' below.) Pulseless patient in sudden cardiac arrest Pulseless ventricular tachycardia and ventricular fibrillation Pulseless VT and VF are non-perfusing rhythms emanating from the ventricles for which early identification is critical. Successful resuscitation of patients with VT/VF requires excellent cardiopulmonary resuscitation (CPR) and rapid defibrillation. The American Heart Association (AHA) algorithm for the management of cardiac arrest can be accessed here ( algorithm 3). The most recent versions of the ACLS algorithms can be accessed online here. Excellent CPR is performed without interruption until the rescuer is ready to perform early defibrillation and is continued until return of spontaneous circulation (ROSC) is achieved. Treatable underlying causes should be identified and managed as quickly as possible ( table 3) [36,54,55]. Agonal breathing or transient convulsive activity may accompany these dysrhythmias, and responders should not delay initiating CPR by misinterpreting these signs. Begin performing excellent chest compressions as soon as cardiac arrest is recognized and continue while the defibrillator is being attached. If a defibrillator is not immediately available, continue CPR until one is obtained. As soon as a defibrillator is available, attach it to the patient ( figure 1) and charge it while continuing CPR, then stop compressions to assess the rhythm and defibrillate if appropriate (eg, VT/VF is present). If asystole or pulseless electrical activity is present, continue CPR. If defibrillation is performed, resume CPR immediately and continue compressions until the next pulse and rhythm check two minutes later. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest", section on 'VF and pulseless VT'.) Decreased time to defibrillation improves the likelihood of successful conversion to a perfusing rhythm and patient survival. For the monitored patient who sustains a witnessed VT/VF arrest, if a defibrillator is immediately available and defibrillator pads are in place, immediately charge the defibrillator and deliver a shock. The 10 seconds or fewer of CPR that might have been applied prior to the shock are unlikely to have generated any meaningful perfusion. Biphasic defibrillators are recommended because of their increased efficacy at lower energy levels [56-58]. The ACLS Guidelines recommend that when employing a biphasic defibrillator clinicians use the initial dose of energy recommended by the manufacturer (120 to 200 J). If this dose is not known, the maximal dose may be used. We suggest a first defibrillation at maximal energy for VT/VF. If a monophasic defibrillator is used, 360 J is the appropriate energy dose for initial and subsequent shocks. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 14/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate ACLS Guidelines recommend the resumption of CPR immediately after defibrillation without checking for a pulse. This recommendation is made because effective cardiac contractility lags restoration of an organized electrical rhythm. Clinicians should stop compressions to perform a rhythm check only after two minutes of CPR, and not before the defibrillator is fully charged if the rhythm is VT/VF. (See "Adult basic life support (BLS) for health care providers", section on 'Phases of resuscitation' and "Adult basic life support (BLS) for health care providers", section on 'Defibrillation'.) |
recommended timing of administration is not specified. We suggest that antiarrhythmic drugs may be administered after a second unsuccessful defibrillation attempt in anticipation of a third shock, particularly among patients with witnessed arrest in whom time to administration may be shorter [47]. (See 'Refractory pulseless ventricular tachycardia or ventricular fibrillation' below.) When used, amiodarone (300 mg IV/IO bolus with a repeat dose of 150 mg IV as indicated) or lidocaine (1 to 1.5 mg/kg IV/IO bolus, then 0.5 to 0.75 mg/kg every 5 to 10 minutes) may be administered in VT/VF unresponsive to defibrillation, CPR, and epinephrine. Magnesium Magnesium sulfate (2 to 4 g IV/IO bolus followed by a maintenance infusion) is used to treat polymorphic VT consistent with torsade de pointes but is not recommended for routine use in adult cardiac arrest patients. (See 'Irregular wide complex' below and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management", section on 'Initial management'.) Other medications Vasopressin Outcomes of patients who receive vasopressin during CPR are not superior to those who receive epinephrine alone, so vasopressin administration is not recommended in the ACLS Guidelines [48]. Among patients who have suffered in-hospital https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 12/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate cardiac arrest, three randomized controlled trials support administration of vasopressin (20 IU IV with each dose of epinephrine) together with glucocorticoids (methylprednisolone 40 mg IV once) as an adjunct to standard CPR [49-51]. Across trials, addition of vasopressin and glucocorticoid to standard care increased the rate of ROSC but did not consistently result in improved survival or functionally favorable recovery. Vasopressin and glucocorticoid administration are not currently recommended by ACLS Guidelines but may be reasonable during resuscitation of in-hospital cardiac arrest. Calcium Calcium chloride has both vasopressor and inotropic effects but has not shown benefit when used to treat cardiac arrest. A randomized trial of calcium chloride versus placebo during resuscitation of out-of-hospital cardiac arrest was terminated early because of a trend towards reduced rates of ROSC in patients receiving calcium [52]. Calcium chloride (1g IV) should not be routinely administered during CPR but may be indicated in some special circumstances (eg, hyperkalemia, calcium-channel blocker toxicity). (See "Treatment and prevention of hyperkalemia in adults" and "Calcium channel blocker poisoning".) Sodium bicarbonate Sodium bicarbonate can mitigate acidosis and hyperkalemia that may incite or worsen during cardiac arrest. However, according to a meta-analysis of four randomized trials and 10 observational studies, routine sodium bicarbonate administration during CPR did not provide a benefit [53]. Selective use of sodium bicarbonate (50 to 100 mEq IV) may be reasonable when there is clinical suspicion or laboratory evidence of significant pre-existing metabolic acidosis or hyperkalemia. (See "Approach to the adult with metabolic acidosis", section on 'Overview of therapy' and "Bicarbonate therapy in lactic acidosis".) MANAGEMENT OF SPECIFIC ARRHYTHMIAS Immediate patient management is algorithmic and does not depend on cardiac rhythm, as detailed above. (See 'Initial management and ECG interpretation' above.) The potential sudden cardiac arrest victim is assessed for responsiveness, breathing, and presence of a pulse. For patients with effective respiration and a palpable pulse, treatment is determined by the ventricular rate (tachycardiac or bradycardia) and clinical assessment of overall stability. (See 'Arrhythmias with a pulse' below.) Pulseless patients are managed initially with cardiopulmonary resuscitation. Patients with pulseless ventricular tachycardia (VT) and ventricular fibrillation (VF) are defibrillated as https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 13/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate rapidly as possible. Additional clinical considerations are discussed in greater detail below. (See 'Pulseless patient in sudden cardiac arrest' below.) Pulseless patient in sudden cardiac arrest Pulseless ventricular tachycardia and ventricular fibrillation Pulseless VT and VF are non-perfusing rhythms emanating from the ventricles for which early identification is critical. Successful resuscitation of patients with VT/VF requires excellent cardiopulmonary resuscitation (CPR) and rapid defibrillation. The American Heart Association (AHA) algorithm for the management of cardiac arrest can be accessed here ( algorithm 3). The most recent versions of the ACLS algorithms can be accessed online here. Excellent CPR is performed without interruption until the rescuer is ready to perform early defibrillation and is continued until return of spontaneous circulation (ROSC) is achieved. Treatable underlying causes should be identified and managed as quickly as possible ( table 3) [36,54,55]. Agonal breathing or transient convulsive activity may accompany these dysrhythmias, and responders should not delay initiating CPR by misinterpreting these signs. Begin performing excellent chest compressions as soon as cardiac arrest is recognized and continue while the defibrillator is being attached. If a defibrillator is not immediately available, continue CPR until one is obtained. As soon as a defibrillator is available, attach it to the patient ( figure 1) and charge it while continuing CPR, then stop compressions to assess the rhythm and defibrillate if appropriate (eg, VT/VF is present). If asystole or pulseless electrical activity is present, continue CPR. If defibrillation is performed, resume CPR immediately and continue compressions until the next pulse and rhythm check two minutes later. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest", section on 'VF and pulseless VT'.) Decreased time to defibrillation improves the likelihood of successful conversion to a perfusing rhythm and patient survival. For the monitored patient who sustains a witnessed VT/VF arrest, if a defibrillator is immediately available and defibrillator pads are in place, immediately charge the defibrillator and deliver a shock. The 10 seconds or fewer of CPR that might have been applied prior to the shock are unlikely to have generated any meaningful perfusion. Biphasic defibrillators are recommended because of their increased efficacy at lower energy levels [56-58]. The ACLS Guidelines recommend that when employing a biphasic defibrillator clinicians use the initial dose of energy recommended by the manufacturer (120 to 200 J). If this dose is not known, the maximal dose may be used. We suggest a first defibrillation at maximal energy for VT/VF. If a monophasic defibrillator is used, 360 J is the appropriate energy dose for initial and subsequent shocks. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 14/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate ACLS Guidelines recommend the resumption of CPR immediately after defibrillation without checking for a pulse. This recommendation is made because effective cardiac contractility lags restoration of an organized electrical rhythm. Clinicians should stop compressions to perform a rhythm check only after two minutes of CPR, and not before the defibrillator is fully charged if the rhythm is VT/VF. (See "Adult basic life support (BLS) for health care providers", section on 'Phases of resuscitation' and "Adult basic life support (BLS) for health care providers", section on 'Defibrillation'.) If VT/VF persists after at least one attempt at defibrillation and two minutes of CPR, administer epinephrine (1 mg intravenous [IV] or intraosseous [IO] every three to five minutes) while CPR is performed [34,59]. Premature treatment with epinephrine (within two minutes of defibrillation) has been associated with decreased survival [60]. VT/VF that persists after defibrillation may be treated with amiodarone or lidocaine. (See 'Epinephrine' above and 'Amiodarone and lidocaine' above.) Refractory pulseless ventricular tachycardia or ventricular fibrillation Coronary artery disease and myocardial infarction are common causes of shock-refractory VT/VF. The likelihood of ROSC and favorable recovery decreases over time as whole-body ischemia causes progressive end-organ damage. Few patients with CPR ongoing after 40 to 50 minutes will recover [61-64]. Defibrillation strategies Defibrillation may be unsuccessful when insufficient energy transits the fibrillating ventricle. Modern biphasic defibrillators adapt to a range of patient characteristics that affect impedance to ensure adequate energy delivery. Nevertheless, if the vector of current between defibrillator pads does not fully capture the ventricles, VT/VF may persist. In such circumstances, changing the location of the defibrillator pads to the anterior- posterior (AP) position from the anterior-lateral position (termed "vector change") or adding a second set of AP pads may improve the chances of successful defibrillation. We prefer the former approach. Outside of a clinical trial, access to multiple defibrillators for a single patient may be limited, and their use adds complexity that might detract from high-quality CPR. In the absence of any proven benefit of double sequential defibrillation compared with vector change, and assuming a biphasic defibrillator is used, it is our opinion that vector change is preferable for the management of shock-refractory VF/VT in most situations. In a trial of patients with VF/VT out-of-hospital cardiac arrest refractory to three consecutive defibrillation attempts with anterior and lateral pad placement, patients were randomly assigned to vector change, the addition of AP pads followed by double sequential defibrillation from both anterior-lateral and AP pad locations, or continued usual care [65]. The study was https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 15/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate halted early because of low recruitment during the COVID-19 pandemic. The preliminary results were that both vector change and double sequential defibrillation improved the primary outcome of survival to hospital discharge compared with usual care (21.7 versus 30.4 versus 13.3 percent, respectively). Rates of VF termination and return of spontaneous circulation were also higher in both intervention arms. Extracorporeal cardiopulmonary resuscitation Patients with refractory VT/VF may achieve ROSC after coronary revascularization. Thus, there is substantial interest in use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) initiated as an adjunct to conventional CPR [66]. VA-ECMO results in substantially better systemic perfusion and oxygen delivery than CPR and may be a useful bridge to coronary revascularization and myocardial recovery. VA-ECMO initiated during CPR is considered extracorporeal CPR (ECPR). (See "Extracorporeal life support in adults: Management of venoarterial extracorporeal membrane oxygenation (V-A ECMO)" and "Extracorporeal life support in adults in the intensive care unit: Overview".) Programs for effective delivery of ECPR are complex and resource intensive, and they require expertise and substantial multidisciplinary coordination between pre-hospital and in-hospital providers [67]. Optimal patient selection and implementation strategies are uncertain. ECPR is most efficacious when initiated prior to development of severe global hypoxic-ischemic injury and as a bridge to intervention to reverse the inciting cause of arrest. Ideal patients have favorable arrest characteristics (eg, witnessed collapse, immediate CPR, and short duration from collapse to cannulation), evidence of adequate intra-arrest perfusion (eg, end-tidal carbon dioxide [EtCO ] less than 10 mmHg, low presenting arterial lactate), and a presumed reversable 2 etiology of arrest (eg, acute coronary syndrome, massive pulmonary embolism). ACLS Guidelines for ECPR were last updated in 2019 and state ECPR may be considered for selected patients when feasible [48]. Multiple observational studies show an association of ECPR with improved short- and long-term outcomes compared with conventional ACLS with both in- and out-of-hospital cardiac arrest [66]. In a single-center randomized trial, survival to hospital discharge occurred significantly more often among those treated with ECPR compared with standard ACLS (6 of 14 versus 1 of 15) [68]. A second single-center randomized trial of 256 participants demonstrated a non-significant improvement in 180-day functionally favorable survival with ECPR and immediate coronary angiography compared with standard ACLS (31.5 versus 22 percent) and superior 30-day functional recovery (30.6 versus 18.2 percent) [69]. Nevertheless, not all trials have found benefit from ECPR. This likely reflects uncertainty about optimal patient selection and the complexity of systems of care necessary to deliver the intervention. A pragmatic, multicenter randomized trial compared ECPR versus conventional CPR https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 16/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate in 160 adults with witnessed out-of-hospital cardiac arrest, an initial shockable rhythm, and failure to regain spontaneous circulation after 15 minutes [70]. At 30 days, there was no significant difference between groups in survival with good neurologic outcome (ECPR group 14 patients [20 percent] versus conventional CPR 10 patients [16 percent]; OR 1.4; 95% CI 0.5-3.5). In explaining the discrepancies in outcome from previous trials, the authors highlighted differences in team experience, logistics, and caseload. Asystole and pulseless electrical activity Asystole is defined as a complete absence of electrical and mechanical cardiac activity. Pulseless electrical activity (PEA) is defined as any one of a heterogeneous group of organized ECG rhythms without sufficient mechanical contraction of the heart to produce a palpable pulse or measurable blood pressure. By definition, asystole and PEA are non-perfusing rhythms requiring immediate initiation of excellent CPR. These rhythms do not respond to defibrillation. The AHA algorithm for the management of cardiac arrest can be accessed here ( algorithm 3). The most recent versions of the ACLS algorithms can be accessed online here. In the ACLS Guidelines, asystole and PEA are addressed together because successful management for both depends on excellent CPR and rapid reversal of underlying causes, such as hypoxia, hyperkalemia, poisoning, and hemorrhage [36,54,55]. Epinephrine is administered as soon as is feasible after chest compressions are begun [4,11]. Asystole may be the result of a primary or secondary cardiac conduction abnormality, possibly from end-stage tissue hypoxia and metabolic acidosis, or, rarely, the result of excessive vagal stimulation. It is crucial to identify and treat all potential secondary causes of asystole or PEA as rapidly as possible. As tension pneumothorax and cardiac tamponade make CPR ineffective and are often rapidly reversible, the clinician should not hesitate to perform immediate needle thoracostomy or pericardiocentesis if thought necessary. Delay in performing either procedure can worsen outcomes, and there is little chance either intervention will make the situation worse. The accompanying tables describe important secondary causes of cardiac arrest ( table 3). After initiating CPR, immediately consider and treat reversible causes as appropriate and administer epinephrine (1 mg IV every three to five minutes) as soon as feasible [4,34,59]. As with VT/VF, studies of epinephrine in patients with asystole or PEA report mixed results, and further study is needed [34,43,71]. Neither asystole nor PEA responds to defibrillation. Atropine is no longer recommended for the treatment of asystole or PEA. Cardiac pacing is ineffective for cardiac arrest and not recommended. Evidence around the management of asystole and PEA, and cardiac arrest generally, is reviewed in detail separately. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest".) https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 17/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Intra-arrest monitoring ACLS Guidelines encourage the use of clinical and physiologic monitoring to optimize performance of CPR and to detect ROSC [15]. Assessment and immediate feedback about the rate and depth of chest compressions, adequacy of chest recoil between compressions, and rate and force of ventilations improve CPR. These parameters should be monitored continuously and any necessary adjustments made immediately. Accelerometers have been integrated into several brands of defibrillator pads or freestanding devices that can be placed on the patient's sternum during chest compressions to provide these metrics and real-time feedback. EtCO measured from continuous waveform capnography can provide a rough estimate of 2 cardiac output (and therefore the quality of CPR). EtCO less than 10mmHg suggests inadequate 2 cardiac output and the need to improve CPR quality or provide other interventions such as needle thoracostomy. Sudden, sustained increases in EtCO >10 mmHg during CPR likely 2 indicate ROSC. (See "Carbon dioxide monitoring (capnography)", section on 'Effectiveness of CPR' and "Carbon dioxide monitoring (capnography)", section on 'Return of spontaneous circulation'.) Data from other physiologic monitors are less likely to be available in patients with sudden cardiac arrest, but measurements obtained from arterial catheters already in place can provide useful feedback about the quality of CPR and ROSC [36]. CPR should not be interrupted to place arterial or central venous catheters. Arterial diastolic pressure is a reasonable proxy for coronary perfusion pressure. A reasonable goal is to maintain an arterial diastolic pressure above 20 mmHg. In the hands of skilled operators, point-of-care ultrasound may be useful during cardiac arrest for identifying underlying pathology, monitoring resuscitation, and determining the presence of cardiac activity and likelihood of recovery [72,73]. However, studies of point-of-care ultrasound in the setting of cardiac arrest are preliminary, and high-quality trials are needed. While such research is ongoing, it is crucial that ultrasound-related interventions not cause interruptions or otherwise interfere with the performance of excellent CPR. Arrhythmias with a pulse Bradycardia Definition and clinical findings Bradycardia is defined as a heart rate below 60 beats per minute, but symptomatic bradycardia generally entails rates below 40 beats per minute. The ACLS Guidelines recommend that clinicians not intervene unless the patient exhibits evidence of inadequate tissue perfusion thought to result from the slow heart rate [36,54,55]. Signs and symptoms of inadequate perfusion include hypotension, lightheadedness or a pre-syncopal https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 18/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate sensation, altered mental status (including syncope), signs of shock, ongoing ischemic chest pain, and evidence of acute pulmonary edema. Hypoxia is a common cause of bradycardia. If peripheral perfusion is adequate, pulse oximetry should be used to assess oxyhemoglobin saturation. If perfusion is inadequate or pulse oximetry is unavailable, assess the patient for signs of respiratory failure (eg, increased or decreased respiratory rate, diminished respiratory volume, retractions, or paradoxical abdominal breathing). Bradycardia in the intubated patient should be considered to represent a malpositioned or displaced endotracheal tube until proven otherwise. Approach to bradycardia The AHA algorithm for the management of bradycardia can be accessed here ( algorithm 4). The most recent versions of the ACLS algorithms can be accessed online here. We generally administer atropine while simultaneously preparing for prompt temporary cardiac pacing (transvenous, if immediately available, or transcutaneous) and/or infusion of a chronotropic agent for bradycardic patients with clinically significant symptoms thought to be due to one of the following etiologies: High vagal tone (eg, inferior myocardial ischemia due to acute coronary syndrome) Medication-induced (supratherapeutic levels of beta blockers, calcium channel blockers, digitalis) High-degree atrioventricular (AV) block with a narrow QRS complex (thought to emanate at or above the AV node) If the bradycardia is thought to be due to a conduction disturbance at or below the bundle of His (wide QRS complex in complete heart block, or Mobitz type II second-degree AV block), we avoid atropine and move directly to cardiac pacing and/or administration of a chronotropic agent. Atropine The initial dose of atropine is 1 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg. (See "Second-degree atrioventricular block: Mobitz type II" and "Third-degree (complete) atrioventricular block".) Temporary pacing If temporary transvenous cardiac pacing can be initiated promptly, prepare for transvenous pacing, and obtain appropriate consultation as available. If transvenous pacing cannot be initiated promptly, initiate transcutaneous pacing, and prepare for chronotropic infusion. Before using transcutaneous pacing, assess whether the patient can perceive the pain associated with this procedure, and if so, provide appropriate sedation and analgesia whenever possible. (See "Procedural sedation in adults: General considerations, preparation, monitoring, and mitigating complications".) https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 19/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Patients requiring transcutaneous or transvenous pacing generally require cardiology consultation and admission for evaluation for possible permanent pacemaker placement unless a reversible cause of bradycardia such as hyperkalemia or overmedication with a beta blocker or calcium channel blocker is identified and corrected. Chronotropic agents For patients who remain symptomatic following atropine administration and for whom temporary cardiac pacing is either not readily available or not successful in alleviating symptoms, continuous infusion of a chronotropic agent is indicated. Either dopamine or epinephrine, but not both, should be initiated. Because of its superior vasoconstrictive effects, we prefer epinephrine as a first-line chronotropic agent when there is concomitant hypotension. The starting dose for infusions of dopamine is from 5 to 20 mcg/kg per minute, while epinephrine is started at 0.025 to 0.125 mcg/kg per minute (2 to 10 mcg per minute). Each should be titrated to the patient's response. Tachycardia Tachycardia is defined as a heart rate above 100 beats per minute, but symptomatic tachycardia generally involves rates over 150 beats per minute unless underlying ventricular dysfunction exists [36,54,55]. Management of tachyarrhythmias is governed by the presence of clinical symptoms and signs caused by the rapid heart rate. The AHA algorithm for the management of tachycardia can be accessed here ( algorithm 5). The most recent versions of the ACLS algorithms can be accessed online here. Approach to tachycardia The fundamental approach is as follows: First, determine if the patient is unstable (eg, manifests ongoing ischemic chest pain, acute mental status changes, hypotension, signs of shock, or evidence of acute pulmonary edema). Hypoxemia is a common cause of unstable tachycardia; look for signs of labored breathing (eg, increased respiratory rate, retractions, paradoxical abdominal breathing) or low oxygen saturation. If instability is present and appears related to the tachycardia, treat immediately with synchronized cardioversion unless the rhythm is sinus tachycardia [74]. Some cases of supraventricular tachycardia (SVT) may respond to immediate treatment with a bolus of adenosine (6 or 12 mg IV) without the need of cardioversion. Whenever possible, assess whether the patient can perceive the pain associated with cardioversion, and if so, provide appropriate sedation and analgesia if time permits. (See "Procedural sedation in adults: General considerations, preparation, monitoring, and mitigating complications".) In the stable patient, use the ECG to determine the nature of the arrhythmia. In the urgent settings in which ACLS algorithms are most often employed, specific rhythm identification may not be possible. Nevertheless, by performing an orderly review of the ECG, one can determine https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 20/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate appropriate management. Three questions provide the basis for assessing the ECG in this setting: Is the patient in a sinus rhythm? Is the QRS complex wide or narrow? Is the rhythm regular or irregular? More detailed approaches to rhythm determination in tachycardia are discussed separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation" and "Wide QRS complex tachycardias: Approach to the diagnosis" and "Overview of the acute management of tachyarrhythmias".) Regular narrow complex A narrow QRS complex implies that a tachycardic rhythm originates at or above the AV node. SVT, including sinus tachycardia, is the major cause of a regular narrow complex arrhythmia [36,54,55]. Sinus tachycardia is a common response to fever, anemia, shock, sepsis, pain, heart failure, or any other physiologic stress. No medication is needed to treat sinus tachycardia; care is focused on treating the underlying cause. (See "Sinus tachycardia: Evaluation and management".) Reentrant SVT is a regular tachycardia most often caused by a reentrant mechanism within the conduction system ( algorithm 5). The QRS interval is usually narrow but can be longer than 120 ms if a bundle branch block (ie, SVT with rate-related aberrancy or fixed bundle branch block) is present. Vagal maneuvers slow conduction through the AV node and may interrupt the reentrant circuit, and they may be employed on appropriate patients while other therapies are prepared. Vagal maneuvers alone (eg, Valsalva, carotid sinus massage) convert up to 25 percent of SVTs to sinus rhythm, while Valsalva followed immediately by supine repositioning with a passive leg raise has been shown to be even more effective. SVT refractory to vagal maneuvers is treated with adenosine [75-77]. (See "Overview of the acute management of tachyarrhythmias" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation" and "Reentry and the development of cardiac arrhythmias" and "Vagal maneuvers".) Because of its extremely short half-life, adenosine (6 or 12 mg IV) is injected as rapidly as possible into a proximal vein followed immediately by a 20 mL saline flush and elevation of the extremity to ensure the drug enters the central circulation before it is metabolized. If the first dose of adenosine does not convert the rhythm, a second and third dose of 12 mg IV may be given. Larger doses (eg, 18 mg IV) may be needed in patients taking theophylline or theobromine or those who consume large amounts of caffeine; smaller doses (eg, 3 mg IV) should be given to patients taking dipyridamole or carbamazepine and those with transplanted hearts, or when injecting via a central vein. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 21/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Prior to injection, warn the patient about transient side effects from adenosine, including dysphoria, chest discomfort, dyspnea, and flushing, and give reassurance that these effects are very brief. Perform continuous ECG recording during administration. If adenosine fails to convert the SVT, consider other etiologies for this rhythm, including atrial flutter or a non- reentrant SVT, which may become apparent on the ECG when AV nodal conduction is slowed. If conversion attempts fail and the patient remains stable, initiate rate control with either an IV nondihydropyridine calcium channel blocker or a beta blocker. Agents to choose from include diltiazem, verapamil, and a number of beta blockers (including metoprolol, atenolol, esmolol, and labetalol). (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Urgent therapy'.) Irregular narrow complex Irregular narrow-complex tachycardias may be caused by atrial fibrillation, atrial flutter with variable AV nodal conduction, multifocal atrial tachycardia (MAT), or sinus tachycardia with frequent premature atrial complexes (PACs; also referred to as premature atrial beats, premature supraventricular complexes, or premature supraventricular beats) ( algorithm 5). Of these, atrial fibrillation is most common [36,54,55]. The initial goal of treatment in stable patients is to control the heart rate using either a nondihydropyridine calcium channel blocker (diltiazem 10 to 20 mg IV over two minutes, repeat at 20 to 25 mg IV after 15 minutes; or verapamil 2.5 to 5 mg IV over two minutes followed by 5 to 10 mg IV every 15 to 30 minutes) or a beta blocker (eg, metoprolol 5 mg IV for three doses every two to five minutes, then up to 200 mg by mouth every 12 hours). The management of atrial fibrillation and SVT is discussed in detail separately. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Management of atrial fibrillation: Rhythm control versus rate control" and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation" and "Multifocal atrial tachycardia".) Calcium channel blockers and beta blockers may cause or worsen hypotension. Patients should be closely monitored while the drug is given, and patients at greater risk of developing severe hypotension (eg, older adults) may require loading doses that are below the usual range. Adequate IV access should be established in case hypotension develops. Combination therapy with a beta blocker and calcium channel blocker increases the risk of severe heart block. Diltiazem is suggested in most instances for the management of acute atrial fibrillation with rapid ventricular response. Beta blockers may also be used and may be preferred in the setting of an acute coronary syndrome. Beta blockers are more effective for chronic rate control. For atrial fibrillation associated with hypotension, amiodarone may be used (150 mg IV over 10 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 22/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate minutes followed by 1 mg/min drip for six hours, and then 0.5 mg/min) but may cause conversion to sinus rhythm, which may result in embolic injury if the atrial fibrillation was not short lived [78]. For atrial fibrillation associated with acute heart failure, amiodarone or digoxin may be used for rate control. Treatment of MAT includes correction of possible precipitants, such as hypokalemia and hypomagnesemia. The ACLS Guidelines recommend consultation with a cardiologist for these arrhythmias. Cardioversion of stable patients with irregular narrow complex tachycardias should not be undertaken without considering the risk of embolic stroke. If the duration of atrial fibrillation is known to be less than 48 hours or the patient has been receiving long-term therapeutic anticoagulation (eg warfarin with an international normalized ratio [INR] known to be therapeutic or a novel oral anticoagulant with good adherence), the risk of embolic stroke is low, and the clinician may consider electrical or chemical cardioversion [79]. A number of medications can be used for chemical cardioversion, and the best drug varies according to clinical circumstance. The questions of whether chemical cardioversion is appropriate and which agent to select are reviewed separately. Regular wide complex A regular wide-complex tachycardia is generally ventricular in etiology ( algorithm 5). Aberrantly conducted SVTs may also be seen. Because differentiation between VT and SVT with aberrancy can be difficult, assume VT is present. Treat clinically stable undifferentiated wide-complex tachycardia with antiarrhythmics or planned synchronized cardioversion [36,54,55]. In cases of regular wide-complex tachycardia with a monomorphic QRS complex, adenosine may be used for diagnosis and treatment. Do not give adenosine (or other AV nodal blocking medications) to patients who are unstable or manifest wide-complex tachycardia with an irregular rhythm or a polymorphic QRS complex. SVT with aberrancy, if definitively identified (eg, old ECG demonstrates bundle branch block), may be treated in the same manner as narrow- complex SVT, with vagal maneuvers, adenosine, or rate control (see 'Irregular narrow complex' above). Adenosine is likely to slow or convert SVT with aberrancy. Dosing is identical to that used for SVT. Adenosine also terminates some cases of VT, particularly those that originate in the left or right ventricular outflow tracts [80]. Thus, adenosine responsiveness cannot be used to confirm a diagnosis of SVT or to exclude VT. (See 'Regular narrow complex' above.) Other antiarrhythmic drugs that may be used to treat stable patients with regular wide-complex tachycardia include procainamide (20 to 50 mg/min IV), amiodarone (150 mg IV given over 10 minutes, repeated as needed to a total of 2.2 g IV over the first 24 hours), and sotalol (100 mg IV over five minutes). A procainamide infusion continues until the arrhythmia is suppressed, the patient becomes hypotensive, the QRS widens 50 percent beyond baseline, or a maximum dose https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 23/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate of 17 mg/kg is administered. Procainamide and sotalol should be avoided in patients with a prolonged QT interval. If the wide-complex tachycardia persists despite pharmacologic therapy, cardioversion may be needed. The ACLS Guidelines recommend expert consultation for all patients with wide complex tachycardia. Irregular wide complex A wide-complex, irregular tachycardia may be atrial fibrillation with preexcitation (eg, Wolf Parkinson White syndrome), atrial fibrillation with aberrancy (bundle branch block), or polymorphic VT/torsades de pointes ( algorithm 5) [36,54,55]. Use of AV nodal blockers in wide-complex, irregular tachycardia of unclear etiology may precipitate VF and death and is contraindicated. Such medications include beta blockers, calcium channel blockers, digoxin, and adenosine. To avoid inappropriate and possibly dangerous treatment, the ACLS Guidelines suggest assuming that any wide-complex, irregular tachycardia is caused by preexcited atrial fibrillation. Patients with a wide-complex, irregular tachycardia caused by preexcited atrial fibrillation usually manifest extremely fast heart rates (generally over 200 beats per minute) and require immediate synchronized electric cardioversion. In cases where electric cardioversion is ineffective or unfeasible, or atrial fibrillation recurs, antiarrhythmic therapy with procainamide, amiodarone, or sotalol may be given. The ACLS Guidelines recommend expert consultation for all patients with wide-complex tachycardia. Dosing for antiarrhythmic medications is described above. (See 'Regular wide complex' above.) Treat polymorphic VT with emergency defibrillation. Interventions to prevent recurrent polymorphic VT include correcting underlying electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) and, if a prolonged QT interval is observed or thought to exist, stopping all medications that increase the QT interval. Magnesium sulfate (2 to 4 g IV administered via rapid IV bolus followed by a maintenance infusion) can be given to prevent polymorphic VT associated with familial or acquired prolonged QT syndrome [81]. A clinically stable patient with atrial fibrillation and a wide QRS interval known to stem from a preexisting bundle branch block (ie, old ECG demonstrates preexisting block with the same QRS morphology) may be treated in the same manner as a narrow-complex atrial fibrillation. Alternative methods for medication administration Although vascular access via the IO route is safe and more easily initiated in the setting of cardiac arrest, administration of medication via the IV route produces more favorable outcomes. Nevertheless, when IV access cannot be established, or its theoretical benefit is mitigated by the time and resources necessary to initiate it, IO lines have been found to be safe and effective according to observational studies [36,54,55,82]. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 24/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate One large observational study reported inferior outcomes among victims of out-of-hospital cardiac arrest receiving IO access, but this finding could have been related to other variables in these patients [83]. More investigation is needed to assess whether proximal humeral IO placement versus pretibial placement results in enhanced medication delivery and survival. Medication doses for IO administration are identical to those for IV therapy. If neither IV nor IO access can be established, some medications may be given via the tracheal tube. (See "Intraosseous infusion", section on 'Indications'.) Multiple studies have demonstrated that lidocaine, epinephrine, atropine, vasopressin, and naloxone are absorbed via the trachea [36]; however, the serum drug concentrations achieved using this route are unpredictable. If the patient already has peripheral, IO, or central venous access, these are always the preferred routes for drug administration. When unable to obtain such access expeditiously, one may use the endotracheal tube while attempting to establish vascular or IO access. At no point should excellent CPR be interrupted to obtain vascular access. Doses for tracheal administration are 2 to 2.5 times the standard IV doses, and medications should be diluted in 5 to 10 mL of sterile water or normal saline before injection down the tracheal tube. USE OF ULTRASOUND AND ECHOCARDIOGRAPHY Bedside echocardiography must never interfere with resuscitation efforts and should not |
22/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate minutes followed by 1 mg/min drip for six hours, and then 0.5 mg/min) but may cause conversion to sinus rhythm, which may result in embolic injury if the atrial fibrillation was not short lived [78]. For atrial fibrillation associated with acute heart failure, amiodarone or digoxin may be used for rate control. Treatment of MAT includes correction of possible precipitants, such as hypokalemia and hypomagnesemia. The ACLS Guidelines recommend consultation with a cardiologist for these arrhythmias. Cardioversion of stable patients with irregular narrow complex tachycardias should not be undertaken without considering the risk of embolic stroke. If the duration of atrial fibrillation is known to be less than 48 hours or the patient has been receiving long-term therapeutic anticoagulation (eg warfarin with an international normalized ratio [INR] known to be therapeutic or a novel oral anticoagulant with good adherence), the risk of embolic stroke is low, and the clinician may consider electrical or chemical cardioversion [79]. A number of medications can be used for chemical cardioversion, and the best drug varies according to clinical circumstance. The questions of whether chemical cardioversion is appropriate and which agent to select are reviewed separately. Regular wide complex A regular wide-complex tachycardia is generally ventricular in etiology ( algorithm 5). Aberrantly conducted SVTs may also be seen. Because differentiation between VT and SVT with aberrancy can be difficult, assume VT is present. Treat clinically stable undifferentiated wide-complex tachycardia with antiarrhythmics or planned synchronized cardioversion [36,54,55]. In cases of regular wide-complex tachycardia with a monomorphic QRS complex, adenosine may be used for diagnosis and treatment. Do not give adenosine (or other AV nodal blocking medications) to patients who are unstable or manifest wide-complex tachycardia with an irregular rhythm or a polymorphic QRS complex. SVT with aberrancy, if definitively identified (eg, old ECG demonstrates bundle branch block), may be treated in the same manner as narrow- complex SVT, with vagal maneuvers, adenosine, or rate control (see 'Irregular narrow complex' above). Adenosine is likely to slow or convert SVT with aberrancy. Dosing is identical to that used for SVT. Adenosine also terminates some cases of VT, particularly those that originate in the left or right ventricular outflow tracts [80]. Thus, adenosine responsiveness cannot be used to confirm a diagnosis of SVT or to exclude VT. (See 'Regular narrow complex' above.) Other antiarrhythmic drugs that may be used to treat stable patients with regular wide-complex tachycardia include procainamide (20 to 50 mg/min IV), amiodarone (150 mg IV given over 10 minutes, repeated as needed to a total of 2.2 g IV over the first 24 hours), and sotalol (100 mg IV over five minutes). A procainamide infusion continues until the arrhythmia is suppressed, the patient becomes hypotensive, the QRS widens 50 percent beyond baseline, or a maximum dose https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 23/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate of 17 mg/kg is administered. Procainamide and sotalol should be avoided in patients with a prolonged QT interval. If the wide-complex tachycardia persists despite pharmacologic therapy, cardioversion may be needed. The ACLS Guidelines recommend expert consultation for all patients with wide complex tachycardia. Irregular wide complex A wide-complex, irregular tachycardia may be atrial fibrillation with preexcitation (eg, Wolf Parkinson White syndrome), atrial fibrillation with aberrancy (bundle branch block), or polymorphic VT/torsades de pointes ( algorithm 5) [36,54,55]. Use of AV nodal blockers in wide-complex, irregular tachycardia of unclear etiology may precipitate VF and death and is contraindicated. Such medications include beta blockers, calcium channel blockers, digoxin, and adenosine. To avoid inappropriate and possibly dangerous treatment, the ACLS Guidelines suggest assuming that any wide-complex, irregular tachycardia is caused by preexcited atrial fibrillation. Patients with a wide-complex, irregular tachycardia caused by preexcited atrial fibrillation usually manifest extremely fast heart rates (generally over 200 beats per minute) and require immediate synchronized electric cardioversion. In cases where electric cardioversion is ineffective or unfeasible, or atrial fibrillation recurs, antiarrhythmic therapy with procainamide, amiodarone, or sotalol may be given. The ACLS Guidelines recommend expert consultation for all patients with wide-complex tachycardia. Dosing for antiarrhythmic medications is described above. (See 'Regular wide complex' above.) Treat polymorphic VT with emergency defibrillation. Interventions to prevent recurrent polymorphic VT include correcting underlying electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) and, if a prolonged QT interval is observed or thought to exist, stopping all medications that increase the QT interval. Magnesium sulfate (2 to 4 g IV administered via rapid IV bolus followed by a maintenance infusion) can be given to prevent polymorphic VT associated with familial or acquired prolonged QT syndrome [81]. A clinically stable patient with atrial fibrillation and a wide QRS interval known to stem from a preexisting bundle branch block (ie, old ECG demonstrates preexisting block with the same QRS morphology) may be treated in the same manner as a narrow-complex atrial fibrillation. Alternative methods for medication administration Although vascular access via the IO route is safe and more easily initiated in the setting of cardiac arrest, administration of medication via the IV route produces more favorable outcomes. Nevertheless, when IV access cannot be established, or its theoretical benefit is mitigated by the time and resources necessary to initiate it, IO lines have been found to be safe and effective according to observational studies [36,54,55,82]. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 24/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate One large observational study reported inferior outcomes among victims of out-of-hospital cardiac arrest receiving IO access, but this finding could have been related to other variables in these patients [83]. More investigation is needed to assess whether proximal humeral IO placement versus pretibial placement results in enhanced medication delivery and survival. Medication doses for IO administration are identical to those for IV therapy. If neither IV nor IO access can be established, some medications may be given via the tracheal tube. (See "Intraosseous infusion", section on 'Indications'.) Multiple studies have demonstrated that lidocaine, epinephrine, atropine, vasopressin, and naloxone are absorbed via the trachea [36]; however, the serum drug concentrations achieved using this route are unpredictable. If the patient already has peripheral, IO, or central venous access, these are always the preferred routes for drug administration. When unable to obtain such access expeditiously, one may use the endotracheal tube while attempting to establish vascular or IO access. At no point should excellent CPR be interrupted to obtain vascular access. Doses for tracheal administration are 2 to 2.5 times the standard IV doses, and medications should be diluted in 5 to 10 mL of sterile water or normal saline before injection down the tracheal tube. USE OF ULTRASOUND AND ECHOCARDIOGRAPHY Bedside echocardiography must never interfere with resuscitation efforts and should not interrupt or delay resumption of cardiopulmonary resuscitation (CPR) except in cases where the ultrasound is being obtained strictly to confirm absence of cardiac activity when a decision to terminate resuscitative efforts is imminent. The 2020 update of the ACLS Guidelines suggests that point-of-care ultrasound and echocardiography be employed to help identify reversible causes of cardiac arrest (eg, cardiac tamponade, tension pneumothorax, pulmonary embolism) and to assist in the identification of return of spontaneous circulation (ROSC) [11,84,85]. (See 'Termination of resuscitative efforts' below.) According to a systematic review of 12 small trials, most of which studied convenience samples of patients with sudden cardiac arrest (n = 568), bedside echocardiography may be helpful to predict ROSC [86]. In this review, the pooled sensitivity and specificity of echocardiography to predict ROSC were 91.6 and 80 percent, respectively (95% CI for sensitivity 84.6-96.1 percent; 95% CI for specificity 76.1-83.6 percent). Of the 190 patients found to have cardiac activity, 98 (51.6 percent) achieved ROSC, whereas only 9 (2.4 percent) of the 378 with cardiac standstill did so. Other studies have reached similar conclusions about the rarity of ROSC in cases with cardiac https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 25/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate standstill on ultrasound [87-89]. Echocardiography should not be the sole basis for terminating resuscitative efforts but may serve as an adjunct to clinical assessment. POST-RESUSCITATION CARE The ACLS Guidelines recommend a combination of goal-oriented interventions provided by an experienced multidisciplinary team for all cardiac arrest patients with return of spontaneous circulation (ROSC) [11,13,54,90]. Important objectives for such care include: Optimizing cardiopulmonary function and perfusion of vital organs Managing acute coronary syndromes Implementing strategies to prevent and manage organ system dysfunction and brain injury Management of the post-cardiac arrest patient is reviewed separately. (See "Initial assessment and management of the adult post-cardiac arrest patient" and "Intensive care unit management of the intubated post-cardiac arrest adult patient".) TERMINATION OF RESUSCITATIVE EFFORTS Criteria for determining whether to stop Determining when to stop resuscitation efforts in cardiac arrest patients is difficult, and little high-quality evidence exists to guide decision-making [91]. Furthermore, decision-making may vary depending on clinical circumstances, including settings discussed in the following topics. (See "Drowning (submersion injuries)" and "Accidental hypothermia in adults" and "Electrical injuries and lightning strikes: Evaluation and management" and "Initial management of the critically ill adult with an unknown overdose".) Physician survey data and clinical practice guidelines suggest that factors influencing the decision to stop resuscitative efforts include [92-96]: Duration of resuscitative effort >30 minutes without a sustained perfusing rhythm Unwitnessed collapse with an initial ECG rhythm of asystole Prolonged interval between time of collapse and initiation of cardiopulmonary resuscitation (CPR) Patient age, severe comorbid disease, or prior functional dependence More objective endpoints of resuscitation have been proposed. Of these, the best predictor of outcome may be the end-tidal carbon dioxide (EtCO ) level following 20 minutes of resuscitation 2 [97-99]. EtCO values are a function of carbon dioxide (CO ) production and venous return to the 2 2 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 26/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate right heart and pulmonary circulation. A very low EtCO (<10 mmHg) following prolonged 2 resuscitation (>20 minutes) is a sign of absent circulation and a strong predictor of acute mortality [97-99]. It is crucial to note that low EtCO levels may also be caused by a misplaced 2 endotracheal tube, and this possibility needs to be excluded as soon as the low CO level is 2 identified and before the decision is made to terminate resuscitative efforts. (See "Carbon dioxide monitoring (capnography)".) Resuscitation in the emergency department does not appear to be superior to field resuscitation by emergency medical services (EMS) personnel. Therefore, EMS personnel should not transport all victims of sudden cardiac arrest to the hospital if further resuscitation is deemed futile [100,101]. Large retrospective cohort studies have assessed criteria (basic life support [BLS] and ALS) for the prehospital termination of resuscitative efforts in cardiac arrest, initially described in the OPALS study [102,103]. Both BLS and ALS criteria demonstrated high specificity for identifying out-of-hospital cardiac arrest patients with little or no chance of survival. Studies of another clinical decision rule suggest that it too accurately predicts survival and would reduce unnecessary transports substantially if implemented [100,104]. The 2020 update of the ACLS guidelines suggests that point-of-care ultrasound and echocardiography may be employed to help identify reversible causes of cardiac arrest but should not be employed for prognostication. (See 'Use of ultrasound and echocardiography' above.) One simple and potentially useful set of criteria for determining the futility of resuscitation following out-of-hospital cardiac arrest is the following: Arrest not witnessed by EMS personnel Non-shockable initial cardiac arrhythmia (eg, asystole, pulseless electrical activity [PEA]) No return of spontaneous circulation (ROSC) prior to administration of third 1 mg dose of epinephrine These criteria were developed by researchers based on data from 6962 cardiac arrest patients included in two large registries (Paris and King County, Washington) and a major multicenter randomized trial [105]. Of the 2800 patients evaluated who met all three criteria, only one survived (survival rate 0 percent; 95% CI 0.0-0.5 percent). Specificity and the positive predictive value for these criteria were both 100 percent. Discussion with family members Guidance for breaking bad news or holding difficult discussions with the patient s family is provided separately. (See "Palliative care for adults in the ED: Goals of care, communication, consultation, and patient death", section on 'Communicating difficult news'.) https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 27/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Basic and advanced cardiac life support in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Ventricular fibrillation (The Basics)") SUMMARY AND RECOMMENDATIONS Key principles and access to algorithms High-quality chest compressions and early defibrillation for treatable arrhythmias remain the cornerstones of basic life support (BLS) and advanced cardiac life support (ACLS). The most recent versions of the ACLS algorithms can be accessed online; access to copies within UpToDate is provided below. (See 'Excellent basic life support and its importance' above.) Cardiac arrest (ventricular fibrillation [VF], pulseless ventricular tachycardia [VT], asystole, pulseless electrical activity) ( algorithm 3) Bradycardia with pulse ( algorithm 4) Tachycardia with pulse ( algorithm 5) https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 28/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Team performance during resuscitation Teams providing ACLS perform better when there is a single designated leader who asks for and accepts helpful suggestions from members of the team, and when the team practices clear, closed-loop communication. (See 'Resuscitation team management' above.) Initial interventions Begin excellent cardiopulmonary resuscitation (CPR) immediately for any patient with suspected cardiac arrest. Excellent chest compressions have few interruptions, are delivered at the correct rate and depth, and allow complete chest recoil ( table 1). Secondary interventions include performing ventilations, administering oxygen, establishing vascular access, initiating appropriate monitoring (cardiac, oxygen saturation, waveform end-tidal carbon dioxide [EtCO ]), and obtaining an 2 electrocardiogram (ECG). (See 'Initial management and ECG interpretation' above.) During initial life support of adults, high-quality chest compressions take priority over ventilation (circulation, airway, breathing [C-A-B]). When ventilating the patient in cardiac arrest, give 100 percent oxygen, use low respiratory rates (approximately six to eight breaths per minute), and avoid hyperventilation, which is harmful. Ventilation using a bag- valve-mask (BVM) or supraglottic airway is preferred when possible. (See 'Airway management' above.) ECG interpretation For the purposes of ACLS, ECG interpretation is guided by three questions: Is the rhythm fast or slow? Are the QRS complexes wide or narrow? Is the rhythm regular or irregular? Arrhythmia management The basic approach and important aspects of management for each arrhythmia covered by the ACLS Guidelines are discussed in the text and summarized in the accompanying algorithms. Patients with VF or VT are defibrillated as rapidly as possible. For patients with effective respiration and a palpable pulse, treatment is determined by the ventricular rate (tachycardiac or bradycardia) and clinical assessment of overall stability (see 'Management of specific arrhythmias' above and 'Medications used during CPR' above): Cardiac arrest (VF, pulseless VT, asystole, pulseless electrical activity) ( algorithm 3) (see 'Pulseless patient in sudden cardiac arrest' above) A single biphasic defibrillation is the treatment for VF or VT. CPR should be performed until the defibrillator is charged and resumed immediately after the shock is given https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 29/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate without pausing to recheck a pulse. Bradycardia with pulse ( algorithm 4) (see 'Bradycardia' above) Tachycardia with pulse ( algorithm 5) (see 'Tachycardia' above) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. DeBard ML. The history of cardiopulmonary resuscitation. Ann Emerg Med 1980; 9:273. 2. Highlights of the History of Cardiopulmonary Resuscitation (CPR). American Heart Associati on 2006. www.americanheart.org (Accessed on March 01, 2007). 3. Hermreck AS. The history of cardiopulmonary resuscitation. Am J Surg 1988; 156:430. 4. Panchal AR, Bartos JA, Caba as JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2020; 142:S366. 5. Soar J, B ttiger BW, Carli P, et al. European Resuscitation Council Guidelines 2021: Adult advanced life support. Resuscitation 2021; 161:115. 6. Soar J, Berg KM, Andersen LW, et al. Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2020; 156:A80. 7. Edelson DP, Sasson C, Chan PS, et al. Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association. Circulation 2020; 141:e933. 8. Hsu A, Sasson C, Kudenchuk PJ, et al. 2021 Interim Guidance to Health Care Providers for Basic and Advanced Cardiac Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19. Circ Cardiovasc Qual Outcomes 2021; 14:e008396. 9. Atkins DL, Sasson C, Hsu A, et al. 2022 Interim Guidance to Health Care Providers for Basic and Advanced Cardiac Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association in Collaboration With the American Academy of Pediatrics, American https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 30/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Association for Respiratory Care, the Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists. Circ Cardiovasc Qual Outcomes 2022; 15:e008900. 10. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ 2004; 328:1490. 11. Merchant RM, Topjian AA, Panchal AR, et al. Part 1: Executive Summary: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2020; 142:S337. 12. Myat A, Song KJ, Rea T. Out-of-hospital cardiac arrest: current concepts. Lancet 2018; 391:970. 13. Hassager C, Nagao K, Hildick-Smith D. Out-of-hospital cardiac arrest: in-hospital intervention strategies. Lancet 2018; 391:989. 14. Perkins GD, Graesner JT, Semeraro F, et al. European Resuscitation Council Guidelines 2021: Executive summary. Resuscitation 2021; 161:1. 15. Hazinski MF, Nolan JP, Billi JE, et al. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2010; 122:S250. 16. Neumar RW, Shuster M, Callaway CW, et al. Part 1: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S315. 17. Valenzuela TD, Kern KB, Clark LL, et al. Interruptions of chest compressions during emergency medical systems resuscitation. Circulation 2005; 112:1259. 18. Eilevstj nn J, Kramer-Johansen J, Eftest l T, et al. Reducing no flow times during automated external defibrillation. Resuscitation 2005; 67:95. 19. Wik L, Kramer-Johansen J, Myklebust H, et al. Quality of cardiopulmonary resuscitation during out-of-hospital cardiac arrest. JAMA 2005; 293:299. 20. Yu T, Weil MH, Tang W, et al. Adverse outcomes of interrupted precordial compression during automated defibrillation. Circulation 2002; 106:368. 21. Abella BS, Sandbo N, Vassilatos P, et al. Chest compression rates during cardiopulmonary resuscitation are suboptimal: a prospective study during in-hospital cardiac arrest. Circulation 2005; 111:428. 22. Pierce AE, Roppolo LP, Owens PC, et al. The need to resume chest compressions immediately after defibrillation attempts: an analysis of post-shock rhythms and duration of pulselessness following out-of-hospital cardiac arrest. Resuscitation 2015; 89:162. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 31/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate 23. Sell RE, Sarno R, Lawrence B, et al. Minimizing pre- and post-defibrillation pauses increases the likelihood of return of spontaneous circulation (ROSC). Resuscitation 2010; 81:822. 24. Berg RA, Hilwig RW, Berg MD, et al. Immediate post-shock chest compressions improve outcome from prolonged ventricular fibrillation. Resuscitation 2008; 78:71. 25. International Liaison Committee on Resuscitation. 2005 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Part 2: Adult basic life support. Resuscitation 2005; 67:187. 26. Neth MR, Idris A, McMullan J, et al. A review of ventilation in adult out-of-hospital cardiac arrest. J Am Coll Emerg Physicians Open 2020; 1:190. 27. Blum RH, Raemer DB, Carroll JS, et al. Crisis resource management training for an anaesthesia faculty: a new approach to continuing education. Med Educ 2004; 38:45. 28. Reznek M, Smith-Coggins R, Howard S, et al. Emergency medicine crisis resource management (EMCRM): pilot study of a simulation-based crisis management course for emergency medicine. Acad Emerg Med 2003; 10:386. 29. Murray WB, Foster PA. Crisis resource management among strangers: principles of organizing a multidisciplinary group for crisis resource management. J Clin Anesth 2000; 12:633. 30. Hunziker S, Johansson AC, Tschan F, et al. Teamwork and leadership in cardiopulmonary resuscitation. J Am Coll Cardiol 2011; 57:2381. 31. DeVita MA, Schaefer J, Lutz J, et al. Improving medical emergency team (MET) performance using a novel curriculum and a computerized human patient simulator. Qual Saf Health Care 2005; 14:326. 32. Pearson DA, Darrell Nelson R, Monk L, et al. Comparison of team-focused CPR vs standard CPR in resuscitation from out-of-hospital cardiac arrest: Results from a statewide quality improvement initiative. Resuscitation 2016; 105:165. 33. Monsieurs KG, Nolan JP, Bossaert LL, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 1. Executive summary. Resuscitation 2015; 95:1. 34. Soar J, Maconochie I, Wyckoff MH, et al. 2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces. Circulation 2019; 140:e826. 35. Wang CH, Lee AF, Chang WT, et al. Comparing Effectiveness of Initial Airway Interventions for Out-of-Hospital Cardiac Arrest: A Systematic Review and Network Meta-analysis of https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 32/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Clinical Controlled Trials. Ann Emerg Med 2020; 75:627. 36. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S729. 37. Jabre P, Penaloza A, Pinero D, et al. Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of- Hospital Cardiorespiratory Arrest: A Randomized Clinical Trial. JAMA 2018; 319:779. 38. Benger JR, Kirby K, Black S, et al. Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional Outcome: The AIRWAYS-2 Randomized Clinical Trial. JAMA 2018; 320:779. 39. Benger JR, Lazaroo MJ, Clout M, et al. Randomized trial of the i-gel supraglottic airway device versus tracheal intubation during out of hospital cardiac arrest (AIRWAYS-2): Patient outcomes at three and six months. Resuscitation 2020; 157:74. 40. Wang HE, Schmicker RH, Daya MR, et al. Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2018; 320:769. 41. Hasegawa K, Hiraide A, Chang Y, Brown DF. Association of prehospital advanced airway management with neurologic outcome and survival in patients with out-of-hospital cardiac arrest. JAMA 2013; 309:257. 42. Andersen LW, Granfeldt A, Callaway CW, et al. Association Between Tracheal Intubation During Adult In-Hospital Cardiac Arrest and Survival. JAMA 2017; 317:494. 43. Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med 2018; 379:711. 44. Hagihara A, Hasegawa M, Abe T, et al. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA 2012; 307:1161. 45. Lin S, Callaway CW, Shah PS, et al. Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation 2014; 85:732. 46. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, Lidocaine, or Placebo in Out-of- Hospital Cardiac Arrest. N Engl J Med 2016; 374:1711. 47. Panchal AR, Berg KM, Kudenchuk PJ, et al. 2018 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Antiarrhythmic Drugs During and Immediately After Cardiac Arrest: An Update to the American Heart Association Guidelines https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 33/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2018; 138:e740. 48. Panchal AR, Berg KM, Hirsch KG, et al. 2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support: Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2019; 140:e881. 49. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med 2009; 169:15. 50. Mentzelopoulos SD, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA 2013; 310:270. 51. Andersen LW, Isbye D, Kj rgaard J, et al. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2021; 326:1586. 52. Vallentin MF, Granfeldt A, Meilandt C, et al. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2021; 326:2268. 53. Alshahrani MS, Aldandan HW. Use of sodium bicarbonate in out-of-hospital cardiac arrest: a systematic review and meta-analysis. Int J Emerg Med 2021; 14:21. 54. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S444. 55. Soar J, Nolan JP, B ttiger BW, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support. Resuscitation 2015; 95:100. 56. Martens PR, Russell JK, Wolcke B, et al. Optimal Response to Cardiac Arrest study: defibrillation waveform effects. Resuscitation 2001; 49:233. 57. Schneider T, Martens PR, Paschen H, et al. Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the resuscitation of out- of-hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators. Circulation 2000; 102:1780. 58. Schwarz B, Bowdle TA, Jett GK, et al. Biphasic shocks compared with monophasic damped sine wave shocks for direct ventricular defibrillation during open heart surgery. Anesthesiology 2003; 98:1063. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 34/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate 59. Holmberg MJ, Issa MS, Moskowitz A, et al. Vasopressors during adult cardiac arrest: A systematic review and meta-analysis. Resuscitation 2019; 139:106. 60. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016; 353:i1577. 61. Reynolds JC, Grunau BE, Rittenberger JC, et al. Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation. Circulation 2016; 134:2084. 62. Reynolds JC, Grunau BE, Elmer J, et al. Prevalence, natural history, and time-dependent outcomes of a multi-center North American cohort of out-of-hospital cardiac arrest extracorporeal CPR candidates. Resuscitation 2017; 117:24. 63. Grunau B, Reynolds JC, Scheuermeyer FX, et al. Comparing the prognosis of those with initial shockable and non-shockable rhythms with increasing durations of CPR: Informing minimum durations of resuscitation. Resuscitation 2016; 101:50. 64. Grunau B, Reynolds J, Scheuermeyer F, et al. Relationship between Time-to-ROSC and Survival in Out-of-hospital Cardiac Arrest ECPR Candidates: When is the Best Time to Consider Transport to Hospital? Prehosp Emerg Care 2016; 20:615. 65. Cheskes S, Verbeek PR, Drennan IR, et al. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med 2022; 387:1947. 66. Abrams D, MacLaren G, Lorusso R, et al. Extracorporeal cardiopulmonary resuscitation in adults: evidence and implications. Intensive Care Med 2022; 48:1. 67. Dennis M, Lal S, Forrest P, et al. In-Depth Extracorporeal Cardiopulmonary Resuscitation in Adult Out-of-Hospital Cardiac Arrest. J Am Heart Assoc 2020; 9:e016521. 68. Yannopoulos D, Bartos J, Raveendran G, et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet 2020; 396:1807. 69. Belohlavek J, Smalcova J, Rob D, et al. Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2022; 327:737. 70. Suverein MM, Delnoij TSR, Lorusso R, et al. Early Extracorporeal CPR for Refractory Out-of- Hospital Cardiac Arrest. N Engl J Med 2023; 388:299. 71. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation 2011; 82:1138. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 35/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate 72. Atkinson P, Bowra J, Milne J, et al. International Federation for Emergency Medicine Consensus Statement: Sonography in hypotension and cardiac arrest (SHoC): An international consensus on the use of point of care ultrasound for undifferentiated hypotension and during cardiac arrest. CJEM 2017; 19:459. 73. Lalande E, Burwash-Brennan T, Burns K, et al. Is point-of-care ultrasound a reliable predictor of outcome during atraumatic, non-shockable cardiac arrest? A systematic review and meta- analysis from the SHoC investigators. Resuscitation 2019; 139:159. 74. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967; 29:469. 75. Delaney B, Loy J, Kelly AM. The relative efficacy of adenosine versus verapamil for the treatment of stable paroxysmal supraventricular tachycardia in adults: a meta-analysis. Eur J Emerg Med 2011; 18:148. 76. Gebril A, Hawes S. Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: is intravenous adenosine effective and safe in patients presenting with unstable paroxysmal supraventricular tachycardia? Emerg Med J 2012; 29:251. 77. Appelboam A, Reuben A, Mann C, et al. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. Lancet 2015; 386:1747. 78. Cybulski J, Ku akowski P, Makowska E, et al. Intravenous amiodarone is safe and seems to be effective in termination of paroxysmal supraventricular tachyarrhythmias. Clin Cardiol 1996; 19:563. 79. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Cardioversion of paroxysmal atrial fibrillation in the emergency department. Ann Emerg Med 1999; 33:379. 80. Lerman BB, Ip JE, Shah BK, et al. Mechanism-specific effects of adenosine on ventricular tachycardia. J Cardiovasc Electrophysiol 2014; 25:1350. 81. Tzivoni D, Banai S, Schuger C, et al. Treatment of torsade de pointes with magnesium sulfate. Circulation 1988; 77:392. 82. Hooper A, Nolan JP, Rees N, et al. Drug routes in out-of-hospital cardiac arrest: A summary of current evidence. Resuscitation 2022; 181:70. 83. Kawano T, Grunau B, Scheuermeyer FX, et al. Intraosseous Vascular Access Is Associated With Lower Survival and Neurologic Recovery Among Patients With Out-of-Hospital Cardiac Arrest. Ann Emerg Med 2018; 71:588. 84. Berg KM, Soar J, Andersen LW, et al. Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 36/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate With Treatment Recommendations. Circulation 2020; 142:S92. 85. Reynolds JC, Issa MS, C Nicholson T, et al. Prognostication with point-of-care echocardiography during cardiac arrest: A systematic review. Resuscitation 2020; 152:56. 86. Blyth L, Atkinson P, Gadd K, Lang E. Bedside focused echocardiography as predictor of survival in cardiac arrest patients: a systematic review. Acad Emerg Med 2012; 19:1119. 87. Gaspari R, Weekes A, Adhikari S, et al. Emergency department point-of-care ultrasound in out-of-hospital and in-ED cardiac arrest. Resuscitation 2016; 109:33. 88. Bolvardi E, Pouryaghobi SM, Farzane R, et al. The Prognostic Value of Using Ultrasonography in Cardiac Resuscitation of Patients with Cardiac Arrest. Int J Biomed Sci 2016; 12:110. 89. Tsou PY, Kurbedin J, Chen YS, et al. Accuracy of point-of-care focused echocardiography in predicting outcome of resuscitation in cardiac arrest patients: A systematic review and meta-analysis. Resuscitation 2017; 114:92. 90. Callaway CW, Donnino MW, Fink EL, et al. Part 8: Post-Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S465. 91. Lauridsen KG, Baldi E, Smyth M, et al. Clinical decision rules for termination of resuscitation during in-hospital cardiac arrest: A systematic review of diagnostic test accuracy studies. Resuscitation 2021; 158:23. |
56. Martens PR, Russell JK, Wolcke B, et al. Optimal Response to Cardiac Arrest study: defibrillation waveform effects. Resuscitation 2001; 49:233. 57. Schneider T, Martens PR, Paschen H, et al. Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the resuscitation of out- of-hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators. Circulation 2000; 102:1780. 58. Schwarz B, Bowdle TA, Jett GK, et al. Biphasic shocks compared with monophasic damped sine wave shocks for direct ventricular defibrillation during open heart surgery. Anesthesiology 2003; 98:1063. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 34/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate 59. Holmberg MJ, Issa MS, Moskowitz A, et al. Vasopressors during adult cardiac arrest: A systematic review and meta-analysis. Resuscitation 2019; 139:106. 60. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016; 353:i1577. 61. Reynolds JC, Grunau BE, Rittenberger JC, et al. Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation. Circulation 2016; 134:2084. 62. Reynolds JC, Grunau BE, Elmer J, et al. Prevalence, natural history, and time-dependent outcomes of a multi-center North American cohort of out-of-hospital cardiac arrest extracorporeal CPR candidates. Resuscitation 2017; 117:24. 63. Grunau B, Reynolds JC, Scheuermeyer FX, et al. Comparing the prognosis of those with initial shockable and non-shockable rhythms with increasing durations of CPR: Informing minimum durations of resuscitation. Resuscitation 2016; 101:50. 64. Grunau B, Reynolds J, Scheuermeyer F, et al. Relationship between Time-to-ROSC and Survival in Out-of-hospital Cardiac Arrest ECPR Candidates: When is the Best Time to Consider Transport to Hospital? Prehosp Emerg Care 2016; 20:615. 65. Cheskes S, Verbeek PR, Drennan IR, et al. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med 2022; 387:1947. 66. Abrams D, MacLaren G, Lorusso R, et al. Extracorporeal cardiopulmonary resuscitation in adults: evidence and implications. Intensive Care Med 2022; 48:1. 67. Dennis M, Lal S, Forrest P, et al. In-Depth Extracorporeal Cardiopulmonary Resuscitation in Adult Out-of-Hospital Cardiac Arrest. J Am Heart Assoc 2020; 9:e016521. 68. Yannopoulos D, Bartos J, Raveendran G, et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet 2020; 396:1807. 69. Belohlavek J, Smalcova J, Rob D, et al. Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2022; 327:737. 70. Suverein MM, Delnoij TSR, Lorusso R, et al. Early Extracorporeal CPR for Refractory Out-of- Hospital Cardiac Arrest. N Engl J Med 2023; 388:299. 71. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation 2011; 82:1138. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 35/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate 72. Atkinson P, Bowra J, Milne J, et al. International Federation for Emergency Medicine Consensus Statement: Sonography in hypotension and cardiac arrest (SHoC): An international consensus on the use of point of care ultrasound for undifferentiated hypotension and during cardiac arrest. CJEM 2017; 19:459. 73. Lalande E, Burwash-Brennan T, Burns K, et al. Is point-of-care ultrasound a reliable predictor of outcome during atraumatic, non-shockable cardiac arrest? A systematic review and meta- analysis from the SHoC investigators. Resuscitation 2019; 139:159. 74. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967; 29:469. 75. Delaney B, Loy J, Kelly AM. The relative efficacy of adenosine versus verapamil for the treatment of stable paroxysmal supraventricular tachycardia in adults: a meta-analysis. Eur J Emerg Med 2011; 18:148. 76. Gebril A, Hawes S. Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: is intravenous adenosine effective and safe in patients presenting with unstable paroxysmal supraventricular tachycardia? Emerg Med J 2012; 29:251. 77. Appelboam A, Reuben A, Mann C, et al. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. Lancet 2015; 386:1747. 78. Cybulski J, Ku akowski P, Makowska E, et al. Intravenous amiodarone is safe and seems to be effective in termination of paroxysmal supraventricular tachyarrhythmias. Clin Cardiol 1996; 19:563. 79. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Cardioversion of paroxysmal atrial fibrillation in the emergency department. Ann Emerg Med 1999; 33:379. 80. Lerman BB, Ip JE, Shah BK, et al. Mechanism-specific effects of adenosine on ventricular tachycardia. J Cardiovasc Electrophysiol 2014; 25:1350. 81. Tzivoni D, Banai S, Schuger C, et al. Treatment of torsade de pointes with magnesium sulfate. Circulation 1988; 77:392. 82. Hooper A, Nolan JP, Rees N, et al. Drug routes in out-of-hospital cardiac arrest: A summary of current evidence. Resuscitation 2022; 181:70. 83. Kawano T, Grunau B, Scheuermeyer FX, et al. Intraosseous Vascular Access Is Associated With Lower Survival and Neurologic Recovery Among Patients With Out-of-Hospital Cardiac Arrest. Ann Emerg Med 2018; 71:588. 84. Berg KM, Soar J, Andersen LW, et al. Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 36/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate With Treatment Recommendations. Circulation 2020; 142:S92. 85. Reynolds JC, Issa MS, C Nicholson T, et al. Prognostication with point-of-care echocardiography during cardiac arrest: A systematic review. Resuscitation 2020; 152:56. 86. Blyth L, Atkinson P, Gadd K, Lang E. Bedside focused echocardiography as predictor of survival in cardiac arrest patients: a systematic review. Acad Emerg Med 2012; 19:1119. 87. Gaspari R, Weekes A, Adhikari S, et al. Emergency department point-of-care ultrasound in out-of-hospital and in-ED cardiac arrest. Resuscitation 2016; 109:33. 88. Bolvardi E, Pouryaghobi SM, Farzane R, et al. The Prognostic Value of Using Ultrasonography in Cardiac Resuscitation of Patients with Cardiac Arrest. Int J Biomed Sci 2016; 12:110. 89. Tsou PY, Kurbedin J, Chen YS, et al. Accuracy of point-of-care focused echocardiography in predicting outcome of resuscitation in cardiac arrest patients: A systematic review and meta-analysis. Resuscitation 2017; 114:92. 90. Callaway CW, Donnino MW, Fink EL, et al. Part 8: Post-Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S465. 91. Lauridsen KG, Baldi E, Smyth M, et al. Clinical decision rules for termination of resuscitation during in-hospital cardiac arrest: A systematic review of diagnostic test accuracy studies. Resuscitation 2021; 158:23. 92. Mohr M, Bahr J, Schmid J, et al. The decision to terminate resuscitative efforts: results of a questionnaire. Resuscitation 1997; 34:51. 93. Marco CA, Bessman ES, Schoenfeld CN, Kelen GD. Ethical issues of cardiopulmonary resuscitation: current practice among emergency physicians. Acad Emerg Med 1997; 4:898. 94. de Vos R, Oosterom L, Koster RW, de Haan RJ. Decisions to terminate resuscitation. Resuscitation Committee. Resuscitation 1998; 39:7. 95. Bailey ED, Wydro GC, Cone DC. Termination of resuscitation in the prehospital setting for adult patients suffering nontraumatic cardiac arrest. National Association of EMS Physicians Standards and Clinical Practice Committee. Prehosp Emerg Care 2000; 4:190. 96. Horsted TI, Rasmussen LS, Lippert FK, Nielsen SL. Outcome of out-of-hospital cardiac arrest- why do physicians withhold resuscitation attempts? Resuscitation 2004; 63:287. 97. Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med 1997; 337:301. 98. Grmec S, Klemen P. Does the end-tidal carbon dioxide (EtCO2) concentration have prognostic value during out-of-hospital cardiac arrest? Eur J Emerg Med 2001; 8:263. https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 37/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate 99. Ahrens T, Schallom L, Bettorf K, et al. End-tidal carbon dioxide measurements as a prognostic indicator of outcome in cardiac arrest. Am J Crit Care 2001; 10:391. 100. Morrison LJ, Visentin LM, Kiss A, et al. Validation of a rule for termination of resuscitation in out-of-hospital cardiac arrest. N Engl J Med 2006; 355:478. 101. Ong ME, Jaffey J, Stiell I, et al. Comparison of termination-of-resuscitation guidelines for basic life support: defibrillator providers in out-of-hospital cardiac arrest. Ann Emerg Med 2006; 47:337. 102. Stiell IG, Nesbitt LP, Pickett W, et al. The OPALS Major Trauma Study: impact of advanced life- support on survival and morbidity. CMAJ 2008; 178:1141. 103. Ruygrok ML, Byyny RL, Haukoos JS, Colorado Cardiac Arrest & Resuscitation Collaborative Study Group and the Denver Metro EMS Medical Directors. Validation of 3 termination of resuscitation criteria for good neurologic survival after out-of-hospital cardiac arrest. Ann Emerg Med 2009; 54:239. 104. Morrison LJ, Verbeek PR, Zhan C, et al. Validation of a universal prehospital termination of resuscitation clinical prediction rule for advanced and basic life support providers. Resuscitation 2009; 80:324. 105. Jabre P, Bougouin W, Dumas F, et al. Early Identification of Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and Consideration for Organ Donation. Ann Intern Med 2016; 165:770. Topic 278 Version 88.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 38/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate GRAPHICS ACLS cardiac arrest algorithm for suspected or confirmed COVID-19 patients https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 39/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 40/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate PPE: personal protective equipment; CPR: cardiopulmonary resuscitation; IV: intravenous; IO: intraosseous. Refer to UpToDate topics on post-cardiac arrest management for additional information. Reproduced with permission. 10.1161/CIRCULATIONAHA.120.047463. Copyright 2020 American Heart Association, Inc. Graphic 127851 Version 9.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 41/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate BLS health care provider adult cardiac arrest algorithm 2020 update BLS: basic life support; AED: automated external defibrillator; CPR: cardiopulmonary resuscitation; ALS: advanced life support. Reprinted with permission. Circulation 2020; 142:S366-S468. Copyright 2020 American Heart Association, Inc. Graphic 105569 Version 8.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 42/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 43/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 44/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 45/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Key principles in the performance of ACLS Excellent CPR is crucial. Anything short of excellent CPR does not achieve adequate cerebral and coronary perfusion. Excellent chest compressions must be performed throughout the resuscitation without interruption, using proper timing (100 to 120 compressions per minute) and force (5 to 6 cm [2 to 2.5 inches] depth), and allowing for complete chest recoil. Excellent chest compressions take priority over ventilation. If a second rescuer is present, ventilations must be performed using proper timing (6 to 8 breaths per minute in the intubated patient; ratio of 30 compressions to 2 ventilations if not intubated) and force (deliver each breath over one second, and only until chest begins to rise). Avoid hyperventilation. Do not stop compressions until the defibrillator is fully charged. Defibrillate VF and pulseless VT as rapidly as possible. Rapidly identify and treat causes of non-shockable arrest (PEA, asystole). Important causes include the 5 H's and 5 T's: Hypoxia, Hypovolemia, Hydrogen ions (acidosis), Hyper/Hypo-kalemia, Hypothermia; Tension pneumothorax, Tamponade-cardiac, Toxins, Thrombosis-coronary (MI), Thrombosis-pulmonary (PE). If immediately reversible causes (eg, tension pneumothorax, cardiac tamponade) are not corrected rapidly, the patient has little chance of survival. ACLS: advanced cardiac life support; CPR: cardiopulmonary resuscitation; VF: ventricular fibrillation; VT: ventricular tachycardia; PEA: pulseless electrical activity; MI: myocardial infarction; PE: pulmonary embolism. Graphic 83671 Version 5.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 46/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Manual defibrillation performance bundle 1. Attach and charge the defibrillator while continuing excellent chest compressions. 2. Stop compressions and assess rhythm (should take no more than 5 seconds). 3. If VF or VT is present, deliver shock; if non-shockable rhythm is present, resume excellent CPR (and clear the charged defibrillator*). 4. Resume excellent chest compressions and CPR immediately after the shock is delivered. Critical point: Interruptions in chest compressions must be kept to a minimum: Do NOT stop compressions while defibrillator is being charged. The defibrillator is charged during CPR in anticipation of treating a shockable arrhythmia and to minimize interruptions in CPR. If a non-shockable arrhythmia is present, the charged defibrillator should be discharged into the machine, rather than the defibrillation pads, according to the manufacturer's instructions. VF: ventricular fibrillation; VT: pulseless ventricular tachycardia. Graphic 83670 Version 7.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 47/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Treatable conditions associated with cardiac arrest Condition Common associated clinical settings Acidosis Diabetes, diarrhea, drug overdose, renal dysfunction, sepsis, shock Anemia Gastrointestinal bleeding, nutritional deficiencies, recent trauma Cardiac Post-cardiac surgery, malignancy, post-myocardial infarction, pericarditis, trauma tamponade Hyperkalemia Drug overdose, renal dysfunction, hemolysis, excessive potassium intake, rhabdomyolysis, major soft tissue injury, tumor lysis syndrome Hypokalemia* Alcohol abuse, diabetes mellitus, diuretics, drug overdose, profound gastrointestinal losses Hypothermia Alcohol intoxication, significant burns, drowning, drug overdose, elder patient, endocrine disease, environmental exposure, spinal cord disease, trauma Hypovolemia Significant burns, diabetes, gastrointestinal losses, hemorrhage, malignancy, sepsis, trauma Hypoxia Upper airway obstruction, hypoventilation (CNS dysfunction, neuromuscular disease), pulmonary disease Myocardial infarction Cardiac arrest Poisoning History of alcohol or drug abuse, altered mental status, classic toxidrome (eg, sympathomimetic), occupational exposure, psychiatric disease Pulmonary embolism Immobilized patient, recent surgical procedure (eg, orthopedic), peripartum, risk factors for thromboembolic disease, recent trauma, presentation consistent with acute pulmonary embolism Tension Central venous catheter, mechanical ventilation, pulmonary disease (eg, asthma, pneumothorax chronic obstructive pulmonary disease), thoracentesis, thoracic trauma CNS: central nervous system. Hypomagnesemia should be assumed in the setting of hypokalemia, and both should be treated. Adapted from: Eisenberg MS, Mengert TJ. Cardiac resuscitation. N Engl J Med 2001; 344:1304. Graphic 52416 Version 8.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 48/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Options for hands-free pacemaker/defibrillator pad positioning Positioning options for hands-free pacemaker/defibrillator pads showing anterior/lateral positioning (left) and anterior/posterior positioning (right). Graphic 103268 Version 2.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 49/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Adult bradycardia algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130748 Version 10.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 50/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Adult tachycardia with a pulse algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130747 Version 10.0 https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 51/52 7/6/23, 11:24 AM Advanced cardiac life support (ACLS) in adults - UpToDate Contributor Disclosures Jonathan Elmer, MD, MS, FNCS Grant/Research/Clinical Trial Support: National Institutes of Health [Post- cardiac arrest care]. All of the relevant financial relationships listed have been mitigated. Ron M Walls, MD, FRCPC, FAAEM Other Financial Interest: Airway Management Education Center [Health care provider education and resources]; First Airway [Health care provider education and resources]. All of the relevant financial relationships listed have been mitigated. Richard L Page, MD No relevant financial relationship(s) with ineligible companies to disclose. Jonathan Grayzel, MD, FAAEM No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/advanced-cardiac-life-support-acls-in-adults/print 52/52 |
7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Approach to sudden cardiac arrest in the absence of apparent structural heart disease : Mark S Link, MD : Peter J Zimetbaum, MD, Scott Manaker, MD, PhD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 30, 2022. INTRODUCTION Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity with hemodynamic collapse due to sustained pulseless ventricular tachycardia/fibrillation, pulseless electrical activity (PEA), or asystole. The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation) restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.) SCA and SCD occur most commonly in patients with structural heart disease (including previously undiagnosed heart disease), particularly coronary artery disease. SCD in the apparently normal heart (at autopsy) is less common and is responsible for, as previously reported, 10 to 15 percent of cases of SCD [1,2]. However, series of SCD in the young show increasing percentages of SCA with an apparently normal hearts, with up to 40 percent of SCD with a normal heart [3,4]. Thus, SCA with an apparently normal heart is more common in younger arrest victims. The majority of SCD patients without apparent structural heart disease likely do not actually have "normal" hearts, but our diagnostic tools limit identification of structural or functional abnormalities. In the past, the etiology of many of these deaths was unknown and deemed "idiopathic." However, more complete evaluation has identified the cause of death as a primary electrical disorder (ie, long QT, Wolff-Parkinson-White [WPW], https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 1/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate catecholaminergic polymorphic ventricular tachycardia [CPVT], and Brugada syndrome) in many of these patients [1,2,5]. (See "Pathophysiology and etiology of sudden cardiac arrest".) SCD in the apparently normal heart will be reviewed here. SCD in patients with heart disease, and the evaluation and options for the management of survivors of SCD, are discussed separately. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Etiology' and "Pathophysiology and etiology of sudden cardiac arrest", section on 'Etiology of SCD' and "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) In addition, sudden death may occur from noncardiac causes (eg, trauma, pulmonary embolism, seizure), and these topics are discussed separately. (See "Overview of acute pulmonary embolism in adults" and "Sudden unexpected death in epilepsy".) EPIDEMIOLOGY Based upon a review of death certificates in the United States during 1998 and 1999, sudden cardiac death (SCD) accounted for over 450,000 deaths annually, which represented 63 percent of cardiac deaths among adults 35 years of age [6]. The incidence of SCD is increased six- to ten-fold in the presence of clinically recognized heart disease ( figure 1); it also increases with age and is two to three times more common in men than women ( figure 2) [7]. Although the risk of SCD is higher in patients with structural heart disease, SCD events occur in individuals with apparently normal hearts. In a series of 121 SCD cases where data on left ventricular function was available, 48 percent had normal left ventricular function [8]. Among these patients, one-half had no history of established coronary heart disease. Autopsy studies of subjects with a presumed diagnosis of SCD have shown high variability in the numbers of subject without a demonstrable cardiac abnormality [1,9-12]. A lower value of about 5 percent has been described in autopsy studies and among survivors of SCD when older patients are included, a population in which coronary heart disease (CHD) is more prevalent but not necessarily the cause of SCD [1,10]. In an autopsy series of 902 cases of SCD (mean age 38 years), 187 (21 percent) had no evidence of cardiac pathology that could cause SCD [11]. In a separate autopsy series of 967 cases of SCD referred to a tertiary cardiac pathologist between 1994 and 2010, 45 percent of cases had a normal cardiac postmortem examination [12]. Atherosclerotic CHD at autopsy is much more commonly found in SCD victims who are older than 35 years (incidence 13.7 per 100,000 person-years versus 0.7 per 100,000 person years without CHD), yet causality is not always clear as autopsy rates of coronary artery disease (CAD) would be high in this age group regardless of cause of death [11]. https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 2/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate The distribution of cardiac causes of SCD varies with age, the population studied, and geography. While CAD is listed as the underlying cause of SCD on the majority of death certificates among the general population in the United States, younger patients, athletes, and those without known prior disease often have a different distribution of causes. The etiology of SCD is discussed in greater detail elsewhere. (See "Pathophysiology and etiology of sudden cardiac arrest".) EVALUATION OF SURVIVORS The evaluation of survivors of sudden cardiac arrest (SCA) with apparently normal hearts involves a variety of tests, generally including multiple of the following tests: Laboratory studies to assess electrolytes Electrocardiogram Echocardiogram Coronary angiography Cardiac magnetic resonance imaging Provocative testing for primary electrical disease Genetic analysis These tests are performed in an effort to find underlying structural heart disease, primary electrical diseases, and drug or toxin exposure that may have contributed to SCA. In addition, a rigorous search for the known causes of SCA should be performed in the apparently healthy person prior to making the diagnosis of idiopathic ventricular fibrillation [2]. An extensive discussion of the evaluation of SCA survivors is presented separately. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".) AUTOPSY AND MOLECULAR GENETIC TESTING Patients who experience sudden cardiac death (SCD), particularly young patients, should undergo an autopsy with extensive cardiac evaluation to evaluate for the presence of structural heart disease. This has importance not only for the proband, but also for the family. Autopsies may demonstrate that there was an underlying heart disease such as hypertrophic cardiomyopathy (HCM) or arrhythmogenic right ventricular cardiomyopathy (ARVC), Wolff- Parkinson-White syndrome (WPW), congenital heart disease coronary anomalies, coronary artery disease, or dilated cardiomyopathies. Subtle cases of these diseases may be missed, particularly with standard autopsies. As noted, inherited arrhythmia syndromes are common in https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 3/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate individuals who experience SCD but whose autopsy reveals no evidence of structural heart disease. Diagnosing such a syndrome would have significant implications for surviving family members, particularly if a specific genetic defect could be identified. (See 'Evaluation of family members' below.) In general, genetic testing of the victim of SCD with a structurally normal heart should occur, ideally prior to the declaration of death, but it may also be done as part of an autopsy if resuscitation is unsuccessful. Although interpretation may be limited by the large number of candidate genes, the number of known mutations in each of these genes and variable gene expression and penetrance, continued development and knowledge of the gene pool database will be important for the management of the surviving relatives. As both genetic testing techniques and our understanding of these heritable disorders improve, genetic screening at specialized centers has yielded diagnoses in up to one-third of young SCD victims without structural heart disease [13-16]. In the largest reported series of 302 cases of sudden death with negative autopsy and negative toxicologic evaluation (median age 24 years, 65 percent male), molecular autopsy was performed, with sequencing for a panel of 77 genes associated with primary electrical disorders and cardiomyopathies [16]. Pathogenic or likely pathogenic variants were identified in 40 patients (13 percent), most commonly variants associated with catecholaminergic polymorphic ventricular tachycardia and congenital long QT syndrome (17 and 11 patients, respectively). When results from the molecular autopsy were combined with clinical evaluation in the screening of surviving family members, the likelihood of making a significant clinical diagnosis increased from 26 to 39 percent. In a study from the Paris Sudden Death Center which included 88 SCA VF survivors with a negative workup after ECG, angiography, and echocardiography, MRI was abnormal in 25 of these (myocarditis = 13, HCM = 4, ARVC = 4, DCM = 2 and CAD = 2) [17]. Additionally, ergonovine caused vasospasm in 12, and pharmacologic provocative testing was positive with ajmaline in one (Brugada) patient and with catecholamine in one (CPVT) patient. POTENTIAL CAUSES Several major diseases must be considered as possible causes of sudden cardiac death (SCD) in patients without evidence of structural heart disease [2]. Many of these disorders are familial and therefore are associated with an increased risk of SCD in first-degree relatives. In multiple series of intensive evaluation, including genetic analysis, the LQTS and CPVT are the most frequently found causes [16,18-20]. https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 4/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Prolonged QT interval Long QT can be primary (genetic/inherited) (the long QT syndrome [LQTS]) or secondary (acquired) ( table 1) and may be associated with a specific form of polymorphic ventricular tachycardia (VT) called torsades de pointes ( waveform 1). Among patients with inherited LQTS, the precipitating factors and prognosis vary with the genetic abnormality. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Congenital long QT syndrome: Pathophysiology and genetics" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) The majority of secondary causes of prolonged QT interval result from an interaction with a drug/electrolyte which interferes with an ion channel involved in repolarization, the same ion channels involved in LQTS. Most of the pharmaceutical agents are prescription drugs; a list can be found at crediblemeds.org, which should be consulted before prescribing new drugs for anyone with a long QT or on another drug known to prolong the QT. Common drugs that increase the QT are anti-psychotics, anti-emetics, quinolones, anti-arrhythmics, and methadone [21]. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Polymorphic VT with normal QT interval Polymorphic VT with a normal QT interval is largely due to either acute cardiac ischemia or catecholaminergic polymorphic VT (CPVT). Ischemia is the cause in the majority of these patients, and thus prompt evaluation for cardiac ischemia is warranted. In those without cardiac ischemia, CPVT, an inherited channelopathy, may be the cause. Affected patients typically present with life-threatening polymorphic VT or ventricular fibrillation occurring during emotional or physical stress, with syncope often being the first manifestation of the disease. Although sporadic cases occur, this is a largely familial disease. The majority of known cases are due to mutations in the cardiac ryanodine receptor, which is the cardiac sarcoplasmic calcium release channel. One report suggested that this disorder may account for at least one in seven cases of sudden unexplained death [13]. (See "Catecholaminergic polymorphic ventricular tachycardia".) Brugada syndrome The Brugada syndrome is characterized by the electrocardiographic findings of right bundle branch block and ST-segment elevation in leads V1 to V3 ( waveform 2), and an increased risk of sudden cardiac death. Brugada syndrome is due to a functional abnormality in repolarization. There may be some overlap with an early subclinical manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC). The Brugada syndrome occurs in families, with genetic transmission consistent with autosomal dominant inheritance with variable penetrance. Mutations in the cardiac sodium channel gene, SCN5A, have been found in several families. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'SCN5A' and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 5/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate A sudden unexpected nocturnal death syndrome (SUNDS) has also been described in young, apparently healthy males from Southeast Asia. This disorder is closely related and indeed may be the same as Brugada syndrome since a majority of affected patients have the ECG manifestations of the Brugada syndrome and the same mutations in the sodium channel gene. Different mutations of the same SCN5A gene have been found in a number of cardiac disorders, including the long QT syndrome, and a unique allele found in African Americans, Y1102. (See "Congenital long QT syndrome: Pathophysiology and genetics", section on 'Type 3 LQTS (LQT3)'.) Commotio cordis Commotio cordis is defined as sudden cardiac death secondary to relatively innocent chest wall impact due to ventricular fibrillation. Affected patients have no underlying heart disease and there is no structural damage to the chest wall, thoracic cavity, or the heart. Early defibrillation of commotio victims is lifesaving, despite historical evidence that resuscitation may be more difficult in commotio cordis than in other forms of SCD. Commotio cordis is discussed in detail separately. (See "Commotio cordis".) WPW and other forms of SVT Both Wolff-Parkinson-White (WPW) syndrome and, very rarely, other forms of supraventricular tachycardia (SVT) can cause sudden cardiac death (SCD). The frequency with which this occurs was assessed in a report of 290 patients with aborted SCD. The mechanism was an arrhythmia associated with the WPW syndrome in 2.1 percent; atrial fibrillation (AF) with a rapid ventricular response was the most common [22]. A similar incidence of preexcitation (3.6 percent) was noted in a report of 273 children and young adults with SCD [23]. The epidemiology and clinical manifestations of the WPW syndrome are discussed in greater detail separately. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) Most patients who have been resuscitated from ventricular fibrillation (VF) secondary to preexcitation have a previous history of syncope, atrioventricular reciprocating tachycardia, and/or AF [24]. However, preexcitation and arrhythmias have been previously undiagnosed in up to 25 percent of such individuals [25,26]. Among patients with WPW syndrome who survive an episode of SCD, ablation of the accessory pathway is the treatment of choice. Treatment options for persons with the WPW syndrome are discussed in detail separately. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome".) Early repolarization syndrome Early repolarization pattern on ECG is common. In 2008 a higher frequency of early repolarization was described in 206 survivors of cardiac arrest without apparent heart disease (31 to 5 percent of controls; p<0.001) [27]. These survivors tended to have increased incidences of recurrent VF compared with those SCA survivors with normal hearts and no early repolarization. Subsequent studies have confirmed the higher incidence of https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 6/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate early repolarization in SCA survivors with normal hearts. Early repolarization in the inferior and lateral leads is associated with an increased risk of SCA. However, large population studies continue to describe a 5 to 10 percent incidence of early repolarization, and when found in the absence of a SCA it is thought benign [28]. Early repolarization ECG pattern is especially common in athletes, and in these individuals it is nearly always benign [29]. An expert consensus panel does not recommend any specific treatment for those with early repolarization without SCA [30]. (See "Early repolarization".) VF secondary to PVCs Short coupled PVCs have been described as a trigger of VF [31]. Generally these arise from the Purkinje fibers, but PVCs from papillary muscles have also been described to trigger VF. Ablation of these triggering PVCs may eliminate recurrent episodes of VF [32]. Idiopathic VF If the above disorders are excluded and the heart is structurally normal, the diagnosis of primary electrical disease is made [2,33,34]. More commonly referred to as idiopathic ventricular fibrillation (VF), this entity is estimated to account for 5 percent of cases of sudden cardiac death (SCD) [33]. In a review of 54 published cases with presumed idiopathic VF, the mean age was 36 years with a male-to-female ratio of 2.5-to-1 [34]. A history of syncope preceded the episode of VF in 25 percent. In a meta-analysis of 639 patients with idiopathic VF from 23 studies, among whom 80 percent had an implantable cardioverter-defibrillator for secondary prevention, 31 percent of patients had recurrent ventricular arrhythmias over a mean follow-up of five years [35]. Other registries have shown a similar high incidence of arrhythmias over time, and pediatric patients appear to have a higher incidence of ICD-treated arrhythmias [36,37]. The diagnosis and treatment of idiopathic VF, particularly as they relate to the early repolarization syndrome, are presented in greater detail separately. (See "Early repolarization".) Familial SCD A family history of sudden cardiac death (SCD) in the absence of apparent structural heart disease is associated with an increased risk for primary SCD [38-40]. It has been estimated that the adjusted relative risk for SCD, compared with controls, is 1.6 to 1.8 in individuals without apparent structural heart disease in whom a first-degree relative had SCD [38,39]. However, the absolute increase in risk is quite small since primary SCD is rare in the general population. The increase in risk is incompletely understood. Some of these families have an inherited cardiac disease, as illustrated in a report in which 147 first-degree relatives of 32 patients with SCD underwent detailed cardiac assessment [40]. Seven (22 percent) of the 32 families had an inherited cardiac disease, including four with long QT syndrome, one with myotonic dystrophy, and one with hypertrophic cardiomyopathy. https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 7/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Genome-wide association studies have demonstrated an increased risk with several loci [41]. Short QT syndrome Short QT syndrome (SQTS) is an extremely rare inherited channelopathy associated with markedly shortened QT intervals and SCD in individuals with a structurally normal heart. In contrast to long QT syndrome, ion channel defects associated with SQTS lead to abnormal abbreviation of repolarization, predisposing affected individuals to a risk of atrial and ventricular arrhythmias. SQTS is discussed in detail separately. (See "Short QT syndrome".) EVALUATION OF FAMILY MEMBERS As noted above, many causes of sudden cardiac death (SCD) in patients with structurally normal hearts are familial, and therefore are associated with an increased risk of SCD in first-degree relatives. In families of victims of unexplained SCD, a general cardiology evaluation of first- and second-degree relatives can yield diagnosis of a heritable disease in up to 40 percent of families. A discussion of the evaluation of family members of victims of unexplained SCD is presented separately. (See "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'Evaluation of family members'.) SUMMARY AND RECOMMENDATIONS Background Sudden cardiac death (SCD) refers to the sudden cessation of cardiac activity with hemodynamic collapse, often due to sustained pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF). SCD is the most common cause of cardiovascular death in the developed world. (See 'Introduction' above.) Epidemiology Although the risk of SCD is higher in patients with structural heart disease, as many as 10 to 15 percent of SCDs occur in individuals with apparently normal hearts. (See 'Epidemiology' above.) Potential causes Causes of SCD with a normal heart are (see 'Potential causes' above): Prolonged QT interval (congenital [long QT syndrome] or acquired) Catecholaminergic polymorphic VT with normal QT interval Brugada syndrome Commotio cordis Wolff-Parkinson-White syndrome Short QT syndrome Early repolarization syndrome https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 8/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Short coupled PVCs Family history A family history of SCD (in first-degree relatives) in the absence of apparent structural heart disease is associated with an increased risk for primary SCD. (See 'Familial SCD' above.) Role of autopsy Patients who experience SCD, particularly young patients, should undergo an autopsy with particular attention to the heart to evaluate the presence of structural heart disease. In young patients, if there is no clear diagnosis after autopsy, genetic testing now can yield a diagnosis in up to one third of young SCD victims and should generally be performed. (See 'Autopsy and molecular genetic testing' above.) SCA survivors Survivors of sudden cardiac arrest (SCA) should undergo extensive testing to exclude drug or toxin exposure or underlying structural heart disease that may have contributed to SCA. Therapy with an implantable cardioverter-defibrillator should generally be recommended in survivors of SCA. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".) Evaluation of family members In families of victims of unexplained SCD, a general cardiology evaluation of first- and second-degree relatives can yield diagnosis of a heritable disease in up to 40 percent of families. (See "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'Evaluation of family members'.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Chugh SS, Kelly KL, Titus JL. Sudden cardiac death with apparently normal heart. Circulation 2000; 102:649. 2. Wever EF, Robles de Medina EO. Sudden death in patients without structural heart disease. J Am Coll Cardiol 2004; 43:1137. 3. Bagnall RD, Weintraub RG, Ingles J, et al. A Prospective Study of Sudden Cardiac Death among Children and Young Adults. N Engl J Med 2016; 374:2441. 4. Landry CH, Allan KS, Connelly KA, et al. Sudden Cardiac Arrest during Participation in Competitive Sports. N Engl J Med 2017; 377:1943. 5. Myerburg RJ. Sudden cardiac death in persons with normal (or near normal) hearts. Am J Cardiol 1997; 79:3. https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 9/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate 6. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158. 7. Kannel WB, Wilson PW, D'Agostino RB, Cobb J. Sudden coronary death in women. Am Heart J 1998; 136:205. 8. Stecker EC, Vickers C, Waltz J, et al. Population-based analysis of sudden cardiac death with and without left ventricular systolic dysfunction: two-year findings from the Oregon Sudden Unexpected Death Study. J Am Coll Cardiol 2006; 47:1161. 9. Drory Y, Turetz Y, Hiss Y, et al. Sudden unexpected death in persons less than 40 years of age. Am J Cardiol 1991; 68:1388. 10. Bowker TJ, Wood DA, Davies MJ, et al. Sudden, unexpected cardiac or unexplained death in England: a national survey. QJM 2003; 96:269. 11. Eckart RE, Shry EA, Burke AP, et al. Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance. J Am Coll Cardiol 2011; 58:1254. 12. Mellor G, Raju H, de Noronha SV, et al. Clinical characteristics and circumstances of death in the sudden arrhythmic death syndrome. Circ Arrhythm Electrophysiol 2014; 7:1078. 13. Tester DJ, Spoon DB, Valdivia HH, et al. Targeted mutational analysis of the RyR2-encoded cardiac ryanodine receptor in sudden unexplained death: a molecular autopsy of 49 medical examiner/coroner's cases. Mayo Clin Proc 2004; 79:1380. 14. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. J Am Coll Cardiol 2007; 49:240. 15. Tester DJ, Medeiros-Domingo A, Will ML, et al. Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy-negative sudden unexplained death referred for postmortem genetic testing. Mayo Clin Proc 2012; 87:524. 16. Lahrouchi N, Raju H, Lodder EM, et al. Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome. J Am Coll Cardiol 2017; 69:2134. 17. Waldmann V, Bougouin W, Karam N, et al. Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation. Eur Heart J 2018; 39:1981. 18. Krahn AD, Healey JS, Chauhan V, et al. Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER). Circulation 2009; 120:278. 19. Christiansen SL, Hertz CL, Ferrero-Miliani L, et al. Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting. Eur J Hum Genet 2016; 24:1797. https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 10/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate 20. Giudicessi JR, Ackerman MJ. Role of genetic heart disease in sentinel sudden cardiac arrest survivors across the age spectrum. Int J Cardiol 2018; 270:214. 21. Chugh SS, Socoteanu C, Reinier K, et al. A community-based evaluation of sudden death associated with therapeutic levels of methadone. Am J Med 2008; 121:66. 22. Wang YS, Scheinman MM, Chien WW, et al. Patients with supraventricular tachycardia presenting with aborted sudden death: incidence, mechanism and long-term follow-up. J Am Coll Cardiol 1991; 18:1711. 23. Basso C, Corrado D, Rossi L, Thiene G. Ventricular preexcitation in children and young adults: atrial myocarditis as a possible trigger of sudden death. Circulation 2001; 103:269. 24. Pappone C, Santinelli V, Rosanio S, et al. Usefulness of invasive electrophysiologic testing to stratify the risk of arrhythmic events in asymptomatic patients with Wolff-Parkinson-White pattern: results from a large prospective long-term follow-up study. J Am Coll Cardiol 2003; 41:239. 25. Klein GJ, Bashore TM, Sellers TD, et al. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. N Engl J Med 1979; 301:1080. 26. Montoya PT, Brugada P, Smeets J, et al. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. Eur Heart J 1991; 12:144. 27. Ha ssaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008; 358:2016. 28. Noseworthy PA, Tikkanen JT, Porthan K, et al. The early repolarization pattern in the general population: clinical correlates and heritability. J Am Coll Cardiol 2011; 57:2284. 29. Quattrini FM, Pelliccia A, Assorgi R, et al. Benign clinical significance of J-wave pattern (early repolarization) in highly trained athletes. Heart Rhythm 2014; 11:1974. 30. Patton KK, Ellinor PT, Ezekowitz M, et al. Electrocardiographic Early Repolarization: A Scientific Statement From the American Heart Association. Circulation 2016; 133:1520. 31. Knecht S, Sacher F, Wright M, et al. Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study. J Am Coll Cardiol 2009; 54:522. 32. Santoro F, Di Biase L, Hranitzky P, et al. Ventricular fibrillation triggered by PVCs from papillary muscles: clinical features and ablation. J Cardiovasc Electrophysiol 2014; 25:1158. 33. Survivors of out-of-hospital cardiac arrest with apparently normal heart. Need for definition and standardized clinical evaluation. Consensus Statement of the Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United States. Circulation 1997; 95:265. 34. Viskin S, Belhassen B. Idiopathic ventricular fibrillation. Am Heart J 1990; 120:661. https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 11/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate 35. Ozaydin M, Moazzami K, Kalantarian S, et al. Long-Term Outcome of Patients With Idiopathic Ventricular Fibrillation: A Meta-Analysis. J Cardiovasc Electrophysiol 2015; 26:1095. 36. Conte G, Belhassen B, Lambiase P, et al. Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry. Europace 2019; 21:1670. 37. Frontera A, Vlachos K, Kitamura T, et al. Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications. J Am Heart Assoc 2019; 8:e011172. 38. Friedlander Y, Siscovick DS, Weinmann S, et al. Family history as a risk factor for primary cardiac arrest. Circulation 1998; 97:155. 39. Jouven X, Desnos M, Guerot C, Ducimeti re P. Predicting sudden death in the population: the Paris Prospective Study I. Circulation 1999; 99:1978. 40. Behr E, Wood DA, Wright M, et al. Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome. Lancet 2003; 362:1457. 41. Wei D, Tao L, Huang M. Genetic variations involved in sudden cardiac death and their associations and interactions. Heart Fail Rev 2016; 21:401. Topic 1019 Version 26.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 12/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate GRAPHICS Risk of SCD is related to clinical manifestations of CHD During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden cardiac death (SCD) in both men and women was related to the clinical manifestations of coronary heart disease (CHD). It was highest in those with a myocardial infarction, intermediate in those with angina and no prior infarction, and lowest in those without overt CHD. Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 52309 Version 2.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 13/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Incidence of sudden death in men and women increases with age During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden death increased with age in both men and women. However, at each age, the incidence of sudden death is higher in men than women. Data from Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 59028 Version 4.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 14/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial ischemia or infarction, GnRH agonist/antagonist therapy Hypomagnesemia Bilateral surgical orchiectomy Hypocalcemia Diuretic therapy via electrolyte disorders particularly hypokalemia and hypomagnesemia especially with prominent T-wave inversions Starvation Anorexia nervosa Herbs Liquid protein diets Cinchona (contains quinine), iboga (ibogaine), licorice extract in overuse via electrolyte disturbances Intracranial disease Hypothyroidism Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate AV block: Second or third degree insecticides Medications* High risk Adagrasib Cisaparide (restricted availability) Lenvatinib Selpercatinib Ajmaline Levoketoconazole Sertindole Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine (intracoronary) Vandetanib Dofetilide Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab ozogamacin Propafenone Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 15/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Certinib Escitalopram Levofloxacin (systemic) Risperidone Chloroquine Etelcalcetide Saquinavir Lofexidine Citalopram Fexinidazole Sevoflurane Meglumine antimoniate Clarithromycin Flecainide Sparfloxacin Clofazimine Floxuridine Sunitinib Midostaurin Clomipramine Fluconazole Tegafur Moxifloxacin Clozapine Fluorouracil (systemic) Terbutaline Nilotinib Crizotinib Thioridazine Olanzapine Flupentixol Dabrafenib Toremifene Ondansetrol (IV > oral) Gabobenate dimeglumine Dasatinib Vemurafenib Deslurane Voriconazole Osimertinib Gemifloxacin Domperidone Oxytocin Gilteritinib Doxepin Pazopanib Halofantrine Doxifluridine Pentamidine Haloperidol (oral) Pilsicainide Imipramine Pimozide Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole (systemic) Romidepsin Anagrelide Foscarnet Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- lumefantrine Glasdegib Mizolastine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine (rare reports) Nortriptyline Benperidol Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus Olodaterol (systemic) Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone Degarelix Lefamulin Pasireotide Triclabendazole https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 16/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- norethindrone Periciazine Tropisetron Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide overdose in Eliglustat Primaquine Vorinostat Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical |
ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry. Europace 2019; 21:1670. 37. Frontera A, Vlachos K, Kitamura T, et al. Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications. J Am Heart Assoc 2019; 8:e011172. 38. Friedlander Y, Siscovick DS, Weinmann S, et al. Family history as a risk factor for primary cardiac arrest. Circulation 1998; 97:155. 39. Jouven X, Desnos M, Guerot C, Ducimeti re P. Predicting sudden death in the population: the Paris Prospective Study I. Circulation 1999; 99:1978. 40. Behr E, Wood DA, Wright M, et al. Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome. Lancet 2003; 362:1457. 41. Wei D, Tao L, Huang M. Genetic variations involved in sudden cardiac death and their associations and interactions. Heart Fail Rev 2016; 21:401. Topic 1019 Version 26.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 12/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate GRAPHICS Risk of SCD is related to clinical manifestations of CHD During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden cardiac death (SCD) in both men and women was related to the clinical manifestations of coronary heart disease (CHD). It was highest in those with a myocardial infarction, intermediate in those with angina and no prior infarction, and lowest in those without overt CHD. Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 52309 Version 2.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 13/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Incidence of sudden death in men and women increases with age During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden death increased with age in both men and women. However, at each age, the incidence of sudden death is higher in men than women. Data from Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 59028 Version 4.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 14/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial ischemia or infarction, GnRH agonist/antagonist therapy Hypomagnesemia Bilateral surgical orchiectomy Hypocalcemia Diuretic therapy via electrolyte disorders particularly hypokalemia and hypomagnesemia especially with prominent T-wave inversions Starvation Anorexia nervosa Herbs Liquid protein diets Cinchona (contains quinine), iboga (ibogaine), licorice extract in overuse via electrolyte disturbances Intracranial disease Hypothyroidism Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate AV block: Second or third degree insecticides Medications* High risk Adagrasib Cisaparide (restricted availability) Lenvatinib Selpercatinib Ajmaline Levoketoconazole Sertindole Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine (intracoronary) Vandetanib Dofetilide Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab ozogamacin Propafenone Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 15/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Certinib Escitalopram Levofloxacin (systemic) Risperidone Chloroquine Etelcalcetide Saquinavir Lofexidine Citalopram Fexinidazole Sevoflurane Meglumine antimoniate Clarithromycin Flecainide Sparfloxacin Clofazimine Floxuridine Sunitinib Midostaurin Clomipramine Fluconazole Tegafur Moxifloxacin Clozapine Fluorouracil (systemic) Terbutaline Nilotinib Crizotinib Thioridazine Olanzapine Flupentixol Dabrafenib Toremifene Ondansetrol (IV > oral) Gabobenate dimeglumine Dasatinib Vemurafenib Deslurane Voriconazole Osimertinib Gemifloxacin Domperidone Oxytocin Gilteritinib Doxepin Pazopanib Halofantrine Doxifluridine Pentamidine Haloperidol (oral) Pilsicainide Imipramine Pimozide Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole (systemic) Romidepsin Anagrelide Foscarnet Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- lumefantrine Glasdegib Mizolastine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine (rare reports) Nortriptyline Benperidol Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus Olodaterol (systemic) Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone Degarelix Lefamulin Pasireotide Triclabendazole https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 16/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- norethindrone Periciazine Tropisetron Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide overdose in Eliglustat Primaquine Vorinostat Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2) available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM 073161.pdf with additional data from CredibleMeds QT drugs list criteria may lead to some agents being classified differently by other sources. [1,2] . The use of other classification Not available in the United States. In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long QT syndrome. Withdrawn from market in most countries due to adverse cardiovascular effects. IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses administered orally as an antipsychotic. Other cyclic antidepressants may also prolong the QT interval; refer to UpToDate clinical topic on cyclic antidepressant pharmacology, side effects, and separate UpToDate topic on tricyclic antidepressant poisoning. The "low risk" category includes drugs with limited evidence of clinically significant QTc prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects or recommendations to avoid use or increase ECG monitoring when combined with other QTc prolonging drugs. https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 17/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use disorder, making buprenorphine a suitable alternative for patients with methadone-associated QTc prolongation. Refer to UpToDate clinical topic reviews. * The United States FDA labeling for the sublingual preparation of dexmedetomidine warns against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not been implicated in TdP. Over-the-counter; available without a prescription. Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical topic for potential adverse cardiovascular (CV) effects in patients with CV disease. Data from: 1. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. 2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/. Graphic 57431 Version 142.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 18/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Single lead electrocardiogram (ECG) showing polymorphic ventricular tachycardia (VT) This is an atypical, rapid, and bizarre form of ventricular tachycardia that is characterized by a continuously changing axis of polymorphic QRS morphologies. Graphic 53891 Version 5.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 19/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 20/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Contributor Disclosures Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 21/21 |
7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Athletes: Overview of sudden cardiac death risk and sport participation : Antonio Pelliccia, MD, Mark S Link, MD : Peter J Zimetbaum, MD, Scott Manaker, MD, PhD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 03, 2022. INTRODUCTION Sudden cardiac death (SCD) associated with athletic activity is a rare but devastating event. Victims can be young and apparently healthy, and while many of these deaths are unexplained, a substantial number harbor underlying previously undiagnosed cardiovascular disease. As a result, there is great interest in early identification of at-risk individuals for whom appropriate activity restrictions can be implemented to minimize the risk of SCD. The majority of SCD events in athletes are due to malignant arrhythmias, usually sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). In individuals with certain cardiac disorders (eg, hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, etc), athletics may increase the likelihood of VT/VF in two ways: In certain susceptible individuals (ie, with inherited arrhythmogenic cardiomyopathy), prolonged exercise training may induce adaptive changes in cardiac structure (eg, interstitial fibrosis, disruption of normal myocardial architecture, dilation of right and left ventricle) that may create pathologic arrhythmogenic substrate. The immediate physiologic demands of intense athletics (eg, mechanical strain, increased myocardial oxygen consumption, hemodynamic overload, catecholamine release, electrolyte imbalance) may trigger malignant arrhythmias in susceptible individuals with underlying cardiac abnormalities. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 1/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate The potential for SCD associated with athletic activity generates two questions: How should individuals be identified prior to initiating athletic activity? What restrictions (if any) should be placed upon individuals with known cardiovascular disease to minimize the SCD risk ? Answers to these questions are complicated and controversial and often based on limited clinical data and thus expert opinion. Answers vary based upon three factors: The age of the individual The nature of the activity (ie, competitive versus recreational athletics) The type of underlying heart disease This topic will review the major etiologies of SCD in athletes and recommendations for participation in sports in the presence of various cardiac abnormalities. The broader range of arrhythmias and conduction disturbances common in athletes, including treatment and return to participation following treatment, are discussed separately. (See "Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances" and "Athletes with arrhythmias: Clinical manifestations and diagnostic evaluation" and "Athletes with arrhythmias: Treatment and returning to athletic participation".) The recommended approaches to preparticipation screening of athletes are also presented separately. (See "Screening to prevent sudden cardiac death in competitive athletes".) DEFINITIONS Although definitions vary from study to study, it is important to define the populations of athletes as well as the level of competition in which the athletes are engaged. Young athletes Most commonly, "young athletes" refers to those in high school and college but applies in general to individuals under age 35 in whom SCD is usually due to a variety of congenital heart diseases. Masters athletes Adult, or "masters," athletes include individuals 35 years of age in whom SCD is most commonly associated with coronary heart disease. Such sports programs primarily include apparently normal and healthy individuals 35 years of age, although many participants are greater than 50 up to 80 years of age. Competitive/elite athletes Competitive/elite athletes engage in organized team or individual sports in which there is regular competition, placing a premium on achievement. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 2/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate This definition implies that individuals are regularly engaged in high-level training and competition and may not have the will or the judgment to limit their activity. This most frequently applies to high school, college, and professional sports. Recreational athletes Recreational athletes generally participate for health and/or enjoyment purposes and do not typically have the same pressures to excel. Activity levels may still be vigorous, and the distinction from competitive athletics may be elusive in the individual case. However, defining recreational athletics separately permits the development of guidelines for noncompetitive athletes with cardiovascular disease. COMPETITIVE VERSUS RECREATIONAL ATHLETICS The literature on SCD during exertion has largely focused on competitive athletics. However, some recreational athletics can be as vigorous as competitive sport, so recreational activity limitations are also important in individuals with one of the cardiovascular diseases commonly associated with SCD [1]. While the incidence of SCD appears higher in competitive versus recreational athletes, the total number of SCDs is greater in recreational athletes, due to the sheer numbers of persons engaging in recreational activity [2]. The balance between the risks and benefits of athletic activity depends upon several factors, including baseline fitness level, the nature and intensity of athletic activity, the presence and extent of cardiac disease, and the psychologic and physical benefit from sport. For patients with a congenital disorder, with either structural or arrhythmic substrate, the possible increased risk associated with participation in athletic activity generally requires some restriction on athletic activity. However, it must be acknowledged that these restrictions are usually based on expert opinion and not controlled studies. Historically, patients with known genetic disorders that may predispose to SCD (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, Marfan syndrome, long QT syndrome) have been advised to avoid recreational activities with the following characteristics: "Burst" exertion, involving rapid acceleration and deceleration, as is common in sprints, basketball, tennis, and soccer. Activities with stable energy expenditure, such as jogging, biking on level terrain, and lap swimming are preferred. Extreme environmental conditions (temperature, humidity, and altitude) that impact blood volume and electrolytes. Systematic and progressive training load focused on achieving higher levels of conditioning and excellence. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 3/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate However, paternalistic guidance has been changed to a contemporary approach for a shared decision-making process, which involves the athlete in the discussion of risk and benefit. Patients with unusual or high-risk clinical features may require greater restriction. These features include a history of syncope or presyncope (especially during exertion), prior arrhythmic episodes, or an implantable cardioverter-defibrillator (ICD). However, for most other individuals, including those with stable coronary heart disease, the overall benefits of regular exercise far outweigh the risks. A prudent and gradually progressive exercise program is appropriate in most cases [2]. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "The benefits and risks of aerobic exercise".) OUR APPROACH TO PARTICIPATION IN ATHLETICS (AND SPORT ACTIVITY IN GENERAL) Our approach to participation in sport activity, either recreationally or competitively, is in general agreement with that of the American Heart Association [2]: Physically active asymptomatic individuals without known cardiovascular disease These individuals may continue their usual moderate or vigorous exercise and progress gradually as tolerated. Those who develop signs or symptoms of cardiovascular disease should discontinue exercise and seek guidance from a medical professional before resuming exercise of any intensity. Physically active asymptomatic individuals with known cardiovascular disease Those who have been medically evaluated within 12 months may continue a moderate- intensity exercise program unless they develop signs or symptoms, which requires immediate cessation of exercise and medical reassessment. Physically inactive individuals without known cardiovascular disease These persons may begin light- to moderate-intensity exercise without medical guidance and, provided they remain asymptomatic, progress gradually in intensity as recommended by current American College of Sports Medicine (ACSM) guidelines. Physically inactive individuals with known cardiovascular disease or signs/symptoms that are suggestive cardiovascular disease Such patients should seek medical guidance before starting an exercise program, regardless of the intensity. INCIDENCE OF SUDDEN CARDIAC DEATH https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 4/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate It is widely acknowledged that SCD is one of the leading medical causes of death in athletes, although its exact incidence remains controversial. The best available evidence, together with a close examination of reporting methods for case identification and population definitions, suggests that an overall incidence of between 1:50,000 and 1:100,000 per year in young athletes is a reasonable estimate based on existing information from retrospective cohort studies and prospective observational and cross-sectional studies [3-5]. This rate is notably higher in older adults, closer to 1:7000 healthy adult athletes per year [2]. Incidence data are imprecise since most are derived from retrospective analyses, and incidence varies depending upon the intensity of exercise, the athletic population considered, the time period of observation, and whether the definition of athletic SCD encompasses SCD outside of sport/exercise [6-10]. Use of media reports or catastrophic insurance claims as the primary method for case identification has been demonstrated to underestimate (by approximately 50 percent) the risk of SCD in athletes [3]. Male athletes are consistently found to be at greater risk, and there appears to be a disproportionately higher risk among male African American athletes. Using data from the Rescue Registry cardiac arrest database, which contains data from all out- of-hospital sudden cardiac arrests (SCA, which includes deaths and resuscitated arrests) attended by paramedics in the province of Ontario, Canada, investigators retrospectively reviewed the incidence of SCA between 2009 and 2014 among an estimated 350,000 competitive athletes ages 12 to 45 years (in total 2.1 million athlete-years) [4]. Among the 3825 out-of- hospital SCA presumed to be cardiac in nature that occurred over the six years, 74 were identified as occurring during or within one hour of sports activities (16 during competitive sports, 58 during recreational sports). Although the overall rate of SCA in athletes was 0.76 per 100,000 athlete-years, 44 percent survived to hospital discharge, leading to an overall rate of SCD of 0.42 per 100,000 athlete-years. The incidence rate was somewhat higher among athletes ages 12 to 17 years (SCA rate 1.17 per 100,000 athlete-years; SCD rate 0.65 per 100,000 athlete- years) but still lower than prior SCD estimates of 1:50,000 athletes per year. The magnitude of the problem and the challenges inherent in screening are illustrated in reports of arrhythmic events associated with major endurance sporting events [8,11]. As an example, in a study examining SCD in 215,413 marathon runners participating in one of two marathons over a 19-year period, the following findings were noted [8]: SCD occurred in four individuals during or immediately following the marathon, an incidence of approximately 1 in 50,000. This is substantially lower than the annual risk of premature death in the general population. None of the four subjects had prior cardiac symptoms. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 5/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Two of the four had completed several previous marathons. Three of the four had coronary artery disease on autopsy, although none had a previous infarction. Although the incidence of SCD among marathon runners is low (one death per 215,000 hours), it is higher than for other types of exercise, such as noncompetitive jogging (one death per 396,000 hours), cross-country skiing (one death per 607,000 hours), or general, noncompetitive exercise (one death per 375,000 hours) [12-15]. ETIOLOGY OF SUDDEN DEATH Structural heart disease SCD in athletes often occurs in the presence of structural heart disease, although the underlying disorder is usually undetected until the presenting arrhythmic event. Structural heart disease can increase the risk for SCD by one or more of the following mechanisms: By far the most frequent mechanisms are ventricular tachyarrhythmias, which are commonly due to reentrant arrhythmias that develop in abnormal myocardium and/or areas of fibrotic replacement of myocardial tissue. Other rare but possible mechanisms include bradyarrhythmia or asystole due to extension of the pathologic process into the conduction system, causing complete heart block without a reliable escape focus. Syncope, in addition to arrhythmic causes, may result from outflow tract obstruction in hypertrophic cardiomyopathy and aortic stenosis, as well as from cyanosis during exercise in the setting of certain congenital lesions with right-to-left shunts. Dissection of the great vessels, as in patients with Marfan syndrome. Athletes <35 years of age Several large series have evaluated SCD in athletes less than 35 years of age [6,16-24] . In most cases, structural heart disease was present, although more contemporary data suggest more sudden arrhythmic death with a structural normal heart [2,22]. When present, the most common structural heart diseases include hypertrophic cardiomyopathy (HCM), anomalous origin of a coronary artery, arrhythmogenic right ventricular cardiomyopathy (ARVC, which commonly also affects the left ventricle), myocarditis, and coronary atherosclerosis, albeit with some variation among the different series. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 6/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Among 1435 young competitive athletes from a United States registry in whom cardiovascular disease was evident on postmortem examination following SCD, HCM (36 percent) and anomalous origin of a coronary artery accounted for more than half of the cases [17]. A separate study showed that among 51 middle school athletes, anomalous origins of a coronary artery accounted for one-third of cases of sudden cardiac arrest and death [24]. However, among 55 college and professional athletes, cardiomyopathies (hypertrophic, arrhythmogenic, dilated, noncompaction, or restrictive) accounted for nearly half of cases. In a cohort of over six million military recruits in the United States (mean age 19, range 17 to 35), among whom 126 nontraumatic sudden deaths occurred (including 108 [86 percent] related to exercise), anomalous origin of a coronary artery (33 percent), myocarditis (20 percent), coronary atherosclerosis (16 percent), and HCM (13 percent) accounted for over three-quarters of the structural abnormalities [25]. In a series from the United Kingdom Regional Registry of 357 consecutive athletes with SCD between 1994 and 2014 (mean age 29 years), sudden arrhythmic death syndrome (SADS), likely including undiagnosed primary electrical disease, was the most prevalent cause of death (42 percent) [22]. Myocardial disease was detected in 40 percent of cases, including idiopathic left ventricular (LV) hypertrophy and/or fibrosis (16 percent), ARVC (13 percent), and HCM (6 percent). A different distribution was noted in a series of 49 athletes under age 35 with SCD from northern Italy [16]. In this series, ARVC (22 percent) was the most common abnormality, followed by coronary atherosclerosis (18 percent) and anomalous origin of a coronary artery (12 percent). Athletes 35 years of age In contrast to these series in young subjects, among those 35 years of age (so-called masters athletes), coronary artery disease is the predominant cause of SCD during exercise [23,26]. (See 'Coronary artery disease' below.) Primary electrical disease SCD during athletics also occurs in the absence of structural heart disease, a situation termed primary electrical disease. Series of patients with SCD have shown an increasing number with normal autopsies, although there is concern that cardiac abnormalities may have been missed. A number of inherited arrhythmic syndromes predispose individuals to SCD, and the heart is usually structurally normal in these patients. Examples include: Long QT syndrome (see "Congenital long QT syndrome: Epidemiology and clinical manifestations") https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 7/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Brugada syndrome (see "Brugada syndrome: Clinical presentation, diagnosis, and evaluation") Catecholaminergic polymorphic ventricular tachycardia (see "Catecholaminergic polymorphic ventricular tachycardia") Short QT syndrome (see "Short QT syndrome") Early repolarization syndrome (see 'Early repolarization syndrome' below) In addition, in individuals with structurally normal hearts, arrhythmic events may be precipitated by trauma or occur as sporadic/idiopathic phenomena, such as commotio cordis, in which SCD results from being struck in the precordium with a projectile object such as a baseball, hockey puck, or fist. (See "Commotio cordis".) Finally, several case reports describe SCD in young athletes who had no previously known heart disease but were taking androgens for performance enhancement; cardiac hypertrophy or myocarditis were found at autopsy [27,28]. It is not possible to establish causality in these sporadic cases. (See "Use of androgens and other hormones by athletes", section on 'Side effects and complications'.) STRUCTURAL ABNORMALITIES ASSOCIATED WITH SCD Hypertrophic cardiomyopathy Our experts agree that low- to moderate-intensity exercise can and should be regularly performed by most individuals with hypertrophic cardiomyopathy (HCM). Historically, persons with a probable or unequivocal clinical diagnosis of HCM have been advised not to participate in most competitive sports with the possible exception of those that are low intensity ( figure 1) [29,30]. A novel and less restrictive approach has been suggested by the 2020 European Society of Cardiology (ESC) sport cardiology guidelines [31]. The guidelines include the option for selective participation in recreational and competitive athletic activity in patients with HCM who have a low-risk profile (ie, without any risk factors that would place them at high risk for SCD), provided that they undergo periodic evaluation. The 2020 ESC guidelines confirm that patients with high- risk markers should not participate in competitive athletics. The 2020 American Heart Association/American College of Cardiology (AHA/ACC) HCM guidelines allow for a shared decision-making approach for patients with HCM, in which the clinician and the athlete share discussion of the potential risks and benefits of exercise [32]. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 8/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Activity advice in patients with HCM has been based largely on expert opinion given limited data. Some moderate-intensity and many low-intensity recreational activities were generally considered to be safe when performed in moderation, including biking, doubles tennis, swimming laps, golf, and skating, and should be considered on a case-by-case basis [31,33]. Lifting weights with weight-training machines may be safe, but intense static (isometric) activity were discouraged because of the possible induction of a Valsalva maneuver and exacerbation of an LV outflow tract gradient. HCM is a relatively common disease, occurring in approximately 1 out of 500 individuals in the general population. In most athletes with SCD due to HCM, the diagnosis of HCM was not previously established. Patients with HCM who are at the highest risk of SCD are those with prior sudden cardiac arrest. In addition, those with unexplained syncope, massive hypertrophy (maximum LV wall thickness >30 mm), family history of SCD due to HCM, significant LV outflow tract obstruction (gradient >50 mmHg), nonsustained ventricular tachyarrhythmias observed on electrocardiogram (ECG) monitoring, including exercise-related VT, apical aneurysms, and extensive scarring on cardiovascular magnetic resonance imaging are at increased risk [31]. Moreover, age is a relevant determinant, with adolescent and young athletes being at higher risk than adult patients. Among patients with HCM, stratification as advised by the AHA and the ESC can identify patients at high and relatively low risk for SCD; however, zero risk does not exist and even patients defined as low risk have a small but nontrivial risk of SCD [34-36]. (See 'Etiology of sudden death' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) Some data suggest a relatively low risk of ventricular arrhythmias and SCD in athletes with HCM regardless of the continuation or discontinuation of training and competition. In a cohort of 88 Italian athletes with HCM who were advised to discontinue training and competition (77 who were low risk by the ESC algorithm, 67 who were low risk by the AHA algorithm), 61 patients stopped exercising, but 27 continued to exercise against clinician advice [37]. Over an average follow-up of seven years, 1.3 percent of patients per year developed symptoms (syncope, palpitations), and only one cardiac arrest occurred (in a detrained patient and not during exercise), with no significant difference in the event rates between the sedentary and exercising groups. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) The natural history is not well defined in individuals with a genetic diagnosis of HCM in the absence of symptoms and phenotypic expression (ie, without LV hypertrophy) of the disease (so- called genotype positive, phenotype negative carriers). At present, no compelling data are available that would preclude these patients from competitive sports, particularly in the absence of a family history of sudden death [38]. Professional societies, and our experts, agree that these https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 9/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate individuals should have periodical clinical and imaging follow-up (annually during adolescence and eventually every two years in adulthood) [1,31,39]. Congenital coronary artery abnormalities Patients with any uncorrected anomalous coronary artery origin, regardless of the presence or absence of symptoms, should generally be advised against participation in competitive sports [40]. These patients may be considered for appropriate management, which in selected cases includes surgical correction with coronary reimplantation or bypass grafting. Participation in sports at least three months after successful operation may be considered on an individual basis for an athlete without prior infarction and in the absence of ischemia, ventricular tachyarrhythmia, or LV dysfunction during maximal exercise testing [40]. Athletes with previously infarcted myocardium need to follow appropriate guidelines for clearance and observation, which primarily depend upon the degree of LV dysfunction and exercise-associated arrhythmias. In such patients, the approach is similar to that in patients with atherosclerotic coronary artery disease [41]. (See 'Coronary artery disease' below and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "Cardiac rehabilitation programs".) Anomalous origin of a coronary artery is found in 12 to 33 percent of young athletes with SCD at autopsy [16,25,42]. The most common anomalies associated with SCD are the origin of the left main coronary artery from the right sinus of Valsalva and the origin of the right coronary artery from the left coronary sinus [43-46]. (See 'Etiology of sudden death' above and "Congenital and pediatric coronary artery abnormalities", section on 'Variations of coronary artery origin from the aorta'.) High-risk coronary anomalies are those in which the anomalous coronary artery originates with a slit-like ostium, has proximal intramural course, makes an acute bend, and courses between the pulmonary artery and aorta [43,46]. The presumed mechanism of SCD involves repeated bouts of silent ischemia secondary to an exaggeration of a sharp angle in the aberrant origin that occurs with exercise, with decreased blood flow in the intramural course and/or in the interarterial course between an expanded aorta and pulmonary arterial trunk. Chronic ischemia is considered responsible for myocardial fibrosis representing the ultimate substrate for induction of tachyarrhythmias during exercise. Patients with congenital coronary anomalies may present with syncope or presyncope, especially with exercise and with angina in a limited proportion of cases. Unfortunately, SCD is often the first clinical symptom. This was illustrated in a report of 18 patients with an anomalous coronary artery origin, only six of whom had a preceding history of angina and/or syncope [45]. In another series of autopsy results on 27 patients with an anomalous coronary artery, 55 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 10/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate percent had no clinical manifestations during life or with testing [47]. In the remaining patients, premonitory symptoms occurred only shortly before SCD. Physical examination and diagnostic studies are usually unrevealing in the absence of myocardial infarction (MI) or symptoms of ongoing ischemia. When anomalous origin of a coronary artery is suspected (usually by echocardiography), noninvasive computed tomography coronary angiography (CTCA) is advised to define anomalous coronary anatomy. Cardiovascular magnetic resonance imaging (CMR) is a noninvasive alternative to CTCA and can include gadolinium contrast imaging for identification of intramyocardial late gadolinium enhancement (LGE). Coronary angiography had been the historical gold standard for the evaluation of the origin and course of the coronary arteries and is still recommended when other studies are not diagnostic [40]. (See "Congenital and pediatric coronary artery abnormalities", section on 'Variations of coronary artery origin from the aorta' and "Cardiac imaging with computed tomography and magnetic resonance in the adult".) Arrhythmogenic (right and/or left) ventricular cardiomyopathy Because of the evidence linking athletic participation with worsened outcomes, patients with arrhythmogenic right/left ventricular cardiomyopathy (ARVC) should not participate in competitive sports ( figure 1) [29- 31]. Similarly, patients with arrhythmogenic cardiomyopathy should not participate in high- intensity noncompetitive sports, including basketball, ice hockey, sprinting, and singles tennis [29-31]. In addition, the risks associated with impaired consciousness (ie, syncope or presyncope) should be considered with regard to activities with the potential for trauma (eg, weight training with free weights, horseback riding) or certain water activities (eg, scuba diving or snorkeling). Patients with ARVC are also advised to avoid most moderate-intensity amateur activities, including biking and doubles tennis. However, they may participate in low-intensity recreational activities (class IA), including golf, skating, and light weightlifting (with weight- training machines). (See "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis".) The condition was initially recognized as a predominantly right ventricular (RV) disease involving fibro-fatty or fibrous infiltration of predominantly the free wall, known as arrhythmogenic RV cardiomyopathy (ARVC). However, it is now well established that in the majority of cases both ventricles are affected, and in some it may only affect the LV. The diagnosis of ARVC is based on task force criteria that encompass electrophysiological, anatomical, functional, and clinical features of the disease. Tachyarrhythmias and SCD are as frequent in patients with ARVC compared with those with a dilated cardiomyopathy or a previous infarction [16,48]. In a cohort of patients with ARVC followed for over 10 years, the mortality rate was 20 percent [49]. ARVC is a significantly more https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 11/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate common cause of SCD in case series from Italy than in those from the United States [16,42]. (See 'Etiology of sudden death' above.) The clinical presentation of patients with ARVC, particularly the athlete, includes exercise- induced palpitations, presyncope, and/or syncope, consistent with the catecholamine-sensitive nature of many of the associated tachyarrhythmias, as well as the wall stretch observed in the right (and left) heart in response to the increased venous return occurring with exercise [50]. The diagnostic evaluation of ARVC is discussed separately. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis".) Among a cohort of 108 patients with ARVC that included 41 competitive athletes, 48 recreational athletes, and 19 inactive patients, the risk of VT or SCD was significantly higher among competitive athletes compared with either recreational athletes (hazard ratio [HR] 2.0, 95% CI 1.2-3.3) or inactive patients (HR 2.1, 95% CI 1.1-3.9) [51]. In addition, there are increasing data that repetitive extreme conditioning/exertion enhances disease progression [51,52]. Any activity, competitive or not, that causes symptoms of palpitations, presyncope, or syncope should be avoided. Marfan syndrome Athletes with Marfan syndrome can selectively participate in low and moderate static/low dynamic competitive sports (classes IA and IIA) ( figure 1) if they do not have one or more of the following: aortic root dilatation, moderate-to-severe mitral regurgitation, or family history of dissection or sudden death in a Marfan relative [53]. These athletes should have an echocardiographic measurement of aortic root dimension repeated every 6 to 12 months (depending upon the size of the aorta, rate of growth, etc) for close surveillance of aortic enlargement. (See "Management of Marfan syndrome and related disorders", section on 'Monitoring MFS'.) Athletes with Marfan syndrome, familial aortic aneurysm or dissection, or congenital bicuspid aortic valve with any degree of ascending aortic enlargement should not participate in sports that involve the potential for bodily collision. On the other hand, some moderate-intensity and many low-intensity recreational activities are generally considered to be safe, including stationary biking, hiking, doubles tennis, swimming laps, golf, and skating. However, intense static (isometric) exertion is associated with increased wall stress; therefore, activities such as weight training with either free weights or weight machines should be avoided. Marfan syndrome is an autosomal dominant condition that is one of the most common inherited disorders of connective tissue. The full phenotype is characterized by arachnodactyly, tall stature, pectus excavatum, kyphoscoliosis, and lenticular dislocation. Malignant arrhythmias are not common in Marfan syndrome, but the cardiovascular manifestations include aortic https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 12/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate dissection, which can lead to sudden death. The genetics, epidemiology, diagnosis, and management of Marfan syndrome are discussed in detail separately. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Management of Marfan syndrome and related disorders".) Myocarditis Persons with probable or definite evidence of myocarditis should be withdrawn from all competitive and recreational sports and undergo a prudent convalescent period of between three and six months following the onset of clinical manifestations [29,31]. Athletes may return to training and competition after this period of time if LV systolic function has returned to normal (based on echocardiography and/or CMR), clinically relevant arrhythmias such as frequent and/or complex repetitive forms of ventricular or supraventricular ectopic activity are absent on ambulatory Holter monitoring and graded exercise testing, and serum markers of inflammation and heart failure have normalized. The impact that persistent LGE on CMR represents following the apparent clinical resolution of myocarditis is still uncertain [29]. As patients with previous myocarditis are at increased risk of recurrence and/or silent progressive myocardial dysfunction, periodic clinical reevaluation (at least annually) is recommended, including clinical assessment and imaging testing [31]. Patients should be advised to seek medical attention for dyspnea on exertion, syncope, or arrhythmic events. Myocarditis has been reported in 6 to 7 percent of cases of SCD in competitive athletes and 20 percent of military recruits [16,25,42]. (See 'Etiology of sudden death' above.) The clinical presentation of myocarditis is quite broad, from subclinical cases with only mild reduction of physical performance or palpitation to more severe presentations with clinical findings of heart failure in an otherwise healthy young person. The ECG usually shows diffuse repolarization abnormalities, and global or regional wall motion abnormalities are present on cardiac imaging. Active myocarditis is associated with atrial and ventricular tachyarrhythmias, bradyarrhythmias, and SCD. Healed myocarditis leading to a dilated cardiomyopathy or persistent segmental abnormalities increases the risk of SCD, and this risk may be proportional to the degree of cardiac dysfunction and severity of clinical presentation. (See "Clinical manifestations and diagnosis of myocarditis in adults".) Myocarditis and other causes of myocardial injury in individuals with coronavirus disease 2019 (COVID-19), the risk of SARS-CoV-2 vaccine-associated myocarditis, and return to play after COVID-19 are discussed separately. (See "COVID-19: Cardiac manifestations in adults" and "COVID-19: Evaluation and management of cardiac disease in adults" and "COVID-19: Arrhythmias and conduction system disease" and "COVID-19: Vaccines", section on 'Myocarditis' and "COVID-19: Return to sport or strenuous activity following infection".) https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 13/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Congenital heart diseases The estimated prevalence of congenital abnormalities in the athlete is 0.2 percent. Recommendations for athletic activity in patients with congenital heart disease, which are based primarily on expert opinion, depend upon the nature of the abnormality [40]. The approach for exercise prescription in adolescents and adults with congenital heart disease should be individualized [54]. However, there is generally a prohibition of competitive sports in those who have: Significant pulmonary hypertension Cyanosis with an arterial saturation <80 percent Symptomatic arrhythmias Symptomatic ventricular dysfunction INHERITED ARRHYTHMIA SYNDROMES There is a partial divergence of opinions on competitive athletics for individuals with inherited arrhythmias, and specifically for long QT syndrome (LQTS) [55-58]. The 2015 American Heart Association/American College of Cardiology (AHA/ACC) Scientific Statement on Eligibility and Disqualification Recommendations for Competitive Athletes discusses participation in competitive events and training sessions in patients with channelopathies (namely, LQTS) as allowable if the patient is asymptomatic and an emergency action plan with an automated external defibrillator (AED) is immediately available on site. However, a different approach is dictated by the European guidelines, which advise precautionary restriction from competitive sports in these instances. Congenital long QT syndrome Guidelines for physical activity and sports participation in congenital LQTS are presented separately. (See "Congenital long QT syndrome: Treatment", section on 'Physical activity and LQTS'.) Brugada syndrome Professional society guidelines allow sports participation in patients with Brugada syndrome who are defined as low risk based on absence of symptoms and events after the clinician and patient participate in a fully informed discussion and shared decision-making process and take all appropriate precautionary measures [55]. In contrast to other inherited arrhythmia syndromes, most moderate- and low-intensity recreational, noncompetitive sports are considered safe for patients with Brugada syndrome or Brugada pattern ECG, except for those that would incur significant risk of trauma with impaired |
athletes, and 19 inactive patients, the risk of VT or SCD was significantly higher among competitive athletes compared with either recreational athletes (hazard ratio [HR] 2.0, 95% CI 1.2-3.3) or inactive patients (HR 2.1, 95% CI 1.1-3.9) [51]. In addition, there are increasing data that repetitive extreme conditioning/exertion enhances disease progression [51,52]. Any activity, competitive or not, that causes symptoms of palpitations, presyncope, or syncope should be avoided. Marfan syndrome Athletes with Marfan syndrome can selectively participate in low and moderate static/low dynamic competitive sports (classes IA and IIA) ( figure 1) if they do not have one or more of the following: aortic root dilatation, moderate-to-severe mitral regurgitation, or family history of dissection or sudden death in a Marfan relative [53]. These athletes should have an echocardiographic measurement of aortic root dimension repeated every 6 to 12 months (depending upon the size of the aorta, rate of growth, etc) for close surveillance of aortic enlargement. (See "Management of Marfan syndrome and related disorders", section on 'Monitoring MFS'.) Athletes with Marfan syndrome, familial aortic aneurysm or dissection, or congenital bicuspid aortic valve with any degree of ascending aortic enlargement should not participate in sports that involve the potential for bodily collision. On the other hand, some moderate-intensity and many low-intensity recreational activities are generally considered to be safe, including stationary biking, hiking, doubles tennis, swimming laps, golf, and skating. However, intense static (isometric) exertion is associated with increased wall stress; therefore, activities such as weight training with either free weights or weight machines should be avoided. Marfan syndrome is an autosomal dominant condition that is one of the most common inherited disorders of connective tissue. The full phenotype is characterized by arachnodactyly, tall stature, pectus excavatum, kyphoscoliosis, and lenticular dislocation. Malignant arrhythmias are not common in Marfan syndrome, but the cardiovascular manifestations include aortic https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 12/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate dissection, which can lead to sudden death. The genetics, epidemiology, diagnosis, and management of Marfan syndrome are discussed in detail separately. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Management of Marfan syndrome and related disorders".) Myocarditis Persons with probable or definite evidence of myocarditis should be withdrawn from all competitive and recreational sports and undergo a prudent convalescent period of between three and six months following the onset of clinical manifestations [29,31]. Athletes may return to training and competition after this period of time if LV systolic function has returned to normal (based on echocardiography and/or CMR), clinically relevant arrhythmias such as frequent and/or complex repetitive forms of ventricular or supraventricular ectopic activity are absent on ambulatory Holter monitoring and graded exercise testing, and serum markers of inflammation and heart failure have normalized. The impact that persistent LGE on CMR represents following the apparent clinical resolution of myocarditis is still uncertain [29]. As patients with previous myocarditis are at increased risk of recurrence and/or silent progressive myocardial dysfunction, periodic clinical reevaluation (at least annually) is recommended, including clinical assessment and imaging testing [31]. Patients should be advised to seek medical attention for dyspnea on exertion, syncope, or arrhythmic events. Myocarditis has been reported in 6 to 7 percent of cases of SCD in competitive athletes and 20 percent of military recruits [16,25,42]. (See 'Etiology of sudden death' above.) The clinical presentation of myocarditis is quite broad, from subclinical cases with only mild reduction of physical performance or palpitation to more severe presentations with clinical findings of heart failure in an otherwise healthy young person. The ECG usually shows diffuse repolarization abnormalities, and global or regional wall motion abnormalities are present on cardiac imaging. Active myocarditis is associated with atrial and ventricular tachyarrhythmias, bradyarrhythmias, and SCD. Healed myocarditis leading to a dilated cardiomyopathy or persistent segmental abnormalities increases the risk of SCD, and this risk may be proportional to the degree of cardiac dysfunction and severity of clinical presentation. (See "Clinical manifestations and diagnosis of myocarditis in adults".) Myocarditis and other causes of myocardial injury in individuals with coronavirus disease 2019 (COVID-19), the risk of SARS-CoV-2 vaccine-associated myocarditis, and return to play after COVID-19 are discussed separately. (See "COVID-19: Cardiac manifestations in adults" and "COVID-19: Evaluation and management of cardiac disease in adults" and "COVID-19: Arrhythmias and conduction system disease" and "COVID-19: Vaccines", section on 'Myocarditis' and "COVID-19: Return to sport or strenuous activity following infection".) https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 13/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Congenital heart diseases The estimated prevalence of congenital abnormalities in the athlete is 0.2 percent. Recommendations for athletic activity in patients with congenital heart disease, which are based primarily on expert opinion, depend upon the nature of the abnormality [40]. The approach for exercise prescription in adolescents and adults with congenital heart disease should be individualized [54]. However, there is generally a prohibition of competitive sports in those who have: Significant pulmonary hypertension Cyanosis with an arterial saturation <80 percent Symptomatic arrhythmias Symptomatic ventricular dysfunction INHERITED ARRHYTHMIA SYNDROMES There is a partial divergence of opinions on competitive athletics for individuals with inherited arrhythmias, and specifically for long QT syndrome (LQTS) [55-58]. The 2015 American Heart Association/American College of Cardiology (AHA/ACC) Scientific Statement on Eligibility and Disqualification Recommendations for Competitive Athletes discusses participation in competitive events and training sessions in patients with channelopathies (namely, LQTS) as allowable if the patient is asymptomatic and an emergency action plan with an automated external defibrillator (AED) is immediately available on site. However, a different approach is dictated by the European guidelines, which advise precautionary restriction from competitive sports in these instances. Congenital long QT syndrome Guidelines for physical activity and sports participation in congenital LQTS are presented separately. (See "Congenital long QT syndrome: Treatment", section on 'Physical activity and LQTS'.) Brugada syndrome Professional society guidelines allow sports participation in patients with Brugada syndrome who are defined as low risk based on absence of symptoms and events after the clinician and patient participate in a fully informed discussion and shared decision-making process and take all appropriate precautionary measures [55]. In contrast to other inherited arrhythmia syndromes, most moderate- and low-intensity recreational, noncompetitive sports are considered safe for patients with Brugada syndrome or Brugada pattern ECG, except for those that would incur significant risk of trauma with impaired consciousness should syncope or presyncope result (eg, weightlifting with free weights, horseback riding, motor races, downhill skiing, scuba diving, or snorkeling). Moreover, patients https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 14/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate should avoid triggering drugs [59], electrolyte imbalance, and increases in core temperature >39 C (eg, by avoiding saunas, steam rooms, and sports in warm/humid conditions, including prolonged endurance events such as marathons in unfavorable atmospheric conditions). Patients with Brugada syndrome have historically been advised to avoid most high-intensity competitive sports, including cycling, rowing, basketball, ice hockey, sprinting, and singles tennis. However, there is no evidence that exercise in patients with Brugada syndrome increases the risk of cardiac arrest. Brugada syndrome is characterized by the ECG findings of right bundle branch block (RBBB) pattern and ST-segment elevation in leads V1 to V3 ( waveform 1), and an increased risk of sudden death. Arrhythmic events generally occur between the ages of 22 and 65 and are more common at night than in the day and during sleep than while awake [60,61]. SCD in Brugada patients is usually not related to exercise [62]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Catecholaminergic polymorphic ventricular tachycardia We agree with professional society recommendations that patients with catecholaminergic polymorphic VT (CPVT) who were previously symptomatic, and asymptomatic patients with exercise-induced ventricular premature beats in a pattern of bigeminy, couplets, or nonsustained VT, should be restricted from competitive sports with the exception of minimal contact, class IA activities ( figure 1) [55]. Among individuals with a genetic diagnosis of CPVT, but who remain asymptomatic with none of the clinical features of inducible VT (so-called genotype positive, phenotype negative patients), the natural history is not well defined. As such, no agreement exists in the guidelines, and specifically, a prudent precautionary restriction from competitive sports is advised by European recommendations with more uncertainty in the AHA/ACC Guidelines. CPVT occurs in the absence of structural heart disease or known associated syndromes. The disorder typically begins in childhood or adolescence, and affected patients may have a family history of juvenile sudden death or stress-induced syncope [63]. The disorder has been linked to mutations in the cardiac ryanodine receptor and calsequestrin 2 genes. (See "Catecholaminergic polymorphic ventricular tachycardia".) Affected patients present with life-threatening VT or ventricular fibrillation (VF) occurring during emotional or physical stress, with syncope often being the first manifestation of the disease [63]. Arrhythmic events during swimming, previously considered to be specific for LQTS type 1, have also been described with CPVT [64]. The VT may have a polymorphic appearance or may be a bidirectional VT that resembles the arrhythmia associated with digitalis toxicity. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 15/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Short QT syndrome Short QT syndrome is an extremely rare inherited channelopathy associated with marked shortened QT intervals and SCD in individuals with a structurally normal heart. Based on expert opinion, short QT syndrome is managed similarly to other inherited arrhythmia syndromes (ie, LQTS), although there is a paucity of data regarding the risks of exercise in this condition. (See 'Inherited arrhythmia syndromes' above.) When an abnormally short QTc interval is identified in an athlete (QTc <320 milliseconds), causes of transient QT shortening (such as hypercalcemia, hyperkalemia, hyperthermia, acidosis, and some drugs [eg, digitalis, anabolic steroids]) must be ruled out. In the absence of acquired causes of short QT interval, the athlete may be referred for familial ECG clinical screening and molecular genetic evaluation. However, the limited specificity of a short QTc must be acknowledged; the vast majority of patients with a short QTc will not have the syndrome. The clinical features and management of short QT syndrome are discussed in detail separately. (See "Short QT syndrome".) Early repolarization syndrome The early repolarization syndrome is the combination of early repolarization pattern and arrhythmic symptoms and/or SCD, not just early repolarization pattern. At present, no data are available regarding the impact of regular exercise programs and sports participation on the natural outcome of the early repolarization syndrome, and a prudent precautionary attitude is advised. The term early repolarization has long been used to characterize a QRS-T variant with J-point elevation on the ECG. Two terms, distinguished by the presence or absence of symptomatic arrhythmias, have been used to describe patients with this ECG finding: the early repolarization pattern describes the patient with appropriate ECG findings in the absence of symptomatic arrhythmias, while the early repolarization syndrome applies to the patient with both appropriate ECG findings and symptomatic ventricular arrhythmias, typically VF. Recommendations regarding participation in athletics apply only to patients with the early repolarization syndrome. (See "Early repolarization".) Early repolarization pattern, meaning the presence of ST-segment elevation in precordial leads, usually preceded by J-point elevation, is a common finding in athletes and is associated with other typical features of the athlete's ECG, such as bradycardia, increased R/S wave voltages, and incomplete RBBB. Typically, early repolarization in athletes disappears during exercise. This ECG pattern is not associated with symptoms or family history of SCD and does not require additional testing for diagnosis. There are no sports restrictions for these individuals. CORONARY ARTERY DISEASE https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 16/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Our approach to participation Patients with clinically proven coronary artery disease (CAD) who are considered to be at low-risk for cardiac events after individual evaluation may be allowed to participate in competitive sports. As a measure of caution, in consideration of the high hemodynamic load and possible electrolyte imbalance, some restrictions may apply on an individual basis for sports with the highest cardiovascular demand, such as extreme power and endurance disciplines. Patients with clinically proven CAD who are considered to be at high risk should be temporarily restricted from competitive sports and receive appropriate management. In situations where full medical therapy has been implemented and persistent ischemia remains, revascularization may be considered on a case-by-case basis. After revascularization, the individual patient should be encouraged to start exercise programs without delay, as per the cardiac rehabilitation guidelines. In the early phase, exercise should be prescribed in a graduated fashion, starting with low-intensity exercise of limited duration and progressively increased. When the clinical situation is stable and the patient is asymptomatic, a more intense training and participation in competition should be considered after a graduated and progressive increase in rehabilitation training load. We recommend a minimum of three months after percutaneous coronary intervention before participation in competitive sports can be resumed. Participation in competitive sports may be selectively advised as per patients with CAD and well-treated risk factors if exercise is not associated with elements of high risk, such as critical coronary artery stenosis (>70 percent), LV dysfunction, inducible ischemia by exercise, or frequent, repetitive ventricular arrhythmias induced by exercise. Contact sports should be avoided while the patient is under dual antiplatelet therapy because of the risk of bleeding, but may be considered afterwards. (See "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary heart disease".) In patients 35 years of age, the most frequent cause of exercise-related SCD is CAD. Ventricular arrhythmias can originate from myocardial scar (from prior MIs), or from acute ischemia. In addition, ischemia during exertion can result either from fixed, chronic coronary stenosis that precludes increased myocardial oxygen delivery during exercise (ie, demand ischemia), or from an acute coronary syndrome. Autopsy examination of adults with exercise-related SCD usually reveals advanced CAD and/or an acute coronary lesion [26]. (See "Pathophysiology and etiology of sudden cardiac arrest" and "Mechanisms of acute coronary syndromes related to atherosclerosis".) Risk assessment Prior to initiating systematic training or competition, athletes with previously documented CAD should have an assessment of LV function. Universal exercise testing is somewhat controversial, although many clinicians state it should be performed, both https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 17/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate to assess exercise capacity to determine the possible induction of signs of ischemia and to ensure the absence of exercise-induced arrhythmias. Whenever possible, such testing should be performed while the patient is taking prescribed medications and should approximate the cardiovascular and metabolic demands of the planned athletic activity. The approach to screening is discussed in detail separately. (See "Screening to prevent sudden cardiac death in competitive athletes".) There are no data that directly relate the presence and severity of CAD to the risk of participating in competitive athletics. However, it is likely that the risk of a cardiac event during exercise increases with the presence of increasingly severe CAD, type of lesion (soft plaques are at higher risk of rupture), LV dysfunction, and ventricular arrhythmias, as well as with the intensity of the competitive sport and the individual's effort. As a result, risk assessment should involve a full evaluation of cardiac status in individual patients. Athletes with CAD are considered to be at low risk if all of the following are true [65]: LV ejection fraction 50 percent. Normal exercise tolerance for age. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease", section on 'Relation to fitness'.) No inducible ischemia with exercise testing. (See "Prognostic features of stress testing in patients with known or suspected coronary disease".) No sustained or nonsustained VT during exercise testing. No hemodynamically significant coronary artery stenosis (ie, no stenosis 70 percent in a major coronary artery and no stenosis 50 percent in the left main coronary artery) if angiography is performed. Patients who have had successful revascularization of prior stenosis are also considered to be at low risk. SUMMARY AND RECOMMENDATIONS Sudden cardiac death (SCD) associated with athletic activity is a rare but devastating event. Victims can be young and apparently healthy, and while many of these deaths are unexplained, a substantial number harbor underlying undiagnosed cardiovascular disease. The majority of SCD events in athletes are due to malignant arrhythmias, usually ventricular tachycardia degenerating into ventricular fibrillation (VF) or primary VF itself. (See 'Introduction' above.) https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 18/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate The balance between the risks and benefits of athletic activity depends upon several factors, including baseline fitness level, the nature and intensity of athletic activity, the presence and extent of cardiac disease, and the psychologic and physical benefit from sport. Although there are exceptions, for most individuals, the overall benefits of regular exercise far outweigh the risks. (See 'Competitive versus recreational athletics' above.) The incidence of SCD among young athletes is actually quite low, estimated to be between 1:50,000 and 1:100,000 young athletes per year. This rate is notably higher in older adults, closer to 1:7000 healthy adult athletes per year. (See 'Incidence of sudden cardiac death' above.) The potential etiologies of SCD include certain structural heart diseases, inherited arrhythmia syndromes, and coronary heart disease; the exact distribution of etiologies varies according to age and geography. (See 'Etiology of sudden death' above and "Pathophysiology and etiology of sudden cardiac arrest".) Some level of activity restriction ( figure 1) is recommended for nearly all individuals with underlying heart disease. The precise restrictions vary depending on the underlying disease process and other comorbidities. (See 'Structural abnormalities associated with SCD' above and 'Inherited arrhythmia syndromes' above and 'Coronary artery disease' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Maron BJ, Chaitman BR, Ackerman MJ, et al. Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases. Circulation 2004; 109:2807. 2. Franklin BA, Thompson PD, Al-Zaiti SS, et al. Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training: Placing the Risks Into Perspective-An Update: A Scientific Statement From the American Heart Association. Circulation 2020; 141:e705. 3. Harmon KG, Drezner JA, Wilson MG, Sharma S. Incidence of sudden cardiac death in athletes: a state-of-the-art review. Br J Sports Med 2014; 48:1185. 4. Landry CH, Allan KS, Connelly KA, et al. Sudden Cardiac Arrest during Participation in Competitive Sports. N Engl J Med 2017; 377:1943. 5. Emery MS, Kovacs RJ. Sudden Cardiac Death in Athletes. JACC Heart Fail 2018; 6:30. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 19/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 6. Maron BJ, Shirani J, Poliac LC, et al. Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. JAMA 1996; 276:199. 7. Van Camp SP, Bloor CM, Mueller FO, et al. Nontraumatic sports death in high school and college athletes. Med Sci Sports Exerc 1995; 27:641. 8. Maron BJ, Poliac LC, Roberts WO. Risk for sudden cardiac death associated with marathon running. J Am Coll Cardiol 1996; 28:428. 9. Phillips M, Robinowitz M, Higgins JR, et al. Sudden cardiac death in Air Force recruits. A 20- year review. JAMA 1986; 256:2696. 10. Mitchell JH, Haskell W, Snell P, Van Camp SP. Task Force 8: classification of sports. J Am Coll Cardiol 2005; 45:1364. 11. Belonje A, Nangrahary M, de Swart H, Umans V. Major adverse cardiac events during endurance sports. Am J Cardiol 2007; 99:849. 12. Hillis WS, McIntyre PD, Maclean J, et al. ABC of sports medicine. Sudden death in sport. BMJ 1994; 309:657. 13. Thompson PD, Funk EJ, Carleton RA, Sturner WQ. Incidence of death during jogging in Rhode Island from 1975 through 1980. JAMA 1982; 247:2535. 14. Vuori I. The cardiovascular risks of physical activity. Acta Med Scand Suppl 1986; 711:205. 15. Gibbons LW, Cooper KH, Meyer BM, Ellison RC. The acute cardiac risk of strenuous exercise. JAMA 1980; 244:1799. 16. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998; 339:364. 17. Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007; 115:1643. 18. Roberts WO, Stovitz SD. Incidence of sudden cardiac death in Minnesota high school athletes 1993-2012 screened with a standardized pre-participation evaluation. J Am Coll Cardiol 2013; 62:1298. 19. Harmon KG, Asif IM, Klossner D, Drezner JA. Incidence of sudden cardiac death in National Collegiate Athletic Association athletes. Circulation 2011; 123:1594. 20. Eckart RE, Shry EA, Burke AP, et al. Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance. J Am Coll Cardiol 2011; 58:1254. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 20/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 21. Maron BJ, Zipes DP, Kovacs RJ. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General Considerations: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2343. 22. Finocchiaro G, Papadakis M, Robertus JL, et al. Etiology of Sudden Death in Sports: Insights From a United Kingdom Regional Registry. J Am Coll Cardiol 2016; 67:2108. 23. Baggish AL, Battle RW, Beckerman JG, et al. Sports Cardiology: Core Curriculum for Providing Cardiovascular Care to Competitive Athletes and Highly Active People. J Am Coll Cardiol 2017; 70:1902. 24. Peterson DF, Kucera K, Thomas LC, et al. Aetiology and incidence of sudden cardiac arrest and death in young competitive athletes in the USA: a 4-year prospective study. Br J Sports Med 2021; 55:1196. 25. Eckart RE, Scoville SL, Campbell CL, et al. Sudden death in young adults: a 25-year review of autopsies in military recruits. Ann Intern Med 2004; 141:829. 26. Karam N, Pechmajou L, Dumas F, et al. Comprehensive Assessment of Coronary Artery Disease in Sports-Related Sudden Cardiac Arrest. Circulation 2018; 138:429. 27. Hausmann R, Hammer S, Betz P. Performance enhancing drugs (doping agents) and sudden death a case report and review of the literature. Int J Legal Med 1998; 111:261. 28. Kennedy MC, Lawrence C. Anabolic steroid abuse and cardiac death. Med J Aust 1993; 158:346. 29. Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 3: Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Other Cardiomyopathies, and Myocarditis: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2362. 30. Priori SG, Blomstr m-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015; 36:2793. 31. Pelliccia A, Solberg EE, Papadakis M, et al. Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2019; 40:19. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 21/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 32. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2020; 142:e558. 33. Dias KA, Link MS, Levine BD. Exercise Training for Patients With Hypertrophic Cardiomyopathy: JACC Review Topic of the Week. J Am Coll Cardiol 2018; 72:1157. 34. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124:e783. 35. Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35:2733. 36. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36:2212. 37. Pelliccia A, Lemme E, Maestrini V, et al. Does Sport Participation Worsen the Clinical Course of Hypertrophic Cardiomyopathy? Clinical Outcome of Hypertrophic Cardiomyopathy in Athletes. Circulation 2018; 137:531. 38. Caselli S, Pelliccia A. The electrocardiogram and the phenotypic expression of hypertrophic cardiomyopathy. Eur Heart J 2019; 40:982. 39. Heidb chel H, Corrado D, Biffi A, et al. Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators. Eur J Cardiovasc Prev Rehabil 2006; 13:676. 40. Van Hare GF, Ackerman MJ, Evangelista JA, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 4: Congenital Heart Disease: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2372. 41. Thompson PD, Myerburg RJ, Levine BD, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 8: Coronary Artery Disease: A Scientific Statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2406. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 22/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 42. Maron BJ, Carney KP, Lever HM, et al. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. J Am Coll Cardiol 2003; 41:974. 43. Taylor AJ, Rogan KM, Virmani R. Sudden cardiac death associated with isolated congenital coronary artery anomalies. J Am Coll Cardiol 1992; 20:640. 44. Liberthson RR. Sudden death from cardiac causes in children and young adults. N Engl J Med 1996; 334:1039. 45. Liberthson RR, Dinsmore RE, Fallon JT. Aberrant coronary artery origin from the aorta. Report of 18 patients, review of literature and delineation of natural history and management. Circulation 1979; 59:748. 46. Taylor AJ, Byers JP, Cheitlin MD, Virmani R. Anomalous right or left coronary artery from the contralateral coronary sinus: "high-risk" abnormalities in the initial coronary artery course and heterogeneous clinical outcomes. Am Heart J 1997; 133:428. 47. Basso C, Maron BJ, Corrado D, Thiene G. Clinical profile of congenital coronary artery anomalies with origin from the wrong aortic sinus leading to sudden death in young competitive athletes. J Am Coll Cardiol 2000; 35:1493. 48. Thiene G, Nava A, Corrado D, et al. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 1988; 318:129. 49. Blomstr m-Lundqvist C, Sabel KG, Olsson SB. A long term follow up of 15 patients with arrhythmogenic right ventricular dysplasia. Br Heart J 1987; 58:477. 50. Douglas PS, O'Toole ML, Hiller WD, Reichek N. Different effects of prolonged exercise on the right and left ventricles. J Am Coll Cardiol 1990; 15:64. 51. Ruwald AC, Marcus F, Estes NA 3rd, et al. Association of competitive and recreational sport participation with cardiac events in patients with arrhythmogenic right ventricular cardiomyopathy: results from the North American multidisciplinary study of arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2015; 36:1735. 52. James CA, Bhonsale A, Tichnell C, et al. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol 2013; 62:1290. 53. Braverman AC, Harris KM, Kovacs RJ, Maron BJ. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 7: Aortic Diseases, Including Marfan Syndrome: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2398. 54. Budts W, B rjesson M, Chessa M, et al. Physical activity in adolescents and adults with congenital heart defects: individualized exercise prescription. Eur Heart J 2013; 34:3669. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 23/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 55. Ackerman MJ, Zipes DP, Kovacs RJ, Maron BJ. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 10: The Cardiac Channelopathies: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2424. 56. Zipes DP, Link MS, Ackerman MJ, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 9: Arrhythmias and Conduction Defects: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2412. 57. Pelliccia A, Fagard R, Bj rnstad HH, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005; 26:1422. 58. Turkowski KL, Bos JM, Ackerman NC, et al. Return-to-Play for Athletes With Genetic Heart Diseases. Circulation 2018; 137:1086. 59. www.brugadadrugs.org (Accessed on December 11, 2019). 60. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. 61. Matsuo K, Kurita T, Inagaki M, et al. The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome. Eur Heart J 1999; 20:465. 62. Corrado D, Basso C, Buja G, et al. Right bundle branch block, right precordial st-segment elevation, and sudden death in young people. Circulation 2001; 103:710. 63. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106:69. 64. Choi G, Kopplin LJ, Tester DJ, et al. Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004; 110:2119. 65. Borjesson M, Dellborg M, Niebauer J, et al. Recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: a position statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2019; 40:13. Topic 986 Version 36.0 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 24/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate GRAPHICS Classification of sports based on peak static and dynamic components during competition This classification is based on peak static and dynamic components achieved during competition; however, higher values may be reached during training. The increasing dynamic component is defined in terms of the estimated percentage of maximal oxygen uptake (VO max) achieved and results in an increasing cardiac output. The 2 increasing static component is related to the estimated percentage of maximal voluntary contraction reached and results in an increasing blood pressure load. The lowest total cardiovascular demands (cardiac output and blood pressure) are shown in the palest color, with increasing dynamic load depicted by increasing blue intensity and increasing static load by increasing red intensity. Note the graded transition between categories, which should be individualized on the basis of player position and style of play. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 25/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Danger of bodily collision (refer to UpToDate content regarding sports according to risk of impact and educational background). Increased risk if syncope occurs. Reproduced from: Levine BD, Baggish AL, Kovacs RJ. Eligibility and disquali cation recommendations for competitive athletes with cardiovascular abnormalities: Task force 1: Classi cation of sports: Dynamic, static, and impact: A scienti c statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2350. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 105651 Version 9.0 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 26/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 27/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Contributor Disclosures |
Med 1996; 334:1039. 45. Liberthson RR, Dinsmore RE, Fallon JT. Aberrant coronary artery origin from the aorta. Report of 18 patients, review of literature and delineation of natural history and management. Circulation 1979; 59:748. 46. Taylor AJ, Byers JP, Cheitlin MD, Virmani R. Anomalous right or left coronary artery from the contralateral coronary sinus: "high-risk" abnormalities in the initial coronary artery course and heterogeneous clinical outcomes. Am Heart J 1997; 133:428. 47. Basso C, Maron BJ, Corrado D, Thiene G. Clinical profile of congenital coronary artery anomalies with origin from the wrong aortic sinus leading to sudden death in young competitive athletes. J Am Coll Cardiol 2000; 35:1493. 48. Thiene G, Nava A, Corrado D, et al. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 1988; 318:129. 49. Blomstr m-Lundqvist C, Sabel KG, Olsson SB. A long term follow up of 15 patients with arrhythmogenic right ventricular dysplasia. Br Heart J 1987; 58:477. 50. Douglas PS, O'Toole ML, Hiller WD, Reichek N. Different effects of prolonged exercise on the right and left ventricles. J Am Coll Cardiol 1990; 15:64. 51. Ruwald AC, Marcus F, Estes NA 3rd, et al. Association of competitive and recreational sport participation with cardiac events in patients with arrhythmogenic right ventricular cardiomyopathy: results from the North American multidisciplinary study of arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2015; 36:1735. 52. James CA, Bhonsale A, Tichnell C, et al. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol 2013; 62:1290. 53. Braverman AC, Harris KM, Kovacs RJ, Maron BJ. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 7: Aortic Diseases, Including Marfan Syndrome: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2398. 54. Budts W, B rjesson M, Chessa M, et al. Physical activity in adolescents and adults with congenital heart defects: individualized exercise prescription. Eur Heart J 2013; 34:3669. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 23/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 55. Ackerman MJ, Zipes DP, Kovacs RJ, Maron BJ. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 10: The Cardiac Channelopathies: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2424. 56. Zipes DP, Link MS, Ackerman MJ, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 9: Arrhythmias and Conduction Defects: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2412. 57. Pelliccia A, Fagard R, Bj rnstad HH, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005; 26:1422. 58. Turkowski KL, Bos JM, Ackerman NC, et al. Return-to-Play for Athletes With Genetic Heart Diseases. Circulation 2018; 137:1086. 59. www.brugadadrugs.org (Accessed on December 11, 2019). 60. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. 61. Matsuo K, Kurita T, Inagaki M, et al. The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome. Eur Heart J 1999; 20:465. 62. Corrado D, Basso C, Buja G, et al. Right bundle branch block, right precordial st-segment elevation, and sudden death in young people. Circulation 2001; 103:710. 63. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106:69. 64. Choi G, Kopplin LJ, Tester DJ, et al. Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004; 110:2119. 65. Borjesson M, Dellborg M, Niebauer J, et al. Recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: a position statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2019; 40:13. Topic 986 Version 36.0 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 24/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate GRAPHICS Classification of sports based on peak static and dynamic components during competition This classification is based on peak static and dynamic components achieved during competition; however, higher values may be reached during training. The increasing dynamic component is defined in terms of the estimated percentage of maximal oxygen uptake (VO max) achieved and results in an increasing cardiac output. The 2 increasing static component is related to the estimated percentage of maximal voluntary contraction reached and results in an increasing blood pressure load. The lowest total cardiovascular demands (cardiac output and blood pressure) are shown in the palest color, with increasing dynamic load depicted by increasing blue intensity and increasing static load by increasing red intensity. Note the graded transition between categories, which should be individualized on the basis of player position and style of play. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 25/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Danger of bodily collision (refer to UpToDate content regarding sports according to risk of impact and educational background). Increased risk if syncope occurs. Reproduced from: Levine BD, Baggish AL, Kovacs RJ. Eligibility and disquali cation recommendations for competitive athletes with cardiovascular abnormalities: Task force 1: Classi cation of sports: Dynamic, static, and impact: A scienti c statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2350. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 105651 Version 9.0 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 26/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 27/28 7/6/23, 11:26 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Contributor Disclosures Antonio Pelliccia, MD No relevant financial relationship(s) with ineligible companies to disclose. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 28/28 |
7/6/23, 11:27 AM Automated external defibrillators - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Automated external defibrillators : Thomas D Rea, MD, MPH, Mickey S Eisenberg, MD, PhD : Richard L Page, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 07, 2021. INTRODUCTION Sudden cardiac arrest (SCA) refers to the sudden cessation of cardiac activity with hemodynamic collapse and is most often due to sustained ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). SCA is a major public health challenge, accounting for approximately 5 to 15 percent of total mortality in industrialized nations [1-3]. (See "Overview of sudden cardiac arrest and sudden cardiac death".) Although survival from SCA remains generally poor, there is evidence from contemporary population-based registries that outcomes following out-of-hospital and in-hospital cardiac arrest have improved compared with historical experiences. However, there is substantial disparity across systems and hence opportunity to improve outcomes. Based on contemporary estimates of out-of-hospital cardiac arrest, approximately 10 percent of emergency medical services-treated patients in any cardiac rhythm and 30 percent of patients whose initial rhythm is VF survive to be discharged from the hospital [2-5]. Based on registry data from the United States and Great Britain, contemporary survival rates for in-hospital arrest are estimated at 20 percent for all rhythms and nearly 50 percent for patients with an initial rhythm of VF [6]. (See "Prognosis and outcomes following sudden cardiac arrest in adults".) Although several interventions can improve the likelihood of VF resuscitation, the single most important is early delivery of an external electric shock to reset the cardiac rhythm and restore spontaneous circulation [7,8]. Early defibrillation is consistently associated with a greater likelihood of survival, which decreases by approximately 5 to 10 percent with each additional minute from collapse to defibrillation [9]. The potential benefit of early defibrillation is best https://www.uptodate.com/contents/automated-external-defibrillators/print 1/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate illustrated by the outcomes following defibrillation at casinos; 74 percent with witnessed VF survived when a shock was delivered within three minutes from collapse [10]. A 2017 review of observational studies reported early defibrillation with automated external defibrillators (AEDs) is associated with an approximate doubling of survival when an AED was applied by lay first responders (survival of 53 percent) compared with professional personnel dispatched by emergency medical dispatch centers (survival of 29 percent) [11]. This topic will review the development, use, allocation, and efficacy of AEDs. Other aspects of electrical cardioversion and defibrillation are discussed separately, as are basic and advanced cardiovascular life support. (See "Basic principles and technique of external electrical cardioversion and defibrillation" and "Cardioversion for specific arrhythmias" and "Adult basic life support (BLS) for health care providers" and "Advanced cardiac life support (ACLS) in adults" and "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest".) AED TRAINING and OPERATION AED training AEDs are designed to be straightforward to operate, and multiple studies have demonstrated that laypersons can operate them safely and effectively [12-15]. Nevertheless, they can be challenging to use, especially for the layperson [16-18]. The best approach for training laypersons to achieve and maintain AED operational proficiency is not well established, although face-to-face, video, and web-based training approaches have demonstrated merit [19,20]. A study of older laypersons previously trained in AED use showed that emergency dispatchers were successfully able to assist rescuers to use AEDs via telephone instructions [12]. Online and in-person classes are available ( https://www.redcross.org/take-a-class/aed) to assist persons with AEDs or those who are considering purchase of an AED. AED operation AEDs utilize two self-adhesive electrode pads placed directly on the bare chest to detect the cardiac rhythm and to deliver shocks when indicated. Patient and background motion can impact diagnostic accuracy, which is why rescuers are instructed to pause CPR during rhythm analysis. International standards require that AEDs have a sensitivity of >90 percent for detecting ventricular fibrillation (VF; at least 0.2 mV in amplitude) and an overall specificity of >95 percent, a level of discrimination that compares favorably with manual field interpretation [21,22]. In a 2015 study comparing four commercially available AEDs, all of the devices correctly identified VF greater than 95 percent of the time; however, there was a wide range of diagnostic accuracy for correctly identifying ventricular tachycardia (VT) and supraventricular tachycardia (SVT) [23]. In a 2018 study of seven different AED models that were https://www.uptodate.com/contents/automated-external-defibrillators/print 2/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate tested in an airplane simulator under different levels of background motion and turbulence, five of the devices correctly identified all rhythms (sinus rhythm, asystole, and VF at five different amplitudes) at all levels of turbulence [24]. Most AEDs deliver between 120 and 360 Joules, with the output depending upon several factors including the number of shocks previously administered, the impedance of the chest wall, and whether a monophasic or biphasic waveform is used. Some AEDs are automatically adjusted to deliver less electricity (intended for children) when pediatric pads are attached. (See "Basic principles and technique of external electrical cardioversion and defibrillation", section on 'Monophasic versus biphasic waveforms'.) AEDs typically provide audio prompts that direct rescuers to stand clear of the victim during rhythm analysis and to press a button to deliver the shock. AEDs are programmed to subsequently reanalyze the electrocardiogram (ECG) rhythm typically every two minutes. During the intervening time period, the AED prompts the rescuer to check for signs of life and, if needed, perform cardiopulmonary resuscitation (CPR). If the patient has an implantable cardioverter-defibrillator (ICD) that is delivering shocks, the ICD should be allowed to complete its treatment cycle (typically 30 to 60 seconds) before the AED is attached. Pad placement The 2010 Advanced Cardiac Life Support (ACLS) guidelines make the following recommendations regarding placement of AED pads [7]: AED pads should be placed in the sternal-apical (anterolateral) position ( figure 1), with the right pad placed on the right superior-anterior chest below the clavicle, and the left pad placed on the inferior-lateral left chest, lateral to the left breast [7]. Acceptable alternatives are biaxillary positioning, with pads placed on the right and left lateral chest walls, or placement of the left pad in the standard apical position, with the other pad on the right or left upper back. Pads should be placed at least 2.5 cm (1 inch) away from any implantable devices. AED pads should NOT be placed directly on top of a transdermal medication patch since it can interfere with therapy and also cause skin burns. The medication patch should be removed and the skin should be wiped clean. Chest hair can potentially interfere with optimal pad adhesion and may need to be removed. This can be done by rapidly removing an adhesive AED pad or by shaving the chest in the area where the pad will be placed. https://www.uptodate.com/contents/automated-external-defibrillators/print 3/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate Other features Additional features present in most AED models include the ability to continuously record the arrest rhythm ECG, derive measures of CPR performance such as chest compressions or ventilations, and record the voices of rescuers involved in the event. The combination of these features enables case review that may be used for quality assurance or research. Such data indicate that CPR often does not meet guideline standards and is frequently interrupted [25-28]. Newer AED models incorporate more dynamic prompts or real-time feedback to guide rescuer CPR actions. Although these real-time prompts can improve CPR performance, it is not yet known if these features will improve survival [29]. AED ALLOCATION STRATEGY AEDs are effective only in those patients who present with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT); pulseless electrical activity and asystole are not effectively treated by defibrillation. Although the proportion of VF/VT arrests is declining relative to nonshockable rhythms, VF/VT arrests still account for tens of thousands of deaths each year in the United States, and the improved resuscitation provided by AEDs can have a significant impact on public health. AEDs enable people who are not trained in rhythm interpretation to provide life-saving therapy, which vastly increases the pool of potential rescuers who can provide early defibrillation. However, their allocation and use require programmatic support, training, and maintenance, all of which can contribute to overall cost. Thus, an important consideration regarding these devices is efficient distribution of AEDs throughout communities. Strategies for AED allocation include providing them to traditional emergency medical services (EMS) and to nonmedical emergency responders (eg, police officers and firefighters), as well as placing them in public locations, in hospitals, and in the homes of individuals. Emergency medical services AED programs The initial large-scale implementation of AEDs was by emergency medical services (EMS) in the 1980s and 1990s. This strategy provided the potential for earlier defibrillation by allocating AEDs to EMS first responders (emergency medical technicians), many of whom were not typically trained in rhythm interpretation. Some EMS AED programs were associated with improvements in survival, but others were not [30-33]. Meta-analyses found that EMS AED programs resulted in a significant 9 percent increase in survival [34,35]. However, weaknesses in individual study design limit the strength of these conclusions. https://www.uptodate.com/contents/automated-external-defibrillators/print 4/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate In some reports, survival from sudden cardiac arrest (SCA) due to VF did not improve despite reductions in the time to defibrillation observed with the adoption of the AED [36,37]. One explanation for this discrepancy is that the resuscitation algorithms that were originally used for AED rhythm analysis and processing required considerable interruptions in cardiopulmonary resuscitation (CPR) compared with treatment with a manual defibrillator [25-28] and that the increase in "hands-off" time reduced the chances of successful resuscitation [38-41]. (See "Advanced cardiac life support (ACLS) in adults", section on 'Excellent basic life support and its importance'.) Police AED programs Police officers can sometimes respond to SCA victims more quickly than EMS providers [42]. A program of providing AEDs to police officers and training them in their use was initially introduced in the late 1980s in Rochester, Minnesota [43]. Police often arrived at SCAs due to ventricular fibrillation (VF) prior to EMS and defibrillated patients an average of 5.5 minutes following collapse [43]. Ten of 14 patients survived to hospital discharge. In a later series of 193 patients, survival from witnessed VF to hospital discharge was 46 percent. Most were neurologically intact [44]. In contrast, survival from SCA not caused by VF was only 5 percent. Implementation of police AED programs in Pittsburgh, Pennsylvania, Miami-Dade County, Florida, King County, Washington, and Zurich, Switzerland, has also been associated with greater survival [45-48]. However, other police AED programs have not shown survival benefits compared with standard EMS, particularly when the police often have not arrived before EMS [49]. Thus, one of the keys to a successful police AED program is committed medical and police leaders who can motivate police about their potential lifesaving role and in turn respond quickly. A meta-analysis of police AED programs, published in 2013, described the potential benefits and challenges of implementation [50]. Public access defibrillation programs Surveillance studies have identified particular locations where SCA occurs with high frequency, including public transit facilities, shopping malls, public sports venues, industrial sites, golf courses, casinos, dialysis centers, airplanes, and fitness centers [51-56]. AEDs strategically located in such places can be used by laypersons to deliver defibrillation prior to EMS arrival, a concept referred to as "public access defibrillation" (PAD). The benefits of PAD on survival rates and neurologic outcomes after SCA are illustrated by the following findings [10,57-61]: The Public Access Defibrillation (PAD) trial, a prospective multi-community randomized trial, evaluated survival to discharge in 526 patients with SCA. Following SCA, survival to discharge rates significantly increased in high-risk public sites where CPR-trained lay responders were equipped with AEDs compared with sites where lay responders were CPR- https://www.uptodate.com/contents/automated-external-defibrillators/print 5/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate trained, but did not have access to AEDs (23.4 versus 14.0 percent) [61]. Furthermore, PAD programs implemented at high-risk sites offer reasonable health benefit for the cost, ranging from $35,000 to $57,000 per quality adjusted life-year, which is comparable to other widely-accepted medical interventions such as bone marrow transplant ($52,000 per quality adjusted life-year) and heart transplant ($59,000 per quality adjusted life-year) [62- 66]. A large, multi-community cohort study evaluated the outcome of over 13,000 patients with an out-of-hospital SCA. Survival to hospital discharge was markedly greater in patients who received an AED-delivered shock from a non-traditional responder (most often layperson) compared with patients receiving bystander CPR alone or those presenting with VF whose initial shock was delivered by EMS (38 versus 9 versus 22 percent, respectively) [60]. Survival with intact neurologic function is higher in patients with SCA who receive treatment with an AED available at the site of the arrest. In a study of 2833 consecutive patients with out-of-hospital SCA, neurologically intact survival was significantly higher among those treated with an on-site AED in addition to basic life support (BLS; 50 versus 14 percent with BLS alone, adjusted odds ratio [OR] 2.72, 95% CI 1.77-4.18) [67]. Nationwide dissemination of AEDs in public places in Japan from 2005 through 2013 was associated with an increase in the proportion of shocks for witnessed VF arrest administered by laypersons with AEDs from 1.1 to 16.5 percent [68]. As public access defibrillation increased, mean time to shock was reduced (from 3.7 to 2.2 minutes), with a significant improvement in one month survival with favorable neurologic function (38.5 percent compared with 18.2 percent for those who did not receive public access defibrillation; adjusted OR 2.0, 95% CI 1.8-2.2) [68,69]. A 2018 report from Japan also noted increased survival and improved neurological outcomes among school-aged patients receiving public access defibrillation [70]. Improvements in time to defibrillation and survival with favorable neurologic function have also been reported from a 2006 to 2012 nationwide study of AED use in the Netherlands [71]. The survival benefit observed in these programs has led to advocacy for lower-risk sites to implement PAD programs. As an example, guidelines have been established for school-based AED programs which have increased substantially over time, partly because of legislation [72- 74]. PAD programs are also mandated in many federal locations. Use at lower-risk sites provides the opportunity to increase the number of SCA survivors but with a lower cost-effectiveness. At https://www.uptodate.com/contents/automated-external-defibrillators/print 6/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate present, PAD program AEDs are involved in only a small fraction of all out-of-hospital SCAs so that strategies that increase their use are a promising strategy to improve survival [59,75]. Smart phone apps for notification of cardiac arrest Smart phone apps now exist to allow a person close to a suspected cardiac arrest to be notified by the 911 emergency dispatch center. These apps (see PulsePoint.org for one example) are downloaded on volunteers' phones, and when a suspected cardiac arrest occurs nearby, volunteers (typically within a quarter mile of the event) are alerted on their smart phone with the location pinpointed on a map. There are anecdotal reports of volunteers starting CPR prior to arrival of EMS personnel from the local media. The strategy can increase early CPR and survival in select communities in public setting and potentially residential setting arrests [76,77]. If public AEDs are nearby, these may also be identified via a dynamic software platform integrated with the smart phone app. The strategy to also link the location of nearby AEDs to those alerted to respond and provide CPR is a promising adjunct, though the approach requires that the AED location be registered and verified via the smart phone app. AEDs for use in private homes Since approximately three-quarters of SCAs occur in private homes, one strategy to reduce mortality is to distribute AEDs for use in the home. Home use of AEDs was investigated in a randomized trial of 7001 patients with previous anterior wall myocardial infarct ion who were not candidates for an implantable cardioverter-defibrillator [78]. The median age was 62 years and the median left ventricular ejection fraction was 45 percent. The designated rescuers were predominantly female (83 percent) and their median age was 58 years. Patients were randomly assigned to AED use followed by calling EMS and performing CPR or to the control response of calling EMS and performing CPR. Access to a home AED did not improve survival as compared with conventional resuscitation (6.4 versus 6.5 percent, hazard ratio 0.97, 95% CI 0.81-1.17). Several factors may have contributed to the lack of benefit in this trial: The incidence of sudden cardiac arrest (2.3 percent) and overall mortality were lower than predicted. One-half of the tachyarrhythmia arrests that took place at home were witnessed (58 of 117), and an AED was used in only 32 patients. Spouses and companions in the control group received training in resuscitation, with frequent reminders. https://www.uptodate.com/contents/automated-external-defibrillators/print 7/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate In determining whether AEDs are appropriate for home use, cost and the increasing role of implantable cardioverter-defibrillators in individuals at high risk of SCA must be taken into consideration. In-hospital AED allocation Delayed defibrillation is common during in-hospital arrest even though medical personnel are often trained in advanced cardiac life support and ECG rhythm interpretation and are capable of implementing manual defibrillation. The frequency of delayed in-hospital defibrillation (defined as greater than two minutes from the time of recognition of arrest) and its adverse effect on survival were illustrated in a study utilizing 6789 patient records from the National Registry of Cardiopulmonary Resuscitation [79]. Delayed defibrillation for ventricular fibrillation or pulseless ventricular tachycardia was observed in 30 percent of SCAs and was associated with a significantly lower probability of survival to discharge compared with survival when defibrillation was performed within two minutes (22 percent versus 39 percent). The possibility that AED could improve survival of in-hospital SCA was suggested by small studies showing that AEDs allocated to specific clinical and non-clinical areas of the hospital allowed for more rapid defibrillation [80,81]. Subsequently, the outcomes of in-hospital SCA were analyzed using data obtained from 253 US and Canadian hospitals as part of the National Registry of Cardiopulmonary Resuscitation. Amongst a cohort of 11,695 hospitalized patients who suffered SCA between 2000 and 2008, 39 percent of cardiac arrests were treated using an AED [82]. Patients with a shockable rhythm (ie, pulseless ventricular tachycardia or ventricular fibrillation) had similar survival to hospital discharge in the AED and non-AED group (38.4 versus 39.8 percent, adjusted relative risk [RR] 1.00, 95% CI 0.88-1.13). Patients without a shockable rhythm (ie, asystole or pulseless electrical activity) had a lower rate of survival to hospital discharge when an AED was employed (10.4 versus 15.4 percent in the non-AED group, adjusted RR 0.74, 95% CI 0.65-0.83). These results suggest that, for patients with a shockable rhythm, AED use was not associated with a survival difference compared with manual external defibrillation in a hospital setting. Among nonshockable rhythms, AED use was associated with a lower survival. The explanation for lower survival may be the disproportionate excess of asystole in the AED group, some other unmeasured confounder, or the potential that AED application and use may truly delay or interrupt other beneficial therapies. https://www.uptodate.com/contents/automated-external-defibrillators/print 8/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate The optimal strategy of AED distribution and its ultimate benefit may depend upon a particular hospital's staffing, geography, and patient profile [83]. AEDs in medical and dental practices Cardiac arrest in a medical or dental setting is an infrequent event. Data from King County, Washington, rank the likelihood of a cardiac arrest occurring, with dialysis centers having the highest risk (approximately one per year). The next highest risk locations are cardiology practices, urgent care centers, internal medicine, and family medicine. The lowest risk locations are dental settings. Despite the low risk in most practices, we believe virtually all medical practices should have an AED, and dialysis centers should definitely have an AED on site. CHALLENGES AND OPPORTUNITIES Although AEDs have saved many lives, they have several potential drawbacks. AEDs require the presence of a bystander to apply and operate. Only about 50 percent of sudden cardiac arrest (SCA) events are witnessed. Thus, effective defibrillation is often not relevant by the time the victim of an unwitnessed SCA is found. AEDs require interruptions in cardiopulmonary resuscitation (CPR) while they assess the cardiac rhythm. This analysis time is typically longer with AEDs than with manual defibrillators. Ongoing efforts are aimed at minimizing this time, and technical advances may eventually enable accurate rhythm interpretation even while CPR is ongoing [84,85]. (See "Advanced cardiac life support (ACLS) in adults", section on 'Excellent basic life support and its importance'.) The cost of AEDs can be an important obstacle to potential health benefits. AEDs intended for personal or public use (such as in an airport or doctor's office) are readily available for approximately $1000. Commercial-grade AEDs (such as for use by EMTs) typically cost $2500 [86]. Prognostic information on SCA patients is available from the shape and pattern of the ventricular fibrillation (VF) waveform recorded in the ECG [87]. AEDs can analyze this information in real-time to potentially guide rescuers to the best course of treatment with CPR, defibrillation, and medications [88]. Although this research is intriguing, the survival effects of dynamic processing of the VF waveform are largely untested. Wearable AEDs have been developed. Their evidence-based role has not been established, and their use is best determined through clinical assessment of risk and benefit for the individual https://www.uptodate.com/contents/automated-external-defibrillators/print 9/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate patient. (See "Wearable cardioverter-defibrillator".) Some advocates of widespread AED dissemination have considered AEDs as compulsory safety equipment along the lines of smoke alarms and fire extinguishers [89]. Such an approach has not been tested and is cost prohibitive. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Basic and advanced cardiac life support in adults" and "Society guideline links: Cardiac arrest in adults".) SUMMARY AND RECOMMENDATIONS Sudden cardiac arrest (SCA) is a major public health challenge for which early defibrillation can improve survival among those with a ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) arrest. (See 'Introduction' above.) Historically, definitive treatment of out-of-hospital SCA with early defibrillation was limited by the small number of qualified rescuers who could interpret cardiac rhythms. Since AEDs analyze cardiac rhythms and directly inform rescuers whether a shock is indicated, their advent has enabled lay rescuers and additional public safety personnel to provide early defibrillation. (See 'AED operation' above.) Successful early defibrillation using an AED, when appropriate, has been shown to significantly improve survival and survival with intact neurologic function following out-of- hospital SCA. (See 'Public access defibrillation programs' above.) Innovative programs using smart phone apps have the potential to deploy AEDs and deliver defibrillation earlier, and thus improve the chances of survival. (See 'Smart phone apps for notification of cardiac arrest' above.) In the hospital setting, AED use was not associated with a survival difference compared with manual external defibrillation among VF arrest and associated with a lower survival among nonshockable arrest. The optimal in-hospital strategy of AED distribution and its ultimate benefit may depend upon a particular hospital's staffing, geography, and patient profile. (See 'In-hospital AED allocation' above.) https://www.uptodate.com/contents/automated-external-defibrillators/print 10/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate While AEDs can be highly effective, appropriate use does require interruptions in cardiopulmonary resuscitation to assess the cardiac rhythm. The increase in "hands-off" time may reduce the chances of successful resuscitation. (See 'Challenges and opportunities' above and "Advanced cardiac life support (ACLS) in adults", section on 'Excellent basic life support and its importance'.) ACKNOWLEDGMENT The editorial staff at UpToDate acknowledge Laura Gold, PhD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158. 2. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol 2004; 93:1455. 3. Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation 2018; 137:e67. 4. Peberdy MA, Kaye W, Ornato JP, et al. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation 2003; 58:297. 5. Nichol G, Thomas E, Callaway CW, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 2008; 300:1423. 6. Peberdy MA, Ornato JP, Larkin GL, et al. Survival from in-hospital cardiac arrest during nights and weekends. JAMA 2008; 299:785. 7. Field JM, Hazinski MF, Sayre MR, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S640. 8. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S444. https://www.uptodate.com/contents/automated-external-defibrillators/print 11/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate 9. Valenzuela TD, Roe DJ, Cretin S, et al. Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation 1997; 96:3308. 10. Valenzuela TD, Roe DJ, Nichol G, et al. Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos. N Engl J Med 2000; 343:1206. 11. B kgaard JS, Viereck S, M ller TP, et al. The Effects of Public Access Defibrillation on Survival After Out-of-Hospital Cardiac Arrest: A Systematic Review of Observational Studies. Circulation 2017; 136:954. 12. Ecker R, Rea TD, Meischke H, et al. Dispatcher assistance and automated external defibrillator performance among elders. Acad Emerg Med 2001; 8:968. 13. Harve H, Jokela J, Tissari A, et al. Can untrained laypersons use a defibrillator with dispatcher assistance? Acad Emerg Med 2007; 14:624. 14. Roppolo LP, Pepe PE, Campbell L, et al. Prospective, randomized trial of the effectiveness and retention of 30-min layperson training for cardiopulmonary resuscitation and automated external defibrillators: The American Airlines Study. Resuscitation 2007; 74:276. 15. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 16. Riegel B, Birnbaum A, Aufderheide TP, et al. Predictors of cardiopulmonary resuscitation and automated external defibrillator skill retention. Am Heart J 2005; 150:927. 17. Meischke HW, Rea TD, Eisenberg MS, Rowe SM. Intentions to use an automated external defibrillator during a cardiac emergency among a group of seniors trained in its operation. Heart Lung 2002; 31:25. 18. Riegel B, Nafziger SD, McBurnie MA, et al. How well are cardiopulmonary resuscitation and automated external defibrillator skills retained over time? Results from the Public Access Defibrillation (PAD) Trial. Acad Emerg Med 2006; 13:254. 19. Lynch B, Einspruch EL, Nichol G, et al. Effectiveness of a 30-min CPR self-instruction program for lay responders: a controlled randomized study. Resuscitation 2005; 67:31. 20. Meischke HW, Rea T, Eisenberg MS, et al. Training seniors in the operation of an automated external defibrillator: a randomized trial comparing two training methods. Ann Emerg Med 2001; 38:216. 21. Kerber RE, Becker LB, Bourland JD, et al. Automatic external defibrillators for public access defibrillation: recommendations for specifying and reporting arrhythmia analysis algorithm https://www.uptodate.com/contents/automated-external-defibrillators/print 12/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate performance, incorporating new waveforms, and enhancing safety. A statement for health professionals from the American Heart Association Task Force on Automatic External Defibrillation, Subcommittee on AED Safety and Efficacy. Circulation 1997; 95:1677. 22. Kramer-Johansen J, Edelson DP, Abella BS, et al. Pauses in chest compression and inappropriate shocks: a comparison of manual and semi-automatic defibrillation attempts. Resuscitation 2007; 73:212. 23. Nishiyama T, Nishiyama A, Negishi M, et al. Diagnostic Accuracy of Commercially Available Automated External Defibrillators. J Am Heart Assoc 2015; 4. 24. Hung KKC, Graham CA, Chan LK, et al. Performance of automated external defibrillators under conditions of in-flight turbulence. Resuscitation 2018; 130:41. 25. Carpenter J, Rea TD, Murray JA, et al. Defibrillation waveform and post-shock rhythm in out- of-hospital ventricular fibrillation cardiac arrest. Resuscitation 2003; 59:189. 26. van Alem AP, Sanou BT, Koster RW. Interruption of cardiopulmonary resuscitation with the use of the automated external defibrillator in out-of-hospital cardiac arrest. Ann Emerg Med 2003; 42:449. 27. Valenzuela TD, Kern KB, Clark LL, et al. Interruptions of chest compressions during emergency medical systems resuscitation. Circulation 2005; 112:1259. 28. Pytte M, Pedersen TE, Ottem J, et al. Comparison of hands-off time during CPR with manual and semi-automatic defibrillation in a manikin model. Resuscitation 2007; 73:131. 29. Hostler D, Everson-Stewart S, Rea TD, et al. Effect of real-time feedback during cardiopulmonary resuscitation outside hospital: prospective, cluster-randomised trial. BMJ 2011; 342:d512. 30. Stults KR, Brown DD, Schug VL, Bean JA. Prehospital defibrillation performed by emergency medical technicians in rural communities. N Engl J Med 1984; 310:219. 31. Weaver WD, Hill D, Fahrenbruch CE, et al. Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest. N Engl J Med 1988; 319:661. 32. Sweeney TA, Runge JW, Gibbs MA, et al. EMT defibrillation does not increase survival from sudden cardiac death in a two-tiered urban-suburban EMS system. Ann Emerg Med 1998; 31:234. 33. Kellermann AL, Hackman BB, Somes G, et al. Impact of first-responder defibrillation in an urban emergency medical services system. JAMA 1993; 270:1708. 34. Watts DD. Defibrillation by basic emergency medical technicians: effect on survival. Ann Emerg Med 1995; 26:635. https://www.uptodate.com/contents/automated-external-defibrillators/print 13/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate 35. Auble TE, Menegazzi JJ, Paris PM. Effect of out-of-hospital defibrillation by basic life support providers on cardiac arrest mortality: a metaanalysis. Ann Emerg Med 1995; 25:642. 36. Cobb LA, Fahrenbruch CE, Walsh TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999; 281:1182. 37. Rea TD, Helbock M, Perry S, et al. Increasing use of cardiopulmonary resuscitation during out-of-hospital ventricular fibrillation arrest: survival implications of guideline changes. Circulation 2006; 114:2760. 38. Tang W, Snyder D, Wang J, et al. One-shock versus three-shock defibrillation protocol significantly improves outcome in a porcine model of prolonged ventricular fibrillation cardiac arrest. Circulation 2006; 113:2683. 39. Berg MD, Clark LL, Valenzuela TD, et al. Post-shock chest compression delays with automated external defibrillator use. Resuscitation 2005; 64:287. 40. Berg RA, Hilwig RW, Kern KB, et al. Automated external defibrillation versus manual defibrillation for prolonged ventricular fibrillation: lethal delays of chest compressions before and after countershocks. Ann Emerg Med 2003; 42:458. 41. Berg RA, Hilwig RW, Berg MD, et al. Immediate post-shock chest compressions improve outcome from prolonged ventricular fibrillation. Resuscitation 2008; 78:71. 42. Waalewijn RA, de Vos R, Koster RW. Out-of-hospital cardiac arrests in Amsterdam and its surrounding areas: results from the Amsterdam resuscitation study (ARREST) in 'Utstein' style. Resuscitation 1998; 38:157. 43. White RD, Vukov LF, Bugliosi TF. Early defibrillation by police: initial experience with measurement of critical time intervals and patient outcome. Ann Emerg Med 1994; 23:1009. 44. White RD, Bunch TJ, Hankins DG. Evolution of a community-wide early defibrillation programme experience over 13 years using police/fire personnel and paramedics as responders. Resuscitation 2005; 65:279. 45. Mosesso VN Jr, Davis EA, Auble TE, et al. Use of automated external defibrillators by police officers for treatment of out-of-hospital cardiac arrest. Ann Emerg Med 1998; 32:200. 46. Myerburg RJ, Fenster J, Velez M, et al. Impact of community-wide police car deployment of automated external defibrillators on survival from out-of-hospital cardiac arrest. Circulation 2002; 106:1058. 47. Becker L, Husain S, Kudenchuk P, et al. Treatment of cardiac arrest with rapid defibrillation by police in King County, Washington. Prehosp Emerg Care 2014; 18:22. 48. Stein P, Spahn GH, M ller S, et al. Impact of city police layperson education and equipment with automatic external defibrillators on patient outcome after out of hospital cardiac https://www.uptodate.com/contents/automated-external-defibrillators/print 14/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate arrest. Resuscitation 2017; 118:27. 49. Groh WJ, Newman MM, Beal PE, et al. Limited response to cardiac arrest by police equipped with automated external defibrillators: lack of survival benefit in suburban and rural Indiana the police as responder automated defibrillation evaluation (PARADE). Acad Emerg Med 2001; 8:324. 50. Husain S, Eisenberg M. Police AED programs: a systematic review and meta-analysis. Resuscitation 2013; 84:1184. 51. Becker L, Eisenberg M, Fahrenbruch C, Cobb L. Public locations of cardiac arrest. Implications for public access defibrillation. Circulation 1998; 97:2106. 52. Frank RL, Rausch MA, Menegazzi JJ, Rickens M. The locations of nonresidential out-of- hospital cardiac arrests in the City of Pittsburgh over a three-year period: implications for automated external defibrillator placement. Prehosp Emerg Care 2001; 5:247. 53. Reed DB, Birnbaum A, Brown LH, et al. Location of cardiac arrests in the public access defibrillation trial. Prehosp Emerg Care 2006; 10:61. 54. Davies CS, Colquhoun M, Graham S, et al. Defibrillators in public places: the introduction of a national scheme for public access defibrillation in England. Resuscitation 2002; 52:13. 55. Davis TR, Young BA, Eisenberg MS, et al. Outcome of cardiac arrests attended by emergency medical services staff at community outpatient dialysis centers. Kidney Int 2008; 73:933. 56. Hansen CM, Lippert FK, Wissenberg M, et al. Temporal trends in coverage of historical cardiac arrests using a volunteer-based network of automated external defibrillators accessible to laypersons and emergency dispatch centers. Circulation 2014; 130:1859. 57. Caffrey SL, Willoughby PJ, Pepe PE, Becker LB. Public use of automated external defibrillators. N Engl J Med 2002; 347:1242. 58. Page RL, Joglar JA, Kowal RC, et al. Use of automated external defibrillators by a U.S. airline. N Engl J Med 2000; 343:1210. |
20. Meischke HW, Rea T, Eisenberg MS, et al. Training seniors in the operation of an automated external defibrillator: a randomized trial comparing two training methods. Ann Emerg Med 2001; 38:216. 21. Kerber RE, Becker LB, Bourland JD, et al. Automatic external defibrillators for public access defibrillation: recommendations for specifying and reporting arrhythmia analysis algorithm https://www.uptodate.com/contents/automated-external-defibrillators/print 12/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate performance, incorporating new waveforms, and enhancing safety. A statement for health professionals from the American Heart Association Task Force on Automatic External Defibrillation, Subcommittee on AED Safety and Efficacy. Circulation 1997; 95:1677. 22. Kramer-Johansen J, Edelson DP, Abella BS, et al. Pauses in chest compression and inappropriate shocks: a comparison of manual and semi-automatic defibrillation attempts. Resuscitation 2007; 73:212. 23. Nishiyama T, Nishiyama A, Negishi M, et al. Diagnostic Accuracy of Commercially Available Automated External Defibrillators. J Am Heart Assoc 2015; 4. 24. Hung KKC, Graham CA, Chan LK, et al. Performance of automated external defibrillators under conditions of in-flight turbulence. Resuscitation 2018; 130:41. 25. Carpenter J, Rea TD, Murray JA, et al. Defibrillation waveform and post-shock rhythm in out- of-hospital ventricular fibrillation cardiac arrest. Resuscitation 2003; 59:189. 26. van Alem AP, Sanou BT, Koster RW. Interruption of cardiopulmonary resuscitation with the use of the automated external defibrillator in out-of-hospital cardiac arrest. Ann Emerg Med 2003; 42:449. 27. Valenzuela TD, Kern KB, Clark LL, et al. Interruptions of chest compressions during emergency medical systems resuscitation. Circulation 2005; 112:1259. 28. Pytte M, Pedersen TE, Ottem J, et al. Comparison of hands-off time during CPR with manual and semi-automatic defibrillation in a manikin model. Resuscitation 2007; 73:131. 29. Hostler D, Everson-Stewart S, Rea TD, et al. Effect of real-time feedback during cardiopulmonary resuscitation outside hospital: prospective, cluster-randomised trial. BMJ 2011; 342:d512. 30. Stults KR, Brown DD, Schug VL, Bean JA. Prehospital defibrillation performed by emergency medical technicians in rural communities. N Engl J Med 1984; 310:219. 31. Weaver WD, Hill D, Fahrenbruch CE, et al. Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest. N Engl J Med 1988; 319:661. 32. Sweeney TA, Runge JW, Gibbs MA, et al. EMT defibrillation does not increase survival from sudden cardiac death in a two-tiered urban-suburban EMS system. Ann Emerg Med 1998; 31:234. 33. Kellermann AL, Hackman BB, Somes G, et al. Impact of first-responder defibrillation in an urban emergency medical services system. JAMA 1993; 270:1708. 34. Watts DD. Defibrillation by basic emergency medical technicians: effect on survival. Ann Emerg Med 1995; 26:635. https://www.uptodate.com/contents/automated-external-defibrillators/print 13/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate 35. Auble TE, Menegazzi JJ, Paris PM. Effect of out-of-hospital defibrillation by basic life support providers on cardiac arrest mortality: a metaanalysis. Ann Emerg Med 1995; 25:642. 36. Cobb LA, Fahrenbruch CE, Walsh TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999; 281:1182. 37. Rea TD, Helbock M, Perry S, et al. Increasing use of cardiopulmonary resuscitation during out-of-hospital ventricular fibrillation arrest: survival implications of guideline changes. Circulation 2006; 114:2760. 38. Tang W, Snyder D, Wang J, et al. One-shock versus three-shock defibrillation protocol significantly improves outcome in a porcine model of prolonged ventricular fibrillation cardiac arrest. Circulation 2006; 113:2683. 39. Berg MD, Clark LL, Valenzuela TD, et al. Post-shock chest compression delays with automated external defibrillator use. Resuscitation 2005; 64:287. 40. Berg RA, Hilwig RW, Kern KB, et al. Automated external defibrillation versus manual defibrillation for prolonged ventricular fibrillation: lethal delays of chest compressions before and after countershocks. Ann Emerg Med 2003; 42:458. 41. Berg RA, Hilwig RW, Berg MD, et al. Immediate post-shock chest compressions improve outcome from prolonged ventricular fibrillation. Resuscitation 2008; 78:71. 42. Waalewijn RA, de Vos R, Koster RW. Out-of-hospital cardiac arrests in Amsterdam and its surrounding areas: results from the Amsterdam resuscitation study (ARREST) in 'Utstein' style. Resuscitation 1998; 38:157. 43. White RD, Vukov LF, Bugliosi TF. Early defibrillation by police: initial experience with measurement of critical time intervals and patient outcome. Ann Emerg Med 1994; 23:1009. 44. White RD, Bunch TJ, Hankins DG. Evolution of a community-wide early defibrillation programme experience over 13 years using police/fire personnel and paramedics as responders. Resuscitation 2005; 65:279. 45. Mosesso VN Jr, Davis EA, Auble TE, et al. Use of automated external defibrillators by police officers for treatment of out-of-hospital cardiac arrest. Ann Emerg Med 1998; 32:200. 46. Myerburg RJ, Fenster J, Velez M, et al. Impact of community-wide police car deployment of automated external defibrillators on survival from out-of-hospital cardiac arrest. Circulation 2002; 106:1058. 47. Becker L, Husain S, Kudenchuk P, et al. Treatment of cardiac arrest with rapid defibrillation by police in King County, Washington. Prehosp Emerg Care 2014; 18:22. 48. Stein P, Spahn GH, M ller S, et al. Impact of city police layperson education and equipment with automatic external defibrillators on patient outcome after out of hospital cardiac https://www.uptodate.com/contents/automated-external-defibrillators/print 14/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate arrest. Resuscitation 2017; 118:27. 49. Groh WJ, Newman MM, Beal PE, et al. Limited response to cardiac arrest by police equipped with automated external defibrillators: lack of survival benefit in suburban and rural Indiana the police as responder automated defibrillation evaluation (PARADE). Acad Emerg Med 2001; 8:324. 50. Husain S, Eisenberg M. Police AED programs: a systematic review and meta-analysis. Resuscitation 2013; 84:1184. 51. Becker L, Eisenberg M, Fahrenbruch C, Cobb L. Public locations of cardiac arrest. Implications for public access defibrillation. Circulation 1998; 97:2106. 52. Frank RL, Rausch MA, Menegazzi JJ, Rickens M. The locations of nonresidential out-of- hospital cardiac arrests in the City of Pittsburgh over a three-year period: implications for automated external defibrillator placement. Prehosp Emerg Care 2001; 5:247. 53. Reed DB, Birnbaum A, Brown LH, et al. Location of cardiac arrests in the public access defibrillation trial. Prehosp Emerg Care 2006; 10:61. 54. Davies CS, Colquhoun M, Graham S, et al. Defibrillators in public places: the introduction of a national scheme for public access defibrillation in England. Resuscitation 2002; 52:13. 55. Davis TR, Young BA, Eisenberg MS, et al. Outcome of cardiac arrests attended by emergency medical services staff at community outpatient dialysis centers. Kidney Int 2008; 73:933. 56. Hansen CM, Lippert FK, Wissenberg M, et al. Temporal trends in coverage of historical cardiac arrests using a volunteer-based network of automated external defibrillators accessible to laypersons and emergency dispatch centers. Circulation 2014; 130:1859. 57. Caffrey SL, Willoughby PJ, Pepe PE, Becker LB. Public use of automated external defibrillators. N Engl J Med 2002; 347:1242. 58. Page RL, Joglar JA, Kowal RC, et al. Use of automated external defibrillators by a U.S. airline. N Engl J Med 2000; 343:1210. 59. Culley LL, Rea TD, Murray JA, et al. Public access defibrillation in out-of-hospital cardiac arrest: a community-based study. Circulation 2004; 109:1859. 60. Weisfeldt ML, Sitlani CM, Ornato JP, et al. Survival after application of automatic external defibrillators before arrival of the emergency medical system: evaluation in the resuscitation outcomes consortium population of 21 million. J Am Coll Cardiol 2010; 55:1713. 61. Hallstrom AP, Ornato JP, Weisfeldt M, et al. Public-access defibrillation and survival after out- of-hospital cardiac arrest. N Engl J Med 2004; 351:637. https://www.uptodate.com/contents/automated-external-defibrillators/print 15/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate 62. Nichol G, Huszti E, Birnbaum A, et al. Cost-effectiveness of lay responder defibrillation for out-of-hospital cardiac arrest. Ann Emerg Med 2009; 54:226. 63. Nichol G, Valenzuela T, Roe D, et al. Cost effectiveness of defibrillation by targeted responders in public settings. Circulation 2003; 108:697. 64. Groeneveld PW, Kwong JL, Liu Y, et al. Cost-effectiveness of automated external defibrillators on airlines. JAMA 2001; 286:1482. 65. Lee SJ, Anasetti C, Kuntz KM, et al. The costs and cost-effectiveness of unrelated donor bone marrow transplantation for chronic phase chronic myelogenous leukemia. Blood 1998; 92:4047. 66. Hornberger J, Best J, Geppert J, McClellan M. Risks and costs of end-stage renal disease after heart transplantation. Transplantation 1998; 66:1763. 67. Berdowski J, Blom MT, Bardai A, et al. Impact of onsite or dispatched automated external defibrillator use on survival after out-of-hospital cardiac arrest. Circulation 2011; 124:2225. 68. Kitamura T, Kiyohara K, Sakai T, et al. Public-Access Defibrillation and Out-of-Hospital Cardiac Arrest in Japan. N Engl J Med 2016; 375:1649. 69. Kitamura T, Iwami T, Kawamura T, et al. Nationwide public-access defibrillation in Japan. N Engl J Med 2010; 362:994. 70. Kiyohara K, Nitta M, Sato Y, et al. Ten-Year Trends of Public-Access Defibrillation in Japanese School-Aged Patients Having Neurologically Favorable Survival After Out-of-Hospital Cardiac Arrest. Am J Cardiol 2018; 122:890. 71. Blom MT, Beesems SG, Homma PC, et al. Improved survival after out-of-hospital cardiac arrest and use of automated external defibrillators. Circulation 2014; 130:1868. 72. Hazinski MF, Markenson D, Neish S, et al. Response to cardiac arrest and selected life- threatening medical emergencies: the medical emergency response plan for schools: A statement for healthcare providers, policymakers, school administrators, and community leaders. Circulation 2004; 109:278. 73. Lotfi K, White L, Rea T, et al. Cardiac arrest in schools. Circulation 2007; 116:1374. 74. Kovach J, Berger S. Automated external defibrillators and secondary prevention of sudden cardiac death among children and adolescents. Pediatr Cardiol 2012; 33:402. 75. Becker L, Gold LS, Eisenberg M, et al. Ventricular fibrillation in King County, Washington: a 30-year perspective. Resuscitation 2008; 79:22. 76. Ringh M, Rosenqvist M, Hollenberg J, et al. Mobile-phone dispatch of laypersons for CPR in out-of-hospital cardiac arrest. N Engl J Med 2015; 372:2316. https://www.uptodate.com/contents/automated-external-defibrillators/print 16/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate 77. Pijls RW, Nelemans PJ, Rahel BM, Gorgels AP. A text message alert system for trained volunteers improves out-of-hospital cardiac arrest survival. Resuscitation 2016; 105:182. 78. Bardy GH, Lee KL, Mark DB, et al. Home use of automated external defibrillators for sudden cardiac arrest. N Engl J Med 2008; 358:1793. 79. Chan PS, Krumholz HM, Nichol G, et al. Delayed time to defibrillation after in-hospital cardiac arrest. N Engl J Med 2008; 358:9. 80. Friedman FD, Dowler K, Link MS. A public access defibrillation programme in non-inpatient hospital areas. Resuscitation 2006; 69:407. 81. Gombotz H, Weh B, Mitterndorfer W, Rehak P. In-hospital cardiac resuscitation outside the ICU by nursing staff equipped with automated external defibrillators the first 500 cases. Resuscitation 2006; 70:416. 82. Chan PS, Krumholz HM, Spertus JA, et al. Automated external defibrillators and survival after in-hospital cardiac arrest. JAMA 2010; 304:2129. 83. Weil MH, Fries M. In-hospital cardiac arrest. Crit Care Med 2005; 33:2825. 84. Li Y, Bisera J, Tang W, Weil MH. Automated detection of ventricular fibrillation to guide cardiopulmonary resuscitation. Crit Pathw Cardiol 2007; 6:131. 85. Berger RD, Palazzolo J, Halperin H. Rhythm discrimination during uninterrupted CPR using motion artifact reduction system. Resuscitation 2007; 75:145. 86. Becker L, Eisenberg M, Fahrenbruch C, Cobb L. Cardiac arrest in medical and dental practices: implications for automated external defibrillators. Arch Intern Med 2001; 161:1509. 87. Callaway CW, Menegazzi JJ. Waveform analysis of ventricular fibrillation to predict defibrillation. Curr Opin Crit Care 2005; 11:192. 88. Eftest l T, Wik L, Sunde K, Steen PA. Effects of cardiopulmonary resuscitation on predictors of ventricular fibrillation defibrillation success during out-of-hospital cardiac arrest. Circulation 2004; 110:10. 89. Eisenberg MS. Is it time for over-the-counter defibrillators? JAMA 2000; 284:1435. Topic 1042 Version 31.0 https://www.uptodate.com/contents/automated-external-defibrillators/print 17/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate GRAPHICS Options for hands-free pacemaker/defibrillator pad positioning Positioning options for hands-free pacemaker/defibrillator pads showing anterior/lateral positioning (left) and anterior/posterior positioning (right). Graphic 103268 Version 2.0 https://www.uptodate.com/contents/automated-external-defibrillators/print 18/19 7/6/23, 11:27 AM Automated external defibrillators - UpToDate Contributor Disclosures Thomas D Rea, MD, MPH Grant/Research/Clinical Trial Support: Philips [Rhythm analysis algorithm]; Stryker [Brain Oximetry]. All of the relevant financial relationships listed have been mitigated. Mickey S Eisenberg, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Richard L Page, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/automated-external-defibrillators/print 19/19 |
7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Brugada syndrome: Clinical presentation, diagnosis, and evaluation : John V Wylie, MD, FACC : Samuel Asirvatham, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 19, 2023. INTRODUCTION Brugada syndrome is a genetic disorder that can cause life-threatening ventricular tachyarrhythmias and thereby sudden cardiac arrest and sudden cardiac death. Patients have abnormal findings on the surface electrocardiogram (ECG) but do not usually have any apparent cardiac structural abnormalities. The clinical manifestations, evaluation, and diagnosis of Brugada syndrome will be reviewed here. The epidemiology, pathogenesis, management, and prognosis of Brugada syndrome, along with a discussion of the other causes of sudden cardiac arrest in apparently normal hearts, are discussed elsewhere. (See "Brugada syndrome: Epidemiology and pathogenesis".) (See "Brugada syndrome or pattern: Management and approach to screening of relatives".) (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease".) BRUGADA PATTERN VERSUS SYNDROME https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 1/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Two terms, distinguished by the presence or absence of symptoms, have been used to describe patients with the typical ECG findings of a pseudo-right bundle branch block and persistent ST- segment elevation in either or both leads V1 to V2 ( waveform 1): Brugada pattern Patients with typical ECG features who are asymptomatic and have no other clinical criteria are said to have the Brugada pattern (sometimes referred to as Brugada phenocopies). Patients with ventricular premature beats or nonsustained ventricular tachycardia with no other types of ventricular arrhythmia (eg, sustained ventricular tachycardia) are generally considered to have Brugada pattern and not Brugada syndrome. Brugada syndrome Patients with typical ECG features who have experienced sudden cardiac death or a sustained ventricular tachyarrhythmia, or who have one or more of the other associated clinical criteria, are said to have Brugada syndrome. Persons with either Brugada pattern or Brugada syndrome can have identical findings on the surface ECG. (See '12-lead ECG' below.) CLINICAL PRESENTATION Demographic information Brugada syndrome is generally diagnosed between 22 and 65 years of age; it is rarely diagnosed in children. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Age at diagnosis'.) Brugada syndrome is more common in males than females. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Male predominance'.) Common scenarios ECG pattern without obvious symptoms Some patients with the Brugada pattern ECG do not present with symptoms. In these patients, Brugada syndrome can be identified as follows: When an ECG is performed for another reason (eg, preoperative evaluation, annual physical examination, etc). Part of the screening of first-degree relatives of a Brugada proband (ie, the first person in a family who brings the concern of a genetic disorder to the attention of healthcare professionals). In first-degree relatives, careful history taking reveals high-risk https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 2/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate symptoms or intermediate-risk factors that guide further testing for risk stratification and confirm the diagnosis. ECG and symptoms Patients with Brugada syndrome typically present with ECG findings characteristic of the Brugada ECG pattern ( waveform 1) and a clinical presentation that suggests ventricular arrhythmia. (See 'Symptoms' below.) Transient ECG pattern In some people, the Brugada pattern ECG may come and go, depending on whether provoking factors are present; such factors include fever, autonomic dysfunction, and exposure to specific prescription and illicit drugs. These are discussed in detail separately. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Pathogenesis'.) In one series of 43 patients with Brugada pattern ECGs in whom 310 ECGs were obtained over a median follow-up of 18 months, the following findings were noted [1]: Among 15 patients with a spontaneous Brugada type 1 ECG at presentation, 14 had at least one nondiagnostic (ie, not type 1) ECG during follow-up. Among 28 patients whose initial ECG was nondiagnostic, eight developed characteristic Brugada type 1 ECG abnormalities during follow-up. In a cohort of 251 patients with Brugada pattern ECG (including 30 percent with spontaneous Brugada type 1 ECG and 70 percent with drug-induced Brugada type 1 ECG) who underwent 12- lead ambulatory monitoring for 24 hours, the Brugada type 1 ECG pattern was frequently intermittent or absent during the 24-hour monitoring period [2]. (See 'Drug challenge for type 2 or equivocal ECG' below.) Symptoms Most clinical manifestations of the Brugada syndrome are related to life- threatening ventricular arrhythmias [3,4]. Specific symptoms are summarized as follows: Sudden cardiac arrest and/or death Sudden cardiac arrest resulting from ventricular tachyarrhythmia is one of the most significant clinical manifestations of Brugada syndrome. Clinical features in Brugada Arrhythmic events and sudden cardiac arrest have the following features: They are more common at night than in the day. They occur more commonly during sleep than while awake [5,6]. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 3/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Ventricular fibrillation and polymorphic ventricular tachycardia are more common than monomorphic ventricular tachycardia [7]. Episodes are not usually secondary to exercise [8]. Premature ventricular beats can initiate ventricular fibrillation [9]. Stored electrograms from implantable cardioverter-defibrillators have shown that frequent spontaneous premature ventricular beats, which are identical in morphology to those that initiate ventricular fibrillation, are often seen before the onset of the arrhythmia [9]. (See 'Conditions causing ventricular arrythmia and no structural heart disease' below.) Sudden unexpected noctural death syndrome Sudden cardiac arrest is more common at night in patients with Brugada syndrome, and sleep-disordered breathing appears to be more commonly seen in patients with Brugada syndrome [10]. A pattern of nocturnal agonal respiration with gasping breaths during sleep has been reported and may represent aborted cardiac arrhythmias. This is generally considered an ominous symptom that should be considered the equivalent of arrhythmogenic syncope or malignant ventricular arrhythmias when evaluating the patient using diagnostic criteria. Sudden unexpected nocturnal death syndrome (SUNDS; also called sudden unexpected death syndrome or SUDS) has been described in young, apparently healthy males from different Asian countries; this syndrome has several names depending on geography, including the following [11-13]: Lai tai (death during sleep) in Thailand Bangungut (to rise and moan in sleep followed by death) in the Philippines Bokkuri (unexpected sudden cardiac death at night) in Japan SUNDS and Brugada syndrome are phenotypically, genetically, and functionally the same disorder [14,15]. Thus, the management of these patients should be the same as that for classic Brugada syndrome. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'High-risk patients'.) A low serum potassium level may contribute to sudden cardiac arrest in these patients [14]. It has been suggested that a high carbohydrate meal may precipitate sudden cardiac arrest, perhaps by increasing the secretion of insulin, which drives extracellular potassium into cells. A relationship between SUNDS and Brugada syndrome was initially suggested by the observation that a majority of patients with SUNDS have the ECG manifestations of Brugada syndrome [13]. This association was confirmed by observations that patients with SUNDS have https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 4/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate mutations in the same cardiac sodium channel gene (SCN5A) that is abnormal in Brugada syndrome [15]. (See "Brugada syndrome: Epidemiology and pathogenesis".) Syncope Syncope resulting from ventricular tachyarrhythmias is a clinically significant clinical manifestation of Brugada syndrome; however, not all episodes of syncope are due to ventricular arrhythmia. One study of patients with Brugada syndrome suggested that 30 percent of syncopal episodes may be due to nonarrhythmic causes (eg, neurocardiogenic) [16]. Palpitations Palpitations related to ventricular tachyarrhythmia are not common in patients with Brugada syndrome and when present may be due to atrial fibrillation. Atrial fibrillation is associated with Brugada syndrome and may be the first presentation of the disease [17,18]. The relationship between atrial arrhythmias and Brugada syndrome results from sodium channel abnormalities that involve both the atria and the ventricles. The incidence of atrial fibrillation is 10 to 20 percent in patients with Brugada syndrome. Among 611 patients with Brugada pattern ECG, the diagnosis of atrial fibrillation preceded the diagnosis of Brugada pattern ECG in 5.7 percent [19]. Patients with Brugada syndrome are also at increased risk of other atrial arrhythmias [17,18,20,21]. The presence of atrial fibrillation has been associated with increased disease severity and a higher risk of ventricular fibrillation. This is discussed in detail separately. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'Intermediate-risk factors'.) Provoking factors Fever Fever can be a trigger for both induction of Brugada pattern ECG abnormalities and cardiac arrest among persons known to have Brugada pattern ECG or Brugada syndrome. Animal models have helped elucidate how hyperthermia causes changes in sodium current function; a reduction in sodium current results in changes to the action potential predisposing to ventricular fibrillation [22]. Brugada pattern is more common in patients with fever In a study of 402 febrile emergency department patients and 909 controls, type I Brugada pattern ECG changes were 20 times more common in febrile patients (2 versus 0.1 percent) [23]. Reassuringly, none of these patients had cardiac events over 30 months of follow-up. Sudden cardiac arrest in febrile patients with Brugada syndrome In a single-center retrospective review of 111 patients with confirmed Brugada syndrome, 22 patients had cardiac arrest, of whom four (18 percent) had a preceding fever [24]. In a subset of 24 of https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 5/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate the 111 patients with ECGs recorded during fever and normothermia, ECGs taken during fever had prolonged QRS and QT intervals and worsening ST elevation ( waveform 2). In the Survey on Arrhythmic Events in Brugada Syndrome (SABRUS), an international multicenter registry of 678 patients with a documented arrhythmic event, 6 percent had an arrhythmic event during febrile illness [25]. The pediatric population displayed the highest rate of fever-related arrhythmic event (age <16 years), with a disproportionally higher event rate in the very young (age 0 to 5 years, 65 percent). Medications The characteristic Brugada pattern ECG abnormalities may be exposed by a sodium channel blocker, such as flecainide, ajmaline, or procainamide ( table 1) [5,14,26- 28]. The known properties of some of these agents allow them to be utilized as part of a drug challenge to confirm the diagnosis. (See 'Drug challenge for type 2 or equivocal ECG' below.) Other common medications that can unmask or modulate the Brugada ECG pattern are beta blockers and tricyclic or tetracyclic antidepressants. Lithium and local anesthetics can also provoke Brugada ( table 1) [14,29,30]. A reference website has been established that identifies drugs that can provoke adverse events in patients with Brugada syndrome [31]. The clinical significance of drug-provoked ECG changes in the absence of symptoms or family history of Brugada syndrome or pattern is undetermined. Toxins Alcohol and cocaine can unmask Brugada syndrome [32,33]. Metabolic disturbances Patients with metabolic disturbances (eg, severe hyperkalemia) may present with Brugada pattern ECG, which is reversible following correction of the underlying metabolic disturbance [34]. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Cocaine abuse' and "Brugada syndrome: Epidemiology and pathogenesis", section on 'Psychotropic drugs'.) DIAGNOSTIC EVALUATION When a patient is suspected to have Brugada syndrome, additional evaluation may be required to confirm the diagnosis ( algorithm 1). In general, all additional diagnostic testing should be performed following consultation with an electrophysiologist or a general cardiologist with specific training and expertise in the diagnosis and management of Brugada syndrome [35]. We perform initial steps in all patients with suspected Brugada syndrome, regardless of our index of suspicion. After these initial steps, our subsequent approach to the evaluation and risk https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 6/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate stratification of patients with Brugada pattern ECG finding ( waveform 1) depends on whether there is an intermediate or low suspicion that the patient has Brugada syndrome. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'Risk factors for arrhythmia or sudden cardiac arrest'.) We do not perform genetic testing as part of our diagnostic work-up. However, there may be a role for genetic testing in screening of first-degree relatives of a person diagnosed with Brugada syndrome. This is discussed separately. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'Screening relatives'.) Initial steps to diagnose Brugada syndrome In all patients in whom Brugada syndrome is suspected, we undertake a medical history, 12-lead ECG, and evaluate for any underlying structural heart disease. Both Brugada pattern ECG findings and clinical features consistent with ventricular arrhythmia are required to make the diagnosis [36,37]. We evaluate for structural heart disease to rule out causes that could underlie the ventricular arrythmia other than Brugada syndrome. If this evaluation does not reveal structural heart disease or myocardial ischemia, and the patient has clinical risk factors and spontaneous type 1 Brugada pattern ECG changes, Brugada syndrome is diagnosed and patients should be treated accordingly. The appearance of typical ECG changes alone without other clinical manifestations or intermediate risk factors is considered to represent the Brugada ECG pattern but not the Brugada syndrome. Medical history The first step in the evaluation of patients with suspected Brugada syndrome is to take a medical history with a central goal of identifying clinical risk factors that would support the diagnosis of Brugada syndrome along with the ECG findings. (See 'Clinical presentation' above.) 12-lead ECG Our initial diagnostic test is a 12-lead ECG. (See "ECG tutorial: Basic principles of ECG analysis" and "ECG tutorial: Electrical components of the ECG".) If the initial ECG is equivocal, we move the right precordial leads up to the second or third intercostal space, as this modification may increase the sensitivity of detecting these abnormalities [14,38]. Two distinct patterns of ST elevation have been recognized in patients with Brugada syndrome ( figure 1 and table 2) [14,39,40]: https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 7/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate In the type 1 Brugada ECG pattern, the elevated ST segment ( 2 mm) descends with an upward convexity to an inverted T wave ( figure 1). This is referred to as the "coved type" Brugada pattern. In the type 2 Brugada ECG pattern (combined from the original designation of types 2 and 3 patterns), the ST segment has a "saddle back" ST-T wave configuration, in which the elevated ST segment descends toward the baseline, then rises again to an upright or biphasic T wave ( figure 1). Other ECG findings characteristic of Brugada syndrome include: J wave There is a high takeoff of the ST segment in the right precordium (ie, a "J" wave rather than a true right bundle branch block) due to abnormal repolarization in the right ventricular outflow tract [41]. Thus, the widened S wave in left lateral leads that is characteristic of right bundle branch block ( waveform 3) is absent in most patients with Brugada pattern ECGs. [42,43]. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Pathogenesis'.) QT interval prolongation This may be seen in the right precordial leads [44]. The degree of prolongation is usually modest, but some patients have genetic abnormalities that cause both Brugada pattern ECG and long QT syndrome [45-47]. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Related disorders with SCN mutations'.) Increased S wave voltage and duration The finding of an S wave in lead 1 that is 0.1 millivolts and 40 milliseconds in duration (thought to represent delayed right ventricular outflow tract conduction) may be a strong predictor of sudden death. In a cohort of 347 asymptomatic patients with spontaneous type 1 Brugada pattern ECGs, 9 percent developed ventricular fibrillation or sudden cardiac death over a mean follow-up of four years [48]. The presence of an S wave in lead 1 (hazard ratio 39.1) was associated with sudden death, with a negative predictive value of nearly 99 percent. This finding has not been confirmed in subsequent studies. Persons with Brugada pattern findings on a surface ECG have some form of a pseudo-right bundle branch block and persistent ST-segment elevation in leads V1 to V2 ( waveform 1) [49]. Testing for underlying heart disease All patients with suspected Brugada syndrome require additional testing to exclude underlying structural heart disease, and many may require testing to exclude myocardial ischemia. It is important to recognize that patients with Brugada syndrome do not typically have structural heart disease. Therefore, standard cardiac testing, including cardiac imaging (with echocardiography and/or cardiac magnetic resonance imaging) https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 8/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate and cardiac stress testing, often reveal no abnormalities or if abnormalities are present, this suggests an alternative diagnosis. (See 'Differential diagnosis' below.) Testing for underlying heart disease will typically include one or more the following: Echocardiogram to evaluate for myocardial diseases and ischemic heart disease. (See "Echocardiographic recognition of cardiomyopathies".) Cardiac stress testing to evaluate suspicion for obstructive coronary artery disease if there is intermediate or high risk of coronary artery disease. (See "Stress testing for the diagnosis of obstructive coronary heart disease".) Cardiac magnetic resonance imaging. Some centers may perform cardiac magnetic resonance imaging in lieu of echocardiography (or as a follow-up if the echocardiogram is of suboptimal technical quality). (See "Clinical utility of cardiovascular magnetic resonance imaging".) Among patients in whom a signal-averaged ECG suggests arrhythmic substrate, we obtain cardiac magnetic resonance imaging to rule out widespread scar and other cardiac structural abnormalities that may make a diagnosis of Brugada syndrome less likely. Patients with Brugada syndrome may have morphological changes in the right ventricular outflow tract related to Brugada syndrome, including dilation and fibrosis, although these are not specific enough to aid in the diagnosis [50]. In 69 patients who underwent cardiac magnetic resonance imaging, those with spontaneous type 1 Brugada pattern ECGs had 2 centimeter larger right ventricular outflow tract dimensions (as well as mildly lower left and right ventricular ejection fractions) compared with patients with drug-induced type 1 Brugada pattern ECGs and controls. Drug challenge for type 2 or equivocal ECG If the initial evaluation of a patient does not reveal structural heart disease or myocardial ischemia, and the patient has spontaneous type 2 Brugada pattern or other equivocal ECG changes, we perform a drug challenge using a sodium channel blocker in an attempt to elicit the type 1 Brugada ECG pattern. Among some patients with the type 2 Brugada ECG pattern, the type 1 Brugada ECG pattern can be unmasked by sodium channel blockers (eg, flecainide, procainamide, ajmaline, pilsicainide) ( waveform 4 and waveform 5) [14,26-28]. The importance of unmasking the type 1 Brugada ECG pattern relates to its relevance for risk stratification in asymptomatic patients and for confirming the diagnosis of Brugada syndrome in symptomatic patients [51]. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 9/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate While drug challenge can be helpful when positive, the reported sensitivity of pharmacologic challenge with these drugs has been variable, ranging from as low as 15 percent to as high as 100 percent [27,52]. The duration of monitoring following the administration of the challenge agent is likely related to the sensitivity of the test. Indications We do perform a drug challenge in the following patients: For asymptomatic patients if the resting ECG shows the type 2 Brugada pattern and there is a family history of sudden cardiac death at less than 45 years of age and/or a family history of type 1 Brugada pattern ECG changes. For symptomatic patients whose resting ECG shows the type 2 Brugada pattern, our experts feel that drug challenge is not always necessary. Patients who are high risk will undergo treatment of Brugada syndrome regardless of the results of drug testing. However, drug testing may be used in these patients to establish a diagnosis, which may guide future management and prompt risk stratification of family members. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'High-risk patients'.) In a study of 245 patients with Brugada syndrome who underwent sodium channel blocker challenge with pilsicainide (181 patients with spontaneous type 1 ECG, 64 patients with non-type 1 ECG), induced ventricular arrhythmias and ST-segment augmentation were associated with an increased risk of the development of ventricular tachycardia/ventricular fibrillation events during a mean follow-up of 113 months [53]. We do not perform a drug challenge in patients with the following: Spontaneous type 1 Brugada pattern ECG findings, with or without symptoms. For asymptomatic patients whose resting ECG shows the type 2 Brugada pattern and who have no known family history of sudden cardiac death, we do not recommend a drug challenge. Procedure A drug challenge should only be performed by clinicians experienced in the administration of sodium-channel-blocking drugs and interpretation of ECGs. During the drug challenge, continuous ECG monitoring is required. The typical duration of monitoring is 30 minutes following intravenous drug administration and up to four hours or longer if oral flecainide is used for the drug challenge. One of several sodium-channel-blocking drugs can be used for the drug challenge [54]. Testing should be performed in a closely monitored setting on telemetry with a code cart readily https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 10/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate accessible, as drug challenge may precipitate ventricular arrhythmias in some patients. Recommended doses for the different drugs include [14]: Flecainide 2 mg/kg over 10 minutes intravenously or 400 mg orally Procainamide 10 mg/kg over 10 minutes intravenously Ajmaline 1 mg/kg over 5 minutes intravenously Pilsicainide 1 mg/kg over 10 minutes intravenously The choice of one agent versus another is typically site specific and based upon availability, as no head-to-head comparisons have been performed. One nonrandomized study of 425 patients referred for drug challenge showed that patients challenged with ajmaline were more likely to develop a type I Brugada ECG pattern than those challenged with procainamide (26 versus 4 percent) [55]. We terminate the drug challenge for the following reasons: Development of a diagnostic type 1 Brugada ECG pattern 2 mm increase in ST-segment elevation in patients with a type 2 Brugada ECG pattern Development of ventricular premature beats or other arrhythmias Widening of the QRS 30 percent above baseline Ventricular arrythmias Sustained ventricular arrhythmias following drug challenge have been reported in 1 to 2 percent of drug challenges and with all of the drugs used for the challenge [27,56-60]. With ajmaline challenge In a systematic review of 16 studies of ajmaline challenge (totalling 3515 tests), 33 patients (0.9 percent) developed ventricular tachycardia or ventricular fibrillation [59]. In a large cohort of 503 patients with unmasking of a Brugada pattern ECG following ajmaline administration, 2 percent developed sustained ventricular arrhythmias requiring defibrillation [58]. Family members of probands with Brugada syndrome Among 672 such patients who were asymptomatic and underwent screening with drug challenge, ventricular tachycardia or fibrillation developed in 10 patients (1.5 percent) [60]. Risk stratification for those with uncertain diagnosis In patients with intermediate risk factors for Brugada syndrome, we undertake risk stratification to establish a diagnosis and to decide therapy ( table 3). Signal-averaged ECG (SAECG) In patients with suspected Brugada syndrome in whom there is a negative drug challenge or in whom the diagnosis is still uncertain (eg, type 1 ECG with https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 11/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate intermediate or other equivocal risk factors), we obtain an SAECG for risk stratification. The SAECG may be helpful in identifying patients with Brugada pattern ECG and an increased risk of future arrhythmic events [61]. A normal SAECG makes the diagnosis of Brugada syndrome highly unlikely. The SAECG is useful for detecting subtle abnormalities in the surface ECG that are not visible to the naked eye. One example of such an abnormality is the "ventricular late potential," a low-amplitude signal near the end of the QRS complex that can be used to stratify risk for ventricular tachyarrhythmias in patients with cardiomyopathies of various etiologies. In a study of 43 patients with Brugada syndrome, the presence of late potentials on SAECG were associated with later arrhythmic events [61]. Patients with late potentials had a greater incidence of arrhythmic events over 34 month of follow-up compared with those without late potentials (72.4 versus 14.3 percent) [62]. (See "Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications".) Electrophysiology testing In certain cases, electrophysiology testing may be offered to patients for further risk stratification in the presence of equivocal symptoms or moderate or possible risk factors; in these cases, an electrophysiologic study may be part of the decision- making process when determining further management. This is discussed in detail separately. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'Intermediate-risk patients'.) Patients with a Brugada ECG pattern and certain high-risk clinical features (ie, a history of sudden cardiac arrest, sustained ventricular tachyarrhythmias, or unexplained syncope) have an indication for implantable cardioverter-defibrillator implantation, so invasive electrophysiology testing is unlikely to impact management [5,41,63-66]. For the majority of asymptomatic patients with Brugada pattern ECG findings, invasive electrophysiology testing is not necessary [61,67]. Indeed, the role of electrophysiology testing in asymptomatic patients remains an area of investigation, and prior studies have been equivocal. In a 2017 systematic review performed as part of the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines, which included six studies of 1138 asymptomatic patients with Brugada ECG findings who had undergone invasive electrophysiology testing with programmed ventricular stimulation, 34.3 percent were found to have inducible ventricular tachycardia during electrophysiology testing [67]. During follow-up, those who had inducible ventricular tachycardia had a higher rate of arrhythmic events (sustained ventricular https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 12/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate tachycardia, sudden cardiac death, or appropriate defibrillator therapy) compared with those with no inducible ventricular tachycardia (3.3 versus 1.6 percent; odds ratio 2.3; 95% CI 0.6-8.7); however, this was not statistically significant. In a 2016 metaanalysis of eight nonrandomized studies of 883 asymptomatic patients with a spontaneous type 1 Brugada pattern ECGs who were followed for 33.8 months, patients had a low incidence of subsequent cardiac arrest or ventricular arrythmia (annual incidence per 100 persons = 1). Those with inducible ventricular arrhythmias on electrophysiology testing had a similar rate compared with patients without inducible arrythmias (hazard ratio 1.70- 95% CI 0.73-3.35) [68]. The overall low event rate is reassuring and suggests asymptomatic patients with Brugada ECG findings have a low risk of future arrhythmic events. There is some evidence that electrophysiology testing combined with myocardial substrate electroanatomic mapping may be a way to more accurately predict inducible arrhythmias [69]; however, this has not been well studied. Insertable cardiac monitor For patients who have nonspecific symptoms for Brugada syndrome (eg, neurocardiogenic syncope, palpitations, or presyncope), the risk of life- threatening arrythmia may be uncertain; in such patients, an insertable cardiac monitor (ICM) may help elucidate a diagnosis. A registry study of 50 patients with Brugada syndrome treated with ICM demonstrated a 22 percent diagnostic yield [70]. The majority of these events were bradyarrhythmias, and only one patient had a concerning ventricular arrhythmia (nonsustained polymorphic ventricular tachycardia) [70]. (See "Ambulatory ECG monitoring", section on 'Insertable cardiac monitor'.) Genetic testing Genetic testing for a mutation in the SCN5A gene or other causative genetic variant should be performed in asymptomatic patients with a Brugada pattern ECG only when a definitive mutation has been identified within the family proband. The genetic and clinical heterogeneity of Brugada syndrome limit the utility of genetic testing, as the absence of a mutation in SCN5A or other pathogenic variant does not exclude Brugada syndrome, and the presence of such a variant does not confirm the diagnosis of Brugada syndrome. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'Screening relatives'.) ALTERNATIVE APPROACHES AND OTHER GUIDELINE GROUPS Because of the clinical variability in presentation and the different ECG manifestations that can be seen in Brugada syndrome, diagnostic criteria have been proposed by professional societies https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 13/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate from both Europe and North America [3,14,39]. In 2013, three major professional societies, the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the Asia Pacific Heart Rhythm Society (APHRS), jointly issued an expert consensus statement on inherited arrhythmia syndromes, which included updated diagnostic criteria for Brugada syndrome [3]. We broadly agree with this statement that suggests that Brugada syndrome should be "definitively diagnosed" with symptoms, and the presence of type I Brugada pattern ECG changes in at least one right precordial lead (specifically V1 or V2), either spontaneously or following drug challenge with a sodium channel blocker, using standard or superior ECG lead placement. (See 'Drug challenge for type 2 or equivocal ECG' above.) For a patient with type I Brugada pattern ECG findings who is otherwise asymptomatic, clinical findings that would support the diagnosis of Brugada syndrome include the following: Presence of first-degree atrioventricular block and left axis deviation on the ECG Atrial fibrillation (see 'Palpitations' above) Late potentials seen on signal-averaged ECG (SAECG) (see "Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications") Fragmented QRS complex ST-T wave alternans with spontaneous ventricular premature beats in a left bundle branch block pattern on prolonged ECG recording Ventricular refractory period <200 milliseconds and HV (His bundle to ventricular myocardium) interval >60 milliseconds during invasive electrophysiology study Absence of structural heart disease, including myocardial ischemia We agree with the 2013 HRS/EHRA/APHRS consensus statement, which updated the 2005 criteria, but the original criteria continue to be frequently cited in clinical practice and more specifically define criteria to diagnose Brugada syndrome [14]. This includes the appearance of type 1 ST-segment elevation (coved type) in more than one right precordial lead (V1 to V2) in the presence or absence of a sodium channel blocker, plus at least one of the following: Documented ventricular fibrillation Polymorphic ventricular tachycardia Family history of sudden cardiac death at less than 45 years of age Family history of type 1 Brugada pattern ECG changes Inducible ventricular tachycardia during electrophysiology study Unexplained syncope suggestive of a tachyarrhythmia Nocturnal agonal respiration https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 14/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate DIFFERENTIAL DIAGNOSIS The differential diagnosis of Brugada syndrome includes conditions that have similar ECG findings with Brugada syndrome and/or conditions that have clinical features consistent with ventricular arrhythmia. Conditions with ECG similar to Brugada pattern The differential diagnosis for Brugada pattern ECG changes includes other conditions that result in apparent conduction and ST- segment abnormalities in leads V1 to V2 on the ECG. Arrhythmogenic right ventricular dysplasia The Brugada pattern on ECG can be seen as an early subclinical manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC) [64]. ARVC is a genetic disorder, usually autosomal dominant, that primarily involves the right ventricle, as the right ventricular myocardium is typically replaced by fat, with scattered residual myocardial cells and fibrous tissue. (See "Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics".) A study of 96 victims of sudden cardiac death who were 35 years and had a baseline ECG available suggested an association between ARVC and the Brugada pattern on ECG [8]. Right precordial ST-segment elevation with or without right bundle branch block was present in 13 percent of patients; at autopsy, all but one had ARVC. However, this study was from southern Italy, where ARVC has a high prevalence and is an important cause of sudden cardiac death. Furthermore, mutations in SCN5A have not been described in ARVC but are a recognized cause of Brugada syndrome. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'SCN5A'.) Patients with ARVC often have abnormalities in the right ventricle that can be seen on echocardiography or cardiac magnetic resonance imaging. In contrast, the vast majority of patients with Brugada syndrome do not have apparent structural heart disease on routine imaging studies [14]. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis", section on 'Diagnostic evaluation'.) Other causes of ST changes in V1 to V2 These include: Right bundle branch block (see "Right bundle branch block", section on 'ECG findings and diagnosis') Early repolarization (see "Early repolarization", section on 'ECG findings') Acute pericarditis (see "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram') https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 15/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Acute myocardial ischemia or infarction (see "Electrocardiogram in the diagnosis of myocardial ischemia and infarction") Left ventricular hypertrophy (see "Left ventricular hypertrophy: Clinical findings and ECG diagnosis") Pectus excavatum (see "Pectus excavatum: Etiology and evaluation", section on 'Cardiac function') Hypothermia (see "ECG tutorial: Miscellaneous diagnoses", section on 'Hypothermia') Blunt chest trauma (eg, driver in an motor vehicle accident) Conditions causing ventricular arrythmia and no structural heart disease The differential |
asymptomatic patients with Brugada ECG findings have a low risk of future arrhythmic events. There is some evidence that electrophysiology testing combined with myocardial substrate electroanatomic mapping may be a way to more accurately predict inducible arrhythmias [69]; however, this has not been well studied. Insertable cardiac monitor For patients who have nonspecific symptoms for Brugada syndrome (eg, neurocardiogenic syncope, palpitations, or presyncope), the risk of life- threatening arrythmia may be uncertain; in such patients, an insertable cardiac monitor (ICM) may help elucidate a diagnosis. A registry study of 50 patients with Brugada syndrome treated with ICM demonstrated a 22 percent diagnostic yield [70]. The majority of these events were bradyarrhythmias, and only one patient had a concerning ventricular arrhythmia (nonsustained polymorphic ventricular tachycardia) [70]. (See "Ambulatory ECG monitoring", section on 'Insertable cardiac monitor'.) Genetic testing Genetic testing for a mutation in the SCN5A gene or other causative genetic variant should be performed in asymptomatic patients with a Brugada pattern ECG only when a definitive mutation has been identified within the family proband. The genetic and clinical heterogeneity of Brugada syndrome limit the utility of genetic testing, as the absence of a mutation in SCN5A or other pathogenic variant does not exclude Brugada syndrome, and the presence of such a variant does not confirm the diagnosis of Brugada syndrome. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'Screening relatives'.) ALTERNATIVE APPROACHES AND OTHER GUIDELINE GROUPS Because of the clinical variability in presentation and the different ECG manifestations that can be seen in Brugada syndrome, diagnostic criteria have been proposed by professional societies https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 13/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate from both Europe and North America [3,14,39]. In 2013, three major professional societies, the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the Asia Pacific Heart Rhythm Society (APHRS), jointly issued an expert consensus statement on inherited arrhythmia syndromes, which included updated diagnostic criteria for Brugada syndrome [3]. We broadly agree with this statement that suggests that Brugada syndrome should be "definitively diagnosed" with symptoms, and the presence of type I Brugada pattern ECG changes in at least one right precordial lead (specifically V1 or V2), either spontaneously or following drug challenge with a sodium channel blocker, using standard or superior ECG lead placement. (See 'Drug challenge for type 2 or equivocal ECG' above.) For a patient with type I Brugada pattern ECG findings who is otherwise asymptomatic, clinical findings that would support the diagnosis of Brugada syndrome include the following: Presence of first-degree atrioventricular block and left axis deviation on the ECG Atrial fibrillation (see 'Palpitations' above) Late potentials seen on signal-averaged ECG (SAECG) (see "Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications") Fragmented QRS complex ST-T wave alternans with spontaneous ventricular premature beats in a left bundle branch block pattern on prolonged ECG recording Ventricular refractory period <200 milliseconds and HV (His bundle to ventricular myocardium) interval >60 milliseconds during invasive electrophysiology study Absence of structural heart disease, including myocardial ischemia We agree with the 2013 HRS/EHRA/APHRS consensus statement, which updated the 2005 criteria, but the original criteria continue to be frequently cited in clinical practice and more specifically define criteria to diagnose Brugada syndrome [14]. This includes the appearance of type 1 ST-segment elevation (coved type) in more than one right precordial lead (V1 to V2) in the presence or absence of a sodium channel blocker, plus at least one of the following: Documented ventricular fibrillation Polymorphic ventricular tachycardia Family history of sudden cardiac death at less than 45 years of age Family history of type 1 Brugada pattern ECG changes Inducible ventricular tachycardia during electrophysiology study Unexplained syncope suggestive of a tachyarrhythmia Nocturnal agonal respiration https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 14/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate DIFFERENTIAL DIAGNOSIS The differential diagnosis of Brugada syndrome includes conditions that have similar ECG findings with Brugada syndrome and/or conditions that have clinical features consistent with ventricular arrhythmia. Conditions with ECG similar to Brugada pattern The differential diagnosis for Brugada pattern ECG changes includes other conditions that result in apparent conduction and ST- segment abnormalities in leads V1 to V2 on the ECG. Arrhythmogenic right ventricular dysplasia The Brugada pattern on ECG can be seen as an early subclinical manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC) [64]. ARVC is a genetic disorder, usually autosomal dominant, that primarily involves the right ventricle, as the right ventricular myocardium is typically replaced by fat, with scattered residual myocardial cells and fibrous tissue. (See "Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics".) A study of 96 victims of sudden cardiac death who were 35 years and had a baseline ECG available suggested an association between ARVC and the Brugada pattern on ECG [8]. Right precordial ST-segment elevation with or without right bundle branch block was present in 13 percent of patients; at autopsy, all but one had ARVC. However, this study was from southern Italy, where ARVC has a high prevalence and is an important cause of sudden cardiac death. Furthermore, mutations in SCN5A have not been described in ARVC but are a recognized cause of Brugada syndrome. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'SCN5A'.) Patients with ARVC often have abnormalities in the right ventricle that can be seen on echocardiography or cardiac magnetic resonance imaging. In contrast, the vast majority of patients with Brugada syndrome do not have apparent structural heart disease on routine imaging studies [14]. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis", section on 'Diagnostic evaluation'.) Other causes of ST changes in V1 to V2 These include: Right bundle branch block (see "Right bundle branch block", section on 'ECG findings and diagnosis') Early repolarization (see "Early repolarization", section on 'ECG findings') Acute pericarditis (see "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram') https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 15/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Acute myocardial ischemia or infarction (see "Electrocardiogram in the diagnosis of myocardial ischemia and infarction") Left ventricular hypertrophy (see "Left ventricular hypertrophy: Clinical findings and ECG diagnosis") Pectus excavatum (see "Pectus excavatum: Etiology and evaluation", section on 'Cardiac function') Hypothermia (see "ECG tutorial: Miscellaneous diagnoses", section on 'Hypothermia') Blunt chest trauma (eg, driver in an motor vehicle accident) Conditions causing ventricular arrythmia and no structural heart disease The differential diagnosis of Brugada syndrome includes a broad range of conditions in which there are clinical manifestations of ventricular tachyarrhythmias (ie, sudden cardiac death, syncope) and no apparent cardiac structural abnormalities. Congenital long QT syndrome (LQTS) Patients with a documented or suspected ventricular arrhythmia associated with prolongation of the QT interval are more likely to have LQTS than Brugada syndrome. Congenital LQTS should be suspected if the patient has no acquired cause of a long QT such as medications of electrolyte imbalance. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations".) Acquired LQTS with polymorphic ventricular tachycardia This diagnosis should be considered if the patient has a QTc prolongation or has been exposed to medications or other triggers, such as electrolyte imbalance, that may prolong the QT interval. Similarly, patients with ventricular tachycardia or sudden cardiac death whose QT interval is markedly shortened are more likely to have short QT syndrome. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Short QT syndrome Patients with a documented or suspected ventricular arrhythmia associated with a short QT interval (usually <360 milliseconds with a range of 220 to 360 milliseconds) are more likely to have a short QT interval rather than Brugada syndrome. (See "Short QT syndrome".) Catecholaminergic polymorphic ventricular tachycardia Patients who experience ventricular tachycardia or sudden cardiac death in the setting of exertion are more likely to have catecholaminergic polymorphic ventricular tachycardia than Brugada syndrome, in which symptomatic tachyarrhythmias are more likely to occur at rest. (See "Catecholaminergic polymorphic ventricular tachycardia".) Commotio cordis Patients with ventricular tachycardia or sudden cardiac death immediately following blunt chest trauma are more likely to have experienced commotio cordis than Brugada https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 16/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate syndrome. Commonly, the blunt trauma is experienced during a sporting event by a projectile object (eg, baseball or hockey puck) traveling at a velocity greater than 20 miles per hour. Often, the patient collapses within two to three seconds of impact. (See "Commotio cordis".) Idiopathic ventricular tachycardia or fibrillation If patients undergo a thorough evaluation for Brugada syndrome and are not found to have spontaneous or drug-induced ECG findings consistent with Brugada syndrome or any other cause of ventricular arrythmia in the absence of structural heart disease, it is possible that idiopathic ventricular tachycardia or ventricular fibrillation are present. It is important to note that both of these are diagnoses of exclusion. (See "Ventricular tachycardia in the absence of apparent structural heart disease" and "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF'.) PEDIATRIC PATIENTS Brugada syndrome is rarely diagnosed in children. In the largest international multicenter registry (SABRUS) of patients with Brugada syndrome with a documented first arrhythmic event, only 0.8 percent of patients were <16 years. [71]. Demographic features In a report from the SABRUS cohort, which included 57 patients age 20 years, pediatric patients (age 12 years) were more likely than adolescents (age 13 to 20 years) to be female (42 versus 13 percent) [72]. Clinical diagnosis and natural history The majority of children diagnosed with Brugada syndrome are identified based on family screening, whereas a smaller subset presented with a clinical event consistent with ventricular arrhythmia. This was illustrated in a cohort of 30 children with Brugada syndrome (mean age eight years) diagnosed at 13 referral centers in Europe [73]. In this study, 17 of 30 were diagnosed based on family screening, 10 had prior unexplained syncope, and one presented with aborted sudden cardiac death. The following are more common among pediatric compared with adolescent patients [72]: Spontaneous type I Brugada ECG pattern (81 versus 52 percent), Fever associated with their arrhythmic event (54 versus 7 percent). Recurrent events earlier Drug challenge Repeat ajmaline challenge following the development of puberty (in patients with a negative result prior to puberty) has been shown to unmask the Brugada https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 17/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate ECG pattern in asymptomatic relatives of Brugada syndrome patients [74]. (See 'Drug challenge for type 2 or equivocal ECG' above.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes".) SUMMARY AND RECOMMENDATIONS Background Brugada syndrome is a genetic disorder that can cause life-threatening ventricular tachyarrhythmias and thereby sudden cardiac arrest and sudden cardiac death; patients have abnormal findings on the surface electrocardiogram (ECG) but do not usually have any apparent cardiac structural abnormalities. (See 'Introduction' above.) Clinical manifestations Brugada syndrome is generally diagnosed between 22 and 65 years of age; it is rarely diagnosed in children. Most clinical manifestations of Brugada syndrome are related to life-threatening ventricular arrhythmias, most often ventricular fibrillation or polymorphic ventricular tachycardia. Patients may also present with syncope, palpitations, atrial fibrillation, nocturnal agonal respiration, or sudden unexpected nocturnal death. (See 'Clinical presentation' above.) Diagnostic evaluation Initial steps In all patients, we take a medical history, perform 12-lead ECG, and rule out any structural causes of heart disease. (See 'Initial steps to diagnose Brugada syndrome' above and 'Diagnostic evaluation' above.) Drug challenge if ECG is type 2 or equivocal If the initial evaluation for a patient does not reveal structural heart disease or myocardial ischemia, and the patient has spontaneous type 2 Brugada pattern or other equivocal ECG changes, we perform a drug challenge using a sodium channel blocker in an attempt to elicit the type 1 Brugada ECG pattern. (See 'Drug challenge for type 2 or equivocal ECG' above.) Further risk stratification in those with a negative drug challenge In patients with intermediate risk factors for Brugada syndrome, we undertake risk stratification in order to establish a diagnosis and decide therapy. (See 'Risk stratification for those with uncertain diagnosis' above.) https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 18/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate We suggest first evaluating with a signal-averaged ECG (SAECG) rather than other tests. If this test is negative, the likelihood of Brugada syndrome is much lower. (See 'Signal-averaged ECG (SAECG)' above.) If the SAECG is positive, we further evaluate with electrophysiologic testing for further risk stratification. (See 'Electrophysiology testing' above.) In some patients, we may use an insertable cardiac monitor (ICM) if there is suspicion of ventricular arrythmia that would indicate a diagnosis of Brugada syndrome, but this has not been yet confirmed. (See 'Insertable cardiac monitor' above.) Genetic testing for a mutation in the SCN5A gene or other causative genetic variant should be performed in asymptomatic patients with a Brugada pattern ECG only when a definitive mutation has been identified within the family proband. (See 'Genetic testing' above.) Differential diagnosis The differential diagnosis of Brugada syndrome includes conditions that have similar ECG findings with Brugada syndrome and/or conditions that have clinical features consistent with ventricular arrhythmia. (See 'Differential diagnosis' above.) Pediatric patients The majority of children diagnosed with Brugada syndrome are identified based on family screening, whereas a smaller subset presented with a clinical event consistent with ventricular arrhythmia. Pediatric patients are more likely to have a spontaneous type I Brugada ECG pattern and fever associated with their arrhythmic events. (See 'Pediatric patients' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Ann Garlitski, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Veltmann C, Schimpf R, Echternach C, et al. A prospective study on spontaneous fluctuations between diagnostic and non-diagnostic ECGs in Brugada syndrome: https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 19/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate implications for correct phenotyping and risk stratification. Eur Heart J 2006; 27:2544. 2. Cerrato N, Giustetto C, Gribaudo E, et al. Prevalence of type 1 brugada electrocardiographic pattern evaluated by twelve-lead twenty-four-hour holter monitoring. Am J Cardiol 2015; 115:52. 3. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932. 4. Brugada J, Campuzano O, Arbelo E, et al. Present Status of Brugada Syndrome: JACC State- of-the-Art Review. J Am Coll Cardiol 2018; 72:1046. 5. Atarashi H, Ogawa S, Harumi K, et al. Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads. Idiopathic Ventricular Fibrillation Investigators. Am J Cardiol 1996; 78:581. 6. Matsuo K, Kurita T, Inagaki M, et al. The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome. Eur Heart J 1999; 20:465. 7. Rodr guez-Ma ero M, Sacher F, de Asmundis C, et al. Monomorphic ventricular tachycardia in patients with Brugada syndrome: A multicenter retrospective study. Heart Rhythm 2016; 13:669. 8. Corrado D, Basso C, Buja G, et al. Right bundle branch block, right precordial st-segment elevation, and sudden death in young people. Circulation 2001; 103:710. 9. Kakishita M, Kurita T, Matsuo K, et al. Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy. J Am Coll Cardiol 2000; 36:1646. 10. Macedo PG, Brugada J, Leinveber P, et al. Sleep-disordered breathing in patients with the Brugada syndrome. Am J Cardiol 2011; 107:709. 11. Kirschner RH, Eckner FA, Baron RC. The cardiac pathology of sudden, unexplained nocturnal death in Southeast Asian refugees. JAMA 1986; 256:2700. 12. Gotoh K. A histopathological study on the conduction system of the so-called "Pokkuri disease" (sudden unexpected cardiac death of unknown origin in Japan). Jpn Circ J 1976; 40:753. 13. Nademanee K, Veerakul G, Nimmannit S, et al. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation 1997; 96:2595. 14. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 20/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Rhythm Association. Circulation 2005; 111:659. 15. Vatta M, Dumaine R, Varghese G, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet 2002; 11:337. 16. Sacher F, Arsac F, Wilton SB, et al. Syncope in Brugada syndrome patients: prevalence, characteristics, and outcome. Heart Rhythm 2012; 9:1272. 17. Bordachar P, Reuter S, Garrigue S, et al. Incidence, clinical implications and prognosis of atrial arrhythmias in Brugada syndrome. Eur Heart J 2004; 25:879. 18. Kusano KF, Taniyama M, Nakamura K, et al. Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. J Am Coll Cardiol 2008; 51:1169. 19. Rodr guez-Ma ero M, Namdar M, Sarkozy A, et al. Prevalence, clinical characteristics and management of atrial fibrillation in patients with Brugada syndrome. Am J Cardiol 2013; 111:362. 20. Morita H, Kusano-Fukushima K, Nagase S, et al. Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. J Am Coll Cardiol 2002; 40:1437. 21. Giustetto C, Cerrato N, Gribaudo E, et al. Atrial fibrillation in a large population with Brugada electrocardiographic pattern: prevalence, management, and correlation with prognosis. Heart Rhythm 2014; 11:259. 22. Morita H, Zipes DP, Morita ST, Wu J. Temperature modulation of ventricular arrhythmogenicity in a canine tissue model of Brugada syndrome. Heart Rhythm 2007; 4:188. 23. Adler A, Topaz G, Heller K, et al. Fever-induced Brugada pattern: how common is it and what does it mean? Heart Rhythm 2013; 10:1375. 24. Amin AS, Meregalli PG, Bardai A, et al. Fever increases the risk for cardiac arrest in the Brugada syndrome. Ann Intern Med 2008; 149:216. 25. Michowitz Y, Milman A, Sarquella-Brugada G, et al. Fever-related arrhythmic events in the multicenter Survey on Arrhythmic Events in Brugada Syndrome. Heart Rhythm 2018; 15:1394. 26. Krishnan SC, Josephson ME. ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol 1998; 9:1167. 27. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 21/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate normal hearts. Circulation 2000; 101:510. 28. Hong K, Brugada J, Oliva A, et al. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation 2004; 110:3023. 29. Darbar D, Yang T, Churchwell K, et al. Unmasking of brugada syndrome by lithium. Circulation 2005; 112:1527. 30. Konigstein M, Rosso R, Topaz G, et al. Drug-induced Brugada syndrome: Clinical characteristics and risk factors. Heart Rhythm 2016; 13:1083. 31. Postema PG, Wolpert C, Amin AS, et al. Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org). Heart Rhythm 2009; 6:1335. 32. Vandael E, Vandenberk B, Vandenberghe J, et al. Risk factors for QTc-prolongation: systematic review of the evidence. Int J Clin Pharm 2017; 39:16. 33. Littmann L, Monroe MH, Svenson RH. Brugada-type electrocardiographic pattern induced by cocaine. Mayo Clin Proc 2000; 75:845. 34. Rivera-Ju rez A, Hern ndez-Romero I, Puertas C, et al. Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia. J Am Heart Assoc 2019; 8:e010115. 35. Letsas KP, Asvestas D, Baranchuk A, et al. Prognosis, risk stratification, and management of asymptomatic individuals with Brugada syndrome: A systematic review. Pacing Clin Electrophysiol 2017; 40:1332. 36. Antzelevitch C, Yan GX, Ackerman MJ, et al. J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 2016; 13:e295. 37. Gray B, Behr ER. New Insights Into the Genetic Basis of Inherited Arrhythmia Syndromes. Circ Cardiovasc Genet 2016; 9:569. 38. Sangwatanaroj S, Prechawat S, Sunsaneewitayakul B, et al. New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives. Eur Heart J 2001; 22:2290. 39. Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J 2002; 23:1648. 40. Bay s de Luna A, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol 2012; 45:433. 41. Alings M, Wilde A. "Brugada" syndrome: clinical data and suggested pathophysiological mechanism. Circulation 1999; 99:666. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 22/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate 42. Chevallier S, Forclaz A, Tenkorang J, et al. New electrocardiographic criteria for discriminating between Brugada types 2 and 3 patterns and incomplete right bundle branch block. J Am Coll Cardiol 2011; 58:2290. 43. Gottschalk BH, Garcia-Niebla J, Anselm DD, et al. Methods for Improving the Diagnosis of a Brugada ECG Pattern. Ann Noninvasive Electrocardiol 2016; 21:210. 44. Pitzalis MV, Anaclerio M, Iacoviello M, et al. QT-interval prolongation in right precordial leads: an additional electrocardiographic hallmark of Brugada syndrome. J Am Coll Cardiol 2003; 42:1632. 45. Bezzina C, Veldkamp MW, van Den Berg MP, et al. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999; 85:1206. 46. Clancy CE, Rudy Y. Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 2002; 105:1208. 47. Grant AO, Carboni MP, Neplioueva V, et al. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest 2002; 110:1201. 48. Cal L, Giustetto C, Martino A, et al. A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I. J Am Coll Cardiol 2016; 67:1427. 49. Laksman Z, Barichello S, Roston TM, et al. Acute Management of Ventricular Arrhythmia in Patients With Suspected Inherited Heart Rhythm Disorders. JACC Clin Electrophysiol 2019; 5:267. 50. Papavassiliu T, Veltmann C, Doesch C, et al. Spontaneous type 1 electrocardiographic pattern is associated with cardiovascular magnetic resonance imaging changes in Brugada syndrome. Heart Rhythm 2010; 7:1790. 51. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 52. Priori SG, Napolitano C, Gasparini M, et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation 2000; 102:2509. 53. Ueoka A, Morita H, Watanabe A, et al. Prognostic Significance of the Sodium Channel Blocker Test in Patients With Brugada Syndrome. J Am Heart Assoc 2018; 7. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 23/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate 54. Obeyesekere MN, Klein GJ, Modi S, et al. How to perform and interpret provocative testing for the diagnosis of Brugada syndrome, long-QT syndrome, and catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol 2011; 4:958. 55. Cheung CC, Mellor G, Deyell MW, et al. Comparison of Ajmaline and Procainamide Provocation Tests in the Diagnosis of Brugada Syndrome. JACC Clin Electrophysiol 2019; 5:504. 56. Morita H, Morita ST, Nagase S, et al. Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome. J Am Coll Cardiol 2003; 42:1624. 57. Gasparini M, Priori SG, Mantica M, et al. Flecainide test in Brugada syndrome: a reproducible but risky tool. Pacing Clin Electrophysiol 2003; 26:338. 58. Conte G, Sieira J, Sarkozy A, et al. Life-threatening ventricular arrhythmias during ajmaline challenge in patients with Brugada syndrome: incidence, clinical features, and prognosis. Heart Rhythm 2013; 10:1869. 59. Dobbels B, De Cleen D, Ector J. Ventricular arrhythmia during ajmaline challenge for the Brugada syndrome. Europace 2016; 18:1501. 60. Therasse D, Sacher F, Petit B, et al. Sodium-channel blocker challenge in the familial screening of Brugada syndrome: Safety and predictors of positivity. Heart Rhythm 2017; 14:1442. 61. Adler A, Rosso R, Chorin E, et al. Risk stratification in Brugada syndrome: Clinical characteristics, electrocardiographic parameters, and auxiliary testing. Heart Rhythm 2016; 13:299. 62. Huang Z, Patel C, Li W, et al. Role of signal-averaged electrocardiograms in arrhythmic risk stratification of patients with Brugada syndrome: a prospective study. Heart Rhythm 2009; 6:1156. 63. Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation 2003; 108:3092. 64. Gussak I, Antzelevitch C, Bjerregaard P, et al. The Brugada syndrome: clinical, electrophysiologic and genetic aspects. J Am Coll Cardiol 1999; 33:5. 65. Brugada J, Brugada R, Antzelevitch C, et al. Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation 2002; 105:73. 66. Brugada P, Brugada R, Mont L, et al. Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart. J Cardiovasc Electrophysiol 2003; https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 24/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate 14:455. 67. Kusumoto FM, Bailey KR, Chaouki AS, et al. Systematic Review for the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:1653. 68. Sroubek J, Probst V, Mazzanti A, et al. Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis. Circulation 2016; 133:622. 69. Pappone C, Ciconte G, Manguso F, et al. Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome. J Am Coll Cardiol 2018; 71:1631. 70. Scrocco C, Ben-Haim Y, Devine B, et al. Role of subcutaneous implantable loop recorder for the diagnosis of arrhythmias in Brugada syndrome: A United Kingdom single-center experience. Heart Rhythm 2022; 19:70. 71. Milman A, Andorin A, Gourraud JB, et al. Age of First Arrhythmic Event in Brugada Syndrome: Data From the SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) in 678 Patients. Circ Arrhythm Electrophysiol 2017; 10. 72. Michowitz Y, Milman A, Andorin A, et al. Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome. J Am Coll Cardiol 2019; 73:1756. 73. Probst V, Denjoy I, Meregalli PG, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007; 115:2042. 74. Conte G, de Asmundis C, Ciconte G, et al. Follow-up from childhood to adulthood of individuals with family history of Brugada syndrome and normal electrocardiograms. JAMA 2014; 312:2039. Topic 106759 Version 31.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 25/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate GRAPHICS 12-lead electrocardiogram Brugada pattern Patient with Brugada pattern ECG. Note the presence of pseudo-right bundle branch block and persistent ST segment elevation in leads V1 to V2. ECG: electrocardiogram Courtesy of Ann C Garlitski, MD, FACC, FHRS. Graphic 122897 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 26/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Sinus tachycardia with ST segment changes due to fever in an 11- month-old child with Brugada syndrome (A) Electrocardiography demonstrating sinus tachycardia and ST segment changes triggered by fever in an 11-month-old child with Brugada syndrome. (B) Electrocardiography reverts to normal with the resolution of fever in the same patient. Graphic 100119 Version 3.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 27/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Drugs that can induce Brugada-like patterns on the surface electrocardiogram (ECG) Antiarrhythmic or antianginal drugs Cardiac sodium channel blockers (some have been used for drug challenge in patients with Brugada type 2 or 3 ECG pattern) Class IC drugs (flecainide, pilsicainide, propafenone) Class IA drugs (ajmaline, procainamide, disopyramide, cibenzoline) Lithium Calcium channel blockers Beta blockers Nitrates Nicorandil (a potassium channel opener) Psychotropic drugs Tricyclic antidepressants Amitriptyline Nortriptyline Desipramine Clomipramine Tetracyclic antidepressants Maprotiline Phenothiazines Perphenazine Cyamemazine Selective serotonin reuptake inhibitors Fluoxetine Other Dimenhydrinate Cocaine intoxication Alcohol intoxication Adapted from: Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 28/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Graphic 73611 Version 5.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 29/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Diagnostic approach to patients with intermediate or high suspicion for Brugada syndrome* ECG: electrocardiogram; VT: ventricular tachycardia. Brugada syndrome is suspected based on the combination of symptoms and typical Brugada pattern ECG changes (either type 1 or 2). Refer to related UpToDate content for further information. This is usually done with stress testing, echocardiography, and sometimes with cardiac magnetic resonance imaging. The presence of structural heart disease makes Brugada syndrome less likely and points to the structural heart disease as the probable diagnosis. A drug challenge typically involves giving a sodium channel- blocking medicine in an attempt to elicit the type 1 Brugada ECG pattern. Refer to related UpToDate content for further information. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 30/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Tests such as electrophysiologic studies and signal-averaged ECG can be used for further risk stratification and evaluation. Refer to related UpToDate content for further information. Graphic 141729 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 31/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate ECG patterns of Brugada syndrome in leads V1-V2 (A) This typical coved pattern present in V1-V2 shows the following: 1. At the end of QRS, an ascending and quick slope with a high take-off 2 mm followed by concave or rectilinear downsloping ST. There are few cases of coved pattern with a high take-off between 1 and 2 mm. 2. There is no clear r' wave. 3. The high take-off often does not correspond with the J point. 4. At 40 milliseconds of high take-off, the decrease in amplitude of ST is 4 mm. In RBBB and athletes, it is much higher. 5. ST at high take-off N ST at 40 milliseconds N ST at 80 milliseconds. 6. ST is followed by negative and symmetric T wave. 7. The duration of QRS is longer than in RBBB, and there is a mismatch between V1 and V6. (B) This typical saddle-back pattern present in V1-V2 shows the following: 1. High take-off of r' (that often does not coincide with J point) 2 mm. 2. Descending arm of r' coincides with beginning of ST (often is not well seen). 3. Minimum ST ascent 0.5 mm. 4. ST is followed by positive T wave in V2 (T peak N ST minimum N 0) and of variable morphology in V1. 5. The characteristics of triangle formed by r' allow to define different criteria useful for diagnosis. angle. Duration of the base of the triangle of r' at 5 mm from the high take- off greater than 3.5 mm. 6. The duration of QRS is longer in BrP type 2 than in other cases with r' in V1, and there is a mismatch between V1 and V6. RBBB: right bundle branch block. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 32/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Reproduced from: Bay s de Luna A, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol 2012; 45:433. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 91152 Version 2.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 33/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Patterns of ST abnormalities in leads V1 to V3 in Brugada syndrome* Feature Type 1 Type 2 2 mm 2 mm J wave amplitude T wave Negative Positive or biphasic ST-T configuration Coved type Saddle back Elevated 1 mm ST segment (terminal portion) Gradually descending ECG: electrocardiographic. In contemporary studies of Brugada syndrome, the focus has generally been on ECG findings in leads V1 and V2 only. Modi ed with permission from: Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J 2002; 23:1648. Copyright 2002 Elsevier Science. Graphic 71258 Version 7.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 34/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Electrocardiogram (ECG) showing common right bundle branch block (RBBB) Electrocardiogram showing characteristic changes in the precordial leads in complete RBBB. The asynchronous activation of the two |
72. Michowitz Y, Milman A, Andorin A, et al. Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome. J Am Coll Cardiol 2019; 73:1756. 73. Probst V, Denjoy I, Meregalli PG, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007; 115:2042. 74. Conte G, de Asmundis C, Ciconte G, et al. Follow-up from childhood to adulthood of individuals with family history of Brugada syndrome and normal electrocardiograms. JAMA 2014; 312:2039. Topic 106759 Version 31.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 25/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate GRAPHICS 12-lead electrocardiogram Brugada pattern Patient with Brugada pattern ECG. Note the presence of pseudo-right bundle branch block and persistent ST segment elevation in leads V1 to V2. ECG: electrocardiogram Courtesy of Ann C Garlitski, MD, FACC, FHRS. Graphic 122897 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 26/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Sinus tachycardia with ST segment changes due to fever in an 11- month-old child with Brugada syndrome (A) Electrocardiography demonstrating sinus tachycardia and ST segment changes triggered by fever in an 11-month-old child with Brugada syndrome. (B) Electrocardiography reverts to normal with the resolution of fever in the same patient. Graphic 100119 Version 3.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 27/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Drugs that can induce Brugada-like patterns on the surface electrocardiogram (ECG) Antiarrhythmic or antianginal drugs Cardiac sodium channel blockers (some have been used for drug challenge in patients with Brugada type 2 or 3 ECG pattern) Class IC drugs (flecainide, pilsicainide, propafenone) Class IA drugs (ajmaline, procainamide, disopyramide, cibenzoline) Lithium Calcium channel blockers Beta blockers Nitrates Nicorandil (a potassium channel opener) Psychotropic drugs Tricyclic antidepressants Amitriptyline Nortriptyline Desipramine Clomipramine Tetracyclic antidepressants Maprotiline Phenothiazines Perphenazine Cyamemazine Selective serotonin reuptake inhibitors Fluoxetine Other Dimenhydrinate Cocaine intoxication Alcohol intoxication Adapted from: Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 28/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Graphic 73611 Version 5.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 29/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Diagnostic approach to patients with intermediate or high suspicion for Brugada syndrome* ECG: electrocardiogram; VT: ventricular tachycardia. Brugada syndrome is suspected based on the combination of symptoms and typical Brugada pattern ECG changes (either type 1 or 2). Refer to related UpToDate content for further information. This is usually done with stress testing, echocardiography, and sometimes with cardiac magnetic resonance imaging. The presence of structural heart disease makes Brugada syndrome less likely and points to the structural heart disease as the probable diagnosis. A drug challenge typically involves giving a sodium channel- blocking medicine in an attempt to elicit the type 1 Brugada ECG pattern. Refer to related UpToDate content for further information. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 30/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Tests such as electrophysiologic studies and signal-averaged ECG can be used for further risk stratification and evaluation. Refer to related UpToDate content for further information. Graphic 141729 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 31/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate ECG patterns of Brugada syndrome in leads V1-V2 (A) This typical coved pattern present in V1-V2 shows the following: 1. At the end of QRS, an ascending and quick slope with a high take-off 2 mm followed by concave or rectilinear downsloping ST. There are few cases of coved pattern with a high take-off between 1 and 2 mm. 2. There is no clear r' wave. 3. The high take-off often does not correspond with the J point. 4. At 40 milliseconds of high take-off, the decrease in amplitude of ST is 4 mm. In RBBB and athletes, it is much higher. 5. ST at high take-off N ST at 40 milliseconds N ST at 80 milliseconds. 6. ST is followed by negative and symmetric T wave. 7. The duration of QRS is longer than in RBBB, and there is a mismatch between V1 and V6. (B) This typical saddle-back pattern present in V1-V2 shows the following: 1. High take-off of r' (that often does not coincide with J point) 2 mm. 2. Descending arm of r' coincides with beginning of ST (often is not well seen). 3. Minimum ST ascent 0.5 mm. 4. ST is followed by positive T wave in V2 (T peak N ST minimum N 0) and of variable morphology in V1. 5. The characteristics of triangle formed by r' allow to define different criteria useful for diagnosis. angle. Duration of the base of the triangle of r' at 5 mm from the high take- off greater than 3.5 mm. 6. The duration of QRS is longer in BrP type 2 than in other cases with r' in V1, and there is a mismatch between V1 and V6. RBBB: right bundle branch block. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 32/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Reproduced from: Bay s de Luna A, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol 2012; 45:433. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 91152 Version 2.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 33/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Patterns of ST abnormalities in leads V1 to V3 in Brugada syndrome* Feature Type 1 Type 2 2 mm 2 mm J wave amplitude T wave Negative Positive or biphasic ST-T configuration Coved type Saddle back Elevated 1 mm ST segment (terminal portion) Gradually descending ECG: electrocardiographic. In contemporary studies of Brugada syndrome, the focus has generally been on ECG findings in leads V1 and V2 only. Modi ed with permission from: Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J 2002; 23:1648. Copyright 2002 Elsevier Science. Graphic 71258 Version 7.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 34/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Electrocardiogram (ECG) showing common right bundle branch block (RBBB) Electrocardiogram showing characteristic changes in the precordial leads in complete RBBB. The asynchronous activation of the two ventricles increases the QRS duration (0.13 seconds). The terminal forces are rightward and anterior due to the delayed activation of the right ventricle, resulting in an rsR' pattern in the anterior-posterior lead V1 and a wide negative S wave in the left-right lead V6 (and, not shown, in lead I). Courtesy of Ary Goldberger, MD. Graphic 64393 Version 7.0 Normal ECG https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 35/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 36/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate ECG Brugada ajmaline challenge The panels display leads V1 to V3 (25 mm/ssecond, 1 cm/mV) acquired at baseline ("pre-test") and up to the 4th minute during intravenous administration of the sodium-channel blocker ajmaline in a 15-year-old female patient with suspected Brugada syndrome and a nondiagnostic baseline ECG. A type 1 Brugada pattern ECG is unmasked, which is important for prognosis and risk stratification purposes. ECG: electrocardiogram. Graphic 116958 Version 2.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 37/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Irregular beat-to-beat variations in the shape and amplitude of the ST-T wave d a positive diagnostic ajmaline test The figure demonstrates visible irregular beat-to-beat variations in the shape and amplitude of the ST-T wave during a positive diagnostic ajmaline test in a 58-year-old female patient with no previous history of arrhythm events. Only leads V1 and V2 recorded from their standard positions, from the 3rd intercostal space (leads V1 and V23, respectively), and 2nd intercostal space (V12 and V22) are presented (12.5 mm/second, 1 cm/mV). N the irregular pattern of ST-T wave variability. Graphic 116875 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 38/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate High- and intermediate-risk factors for arrhythmia or sudden cardiac arrest in patients with Brugada syndrome or pattern High-risk symptoms Intermediate-risk factors Sudden cardiac arrest Syncope that may be nonarrhythmic in origin* Syncope Family history of sudden cardiac arrest and/or Brugada syndrome Sustained ventricular tachycardia Spontaneous type 1 ECG pattern Atrial fibrillation This symptom is the most concerning of the intermediate-risk factors. Graphic 141594 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 39/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Contributor Disclosures John V Wylie, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Samuel Asirvatham, MD Grant/Research/Clinical Trial Support: Medtronic [Defibrillators]; St Jude's [Sudden Cardiac Death]. Consultant/Advisory Boards: BioTronik [Defibrillators]; Boston Scientific [Sudden Cardiac Death]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 40/40 |
7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Brugada syndrome: Epidemiology and pathogenesis : John V Wylie, MD, FACC : Scott Manaker, MD, PhD, Samuel Asirvatham, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 14, 2023. INTRODUCTION The vast majority of cases of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) are caused by ventricular tachyarrhythmias, with most of these associated with structural heart disease, particularly coronary heart disease. SCA in the apparently normal heart is an uncommon occurrence, accounting for only 5 to 10 percent of SCA cases. (See "Pathophysiology and etiology of sudden cardiac arrest".) Some causes of SCA in patients with apparently normal hearts have been identified and include: Brugada syndrome Congenital long QT syndrome (LQTS) (see "Congenital long QT syndrome: Epidemiology and clinical manifestations") Acquired LQTS with polymorphic ventricular tachycardia (VT) (see "Acquired long QT syndrome: Definitions, pathophysiology, and causes") Catecholaminergic polymorphic VT (see "Catecholaminergic polymorphic ventricular tachycardia") Idiopathic VT (see "Ventricular tachycardia in the absence of apparent structural heart disease") Idiopathic ventricular fibrillation Short QT syndrome (see "Short QT syndrome") Commotio cordis (see "Commotio cordis") https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 1/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate The epidemiology and pathogenesis of the Brugada syndrome will be reviewed here. The clinical manifestations, evaluation, diagnosis, management, and prognosis of the Brugada syndrome, along with a discussion of the other causes of SCA in apparently normal hearts, are discussed elsewhere. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease" and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation" and "Brugada syndrome or pattern: Management and approach to screening of relatives".) DEFINITION The Brugada syndrome is an autosomal dominant genetic disorder with variable expression characterized by abnormal findings on the surface electrocardiogram (ECG) in conjunction with an increased risk of ventricular tachyarrhythmias and sudden cardiac death [1]. Typically, the ECG findings consist of a pseudo-right bundle branch block and persistent ST segment elevation in leads V1 to V2 ( waveform 1), although isolated cases have described similar findings involving the inferior ECG leads [2-5]. Brugada pattern versus Brugada syndrome Two terms, distinguished by the presence or absence of symptoms, have been used to describe patients with the typical ECG findings of a pseudo-right bundle branch block and persistent ST segment elevation in leads V1 to V2: Patients with typical ECG features who are asymptomatic and have no other clinical criteria are said to have the Brugada pattern. Patients with typical ECG features who have experienced sudden cardiac death or a sustained ventricular tachyarrhythmia, or who have one or more of the other associated clinical criteria, are said to have the Brugada syndrome. Patients with ventricular premature beats or nonsustained ventricular tachycardia, however, are generally not considered to have Brugada syndrome but only the Brugada pattern. Persons with either the Brugada pattern or the Brugada syndrome can have identical findings on the surface ECG. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on '12-lead ECG'.) EPIDEMIOLOGY Prevalence The prevalence of the asymptomatic Brugada ECG pattern has been evaluated in a number of different populations and appears to be between 0.1 and 1 percent depending https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 2/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate upon the population studied [5-12]. The prevalence of symptomatic Brugada syndrome is significantly lower than the prevalence of the Brugada pattern but is less well studied [13,14]. Studies in heterogeneous populations suggest that the majority of affected individuals are of Asian descent, with the highest prevalence in Southeast Asia [5]. In two reports from Japan, the prevalence was 0.7 and 1.0 percent [6,7]; 0.12 to 0.16 percent of the Japanese population have type 1 (coved type) ST segment elevation [6,8,9]. In a Finnish cohort, the prevalence of type 2 ST segment elevation was 0.6 percent; no type 1 patients were found in a screen of over 3000 apparently healthy individuals [10]. In two samples of urban populations in the United States, the prevalence was 0.4 and 0.012 percent, respectively [11]. The prevalence of Brugada syndrome among patients with Brugada pattern ECGs has not been well studied, but a meta-analysis of 30 published reports of patients with Brugada pattern ECGs demonstrated a 10 percent event rate at 2.5 years [13]. The prevalence of the Brugada pattern is much greater in patients who present with apparent idiopathic ventricular fibrillation (VF; 3 to 24 percent in one series of 37 patients, depending upon the diagnostic criteria used) [14]. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF'.) Male predominance The Brugada ECG pattern is more common in men than in women, with estimates ranging from 2 to 9 times more likely in men [12,15-18]. Among a Japanese cohort of 4788 persons without baseline ECG abnormalities who were less than 50 years of age at enrollment and were followed for up to 41 years, 32 persons developed a Brugada pattern on ECG (at an average age of 45 years), with the incidence in men being 9 times higher than the incidence in women [9]. Among a series of 384 persons identified with Brugada pattern ECGs at one of two high volume referral centers in Belgium and Spain, men represented over 70 percent of the cases (n = 272) [15]. Among the 83 patients in this series with Brugada syndrome at the time of diagnosis, 66 (80 percent) were men. Among a series of 542 persons identified with Brugada pattern ECGs at a single high volume referral center in Belgium from 1992 to 2013 (which likely included some of the same patients as the study above), men represented 58 percent of the cases (n = 314) [16]. Among the 156 patients in this series who presented with syncope or sudden cardiac death, 99 (63 percent) were men. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 3/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate Females may have lower event rates than males. In a multicenter retrospective study of 770 patients with Brugada syndrome, 23 percent were female. Over a follow-up of 10 years, females presented less frequently with type 1 ECG pattern (30.5 versus 55 percent) and had lower cardiovascular event rates over mean follow-up of 10 years (2.8 versus 7.1 percent) than males [19]. Reasons for the prominent male predominance in an autosomal dominant disorder are unclear. Animal models suggest that the impact of testosterone on ion currents, particularly outward potassium currents, may contribute to the increased incidence of clinical manifestations of Brugada syndrome in males [20,21]. (See 'Genetics' below.) Age at diagnosis Brugada pattern ECG and Brugada syndrome are usually diagnosed in adulthood. In two of the larger series of patients, which combined those with Brugada pattern ECGs as well as those with symptomatic Brugada syndrome, the average patient age was 41 years [22,23]. However, Brugada syndrome can be diagnosed in children. A single-center case series from Italy of 43 patients younger than 12 years reported a higher incidence of malignant arrhythmia events in patients with syncope (37.5 percent) than in patients without syncope (0 percent). No significant difference in outcomes was observed in patients with drug- or fever-induced type 1 pattern versus spontaneous, or between males and females in this young population followed for a mean of four years [24]. Association with schizophrenia Patients with schizophrenia appear significantly more likely to have Brugada pattern ECGs than the general population. Among a cohort of 275 patients with schizophrenia (with two separate cohorts of nonschizophrenic patients serving as control groups), Brugada pattern ECGs were significantly more common (11.6 percent of patients with schizophrenia versus 1.1 and 2.4 percent of the cohorts without schizophrenia, respectively), with no significant impact of antipsychotic medications with sodium channel blocking activity used to treat schizophrenia [25]. The clinical relevance of this association remains undetermined, but there may be an association between this finding and the risk of sudden death in patients with schizophrenia. (See "Schizophrenia in adults: Epidemiology and pathogenesis" and "Schizophrenia in adults: Clinical manifestations, course, assessment, and diagnosis".) PATHOGENESIS A variety of factors may contribute to the electrocardiographic and clinical manifestations of Brugada syndrome including mutations in the cardiac sodium channel SCN genes, right https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 4/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate ventricular (RV) abnormalities, autonomic tone, fever, and the use of cocaine and certain psychotropic drugs. Genetics The Brugada syndrome demonstrates autosomal dominant inheritance with variable expression [12]. Genetic analysis has led to the identification of purportedly causative mutations in the SCN genes SCN5A and SCN10A, encoding subunits of a cardiac sodium channel. Reasons for the variable expression of Brugada syndrome are not completely understood, although compound heterozygosity (manifestation of a recessive disease due to two different mutations in the same gene) had been described in one family [26]. Sodium channel genes The defective myocardial sodium channels reduce sodium inflow currents, thereby reducing the duration of normal action potentials. In the RV outflow tract (RVOT) epicardium, there is a prominent transient outward current, called I , which causes to marked shortening of the action potential in the setting of reduced sodium inflow [27]. The relationship between sodium channel abnormalities and ST segment elevation is not fully understood. The ventricular myocardium is composed of at least three electrophysiologically distinct cell types: Epicardial cells Endocardial cells M cells The ST segment elevation and T wave inversions seen in the right precordial leads in Brugada pattern ECGs are thought to be due to an alteration in the action potential in the epicardial and possibly the M cells, but not the endocardial cells [5,27-29]. The resulting dispersion of repolarization across the ventricular wall, which on noninvasive ECG mapping is isolated in the RVOT, results in a transmural voltage gradient that is manifested in the electrocardiogram as ST segment elevation [30]. In addition, noninvasive ECG mapping has also shown evidence of an arrhythmogenic substrate in the RVOT with delayed activation, slow conduction, and steep repolarization gradients between the RVOT and the rest of the RV [30]. This substrate may predispose to local reentry and ventricular arrhythmias. SCN5A Mutations in SCN5A, the gene that encodes the Na 1.5 subunit of the cardiac v sodium channel gene, have been found in 15 to 30 percent of families with Brugada syndrome [22,31-34]. The gene locus is on chromosome 3p21-24. The SCN5A mutations seen in Brugada syndrome are "loss of function" mutations and result in a variety of abnormalities in sodium channel activity including failure of expression, alterations in the voltage and time dependence of activation, and accelerated or prolonged recovery from https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 5/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate inactivation [31]. In addition, mutations may explain the ability of sodium channel blockers to expose the ECG changes in some patients with this disorder [3,31,35-37]. Probands with SCN5A mutations have been reported to have higher rates of cardiac events beginning at a younger age [34]. Women with Brugada syndrome have a higher rate of SCN5A mutations than men (48 versus 28 percent) [18]. A critical appraisal of all candidate genes identified SCN5a as the only gene with definitive evidence for causation of Brugada syndrome [38]. SCN10A Mutations in SCN10A, the gene that encodes the Na 1.8 subunit of the cardiac v sodium channel gene, have been reported in 17 percent of Brugada syndrome probands, which is comparable to the 20 percent of probands found to have SCN5A mutations [39]. Coexpression of the mutant SCN10A gene with wild-type SCN5A causes a major loss of function of the sodium channel, with reduced current and slower recovery from inactivation. A longer PR interval, longer QRS duration, and higher incidence of ventricular tachyarrhythmias and sudden death were noted in patients carrying mutations of SCN10A compared with gene-negative patients with Brugada syndrome. Other sodium channel mutations Other mutations that decrease the sodium channel current have been identified in isolated kindreds with Brugada syndrome. These include a mutation in SCN1B, an accessory subunit that interacts with the sodium channel and is also associated with conduction system disease [40], and a mutation in GPD1-L, a gene that affects trafficking of the sodium channel [41]. Related disorders with SCN mutations Mutations in the SCN5 gene have also been associated with other electrophysiologic abnormalities: Isolated atrioventricular (AV) conduction defect Congenital long QT syndrome type 3 (LQT3) [42-44] Congenital sinus node dysfunction (SND) Familial dilated cardiomyopathy with conduction defects and susceptibility to atrial fibrillation Early repolarization syndrome The differences in clinical manifestations are probably due to differences in the electrophysiologic abnormalities induced by the specific mutations [44-48]. Certain SCN5A and SCN10A mutations have been associated with an "overlap" syndrome, with affected patients exhibiting SND or complete heart block as well as Brugada syndrome [46-49]. Patients with longer PR intervals may be more likely to have a SNC10A mutation [39]. (See "Etiology of atrioventricular block", section on 'Familial disease' and "Congenital long QT syndrome: Pathophysiology and genetics", section on 'Type 3 LQTS (LQT3)' and "Genetics of dilated https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 6/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate cardiomyopathy" and "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Childhood and familial disease' and "Early repolarization".) Non-sodium channel genes Since only a minority of affected families have an identified abnormality of SCN, it is possible that additional genetic abnormalities may produce the phenotypic characteristics of Brugada syndrome. Cardiac calcium channel gene In a series of 82 probands with a clinical diagnosis of Brugada syndrome, seven individuals (8.5 percent) were found to have mutations in the alpha1 or beta2 subunit of the cardiac L-type calcium channel [50]. Three of these patients had a unique phenotype in that in association with the typical ECG findings of Brugada syndrome, they also had shortened QT intervals ( 360 milliseconds). The relationship of this disorder to the usual form of Brugada syndrome and to short QT syndrome remains to be defined. A locus on chromosome 3p22-25 has been identified in a large family with an autosomal dominant syndrome similar to Brugada syndrome (RBBB and ventricular arrhythmias) [51]. The mutation is also associated with progressive conduction disease. Compared with patients with SCN5A mutations, affected members of this family had a good prognosis with a very low incidence of sudden cardiac death (SCD). A specific disease-causing gene at this locus has not yet been identified, which limits full characterization of this disorder and its relationship to the usual form of Brugada syndrome. Mutations in KCNE3 and KCNE2 causing gain of function in the transient outward current (I ) and Brugada Syndrome have been identified in rare probands [52,53]. As discussed to below, increased I current may lead to arrhythmias in Brugada. to Microscopic structural abnormalities and fibrosis Brugada syndrome is not usually associated with structural heart disease. Standard cardiac testing, including echocardiography, stress testing, and cardiac magnetic resonance imaging often reveal no abnormalities. However, it is probably more accurate to categorize Brugada syndrome as a disorder that occurs in hearts that are apparently normal since there is some evidence that subtle structural or microscopic abnormalities occur, including dilation of the RVOT and localized inflammation and fibrosis [54- 58]. Supporting a pathogenic role of fibrosis in Brugada syndrome, a mouse model of heterozygous SCN5A knockout revealed age-dependent fibrosis and marked slowing of conduction velocity in the RV [55]. Similarly, evaluation of an explanted heart from a transplant recipient with Brugada syndrome revealed microscopic fibrosis and conduction abnormalities [59]. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 7/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate Evidence of microscopic abnormalities in Brugada syndrome comes from a series of 18 patients who underwent endomyocardial biopsy [54]. Although noninvasive evaluation was normal in each patient, all had evidence of microscopic structural abnormalities, including signs of RV myocarditis in 14. The ECG changes resolved at follow-up in 8 of the 14 patients with signs of RV myocarditis, raising the possibility that the Brugada pattern ECG seen in these patients at presentation may have been a manifestation of RV myocarditis rather than an intrinsic cardiac ion channel abnormality. A study of six post-mortem hearts from patients thought to have Brugada syndrome and six patients undergoing epicardial ablation via thoracotomy for Brugada syndrome demonstrated further evidence for fibrosis in the pathogenesis of Brugada syndrome. These patients showed increased collagen and fibrosis in the RVOT epicardium and reduced Connexin 43 signal in the RVOT. Fibrosis was located in areas of abnormal potentials during in vivo mapping [59]. Ventricular arrhythmias and phase 2 reentry Ventricular arrhythmias may result from the heterogeneity of myocardial refractory periods in the RV. This heterogeneity arises from the presence of both normal and abnormal sodium channels in the same tissue, and from the differential impact of the sodium current in the three layers of the myocardium [27,28,60]. (See 'Sodium channel genes' above.) Within the epicardium, the juxtaposition of myocytes with different refractory periods can produce the triggers that initiate sustained arrhythmias (eg, closely-coupled premature beats) via a unique type of reentry called phase two reentry. In cardiac myocytes with defective sodium channels, initial depolarization is blunted (phase zero), and the counterbalancing effect of I to (phase 1) may be more significant. This phenomenon is more dramatic in the RVOT epicardium where I currents are greater. In combination, this results in less initial depolarization and to reduced activation of the calcium channels that maintain the depolarized state during phase 2. Thus, phase 2 of the cardiac action potential can be dramatically shortened. The cells with impaired sodium channel function may fail to propagate the action potential, resulting in localized conduction block. However, due to the abbreviation of phase 2, these same cells have a much shorter refractory period and recover excitability before the surrounding cells. The combination of localized conduction block and a shortened refractory period provides the substrate for localized reentry, which, in this case, is referred to as phase 2 reentry. The closely- coupled ventricular premature beats that result from phase 2 reentry may precipitate sustained ventricular arrhythmias. Noninvasive ECG mapping has also revealed delayed activation, slow conduction, and steep repolarization gradients between the RVOT and the rest of the RV, further supporting the role of the RVOT as the location of abnormal electrophysiologic substrate in Brugada syndrome [30]. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 8/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate Autonomic tone An imbalance between sympathetic and parasympathetic tone may be important in the pathogenesis of Brugada ECG pattern and Brugada syndrome, as suggested by the nocturnal occurrence of the associated tachyarrhythmias and the alteration of typical ECG changes by pharmacologic modulation of autonomic tone [61-63]. Further support for the role of autonomic dysfunction comes from a study of 17 patients with Brugada syndrome who underwent scanning with iobenguane I-123 (diagnostic), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals [62]. A segmental reduction in MIBG uptake was seen in 8 of the 17 patients but in none of 10 controls. Augmentation of ST elevation 0.05 mV in leads V1-V2 during recovery from exercise is seen in some patients with Brugada syndrome and has been associated with worse arrhythmic outcomes. In a study of 93 patients with Brugada syndrome (57 patients) or asymptomatic Brugada pattern (36 patients), 37 percent had augmentation of ST elevation in exercise recovery, and during follow-up, 44 percent of these patients versus 17 percent of patients without ST augmentation had arrhythmic events [64]. The mechanism may be a response to parasympathetic reactivation during recovery from exercise. Fever Fever can be a trigger for both induction of Brugada pattern ECG abnormalities and cardiac arrest among persons known to have Brugada pattern ECG or Brugada syndrome. The clinical impact of fever in patients with Brugada pattern ECGs is discussed separately. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Drugs A 2020 scientific statement from the American Heart Association details drugs associated with the Brugada syndrome [65]. Cocaine abuse The ECG findings of Brugada pattern can be transiently induced by cocaine use [66]. Cocaine acts like a class I antiarrhythmic agent, producing local anesthetic effects via sodium channel blockade in the heart; this could explain the relation to the Brugada pattern. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".) Psychotropic drugs Other drugs that block cardiac sodium channels have been associated with a transient Brugada pattern ECG, including overdoses with neuroleptic drugs or cyclic antidepressants [67-70]. In one report, a Brugada pattern was seen in 15 of 98 cases (15.3 percent) of a cyclic antidepressant overdose [68]. One patient with the Brugada pattern and one without died of refractory ventricular fibrillation. SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 9/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate Definition The Brugada syndrome is an autosomal dominant genetic disorder with variable expression characterized by abnormal findings on the surface electrocardiogram (ECG) in conjunction with an increased risk of ventricular tachyarrhythmias and sudden cardiac death. Typically, the ECG findings consist of a pseudo-right bundle branch block and persistent ST segment elevation in leads V1 to V2 ( waveform 1), although isolated cases have described similar findings involving the inferior ECG leads. Brugada syndrome versus pattern Patients with typical ECG features who have experienced sudden cardiac death or a sustained ventricular tachyarrhythmia, or who have one or more of the other associated clinical criteria, are said to have the Brugada syndrome, whereas patients with typical ECG features who are asymptomatic and have no other clinical criteria are said to have the Brugada pattern. (See 'Definition' above.) Epidemiology Prevalence of asymptomatic Brugada ECG pattern is between 0.1 and 1 percent, depending upon the population studied. (See 'Epidemiology' above.) Prevalence of symptomatic Brugada syndrome is significantly lower than the prevalence of the Brugada pattern but is less well studied. The Brugada ECG pattern is more common in men than in women, with estimates ranging from two to nine times more likely in men. Pathogenesis A variety of factors may contribute to the electrocardiographic and clinical manifestations of Brugada syndrome including mutations in the cardiac sodium channel SCN genes, right ventricular abnormalities, autonomic tone, fever, and the use of cocaine and certain psychotropic drugs. (See 'Pathogenesis' above.) Genetics The Brugada syndrome demonstrates autosomal dominant inheritance with variable expression. Genetic analysis has led to the identification of purportedly causative mutations in the SCN gene SCN5A, encoding subunits of a cardiac sodium channel. Reasons for the variable expression of Brugada syndrome are not completely understood. (See 'Genetics' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Ann Garlitski, MD, who contributed to earlier versions of this topic review. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 10/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Brugada J, Campuzano O, Arbelo E, et al. Present Status of Brugada Syndrome: JACC State- of-the-Art Review. J Am Coll Cardiol 2018; 72:1046. 2. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992; 20:1391. 3. Atarashi H, Ogawa S, Harumi K, et al. Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads. Idiopathic Ventricular Fibrillation Investigators. Am J Cardiol 1996; 78:581. 4. Brugada J, Brugada P. What to do in patients with no structural heart disease and sudden arrhythmic death? Am J Cardiol 1996; 78:69. 5. Alings M, Wilde A. "Brugada" syndrome: clinical data and suggested pathophysiological mechanism. Circulation 1999; 99:666. 6. Miyasaka Y, Tsuji H, Yamada K, et al. Prevalence and mortality of the Brugada-type electrocardiogram in one city in Japan. J Am Coll Cardiol 2001; 38:771. 7. Matsuo K, Akahoshi M, Nakashima E, et al. Clinical characteristics of subjects with the Brugada-type electrocardiogram:. J Cardiovasc Electrophysiol 2004; 15:653. 8. Atarashi H, Ogawa S, Harumi K, et al. Three-year follow-up of patients with right bundle branch block and ST segment elevation in the right precordial leads: Japanese Registry of Brugada Syndrome. Idiopathic Ventricular Fibrillation Investigators. J Am Coll Cardiol 2001; 37:1916. 9. Matsuo K, Akahoshi M, Nakashima E, et al. The prevalence, incidence and prognostic value of the Brugada-type electrocardiogram: a population-based study of four decades. J Am Coll Cardiol 2001; 38:765. 10. Junttila MJ, Raatikainen MJ, Karjalainen J, et al. Prevalence and prognosis of subjects with Brugada-type ECG pattern in a young and middle-aged Finnish population. Eur Heart J 2004; 25:874. 11. Patel SS, Anees S, Ferrick KJ. Prevalence of a Brugada pattern electrocardiogram in an urban population in the United States. Pacing Clin Electrophysiol 2009; 32:704. 12. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 11/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932. 13. Gehi AK, Duong TD, Metz LD, et al. Risk stratification of individuals with the Brugada electrocardiogram: a meta-analysis. J Cardiovasc Electrophysiol 2006; 17:577. 14. Remme CA, Wever EF, Wilde AA, et al. Diagnosis and long-term follow-up of the Brugada syndrome in patients with idiopathic ventricular fibrillation. Eur Heart J 2001; 22:400. 15. Benito B, Sarkozy A, Mont L, et al. Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol 2008; 52:1567. 16. Sieira J, Conte G, Ciconte G, et al. Clinical characterisation and long-term prognosis of women with Brugada syndrome. Heart 2016; 102:452. 17. Berthome P, Tixier R, Briand J, et al. Clinical presentation and follow-up of women affected by Brugada syndrome. Heart Rhythm 2019; 16:260. 18. Milman A, Gourraud JB, Andorin A, et al. Gender differences in patients with Brugada syndrome and arrhythmic events: Data from a survey on arrhythmic events in 678 patients. Heart Rhythm 2018; 15:1457. 19. Rodr guez-Ma ero M, Jord P, Hernandez J, et al. Long-term prognosis of women with Brugada syndrome and electrophysiological study. Heart Rhythm 2021; 18:664. 20. Di Diego JM, Cordeiro JM, Goodrow RJ, et al. Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males. Circulation 2002; 106:2004. 21. Bai CX, Kurokawa J, Tamagawa M, et al. Nontranscriptional regulation of cardiac repolarization currents by testosterone. Circulation 2005; 112:1701. 22. Priori SG, Napolitano C, Gasparini M, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002; 105:1342. 23. Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation 2003; 108:3092. 24. Righi D, Porco L, Calvieri C, et al. Clinical characteristics and risk of arrhythmic events in patients younger than 12 years diagnosed with Brugada syndrome. Heart Rhythm 2021; 18:1691. 25. Blom MT, Cohen D, Seldenrijk A, et al. Brugada syndrome ECG is highly prevalent in schizophrenia. Circ Arrhythm Electrophysiol 2014; 7:384. 26. Cordeiro JM, Barajas-Martinez H, Hong K, et al. Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome. Circulation 2006; 114:2026. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 12/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate 27. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999; 100:1660. 28. Gussak I, Antzelevitch C, Bjerregaard P, et al. The Brugada syndrome: clinical, electrophysiologic and genetic aspects. J Am Coll Cardiol 1999; 33:5. 29. Nagase S, Kusano KF, Morita H, et al. Longer repolarization in the epicardium at the right ventricular outflow tract causes type 1 electrocardiogram in patients with Brugada syndrome. J Am Coll Cardiol 2008; 51:1154. 30. Zhang J, Sacher F, Hoffmayer K, et al. Cardiac electrophysiological substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients. Circulation 2015; 131:1950. 31. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. 32. Priori SG, Napolitano C, Gasparini M, et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation 2000; 102:2509. 33. Sonoda K, Ohno S, Ozawa J, et al. Copy number variations of SCN5A in Brugada syndrome. Heart Rhythm 2018; 15:1179. 34. Yamagata K, Horie M, Aiba T, et al. Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry. Circulation 2017; 135:2255. 35. Krishnan SC, Josephson ME. ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol 1998; 9:1167. 36. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101:510. 37. Hong K, Brugada J, Oliva A, et al. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation 2004; 110:3023. 38. Hosseini SM, Kim R, Udupa S, et al. Reappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome. Circulation 2018; 138:1195. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 13/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate 39. Hu D, Barajas-Mart nez H, Pfeiffer R, et al. Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. J Am Coll Cardiol 2014; 64:66. 40. Watanabe H, Koopmann TT, Le Scouarnec S, et al. Sodium channel 1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest 2008; 118:2260. 41. London B, Michalec M, Mehdi H, et al. Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation 2007; 116:2260. 42. Bezzina C, Veldkamp MW, van Den Berg MP, et al. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999; 85:1206. 43. Clancy CE, Rudy Y. Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 2002; 105:1208. 44. Desch nes I, Baroudi G, Berthet M, et al. Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes. Cardiovasc Res 2000; 46:55. 45. Clancy CE, Kass RS. Defective cardiac ion channels: from mutations to clinical syndromes. J Clin Invest 2002; 110:1075. 46. Priori SG, Napolitano C, Schwartz PJ, et al. The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation 2000; 102:945. 47. Makiyama T, Akao M, Tsuji K, et al. High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol 2005; 46:2100. 48. Smits JP, Koopmann TT, Wilders R, et al. A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J Mol Cell Cardiol 2005; 38:969. 49. Grant AO, Carboni MP, Neplioueva V, et al. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest 2002; 110:1201. 50. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442. 51. Weiss R, Barmada MM, Nguyen T, et al. Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. Circulation 2002; 105:707. 52. Wu J, Shimizu W, Ding WG, et al. KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. Heart Rhythm 2010; 7:199. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 14/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate 53. Delp n E, Cordeiro JM, N ez L, et al. Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ Arrhythm Electrophysiol 2008; 1:209. 54. Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation 2005; 112:3680. 55. van Veen TA, Stein M, Royer A, et al. Impaired impulse propagation in Scn5a-knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging. Circulation 2005; 112:1927. 56. Coronel R, Casini S, Koopmann TT, et al. Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study. Circulation 2005; 112:2769. 57. Takagi M, Aihara N, Kuribayashi S, et al. Localized right ventricular morphological abnormalities detected by electron-beam computed tomography represent arrhythmogenic substrates in patients with the Brugada syndrome. Eur Heart J 2001; 22:1032. 58. Papavassiliu T, Wolpert C, Fl chter S, et al. Magnetic resonance imaging findings in patients with Brugada syndrome. J Cardiovasc Electrophysiol 2004; 15:1133. 59. Nademanee K, Raju H, de Noronha SV, et al. Fibrosis, Connexin-43, and Conduction Abnormalities in the Brugada Syndrome. J Am Coll Cardiol 2015; 66:1976. 60. Ha ssaguerre M, Extramiana F, Hocini M, et al. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation 2003; 108:925. 61. Mizumaki K, Fujiki A, Tsuneda T, et al. Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome. J Cardiovasc Electrophysiol 2004; 15:667. 62. Miyazaki T, Mitamura H, Miyoshi S, et al. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol 1996; 27:1061. 63. Matsuo K, Kurita T, Inagaki M, et al. The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome. Eur Heart J 1999; 20:465. 64. Makimoto H, Nakagawa E, Takaki H, et al. Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome. J Am Coll Cardiol 2010; 56:1576. 65. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 66. Littmann L, Monroe MH, Svenson RH. Brugada-type electrocardiographic pattern induced by cocaine. Mayo Clin Proc 2000; 75:845. |
27. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999; 100:1660. 28. Gussak I, Antzelevitch C, Bjerregaard P, et al. The Brugada syndrome: clinical, electrophysiologic and genetic aspects. J Am Coll Cardiol 1999; 33:5. 29. Nagase S, Kusano KF, Morita H, et al. Longer repolarization in the epicardium at the right ventricular outflow tract causes type 1 electrocardiogram in patients with Brugada syndrome. J Am Coll Cardiol 2008; 51:1154. 30. Zhang J, Sacher F, Hoffmayer K, et al. Cardiac electrophysiological substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients. Circulation 2015; 131:1950. 31. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. 32. Priori SG, Napolitano C, Gasparini M, et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation 2000; 102:2509. 33. Sonoda K, Ohno S, Ozawa J, et al. Copy number variations of SCN5A in Brugada syndrome. Heart Rhythm 2018; 15:1179. 34. Yamagata K, Horie M, Aiba T, et al. Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry. Circulation 2017; 135:2255. 35. Krishnan SC, Josephson ME. ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol 1998; 9:1167. 36. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101:510. 37. Hong K, Brugada J, Oliva A, et al. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation 2004; 110:3023. 38. Hosseini SM, Kim R, Udupa S, et al. Reappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome. Circulation 2018; 138:1195. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 13/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate 39. Hu D, Barajas-Mart nez H, Pfeiffer R, et al. Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. J Am Coll Cardiol 2014; 64:66. 40. Watanabe H, Koopmann TT, Le Scouarnec S, et al. Sodium channel 1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest 2008; 118:2260. 41. London B, Michalec M, Mehdi H, et al. Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation 2007; 116:2260. 42. Bezzina C, Veldkamp MW, van Den Berg MP, et al. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999; 85:1206. 43. Clancy CE, Rudy Y. Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 2002; 105:1208. 44. Desch nes I, Baroudi G, Berthet M, et al. Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes. Cardiovasc Res 2000; 46:55. 45. Clancy CE, Kass RS. Defective cardiac ion channels: from mutations to clinical syndromes. J Clin Invest 2002; 110:1075. 46. Priori SG, Napolitano C, Schwartz PJ, et al. The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation 2000; 102:945. 47. Makiyama T, Akao M, Tsuji K, et al. High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol 2005; 46:2100. 48. Smits JP, Koopmann TT, Wilders R, et al. A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J Mol Cell Cardiol 2005; 38:969. 49. Grant AO, Carboni MP, Neplioueva V, et al. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest 2002; 110:1201. 50. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442. 51. Weiss R, Barmada MM, Nguyen T, et al. Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. Circulation 2002; 105:707. 52. Wu J, Shimizu W, Ding WG, et al. KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. Heart Rhythm 2010; 7:199. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 14/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate 53. Delp n E, Cordeiro JM, N ez L, et al. Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ Arrhythm Electrophysiol 2008; 1:209. 54. Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation 2005; 112:3680. 55. van Veen TA, Stein M, Royer A, et al. Impaired impulse propagation in Scn5a-knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging. Circulation 2005; 112:1927. 56. Coronel R, Casini S, Koopmann TT, et al. Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study. Circulation 2005; 112:2769. 57. Takagi M, Aihara N, Kuribayashi S, et al. Localized right ventricular morphological abnormalities detected by electron-beam computed tomography represent arrhythmogenic substrates in patients with the Brugada syndrome. Eur Heart J 2001; 22:1032. 58. Papavassiliu T, Wolpert C, Fl chter S, et al. Magnetic resonance imaging findings in patients with Brugada syndrome. J Cardiovasc Electrophysiol 2004; 15:1133. 59. Nademanee K, Raju H, de Noronha SV, et al. Fibrosis, Connexin-43, and Conduction Abnormalities in the Brugada Syndrome. J Am Coll Cardiol 2015; 66:1976. 60. Ha ssaguerre M, Extramiana F, Hocini M, et al. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation 2003; 108:925. 61. Mizumaki K, Fujiki A, Tsuneda T, et al. Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome. J Cardiovasc Electrophysiol 2004; 15:667. 62. Miyazaki T, Mitamura H, Miyoshi S, et al. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol 1996; 27:1061. 63. Matsuo K, Kurita T, Inagaki M, et al. The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome. Eur Heart J 1999; 20:465. 64. Makimoto H, Nakagawa E, Takaki H, et al. Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome. J Am Coll Cardiol 2010; 56:1576. 65. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 66. Littmann L, Monroe MH, Svenson RH. Brugada-type electrocardiographic pattern induced by cocaine. Mayo Clin Proc 2000; 75:845. https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 15/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate 67. Rouleau F, Asfar P, Boulet S, et al. Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. J Cardiovasc Electrophysiol 2001; 12:61. 68. Goldgran-Toledano D, Sideris G, Kevorkian JP. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med 2002; 346:1591. 69. Konigstein M, Rosso R, Topaz G, et al. Drug-induced Brugada syndrome: Clinical characteristics and risk factors. Heart Rhythm 2016; 13:1083. 70. Russo CR, Welch TD, Sangha RS, Greenberg ML. Brugada Syndrome Presenting as Polymorphic Ventricular Tachycardia-Ventricular Fibrillation Lasting 94 Seconds Recorded on an Ambulatory Monitor. JAMA Intern Med 2015; 175:1951. Topic 1020 Version 37.0 https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 16/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate GRAPHICS 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 17/18 7/6/23, 11:29 AM Brugada syndrome: Epidemiology and pathogenesis - UpToDate Contributor Disclosures John V Wylie, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Samuel Asirvatham, MD Grant/Research/Clinical Trial Support: Medtronic [Defibrillators]; St Jude's [Sudden Cardiac Death]. Consultant/Advisory Boards: BioTronik [Defibrillators]; Boston Scientific [Sudden Cardiac Death]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/brugada-syndrome-epidemiology-and-pathogenesis/print 18/18 |
7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Brugada syndrome or pattern: Management and approach to screening of relatives : John V Wylie, MD, FACC : Samuel Asirvatham, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 09, 2023. INTRODUCTION The Brugada syndrome is a genetic disorder that can cause life-threatening ventricular tachyarrhythmias and thereby sudden cardiac arrest (SCA) and sudden cardiac death (SCD); patients have abnormal findings on the surface electrocardiogram (ECG) but do not usually have any apparent cardiac structural abnormalities. The prognosis and management of the Brugada syndrome along with our approach to screening first-degree relatives will be reviewed here. The following topics discuss other aspects of Brugada syndrome in detail separately: (See "Brugada syndrome: Epidemiology and pathogenesis".) (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Other causes of SCA in patients with apparently normal hearts are discussed in detail separately. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease".) DEFINITIONS The following two terms, distinguished by the presence or absence of symptoms, have been used to describe patients with the typical electrocardiogram (ECG) findings of a pseudo-right bundle branch block and persistent ST-segment elevation in leads V1 to V2 ( figure 1): https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 1/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Brugada pattern Patients with typical ECG features ( figure 1) who are asymptomatic and have no other clinical criteria are said to have the Brugada pattern (sometimes referred to as Brugada phenocopies). Distinguishing Brugada syndrome from Brugada pattern is discussed separately. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Brugada pattern versus syndrome'.) Brugada syndrome Patients with typical ECG features ( figure 1) who have experienced sudden cardiac arrest (SCA) and/or sudden cardiac death (SCD) or a documented sustained ventricular tachyarrhythmia, or who have one or more of the other associated clinical criteria, are said to have the Brugada syndrome. Patients with premature ventricular beats or nonsustained ventricular tachycardia are generally not considered to have Brugada syndrome but only the Brugada pattern. Persons with either the Brugada pattern or the Brugada syndrome can have identical findings on the surface ECG; the ECG will have one of two distinct patterns of ST elevation described below: Type 1 Brugada ECG pattern The elevated ST segment ( 2 mm) descends with an upward convexity to an inverted T wave ( figure 1). This is referred to as the "coved type" Brugada pattern. Type 2 Brugada ECG pattern The ST segment has a "saddle back" ST-T wave configuration, in which the elevated ST segment descends toward the baseline and then rises again to an upright or biphasic T wave ( figure 1). The definitions of SCA and SCD are presented and discussed in detail separately. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.) RISK FACTORS FOR ARRHYTHMIA OR SUDDEN CARDIAC ARREST The management of patients with Brugada syndrome depends on their level of risk for future sustained ventricular arrhythmia, sudden cardiac arrest (SCA), or sudden cardiac death (SCD); therefore, early risk assessment is important to guide treatment strategy. High-risk symptoms Among patients with Brugada pattern electrocardiogram (ECG), the following symptoms represent high-risk markers for subsequent arrhythmic events and SCD: https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 2/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate SCA Compared with asymptomatic patients, those with a previous history of SCA have the highest risk of subsequent arrhythmic events. Two larger studies illustrate these findings [1,2]. In one series of 1029 patients (median age 45 years at diagnosis) with Brugada pattern ECG in the FINGER European Registry, 654 patients were asymptomatic and 62 had prior SCA [2]. Over a median follow-up of 32 months, patients with prior SCA were at higher risk for experiencing a future arrhythmic event compared with asymptomatic patients (7.7 versus 0.5 events per year; hazard ratio [HR] 11; 95% CI 4.8-24.3). Syncope Compared with asymptomatic patients, those with a previous history of arrhythmic syncope (unexplained syncope suggestive of a tachyarrhythmia) have the second highest risk of subsequent arrhythmic events after those with SCA [1-4]. In the FINGER European Registry of 1029 patients, 313 had prior syncope [2]. Over a median follow-up of 32 months, patients with syncope were at higher risk for experiencing a future arrhythmic event compared with asymptomatic patients (1.9 versus 0.5 events per year; HR 3.4; 95% CI 1.6-7.4). A separate study of 334 patients was similar in that patients with SCA had the highest risk of life-threatening arrhythmic events (SCD or documented ventricular fibrillation), followed by patients with syncope; those who were asymptomatic had the lowest risk of arrhythmic events ( figure 2) [1]. Sustained ventricular tachycardia This includes any such arrythmias that are documented on 12-lead ECG or cardiac monitoring (eg, telemetry or ambulatory ECG monitors) [5]. Sustained ventricular tachycardia is assumed to have a high likelihood of leading to SCD in patients with Brugada syndrome. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation".) Nocturnal agonal respiration is a rare finding, but if present it is also considered a high-risk symptom. Nocturnal agonal respiration can be related to sudden unexpected nocturnal death syndrome (SUNDS; also called sudden unexpected death syndrome). These conditions are described in detail separately. Intermediate-risk factors The following risk factors place a person at moderate risk of subsequent arrhythmic events and SCD. This is based on our clinical experience and/or supportive studies. In our experience, more concerning intermediate-risk factors are: Syncope that may be nonarrhythmic in origin When there is uncertainty if syncope is due to an underlying arrhythmia, there is still an intermediate likelihood that the syncope https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 3/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate may have been cause by an arrhythmic event. The following risk factors still represent intermediate-risk factors for subsequent arrhythmic events and SCD but are less concerning than syncope: Family history of SCA and/or Brugada Syndrome Patients with Brugada syndrome who report a familial history of SCA or SCD may be at higher risk for SCA; however, data are mixed [6-8]. In some studies, familial history was not shown to be a strong risk factor for future malignant arrythmia [6,7]. However, in a separate multicenter registry of patients with Brugada syndrome treated with implantable cardiac defibrillator (ICD), familial history of SCD was associated with arrhythmic events [8]. Drug-induced type 1 ECG pattern Some studies have suggested that a type 1 "coved type" Brugada ECG pattern is associated with increased arrhythmic risk ( figure 1). (See 'Definitions' above.) Patients with a spontaneous type 1 ECG pattern may have a higher arrhythmic risk compared with patients who develop this pattern with a drug challenge; however, evidence is mixed [2,9,10]. A cohort of 421 patients with type 1 Brugada pattern ECG (19 percent spontaneous) were followed over a median of 63 months. Arrhythmic event rates were higher among patients with spontaneous type 1 ECG compared with a drug-induced type 1 Brugada pattern (2.3 versus 1.1 percent per year) [9]. In the FINGER Brugada registry of 1029 patients with Brugada pattern ECGs, the arrhythmic event rate for asymptomatic patients was low (0.5 percent per year). Patients with spontaneous type 1 ECG had similar rates of arrhythmic events compared with those with drug-induced type 1 ECG pattern (0.8 versus 0.4 percent). [2]. Atrial fibrillation (AF) AF occurs more frequently in patients with the Brugada ECG pattern compared with the general population. Additionally, patients with the Brugada ECG pattern who experience AF have a higher risk of future ventricular tachyarrhythmias; this was shown in a series of 73 patients with Brugada syndrome in whom 14 percent had AF [11]. Compared with patients free of AF, those with AF had a higher incidence of syncope (60 versus 22 percent) and ventricular fibrillation (40 versus 14 percent). Possible risk factors Whereas male sex [3,12] and presence of inferolateral ECG abnormalities [13] may also be markers of increased risk in patients with a Brugada pattern ECG, there is limited evidence that these have clinical utility. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 4/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate MANAGEMENT General measures in all patients All patients with Brugada syndrome or Brugada pattern electrocardiogram (ECG) in the absence of symptoms or other risk factors should undergo routine follow-up and be counseled on the following general measures aimed at preventing potential malignant arrythmia: Antipyretics If they develop a fever for any reason, it should be promptly treated with an antipyretic agent. (See "Pathophysiology and treatment of fever in adults", section on 'Selection of antipyretic'.) Avoiding specific medications Patients should avoid medications that are known to increase the risk of ventricular arrhythmias in patients with Brugada pattern ECG (a full list is available at www.brugadadrugs.org) [14,15]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) Selected drugs that should be avoided in patients with Brugada syndrome or pattern are summarized below: Class I antiarrhythmic drugs aside from quinidine In particular, sodium channel blockers may be deleterious and should not be used for therapy (eg, flecainide, ajmaline, or procainamide); these can transiently induce the characteristic type 1 ECG changes and are frequently used as part of a drug challenge to diagnose the Brugada ECG pattern ( table 1) [16-20]. In addition, sodium channel blockade can induce premature ventricular beats or ventricular tachycardia in patients with Brugada syndrome, particularly in symptomatic patients (6 out of 10 in one report) [21]. Some psychotropic drugs Tricyclic antidepressants, lithium, and oxcarbazepine should be avoided. These drugs can also cause sodium channel blockade and potentially precipitate arrhythmias. Some anesthesia medications Procaine, bupivacaine, and prolonged propofol infusion should be avoided. Avoid excessive alcohol intake Patients with Brugada pattern ECG should avoid excessive alcohol intake, as this has been shown to trigger arrythmia [22,23]. High-risk patients The treatment of high-risk patients with Brugada syndrome is primarily focused on the prevention of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 5/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate through termination of any ventricular tachyarrhythmias. Initial therapy with implantable cardiac defibrillator For high-risk patients with the Brugada syndrome (ie, those who have survived SCA or those with a history of syncope from ventricular tachyarrhythmias), we recommend an implantable cardiac defibrillator (ICD) rather than antiarrhythmic drug therapy. (See 'High-risk symptoms' above.) This recommendation is consistent with society guidelines published in 2013 and 2017 ( algorithm 1) and is endorsed by numerous professional societies and experts worldwide [5,24-26]. Patients with the Brugada syndrome who experience recurrent ventricular arrhythmias resulting in ICD shocks may require additional therapy with an antiarrhythmic drug or catheter ablation to reduce the frequency of ICD shocks. (See 'Patients with ICD with high arrhythmic burden' below.) We approach treatment of patients with sudden unexpected nocturnal death syndrome (SUNDS; also called sudden unexpected death syndrome) in an identical fashion as patients with Brugada syndrome with high-risk features. (See 'High-risk symptoms' above.) In patients with the Brugada syndrome, ICDs are effective for terminating life-threatening arrhythmias [5,8,17,27-29]. While several studies have looked at the effectiveness of ICD therapy in patients with the Brugada syndrome, there are no randomized trials comparing ICDs with antiarrhythmic drug therapy (or no drug therapy) in patients with Brugada syndrome. Evidence for efficacy of ICDs for specific patient subgroups includes the following: Efficacy Adult patients In a 2019 meta-analysis of 1539 patients from 28 nonrandomized studies, 79 percent had an ICD for primary prevention after a mean follow-up of nearly five years; 18 percent of patients received an appropriate shock [29]. There was a very low cardiac mortality rate of 0.03 per 100 patient-years. Another study with a longer follow up of 10 years described higher rates of appropriate shocks, ranging from 19 percent for patients with an ICD placed for syncope to 48 percent for patients with an ICD placed for SCA [30]. Pediatric patients In one series of 35 patients 20 years of age (mean age 14 years, 92 percent symptomatic) who underwent ICD implantation and were followed for an average of 7.3 years, 26 percent received appropriate ICD therapy [31]. Nine percent of patients died in an electrical storm, 20 percent experienced inappropriate shocks, and 14 percent had device-related complications. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 6/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Patients with SUNDS ICD therapy is also beneficial for patients with SUNDS. In the DEBUT trial, which randomized 66 patients who were considered definite or probable SUNDS survivors to treatment with an ICD or beta blockers, the trial was prematurely terminated after a mean follow-up of 24 months because of four deaths in the beta blocker arm, compared with none in the ICD arm [32]. Seven patients in the latter group had recurrent ventricular fibrillation that was appropriately terminated by the ICD. Complications Although ICD therapy is generally safe in patients with Brugada syndrome, the following complications have been described in this patient population: Inappropriate ICD shocks In patients with Brugada syndrome who have an ICD, the rate of inappropriate shocks is relatively high. In a metanalysis of 1539 nonrandomized studies, 18 percent received inappropriate shocks after an average of 2.5 years [29]. Another cohort study of 378 patients with Brugada syndrome who had an ICD showed that 37 percent received an inappropriate shock after an average of 13 years [30]. Lead complications In a series of 41 adult patients with Brugada syndrome, 20 percent had a lead-related complication (eg, lead fracture, subclavian stenosis, lead dislodgement, lead/ device infection) [33]. In a separate series of 35 pediatric patients with Brugada syndrome who underwent ICD implantation (mean age 14 years), 29 percent had a lead complication (including three with lead fractures and one patient with lead dislodgement) [31]. It is uncertain whether a subcutaneous ICD system reduces the risk of some lead complications in patients with Brugada syndrome. (See "Subcutaneous implantable cardioverter defibrillators".) Other rare complications Pulse generator migration has been described but is probably less common [31]. The periprocedural and long-term complications of ICDs are described in detail separately. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions", section on 'Complications' and "Cardiac implantable electronic devices: Long- term complications".) Alternative initial therapy with antiarrythmics Pharmacologic therapy for ventricular tachyarrhythmia prevention is not usually first-line therapy for patients at high risk of SCA; this approach has been tried in the Brugada syndrome with relatively little success. The exception is if the patient is not a suitable candidate for an ICD or does not want to have one placed after a https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 7/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate detailed shared decision-making discussion. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions", section on 'ICD not recommended'.) In both circumstances, we suggest initial therapy with either quinidine or amiodarone, although catheter ablation is also an option. (See 'Catheter ablation' below.) For patients with Brugada syndrome, there have not been any clinical trials comparing initial antiarrhythmic therapy with initial ICD placement. The evidence for efficacy of quinidine and amiodarone in patients with Brugada syndrome is largely extrapolated from studies of these medications in other ventricular tachyarrhythmia syndromes. The doses and rationale for the use of these medications in patients with Brugada syndrome are described as follows: Quinidine The dose is 1 to 1.5 g/day of quinidine sulfate or 600 to 900 mg/day of hydroquinidine (not available in the United States), typically divided into two or three equal daily doses. Small studies have suggested that lower doses of quinidine (300 to 600 mg/day) may be effective in some patients [34]. The beneficial effect of quinidine may be mediated by its blockade of I , which is a to transient outward electrical current in myocardial cells. This current may promote premature ventricular beats that act as the trigger for ventricular tachycardia or fibrillation [35].The potential efficacy of quinidine in patients with Brugada syndrome has been shown only in small series of patients. In one study, invasive electrophysiologic testing was performed on 25 patients with Brugada pattern ECGs (15 symptomatic and 10 asymptomatic) before and after treatment with quinidine bisulfate (mean dose 1.4 g/per day) [36]. Ventricular fibrillation was inducible in all patients at baseline compared with only three patients after quinidine loading. In the 19 patients who continued treatment with quinidine for an average of 56 months, none had a ventricular arrhythmia or arrhythmic syncope. In another small study of 50 patients who completed a 36-month, double-blind, placebo-controlled study of hydroquinidine (with crossover to the other group for all patients at 18 months), there were no arrhythmic events in the hydroquinidine group while on treatment [37]. However, 26 percent of patients stopped the medication due to side effects. Adverse effects of quinidine are discussed in detail separately. (See "Major side effects of class I antiarrhythmic drugs", section on 'Quinidine'.) Amiodarone The dose is 200 mg daily after an appropriate initial loading dose (typically 400 mg twice daily or 200 mg three times daily for one to two weeks). https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 8/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Amiodarone is the most effective agent for the prevention of ventricular tachyarrhythmias, although there are more potential side effects with its use than with most other antiarrhythmic agents, particularly in younger patients in whom therapy might be expected to last for decades. The efficacy of amiodarone for treatment of ventricular arrythmias is discussed in greater detail elsewhere. (See "Amiodarone: Clinical uses", section on 'Amiodarone for ventricular arrhythmias' and "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) Patients with ICD with high arrhythmic burden In patients with an ICD for Brugada syndrome who have recurrent arrhythmias resulting in repeated or concerning ICD shocks, we suggest catheter ablation of arrhythmogenic substrate in the right ventricular outflow tract and right ventricular free wall. Therapy with quinidine or amiodarone is also an option. (See 'Catheter ablation' below.) In some patients, both catheter ablation and antiarrhythmic therapy may be required to terminate arrhythmia. Catheter ablation Radiofrequency catheter ablation for ventricular arrhythmias in patients with the Brugada syndrome can effectively reduce the burden of ventricular arrhythmias and is endorsed as a treatment option (along with quinidine) for patients with or without an ICD who experience recurrent ventricular tachyarrhythmias [26]. We also consider radiofrequency catheter ablation for patients with a Brugada syndrome and significant arrhythmic burden in whom antiarrhythmic drugs have failed. Catheter ablation may also be considered as first-line therapy in patients with a large arrhythmia burden. (See "Overview of catheter ablation of cardiac arrhythmias".) Radiofrequency ablation of the right ventricular substrate in these patients should be performed at centers experienced in epicardial mapping and ablation. In patients with Brugada syndrome, observational and nonrandomized trials have shown that catheter ablation is effective at treating ventricular arrhythmia [38,39]. In a systematic review of 22 nonrandomized studies including 233 patients who underwent catheter ablation for symptomatic Brugada syndrome, the efficacy of ablation differed according to mapping and ablation approach [38]. Epicardial mapping with substrate ablation was shown to be highly effective at eliminating ventricular arrhythmia in 97 percent of patients, ventricular fibrillation triggering-premature ventricular contraction ablation was effective in 80 percent, and endocardial mapping with substrate ablation in only 71 percent of patients. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 9/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate In a large single-cohort procedural study of 135 symptomatic patients with Brugada syndrome, complete ablation of all arrhythmogenic substrate was performed in all patients. After catheter ablation, patients no longer demonstrated Brugada pattern on ECG and did not have inducible ventricular tachycardia and ventricular fibrillation [39]. Drug therapy Quinidine and amiodarone are two antiarrhythmic options for the treatment of ventricular tachyarrhythmias in patients with the Brugada syndrome who have recurrent arrhythmias resulting in ICD shocks [5,34,36]. While either drug may be effective, we suggest initial adjunctive therapy with quinidine for most patients, particularly younger patients in whom there is a desire to avoid the potential toxicities associated with long-term amiodarone. The doses of and rationale for the use of quinidine and amiodarone are discussed above. (See 'Alternative initial therapy with antiarrythmics' above.) Adverse effect of quinidine and amiodarone are presented separately. (See "Major side effects of class I antiarrhythmic drugs", section on 'Quinidine' and "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) Intermediate-risk patients For patients Brugada pattern ECG and intermediate-risk factors for future arrythmia and SCA, we perform shared decision-making and consider further risk stratification with a signal averaged ECG, possible electrophysiologic study, and other tests (ie, cardiac monitoring) to further guide diagnosis and therapy. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Risk stratification for those with uncertain diagnosis' and 'Risk factors for arrhythmia or sudden cardiac arrest' above.) The reason that shared decision-making is important is because tests such as signal-averaged ECG and electrophysiologic studies do not always lead to a definitive diagnosis; they may also have spurious results that could lead to treatments with potential complications and/or adverse effects (eg, ICD or antiarrhythmic medications). For example, although ICDs can prevent SCA/SCD in patients with Brugada syndrome, the rate of inappropriate shocks is relatively high, and therefore when the diagnosis of Brugada syndrome is uncertain, placement of an ICD could have a low ratio of potential benefit relative to harm. If a patient with suspected Brugada syndrome has intermediate-risk factors for subsequent arrhythmic events, we may perform further risk stratification prior to making therapeutic decisions. This is consistent with 2013 Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society (HRS/EHRA/APHRS) expert consensus statement [5]. (See 'Intermediate-risk factors' above.) https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 10/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate If after electrophysiologic study a patient has confirmed Brugada syndrome, we place an ICD and treat the patient as having Brugada syndrome with high-risk features. If a patient has a negative electrophysiologic study, we perform routine follow-up. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Electrophysiology testing'.) Management of patients with Brugada pattern In contrast to patients with the Brugada syndrome or SUNDS, asymptomatic patients with only the Brugada ECG pattern and no high- or intermediate-risk factors do not require any specific therapy other than the general measures described in detail separately. (See 'General measures in all patients' above.) ALTERNATIVE APPROACHES: OTHER GUIDELINE GROUPS Several professional societies have discussed their approach to the treatment of patients with the Brugada syndrome [5,17,26,40]. These approaches are largely consistent with our approach, but there are also some key differences. Similar to our approach, the 2013 Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society (HRS/EHRA/APHRA) most strongly recommend implantable cardioverter-defibrillator (ICD) for patients with Brugada syndrome who have survived sudden cardiac arrest (SCA) or who have documented spontaneous sustained ventricular tachycardia [5]. (See 'High-risk symptoms' above and 'Initial therapy with implantable cardiac defibrillator' above.) The HRS/EHRA/APRA recommendation for ICD implantation for patients with Brugada pattern electrocardiogram (ECG) and a history of syncope is less strong compared with ours. Also, this guideline does not advocate for a role of considering family history of SCA/sudden cardiac death (SCD) or Brugada syndrome in risk stratification, whereas we consider family history an intermediate-risk factor, and we may use this as a reason to perform further risk stratification (in the context of shared decision-making). (See 'Intermediate-risk patients' above.) Also different from our approach, the second consensus conference on Brugada syndrome, endorsed in 2005 by the HRS and the EHRA, recommended ICD implantation for nearly all patients with the Brugada syndrome, including many with asymptomatic patients [17]. SCREENING RELATIVES Because of relatively limited data regarding the best approach to screening of first-degree relatives, guidance is primarily based on expert opinion [26]. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 11/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Clinical and ECG screening Since Brugada syndrome follows an autosomal dominant genetic pattern with variable penetrance, all first-degree relatives of patients with confirmed Brugada syndrome should undergo screening with a clinical history and 12-lead electrocardiogram (ECG). The clinical history should carefully screen for any prior episodes of syncope, and the 12-lead ECG should be carefully scrutinized for findings characteristic of the Brugada ECG pattern ( figure 1). Genetic testing We suggest genetic testing for all patients with Brugada syndrome, and if a pathogenic variant is identified, we test all first-degree relatives. We advocate a strategy of testing the proband, then performing targeted genetic testing of family members only if testing of the proband is positive for a known associated mutation. Pathogenic variants in potassium channels are less commonly seen in patients with Brugada syndrome [41]. Pathogenic variants in sodium channel genes can lead to some of the ECG and clinical manifestations of Brugada syndrome; this is discussed in detail separately. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Genetics'.) Still, we do not advocate universal genetic testing of asymptomatic first-degree relatives of patients with confirmed Brugada syndrome, as evidence does not support this approach [42]. In a study of 2022 patients who underwent DNA sequencing for an inherited arrythmia syndrome, 63 persons had a potentially pathogenic variant in SCN5A and/or KCNH2 genes. Patients with potentially pathogenic variants had a similar rate of arrhythmia diagnosis (17 versus 13 percent) compared with patients without these variants [42]. Repeat screening For first-degree relatives of a patient with Brugada syndrome who initially screen negative, we repeat screening with a clinical history and ECG every one to two years. This is because a Brugada ECG may not develop until later in life. We decrease the frequency of screening after the fifth decade of life, when the incidence of new-onset Brugada syndrome is lower. However, lifelong vigilance for syncope is required in patients with a family history of Brugada. While provocative pharmacologic testing is also available, we do not perform this part of the screening process for the majority of the first-degree relatives that we screen. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) Management based on screening result The management of first-degree relatives of patients with Brugada syndrome depends on the results of screening. Positive results Screening may identify patients with both symptomatic Brugada syndrome and asymptomatic Brugada pattern ECGs. The management of relatives at this https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 12/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate point is similar to other patients determined to have suspected or confirmed Brugada syndrome. (See 'Risk factors for arrhythmia or sudden cardiac arrest' above and 'Management' above.) Negative results Screening may identify patients in whom Brugada syndrome (and Brugada pattern ECG) can be confidently excluded: First-degree relatives with no history of syncope and a normal ECG are considered to have a negative screening result. These patients should undergo repeat screening with a clinical history and ECG every one to two years until at least the fifth decade of life, since a Brugada ECG may not develop until later in life. (See 'Screening relatives' above.) Indeterminate results Screening may identify patients in whom Brugada syndrome (and Brugada pattern ECG) can neither be diagnosed nor confidently excluded. In such patients, additional testing or ongoing surveillance is needed. First-degree relatives with a history of syncope of suspected arrhythmic origin and a type 2 Brugada ECG pattern or a normal ECG should undergo drug-challenge testing. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) First-degree relatives with a concerning history of syncope but a normal-appearing ECG have an indeterminate screening result but may continue to have a high suspicion for the Brugada syndrome. Such patients should have ongoing screening with serial ECGs performed over three to four visits over the course of one to two years. First-degree relatives with indeterminate screening should also be considered for provocative testing with a pharmacologic challenge. A negative drug challenge has a specificity of 94 percent and negative predictive value of 83 percent in a similar population, and therefore a negative test makes Brugada syndrome unlikely, and ongoing screening is not mandatory in such patients [20]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) Since the diagnostic ECG changes of Brugada syndrome can appear later in life (in the fourth and fifth decade), symptomatic younger patients (ie, in their teens or 20s) with a first-degree relative with Brugada syndrome should continue to receive annual screening ECGs. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 13/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Risk factors for arrythmia of sudden cardiac arrest (SCA) The most important prognostic risk factors for patients with the Brugada electrocardiogram (ECG) pattern or Brugada syndrome are history of prior SCA, syncope from ventricular tachyarrhythmia, and/or documented sustained ventricular tachycardia. The risk of having a later ventricular arrhythmia is much lower in asymptomatic patients with Brugada pattern ECGs, although subgroups of asymptomatic patients with increased risk can be identified. (See 'Risk factors for arrhythmia or sudden cardiac arrest' above.) General measures If a patient has Brugada pattern ECG or Brugada syndrome, we counsel them to treat fevers with antipyretics, to avoid medications that provoke Brugada ECG changes, and to avoid excessive alcohol consumption. (See 'General measures in all patients' above.) Management of high-risk patients Treatment for patients diagnosed with the Brugada syndrome is primarily focused on prevention of SCA ( algorithm 1). (See 'Initial therapy with implantable cardiac defibrillator' above.) Initial therapy For patients with the Brugada syndrome who have survived SCA or those with a history of syncope from ventricular tachyarrhythmias, we recommend implantation of an implantable cardioverter-defibrillator (ICD) rather than antiarrhythmic drug therapy (Grade 1A). (See 'Initial therapy with implantable cardiac defibrillator' above.) Alternative initial therapy with antiarrhythmics In patients who refuse ICD implantation or are not considered a candidate for ICD implantation due to reduced life expectancy or significant comorbidities, we suggest initial therapy with either quinidine or amiodarone (Grade 2C). (See 'Alternative initial therapy with antiarrythmics' above.) High arrhythmic burden In patients with an ICD who have recurrent arrhythmias resulting in ICD shocks, we suggest catheter ablation of arrhythmogenic substrate in https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 14/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate the right ventricular outflow tract and right ventricular free wall. (Grade 2C). Therapy with quinidine or amiodarone is also an option. (See 'Catheter ablation' above.) Intermediate-risk patients For these patients, we perform shared decision-making and consider further risk stratification with signal-averaged ECG, electrophysiologic study, and possibly other tests in order to further guide therapy. (See 'Intermediate-risk patients' above and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Risk stratification for those with uncertain diagnosis'.) Patients with Brugada pattern ECG who are asymptomatic For patients with the Brugada ECG pattern who are otherwise asymptomatic and have none of the criteria that would suggest Brugada syndrome (ie, family history of sudden cardiac death [SCD] or type 1 Brugada ECG pattern), we recommend no treatment (Grade 1B). (See 'Intermediate-risk patients' above.) In these patients, we perform general measures. (See 'General measures in all patients' above.) First-degree relatives Since Brugada syndrome follows an autosomal dominant genetic pattern with variable penetrance, all first-degree relatives of patients with confirmed Brugada syndrome should undergo screening with a clinical history and 12-lead ECG. While provocative pharmacologic testing and genetic testing are available, we do not proceed with these tests as part of the screening process for the majority of patients. (See 'Screening relatives' above.) For first-degree relatives of a patient with Brugada syndrome who initially screen negative, we repeat screening with a clinical history and ECG every year, since a Brugada ECG may not develop until later in life. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Ann Garlitski, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 15/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate 1. Brugada J, Brugada R, Antzelevitch C, et al. Long-term follow-up of individuals with the |
2 or equivocal ECG'.) Management based on screening result The management of first-degree relatives of patients with Brugada syndrome depends on the results of screening. Positive results Screening may identify patients with both symptomatic Brugada syndrome and asymptomatic Brugada pattern ECGs. The management of relatives at this https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 12/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate point is similar to other patients determined to have suspected or confirmed Brugada syndrome. (See 'Risk factors for arrhythmia or sudden cardiac arrest' above and 'Management' above.) Negative results Screening may identify patients in whom Brugada syndrome (and Brugada pattern ECG) can be confidently excluded: First-degree relatives with no history of syncope and a normal ECG are considered to have a negative screening result. These patients should undergo repeat screening with a clinical history and ECG every one to two years until at least the fifth decade of life, since a Brugada ECG may not develop until later in life. (See 'Screening relatives' above.) Indeterminate results Screening may identify patients in whom Brugada syndrome (and Brugada pattern ECG) can neither be diagnosed nor confidently excluded. In such patients, additional testing or ongoing surveillance is needed. First-degree relatives with a history of syncope of suspected arrhythmic origin and a type 2 Brugada ECG pattern or a normal ECG should undergo drug-challenge testing. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) First-degree relatives with a concerning history of syncope but a normal-appearing ECG have an indeterminate screening result but may continue to have a high suspicion for the Brugada syndrome. Such patients should have ongoing screening with serial ECGs performed over three to four visits over the course of one to two years. First-degree relatives with indeterminate screening should also be considered for provocative testing with a pharmacologic challenge. A negative drug challenge has a specificity of 94 percent and negative predictive value of 83 percent in a similar population, and therefore a negative test makes Brugada syndrome unlikely, and ongoing screening is not mandatory in such patients [20]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) Since the diagnostic ECG changes of Brugada syndrome can appear later in life (in the fourth and fifth decade), symptomatic younger patients (ie, in their teens or 20s) with a first-degree relative with Brugada syndrome should continue to receive annual screening ECGs. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 13/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Risk factors for arrythmia of sudden cardiac arrest (SCA) The most important prognostic risk factors for patients with the Brugada electrocardiogram (ECG) pattern or Brugada syndrome are history of prior SCA, syncope from ventricular tachyarrhythmia, and/or documented sustained ventricular tachycardia. The risk of having a later ventricular arrhythmia is much lower in asymptomatic patients with Brugada pattern ECGs, although subgroups of asymptomatic patients with increased risk can be identified. (See 'Risk factors for arrhythmia or sudden cardiac arrest' above.) General measures If a patient has Brugada pattern ECG or Brugada syndrome, we counsel them to treat fevers with antipyretics, to avoid medications that provoke Brugada ECG changes, and to avoid excessive alcohol consumption. (See 'General measures in all patients' above.) Management of high-risk patients Treatment for patients diagnosed with the Brugada syndrome is primarily focused on prevention of SCA ( algorithm 1). (See 'Initial therapy with implantable cardiac defibrillator' above.) Initial therapy For patients with the Brugada syndrome who have survived SCA or those with a history of syncope from ventricular tachyarrhythmias, we recommend implantation of an implantable cardioverter-defibrillator (ICD) rather than antiarrhythmic drug therapy (Grade 1A). (See 'Initial therapy with implantable cardiac defibrillator' above.) Alternative initial therapy with antiarrhythmics In patients who refuse ICD implantation or are not considered a candidate for ICD implantation due to reduced life expectancy or significant comorbidities, we suggest initial therapy with either quinidine or amiodarone (Grade 2C). (See 'Alternative initial therapy with antiarrythmics' above.) High arrhythmic burden In patients with an ICD who have recurrent arrhythmias resulting in ICD shocks, we suggest catheter ablation of arrhythmogenic substrate in https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 14/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate the right ventricular outflow tract and right ventricular free wall. (Grade 2C). Therapy with quinidine or amiodarone is also an option. (See 'Catheter ablation' above.) Intermediate-risk patients For these patients, we perform shared decision-making and consider further risk stratification with signal-averaged ECG, electrophysiologic study, and possibly other tests in order to further guide therapy. (See 'Intermediate-risk patients' above and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Risk stratification for those with uncertain diagnosis'.) Patients with Brugada pattern ECG who are asymptomatic For patients with the Brugada ECG pattern who are otherwise asymptomatic and have none of the criteria that would suggest Brugada syndrome (ie, family history of sudden cardiac death [SCD] or type 1 Brugada ECG pattern), we recommend no treatment (Grade 1B). (See 'Intermediate-risk patients' above.) In these patients, we perform general measures. (See 'General measures in all patients' above.) First-degree relatives Since Brugada syndrome follows an autosomal dominant genetic pattern with variable penetrance, all first-degree relatives of patients with confirmed Brugada syndrome should undergo screening with a clinical history and 12-lead ECG. While provocative pharmacologic testing and genetic testing are available, we do not proceed with these tests as part of the screening process for the majority of patients. (See 'Screening relatives' above.) For first-degree relatives of a patient with Brugada syndrome who initially screen negative, we repeat screening with a clinical history and ECG every year, since a Brugada ECG may not develop until later in life. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Ann Garlitski, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 15/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate 1. Brugada J, Brugada R, Antzelevitch C, et al. Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation 2002; 105:73. 2. Probst V, Veltmann C, Eckardt L, et al. Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry. Circulation 2010; 121:635. 3. Priori SG, Napolitano C, Gasparini M, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002; 105:1342. 4. Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation 2003; 108:3092. 5. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932. 6. Eckardt L, Probst V, Smits JP, et al. Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation 2005; 111:257. 7. Priori SG, Gasparini M, Napolitano C, et al. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol 2012; 59:37. 8. Milman A, Andorin A, Gourraud JB, et al. Profile of patients with Brugada syndrome presenting with their first documented arrhythmic event: Data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS). Heart Rhythm 2018; 15:716. 9. Sieira J, Ciconte G, Conte G, et al. Long-term prognosis of drug-induced Brugada syndrome. Heart Rhythm 2017; 14:1427. 10. Andorin A, Behr ER, Denjoy I, et al. Impact of clinical and genetic findings on the management of young patients with Brugada syndrome. Heart Rhythm 2016; 13:1274. 11. Kusano KF, Taniyama M, Nakamura K, et al. Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. J Am Coll Cardiol 2008; 51:1169. 12. Sieira J, Conte G, Ciconte G, et al. Clinical characterisation and long-term prognosis of women with Brugada syndrome. Heart 2016; 102:452. 13. Georgopoulos S, Letsas KP, Liu T, et al. A meta-analysis on the prognostic significance of inferolateral early repolarization pattern in Brugada syndrome. Europace 2018; 20:134. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 16/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate 14. Dendramis G, Paleologo C, Sgarito G, et al. Anesthetic and Perioperative Management of Patients With Brugada Syndrome. Am J Cardiol 2017; 120:1031. 15. www.brugadadrugs.org (Accessed on July 03, 2019). 16. Atarashi H, Ogawa S, Harumi K, et al. Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads. Idiopathic Ventricular Fibrillation Investigators. Am J Cardiol 1996; 78:581. 17. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. 18. Krishnan SC, Josephson ME. ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol 1998; 9:1167. 19. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101:510. 20. Hong K, Brugada J, Oliva A, et al. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation 2004; 110:3023. 21. Morita H, Morita ST, Nagase S, et al. Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome. J Am Coll Cardiol 2003; 42:1624. 22. Wu Q, Hayashi H, Hira D, et al. Genetic variants of alcohol-metabolizing enzymes in Brugada syndrome: Insights into syncope after drinking alcohol. J Arrhythm 2019; 35:752. 23. Achaiah A, Andrews N. Intoxication with alcohol: An underestimated trigger of Brugada syndrome? JRSM Open 2016; 7:2054270416640153. 24. Brugada J, Campuzano O, Arbelo E, et al. Present Status of Brugada Syndrome: JACC State- of-the-Art Review. J Am Coll Cardiol 2018; 72:1046. 25. Letsas KP, Asvestas D, Baranchuk A, et al. Prognosis, risk stratification, and management of asymptomatic individuals with Brugada syndrome: A systematic review. Pacing Clin Electrophysiol 2017; 40:1332. 26. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 17/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate 27. Brugada J, Brugada R, Brugada P. Right bundle-branch block and ST-segment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. Circulation 1998; 97:457. 28. Hernandez-Ojeda J, Arbelo E, Borras R, et al. Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators: Long-Term Follow-Up. J Am Coll Cardiol 2017; 70:1991. 29. Dereci A, Yap SC, Schinkel AFL. Meta-Analysis of Clinical Outcome After Implantable Cardioverter-Defibrillator Implantation in Patients With Brugada Syndrome. JACC Clin Electrophysiol 2019; 5:141. 30. Sacher F, Probst V, Maury P, et al. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study-part 2. Circulation 2013; 128:1739. 31. Gonzalez Corcia MC, Sieira J, Pappaert G, et al. Implantable Cardioverter-Defibrillators in Children and Adolescents With Brugada Syndrome. J Am Coll Cardiol 2018; 71:148. 32. Nademanee K, Veerakul G, Mower M, et al. Defibrillator Versus beta-Blockers for Unexplained Death in Thailand (DEBUT): a randomized clinical trial. Circulation 2003; 107:2221. 33. Miyazaki S, Uchiyama T, Komatsu Y, et al. Long-term complications of implantable defibrillator therapy in Brugada syndrome. Am J Cardiol 2013; 111:1448. 34. M rquez MF, Bonny A, Hern ndez-Castillo E, et al. Long-term efficacy of low doses of quinidine on malignant arrhythmias in Brugada syndrome with an implantable cardioverter-defibrillator: a case series and literature review. Heart Rhythm 2012; 9:1995. 35. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999; 100:1660. 36. Belhassen B, Glick A, Viskin S. Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation 2004; 110:1731. 37. Andorin A, Gourraud JB, Mansourati J, et al. The QUIDAM study: Hydroquinidine therapy for the management of Brugada syndrome patients at high arrhythmic risk. Heart Rhythm 2017; 14:1147. 38. Fernandes GC, Fernandes A, Cardoso R, et al. Ablation strategies for the management of symptomatic Brugada syndrome: A systematic review. Heart Rhythm 2018; 15:1140. 39. Pappone C, Brugada J, Vicedomini G, et al. Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome. Circ Arrhythm Electrophysiol 2017; 10:e005053. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 18/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate 40. Russo AM, Stainback RF, Bailey SR, et al. ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy: a report of the American College of Cardiology Foundation appropriate use criteria task force, Heart Rhythm Society, American Heart Association, American Society of Echocardiography, Heart Failure Society of America, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol 2013; 61:1318. 41. Wang QI, Ohno S, Ding WG, et al. Gain-of-function KCNH2 mutations in patients with Brugada syndrome. J Cardiovasc Electrophysiol 2014; 25:522. 42. Van Driest SL, Wells QS, Stallings S, et al. Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records. JAMA 2016; 315:47. Topic 106760 Version 26.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 19/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate GRAPHICS ECG patterns of Brugada syndrome in leads V1-V2 (A) This typical coved pattern present in V1-V2 shows the following: 1. At the end of QRS, an ascending and quick slope with a high take-off 2 mm followed by concave or rectilinear downsloping ST. There are few cases of coved pattern with a high take-off between 1 and 2 mm. 2. There is no clear r' wave. 3. The high take-off often does not correspond with the J point. 4. At 40 milliseconds of high take-off, the decrease in amplitude of ST is 4 mm. In RBBB and athletes, it is much higher. 5. ST at high take-off N ST at 40 milliseconds N ST at 80 milliseconds. 6. ST is followed by negative and symmetric T wave. 7. The duration of QRS is longer than in RBBB, and there is a mismatch between V1 and V6. (B) This typical saddle-back pattern present in V1-V2 shows the following: 1. High take-off of r' (that often does not coincide with J point) 2 mm. 2. Descending arm of r' coincides with beginning of ST (often is not well seen). 3. Minimum ST ascent 0.5 mm. 4. ST is followed by positive T wave in V2 (T peak N ST minimum N 0) and of variable morphology in V1. 5. The characteristics of triangle formed by r' allow to define different criteria useful for diagnosis. angle. Duration of the base of the triangle of r' at 5 mm from the high take- off greater than 3.5 mm. 6. The duration of QRS is longer in BrP type 2 than in other cases with r' in V1, and there is a mismatch between V1 and V6. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 20/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate RBBB: right bundle branch block. Reproduced from: Bay s de Luna A, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol 2012; 45:433. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 91152 Version 2.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 21/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Outcome of patients with Brugada syndrome depends upon the clinical presentation In a study of 334 patients with the Brugada syndrome, the incidence of arrhythmic events (sudden cardiac death or documented ventricular fibrillation) during follow-up depended upon the clinical presentation. The outcome was best for those who were asymptomatic and presented with an abnormal ECG, intermediate for those presenting with syncope, and worst in patients with aborted sudden cardiac death. ECG: electrocardiogram. Data from: Brugada J, Brugada R, Antzelevitch C, et al. Circulation 2002; 105:73. Graphic 80714 Version 4.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 22/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 23/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 24/26 7/6/23, 11:28 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Consensus recommendations for implantable cardioverter-defibrillators (ICDs) in patients diagnosed with Brugada syndrome ECG: electrocardiogram; EP: electrophysiology; ICD: implantable cardioverter-defibrillator; SCD: sudden cardiac death; VF: ventricular fibrillation; VT: ventricular tachycardia. Reproduced from: Priori S, Wilde A, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm 2013; 10:1932. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 99533 Version 2.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 25/26 7/6/23, 11:28 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Contributor Disclosures John V Wylie, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Samuel Asirvatham, MD Grant/Research/Clinical Trial Support: Medtronic [Defibrillators]; St Jude's [Sudden Cardiac Death]. Consultant/Advisory Boards: BioTronik [Defibrillators]; Boston Scientific [Sudden Cardiac Death]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 26/26 |
7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Cardiac evaluation of the survivor of sudden cardiac arrest : Philip J Podrid, MD, FACC : Brian Olshansky, MD, Scott Manaker, MD, PhD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 26, 2020. INTRODUCTION Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity with hemodynamic collapse, typically due to sustained ventricular tachycardia/ventricular fibrillation. These events mostly occur in patients with structural heart disease (that may not have been previously diagnosed), particularly coronary heart disease. (See "Pathophysiology and etiology of sudden cardiac arrest".) The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation) or spontaneous reversion restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.) Evaluation of the survivor of SCD includes the following: Identification and treatment of acute reversible causes Evaluation for structural heart disease In patients without obvious arrhythmic triggers or cardiac structural abnormalities, an evaluation for primary electrical diseases Neurologic and psychologic assessment In selected patients with a suspected or confirmed heritable syndrome, evaluation of family members https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 1/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate The evaluation of the survivor of SCD will be reviewed here. The pathophysiology of SCD and the management of survivors of SCD are discussed separately. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Pathophysiology and etiology of sudden cardiac arrest" and "Approach to sudden cardiac arrest in the absence of apparent structural heart disease" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) ETIOLOGY OF SCD Accurate and precise measures of the relative frequencies of various causes of SCD are difficult to obtain. Case definitions are inconsistent and etiologies vary according to the population studied. Common causes of SCD include coronary heart disease, structural heart disease not related to CHD (eg, hypertrophic cardiomyopathy, nonischemic cardiomyopathy, etc), arrhythmias caused by primarily electrical disease (eg, Brugada syndrome, long QT syndrome, etc), and transient or reversible causes (eg, medication toxicity, electrolyte abnormalities, etc). A detailed review of the causes of SCD is presented separately. (See "Pathophysiology and etiology of sudden cardiac arrest", section on 'Etiology of SCD'.) INITIAL EVALUATION The evaluation begins immediately after resuscitation. The first concern is to exclude any obvious reversible factors that may have led to the event ( table 1). History and physical examination The patient (if awake) and family should be questioned, with particular attention to the following: Prior diagnoses of heart disease Use of any medications, especially antiarrhythmic drugs, diuretics, and drugs that might produce long QT syndrome Ingestion of toxins or illicit drugs Antecedent symptoms, especially evidence of ischemia Antecedent stressful events or activities Unfortunately, the cardiac arrest is frequently unwitnessed. In addition, the patient resuscitated from VF often has retrograde amnesia and is unable to remember what occurred prior to the cardiac arrest. Thus, a coherent history may not be ascertainable. Obtaining a history from an observer, when available, is important. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 2/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Laboratory testing Immediate evaluation should include standard laboratory testing and, in many cases, an arterial blood gas to exclude electrolyte abnormalities and acidosis. Any reversible metabolic abnormalities should be identified and corrected, particularly hypokalemia and hypomagnesemia which can predispose to ventricular tachyarrhythmias [1,2]. Toxicologic screening for drugs of abuse should be considered when relevant as drug overdose has been documented in significant numbers of patients with apparent sudden cardiac death [3]. When interpreting the test results, two important limitations should be considered: Electrolyte abnormalities during and shortly after resuscitation may be secondary to cardiac arrest and hypoperfusion as opposed to a cause of SCD [4]. Electrolyte abnormalities by themselves are usually insufficient to cause SCD. Clinical settings that increase the proarrhythmic effect of hypokalemia and hypomagnesemia include acute myocardial infarction [5], overt heart failure, and long QT syndrome. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes", section on 'Metabolic abnormalities'.) It is potentially hazardous to ascribe a cardiac arrest to an electrolyte or metabolic derangement alone, unless there is compelling evidence of an association. Mistaken attribution of a major arrhythmia to an innocent or merely potentiating laboratory abnormality can place the patient at high risk if appropriate therapy to prevent recurrent SCD is delayed or not given. Importantly, electrolyte and pH abnormalities may be secondary to the arrhythmia itself. This risk was illustrated in a review of 169 patients treated with an ICD for sustained ventricular arrhythmia in whom the plasma potassium concentration was measured on the day of the arrhythmia [6]. The likelihood of a recurrent sustained ventricular arrhythmia was 82 percent at five years. The long-term risk was similar in patients with low, normal, and high plasma potassium concentrations at presentation. Electrocardiogram The ECG can reveal evidence of both acute abnormalities and chronic conditions. It should be part of the immediate evaluation and repeated as necessary once the patient's cardiac, hemodynamic, and metabolic condition stabilizes. The ECG should be evaluated for evidence of the following: Ongoing ischemia or prior myocardial infarction. (See 'Coronary angiography' below and "Electrocardiogram in the diagnosis of myocardial ischemia and infarction".) Conduction system disease, including bundle branch block, second degree heart block, and third degree heart block. (See "Left bundle branch block" and "Right bundle branch block" https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 3/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate and "Second-degree atrioventricular block: Mobitz type II" and "Third-degree (complete) atrioventricular block".) Less common abnormalities that also may be evident include: Brugada syndrome, evidenced by a pseudo-RBBB and J point elevation with a downsloping ST segment to a negative T wave in lead V1 and often lead V2. In contrast, with an ST segment myocardial infarction the J point is elevated and the ST segment remains elevated as well ( waveform 1). (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Wolff-Parkinson-White syndrome, evidenced by a short PR interval and a slurred QRS complex upstroke known as a delta wave (as a result the QRS complex has a broad base and narrow peak) ( waveform 2). (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) Arrhythmogenic right ventricular cardiomyopathy (ARVC), suggested by VT or ventricular ectopy with a left bundle branch block configuration and an inferior axis. In addition, abnormalities of the baseline QRS may be present, including an epsilon wave in the right precordial leads (ie, leads V1-V2) ( waveform 3A-B). Long QT syndrome ( waveform 4), possibly with torsades de pointes ( waveform 5). (See "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".) EVALUATION FOR STRUCTURAL HEART DISEASE Excluding patients with an obvious noncardiac etiology (eg, trauma, hemorrhage, or pulmonary embolus), structural heart disease is present in up to 90 percent of patients with SCD ( table 2) [7-13]. (See "Pathophysiology and etiology of sudden cardiac arrest".) It is essential that all survivors of SCD undergo a complete cardiac examination to determine the nature and extent of underlying heart disease. The initial history, physical examination, and laboratory tests may provide evidence of one of these disorders, but further testing is usually necessary to confirm a diagnosis. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 4/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate The standard evaluation typically includes: ECG (see 'Electrocardiogram' above) Cardiac catheterization with coronary angiography Echocardiography In the appropriate clinical setting, coronary angiography and echocardiography may be part of the urgent initial evaluation. In selected patients, cardiac magnetic resonance imaging (MRI) and, rarely, myocardial biopsy are performed. (See 'Cardiac MR' below.) Coronary angiography Coronary angiography is performed in most survivors of SCD for one of two indications: management of an acute coronary syndrome or diagnosis of chronic CHD. Acute coronary syndrome Patients with evidence of STEMI following resuscitation from SCD should undergo urgent cardiac catheterization and, when indicated by the anatomy, revascularization with primary PCI or surgical revascularization [14]. Similarly, patients with a confirmed NSTEMI and those with a high suspicion of ongoing myocardial ischemia should also undergo cardiac catheterization with revascularization as indicated. (See "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction: Determinants of outcome" and "Non-ST-elevation acute coronary syndromes: Selecting an approach to revascularization".) SCD may be the presenting manifestation of an acute coronary syndrome (ACS). Among patients with an ACS, malignant arrhythmias are significantly more common in the setting of an acute ST elevation MI (STEMI), but are also seen in approximately 2 percent of patients with a non-ST elevation MI (NSTEMI). In patients with an ACS and ischemia, the arrhythmia is usually polymorphic VT, rapid VT (ventricular flutter), or VF. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) Patients who experience SCD during the first 48 hours after an STEMI have a higher in-hospital mortality compared with STEMI patients who do not experience sustained VT or VF. However, among patients who survive to hospital discharge there is little or no difference in mortality at one to two years. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) Diagnostic angiography In SCD survivors without an ACS, angiography is still considered to exclude stable, chronic CHD, which, as indicated above, is the leading cause for SCD [15]. Malignant arrhythmias and SCD occur in such patients, usually those who have had a prior infarction with residual myocardial scar. In contrast to patients with an ACS, the culprit arrhythmia is usually scar-related monomorphic VT, which is not the result of ischemia. However, https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 5/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate monomorphic VT can ultimately degenerate to VF, particularly if the arrhythmia induces ischemia. Because SCD may be the first clinical evidence of chronic CHD, most SCD survivors undergo diagnostic angiography prior to discharge. Even for patients arriving at the hospital in refractory VT/VF who are receiving ongoing cardiopulmonary resuscitation (CPR), immediate coronary angiography appears beneficial in a carefully selected group of patients (18 to 75 years of age with VT/VF as initial rhythm who received three shocks and amiodarone loading dose and who can be in the catheterization lab in <30 minutes post-arrest) [16]. Among a cohort of 55 patients who met these criteria (after excluding 7 of 62 who were declared deceased on arrival to the catheterization lab), all of whom were started on extracorporeal life support and underwent immediate coronary angiography, 46 patients (84 percent) had significant obstructive CHD, including 35 patients (64 percent) with acute thrombus, all of whom underwent percutaneous coronary intervention [16]. Among the cohort, 26 patients (42 percent) were discharged alive with favorable neurologic function, compared with 15 percent of historical controls. Diagnostic coronary angiography may not be necessary in selected patients without signs or symptoms of CHD if another clear cause for SCD is identified (eg, long QT syndrome, WPW, Brugada, hypertrophic cardiomyopathy, left ventricular noncompaction, or arrhythmogenic right ventricular cardiomyopathy). Angiography is suggested in younger patients without an apparent cause for SCD in whom angiography may also detect an anomalous origin of a coronary artery. Among competitive athletes under age 35, anomalous origin of a coronary artery was present in 13 percent of SCD survivors in one series [17]. (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Etiology of sudden death'.) Patients with stable CHD who experience an episode of primary SCD without evidence of simultaneous ischemia are at high risk for recurrent malignant arrhythmias, even after percutaneous or surgical revascularization [18-21]. As a result, such patients are treated with an ICD. (See "Risk stratification after acute ST-elevation myocardial infarction".) Echocardiography Echocardiography can detect abnormalities that suggest or confirm the diagnosis of many of the important causes of SCD. Since global left ventricular dysfunction due to myocardial stunning can be induced by cardiac arrest and cardiopulmonary resuscitation, evaluation of left ventricular function should be performed at least 48 hours after resuscitation [22]. Detailed review of the diagnostic criteria for each disorder is presented separately. Potential causes of SCD that can be detected with echocardiography include the following: https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 6/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate CHD Left ventricular dysfunction with wall motion abnormalities suggest prior myocardial infarction. Dyskinetic wall motion is consistent with an aneurysm. Hypertrophic cardiomyopathy (see "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation") Arrhythmogenic right ventricular cardiomyopathy Aortic stenosis (see "Echocardiographic evaluation of the aortic valve") Dilated cardiomyopathy (see "Echocardiographic recognition of cardiomyopathies" and "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy") Cardiac MR Cardiac magnetic resonance imaging (CMR) is indicated for selected patients in whom a diagnosis is uncertain after the above evaluation. (See "Clinical utility of cardiovascular magnetic resonance imaging".) CMR is useful in the evaluation of the following disorders: Hypertrophic cardiomyopathy (see "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation") Myocarditis Arrhythmogenic right ventricular cardiomyopathy Dilated cardiomyopathy Congenital heart disease, including anomalous origin of coronary arteries (see "Congenital and pediatric coronary artery abnormalities" and "Cardiac imaging with computed tomography and magnetic resonance in the adult") Cardiac sarcoidosis Cardiac amyloidosis (see "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis", section on 'Cardiovascular magnetic resonance') The utility of CMR angiography as an alternative to invasive coronary angiography is not well defined. Alternatively, cardiac computed tomography angiography may be used to assess both congenital and acquired coronary abnormalities. (See "Cardiac imaging with computed tomography and magnetic resonance in the adult".) https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 7/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Summary In 1997, the Joint steering committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United States published recommendations for the evaluation of SCD survivors [12]. These recommendations included the following tests, all of which are described above: History and physical examination Blood biochemistries ECG Echocardiography Coronary angiography Since the publication of these recommendations, cardiac MR has come into wider use and is now a common component of this evaluation when standard tests are inconclusive. When this evaluation has not provided a diagnosis, the patient is evaluated for primary electrical disease. EVALUATION FOR PRIMARY ELECTRICAL DISEASES General issues Approximately 5 to 10 percent of SCD survivors have no evidence of a noncardiac etiology or of structural heart disease after the above evaluation. Such patients are considered to have a primary electrical disorder. A detailed discussion of SCD in patients with a structurally normal heart is presented separately. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease".) The majority of these patients do not actually have "normal" hearts, but historically our diagnostic tools have been unable to identify the structural or functional derangement. In the past, the etiology of many of these deaths was unknown and deemed "idiopathic." Subsequent discoveries have identified the cause of death in many of these patients [11,23,24]. As our understanding of the mechanisms of primary electrical disorders has improved, so have our diagnostic capabilities, with important benefits for both the victims of SCD and their families. These disorders are often detected by characteristic changes on the ECG. (See 'Electrocardiogram' above.) Several of the disorders that cause SCD in the absence of structural heart disease are due to abnormalities of cardiac ion channels, including the following: https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 8/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Brugada syndrome (see "Brugada syndrome: Clinical presentation, diagnosis, and evaluation") Long QT syndrome (see "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes") Short QT syndrome (see "Short QT syndrome") Catecholaminergic polymorphic VT (see "Catecholaminergic polymorphic ventricular tachycardia") Disorders associated with SCD that are not due to ion channel abnormalities include: Wolff-Parkinson-White syndrome (see "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis") Commotio cordis (see "Commotio cordis") Patients without evidence of any of the above structural or electrical abnormalities are said to have idiopathic VF or primary electrical disease. Identification of a primary electrical disorder in a SCD survivor has two important benefits: Directing medical treatment to prevent arrhythmia recurrence (eg, beta blockers for catecholaminergic polymorphic VT). Although medical therapy alone is now uncommon in SCD survivors (the vast majority of patients receive an ICD), adjunctive medical therapy can be useful to reduce the frequency of ICD shocks. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Other treatment options'.) Guiding the evaluation and management of family members. EP study Electrophysiologic (EP) testing is not usually performed in patients with an established etiology of SCD. However, EP study can be valuable in those whose initial evaluation reveals no etiology, and in selected patients with a previously identified disorder. In SCD survivors with an apparently normal heart, EP testing may reveal the following: Abnormalities of atrioventricular conduction The presence of severe conducting system disease suggests that a serious bradyarrhythmia may have contributed to the SCD event. However, such patients typically present with syncope rather than SCD. Furthermore, even when conduction disease is identified, VT/VF may be the real culprit and ventricular stimulation to induce ventricular arrhythmias may be warranted. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 9/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate An accessory pathway in patients with Wolff-Parkinson-White syndrome An accessory pathway can result in rapid conduction to the ventricle of a supraventricular arrhythmia, primarily atrial fibrillation, producing a very rapid ventricular rate that can degenerate to VF. Such patients usually have evidence of preexcitation on their ECG. If preexcitation is evident on an ECG in a survivor of SCD, EP study and ablation of the accessory pathway are usually indicated. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Ventricular fibrillation and sudden death'.) Inducible ventricular arrhythmias VT and VF may be induced in patients with a number of underlying cardiac abnormalities. The prognostic value of inducible arrhythmias is best established in patients with prior myocardial infarction and reduced LV systolic function. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction", section on 'Inducible VT/VF'.) There is evidence that inducible VF, particularly when induced repeatedly with nonaggressive protocols, suggests the diagnosis of idiopathic VF and may predict recurrent arrhythmic events [25,26]. In a review of the literature, 69 percent of patients with idiopathic VF had a sustained ventricular tachyarrhythmia induced with a nonaggressive protocol; induced arrhythmia was generally polymorphic in configuration and poorly tolerated [25]. In some other conditions it is not clear that inducible VT or VF has prognostic significance (eg, Brugada syndrome, infiltrative diseases, HCM). Furthermore, aggressive stimulation protocols can induce polymorphic VT or VF in some individuals without cardiac disease. Thus, inducible arrhythmias can be a nonspecific finding. For this reason, the significance of inducible ventricular arrhythmias in patients with apparently normal hearts is unclear. On the other hand, the absence of inducible VT/VF may not preclude ICD implantation since lack of inducibility does not predict low risk. Myocardial scar Substrate mapping may identify areas of scar indicating abnormal substrate and a predisposition to ventricular arrhythmia. These abnormalities are more commonly seen in patients with CHD, HCM, ARVC, or infiltrative diseases, but also occur in some cases of idiopathic VF [27]. In addition, some patients with idiopathic VF have other electrophysiologic abnormalities, including areas of slow conduction, regionally delayed repolarization, or dispersion in repolarization [28]. Supraventricular arrhythmias Patients in whom VT or VF was not well documented at the time of SCD may have another culprit arrhythmia, usually a supraventricular tachycardia (SVT). In such patients, SVT may be inducible during EP study [29]. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 10/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Exercise testing Exercise testing is not usually part of the CHD evaluation in SCD survivors, since most undergo coronary angiography. However, it may be of importance for the SCD survivor in whom the sudden death episode occurred during exercise or physical activity. In addition, the provocation of ischemia with exercise, independently of coronary anatomy, is of importance in the evaluation of the SCD survivor. Although angiography alone does not prove a causal relationship to SCD or the presence of ischemia, the observation that revascularization appears to improve outcomes [9,20,21] means that a negative exercise test in a patient with significant coronary disease on angiography is not likely to affect the decision on revascularization. Also of great importance is the provocation of VT or VF in these patients, which would predict a higher recurrence rate. It is also a target for adjunctive antiarrhythmic therapy, particularly a beta blocker, in addition to an ICD. While VT (which is often scar mediated and provoked by catecholamines) may be provoked during exercise, VF most commonly occurs after exercise in the recovery period (when ischemia is more common). In patients with apparently normal hearts, exercise testing can assist in the diagnosis of long QT syndrome (QT interval fails to shorten or may even lengthen with an increase in heart rate) and catecholaminergic polymorphic VT. It is also useful in patients with Wolff-Parkinson-White pattern as the resolution of the delta wave with exercise generally correlates with low likelihood of a rapid ventricular rate with atrial fibrillation which is the etiology for VF and SCD in these patients. (See "Congenital long QT syndrome: Diagnosis", section on 'Exercise testing' and "Catecholaminergic polymorphic ventricular tachycardia" and "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Evaluation'.) Ambulatory monitoring In patients without a clear etiology for SCD, ambulatory monitoring may reveal recurrent sustained or nonsustained arrhythmias. However, most patients without an established diagnosis will have an ICD placed prior to discharge, and the memory features in these devices may preclude the need for ambulatory monitoring. Pharmacologic challenge As noted above, some of the primary electrical disorders may still be present despite no evidence of abnormalities on any of the preceding tests. ECG abnormalities may be intermittent or latent, and genetic testing is not yet comprehensive enough to exclude all possible disorders. Investigators have evaluated the role of pharmacologic challenge to elicit diagnostic ECG changes or arrhythmias in selected SCD survivors. One report included 18 SCD survivors with no evidence of structural heart disease [30]. All patients had a normal ECG, echocardiogram, coronary angiography, and cardiac MR. Patients were infused with epinephrine (0.05 to 0.5 microg/kg per minute) and then procainamide (1 g over 30 minutes). Epinephrine was intended to induce catecholaminergic polymorphic VT and procainamide to induce the characteristic ECG https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 11/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate abnormalities of Brugada syndrome. (See "Catecholaminergic polymorphic ventricular tachycardia" and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) The following findings were noted: Ten patients were diagnosed with catecholaminergic polymorphic VT based upon an abnormal response to epinephrine infusion (frequent or polymorphic ventricular ectopy, nonsustained VT, or sustained VT). Four of these patients had ventricular ectopy during exercise testing, but none had sustained or nonsustained VT. Two patients were diagnosed with Brugada syndrome. Six patients were left with a diagnosis of idiopathic VF. Among 55 family members who were tested, eight affected members from one family were diagnosed with catecholaminergic polymorphic VT, and one relative was diagnosed with Brugada syndrome. In summary, two-thirds of patients whose standard evaluation provided no etiology for SCD had a diagnosis established with pharmacologic provocative testing. This allowed for the addition of appropriate adjunctive therapy (beta blockers for catecholaminergic polymorphic VT) and the identification of nine additional affected family members. MINOR CARDIAC ABNORMALITIES NOT ASSOCIATED WITH SCD During the course of the cardiac evaluation, minor cardiac abnormalities are often detected that do not have a clear causal relationship to SCD. These findings do not preclude the diagnosis of idiopathic VF; however, their severity must be considered and monitoring is warranted since these disorders may be the initial manifestations of an underlying structural heart disease that will become clinically apparent at a later date [12]. Disorders such as first degree atrioventricular (AV) block, transient second degree Mobitz type II AV block without bradycardia, and isolated bundle branch block do not exclude idiopathic VF. Thickening of the left ventricle less than 10 percent above normal and hypertension without LV hypertrophy are not clearly associated with SCD. A direct link between mitral valve prolapse and SCD has not been established unless there is valve redundancy or thickening, a family history of SCD, or perhaps significant mitral https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 12/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate regurgitation, QT interval prolongation, or ST-T waves changes. (See "Arrhythmic complications of mitral valve prolapse".) AF in the absence of ventricular preexcitation or hyperthyroidism is associated with an increase in total mortality, but not SCD [12,31]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) Isolated ventricular premature beats, and more importantly repetitive forms (ie, couplets or nonsustained ventricular tachycardia), are associated with an increased risk of subsequent SCD only in patients with structural heart disease or with risk factors for CHD. (See "Premature ventricular complexes: Treatment and prognosis", section on 'Prognosis'.) EVALUATION OF FAMILY MEMBERS Some causes of SCD are familial, including a genetic predisposition to premature coronary heart disease, a cardiomyopathy or an electrophysiologic abnormality (eg, long QT syndrome or Brugada), and the risk of cardiovascular disease appears significantly higher in first- and second- degree relatives of the SCD victims, particularly young victims. In a nationwide Danish study from 2000 to 2006, 470 victims of SCD were identified who were 35 years of age or younger [32]. Among a cohort of 3073 first- and second-degree relatives of the SCD victims who were followed for up to 11 years, cardiovascular disease (CVD) was significantly more likely to be present than in the general population (standardized incidence ratio [SIR] for CVD 3.5, 95% CI 2.7-4.7). In contrast, among relatives of elderly (greater than 60 years of age) victims of SCD, there was no difference in the rates of CVD compared with the general population (SIR 0.9, 95% CI 0.8-1.1). A general cardiologic evaluation of first- and second-degree relatives of victims of unexplained SCD can yield the diagnosis of a heritable disease in up to 40 percent of families as illustrated by the following observations [33-35]. In a study of 32 families of victims of unexplained SCD, a general cardiologic evaluation (ECG, echocardiogram, Holter monitor and, less commonly, stress testing) was completed in 107 first-degree relatives [33]. Seven families (22 percent) were diagnosed with a heritable disease: four with long QT syndrome, one with nonstructural cardiac disease, one with myotonic dystrophy, and one with HCM. These findings were extended in a second report that evaluated 43 families with 183 surviving first- and second-degree relatives of victims of unexplained SCD at age 40 [34]. Careful history identified 26 additional cases of unexplained SCD at age 40. Cardiology evaluation included ECG, echocardiogram, exercise tolerance testing (ETT), and https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 13/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate measurement of serum lipids. Additional testing, as indicated, included flecainide challenge for suspected Brugada syndrome or cardiac MR for suspected ARVC. (See "Brugada syndrome or pattern: Management and approach to screening of relatives".) When a clinical diagnosis was established, genetic testing for the suspected disease was performed. Where a genetic abnormality was confirmed, additional screening was done in another 150 family members. The following findings were noted: A heritable disease was identified in 17 families (40 percent): five with catecholaminergic polymorphic VT, four with long QT syndrome, two with Brugada syndrome, one with Brugada/long QT syndrome, three with ARVC, one with HCM, and one with familial hypercholesterolemia. Genetic analysis confirmed the diagnosis in 10 families. An average of 8.9 asymptomatic carriers per family was identified, many through the secondary genetic analysis. Identification of a specific disease was more likely if 2 unexplained SCD events occurred in the family, and if more family members underwent evaluation. The increased yield in the second study may reflect the more extensive evaluation, including ETT, and the inclusion of more family members. Consistent with these findings, it has been recommended that first-degree family members of patients with SCD in the absence of structural heart disease be informed of the potentially increased risk and that an assessment should be offered at a center with experience in the diagnosis and management of inherited cardiac diseases [24]. Routine genetic screening for inherited disorders is not feasible although, in the presence of an identifiable condition, the genetic evaluation of family members may be undertaken at some centers. NEUROLOGIC AND PSYCHOLOGIC ASSESSMENT Patients who have been resuscitated from sudden death should be given a complete neurologic examination to establish the nature and extent of impairment resulting from the arrest. The physical examination, rather than imaging studies or other testing, is the most useful way of elucidating the patient's degree of neurologic function, mental impairment, and of determining prognosis. A 2004 meta-analysis of 11 studies found that the following clinical signs predicted a poor clinical outcome following cardiac arrest with 97 percent specificity [36]: Absence of pupillary light response after 24 hours Absence of corneal reflex after 24 hours https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 14/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Absent motor responses to pain after 24 hours Absent motor responses after 72 hours (See "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis".) Equally important is an assessment of the patient's psychologic state. Posttraumatic stress disorder (PTSD) may occur in SCD survivors. This was suggested in a study of 143 patients who had been resuscitated and discharged with no or only moderate neurologic disability [37]. All patients completed a self-rating questionnaire at a mean of 45 months after cardiac arrest: 39 (27 percent) fulfilled criteria for PTSD. (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis" and "Management of posttraumatic stress disorder in adults".) MANAGEMENT At present, most survivors of SCD are treated with an ICD. The use of ICDs in SCD survivors, the role of adjunctive antiarrhythmic medications and catheter ablation, and exceptions to the use of ICDs are discussed in detail separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) SUMMARY AND RECOMMENDATIONS Evaluation of the survivor of SCD includes the following: Identification and treatment of acute reversible causes, including (see 'Etiology of SCD' above and "Pathophysiology and etiology of sudden cardiac arrest", section on 'Etiology of SCD'): Acute cardiac ischemia and myocardial infarction Antiarrhythmic drugs or other medication (eg, QT prolonging drugs), toxin, or illicit drug ingestion Electrolyte abnormalities, most notably hypokalemia, hyperkalemia, and hypomagnesemia Heart failure Autonomic nervous system factors, especially sympathetic activation (eg, physical or psychologic stress) https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 15/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Evaluation for structural heart disease Initial evaluation including history, physical examination, laboratory testing (eg, electrolytes, blood gas, toxin screen, etc), and electrocardiogram (see 'Initial evaluation' above) Evaluation for structural heart disease, which may include one or more of echocardiography, coronary angiography, cardiac magnetic resonance imaging, depending of the clinical scenario (see 'Evaluation for structural heart disease' above) In patients without obvious arrhythmic triggers or cardiac structural abnormalities, an evaluation for primary electrical diseases Primary electrical diseases include Brugada syndrome, long QT syndrome, short QT syndrome, Wolff-Parkinson-White, catecholaminergic polymorphic VT, commotio cordis, and idiopathic ventricular fibrillation (see 'General issues' above) The evaluation for primary electrical disease may include one or more of electrophysiology studies, exercise testing, ambulatory ECG monitoring, and pharmacologic challenge (see 'Evaluation for primary electrical diseases' above) Neurologic and psychologic assessment (see 'Neurologic and psychologic assessment' above) In selected patients with a suspected or confirmed heritable syndrome, evaluation of family members (see 'Evaluation of family members' above) ACKNOWLEDGMENT The editorial staff at UpToDate acknowledges Jie Cheng, MD, who contributed to an earlier version of this topic review. |
degree relatives of the SCD victims, particularly young victims. In a nationwide Danish study from 2000 to 2006, 470 victims of SCD were identified who were 35 years of age or younger [32]. Among a cohort of 3073 first- and second-degree relatives of the SCD victims who were followed for up to 11 years, cardiovascular disease (CVD) was significantly more likely to be present than in the general population (standardized incidence ratio [SIR] for CVD 3.5, 95% CI 2.7-4.7). In contrast, among relatives of elderly (greater than 60 years of age) victims of SCD, there was no difference in the rates of CVD compared with the general population (SIR 0.9, 95% CI 0.8-1.1). A general cardiologic evaluation of first- and second-degree relatives of victims of unexplained SCD can yield the diagnosis of a heritable disease in up to 40 percent of families as illustrated by the following observations [33-35]. In a study of 32 families of victims of unexplained SCD, a general cardiologic evaluation (ECG, echocardiogram, Holter monitor and, less commonly, stress testing) was completed in 107 first-degree relatives [33]. Seven families (22 percent) were diagnosed with a heritable disease: four with long QT syndrome, one with nonstructural cardiac disease, one with myotonic dystrophy, and one with HCM. These findings were extended in a second report that evaluated 43 families with 183 surviving first- and second-degree relatives of victims of unexplained SCD at age 40 [34]. Careful history identified 26 additional cases of unexplained SCD at age 40. Cardiology evaluation included ECG, echocardiogram, exercise tolerance testing (ETT), and https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 13/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate measurement of serum lipids. Additional testing, as indicated, included flecainide challenge for suspected Brugada syndrome or cardiac MR for suspected ARVC. (See "Brugada syndrome or pattern: Management and approach to screening of relatives".) When a clinical diagnosis was established, genetic testing for the suspected disease was performed. Where a genetic abnormality was confirmed, additional screening was done in another 150 family members. The following findings were noted: A heritable disease was identified in 17 families (40 percent): five with catecholaminergic polymorphic VT, four with long QT syndrome, two with Brugada syndrome, one with Brugada/long QT syndrome, three with ARVC, one with HCM, and one with familial hypercholesterolemia. Genetic analysis confirmed the diagnosis in 10 families. An average of 8.9 asymptomatic carriers per family was identified, many through the secondary genetic analysis. Identification of a specific disease was more likely if 2 unexplained SCD events occurred in the family, and if more family members underwent evaluation. The increased yield in the second study may reflect the more extensive evaluation, including ETT, and the inclusion of more family members. Consistent with these findings, it has been recommended that first-degree family members of patients with SCD in the absence of structural heart disease be informed of the potentially increased risk and that an assessment should be offered at a center with experience in the diagnosis and management of inherited cardiac diseases [24]. Routine genetic screening for inherited disorders is not feasible although, in the presence of an identifiable condition, the genetic evaluation of family members may be undertaken at some centers. NEUROLOGIC AND PSYCHOLOGIC ASSESSMENT Patients who have been resuscitated from sudden death should be given a complete neurologic examination to establish the nature and extent of impairment resulting from the arrest. The physical examination, rather than imaging studies or other testing, is the most useful way of elucidating the patient's degree of neurologic function, mental impairment, and of determining prognosis. A 2004 meta-analysis of 11 studies found that the following clinical signs predicted a poor clinical outcome following cardiac arrest with 97 percent specificity [36]: Absence of pupillary light response after 24 hours Absence of corneal reflex after 24 hours https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 14/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Absent motor responses to pain after 24 hours Absent motor responses after 72 hours (See "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis".) Equally important is an assessment of the patient's psychologic state. Posttraumatic stress disorder (PTSD) may occur in SCD survivors. This was suggested in a study of 143 patients who had been resuscitated and discharged with no or only moderate neurologic disability [37]. All patients completed a self-rating questionnaire at a mean of 45 months after cardiac arrest: 39 (27 percent) fulfilled criteria for PTSD. (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis" and "Management of posttraumatic stress disorder in adults".) MANAGEMENT At present, most survivors of SCD are treated with an ICD. The use of ICDs in SCD survivors, the role of adjunctive antiarrhythmic medications and catheter ablation, and exceptions to the use of ICDs are discussed in detail separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) SUMMARY AND RECOMMENDATIONS Evaluation of the survivor of SCD includes the following: Identification and treatment of acute reversible causes, including (see 'Etiology of SCD' above and "Pathophysiology and etiology of sudden cardiac arrest", section on 'Etiology of SCD'): Acute cardiac ischemia and myocardial infarction Antiarrhythmic drugs or other medication (eg, QT prolonging drugs), toxin, or illicit drug ingestion Electrolyte abnormalities, most notably hypokalemia, hyperkalemia, and hypomagnesemia Heart failure Autonomic nervous system factors, especially sympathetic activation (eg, physical or psychologic stress) https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 15/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Evaluation for structural heart disease Initial evaluation including history, physical examination, laboratory testing (eg, electrolytes, blood gas, toxin screen, etc), and electrocardiogram (see 'Initial evaluation' above) Evaluation for structural heart disease, which may include one or more of echocardiography, coronary angiography, cardiac magnetic resonance imaging, depending of the clinical scenario (see 'Evaluation for structural heart disease' above) In patients without obvious arrhythmic triggers or cardiac structural abnormalities, an evaluation for primary electrical diseases Primary electrical diseases include Brugada syndrome, long QT syndrome, short QT syndrome, Wolff-Parkinson-White, catecholaminergic polymorphic VT, commotio cordis, and idiopathic ventricular fibrillation (see 'General issues' above) The evaluation for primary electrical disease may include one or more of electrophysiology studies, exercise testing, ambulatory ECG monitoring, and pharmacologic challenge (see 'Evaluation for primary electrical diseases' above) Neurologic and psychologic assessment (see 'Neurologic and psychologic assessment' above) In selected patients with a suspected or confirmed heritable syndrome, evaluation of family members (see 'Evaluation of family members' above) ACKNOWLEDGMENT The editorial staff at UpToDate acknowledges Jie Cheng, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Siscovick DS, Raghunathan TE, Psaty BM, et al. Diuretic therapy for hypertension and the risk of primary cardiac arrest. N Engl J Med 1994; 330:1852. 2. Hoes AW, Grobbee DE, Lubsen J, et al. Diuretics, beta-blockers, and the risk for sudden cardiac death in hypertensive patients. Ann Intern Med 1995; 123:481. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 16/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate 3. Rodriguez RM, Montoy JCC, Repplinger D, et al. Occult Overdose Masquerading as Sudden Cardiac Death: From the POstmortem Systematic InvesTigation of Sudden Cardiac Death Study. Ann Intern Med 2020; 173:941. 4. Salerno DM, Asinger RW, Elsperger J, et al. Frequency of hypokalemia after successfully resuscitated out-of-hospital cardiac arrest compared with that in transmural acute myocardial infarction. Am J Cardiol 1987; 59:84. 5. Gettes LS. Electrolyte abnormalities underlying lethal and ventricular arrhythmias. Circulation 1992; 85:I70. 6. Michaud GF, Sticherling C, Tada H, et al. Relationship between serum potassium concentration and risk of recurrent ventricular tachycardia or ventricular fibrillation. J Cardiovasc Electrophysiol 2001; 12:1109. 7. Centers for Disease Control and Prevention (CDC). State-specific mortality from sudden cardiac death United States, 1999. MMWR Morb Mortal Wkly Rep 2002; 51:123. 8. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158. 9. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336:1629. 10. Drory Y, Turetz Y, Hiss Y, et al. Sudden unexpected death in persons less than 40 years of age. Am J Cardiol 1991; 68:1388. 11. Chugh SS, Kelly KL, Titus JL. Sudden cardiac death with apparently normal heart. Circulation 2000; 102:649. 12. Survivors of out-of-hospital cardiac arrest with apparently normal heart. Need for definition and standardized clinical evaluation. Consensus Statement of the Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United States. Circulation 1997; 95:265. 13. Kuisma M, Alasp A. Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome. Eur Heart J 1997; 18:1122. 14. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019; 40:87. 15. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 17/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate 16. Yannopoulos D, Bartos JA, Raveendran G, et al. Coronary Artery Disease in Patients With Out-of-Hospital Refractory Ventricular Fibrillation Cardiac Arrest. J Am Coll Cardiol 2017; 70:1109. 17. Maron BJ, Carney KP, Lever HM, et al. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. J Am Coll Cardiol 2003; 41:974. 18. Natale A, Sra J, Axtell K, et al. Ventricular fibrillation and polymorphic ventricular tachycardia with critical coronary artery stenosis: does bypass surgery suffice? J Cardiovasc Electrophysiol 1994; 5:988. 19. Daoud EG, Niebauer M, Kou WH, et al. Incidence of implantable defibrillator discharges after coronary revascularization in survivors of ischemic sudden cardiac death. Am Heart J 1995; 130:277. 20. Every NR, Fahrenbruch CE, Hallstrom AP, et al. Influence of coronary bypass surgery on subsequent outcome of patients resuscitated from out of hospital cardiac arrest. J Am Coll Cardiol 1992; 19:1435. 21. Kelly P, Ruskin JN, Vlahakes GJ, et al. Surgical coronary revascularization in survivors of prehospital cardiac arrest: its effect on inducible ventricular arrhythmias and long-term survival. J Am Coll Cardiol 1990; 15:267. 22. Kern KB, Hilwig RW, Rhee KH, Berg RA. Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning. J Am Coll Cardiol 1996; 28:232. 23. Myerburg RJ. Sudden cardiac death in persons with normal (or near normal) hearts. Am J Cardiol 1997; 79:3. 24. Wever EF, Robles de Medina EO. Sudden death in patients without structural heart disease. J Am Coll Cardiol 2004; 43:1137. 25. Viskin S, Belhassen B. Idiopathic ventricular fibrillation. Am Heart J 1990; 120:661. 26. DiCarlo LA Jr, Morady F, Schwartz AB, et al. Clinical significance of ventricular fibrillation- flutter induced by ventricular programmed stimulation. Am Heart J 1985; 109:959. 27. Josephson ME, Horowitz LN, Spielman SR, et al. Comparison of endocardial catheter mapping with intraoperative mapping of ventricular tachycardia. Circulation 1980; 61:395. 28. Peeters HA, Sippensgroenewegen A, Wever EF, et al. Electrocardiographic identification of abnormal ventricular depolarization and repolarization in patients with idiopathic ventricular fibrillation. J Am Coll Cardiol 1998; 31:1406. 29. Becker R, Melkumov M, Senges-Becker JC, et al. Are electrophysiological studies needed prior to defibrillator implantation? Pacing Clin Electrophysiol 2003; 26:1715. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 18/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate 30. Krahn AD, Gollob M, Yee R, et al. Diagnosis of unexplained cardiac arrest: role of adrenaline and procainamide infusion. Circulation 2005; 112:2228. 31. Kannel WB, Thomas HE Jr. Sudden coronary death: the Framingham Study. Ann N Y Acad Sci 1982; 382:3. 32. Ranthe MF, Winkel BG, Andersen EW, et al. Risk of cardiovascular disease in family members of young sudden cardiac death victims. Eur Heart J 2013; 34:503. 33. Behr E, Wood DA, Wright M, et al. Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome. Lancet 2003; 362:1457. 34. Tan HL, Hofman N, van Langen IM, et al. Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives. Circulation 2005; 112:207. 35. Giudici V, Spanaki A, Hendry J, et al. Sudden arrhythmic death syndrome: diagnostic yield of comprehensive clinical evaluation of pediatric first-degree relatives. Pacing Clin Electrophysiol 2014; 37:1681. 36. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA 2004; 291:870. 37. Gamper G, Willeit M, Sterz F, et al. Life after death: posttraumatic stress disorder in survivors of cardiac arrest prevalence, associated factors, and the influence of sedation and analgesia. Crit Care Med 2004; 32:378. Topic 970 Version 35.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 19/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate GRAPHICS Treatable conditions associated with cardiac arrest Condition Common associated clinical settings Acidosis Diabetes, diarrhea, drug overdose, renal dysfunction, sepsis, shock Anemia Gastrointestinal bleeding, nutritional deficiencies, recent trauma Cardiac Post-cardiac surgery, malignancy, post-myocardial infarction, pericarditis, trauma tamponade Hyperkalemia Drug overdose, renal dysfunction, hemolysis, excessive potassium intake, rhabdomyolysis, major soft tissue injury, tumor lysis syndrome Hypokalemia* Alcohol abuse, diabetes mellitus, diuretics, drug overdose, profound gastrointestinal losses Hypothermia Alcohol intoxication, significant burns, drowning, drug overdose, elder patient, endocrine disease, environmental exposure, spinal cord disease, trauma Hypovolemia Significant burns, diabetes, gastrointestinal losses, hemorrhage, malignancy, sepsis, trauma Hypoxia Upper airway obstruction, hypoventilation (CNS dysfunction, neuromuscular disease), pulmonary disease Myocardial infarction Cardiac arrest Poisoning History of alcohol or drug abuse, altered mental status, classic toxidrome (eg, sympathomimetic), occupational exposure, psychiatric disease Pulmonary embolism Immobilized patient, recent surgical procedure (eg, orthopedic), peripartum, risk factors for thromboembolic disease, recent trauma, presentation consistent with acute pulmonary embolism Tension pneumothorax Central venous catheter, mechanical ventilation, pulmonary disease (eg, asthma, chronic obstructive pulmonary disease), thoracentesis, thoracic trauma CNS: central nervous system. Hypomagnesemia should be assumed in the setting of hypokalemia, and both should be treated. Adapted from: Eisenberg MS, Mengert TJ. Cardiac resuscitation. N Engl J Med 2001; 344:1304. Graphic 52416 Version 8.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 20/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 21/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate 12-lead electrocardiogram showing the Wolff-Parkinson- White pattern The 2 main electrocardiographic features of Wolff-Parkinson-White pattern include a short PR interval (<0.12 seconds) and a delta wave (arrows). The QRS complex is wide (>0.12 seconds) and represents a fusion beat; the initial portion (delta wave) results from rapid ventricular activation via the accessory pathway (preexcitation), while the termination of ventricular activation is via the normal conduction system, leading to a fairly normal terminal portion of the QRS. Graphic 75578 Version 10.0 ECG of sinus rhythm to Normal electrocardiogram (ECG) Normal sinus rhythm at a rate of 71 beats/minute, a P wave axis of 45 , and a PR interval of 0.15 seconds. https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 22/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate ECG: electrocardiogram. Courtesy of Morton Arnsdorf, MD. Graphic 58149 Version 5.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 23/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate 12-lead electrocardiogram showing ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy Ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy usually arises from the free wall of the right ventricle, resulting in a left bundle branch morphology. With permission from Podrid PJ, Kowey PR (Eds), Cardiac Arrhythmia - Mechanisms, Diagnosis, and Management, Williams & Wilkins, Baltimore, 1995. Graphic 56591 Version 9.0 Normal ECG https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 24/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 25/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate 12-lead electrocardiogram showing epsilon wave and T wave inversions in arrhythmogenic right ventricular cardiomyopathy 12-lead electrocardiogram in a patient with arrhythmogenic right ventricular cardiomyopathy showing deep T wave inversions in V2 to V4, compatible with right ventricular disease, and epsilon waves representing delayed right ventricular depolarization just after the QRS complex (arrows). Data from: Jaoude S, Leclercq JF, Coumel P. Eur Heart J 1996; 17:1717. Graphic 60781 Version 9.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 26/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Single-lead electrocardiogram showing a prolonged QT interval The corrected QT interval (QTc) is calculated by dividing the QT interval (0.60 seconds) by the square root of the preceding RR interval (0.92 seconds). In this case, the QTc is 0.625 seconds (625 milliseconds). Graphic 77018 Version 7.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 27/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Single lead electrocardiogram (ECG) showing polymorphic ventricular tachycardia (VT) This is an atypical, rapid, and bizarre form of ventricular tachycardia that is characterized by a continuously changing axis of polymorphic QRS morphologies. Graphic 53891 Version 5.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 28/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Major causes of sudden death Ischemic heart disease Coronary artery disease with myocardial infarction or angina Coronary artery embolism Nonatherogenic coronary artery disease (arteritis, dissection, congenital coronary artery anomalies) Coronary artery spasm Nonischemic heart disease Hypertrophic cardiomyopathy Dilated cardiomyopathy Valvular heart disease Congenital heart disease Arrhythmogenic right ventricular dysplasia Myocarditis Acute pericardial tamponade Acute myocardial rupture Aortic dissection No structural heart disease Primary electrical disease (idiopathic ventricular fibrillation) Brugada syndrome (right bundle branch block and ST segment elevation in leads V1 to V3) Long QT syndrome Preexcitation syndrome Complete heart block Familial sudden cardiac death Chest wall trauma (commotio cordis) Noncardiac disease Pulmonary embolism Intracranial hemorrhage Drowning Pickwickian syndrome Drug-induced https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 29/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Central airway obstruction Sudden infant death syndrome Sudden unexplained death in epilepsy (SUDEP) Graphic 62184 Version 3.0 https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 30/31 7/6/23, 11:29 AM Cardiac evaluation of the survivor of sudden cardiac arrest - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/cardiac-evaluation-of-the-survivor-of-sudden-cardiac-arrest/print 31/31 |
7/6/23, 1:36 PM Commotio cordis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Commotio cordis : Christopher Madias, MD : Peter J Zimetbaum, MD, Mark S Link, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 07, 2023. INTRODUCTION Commotio cordis, which translates from Latin as "agitation of the heart," is defined as sudden cardiac death secondary to a blunt, nonpenetrating precordial impact. The epidemiology, potential mechanisms, treatment, and prevention of commotio cordis will be discussed here. Other causes of sudden cardiac death are discussed in detail separately: (See "Overview of sudden cardiac arrest and sudden cardiac death".) (See "Athletes: Overview of sudden cardiac death risk and sport participation".) (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease".) EPIDEMIOLOGY While the exact incidence of commotio cordis remains unknown due to a lack of systematic reporting, commotio cordis is among the most common causes of sudden death during athletic participation [1,2]. Commotio cordis can also occur during nonsport activities (eg, impact to the chest during fights) [3]. Commotio cordis is most common among young males and is typically provoked by hard projectiles and high energy physical contact (eg, tackles during football). Commotio cordis https://www.uptodate.com/contents/commotio-cordis/print 1/14 7/6/23, 1:36 PM Commotio cordis - UpToDate caused by blows to the chest by air-filled balls is less common. Younger individuals and males are likely more susceptible to commotio cordis due to a number of factors including more frequent participation in projectile sports. In addition, larger body size and increased stiffness of the chest wall (eg, chest wall maturation) may protect against commotio cordis [4]. Registries are the primary source of information on the epidemiology and risk factors for commotio cordis: The National Commotio Cordis Registry was established in the United States (US) and contains data on over 200 confirmed cases of commotio cordis and cases from other countries [5-8]. Notable findings from the registry include: Young persons are the most commonly affected (mean age of registry cases was 15 years); only 9 percent of reported cases occurred in those older than 25 years of age. 95 percent of cases occurred in males. 75 percent of cases occurred during athletics (50 percent during competitive sports, 25 percent during recreational sports). Most cases have been reported in sports with blunt projectiles (eg, baseball, lacrosse, hockey) or high-energy body contact (eg, football). Survival from commotio cordis has increased over time, likely owing to more rapid response times and wider access to defibrillation (eg, on-site automated external defibrillators), as well as greater public awareness of this condition. In the most recent published data from the Commotio Cordis Registry, survival was up to 58 percent [9]. Patient demographics and survival between US and non-US victims were similar, though non-US victims were somewhat older (mean 19 versus 15 years of age), and a significantly greater number of non-US cases occurred during soccer (20 percent versus 3 percent of US cases). In a report of sudden death cases from the Cardiac Risk in the Young Centre for Cardiovascular Pathology in the United Kingdom (UK), 17 cases of commotio cordis were identified [8]. When cases from this registry were compared to the US registry, the circumstances and age profile were similar. In the UK registry, the type of sports included cricket, football (ie, soccer), and rugby. In the F d ration internationale de football association (FIFA) Sudden Death Registry, commotio cordis was confirmed in seven cases and was highly suspected in seven https://www.uptodate.com/contents/commotio-cordis/print 2/14 7/6/23, 1:36 PM Commotio cordis - UpToDate additional cases [10]. In 152 football (ie, soccer) players <35 years old with an episode of sudden death, commotio cordis was the cause in 9 percent of cases. In 11 of 14 cases of commotio cordis, the cause was a ball strike to the chest, while the others were due to a chest blow from an elbow or fist. Six patients survived the episode [10]. MECHANISM Commotio cordis is provoked by the simultaneous occurrence of specific mechanistic elements (eg, timing, location, and velocity of impact) that result in ventricular fibrillation (VF). Thus, despite its traumatic appearance, commotio cordis is primarily an electrical event [6,11,12]. The underlying mechanism is likely increased dispersion of ventricular repolarization caused by the blow, which may activate adenosine triphosphate (ATP)-sensitive potassium channels [13,14]. There are hypotheses that VF may be caused by stretch-activated ion channels (eg, calcium), and the autonomic nervous system, but these hypotheses have not been substantiated [15,16]. In experimental models, several critical variables appear to influence the likelihood of commotio cordis ( figure 1): Timing of impact The most important variable in the development of VF in commotio cordis appears to be the timing of chest wall impact within the cardiac cycle. Only impacts that occur during a 20 to 40 millisecond window on the upslope of the T wave (early ventricular repolarization) result in VF [11,17]. Location of impact Only impacts that occur directly over the cardiac silhouette result in VF [18]. Velocity of impact While there is no defined force of chest trauma which results in commotio cordis, the velocity of the projectile appears to be important. In an experimental model, VF did not occur at 20 miles per hour (mph), but, as projectile velocity increased, the likelihood of VF increased (7 percent at 25 mph, 68 percent at 40 mph) [19]. However, at impact velocities greater than 40 mph, the likelihood of VF decreased and the frequency of structural damage including myocardial rupture and cardiac contusion increased. Hardness of impact object Harder objects are more likely to cause VF [11,20]. Shape of impact object Smaller diameter spheres are more likely to cause VF [21]. CHARACTERISTIC CHEST BLOW https://www.uptodate.com/contents/commotio-cordis/print 3/14 7/6/23, 1:36 PM Commotio cordis - UpToDate The types of chest blows that cause commotio cordis vary, but the most common scenario occurs in sports when a dense projectile (eg, baseball, lacrosse ball, hockey puck), impacts the chest wall directly over the heart and the patient collapses within seconds after the impact. (See 'Diagnosis' below.) Notably, approximately one-third of patients who suffered commotio cordis were wearing standard chest protection equipment appropriate for their sport [22]. Thus, the presence of protective gear does not exclude the diagnosis of commotio cordis. (See 'Prevention' below.) EVALUATION FOR HEART DISEASE Survivors of commotio cordis should undergo a comprehensive cardiac evaluation to exclude underlying heart disease such as (see "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Diagnostic evaluation'): Hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".) Arrhythmogenic right ventricular dysplasia. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis".) Anomalous coronary arteries. (See "Congenital and pediatric coronary artery abnormalities".) Ion channel gene mutations, such as the long QT syndrome and Brugada syndrome. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management" and "Congenital long QT syndrome: Diagnosis" and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Catecholaminergic polymorphic ventricular tachycardia. (See "Catecholaminergic polymorphic ventricular tachycardia".) This evaluation should include a 12-lead electrocardiogram (ECG), ambulatory ECG monitoring, echocardiogram, cardiovascular magnetic resonance imaging, and exercise stress testing. If the presence of a channelopathy (eg, Brugada syndrome, long QT syndrome) is suggested by ECG, further testing for those diseases should be performed. DIAGNOSIS https://www.uptodate.com/contents/commotio-cordis/print 4/14 7/6/23, 1:36 PM Commotio cordis - UpToDate The diagnosis of commotio cordis is based upon the presence of a witnessed blunt chest impact followed by collapse within five to eight seconds, ECG data demonstrating ventricular fibrillation (if available), absence of underlying heart disease, and no evidence (eg, imaging studies, autopsy) of myocardial trauma [12]. Thus, the diagnosis of commotio cordis cannot be established in the presence of an underlying cardiac condition or severe trauma causing myocardial contusion or rupture. (See 'Mechanism' above and "Initial evaluation and management of blunt thoracic trauma in adults", section on 'Cardiac injury'.) MANAGEMENT Immediate resuscitation Following the identification of sudden cardiac arrest, the management of persons with commotio cordis follows the standard basic and advanced life support algorithms. In patients with commotio cordis, ventricular fibrillation (VF) is the most commonly documented arrhythmia. Management should include chest compressions with early defibrillation, as indicated in resuscitation guidelines. (See "Adult basic life support (BLS) for health care providers" and "Pediatric basic life support (BLS) for health care providers".) Postarrest care Similar to other patients who survive cardiac arrest, patients with commotio cordis require comprehensive evaluation for underlying heart disease and appropriate treatment. The approach to management of cardiac arrest is presented separately. (See 'Evaluation for heart disease' above and "Initial assessment and management of the adult post- cardiac arrest patient".) In patients who survive an episode of cardiac arrest attributed to commotio cordis and whose evaluation does not suggest an underlying cardiac etiology (eg, underlying cardiomyopathy, ion channel disorder), implantable cardioverter-defibrillator (ICD) placement is not required to prevent further episodes of commotio cordis. Other indications for ICDs are discussed separately. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions", section on 'Indications'.) Return to athletics In individuals who survive a commotio cordis event without cardiac complications and who wish to continue athletics, the decision to return to athletics is individualized. For those who choose to resume athletics, it is prudent to adopt all available measures to reduce the risk of chest wall impact. (See 'Prevention' below.) This approach is similar to the American Heart Association/American College of Cardiology consensus statement on eligibility and disqualification recommendations for competitive https://www.uptodate.com/contents/commotio-cordis/print 5/14 7/6/23, 1:36 PM Commotio cordis - UpToDate athletes, which recommends that athletes can resume training and competition following commotio cordis if the evaluation for cardiac pathology is entirely unrevealing [12]. Our approach is based on the rarity of commotio cordis, which is unlikely to recur in an individual due to its mechanism (see 'Mechanism' above). However, there is insufficient data to determine whether certain individuals may be predisposed to commotio cordis. Rare reports of recurrent commotio cordis include: In an experimental model, a small number of animals were uniquely susceptible to chest blow induction of VF [23]. In addition, there is a case report of an individual who possibly experienced two episodes of commotio cordis [24]. PREVENTION Because many different types of blows to the chest can cause commotio cordis, there is no universal means to reliably prevent commotio cordis. For participants in activities associated with a higher risk of commotio cordis (particularly projectile sports), a combination of safety measures may reduce the risk of commotio cordis: Coaching Coaching measures should encourage athletes to turn away from oncoming projectiles (ie, baseballs, lacrosse balls) whenever possible to avoid contact to the chest [6,12]. Softer and less dense balls Softer and less dense balls should be used whenever possible. As an example, age-appropriate safety baseballs have been shown to decrease the risk of commotio cordis ( figure 2) [11,20]. Protective gear Historically, commercially available chest wall protectors did not clearly prevent commotio cordis during sports participation or in laboratory animal studies [5,22,25,26]. Many of the commotio cordis victims reported to the National Commotio Cordis Registry were wearing protective equipment at the time of their event [5]. The National Operating Committee on Standards for Athletic Equipment has a standard for chest protection, which is based on findings from an experimental animal model that may improve the efficacy of chest protective gear [27]. SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/commotio-cordis/print 6/14 7/6/23, 1:36 PM Commotio cordis - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Epidemiology The exact incidence of commotio cordis remains unknown, mostly due to a lack of systematic reporting of cases. Commotio cordis is among the most common causes of sudden death during athletic participation and can also occur during non-sports-related activities (eg, impact to chest during fights). Commotio cordis is most common among young males and is typically provoked by hard projectiles and high-energy physical contact (eg, tackles during football); blows to the chest by soccer balls can also provoke commotio cordis. (See 'Epidemiology' above.) Mechanism Commotio cordis is provoked by the simultaneous occurrence of specific mechanistic elements (eg, timing, location, velocity of impact, shape and hardness of the projectile) that result in ventricular fibrillation (VF) ( figure 1 and figure 2). Thus, despite its traumatic appearance, commotio cordis is primarily an electrical event. The underlying mechanism is likely increased dispersion of ventricular repolarization caused by the blow, which may activate adenosine triphosphate (ATP)-sensitive potassium channels ( figure 1). (See 'Mechanism' above.) Prevention Because many different types of blows to the chest can cause commotio cordis, there is no universal means to reliably prevent commotio cordis. For participants in activities associated with a higher risk of commotio cordis (particularly projectile sports), coaching to avoid chest blows and softer balls and equipment may reduce the risk. Commercially available chest wall protectors may reduce the risk of commotio cordis but are not uniformly effective. (See 'Prevention' above.) Characteristic chest blow The types of chest blows that cause commotio cordis vary, but the most common scenario occurs in sports when a dense projectile (eg, baseball, lacrosse ball, hockey puck), impacts the chest wall directly over the heart and the patient collapses within seconds after the impact. (See 'Diagnosis' above.) Evaluation for heart disease Survivors of commotio cordis should undergo a comprehensive cardiac evaluation to exclude underlying heart disease such as (see https://www.uptodate.com/contents/commotio-cordis/print 7/14 7/6/23, 1:36 PM Commotio cordis - UpToDate 'Evaluation for heart disease' above and "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Diagnostic evaluation'): Hypertrophic cardiomyopathy Arrhythmogenic right ventricular dysplasia Anomalous coronary arteries Ion channel gene mutations such as the long QT syndrome and Brugada syndrome Catecholaminergic polymorphic ventricular tachycardia Diagnosis The diagnosis of commotio cordis is based upon the presence of a witnessed blunt chest impact followed by collapse within five to eight seconds, ECG data demonstrating VF (if available), absence of underlying heart disease, and no evidence (eg, imaging studies, autopsy) of myocardial trauma. Management Immediate resuscitation Following the identification of sudden cardiac arrest, the management of persons with commotio cordis follows standard basic and advanced life-support algorithms. (See "Adult basic life support (BLS) for health care providers" and "Pediatric basic life support (BLS) for health care providers".) Postarrest care Similar to other patients who survive cardiac arrest, patients with commotio cordis require comprehensive evaluation for underlying heart disease and appropriate treatment. (See 'Evaluation for heart disease' above and "Initial assessment and management of the adult post-cardiac arrest patient".) Return to athletics In individuals who survive a commotio cordis event without cardiac complications and who wish to continue athletics, the decision to return to athletics is individualized. For those who choose to resume athletics, it is prudent to adopt all available measures to reduce the risk of chest wall impact. (See 'Return to athletics' above and 'Prevention' above.) In patients who survive an episode of cardiac arrest attributed to commotio cordis and whose evaluation does not suggest an underlying cardiac etiology (eg, underlying cardiomyopathy, ion channel disorder), implantable cardioverter-defibrillator (ICD) placement is not required to prevent further episodes of commotio cordis. Other indications for ICDs are discussed separately. (See "Implantable cardioverter- defibrillators: Overview of indications, components, and functions", section on 'Indications'.) https://www.uptodate.com/contents/commotio-cordis/print 8/14 7/6/23, 1:36 PM Commotio cordis - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Maron BJ, Doerer JJ, Haas TS, et al. Historical observation on commotio cordis. Heart Rhythm 2006; 3:605. 2. Maron BJ. Sudden death in young athletes. N Engl J Med 2003; 349:1064. 3. Maron BJ, Link MS. Don't Forget Commotio Cordis. Am J Cardiol 2021; 156:134. 4. Madias C, Maron BJ, Dau N, et al. Size as an Important Determinant of Chest Blow-induced Commotio Cordis. Med Sci Sports Exerc 2018; 50:1767. 5. Maron BJ, Estes NA 3rd. Commotio cordis. N Engl J Med 2010; 362:917. 6. Link MS. Commotio cordis: ventricular fibrillation triggered by chest impact-induced abnormalities in repolarization. Circ Arrhythm Electrophysiol 2012; 5:425. 7. Maron BJ, Ahluwalia A, Haas TS, et al. Global epidemiology and demographics of commotio cordis. Heart Rhythm 2011; 8:1969. 8. Cooper S, Woodford NW, Maron BJ, et al. A Lethal Blow to the Chest as an Underdiagnosed Cause of Sudden Death in United Kingdom Sports (Football, Cricket, Rugby). Am J Cardiol 2019; 124:808. 9. Maron BJ, Haas TS, Ahluwalia A, et al. Increasing survival rate from commotio cordis. Heart Rhythm 2013; 10:219. 10. Egger F, Scharhag J, K stner A, et al. FIFA Sudden Death Registry (FIFA-SDR): a prospective, observational study of sudden death in worldwide football from 2014 to 2018. Br J Sports Med 2022; 56:80. 11. Link MS, Wang PJ, Pandian NG, et al. An experimental model of sudden death due to low- energy chest-wall impact (commotio cordis). N Engl J Med 1998; 338:1805. 12. Link MS, Estes NA 3rd, Maron BJ, American Heart Association Electrocardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and American College of Cardiology. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 13: Commotio Cordis: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation 2015; 132:e339. 13. Bode F, Franz MR, Wilke I, et al. Ventricular fibrillation induced by stretch pulse: implications for sudden death due to commotio cordis. J Cardiovasc Electrophysiol 2006; 17:1011. https://www.uptodate.com/contents/commotio-cordis/print 9/14 7/6/23, 1:36 PM Commotio cordis - UpToDate 14. Link MS, Wang PJ, VanderBrink BA, et al. Selective activation of the K(+)(ATP) channel is a mechanism by which sudden death is produced by low-energy chest-wall impact (Commotio cordis). Circulation 1999; 100:413. 15. Garan AR, Maron BJ, Wang PJ, et al. Role of streptomycin-sensitive stretch-activated channel in chest wall impact induced sudden death (commotio cordis). J Cardiovasc Electrophysiol 2005; 16:433. 16. Stout CW, Maron BJ, Vanderbrink BA, et al. Importance of the autonomic nervous system in an experimental model of commotio cordis. Med Sci Monit 2007; 13:BR11. 17. Madias C, Maron BJ, Weinstock J, et al. Commotio cordis sudden cardiac death with chest wall impact. J Cardiovasc Electrophysiol 2007; 18:115. 18. Link MS, Maron BJ, VanderBrink BA, et al. Impact directly over the cardiac silhouette is necessary to produce ventricular fibrillation in an experimental model of commotio cordis. J Am Coll Cardiol 2001; 37:649. 19. Link MS, Maron BJ, Wang PJ, et al. Upper and lower limits of vulnerability to sudden arrhythmic death with chest-wall impact (commotio cordis). J Am Coll Cardiol 2003; 41:99. 20. Link MS, Maron BJ, Wang PJ, et al. Reduced risk of sudden death from chest wall blows (commotio cordis) with safety baseballs. Pediatrics 2002; 109:873. 21. Kalin J, Madias C, Alsheikh-Ali AA, Link MS. Reduced diameter spheres increases the risk of chest blow-induced ventricular fibrillation (commotio cordis). Heart Rhythm 2011; 8:1578. 22. Doerer JJ, Haas TS, Estes NA 3rd, et al. Evaluation of chest barriers for protection against sudden death due to commotio cordis. Am J Cardiol 2007; 99:857. 23. Alsheikh-Ali AA, Madias C, Supran S, Link MS. Marked variability in susceptibility to ventricular fibrillation in an experimental commotio cordis model. Circulation 2010; 122:2499. 24. Maron BJ, Link MS. Recurrent commotio cordis: D j vu. HeartRhythm Case Rep 2015; 1:249. 25. Weinstock J, Maron BJ, Song C, et al. Failure of commercially available chest wall protectors to prevent sudden cardiac death induced by chest wall blows in an experimental model of commotio cordis. Pediatrics 2006; 117:e656. 26. Drewniak EI, Spenciner DB, Crisco JJ. Mechanical properties of chest protectors and the likelihood of ventricular fibrillation due to commotio cordis. J Appl Biomech 2007; 23:282. 27. McCalley E, Dau N, Kumar KR, et al. Development and Validation of a Mechanical Surrogate to Assess the Ability of Chest Protectors to Prevent Commotio Cordis, Sudden Cardiac Death With Chest Wall Impact. Circulation 2016; 134:A17799. https://www.uptodate.com/contents/commotio-cordis/print 10/14 7/6/23, 1:36 PM Commotio cordis - UpToDate Topic 15853 Version 20.0 https://www.uptodate.com/contents/commotio-cordis/print 11/14 7/6/23, 1:36 PM Commotio cordis - UpToDate GRAPHICS Mechanisms of commotio cordis From: Link MS, Estes NA. Athletes and arrhythmis. J Cardiovasc Electrophysiol 2010; 21:1184. Copyright 2010. Reproduced with permission of John Wiley & Sons, Inc. Graphic 52268 Version 2.0 https://www.uptodate.com/contents/commotio-cordis/print 12/14 7/6/23, 1:36 PM Commotio cordis - UpToDate Chest wall trauma causes ventricular fibrillation Differences in the frequency with which ventricular fibrillation resulted from chest-wall impact at 30 miles per hour during the period of cardiac cycle vulnerable to induction of ventricular fibrillation, ie, from 30 to 15 ms before T- wave peak. p<0.03 for the differences between regulation baseball and very soft baseball. p<0.01 for the differences between wooden object and each type of baseball. Data from: Link MS, Wang PJ, Pandian NG, et al. An experimental model of sudden death due to low- energy chest-wall impact (commotio cordis). N Engl J Med 1998; 338:1805. Graphic 61105 Version 5.0 https://www.uptodate.com/contents/commotio-cordis/print 13/14 7/6/23, 1:36 PM Commotio cordis - UpToDate Contributor Disclosures Christopher Madias, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/commotio-cordis/print 14/14 |
7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients : Charles A Herzog, MD, Rod Passman, MD, MSCE : Jeffrey S Berns, MD : Eric N Taylor, MD, MSc, FASN, Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 23, 2021. OVERVIEW Dialysis patients are at extraordinarily high risk for death. In 2016, the annual mortality rate for all United States dialysis patients was 179 deaths/1000 patient-years [1,2]. Cardiac disease is the major cause of death, accounting for approximately 37 percent of all- cause mortality in patients receiving either hemodialysis or peritoneal dialysis [1]. In the United States Renal Data System (USRDS) database, the single, largest, specific cause of death is attributed to arrhythmic mechanisms or sudden cardiac arrest (SCA) [1]. (See "Patient survival and maintenance dialysis".) The epidemiology, clinical manifestations, and evaluation of SCA and sudden cardiac death (SCD) in the dialysis population are provided in this topic review. Detailed discussions of treatment and prevention of SCA and SCD are presented separately. (See "Overview of sudden cardiac arrest and sudden cardiac death".) DEFINITION AND EPIDEMIOLOGY In the general population, the term "sudden cardiac death" (SCD) is commonly used to describe SCA in the setting of heart disease (although some have structurally normal hearts) with cessation of cardiac function whether or not resuscitation or spontaneous reversion occurs. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 1/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Previously, the term "sudden cardiac death" has been used even if a patient was successfully resuscitated. Such cases have been referred to as "aborted SCD" or "resuscitated SCD," and patients who experienced such events were said to be "sudden death survivors." Clearer and more rational definitions of SCA and SCD were proposed in 2006 by the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) [3] (see "Overview of sudden cardiac arrest and sudden cardiac death"): "[Sudden] cardiac arrest is the sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation. If corrective measures are not taken rapidly, this condition progresses to sudden death. Cardiac arrest should be used to signify an event as described above, that is reversed, usually by CPR and/or defibrillation or cardioversion, or cardiac pacing. Sudden cardiac death should not be used to describe events that are not fatal." Except where noted, we will use the terms "SCA" and "SCD" as defined in the 2006 ACC/AHA/HRS document. However, most of the available epidemiologic data were published prior to this standardization and are therefore based upon different standards. In the United States Renal Data System (USRDS) database, the cause of death attributed to arrhythmic mechanisms is noted in the Centers for Medicare and Medicaid Services (CMS) death notification form 2746 by either "cardiac arrest/cause unknown" or arrhythmia. Based upon this definition, arrhythmias may therefore be responsible for [1]: Seventy-four percent of all cardiac deaths or 28 percent of all-cause mortality in peritoneal dialysis patients Seventy-eight percent of all cardiac deaths or 29 percent of all-cause mortality in hemodialysis patients However, death attributed to arrhythmias that is based entirely upon the CMS death notification form has obvious limitations and may be inaccurate. Thus, in addition to this definition, the USRDS Cardiovascular Special Studies Center (CVSSC) has used a more complex method in the 2006 USRDS annual data report, which incorporates cause of death in the context of death location (eg, a patient succumbing to myocardial infarction on an ambulance run would be identified as sustaining SCD) and excludes patients with deaths occurring in the setting of sepsis, malignancy, hyperkalemia, and, importantly, withdrawal from dialysis. Using this method, it has been estimated that 29.7 percent of deaths in prevalent dialysis patients are related to SCD [4,5]. The USRDS CVSSC method, however, has not been applied to contemporary data. We think that the overall best estimate is that SCD is responsible for 29 percent of all-cause mortality in dialysis patients. Similar findings on the relative contribution (22 to 26 percent) of https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 2/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate sudden death to all-cause mortality in dialysis patients have been reported in multiple studies including HEMO, 4D trial, the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) cohort, and the Dialysis Outcomes and Practice Patterns Study (DOPPS) [6-9] and the Evaluation of Cinacalcet HCL Therapy to Lower Cardiovascular Events (EVOLVE) trial [10]. EVOLVE, which enrolled 3883 hemodialysis patients and provided formal adjudication of cause- specific mortality, was the largest randomized, clinical trial ever performed in hemodialysis patients. In EVOLVE, 25 percent of all deaths were adjudicated as "sudden deaths." The rate due to SCD is approximately 54 deaths/1000 patient-years in combined 2013 to 2015 dialysis cause-specific mortality data, which is essentially identical to that reported in 2011 [1,11]. The CVSSC has also previously estimated that the rate of SCD for period prevalent dialysis patients in 2002 was 6.9 percent per year [4]. It is noteworthy that there has been a slow, steady decline in the overall cardiac mortality rate over time in the US dialysis population, and this finding is reflected in the most current estimate of the SCD rate in dialysis patients. One possible explanation is the increase in the use of "evidence-based therapies" (including beta blockers) in dialysis patients [11]. In the CHOICE cohort, it was 37 SCD events/1000 years (which excluded in- hospital deaths, potentially underestimating the "true" frequency of SCD) [8]. One noteworthy trend is the "disconnect" between the rates of SCD and cardiovascular death ( figure 1 and figure 2). Between 2000 and 2013, there was a decline in the rates of all- cause and cardiovascular mortality in the US over approximately 13 years. Historically, approximately 25 to 27 percent of all-cause mortality was attributed to SCD. Since 2009 ( figure 2), cardiovascular death rates continued to decline with little change in SCD rates. For this reason, the attributable percentage of SCD to cardiovascular and all-cause mortality has increased. For whatever reason, the decade-long improvement in all-cause and cardiovascular mortality is no longer reflected in SCD rates in the current decade. This rate is significantly higher than that observed in the general population. In one population- based study, for example, the overall incidence of out-of-hospital cardiac arrest was 1.89 per 1000 patient-years [12]. The risk for prevalent dialysis patients is roughly comparable with that observed in patients in the general population with a history of an adverse cardiovascular event. (See "Overview of sudden cardiac arrest and sudden cardiac death".) There is also an enhanced risk of SCD in the first hemodialysis session of the week. Compared with the average risk of SCD, there is a 50 percent increased frequency of SCD on Monday (for patients dialyzing Monday, Wednesday, and Friday) and on Tuesday (for patients having hemodialysis Tuesday, Thursday, and Saturday) [13]. In addition, one study reported a threefold https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 3/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate increased risk of sudden death in the 12 hours before the end of the long weekend interval and a 1.7-fold increased risk of SCD in the 12 hours starting with the dialysis procedure following this long interval [14]. The initiation of hemodialysis is a special period of heightened risk for both all-cause mortality and SCD. In 2015, the annualized death rate for US dialysis patients in the first 90 days after dialysis initiation was 312 deaths/1000 patient-years [1]. As shown in the figures ( figure 3 and figure 4), the highest rate of sudden death is in the first month after dialysis initiation, with at least 30 percent of all deaths being attributable to SCD. MECHANISMS In the general as well as the dialysis population, most SCA events are believed to be due to ventricular arrhythmias; that is, ventricular tachycardia (VT) or ventricular fibrillation (VF). A minority may have been attributed to bradyarrhythmias. (See "Pathophysiology and etiology of sudden cardiac arrest".) However, two independent groups of investigators using insertable cardiac monitors (sometimes referred to as implantable cardiac monitors or implantable loop recorders) may force a reconsideration of the importance of bradyarrhythmia as a contributing mechanism to SCD [15-17]. However, the study population of one of these studies had a mean time on dialysis of six years, potentially biasing the population away from one with more ventricular tachyarrhythmias. Additionally, we do not know if the patients died from bradyarrhythmias or with bradyarrhythmias [18]. It is our opinion that this older vintage cohort may be very different from newly incident hemodialysis patients, both in terms of structural heart disease and underlying arrhythmic mechanisms potentially leading to SCD. Although SCA can occur in patients with structurally normal hearts, most patients with SCA have some form of underlying heart disease. A triggering event or condition interacts with the underlying substrate to produce the fatal arrhythmia [19]. Although many triggers have been identified, acute myocardial ischemia is felt to be the most common initiating event in the general population [20]. As will be discussed, the end-stage kidney disease (ESKD) patient has some unique factors that can both alter the underlying substrate as well as trigger ventricular arrhythmic events. RISK FACTORS AND CAUSES https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 4/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate In the general population, abnormalities of the coronary arteries, myocardium, and cardiac conduction system are the most common underlying causes of the life-threatening arrhythmias that result in SCA. (See "Pathophysiology and etiology of sudden cardiac arrest" and "Overview of screening and diagnosis of heart disease in patients on dialysis" and "Valvular heart disease in patients with end-stage kidney disease".) Predictors of SCD among hemodialysis patients were evaluated using data from the HEMO study [21]. Among 1745 enrolled hemodialysis patients, 808 died over a median follow-up of 2.5 years, 22 percent of which were due to SCD. Age, diabetes, peripheral vascular disease, ischemic heart disease, a low serum creatinine (reflecting decreased muscle mass and poor nutrition), and an elevated alkaline phosphatase predicted a higher risk for SCD. Traditional cardiovascular risk factors such as smoking and cholesterol did not, but risks conferred by these factors may have been incorporated into the overall increased risk associated with ischemic heart disease. This study did not adjust for dialysis-related risk factors (such as potassium dialysate) nor for other known risk factors such as left ventricular (LV) hypertrophy. The major results of the HEMO study are discussed elsewhere. (See "Prescribing and assessing adequate hemodialysis", section on 'Target Kt/V'.) The following is a brief overview of the more important abnormalities found in the dialysis population that may underlie their increased incidence of SCA: Obstructive coronary artery disease is likely an important contributor to SCA. However, data from the United States Renal Data System Cardiovascular Special Studies Center (USRDS CVSSC) have found an unexplained high mortality due to arrhythmic mechanisms after successful coronary revascularization, suggesting that other factors must be significant [22,23]. In the dialysis population, for example, there was a two-year mortality of 48 and 43 percent after nondrug eluting coronary artery stents and coronary artery bypass surgery (CABG) incorporating internal mammary graft use, respectively. The annual mortality attributed to arrhythmic mechanisms was 8.5 and 7 percent after stenting and CABG, respectively, which is higher than that observed in the general population. This implies that reliance solely upon ameliorating myocardial ischemia by coronary revascularization may be an inadequate clinical strategy for the prevention of SCD in dialysis patients. There is a markedly increased incidence of myocardial abnormalities, such as LV hypertrophy (approximately 75 percent of dialysis patients) and alterations in myocardial ultrastructure and function (including endothelial dysfunction, interstitial fibrosis, decreased perfusion reserve, and diminished ischemia tolerance). (See "Overview of https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 5/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate screening and diagnosis of heart disease in patients on dialysis" and "Hypertension in dialysis patients".) Rapid electrolyte shifts during hemodialysis sessions and the presence of hyperkalemia due to renal failure increase the risk of arrhythmias. This enhanced risk is not surprising given the profound fluid and electrolyte derangements before hemodialysis and the physiologic demands of the hemodialysis session. The nonphysiologic nature of conventional, thrice-weekly hemodialysis sessions may further increase the risk of SCA. This is supported by the observational data previously mentioned showing an increased risk surrounding the first hemodialysis session of the week. (See 'Definition and epidemiology' above.) The interplay between the type of renal replacement therapy and dialysis vintage appears to have an impact upon the risk of SCA, with the relative hazard of cardiac arrest in hemodialysis compared with peritoneal dialysis varying with time after initiation of renal replacement therapy. The rate of cardiac arrest is approximately 50 percent higher in hemodialysis patients three months after dialysis initiation, but they are similar at two years. Three years after dialysis initiation, the rate of cardiac arrest is higher in peritoneal dialysis patients ( figure 5). There is a strikingly higher adjusted mortality rate in hemodialysis versus peritoneal dialysis early after initiation of renal replacement therapy ( figure 6). Risk factors related to dialysis prescription Risk factors related to the dialysis prescription were identified in two large cohorts [9,24]. In one case-control study of 43,200 patients, low- potassium dialysate (<2 mEq/L) was an independent risk factor for SCA [24]. The increased risk associated with low-potassium dialysate was greatest at lower levels of predialysis serum potassium. Increased ultrafiltration volume and low-calcium dialysate were also linked to SCA in this study. Compared with dialysate potassium 3 mEq/L, dialysate potassium concentrations 1.5 and 2 to 2.5 mEq/L were associated with increased risk of SCD (hazard ratios [HRs] 1.39, 95% CI 1.12-1.74 and 1.17, 95% CI 1.01-1.37, respectively). The magnitude of the association of SCD with dialysis potassium 1.5 was greater among patients with serum potassium <5 mEq/L. The Dialysis Outcomes and Practice Patterns Study (DOPPS) including 55,183 patients did not demonstrate a significant difference in clinical outcome related to the use of dialysate potassium concentrations of 2 versus 3 mEq/L [25]. In DOPPS, among 37,765 participants, SCD was associated with a treatment time <3.5 hours (HR 1.13, 95% CI 1.00-1.27), ultrafiltration volume >5.7 percent of postdialysis weight (HR 1.15, 95% CI 1.00-1.32), and Kt/V <1.2 (HR 1.06, 95% CI 1.00-1.12) [9]. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 6/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Dialysate cooling has been advocated to reduce intradialytic hypotension and myocardial stunning; however, the putative benefit on reduction of subsequent cardiac events (including sudden death) remains to be established by adequately powered randomized clinical trials. Similarly, frequent hemodialysis (which reduces LV mass) has not been shown to reduce cardiac events, including sudden death [26,27]. These observational studies suggest that avoiding these prescriptions when possible may reduce the risk of SCA [24,28]. CLINICAL MANIFESTATIONS In patients with and without end-stage kidney disease (ESKD), most individuals suffering from SCA become unconscious within seconds to minutes as a result of insufficient cerebral blood flow. There are usually no premonitory symptoms. Symptoms, if present, are nonspecific and include chest discomfort, palpitations, shortness of breath, and weakness. (See "Overview of sudden cardiac arrest and sudden cardiac death".) EVALUATION Survivor of sudden cardiac arrest In the general population, the evaluation of the survivor of SCA includes the following (see "Cardiac evaluation of the survivor of sudden cardiac arrest"): Identification and treatment of acute reversible causes Evaluation for structural heart disease In patients without obvious arrhythmic triggers or cardiac structural abnormalities, an evaluation for primary electrical diseases Neurologic and psychologic assessment In selected patients with a suspected or confirmed heritable syndrome, evaluation of family members The evaluation in the dialysis patient who survives SCA is generally the same as that in the patient without renal failure. However, close attention should be paid to the presence of myocardial dysfunction and/or ischemia (since they are so common), the possibility of improper medication dosing in the patient with renal failure, and the circumstances associated with the event, particularly if it occurred during and/or surrounding a hemodialysis session. As examples: https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 7/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Since both myocardial ischemia and/or dysfunction are relatively common in the dialysis patient, their presence, either alone or in combination, may markedly enhance the risk of SCA. However, retrospective analysis has shown that 71 percent of dialysis patients who experienced SCD had either normal or only mild to moderate left ventricular (LV) dysfunction, suggesting that other factors may underlie SCA in many dialysis patients [29]. (See 'Identification of the high-risk dialysis patient' below.) Increased electrical instability resulting in SCA may have been due to fluid shifts, autonomic imbalance/increased sympathetic activity (including sleep apnea), acid/base disturbances, and electrolyte abnormalities [24,30-36]. An increased risk of cardiac arrest may be particularly associated with a low-potassium concentration in the dialysate. (See "Acute complications during hemodialysis".) Improper dosing of certain medications may predispose the patient with renal failure to brady/tachyarrhythmias and/or proarrhythmic effects, thereby causing SCA. (See "Overview of sudden cardiac arrest and sudden cardiac death".) One study reported that low predialysis serum potassium (<4.3 mEq/L) was associated with an increased mortality hazard in hemodialysis patients receiving digoxin, suggesting that even low "normal" potassium levels may enhance the proarrhythmic risk of digoxin [37]. In this study, the mortality risk associated with digoxin was attenuated in dialysis patients with serum potassium >4.6 mEq/L. Digoxin should be used with extreme caution in such patients. Identification of the high-risk dialysis patient In the general population, it is known that reduced LV function is the strongest predictor of SCA. Clinically, the presence of heart failure also identifies patients who are at high risk of SCA, perhaps by additional arrhythmogenic factors, such as activation of the neurohormonal cascade and electrolyte shifts. Identification of the high-risk patient is most useful if therapy can provide significant benefits. In the nondialysis population, most primary prevention implantable cardioverter-defibrillator (ICD) trials have shown significant improvement in survival in the following high-risk groups who received ICDs: The earlier primary prevention trials enrolled nondialysis patients with decreased systolic function, prior myocardial infarction, nonsustained ventricular tachycardia (VT), and positive electrophysiology (EP) study for induction of VT. In later trials, enrollment did not require nonsustained VT or positive EP studies. Instead, enrollment was based upon decreased systolic function and/or heart failure. In addition, https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 8/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate nonischemic cardiomyopathy patients were included. Thus, in the nondialysis population, primary prevention ICD trials have principally demonstrated survival improvement in groups with decreased systolic function who receive ICDs. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) However, it is unclear if dialysis patients with decreased systolic function also receive survival benefits with ICD. There are no prospective studies that have examined this issue, although retrospective studies suggest some benefit. In addition, despite the very high annual mortality from SCD, the dialysis patient with reduced LV function is not typical of the general dialysis population. Fifteen percent or fewer dialysis patients have significantly decreased LV function [38-40]. In the largest study to date, among 1254 consecutive patients starting hemodialysis in Japan, 5 percent had LV ejection fractions of less than 40 percent [40]. Thus, other unique factors/circumstances may contribute to the general increased risk of SCA in end-stage kidney disease (ESKD) patients in dialysis. Possibilities include the following: There is additional substrate (myocardial) modification, such as interstitial fibrosis due to chronic uremia, microvascular disease, or endothelial dysfunction; increased calcium/phosphate deposition; and significant LV hypertrophy due to hypertension and/or anemia [41-46]. Increased electrical instability may be present due to fluid shifts, autonomic imbalance/increased sympathetic activity (including sleep apnea), inflammatory state, acid/base disturbances, and/or electrolyte abnormalities [24,30-36,47]. It is likely that the increased risk of ventricular arrhythmias in ESKD patients is due to a combination of these many interacting factors ( table 1). In addition, while an ejection fraction of <35 to 40 percent is considered the major risk factor for SCA in nondialysis patients, it is likely that more mild LV dysfunction imparts a greater risk of cardiovascular events in the dialysis population, regardless of the etiology and despite optimal management. As an example, one study found that the best predictor of SCD risk in peritoneal dialysis patients was an LV ejection fraction of 48 percent [48]. Risk-stratification studies within the dialysis population are required to better identify those patients at highest risk of SCA and in whom prophylactic interventions may be beneficial. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 9/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate We agree with recommendations concerning evaluation as noted in the 2005 National Kidney Foundation Dialysis Outcome Quality Initiative (KDOQI) Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients [49]. We recommend that, at initiation of dialysis, all patients should undergo baseline echocardiography and electrocardiography. Echocardiography should be performed after dry weight is attained (which usually occurs after one to three months) and should be repeated routinely at three-year intervals. Additional evaluation of LV systolic function should be performed following a change in cardiac status or after an intercurrent cardiac event. Findings of a decreased ejection fraction (<40 percent) or significant regional wall motion abnormalities with or without ischemic symptoms require an evaluation for the presence of coronary artery disease, which may underlie myocardial dysfunction in many dialysis patients. If these surveillance guidelines are met, all dialysis patients with reduced LV function should be identified by echocardiography. Once identified, the main question is whether patients with significantly reduced LV function should be treated with aggressive primary prevention measures, including placement of an ICD. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) The use of biomarkers for identification of dialysis patients at high risk for SCD deserves further study. Cardiac troponin T is a strong independent predictor of all-cause mortality [50], and high- sensitivity C-reactive protein (CRP) is associated with the risk of SCD [8]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".) SUMMARY AND RECOMMENDATIONS Cardiac disease is the major cause of death among dialysis patients. In the United States Renal Data System (USRDS) database, the single, largest, specific cause of death is attributed to arrhythmic mechanisms or sudden cardiac death (SCD). The overall best estimate is that SCD is responsible for approximately 29 percent of all-cause mortality in dialysis patients. (See 'Definition and epidemiology' above.) Many causes of and risk factors for sudden cardiac arrest (SCA) are shared among patients with and without end-stage kidney disease (ESKD), although dialysis patients frequently https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 10/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate have a relatively increased incidence of abnormalities of the coronary arteries, myocardium, and cardiac conduction system. There are also issues unique to dialysis patients. (See 'Evaluation' above.) The evaluation in the dialysis patient who survives SCA is generally the same as that in the patient without renal failure. However, close attention should be paid to the presence of myocardial dysfunction and/or ischemia, the possibility of improper medication dosing in the patient with renal failure, and the circumstances associated with the event, particularly if it occurred during and/or surrounding a hemodialysis session. (See "Cardiac evaluation of the survivor of sudden cardiac arrest" and 'Evaluation' above.) Rapid electrolyte shifts during hemodialysis sessions increase the risk of arrhythmias. Variables in the hemodialysis prescription such as the use of low-potassium dialysate, low- calcium dialysate, or large ultrafiltration volumes may be modifiable risk factors for SCA. (See 'Risk factors and causes' above.) To help identify the dialysis patient at increased risk of SCA, we recommend that, at initiation of dialysis, all patients should undergo baseline echocardiography and electrocardiography, with echocardiography repeated routinely at three-year intervals. Additional evaluation of left ventricular (LV) systolic function should be performed following a change in cardiac status or after an intercurrent cardiac event. Findings of a decreased ejection fraction (<40 percent) or significant regional wall motion abnormalities (with or without ischemic symptoms) require an evaluation for the presence of coronary artery disease. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. United States Renal Data System. 2018 USRDS annual data report: Epidemiology of kidney d isease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, MD 2018. 2. United States Renal Data System. USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. National Institutes of Health; Nat ional Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2013. 3. American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology), Buxton AE, Calkins H, et al. ACC/AHA/HRS 2006 key data elements and https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 11/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate definitions for electrophysiological studies and procedures: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology). Circulation 2006; 114:2534. 4. US Renal Data System. USRDS 2006 Annual Data Report. National Institutes of Health; Natio nal Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2006. 5. Herzog CA. Sudden cardiac death in dialysis patients http://www.usrds.org/presentations.ht m (Accessed on January 04, 2007). 6. Cheung AK, Sarnak MJ, Yan G, et al. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study. Kidney Int 2004; 65:2380. 7. Wanner C, Krane V, M rz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353:238. 8. Parekh RS, Plantinga LC, Kao WH, et al. The association of sudden cardiac death with inflammation and other traditional risk factors. Kidney Int 2008; 74:1335. 9. Jadoul M, Thumma J, Fuller DS, et al. Modifiable practices associated with sudden death among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Clin J Am Soc Nephrol 2012; 7:765. 10. Wheeler DC, London GM, Parfrey PS, et al. Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. J Am Heart Assoc 2014; 3:e001363. 11. US Renal Data System. USRDS 2011 Annual Data Report. National Institutes of Heatlh; Natio nal Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2011. 12. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol 2004; 93:1455. 13. Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int 1999; 55:1553. 14. Bleyer AJ, Hartman J, Brannon PC, et al. Characteristics of sudden death in hemodialysis patients. Kidney Int 2006; 69:2268. 15. Wong MC, Kalman JM, Pedagogos E, et al. Bradycardia and asystole is the predominant mechanism of sudden cardiac death in patients with chronic kidney disease. J Am Coll Cardiol 2015; 65:1263. 16. Wong MC, Kalman JM, Pedagogos E, et al. Temporal distribution of arrhythmic events in chronic kidney disease: Highest incidence in the long interdialytic period. Heart Rhythm https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 12/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate 2015; 12:2047. 17. Charytan DM, Koplan BA, Podoll AS, et al. Greater frequency of clinically significant bradycar dia than ventricular tachycardia in hemodialysis patients: Preliminary results of the monitori ng in dialysis (MiD) study. J Am Society of Nephrology 2014; 25 (Abstract). 18. Passman RS, Herzog CA. Bad things come to those who wait: Dialysis, sudden death, and the long interdialytic period. Heart Rhythm 2015; 12:2056. 19. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med 2001; 345:1473. 20. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336:1629. 21. Shastri S, Tangri N, Tighiouart H, et al. Predictors of sudden cardiac death: a competing risk approach in the hemodialysis study. Clin J Am Soc Nephrol 2012; 7:123. 22. Herzog CA, Strief J, Gilbertson DT. Cause-specific mortality of dialysis patients after coronary revascularization: Why don't dialysis patients have better survival after coronary intervention? [Abstract]. Circulation Suppl 2004; 110:493. 23. Herzog CA, Strief JW, Collins AJ, Gilbertson DT. Cause-specific mortality of dialysis patients after coronary revascularization: why don't dialysis patients have better survival after coronary intervention? Nephrol Dial Transplant 2008; 23:2629. 24. Pun PH, Lehrich RW, Honeycutt EF, et al. Modifiable risk factors associated with sudden cardiac arrest within hemodialysis clinics. Kidney Int 2011; 79:218. 25. Karaboyas A, Zee J, Brunelli SM, et al. Dialysate Potassium, Serum Potassium, Mortality, and Arrhythmia Events in Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2017; 69:266. 26. Makar MS, Pun PH. Sudden Cardiac Death Among Hemodialysis Patients. Am J Kidney Dis 2017; 69:684. 27. FHN Trial Group, Chertow GM, Levin NW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med 2010; 363:2287. 28. Young BA. Prevention of sudden cardiac arrest in dialysis patients: can we do more to improve outcomes? Kidney Int 2011; 79:147. 29. Mangrum JM, Lin D, Dimarco J, et al. Prognostic value of left ventricular systolic function in renal dialysis patients [Abstract]. Heart Rhythm 2006; 3:S154. 30. Zoccali C, Mallamaci F, Parlongo S, et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 2002; 105:1354. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 13/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate 31. Stenvinkel P. Inflammation in end-stage renal disease: the hidden enemy. Nephrology (Carlton) 2006; 11:36. 32. Bellomo G, Lippi G, Saronio P, et al. Inflammation, infection and cardiovascular events in chronic hemodialysis patients: a prospective study. J Nephrol 2003; 16:245. 33. Rodriguez-Benot A, Martin-Malo A, Alvarez-Lara MA, et al. Mild hyperphosphatemia and mortality in hemodialysis patients. Am J Kidney Dis 2005; 46:68. 34. Packer M, Lee WH. Provocation of hyper- and hypokalemic sudden death during treatment with and withdrawal of converting-enzyme inhibition in severe chronic congestive heart failure. Am J Cardiol 1986; 57:347. 35. Reiter MJ, Mann DE, Williams GR. Interaction of hypokalemia and ventricular dilatation in isolated rabbit hearts. Am J Physiol 1993; 265:H1544. 36. Halperin BD, Adler SW, Mann DE, Reiter MJ. Mechanical correlates of contraction-excitation feedback during acute ventricular dilatation. Cardiovasc Res 1993; 27:1084. 37. Chan KE, Lazarus JM, Hakim RM. Digoxin associates with mortality in ESRD. J Am Soc Nephrol 2010; 21:1550. 38. Parfrey PS, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol 1999; 10:1606. 39. Mangrum AJ, Lin D, Dimarco J. Sudden cardiac death and left ventricular function in hemodialysis patients [Abstract]. Heart Rhythm 2006; 2:S33. 40. Yamada S, Ishii H, Takahashi H, et al. Prognostic value of reduced left ventricular ejection fraction at start of hemodialysis therapy on cardiovascular and all-cause mortality in end- stage renal disease patients. Clin J Am Soc Nephrol 2010; 5:1793. 41. Ganesh SK, Stack AG, Levin NW, et al. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001; 12:2131. 42. Kruger A, Stewart J, Sahityani R, et al. Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk. Kidney Int 2006; 70:157. 43. Levin A, Singer J, Thompson CR, et al. Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Am J Kidney Dis 1996; 27:347. 44. Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974; 290:697. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 14/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate 45. Mall G, Huther W, Schneider J, et al. Diffuse intermyocardiocytic fibrosis in uraemic patients. Nephrol Dial Transplant 1990; 5:39. 46. Schietinger BJ, Brammer GM, Wang H, et al. Patterns of late gadolinium enhancement in chronic hemodialysis patients. JACC Cardiovasc Imaging 2008; 1:450. 47. Friedman AN, Groh WJ, Das M. A pilot study in hemodialysis of an electrophysiological tool to measure sudden cardiac death risk. Clin Nephrol 2007; 68:159. 48. Wang AY, Lam CW, Chan IH, et al. Sudden cardiac death in end-stage renal disease patients: a 5-year prospective analysis. Hypertension 2010; 56:210. 49. K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005; 45:S1. 50. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 2002; 106:2941. Topic 1922 Version 29.0 |
among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Clin J Am Soc Nephrol 2012; 7:765. 10. Wheeler DC, London GM, Parfrey PS, et al. Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. J Am Heart Assoc 2014; 3:e001363. 11. US Renal Data System. USRDS 2011 Annual Data Report. National Institutes of Heatlh; Natio nal Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2011. 12. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol 2004; 93:1455. 13. Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int 1999; 55:1553. 14. Bleyer AJ, Hartman J, Brannon PC, et al. Characteristics of sudden death in hemodialysis patients. Kidney Int 2006; 69:2268. 15. Wong MC, Kalman JM, Pedagogos E, et al. Bradycardia and asystole is the predominant mechanism of sudden cardiac death in patients with chronic kidney disease. J Am Coll Cardiol 2015; 65:1263. 16. Wong MC, Kalman JM, Pedagogos E, et al. Temporal distribution of arrhythmic events in chronic kidney disease: Highest incidence in the long interdialytic period. Heart Rhythm https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 12/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate 2015; 12:2047. 17. Charytan DM, Koplan BA, Podoll AS, et al. Greater frequency of clinically significant bradycar dia than ventricular tachycardia in hemodialysis patients: Preliminary results of the monitori ng in dialysis (MiD) study. J Am Society of Nephrology 2014; 25 (Abstract). 18. Passman RS, Herzog CA. Bad things come to those who wait: Dialysis, sudden death, and the long interdialytic period. Heart Rhythm 2015; 12:2056. 19. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med 2001; 345:1473. 20. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336:1629. 21. Shastri S, Tangri N, Tighiouart H, et al. Predictors of sudden cardiac death: a competing risk approach in the hemodialysis study. Clin J Am Soc Nephrol 2012; 7:123. 22. Herzog CA, Strief J, Gilbertson DT. Cause-specific mortality of dialysis patients after coronary revascularization: Why don't dialysis patients have better survival after coronary intervention? [Abstract]. Circulation Suppl 2004; 110:493. 23. Herzog CA, Strief JW, Collins AJ, Gilbertson DT. Cause-specific mortality of dialysis patients after coronary revascularization: why don't dialysis patients have better survival after coronary intervention? Nephrol Dial Transplant 2008; 23:2629. 24. Pun PH, Lehrich RW, Honeycutt EF, et al. Modifiable risk factors associated with sudden cardiac arrest within hemodialysis clinics. Kidney Int 2011; 79:218. 25. Karaboyas A, Zee J, Brunelli SM, et al. Dialysate Potassium, Serum Potassium, Mortality, and Arrhythmia Events in Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2017; 69:266. 26. Makar MS, Pun PH. Sudden Cardiac Death Among Hemodialysis Patients. Am J Kidney Dis 2017; 69:684. 27. FHN Trial Group, Chertow GM, Levin NW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med 2010; 363:2287. 28. Young BA. Prevention of sudden cardiac arrest in dialysis patients: can we do more to improve outcomes? Kidney Int 2011; 79:147. 29. Mangrum JM, Lin D, Dimarco J, et al. Prognostic value of left ventricular systolic function in renal dialysis patients [Abstract]. Heart Rhythm 2006; 3:S154. 30. Zoccali C, Mallamaci F, Parlongo S, et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 2002; 105:1354. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 13/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate 31. Stenvinkel P. Inflammation in end-stage renal disease: the hidden enemy. Nephrology (Carlton) 2006; 11:36. 32. Bellomo G, Lippi G, Saronio P, et al. Inflammation, infection and cardiovascular events in chronic hemodialysis patients: a prospective study. J Nephrol 2003; 16:245. 33. Rodriguez-Benot A, Martin-Malo A, Alvarez-Lara MA, et al. Mild hyperphosphatemia and mortality in hemodialysis patients. Am J Kidney Dis 2005; 46:68. 34. Packer M, Lee WH. Provocation of hyper- and hypokalemic sudden death during treatment with and withdrawal of converting-enzyme inhibition in severe chronic congestive heart failure. Am J Cardiol 1986; 57:347. 35. Reiter MJ, Mann DE, Williams GR. Interaction of hypokalemia and ventricular dilatation in isolated rabbit hearts. Am J Physiol 1993; 265:H1544. 36. Halperin BD, Adler SW, Mann DE, Reiter MJ. Mechanical correlates of contraction-excitation feedback during acute ventricular dilatation. Cardiovasc Res 1993; 27:1084. 37. Chan KE, Lazarus JM, Hakim RM. Digoxin associates with mortality in ESRD. J Am Soc Nephrol 2010; 21:1550. 38. Parfrey PS, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol 1999; 10:1606. 39. Mangrum AJ, Lin D, Dimarco J. Sudden cardiac death and left ventricular function in hemodialysis patients [Abstract]. Heart Rhythm 2006; 2:S33. 40. Yamada S, Ishii H, Takahashi H, et al. Prognostic value of reduced left ventricular ejection fraction at start of hemodialysis therapy on cardiovascular and all-cause mortality in end- stage renal disease patients. Clin J Am Soc Nephrol 2010; 5:1793. 41. Ganesh SK, Stack AG, Levin NW, et al. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001; 12:2131. 42. Kruger A, Stewart J, Sahityani R, et al. Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk. Kidney Int 2006; 70:157. 43. Levin A, Singer J, Thompson CR, et al. Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Am J Kidney Dis 1996; 27:347. 44. Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974; 290:697. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 14/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate 45. Mall G, Huther W, Schneider J, et al. Diffuse intermyocardiocytic fibrosis in uraemic patients. Nephrol Dial Transplant 1990; 5:39. 46. Schietinger BJ, Brammer GM, Wang H, et al. Patterns of late gadolinium enhancement in chronic hemodialysis patients. JACC Cardiovasc Imaging 2008; 1:450. 47. Friedman AN, Groh WJ, Das M. A pilot study in hemodialysis of an electrophysiological tool to measure sudden cardiac death risk. Clin Nephrol 2007; 68:159. 48. Wang AY, Lam CW, Chan IH, et al. Sudden cardiac death in end-stage renal disease patients: a 5-year prospective analysis. Hypertension 2010; 56:210. 49. K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005; 45:S1. 50. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 2002; 106:2941. Topic 1922 Version 29.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 15/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate GRAPHICS Trends in death rates in dialysis patients per 100 patient-years and annual perce change from 1996 to 2013 Adapted from: Peer Dialysis Initiative. Peer Report: Dialysis Care and Outcomes in the United States, 2016, Chronic Disease Research Group, Minneapolis, MN, 2016. Graphic 116349 Version 1.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 16/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate All-cause cardiovascular versus sudden cardiac death in dialysis patients per 100 patient-years in the United States SCD: sudden cardiac death. Adapted with permission from: Peer Kidney Care Initiative. Peer Report: Dialysis Care and Outcomes in the United States 2016. Chronic Disease Research Group, Minneapolis, MN, 2016. Copyright 2016 Chronic Disease Research Group. Graphic 116351 Version 1.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 17/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Cause-specific mortality in incident dialysis patients after first dialysis session in a freestanding facility https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 18/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate According to the Death Notification Form; 2011. https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 19/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Reproduced from: Weinhandl E, Constantini E, Everson S, et al. Peer kidney care initiative 2014 report: Dialysis care and outcomes in the United States. Am J Kidney Dis 2015; 65(6 Suppl 1): S1. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 106384 Version 1.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 20/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Distribution of causes of death during the first year of dialysis According to the Death Notification Form; 2011. Reproduced from: Weinhandl E, Constantini E, Everson S, et al. Peer kidney care initiative 2014 report: Dialysis care and outcomes in the United States. Am J Kidney Dis 2015; 65(6 Suppl 1): S1. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 106385 Version 1.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 21/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Figure showing risk of cardiac arrest among hemodialysis patients Incident Medicare dialysis patients age 20 years and older, 2000 to 2002 combined. Monthly event rates during the first six months and mean monthly event rates during each following six-month interval. Adjusted for age, gender, race, and diabetic status. Data from US Renal Data System. USRDS 2006 Annual Data Report. Bethesda (MD): National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2006. Graphic 81852 Version 3.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 22/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Adjusted mortality by treatment modality and number of months after treatment initiation among ESRD patients, 2014 Data source: Special analyses, USRDS ESRD database. Adjusted (age, race, sex, ethnicity, and primary diagnosis) mortality among 2013 incident ESRD patients during the first year https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 23/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate of therapy. Reference population: incident ESRD patients, 2011. ESRD: end-stage renal disease; USRDS: United States Renal Data System; PD: peritoneal dialysis; HD: hemodialysis. Reproduced from: United States Renal Data System. 2017 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2017. Graphic 116354 Version 3.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 24/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Factors that contribute to sudden cardiac death (SCD) in dialysis patients Coronary artery disease/myocardial infarction Significant left ventricular hypertrophy Anemia/calcium/phosphorus/parathyroid hormone Uremia Chronic fluid overload Inflammation Electrolyte abnormalities Autonomic imbalance Heart failure/decreased left ventricular function Graphic 63859 Version 3.0 https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 25/26 7/6/23, 1:37 PM Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients - UpToDate Contributor Disclosures Charles A Herzog, MD Equity Ownership/Stock Options: Boston Scientific [Medical devices]; GE [Medical devices, echo contrast]; Johnson & Johnson [Pharmaceuticals, medical devices]; Merck [Pharmaceuticals]; Pfizer [Pharmaceuticals]. Grant/Research/Clinical Trial Support: Relypsa [Pharmaceuticals, hypo- and hyperkalemia]. Consultant/Advisory Boards: AstraZeneca [Pharmaceuticals, potassium binders]; Bayer [Diabetes, chronic kidney disease, heart failure/pharmaceuticals]; Diamedica [Diabetes, pharmaceuticals]; Fibrogen/DSMB [Pharmaceuticals, anemia]; Merck [Pharmaceuticals]; NxStage [Medical devices]; Relypsa /Vifor [Pharmaceuticals, hyperkalemia]. All of the relevant financial relationships listed have been mitigated. Rod Passman, MD, MSCE Grant/Research/Clinical Trial Support: Abbott [Ablation]; AHA [Ablation]; NIH [Stroke prevention]. Consultant/Advisory Boards: Abbott [Ablation]; iRhythm [Monitoring]; Janssen [Atrial fibrillation detection]; Medtronic [Implantable cardiac monitors]. Speaker's Bureau: iRhythm [Monitoring]. All of the relevant financial relationships listed have been mitigated. Jeffrey S Berns, MD No relevant financial relationship(s) with ineligible companies to disclose. Eric N Taylor, MD, MSc, FASN No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/evaluation-of-sudden-cardiac-arrest-and-sudden-cardiac-death-in-dialysis-patients/print 26/26 |
7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk : Martin S Maron, MD : Samuel L vy, MD, William J McKenna, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 24, 2020. INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease caused by mutations in one of several sarcomere genes that encode components of the contractile apparatus of the heart. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) HCM is characterized by left ventricular (LV) hypertrophy of various morphologies, with a wide array of clinical manifestations and hemodynamic abnormalities ( figure 1). Depending in part upon the site and extent of cardiac hypertrophy, patients with HCM can develop one or more of the following abnormalities: LV outflow obstruction. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction".) Diastolic and systolic dysfunction. Myocardial ischemia. Mitral regurgitation. These structural and functional abnormalities can produce a variety of symptoms, including: Fatigue Dyspnea Chest pain Palpitations https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 1/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Presyncope or syncope In broad terms, the symptoms related to HCM can be categorized as those related to heart failure (HF), chest pain, or arrhythmias. Patients with HCM are prone to both atrial and ventricular arrhythmias. Many of these arrhythmias are asymptomatic, but some can precipitate hemodynamic collapse and sudden cardiac death (SCD). SCD is a catastrophic and unpredictable complication of HCM and in some patients may be the first presentation of the disease. The management of patients following risk assessment and following a documented ventricular arrhythmia will be reviewed here. The assessment of risk for arrhythmic SCD is a critical component of the clinical evaluation of nearly all patients with HCM and is reviewed separately. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) Other issues related to ventricular arrhythmias and SCD, as well as other clinical manifestations, natural history, diagnosis and evaluation, and treatment of patients with HCM, are discussed separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Natural history and prognosis" and "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction" and "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".) MANAGEMENT The management of the risk for SCD and ventricular arrhythmias in patients with HCM is centered around minimizing risk associated with physical activity and targeted interventions, primarily implantation of an ICD when indicated. There are limited roles for other nonpharmacologic therapies (eg, septal reduction therapy and catheter ablation) and medical therapy in the management of ventricular arrhythmias and risk of SCD. The overall role of nonpharmacologic therapies and medical therapy in patients with HCM is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction" and "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction".) Implantable cardioverter-defibrillators (ICDs) The ICD is the best available therapy for patients with HCM who have survived SCD or who are at high risk of ventricular arrhythmias and SCD. Randomized trials of ICD therapy have not been performed in patients with HCM; as a result, the indications for an ICD are derived from largely retrospective observational data that define strength of the noninvasive risk factors in identifying high-risk patients. In addition, efficacy of ICDs in patients with HCM is also derived from the incidence of appropriate ICD https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 2/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate therapies in patients who have had an ICD implanted [1-3]. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Recommendations for ICD therapy For patients who survive an episode of sustained ventricular tachycardia (VT) or SCD, we recommend implantation of an ICD for the secondary prevention of SCD. (See 'Secondary prevention ICD' below.) In patients with HCM with 1 of the major noninvasive risk markers ( table 1), it is reasonable to offer an ICD for primary prevention of SCD, taking into account the individual patient's age, clinical profile, and values/preferences regarding device therapy. (See 'Primary prevention ICD' below.) In patients with 1 major risk marker, but who remain ambivalent or uncertain regarding ICD implantation, magnitude of LV outflow tract gradient, abnormal blood pressure response to exercise, and the results of contrast-enhanced cardiovascular magnetic resonance imaging are important arbitrators in resolving high-risk status and the need for primary prevention ICD therapy. Age is also an important factor in considering patients at risk. Patients with HCM who have achieved an advanced age of 60 years are at very low risk for disease-related adverse events, including SCD, even in the presence of conventional risk factors. Therefore, a high threshold is necessary to consider older patients with HCM at high risk and candidates for ICD therapy for primary prevention of SCD. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) If a patient with HCM develops a clinical indication for permanent pacing, and is otherwise low risk for SCD based on risk stratification strategy, there would be no indication for upgrading the pacemaker to include ICD functionality. Certain other subsets of patients with HCM, namely patients with end-stage HCM with LV ejection fraction <50 percent and patients with HCM and an LV apical aneurysm, are at high risk for SCD [4]. Patients with HCM and an LV apical aneurysm have a fivefold higher risk of life-threatening ventricular arrhythmias and SCD compared with patients with HCM who do not have an LV apical aneurysm. For this reason, many HCM patients with apical aneurysms have sufficiently increased risk of SCD to warrant implantation of an ICD for primary prevention of SCD. As is the case in similar management scenarios where prospective randomized trials are not possible, decisions regarding high-risk status should be made on an individual basis, taking into consideration the entire clinical profile of the patient. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 3/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Secondary prevention ICD Patients with HCM who have survived cardiac arrest due to VT or ventricular fibrillation (VF) are at an increased risk for recurrent events and should undergo ICD implantation for secondary prevention [1,5-12]. This risk was illustrated in a series of 33 patients successfully resuscitated from a cardiac arrest prior to the widespread use of ICDs [8]. They were treated with a variety of strategies, including septal myotomy and medical therapy. Despite treatment, recurrent arrhythmias were common. The survival rates free of recurrent cardiac arrest or death after 1, 5, and 10 years were 83, 65, and 53 percent, respectively. A high rate of recurrent ventricular arrhythmias in patients with HCM and a history of cardiac arrest or sustained VT are further supported by the frequency of appropriate shocks in patients who received an ICD for secondary prevention of SCD [10]. In a study of 160 selected high-risk patients with HCM and an ICD, including 94 patients with 24- or 48-hour ambulatory electrocardiogram (ECG) monitoring pre-ICD implant, nonsustained VT (NSVT) was detected in 86 patients (54 percent) during an average follow-up of four years [13]. Patients with documented NSVT were significantly more likely to develop sustained VT/VF requiring ICD therapy (21 versus 8 percent; adjusted hazard ratio [HR] 3.6, 95% CI 1.3-10.2). Factors associated with a significantly higher likelihood of requiring ICD therapy include NSVT duration >7 beats, rate >200 beats per minute, or more than one NSVT run. Primary prevention ICD In HCM patients with 1 major risk marker, an ICD can be beneficial for primary prevention of SCD. ( algorithm 1) [5,6,12]. The American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of ventricular arrhythmias and the prevention of SCD note that an ICD is reasonable in patients with one or more major risk factors [12]. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Impact of number of risk factors' and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk modifiers'.) In a multicenter registry of 506 patients with HCM and an ICD (24 percent for secondary prevention) who were followed for an average of 3.7 years, 20 percent of patients received appropriate ICD interventions [2]. The rate of appropriate device activation was 10.6 percent per year when used for secondary prevention of SCD, and 3.6 percent per year when used for primary prevention. Similar rates of ICD intervention have been reported using registry data in a pediatric population; among 224 children and adolescents with HCM and an ICD (including 188 patients [84 percent] placed for primary prevention) who were followed for an average of 4.3 years, 43 patients (19 percent; 4.5 percent per year) received an appropriate ICD intervention [14]. Choice of device Traditionally, most patients with HCM who underwent ICD implantation received a transvenous ICD system, with the vast majority of long-term safety and efficacy of ICD https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 4/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate therapy in HCM patients being derived from studies with transvenous ICDs. Some patients with HCM may also be candidates for a subcutaneous ICD (S-ICD) rather than the standard ICD with transvenous leads [15]. The S-ICD provides patients the opportunity to avoid intravascular complications from long-term lead placement, a particular relevant point for patients with HCM who are young and often have many decades of risk and the need for primary prevention ICDs. In addition, the S-ICD can be extracted with minimal risk if an indication for device removal emerges at any point in patients' clinical course. However, prior to implantation, the surface ECG must be rigorously scrutinized to determine eligibility for the S- ICD in order to avoid inappropriate shocks related to T-wave oversensing [16]. (See "Subcutaneous implantable cardioverter defibrillators".) Early data from small cohort studies of S-ICD use in patients with HCM are promising: In a cohort of 872 patients (99 with HCM), similar implantation success and one-year complication rates following S-ICD implantation were seen for patients with and without HCM; additionally, 3 of the 99 patients with HCM had VT that was successfully terminated following the initial shock [17]. In a multicenter cohort of 88 patients with HCM who received an S-ICD and were followed for an average of 2.7 years, two patients received appropriate shocks terminating VT, while inappropriate shocks occurred in five patients (due to T-wave oversensing or supraventricular tachycardias with rates in the shock range) [18]. Among 122 consecutive patients with HCM who met criteria for ICD implantation (3 for secondary prevention, 119 for primary prevention based on one or more major risk markers) and were eligible for either S-ICD or transvenous ICD, 47 patients chose S-ICD while 75 chose transvenous ICD [19]. Rate of appropriate shocks was not different between S-ICD and transvenous ICD. Five patients (11 percent) with S-ICD received a total of 10 appropriate shocks, while 15 patients (20 percent) with a transvenous ICD received appropriate therapies (shocks in three patients, antitachycardia pacing in 12 patients). Inappropriate shocks were more common in S-ICD recipients (eight patients [17 percent) versus two patients [3 percent]). Although preliminary, this study demonstrates that despite the absence of antitachycardia pacing with the S-ICD, appropriate shock rates were not greater with the S-ICD compared to transvenous ICD. Our approach to device selection in high-risk HCM patients In patients with an indication for bradycardia pacing, or in whom monomorphic VT is most likely the initiating ventricular arrhythmia (ie, patients with HCM with LV apical aneurysm), https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 5/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate we place a transvenous ICD given the ability to provide bradycardia pacing and antitachycardia pacing. In patients with massive LV hypertrophy (LVH), defined as LV wall thickness 30 mm anywhere in the LV wall, we favor the transvenous ICD given that patients with HCM and massive LVH have not yet been well-represented in prospective S-ICD studies and the theoretical concern regarding long-term efficacy of the S-ICD in aborting life-threatening arrhythmias, particularly in patients with extreme disease expression. In patients with apical aneurysm, monomorphic VT is the most common initiating ventricular tachyarrhythmia, and for this reason we favor transvenous ICD, given the opportunity this device provides for anti-tachycardia pacing treatment to abort VT. For younger, active HCM patients without massive LVH in whom device therapy will be required over many decades of life, we employ a shared decision-making strategy in which patients are fully informed about the strengths and limitations of both devices to enable a transparent and reliable choice regarding selection of ICD. In middle-aged or older high-risk patients with HCM, the overall benefit of S-ICD is generally less compared with the transvenous device and for this reason we generally favor transvenous ICD for this subgroup, although it is reasonable to evaluate for S-ICD placement, incorporating similar shared decision-making strategy as discussed with younger patients. Complications of device therapy Long-term complications following ICD placement include the following [20-22]: Approximately 25 percent of patients experience inappropriate ICD discharge 6 to 13 percent experience lead complications (eg, fracture, dislodgment, oversensing) 4 to 5 percent develop device-related infection 2 to 3 percent experience bleeding or thrombosis By contrast to the experience among ICD recipients with other nonischemic and ischemic etiologies for cardiomyopathy, patients with HCM implanted for primary prevention ICDs do not appear to have a significant increase in all-cause or cardiac mortality following appropriate ICD shocks. Among a cohort of 486 patients with HCM felt to be at high risk for SCD and who received primary prevention ICDs, 94 patients (19 percent) received an appropriate ICD intervention (shock or antitachycardia pacing) over an average follow-up of 6.4 years (3.7 percent per year risk of appropriate ICD intervention) [23]. Freedom from HCM-related mortality at 1, 5, and 10 years was 100, 97, and 92 percent, respectively. The favorable outcome after https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 6/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate appropriate ICD shocks in HCM is likely related to the otherwise preserved myocardial substrate in HCM, in which systolic function is normal and risk of developing advanced HF is low. The rate of inappropriate shocks and lead fractures appears to be higher in children than in adults, largely because their activity level and body growth place continual strain on the leads, which are the weakest link in the system [22]. This issue is of particular concern, given the long periods that young patients will have prophylactically implanted devices. (See "Cardiac implantable electronic devices: Long-term complications".) Nonpharmacologic treatment of LV outflow tract obstruction Nonpharmacologic therapies for LV outflow tract obstruction are discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".) Medical treatment Medical therapy for ventricular arrhythmias in patients with HCM has an important role in select clinical scenarios, including: Patients with symptomatic arrhythmias Patients with an ICD who have frequent arrhythmias or antitachyarrhythmia therapies Patients at high risk of ventricular arrhythmias who are not candidates for, or choose not to have, an ICD There is no evidence that pharmacologic therapy provides absolute protection against sudden death due to malignant ventricular arrhythmias in patients with HCM [24]. Thus, for patients with asymptomatic ventricular premature beats (VPBs) or NSVT, we recommend that pharmacologic therapy not be given for the purpose of arrhythmia suppression. However, for patients with symptoms due to VPBs or NSVT, we suggest pharmacologic treatment for symptom control, typically with a beta blocker or an antiarrhythmic drug. Patients with frequent sustained ventricular arrhythmias resulting in ICD shocks should be treated with adjunctive antiarrhythmic therapy, most often sotalol or amiodarone. Our general approach is as follows: For patients with symptomatic VPBs, we use beta blockers. (See "Premature ventricular complexes: Treatment and prognosis".) Patients with symptomatic NSVT can be treated with beta blockers, or in selected patients, sotalol or amiodarone, for the purpose of symptom control [25,26]. If antiarrhythmic therapy is required, we generally prefer sotalol in younger patients (<50 years of age) due to the potential toxicities associated with the long-term use (ie, years to decades) of amiodarone. There is a small risk of proarrhythmia with sotalol due to the potential for QT prolongation, although our experts feel the risks of sotalol in younger patients are https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 7/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate generally lower than the potential long-term toxicities of amiodarone. As such, sotalol remains an option, even in the absence of an ICD, although clinical experience and published data are limited. Because NSVT is associated with an increased risk of SCD, its presence should be taken into account when considering an individual's risk for SCD and the need for ICD therapy. Pharmacologic therapies directed at symptomatic NSVT do not reduce the risk of SCD and should not be used alone as an alternative to ICD therapy. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk stratification'.) Sustained VT in the absence of an identifiable provoking factor is generally regarded as a major risk factor for SCD. Nearly all such patients receive an ICD for secondary prevention. For patients with frequent arrhythmia recurrences who experience multiple shocks, adjunctive antiarrhythmic therapy is indicated, with sotalol or amiodarone and/or a beta blocker as therapeutic options [6,12,26]. Electrical storm and/or incessant VT are highly unusual in patients with HCM, and given the diffusely abnormal myocardial substrate in this disease, the efficacy of radiofrequency ablation is uncertain. One exception is those patients with HCM and LV apical aneurysms, in whom the focus of incessant ventricular tachyarrhythmias can often be reliably identified with mapping techniques (junction of the aneurysm rim with myocardium) and successfully treated with radiofrequency ablation [27,28]. (See "Electrical storm and incessant ventricular tachycardia", section on 'Catheter ablation'.) Catheter ablation Radiofrequency catheter ablation for recurrent VT in patients with HCM has largely been reserved for the subgroup of patients with LV apical aneurysm [28]. Among 13 patients with LV apical aneurysm and recurrent VT, seven underwent catheter ablation for VT, with six of the seven remaining free of subsequent VT at an average of 1.9 years of follow-up [29]. The success of catheter ablation in this subgroup of patients is due to the fact that the structural nidus for VT is commonly at the junction of the aneurysm rim and LV myocardium, providing an identifiable target for ablation. On the other hand, in the remainder of the HCM population, the diffuse abnormal myocardial substrate results in multiple foci for VT and therefore little evidence that catheter ablation would be successful [28]. The use of catheter ablation for ventricular arrhythmias is largely focused in other populations (eg, post-myocardial infarction) and is discussed in detail separately. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation'.) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 8/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Restriction of physical activity Due to the potential risk of SCD associated with exercise in patients with HCM, activity restriction is an important component of patient management. Competitive athletes with a probable or unequivocal clinical diagnosis of HCM should not participate in most competitive sports, with the possible exception of those that are low intensity ( figure 2). Activity restriction in competitive athletes with HCM is discussed separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Hypertrophic cardiomyopathy'.) Among patients with HCM who are not competitive athletes, there is frequently a desire to exercise for both recreation and personal fitness. Additionally, exercise may be an important mechanism to prevent cardiometabolic heart disease as most patients with HCM have an expected longevity that is similar to the general population. Historically, patients with HCM have been instructed to confine themselves to mild to moderate recreational level activities, always engaging in a noncompetitive manner. To provide a more concrete guide to the appropriate limits of exercise in HCM patients, some experts have suggested that at peak exertion, HCM patients should still be able to complete full sentences without straining to complete words. Several studies have suggested that exercise, either moderate- or high-intensity, is safe in carefully selected patients with HCM [30-34]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Catheter ablation of arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 9/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Hypertrophic cardiomyopathy in adults (The Basics)") Beyond the Basics topic (see "Patient education: Hypertrophic cardiomyopathy (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Patients with hypertrophic cardiomyopathy (HCM) are prone to ventricular arrhythmias. Ventricular arrhythmias can range from isolated ventricular premature beats (VPBs) to nonsustained ventricular tachycardia (NSVT) to sustained VT and ventricular fibrillation (VF). While the frequency of ventricular arrhythmias is highly variable, the annual incidence of sudden cardiac death (SCD) in the clinically identified general HCM patient population is approximately 1 percent. (See 'Introduction' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Epidemiology'.) SCD is the most-feared complication of HCM. The implantable cardioverter-defibrillator (ICD) is the best available therapy for patients with HCM who have survived SCD or who are at high risk of life-threatening ventricular arrhythmias. Persons with a probable or unequivocal clinical diagnosis of HCM should not participate in most competitive sports, with the possible exception of those that are low intensity ( figure 2). (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Hypertrophic cardiomyopathy'.) For patients who survive an episode of sustained VT or sudden cardiac arrest, we recommend implantation of an ICD for secondary prevention of SCD (Grade 1B). (See 'Implantable cardioverter-defibrillators (ICDs)' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) In patients with HCM with 1 of the major noninvasive risk markers, we suggest implantation of an ICD for primary prevention of SCD (Grade 2C). ICD decision making in HCM should almost always take into account the individual patient's age, clinical profile, and values/preferences regarding device therapy. (See 'Recommendations for ICD therapy' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Established major risk markers'.) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 10/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate In patients with one major risk marker, but who remain ambivalent or uncertain regarding ICD implantation, magnitude of LV outflow tract gradient, abnormal blood pressure response to exercise, and the results of contrast-enhanced cardiovascular magnetic resonance imaging are important arbitrators in resolving high-risk status and the need for primary prevention ICD therapy. Age is also an important factor in considering patients at risk. (See 'Recommendations for ICD therapy' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk modifiers'.) Certain other subsets of patients with HCM, namely patients with end-stage HCM with LV ejection fraction <50 percent and patients with HCM and an LV apical aneurysm, are at high risk for SCD and therefore are also candidates for ICD therapy [4]. In patients with HCM and an LV apical aneurysm, we suggest implantation of an ICD for primary prevention of SCD (Grade 2C). (See 'Recommendations for ICD therapy' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Established major risk markers'.) Our approach to the selection of a particular type of ICD is presented in the text. (See 'Our approach to device selection in high-risk HCM patients' above.) There is no evidence that pharmacologic therapy provides absolute protection against SCD due to malignant ventricular arrhythmias in patients with HCM. However, medical therapy for ventricular arrhythmias in patients with HCM has an important role in select clinical scenarios: For patients with asymptomatic VPBs or NSVT, we recommend that pharmacologic therapy not be given for the purpose of arrhythmia suppression (Grade 1B). However, because NSVT is associated with an increased risk of SCD, its presence should be taken into account when considering the need for ICD therapy for primary prevention of sudden death. (See 'Medical treatment' above.) For patients with symptoms due to VPBs or NSVT, we suggest pharmacologic treatment for symptom control (Grade 2C). Beta blockers are the preferred initial therapy, and in refractory cases, we suggest sotalol or amiodarone. The purpose of medical therapy is the control of symptoms; it should not be considered an alternative to an ICD in patients at high risk of SCD. (See 'Medical treatment' above.) Patients with frequent sustained ventricular arrhythmias resulting in ICD shocks should be treated with adjunctive antiarrhythmic therapy, most often sotalol or amiodarone. Radiofrequency ablation is an option to abolish or mitigate recurrent ventricular https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 11/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate arrhythmias in patients with HCM and an apical aneurysm, although the efficacy of VT ablation in patients without an apical aneurysm is uncertain. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Other treatment options'.) ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Perry Elliott, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest or sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1999; 33:1596. 2. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298:405. 3. Begley DA, Mohiddin SA, Tripodi D, et al. Efficacy of implantable cardioverter defibrillator therapy for primary and secondary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 2003; 26:1887. 4. Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ 2006; 332:1251. 5. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124:e783. 6. Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35:2733. 7. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000; 342:365. 8. Cecchi F, Maron BJ, Epstein SE. Long-term outcome of patients with hypertrophic cardiomyopathy successfully resuscitated after cardiac arrest. J Am Coll Cardiol 1989; 13:1283. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 12/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate 9. Primo J, Geelen P, Brugada J, et al. Hypertrophic cardiomyopathy: role of the implantable cardioverter-defibrillator. J Am Coll Cardiol 1998; 31:1081. 10. Magnusson P, Gadler F, Liv P, M rner S. Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy. Pacing Clin Electrophysiol 2016; 39:291. 11. Thavikulwat AC, Tomson TT, Knight BP, et al. Appropriate Implantable Defibrillator Therapy in Adults With Hypertrophic Cardiomyopathy. J Cardiovasc Electrophysiol 2016; 27:953. 12. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 13. Wang W, Lian Z, Rowin EJ, et al. Prognostic Implications of Nonsustained Ventricular Tachycardia in High-Risk Patients With Hypertrophic Cardiomyopathy. Circ Arrhythm Electrophysiol 2017; 10. 14. Maron BJ, Spirito P, Ackerman MJ, et al. Prevention of sudden cardiac death with implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol 2013; 61:1527. 15. Weinstock J, Bader YH, Maron MS, et al. Subcutaneous Implantable Cardioverter Defibrillator in Patients With Hypertrophic Cardiomyopathy: An Initial Experience. J Am Heart Assoc 2016; 5. 16. Maurizi N, Olivotto I, Olde Nordkamp LR, et al. Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:457. 17. Lambiase PD, Gold MR, Hood M, et al. Evaluation of subcutaneous ICD early performance in hypertrophic cardiomyopathy from the pooled EFFORTLESS and IDE cohorts. Heart Rhythm 2016; 13:1066. 18. Nazer B, Dale Z, Carrassa G, et al. Appropriate and inappropriate shocks in hypertrophic cardiomyopathy patients with subcutaneous implantable cardioverter-defibrillators: An international multicenter study. Heart Rhythm 2020; 17:1107. 19. Maron MS, Steiger N, Burrows A, et al. Evidence That Subcutaneous Implantable Cardioverter-Defibrillators Are Effective and Reliable in Hypertrophic Cardiomyopathy. JACC Clin Electrophysiol 2020; 6:1019. 20. Schinkel AF, Vriesendorp PA, Sijbrands EJ, et al. Outcome and complications after implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: systematic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 13/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate review and meta-analysis. Circ Heart Fail 2012; 5:552. 21. Vriesendorp PA, Schinkel AF, Van Cleemput J, et al. Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: patient outcomes, rate of appropriate and inappropriate interventions, and complications. Am Heart J 2013; 166:496. 22. Berul CI, Van Hare GF, Kertesz NJ, et al. Results of a multicenter retrospective implantable cardioverter-defibrillator registry of pediatric and congenital heart disease patients. J Am Coll Cardiol 2008; 51:1685. 23. Maron BJ, Casey SA, Olivotto I, et al. Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators. Circ Arrhythm Electrophysiol 2018; 11:e005820. 24. Maron BJ, Maron MS. Contemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:1155. 25. McKenna WJ, Oakley CM, Krikler DM, Goodwin JF. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Br Heart J 1985; 53:412. 26. McKenna WJ, Harris L, Rowland E, et al. Amiodarone for long-term management of patients with hypertrophic cardiomyopathy. Am J Cardiol 1984; 54:802. 27. Mantica M, Della Bella P, Arena V. Hypertrophic cardiomyopathy with apical aneurysm: a case of catheter and surgical therapy of sustained monomorphic ventricular tachycardia. Heart 1997; 77:481. 28. Rodriguez LM, Smeets JL, Timmermans C, et al. Radiofrequency catheter ablation of sustained monomorphic ventricular tachycardia in hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol 1997; 8:803. 29. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management. J Am Coll Cardiol 2017; 69:761. 30. Saberi S, Wheeler M, Bragg-Gresham J, et al. Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy: A Randomized Clinical Trial. JAMA 2017; 317:1349. 31. Klempfner R, Kamerman T, Schwammenthal E, et al. Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center. Eur J Prev Cardiol 2015; 22:13. 32. Sheikh N, Papadakis M, Schnell F, et al. Clinical Profile of Athletes With Hypertrophic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 14/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Cardiomyopathy. Circ Cardiovasc Imaging 2015; 8:e003454. |
ablation in patients without an apical aneurysm is uncertain. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Other treatment options'.) ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Perry Elliott, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest or sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1999; 33:1596. 2. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298:405. 3. Begley DA, Mohiddin SA, Tripodi D, et al. Efficacy of implantable cardioverter defibrillator therapy for primary and secondary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 2003; 26:1887. 4. Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ 2006; 332:1251. 5. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124:e783. 6. Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35:2733. 7. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000; 342:365. 8. Cecchi F, Maron BJ, Epstein SE. Long-term outcome of patients with hypertrophic cardiomyopathy successfully resuscitated after cardiac arrest. J Am Coll Cardiol 1989; 13:1283. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 12/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate 9. Primo J, Geelen P, Brugada J, et al. Hypertrophic cardiomyopathy: role of the implantable cardioverter-defibrillator. J Am Coll Cardiol 1998; 31:1081. 10. Magnusson P, Gadler F, Liv P, M rner S. Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy. Pacing Clin Electrophysiol 2016; 39:291. 11. Thavikulwat AC, Tomson TT, Knight BP, et al. Appropriate Implantable Defibrillator Therapy in Adults With Hypertrophic Cardiomyopathy. J Cardiovasc Electrophysiol 2016; 27:953. 12. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 13. Wang W, Lian Z, Rowin EJ, et al. Prognostic Implications of Nonsustained Ventricular Tachycardia in High-Risk Patients With Hypertrophic Cardiomyopathy. Circ Arrhythm Electrophysiol 2017; 10. 14. Maron BJ, Spirito P, Ackerman MJ, et al. Prevention of sudden cardiac death with implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol 2013; 61:1527. 15. Weinstock J, Bader YH, Maron MS, et al. Subcutaneous Implantable Cardioverter Defibrillator in Patients With Hypertrophic Cardiomyopathy: An Initial Experience. J Am Heart Assoc 2016; 5. 16. Maurizi N, Olivotto I, Olde Nordkamp LR, et al. Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:457. 17. Lambiase PD, Gold MR, Hood M, et al. Evaluation of subcutaneous ICD early performance in hypertrophic cardiomyopathy from the pooled EFFORTLESS and IDE cohorts. Heart Rhythm 2016; 13:1066. 18. Nazer B, Dale Z, Carrassa G, et al. Appropriate and inappropriate shocks in hypertrophic cardiomyopathy patients with subcutaneous implantable cardioverter-defibrillators: An international multicenter study. Heart Rhythm 2020; 17:1107. 19. Maron MS, Steiger N, Burrows A, et al. Evidence That Subcutaneous Implantable Cardioverter-Defibrillators Are Effective and Reliable in Hypertrophic Cardiomyopathy. JACC Clin Electrophysiol 2020; 6:1019. 20. Schinkel AF, Vriesendorp PA, Sijbrands EJ, et al. Outcome and complications after implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: systematic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 13/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate review and meta-analysis. Circ Heart Fail 2012; 5:552. 21. Vriesendorp PA, Schinkel AF, Van Cleemput J, et al. Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: patient outcomes, rate of appropriate and inappropriate interventions, and complications. Am Heart J 2013; 166:496. 22. Berul CI, Van Hare GF, Kertesz NJ, et al. Results of a multicenter retrospective implantable cardioverter-defibrillator registry of pediatric and congenital heart disease patients. J Am Coll Cardiol 2008; 51:1685. 23. Maron BJ, Casey SA, Olivotto I, et al. Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators. Circ Arrhythm Electrophysiol 2018; 11:e005820. 24. Maron BJ, Maron MS. Contemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:1155. 25. McKenna WJ, Oakley CM, Krikler DM, Goodwin JF. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Br Heart J 1985; 53:412. 26. McKenna WJ, Harris L, Rowland E, et al. Amiodarone for long-term management of patients with hypertrophic cardiomyopathy. Am J Cardiol 1984; 54:802. 27. Mantica M, Della Bella P, Arena V. Hypertrophic cardiomyopathy with apical aneurysm: a case of catheter and surgical therapy of sustained monomorphic ventricular tachycardia. Heart 1997; 77:481. 28. Rodriguez LM, Smeets JL, Timmermans C, et al. Radiofrequency catheter ablation of sustained monomorphic ventricular tachycardia in hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol 1997; 8:803. 29. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management. J Am Coll Cardiol 2017; 69:761. 30. Saberi S, Wheeler M, Bragg-Gresham J, et al. Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy: A Randomized Clinical Trial. JAMA 2017; 317:1349. 31. Klempfner R, Kamerman T, Schwammenthal E, et al. Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center. Eur J Prev Cardiol 2015; 22:13. 32. Sheikh N, Papadakis M, Schnell F, et al. Clinical Profile of Athletes With Hypertrophic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 14/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Cardiomyopathy. Circ Cardiovasc Imaging 2015; 8:e003454. 33. Dejgaard LA, Haland TF, Lie OH, et al. Vigorous exercise in patients with hypertrophic cardiomyopathy. Int J Cardiol 2018; 250:157. 34. Pelliccia A, Solberg EE, Papadakis M, et al. Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2019; 40:19. Topic 119625 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 15/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate GRAPHICS Morphologic variants of hypertrophic cardiomyopathy HCM typically presents with asymmetric or localized areas of LV hypertrophy, which are diagrammed in B to J. (A) Normal LV wall thickness. (B) ASH. (C) Sigmoid septum, which is more common in older adults. (D) Midcavity hypertrophy associated with midcavity obstruction. (E) Predominantly free wall hypertrophy, an unusual pattern in HCM. (F) LV wall thinning (associated with low LV ejection fraction) and biatrial enlargement. (G) Predominantly apical LV hypertrophy. (H) Severe concentric hypertrophy with cavity obliteration. (I) Biventricular hypertrophy. (J) Mild to moderate symmetric hypertrophy. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 16/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate HCM: hypertrophic cardiomyopathy; LV: left ventricular; ASH: asymmetrical septal hypertrophy. Graphic 58156 Version 6.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 17/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Established major risk markers and risk modifiers associated with increased risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) Risk factor Comment Major risk factors Family history of HCM- related SCD SCD due to HCM in a close relative, particularly if <40 years of age, should be considered evidence for increased risk of SCD in other related family members. Syncope Unexplained syncope that, based on clinical history, appears to be due to arrhythmia (and not neurally mediated) is associated with increased SCD risk, particularly in young patients and when the event occurred close to the time of evaluation (<6 months). Massive LV hypertrophy An increased risk of SCD in patients with HCM is seen in patients with echocardiographic evidence of 30 mm wall thickness anywhere in the LV chamber. If maximal wall thickness is not clearly defined using echocardiography, additional evaluation with CMR to clarify the extent of LV wall thickening may be warranted. LV apical aneurysm Uncommon subgroup with thin-walled dyskinetic LV apex with regional scarring. LV apical aneurysm is associated with increased risk for sustained monomorphic VT and warrants consideration for ICD. End-stage HCM (LVEF <50 percent) Higher incidence of life-threatening VT associated with this uncommon phase of HCM. These patients often develop advanced heart failure at a young age and therefore are often considered for ICD as a bridge to definitive therapy with heart transplant. Risk Modifiers Extensive LGE (ie, myocardial fibrosis) occupying 15 percent of LV mass is associated with markers of disease severity and adverse Extensive LGE by contrast-enhanced CMR outcomes including increased risk for SCD and should be considered an important arbitrator to resolving ICD decision-making when uncertain following assessment with established major risk markers. Age at time of SCD risk assessment Risk of SCD is greatest in young patients <30 years old and lessens through mid-life. In patients who have achieved advanced age ( 60 years), risk of SCD is low, even in the presence of other risk factors. Defined as 3 consecutive ventricular beats at >120 beats per minute, lasting less than 30 seconds. Multiple bursts identified on ambulatory monitoring are associated with increased risk, particularly in younger patients. Although the data relating characteristics of NSVT to SCD risk NSVT on ambulatory monitoring remain poorly defined, it would be reasonable to give greater weight to increased SCD risk in those patients with HCM with NSVT that is https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 18/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate frequent (>1 burst), of long duration (>7 beats), or particularly fast (>200 beats per minute). LVEF: left ventricular ejection fraction; CMR: cardiovascular magnetic resonance; NSVT: nonsustained ventricular tachycardia; BP: blood pressure; ICD: implantable cardioverter-defibrillator; LGE: late gadolinium enhancement; LVOT: left ventricular outflow tract obstruction. Graphic 102357 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 19/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Algorithm showing the indications for implantable cardioverter-defibrillator (ICD) placement in patients with hypertrophic cardiomyopathy (HCM) Regardless of the level of recommendation put forth in these guidelines, the decision for placement of an ICD must involve prudent application of individual clinical judgment, thorough discussions of the strength of evidence, the benefits, and the risks (including but not limited to inappropriate discharges, lead and procedural complications) to allow active participation of the fully informed patient in ultimate decision making. ICD: implantable cardioverter-defibrillator; HCM: hypertrophic cardiomyopathy; VT: ventricular tachycardia; SD: sudden death; LV: left ventricular; BP: blood pressure; SCD: sudden cardiac death. SCD risk modifiers include established risk factors and emerging risk modifiers. Reproduced from: Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 20/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Coll Cardiol 2011; 58:e212. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 102271 Version 3.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 21/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Classification of sports based on peak static and dynamic components during competition This classification is based on peak static and dynamic components achieved during competition; however, higher values may be reached during training. The increasing dynamic component is defined in terms of the estimated percentage of maximal oxygen uptake (VO max) achieved and results in an increasing cardiac output. The increasing static component is related to the estimated percentage of maximal voluntary contraction reached and results in an increasing blood pressure load. The lowest total cardiovascular demands (cardiac output and blood pressure) are shown 2 in the palest color, with increasing dynamic load depicted by increasing blue intensity and increasing static load by increasing red intensity. Note the graded transition between categories, which should be individualized on the basis of player position and style of play. Danger of bodily collision (refer to UpToDate content regarding sports according to risk of impact and educational background). https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 22/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Increased risk if syncope occurs. Reproduced from: Levine BD, Baggish AL, Kovacs RJ. Eligibility and disquali cation recommendations for competitive athletes with cardiovascular abnormalities: Task force 1: Classi cation of sports: Dynamic, static, and impact: A scienti c statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2350. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 105651 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 23/24 7/6/23, 1:38 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Contributor Disclosures Martin S Maron, MD Grant/Research/Clinical Trial Support: iRhythm [Hypertrophic cardiomyopathy]. Consultant/Advisory Boards: Cytokinetics [Steering committee, REDWOOD-HCM]; Edgewise Pharmaceuticals [Myosin inhibitor for treatment of symptomatic hypertrophic cardiomyopathy]; Imbria Pharmaceuticals [Hypertrophic cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. William J McKenna, MD Consultant/Advisory Boards: Bristol Meyers Squibb [Novel pharmacological treatments for HCM]; Cytokinetics [Novel pharmacological treatments for HCM]; Health in Code [Genetic testing in inherited cardiac disease]; Tenaya Therapeutics [Gene therapy in cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 24/24 |
7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death : Martin S Maron, MD : Samuel L vy, MD, William J McKenna, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 26, 2020. INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease caused by mutations in one of several sarcomere genes that encode components of the contractile apparatus of the heart. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) HCM is characterized by left ventricular (LV) hypertrophy of various morphologies, with a wide array of clinical manifestations and hemodynamic abnormalities ( figure 1). Depending in part upon the site and extent of cardiac hypertrophy, patients with HCM can develop one or more of the following abnormalities: LV outflow obstruction. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction".) Diastolic and systolic dysfunction. Myocardial ischemia. Mitral regurgitation. These structural and functional abnormalities can produce a variety of symptoms, including: Fatigue Dyspnea Chest pain Palpitations https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 1/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Presyncope or syncope In broad terms, the symptoms related to HCM can be categorized as those related to heart failure (HF), chest pain, or arrhythmias. Patients with HCM are prone to both atrial and ventricular arrhythmias. Many of these arrhythmias are asymptomatic, but some can precipitate hemodynamic collapse and sudden cardiac death (SCD). SCD is a catastrophic and unpredictable complication of HCM and in some patients may be the first presentation of the disease. The assessment of risk for arrhythmic SCD is a critical component of the clinical evaluation of nearly all patients with HCM and will be reviewed here. The management of patients following risk assessment and following a documented ventricular arrhythmia is discussed separately. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".) Other issues related to ventricular arrhythmias and SCD, as well as other clinical manifestations, natural history, diagnosis and evaluation, and treatment of patients with HCM, are discussed separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Natural history and prognosis" and "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction" and "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".) EPIDEMIOLOGY Ventricular arrhythmias are common in patients with HCM and can range from isolated ventricular premature beats (VPBs) to nonsustained ventricular tachycardia (NSVT) to sustained VT and ventricular fibrillation. While the frequency of ventricular arrhythmias is highly variable, clinically documented sustained VT is relatively rare, with the annual incidence of sudden cardiac arrest (SCA) in clinically identified HCM referral populations being approximately 1 percent, with even lower reported rate in HCM patients in the general community [1-5]. The frequency of ventricular tachyarrhythmias detected by ambulatory monitoring in patients with HCM has been evaluated in a variety of studies [1,6-12]. As an example, in a study of 178 patients who underwent 24-hour ambulatory monitoring, VPBs were highly prevalent (seen in 88 percent; 12 percent had 500 VPBs) and NSVT was present in 31 percent [1]. However, there is no evidence to suggest that frequent VPBs are, by themselves, indicative of an increased risk of sustained ventricular arrhythmia. This is similar to other forms of heart disease in which treatment of VPBs alone is warranted only in symptomatic patients. (See "Premature ventricular complexes: Treatment and prognosis".) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 2/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Other studies have shown lower rates of NSVT (typically asymptomatic), with ranges of 15 to 31 percent of patients with HCM [1,6-8]. NSVT is more likely in older patients and is associated with greater LV wall thickening and New York Heart Association (NYHA) class III or IV symptoms ( table 1). Episodes are most frequent during sleep and other periods of heightened vagal tone. The prevalence of NSVT is less common in young patients (<40 years old) with HCM, and therefore when present is of greater predictive value for SCD than when it occurs in older patients. Among one cohort of 428 patients 60 years of age with HCM, the risk of arrhythmic SCD was 0.2 percent per year, lower than the younger HCM population and significantly lower than the risk of non-HCM-related death [13]. PATHOGENESIS OF ARRHYTHMIAS An abnormal myocardial substrate comprised of myocyte disarray ( picture 1), interstitial fibrosis, and replacement fibrosis provides the likely structural nidus for the generation of ventricular arrhythmias in patients with HCM. This substrate can be acted upon by potential triggers and/or modifiers, including myocardial ischemia, LV outflow tract obstruction, and abnormal vascular response with inappropriate vasodilatation, as well as the impact of high adrenergic states (eg, during competitive sports, etc) that can lower the threshold for initiating VT/ventricular fibrillation. CLINICAL MANIFESTATIONS The presentation of ventricular arrhythmias in patients with HCM is highly variable, ranging from an absence of symptoms to palpitations to SCA, but in general the presentation of ventricular arrhythmias is similar to their presentation in other types of patients without HCM. Most patients with ventricular premature beats (VPBs) or nonsustained VT (NSVT) will be asymptomatic or have intermittent palpitations. Sustained VT most often results in palpitations, presyncope, or syncope. SCA, although rare, can be the initial presentation of sustained VT or ventricular fibrillation (VF). More detailed discussions of the presenting symptoms of VPBs, NSVT, sustained VT, and VF are discussed elsewhere. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Symptoms' and "Nonsustained ventricular tachycardia: https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 3/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Clinical manifestations, evaluation, and management", section on 'History and associated symptoms' and "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'History and associated symptoms'.) EVALUATION Since the underlying abnormal myocardial substrate in HCM can evolve over time, nearly all patients with known or suspected HCM should undergo serial evaluations assessing SCD risk every 12 to 24 months, particularly young and middle-aged HCM patients who were previously considered low or intermediate risk, but who still remain eligible for primary prevention implantable cardioverter-defibrillator (ICD) therapy [14]. Such evaluations should include the following (see "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Diagnostic evaluation'): History and physical examination. Interim family history, with emphasis on any relatives with SCD, syncope, or ICD placement, as well as any new diagnoses of HCM. Echocardiography. 24- to 48-hour ambulatory electrocardiographic (ECG) monitoring. Although the benefit of performing longer-term ambulatory monitoring initially to identify nonsustained ventricular tachycardia (NSVT) can be considered, this strategy has not been systematically evaluated. Exercise (stress) echocardiography testing at initial evaluation to assess for symptoms, provoked LV outflow tract (LVOT) obstruction, arrhythmias, myocardial ischemia, and blood pressure (BP) response. Exercise testing is not generally repeated on an annual basis, unless warranted by the presence of new limiting symptoms, for the purpose of evaluating for a provoked LVOT gradient. Cardiac magnetic resonance (CMR) imaging. Our experts have differing approaches to utilizing CMR in HCM, with currently no clear consensus on how to best apply this advanced imaging technique for HCM diagnosis. Some experts proceed with CMR only when diagnosis of HCM remains uncertain following echocardiography while other experts perform CMR in all patients with suspected or diagnosed HCM to most reliably assess LV morphology, including maximal LV wall thickness, as well as to further inform risk https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 4/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate stratification with assessment of extent of late gadolinium enhancement. (See 'Risk stratification' below.) In a patient who has an ICD, tests for the purpose of risk stratification of sudden death (eg, ambulatory monitoring for NSVT and exercise testing to assess BP response) are not typically repeated. RISK STRATIFICATION Patients with HCM have an increased risk of death from several causes, including SCD, HF, and stroke. Established major risk factors and risk modifiers for SCD include: Prior cardiac arrest or sustained ventricular arrhythmias Family history of first-degree or close relative <50 years of age with SCD judged definitely or likely due to HCM Recent syncope suspected to be arrhythmic in origin Massive LV hypertrophy (LVH) 30 mm anywhere in LV wall LV apical aneurysm of any size End-stage HCM with LV ejection fraction (LVEF) <50 percent Risk modifiers include: Late gadolinium enhancement on cardiac magnetic resonance imaging Patient Age Multiple bursts of NSVT on ambulatory monitoring These established risk factors have greatest weight in young and middle age patients, but risk stratification for SCD should still be performed in all patients with HCM, independent of symptoms or hemodynamic status. The risk factors associated with SCD have also been evaluated for their more general association with overall mortality and outcomes. Several society guidelines for HCM as well as ventricular arrhythmias and SCD have outlined the risk factors for SCD in patients with HCM ( figure 2) [3,6,14-18]. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) Prior arrhythmic events Patients with HCM who are at the highest risk of SCD are those with prior SCA or sustained ventricular tachyarrhythmias [14]. In the absence of a clearly identifiable and reversible cause for SCD, such patients do not require additional risk stratification and should undergo implantation of an ICD for secondary prevention of SCD. (See "Hypertrophic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 5/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Implantable cardioverter-defibrillators (ICDs)'.) Established major risk markers Because ventricular arrhythmias can be life-threatening, the ability to identify patients at high risk for SCD due to ventricular arrhythmias is critical among patients with HCM. Retrospective observational cohort studies have demonstrated that the presence of 1 of the major risk factors is associated with an elevated SCD risk, and it is reasonable to consider primary prevention ICD therapy ( table 2) after taking into account the overall clinical profile of the individual patient, including age and the benefits and risks of long- term device therapy. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Implantable cardioverter-defibrillators (ICDs)'.) The major risk factors for SCD that are most commonly cited include the following ( table 3) [3,14-16,19]: Family history of SCD A family history of HCM-related SCD is associated with an increased risk of SCD in other affected family members [20,21]. This risk is particularly high if there are multiple SCD events in one family, and if the events occurred in younger patients [20,21]. In a report of 41 relatives from eight families, 31 (75 percent) died from their heart disease, including 18 before 25 years of age, 23 with SCD, and in 15 of these 23 patients, SCD was the initial manifestation of the disease [21]. Families with multiple sudden deaths under the age of 40 years, however, are uncommon (approximately 5 percent), whereas a single sudden death is seen in up to 25 percent of families, but is of low positive predictive accuracy (<15 percent) [6,22]. Syncope Syncope, if it is not clearly attributable to another cause (eg, neurocardiogenic syncope), is a risk factor for SCD in patients with HCM [6,23]. The predictive power for syncope is greatest when it occurs in relatively close proximity to the clinical evaluation (<6 months) and in young patients. Its predictive strength is significantly less when the event has occurred remote to the time of visit and/or it has occurred in older patients [23]. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".) Massive LVH LV wall thickness 30 mm is seen in approximately 10 percent of patients with HCM and is associated in the majority of studies with an increased risk of SCD, particularly in patients less than 30 years of age [24-28]. The positive predictive value of massive LVH, however, is relatively low [24,25], although expert opinion would support strong consideration for ICD if massive LVH is confirmed, particularly in young patients [26]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 6/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Both echocardiography and cardiac magnetic resonance (CMR) imaging are used in clinical practice to determine maximal wall thickness [29]. One report from a large HCM referral center suggested a discrepancy between echocardiography and CMR imaging in the classification of massive LVH in 70 percent of patients (44 of 63 patients), with massive LVH identified more commonly on CMR (83 versus 48 percent) [30]. However, the data pertaining to increased sudden death risk in patients with HCM and massive LVH are derived from echocardiographic studies. For this reason, we recommend that if massive LVH ( 30 mm) is identified by echocardiography, using reliable measurements, the patients should be considered high risk with consideration of primary prevention ICD therapy. In patients with echo-derived measurements that are <30 mm but in whom CMR demonstrates massive LVH (echocardiography underestimated wall thickness), it would be reasonable to consider an increased risk for SCD as well, with consideration given to placement of an ICD for primary prevention. The relation of massive LVH and sudden death has been highlighted in a number of studies: In a single-center referral population of 1766 patients with HCM, including 92 with massive LVH, who were initially seen between 2004 and 2015 and followed for an average of 5.3 years, SCD events were significantly more common in patients with massive LVH (3 versus 0.8 percent per year) [31]. In a study of 480 patients, including 43 with massive LVH, who were followed for a mean of 6.5 years, the risk of SCD was zero for a wall thickness 15 mm, compared with 1.8 percent per year for a wall thickness 30 mm; the incidence of SCD almost doubled for each 5 mm increase in wall thickness ( figure 3) [24]. The cumulative risk 20 years after the initial diagnosis was close to 0 for those with a thickness 19 mm, compared with 40 percent for a wall thickness 30 mm. In a similar study of 630 patients, maximal wall thickness 30 mm was associated with sudden death, but only in the cohort who had an additional risk factor (ie, adverse family history, NSVT on Holter, syncope, or abnormal BP response on exercise) [25]. LV apical aneurysm Patients with HCM who have an LV apical aneurysm include a cohort in whom the risk of life-threatening arrhythmia appears increased [29,32,33]. Patients with HCM and LV apical aneurysm constitute a small number of patients, with outcome data supported by a small number of observational studies. Therefore, decisions regarding high-risk status should be considered on an individual basis, taking into consideration the entire clinical profile of the patient. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 7/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Thin-walled apical aneurysms are almost always associated with transmural scar (ie, apical late gadolinium enhancement [LGE]), which represent a structural nidus for the generation of sustained monomorphic VT. Apical aneurysms most notably occur in association with midventricular hypertrophy, which often produces mid-cavitary obstruction resulting in high apical systolic pressures, which likely promotes the adverse LV remodeling that ultimately develops into a thin-walled scarred akinetic apex. Patients with apical aneurysms often come to medical attention because of the dramatically abnormal ECG with precordial ST segment elevation and giant T wave inversions, most notably in leads V3 and V4, a similar ECG pattern to HCM patients with only hypertrophy at the apex (without aneurysm). This phenotype is distinct from HCM patients with increased wall thickness confined to the apex, without associated wall thinning (ie, apical HCM). (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction", section on 'Apical HCM'.) Among a cohort of 1940 consecutive patients with HCM seen at one of two high-volume referral centers and who underwent echocardiography with LV opacification and/or CMR, 93 patients (4.8 percent) were found to have an LV apical aneurysm [33]. Of the 54 patients who received an ICD for primary prevention, 18 patients (33 percent) experienced a life- threatening ventricular arrhythmia requiring ICD intervention, resulting in an arrhythmic event rate of 4.7 percent per year (compared with 0.9 percent per year in the patients without an LV apical aneurysm), with no difference in the risk of SCD based on the size of the aneurysm. In contrast to the general population of patients with HCM without an apical aneurysm, risk of SCD persists into the seventh decade of life (and beyond) among patients with HCM and LV apical aneurysm. In one cohort of 118 such patients, 36 percent of SCD (and aborted SCD) events occurred in patients 60 years of age [34]. In addition, patients with HCM with apical aneurysm represent the only subgroup of patients with HCM in whom radiofrequency ablation appears successful at treating life- threatening recurrent VT. In this series, recurrent VT requiring 2 ICD shocks occurred in 13 patients, of which six underwent radiofrequency ablation with no recurrence of VT. Of note, the high-risk phenotype of HCM with apical aneurysm stands in contrast to apical HCM patients who, in the absence of any of the conventional sudden death risk factors, are in fact at low risk for experiencing life-threatening VT/VF. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction", section on 'Apical HCM' and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Implantable cardioverter- defibrillators (ICDs)' and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Catheter ablation'.) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 8/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate End-stage with LVEF <50 percent A small proportion of patients with HCM (<5 percent) eventually progress to a stage of disease associated with adverse LV remodeling with reduced systolic performance (LVEF <50 percent). This phase has been termed "end-stage" or "burned out" HCM. Once end-stage HCM develops, further deterioration is progressive in a subset of patients, with death from progressive HF, SCD, or the need for heart transplantation. With conventional cardiovascular therapies, some end-stage patients can experience a relatively benign course in which HF symptoms can remain stable over many years. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'HCM with LV systolic dysfunction (ejection fraction <50 percent)'.) Risk modifiers Several other factors contribute to the overall SCD risk profile of patients with HCM: LGE on CMR imaging LGE on CMR imaging is common in HCM and appears to represent the structural nidus for ventricular tachyarrhythmias in patients with HCM with myocardial fibrosis [35,36]. The presence and extent of LGE is associated with markers of disease severity, including the magnitude of LVH and the presence of nonsustained ventricular arrhythmias. How best to integrate LGE in HCM management strategies remains controversial, even among HCM experts. However, based on the totality of data evaluating LGE and outcomes in HCM, we suggest considering the results of contrast-enhanced CMR with LGE in assessing risk of SCD to provide a more complete evaluation of patients who may benefit from primary prevention ICD therapy. More data to inform this management issue will also be forthcoming following the completion of a Nation Institutes of Health (NIH)-funded study, Novel Markers of Prognosis in Hypertrophic Cardiomyopathy (HCMR), involving 40 centers and more than 2500 patients, anticipated to be completed over the next seven years [37]. In addition, there are a number of methods that have been used to quantify LGE in HCM, but there is no expert consensus on which technique should be universally employed in clinical practice. The lack of standardization with respect to the preferred strategy for quantification of LGE in HCM represents a challenge. The two most commonly employed methods to identify high-signal intensity LGE pixels in the LV wall include applying a grayscale threshold several standard deviations (five or six) above mean signal intensity within a region of "nulled" myocardium and the full-width at half maximum method. Both of these techniques are highly reproducible and reliably represent total fibrosis burden as demonstrated by histopathologic analysis of ventricular septal tissue removed in HCM patients undergoing surgical myectomy [38]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 9/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate In patients without any of the conventional SCD risk markers, the presence of extensive LGE on CMR may identify high-risk status and prompt consideration for primary prevention ICD therapy. In patients with HCM in whom risk assessment remains ambiguous or uncertain after assessment with the conventional risk factors, extensive LGE can be utilized as a potential arbitrator to help resolve difficult ICD decision-making, with extensive LGE swaying decision-making potentially toward ICD, and no (or minimal) LGE swaying decision-making potentially away from an ICD. The absolute amount of LGE is highly predictive of SCD. However, the pattern of LGE is more variable, with the only consistent LGE pattern observed in HCM being LGE confined to the right ventricular insertion point area, where it has been shown not to be associated with increased risk for SCD. Of note, decisions regarding device therapy in both of these clinical scenarios should be made in the context of a fully informed patient, taking into account the desires and wishes of the patient in a shared decision-making manner. In a cohort of 1293 patients with HCM who underwent CMR and were followed for a median of 3.3 years, LGE was present in 548 patients (42 percent), and the primary end point of SCD events (including SCD and appropriate ICD shocks for documented VT or VF) occurred in 37 patients (3 percent) [39]. Risk of SCD events increased with the amount of LGE present (adjusted hazard ratio 1.46 for each 10 percent increase in LGE, 95% CI 1.12-1.92), particularly among patients with apparent low risk based on the traditional clinical features. In addition, the absence of LGE was associated with lower risk and a source of reassurance for patients. In a 2018 cohort study from a single, high-volume referral center, which included 1423 adult patients (age 18 years) who underwent CMR between 2008 and 2015, 706 patients (50 percent) had LGE identified on CMR imaging [40]. LGE involving 15 percent of the myocardium was associated with a significantly greater risk of SCD or appropriate ICD therapy. In a 2016 meta-analysis, which included 2993 patients from five cohorts, the presence of LGE on CMR imaging was associated with significantly greater risk for total mortality (OR 1.8, 95% CI 1.2-2.7), cardiovascular mortality (OR 2.9, 95% CI 1.5-5.6), and SCD (OR 3.4, 95% CI 2.0-5.9) [41]. For every additional 10 percent of the myocardium affected by LGE, there was an incremental increase in total mortality of approximately 30 percent, with an incremental increase of nearly 60 percent in cardiovascular mortality, SCD, and https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 10/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate HF death. Patients with LGE have also been shown to be more likely to have SCD or aborted SCD with an ICD shock [42]. Age at time of SCD risk assessment Risk of SCD is greatest in young patients with HCM (<30 years of age), and this risk decreases but is not eliminated through mid-life [20]. Patients with HCM who are >60 years of age are at a very low risk for any HCM-related adverse events, including SCD [13]. Indeed, risk of SCD in older patients is very low (<1 percent), even among those patients with one or more of the conventional risk factors [13,43,44]. Conversely, the presence of the major risk factors is of greater prognostic significance in young and middle-aged patients with HCM. The impact of age at HCM diagnosis on overall mortality risk (ie, in addition to SCD) is discussed separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Age at diagnosis'.) NSVT The presence of multiple asymptomatic runs of NSVT (most commonly defined as 3 beats at >120 beats per minute) is associated with an increased risk for SCD in patients with HCM, although the effect of a patient's age plays a role in the associated risk [8-11,45]. Multiple bursts of NSVT are associated with increased risk, particularly in young patients and in patients with symptoms of impaired consciousness [1,7-10,46,47]. Although the data for relating characteristics of NSVT to SCD risk are scant, it would be reasonable to give greater weight to increased risk of SCD in patients with HCM with NSVT that is frequent, prolonged, and particularly fast, while a single, slow, short burst of NSVT on ambulatory monitoring is itself not associated with increased risk of future life-threatening VT/ventricular fibrillation (VF), and in the absence of any other conventional risk factors does not form the basis for primary prevention ICD. For patients with HCM and an ICD, NSVT is associated with an increased risk of appropriate ICD therapies for VT/VF [48]. In a study of 178 adult patients with HCM aged 20 to 50 years who underwent 24-hour ambulatory ECG monitoring and were followed for an average of 5.5 years, NSVT was common (31 percent), with a relatively low annual sudden death rate (1.1 percent). In this cohort of older patients, there was a smaller increase in risk with NSVT (1.6 versus 0.9 percent per year in patients with and without NSVT, defined as 3 beats at 120 beats per minute) [1]. In a series of 531 patients with HCM, of whom 104 had NSVT, the presence of NSVT was associated with an increased risk of SCD in patients less than 30 years of age (odds ratio [OR] 4.4 compared with no NSVT, 95% CI 1.5-12.3) [8]. There was, however, no relation among duration, frequency, or rate of NSVT episodes and prognosis at any age. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 11/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Uncertain risk modifiers Several other clinical factors contribute in an uncertain way to the overall SCD risk profile of patients with HCM: Myocardial ischemia There are conflicting data as to whether myocardial ischemia is a risk factor for SCD in patients with HCM. In a series of 23 young patients with HCM (age 6 to 23 years), ischemia was associated with a history of cardiac arrest or syncope [49]. In contrast, there was no relation between the presence of ischemia and outcomes in a larger prospective series of 216 unselected patients with HCM [50]. The relationship between ischemia and outcomes is likely dependent upon both the age of the patient and the etiology of ischemia (eg, severe small vessel-mediated ischemia versus atherosclerotic obstructive coronary artery disease [CAD]). Patients with HCM and coincident CAD have mortality rates that exceed those of CAD patients with normal LV function [51]. The impact of stress-induced ischemia on overall mortality risk (ie, in addition to SCD) is presented separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) Genotype There appear to be high-risk genotypes for SCD, particularly related to troponin T disease and several of the beta myosin-heavy chain mutations [52]. However, the available data are derived from a small number of families and may be skewed on this basis [14,16]. Moreover, most mutations are novel (ie, "private mutations"), and thus a certain genotype may be associated with higher risk in a specific family but would not be associated with the same consequences in other unrelated patients and families. For this reason, clinical decisions about risk for sudden death and need for primary prevention ICD are not made based on the results of genetic testing. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) LV outflow tract (LVOT) gradient The majority of natural history studies involving patients with HCM have failed to show an association between LVOT gradient and adverse prognosis [20,44,46,47,53]. Two large studies, however, have shown a weak association of LVOT gradients with overall disease-related mortality and sudden death [54,55]. The impact of LVOT obstruction on overall morbidity (ie, HF symptoms and risk for atrial fibrillation) is discussed separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) In a multicenter, multinational study of 1101 patients (273 [25 percent] with resting LVOT gradient 30 mmHg) followed for a mean of six years, the probability of HCM- related death and of SCD was slightly greater in those with LVOT gradient of at least 30 mmHg (relative risk [RR] 2) [55]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 12/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate In a single-center study of 917 patients (288 [31 percent] with resting LVOT gradient 30 mmHg) followed for a median of 61 months, survival free from mortality/transplant was significantly lower in patients with LVOT gradients (87 versus 90 percent), as was survival free from sudden death/ICD discharge (91 versus 96 percent) [54]. LVOT obstruction was independently associated with SCD, and there was a significant trend towards lower sudden death/ICD survival in patients with increasing LVOT obstruction. The incidence of SCD in patients with obstruction also varies substantially based upon the number of additional risk factors ( figure 4) [54]. For patients with an outflow gradient 30 mmHg but no additional risk factors, the annual incidence of SCD or ICD discharge was low. There are also a number of practical limitations to using LVOT gradient as a clinical risk factor for sudden death. Gradients are present in large numbers of patients, which would ultimately lead to significant overtreatment with ICDs in this disease. Additionally, gradients can be abolished and/or significantly mitigated with drugs or invasive septal reduction therapy. Nonrandomized retrospective cohort studies suggest that risk of SCD or appropriate ICD shocks is very low following septal myectomy [56,57]. However, surgical myectomy in asymptomatic or mildly symptomatic patients is not indicated solely as a therapy to decrease sudden death risk. In contrast, septal ablation has not been demonstrated to reduce SCD or ICD discharge rates. However, for those patients in whom risk remains ambiguous after assessment with the conventional sudden death risk factors, the presence of a high LVOT gradient can be used as a potential arbitrator to help resolve difficult ICD decision-making. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Nonpharmacologic treatment of LV outflow tract obstruction'.) Impact of number of risk factors It is reasonable to consider ICD in patients with one major risk factor, since SCD risk is increased. Decisions about high-risk status in patients with one risk factor should be individualized based on the strength of the specific risk factor and the individual patient situation. The presence of two or more risk factors for SCD is associated with even greater SCD risk. In patients in whom sudden death risk remains uncertain after assessment with the major risk markers or who are uncertain about pursuing ICD therapy, the presence of a risk modifier may be associated with additional sudden death risk and therefore may help resolve ICD decision-making. Identification of high-risk patients may be improved by using multiple factors [6,54,58,59]. In a study of 368 patients (mean age 37 years) who were followed for a mean of 3.6 years, estimated https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 13/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate six-year SCD-free survival was associated with the number of risk factors ( figure 5) [6]: Zero risk factors (55 percent of the cohort) 95 percent survival One risk factor (33 percent of the cohort) 93 percent survival Two or three risk factors (12 percent of the cohort) 72 percent survival Data from a multicenter registry of ICDs in patients with HCM published in 2007 suggested that a single risk factor may be sufficient justification for consideration of ICD implantation [60]. Subsequently, in a 2019 single-center study of 2094 consecutive patients evaluated over a 17- year period at a tertiary HCM referral center, 527 patients were implanted with a primary prevention ICD based on clinical evaluation and the presence of one or more high-risk markers [61]. Cumulative five-year likelihood of appropriate ICD intervention was 10.5 percent, with 82 primary prevention ICD recipients (15.6 percent) experiencing VT or VF requiring ICD therapy, whereas only five patients (0.3 percent) without an ICD experienced SCD (including two patients in whom primary prevention ICD was declined by the patient). Data in low-risk patients are limited, but those meeting the following profile probably have an incidence of SCD of <0.5 percent per year [14,16,62]: None of the five major risk factors No or only mild symptoms of HF Left atrium 45 mm LV wall thickness <20 mm LV outflow gradient <50 mmHg Risk prediction model While the risk of SCD in patients with HCM can be estimated from large populations, individualized risk prediction offers the hope of the most accurate risk assessment and appropriate interventions. Given the complexity of SCD risk assessment in patients with HCM and the mixed data on the HCM Risk-SCD calculator, we feel that additional studies are warranted to further validate and refine this risk model in other HCM populations, along with the need for additional comparisons with the current United States guideline-based approach using a number of noninvasive risk markers [63,64]. As with risk prediction in any situation, the ability to discriminate patients with HCM at risk of SCD has been most successful in patients deemed at higher risk. In a retrospective cohort study involving 3675 patients from six European centers (2082 in the development cohort and 1593 in the validation cohort) with a median follow-up of 5.7 years, the primary outcome of SCD or appropriate ICD shock occurred in 198 patients (118 patients with SCD, 27 with aborted SCD, and 53 with appropriate ICD shock) [65]. Using the derived model (which incorporated parameters of age, maximal LV wall thickness, left atrial diameter, LVOT https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 14/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate gradient, family history of SCD, NSVT, and unexplained syncope), which can be accessed online, investigators predicted that for every 16 ICDs implanted, one patient would be saved from SCD every five years. Subsequent studies looking at validation of the HCM Risk-SCD calculator have reported widely varying results in terms of the accuracy of the score for predicting SCD [66-69]. In the largest reported validation cohort (International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy [EVIDENCE-HCM] cohort), which included 2147 patients with |
reason, clinical decisions about risk for sudden death and need for primary prevention ICD are not made based on the results of genetic testing. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) LV outflow tract (LVOT) gradient The majority of natural history studies involving patients with HCM have failed to show an association between LVOT gradient and adverse prognosis [20,44,46,47,53]. Two large studies, however, have shown a weak association of LVOT gradients with overall disease-related mortality and sudden death [54,55]. The impact of LVOT obstruction on overall morbidity (ie, HF symptoms and risk for atrial fibrillation) is discussed separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) In a multicenter, multinational study of 1101 patients (273 [25 percent] with resting LVOT gradient 30 mmHg) followed for a mean of six years, the probability of HCM- related death and of SCD was slightly greater in those with LVOT gradient of at least 30 mmHg (relative risk [RR] 2) [55]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 12/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate In a single-center study of 917 patients (288 [31 percent] with resting LVOT gradient 30 mmHg) followed for a median of 61 months, survival free from mortality/transplant was significantly lower in patients with LVOT gradients (87 versus 90 percent), as was survival free from sudden death/ICD discharge (91 versus 96 percent) [54]. LVOT obstruction was independently associated with SCD, and there was a significant trend towards lower sudden death/ICD survival in patients with increasing LVOT obstruction. The incidence of SCD in patients with obstruction also varies substantially based upon the number of additional risk factors ( figure 4) [54]. For patients with an outflow gradient 30 mmHg but no additional risk factors, the annual incidence of SCD or ICD discharge was low. There are also a number of practical limitations to using LVOT gradient as a clinical risk factor for sudden death. Gradients are present in large numbers of patients, which would ultimately lead to significant overtreatment with ICDs in this disease. Additionally, gradients can be abolished and/or significantly mitigated with drugs or invasive septal reduction therapy. Nonrandomized retrospective cohort studies suggest that risk of SCD or appropriate ICD shocks is very low following septal myectomy [56,57]. However, surgical myectomy in asymptomatic or mildly symptomatic patients is not indicated solely as a therapy to decrease sudden death risk. In contrast, septal ablation has not been demonstrated to reduce SCD or ICD discharge rates. However, for those patients in whom risk remains ambiguous after assessment with the conventional sudden death risk factors, the presence of a high LVOT gradient can be used as a potential arbitrator to help resolve difficult ICD decision-making. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Nonpharmacologic treatment of LV outflow tract obstruction'.) Impact of number of risk factors It is reasonable to consider ICD in patients with one major risk factor, since SCD risk is increased. Decisions about high-risk status in patients with one risk factor should be individualized based on the strength of the specific risk factor and the individual patient situation. The presence of two or more risk factors for SCD is associated with even greater SCD risk. In patients in whom sudden death risk remains uncertain after assessment with the major risk markers or who are uncertain about pursuing ICD therapy, the presence of a risk modifier may be associated with additional sudden death risk and therefore may help resolve ICD decision-making. Identification of high-risk patients may be improved by using multiple factors [6,54,58,59]. In a study of 368 patients (mean age 37 years) who were followed for a mean of 3.6 years, estimated https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 13/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate six-year SCD-free survival was associated with the number of risk factors ( figure 5) [6]: Zero risk factors (55 percent of the cohort) 95 percent survival One risk factor (33 percent of the cohort) 93 percent survival Two or three risk factors (12 percent of the cohort) 72 percent survival Data from a multicenter registry of ICDs in patients with HCM published in 2007 suggested that a single risk factor may be sufficient justification for consideration of ICD implantation [60]. Subsequently, in a 2019 single-center study of 2094 consecutive patients evaluated over a 17- year period at a tertiary HCM referral center, 527 patients were implanted with a primary prevention ICD based on clinical evaluation and the presence of one or more high-risk markers [61]. Cumulative five-year likelihood of appropriate ICD intervention was 10.5 percent, with 82 primary prevention ICD recipients (15.6 percent) experiencing VT or VF requiring ICD therapy, whereas only five patients (0.3 percent) without an ICD experienced SCD (including two patients in whom primary prevention ICD was declined by the patient). Data in low-risk patients are limited, but those meeting the following profile probably have an incidence of SCD of <0.5 percent per year [14,16,62]: None of the five major risk factors No or only mild symptoms of HF Left atrium 45 mm LV wall thickness <20 mm LV outflow gradient <50 mmHg Risk prediction model While the risk of SCD in patients with HCM can be estimated from large populations, individualized risk prediction offers the hope of the most accurate risk assessment and appropriate interventions. Given the complexity of SCD risk assessment in patients with HCM and the mixed data on the HCM Risk-SCD calculator, we feel that additional studies are warranted to further validate and refine this risk model in other HCM populations, along with the need for additional comparisons with the current United States guideline-based approach using a number of noninvasive risk markers [63,64]. As with risk prediction in any situation, the ability to discriminate patients with HCM at risk of SCD has been most successful in patients deemed at higher risk. In a retrospective cohort study involving 3675 patients from six European centers (2082 in the development cohort and 1593 in the validation cohort) with a median follow-up of 5.7 years, the primary outcome of SCD or appropriate ICD shock occurred in 198 patients (118 patients with SCD, 27 with aborted SCD, and 53 with appropriate ICD shock) [65]. Using the derived model (which incorporated parameters of age, maximal LV wall thickness, left atrial diameter, LVOT https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 14/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate gradient, family history of SCD, NSVT, and unexplained syncope), which can be accessed online, investigators predicted that for every 16 ICDs implanted, one patient would be saved from SCD every five years. Subsequent studies looking at validation of the HCM Risk-SCD calculator have reported widely varying results in terms of the accuracy of the score for predicting SCD [66-69]. In the largest reported validation cohort (International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy [EVIDENCE-HCM] cohort), which included 2147 patients with HCM and no prior history of SCD from 14 centers in the United States, Europe, the Middle East, and Asia, 44 patients experienced an SCD event (defined as SCD, successful resuscitation from SCA, or appropriate ICD intervention for VT/VF) over the five-year follow- up (0.5 percent per year) [70]. Among patients with high predicted risk ( 6 percent, n = 297), the five-year incidence of SCD was significantly higher (8.9 percent) compared with patients with intermediate (4 to 6 percent, n = 326) or low (<4 percent, n = 1524) predicted risk (five-year incidence 1.8 and 1.4 percent, respectively). In a cohort of 706 patients with HCM and no prior history of SCD who were seen at two European referral centers, 42 patients (5.9 percent) experienced an SCD event (defined as SCD, successful resuscitation from SCA, or appropriate ICD intervention for VT/VF) over the five-year follow-up (1.2 percent per year) [66]. Patients with an SCD event had significantly greater estimated five-year risk of SCD using the HCM Risk-SCD calculator (4.9 versus 2.8 percent in patients without SCD), with the calculator resulting in improved risk assessment compared with 2003 and 2011 society guidelines. The HCM Risk-SCD calculator has also been retrospectively applied to a cohort of 2094 patients with HCM seen at a large United States referral center [61]. The HCM Risk-SCD calculator accurately predicted patients at low risk without SCD events (92 percent specificity), but the sensitivity of a high-risk classification was only 34 percent for predicting SCD events, suggesting that the majority of patients at risk for SCD would have been missed using only the calculator to quantify risk. In contrast, the enhanced 2011 ACC/AHA guideline criteria had sensitivity and specificity of 87 and 78 percent, respectively, suggesting greater likelihood of preventing SCD with an ICD at the expense of slightly higher use of ICDs in patients without SCD events. The HCM Risk-SCD model and the conventional risk factors from the American College of Cardiology/American Heart Association (ACC/AHA) guidelines were compared in a cohort of 288 patients (mean age 52 years, 66 percent male, 25 percent with LVOT obstruction 30 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 15/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate mmHg) with HCM from a single referral center in the United Kingdom, among whom 14 patients experienced SCD or equivalent (resuscitation from cardiac arrest or appropriate ICD shock for VF or VT >200 beats per minute) over a mean follow-up of 5.6 years [71]. Compared with the conventional ACC/AHA risk factors, the HCM Risk-SCD model more accurately predicted low-risk patients who did not require an ICD (220 of 274 patients [82 percent] compared with 157 of 274 patients [57 percent]) but also failed to identify a significantly greater number of high-risk patients who experienced SCD or equivalent (6 of 14 patients [43 percent] compared with 1 of 14 patients [7 percent]). The presence of LGE identified on CMR may aid in further risk stratifying patients following calculation of the HCM Risk-SCD score. Among 354 patients with HCM and calculated HCM Risk SCD score suggesting low to intermediate five-year risk (<6 percent), patients with LGE extent 10 percent had much higher five-year rates of hard cardiac events including SCD, resuscitated cardiac arrest, appropriate ICD therapies, and sustained VT (23 versus 3 percent) [72]. (See 'Risk modifiers' above.) In a 2019 meta-analysis which included 7291 patients with HCM (including the original HCM Risk- SCD cohort and five subsequent cohorts), 70 percent of patients were identified as low risk, 15 percent as intermediate risk, and 15 percent as high risk [73]. In total, 184 SCD events occurred, with 68 percent occurring in the intermediate and high risk (prevalence of SCD events 1, 2.4, and 8.4 percent in low, intermediate, and high risk groups, respectively). The majority of patients with HCM are stratified as low risk for SCD, but the greatest number of appropriate ICD therapies occur in this low-risk group. Conversely, patients identified as being at high risk of SCD are more likely to receive an appropriate ICD shock, but overall this group receives the lowest number of appropriate ICD therapies. However, proportionally, since the denominator is much larger in low-risk patients, the percentage of patients with ICD shocks is greatest in the high-risk group. This essentially means that, similar to other risk prediction scenarios, the risk score discriminates best those patients with HCM at highest risk for sudden death, but may fail to identify a significant number of patients who have low-risk scores but who are at high risk for sudden death. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 16/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Hypertrophic cardiomyopathy in adults (The Basics)") Beyond the Basics topic (see "Patient education: Hypertrophic cardiomyopathy (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Patients with hypertrophic cardiomyopathy (HCM) are prone to ventricular arrhythmias. Ventricular arrhythmias can range from isolated ventricular premature beats (VPBs) to nonsustained ventricular tachycardia (NSVT) to sustained VT and ventricular fibrillation (VF). While the frequency of ventricular arrhythmias is highly variable, the annual incidence of sudden cardiac death (SCD) in the clinically identified general HCM patient population is approximately 1 percent. (See 'Introduction' above and 'Epidemiology' above.) The presentation of ventricular arrhythmias in patients with HCM is highly variable, ranging from an absence of symptoms to palpitations to SCD. Most patients with VPBs or NSVT will be asymptomatic or have intermittent palpitations, while on rare occasions SCD can be the initial presentation of sustained VT or VF. (See 'Clinical manifestations' above.) Since the underlying abnormal myocardial substrate in HCM can evolve over time, all patients with known or suspected HCM should undergo serial evaluations for SCD risk stratification, including history and physical examination, interim family history, echocardiography, ambulatory electrocardiographic (ECG) monitoring, and exercise testing (on a case-by-case basis). With the emerging role of extensive late gadolinium https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 17/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate enhancement (LGE) informing risk assessment, contrast-enhanced cardiac magnetic resonance (CMR) should also be considered. It is reasonable to repeat SCD risk assessment every 12 to 24 months in patients who remain at risk and potentially eligible for an implantable cardioverter-defibrillator (ICD) for primary prevention of SCD. (See 'Evaluation' above.) Major risk factors and risk modifiers associated with an increased risk of SCD in patients with HCM include (see 'Risk stratification' above): Prior or sustained ventricular arrhythmias. Family history of close relative with SCD due to HCM. Syncope suspected to be arrhythmic in origin, particularly when occurring relatively recently to time of evaluation and in younger patients. Multiple bursts of NSVT on ambulatory ECG monitoring. Massive LV hypertrophy 30 mm anywhere in LV wall. LV apical aneurysm. End-stage HCM with LV ejection fraction <50 percent. The results of contrast-enhanced CMR with extensive LGE (ie, myocardial scarring) can be used to help arbitrate ICD decision-making if risk remains ambiguous or uncertain following conventional risk stratification assessment. Age at time of sudden death risk assessment ACKNOWLEDGMENT The editorial staff at UpToDate acknowledges Perry Elliott, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Adabag AS, Casey SA, Kuskowski MA, et al. Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy. J Am https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 18/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Coll Cardiol 2005; 45:697. 2. Elliott PM, Gimeno JR, Thaman R, et al. Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy. Heart 2006; 92:785. 3. Elliott P, McKenna WJ. Hypertrophic cardiomyopathy. Lancet 2004; 363:1881. 4. Maron BJ. Clinical Course and Management of Hypertrophic Cardiomyopathy. N Engl J Med 2018; 379:655. 5. Weissler-Snir A, Allan K, Cunningham K, et al. Hypertrophic Cardiomyopathy-Related Sudden Cardiac Death in Young People in Ontario. Circulation 2019; 140:1706. 6. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36:2212. 7. Cecchi F, Olivotto I, Montereggi A, et al. Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population. Heart 1998; 79:331. 8. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. J Am Coll Cardiol 2003; 42:873. 9. Fananapazir L, Chang AC, Epstein SE, McAreavey D. Prognostic determinants in hypertrophic cardiomyopathy. Prospective evaluation of a therapeutic strategy based on clinical, Holter, hemodynamic, and electrophysiological findings. Circulation 1992; 86:730. 10. Spirito P, Rapezzi C, Autore C, et al. Prognosis of asymptomatic patients with hypertrophic cardiomyopathy and nonsustained ventricular tachycardia. Circulation 1994; 90:2743. 11. Maron BJ, Savage DD, Wolfson JK, Epstein SE. Prognostic significance of 24 hour ambulatory electrocardiographic monitoring in patients with hypertrophic cardiomyopathy: a prospective study. Am J Cardiol 1981; 48:252. 12. McKenna WJ, England D, Doi YL, et al. Arrhythmia in hypertrophic cardiomyopathy. I: Influence on prognosis. Br Heart J 1981; 46:168. 13. Maron BJ, Rowin EJ, Casey SA, et al. Risk stratification and outcome of patients with hypertrophic cardiomyopathy >=60 years of age. Circulation 2013; 127:585. 14. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124:e783. 15. Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ 2006; 332:1251. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 19/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate 16. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287:1308. 17. Veselka J, Anavekar NS, Charron P. Hypertrophic obstructive cardiomyopathy. Lancet 2017; 389:1253. 18. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 19. Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35:2733. 20. McKenna W, Deanfield J, Faruqui A, et al. Prognosis in hypertrophic cardiomyopathy: role of age and clinical, electrocardiographic and hemodynamic features. Am J Cardiol 1981; 47:532. 21. Maron BJ, Lipson LC, Roberts WC, et al. "Malignant" hypertrophic cardiomyopathy: identification of a subgroup of families with unusually frequent premature death. Am J Cardiol 1978; 41:1133. 22. McKenna WJ, Behr ER. Hypertrophic cardiomyopathy: management, risk stratification, and prevention of sudden death. Heart 2002; 87:169. 23. Priori SG, Aliot E, Blomstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22:1374. 24. Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000; 342:1778. 25. Elliott PM, Gimeno Blanes JR, Mahon NG, et al. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 2001; 357:420. 26. Sorajja P, Nishimura RA, Ommen SR, et al. Use of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy. J Am Soc Echocardiogr 2006; 19:788. 27. Olivotto I, Gistri R, Petrone P, et al. Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2003; 41:315. 28. O'Mahony C, Jichi F, Monserrat L, et al. Inverted U-Shaped Relation Between the Risk of Sudden Cardiac Death and Maximal Left Ventricular Wall Thickness in Hypertrophic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 20/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Cardiomyopathy. Circ Arrhythm Electrophysiol 2016; 9. 29. Tower-Rader A, Kramer CM, Neubauer S, et al. Multimodality Imaging in Hypertrophic Cardiomyopathy for Risk Stratification. Circ Cardiovasc Imaging 2020; 13:e009026. 30. Bois JP, Geske JB, Foley TA, et al. Comparison of Maximal Wall Thickness in Hypertrophic Cardiomyopathy Differs Between Magnetic Resonance Imaging and Transthoracic Echocardiography. Am J Cardiol 2017; 119:643. 31. Rowin EJ, Maron BJ, Romashko M, et al. Impact of Effective Management Strategies on Patients With the Most Extreme Phenotypic Expression of Hypertrophic Cardiomyopathy. Am J Cardiol 2019; 124:113. 32. Maron MS, Finley JJ, Bos JM, et al. Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy. Circulation 2008; 118:1541. 33. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management. J Am Coll Cardiol 2017; 69:761. 34. Rowin EJ, Maron BJ, Chokshi A, Maron MS. Left ventricular apical aneurysm in hypertrophic cardiomyopathy as a risk factor for sudden death at any age. Pacing Clin Electrophysiol 2018. 35. Maron BJ, Maron MS, Lesser JR, et al. Sudden cardiac arrest in hypertrophic cardiomyopathy in the absence of conventional criteria for high risk status. Am J Cardiol 2008; 101:544. 36. Weissler-Snir A, Hindieh W, Spears DA, et al. The relationship between the quantitative extent of late gadolinium enhancement and burden of nonsustained ventricular tachycardia in hypertrophic cardiomyopathy: A delayed contrast-enhanced magnetic resonance study. J Cardiovasc Electrophysiol 2019; 30:651. 37. Kramer CM, Neubauer S. Further Refining Risk in Hypertrophic Cardiomyopathy With Late Gadolinium Enhancement by CMR. J Am Coll Cardiol 2018; 72:871. 38. Moravsky G, Ofek E, Rakowski H, et al. Myocardial fibrosis in hypertrophic cardiomyopathy: accurate reflection of histopathological findings by CMR. JACC Cardiovasc Imaging 2013; 6:587. 39. Chan RH, Maron BJ, Olivotto I, et al. Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 2014; 130:484. 40. Mentias A, Raeisi-Giglou P, Smedira NG, et al. Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Preserved Systolic Function. J Am Coll Cardiol 2018; 72:857. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 21/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate 41. Weng Z, Yao J, Chan RH, et al. Prognostic Value of LGE-CMR in HCM: A Meta-Analysis. JACC Cardiovasc Imaging 2016; 9:1392. 42. Briasoulis A, Mallikethi-Reddy S, Palla M, et al. Myocardial fibrosis on cardiac magnetic resonance and cardiac outcomes in hypertrophic cardiomyopathy: a meta-analysis. Heart 2015; 101:1406. 43. Maron BJ, Ackerman MJ, Nishimura RA, et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol 2005; 45:1340. 44. McKenna WJ, Camm AJ. Sudden death in hypertrophic cardiomyopathy. Assessment of patients at high risk. Circulation 1989; 80:1489. 45. Yetman AT, Hamilton RM, Benson LN, McCrindle BW. Long-term outcome and prognostic determinants in children with hypertrophic cardiomyopathy. J Am Coll Cardiol 1998; 32:1943. 46. Cecchi F, Olivotto I, Montereggi A, et al. Hypertrophic cardiomyopathy in Tuscany: clinical course and outcome in an unselected regional population. J Am Coll Cardiol 1995; 26:1529. 47. Spirito P, Chiarella F, Carratino L, et al. Clinical course and prognosis of hypertrophic cardiomyopathy in an outpatient population. N Engl J Med 1989; 320:749. 48. Wang W, Lian Z, Rowin EJ, et al. Prognostic Implications of Nonsustained Ventricular Tachycardia in High-Risk Patients With Hypertrophic Cardiomyopathy. Circ Arrhythm Electrophysiol 2017; 10. 49. Dilsizian V, Bonow RO, Epstein SE, Fananapazir L. Myocardial ischemia detected by thallium scintigraphy is frequently related to cardiac arrest and syncope in young patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1993; 22:796. 50. Yamada M, Elliott PM, Kaski JC, et al. Dipyridamole stress thallium-201 perfusion abnormalities in patients with hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome. Eur Heart J 1998; 19:500. 51. Sorajja P, Ommen SR, Nishimura RA, et al. Adverse prognosis of patients with hypertrophic cardiomyopathy who have epicardial coronary artery disease. Circulation 2003; 108:2342. 52. Fananapazir L. Advances in molecular genetics and management of hypertrophic cardiomyopathy. JAMA 1999; 281:1746. 53. Maron BJ, Bonow RO, Cannon RO 3rd, et al. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N Engl J Med 1987; 316:780. 54. Elliott PM, Gimeno JR, Tom MT, et al. Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J 2006; 27:1933. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 22/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate 55. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003; 348:295. 56. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005; 46:470. 57. McLeod CJ, Ommen SR, Ackerman MJ, et al. Surgical septal myectomy decreases the risk for appropriate implantable cardioverter defibrillator discharge in obstructive hypertrophic cardiomyopathy. Eur Heart J 2007; 28:2583. 58. O'Mahony C, Tome-Esteban M, Lambiase PD, et al. A validation study of the 2003 American College of Cardiology/European Society of Cardiology and 2011 American College of Cardiology Foundation/American Heart Association risk stratification and treatment algorithms for sudden cardiac death in patients with hypertrophic cardiomyopathy. Heart 2013; 99:534. 59. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000; 342:365. 60. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298:405. 61. Maron MS, Rowin EJ, Wessler BS, et al. Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy. JAMA Cardiol 2019; 4:644. 62. Spirito P, Seidman CE, McKenna WJ, Maron BJ. The management of hypertrophic cardiomyopathy. N Engl J Med 1997; 336:775. 63. Grace A. Prophylactic implantable defibrillators for hypertrophic cardiomyopathy: disarray in the era of precision medicine. Circ Arrhythm Electrophysiol 2015; 8:763. 64. Weissler-Snir A, Adler A, Williams L, et al. Prevention of sudden death in hypertrophic cardiomyopathy: bridging the gaps in knowledge. Eur Heart J 2017; 38:1728. 65. O'Mahony C, Jichi F, Pavlou M, et al. A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur Heart J 2014; 35:2010. 66. Vriesendorp PA, Schinkel AF, Liebregts M, et al. Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol 2015; 8:829. 67. Maron BJ, Casey SA, Chan RH, et al. Independent Assessment of the European Society of Cardiology Sudden Death Risk Model for Hypertrophic Cardiomyopathy. Am J Cardiol 2015; https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 23/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate 116:757. 68. Ruiz-Salas A, Garc a-Pinilla JM, Cabrera-Bueno F, et al. Comparison of the new risk prediction model (HCM Risk-SCD) and classic risk factors for sudden death in patients with hypertrophic cardiomyopathy and defibrillator. Europace 2016; 18:773. 69. Fern ndez A, Quiroga A, Ochoa JP, et al. Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model in Hypertrophic Cardiomyopathy in a Reference Center in South America. Am J Cardiol 2016; 118:121. 70. O'Mahony C, Jichi F, Ommen SR, et al. International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM). Circulation 2018; 137:1015. 71. Leong KMW, Chow JJ, Ng FS, et al. Comparison of the Prognostic Usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation Risk Stratification Systems for Patients With Hypertrophic Cardiomyopathy. Am J Cardiol 2018; 121:349. 72. Todiere G, Nugara C, Gentile G, et al. Prognostic Role of Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Low-to-Intermediate Sudden Cardiac Death Risk Score. Am J Cardiol 2019; 124:1286. 73. O'Mahony C, Akhtar MM, Anastasiou Z, et al. Effectiveness of the 2014 European Society of Cardiology guideline on sudden cardiac death in hypertrophic cardiomyopathy: a systematic review and meta-analysis. Heart 2019; 105:623. Topic 4952 Version 37.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 24/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate GRAPHICS Morphologic variants of hypertrophic cardiomyopathy HCM typically presents with asymmetric or localized areas of LV hypertrophy, which are diagrammed in B to J. (A) Normal LV wall thickness. (B) ASH. (C) Sigmoid septum, which is more common in older adults. (D) Midcavity hypertrophy associated with midcavity obstruction. (E) Predominantly free wall hypertrophy, an unusual pattern in HCM. (F) LV wall thinning (associated with low LV ejection fraction) and biatrial enlargement. (G) Predominantly apical LV hypertrophy. (H) Severe concentric hypertrophy with cavity obliteration. (I) Biventricular hypertrophy. (J) Mild to moderate symmetric hypertrophy. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 25/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate HCM: hypertrophic cardiomyopathy; LV: left ventricular; ASH: asymmetrical septal hypertrophy. Graphic 58156 Version 6.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 26/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate NYHA and other classifications of cardiovascular disability Canadian NYHA functional [1] Cardiovascular Specific activity Class [3] classification Society functional scale [2] classification I Patients with cardiac Ordinary physical Patients can perform to disease but without activity, such as completion any activity requiring 7 metabolic equivalents (ie, can resulting limitations of physical activity. walking and climbing stairs, does not cause Ordinary physical activity does not cause angina. Angina with strenuous or rapid carry 24 lb up 8 steps; do outdoor work undue fatigue, palpitation, dyspnea, or prolonged exertion at work or recreation. [shovel snow, spade soil]; do recreational anginal pain. activities [skiing, basketball, squash, handball, jog/walk 5 mph]). II Patients with cardiac disease resulting in Slight limitation of ordinary activity. Patients can perform to completion any activity requiring 5 metabolic equivalents (eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance foxtrot, walk at 4 mph slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal Walking or climbing stairs rapidly, walking uphill, walking or stair- climbing after meals, in cold, in wind, or when under emotional stress, or only during pain. the few hours after awakening. Walking more than 2 blocks on on level ground) but cannot and do not perform to completion activities requiring 7 metabolic equivalents. the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. III Patients with cardiac disease resulting in Marked limitation of ordinary physical Patients can perform to completion any activity requiring 2 metabolic equivalents (eg, shower without stopping, strip marked limitation of activity. Walking 1 to 2 physical activity. They are comfortable at rest. blocks on the level and climbing 1 flight in Less-than-ordinary physical activity causes normal conditions. and make bed, clean windows, walk 2.5 fatigue, palpitation, mph, bowl, play golf, https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 27/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate dyspnea, or anginal dress without stopping) pain. but cannot and do not perform to completion any activities requiring >5 metabolic equivalents. IV Patients with cardiac Inability to carry on any Patients cannot or do disease resulting in physical activity not perform to inability to carry on any physical activity without discomfort. Anginal syndrome may completion activities requiring >2 metabolic without discomfort. Symptoms of cardiac be present at rest. equivalents. Cannot carry out activities insufficiency or of the anginal syndrome may listed above (specific activity scale III). be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA: New York Heart Association. References: 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the th Heart and Great Vessels, 9 ed, Little, Brown & Co, Boston 1994. p.253. 2. Campeau L. Grading of angina pectoris. Circulation 1976 54:522. 3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new speci c activity scale. Circulation 1981; 64:1227. Graphic 52683 Version 19.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 28/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Myocyte disarray in hypertrophic cardiomyopathy Microscopic appearance of the myocardium in hypertrophic cardiomyopathy, stained with hematoxylin and eosin, shows myocyte disarray with an irregular arrangement of abnormal shaped myocytes that contain bizarre nuclei and surrounding areas of increased connective tissue. Courtesy of Professor Michael Davies, St. George's Hospital, London. Graphic 55914 Version 2.0 Normal endomyocardial biopsy Normal endomyocardial biopsy in longitudinal section. Courtesy of Helmut Rennke, MD. Graphic 61625 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 29/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Pyramid profile of risk stratification model currently used to identify patients a sudden cardiac death (SCD) risk who may be candidates for an implantable card defibrillator (ICD) Major and minor risk markers appear in boxes at the left. At the right are the results of ICD therapy in 730 ch adolescents, and adults assembled from two registry studies. |
model (HCM Risk-SCD) and classic risk factors for sudden death in patients with hypertrophic cardiomyopathy and defibrillator. Europace 2016; 18:773. 69. Fern ndez A, Quiroga A, Ochoa JP, et al. Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model in Hypertrophic Cardiomyopathy in a Reference Center in South America. Am J Cardiol 2016; 118:121. 70. O'Mahony C, Jichi F, Ommen SR, et al. International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM). Circulation 2018; 137:1015. 71. Leong KMW, Chow JJ, Ng FS, et al. Comparison of the Prognostic Usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation Risk Stratification Systems for Patients With Hypertrophic Cardiomyopathy. Am J Cardiol 2018; 121:349. 72. Todiere G, Nugara C, Gentile G, et al. Prognostic Role of Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Low-to-Intermediate Sudden Cardiac Death Risk Score. Am J Cardiol 2019; 124:1286. 73. O'Mahony C, Akhtar MM, Anastasiou Z, et al. Effectiveness of the 2014 European Society of Cardiology guideline on sudden cardiac death in hypertrophic cardiomyopathy: a systematic review and meta-analysis. Heart 2019; 105:623. Topic 4952 Version 37.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 24/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate GRAPHICS Morphologic variants of hypertrophic cardiomyopathy HCM typically presents with asymmetric or localized areas of LV hypertrophy, which are diagrammed in B to J. (A) Normal LV wall thickness. (B) ASH. (C) Sigmoid septum, which is more common in older adults. (D) Midcavity hypertrophy associated with midcavity obstruction. (E) Predominantly free wall hypertrophy, an unusual pattern in HCM. (F) LV wall thinning (associated with low LV ejection fraction) and biatrial enlargement. (G) Predominantly apical LV hypertrophy. (H) Severe concentric hypertrophy with cavity obliteration. (I) Biventricular hypertrophy. (J) Mild to moderate symmetric hypertrophy. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 25/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate HCM: hypertrophic cardiomyopathy; LV: left ventricular; ASH: asymmetrical septal hypertrophy. Graphic 58156 Version 6.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 26/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate NYHA and other classifications of cardiovascular disability Canadian NYHA functional [1] Cardiovascular Specific activity Class [3] classification Society functional scale [2] classification I Patients with cardiac Ordinary physical Patients can perform to disease but without activity, such as completion any activity requiring 7 metabolic equivalents (ie, can resulting limitations of physical activity. walking and climbing stairs, does not cause Ordinary physical activity does not cause angina. Angina with strenuous or rapid carry 24 lb up 8 steps; do outdoor work undue fatigue, palpitation, dyspnea, or prolonged exertion at work or recreation. [shovel snow, spade soil]; do recreational anginal pain. activities [skiing, basketball, squash, handball, jog/walk 5 mph]). II Patients with cardiac disease resulting in Slight limitation of ordinary activity. Patients can perform to completion any activity requiring 5 metabolic equivalents (eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance foxtrot, walk at 4 mph slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal Walking or climbing stairs rapidly, walking uphill, walking or stair- climbing after meals, in cold, in wind, or when under emotional stress, or only during pain. the few hours after awakening. Walking more than 2 blocks on on level ground) but cannot and do not perform to completion activities requiring 7 metabolic equivalents. the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. III Patients with cardiac disease resulting in Marked limitation of ordinary physical Patients can perform to completion any activity requiring 2 metabolic equivalents (eg, shower without stopping, strip marked limitation of activity. Walking 1 to 2 physical activity. They are comfortable at rest. blocks on the level and climbing 1 flight in Less-than-ordinary physical activity causes normal conditions. and make bed, clean windows, walk 2.5 fatigue, palpitation, mph, bowl, play golf, https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 27/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate dyspnea, or anginal dress without stopping) pain. but cannot and do not perform to completion any activities requiring >5 metabolic equivalents. IV Patients with cardiac Inability to carry on any Patients cannot or do disease resulting in physical activity not perform to inability to carry on any physical activity without discomfort. Anginal syndrome may completion activities requiring >2 metabolic without discomfort. Symptoms of cardiac be present at rest. equivalents. Cannot carry out activities insufficiency or of the anginal syndrome may listed above (specific activity scale III). be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA: New York Heart Association. References: 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the th Heart and Great Vessels, 9 ed, Little, Brown & Co, Boston 1994. p.253. 2. Campeau L. Grading of angina pectoris. Circulation 1976 54:522. 3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new speci c activity scale. Circulation 1981; 64:1227. Graphic 52683 Version 19.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 28/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Myocyte disarray in hypertrophic cardiomyopathy Microscopic appearance of the myocardium in hypertrophic cardiomyopathy, stained with hematoxylin and eosin, shows myocyte disarray with an irregular arrangement of abnormal shaped myocytes that contain bizarre nuclei and surrounding areas of increased connective tissue. Courtesy of Professor Michael Davies, St. George's Hospital, London. Graphic 55914 Version 2.0 Normal endomyocardial biopsy Normal endomyocardial biopsy in longitudinal section. Courtesy of Helmut Rennke, MD. Graphic 61625 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 29/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Pyramid profile of risk stratification model currently used to identify patients a sudden cardiac death (SCD) risk who may be candidates for an implantable card defibrillator (ICD) Major and minor risk markers appear in boxes at the left. At the right are the results of ICD therapy in 730 ch adolescents, and adults assembled from two registry studies. BP: blood pressure; CAD: coronary artery disease; EF: ejection fraction; ICD: implantable cardioverter-defibril ventricular; LGE: late gadolinium enhancement; LVH: left ventricular hypertrophy; NSVT: nonsustained ventri tachycardia; SD: sudden death; VT/VF: ventricular tachycardia/ventricular fibrillation. Extensive LGE is a novel primary risk marker that can also be used as an arbitrator when conventional risk a ambiguous. SD events are uncommon after 60 years of age, even with conventional risk factors. Reproduced from: Maron B, Ommen S, Semsarian C. Hypertrophic cardiomyopathy: Present and future, with translation into contempo medicine. J Am Coll Cardiol 2014; 64:83. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 99534 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 30/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate The recognized markers of risk in HCM and their sensitivity, specificity, and positive and negative predictive accuracy (PPA and NPA) Sensitivity, Specificity, PPA, NPA, Risk factor percent percent percent percent Abnormal blood pressure [1] response: <40 years old 75 66 15 97 [2] NSVT: adult <45 years old 69 80 22 97 [3] NSVT: 21 years old <10 89 <10 85 Inducible VT/VF: high risk [4] population 82 68 17 98 [5] Syncope: <45 years old* 35 82 25 86 Family history: at least one unexplained sudden death HCM* 42 79 28 88 [5] [6] LVH 3 cm 26 88 13 95 [7] Two or more risk factors 45 90 23 96 HCM: hypertrophic cardiomyopathy; LVH: left ventricular hypertrophy; ICD: implantable cardioverter- defibrillator; NPA: negative predictive accuracy; NSVT: nonsustained ventricular tachycardia; PPA: positive predictive accuracy; VF: ventricular fibrillation; VT: ventricular tachycardia. Figures provided are for the risk of death from all causes rather than sudden death only. Figures provided are for risk of sudden death and/or appropriate ICD discharge. In this data set from Elliott and colleagues, family history and syncope were combined in order to achieve statistical significance of relative risk. 1. McKenna WJ, Franklin RC, Nihoyannopoulos P, et al. Arrhythmia and prognosis in infants, children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol 1988; 11:147. 2. Maron BJ, Savage DD, Wolfson JK, et al. Prognostic signi cance of 24 hour ambulatory electrocardiographic monitoring in patients with hypertrophic cardiomyopathy: a prospective study. Am J Cardiol 1981; 48:252. 3. McKenna WJ, Oakley CM, Krikler DM, et al. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Br Heart J 1985; 53:412. 4. Fananapazir L, Chang AC, Epstein SE, McAreavey D. Prognostic determinants in hypertrophic cardiomyopathy. Prospective evaluation of a therapeutic strategy based on clinical, Holter, hemodynamic, and electrophysiological ndings. Circulation 1992; 86:730. 5. McKenna W, Dean eld J, Faruqui A, et al. Prognosis in hypertrophic cardiomyopathy: role of age and clinical, electrocardiographic and hemodynamic features. Am J Cardiol 1981; 47:532. 6. Elliott PM, Gimeno BJ, Mahon NG, et al. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 2001; 357:420. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 31/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate 7. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identi cation of high risk patients. J Am Coll Cardiol 2000; 36:2212. Reproduced with permission from: McKenna, WJ, Behr, ER. Hypertrophic cardiomyopathy: management, risk strati cation, and prevention of sudden death. Heart 2002; 87:169. Copyright 2002 BMJ Publishing Group, Ltd. Graphic 80617 Version 3.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 32/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Established major risk markers and risk modifiers associated with increased risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) Risk factor Comment Major risk factors Family history of HCM- SCD due to HCM in a close relative, particularly if <40 years of age, related SCD should be considered evidence for increased risk of SCD in other related family members. Syncope Unexplained syncope that, based on clinical history, appears to be due to arrhythmia (and not neurally mediated) is associated with increased SCD risk, particularly in young patients and when the event occurred close to the time of evaluation (<6 months). Massive LV hypertrophy An increased risk of SCD in patients with HCM is seen in patients with echocardiographic evidence of 30 mm wall thickness anywhere in the LV chamber. If maximal wall thickness is not clearly defined using echocardiography, additional evaluation with CMR to clarify the extent of LV wall thickening may be warranted. LV apical aneurysm Uncommon subgroup with thin-walled dyskinetic LV apex with regional scarring. LV apical aneurysm is associated with increased risk for sustained monomorphic VT and warrants consideration for ICD. End-stage HCM (LVEF <50 percent) Higher incidence of life-threatening VT associated with this uncommon phase of HCM. These patients often develop advanced heart failure at a young age and therefore are often considered for ICD as a bridge to definitive therapy with heart transplant. Risk Modifiers Extensive LGE (ie, myocardial fibrosis) occupying 15 percent of LV mass is associated with markers of disease severity and adverse outcomes including increased risk for SCD and should be considered Extensive LGE by contrast-enhanced CMR an important arbitrator to resolving ICD decision-making when uncertain following assessment with established major risk markers. Age at time of SCD risk assessment Risk of SCD is greatest in young patients <30 years old and lessens through mid-life. In patients who have achieved advanced age ( 60 years), risk of SCD is low, even in the presence of other risk factors. Defined as 3 consecutive ventricular beats at >120 beats per minute, lasting less than 30 seconds. Multiple bursts identified on ambulatory NSVT on ambulatory monitoring monitoring are associated with increased risk, particularly in younger patients. Although the data relating characteristics of NSVT to SCD risk remain poorly defined, it would be reasonable to give greater weight to increased SCD risk in those patients with HCM with NSVT that is https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 33/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate frequent (>1 burst), of long duration (>7 beats), or particularly fast (>200 beats per minute). LVEF: left ventricular ejection fraction; CMR: cardiovascular magnetic resonance; NSVT: nonsustained ventricular tachycardia; BP: blood pressure; ICD: implantable cardioverter-defibrillator; LGE: late gadolinium enhancement; LVOT: left ventricular outflow tract obstruction. Graphic 102357 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 34/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Left ventricular wall thickness predicts sudden death in HCM In a study of 480 patients with an HCM, the incidence of sudden death during a 6.5-year follow-up was directly related to maximal wall thickness. The incidence of sudden death almost doubled for each 5 mm increase in wall thickness. HCM: hypertrophic cardiomyopathy. Data from Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000; 342:1778. Graphic 75913 Version 4.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 35/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Sudden cardiac death and risk factors in hypertrophic cardiomyopathy Kaplan-Meier estimates of the proportions of patients surviving from sudden cardiac death, appropriate ICD discharge, or resuscitated ventricular fibrillation in relation to number of risk factors in patients with obstruction. ICD: implantable cardioverter-defibrillator. Reproduced with permission from: Elliott PM, Gimeno JR, Tome MT, et al. Left ventricular out ow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J 2006; 27:1933. Copyright 2006 Oxford University Press. Graphic 65115 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 36/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Risk of sudden death in HCM A set of four predictors of sudden death were analyzed to develop a risk stratification algorithm in a study of 368 patients with HCM. The predictors included a history of syncope and/or a family history of sudden death, a left ventricular wall thickness 30 mm, nonsustained ventricular tachycardia on ambulatory monitoring, and an abnormal blood pressure response to exercise (refer to text). This bar graph shows the percentage of each risk factor group (zero, one, two, and three risk factors) in which patients died during follow-up (black bars = sudden death; hatched bars = congestive cardiac failure or transplant; white = all deaths). The majority of deaths were sudden, and the greatest proportion occurred in patients with multiple risk factors. HCM: hypertrophic cardiomyopathy. Data from Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identi cation of high risk patients. J Am Coll Cardiol 2000; 36:2212. Graphic 75731 Version 3.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 37/38 7/6/23, 1:39 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Contributor Disclosures Martin S Maron, MD Grant/Research/Clinical Trial Support: iRhythm [Hypertrophic cardiomyopathy]. Consultant/Advisory Boards: Cytokinetics [Steering committee, REDWOOD-HCM]; Edgewise Pharmaceuticals [Myosin inhibitor for treatment of symptomatic hypertrophic cardiomyopathy]; Imbria Pharmaceuticals [Hypertrophic cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. William J McKenna, MD Consultant/Advisory Boards: Bristol Meyers Squibb [Novel pharmacological treatments for HCM]; Cytokinetics [Novel pharmacological treatments for HCM]; Health in Code [Genetic testing in inherited cardiac disease]; Tenaya Therapeutics [Gene therapy in cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 38/38 |
7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Incidence of and risk stratification for sudden cardiac death after myocardial infarction : Philip J Podrid, MD, FACC : Peter J Zimetbaum, MD, Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 13, 2022. INTRODUCTION The process of risk stratification in a patient who has had an acute myocardial infarction (MI) has two components: Early in-hospital identification of patients at increased risk for recurrent ischemic events Identification of patients at increased risk for arrhythmic or nonarrhythmic death Patients who have had an acute MI are at increased risk for sudden cardiac death (SCD), most often due to a ventricular tachyarrhythmia. However, not all post-MI patients have the same risk of SCD. Thus, the therapeutic approach to the prevention of SCD depends upon the identification of those patients who are most likely to have a ventricular tachyarrhythmia and the effectiveness of the available preventive measures [1,2]. The incidence of SCD after acute MI and identification of patients at increased risk for SCD will be reviewed here. The approach to primary and secondary prevention of SCD post-MI, as well to risk stratification for recurrent ischemic events after ST elevation and non-ST elevation infarctions, are discussed separately. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Risk stratification after acute ST-elevation myocardial infarction" and "Risk stratification after non-ST elevation acute coronary syndrome".) https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 1/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate OUR APPROACH TO RISK STRATIFICATION Although a large number of risk factors for SCD have been identified, significantly reduced left ventricular ejection fraction (LVEF) is the most widespread clinical identifier of patients at increased risk for SCD. Our approach to risk stratification of SCD post-MI is in general agreement with the recommendations of various professional societies [3-6]. We recommend evaluation of LV function, including LVEF, prior to discharge post-MI and again at 90 days post-MI. (See 'LV dysfunction' below.) While invasive electrophysiology studies (EPS) are not routinely performed post-MI in contemporary practice, EPS can aid in the decision regarding implantable cardioverter- defibrillator (ICD) implantation in patients with nonsustained ventricular tachycardia who do not meet MADIT-2 or SCD-HeFT criteria and in patients with syncope or other symptoms (such as palpitations, lightheadedness or presyncope associated with NSVT) of suspected but not confirmed arrhythmic etiology. (See 'Inducible VT/VF' below.) INCIDENCE OF SCD One-year mortality following acute coronary syndrome (ACS) is approximately 5 percent, with three-quarters of the deaths due to a cardiovascular event [7]. Among all deaths in the first year, SCD (36 percent) and recurrent MI (23 percent) are the most commonly reported causes, with the relative contribution of SCD increasing more than 30 days post-ACS. Mortality after acute MI, including SCD, has declined substantially since the 1970s due primarily to changes in the care of these patients [8-10]. These include: The initial treatment of acute MI with dual antiplatelet therapy, beta blockers, statins, and reperfusion using catheter-based treatments (eg, angioplasty and stents) and fibrinolytic agents. Secondary prevention measures. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".) The incidence of ventricular arrhythmias after an MI remains elevated for months to years, if not indefinitely. Ventricular tachycardia (VT) and ventricular fibrillation (VF) are most frequent in the first hours of an infarction, and the incidence then declines in phases during the days, weeks, and months after the event. This pattern reflects the electrophysiologic manifestations of the evolving interactions between ischemia, infarction, reperfusion, and scar formation. A detailed https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 2/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate discussion of ventricular arrhythmias in the acute phase of an MI is presented separately. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) For the purposes of long-term risk stratification, the time since an MI is relevant for two reasons: The clinical significance of risk factors may vary over time. The overall risk of events, regardless of risk profile, varies over time. Elevated early risk The definition of the "early" post-MI period has varied across studies over the years. UpToDate authors consider the "early" acute period as <48 hours post-MI and the "late" acute period as 48 hours to seven days post-MI, although some studies have defined the "early" risk to include as long as 30 days post-MI. The increased risk of SCD in the first months post-MI was illustrated in reports from the VALIANT trial, from a community-based cohort, and from a pooled analysis: In the VALIANT population, which included 14,609 patients with LV dysfunction or heart failure (HF) after acute MI, the rate of SCD or resuscitated cardiac arrest was 1.4 percent in the first month compared with 0.14 percent per month after two years [11]. The event rate in the first month was higher (2.3 percent) in patients with an LVEF <30 percent. In a community-based (Olmsted County, MN) cohort of 2997 post-MI patients, which included patients with normal LV function, the 30-day cumulative incidence of SCD was 1.2 percent [10]. Following the first month, the risk of SCD fell to 1.2 percent per year. In a pooled analysis of 3104 patients with a recent MI and either an LVEF 40 percent or frequent ventricular ectopy, the rate of arrhythmic death during the first six months post- MI was 8 per 100 person years [12]. The rate declined and stabilized in the ensuing 18 months at approximately 4 per 100 person years. Limitations of early risk stratification Both risk assessment and treatment decisions during this early stage are complicated for several reasons: The arrhythmic substrate evolves as stunned myocardium recovers and scar formation occurs in regions of necrosis [13,14]. With this physiologic evolution, the findings and implications of risk stratification tests (eg, nonsustained ventricular tachycardia, LV function) also change, leading to uncertainty regarding the prognostic significance of abnormal findings in the early postinfarction period. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 3/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate Consistent with these concerns, two randomized trials that directly addressed the issue of early ICD placement for primary prevention of SCD (DINAMIT and IRIS) did not show an improvement in survival in patients with LV dysfunction randomly assigned to receive ICD placement within 31 or 40 days after an acute MI [15,16]. At present, ICD therapy for primary prevention is not recommended less than 40 days after MI. While not standard contemporary practice in all patients, early electrophysiologic (EP) testing (more than 48 hours post-MI) may help stratify patients post-MI for ICD placement with suspected increased risk of SCD but in whom the traditional indications for ICD are not satisfied. In an observational study of 360 patients without sustained ventricular tachyarrhythmia who underwent EP testing with programmed ventricular stimulation on day nine post-MI, 39 percent of early post-MI patients had inducible monomorphic VT (EP positive group, of which 71 percent received an ICD) while 61 percent were noninducible (EP negative group, of which only six percent received an ICD) [17]. After two-year follow-up, the EP negative group had a lower risk of the primary combined endpoint of sudden death and spontaneous ventricular tachyarrhythmia (adjusted hazard ratio 0.46, 95% CI 0.22 to 0.95). RISK FACTORS FOR CHRONIC PHASE (>7 DAYS) SCD LV systolic function, evaluated using the LVEF, is the most commonly used marker for assessing the risk of late SCD post-MI. In addition to LVEF, a number of clinical features have been evaluated as possible risk factors for the development of a fatal arrhythmia following an acute MI: VT induced by electrophysiologic study (EPS) Spontaneous ventricular premature beats (VPBs) and more importantly nonsustained ventricular tachycardia documented on 24-hour ambulatory monitoring Late potentials on a signal averaged electrocardiogram (ECG) Reduced heart rate variability, assessed by ambulatory monitoring T wave (repolarization) alternans, especially seen with exercise testing Sustained ventricular arrhythmias are not included on this list of risk factors, which may seem counterintuitive. However, sustained arrhythmias that occur in the early post-MI phase (usually defined as the first 48 hours) are generally considered epiphenomena of the MI and are not consistently associated with long-term prognosis. This lack of association with long term prognosis is more clearly established for early ventricular fibrillation (VF) and polymorphic VT. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 4/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate These arrhythmias are the only arrhythmias that are provoked by active ischemia, as occurs with an acute MI. Sustained monomorphic VT, even when it occurs early, may reflect permanent arrhythmic substrate. This substrate is most commonly myocardial fibrosis resulting in reentry. Patients with sustained arrhythmias after the early phase are managed according to secondary prevention strategies, and therefore are not included in primary prevention risk stratification protocols. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) The advent of reperfusion therapy (thrombolysis and percutaneous coronary intervention [PCI]) reduced the prognostic significance of many of the variables that have been useful for risk stratification in the past. (See 'Our approach to risk stratification' above.) LV dysfunction We recommend evaluation of LV function, including LVEF, prior to discharge post-MI and again at 90 days post-MI. Significant LV dysfunction, as measured by an LVEF <35 percent, is one of the most powerful predictors of mortality at six months ( figure 1) and one year after MI [18-21]. However, early measurements may be misleading, since improvement in LVEF, beginning within three days and largely complete by 14 days, is common in patients who have been reperfused and can sometimes be seen even in those who are not acutely reperfused. This improvement is presumed to reflect recovery from myocardial stunning [13,14]. (See "Clinical syndromes of stunned or hibernating myocardium", section on 'Acute myocardial infarction'.) Echocardiography is the most commonly used modality for assessing LV function after an acute MI. Other methods such as radionuclide angiography, computed tomography scans, or magnetic resonance imaging have equivalent prognostic value. (See "Risk factors for adverse outcomes after non-ST elevation acute coronary syndromes", section on 'Heart failure'.) LV dysfunction was an entry criterion in the major trials that have evaluated the possible efficacy of an ICD for primary prevention of SCD in patients who have had an MI: MUSTT, MADIT I, and MADIT II; in all of these trials, patients with significant LV dysfunction benefited from ICD placement [22-24]. It was also an entry criterion for the SCD-HeFT trial, which included patients with either an ischemic or nonischemic cardiomyopathy and New York Heart Association (NYHA) class II to III HF. Consistent with the results of these trials, LV dysfunction is a component of all current indications for prophylactic ICD implantation for primary prevention of SCD in patients with a prior MI. Thus, an assessment of LV function is among the most important steps in initial risk stratification. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 5/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate The relationship between LV dysfunction and mortality has been shown in various trials including patients receiving standard medical therapy, such as ACE inhibitors and beta blockers [24-26]. The relationship between LV dysfunction and short-term arrhythmic risk has also been assessed in a post hoc analysis from the VALIANT trial, in which 11,256 patients had an assessment of LV function prior to discharge [11]. In the first 30 days after MI, patients with an LVEF <30 percent had the highest rates of SCD or resuscitated cardiac arrest (2.3 percent/month), and each decrease of 5 percent in LVEF was associated with a 21 percent increase in the risk of SCD or resuscitated cardiac arrest in the first 30 days. (See 'Incidence of SCD' above.) Inducible VT/VF Invasive EPS for risk stratification is not routinely performed in contemporary practice; however, the ability to induce ventricular tachyarrhythmias may play a role in the risk stratification for ICD placement in the subset of patients where the role of an ICD is still questionable (ie, LVEF of 35 percent or slightly below or above). Settings in which EPS in post-MI patients can aid in the decision regarding ICD implantation include: Patients with nonsustained ventricular tachycardia (NSVT) who do not meet MADIT-2 or SCD-HeFT criteria, including: Patients with an LVEF 30-35 percent and NYHA class I HF symptoms Patients with an LVEF 36-40 percent and NSVT (MUSTT patients) Some patients with an LVEF >40 percent who also have NSVT (typically identified from in-hospital telemetry or outpatient ambulatory ECG monitoring if performed for symptoms suggesting an arrhythmia. In contemporary practice most asymptomatic patients do not have routine outpatient ambulatory ECG monitoring). Even if EPS is positive for inducible VT/VF (typically with inducible monomorphic VT posing a higher risk than polymorphic VT or VF), no prospective randomized clinical trial data have shown that ICDs improve survival, but this is considered clinically significant VT and an ICD can be placed for secondary prevention. Patients with syncope of suspected but not confirmed arrhythmic etiology. The ability to induce ventricular arrhythmias (particularly monomorphic VT with one or two extrastimuli) with programmed electrical stimulation during an invasive electrophysiology study suggests the presence of arrhythmic substrate and an increased risk of malignant arrhythmias. The likelihood of inducible VT/VF varies according to several clinical variables including LVEF and NSVT (with more frequent runs, longer runs, faster ventricular rates, and accelerating ventricular rates all suggesting greater risk of sustained VT and SCD). In general, inducibility has a low https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 6/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate positive predictive value, but a higher negative predictive value [22,27-30]. (See "Invasive diagnostic cardiac electrophysiology studies".) Among several studies prior to the widespread use of primary reperfusion therapies, approximately one-third of post-MI patients had inducible VT or VF [31-35]. At one year follow- up, arrhythmic events were more common in patients with inducible VT/VF (average 18 percent, range 6 to 41 percent) than in those who were not inducible (average 7 percent, range 0 to 14 percent). Inducibility appears to be less common in the primary reperfusion era; however, when present, still predicts an increased risk of SCD [36]. Some clinical equipoise exists regarding the risk of VT and SCD post-MI or patients with an LVEF <40 percent in the first 40 days post-MI. An ongoing study, the PROTECT-ICD study, is evaluating the role of EPS and inducible VT/VF in the risk stratification for ICD placement in this patient population [37]. Other risk modifiers/approaches to risk stratification VPBs Ventricular premature beats (VPBs), particularly if frequent (more than 30 per hour) or complex (eg, multifocal, couplets, or NSVT), appear to be associated with a worse prognosis in patients with a prior MI. Although VPBs are associated with increased mortality, there is no role for chronic antiarrhythmic drug therapy to suppress asymptomatic VPBs. (See "Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment".) NSVT Due to the limited predictive value and reproducibility of NSVT, combined with the evolution of broader ICD indications based upon LVEF and HF alone, the role of NSVT in risk stratification is largely limited. Though not frequently performed in contemporary practice, periodic ambulatory monitoring may be considered for post-MI patients with an LVEF <40 percent or symptoms suggesting arrhythmia, with invasive EP testing to search for inducible VT an option for patients who manifest NSVT. For patients with mild LV dysfunction post-MI (LVEF 40 to 49 percent), no data exist to guide the using of ambulatory monitoring; for these patients, our approach is to optimize medical therapy without any ambulatory monitoring, unless arrhythmic symptoms arise. (See 'Inducible VT/VF' above.) The significance of NSVT following an MI is dependent upon the proximity of the arrhythmia to the time of the MI. In the first 24 to 48 hours after an infarction, NSVT is usually due to transient abnormalities of automaticity or triggered activity in the region of ischemia or infarction; in comparison, NSVT that occurs later is more often due to reentry and permanent arrhythmic substrate (ie, fibrosis). https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 7/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate In the era prior to reperfusion, NSVT detected post-MI was associated with an increased risk of SCD, in particular in patients with LVEF <40 percent [38,39]. However, NSVT has become less significant in risk stratification algorithms for several reasons: The incidence and prognostic significance of NSVT appear lower with contemporary primary reperfusion therapies [40,41]. NSVT on Holter monitoring has low reproducibility (50 percent overall in one study) [42]. Primary prevention ICD trials (eg, MADIT II and SCD-HeFT) demonstrated a survival benefit with ICD therapy in selected patients even in the absence of NSVT or an abnormal EP study (LVEF 30 percent in patients with a prior MI in MADIT II, and LVEF 35 percent in patients with NYHA class II or III HF in SCD-HeFT). Sustained ventricular arrhythmias The importance of sustained ventricular arrhythmias on management after MI depends upon the morphology (eg, monomorphic VT, polymorphic VT, or ventricular fibrillation [VF]) and the temporal relationship to the infarction (eg, early or late, usually defined at a cutoff of 48 hours). Most patients with sustained monomorphic VT are at increased risk for future SCD and therefore warrant further risk stratification (eg, EP study) or placement of an ICD for secondary prevention. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Monomorphic ventricular tachycardia'.) Early Early sustained ventricular tachyarrhythmias are usually considered to be related to transient arrhythmogenic phenomena associated with the evolving infarction. They are associated with increased in-hospital and 30-day mortality, but among patients with early arrhythmias who survive 30 days, long-term SCD risks are unclear and may vary with the type of arrhythmia. Early VF alone does not appear to predict adverse late outcomes, but this may not apply to early sustained monomorphic VT. Late Late sustained arrhythmias, particularly VF, polymorphic VT, and symptomatic monomorphic VT, predict an increased risk of SCD. Patients with these arrhythmias do not require further risk stratification and should be treated with an ICD for secondary prevention. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Late potentials Late potentials on the signal-averaged ECG (SAECG) are indicative of late and slow impulse conduction through diseased or scarred myocardium. They indicate the potential for reentry, and their presence may identify patients after MI who are at risk for https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 8/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate sustained VT and/or SCD [43]. However, the predictive value of SAECG alone is low, and in practice this test is now rarely used for risk stratification. Reduced HRV Heart rate variability (HRV) is related to the balance between sympathetic and parasympathetic neural inputs, and is measured as the beat to beat variation in heart rate, which is attributable to effects of respiration and to normal blood pressure fluctuations. A reduction in HRV post-MI may be due to a decrease in parasympathetic tone and/or an increase in sympathetic neural activity, both of which can facilitate arrhythmia initiation [15,44,45]. However, the predictive value of HRV alone is low, and in practice this test is now rarely used for risk stratification. (See "Evaluation of heart rate variability".) T wave alternans T wave or repolarization alternans (TWA) refers to variability in the timing or morphology of repolarization occurring in alternate beats on the surface ECG [46]. TWA is indicative of repolarization heterogeneity, which increases susceptibility to ventricular tachyarrhythmias. The presence of TWA has high sensitivity and specificity for predicting inducible ventricular arrhythmias on EPS. However, the predictive value of TWA alone is low, and in practice this test is now rarely used for risk stratification. (See "T wave (repolarization) alternans: Overview of technical aspects and clinical applications".) Cardiac imaging Cardiac magnetic resonance (CMR) imaging offers excellent characterization of myocardial function and the extent of scar after an MI. As these features may characterize arrhythmic substrate, efforts are underway to correlate CMR findings with arrhythmic risk. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Prediction of post-MI mortality'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 9/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate Basics topics (see "Patient education: What can go wrong after a heart attack? (The Basics)") SUMMARY AND RECOMMENDATIONS With regard to primary prevention of sudden cardiac death (SCD), the most important initial parameter is left ventricular ejection fraction (LVEF). We recommend evaluation of LV function, including LVEF, prior to discharge post-myocardial infarction (MI) and again at 90 days post-MI. (See 'LV dysfunction' above.) Invasive electrophysiology study (EPS) for risk stratification is not routinely performed in contemporary practice; however, settings in which EPS in post-MI patients can aid in the decision regarding implantable cardioverter-defibrillator (ICD) implantation include patients with nonsustained ventricular tachycardia who do not meet MADIT-2 or SCD-HeFT criteria (including LVEF 40 percent and LVEF >40 percent) and patients with syncope of suspected but not confirmed arrhythmic etiology. (See 'Inducible VT/VF' above.) The indications for ICD implantation are discussed in detail elsewhere. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) A number of additional risk factors are associated with the risk of SCD after an acute MI, including microvolt T wave alternans, signal-averaged ECG, and heart rate variability. However, because the results of these studies do not usually affect management decisions, we do not recommend their routine use. Such studies may provide additional insight into a given patient's arrhythmic risk, but data do not support using this information to guide decisions regarding ICD or antiarrhythmic drug therapy. (See 'Risk factors for chronic phase (>7 days) SCD' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 10/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 1. Bailey JJ, Berson AS, Handelsman H, Hodges M. Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction. J Am Coll Cardiol 2001; 38:1902. 2. Reynolds MR, Josephson ME. MADIT II (second Multicenter Automated Defibrillator Implantation Trial) debate: risk stratification, costs, and public policy. Circulation 2003; 108:1779. 3. Priori SG, Blomstr m-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015; 36:2793. 4. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 64:e139. 5. American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, O'Gara PT, et al. 2013 ACCF/AHA guideline for the management of ST- elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61:e78. 6. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 7. Berg DD, Wiviott SD, Braunwald E, et al. Modes and timing of death in 66 252 patients with non-ST-segment elevation acute coronary syndromes enrolled in 14 TIMI trials. Eur Heart J 2018; 39:3810. 8. McGovern PG, Jacobs DR Jr, Shahar E, et al. Trends in acute coronary heart disease mortality, morbidity, and medical care from 1985 through 1997: the Minnesota heart survey. Circulation 2001; 104:19. 9. Capewell S, Morrison CE, McMurray JJ. Contribution of modern cardiovascular treatment and risk factor changes to the decline in coronary heart disease mortality in Scotland between 1975 and 1994. Heart 1999; 81:380. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 11/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 10. Adabag AS, Therneau TM, Gersh BJ, et al. Sudden death after myocardial infarction. JAMA 2008; 300:2022. 11. Solomon SD, Zelenkofske S, McMurray JJ, et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 2005; 352:2581. 12. Yap YG, Duong T, Bland M, et al. Temporal trends on the risk of arrhythmic vs. non- arrhythmic deaths in high-risk patients after myocardial infarction: a combined analysis from multicentre trials. Eur Heart J 2005; 26:1385. 13. Sheehan FH, Doerr R, Schmidt WG, et al. Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival. J Am Coll Cardiol 1988; 12:289. 14. Solomon SD, Glynn RJ, Greaves S, et al. Recovery of ventricular function after myocardial infarction in the reperfusion era: the healing and early afterload reducing therapy study. Ann Intern Med 2001; 134:451. 15. Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter- defibrillator after acute myocardial infarction. N Engl J Med 2004; 351:2481. 16. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med 2009; 361:1427. 17. Kumar S, Sivagangabalan G, Zaman S, et al. Electrophysiology-guided defibrillator implantation early after ST-elevation myocardial infarction. Heart Rhythm 2010; 7:1589. 18. Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983; 309:331. 19. Mukharji J, Rude RE, Poole WK, et al. Risk factors for sudden death after acute myocardial infarction: two-year follow-up. Am J Cardiol 1984; 54:31. 20. Zaret BL, Wackers FJ, Terrin ML, et al. Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study. The TIMI Study Group. J Am Coll Cardiol 1995; 26:73. 21. Burns RJ, Gibbons RJ, Yi Q, et al. The relationships of left ventricular ejection fraction, end- systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction treated by thrombolysis. J Am Coll Cardiol 2002; 39:30. 22. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 12/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 23. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335:1933. 24. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346:877. 25. Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)- Prevenzione. Circulation 2002; 105:1897. 26. Torp-Pedersen C, K ber L. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation. Lancet 1999; 354:9. 27. Wilber DJ, Kopp D, Olshansky B, et al. Nonsustained ventricular tachycardia and other high- risk predictors following myocardial infarction: implications for prophylactic automatic implantable cardioverter-defibrillator use. Prog Cardiovasc Dis 1993; 36:179. 28. Buxton AE, Hafley GE, Lehmann MH, et al. Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables. Circulation 1999; 99:1843. 29. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 2000; 342:1937. 30. Schmitt H, Hurst T, Coch M, et al. Nonsustained, asymptomatic ventricular tachycardia in patients with coronary artery disease: prognosis and incidence of sudden death of patients who are noninducible by electrophysiological testing. Pacing Clin Electrophysiol 2000; 23:1220. 31. Denniss AR, Richards DA, Cody DV, et al. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 1986; 74:731. 32. Marchlinski FE, Buxton AE, Waxman HL, Josephson ME. Identifying patients at risk of sudden death after myocardial infarction: value of the response to programmed stimulation, degree of ventricular ectopic activity and severity of left ventricular dysfunction. Am J Cardiol 1983; 52:1190. 33. Roy D, Marchand E, Th roux P, et al. Programmed ventricular stimulation in survivors of an acute myocardial infarction. Circulation 1985; 72:487. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 13/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 34. Bhandari AK, Rose JS, Kotlewski A, et al. Frequency and significance of induced sustained ventricular tachycardia or fibrillation two weeks after acute myocardial infarction. Am J Cardiol 1985; 56:737. 35. Kowey PR, Waxman HL, Greenspon A, et al. Value of electrophysiologic testing in patients with previous myocardial infarction and nonsustained ventricular tachycardia. Philadelphia Arrhythmia Group. Am J Cardiol 1990; 65:594. 36. Andresen D, Steinbeck G, Br ggemann T, et al. Risk stratification following myocardial infarction in the thrombolytic era: a two-step strategy using noninvasive and invasive methods. J Am Coll Cardiol 1999; 33:131. 37. https://clinicaltrials.gov/ct2/show/NCT03588286?term=PROTECT-ICD&rank=1 (Accessed on J une 14, 2019). 38. Anderson KP, DeCamilla J, Moss AJ. Clinical significance of ventricular tachycardia (3 beats or longer) detected during ambulatory monitoring after myocardial infarction. Circulation 1978; 57:890. 39. Bigger JT Jr, Fleiss JL, Rolnitzky LM. Prevalence, characteristics and significance of ventricular tachycardia detected by 24-hour continuous electrocardiographic recordings in the late hospital phase of acute myocardial infarction. Am J Cardiol 1986; 58:1151. 40. Maggioni AP, Zuanetti G, Franzosi MG, et al. Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results. Circulation 1993; 87:312. 41. Hohnloser SH, Klingenheben T, Zabel M, et al. Prevalence, characteristics and prognostic value during long-term follow-up of nonsustained ventricular tachycardia after myocardial infarction in the thrombolytic era. J Am Coll Cardiol 1999; 33:1895. 42. Senges JC, Becker R, Schreiner KD, et al. Variability of Holter electrocardiographic findings in patients fulfilling the noninvasive MADIT criteria. Multicenter Automatic Defibrillator Implantation Trial. Pacing Clin Electrophysiol 2002; 25:183. 43. Hohnloser SH, Gersh BJ. Changing late prognosis of acute myocardial infarction: impact on management of ventricular arrhythmias in the era of reperfusion and the implantable cardioverter-defibrillator. Circulation 2003; 107:941. 44. Malik M, Camm AJ, Janse MJ, et al. Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: a substudy of EMIAT (The European Myocardial Infarct Amiodarone Trial). J Am Coll Cardiol 2000; 35:1263. 45. Gillis AM. Prophylactic implantable cardioverter-defibrillators after myocardial infarction not for everyone. N Engl J Med 2004; 351:2540. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 14/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 46. Armoundas AA, Tomaselli GF, Esperer HD. Pathophysiological basis and clinical application of T-wave alternans. J Am Coll Cardiol 2002; 40:207. Topic 1052 Version 30.0 https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 15/17 7/6/23, 1:39 PM |
16. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med 2009; 361:1427. 17. Kumar S, Sivagangabalan G, Zaman S, et al. Electrophysiology-guided defibrillator implantation early after ST-elevation myocardial infarction. Heart Rhythm 2010; 7:1589. 18. Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983; 309:331. 19. Mukharji J, Rude RE, Poole WK, et al. Risk factors for sudden death after acute myocardial infarction: two-year follow-up. Am J Cardiol 1984; 54:31. 20. Zaret BL, Wackers FJ, Terrin ML, et al. Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study. The TIMI Study Group. J Am Coll Cardiol 1995; 26:73. 21. Burns RJ, Gibbons RJ, Yi Q, et al. The relationships of left ventricular ejection fraction, end- systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction treated by thrombolysis. J Am Coll Cardiol 2002; 39:30. 22. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 12/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 23. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335:1933. 24. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346:877. 25. Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)- Prevenzione. Circulation 2002; 105:1897. 26. Torp-Pedersen C, K ber L. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation. Lancet 1999; 354:9. 27. Wilber DJ, Kopp D, Olshansky B, et al. Nonsustained ventricular tachycardia and other high- risk predictors following myocardial infarction: implications for prophylactic automatic implantable cardioverter-defibrillator use. Prog Cardiovasc Dis 1993; 36:179. 28. Buxton AE, Hafley GE, Lehmann MH, et al. Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables. Circulation 1999; 99:1843. 29. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 2000; 342:1937. 30. Schmitt H, Hurst T, Coch M, et al. Nonsustained, asymptomatic ventricular tachycardia in patients with coronary artery disease: prognosis and incidence of sudden death of patients who are noninducible by electrophysiological testing. Pacing Clin Electrophysiol 2000; 23:1220. 31. Denniss AR, Richards DA, Cody DV, et al. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 1986; 74:731. 32. Marchlinski FE, Buxton AE, Waxman HL, Josephson ME. Identifying patients at risk of sudden death after myocardial infarction: value of the response to programmed stimulation, degree of ventricular ectopic activity and severity of left ventricular dysfunction. Am J Cardiol 1983; 52:1190. 33. Roy D, Marchand E, Th roux P, et al. Programmed ventricular stimulation in survivors of an acute myocardial infarction. Circulation 1985; 72:487. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 13/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 34. Bhandari AK, Rose JS, Kotlewski A, et al. Frequency and significance of induced sustained ventricular tachycardia or fibrillation two weeks after acute myocardial infarction. Am J Cardiol 1985; 56:737. 35. Kowey PR, Waxman HL, Greenspon A, et al. Value of electrophysiologic testing in patients with previous myocardial infarction and nonsustained ventricular tachycardia. Philadelphia Arrhythmia Group. Am J Cardiol 1990; 65:594. 36. Andresen D, Steinbeck G, Br ggemann T, et al. Risk stratification following myocardial infarction in the thrombolytic era: a two-step strategy using noninvasive and invasive methods. J Am Coll Cardiol 1999; 33:131. 37. https://clinicaltrials.gov/ct2/show/NCT03588286?term=PROTECT-ICD&rank=1 (Accessed on J une 14, 2019). 38. Anderson KP, DeCamilla J, Moss AJ. Clinical significance of ventricular tachycardia (3 beats or longer) detected during ambulatory monitoring after myocardial infarction. Circulation 1978; 57:890. 39. Bigger JT Jr, Fleiss JL, Rolnitzky LM. Prevalence, characteristics and significance of ventricular tachycardia detected by 24-hour continuous electrocardiographic recordings in the late hospital phase of acute myocardial infarction. Am J Cardiol 1986; 58:1151. 40. Maggioni AP, Zuanetti G, Franzosi MG, et al. Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results. Circulation 1993; 87:312. 41. Hohnloser SH, Klingenheben T, Zabel M, et al. Prevalence, characteristics and prognostic value during long-term follow-up of nonsustained ventricular tachycardia after myocardial infarction in the thrombolytic era. J Am Coll Cardiol 1999; 33:1895. 42. Senges JC, Becker R, Schreiner KD, et al. Variability of Holter electrocardiographic findings in patients fulfilling the noninvasive MADIT criteria. Multicenter Automatic Defibrillator Implantation Trial. Pacing Clin Electrophysiol 2002; 25:183. 43. Hohnloser SH, Gersh BJ. Changing late prognosis of acute myocardial infarction: impact on management of ventricular arrhythmias in the era of reperfusion and the implantable cardioverter-defibrillator. Circulation 2003; 107:941. 44. Malik M, Camm AJ, Janse MJ, et al. Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: a substudy of EMIAT (The European Myocardial Infarct Amiodarone Trial). J Am Coll Cardiol 2000; 35:1263. 45. Gillis AM. Prophylactic implantable cardioverter-defibrillators after myocardial infarction not for everyone. N Engl J Med 2004; 351:2540. https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 14/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate 46. Armoundas AA, Tomaselli GF, Esperer HD. Pathophysiological basis and clinical application of T-wave alternans. J Am Coll Cardiol 2002; 40:207. Topic 1052 Version 30.0 https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 15/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate GRAPHICS LVEF predicts six-month mortality after STEMI In a study of 1194 patients with an acute ST segment elevation myocardial infarction (STEMI) treated with thrombolysis, the resting left ventricular ejection fraction (LVEF) measured by radionuclide angiography (RNA) was a powerful predictor of six-month mortality. The highest risk group was those with an LVEF <30 percent. Data from Burns RJ, Gibbons RJ, Yi Q, et al. The relationships of left ventricular ejection fraction, end-systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction treated by thrombolysis. J Am Coll Cardiol 2002; 39:30. Graphic 75743 Version 5.0 https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 16/17 7/6/23, 1:39 PM Incidence of and risk stratification for sudden cardiac death after myocardial infarction - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC Consultant/Advisory Boards: Bain Institute [CRO for trials involving Edwards percutaneous valve devices]; Cardiovascular Research Foundation [Data safety monitoring board (RELIEVE-HF Trial)]; Caristo Diagnostics Limited [Imaging and inflammation/atherosclerosis]; Philips Image Guided Therapy Corporation [Imaging]; Sirtex Med Limited [General consulting]; Thrombosis Research Institute [Data safety monitoring board (GARFIELD study)]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/incidence-of-and-risk-stratification-for-sudden-cardiac-death-after-myocardial-infarction/print 17/17 |
7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of sudden cardiac arrest and sudden cardiac death : Philip J Podrid, MD, FACC : Brian Olshansky, MD, Scott Manaker, MD, PhD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jan 27, 2023. INTRODUCTION Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity. These events mostly occur in patients with structural heart disease (that may not have been previously diagnosed), particularly coronary heart disease. (See "Pathophysiology and etiology of sudden cardiac arrest".) The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation) or spontaneous reversion restores circulation, and the event is called SCD if the patient dies [1]. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. The specific causes of SCA vary with the population studied and patient age ( table 1). SCA most commonly results from hemodynamic collapse due to primary ventricular fibrillation (VF) or polymorphic or monomorphic ventricular tachycardia (VT) degenerating into VF. This usually occurs in the setting of structural heart disease ( waveform 1) [2]. Less commonly, SCA may occur with bradycardia/asystole or pulseless electrical activity or electromechanical dissociation. (See "Pathophysiology and etiology of sudden cardiac arrest".) The outcome following SCA depends upon numerous factors including the underlying cause and the rapidity of resuscitation. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest" and "Prognosis and outcomes following sudden cardiac arrest in adults".) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 1/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate A patient is more likely to be resuscitated if they have ventricular tachycardia or VF rather than asystole or pulseless electrical activity. However, if the patient has a poorly tolerated cardiac rhythm, this may be the inevitable consequence of a dying heart. Thus, even early resuscitation may not be successful. Most individuals suffering from SCA become unconscious within seconds to minutes as a result of insufficient cerebral blood flow. There are usually no premonitory symptoms. If symptoms are present, they are nonspecific and include chest discomfort, palpitations, shortness of breath, and weakness. DEFINITIONS Various criteria have been used to define SCA and SCD [3]. Difficulties in deriving a specific definition include the following: Events are witnessed in only one-third of cases, making the diagnosis difficult to establish in many instances [4]. It is not possible to restrict the definition of SCA to documented cases of VT-VF or VF since the cardiac rhythm at clinical presentation is unknown in many cases. The duration of symptoms prior to SCA generally defines the suddenness of death. However, the duration of symptoms is unknown in approximately one-third of cases. For these reasons, operational criteria for SCA and SCD have been proposed that do not rely upon the cardiac rhythm at the time of the event. The criteria focus on the out-of-hospital occurrence of a presumed sudden pulseless condition and the absence of evidence of a noncardiac condition (eg, central airway obstruction, intracranial hemorrhage, pulmonary embolism) as the cause of cardiac arrest. The 2006 American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) to establish data standards for electrophysiology included definitions to guide documentation in research and clinical practice. The following definitions of SCA and SCD were presented: "[Sudden] cardiac arrest is the sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation. If corrective measures are not taken rapidly, this condition progresses to sudden death. Cardiac arrest should be used to signify an event as described above, that is reversed, usually by CPR and/or defibrillation or https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 2/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate cardioversion, or cardiac pacing. Sudden cardiac death should not be used to describe events that are not fatal." Throughout this topic we will use the terms SCA and SCD as defined in the 2006 ACC/AHA/HRS document. However, many continue to use SCD to describe both fatal and nonfatal cardiac arrest. EPIDEMIOLOGY Death certificate data suggest that SCD accounts for approximately 13 to 15 percent of the total mortality in the United States and other industrialized countries [5,6]. However, death certificate data may overestimate the prevalence of SCD [7,8]. In a prospective evaluation of deaths in one county in Oregon, SCD was implicated in 5.6 percent of annual mortality [7]. In absolute terms, the number of sudden cardiac deaths in the United States in 2019 was approximately 370,000 [6]. Despite advances in the treatment of heart disease, the outcome of patients experiencing SCA remains poor, although the prognosis varies significantly according to the initial rhythm and underlying cardiovascular disease. (See "Prognosis and outcomes following sudden cardiac arrest in adults".) The risk of SCA is dependent on several factors [5,8,9]. The incidence increases dramatically with age and underlying cardiovascular disease, as well as specific comorbidities (eg, diabetes) ( figure 1 and figure 2). In addition, men are two to three times more likely to experience SCA than women ( figure 1). Among 161,808 postmenopausal women participating in the Women's Health Initiative who were followed for an average of 10.8 years, the rate of SCD was 2.4 per 10,000 women/year. Nearly half who had SCD did not have clinically recognized coronary heart disease [10]. The magnitude of the influence of cardiovascular disease on the risk of SCA is illustrated by several observations: The risk of SCA is increased 6- to 10-fold in the presence of clinically recognized heart disease, and two- to four-fold in the presence of coronary heart disease (CHD) risk factors [8,11]. SCD is the mechanism of death in over 60 percent of patients with known CHD [5,12,13]. In addition, SCA is the initial clinical manifestation of CHD in approximately 15 percent [14]. ETIOLOGY https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 3/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate SCA usually occurs in people with some form of underlying structural heart disease, most notably CHD ( table 1). The etiologies of SCA are discussed in detail separately, but will be briefly reviewed here. (See "Pathophysiology and etiology of sudden cardiac arrest".) Coronary heart disease The majority of SCAs have been attributed to CHD. Among patients with CHD, SCA can occur both during an acute coronary syndrome (ACS) and in the setting of chronic, otherwise stable CHD (often such patients have had prior myocardial damage and scar that serves as a substrate for SCA) [4]. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features" and "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) The arrhythmic mechanisms and the implications for SCA survivors are different in these two settings. (See "Prognosis and outcomes following sudden cardiac arrest in adults".) Other structural heart disease Other forms of structural heart disease, both acquired and hereditary, account for approximately 10 percent of cases of SCA. Examples of such disorders include the following: Heart failure and dilated cardiomyopathy of any etiology in which SCD is responsible for approximately one-third of deaths. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".) Left ventricular hypertrophy due to hypertension or other causes. (See "Left ventricular hypertrophy and arrhythmia".) Myocarditis. Infiltrative cardiomyopathy (eg, cardiac sarcoid, cardiac amyloid). (See "Management and prognosis of cardiac sarcoidosis" and "Management and prognosis of cardiac sarcoidosis", section on 'Management of arrhythmias and conduction system disease' and "Amyloid cardiomyopathy: Treatment and prognosis".) Hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) Arrhythmogenic right ventricular cardiomyopathy. (See "Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics".) Congenital coronary artery anomalies. (See "Congenital and pediatric coronary artery abnormalities".) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 4/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Mitral valve prolapse. (See "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet".) Valvular heart disease (eg, aortic stenosis). Congenital heart disease (eg, tetralogy of Fallot). Absence of structural heart disease In different reports, approximately 10 to 12 percent of cases of SCA among subjects under age 45 without defined structural heart disease [15,16], while a lower value of about 5 percent has been described when older patients are included [17,18]. San Francisco County between February 2011 and March 2014 suggested greater than 40 percent of clinically-defined SCD was non-arrhythmic in origin, due to causes including occult overdose, neurologic disorders, infection, etc [4]. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease".) SCA can occur due to: Brugada syndrome (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Idiopathic VF, also called primary electrical disease (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF'.) Congenital or acquired long QT syndrome ( table 2) (See "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Familial polymorphic ventricular tachycardia, also called "catecholaminergic polymorphic VT" (See "Catecholaminergic polymorphic ventricular tachycardia".) Familial SCD of uncertain cause Wolff-Parkinson-White syndrome (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Ventricular fibrillation and sudden death'.) Acute triggers In addition to the presence of the underlying disorders of structural heart disease, superimposed triggers for SCA appear to play a major role. These include ischemia, electrolyte disturbances (particularly hypokalemia and hypomagnesemia), proarrhythmic effects of some antiarrhythmic drugs, autonomic https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 5/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate nervous system activation, and psychosocial factors. (See "Pathophysiology and etiology of sudden cardiac arrest", section on 'Transient or reversible causes'.) Commotio cordis SCA can also result from commotio cordis in which VF is precipitated by direct trauma over precordium. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Commotio cordis'.) Circadian pattern SCA has a circadian pattern with a reported peak during the waking hours of 7 to 11 am [19-21]. Among 5200 Framingham Heart Study participants over a 38- year period, 429 cases of SCD were 70 percent higher at 7 to 9 am than they were at other times of day or night [21]. A separate study of 1200 in- and out-of-hospital arrests in Pittsburgh showed the lowest risk of SCA was during early morning sleep hours, between 12 and 6 am [22]. The circadian pattern of SCD mirrors that of other cardiac issues (such as angina, heart failure, and other arrhythmias) that are also more common in the morning [23]. The circadian pattern may result from pineal gland secretion of melatonin-stimulating hormone, resulting in increased melatonin levels and from a morning cortisol surge. Melatonin increases vagal tone, causing lower sympathetic tone and a slower heart rate at night. Melatonin levels are lower in morning (when natural light hits retina suppressing pineal activity) and hence vagal tone is lower. At the same time, the morning cortisol surge also increases as a result of increased sympathetic tone. Warning symptoms "Warning" symptoms may precede the SCA event in a large number of patients, but symptoms may be unrecognized or minimized by patients, and subsequent ascertainment of symptoms is often limited, particularly in patients who do not survive the event. In addition, patients who have SCA and are resuscitated often have a retrograde amnesia and hence do not remember events or symptoms that may have been present. In a community- based study of 839 patients with SCA between 2002 and 2012 in whom symptom assessment could be ascertained (either from the surviving patient or from family members, witnesses at the scene of the event, or medical records from the four weeks leading up to the event), 430 patients (51 percent) were identified as having warning symptoms within four weeks preceding SCA [24]. Eighty percent of patients experienced symptoms at least one hour before SCA, with 34 percent having symptoms more than 24 hours before SCA. Chest pain (46 percent) and dyspnea (18 percent) were the most common symptoms, with women more likely to have experienced dyspnea than chest pain (31 versus 24 percent). Patients with symptoms concerning for cardiac disease, particularly new or unstable symptoms, should seek prompt medical care for potentially life-saving evaluation and treatment. (See "Outpatient evaluation of the adult with chest pain", https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 6/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate section on 'Cardiac conditions' and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".) As symptoms are nonspecific and may reflect benign conditions, and as these symptoms may not necessarily occur before all episodes of cardiac arrest (insensitive), their presence may not be of value in helping offset or prevent episodes. A causal or temporal relationship between symptoms and sudden death has not been established. RISK FACTORS A number of clinical characteristics and other factors are associated with an increased risk of SCA among persons without prior clinically recognized heart disease [25-30]. It should be noted that these risk factors are neither specific nor highly sensitive for SCA prediction. Most risk factors for CHD are also risk factors for SCA. These include dyslipidemia, hypertension, cigarette smoking, physical inactivity, obesity, diabetes mellitus, and a family history of premature CHD or myocardial infarction ( figure 3) [10,25-27,31,32]. (See "Overview of established risk factors for cardiovascular disease".) Cigarette smoking Current cigarette smoking and the number of cigarettes smoked per day among current smokers are strongly related to the risk of SCA in patients with CHD. As an example, among 101,018 women followed for 30 years in the Nurses' Health Study, current smokers had a significantly greater risk of SCD than women who had never smoked (adjusted hazard ratio 2.44, 95% CI 1.80-3.31), and there was an increased risk even among those women who smoked 1 to 14 cigarettes per day (adjusted hazard ratio 1.84, 95% CI 1.16-2.92) [33]. For women in this study who stopped smoking, the risk of SCD declined over time in a linear fashion; these women had the same risk of SCD as never smokers 20 years after quitting [33]. Based upon the observations that the risk of SCA is particularly high among current smokers and declines rapidly after stopping smoking, smoking cessation should be viewed as a critical component of efforts to reduce the risk of SCA as well as a multitude of other complications. (See "Cardiovascular risk of smoking and benefits of smoking cessation" and "Overview of smoking cessation management in adults".) Exercise The risk of SCA is transiently increased during and up to 30 minutes after strenuous exercise compared to other times [27,34]. However, the actual risk during any one episode of vigorous exercise is very low (1 per 1.51 million episodes of exercise) [34]. Furthermore, the magnitude of the transient increase in risk during acute exercise is lower among men who are regular exercisers compared with men for whom exercise is unusual [27,34]. (See "The benefits and risks of aerobic exercise".) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 7/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate The small transient increase in risk during exercise is outweighed by a reduction in the risk of SCA at other times [25,35]. Regular exercise is associated with a lower resting heart rate and increased heart rate variability, characteristics associated with a reduced risk of SCD. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease".) One exception to the lower overall risk associated with intensive exercise occurs in patients with certain, often unrecognized underlying heart diseases. Examples include hypertrophic cardiomyopathy, anomalous coronary artery of wrong sinus origin, myocarditis, and arrhythmogenic right ventricular cardiomyopathy [36,37]. (See "Athletes: Overview of sudden cardiac death risk and sport participation".) Family history of SCA A family history of SCA, either alone or with myocardial infarction, is associated with a 1.5 to 1.8-fold increased risk of SCA [26,32]. The increase in risk is not explained by traditional risk factors that tend to aggregate in families, such as hypercholesterolemia, hypertension, diabetes mellitus, and obesity. The magnitude of the increase in risk associated with the presence of a family history is modest compared to the two- to five-fold increase in risk associated with other modifiable risk factors such as physical inactivity and current cigarette smoking. Few studies have examined potential gene-environment interactions related to the risk of SCD. Nevertheless, it is likely that interactions of mutations or polymorphisms in specific genes and environmental factors influence this risk. Diabetes Among patients with diabetes, type 1 diabetes was more strongly associated with SCA compared with type 2 diabetes and had less favorable outcomes following resuscitation. In a community-based case-control study, 2771 people with SCA were compared with 8313 demographic-matched controls [38]. The following findings were noted: People with diabetes were associated with 1.5 times higher odds of SCA. Among those with diabetes, the odds of having SCA were 2.41 times higher in type 1 than in type 2 diabetes (95% CI 1.53-3.80; p<0.001). People with SCA with type 1 diabetes were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with type 2 diabetes. Serum CRP Chronic inflammation, as manifested in part by higher serum concentrations of C- reactive protein (CRP), has been implicated as a risk factor for a variety of cardiovascular https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 8/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate diseases (including acute coronary syndromes and stroke). Elevated serum CRP is also associated with an increased risk of SCA [39]. (See "C-reactive protein in cardiovascular disease".) Excess alcohol intake Moderate alcohol intake (eg, one to two drinks per day and avoidance of binge drinking) may decrease the risk of SCD [40,41]. In comparison, heavy alcohol consumption (four to six or more drinks per day) or binge drinking increases the risk for SCD. This may be a result of alcohol withdrawal that occurs with heavy alcohol use or binge drinking (which has been termed the "holiday heart syndrome"). Alcohol withdrawal is associated with an elevation of sympathetic neural activity and circulating catecholamines. Each specific type of alcoholic drink (eg, beer, wine, spirits) may have different associations with SCD. In a study from the United Kingdom Biobank, 408,712 middle-aged participants were followed for a median of 12 years for the development of SCD [40]. There were 2044 SCD events. Total alcohol consumption had a U-shaped association with SCD, with the lowest-risk group reporting <26 drinks per week. Consumption of greater amounts of beer, cider, and spirits were associated with increasing SCD risk, whereas increasing wine intake was associated with reduced risk. The association of alcohol with other cardiovascular disease is discussed separately. (See "Cardiovascular benefits and risks of moderate alcohol consumption".) Psychosocial factors Clinical observations have suggested a possible relation between acutely stressful situations and the risk of SCA. Major disasters, such as earthquakes and war, result in a rapid transient increase in the rate of SCA in populations [28,29]. The level of educational attainment and social support from others may alter the risk associated with stressful life events. (See "Psychosocial factors in sudden cardiac arrest".) Caffeine Excessive caffeine intake has been investigated as a potential risk factor for SCA [42]. In the limited data available, no significant association between caffeine intake and SCA have been found. Fatty acids Elevated plasma nonesterified fatty acid (free fatty acid) concentrations were associated with ventricular arrhythmias and SCD after a myocardial infarction [43]. However, nonesterified fatty acids were not associated with SCD in the Cardiovascular Health Study, a population-based cohort of older adults [44]. In addition, in a population-based case-control study among persons without prior clinically recognized heart disease, SCA cases had higher concentrations of trans isomers of linoleic acid in red blood cell membranes [45]. (See "Dietary fat".) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 9/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate In contrast, a higher dietary intake and higher levels of long-chain n-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in plasma and the red blood cell membrane are associated with a lower risk of SCD [30,46-48]. (See 'Fish intake and fish oil' below.) MANAGEMENT The acute management of cardiac arrest is discussed in detail separately. (See "Initial assessment and management of the adult post-cardiac arrest patient".) Management issues for survivors of SCA include the following: Identification and treatment of acute reversible causes Evaluation for structural heart disease In patients without obvious arrhythmic triggers or cardiac structural abnormalities, an evaluation for primary electrical diseases Neurologic and psychologic assessment In selected patients with a suspected or confirmed heritable syndrome, evaluation of family members These issues are discussed in detail separately. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".) PRIMARY PREVENTION The optimal approach to the primary prevention of SCA varies depending on the patient group, as discussed in the sections below. General population There are two approaches to reduce the risk of SCA in the general population: Screening and risk stratification to identify high-risk individuals who may benefit from specific interventions (eg, stress testing, screening ECGs). Interventions that may be expected to reduce SCA risk in any individual (eg, smoking cessation or other lifestyle modifications). Such interventions generally target the underlying disorders that predispose to SCA. https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 10/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Screening and risk stratification Among populations already known to be at an elevated risk of SCA (eg, patients with a prior myocardial infarction), further risk stratification with a variety of tests can identify subgroups that benefit from specific therapies, such as primary prevention with an ICD, particularly those with an ischemic cardiomyopathy and left ventricular ejection fraction <35 percent. (See 'Ischemic heart disease' below and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) However, in the general population without known cardiovascular disease, there is no evidence that routine screening with any test (eg, 12-lead electrocardiography, exercise stress testing, or Holter monitoring) effectively identifies populations at an increased risk of SCA. With regard to risk stratification of the general population, we suggest the following: Screening for risk factors for cardiovascular disease according to standard guidelines. (See "Screening for lipid disorders in adults".) The USPSTF clinical practice guideline for screening for high blood pressure, as well as other USPSTF guidelines, can be accessed through the website for the Agency for Healthcare Research and Quality at www.uspreventiveservicestaskforce.org/. Screening for CHD as appropriate in selected patients, according to standard guidelines. (See "Screening for coronary heart disease".) Routine additional testing for the purpose of SCA risk stratification is not recommended. An issue that merits special consideration is the pre-participation evaluation of athletes. This is a complex issue and there are conflicting opinions regarding whether to screen and, if so, the appropriate nature of a screening evaluation, such as with an electrocardiogram or echocardiogram. (See "Screening to prevent sudden cardiac death in competitive athletes".) Risk factor reduction Many of the traditional risk factors associated with the development of CHD are also associated with SCA. (See 'Risk factors' above and "Overview of primary prevention of cardiovascular disease".) Thus, management of these risk factors may reduce the incidence of SCA in the general public. Such interventions include: Effective treatment of hypercholesterolemia Effective treatment of hypertension Adoption of a heart-healthy diet Regular exercise Smoking cessation https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 11/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Moderation of alcohol consumption Effective treatment of diabetes These interventions are generally in agreement with guidelines published in 2001 by a task force of the European Society of Cardiology [49]. There is no definitive evidence that risk factor reduction in the general population lowers the rate of SCA. However, a number of studies have demonstrated that interventions to treat risk factors can lower total cardiovascular and coronary mortality. Since the majority of CHD mortality is due to SCD, these results suggest that interventions to reduce risk factors will reduce SCA rates as well. (See "Overview of primary prevention of cardiovascular disease".) As an example, a multifactorial, controlled, randomized trial from the Belgian component of the World Health Organization evaluated the effect of efforts aimed at reducing serum cholesterol (via dietary changes), increasing physical activity, and controlling smoking, hypertension, and weight (in those who were overweight) on risk factors and mortality [50]. Compared to the control group, the intervention group had significant reductions in the incidence of CHD and coronary mortality. Moderate alcohol intake Excess alcohol intake increases the risk of SCA, while light-to- moderate alcohol consumption (ie, 2 drinks per day) is associated with a lower risk of coronary heart disease and cardiovascular mortality [41,51]. (See 'Excess alcohol intake' above.) It is reasonable to expect that moderate alcohol intake will also reduce SCA. This effect was documented by the Physicians Health Study, which evaluated 21,537 men who were free of known cardiovascular disease [41]. Compared to men who rarely or never drank, those who had two to four drinks per week or five to six drinks per week had a significantly reduced risk for SCD (relative risks 0.40 and 0.21, respectively); the risk approached unity at 2 drinks per day. (See "Cardiovascular benefits and risks of moderate alcohol consumption".) Regular exercise There are no data from long-term exercise intervention trials among apparently healthy persons that focus upon major disease end points. Nevertheless, regular exercise should be encouraged for the primary prevention of CHD and SCA. Although there is a small transient increase in risk during and shortly after strenuous exercise, there is an overall reduction in SCD among exercisers compared with sedentary men [25,27,35,52]. It is unclear if more exercise (higher intensity or longer duration) is better than less (non-strenuous physical activity, such as walking for exercise 30 minutes most days). (See 'Exercise' above and "The benefits and risks of aerobic exercise" and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease".) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 12/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Patients should be advised to pay attention to potential symptoms of CHD, even if they have engaged in regular exercise without limitations for an extended period of time. In addition, patients with known heart disease should be encouraged to engage in regular exercise in a supervised setting such as a cardiac rehabilitation program. (See "Cardiac rehabilitation programs".) Fish intake and fish oil In observational studies of populations at low cardiovascular risk, greater dietary fatty fish intake was associated with lower cardiac mortality [30,47,48,53,54]. This benefit is due in part to a reduced risk of SCD. Based upon these results, subsequent randomized trials evaluated the benefit of fish oil supplements in various high-risk populations [55,56]. These issues are discussed in detail separately. (See "Fish oil: Physiologic effects and administration".) For most individuals, there is little evidence that the pharmacologic doses of n-3 polyunsaturated fatty acids found in fish oil supplements (approximately 10 to 20 times the nutritional dose from fish) provide more protection than the intake of one to two servings of fatty fish (eg, salmon) per week. The pharmacologic use of fish oils supplements should be restricted to patients with refractory hypertriglyceridemia and, in such patients, the periodic monitoring of apolipoprotein B levels is recommended. (See "Healthy diet in adults" and "Hypertriglyceridemia in adults: Management", section on 'Treatment goals'.) Ischemic heart disease Patients who have ischemic heart disease, particularly those who have had an MI, are at an increased risk of SCA. However, among post-MI patients, this risk varies significantly according to a number of factors. The approach to the prevention of SCA in such patients includes the following: Standard medical therapies. Both beta blockers and ACE inhibitors (or angiotensin II receptor blockers) reduce overall mortality after an MI and are routinely administered. These agents also lower the incidence of SCD. However, the benefit may be limited to three years post MI. Beta blockers post-MI are useful for a longer period of time in patients with post-MI heart failure or ongoing chronic angina. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Guideline-directed medical therapy' and "Acute myocardial infarction: Role of beta blocker therapy".) Risk stratification to identify those patients at the highest risk of SCA. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 13/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate ICD implantation in selected patients, ie, those with an ischemic cardiomyopathy and LVEF <35 percent. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Heart failure and cardiomyopathy Patients with heart failure and left ventricular systolic dysfunction, regardless of the etiology, are at an increased risk of SCA. Primary prevention with an ICD is recommended in selected patients with either ischemic or nonischemic cardiomyopathy, although recent studies have shown less if any benefit of an ICD in those with a nonischemic cardiomyopathy. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Use of an ICD'.) In addition, as with patients with CHD, standard medical therapies for HF (beta blockers, ACE inhibitors or angiotensin II receptor blockers, and aldosterone inhibitors such as spironolactone or eplerenone) may lower the risk of SCA. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy", section on 'Heart failure therapy'.) Inherited arrythmia syndromes Patients with one of the congenital disorders associated with an increased risk of SCA (eg, Brugada syndrome, congenital long QT syndrome, Wolff- Parkinson-White syndrome) are at increased risk for SCA. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation" and "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) Counseling patients and families Given the mounting evidence related to the primary prevention of SCA, it now is clear that primary care clinicians can influence the occurrence of these events. As discussed above, there are clinical recommendations for those at risk of SCA that are likely to reduce risk. (See 'Risk factor reduction' above.) SECONDARY PREVENTION ICD therapy An implantable cardioverter-defibrillator (ICD) is the preferred therapeutic modality in most survivors of SCA. The ICD does not prevent the recurrence of malignant ventricular arrhythmias, but it effectively terminates these arrhythmias when they do recur. The role of the ICD in survivors of SCA is presented separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) ICD patients who have frequent arrhythmia recurrences and device discharges may benefit from adjunctive therapies, such as antiarrhythmic drugs or catheter ablation. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 14/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate 'Antiarrhythmic drugs' and "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Treatment of breakthrough arrhythmias' and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation'.) Other antiarrhythmic therapies Antiarrhythmic drugs are less effective than an ICD for secondary prevention of SCD. Thus, their use in this setting is limited to the adjunctive role described above, or in patients who do not want or are not candidates for an ICD (eg, due to marked comorbidities or end-stage heart failure that make death likely). Patients in whom ventricular arrhythmias result in recurrent shocks despite antiarrhythmic medications may be candidates for catheter ablation in an effort to reduce the arrhythmic burden. (See "Pharmacologic therapy in survivors of sudden cardiac arrest" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Sudden cardiac arrest (The Basics)") SUMMARY AND RECOMMENDATIONS The following summary and recommendations address general issues related to sudden cardiac arrest (SCA) and sudden cardiac death (SCD). https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 15/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Background SCA and SCD refer to the sudden cessation of cardiac activity with hemodynamic collapse. Events that are successfully treated with patient survival are referred to as SCA, while those that lead to death are referred to as SCD. (See 'Definitions' above.) Epidemiology SCD is common, accounting for up to 15 percent of total mortality in industrialized countries, based upon review of death certificate data. Smaller prospective studies, however, have suggested a lower incidence. (See 'Epidemiology' above.) Etiology SCA is most commonly due to ventricular tachyarrhythmias (ie, ventricular |
polyunsaturated fatty acids found in fish oil supplements (approximately 10 to 20 times the nutritional dose from fish) provide more protection than the intake of one to two servings of fatty fish (eg, salmon) per week. The pharmacologic use of fish oils supplements should be restricted to patients with refractory hypertriglyceridemia and, in such patients, the periodic monitoring of apolipoprotein B levels is recommended. (See "Healthy diet in adults" and "Hypertriglyceridemia in adults: Management", section on 'Treatment goals'.) Ischemic heart disease Patients who have ischemic heart disease, particularly those who have had an MI, are at an increased risk of SCA. However, among post-MI patients, this risk varies significantly according to a number of factors. The approach to the prevention of SCA in such patients includes the following: Standard medical therapies. Both beta blockers and ACE inhibitors (or angiotensin II receptor blockers) reduce overall mortality after an MI and are routinely administered. These agents also lower the incidence of SCD. However, the benefit may be limited to three years post MI. Beta blockers post-MI are useful for a longer period of time in patients with post-MI heart failure or ongoing chronic angina. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Guideline-directed medical therapy' and "Acute myocardial infarction: Role of beta blocker therapy".) Risk stratification to identify those patients at the highest risk of SCA. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 13/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate ICD implantation in selected patients, ie, those with an ischemic cardiomyopathy and LVEF <35 percent. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Heart failure and cardiomyopathy Patients with heart failure and left ventricular systolic dysfunction, regardless of the etiology, are at an increased risk of SCA. Primary prevention with an ICD is recommended in selected patients with either ischemic or nonischemic cardiomyopathy, although recent studies have shown less if any benefit of an ICD in those with a nonischemic cardiomyopathy. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Use of an ICD'.) In addition, as with patients with CHD, standard medical therapies for HF (beta blockers, ACE inhibitors or angiotensin II receptor blockers, and aldosterone inhibitors such as spironolactone or eplerenone) may lower the risk of SCA. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy", section on 'Heart failure therapy'.) Inherited arrythmia syndromes Patients with one of the congenital disorders associated with an increased risk of SCA (eg, Brugada syndrome, congenital long QT syndrome, Wolff- Parkinson-White syndrome) are at increased risk for SCA. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation" and "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) Counseling patients and families Given the mounting evidence related to the primary prevention of SCA, it now is clear that primary care clinicians can influence the occurrence of these events. As discussed above, there are clinical recommendations for those at risk of SCA that are likely to reduce risk. (See 'Risk factor reduction' above.) SECONDARY PREVENTION ICD therapy An implantable cardioverter-defibrillator (ICD) is the preferred therapeutic modality in most survivors of SCA. The ICD does not prevent the recurrence of malignant ventricular arrhythmias, but it effectively terminates these arrhythmias when they do recur. The role of the ICD in survivors of SCA is presented separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) ICD patients who have frequent arrhythmia recurrences and device discharges may benefit from adjunctive therapies, such as antiarrhythmic drugs or catheter ablation. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 14/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate 'Antiarrhythmic drugs' and "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Treatment of breakthrough arrhythmias' and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation'.) Other antiarrhythmic therapies Antiarrhythmic drugs are less effective than an ICD for secondary prevention of SCD. Thus, their use in this setting is limited to the adjunctive role described above, or in patients who do not want or are not candidates for an ICD (eg, due to marked comorbidities or end-stage heart failure that make death likely). Patients in whom ventricular arrhythmias result in recurrent shocks despite antiarrhythmic medications may be candidates for catheter ablation in an effort to reduce the arrhythmic burden. (See "Pharmacologic therapy in survivors of sudden cardiac arrest" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Sudden cardiac arrest (The Basics)") SUMMARY AND RECOMMENDATIONS The following summary and recommendations address general issues related to sudden cardiac arrest (SCA) and sudden cardiac death (SCD). https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 15/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Background SCA and SCD refer to the sudden cessation of cardiac activity with hemodynamic collapse. Events that are successfully treated with patient survival are referred to as SCA, while those that lead to death are referred to as SCD. (See 'Definitions' above.) Epidemiology SCD is common, accounting for up to 15 percent of total mortality in industrialized countries, based upon review of death certificate data. Smaller prospective studies, however, have suggested a lower incidence. (See 'Epidemiology' above.) Etiology SCA is most commonly due to ventricular tachyarrhythmias (ie, ventricular fibrillation or ventricular tachycardia). The risk of such arrhythmic events is increased in patients with coronary heart disease or other forms of structural heart disease. In patients with hearts that appear structurally normal, relatively uncommon primary arrhythmia syndromes can cause SCA. (See 'Etiology' above and "Approach to sudden cardiac arrest in the absence of apparent structural heart disease".) Risk factors The risk factors for SCA are similar to those for coronary heart disease. (See 'Risk factors' above.) Management The acute management of SCA involves standard cardiopulmonary resuscitation protocols. (See "Advanced cardiac life support (ACLS) in adults".) Primary prevention A heart-healthy lifestyle, including habitual physical activity, a heart- healthy diet, and abstinence or cessation of cigarette smoking, is recommended for the primary prevention of SCD. General population without known cardiac disease: Apart from standard screening and management of risk factors for CHD (eg, measurement of lipids, BP, and glucose), in patients without known cardiac disease we recommend no additional screening tests or treatment for the purpose of primary prevention of SCD (Grade 1B). (See 'General population' above.) Preparticipation screening of athletes for the purpose of preventing SCD is a unique issue that is discussed in detail separately. (See "Screening to prevent sudden cardiac death in competitive athletes".) Patients with known cardiac disease (eg, prior MI, cardiomyopathy, or heart failure) are at an increased risk of SCA. (See 'Ischemic heart disease' above and 'Heart failure and cardiomyopathy' above.) https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 16/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate The approach to the primary prevention of SCA in such patients includes the following: Standard medical therapies that lower the incidence of SCA. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy", section on 'Heart failure therapy' and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Guideline-directed medical therapy'.) Testing for the purpose of SCA risk stratification in selected subgroups. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) ICD implantation in selected patients. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy", section on 'Prevention of SCD' and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Secondary prevention Management of survivors of SCA includes the identification and treatment of acute reversible causes, evaluation for structural heart disease and/or primary electrical diseases, neurologic and psychologic assessment, and evaluation of family members in selected cases. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".) Secondary prevention of SCD, usually with an ICD, is appropriate for most SCA survivors. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges David Siscovick, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology), Buxton AE, Calkins H, et al. ACC/AHA/HRS 2006 key data elements and https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 17/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate definitions for electrophysiological studies and procedures: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology). Circulation 2006; 114:2534. 2. Demirovic J, Myerburg RJ. Epidemiology of sudden coronary death: an overview. Prog Cardiovasc Dis 1994; 37:39. 3. Siscovick DS. Challenges in cardiac arrest research: data collection to assess outcomes. Ann Emerg Med 1993; 22:92. 4. Tseng ZH, Olgin JE, Vittinghoff E, et al. Prospective Countywide Surveillance and Autopsy Characterization of Sudden Cardiac Death: POST SCD Study. Circulation 2018; 137:2689. 5. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158. 6. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation 2022; 145:e153. 7. Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardiol 2004; 44:1268. 8. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol 2004; 93:1455. 9. Kannel WB, Wilson PW, D'Agostino RB, Cobb J. Sudden coronary death in women. Am Heart J 1998; 136:205. 10. Bertoia ML, Allison MA, Manson JE, et al. Risk factors for sudden cardiac death in post- menopausal women. J Am Coll Cardiol 2012; 60:2674. 11. Kuller LH. Sudden death definition and epidemiologic considerations. Prog Cardiovasc Dis 1980; 23:1. 12. Centers for Disease Control and Prevention (CDC). State-specific mortality from sudden cardiac death United States, 1999. MMWR Morb Mortal Wkly Rep 2002; 51:123. 13. Gillum RF. Sudden coronary death in the United States: 1980-1985. Circulation 1989; 79:756. 14. Kannel WB, Doyle JT, McNamara PM, et al. Precursors of sudden coronary death. Factors related to the incidence of sudden death. Circulation 1975; 51:606. 15. Drory Y, Turetz Y, Hiss Y, et al. Sudden unexpected death in persons less than 40 years of age. Am J Cardiol 1991; 68:1388. 16. Topaz O, Edwards JE. Pathologic features of sudden death in children, adolescents, and young adults. Chest 1985; 87:476. https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 18/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate 17. Chugh SS, Kelly KL, Titus JL. Sudden cardiac death with apparently normal heart. Circulation 2000; 102:649. 18. Survivors of out-of-hospital cardiac arrest with apparently normal heart. Need for definition and standardized clinical evaluation. Consensus Statement of the Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United States. Circulation 1997; 95:265. 19. Muller JE, Ludmer PL, Willich SN, et al. Circadian variation in the frequency of sudden cardiac death. Circulation 1987; 75:131. 20. Willich SN. Epidemiologic studies demonstrating increased morning incidence of sudden cardiac death. Am J Cardiol 1990; 66:15G. 21. Willich SN, Levy D, Rocco MB, et al. Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population. Am J Cardiol 1987; 60:801. 22. Tang Y, Tertulien T, Bhonsale A, et al. Comparison of Circadian Variation for In-Hospital Versus Out-of-Hospital Sudden Cardiac Arrest Survivors. Am J Cardiol 2021; 160:1. 23. Fabbian F, Bhatia S, De Giorgi A, et al. Circadian Periodicity of Ischemic Heart Disease: A Systematic Review of the Literature. Heart Fail Clin 2017; 13:673. 24. Marijon E, Uy-Evanado A, Dumas F, et al. Warning Symptoms Are Associated With Survival From Sudden Cardiac Arrest. Ann Intern Med 2016; 164:23. 25. Siscovick DS, Weiss NS, Hallstrom AP, et al. Physical activity and primary cardiac arrest. JAMA 1982; 248:3113. 26. Friedlander Y, Siscovick DS, Weinmann S, et al. Family history as a risk factor for primary cardiac arrest. Circulation 1998; 97:155. 27. Siscovick DS, Weiss NS, Fletcher RH, Lasky T. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984; 311:874. 28. Trichopoulos D, Katsouyanni K, Zavitsanos X, et al. Psychological stress and fatal heart attack: the Athens (1981) earthquake natural experiment. Lancet 1983; 1:441. 29. Kark JD, Goldman S, Epstein L. Iraqi missile attacks on Israel. The association of mortality with a life-threatening stressor. JAMA 1995; 273:1208. 30. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long- chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA 1995; 274:1363. 31. Kannel WB, Thomas HE Jr. Sudden coronary death: the Framingham Study. Ann N Y Acad Sci 1982; 382:3. https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 19/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate 32. Jouven X, Desnos M, Guerot C, Ducimeti re P. Predicting sudden death in the population: the Paris Prospective Study I. Circulation 1999; 99:1978. 33. Sandhu RK, Jimenez MC, Chiuve SE, et al. Smoking, smoking cessation, and risk of sudden cardiac death in women. Circ Arrhythm Electrophysiol 2012; 5:1091. 34. Albert CM, Mittleman MA, Chae CU, et al. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 2000; 343:1355. 35. Lemaitre RN, Siscovick DS, Raghunathan TE, et al. Leisure-time physical activity and the risk of primary cardiac arrest. Arch Intern Med 1999; 159:686. 36. Maron BJ, Carney KP, Lever HM, et al. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. J Am Coll Cardiol 2003; 41:974. 37. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998; 339:364. 38. Norby FL, Reinier K, Uy-Evanado A, et al. Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes. Mayo Clin Proc 2022; 97:2271. 39. Albert CM, Ma J, Rifai N, et al. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 2002; 105:2595. 40. Tu SJ, Gallagher C, Elliott AD, et al. Alcohol consumption and risk of ventricular arrhythmias and sudden cardiac death: An observational study of 408,712 individuals. Heart Rhythm 2022; 19:177. 41. Albert CM, Manson JE, Cook NR, et al. Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians. Circulation 1999; 100:944. 42. Weinmann S, Siscovick DS, Raghunathan TE, et al. Caffeine intake in relation to the risk of primary cardiac arrest. Epidemiology 1997; 8:505. 43. Jouven X, Charles MA, Desnos M, Ducimeti re P. Circulating nonesterified fatty acid level as a predictive risk factor for sudden death in the population. Circulation 2001; 104:756. 44. Djouss L, Biggs ML, Ix JH, et al. Nonesterified fatty acids and risk of sudden cardiac death in older adults. Circ Arrhythm Electrophysiol 2012; 5:273. 45. Lemaitre RN, King IB, Raghunathan TE, et al. Cell membrane trans-fatty acids and the risk of primary cardiac arrest. Circulation 2002; 105:697. 46. Harper CR, Jacobson TA. The fats of life: the role of omega-3 fatty acids in the prevention of coronary heart disease. Arch Intern Med 2001; 161:2185. 47. Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002; 346:1113. https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 20/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate 48. Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med 1997; 336:1046. 49. Priori SG, Aliot E, Blomstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22:1374. 50. De Backer G, Kornitzer M, Dramaix M, et al. The Belgian Heart Disease Prevention Project: 10-year mortality follow-up. Eur Heart J 1988; 9:238. 51. Wannamethee G, Shaper AG. Alcohol and sudden cardiac death. Br Heart J 1992; 68:443. 52. Shephard RJ, Balady GJ. Exercise as cardiovascular therapy. Circulation 1999; 99:963. 53. Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985; 312:1205. 54. Albert CM, Hennekens CH, O'Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA 1998; 279:23. 55. Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)- Prevenzione. Circulation 2002; 105:1897. 56. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999; 354:447. Topic 963 Version 33.0 https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 21/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate GRAPHICS Major causes of sudden death Ischemic heart disease Coronary artery disease with myocardial infarction or angina Coronary artery embolism Nonatherogenic coronary artery disease (arteritis, dissection, congenital coronary artery anomalies) Coronary artery spasm Nonischemic heart disease Hypertrophic cardiomyopathy Dilated cardiomyopathy Valvular heart disease Congenital heart disease Arrhythmogenic right ventricular dysplasia Myocarditis Acute pericardial tamponade Acute myocardial rupture Aortic dissection No structural heart disease Primary electrical disease (idiopathic ventricular fibrillation) Brugada syndrome (right bundle branch block and ST segment elevation in leads V1 to V3) Long QT syndrome Preexcitation syndrome Complete heart block Familial sudden cardiac death Chest wall trauma (commotio cordis) Noncardiac disease Pulmonary embolism Intracranial hemorrhage Drowning Pickwickian syndrome https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 22/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Drug-induced Central airway obstruction Sudden infant death syndrome Sudden unexplained death in epilepsy (SUDEP) Graphic 62184 Version 3.0 https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 23/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate ECG 12-lead ventricular fibrillation 12-lead ECG showing course ventricular fibrillation. ECG: electrocardiogram. Graphic 118944 Version 1.0 https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 24/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Incidence of sudden death in men and women increases with age During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden death increased with age in both men and women. However, at each age, the incidence of sudden death is higher in men than women. Data from Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 59028 Version 4.0 https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 25/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Risk of SCD is related to clinical manifestations of CHD During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden cardiac death (SCD) in both men and women was related to the clinical manifestations of coronary heart disease (CHD). It was highest in those with a myocardial infarction, intermediate in those with angina and no prior infarction, and lowest in those without overt CHD. Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 52309 Version 2.0 https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 26/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial GnRH agonist/antagonist therapy ischemia or infarction, Hypomagnesemia Bilateral surgical orchiectomy Hypocalcemia Diuretic therapy via electrolyte disorders especially with Starvation particularly hypokalemia and hypomagnesemia prominent T-wave inversions Anorexia nervosa Herbs Liquid protein diets Cinchona (contains quinine), iboga (ibogaine), licorice extract in overuse via electrolyte disturbances Intracranial disease Hypothyroidism Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate insecticides AV block: Second or third degree Medications* High risk Adagrasib Cisaparide Lenvatinib Selpercatinib (restricted availability) Ajmaline Levoketoconazole Sertindole Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine Vandetanib Dofetilide (intracoronary) Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab ozogamacin Propafenone Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 27/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Certinib Escitalopram Levofloxacin Risperidone (systemic) Chloroquine Etelcalcetide Saquinavir Lofexidine Citalopram Fexinidazole Sevoflurane Meglumine Clarithromycin Flecainide Sparfloxacin antimoniate Clofazimine Floxuridine Sunitinib Midostaurin Clomipramine Fluconazole Tegafur Moxifloxacin Clozapine Fluorouracil Terbutaline Nilotinib (systemic) Crizotinib Thioridazine Olanzapine Flupentixol Dabrafenib Toremifene Ondansetrol (IV > Gabobenate dimeglumine Dasatinib Vemurafenib oral) Deslurane Voriconazole Osimertinib Gemifloxacin Domperidone Oxytocin Gilteritinib Doxepin Pazopanib Halofantrine Doxifluridine Pentamidine Haloperidol (oral) Pilsicainide Imipramine Pimozide Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole (systemic) Romidepsin Anagrelide Foscarnet Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- Glasdegib Mizolastine lumefantrine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine Nortriptyline Benperidol (rare reports) Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus Olodaterol (systemic) Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone Degarelix Lefamulin Pasireotide Triclabendazole https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 28/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- Periciazine Tropisetron norethindrone Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide overdose in Eliglustat Primaquine Vorinostat Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2) available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM 073161.pdf with additional data from CredibleMeds QT drugs list criteria may lead to some agents being classified differently by other sources. [1,2] . The use of other classification Not available in the United States. In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long QT syndrome. Withdrawn from market in most countries due to adverse cardiovascular effects. IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses administered orally as an antipsychotic. Other cyclic antidepressants may also prolong the QT interval; refer to UpToDate clinical topic on cyclic antidepressant pharmacology, side effects, and separate UpToDate topic on tricyclic antidepressant poisoning. The "low risk" category includes drugs with limited evidence of clinically significant QTc prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects or recommendations to avoid use or increase ECG monitoring when combined with other QTc prolonging drugs. https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 29/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use disorder, making buprenorphine a suitable alternative for patients with methadone-associated QTc prolongation. Refer to UpToDate clinical topic reviews. * The United States FDA labeling for the sublingual preparation of dexmedetomidine warns against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not been implicated in TdP. Over-the-counter; available without a prescription. Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical topic for potential adverse cardiovascular (CV) effects in patients with CV disease. Data from: 1. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. 2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/. Graphic 57431 Version 142.0 https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 30/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Additive effects of risk factors on cardiovascular disease at 5 years Cumulative absolute risk of CVD at 5 years according to systolic blood pressure and specified levels of other risk factors. The reference category is a non-diabetic, non-smoking 50-year-old woman with a serum TC of 154 mg/dL (4.0 mmol/L) and HDL cholesterol of 62 mg/dL (1.6 mmol/L). The CVD risks are given for systolic blood pressure levels of 110, 130, 150, and 170 mmHg. In the other categories, the additional risk factors are added consecutively. As an example, the diabetes category is a 50-year-old diabetic man who is a smoker and has a TC of 270 mg/dL (7 mmol/L) and HDL cholesterol of 39 mg/dL (1 mmol/L). BP: blood pressure; CVD: cardiovascular disease; HDL: high-density lipoprotein; TC: total cholesterol. Adapted from: Jackson R, Lawes CM, Bennett DA, et al. Lancet 2005; 365:434. Graphic 55353 Version 12.0 https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 31/32 7/6/23, 1:40 PM Overview of sudden cardiac arrest and sudden cardiac death - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-sudden-cardiac-arrest-and-sudden-cardiac-death/print 32/32 |
7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Pathophysiology and etiology of sudden cardiac arrest : Philip J Podrid, MD, FACC : Brian Olshansky, MD, Scott Manaker, MD, PhD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 15, 2023. INTRODUCTION Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity with hemodynamic collapse, typically due to sustained ventricular tachycardia/ventricular fibrillation. These events mostly occur in patients with structural heart disease (that may not have been previously diagnosed), particularly coronary heart disease. The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation) or spontaneous reversion restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.) The cardiac diseases that lead to the genesis of the arrhythmia resulting in cardiac collapse and sudden death are varied, and the association with sudden death in some cases is poorly understood [1]. Identification of the patient at risk for sudden death and identification of the factors that precipitate the fatal arrhythmia continue to represent a major challenge. This topic will review the mechanisms and etiology of SCA. Treatment for SCA, the evaluation of survivors, and the outcomes of SCA are discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Cardiac evaluation of the survivor of sudden cardiac arrest" and "Prognosis and outcomes following sudden cardiac arrest in adults".) TYPES OF ARRHYTHMIAS LEADING TO SUDDEN CARDIAC DEATH https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 1/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate The exact mechanism of collapse in an individual patient is often impossible to establish since, for the vast majority of patients who die suddenly, cardiac activity is not being monitored at the time of their collapse. As a result, the mechanism can only be inferred based upon information obtained after the process has been initiated. However, there have been many cases in which the initiating event has been witnessed or recorded [2-4]. This has usually occurred in patients being continually monitored in the coronary care unit, those with a 24-hour ambulatory electrocardiogram (ECG) recording device, or those with an implantable cardioverter-defibrillator (ICD). Ventricular tachycardia (VT) or ventricular fibrillation (VF) account for the majority of episodes [2,4]. However, a bradyarrhythmia is responsible for some cases of SCD. A bradyarrhythmia and asystole were, in initial studies, less common causes of SCD, being observed in only about 10 percent of cases documented on an ambulatory monitor [2]. A bradyarrhythmia is more often associated with a nonischemic cardiomyopathy [5], while pulseless electrical activity, electromechanical dissociation, or asystole are the most common rhythms seen with a pulmonary embolism [6]. Other causes for pulseless electrical activity include myocardial rupture, tamponade, pneumothorax, hypoxemia, or drug overdose. In some cases, the bradyarrhythmia may result in a ventricular tachyarrhythmia as an escape mechanism. The distribution is different among patients with an ICD. Arrhythmic death accounts for 20 to 35 percent of deaths; post-shock or primary pulseless electrical activity (PEA, also called electromechanical dissociation) is a frequent cause of SCD in this setting [7]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Epidemiology'.) The distribution of causes is also different with unmonitored out-of-hospital SCD. VF and pulseless VT appear to be responsible for 25 to 35 percent of episodes, although estimates vary widely. PEA accounts for as much as 25 percent of all cases of SCD. Among patients who collapse in an unmonitored setting in whom the exact time of onset and the etiologic arrhythmia are uncertain, asystole is often the first rhythm observed [8]. Asystole correlates with the duration of the arrest and may be the result of VF that has been present for several minutes or longer and then leads to loss of all electrical activity as a result of hypoxia, acidosis, and death of myocardial tissue ( waveform 1) [9]. ARRHYTHMIC MECHANISMS https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 2/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Mechanism of ventricular tachycardia In approximately 80 percent of patients with VT/VF, the sustained ventricular arrhythmia is preceded by an increase in ventricular ectopy and the development of repetitive ventricular arrhythmia, particularly runs of nonsustained VT [2]. These spontaneous arrhythmias are present for a variable period of time prior to the development of VT/VF. Sustained monomorphic VT can accelerate to a rapid rate and then degenerate into VF. However, the relationship between monomorphic VT and SCD has been debated, with some studies suggesting that this arrhythmia is present in only a minority of patients with SCD [10,11]. Thus, sustained monomorphic VT may simply be the company kept by VF or, in the appropriate setting such as recurrent coronary ischemia, it may provide a rapid wavefront that becomes fractionated, leading to VF [11]. A sustained polymorphic VT can degenerate into VF. This is most often the result of underlying ischemia (ie, polymorphic VT without QT prolongation or a short QT interval of the sinus QRS complex), although it may also result from acquired or congenital QT prolongation or congenital short QT interval. A very rare cause of polymorphic VT without QT prolongation is a genetic abnormality associated with catecholaminergic polymorphic VT (a result of an abnormality of a ryanodine or calsequestrin gene). (See "Catecholaminergic polymorphic ventricular tachycardia" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) VF can develop as a primary event. In approximately one-third of cases, the tachyarrhythmia is initiated by an early R on T premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations); in the remaining two-thirds, the arrhythmia is initiated by a late cycle PVC [2]. Mechanism of ventricular fibrillation VF results from multiple localized areas of microreentry without any organized electrical activity [12]. The most likely mechanism is rotating spiral waves [13]. This almost always occurs in the setting of underlying myocardial disease (or abnormalities in repolarization as in the long QT syndrome) that is often diffuse, resulting in heterogeneity of depolarization and the dispersion of repolarization. This disparity of electrophysiologic properties is a precondition for reentry. A triggering event is usually necessary to precipitate the arrhythmia in a vulnerable heart [14]. The identification of a precipitating factor is more likely if there is less heart disease, and when there is more heart disease, a precipitating factor may be more difficult to define. (See "Reentry and the development of cardiac arrhythmias".) https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 3/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate The diversity in conduction and recovery parameters (myocardial heterogeneity) results in fragmentation of the impulse as it travels through the myocardium, producing multiple areas of localized reentry or multiple spiral wavelets of myocardial activation [12]. Since there is no organized electrical activity or myocardial depolarization, there is no uniform ventricular contraction resulting in failure of the heart to generate a cardiac output. With the development of global ischemia, the rate of VF decreases because of a reduction in the rotation period of the spiral waves which results from the increase in their core area [13]. The ECG in established VF shows high-frequency undulations or fibrillatory waves that are irregular in amplitude, morphology, and periodicity, occurring at a rate above 320/minute; organized QRS complexes are not seen ( waveform 1) [15]. However, at the very onset of VF, the irregular fibrillatory waves may be coarse with a tall amplitude (and may resemble polymorphic VT) or may occasionally appear to be regular ( waveform 2). The QRS complexes in this latter setting are indistinguishable from the T waves, and they appear to be sinusoidal in configuration. This finding may represent a brief period of an organized ventricular flutter, with a rate exceeding 260 beats per minute. In cases where the coarse fibrillatory waves resemble polymorphic VT, these initial ECG changes are collectively referred to as type I VF and may be associated with spontaneous defibrillation [16,17]. Importantly, polymorphic VT may spontaneously terminate, while VF never self-terminates but only responds to defibrillation. (See "Cardioversion for specific arrhythmias".) As the duration of VF increases, progressive cellular ischemia and acidosis develop, resulting in an electrophysiologic deterioration, manifested by an increase in fibrillation cycle length and prolonged diastole duration between fibrillation action potentials [9,17,18]. During this later (type II) VF, the fibrillatory waves rapidly become finer and more irregular in amplitude, duration, and cycle length; spontaneous resolution or reversion with an antiarrhythmic drug has not been observed [16,17]. Over a period of several minutes, the fibrillatory waves become so fine that there does not appear to be any electrical activity ( waveform 1) [15]. ETIOLOGY OF SCD There are many cardiac and noncardiac causes for a sustained ventricular tachyarrhythmia that can result in sudden cardiac death (SCD) ( table 1). Common causes of SCD The following approximate frequency of causes of out-of-hospital SCDs have been described [19-25]: Sixty-five to 70 percent of all SCDs are attributable to coronary heart disease (CHD) [19,20]. Most often, there is no evidence for an acute myocardial infarction, although acute https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 4/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate ischemia may be the precipitating cause. Cardiac biomarkers are often elevated as a result of ischemia due to the arrhythmia or the result of defibrillation, making the diagnosis of an acute myocardial infarction preceding the event difficult to establish. However, the frequency of CHD is much lower in SCDs occurring under the age of 30 to 40 (eg, 24 percent under the age of 30 in a review of SCDs in the United States in 1999, and 8 percent in a series of autopsies in military recruits) [19,26]. These observations were largely made from analyses of all reported SCDs in the United States using the diagnosis on the death certificate, which is of uncertain accuracy. A similar frequency of CHD was noted in a study of 84 consecutive survivors of out-of-hospital cardiac arrest [21]. Immediate coronary angiography revealed clinically significant coronary disease in 60 (71 percent) of the patients, 40 of whom (48 percent of all patients) had an occluded coronary artery. The absence of an occluded coronary artery in the other 20 patients does not preclude an acute coronary syndrome (or ischemia) since absence of occlusion on early angiography is seen in 60 to 85 percent of patients with a non-ST elevation acute coronary syndrome and in up to 28 percent of patients with an ST elevation MI. Ten percent of SCDs are due to other types of structural heart disease (eg, any type of cardiomyopathy, congenital coronary artery anomalies, myocarditis, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) [19,20,26]. The frequency is much higher in subjects under the age of 30 (over 35 percent in a review of SCDs in the United States in 1999, and over 40 percent in a series of autopsies in military recruits) [19,26]. Five to 10 percent of SCDs are primary arrhythmogenic, occurring in the absence of structural heart disease (eg, long QT syndrome, Brugada syndrome, Wolff-Parkinson-White syndrome, catecholaminergic polymorphic ventricular tachycardia [VT]). In the absence of any structural abnormality or electrophysiologic abnormality on the ECG, these entities are often termed primary electrical disease [22-24]. Fifteen to 25 percent of cardiac arrests are noncardiac in origin [22,25]. The causes include trauma, bleeding, drug intoxication, intracranial hemorrhage, pulmonary embolism, near- drowning, and central airway obstruction. Although not specifically mentioned in most of these studies, heart failure (HF) is a relatively common cause of SCD. SCD accounts for 30 to 50 percent of deaths in patients with heart failure (HF) [27], and the incidence of SCD appears to be increased during periods of worsening HF symptoms [28]. Although the risk of both arrhythmic and nonarrhythmic death can be reduced https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 5/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate with appropriate chronic HF therapy, the SCD risk remains elevated. Thus, virtually all SCD survivors with HF receive an ICD. A detailed discussion of arrhythmic events and the effect of medical therapy in HF patients is presented separately. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".) The incidence of SCD increases with age in both men and women; however, at any level of multivariate risk, women are less vulnerable to sudden death than men and a higher fraction of sudden deaths in women occur in the absence of prior overt CHD ( figure 1) [18,29]. Transient or reversible causes A number of transient or reversible conditions may precipitate arrhythmic events and SCD. Identification of such conditions is critical both for the management of the underlying disorder and for determining the likelihood of recurrent SCD. (See "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'Initial evaluation'.) In some of these cases, management of the underlying disorder is all that is necessary to reduce the risk of recurrent events. However, despite an apparently reversible trigger for SCD, many patients have a persistent risk of recurrent events (due to the presence of irreversible structural heart disease) and may benefit from implantable cardioverter-defibrillator (ICD) therapy or, in some cases, pharmacologic therapy with an antiarrhythmic drug. (See "Prognosis and outcomes following sudden cardiac arrest in adults".) Potentially reversible triggers for SCD include the following: Acute cardiac ischemia and myocardial infarction Because CHD is the most common cause of SCD, acute coronary ischemia, even in the absence of evidence for an acute myocardial infarction, should be considered in all survivors of SCD. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features" and "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'Coronary angiography'.) Antiarrhythmic drugs All antiarrhythmic drugs have proarrhythmic properties, particularly in patients with underlying cardiac disease, especially when heart failure is present [30-32]. Among SCD survivors who have been taking antiarrhythmic medications, it is difficult to be certain if the arrest was provoked by the drug or occurred despite its use [33]. Thus, it is often difficult to know if antiarrhythmic medications should be discontinued, increased, or adjusted. In such patients, involvement of an arrhythmia specialist is recommended. Medication (eg, QT prolonging drugs), toxin, or illicit drug ingestion [34,35]. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 6/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Electrolyte abnormalities, most notably hypokalemia, hyperkalemia, and hypomagnesemia. pH changes, especially acidemia (respiratory or metabolic). Heart failure The incidence of SCD appears to be increased during periods of worsening HF symptoms [28]. However, HF is a chronic disease, and although acute episodes may be managed, the condition is not truly transient or reversible. Even with appropriate chronic HF therapy, the SCD risk remains elevated. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".) Severe hypoxemia. Autonomic nervous system activation, especially sympathetic neural inputs. Autopsy studies The distribution of cardiac causes of SCD varies with age, the population studied, and geography. While coronary heart disease (CHD) is listed as the underlying cause of SCD on 62 percent of death certificates among the general population in the United States [20], younger patients, athletes, and those without known prior disease have a different distribution of causes [22,36,37]: In an autopsy study of 902 persons with suspected SCD (mean age 38 years), 715 cases (79 percent) occurred in persons with underlying cardiac pathology [38]. CHD was felt to be the primary cause of SCD in 511 patients (57 percent); however, CHD was far more common in persons 35 years of age or older (73 percent versus 23 percent in those <35 years), whereas those under 35 years of age were significantly more likely to die from non-CHD causes such as sudden unexplained death (primary arrhythmic death, 41 versus 11 percent), hypertrophic cardiomyopathy (13 versus 3 percent), or myocarditis (6 versus 2 percent). An autopsy study from Israel evaluated 162 subjects aged 9 to 39 years with SCD; none had previously diagnosed underlying cardiac disease, and death occurred in the absence of trauma within 24 hours of onset of symptoms [22]. Approximately 15 percent of deaths were noncardiac (most often intracranial hemorrhage), and 73 percent were cardiac. Among those 20 to 29 years of age, CHD was found in 24 percent, myocarditis in 22 percent, and hypertrophic cardiomyopathy (HCM) in 13 percent. Among those 30 to 39 years of age, CHD was found in 58 percent, myocarditis in 11 percent, and HCM in 2 percent. An autopsy series from the United States evaluated 286 competitive athletes under age 35 in whom cardiovascular disease was shown to be the cause of SCD [36]. The most common underlying disorders were HCM (36 percent, with possible HCM in another 10 percent), an https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 7/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate anomalous origin of a coronary artery (13 percent), and myocarditis (7 percent). (See "Athletes: Overview of sudden cardiac death risk and sport participation".) A markedly different distribution was noted in a report from northern Italy where arrhythmogenic right ventricular cardiomyopathy or dysplasia (ARVC or ARVD) is relatively common [37]. Among 49 sudden deaths in young athletes, ARVC was most common (22 percent), followed by coronary atherosclerosis (18 percent), an anomalous origin of a coronary artery (12 percent), and HCM in only 2 percent. Myocardial ischemia and infarction Approximately 65 to 70 percent of SCDs are attributable to CHD [19,20], and it is estimated that SCD accounts for 30 to 50 percent of coronary deaths [18,39]. The incidence of SCD is related to the clinical manifestations of preexisting CHD, being highest in those with a prior myocardial infarction (MI) and intermediate in those who have angina without a prior infarction ( figure 2) [18]. However, SCD can occur in patients with silent (or discomfortless) ischemia and can be the initial manifestation of CHD. (See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".) Among SCD episodes that occur without warning, angiography demonstrates an occluded coronary artery in almost one-half of patients [21]. Clinical and ECG changes appear to correlate poorly with coronary occlusion. Furthermore, among patients with typical ECG changes or cardiac enzyme elevations after resuscitation, it may be difficult on clinical grounds alone to determine whether an acute MI caused ventricular fibrillation (VF), or if VF resulted in myocardial injury because of the absence of coronary artery blood flow and/or the result of defibrillation. Among patients who present with an acute MI rather than SCD, the incidence of VF varies with the type of infarct and time. This topic is discussed in detail separately but will be briefly reviewed here. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Incidence'.) The largest experience with acute ST elevation MI comes from the GUSTO-1 trial of 40,895 patients who were treated with thrombolytic therapy [40]. The overall incidence of VT or VF was 10.2 percent: 3.5 percent developed VT, 4.1 percent VF, and 2.7 percent both VT and VF. Approximately 80 to 85 percent of these arrhythmias occurred in the first 48 hours. The best data in non-ST elevation acute coronary syndrome come from a pooled analysis of four major trials of over 25,000 patients [41]. The overall incidence of VT or VF was 2.1 percent: VT occurred in 0.8 percent, VF in 1 percent, and VT and VF in 0.3 percent. The median time to arrhythmia was 78 hours, with the 25th and 75th percentiles being 16 hours and seven days. https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 8/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate A peak incidence of VF within the first 48 hours after acute MI has also been noted in other reports [42,43]. These episodes are presumably due to ischemia, while later onset VF may be related to healing of the infarct with the development of scar (and an increased risk of monomorphic VT) and associated with an increased risk of late SCD. Late SCD most often occurs in the first year, with the majority of events seen within the first few months and being due to a ventricular tachyarrhythmia [44,45]. The risk of late VT/VF appears to be equivalent in patients with ST elevation and non-ST elevation infarctions [44]. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) These data do not include patients with SCD who do not survive until hospitalization. It has been estimated that more than 50 percent of deaths due to acute MI occur out of the hospital, and most episodes occur within one hour of symptom onset [46]. Among patients with out-of- hospital cardiac arrest, the risk is greater in those with acute occlusion of the left anterior descending or left circumflex arteries (odds ratio 4.82 and 4.92, respectively, compared with those with a right coronary artery occlusion). In addition, there are patients who have unstable coronary lesions that may be responsible for acute ischemic events, short of infarction, and that can cause electrical instability [21,47,48]. The potential frequency of this effect was illustrated in a report of 84 resuscitated patients who underwent coronary angiography immediately upon admission: 76 percent had significant coronary disease, spasm, or an unstable lesion, and almost one-half had coronary occlusion [21]. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".) The importance of unstable plaques has been confirmed in a number of autopsy studies of men and women with coronary disease who died suddenly [48-52]. (See "Mechanisms of acute coronary syndromes related to atherosclerosis".) In a report of 113 such men: 59 had an acute coronary thrombus and 54 had severe narrowing of the coronary artery by an atherosclerotic plaque without acute thrombosis (stable plaque) [48]. Among those with acute thrombosis, 41 resulted from rupture of a vulnerable plaque (a thin fibrous cap overlying a lipid-rich core) and 18 from erosion of a fibrous plaque rich in smooth-muscle cells and proteoglycans. The likelihood of plaque rupture may vary in different subgroups. In a review of 141 men with SCD associated with coronary artery disease, the 25 patients who died during exertion were significantly more likely to have plaque rupture (72 versus 23 percent in those who died at rest) and hemorrhage into the plaque (72 versus 41 percent) [50]. Among patients with SCD associated with unstable angina, the thrombi typically have a layered appearance indicative of episodic growth [51]. Episodic growth may alternate with https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 9/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate intermittent fragmentation of the thrombus, leading to distal embolization of both thrombus and platelet aggregates and microinfarction [51,52]. The presence of severe coronary disease alone in a survivor of SCD does not prove a cause-and- effect relationship. Among patients who are not in the acute phase of a myocardial infarction, an appreciable risk of recurrent VT/VF may persist despite successful revascularization as a result of underlying myocardial disease and fibrosis [53,54]. Heart failure The presence of heart failure (HF), regardless of etiology, increases overall mortality and the incidence of SCD in both men and women. This was illustrated in a 38-year follow-up of patients in the Framingham Heart Study: the incidence of SCD in those with HF, compared with those without HF, was increased fivefold in both sexes, although the absolute risk in women was only one-third that of men ( figure 3) [18]. The SCD death potential in men and women with HF was as great as that noted in patients with overt coronary heart disease (13.7 and 3.8 versus 12.9 and 2.4 per 1000 patients, respectively). (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".) Published series suggest a relatively consistent pattern with 30 to 50 percent of all cardiac deaths in patients with HF being categorized as sudden deaths, with or without preceding symptoms. However, it is often difficult to distinguish those dying suddenly and unexpectedly from those experiencing terminal arrhythmias in the setting of progressive hemodynamic deterioration. It has been suggested that progressive pump failure, sudden arrhythmic death, and sudden death during episodes of clinical worsening each account for approximately one- third of deaths [27]. In the AIRE trial, for example, only 39 percent of sudden deaths were thought to be due to arrhythmia [28]. VT degenerating into VF is the most common cause of SCD; a bradyarrhythmia or PEA is responsible in 5 to 33 percent of cases [27]. An acute coronary event appears to be the precipitating factor in some patients with HF. The prevalence of coronary thrombus, ruptured plaque, or myocardial infarction and its relationship to SCD was examined in an autopsy study of 171 patients with HF in the ATLAS trial [55]. In patients with significant coronary artery disease, an acute coronary finding was found in 54 percent who died suddenly and in 32 percent who died of myocardial failure, although an acute coronary event had not been clinically diagnosed before death. In contrast, an acute coronary finding was uncommon in those without coronary disease, occurring in only 5 percent of those who died suddenly and in 10 percent of those who died of myocardial failure. Left ventricular hypertrophy Hypertension with left ventricular hypertrophy (LVH) appears to increase the risk of SCD. Myocardial hypertrophy due to hypertension is often associated with myocardial fibrosis and may be a precondition for ventricular arrhythmia. In addition, chronic https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 10/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate subendocardial ischemia (accounting for the ST-T wave changes that are often seen) is often present with the hypertrophy and the increased oxygen demands; the subendocardium, which is the last part of the myocardium to receive blood supply, may have a reduced oxygen supply resulting in ischemia. In addition, many patients with hypertension and LVH have underlying coronary artery disease. Such patients appear to be less likely to have coronary thrombi than normotensives who had SCD [56]. However, most such patients have severe coronary disease suggesting that the hypertrophied myocardium is more susceptible than normal myocardium to the effects of ischemia [56]. SCD also occurs more commonly in patients with hypertrophic cardiomyopathy. Among competitive athletes who die from SCD due to proven cardiac cause, hypertrophic cardiomyopathy may be one of the most common underlying disorders, accounting for 36 percent of 286 cases in an autopsy series [36]. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) Absence of known structural heart disease Sudden cardiac death can occur in patients who have no previous history of heart disease [22,29,57]. Other causes of death that could be misinterpreted as SCD (eg, acute drug overdose or intoxication) should also be excluded [58]. However, most of these patients with SCD have underlying structural heart disease. (See "General approach to drug poisoning in adults" and "Acute opioid intoxication in adults".) The frequency with which this occurs was illustrated in an autopsy study that evaluated 162 subjects aged 9 to 39 years with SCD; none had previously diagnosed underlying disease and death occurred in the absence of trauma and within 24 hours of onset of symptoms [22]. The following findings were noted: Approximately 15 percent of deaths were noncardiac (most often intracranial hemorrhage) and 73 percent were cardiac. The most common causes of heart disease were coronary disease (58 percent in those over age 30 compared with 22 percent in younger subjects), myocarditis (11 and 22 percent in the two age groups), hypertrophic cardiomyopathy (13 percent in younger subjects), sarcoidosis, and arrhythmogenic right ventricular cardiomyopathy. Approximately one-half had some prodromal symptoms, such as chest pain or dizziness. SCD occurred during routine activity in 49 percent, during sleep in 23 percent, and in relation to exercise in 23 percent. The association with exercise has also been described in competitive athletes. In a United States registry of SCD in 286 competitive athletes under age 35 in whom cardiovascular disease was https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 11/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate shown to be the cause at autopsy, the most common underlying disorders were hypertrophic cardiomyopathy (36 percent, with possible HCM in another 10 percent), an anomalous coronary artery of wrong sinus origin (13 percent), and myocarditis (7 percent) [36]. (See "Athletes: Overview of sudden cardiac death risk and sport participation".) A different distribution of causes was noted in a series of 49 athletes under age 35 with SCD from northern Italy [37]. The most common causes were arrhythmogenic right ventricular cardiomyopathy (22 percent, which occurs more frequently in this region), coronary atherosclerosis (18 percent), anomalous origin of a coronary artery (12 percent), mitral valve prolapse (10 percent), myocarditis (6 percent), and hypertrophic cardiomyopathy (2 percent). Absence of structural heart disease In different reports, 10 to 12 percent of younger patients have VF in the true absence of structural heart disease [22,59], while a lower value of approximately 5 percent has been described when older patients are included [23,24]. This can occur in a variety of settings: Brugada syndrome (see "Brugada syndrome: Clinical presentation, diagnosis, and evaluation") Commotio cordis (see "Commotio cordis") Idiopathic VF, also called primary electrical disease (see "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF') Catecholaminergic polymorphic VT (see "Catecholaminergic polymorphic ventricular tachycardia") Congenital or acquired long QT syndrome (see "Congenital long QT syndrome: Diagnosis" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes") Short QT syndrome (see "Short QT syndrome") Wolff-Parkinson-White syndrome (see "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis") INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 12/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Ventricular fibrillation (The Basics)") SUMMARY Background Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of organized cardiac electrical activity with hemodynamic collapse. The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation, cardioversion, antiarrhythmic drug) or spontaneous reversion restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See 'Introduction' above.) Mechanisms The exact mechanism of collapse in an individual patient is often impossible to establish since, for the vast majority of patients who die suddenly, cardiac electrical activity is not being monitored at the time of their collapse. However, in studies of patients who were having cardiac electrical activity monitored at the time of their event, ventricular tachycardia (VT) or ventricular fibrillation (VF) accounted for the majority of episodes, with bradycardia or asystole accounting for nearly all of the remainder. (See 'Arrhythmic mechanisms' above.) Arrhythmic mechanisms In the majority of patients with VT/VF, sustained ventricular arrhythmia is preceded by an increase in ventricular ectopy and the development of repetitive ventricular arrhythmia, particularly runs of nonsustained VT. In approximately one-third of cases, the tachyarrhythmia is initiated by an early R on T PVC; in the remaining two-thirds, the arrhythmia is initiated by a late cycle PVC. (See 'Arrhythmic mechanisms' above.) Common causes There are many cardiac and noncardiac causes for a sustained ventricular tachyarrhythmia that can result in SCD ( table 1). Among all SCD in all age groups, the majority (65 to 70 percent) are related to coronary heart disease, with other structural cardiac disease (approximately 10 percent), arrhythmias in the absence of structural heart disease (5 to 10 percent), and noncardiac causes (15 to 25 percent) responsible for the remaining deaths. (See 'Etiology of SCD' above.) https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 13/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate ACKNOWLEDGMENT The UpToDate editorial staff thank Dr. Jie Cheng for his past contributions as an author to prior versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kannel WB, Schatzkin A. Sudden death: lessons from subsets in population studies. J Am Coll Cardiol 1985; 5:141B. 2. Bay s de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J 1989; 117:151. 3. Dubner SJ, Pinski S, Palma S, et al. Ambulatory electrocardiographic findings in out-of- hospital cardiac arrest secondary to coronary artery disease. Am J Cardiol 1989; 64:801. 4. Wood MA, Stambler BS, Damiano RJ, et al. Lessons learned from data logging in a multicenter clinical trial using a late-generation implantable cardioverter-defibrillator. The Guardian ATP 4210 Multicenter Investigators Group. J Am Coll Cardiol 1994; 24:1692. 5. Luu M, Stevenson WG, Stevenson LW, et al. Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 1989; 80:1675. 6. K rkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med 2000; 160:1529. 7. Mitchell LB, Pineda EA, Titus JL, et al. Sudden death in patients with implantable cardioverter defibrillators: the importance of post-shock electromechanical dissociation. J Am Coll Cardiol 2002; 39:1323. 8. Cummins RO, Ornato JP, Thies WH, Pepe PE. Improving survival from sudden cardiac arrest: the "chain of survival" concept. A statement for health professionals from the Advanced Cardiac Life Support Subcommittee and the Emergency Cardiac Care Committee, American Heart Association. Circulation 1991; 83:1832. 9. Tovar OH, Jones JL. Electrophysiological deterioration during long-duration ventricular fibrillation. Circulation 2000; 102:2886. 10. Weaver WD, Hill D, Fahrenbruch CE, et al. Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest. N Engl J Med 1988; 319:661. https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 14/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate 11. Raitt MH, Dolack GL, Kudenchuk PJ, et al. Ventricular arrhythmias detected after transvenous defibrillator implantation in patients with a clinical history of only ventricular fibrillation. Implications for use of implantable defibrillator. Circulation 1995; 91:1996. |
Pathophysiology and etiology of sudden cardiac arrest - UpToDate shown to be the cause at autopsy, the most common underlying disorders were hypertrophic cardiomyopathy (36 percent, with possible HCM in another 10 percent), an anomalous coronary artery of wrong sinus origin (13 percent), and myocarditis (7 percent) [36]. (See "Athletes: Overview of sudden cardiac death risk and sport participation".) A different distribution of causes was noted in a series of 49 athletes under age 35 with SCD from northern Italy [37]. The most common causes were arrhythmogenic right ventricular cardiomyopathy (22 percent, which occurs more frequently in this region), coronary atherosclerosis (18 percent), anomalous origin of a coronary artery (12 percent), mitral valve prolapse (10 percent), myocarditis (6 percent), and hypertrophic cardiomyopathy (2 percent). Absence of structural heart disease In different reports, 10 to 12 percent of younger patients have VF in the true absence of structural heart disease [22,59], while a lower value of approximately 5 percent has been described when older patients are included [23,24]. This can occur in a variety of settings: Brugada syndrome (see "Brugada syndrome: Clinical presentation, diagnosis, and evaluation") Commotio cordis (see "Commotio cordis") Idiopathic VF, also called primary electrical disease (see "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF') Catecholaminergic polymorphic VT (see "Catecholaminergic polymorphic ventricular tachycardia") Congenital or acquired long QT syndrome (see "Congenital long QT syndrome: Diagnosis" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes") Short QT syndrome (see "Short QT syndrome") Wolff-Parkinson-White syndrome (see "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis") INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 12/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Ventricular fibrillation (The Basics)") SUMMARY Background Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of organized cardiac electrical activity with hemodynamic collapse. The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation, cardioversion, antiarrhythmic drug) or spontaneous reversion restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See 'Introduction' above.) Mechanisms The exact mechanism of collapse in an individual patient is often impossible to establish since, for the vast majority of patients who die suddenly, cardiac electrical activity is not being monitored at the time of their collapse. However, in studies of patients who were having cardiac electrical activity monitored at the time of their event, ventricular tachycardia (VT) or ventricular fibrillation (VF) accounted for the majority of episodes, with bradycardia or asystole accounting for nearly all of the remainder. (See 'Arrhythmic mechanisms' above.) Arrhythmic mechanisms In the majority of patients with VT/VF, sustained ventricular arrhythmia is preceded by an increase in ventricular ectopy and the development of repetitive ventricular arrhythmia, particularly runs of nonsustained VT. In approximately one-third of cases, the tachyarrhythmia is initiated by an early R on T PVC; in the remaining two-thirds, the arrhythmia is initiated by a late cycle PVC. (See 'Arrhythmic mechanisms' above.) Common causes There are many cardiac and noncardiac causes for a sustained ventricular tachyarrhythmia that can result in SCD ( table 1). Among all SCD in all age groups, the majority (65 to 70 percent) are related to coronary heart disease, with other structural cardiac disease (approximately 10 percent), arrhythmias in the absence of structural heart disease (5 to 10 percent), and noncardiac causes (15 to 25 percent) responsible for the remaining deaths. (See 'Etiology of SCD' above.) https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 13/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate ACKNOWLEDGMENT The UpToDate editorial staff thank Dr. Jie Cheng for his past contributions as an author to prior versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kannel WB, Schatzkin A. Sudden death: lessons from subsets in population studies. J Am Coll Cardiol 1985; 5:141B. 2. Bay s de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J 1989; 117:151. 3. Dubner SJ, Pinski S, Palma S, et al. Ambulatory electrocardiographic findings in out-of- hospital cardiac arrest secondary to coronary artery disease. Am J Cardiol 1989; 64:801. 4. Wood MA, Stambler BS, Damiano RJ, et al. Lessons learned from data logging in a multicenter clinical trial using a late-generation implantable cardioverter-defibrillator. The Guardian ATP 4210 Multicenter Investigators Group. J Am Coll Cardiol 1994; 24:1692. 5. Luu M, Stevenson WG, Stevenson LW, et al. Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 1989; 80:1675. 6. K rkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med 2000; 160:1529. 7. Mitchell LB, Pineda EA, Titus JL, et al. Sudden death in patients with implantable cardioverter defibrillators: the importance of post-shock electromechanical dissociation. J Am Coll Cardiol 2002; 39:1323. 8. Cummins RO, Ornato JP, Thies WH, Pepe PE. Improving survival from sudden cardiac arrest: the "chain of survival" concept. A statement for health professionals from the Advanced Cardiac Life Support Subcommittee and the Emergency Cardiac Care Committee, American Heart Association. Circulation 1991; 83:1832. 9. Tovar OH, Jones JL. Electrophysiological deterioration during long-duration ventricular fibrillation. Circulation 2000; 102:2886. 10. Weaver WD, Hill D, Fahrenbruch CE, et al. Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest. N Engl J Med 1988; 319:661. https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 14/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate 11. Raitt MH, Dolack GL, Kudenchuk PJ, et al. Ventricular arrhythmias detected after transvenous defibrillator implantation in patients with a clinical history of only ventricular fibrillation. Implications for use of implantable defibrillator. Circulation 1995; 91:1996. 12. Kuo CS, Munakata K, Reddy CP, Surawicz B. Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations. Circulation 1983; 67:1356. 13. Mandapati R, Asano Y, Baxter WT, et al. Quantification of effects of global ischemia on dynamics of ventricular fibrillation in isolated rabbit heart. Circulation 1998; 98:1688. 14. Kuo CS, Amlie JP, Munakata K, et al. Dispersion of monophasic action potential durations and activation times during atrial pacing, ventricular pacing, and ventricular premature stimulation in canine ventricles. Cardiovasc Res 1983; 17:152. 15. Bardy GH, Olson WH. Clinical characteristics of spontaneous-onset sustained ventricular tac hycardia and ventricular fibrillation in survivors of cardiac arrest. In: Cardiac Electrophysiolo gy: From Cell to Bedside, Zipes DP, Jalife J (Eds), WB Saunders, Philadelphia 1990. p.778. 16. Wu TJ, Lin SF, Weiss JN, et al. Two types of ventricular fibrillation in isolated rabbit hearts: importance of excitability and action potential duration restitution. Circulation 2002; 106:1859. 17. Chen PS, Wu TJ, Ting CT, et al. A tale of two fibrillations. Circulation 2003; 108:2298. 18. Kannel WB, Wilson PW, D'Agostino RB, Cobb J. Sudden coronary death in women. Am Heart J 1998; 136:205. 19. Centers for Disease Control and Prevention (CDC). State-specific mortality from sudden cardiac death United States, 1999. MMWR Morb Mortal Wkly Rep 2002; 51:123. 20. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation 2001; 104:2158. 21. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336:1629. 22. Drory Y, Turetz Y, Hiss Y, et al. Sudden unexpected death in persons less than 40 years of age. Am J Cardiol 1991; 68:1388. 23. Chugh SS, Kelly KL, Titus JL. Sudden cardiac death with apparently normal heart. Circulation 2000; 102:649. 24. Survivors of out-of-hospital cardiac arrest with apparently normal heart. Need for definition and standardized clinical evaluation. Consensus Statement of the Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United States. Circulation 1997; 95:265. https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 15/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate 25. Kuisma M, Alasp A. Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome. Eur Heart J 1997; 18:1122. 26. Eckart RE, Scoville SL, Campbell CL, et al. Sudden death in young adults: a 25-year review of autopsies in military recruits. Ann Intern Med 2004; 141:829. 27. Narang R, Cleland JG, Erhardt L, et al. Mode of death in chronic heart failure. A request and proposition for more accurate classification. Eur Heart J 1996; 17:1390. 28. Cleland JG, Erhardt L, Murray G, et al. Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators. Eur Heart J 1997; 18:41. 29. Albert CM, Chae CU, Grodstein F, et al. Prospective study of sudden cardiac death among women in the United States. Circulation 2003; 107:2096. 30. Velebit V, Podrid P, Lown B, et al. Aggravation and provocation of ventricular arrhythmias by antiarrhythmic drugs. Circulation 1982; 65:886. 31. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781. 32. Flaker GC, Blackshear JL, McBride R, et al. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 1992; 20:527. 33. Ruskin JN, McGovern B, Garan H, et al. Antiarrhythmic drugs: a possible cause of out-of- hospital cardiac arrest. N Engl J Med 1983; 309:1302. 34. Kloner RA, Hale S, Alker K, Rezkalla S. The effects of acute and chronic cocaine use on the heart. Circulation 1992; 85:407. 35. Bauman JL, Grawe JJ, Winecoff AP, Hariman RJ. Cocaine-related sudden cardiac death: a hypothesis correlating basic science and clinical observations. J Clin Pharmacol 1994; 34:902. 36. Maron BJ, Carney KP, Lever HM, et al. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. J Am Coll Cardiol 2003; 41:974. 37. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998; 339:364. 38. Eckart RE, Shry EA, Burke AP, et al. Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance. J Am Coll Cardiol 2011; 58:1254. 39. Gillum RF. Sudden coronary death in the United States: 1980-1985. Circulation 1989; 79:756. https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 16/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate 40. Newby KH, Thompson T, Stebbins A, et al. Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators. Circulation 1998; 98:2567. 41. Al-Khatib SM, Granger CB, Huang Y, et al. Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes. Circulation 2002; 106:309. 42. Volpi A, Cavalli A, Santoro L, Negri E. Incidence and prognosis of early primary ventricular fibrillation in acute myocardial infarction results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) database. Am J Cardiol 1998; 82:265. 43. Goldberg RJ, Gore JM, Haffajee CI, et al. Outcome after cardiac arrest during acute myocardial infarction. Am J Cardiol 1987; 59:251. 44. Berger CJ, Murabito JM, Evans JC, et al. Prognosis after first myocardial infarction. Comparison of Q-wave and non-Q-wave myocardial infarction in the Framingham Heart Study. JAMA 1992; 268:1545. 45. Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)- Prevenzione. Circulation 2002; 105:1897. 46. Gheeraert PJ, Henriques JP, De Buyzere ML, et al. Out-of-hospital ventricular fibrillation in patients with acute myocardial infarction: coronary angiographic determinants. J Am Coll Cardiol 2000; 35:144. 47. Stevenson WG, Wiener I, Yeatman L, et al. Complicated atherosclerotic lesions: a potential cause of ischemic ventricular arrhythmias in cardiac arrest survivors who do not have inducible ventricular tachycardia? Am Heart J 1988; 116:1. 48. Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 336:1276. 49. Burke AP, Farb A, Malcom GT, et al. Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation 1998; 97:2110. 50. Burke AP, Farb A, Malcom GT, et al. Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 1999; 281:921. 51. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 1985; 71:699. https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 17/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate 52. Davies MJ, Thomas AC, Knapman PA, Hangartner JR. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 1986; 73:418. 53. Natale A, Sra J, Axtell K, et al. Ventricular fibrillation and polymorphic ventricular tachycardia with critical coronary artery stenosis: does bypass surgery suffice? J Cardiovasc Electrophysiol 1994; 5:988. 54. Daoud EG, Niebauer M, Kou WH, et al. Incidence of implantable defibrillator discharges after coronary revascularization in survivors of ischemic sudden cardiac death. Am Heart J 1995; 130:277. 55. Uretsky BF, Thygesen K, Armstrong PW, et al. Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. Circulation 2000; 102:611. 56. Burke AP, Farb A, Liang YH, et al. Effect of hypertension and cardiac hypertrophy on coronary artery morphology in sudden cardiac death. Circulation 1996; 94:3138. 57. Viskin S, Belhassen B. Idiopathic ventricular fibrillation. Am Heart J 1990; 120:661. 58. Rodriguez RM, Montoy JCC, Repplinger D, et al. Occult Overdose Masquerading as Sudden Cardiac Death: From the POstmortem Systematic InvesTigation of Sudden Cardiac Death Study. Ann Intern Med 2020; 173:941. 59. Topaz O, Edwards JE. Pathologic features of sudden death in children, adolescents, and young adults. Chest 1985; 87:476. Topic 974 Version 31.0 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 18/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate GRAPHICS Continuous electrocardigraphic (ECG) strip during an episode of ventricular fibrillation (VF) that progresses to fine VF and then asystole At the onset of ventricular fibrillation (VF), the QRS complexes are regular, widened, and of tall amplitude, suggesting a more organized ventricular tachyarrhythmia. Over a brief period of time, the rhythm becomes more disorganized with high amplitude fibrillatory waves; this is coarse VF. After a longer period of time, the fibrillatory waves become fine, culminating in asystole. Graphic 67777 Version 3.0 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 19/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate ECG 12-lead ventricular fibrillation 12-lead ECG showing course ventricular fibrillation. ECG: electrocardiogram. Graphic 118944 Version 1.0 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 20/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Major causes of sudden death Ischemic heart disease Coronary artery disease with myocardial infarction or angina Coronary artery embolism Nonatherogenic coronary artery disease (arteritis, dissection, congenital coronary artery anomalies) Coronary artery spasm Nonischemic heart disease Hypertrophic cardiomyopathy Dilated cardiomyopathy Valvular heart disease Congenital heart disease Arrhythmogenic right ventricular dysplasia Myocarditis Acute pericardial tamponade Acute myocardial rupture Aortic dissection No structural heart disease Primary electrical disease (idiopathic ventricular fibrillation) Brugada syndrome (right bundle branch block and ST segment elevation in leads V1 to V3) Long QT syndrome Preexcitation syndrome Complete heart block Familial sudden cardiac death Chest wall trauma (commotio cordis) Noncardiac disease Pulmonary embolism Intracranial hemorrhage Drowning Pickwickian syndrome Drug-induced https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 21/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Central airway obstruction Sudden infant death syndrome Sudden unexplained death in epilepsy (SUDEP) Graphic 62184 Version 3.0 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 22/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Incidence of sudden death in men and women increases with age During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden death increased with age in both men and women. However, at each age, the incidence of sudden death is higher in men than women. Data from Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 59028 Version 4.0 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 23/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Risk of SCD is related to clinical manifestations of CHD During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden cardiac death (SCD) in both men and women was related to the clinical manifestations of coronary heart disease (CHD). It was highest in those with a myocardial infarction, intermediate in those with angina and no prior infarction, and lowest in those without overt CHD. Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 52309 Version 2.0 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 24/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Heart failure predicts increased sudden cardiac death and overall mortality During a 38-year old follow-up of subjects in the Framingham Heart Study, the presence of heart failure (HF) significantly increased sudden death and overall mortality in both men and women. p <0.01. p <0.001. Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 58658 Version 4.0 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 25/26 7/6/23, 1:41 PM Pathophysiology and etiology of sudden cardiac arrest - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/pathophysiology-and-etiology-of-sudden-cardiac-arrest/print 26/26 |
7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Pharmacologic therapy in survivors of sudden cardiac arrest : Philip J Podrid, MD, FACC : Scott Manaker, MD, PhD, Samuel L vy, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 24, 2021. INTRODUCTION Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity with hemodynamic collapse, typically due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation, cardioversion, or drug therapy) or spontaneous reversion restores circulation, while the SCD terminology is employed if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest often persists by convention. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.) The treatment of SCA consists of acute resuscitation using standardized advanced cardiac life- support protocols, followed by therapy to prevent recurrent arrhythmias and SCD. Patients who survive SCA caused by VT/VF not due to a reversible cause generally receive an implantable cardioverter-defibrillator (ICD). Antiarrhythmic drugs are used in select patients as adjunctive therapy, or as primary therapy when an ICD is not indicated or refused by the patient. This approach, endorsed by numerous professional societies, is based on the significant survival benefit of patients receiving an ICD compared with antiarrhythmic drugs alone or no therapy. This topic will review the role of pharmacologic therapy in survivors of SCA, with an emphasis on the role of antiarrhythmic drugs. Issues related to the acute management of SCA, the evaluation of survivors, and the utility of an ICD, arrhythmic surgery, or radiofrequency ablation are discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Cardiac https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 1/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate evaluation of the survivor of sudden cardiac arrest" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) INDICATIONS FOR PHARMACOLOGIC THERAPY Nearly all survivors of SCA without a reversible cause should be evaluated for placement of an ICD. Because an ICD treats, but does not prevent, arrhythmias, patients who have arrhythmias with symptoms or device discharges may require adjunctive antiarrhythmic therapy. In addition to ICD therapy for survivors of SCA, there are three main indications for concomitant antiarrhythmic drug therapy [1-3]: To reduce the frequency of ventricular arrhythmias in patients with frequent ICD shocks. In one analysis, the occurrence of frequent ICD shocks was the primary reason for adding an antiarrhythmic drug (64 percent) [3]. To suppress supraventricular arrhythmias that may cause symptoms or interfere with ICD function, potentially resulting in "inappropriate" shocks. "Inappropriate" shocks result from non-life-threatening arrhythmias which meet the programmed parameters for ICD therapy, primarily based upon rate (eg, atrial fibrillation with a rapid ventricular response exceeding the programmed threshold for delivering a shock). "Inappropriate" shocks have been reported in up to 29 percent of ICD patients and can have a substantial impact on the patient s quality of life [4]. These shocks are caused by a variety of arrhythmias including sinus tachycardia, atrial tachycardia, atrial flutter, atrial fibrillation, and nonsustained VT (NSVT) [4,5]. (See "Cardiac implantable electronic devices: Long-term complications", section on 'Inappropriate shocks'.) More sophisticated programming features of current-generation ICDs may allow the device to ignore clinically unimportant and non-life-threatening arrhythmias rather than delivering an unnecessary shock. (See "Implantable cardioverter-defibrillators: Optimal programming".) To reduce the ventricular rate of VT so that it is better tolerated hemodynamically and/or more amenable to termination by anti-tachycardia pacing or low energy cardioversion. CHOICE OF PHARMACOLOGIC THERAPY For patients with an ICD who require adjunctive antiarrhythmic therapy due to ongoing ventricular arrhythmias, we recommend treatment with the combination of amiodarone plus a https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 2/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate beta blocker rather than treatment with amiodarone alone or other antiarrhythmic agents. On occasion, therapy with mexiletine or sotalol may be useful. In general, the class I antiarrhythmic drugs are not used as the majority of patients with SCA have structural heart disease, and these drugs are not recommended in patients with structural heart disease. Pharmacologic therapy, in the form of beta blockers and antiarrhythmic medications, can be helpful in controlling ventricular arrhythmias in survivors of SCA. Virtually all patients who have survived SCA should be considered for beta blocker therapy. However, due to the efficacy of the ICD in treating sustained ventricular tachyarrhythmias and improving mortality, antiarrhythmic drugs are generally reserved for use in select patients as adjunctive therapy, or as primary therapy when an ICD is not indicated or refused by the patient. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Empiric versus guided pharmacologic therapy Empiric pharmacologic therapy for SCA survivors, primarily with beta blockers and/or an antiarrhythmic drug, is an effective approach for survivors of SCA who have refused ICD placement or are not candidates for an ICD. Beta blockers have some efficacy with relatively few side effects, while for most patients amiodarone is the most efficacious antiarrhythmic drug for preventing recurrent ventricular arrhythmias. In the past, the choice of antiarrhythmic drug was guided by objective criteria based upon either noninvasive (ambulatory electrocardiogram [ECG] monitoring) or invasive testing (electrophysiologic studies). An effective drug, identified by either technique, was noted to prevent recurrent arrhythmia and potentially improve survival compared with no therapy or an ineffective drug [6-13]. In current practice, however, when pharmacologic therapy is administered to a patient with or without (because of refusal or noncandidacy for) an ICD, empiric treatment with beta blockers and/or amiodarone is the preferred approach. Other antiarrhythmic drugs (for example mexiletine or sotalol) are considered if there is recurrent arrhythmia despite therapy with amiodarone and/or a beta blocker. Beta blockers Nearly all patients who have survived SCA should receive a beta blocker as part of their therapy. Beta blockers are not generally considered to be adequate monotherapy and should be used in conjunction with an antiarrhythmic drug for most patients resuscitated from SCA due to VT or ventricular fibrillation (VF). However, the associated anti-adrenergic effects of beta blockers may be effective at reducing both arrhythmias and SCA when no specific antiarrhythmic treatment is given. In an analysis from the AVID trial, patients who were discharged from the hospital on a beta blocker had a mortality reduction compared with those patients not receiving a beta blocker [14]. https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 3/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Most SCA survivors will have multiple indications for a beta blocker (eg, post-myocardial infarction, heart failure, etc) from which they derive clinical benefit. Beta blockers reduce the incidence of sudden death and total mortality in patients with a recent myocardial infarction and in those with symptomatic heart failure or congenital long QT syndrome. However, even in the absence of any additional indications, beta blockers should be used as part of the medical regimen following SCA due to VT/VF. (See "Acute myocardial infarction: Role of beta blocker therapy" and "Congenital long QT syndrome: Treatment".) Beta blockers can potentiate the effects of class I antiarrhythmic drugs by preventing the effect of sympathetic stimulation on reversing the depressant effect on slowing conduction. They can also potentiate the action of class III antiarrhythmic drugs by preventing the sympathetic effect on shortening repolarization. Antiarrhythmic drugs Among antiarrhythmic medications, amiodarone is the most effective for preventing recurrent ventricular tachyarrhythmias, although mexiletine or sotalol are also efficacious for reducing recurrent ventricular arrhythmias. We prefer empiric therapy with amiodarone for treatment immediately following SCA in patients with recurrent ventricular tachyarrhythmias as well as for those who have refused (or are not candidates for) ICD placement [15]. Following stabilization of the patient, if there are concerns about potential toxicity related to amiodarone, particularly for anticipated long-term use, mexiletine or sotalol may be considered. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) Efficacy Several clinical trials and systematic reviews have evaluated the efficacy of antiarrhythmic drugs as adjuvant therapy in ICD patients [5,16-21]. There were significant differences in trial methodologies, which limit direct comparisons. Amiodarone has generally been the most effective antiarrhythmic drug for preventing ventricular arrhythmias (and associated ICD shocks). In one systematic review which included eight randomized trials involving 1889 patients, there was significant heterogeneity among the trials, including variation on the active therapy, control therapy, and outcomes assessed, and the results were divided into those trials that compared class III antiarrhythmic drugs (usually sotalol and amiodarone) with beta blockers, and those trials that compared class III drugs (sotalol, dofetilide, and azimilide) with placebo or no antiarrhythmic therapy [20]. Key findings included: Amiodarone in combination with a beta blocker significantly reduced the incidence of shocks compared with beta blocker alone (hazard ratio [HR] 0.27, 95% CI 0.14-0.52). These results were largely driven by the OPTIC trial. https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 4/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Sotalol reduced the incidence of ICD shocks when compared with placebo (HR 0.55, 95% CI 0.4-0.78). There was also a trend toward fewer shocks in patients treated with sotalol versus another beta blocker. Treatment with either azimilide or dofetilide resulted in nonsignificant trends towards reduction in total ICD shocks (generally due to a decrease in supraventricular arrhythmias) compared with placebo. However, the incidence of appropriate ICD therapies (shocks plus antitachycardia pacing) was significantly reduced by azimilide (HR 0.31, 95% CI 0.29-0.34). In a second systematic review of 17 randomized trials involving 5875 patients, patients taking an antiarrhythmic drug had significantly fewer ICD shocks compared with those not on an antiarrhythmic (odds ratio [OR] 0.59, 95% CI 0.36-0.96) [22]. However, the reduction in shocks seen in patients receiving an antiarrhythmic drug was not associated with improved survival (OR 1.07, 95% CI 0.72-1.59). In the OPTIC trial, a multicenter trial that randomized 412 patients with an ICD to treatment with a beta blocker alone, a beta blocker plus amiodarone, or sotalol alone, the rate of any ICD shock at one year was significantly lower with amiodarone plus a beta blocker than with sotalol or a beta blocker alone (10.3 versus 24.3 and 38.5 percent, respectively) [16]. There was a trend toward fewer total ICD shocks in the sotalol group compared with beta blockers alone; however, sotalol had no significant effect compared with a beta blocker alone in reducing the incidence of appropriate shocks or antitachycardia pacing. Another major advantage of amiodarone is a very low frequency of proarrhythmia. Although amiodarone can markedly prolong the QT/QTc interval, torsades de pointes is rare. However, caution is necessary when amiodarone is given with other drugs that can prolong the QT interval or therapy is complicated by hypokalemia or hypomagnesemia. Caution is necessary when combining amiodarone with a beta blocker, as amiodarone also has beta blocking effects and significant bradycardia or AV block may occur. This is not a concern in patients who have an ICD, as there is backup pacing. However, for patients without an ICD or pacemaker this should be considered and patients should be monitored carefully. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Administration When patients are started on an antiarrhythmic drug, they should have a baseline ECG prior to drug initiation and then serial ECGs for the first two to three days, particularly to monitor heart rate and assess for any significant QT/QTc interval prolongation. https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 5/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Amiodarone The initial dosing of amiodarone will vary depending on the route (intravenous [IV] or oral) as well as the clinical situation ( table 1): For patients with electrical storm or incessant VT, we recommend IV amiodarone (150 mg IV push, followed by 1 mg/minute IV infusion for six hours, followed by 0.5 mg/minute IV infusion for 18 additional hours) as the initial antiarrhythmic agent. (See "Electrical storm and incessant ventricular tachycardia", section on 'Initial antiarrhythmic medical therapy'.) For patients who have been on IV therapy for more than two weeks, we start maintenance oral amiodarone at a dose of 200 to 400 mg/day. (See "Amiodarone: Clinical uses", section on 'Amiodarone for ventricular arrhythmias'.) For patients who have been on IV therapy for one to two weeks, we start an intermediate maintenance oral amiodarone dose of 400 to 800 mg/day until an adequate loading dose has been achieved, then the dose should be reduced to the usual maintenance dose of 200 mg/day. The recommended IV loading dose is 10 grams or the oral equivalent. As oral amiodarone is approximately 50 percent bioavailable, a total of 20 to 30 grams of oral amiodarone is equivalent to the IV loading dose. For patients who have been on IV therapy for one week or less, we usually start with a full oral amiodarone loading dose of 400 to 1200 mg/day (typically in two or three divided doses). This should be continued until a total loading dose of 10 grams has been received, then the dose should be reduced to the usual maintenance dose of 200 mg/day. Sotalol In contrast to amiodarone, sotalol is not universally available in IV form. Bradycardic and proarrhythmic events (especially due to QT/QTc prolongation) can occur after the initiation of sotalol therapy and with each upward dosing adjustment. As a result, sotalol should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment. We start sotalol at a dose of 80 mg twice daily, with dose adjustments at three-day intervals once steady-state plasma concentrations have been achieved and the QT interval has been reviewed on a surface ECG. Patients with renal insufficiency require a modification of the dosing interval. (See "Clinical uses of sotalol", section on 'Dosing'.) Mexiletine Mexiletine, which is a lidocaine-like antiarrhythmic drug, is only available for oral use. It is often used with or without amiodarone for treating patients with an ICD who have ventricular arrhythmias that are of concern. The usual dose is 200 to 400 mg three times daily. Treatment of breakthrough arrhythmias Patients who have recurrent, or breakthrough, arrhythmias resulting in repeat ICD shocks or sudden cardiac arrest in spite of therapy with a https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 6/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate beta blocker and/or antiarrhythmic drug represent a significant clinical challenge. As with the occurrence of any ventricular arrhythmia, any identifiable reversible causes (eg, myocardial ischemia, electrolyte disturbances) should be corrected. In the absence of any reversible causes, we approach treatment in the following way: For patients who are taking only a beta blocker, we add an antiarrhythmic drug, ideally amiodarone. For patients who are taking only an antiarrhythmic drug, we add a beta blocker. For patients who are taking both a beta blocker and an antiarrhythmic drug, treatment options include upward titration of either or both existing drugs or the discontinuation of the current antiarrhythmic drug in favor of an alternative antiarrhythmic drug. We prefer to first increase the dose of the beta blocker and the current antiarrhythmic drug to the maximum recommended dose (or maximum tolerated dose if side effects arise). If this approach is ineffective and the patient continues to have recurrent ventricular arrhythmias and shocks, we would consider stopping the current antiarrhythmic drug and initiating treatment with another agent. Another important option for patients with recurrent arrhythmia despite amiodarone and beta blocker is the addition of a class I antiarrhythmic agent ( table 2) that does not alter the QT/QTc interval (ie, mexiletine or propafenone). For patients with recurrent ventricular tachyarrhythmia despite the use of multiple antiarrhythmic drugs, cardiac ablation is often the next step in management. Further details on the treatment of refractory VT can be found elsewhere. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation'.) IMPACT ON ICD THERAPIES The primary goal of using blockers and/or antiarrhythmic drugs in patients with an ICD is to minimize the frequency of recurrent ventricular arrhythmias, thereby decreasing the likelihood of the patient receiving additional ICD shocks. Beyond reducing the likelihood of ICD shocks, however, antiarrhythmic drug therapy may impact the efficacy of ICD therapies by potentially increasing defibrillation thresholds beyond the device s capability to defibrillate or by slowing the ventricular rates of any recurrent sustained tachyarrhythmias below the device s threshold for arrhythmia detection. https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 7/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Alterations in DFTs Any antiarrhythmic drug can potentially alter the defibrillation threshold (DFT), although the effect has been most pronounced with amiodarone and its major metabolite desethylamiodarone, which increase the DFT in a dose-dependent fashion [23-25]. DFT testing has historically been performed at the time of ICD implantation, although the routine necessity for this evaluation with the current generation of ICDs has been questioned. However, repeat DFT testing may be warranted after the initiation of amiodarone if there is concern about rising DFT thresholds (as may occur in certain clinical situations, including atrial fibrillation, hypertension, and left ventricular hypertrophy). In the report on the efficacy of routine ICD testing discussed above, 71 patients had an ICD test due to the initiation or dose-adjustment of an antiarrhythmic drug (primarily amiodarone or sotalol), and the ICD failed to defibrillate only two patients [26]. The role of ICD testing after the initiation of antiarrhythmic therapy was more directly assessed in a substudy of the OPTIC trial, in which 94 patients underwent serial ICD testing to determine the impact of each of three drug regimens (beta blockers, amiodarone plus a beta blocker, and sotalol) on DFTs [27]. At a mean follow-up of 60 days after drug initiation, the mean DFT decreased from baseline in the patients assigned to beta blockers or sotalol (8.8 to 7.1 and 8.1 to 7.2 joules, respectively), while among patients taking amiodarone there was a nonsignificant increase in the mean DFT from 8.5 to 9.8 joules. Given the relatively small number of patients in each arm of this study, the small mean increase in DFT does not preclude the possibility that there may be a larger increase in some patients. Thus, the necessity for ICD testing after the initiation of antiarrhythmic drugs, primarily amiodarone, remains uncertain. Programming changes for VT detection In patients receiving chronic antiarrhythmic drug therapy, the rate of recurrent VT is often slower than the rate seen during the index arrhythmia. Thus, it is common practice to lower the VT detection rate when initiating antiarrhythmic drug therapy; the specific detection threshold rate is determined by the characteristics of the patient s prior events. However, reducing the VT detection rate can have both positive and negative consequences for the patient: If the VT detection rate is reduced and the ICD therapy program includes antitachycardia pacing (ATP), episodes of slow VT may be terminated with ATP before the patient is aware of the event. If the detection rate is set too low, the ICD will not treat the arrhythmia unless it accelerates above the detection rate or progresses to ventricular fibrillation (VF). Thus, some patients who have their detection threshold rate decreased may not receive ICD treatments during episodes of slow VT and may have symptomatic VT (eg, syncope, palpitations, chest pain, dyspnea, or even SCA). https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 8/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Close follow-up with remote device interrogation can help determine whether new VT detection settings are appropriate. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Basic and advanced cardiac life support in adults".) SUMMARY AND RECOMMENDATIONS Because of the survival benefit associated with an implantable cardioverter-defibrillator (ICD) compared with antiarrhythmic therapy alone, most survivors of sudden cardiac arrest (SCA) due to ventricular tachycardia (VT) or ventricular fibrillation (VF) not associated with a reversible cause should receive an ICD. Antiarrhythmic drugs can be considered as the primary therapy when an ICD is not indicated or refused by the patient. (See 'Indications for pharmacologic therapy' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Nearly all patients who have survived SCA should receive a beta blocker as part of their therapy, which may also provide additional antiarrhythmic benefits. (See 'Empiric versus guided pharmacologic therapy' above.) Because an ICD does not prevent arrhythmias, patients who have arrhythmias (ventricular or supraventricular) with symptoms or device discharges may require adjunctive antiarrhythmic therapy or consideration of catheter ablation. The three main indications for concomitant antiarrhythmic drug therapy are (see 'Indications for pharmacologic therapy' above): To reduce the frequency of ventricular arrhythmias in patients with frequent ICD shocks. To suppress other arrhythmias that cause symptoms or interfere with ICD function (eg, causing "inappropriate" shocks). To reduce the ventricular rate of VT so that it is better tolerated hemodynamically and more amenable to termination by anti-tachycardia pacing or low-energy cardioversion. https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 9/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate For patients with an ICD who require adjunctive antiarrhythmic therapy due to ongoing arrhythmias, we recommend treatment with the combination of amiodarone plus a beta blocker rather than treatment with amiodarone alone or other antiarrhythmic agents (Grade 1B). This approach is especially preferred in patients with significant left ventricular dysfunction who require adjunctive antiarrhythmic therapy, since amiodarone does not exacerbate heart failure and is less proarrhythmic than other agents. (See 'Choice of pharmacologic therapy' above.) Antiarrhythmic drug therapy may impact the efficacy of ICD therapies by potentially increasing defibrillation thresholds beyond the device s capability to defibrillate or by slowing the ventricular rates of any recurrent sustained tachyarrhythmias below the device s threshold for arrhythmia detection.(See 'Impact on ICD therapies' above.) ACKNOWLEDGMENT The UpToDate editorial staff thanks Jie Cheng, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Knilans TK, Prystowsky EN. Antiarrhythmic drug therapy in the management of cardiac arrest survivors. Circulation 1992; 85:I118. 2. Manz M, Jung W, L deritz B. Interactions between drugs and devices: experimental and clinical studies. Am Heart J 1994; 127:978. 3. Steinberg JS, Martins J, Sadanandan S, et al. Antiarrhythmic drug use in the implantable defibrillator arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study. Am Heart J 2001; 142:520. 4. Nanthakumar K, Paquette M, Newman D, et al. Inappropriate therapy from atrial fibrillation and sinus tachycardia in automated implantable cardioverter defibrillators. Am Heart J 2000; 139:797. 5. Pacifico A, Hohnloser SH, Williams JH, et al. Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group. N Engl J Med 1999; 340:1855. 6. Kim SG. The management of patients with life-threatening ventricular tachyarrhythmias: https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 10/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate programmed stimulation or Holter monitoring (either or both)? Circulation 1987; 76:1. 7. Wilber DJ, Garan H, Finkelstein D, et al. Out-of-hospital cardiac arrest. Use of electrophysiologic testing in the prediction of long-term outcome. N Engl J Med 1988; 318:19. 8. Graboys TB, Lown B, Podrid PJ, DeSilva R. Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs. Am J Cardiol 1982; 50:437. 9. Lampert S, Lown B, Graboys TB, et al. Determinants of survival in patients with malignant ventricular arrhythmia associated with coronary artery disease. Am J Cardiol 1988; 61:791. 10. Vlay SC, Kallman CH, Reid PR. Prognostic assessment of survivors of ventricular tachycardia and ventricular fibrillation with ambulatory monitoring. Am J Cardiol 1984; 54:87. 11. Mason JW. A comparison of electrophysiologic testing with Holter monitoring to predict antiarrhythmic-drug efficacy for ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. N Engl J Med 1993; 329:445. 12. Mason JW. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. N Engl J Med 1993; 329:452. 13. Swerdlow CD, Winkle RA, Mason JW. Determinants of survival in patients with ventricular tachyarrhythmias. N Engl J Med 1983; 308:1436. 14. Exner DV, Reiffel JA, Epstein AE, et al. Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 1999; 34:325. 15. Weinberg BA, Miles WM, Klein LS, et al. Five-year follow-up of 589 patients treated with amiodarone. Am Heart J 1993; 125:109. 16. Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus beta- blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 2006; 295:165. 17. Dorian P, Borggrefe M, Al-Khalidi HR, et al. Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. Circulation 2004; 110:3646. 18. Singer I, Al-Khalidi H, Niazi I, et al. Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators. J Am Coll Cardiol 2004; 43:39. 19. K hlkamp V, Mewis C, Mermi J, et al. Suppression of sustained ventricular tachyarrhythmias: a comparison of d,l-sotalol with no antiarrhythmic drug treatment. J Am Coll Cardiol 1999; https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 11/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate 33:46. 20. Ferreira-Gonz lez I, Dos-Subir L, Guyatt GH. Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators: a systematic review. Eur Heart J 2007; 28:469. 21. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study). The CASCADE Investigators. Am J Cardiol 1993; 72:280. 22. Ha AH, Ham I, Nair GM, et al. Implantable cardioverter-defibrillator shock prevention does not reduce mortality: a systemic review. Heart Rhythm 2012; 9:2068. 23. Zhou L, Chen BP, Kluger J, et al. Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold. J Am Coll Cardiol 1998; 31:1672. 24. Pelosi F Jr, Oral H, Kim MH, et al. Effect of chronic amiodarone therapy on defibrillation energy requirements in humans. J Cardiovasc Electrophysiol 2000; 11:736. 25. Nielsen TD, Hamdan MH, Kowal RC, et al. Effect of acute amiodarone loading on energy requirements for biphasic ventricular defibrillation. Am J Cardiol 2001; 88:446. 26. Brunn J, B cker D, Weber M, et al. Is there a need for routine testing of ICD defibrillation capacity? Results from more than 1000 studies. Eur Heart J 2000; 21:162. 27. Hohnloser SH, Dorian P, Roberts R, et al. Effect of amiodarone and sotalol on ventricular defibrillation threshold: the optimal pharmacological therapy in cardioverter defibrillator patients (OPTIC) trial. Circulation 2006; 114:104. Topic 972 Version 27.0 https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 12/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate GRAPHICS Amiodarone dosing in adults by indication Indications Loading dose Maintenance dose Atrial arrhythmias Prevention of recurrent PAF Total loading dose: 6 to 10 grams Lowest effective dose, usually 100 to 200 mg orally once per day Pharmacologic cardioversion of PAF Outpatient: Given as 400 to 600 mg orally per day in divided doses with meals Maximum 200 mg orally per day Inpatient: Given as 400 to 1200 mg orally per day in divided doses with meals Pretreatment before elective cardioversion or Total loading dose: 6 to 10 grams orally over 2 to 6 Lowest effective dose, usually 100 to 200 mg orally catheter ablation of AF weeks once per day Given as 400 to 1200 mg Maximum 400 mg orally per orally per day in divided doses day in most circumstances Restoration and maintenance of NSR in critically ill patients with AF Total IV loading dose: 1050 mg Given as 150 mg IV bolus over 10 to 30 minutes, followed by continuous IV infusion at 1 mg per minute for 6 hours, then 0.5 mg per Ventricular rate control in critically ill patients with AF and rapid ventricular response minute for 18 hours* IV infusion (0.5 mg per minute) may need to be extended past 24 hours if unable to transition to oral therapy If amiodarone will be used chronically: Following IV infusion, give 400 to 1200 mg orally per day in divided doses to complete a total (IV plus oral) loading dose of 10 grams; consider overlapping IV and oral amiodarone for 24 to 48 hours https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 13/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Ventricular arrhythmias Primary and secondary prevention of SCD in patients with LV dysfunction who are not candidates for or refuse ICD implantation Total oral loading dose: 6 to 10 grams Maximum 400 mg orally per day in most circumstances Outpatient: 400 to 600 mg orally per day in divided doses with meal Lowest effective dose, ideally 200 mg or less orally once per day or in divided doses Inpatient: 400 to 1200 mg orally per day in divided doses with meals for 1 to 2 weeks Prevention of ventricular arrhythmias in patients Total loading dose: 6 to 10 grams Maximum 400 mg orally per day in most circumstances with ICDs to decrease risk of shocks Outpatient: Given as 400 to 600 mg orally per day in Lowest effective dose, ideally 200 mg or less orally per day divided doses with meals Inpatient: Given as 400 to 1200 mg orally per day in divided doses with meals until desired dose is achieved Cardiac arrest associated with VF or pulseless VT 300 mg IV or IO rapid bolus with a repeat dose of 150 mg as indicated Upon return of spontaneous circulation follow with an infusion of 1 mg per minute for 6 hours and then 0.5 mg per minute for 18 hours* Electrical (VT) storm and incessant VT in hemodynamically stable Total IV loading dose: 1050 mg If amiodarone is used chronically: Lowest effective dose, ideally 200 mg or less 150 mg IV bolus over 10 minutes, followed by continuous IV infusion at 1 mg per minute for 6 hours, patients orally per day; maximum 400 mg orally per day in most circumstances then 0.5 mg per minute for 18 hours IV infusion (0.5 mg per minute) may need to be extended past 24 hours if unable to transition to oral therapy https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 14/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Additional 150 mg boluses may be given if VT storm recurs If amiodarone will be used chronically: Following IV infusion 400 to 1200 mg orally per day in divided doses to complete a total (IV plus oral) loading dose of 10 grams. Consider overlapping IV and oral amiodarone for 24-48 hours PAF: paroxysmal atrial fibrillation; AF: atrial fibrillation; NSR: normal sinus rhythm; IV: intravenous; SCD: sudden cardiac death; LV: left ventricular; ICD: implantable cardioverter-defibrillator; VF: ventricular fibrillation; VT: ventricular tachycardia; IO: intraosseous. When administered to critically ill patients with atrial fibrillation and rapid ventricular response, repeated 150 mg boluses can be given over 10 to 30 minutes if needed, but no more than six to eight additional boluses should be administered in any 24-hour period. Typically, patients are given 1 or 2 doses of oral amiodarone prior to discontinuation of the IV infusion. Graphic 117524 Version 5.0 https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 15/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 16/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 17/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. |
12/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate GRAPHICS Amiodarone dosing in adults by indication Indications Loading dose Maintenance dose Atrial arrhythmias Prevention of recurrent PAF Total loading dose: 6 to 10 grams Lowest effective dose, usually 100 to 200 mg orally once per day Pharmacologic cardioversion of PAF Outpatient: Given as 400 to 600 mg orally per day in divided doses with meals Maximum 200 mg orally per day Inpatient: Given as 400 to 1200 mg orally per day in divided doses with meals Pretreatment before elective cardioversion or Total loading dose: 6 to 10 grams orally over 2 to 6 Lowest effective dose, usually 100 to 200 mg orally catheter ablation of AF weeks once per day Given as 400 to 1200 mg Maximum 400 mg orally per orally per day in divided doses day in most circumstances Restoration and maintenance of NSR in critically ill patients with AF Total IV loading dose: 1050 mg Given as 150 mg IV bolus over 10 to 30 minutes, followed by continuous IV infusion at 1 mg per minute for 6 hours, then 0.5 mg per Ventricular rate control in critically ill patients with AF and rapid ventricular response minute for 18 hours* IV infusion (0.5 mg per minute) may need to be extended past 24 hours if unable to transition to oral therapy If amiodarone will be used chronically: Following IV infusion, give 400 to 1200 mg orally per day in divided doses to complete a total (IV plus oral) loading dose of 10 grams; consider overlapping IV and oral amiodarone for 24 to 48 hours https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 13/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Ventricular arrhythmias Primary and secondary prevention of SCD in patients with LV dysfunction who are not candidates for or refuse ICD implantation Total oral loading dose: 6 to 10 grams Maximum 400 mg orally per day in most circumstances Outpatient: 400 to 600 mg orally per day in divided doses with meal Lowest effective dose, ideally 200 mg or less orally once per day or in divided doses Inpatient: 400 to 1200 mg orally per day in divided doses with meals for 1 to 2 weeks Prevention of ventricular arrhythmias in patients Total loading dose: 6 to 10 grams Maximum 400 mg orally per day in most circumstances with ICDs to decrease risk of shocks Outpatient: Given as 400 to 600 mg orally per day in Lowest effective dose, ideally 200 mg or less orally per day divided doses with meals Inpatient: Given as 400 to 1200 mg orally per day in divided doses with meals until desired dose is achieved Cardiac arrest associated with VF or pulseless VT 300 mg IV or IO rapid bolus with a repeat dose of 150 mg as indicated Upon return of spontaneous circulation follow with an infusion of 1 mg per minute for 6 hours and then 0.5 mg per minute for 18 hours* Electrical (VT) storm and incessant VT in hemodynamically stable Total IV loading dose: 1050 mg If amiodarone is used chronically: Lowest effective dose, ideally 200 mg or less 150 mg IV bolus over 10 minutes, followed by continuous IV infusion at 1 mg per minute for 6 hours, patients orally per day; maximum 400 mg orally per day in most circumstances then 0.5 mg per minute for 18 hours IV infusion (0.5 mg per minute) may need to be extended past 24 hours if unable to transition to oral therapy https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 14/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Additional 150 mg boluses may be given if VT storm recurs If amiodarone will be used chronically: Following IV infusion 400 to 1200 mg orally per day in divided doses to complete a total (IV plus oral) loading dose of 10 grams. Consider overlapping IV and oral amiodarone for 24-48 hours PAF: paroxysmal atrial fibrillation; AF: atrial fibrillation; NSR: normal sinus rhythm; IV: intravenous; SCD: sudden cardiac death; LV: left ventricular; ICD: implantable cardioverter-defibrillator; VF: ventricular fibrillation; VT: ventricular tachycardia; IO: intraosseous. When administered to critically ill patients with atrial fibrillation and rapid ventricular response, repeated 150 mg boluses can be given over 10 to 30 minutes if needed, but no more than six to eight additional boluses should be administered in any 24-hour period. Typically, patients are given 1 or 2 doses of oral amiodarone prior to discontinuation of the IV infusion. Graphic 117524 Version 5.0 https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 15/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 16/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 17/18 7/6/23, 1:41 PM Pharmacologic therapy in survivors of sudden cardiac arrest - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/pharmacologic-therapy-in-survivors-of-sudden-cardiac-arrest/print 18/18 |
7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Prognosis and outcomes following sudden cardiac arrest in adults : Philip J Podrid, MD, FACC : Brian Olshansky, MD, Scott Manaker, MD, PhD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 16, 2023. INTRODUCTION Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac mechanical activity with hemodynamic collapse, often due to sustained ventricular tachycardia/ventricular fibrillation. These events mostly occur in patients with evidence for ischemia due to coronary artery disease, disease of the myocardium (due to hypertrophy, fibrosis, scar replacement, or other myocardial abnormality that may or may not have been previously diagnosed), valvular abnormalities, or congenital heart disease or congenital or genetic electrical abnormalities or channelopathies. (See "Pathophysiology and etiology of sudden cardiac arrest".) The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation) or spontaneous reversion of the heart rhythm restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.) The prognosis of patients who have SCA will be reviewed here. The issues related to acute therapy for SCA, including guidelines for advanced cardiovascular life support (ACLS), and issues related to prevention of recurrent sudden cardiac death, are discussed separately. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest" and https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 1/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate "Advanced cardiac life support (ACLS) in adults" and "Pharmacologic therapy in survivors of sudden cardiac arrest".) PROGNOSIS FOLLOWING SUDDEN CARDIAC ARREST Despite advances in the treatment of heart disease, the outcome of patients experiencing SCA remains poor [1-5]. As examples: A report analyzed outcomes for over 12,000 patients treated by emergency medical services (EMS) personnel in Seattle over 24 years [1]. Survival to hospital discharge for those treated between 1998 and 2001 was not significantly better than for those treated between 1977 and 1981 (15.7 versus 17.5 percent). In contrast, the long-term outcome among patients who survive until hospital discharge following SCA appears to be improving [2]. Among a nationwide cohort of 547,153 patients in Japan with out-of-hospital SCA between 2005 and 2009, survival to hospital discharge with favorable neurologic status improved approximately twofold in several groups over the five-year period (from 1.6 to 2.8 percent among all patients with out-of-hospital SCA, from 2.1 to 4.3 percent among bystander- witnessed SCA, and from 9.8 to 20.6 percent among bystander-witnessed SCA with ventricular fibrillation as the initial rhythm) [3]. However, in spite of this doubling of neurologically favorable survival, overall survival following SCA remains poor. Among 70,027 United States patients prospectively enrolled in the CARES registry following out-of-hospital SCA between 2005 and 2012, survival to hospital discharge improved significantly from 5.7 percent in 2005 to 8.3 percent in 2012 [4]. Improvements were also noted in pre-hospital survival and neurologic function at hospital discharge. In a Canadian study of 34,291 patients who arrived at the hospital alive following out-of- hospital cardiac arrest between 2002 and 2011, survival at both 30-day and one-year increased significantly between 2002 and 2011 (from 7.7 to 11.8 percent for one-year survival) [5]. Similarly, among a cohort of 6999 Australian patients with out-of-hospital SCA resuscitated by EMS between 2010 and 2012, 851 patients (12.2 percent) survived for at least one year, with more than half of patients reporting good neurologic recovery and functional status at one year [6]. The reasons for the continued poor survival of patients with SCA are not certain [1]. Although some aspects of acute resuscitation have improved over time (increased bystander cardiopulmonary resuscitation [CPR] and shortened time to defibrillation), these positive trends https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 2/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate have been off-set by adverse trends in clinical features of patients presenting with SCA (such as increasing age and decreasing proportion presenting with ventricular fibrillation) [1,7]. In addition, the response times of both basic life support (BLS) and advanced life support (ALS) services have increased, possibly as a result of population growth and urbanization [8]. Marked regional differences in the incidence and outcome of SCA have been observed. In a prospective observational study of 10 North American regions, the adjusted incidence of EMS- treated out-of-hospital SCA ranged from 40.3 to 86.7 (median 52.1) per 100,000 census population; known survival to discharge ranged from 3.0 to 16.3 percent (median 8.4 percent) [9]. The adjusted incidence of ventricular fibrillation ranged from 9.3 to 19.0 (median 12.6) per 100,000 census population; known survival to discharge ranged from 7.7 to 39.9 (median 22) percent. These regional differences highlight the importance of local health care and EMS systems to SCA outcomes. A pilot study comparing the feasibility of EMS transport to a regional cardiac arrest center (with increased transit time) versus transport to the closest hospital suggested no difference in 30-day mortality or major adverse cardiac events, results which should be considered hypothesis-generating for larger scale studies [10]. Neurologic prognosis following sudden cardiac arrest Survivors of SCA have variable susceptibility to hypoxic-ischemic brain injury, depending on the duration of circulatory arrest, extent of resuscitation efforts, and underlying comorbidities. The prognosis following hypoxic- ischemic brain injury is discussed in detail separately. (See "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis".) OUTCOME ACCORDING TO ETIOLOGY There is an association between the mechanism of SCA and the outcome of initial resuscitation. Asystole When the initial observed rhythm is asystole (even if preceded by ventricular tachycardia or ventricular fibrillation), the likelihood of successful resuscitation is low. The longer ventricular fibrillation is present, the finer are the fibrillatory waves, and ultimately asystole occurs. The duration of ventricular fibrillation impacts the success of defibrillation (see below). Only 10 percent of patients with out-of-hospital arrests and initial asystole survive until hospital admission [11,12] and less than 5 percent survive until hospital discharge with good neurologic function [12-14]. The poor outcome in patients with asystole or bradycardia due to a very slow idioventricular rhythm probably reflects the prolonged duration of the cardiac arrest (usually more than four minutes) and the presence of severe, irreversible myocardial, brain and other end-organ damage. (See "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis".) https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 3/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Factors associated with successful resuscitation of patients presenting with asystole include spontaneous conversion to a shockable rhythm, witnessed arrest, younger patient age, shorter time to arrival of emergency medical services (EMS) personnel, and no further need for treatment with atropine for a bradyarrhythmia after initial resuscitation [12,15,16]. In a systematic review of 1,108,281 patients (from 12 studies) with SCA and initial nonshockable rhythms, approximately 4.6 percent of patients had spontaneous conversion to a shockable rhythm, which was associated with a greater chance of return of spontaneous circulation (odds ratio 1.47, 95% CI 1.40-1.55) as well as greater odds of survival and favorable neurologic status at 30 days [16]. Pulseless electrical activity Patients who have SCA due to pulseless electrical activity (also called electrical-mechanical dissociation) also have a poor outcome due to absence of cardiac output and organ perfusion. In one study of 150 such patients, 23 percent were resuscitated and survived to hospital admission; only 11 percent survived until hospital discharge [17]. Ventricular tachyarrhythmia The outcome is much better when the initial rhythm is a sustained ventricular tachyarrhythmia, especially ventricular tachycardia as there is some cardiac output and organ perfusion. The most frequent etiology is ventricular fibrillation (VF). Approximately 25 to 40 percent of patients with SCA caused by VF survive until hospital discharge [1,18,19]. Survival is dependent upon the duration of VF and time to defibrillation. In the Seattle series cited above of over 12,000 EMS-treated patients with SCA, 38 percent had witnessed VF [1]. Patients with witnessed VF (in whom time to defibrillation is shorter) had a significantly greater likelihood of surviving to hospital discharge than those with other rhythms (34 versus 6 percent). Acute myocardial infarction (MI) or myocardial ischemia is the underlying cause of VF for many of the patients who survive to hospital discharge. In a series of 79 such patients from the Mayo Clinic, 47 percent had an acute MI, while in a series of 47 such patients from the Netherlands, 51 percent had an acute MI [18,19]. Survival is approximately 65 to 70 percent in patients who present with hemodynamically unstable ventricular tachycardia (VT) [20]. The prognosis may be better in patients found in monomorphic VT because of the potential for some systemic perfusion during this more organized arrhythmia. In addition, patients with VT tend to have a lower incidence of a previous infarction and may have a higher ejection fraction when compared with those with VF [21]. SCA due to noncardiac causes As many as one-third of cases of SCA are due to noncardiac causes [1,22]. Trauma, nontraumatic bleeding, intoxication, near drowning, and pulmonary embolism are the most common noncardiac etiologies. In one series, 40 percent of such https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 4/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate patients were successfully resuscitated and hospitalized; however, only 11 percent were discharged from the hospital and only 6 percent were neurologically intact or had mild disability. FACTORS AFFECTING OUT-OF-HOSPITAL SCA OUTCOME Despite the efforts of emergency personnel, resuscitation from out-of-hospital SCA is successful in only one-third of patients, and only about 10 percent of all patients are ultimately discharged from the hospital, many of whom are neurologically impaired [4,5,7,23-27]. (See "Hypoxic- ischemic brain injury in adults: Evaluation and prognosis".) The cause of death in-hospital is most often noncardiac, usually anoxic encephalopathy from poor or absent cerebral perfusion or respiratory complications from long-term ventilator dependence [28]. Only about 10 percent of patients die primarily from recurrent arrhythmia, while approximately 30 percent die primarily from a low cardiac output or cardiogenic shock as the consequence of mechanical failure. Recurrence of severe arrhythmia in the hospital is associated with a worse outcome [29]. Race-ethnic differences in out-of-hospital CPR Across all neighborhood income strata, the frequency of bystander CPR at home and in public locations was lower among Black and Hispanic persons with out-of-hospital cardiac arrest than among White persons [30]. Within a large United States registry, out of 35,469 witnessed out-of-hospital cardiac arrests from 2013 to 2019, 32.2 percent occurred in Black or Hispanic persons. Black and Hispanic persons were less likely to receive bystander CPR at home than White persons (38.5 versus 47.4 percent; odds ratio [OR] 0.74; 95% CI 0.72-0.76) and less likely to receive bystander CPR in public locations than White persons (45.6 versus 60 percent; OR 0.63; 95% CI 0.60-0.66). The incidence of bystander CPR among Black and Hispanic persons was less than that among White persons in the following settings: In predominantly White neighborhoods at home (43.8 versus 49.1 percent; OR 0.82; 95% CI 0.74-0.90) and in public locations (50.7 versus 61.8 percent; OR 0.68; 95% CI 0.60-0.75). In majority Black or Hispanic neighborhoods at home (37.3 versus 43.4; OR 0.79; 95% CI 0.75-0.83) and in public locations (41.7 versus 55.7 percent; OR 0.63; 95% CI 0.59-0.68). In integrated neighborhoods at home (40.9 versus 47.1 percent; OR 0.78; 95% CI 0.74-0.81) and in public locations (50.4 versus 60.3 percent; OR 0.73; 95% CI 0.68-0.77). The investigators suggested that public health interventions that go beyond CPR training in Black and Hispanic communities, including use of linguistically and culturally appropriate CPR https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 5/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate training, funding for dispatcher-assisted CPR in majority Black and Hispanic neighborhoods, and engagement of community leaders, may be indicated to reduce racial and ethnic differences in bystander CPR. Risk scores to assess likelihood of survival In addition to later initiation of CPR and the presence of asystole or pulseless electrical activity (electromechanical dissociation) [11-13,17], there are a number of other factors that are associated with a decreased likelihood of survival with neurologic function intact following out-of-hospital SCA [19,31-35]: Absence of any vital signs Sepsis Cerebrovascular accident with severe neurologic deficit Cancer or Alzheimer disease History of more than two chronic diseases A history of cardiac disease Prolonged CPR more than five minutes There are also several poor prognostic features in patients with SCA who survive until admission: Persistent coma after CPR (see "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis") Hypotension, pneumonia, and/or renal failure after CPR Need for intubation or pressors History of class III or IV heart failure Older age Clinical risk scores incorporating a variety of patient characteristics have been developed in an effort to predict survival post-SCA [36-39]. Risk scores, when used, should be interpreted in conjunction with the overall clinical assessment. As examples: The NULL-PLEASE score (from 0 to 10), retrospectively validated in a single-center cohort of 547 patients with out-of-hospital SCA between 2013 and 2016, stratifies risk of mortality [36]. Nonshockable rhythm Unwitnessed arrest Long no-flow period (no bystander CPR) Long low-flow period (>30 minutes before return of spontaneous circulation [ROSC]) pH (arterial) <7.2 Lactate >7 mmol/L https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 6/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate End-stage kidney disease on dialysis Age 85 years Still (ongoing) CPR on arrival to hospital Extracardiac cause Patients with 5 features on the NULL-PLEASE score had a greater than threefold risk of mortality compared with patients with a score from 0 to 4 (odds ratio [OR] 3.3, 95% CI 2.3- 4.9). The CREST score (from 0 to 5), derived from 638 patients and validated in 318 patients who experienced out-of-hospital cardiac arrest and were enrolled in the International Cardiac Arrest Registry (INTCAR), stratifies patients on risk of circulatory death following ROSC [37]. Coronary artery disease (preexisting) Rhythm nonshockable Ejection fraction <30 percent Shock at presentation Time (ischemic time prior to ROSC) >25 minutes Risk of circulatory death increased with every additional point, from 10 percent mortality with CREST = 0 up to 50 percent mortality with CREST = 5. VF duration Ventricular fibrillation (VF) in the human heart rarely, if ever terminates spontaneously or reverts with an antiarrhythmic drug, and survival is therefore dependent upon the prompt delivery of effective CPR. Electrical defibrillation is the only way to reestablish organized electrical activity and myocardial contraction. (See "Cardioversion for specific arrhythmias".) Increasing duration of VF has two major adverse effects: it reduces the ability to terminate the arrhythmia and, as with prolonged VF, the fibrillatory waves become finer and ultimately become absent, reflecting less electrical activity and thus less responsiveness to defibrillation, and, if VF continues for more than four minutes, there is the beginning of irreversible damage to the central nervous system and other organs [40-42]. As a result, the longer the duration of the cardiac arrest, the lower the likelihood of resuscitation or survival with or without neurologic impairment even if CPR is successful. It has been suggested that without CPR, survival from a cardiac arrest caused by VF declines by approximately 10 percent for each minute without defibrillation, and after more than 12 minutes without CPR, the survival rate is only 2 to 5 percent [43-45]. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 7/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Time to resuscitation These observations constitute the rationale for attempts to provide more rapid resuscitation in patients with out-of-hospital SCA, especially more prompt defibrillation. One approach is optimizing the EMS system within a community to reduce the response interval to less than eight minutes [46]. However, in some areas, the response times of both BLS and ALS services have actually increased, possibly as a result of population growth and urbanization. In the Seattle series of over 12,000 EMS-treated patients, the BLS response interval increased from 3.8 to 5.1 minutes between 1977 and 2001, and the ALS response interval increased from 8.4 to 9.0 minutes [1]. Thus, bystander CPR and even defibrillation (using an automatic external defibrillator or AED) have been recommended and have been implemented in some settings. Such interventions permit more rapid responses than those provided by ALS or BLS personnel, with better survival as a result. In the Seattle series, the OR for survival to discharge for patients who received bystander CPR to those who did not was 1.85 [1]. Bystander CPR The administration of CPR by a layperson bystander (bystander CPR or bystander-initiated CPR) and prompt defibrillation with an AED are important factors in determining patient outcome after out-of-hospital SCA. Survival after SCA is greater among those who have bystander CPR when compared with those who initially receive more delayed CPR from EMS personnel [47]. In addition to improved survival, early restoration or improvement in circulation is associated with better neurologic function among survivors [48-50]. For adults with sudden out-of-hospital SCA, compression-only bystander CPR (without rescue breathing) appears to have equal or possibly greater efficacy compared with standard bystander CPR (compressions plus rescue breathing). With prompt chest compression, there is some cardiac output and systemic blood flow to organs. The 2010 American Heart Association (AHA) Guidelines for CPR, along with subsequent professional society guidelines, recommended that bystanders perform compression-only CPR to provide high-quality chest compressions prior to the arrival of emergency personnel [51-55]. (See 'Chest compression-only CPR' below.) The importance of bystander CPR and support for compression-only bystander CPR comes from a combination of retrospective and prospective studies. An initial report from the Seattle Heart Watch program in the late 1970s evaluated 109 consecutive patients resuscitated at the scene by a bystander trained in CPR and compared their outcomes with those of 207 patients who initially received CPR from EMS personnel [56]. There was no difference between the two groups in the percentage of patients resuscitated at the scene and admitted alive to the hospital (67 versus 61 percent), but the percentage discharged alive was significantly higher among those with bystander CPR (43 versus 22 percent). The most important reason for the improvement in https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 8/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate survival in this study was that earlier CPR and prompt defibrillation were associated with less damage to the central nervous system and other organs, including the heart. More patients with bystander CPR were conscious at the time of hospital admission (50 versus 9 percent), and more regained consciousness by the end of hospitalization (81 versus 52 percent). These observations were subsequently confirmed in larger studies [49,50,57-63]. In a nationwide study of out-of-hospital cardiac arrest in Japan between 2005 and 2012, during which time the number of out-of-hospital cardiac arrests grew by 33 percent (n = 17,882 in 2005 compared with n = 23,797 in 2012), rates of bystander CPR increased (from 39 to 51 percent), and recipients of bystander CPR had a significantly greater chance of neurologically intact survival (8.4 versus 4.1 percent without bystander CPR; OR 1.52, 95% CI 1.45-1.60) [49]. Early defibrillation by bystanders was also associated with a significantly greater odds of neurologically intact survival. In a cohort of 25,505 persons with out-of-hospital cardiac arrest in Denmark between 2001 and 2010 which was not witnessed by EMS personnel (from the nationwide Danish Cardiac Arrest Registry), the frequency of bystander CPR increased significantly from 2001 to 2014 in both public locations (from 36 to 83 percent) and private residences (from 16 to 61 percent), with a corresponding significant increase in survival at 30 days (from 6.4 to 25.2 percent in public locations and from 2.9 to 10 percent in private residences) [62]. In a nationwide cohort of 30,445 bystander-witnessed cardiac arrests in Sweden between 2000 and 2017, the frequency of bystander CPR prior to EMS arrival improved significantly over time, from 40.8 percent between 2000 and 2005 to 68.2 percent between 2011 and 2017 [47]. While the number of patients receiving standard CPR improved by 3 percent over the same time period (from 35.4 to 38.1 percent), administration of compression-only CPR increased from 5.4 to 30.1 percent. Both standard CPR and compression only CPR administered by bystanders were associated with more than twofold increased likelihood of survival compared with no CPR prior to EMS arrival. Despite the benefits of bystander CPR, it is not always performed. Reasons for this include the bystander's lack of CPR training and concerns about possible transmission of disease while performing rescue breathing [64]. Neighborhood demographics (eg, income level) also appear to be a factor in the rates of bystander CPR performance. In an analysis of 14,225 patients with cardiac arrest in 29 United States sites participating in Cardiac Arrest Registry to Enhance Survival (CARES), bystander CPR was significantly more likely to be performed in higher-income (above 40,000 USD per year) than in lower-income (less than 40,000 USD per year) neighborhoods [65]. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 9/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Interventions that appear to improve the rate of bystander CPR include verbal encouragement and instruction in CPR by EMS dispatchers, and public campaigns to promote the delivery of bystander CPR [64]: In a series of over 12,000 EMS-treated patients from Seattle, bystanders not trained in CPR were given instructions by telephone from the EMS dispatcher [1]. The proportion of patients receiving bystander CPR increased from 27 to 50 percent, almost entirely as a result of the implementation of dispatcher-assisted CPR in that interval. A prospective observational study of 4400 adults with out-of-hospital sudden cardiac death noted a rise in the delivery of bystander CPR from 28 to 40 percent over the course of a five-year public campaign to encourage bystander compression-only CPR [66]. Chest compression-only CPR Bystander CPR with chest compressions alone results in improved survival to hospital discharge, compared with chest compressions with interruptions for rescue breathing, with an absolute improvement in mortality of 2.4 percent (NNT = 42 to save one additional life) [67]. With continuous chest compressions, there is better systemic circulation. Initial observational studies that evaluated the delivery of compression-only CPR versus standard CPR including rescue breathing found no significant differences in survival or long- term neurologic function between the two groups, suggesting that compression-only CPR could be safely delivered [66,68-70]. Three randomized trials of compression-only CPR versus standard CPR all showed a trend toward improved outcomes in the compression-only CPR group [71-73]. The trends toward improved survival to discharge with compression-only CPR became statistically significant when the results of the three trials (thereby increasing the number of patients) were combined in a meta-analysis (14 versus 12 percent in the standard CPR group; risk ratio 1.22, 95% CI 1.01-1.46) [74,75]. Nationwide cohort studies of out-of-hospital cardiac arrest victims in both Japan and Sweden have demonstrated improvements in the number of SCA victims receiving bystander CPR, as well as the number of patients surviving with chest compression-only CPR [47,76]. These findings hold promise for improving the delivery of bystander CPR. Further data are required to determine if bystander-delivered compression-only CPR (rather than standard CPR) will translate into better neurologic outcomes for patients with out-of-hospital cardiac arrest. (See "Adult basic life support (BLS) for health care providers".) Automated mechanical CPR devices Several automated devices that deliver chest compressions have been developed in an attempt to improve upon chest compressions delivered by humans as well as to allow rescuers to perform other interventions simultaneously. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 10/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate While a 2013 meta-analysis of 12 studies (only 3 of which were randomized clinical trials) suggested higher rates of the ROSC when an automated device was used, subsequent randomized trials showed no significant differences in survival between the mechanical CPR and manual CPR groups. Additional discussion of automated mechanical CPR devices is presented separately. (See "Therapies of uncertain benefit in basic and advanced cardiac life support", section on 'Mechanical compression devices'.) Timing of defibrillation The standard of care for resuscitation from ventricular fibrillation has been defibrillation as soon as possible. In the Seattle series of over 12,000 EMS-treated patients, 4546 had witnessed VF. For these patients, the defibrillation response interval was significantly correlated with survival to hospital discharge (OR 0.88 for every one-minute increase in response time) [1]. Subsequent studies have shown similar benefits, with earlier defibrillation being associated with improved survival and neurologic outcomes [49,57,77,78]. Despite these findings, it has been suggested that outcomes may be improved by performing CPR before defibrillation, at least in patients in whom defibrillation is delayed for more than four to five minutes [79,80]. An initial report from Seattle compared outcomes in two time periods: when an initial shock was given as soon as possible; and, subsequently, when the initial shock was delayed until 90 seconds of CPR had been performed [79]. Survival to hospital discharge was significantly increased with routine CPR before defibrillation, primarily in patients in whom the initial response interval was four minutes or longer (27 versus 17 percent without prior CPR). However, in the largest study to date comparing shorter versus longer periods of initial CPR prior to defibrillation in 9933 patients with SCA, patients were randomly assigned to receive 30 to 60 seconds versus 180 seconds of CPR prior to cardiac rhythm analysis and defibrillation (if indicated) [81]. There was no significant difference in the primary endpoint of survival to hospital discharge with satisfactory functional status (5.9 percent in both groups). For patients with SCA and ventricular tachyarrhythmia, we perform early defibrillation and CPR as recommended in the 2010 advanced cardiovascular life support (ACLS) guidelines ( algorithm 1). (See "Advanced cardiac life support (ACLS) in adults".) Automated external defibrillators The use of automated external defibrillators (AEDs) by early responders is another approach to more rapid resuscitation. In most but not all studies, AEDs have been found to improve survival after out-of-hospital cardiac arrest. The development, use, allocation, and efficacy of AEDs are discussed elsewhere. (See "Automated external defibrillators".) One example of the efficacy of AEDs when used by bystanders prior to the arrival of emergency responders comes from a study of 49,555 out-of-hospital cardiac arrests at nine regional centers https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 11/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate from 2011 to 2015, of which 4115 (8.3 percent) were observed in public by bystanders. Among the observed public arrests, 60 percent had an initially shockable rhythm, and 19 percent were shocked with an AED. Patients shocked by bystanders using the AED were significantly more likely to survive to hospital discharge (67 versus 43 percent) and to have favorable neurologic function (defined as modified Rankin score 2) at discharge (57 versus 33 percent) [82]. Predictive value of BLS and ALS rules The OPALS study group has proposed two termination of resuscitation rules for use by EMS personnel. The rule for BLS providers equipped with AEDs includes the following three criteria: event not witnessed by emergency medical services personnel; no AED used or manual shock applied in out-of-hospital setting; and no ROSC in out-of-hospital setting [83]. The advanced life support (ALS) rule includes the BLS criteria as well as two additional criteria: arrest not witnessed by bystander and no bystander- administered CPR [84]. Validation of the predictive value of the BLS and ALS termination rules was performed with data from a retrospective cohort study that included 5505 adults with out-of-hospital SCA [85]. The overall rate of survival to hospital discharge was 7 percent. Of 2592 patients (47 percent) who met BLS criteria for termination of resuscitation efforts, only 5 survived to hospital discharge. Of 1192 patients (22 percent) who met ALS criteria, none survived to hospital discharge. However, the validity of these termination rules may be reduced with improvements in EMS and postresuscitation care. One potential target for understanding and ameliorating current limitations to postarrest care is the observed marked regional variation in prognosis following SCA. (See 'Prognosis following sudden cardiac arrest' above.) Adequacy of CPR The adequacy of CPR delivered to a victim of cardiac arrest and outcomes related to resuscitation efforts may depend on a variety of factors (eg, rate and depth of chest compressions, amount of time without performing chest compressions while performing other tasks such as defibrillation, etc). The American Heart Association (AHA) 2010 Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care emphasized early defibrillation (when available) and high-quality chest compressions (rate at least 100 per minute, depth of two inches or more) with minimal interruptions [52]. The effect of CPR quality has been evaluated in several studies [86-88]: In a 2013 systematic review and meta-analysis which included 10 studies (4722 patients total, 4516 of whom experienced out-of-hospital cardiac arrest), persons surviving cardiac arrest were significantly more likely than nonsurvivors to have received deeper chest compressions and have had compression rates between 85 and 100 compressions per minute (compared with shallower and slower compression rates) [86]. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 12/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate In a study of 3098 patients with out-of-hospital cardiac arrest, ROSC was highest at a rate of 125 compressions per minute [87]. However, higher chest compression rates were not significantly associated with survival to hospital discharge, which is consistent with the finding in the systematic review and meta-analysis above. (See "Adult basic life support (BLS) for health care providers", section on 'Performance of excellent chest compressions'.) End-tidal carbon dioxide levels have an excellent correlation with very low cardiac outputs when measured after at least 10 minutes of CPR and may provide prognostic information, suggesting that the cardiac output maintained during CPR is a determinant of outcome. This concept is discussed in greater detail elsewhere. (See "Carbon dioxide monitoring (capnography)", section on 'Effectiveness of CPR'.) Body temperature An increase in body temperature is associated with unfavorable functional neurologic recovery after successful CPR. The increase in temperature may be neurally-mediated and can exacerbate the degree of neural injury associated with brain ischemia. For the highest temperature within 48 hours, each degree Celsius higher than 37 C increases the risk of an unfavorable neurologic recovery (OR of 2.26 in one report) [89]. On the other hand, the induction of mild to moderate hypothermia (target temperature 32 to 34 C for 24 hours) may be beneficial in patients successfully resuscitated after a cardiac arrest, although studies have shown variable outcomes. This issue is discussed in greater detail elsewhere. (See "Initial assessment and management of the adult post-cardiac arrest patient", section on 'Temperature management'.) Prehospital ACLS The incremental benefit of deploying EMS personnel trained in ACLS interventions (intubation, insertion of intravenous lines, and intravenous medication administration) on survival after cardiac arrest probably depends upon the quality of other prehospital services. In the OPALS study, ACLS interventions were added to an optimized emergency medical services program of rapid defibrillation [57]. No improvement in the rate of survival for out- of-hospital cardiac arrest was observed with addition of an ACLS program. In a retrospective report from Queensland with an emergency services program not optimized for early defibrillation, the presence of ACLS-skilled EMS personnel was associated with improved survival for out-of-hospital cardiac arrest [90]. Effect of older age The risk of SCA increases with age, and older age has been associated with a poorer survival in some, but not all studies of out-of-hospital cardiac arrests [1,91-95]: https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 13/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate In one study of 5882 patients who experienced an out-of-hospital cardiac arrest, 22 percent were >80 years of age [96]. Compared with patients <80 years of age, octogenarians and nonagenarians had a lower rate of hospital discharge (9.4 and 4.4 versus 19 percent for those <80). The discharge rate was higher in those with VF or pulseless ventricular tachycardia (VT) as the initial rhythm. Very old patients still had a poorer survival (24 and 17 versus 36 percent), but age was a weaker predictor than the initial rhythm. In the Seattle series of over 12,000 EMS-treated patients, every one-year increase in age was associated with a lower likelihood of survival to hospital discharge for all patients (OR 0.97 per year) and for those with witnessed VF (OR 0.98 per year) [1]. In a study of 36,605 patients ages 70 years or older enrolled in a Swedish registry between 1990 and 2013 following SCA, 30-day survival was significantly higher in patients ages 70 to 79 years (6.7 percent) compared with patients ages 80 to 89 years (4.4 percent) and those over 90 years of age (2.4 percent) [95]. Effect of sex The incidence of SCA is greater in males than females [1,97]. The effect of sex on outcome has been examined in multiple cohorts, with the following findings [97-99]: Males are more likely than females to have VF or VT as an initial rhythm. Males are more likely than females to have a witnessed arrest. Males have a higher one-month survival than females following SCA, due to the higher likelihood of VF/VT as their presenting rhythm. However, when considering only patients with VF/VT as the initial rhythm, females have a greater survival with favorable neurologic outcome. Effect of comorbidities The impact of preexisting chronic conditions on the outcome of out- of-hospital SCA was evaluated in a series of 1043 SCA victims in King County, Washington, in the United States [100]. There was a statistically significant reduction in the probability of survival to hospital discharge with increasing numbers of chronic conditions, such as congestive heart failure, prior MI, hypertension, and diabetes (OR 0.84 for each additional chronic condition). The impact of comorbidities was more prominent with longer EMS response intervals. Association of depression and anxiety with long-term outcomes In a study of 2373 patients from South Korea with out-of-hospital cardiac arrest followed for a median of 5.1 years for the outcome of mortality, 16.7 percent were diagnosed with depression or anxiety [101]. |
services personnel; no AED used or manual shock applied in out-of-hospital setting; and no ROSC in out-of-hospital setting [83]. The advanced life support (ALS) rule includes the BLS criteria as well as two additional criteria: arrest not witnessed by bystander and no bystander- administered CPR [84]. Validation of the predictive value of the BLS and ALS termination rules was performed with data from a retrospective cohort study that included 5505 adults with out-of-hospital SCA [85]. The overall rate of survival to hospital discharge was 7 percent. Of 2592 patients (47 percent) who met BLS criteria for termination of resuscitation efforts, only 5 survived to hospital discharge. Of 1192 patients (22 percent) who met ALS criteria, none survived to hospital discharge. However, the validity of these termination rules may be reduced with improvements in EMS and postresuscitation care. One potential target for understanding and ameliorating current limitations to postarrest care is the observed marked regional variation in prognosis following SCA. (See 'Prognosis following sudden cardiac arrest' above.) Adequacy of CPR The adequacy of CPR delivered to a victim of cardiac arrest and outcomes related to resuscitation efforts may depend on a variety of factors (eg, rate and depth of chest compressions, amount of time without performing chest compressions while performing other tasks such as defibrillation, etc). The American Heart Association (AHA) 2010 Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care emphasized early defibrillation (when available) and high-quality chest compressions (rate at least 100 per minute, depth of two inches or more) with minimal interruptions [52]. The effect of CPR quality has been evaluated in several studies [86-88]: In a 2013 systematic review and meta-analysis which included 10 studies (4722 patients total, 4516 of whom experienced out-of-hospital cardiac arrest), persons surviving cardiac arrest were significantly more likely than nonsurvivors to have received deeper chest compressions and have had compression rates between 85 and 100 compressions per minute (compared with shallower and slower compression rates) [86]. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 12/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate In a study of 3098 patients with out-of-hospital cardiac arrest, ROSC was highest at a rate of 125 compressions per minute [87]. However, higher chest compression rates were not significantly associated with survival to hospital discharge, which is consistent with the finding in the systematic review and meta-analysis above. (See "Adult basic life support (BLS) for health care providers", section on 'Performance of excellent chest compressions'.) End-tidal carbon dioxide levels have an excellent correlation with very low cardiac outputs when measured after at least 10 minutes of CPR and may provide prognostic information, suggesting that the cardiac output maintained during CPR is a determinant of outcome. This concept is discussed in greater detail elsewhere. (See "Carbon dioxide monitoring (capnography)", section on 'Effectiveness of CPR'.) Body temperature An increase in body temperature is associated with unfavorable functional neurologic recovery after successful CPR. The increase in temperature may be neurally-mediated and can exacerbate the degree of neural injury associated with brain ischemia. For the highest temperature within 48 hours, each degree Celsius higher than 37 C increases the risk of an unfavorable neurologic recovery (OR of 2.26 in one report) [89]. On the other hand, the induction of mild to moderate hypothermia (target temperature 32 to 34 C for 24 hours) may be beneficial in patients successfully resuscitated after a cardiac arrest, although studies have shown variable outcomes. This issue is discussed in greater detail elsewhere. (See "Initial assessment and management of the adult post-cardiac arrest patient", section on 'Temperature management'.) Prehospital ACLS The incremental benefit of deploying EMS personnel trained in ACLS interventions (intubation, insertion of intravenous lines, and intravenous medication administration) on survival after cardiac arrest probably depends upon the quality of other prehospital services. In the OPALS study, ACLS interventions were added to an optimized emergency medical services program of rapid defibrillation [57]. No improvement in the rate of survival for out- of-hospital cardiac arrest was observed with addition of an ACLS program. In a retrospective report from Queensland with an emergency services program not optimized for early defibrillation, the presence of ACLS-skilled EMS personnel was associated with improved survival for out-of-hospital cardiac arrest [90]. Effect of older age The risk of SCA increases with age, and older age has been associated with a poorer survival in some, but not all studies of out-of-hospital cardiac arrests [1,91-95]: https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 13/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate In one study of 5882 patients who experienced an out-of-hospital cardiac arrest, 22 percent were >80 years of age [96]. Compared with patients <80 years of age, octogenarians and nonagenarians had a lower rate of hospital discharge (9.4 and 4.4 versus 19 percent for those <80). The discharge rate was higher in those with VF or pulseless ventricular tachycardia (VT) as the initial rhythm. Very old patients still had a poorer survival (24 and 17 versus 36 percent), but age was a weaker predictor than the initial rhythm. In the Seattle series of over 12,000 EMS-treated patients, every one-year increase in age was associated with a lower likelihood of survival to hospital discharge for all patients (OR 0.97 per year) and for those with witnessed VF (OR 0.98 per year) [1]. In a study of 36,605 patients ages 70 years or older enrolled in a Swedish registry between 1990 and 2013 following SCA, 30-day survival was significantly higher in patients ages 70 to 79 years (6.7 percent) compared with patients ages 80 to 89 years (4.4 percent) and those over 90 years of age (2.4 percent) [95]. Effect of sex The incidence of SCA is greater in males than females [1,97]. The effect of sex on outcome has been examined in multiple cohorts, with the following findings [97-99]: Males are more likely than females to have VF or VT as an initial rhythm. Males are more likely than females to have a witnessed arrest. Males have a higher one-month survival than females following SCA, due to the higher likelihood of VF/VT as their presenting rhythm. However, when considering only patients with VF/VT as the initial rhythm, females have a greater survival with favorable neurologic outcome. Effect of comorbidities The impact of preexisting chronic conditions on the outcome of out- of-hospital SCA was evaluated in a series of 1043 SCA victims in King County, Washington, in the United States [100]. There was a statistically significant reduction in the probability of survival to hospital discharge with increasing numbers of chronic conditions, such as congestive heart failure, prior MI, hypertension, and diabetes (OR 0.84 for each additional chronic condition). The impact of comorbidities was more prominent with longer EMS response intervals. Association of depression and anxiety with long-term outcomes In a study of 2373 patients from South Korea with out-of-hospital cardiac arrest followed for a median of 5.1 years for the outcome of mortality, 16.7 percent were diagnosed with depression or anxiety [101]. Patients with depression or anxiety had a higher rate of long-term mortality versus those without these conditions (35.5 versus 27 percent; adjusted hazard ratio 1.41; 95% CI 1.17-1.70). https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 14/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate FACTORS AFFECTING IN-HOSPITAL SCA OUTCOME The outcome of patients who experience SCA in the hospital is poor, with reported survival to hospital discharge rates of 6 to 19 percent [102-107]. However, outcomes appear to be improving over time [106,108]. In a cohort of 64,339 patients at 435 hospitals who had in-hospital SCA between 2000 and 2008 and underwent standard resuscitation procedures, 49 percent had return of spontaneous circulation (ROSC), with 15 percent overall survival to hospital discharge [105]. In a cohort of 151,071 adults at 470 United States hospitals who had in-hospital SCA between 2000 and 2014, 62 percent had ROSC, with 19 percent overall survival to hospital discharge [106]. In this study, patients with SCA during "on hours" (Monday through Friday from 7 AM through 11 PM) had significantly greater survival compared with SCA occurring during "off hours" (Monday through Friday from 11:00 PM through 7:00 AM and all day Saturday and Sunday); this difference did not significantly change between 2000 (16 versus 11.9 percent, respectively) and 2014 (25.2 versus 21.9 percent, respectively). Specific factors Several clinical factors have been identified that predict a greater likelihood of survival to hospital discharge [102,105,106,109]: Witnessed arrest. Ventricular tachycardia (VT) or ventricular fibrillation (VF) as initial rhythm. Pulse regained during first 10 minutes of CPR. Arrest during "on hours" (Monday through Friday from 7:00 AM through 11:00 PM). Identification of early warning signs. The presence of a dedicated resuscitation team with diverse team composition, clearly defined roles and communication, and ongoing training [110]. Other factors have been identified that predict a lower likelihood of survival to hospital discharge [109,111]: Longer duration of overall resuscitation efforts. Multiple resuscitation efforts. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 15/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Delays in providing initial defibrillation have been associated with worse outcomes. This was illustrated in a report of 6789 patients with in-hospital SCA due to VT or VF from 369 hospitals participating in the National Registry of Cardiopulmonary Resuscitation [111]. Delayed defibrillation (more than two minutes after SCA) occurred in 30 percent of patients and was associated with a significantly lower probability of surviving to hospital discharge (22.2 versus 39.3 percent). Delayed defibrillation was more common with noncardiac admitting diagnosis, cardiac arrest at a hospital with fewer than 250 beds, an unmonitored hospital unit, and arrest during after-hours periods. A national early warning score (NEWS) was developed in the United Kingdom in 2012 and updated in 2017 in an effort to standardize early detection of patients at risk for in-hospital SCA [112]. The score incorporates seven vital signs (respiratory rate, oxygen saturation, supplemental oxygen, heart rate, systolic blood pressure, temperature, and level of consciousness), with a maximal score of 20 points (0 to 4, 5 to 6, and 7 or more considered low, medium, and high scores, respectively). In a single-center study of all in-hospital SCA in 2014 and 2015, patients had markedly high risk of dying from SCA if they had a medium (odds ratio [OR] 4.4, 95% CI 1.8- 10.8) or high (OR 9.9, 95% CI 2.8-35.3) NEWS score compared with patients with a low NEWS score [113]. Multiple resuscitations involving CPR have also been associated with worse outcomes. Among 166,519 hospitalized patients (from the Nationwide Inpatient Sample, an all-payer United States hospital database) who underwent CPR while hospitalized between 2000 and 2009, 3.4 percent survived the initial CPR and ultimately had multiple rounds of CPR during their hospitalization [109]. Patients who had multiple rounds of CPR had a significantly lower likelihood of survival to discharge (OR 0.41, 95% CI 0.37-0.44), and those who survived multiple rounds of CPR had high hospitalization costs and were more likely to be discharged to hospice care. Survival following in-hospital SCA treated with an automated external defibrillator (AED) has also been evaluated using data derived from the National Registry of Cardiopulmonary Resuscitation [114]. When compared with usual resuscitative care, the use of an AED did not improve survival among patients with a shockable rhythm and was associated with a lower survival to hospital discharge among patients with a nonshockable rhythm. (See "Automated external defibrillators", section on 'In-hospital AED allocation'.) In 2013 the American Heart Association issued consensus recommendations regarding strategies for improving outcomes following in-hospital SCA [115]. While the consensus recommendations focused on many of the same factors as out-of-hospital cardiac arrest (ie, early identification of SCA, provision of high-quality CPR, early defibrillation [when indicated]), the authors commented on a lack of evidence specifically focused on in-hospital SCA, with many https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 16/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate of the current guideline recommendations based on extrapolations of data from out-of-hospital SCA. Further data specifically focusing on in-hospital SCA are required prior to making any additional recommendations. GO-FAR score to predict neurologically intact survival The ability to predict neurologically favorable survival following in-hospital SCA has not been well-defined, with most estimates based on clinical judgment of the treating clinician(s). However, it seems most likely that no single factor can effectively predict outcomes but rather a combination of factors. Using data obtained from 366 United States hospitals participating in the Get With The Guidelines-Resuscitation registry, 51,240 patients were identified who experienced in-hospital SCA during the period from 2007 to 2009 [116]. The data were used to derive (44.4 percent), test (22.2 percent) and validate (33.4 percent) the GO-FAR score predicting the likelihood of survival with good neurologic function following SCA based on 13 clinical variables. Patients were divided into the following groups based on likelihood of survival to discharge: Very low likelihood of survival (<1 percent chance) Score of 24 or greater Low likelihood of survival (1 to 3 percent chance) Score 14 to 23 Average likelihood of survival (>3 to 15 percent chance) Score -5 to 13 Higher than average likelihood of survival (>15 percent chance) Score -15 to -6 In general, younger patients with normal baseline neurologic function and fewer medical comorbidities had a greater likelihood of survival following in-hospital SCA [117]. A subsequent prospective registry study of 62,131 patients with in-hospital SCA between 2010 and 2016 validated the ability of the GO-FAR score to predict the chance of survival; survival rates were slightly higher, likely related to ongoing improvements in postresuscitation care [118]. The GO- FAR score appears to be an effective aid for patients and/or caregivers to better understand the likely goals and outcomes of care. (See "Communication in the ICU: Holding a meeting with families and caregivers", section on 'Sharing clinical information'.) IMPACT OF ARTERIAL OXYGEN LEVEL Oxygenation goals should be individualized and hyperoxia should be avoided. Arterial hyperoxia early after SCA may have deleterious effects, perhaps due to oxidative injury. The 2008 International Liaison Committee on Resuscitation cited preclinical evidence of harm from hyperoxia and suggested a goal arterial oxygenation of 94 to 96 percent post SCA [119]. A more detailed discussion of oxygenation with mechanical ventilation is presented separately. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit", section on 'Fraction of inspired oxygen'.) https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 17/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate A study to examine this issue was performed using a multicenter database including 6326 patients with arterial blood gas analysis within 24 hours after ICU arrival following cardiac arrest [120]. The study included patients with in-hospital and out-of-hospital SCA (57 percent were hospital inpatients and 43 percent were from the emergency department). Oxygenation status was categorized according to the first ICU arterial blood gas value, with hyperoxia defined as PaO2 300 mmHg, hypoxia as PaO2 <60 mmHg, and the remaining as normoxia. The majority of patients had hypoxia (63 percent) with similar numbers having hyperoxia (18 percent) and normoxia (19 percent). The hyperoxia group had higher in-hospital mortality compared with the normoxia and the hypoxia groups (63 percent versus 45 percent and 57 percent). In a multivariable model, hyperoxia was an independent risk factor for death (odds ratio [OR] 1.8, 95% CI 1.5-2.2). Hypoxia was also an independent risk factor (OR 1.3, 95% CI 1.1-1.5). Further data are needed to determine the impact of oxygen titration during and after resuscitation. In a subsequent, smaller, prospective cohort study of 280 patients with cardiac arrest, among whom 105 patients (38 percent) were exposed to hyperoxia (defined as PaO2 >300 mmHg) during the first six hours of care after return of spontaneous circulation, death or poor neurologic function at discharge (defined as modified Rankin score >3) was significantly more likely in patients exposed to hyperoxia (77 versus 65 percent) [121]. LONG-TERM OUTCOME The reported long-term survival of resuscitated SCD is variable and may depend upon multiple factors: In patients with out-of-hospital ventricular fibrillation, was early defibrillation achieved? Do the data come from randomized trials, in which many, often sicker, patients are excluded, or from community-based observations? Was the patient treated with early revascularization, antiarrhythmic drugs, or an implantable cardioverter-defibrillator (ICD)? Does the patient have other risk factors, particularly a reduced left ventricular ejection fraction? Do patients with seemingly transient or reversible causes of SCA have a better prognosis? Did the episode of SCA begin as ventricular fibrillation (VF) or ventricular tachycardia (VT)? The potential effect of successful early defibrillation on long-term outcome following out-of- hospital cardiac arrest due to VF was assessed in a population-based study of 200 patients [122]. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 18/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Over 70 percent of these patients survived until hospital admission, and 40 percent of these patients were discharged with mild or absent neurologic impairment. Among these 79 patients, 43 underwent coronary revascularization and 35 received an ICD, 13 of whom had subsequent shocks for VT or VF. The expected five-year survival of the study population (79 percent) was the same as that of age-, sex-, and disease-matched controls who did not have out-of-hospital cardiac arrest, but significantly lower than age- and sex-matched controls in the general population. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Sudden cardiac arrest (The Basics)") SUMMARY AND RECOMMENDATIONS Prognosis following cardiac arrest Despite advances in the treatment of heart disease, the outcome of patients experiencing sudden cardiac arrest (SCA) remains poor. The reasons for the continued poor outcomes are likely multifactorial (eg, delayed bystander cardiopulmonary resuscitation [CPR], delayed defibrillation, advanced age, decreased proportion presenting with ventricular fibrillation [VF]). (See 'Prognosis following sudden cardiac arrest' above.) Outcome When SCA is due to a ventricular tachyarrhythmia, the outcome of resuscitation is better compared with those with asystole or pulseless electrical activity. (See 'Outcome according to etiology' above.) https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 19/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Factors affecting outcome Among the many factors that appear to have an influence on the outcome of SCA, the elapsed time prior to effective resuscitation (ie, establishment of an effective pulse) appears to be the most critical element. There are several ways to decrease the time to the onset of resuscitative efforts: Rapid emergency medical services (EMS) response Optimizing the EMS system within a community to reduce the response interval to eight minutes or less has been proposed as a way to improve the outcomes of SCA. However, due to a variety of factors, EMS response time of eight minutes or less cannot always be achieved. (See 'Time to resuscitation' above.) Bystander CPR The administration of CPR by a layperson bystander (bystander CPR) is an important factor in determining patient outcome after out-of-hospital SCA, as early restoration or improvement in circulation has been shown to result in greater survival and better neurologic function among survivors. Bystander CPR, however, is not always performed, primarily due to the bystander s lack of CPR training and/or concerns about possible transmission of disease while performing rescue breathing. (See 'Bystander CPR' above.) Early defibrillation The standard of care for resuscitation of SCA has been defibrillation as soon as possible when indicated. Shorter defibrillation response intervals correlate with greater survival to hospital discharge. (See 'Timing of defibrillation' above and "Advanced cardiac life support (ACLS) in adults".) Automated external defibrillators The use of automated external defibrillators (AEDs) by early responders is another approach to more rapid resuscitation. In most, but not all studies, AEDs have been found to improve survival after out-of-hospital cardiac arrest. (See "Automated external defibrillators".) Cardiopulmonary resuscitation Several observational studies evaluating compression- only CPR versus standard CPR including rescue breathing reported no significant differences in survival or long-term neurologic function between the two groups, suggesting that compression-only CPR could be safely delivered (as long as the arrest is not a respiratory arrest). Three randomized trials of compression-only CPR versus standard CPR have all shown a trend toward improved outcomes in the compression-only CPR group, and a 2010 meta-analysis of the three randomized trials reported an increased survival to hospital discharge among patients who received compression-only CPR. As such, if a sole bystander is present or multiple bystanders are reluctant to perform mouth- to-mouth ventilation, we encourage the performance of CPR using chest compressions https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 20/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate only. (See 'Bystander CPR' above and "Adult basic life support (BLS) for health care providers", section on 'Chest compressions'.) Temperature management The induction of mild to moderate hypothermia (target temperature 32 to 34 C for 24 hours) may be beneficial in patients successfully resuscitated after a cardiac arrest. Improved neurologic outcome and reduced mortality has been demonstrated in series of patients with VF arrest in whom spontaneous circulation was restored, even when the patient remains comatose after resuscitation. (See "Initial assessment and management of the adult post-cardiac arrest patient", section on 'Temperature management'.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Jie Cheng, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Rea TD, Eisenberg MS, Becker LJ, et al. Temporal trends in sudden cardiac arrest: a 25-year emergency medical services perspective. Circulation 2003; 107:2780. 2. Rea TD, Crouthamel M, Eisenberg MS, et al. Temporal patterns in long-term survival after resuscitation from out-of-hospital cardiac arrest. Circulation 2003; 108:1196. 3. Kitamura T, Iwami T, Kawamura T, et al. Nationwide improvements in survival from out-of- hospital cardiac arrest in Japan. Circulation 2012; 126:2834. 4. Chan PS, McNally B, Tang F, et al. Recent trends in survival from out-of-hospital cardiac arrest in the United States. Circulation 2014; 130:1876. 5. Wong MK, Morrison LJ, Qiu F, et al. Trends in short- and long-term survival among out-of- hospital cardiac arrest patients alive at hospital arrival. Circulation 2014; 130:1883. 6. Smith K, Andrew E, Lijovic M, et al. Quality of life and functional outcomes 12 months after out-of-hospital cardiac arrest. Circulation 2015; 131:174. 7. Herlitz J, Andersson E, B ng A, et al. Experiences from treatment of out-of-hospital cardiac arrest during 17 years in G teborg. Eur Heart J 2000; 21:1251. 8. Eckstein M, Stratton SJ, Chan LS. Cardiac Arrest Resuscitation Evaluation in Los Angeles: CARE-LA. Ann Emerg Med 2005; 45:504. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 21/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 9. Nichol G, Thomas E, Callaway CW, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 2008; 300:1423. 10. Patterson T, Perkins GD, Joseph J, et al. A Randomised tRial of Expedited transfer to a cardiac arrest centre for non-ST elevation ventricular fibrillation out-of-hospital cardiac arrest: The ARREST pilot randomised trial. Resuscitation 2017; 115:185. 11. Weaver WD, Cobb LA, Hallstrom AP, et al. Factors influencing survival after out-of-hospital cardiac arrest. J Am Coll Cardiol 1986; 7:752. 12. Engdahl J, B ng A, Lindqvist J, Herlitz J. Can we define patients with no and those with some chance of survival when found in asystole out of hospital? Am J Cardiol 2000; 86:610. 13. Gray WA, Capone RJ, Most AS. Unsuccessful emergency medical resuscitation are continued efforts in the emergency department justified? N Engl J Med 1991; 325:1393. 14. Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation 2018; 137:e67. 15. Myerburg RJ, Estes D, Zaman L, et al. Outcome of resuscitation from bradyarrhythmic or asystolic prehospital cardiac arrest. J Am Coll Cardiol 1984; 4:1118. 16. Luo S, Zhang Y, Zhang W, et al. Prognostic significance of spontaneous shockable rhythm conversion in adult out-of-hospital cardiac arrest patients with initial non-shockable heart rhythms: A systematic review and meta-analysis. Resuscitation 2017; 121:1. 17. Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med 1997; 337:301. 18. Bunch TJ, White RD, Gersh BJ, et al. Outcomes and in-hospital treatment of out-of-hospital cardiac arrest patients resuscitated from ventricular fibrillation by early defibrillation. Mayo Clin Proc 2004; 79:613. 19. de Vreede-Swagemakers JJ, Gorgels AP, Dubois-Arbouw WI, et al. Circumstances and causes of out-of-hospital cardiac arrest in sudden death survivors. Heart 1998; 79:356. 20. Goldstein S, Landis JR, Leighton R, et al. Characteristics of the resuscitated out-of-hospital cardiac arrest victim with coronary heart disease. Circulation 1981; 64:977. 21. Adhar GC, Larson LW, Bardy GH, Greene HL. Sustained ventricular arrhythmias: differences between survivors of cardiac arrest and patients with recurrent sustained ventricular tachycardia. J Am Coll Cardiol 1988; 12:159. 22. Kuisma M, Alasp A. Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome. Eur Heart J 1997; 18:1122. 23. Liberthson RR, Nagel EL, Hirschman JC, Nussenfeld SR. Prehospital ventricular defibrillation. Prognosis and follow-up course. N Engl J Med 1974; 291:317. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 22/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 24. Taffet GE, Teasdale TA, Luchi RJ. In-hospital cardiopulmonary resuscitation. JAMA 1988; 260:2069. 25. Bedell SE, Delbanco TL, Cook EF, Epstein FH. Survival after cardiopulmonary resuscitation in the hospital. N Engl J Med 1983; 309:569. 26. Murphy DJ, Murray AM, Robinson BE, Campion EW. Outcomes of cardiopulmonary resuscitation in the elderly. Ann Intern Med 1989; 111:199. 27. Dorian P, Cass D, Schwartz B, et al. Amiodarone as compared with lidocaine for shock- resistant ventricular fibrillation. N Engl J Med 2002; 346:884. 28. Myerburg RJ, Conde CA, Sung RJ, et al. Clinical, electrophysiologic and hemodynamic profile of patients resuscitated from prehospital cardiac arrest. Am J Med 1980; 68:568. 29. Myerburg RJ, Kessler KM, Zaman L, et al. Survivors of prehospital cardiac arrest. JAMA 1982; 247:1485. 30. Garcia RA, Spertus JA, Girotra S, et al. Racial and Ethnic Differences in Bystander CPR for Witnessed Cardiac Arrest. N Engl J Med 2022; 387:1569. 31. Greene HL. Sudden arrhythmic cardiac death mechanisms, resuscitation and classification: the Seattle perspective. Am J Cardiol 1990; 65:4B. 32. Marwick TH, Case CC, Siskind V, Woodhouse SP. Prediction of survival from resuscitation: a prognostic index derived from multivariate logistic model analysis. Resuscitation 1991; 22:129. 33. Herlitz J, Eek M, Holmberg M, et al. Characteristics and outcome among patients having out of hospital cardiac arrest at home compared with elsewhere. Heart 2002; 88:579. 34. Rea TD, Paredes VL. Quality of life and prognosis among survivors of out-of-hospital cardiac arrest. Curr Opin Crit Care 2004; 10:218. 35. Isenschmid C, Luescher T, Rasiah R, et al. Performance of clinical risk scores to predict mortality and neurological outcome in cardiac arrest patients. Resuscitation 2019; 136:21. 36. Potpara TS, Mihajlovic M, Stankovic S, et al. External Validation of the Simple NULL-PLEASE Clinical Score in Predicting Outcome of Out-of-Hospital Cardiac Arrest. Am J Med 2017; 130:1464.e13. 37. Bascom KE, Dziodzio J, Vasaiwala S, et al. Derivation and Validation of the CREST Model for Very Early Prediction of Circulatory Etiology Death in Patients Without ST-Segment-Elevation Myocardial Infarction After Cardiac Arrest. Circulation 2018; 137:273. 38. Bae DH, Lee HY, Jung YH, et al. PROLOGUE (PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages): Development and https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 23/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate validation of a scoring system for early prognostication in unselected adult cardiac arrest patients. Resuscitation 2021; 159:60. 39. Mody P, Pandey A, Slutsky AS, et al. Gender-Based Differences in Outcomes Among Resuscitated Patients With Out-of-Hospital Cardiac Arrest. Circulation 2021; 143:641. 40. Niemann JT, Cairns CB, Sharma J, Lewis RJ. Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock. Circulation 1992; 85:281. 41. Baum RS, Alvarez H 3rd, Cobb LA. Survival after resuscitation from out-of-hospital ventricular fibrillation. Circulation 1974; 50:1231. 42. Olson DW, LaRochelle J, Fark D, et al. EMT-defibrillation: the Wisconsin experience. Ann Emerg Med 1989; 18:806. 43. Callans DJ. Out-of-hospital cardiac arrest the solution is shocking. N Engl J Med 2004; 351:632. 44. Eisenberg MS, Horwood BT, Cummins RO, et al. Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990; 19:179. 45. Thompson RJ, McCullough PA, Kahn JK, O'Neill WW. Prediction of death and neurologic outcome in the emergency department in out-of-hospital cardiac arrest survivors. Am J Cardiol 1998; 81:17. 46. Stiell IG, Wells GA, Field BJ, et al. Improved out-of-hospital cardiac arrest survival through the inexpensive optimization of an existing defibrillation program: OPALS study phase II. Ontario Prehospital Advanced Life Support. JAMA 1999; 281:1175. 47. Riva G, Ringh M, Jonsson M, et al. Survival in Out-of-Hospital Cardiac Arrest After Standard Cardiopulmonary Resuscitation or Chest Compressions Only Before Arrival of Emergency Medical Services: Nationwide Study During Three Guideline Periods. Circulation 2019. 48. Aufderheide TP, Yannopoulos D, Lick CJ, et al. Implementing the 2005 American Heart Association Guidelines improves outcomes after out-of-hospital cardiac arrest. Heart Rhythm 2010; 7:1357. 49. Nakahara S, Tomio J, Ichikawa M, et al. Association of Bystander Interventions With Neurologically Intact Survival Among Patients With Bystander-Witnessed Out-of-Hospital Cardiac Arrest in Japan. JAMA 2015; 314:247. 50. Malta Hansen C, Kragholm K, Pearson DA, et al. Association of Bystander and First- Responder Intervention With Survival After Out-of-Hospital Cardiac Arrest in North Carolina, 2010-2013. JAMA 2015; 314:255. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 24/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 51. Sayre MR, Berg RA, Cave DM, et al. Hands-only (compression-only) cardiopulmonary resuscitation: a call to action for bystander response to adults who experience out-of- hospital sudden cardiac arrest: a science advisory for the public from the American Heart Association Emergency Cardiovascular Care Committee. Circulation 2008; 117:2162. 52. Field JM, Hazinski MF, Sayre MR, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S640. 53. Olasveengen TM, de Caen AR, Mancini ME, et al. 2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary. Resuscitation 2017; 121:201. 54. Perkins GD, Olasveengen TM, Maconochie I, et al. European Resuscitation Council Guidelines for Resuscitation: 2017 update. Resuscitation 2018; 123:43. 55. Kleinman ME, Goldberger ZD, Rea T, et al. 2017 American Heart Association Focused Update on Adult Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2018; 137:e7. 56. Thompson RG, Hallstrom AP, Cobb LA. Bystander-initiated cardiopulmonary resuscitation in the management of ventricular fibrillation. Ann Intern Med 1979; 90:737. 57. Stiell IG, Wells GA, Field B, et al. Advanced cardiac life support in out-of-hospital cardiac arrest. N Engl J Med 2004; 351:647. 58. Valenzuela TD, Roe DJ, Cretin S, et al. Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation 1997; 96:3308. 59. Adielsson A, Hollenberg J, Karlsson T, et al. Increase in survival and bystander CPR in out-of- hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective. Heart 2011; 97:1391. 60. Wissenberg M, Lippert FK, Folke F, et al. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of- hospital cardiac arrest. JAMA 2013; 310:1377. 61. Hasselqvist-Ax I, Riva G, Herlitz J, et al. Early cardiopulmonary resuscitation in out-of- hospital cardiac arrest. N Engl J Med 2015; 372:2307. 62. Sondergaard KB, Wissenberg M, Gerds TA, et al. Bystander cardiopulmonary resuscitation and long-term outcomes in out-of-hospital cardiac arrest according to location of arrest. Eur Heart J 2019; 40:309. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 25/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 63. Kragholm K, Wissenberg M, Mortensen RN, et al. Bystander Efforts and 1-Year Outcomes in Out-of-Hospital Cardiac Arrest. N Engl J Med 2017; 376:1737. 64. Sasson C, Meischke H, Abella BS, et al. Increasing cardiopulmonary resuscitation provision in communities with low bystander cardiopulmonary resuscitation rates: a science advisory from the American Heart Association for healthcare providers, policymakers, public health departments, and community leaders. Circulation 2013; 127:1342. 65. Sasson C, Magid DJ, Chan P, et al. Association of neighborhood characteristics with bystander-initiated CPR. N Engl J Med 2012; 367:1607. 66. Bobrow BJ, Spaite DW, Berg RA, et al. Chest compression-only CPR by lay rescuers and survival from out-of-hospital cardiac arrest. JAMA 2010; 304:1447. 67. Zhan L, Yang LJ, Huang Y, et al. Continuous chest compression versus interrupted chest compression for cardiopulmonary resuscitation of non-asphyxial out-of-hospital cardiac arrest. Cochrane Database Syst Rev 2017; 3:CD010134. 68. SOS-KANTO study group. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study. Lancet 2007; 369:920. 69. Iwami T, Kawamura T, Hiraide A, et al. Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest. Circulation 2007; 116:2900. 70. Bohm K, Rosenqvist M, Herlitz J, et al. Survival is similar after standard treatment and chest compression only in out-of-hospital bystander cardiopulmonary resuscitation. Circulation 2007; 116:2908. |
mortality and neurological outcome in cardiac arrest patients. Resuscitation 2019; 136:21. 36. Potpara TS, Mihajlovic M, Stankovic S, et al. External Validation of the Simple NULL-PLEASE Clinical Score in Predicting Outcome of Out-of-Hospital Cardiac Arrest. Am J Med 2017; 130:1464.e13. 37. Bascom KE, Dziodzio J, Vasaiwala S, et al. Derivation and Validation of the CREST Model for Very Early Prediction of Circulatory Etiology Death in Patients Without ST-Segment-Elevation Myocardial Infarction After Cardiac Arrest. Circulation 2018; 137:273. 38. Bae DH, Lee HY, Jung YH, et al. PROLOGUE (PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages): Development and https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 23/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate validation of a scoring system for early prognostication in unselected adult cardiac arrest patients. Resuscitation 2021; 159:60. 39. Mody P, Pandey A, Slutsky AS, et al. Gender-Based Differences in Outcomes Among Resuscitated Patients With Out-of-Hospital Cardiac Arrest. Circulation 2021; 143:641. 40. Niemann JT, Cairns CB, Sharma J, Lewis RJ. Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock. Circulation 1992; 85:281. 41. Baum RS, Alvarez H 3rd, Cobb LA. Survival after resuscitation from out-of-hospital ventricular fibrillation. Circulation 1974; 50:1231. 42. Olson DW, LaRochelle J, Fark D, et al. EMT-defibrillation: the Wisconsin experience. Ann Emerg Med 1989; 18:806. 43. Callans DJ. Out-of-hospital cardiac arrest the solution is shocking. N Engl J Med 2004; 351:632. 44. Eisenberg MS, Horwood BT, Cummins RO, et al. Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990; 19:179. 45. Thompson RJ, McCullough PA, Kahn JK, O'Neill WW. Prediction of death and neurologic outcome in the emergency department in out-of-hospital cardiac arrest survivors. Am J Cardiol 1998; 81:17. 46. Stiell IG, Wells GA, Field BJ, et al. Improved out-of-hospital cardiac arrest survival through the inexpensive optimization of an existing defibrillation program: OPALS study phase II. Ontario Prehospital Advanced Life Support. JAMA 1999; 281:1175. 47. Riva G, Ringh M, Jonsson M, et al. Survival in Out-of-Hospital Cardiac Arrest After Standard Cardiopulmonary Resuscitation or Chest Compressions Only Before Arrival of Emergency Medical Services: Nationwide Study During Three Guideline Periods. Circulation 2019. 48. Aufderheide TP, Yannopoulos D, Lick CJ, et al. Implementing the 2005 American Heart Association Guidelines improves outcomes after out-of-hospital cardiac arrest. Heart Rhythm 2010; 7:1357. 49. Nakahara S, Tomio J, Ichikawa M, et al. Association of Bystander Interventions With Neurologically Intact Survival Among Patients With Bystander-Witnessed Out-of-Hospital Cardiac Arrest in Japan. JAMA 2015; 314:247. 50. Malta Hansen C, Kragholm K, Pearson DA, et al. Association of Bystander and First- Responder Intervention With Survival After Out-of-Hospital Cardiac Arrest in North Carolina, 2010-2013. JAMA 2015; 314:255. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 24/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 51. Sayre MR, Berg RA, Cave DM, et al. Hands-only (compression-only) cardiopulmonary resuscitation: a call to action for bystander response to adults who experience out-of- hospital sudden cardiac arrest: a science advisory for the public from the American Heart Association Emergency Cardiovascular Care Committee. Circulation 2008; 117:2162. 52. Field JM, Hazinski MF, Sayre MR, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S640. 53. Olasveengen TM, de Caen AR, Mancini ME, et al. 2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary. Resuscitation 2017; 121:201. 54. Perkins GD, Olasveengen TM, Maconochie I, et al. European Resuscitation Council Guidelines for Resuscitation: 2017 update. Resuscitation 2018; 123:43. 55. Kleinman ME, Goldberger ZD, Rea T, et al. 2017 American Heart Association Focused Update on Adult Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2018; 137:e7. 56. Thompson RG, Hallstrom AP, Cobb LA. Bystander-initiated cardiopulmonary resuscitation in the management of ventricular fibrillation. Ann Intern Med 1979; 90:737. 57. Stiell IG, Wells GA, Field B, et al. Advanced cardiac life support in out-of-hospital cardiac arrest. N Engl J Med 2004; 351:647. 58. Valenzuela TD, Roe DJ, Cretin S, et al. Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation 1997; 96:3308. 59. Adielsson A, Hollenberg J, Karlsson T, et al. Increase in survival and bystander CPR in out-of- hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective. Heart 2011; 97:1391. 60. Wissenberg M, Lippert FK, Folke F, et al. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of- hospital cardiac arrest. JAMA 2013; 310:1377. 61. Hasselqvist-Ax I, Riva G, Herlitz J, et al. Early cardiopulmonary resuscitation in out-of- hospital cardiac arrest. N Engl J Med 2015; 372:2307. 62. Sondergaard KB, Wissenberg M, Gerds TA, et al. Bystander cardiopulmonary resuscitation and long-term outcomes in out-of-hospital cardiac arrest according to location of arrest. Eur Heart J 2019; 40:309. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 25/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 63. Kragholm K, Wissenberg M, Mortensen RN, et al. Bystander Efforts and 1-Year Outcomes in Out-of-Hospital Cardiac Arrest. N Engl J Med 2017; 376:1737. 64. Sasson C, Meischke H, Abella BS, et al. Increasing cardiopulmonary resuscitation provision in communities with low bystander cardiopulmonary resuscitation rates: a science advisory from the American Heart Association for healthcare providers, policymakers, public health departments, and community leaders. Circulation 2013; 127:1342. 65. Sasson C, Magid DJ, Chan P, et al. Association of neighborhood characteristics with bystander-initiated CPR. N Engl J Med 2012; 367:1607. 66. Bobrow BJ, Spaite DW, Berg RA, et al. Chest compression-only CPR by lay rescuers and survival from out-of-hospital cardiac arrest. JAMA 2010; 304:1447. 67. Zhan L, Yang LJ, Huang Y, et al. Continuous chest compression versus interrupted chest compression for cardiopulmonary resuscitation of non-asphyxial out-of-hospital cardiac arrest. Cochrane Database Syst Rev 2017; 3:CD010134. 68. SOS-KANTO study group. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study. Lancet 2007; 369:920. 69. Iwami T, Kawamura T, Hiraide A, et al. Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest. Circulation 2007; 116:2900. 70. Bohm K, Rosenqvist M, Herlitz J, et al. Survival is similar after standard treatment and chest compression only in out-of-hospital bystander cardiopulmonary resuscitation. Circulation 2007; 116:2908. 71. Rea TD, Fahrenbruch C, Culley L, et al. CPR with chest compression alone or with rescue breathing. N Engl J Med 2010; 363:423. 72. Svensson L, Bohm K, Castr n M, et al. Compression-only CPR or standard CPR in out-of- hospital cardiac arrest. N Engl J Med 2010; 363:434. 73. Hallstrom A, Cobb L, Johnson E, Copass M. Cardiopulmonary resuscitation by chest compression alone or with mouth-to-mouth ventilation. N Engl J Med 2000; 342:1546. 74. H pfl M, Selig HF, Nagele P. Chest-compression-only versus standard cardiopulmonary resuscitation: a meta-analysis. Lancet 2010; 376:1552. 75. Dumas F, Rea TD, Fahrenbruch C, et al. Chest compression alone cardiopulmonary resuscitation is associated with better long-term survival compared with standard cardiopulmonary resuscitation. Circulation 2013; 127:435. 76. Iwami T, Kitamura T, Kiyohara K, Kawamura T. Dissemination of Chest Compression-Only Cardiopulmonary Resuscitation and Survival After Out-of-Hospital Cardiac Arrest. Circulation 2015; 132:415. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 26/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 77. Berdowski J, ten Haaf M, Tijssen JG, et al. Time in recurrent ventricular fibrillation and survival after out-of-hospital cardiac arrest. Circulation 2010; 122:1101. 78. Lee SGW, Park JH, Ro YS, et al. Time to first defibrillation and survival outcomes of out-of- hospital cardiac arrest with refractory ventricular fibrillation. Am J Emerg Med 2021; 40:96. 79. Cobb LA, Fahrenbruch CE, Walsh TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999; 281:1182. 80. Wik L, Hansen TB, Fylling F, et al. Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation: a randomized trial. JAMA 2003; 289:1389. 81. Stiell IG, Nichol G, Leroux BG, et al. Early versus later rhythm analysis in patients with out- of-hospital cardiac arrest. N Engl J Med 2011; 365:787. 82. Pollack RA, Brown SP, Rea T, et al. Impact of Bystander Automated External Defibrillator Use on Survival and Functional Outcomes in Shockable Observed Public Cardiac Arrests. Circulation 2018; 137:2104. 83. Verbeek PR, Vermeulen MJ, Ali FH, et al. Derivation of a termination-of-resuscitation guideline for emergency medical technicians using automated external defibrillators. Acad Emerg Med 2002; 9:671. 84. Morrison LJ, Verbeek PR, Vermeulen MJ, et al. Derivation and evaluation of a termination of resuscitation clinical prediction rule for advanced life support providers. Resuscitation 2007; 74:266. 85. Sasson C, Hegg AJ, Macy M, et al. Prehospital termination of resuscitation in cases of refractory out-of-hospital cardiac arrest. JAMA 2008; 300:1432. 86. Wallace SK, Abella BS, Becker LB. Quantifying the effect of cardiopulmonary resuscitation quality on cardiac arrest outcome: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2013; 6:148. 87. Idris AH, Guffey D, Aufderheide TP, et al. Relationship between chest compression rates and outcomes from cardiac arrest. Circulation 2012; 125:3004. 88. Brouwer TF, Walker RG, Chapman FW, Koster RW. Association Between Chest Compression Interruptions and Clinical Outcomes of Ventricular Fibrillation Out-of-Hospital Cardiac Arrest. Circulation 2015; 132:1030. 89. Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med 2001; 161:2007. 90. Woodall J, McCarthy M, Johnston T, et al. Impact of advanced cardiac life support-skilled paramedics on survival from out-of-hospital cardiac arrest in a statewide emergency https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 27/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate medical service. Emerg Med J 2007; 24:134. 91. Tresch DD, Thakur RK, Hoffmann RG, et al. Comparison of outcome of paramedic-witnessed cardiac arrest in patients younger and older than 70 years. Am J Cardiol 1990; 65:453. 92. Longstreth WT Jr, Cobb LA, Fahrenbruch CE, Copass MK. Does age affect outcomes of out- of-hospital cardiopulmonary resuscitation? JAMA 1990; 264:2109. 93. Wuerz RC, Holliman CJ, Meador SA, et al. Effect of age on prehospital cardiac resuscitation outcome. Am J Emerg Med 1995; 13:389. 94. Van Hoeyweghen RJ, Bossaert LL, Mullie A, et al. Survival after out-of-hospital cardiac arrest in elderly patients. Belgian Cerebral Resuscitation Study Group. Ann Emerg Med 1992; 21:1179. 95. Libungan B, Lindqvist J, Str ms e A, et al. Out-of-hospital cardiac arrest in the elderly: A large-scale population-based study. Resuscitation 2015; 94:28. 96. Kim C, Becker L, Eisenberg MS. Out-of-hospital cardiac arrest in octogenarians and nonagenarians. Arch Intern Med 2000; 160:3439. 97. Akahane M, Ogawa T, Koike S, et al. The effects of sex on out-of-hospital cardiac arrest outcomes. Am J Med 2011; 124:325. 98. Kim C, Fahrenbruch CE, Cobb LA, Eisenberg MS. Out-of-hospital cardiac arrest in men and women. Circulation 2001; 104:2699. 99. Bougouin W, Mustafic H, Marijon E, et al. Gender and survival after sudden cardiac arrest: A systematic review and meta-analysis. Resuscitation 2015; 94:55. 100. Carew HT, Zhang W, Rea TD. Chronic health conditions and survival after out-of-hospital ventricular fibrillation cardiac arrest. Heart 2007; 93:728. 101. Lee J, Cho Y, Oh J, et al. Analysis of Anxiety or Depression and Long-term Mortality Among Survivors of Out-of-Hospital Cardiac Arrest. JAMA Netw Open 2023; 6:e237809. 102. van Walraven C, Forster AJ, Parish DC, et al. Validation of a clinical decision aid to discontinue in-hospital cardiac arrest resuscitations. JAMA 2001; 285:1602. 103. Brindley PG, Markland DM, Mayers I, Kutsogiannis DJ. Predictors of survival following in- hospital adult cardiopulmonary resuscitation. CMAJ 2002; 167:343. 104. Bloom HL, Shukrullah I, Cuellar JR, et al. Long-term survival after successful inhospital cardiac arrest resuscitation. Am Heart J 2007; 153:831. 105. Goldberger ZD, Chan PS, Berg RA, et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet 2012; 380:1473. 106. Ofoma UR, Basnet S, Berger A, et al. Trends in Survival After In-Hospital Cardiac Arrest During Nights and Weekends. J Am Coll Cardiol 2018; 71:402. https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 28/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate 107. Schluep M, Gravesteijn BY, Stolker RJ, et al. One-year survival after in-hospital cardiac arrest: A systematic review and meta-analysis. Resuscitation 2018; 132:90. 108. Thompson LE, Chan PS, Tang F, et al. Long-Term Survival Trends of Medicare Patients After In-Hospital Cardiac Arrest: Insights from Get With The Guidelines-Resuscitation . Resuscitation 2018; 123:58. 109. Kazaure HS, Roman SA, Sosa JA. A population-level analysis of 5620 recipients of multiple in- hospital cardiopulmonary resuscitation attempts. J Hosp Med 2014; 9:29. 110. Nallamothu BK, Guetterman TC, Harrod M, et al. How Do Resuscitation Teams at Top- Performing Hospitals for In-Hospital Cardiac Arrest Succeed? A Qualitative Study. Circulation 2018; 138:154. 111. Chan PS, Krumholz HM, Nichol G, et al. Delayed time to defibrillation after in-hospital cardiac arrest. N Engl J Med 2008; 358:9. 112. https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2 (Access ed on April 12, 2018). 113. Roberts D, Dj rv T. Preceding national early warnings scores among in-hospital cardiac arrests and their impact on survival. Am J Emerg Med 2017; 35:1601. 114. Chan PS, Krumholz HM, Spertus JA, et al. Automated external defibrillators and survival after in-hospital cardiac arrest. JAMA 2010; 304:2129. 115. Morrison LJ, Neumar RW, Zimmerman JL, et al. Strategies for improving survival after in- hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the American Heart Association. Circulation 2013; 127:1538. 116. Ebell MH, Jang W, Shen Y, et al. Development and validation of the Good Outcome Following Attempted Resuscitation (GO-FAR) score to predict neurologically intact survival after in- hospital cardiopulmonary resuscitation. JAMA Intern Med 2013; 173:1872. 117. Piscator E, G ransson K, Bruchfeld S, et al. Predicting neurologically intact survival after in- hospital cardiac arrest-external validation of the Good Outcome Following Attempted Resuscitation score. Resuscitation 2018; 128:63. 118. Thai TN, Ebell MH. Prospective validation of the Good Outcome Following Attempted Resuscitation (GO-FAR) score for in-hospital cardiac arrest prognosis. Resuscitation 2019; 140:2. 119. Neumar RW, Nolan JP, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 29/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation 2008; 118:2452. 120. Kilgannon JH, Jones AE, Shapiro NI, et al. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA 2010; 303:2165. 121. Roberts BW, Kilgannon JH, Hunter BR, et al. Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study. Circulation 2018; 137:2114. 122. Bunch TJ, White RD, Gersh BJ, et al. Long-term outcomes of out-of-hospital cardiac arrest after successful early defibrillation. N Engl J Med 2003; 348:2626. Topic 973 Version 53.0 https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 30/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate GRAPHICS Adult cardiac arrest algorithm https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 31/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 32/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 33/34 7/6/23, 1:42 PM Prognosis and outcomes following sudden cardiac arrest in adults - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/prognosis-and-outcomes-following-sudden-cardiac-arrest-in-adults/print 34/34 |
7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate Psychosocial factors in sudden cardiac arrest : Geoffrey H Tofler, MD : Jonathan M Silver, MD : David Solomon, MD Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 28, 2023. INTRODUCTION Awareness of the ability of severe emotional stress to provoke sudden death has been present throughout recorded history. However, the relationship of psychosocial factors to cardiovascular disease, and in particular sudden cardiac death, has been difficult to quantify. This has been due to several reasons: It is difficult to objectively quantify emotional stress. Research has until recently been more focused on the chronic factors leading to the development of coronary artery disease rather than on the precipitation of acute coronary syndromes once such disease is present. The division between the social science and medical science investigators have impeded dialogue. There are inherent difficulties in accurately assessing the triggers of sudden death. Despite these limitations, the weight of evidence for a role for psychosocial factors in sudden cardiac death has become compelling and in one review of 96 published studies on this topic, a positive association was observed in 92 percent [1]. New studies are therefore warranted to determine whether behavioral and pharmacologic interventions will lower cardiovascular risk [2]. Since acute myocardial infarction is an important precipitant of ventricular fibrillation and sudden death, many of the advances in understanding the pathophysiology of acute myocardial infarction are applicable for sudden death (see "Psychosocial factors in acute https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 1/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate coronary syndrome"). In addition, emotional stress may lower the threshold for arrhythmia both directly and secondary to the provocation of transient myocardial ischemia. CIRCADIAN VARIATION The task of accurately determining the time of occurrence of sudden cardiac death is often difficult for two main reasons: a possible inability to ascertain if a sudden cardiac event is actually the cause of death; and the occurrence of unwitnessed deaths, often at night, for which time of death is uncertain. Despite these limitations, a circadian variation has been found for sudden cardiac death that parallels that of myocardial infarction, with a peak in the morning. It has been suggested that a primary arrhythmic event is more likely to occur in the morning because increased adrenergic activity at this time may increase electrical instability or induce myocardial ischemia without infarction. Evidence in support of this relationship was initially obtained from data from two large databases and from a number of other studies with a lower specificity of diagnosis. Mortality reports of the Massachusetts Department of Public Health were utilized to determine the time of sudden death [3]. Analysis was performed in the group of 2203 individuals who in 1983 died an out-of-hospital death from ischemic heart disease one hour or less after the onset of symptoms. The peak frequency of sudden death was between 9 and 11 AM ( figure 1). A report from the Framingham Heart Study evaluated coding forms of 264 "definite" sudden cardiac deaths (11 percent of total deaths) and 165 "possible" sudden cardiac deaths (7 percent of total deaths) [4]. The exact time of death was known in most cases but, for some, it was necessary to estimate the interval in which the death occurred. In such instances, the probability of death was evenly distributed over the estimated interval. The time of occurrence of definite sudden cardiac death exhibited a prominent circadian variation with a low frequency during the night, as would be expected from the requirement that the death be witnessed. However, a circadian variation remained when patients with possible sudden cardiac death (particularly those with unwitnessed deaths between midnight and 6 AM) were added to those with definite and witnessed sudden cardiac death. The hourly risk of sudden cardiac death was at least 70 percent greater between 7 and 9 AM than the average risk during the remaining 22 hours of the day. Similar observations were made in later studies [5-8]. As an example, data from the Berlin emergency care system found a peak frequency of ventricular fibrillation between 6 AM and noon; in contrast, asystolic episodes were more evenly distributed throughout the day [6]. The https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 2/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate morning peak in sudden death is particularly related to the first three hours after awakening and onset of activity [7]; a similar relationship has been noted with myocardial ischemia (see below). Data from the Seattle Fire Department, based upon 6603 cases of out-of-hospital cardiac arrest, of which 3690 were witnessed, also exhibited a diurnal variation, with a low incidence at night and two peaks of approximately the same size [9]. An evening peak at 4 to 7 PM was attributed primary to patients found in ventricular fibrillation, while arrests that showed other rhythms exhibited mainly a morning peak from 8 to 11 AM. There were 597 patients who had at least two separate cardiac arrests, but there was no association between the times of the first and second arrests, suggesting that the diurnal patterns for cardiac arrest are associated with patterns of daily activity rather than characteristic of the underlying cardiac disease ( figure 2). Seasonal variation In addition to the diurnal variation, cardiac arrests also show a weekly and seasonal variation; the daily incidence peaks on Monday and the seasonal incidence is greatest in the winter [8,10]. As an example, one 12-year analysis of 222,265 cases of death from coronary heart disease found that there were approximately 33 percent more deaths in December and January than in June through September; this was only partly explained by temperature variability [11]. Holter monitoring and ICD The above studies are somewhat limited by their frequent reliance on eyewitnesses to determine the timing of sudden cardiac death. More objective data has come from Holter monitoring and the implantable cardioverter-defibrillator (ICD). In a study of 164 ambulatory patients evaluated with 24-hour Holter monitoring, for example, a morning peak of ventricular premature beats was consistently present for each of three consecutive days of observation [12]. In another series, the peak incidence of sustained symptomatic ventricular tachycardic episodes in 68 patients occurred between 10 AM and noon [13]. The ICD provides a better opportunity to firmly establish the timing of malignant tachyarrhythmias, which are the most common cause of sudden cardiac death [14-16]. As an example, a prominent circadian pattern of ventricular arrhythmias was demonstrated in a series of 483 patients who had an ICD implanted between 1990 and 1993 [14]: For rapid tachyarrhythmias (>250 beats/min), a three-hour peak was present between 9 AM and noon (22 percent of total episodes) and a three-hour minimum occurred between 3 and 6 AM (4 percent of episodes, p <0.001). https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 3/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate A similar circadian pattern characterized by a 9 AM to noon peak was also observed for less rapid tachyarrhythmias. The circadian pattern is similar for those with ischemic or nonischemic heart disease [16]. Depression appears to increase the rate of appropriate shocks in patients with an ICD. This was illustrated in a report from the Triggers of Ventricular Arrhythmia Study (TOVA) in which 645 patients were followed, 4 percent of whom had moderate to severe depression [17]. Moderate to severe depression was significantly associated with the time to first shock and with all shocks for VT/VF (hazard ratio 3.2 overall and 6.4 in the 476 patients with coronary heart disease). Myocardial ischemia In some cases, sudden cardiac death may be provoked by transient myocardial ischemia in the absence of infarction. Several series have found that the frequency of both symptomatic and asymptomatic ST-segment depression is maximal in the morning [18,19]. The hypothesis that the morning increase in myocardial ischemia is related to time of awakening rather than to the time of day was evaluated in 32 patients with angina in whom the time of awakening was known [20]. The peak activity was found to occur in the first two hours after rising. Another study investigated the relationship between the patient's perceived level of mental activity and ST depression during daily life [21]. Most ischemic episodes occurred during activities classified as "usual" physical or "usual" mental activity; and only a minority occurred during situations that the patient described as stressful. However, when the duration of ST depression was divided by the total time spent in each category, transient ischemia was more likely to occur as the intensity level of mental activity increased. Mental activities appear to be as potent as physical activities in triggering ischemia. Beta blockers affect this circadian pattern, blunting the morning increase in sudden death and ventricular tachyarrhythmias [22,23]. However, other antiarrhythmic drugs do not have the same effect. In the CAST study, for example, a prominent morning peak was present in patients receiving encainide, flecainide, and moricizine [24]. Amiodarone also appears to have no effect on the circadian pattern of sudden cardiac death [25]. EMOTIONAL STRESS AND ARRHYTHMIA https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 4/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate Despite the numerous anecdotes relating emotional stress to the precipitation of arrhythmia, there has not been much systematic study of this relationship. One report evaluated the psychologic precipitants in 117 patients with life-threatening arrhythmias [26]. In 25 subjects (21 percent), a presumed psychologic trigger was found, the most common of which was anger. The lack of a control group in this study prevented estimation of the relative risk of anger. However, in a series of patients with nonfatal myocardial infarction in which control data were available, episodes of anger were associated with a doubling of risk which was present for two hours prior to onset of symptoms [27]. The role of stress on the occurrence of arrhythmia is likely mediated by sympathetic activation and an increase in circulating catecholamines, which can alter the induction, rate, and termination of ventricular arrhythmia. This was evaluated in 18 patients with a history of ventricular tachycardia and an ICD who underwent noninvasive electrophysiologic test in baseline and during mental stress [28]. During mental stress the ventricular tachycardia was faster and more difficult to terminate, and correlated with an increase in norepinephrine levels >50 percent above baseline. Intense stressors, such as earthquakes, have been associated with increased cardiac mortality [29]. In one study of patients with ICDs, the destruction of the World Trade Center in New York City on September 11, 2001 was associated with a significant increase in episodes of tachyarrhythmia, both among patients living in the New York City area and remotely [30,31]. Similar effects have been noted for the frequency of acute myocardial infarction. (See "Psychosocial factors in acute coronary syndrome".) A diagnosis of cancer may increase the risk of cardiovascular death. A cohort study using multiple registries examined the risk in more than 6,000,000 Swedes from 1991 through 2006; compared with cancer-free individuals, patients diagnosed with cancer were six times more likely to die from cardiovascular causes within one week of receiving the diagnosis (relative risk 5.6, 95% CI 5.2-5.9) [32]. Several large-scale, community based studies have found a significant dose-dependent relationship between anxiety disorders and cardiac death [33]; the excess risk was confined to sudden death and the relative risk for men with high phobic levels was 6.08 after adjusting for other cardiovascular risk factors [34,35]. Although certain behavior patterns, such as type A behavior, have been implicated in sudden death, these relationships have not been widely accepted as causal. There are several reasons for this lack of acceptance including certain components, such as hostility, appearing more predictive, and the difficulty in standardizing measures for these behavior patterns and in https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 5/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate extrapolating the results of laboratory studies of reactivity to the "real world." In addition, changes leading to sudden death may be transient, thereby limiting their ability to be well evaluated in the chronic state. Despite these limitations, a large body of data convincingly demonstrates that depression and hostility are behaviors that are associated with an increased risk of coronary heart disease related events [33,36-38]. As an example, a prospective study using an interview measure of depression found that the 16 percent of patients with major depression had a five-fold higher mortality that was independent of their underlying cardiac status; sudden death as the mode of death was particularly increased in these patients [38]. Other psychosocial factors, such as low education attainment (less than high school graduation), social isolation, and absence of emotional support have also been associated with increased mortality following myocardial infarction [36,39-41]. In addition, bereavement, divorce, and job loss have been associated with an increased risk of sudden death, which may be related to a combination of both arousal and depressive states [42,43]. One area of potential intersection between emotional stress and sudden death that has received relatively little attention has been dreaming and REM sleep. Anger or fear are expressed in over one-half of all dreams [44,45], and there may be marked surges in sympathetic activity during REM sleep [46]. While sleep is overall a protected time with regard to cardiovascular events, violent or frightening dreams have been associated with ventricular fibrillation [47]. The increased morning frequency of cardiovascular events described above could in part be due to bursts of REM sleep prior to awakening. Pathophysiology Controlled animal experiments provide considerable support for anger as a trigger of arrhythmia, particularly in the presence of coronary narrowing. As examples: Stimulation of the hypothalamus, which plays a major role in the regulation of the autonomic nervous system, can induce ventricular tachyarrhythmias [48,49]. This response is inhibited by beta blockade, suggesting that increased sympathetic activity is the likely cause [50]. Provocation of anger in dogs resulted in a 30 to 40 percent reduction in the threshold for inducing repetitive extrasystoles, which is a surrogate measure of the ventricular fibrillation threshold [51]. This enhanced vulnerability, which was associated with an increased magnitude of T-wave alternans, was also markedly reduced by beta blockade. A figure provides a schema for considering the mechanism by which acute emotional stressors such as anger may trigger ventricular arrhythmia ( figure 3). While a https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 6/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate tachyarrhythmia is the major response to an emotional stressor, a vagal response leading to bradycardia and hypotension may lead to syncope. This vasovagal condition is usually benign, unless occurring in the presence of significant conduction system disease [52]. An increase in sympathetic activity and a decrease in vagal tone are principal components of the response to anger. The result is a significant elevation in heart rate and blood pressure which could lead to increased myocardial oxygen demand and transient ischemia. The magnitude of the heart rate response and the double-product (heart rate x blood pressure) are typically less during mental tasks than during exercise stress. This suggests that a primary reduction in myocardial oxygen supply might be present during mental stress-induced ischemia. Constriction of atherosclerotic coronary artery segments has been demonstrated in dogs two to three minutes following elicitation of anger [53]. The coronary vasoconstriction persisted after the return of heart rate and blood pressure to baseline and could be blocked by the alpha-receptor antagonist prazosin. Sympathetic nervous system stimulation increases cardiac vulnerability in the normal and ischemic heart [54,55]. This response is manifested by the spontaneous occurrence of arrhythmia, reduction in the ventricular fibrillation threshold, and increase in the magnitude of T-wave alternans [56,57]. A second peak of vulnerability has been described after reperfusion of an occluded coronary vessel, possibly due to the washout of ischemic byproducts [58]. Increased sympathetic activity enhances cardiac vulnerability in several ways: An imbalance of oxygen supply-demand due to increased cardiac metabolic activity and coronary vasoconstriction, particularly in vessels with injured endothelium. Direct profibrillatory influences may result from changes in impulse formation, conduction, or both [59]. Potentiation of Purkinje fiber automaticity, early depolarizations, and prolongation of the QT interval may lead to a reduced threshold for ventricular fibrillation. Catecholamine-induced hypokalemia, resulting from the intracellular movement of potassium in response to beta-2-adrenergic stimulation, may potentiate arrhythmia, and may provide insight into the protective effect of beta blockade [60]. Lowering of vagal activity with stress may also contribute via the following effects: reduced presynaptic inhibition of norepinephrine release; increase in heart rate with its attendant cardiac metabolic demands, and lowering of the threshold for ventricular fibrillation [61]. In https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 7/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate humans, reduced vagal tone, as assessed by heart rate variability, is associated with increases in mortality and the incidence of sudden death among postinfarction patients [62]. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) Acute psychologic stress may also lead to plaque rupture and thrombosis, possibly triggering the onset of ventricular fibrillation [63]. (See "Mechanisms of acute coronary syndromes related to atherosclerosis".) A prothrombotic contribution was supported by the finding of increases in fibrinogen, von Willebrand factor and D-dimer in individuals subject to the Hanshin-Awaji earthquake [64]. PREVENTIVE MEASURES In summary, considerable data supports a role for psychosocial factors in sudden death both acutely with anger and chronically with states of depression, hostility, and social isolation. Although successful interventions remain less well established, an important mechanism of the cardioprotective effect of beta blockers after myocardial infarction may be through modification of acute stressors. Beta blockade is more protective against sudden death than non-sudden death, reducing non-sudden death by 20 percent, sudden death postinfarction by 33 percent, and witnessed instantaneous death by 46 percent [65,66]. However, a recent study of patients with an ICD found that standard doses of beta blockers did not appear to alter the circadian pattern in the onset of sustained ventricular tachycardia [67]. The mode of action of beta blockers is not completely understood, but includes: Direct sympathetic blockade A membrane stabilizing effect A reduction in ischemic potential An increase in heart rate variability and baroreflex sensitivity [68-70] A shorter corrected QT interval Prevention of stress-induced hypokalemia [60] Other pharmacologic therapies show some promise. In the ONSET study, aspirin was noted to reduce the relative risk of nonfatal myocardial infarction following anger [27]. Parasympathomimetic stimulation with low dose scopolamine show some promise in increasing vagal activity and heart rate variability, and trials evaluating antidepressant therapy with serotonin uptake inhibitors may be appropriate in selected individuals. https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 8/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate Implementation of low-cost psychosocial interventions warrants serious consideration postmyocardial infarction, although current evidence is insufficient to justify widespread implementation. An initial report suggested benefit from such an approach; however, this was not confirmed in a later trial [71]. It is hoped that more definitive information will be provided by a multicenter psychologic intervention trial begun by the National Institutes of Health to test practical strategies in patients following myocardial infarction. There are patients in whom an avoidable potential trigger occurs with such regularity that the accumulated risk becomes substantial and intervention may be helpful. As an example, a patient who experiences anger, a known trigger, many times per day might benefit from stress management instruction. In addition, patients taking anti-ischemic or antiarrhythmic medication should have adequate pharmacologic coverage during the full 24-hour period, particularly during the morning period of increased risk. From a research perspective, further attempts to identify the mechanism by which psychosocial factors increase risk of sudden death are needed, as well as the testing of interventions to lower the risk. Interventional trials are currently limited. Such strategies may work indirectly by promoting healthy behavior such as smoking cessation, diet control, and compliance with other medical recommendations or directly by modifying physiologic factors such as sympathetic nervous system activity, coronary blood flow and resistance, platelet aggregation and thrombotic potential, plaque stability, and lipid metabolism. SUMMARY AND RECOMMENDATIONS Evidence suggests a possible role for psychosocial factors in sudden cardiac death. (See 'Introduction' above.) A circadian variation has been found for sudden cardiac death that parallels that of myocardial infarction, with a peak in the morning. It has been suggested that a primary arrhythmic event is more likely to occur in the morning because increased adrenergic activity at this time may increase electrical instability or induce myocardial ischemia without infarction. (See 'Circadian variation' above.) Cardiac arrests also show a weekly and seasonal variation. The daily incidence peaks on Monday and the seasonal incidence is greatest in winter. (See 'Seasonal variation' above.) Data from an implantable cardioverter-defibrillator (ICD) study found that depression appears to increase the rate of appropriate shocks in patients with an ICD. (See 'Holter monitoring and ICD' above.) https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 9/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate There have been few studies of the relationship between emotional stress and precipitation of arrhythmia. The hypothesized role of stress in the occurrence of arrhythmia is likely mediated by sympathetic activation and an increase in circulating catecholamines, which can alter the induction, rate, and termination of ventricular arrhythmia. (See 'Emotional stress and arrhythmia' above.) There are no well-established interventions for ameliorating the possible role of psychosocial factors (such as anger, depression, and social isolation) in sudden death. The cardioprotective effect of beta blockers after myocardial infarction may work through modification of acute stressors. (See 'Preventive measures' above.) There are patients in whom an avoidable potential trigger occurs regularly that an intervention may be helpful. As an example, a patient who experiences anger many times per day might benefit from stress management instruction. (See 'Preventive measures' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Hemingway H, Malik M, Marmot M. Social and psychosocial influences on sudden cardiac death, ventricular arrhythmia and cardiac autonomic function. Eur Heart J 2001; 22:1082. 2. Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99:2192. 3. Muller JE, Ludmer PL, Willich SN, et al. Circadian variation in the frequency of sudden cardiac death. Circulation 1987; 75:131. 4. Willich SN, Levy D, Rocco MB, et al. Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population. Am J Cardiol 1987; 60:801. 5. Levine RL, Pepe PE, Fromm RE Jr, et al. Prospective evidence of a circadian rhythm for out-of-hospital cardiac arrests. JAMA 1992; 267:2935. 6. Arntz HR, Willich SN, Oeff M, et al. Circadian variation of sudden cardiac death reflects age-related variability in ventricular fibrillation. Circulation 1993; 88:2284. 7. Willich SN, Goldberg RJ, Maclure M, et al. Increased onset of sudden cardiac death in the https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 10/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate first three hours after awakening. Am J Cardiol 1992; 70:65. 8. Arntz HR, Willich SN, Schreiber C, et al. Diurnal, weekly and seasonal variation of sudden death. Population-based analysis of 24,061 consecutive cases. Eur Heart J 2000; 21:315. 9. Peckova M, Fahrenbruch CE, Cobb LA, Hallstrom AP. Circadian variations in the occurrence of cardiac arrests: initial and repeat episodes. Circulation 1998; 98:31. 10. Peckova M, Fahrenbruch CE, Cobb LA, Hallstrom AP. Weekly and seasonal variation in the incidence of cardiac arrests. Am Heart J 1999; 137:512. 11. Kloner RA, Poole WK, Perritt RL. When throughout the year is coronary death most likely to occur? A 12-year population-based analysis of more than 220 000 cases. Circulation 1999; 100:1630. 12. Canada WB, Woodward W, Lee G, et al. Circadian rhythm of hourly ventricular arrhythmia frequency in man. Angiology 1983; 34:274. 13. Twidale N, Taylor S, Heddle WF, et al. Morning increase in the time of onset of sustained ventricular tachycardia. Am J Cardiol 1989; 64:1204. 14. Tofler GH, Gebara OC, Mittleman MA, et al. Morning peak in ventricular tachyarrhythmias detected by time of implantable cardioverter/defibrillator therapy. The CPI Investigators. Circulation 1995; 92:1203. 15. Lampert R, Rosenfeld L, Batsford W, et al. Circadian variation of sustained ventricular tachycardia in patients with coronary artery disease and implantable cardioverter- defibrillators. Circulation 1994; 90:241. 16. Englund A, Behrens S, Wegscheider K, Rowland E. Circadian variation of malignant ventricular arrhythmias in patients with ischemic and nonischemic heart disease after cardioverter defibrillator implantation. European 7219 Jewel Investigators. J Am Coll Cardiol 1999; 34:1560. 17. Whang W, Albert CM, Sears SF Jr, et al. Depression as a predictor for appropriate shocks among patients with implantable cardioverter-defibrillators: results from the Triggers of Ventricular Arrhythmias (TOVA) study. J Am Coll Cardiol 2005; 45:1090. 18. Selwyn AP, Shea M, Deanfield JE, et al. Character of transient ischemia in angina pectoris. Am J Cardiol 1986; 58:21B. https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 11/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate 19. Nademanee K, Intarachot V, Josephson MA, Singh BN. Circadian variation in occurrence of transient overt and silent myocardial ischemia in chronic stable angina and comparison with Prinzmetal angina in men. Am J Cardiol 1987; 60:494. 20. Rocco MB, Barry J, Campbell S, et al. Circadian variation of transient myocardial ischemia in patients with coronary artery disease. Circulation 1987; 75:395. 21. Barry J, Selwyn AP, Nabel EG, et al. Frequency of ST-segment depression produced by mental stress in stable angina pectoris from coronary artery disease. Am J Cardiol 1988; 61:989. 22. Peters RW, Muller JE, Goldstein S, et al. Propranolol and the morning increase in the frequency of sudden cardiac death (BHAT Study). Am J Cardiol 1989; 63:1518. 23. Behrens S, Ehlers C, Br ggemann T, et al. Modification of the circadian pattern of ventricular tachyarrhythmias by beta-blocker therapy. Clin Cardiol 1997; 20:253. 24. Peters RW, Mitchell LB, Brooks MM, et al. Circadian pattern of arrhythmic death in patients receiving encainide, flecainide or moricizine in the Cardiac Arrhythmia Suppression Trial (CAST). J Am Coll Cardiol 1994; 23:283. 25. Behrens S, Ney G, Fisher SG, et al. Effects of amiodarone on the circadian pattern of sudden cardiac death (Department of Veterans Affairs Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy). Am J Cardiol 1997; 80:45. 26. Reich P, DeSilva RA, Lown B, Murawski BJ. Acute psychological disturbances preceding life-threatening ventricular arrhythmias. JAMA 1981; 246:233. 27. Mittleman MA, Maclure M, Sherwood JB, et al. Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators. Circulation 1995; 92:1720. 28. Lampert R, Jain D, Burg MM, et al. Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Circulation 2000; 101:158. 29. Kloner RA, Leor J, Poole WK, Perritt R. Population-based analysis of the effect of the Northridge Earthquake on cardiac death in Los Angeles County, California. J Am Coll Cardiol 1997; 30:1174. https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 12/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate 30. Steinberg JS, Arshad A, Kowalski M, et al. Increased incidence of life-threatening ventricular arrhythmias in implantable defibrillator patients after the World Trade Center attack. J Am Coll Cardiol 2004; 44:1261. 31. Shedd OL, Sears SF Jr, Harvill JL, et al. The World Trade Center attack: increased frequency of defibrillator shocks for ventricular arrhythmias in patients living remotely from New York City. J Am Coll Cardiol 2004; 44:1265. 32. Fang F, Fall K, Mittleman MA, et al. Suicide and cardiovascular death after a cancer diagnosis. N Engl J Med 2012; 366:1310. 33. Januzzi JL Jr, Stern TA, Pasternak RC, DeSanctis RW. The influence of anxiety and depression on outcomes of patients with coronary artery disease. Arch Intern Med 2000; 160:1913. 34. Kawachi I, Colditz GA, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89:1992. 35. Kawachi I, Sparrow D, Vokonas PS, Weiss ST. Symptoms of anxiety and risk of coronary heart disease. The Normative Aging Study. Circulation 1994; 90:2225. 36. Ruberman W, Weinblatt E, Goldberg JD, Chaudhary BS. Psychosocial influences on mortality after myocardial infarction. N Engl J Med 1984; 311:552. 37. Barefoot JC, Dahlstrom WG, Williams RB Jr. Hostility, CHD incidence, and total mortality: a 25-year follow-up study of 255 physicians. Psychosom Med 1983; 45:59. 38. Frasure-Smith N. In-hospital symptoms of psychological stress as predictors of long-term outcome after acute myocardial infarction in men. Am J Cardiol 1991; 67:121. 39. Tofler GH, Muller JE, Stone PH, et al. Comparison of long-term outcome after acute myocardial infarction in patients never graduated from high school with that in more educated patients. Multicenter Investigation of the Limitation of Infarct Size (MILIS). Am J Cardiol 1993; 71:1031. 40. Williams RB, Barefoot JC, Califf RM, et al. Prognostic importance of social and economic resources among medically treated patients with angiographically documented coronary artery disease. JAMA 1992; 267:520. 41. Berkman LF, Leo-Summers L, Horwitz RI. Emotional support and survival after myocardial infarction. A prospective, population-based study of the elderly. Ann Intern https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 13/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate Med 1992; 117:1003. 42. Rahe RH, Romo M, Bennett L, Siltanen P. Recent life changes, myocardial infarction, and abrupt coronary death. Studies in Helsinki. Arch Intern Med 1974; 133:221. 43. Parkes CM, Benjamin B, Fitzgerald RG. Broken heart: a statistical study of increased mortality among widowers. Br Med J 1969; 1:740. 44. Merritt JM, Stickgold R, Pace-Schott E, et al. Emotional profiles in the dreams of men and women. Conscious Cogn 1994; 3:46. 45. MacWilliam, JA. Blood pressure and heart action in sleep and dreams: Their relation to hemorrhages, angina and sudden death. Br Med J 1923; 22:1196. 46. Hobson JA. Sleep and dreaming. J Neurosci 1990; 10:371. 47. Lown B, Temte JV, Reich P, et al. Basis for recurring ventricular fibrillation in the absence of coronary heart disease and its management. N Engl J Med 1976; 294:623. 48. Smith OA, DeVito JL. Central neural integration for the control of autonomic responses associated with emotion. Annu Rev Neurosci 1984; 7:43. 49. Hockman CH, Mauck HP Jr, Hoff EC. ECG changes resulting from cerebral stimulation. II. A spectrum of ventricular arrhythmias of sympathetic origin. Am Heart J 1966; 71:695. 50. Verrier RL, Calvert A, Lown B. Effect of posterior hypothalamic stimulation on ventricular fibrillation threshold. Am J Physiol 1975; 228:923. 51. Verrier RL, Hagestad EL, Lown B. Delayed myocardial ischemia induced by anger. Circulation 1987; 75:249. 52. Milstein S, Buetikofer J, Lesser J, et al. Cardiac asystole: a manifestation of neurally mediated hypotension-bradycardia. J Am Coll Cardiol 1989; 14:1626. 53. Boltwood MD, Taylor CB, Burke MB, et al. Anger report predicts coronary artery vasomotor response to mental stress in atherosclerotic segments. Am J Cardiol 1993; 72:1361. 54. Verrier RL, Thompson PL, Lown B. Ventricular vulnerability during sympathetic stimulation: role of heart rate and blood pressure. Cardiovasc Res 1974; 8:602. https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 14/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate 55. Lown B, Verrier R, Corbalan R. Psychologic stress and threshold for repetitive ventricular response. Science 1973; 182:834. 56. Lombardi F, Verrier RL, Lown B. Relationship between sympathetic neural activity, coronary dynamics, and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion. Am Heart J 1983; 105:958. 57. Nearing BD, Huang AH, Verrier RL. Dynamic tracking of cardiac vulnerability by complex demodulation of the T wave. Science 1991; 252:437. 58. Corbalan R, Verrier RL, Lown B. Differing mechanisms for ventricular vulnerability during coronary artery occlusion and release. Am Heart J 1976; 92:223. 59. Corr PB, Yamada KA, Witkowski FX. Mechanisms controlling cardiac autonomic function a nd their relation to arrhythmogenesis. In: The heart and cardiovascular system, Fozzard HA, Haber H, Jennings RB, et al (Eds), Raven Press, 1986. 60. Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med 1983; 309:1414. 61. Kent KM, Smith ER, Redwood DR, Epstein SE. Electrical stability of acutely ischemic myocardium. Influences of heart rate and vagal stimulation. Circulation 1973; 47:291. 62. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987; 59:256. 63. Muller JE, Abela GS, Nesto RW, Tofler GH. Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier. J Am Coll Cardiol 1994; 23:809. 64. Kario K, Matsuo T, Kobayashi H, et al. Earthquake-induced potentiation of acute risk factors in hypertensive elderly patients: possible triggering of cardiovascular events after a major earthquake. J Am Coll Cardiol 1997; 29:926. 65. Hansteen V, M inichen E, Lorentsen E, et al. One year's treatment with propranolol after myocardial infarction: preliminary report of Norwegian multicentre trial. Br Med J (Clin Res Ed) 1982; 284:155. 66. Frishman WH. Multifactorial actions of beta-adrenergic blocking drugs in ischemic heart disease: current concepts. Circulation 1983; 67:I11. https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 15/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate 67. Nanthakumar K, Newman D, Paquette M, et al. Circadian variation of sustained ventricular tachycardia in patients subject to standard adrenergic blockade. Am Heart J 1997; 134:752. 68. Schwartz PJ, La Rovere MT, Vanoli E. Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation 1992; 85:I77. 69. Cook JR, Bigger JT Jr, Kleiger RE, et al. Effect of atenolol and diltiazem on heart period variability in normal persons. J Am Coll Cardiol 1991; 17:480. 70. Coumel P, Hermida JS, Wennerbl m B, et al. Heart rate variability in left ventricular hypertrophy and heart failure, and the effects of beta-blockade. A non-spectral analysis of heart rate variability in the frequency domain and in the time domain. Eur Heart J 1991; 12:412. 71. Frasure-Smith N, Lesp rance F, Gravel G, et al. Long-term survival differences among low-anxious, high-anxious and repressive copers enrolled in the Montreal heart attack readjustment trial. Psychosom Med 2002; 64:571. Topic 4851 Version 16.0 https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 16/17 7/6/23, 1:43 PM Psychosocial factors in sudden cardiac arrest - UpToDate https://www.uptodate.com/contents/psychosocial-factors-in-sudden-cardiac-arrest 17/17 |
7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate Screening to prevent sudden cardiac death in competitive athletes : Mark S Link, MD, Antonio Pelliccia, MD : Peter J Zimetbaum, MD, Scott Manaker, MD, PhD, Francis G O'Connor, MD, MPH, FACSM, FAMSSM : Todd F Dardas, MD, MS Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 21, 2023. INTRODUCTION In individuals with latent cardiac conditions, participation in athletic activity may provoke a potentially fatal arrhythmia. Athletes engaged in competitive athletics may be particularly prone to sudden cardiac death (SCD) as the result of pressure to perform at a high level. As a result, there is great interest in identification of individuals who may be at risk of SCD and whose risk of SCD may be decreased by implementing appropriate exercise restrictions or proper medical management. This topic reviews approaches to screening for cardiac abnormalities in competitive athletes. Screening in recreational athletes is discussed separately. (See "Exercise for adults: Terminology, patient assessment, and medical clearance", section on 'Medical assessment and clearance for exercise' and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease", section on 'The exercise prescription'.) Issues related to the management of athletes with known cardiovascular disease (CVD) as well as the broader range of arrhythmias and conduction disturbances that occur in athletes are discussed separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation" and "Athletes with arrhythmias: Treatment and returning to athletic participation".) Return to sports after recovery from coronavirus disease 2019 (COVID-19) is discussed separately. (See "COVID-19: Return to sport or strenuous activity following infection".) https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 1/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate DEFINITIONS Athletes may be classified by their age and by the competitive nature of their exercise activity: Young athletes Most commonly, the term "young athletes" refers to those in high school and college but applies in general to individuals under age 35 in whom SCD is usually due to a congenital or inherited heart disease (eg, channelopathy, anomalous coronary artery). Masters athletes Adult, or "masters," athletes include individuals 35 years of age and older in whom SCD is most commonly due to coronary artery disease (CAD). These athletes are apparently normal and healthy individuals, although many are greater than 50 years of age. These athletes may also prioritize winning and ignore specific warning symptoms. Competitive athletes Competitive athletes engage in organized team or individual sports in which there is regular competition that places a premium on achievement. This definition implies that such individuals may not appreciate symptoms or limitations indicative of underlying CVD nor have the will or judgment to limit their activity in response to symptoms of CVD. This most frequently applies to high school, college, and professional sports, but may apply to certain occupations (eg, military service, firefighters, underwater industrial work, specific roles in law enforcement). Recreational athletes Recreational athletes generally participate for health or enjoyment purposes and do not typically have the same pressures to excel compared with competitive athletes. Nonetheless, activity levels in recreational sports may be vigorous, and in some individuals or sports, the difference in intensity of exercise between recreational and competitive athletics may be minimal (eg, mountaineering). GOALS OF SCREENING As with screening for any condition, the primary purpose of screening athletes for cardiac pathology is to identify patients at higher risk of SCD whose prognosis may be improved with an intervention such as exercise modification or specific therapy targeted at the underlying pathology. ATHLETES LESS THAN 35 YEARS OLD https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 2/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate History and physical examination In competitive athletes 34 years or younger, we suggest screening with a complete history, family history, social history, and physical examination rather than no screening. Ideally, this assessment should occur prior to participation and should be performed by a trained clinician. The elements of the history and physical examination related to cardiac screening include: History Syncope, presyncope, palpitations. Chest discomfort and dyspnea. History of murmur or valve disease. Exercise tolerance and limitations. Family history Known genetic diseases of the myocardium. Family history (eg, first- or second-degree relatives) of SCD or unexplained death with features suspicious for SCD before the age of 50. Family history of CAD before the age of 50 or heart failure, heart transplantation, pacemaker placement, or internal-cardioverter defibrillator placement at any age. Social history Substance use (eg, tobacco, methamphetamine, alcohol) Physical examination Blood pressure (both arms), heart rate. Chest wall abnormalities, cardiac displacement or enlargement. Cardiac murmurs at rest and with Valsalva or change in position. Signs of heart failure (eg, jugular venous distension, edema). Signs of malperfusion (eg, cyanosis, clubbing). Radial or femoral arterial pulse deficits or differences. https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 3/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate Stigmata of Marfan syndrome. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders", section on 'Clinical manifestations of MFS'.) Screening with a history and physical examination is consistent with most professional guidelines (eg, American Heart Association, American College of Cardiology, European Society of Cardiology [ESC]) [1,2]. Of note, North American guidelines provide specific historical and examination elements that may be required depending on the location of screening [3]. In contrast, Denmark does not screen athletes with a history or examination, and the American College of Sports Medicine and the American Academy of Family Physicians guidelines do not recommend an evaluation in patients who are active, asymptomatic, and without CVD risk factors [4,5]. Our preference for screening with a history and examination is based on our experience and the prevailing norms in the United States. The evidence on screening with history and physical examination alone is limited to observational studies [6]. Most screening studies also performed an electrocardiogram (ECG) [7]. ECG screening (controversial) Additional screening with an ECG prior to participation is controversial, and the authors and editors of this topic have differing approaches to screening: Most of the authors and editors of this topic do not perform ECG screening for competitive athletes less than 35 years of age. This approach agrees with North American professional guidelines [1,8], which do not recommend broad national screening with ECG, echocardiography, or exercise testing. However, one guideline-writing group did not oppose smaller-scale screening programs, provided that they are "well designed and prudently implemented" [1]. The National Collegiate Athletic Association describes ECG screening as an option for screening that should only be conducted under standards set by North American professional societies [9]. Our experts who do not endorse ECG screening interpret the evidence on screening as inconclusive regarding its efficacy (eg, low event rates of SCD among competitive athletes, presumed high false negative and false positive rates). In addition, they note that large-scale screening is unattractive for reasons that include prohibitively high expense due to the large number of competitive athletes (eg, difficulties in large-scale implementation, including test interpretation), assignment of responsibility and liability (eg, false negative and false positive screens) to individual clinicians, and questionable https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 4/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate ethical standing given the similar rate of SCD in noncompetitive athletes and nonathletes who would not receive screening. Some experts, including one contributor to this topic, obtain ECG screening for all competitive athletes less than 35 years of age. These experts repeat screening at least every two years after the initial screen. Thus, the ECG prior to participation is likely the most important evaluation, and after participating in competitive athletics without signs or symptoms of cardiovascular disease, the value of continued screening decreases. The ESC guidelines, most international federations, and the International Olympic Committee endorse screening with an ECG prior to competitive sport participation for all young athletes [2,10]. Experts who support routine ECG screening interpret the yield and efficacy of ECG screening to be sufficiently high. In addition, the low cost and wide availability of ECGs make such screening an attractive option. While our experts have differing views of the same evidence, there is agreement that the incidence of SCD related to competitive sports is generally low, but may be higher in the presence of specific diseases (eg, arrhythmogenic cardiomyopathy, catecholaminergic polymorphic ventricular tachycardia). The evidence on the yield and efficacy of ECG screening is composed of cross-sectional studies that have conflicting findings: In a study that included 22,324 children (62 percent males; mean age 12 years at first screening) who underwent a total of 65,397 annual evaluations (median 2.9 per child), cardiovascular diseases increasing the risk of SCD were identified in 69 children (0.3 percent) [11]. The diseases detected included congenital heart diseases (n = 17), channelopathies (n = 14), cardiomyopathies (n = 15), nonischemic left ventricular scar with ventricular arrhythmias (n = 18), and others (n = 5). Among those who had CVD detected by screening, most were 12 years old (n = 63, 91 percent) and were detected by repeat evaluation (n = 44, 64 percent). The estimated cost per diagnosis was 73,312 euros. One child with normal screening studies experienced a cardiac arrest during sports activity and was resuscitated. In an observational study that recorded SCD in athletic and nonathletic populations after the advent of screening in 1982, the annual incidence of SCD in athletes decreased from 3.6/100,000 person-years in 1979 to 1980 to 0.4/100,000 person-years in 2003 to 2004 [12]. Notably, there was no change in the incidence of SCD among nonathletes who were not screened over the same time period. https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 5/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate In a population of athletes who underwent preparticipation screening beginning in 1996, the estimated incidence of SCD in athletes was similar after the onset of screening (2.54 versus 2.66 events/100,000 person years) [13]. In a study that included 11,168 adolescent athletes (mean age 16.4 years) who underwent comprehensive cardiac screening (including a health questionnaire, physical examination, ECG, and echocardiography), 42 athletes (0.4 percent) were found to have disorders associated with SCD, and 225 (2 percent) were found to have a congenital or valvular abnormality [14]. After screening began, SCD occurred in eight athletes after a mean interval of 6.8 years (approximately one SCD event per 14,800 person-years). A total of six athletes with a previously negative screen suffered SCD within approximately seven years of their initial screening evaluation. Among the eight athletes who suffered SCD, six had normal initial screening results and died from cardiomyopathies. Repeat evaluations were not performed after the initial evaluation. The yield and efficacy of ECG screening depends on the population screened, tests used for screening, definition of a cardiac abnormality, and frequency of testing. In general, cardiac abnormalities are detected by screening in approximately 2 to 5 percent of individuals screened, and there is evidence that repeat screening increases the number of cardiac abnormalities detected by threefold: In a systematic review and meta-analysis of screening strategies that included data from 15 studies and 47,137 athletes, there were 160 potentially lethal abnormalities identified (0.3 percent). Screening athletes with an ECG was more sensitive than history alone or physical examination alone, and ECG, history, and physical examination had similar specificity (ie, >90 percent) [7]. There was a moderate amount of heterogeneity among the studies reviewed, and the criteria for an abnormal ECG result varied between studies. Among a series of 32,652 young people who underwent routine preparticipation screening that included an ECG, the prevalence of ECG patterns suggestive of significant structural heart disease was <5 percent [15]. In a series of 33,735 athletes who were screened with history, physical examination, ECG, and modified stress test over a 17-year period, an abnormal ECG was found in 8.9 percent of persons screened [16]. The most common cardiovascular abnormalities were arrhythmias and conduction abnormalities (38 percent), hypertension (27 percent), and mitral valve disease (21 percent). https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 6/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate ATHLETES 35 YEARS OR OLDER History and physical examination In asymptomatic athletes 35 years of age who plan to participate in competitive sports, we suggest a complete personal history, family history, and physical examination rather than no screening. Ideally, this assessment should occur prior to participation. The components of the history and physical examination are the same as those in younger patients. (See 'History and physical examination' above.) We also perform an age-appropriate evaluation for atherosclerotic cardiovascular disease (ASCVD). The approach to primary prevention of ASCVD is discussed separately. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".) Our approach is based on norms in North America and Europe [15,17]. The yield of screening with history, physical examination, and age-appropriate ASCVD testing is unknown, and there are no high-quality studies of the efficacy of screening in this population. Additional testing For this group of athletes, the approach to additional screening is determined by age, 10-year risk of ASCVD (calculator 1), and intensity of exercise ( figure 1): Age 35 to 64, low ASCVD risk, and low- to moderate-intensity sports In patients 35 to 64 years of age with a 10-year risk of ASCVD <5 percent and who plan to compete in low- to moderate- intensity sports, we suggest screening with an ECG alone. Age 35 to 64, elevated ASCVD risk, or high-intensity sports Our authors and editors have different approaches to screening in this group of patients: Most authors and editors screen with an exercise stress ECG in patients 35 to 64 years of age who have a 10-year risk of ASCVD 5 percent or who plan to compete in high- intensity sports. In the United States, treadmill stress testing is the most common, while in Europe, bicycle stress testing is the norm. Another contributor to this topic screens such patients with a resting ECG but does not obtain an exercise stress ECG. Age 65 and above Similar to patients 35 to 64 years of age, our authors and editors have differing approaches; most screen with an exercise stress ECG, while another contributor screens with only a resting ECG. https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 7/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate Repeat screening with an ECG or exercise stress ECG is controversial. Most of our experts do not advocate for repeat screening, and one expert recommends repeat screening approximately every four years with the test initially used to screen; the precise interval may be less or more frequent depending on ASCVD risk. Many professional societies provide recommendations on preparticipation screening in older athletes, and there are varying approaches to ECG and exercise treadmill testing. The European guidelines advocate for ECG screening in all athletes prior to competition ( algorithm 1) [2]. Other societies advocate for no ECG screening [17]. Some societies advocate for ECG screening in older patients at low ASCVD risk who plan to participate in low- to moderate-intensity exercise and exercise ECG testing in patients with higher age, ASCVD risk, or participation in high-intensity sports [1,2]. There are no North American guidelines that recommend repeat screening. There are few studies that evaluate the effect of screening in athletes 35 years or older. Those who support screening in this age group note the higher incidence of CAD in this population that may increase the risk of SCD, while those who do not support screening note that most competitive athletes in this age group have exercised for many years without adverse cardiovascular effects. INTERPRETATION OF SCREENING TESTS History and examination In patients who undergo screening appropriate for age and risk, patients with a normal history and examination may participate in competitive sports with the knowledge that screening does not completely exclude the presence of conditions that may lead to SCD. Patients with an abnormal screening history or examination require further testing appropriate for any diseases suspected. ECG In patients with a normal screening ECG, no further testing is required, and athletes can participate with the knowledge that screening does not completely exclude the presence of conditions that may lead to SCD. In athletes with an abnormal screening ECG, participation in competitive athletics should be restricted until review of the ECG by a clinician experienced in the interpretation of athletes ECGs. Competitive athletes (especially young athletes) may have seemingly abnormal ECG findings that may be appropriate for age or level of training. The specialized approach to ECG interpretation in athletes is discussed in detail separately. (See "Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances".) https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 8/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate Exercise stress ECG In asymptomatic patients who undergo screening with an exercise treadmill test, the test findings include: Negative for ischemia In patients with an exercise treadmill test negative for ischemia, no further testing for ischemia is required, and athletes may participate with the knowledge that screening does not completely exclude the presence of conditions that may lead to SCD. Positive for ischemia In patients with a test that suggests the presence of ischemia, the specific findings from the exercise test (eg, downsloping ST depression) and the pretest probability of CAD are used to guide further testing for ischemia. Such patients require a diagnostic assessment from a cardiologist before engaging in recreational or competitive exercise. Poor exercise tolerance In patients whose exercise treadmill test is negative for ischemia but who have poor exercise tolerance (eg, unable to reach 85 percent of age- predicted heart rate, short exercise effort), we provide the patient an individualized exercise prescription and encourage appropriate training before participation in competitive athletics. The markers of poor cardiovascular fitness that can be obtained from a standardized exercise test and the approach to exercise prescription are discussed separately. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Exercise ECG' and "Exercise prescription and guidance for adults".) Nondiagnostic test In patients with a nondiagnostic test (eg, uninterpretable ECG), the approach to further testing is individualized. SOCIETY AND GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Exercise in adults".) SUMMARY AND RECOMMENDATIONS Competitive athletes This topic covers cardiovascular screening for competitive athletes who engage in organized team or individual sports in which there is regular competition that places a premium on achievement. This definition implies that such individuals may not appreciate symptoms or limitations indicative of underlying https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 9/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate cardiovascular disease (CVD) nor have the will or judgment to limit their activity in response to symptoms of CVD. This most frequently applies to high school, college, and professional sports, but may apply to certain occupations (eg, military service, firefighters, underwater industrial work, specific roles in law enforcement). (See 'Definitions' above.) All athletes In competitive athletes, we suggest screening with a complete history, family history, social history, and physical examination rather than no screening (Grade 2C). (See 'History and physical examination' above.) Additional screening For competitive athletes, the approach to additional screening (eg, ECG, stress testing) is determined by age, 10-year risk of atherosclerotic cardiovascular disease (ASCVD) (calculator 1), and intensity of exercise ( figure 1) (see 'Additional testing' above): Age <35 years ECG screening is controversial. Most of the authors and editors of this topic do not perform ECG screening for competitive athletes less than 35 years of age. Some experts, including one contributor to this topic, endorse ECG screening for all competitive athletes less than 35 years of age. Both approaches to screening are supported by professional guidelines, which differ in their recommendations. (See 'ECG screening (controversial)' above.) Age 35 to 64, low ASCVD risk, and low- to moderate-intensity sports In patients 35 to 64 years of age with a 10-year risk of ASCVD <5 percent and who plan to compete in low- to moderate-intensity sports, we suggest screening with an ECG (Grade 2C). Age 35 to 64, elevated ASCVD risk, or high-intensity sports In patients 35 to 64 years of age who plan to participate in competitive sports, we suggest screening, at minimum, with a resting ECG (Grade 2C). Our authors and editors have different approaches to exercise testing in this group of patients. Most contributors to this topic screen with an exercise stress ECG in patients who have a 10-year risk of ASCVD 5 percent or who plan to compete in high-intensity sports. In the United States, treadmill stress testing is the most common, while in Europe, bicycle stress testing is more common. Another contributor to this topic obtains a resting ECG but does not obtain an exercise stress ECG in older adults. https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 10/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate Age 65 and above Similar to patients 35 to 64 years of age, our authors and editors have differing approaches; most screen with an exercise stress ECG, while another only screens with a resting ECG. Repeat screening with an ECG or exercise stress ECG is controversial. (See 'Additional testing' above.) Normal screening test results Competitive athletes with a normal screening history, physical examination, ECG, or exercise stress ECG require no further testing and can participate with the knowledge that screening does not completely exclude the presence of conditions that may lead to sudden cardiac death (SCD). Abnormal screening test results Competitive athletes with abnormal test results require further testing and evaluation that may include specialist interpretation of the ECG or detailed evaluation of the exercise stress ECG results. (See 'Interpretation of screening tests' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Maron BJ, Levine BD, Washington RL, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular Disease in Competitive Athletes: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2356. 2. Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021; 42:17. 3. Maron BJ, Friedman RA, Kligfield P, et al. Assessment of the 12-lead ECG as a screening test for detection of cardiovascular disease in healthy general populations of young people (12-25 Years of Age): a scientific statement from the American Heart Association and the American College of Cardiology. Circulation 2014; 130:1303. 4. Maron BJ. Diversity of views from Europe on national preparticipation screening for competitive athletes. Heart Rhythm 2010; 7:1372. https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 11/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate 5. Riebe D, Franklin BA, Thompson PD, et al. Updating ACSM's Recommendations for Exercise Preparticipation Health Screening. Med Sci Sports Exerc 2015; 47:2473. 6. Stormholt ER, Svane J, Lynge TH, Tfelt-Hansen J. Symptoms Preceding Sports-Related Sudden Cardiac Death in Persons Aged 1-49 Years. Curr Cardiol Rep 2021; 23:8. 7. Harmon KG, Zigman M, Drezner JA. The effectiveness of screening history, physical exam, and ECG to detect potentially lethal cardiac disorders in athletes: a systematic review/meta-analysis. J Electrocardiol 2015; 48:329. 8. American Academy of Family Physicians, American Academy of Pediatrics, American Coll ege of Sports Me. Preparticipation Physical Evaluation, 4th ed, Bernhardt D, Roberts W (E ds), American Academy of Pediatrics, Elk Grove Village, IL 2010. 9. Hainline B, Drezner J, Baggish A, et al. Interassociation consensus statement on cardiovascular care of college student-athletes. Br J Sports Med 2017; 51:74. 10. Ljungqvist A, Jenoure PJ, Engebretsen L, et al. The International Olympic Committee (IOC) consensus statement on periodic health evaluation of elite athletes, March 2009. Clin J Sport Med 2009; 19:347. 11. Sarto P, Zorzi A, Merlo L, et al. Value of screening for the risk of sudden cardiac death in young competitive athletes. Eur Heart J 2023; 44:1084. 12. Corrado D, Basso C, Pavei A, et al. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 2006; 296:1593. 13. Steinvil A, Chundadze T, Zeltser D, et al. Mandatory electrocardiographic screening of athletes to reduce their risk for sudden death proven fact or wishful thinking? J Am Coll Cardiol 2011; 57:1291. 14. Malhotra A, Dhutia H, Finocchiaro G, et al. Outcomes of Cardiac Screening in Adolescent Soccer Players. N Engl J Med 2018; 379:524. 15. Pelliccia A, Culasso F, Di Paolo FM, et al. Prevalence of abnormal electrocardiograms in a large, unselected population undergoing pre-participation cardiovascular screening. Eur Heart J 2007; 28:2006. 16. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998; 339:364. https://www.uptodate.com/contents/screening-to-prevent-sudden-cardiac-death-in-competitive-athletes 12/13 7/6/23, 1:43 PM Screening to prevent sudden cardiac death in competitive athletes - UpToDate 17. Maron BJ, Ara jo CG, Thompson PD, et al. Recommendations for preparticipation screening and the assessment of cardiovascular disease in masters athletes: an advisory for healthcare professionals from the working groups of the World Heart Federation, the International Federation of Sports Medicine, and the American Heart Association Committee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation 2001; 103:327. 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7/6/23, 1:45 PM Short QT syndrome - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Short QT syndrome : Charles Antzelevitch, PhD, FACC, FAHA, FHRS : Mark S Link, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 02, 2022. INTRODUCTION Short QT Syndrome (SQTS) is a rare inherited channelopathy (a disorder that affects the movement of ions through channels within the cell membrane) associated with marked shortened QT intervals and sudden cardiac death (SCD) in individuals with a structurally normal heart. In contrast to long QT syndrome, another channelopathy, ion channel defects associated with SQTS lead to abnormal abbreviation of repolarization, predisposing affected individuals to a risk of atrial and ventricular arrhythmias. Since its first report in 2000, significant progress has been made in defining the genetic and cellular basis of SQTS as well as in therapeutic approaches to treating this syndrome. SQTS is a genetically heterogeneous disease associated with eight different genes encoding various cardiac ion channels, a carnitine transporter, and a chloride-bicarbonate anion exchanger. Data regarding genotype-phenotype correlation and genotype-specific treatment are promising but limited, primarily due to the lack of clinical cases. The clinical presentation, diagnostic approach, and treatment modalities for SQTS will be discussed here. SCD and other channelopathies are discussed separately. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Congenital long QT syndrome: Epidemiology and clinical manifestations".) HISTORICAL BACKGROUND AND INITIAL REPORT https://www.uptodate.com/contents/short-qt-syndrome/print 1/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate In 1993, it was first proposed that shorter than normal QT intervals (<400 milliseconds) are associated with a 2.4-fold increased risk for SCD [1]. An abnormally short QT interval observed before and after runs of VT/VF has been reported anecdotally [2,3]. Interestingly, certain species of kangaroo, known to have a high incidence of SCD, display an abnormally short QT interval as a normal feature on their electrocardiogram (ECG) [4,5]. SQTS was first described as a clinical entity in a report of four patients with extremely short QT intervals in association with paroxysmal atrial fibrillation and SCD [6,7]. In 2003, another study further described SQTS in two unrelated European families (six patients total) with a strong family history of sudden death in association with short QT interval on ECG [8]. Since then, over 200 cases of SQTS have been reported, and the existence of this novel channelopathy has been validated. DEFINITION Abbreviation of the QT interval, the time elapsed between ventricular depolarization and repolarization, on the surface ECG is caused by a decrease in the action potential duration (APD) of ventricular myocytes ( figure 1). The upper limit of the normal QT interval is now fairly well defined, but the lower limit of the normal QT interval and the value below which it could be considered arrhythmogenic remain unclear [9,10]. The ECGs of the first few patients with SQTS showed extremely short QT and QTc intervals of less than 300 milliseconds. Since then, patients with SQTS with QT interval longer than 300 milliseconds have been reported; however, in most cases the QT and QTc interval have been less than 360 milliseconds. Yet the diagnosis of SQTS is complicated due to the overlapping QT range of affected individuals and apparently healthy individuals. To define the lower limit of the QT interval, many experts refer to a comprehensive study that investigated the distribution of normal QT interval in 14,379 healthy individuals [11]. The study established the formula (Rautaharju's formula) by which the QT interval can be predicted as: QT predicted (QTp) = 656/(1+ heart rate/100) The prevalence of QT interval shorter than 88 percent of QTp (QT/QTp <88 percent, which is equivalent to two standard deviations below the mean) was 0.03 percent. Based on this observation, it was suggested that QT intervals less than 88 percent of QTp (two standard deviations below mean predicted value) at a particular heart rate may be considered as short QT intervals. For example, at a heart rate of 60 beats per minute (bpm), per Rautaharju's formula, QTp would be 410 milliseconds. Eighty-eight percent of QTp (410 milliseconds) would be 360 https://www.uptodate.com/contents/short-qt-syndrome/print 2/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate milliseconds. QT interval values less than 80 percent of QTp may be considered extremely short (which is equivalent to 330 milliseconds at a heart rate of 60 beats per minute) [12-15]. Clinical experience clearly indicates that the vast majority of patients with QTc values in the 330 to 360 range are not at risk, although a select few may be. (See 'Differential diagnosis' below.) PREVALENCE OF A SHORT QT INTERVAL In contrast to the epidemiologic data available for many other ECG parameters, including long QT intervals, the precise prevalence of a short QT interval in the general population is unknown but appears to be 2 percent or less when using a cutoff of 360 milliseconds. This is largely the case due to the long-standing failure to identify any risk associated with shorter-than-normal QT intervals as well as the varying definitions of what constitutes a shorter-than-normal QT interval. Several large cohorts have attempted to identify the frequency of short QT interval in the general population [16-19]. The precise definition of a short QT has varied slightly in each of the cohorts, but in all of the studies, patients classified as having a short QT interval had a rate- corrected QTc of 369 milliseconds or less. The prevalence was estimated as follows: In a Finnish cohort of 10,822 middle-aged (mean 44 years) patients, 0.4 percent had a short QTc interval (<340 milliseconds), and 0.1 percent had a very short QTc interval (<320 milliseconds) [16]. In a Swiss cohort of 41,767 army conscripts (99.6 percent male, mean age 19 years), 1 percent had a short QTc interval (<347 milliseconds), and 0.02 percent had a very short QTc interval (<320 milliseconds) [17]. In an American cohort of 46,129 healthy volunteers (53 percent female), 2 percent had a QTc interval 360 milliseconds [19]. In a Japanese cohort of 114,334 patients with ECGs stored in an electronic database, 0.37 percent were found to have short QTc intervals ( 357 milliseconds in males, 364 milliseconds in females) [18]. GENETIC BASIS SQTS is a genetically heterogeneous disease with mutations in eight different genes (three gain of function and five loss of function) that encode different cardiac ion channels, a carnitine transporter, and a chloride-bicarbonate anion exchanger (AE3), having been identified and https://www.uptodate.com/contents/short-qt-syndrome/print 3/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate termed SQT1 to SQT8 based on the chronology of their discovery ( table 1). SQT1 and SQT3-8 have been reported in a familial setting, and SQT2 is reported only in a single patient in a sporadic setting. SQTS traits are transmitted in an autosomal dominant fashion. Many of the genes involved in SQTS are the same as those responsible for LQTS; however, the net effect of the pathogenic variants in SQTS is to increase repolarizing forces, an effect opposite to that encountered in LQTS. (See "Congenital long QT syndrome: Pathophysiology and genetics", section on 'Types of congenital LQTS'.) The largest available case series of SQTS describes the clinical presentation of 29 patients with SQTS [20]. The most common form of SQTS (SQT1) was linked to pathogenic variants in KCNH2, + the gene encoding the -subunit of the rapid delayed rectifier K channel (I ) ( figure 2). Kr Approximately 25 percent of patients had a mutation in KCNH2, and no pathogenic variant was found in the rest of the patients. Mutations in KCNQ1 and KCNJ2 were not detected, and CACNA1c, CACNB2b, and CACNA2D1 were not screened. A genetic cause remains to be identified in the majority of SQTS cases [21]. The N588K pathogenic variant in KCNH2 was first identified in three separate families with shorter than normal QT intervals and a high incidence of ventricular arrhythmias and sudden death [8,22]. Patch clamp analysis of N588K revealed this mutation completely removed inactivation over a physiological range of potentials, resulting in a dramatic increase in I Kr [23,24]. A second mutation at T618I in KCNH2 has been discovered and linked to SQT1 [25]. The T618I-KCNH2 missense mutation was recently designated as a hotspot, having been identified in 18 members of seven unrelated families [26]. Many patients with SQTS carrying pathogenic variants in the L-type calcium channel genes (CACNA1C, CACNB2 and CACNA2D1) manifest an ST segment elevation on the surface ECG in addition to a shorter than normal QT interval and have a combined Brugada/Short QT syndrome [27,28]. Most patients harboring a calcium channel mutation who display normal QT intervals have been shown to carry secondary genetic variations that are known to prolong the QT interval. QT-prolonging variations (p.D601E-CACNB2b, p.K897T-KNCH2, p.T10M-KCNE2, p.R1047L- KCNH2, p.D76N-KCNE1, p.G643S-KCNQ1) were found in 12 of the 14 BrS probands presenting with a normal QTc [29]. Initially, only pathogenic variants in genes encoding the cardiac potassium and calcium channels were implicated in SQTS. However, a subsequent report provides evidence that a disturbance of long-chain fatty acid metabolism can influence the morphology and the electrical function of the heart, leading to development of SQTS [30]. In this case series, three patients affected by primary systemic carnitine deficiency presented with SQTS associated with ventricular fibrillation. Primary carnitine deficiency is a rare (1:50,000) autosomal recessive disorder caused https://www.uptodate.com/contents/short-qt-syndrome/print 4/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate by defective transport of carnitine into the cell, in which mutations in SLC22A5 have been implicated [31,32]. Administration of oral DL-carnitine or L-carnitine supplements (5 g/day) over a period of months abolished the ECG and arrhythmic manifestations of the syndrome. Additional evidence in support of the relationship between carnitine deficiency and SQTS was obtained by using a mouse model of carnitine deficiency induced by long-term subcutaneous perfusion of MET88 [30]. Previous studies have reported that the absence of long-chain fatty acids leads to an increase in the rapidly activating delayed rectifier potassium channel current (I ) [33], which may participate in the abbreviation of the QT interval in primary carnitine Kr deficiency. This study suggests that long-chain fatty acids can directly regulate I . The effects of Kr Class III antiarrhythmic agents have not been tested either in humans with primary carnitine deficiency or in the mouse model of the syndrome. (See "Specific fatty acid oxidation disorders", section on 'Carnitine transporter deficiency'.) Another study has implicated loss-of-function mutations in the chloride bicarbonate anion exchanger (AE3) encoded by SLC4A3 gene in two unrelated three and four-generation families with SQTS [26]. The SLC4A3 c.1109 G >A, p.R370H variant caused reduced surface expression of the anion exchanger and reduced membrane bicarbonate transport. Additional evidence in support of this as a cause of SQTS derives from the demonstration that SLC4A3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype SLC4A3. Furthermore, experimental data suggested that an increase in pHi and decrease in [Cl ]i abbreviate the action potential duration [26]. Cascade screening in the two families identified a total of 23 carriers of the SLC4A3 variant. Mutation carriers displayed a mean QTc of 340 18 ms compared to a mean QTc of 402 24 ms in the 19 non-carrier family members. In a 2019 study of variants previously catalogued as pathogenic in SQTS according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, only 9 of the 32 variants studied (28 percent) were shown to have a conclusive pathogenic role [34]. All nine definitively pathogenic variants were located in the genes encoding for the three potassium channel genes KCNQ1, KCNH2, or KCNJ2. Variants in genes encoding calcium or sodium channels were associated with electrical alterations concomitant with shortened QT intervals but not necessarily SQTS. In 2021, a study with a similar evidence-based reappraisal of previously reported genes found that only one gene studied (KCNH2) was definitively linked to short QT pathogenesis [35]. Three other pathogenic variants (KCNQ1, KCNJ2, SLC4A3) had strong to moderate evidence of being causative of SQTS. It is noteworthy that the majority of genetic evidence was derived from very few variants (five in KCNJ2, two in KCNH2, one in KCNQ1/SLC4A3). https://www.uptodate.com/contents/short-qt-syndrome/print 5/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate CELLULAR BASIS OF ARRHYTHMOGENESIS The QT interval is determined by the ventricular action potential duration, which in turn is dependent upon a delicate balance of currents active during the repolarization phase of the action potential ( figure 1). An increase in net outward current due to either a reduction in inward depolarizing currents like I (SQT4- SQT6) or augmentation of outward repolarizing Ca currents such as I (SQT1), I (SQT2), I (SQT3), or a combination thereof, can shift the balance Kr Ks K1 of current favoring early repolarization, thus leading to abbreviation of action potential duration, refractoriness, and QT interval ( figure 2). Available data suggest that abbreviation of the action potential in SQTS is heterogeneous with preferential abbreviation of either epicardial or endocardial cells as compared with subendocardial M cells, resulting in tall, positive T waves on the ECG and an increase in transmural dispersion of repolarization (TDR) [36,37]. Dispersion of repolarization serves as substrate, and abbreviation of wavelength (product of refractory period and conduction velocity) promotes the initiation and maintenance of reentry under conditions of SQTS. The trigger responsible for generating the premature beat that precipitates polymorphic ventricular tachycardia (VT) in SQTS is not known but may involve a phase 2 reentry or late phase 3 early afterdepolarization mechanism, which may give rise to R-on-T extrasystoles [37,38]. Alternatively, re-excitation of the ventricles from the Purkinje fiber network may initiate the arrhythmia [23,39]. In the experimental setting, shortening of the action potential duration (and thus QT interval) results in a reduction in contractility [40,41]. However, reports have shown that while electrical repolarization in SQTS patient is abbreviated, mechanical contraction is not, suggesting an electromechanical dissociation [42]. A gain-of-function mutation augments outward potassium current in SQT1-3, and a loss-of- function mutation reduces I in SQT4-6 [22,27,28,43,44]. Carnitine deficiency is thought to Ca increase I in LQT7 and a combination of an increase in pH and reduction in intracellular Cl Kr contributes to action potential duration abbreviation in LQT8. T T peak end /QT ratio, an ECG index of spatial dispersion of repolarization, is significantly augmented in most cases of SQTS, suggesting an increase in TDR at the cellular level [26,45,46]. Interestingly, this ratio is amplified in patients who are symptomatic [47]. The increase in TDR is known to predispose to phase 2 reentry and may be responsible for the closely-coupled premature ventricular extrasystole that precedes the onset of polymorphic VT in patients with SQTS [48,49]. https://www.uptodate.com/contents/short-qt-syndrome/print 6/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate The preclinical models discussed above and others, including transgenic rabbits generated by oocyte-microinjection of beta-myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs, offer opportunities to improve the diagnosis and treatment of patients with SQTS. They have proven useful in identification of genotype phenotype associations and have uncovered disease mechanisms and revealed underlying pathophysiology of SQTS. These discoveries have been leveraged in drug development for treatment of patients with SQTS [21,50,51]. CLINICAL PRESENTATION The clinical presentation of SQTS is variable, and many patients are asymptomatic [7]. Typical presentation The initial presentation and subsequent clinical course of SQTS varies among different families and even within different members of the same family, as shown in the following case series of 29 patients [20]: The first manifestation of the disease was reported at an age as young as one month or as old as 80 years. Sixty-two percent of the patients (18 out of 29) were symptomatic. The most frequently reported symptoms were: Cardiac arrest 34 percent (this was the initial symptom in 28 percent) Palpitations 31 percent Syncope 24 percent Atrial fibrillation 17 percent 38 percent of the patients (11 out of 29) were asymptomatic and were diagnosed based on a strong family history of arrhythmic symptoms including SCD, a common finding in familial forms of SQTS. The circumstances surrounding the onset of symptoms are highly variable, and episodes of sudden cardiac death (SCD) have been reported at rest, following a loud noise, during exercise, and during routine daily activities. SCD occurred in the first month of life in two patients, suggesting that SQTS may contribute to sudden infant death syndrome (SIDS) [20]. Arrhythmogenic events have been reported at all ages from infants to octogenarians, but the first year of life appears to be the most worrisome, with a 4 percent rate of cardiac arrest [52]. One-third of cases present with SCD as their first event, and up to 80 percent show a personal or family history of SCD [53]. Lethal events occur in both sexes, but a slight male predominance appears to exist which may be due to testosterone modulation of potassium currents as seen in https://www.uptodate.com/contents/short-qt-syndrome/print 7/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate other channelopathies [54-56]. Male patients with SQTS presented more often with syncope as compared with female patients (24 percent versus 7 percent) and other presenting symptoms such as palpitations as well as SCD were not significantly different between the sexes [55]. The following findings were noted in a report of 53 patients from the European Short QT Registry (75 percent males; median age 26 years) who were followed for up to 64 27 months [57]: A familial or personal history of cardiac arrest was present in 89 percent Sudden death was the clinical presentation in 32 percent The average QTc was 314 23 milliseconds Symptomatic patients were found to have a high risk of recurrent arrhythmic events, with a high risk of sudden death in all age groups [57]. In a Japanese cohort of 65 mutation-positive patients, SQT1 patients first presented at an older age (SQT1: 35 19years; SQT2: 17 25years; SQT3-6: 19 15years). SQT2 exhibited a higher prevalence of bradyarrhythmia (SQT2: 6/8, 75 percent; non-SQT2: 5/57, 9 percent) and atrial fibrillation (SQT2: 5/8, 63 percent; non-SQT2: 12/57, 21 percent) [58]. Echocardiographic insights point to mechanical correlates, suggesting that systolic function may be affected as well, as shown in a study of 15 SQTS patients which identified a significant dispersion of myocardial contraction [59]. DIAGNOSTIC EVALUATION As with any survivor of sudden cardiac death (SCD), a history and physical examination focusing on potential underlying etiologies of SCD (eg, myocardial ischemia, myocarditis, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, intoxications) should be performed, along with a routine surface ECG. Paroxysmal atrial fibrillation is very common in patients with SQTS; thus, diagnosis of SQTS should be considered in young individuals with lone atrial fibrillation with shorter than normal QT intervals. A history of arrhythmic symptoms, family history of lone atrial fibrillation, or primary or resuscitated ventricular fibrillation (VF) or SCD may provide additional clues. The isolated presence of short QT interval without associated arrhythmogenic complication warrants further interrogation to rule out SQTS. Our approach to additional testing, which may include exercise stress testing, invasive electrophysiology studies, echocardiography, 24-hour ambulatory monitoring, and cardiac https://www.uptodate.com/contents/short-qt-syndrome/print 8/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate magnetic resonance imaging, is discussed separately. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".) Electrocardiographic findings Typical ECG findings associated with SQTS include the following ( waveform 1) [6,8,20,60]: Abnormally short QT interval, usually <360 milliseconds with a range of 220 to 360 milliseconds Absence of ST segment Tall and peaked T waves in the precordial leads, which can be positive or negative, symmetrical or asymmetrical Poor rate adaptation of QT interval (diminished rate dependence) [61] Prolonged T T peak end interval and T T peak end /QT ratio [45,46] The reduced rate adaptation of the QT interval makes SQTS difficult to diagnose at fast heart rates. Calculation of QTc using Bazett s correction is invalid and when applied erroneously brings QTc into the normal range. Because of the impaired QT adaptation to heart rate changes in patients with SQTS, we recommend measurement of the QT interval at a heart rate between 50 and 70 beats per minute. ECG patterns that support the diagnosis include PQ segment deviation, tall and symmetrical T waves with a very short or negligible ST segment, early repolarization pattern, and impaired adaptation of the QT interval during exercise [16,42,61-63]. Most patients with SQTS have QTc <340 milliseconds with a range of 210 to 320 milliseconds. However, in patients with SQT4, SQT5, and SQT8, QTc intervals are slightly longer (340 to 360 milliseconds). Depression of the PQ segment, rarely seen in the ECG of apparently healthy individuals but which is seen in patients with acute pericarditis and inferior myocardial infarction, has been reported in patients with SQTS. Among a cohort of 64 patients with SQTS (75 percent male, mean QTc 321 milliseconds) who were compared with 117 healthy controls with normal QT intervals, PQ depression was seen in at least one lead in 81 percent of patients (compared with 24 percent of controls) [62]. PQ depression was most commonly seen in leads II, V3, aVF, V4, and I (67, 47, 42, 39, and 39 percent of patients with SQTS, respectively). The presence of PQ depression in asymptomatic patients or those with syncope or an arrhythmia should prompt close scrutiny of the QT interval for the possibility of a short QT interval. PQ dispersion in this setting is thought to reflect spatial dispersion of repolarization within the atria. In cases of SQT4, 5, and 6, short QT intervals may appear together with a Brugada type ST segment elevation in the right precordial leads V1-V3 at baseline or after administration of a potent sodium channel blocker ( waveform 1) or other unmasking agent, such as a potassium https://www.uptodate.com/contents/short-qt-syndrome/print 9/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate channel opener (I activator) [28]. Approximately 65 percent of patients with SQTS have ECG KATP features of early repolarization, characterized by J-point elevation in the inferolateral leads, which may also be associated with an increased likelihood of increased arrhythmic events [63,64]. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Brugada pattern versus Brugada syndrome'.) When the diagnosis of SQTS is suspected, a resting 12-lead ECG should be performed at a heart rate within normal limits, preferably 50 to 70 beats per minute. In patients with SQTS, the QT interval fails to lengthen appropriately with a decrease in the heart rate [61]. As a consequence, QT correction using Bazett's or comparable formulas (calculator 1) will overcorrect at initially fast rates, leading to a false negative diagnosis. Overnight Holter monitoring or long-term ECG monitoring may prove helpful in such cases as this allows for analysis of the QT interval during periods of slower heart rate (ie, sleep) and also allows for patient-specific QT correction for heart rate. (See "ECG tutorial: Basic principles of ECG analysis", section on 'QT interval'.) While data are relatively sparse, owing to the rarity of the syndrome, the picture that appears to be developing is that SQT1 and 2 probands generally manifest symmetrical tall peaked T waves, whereas SQT3 probands display asymmetrical tall peaked T waves with a more rapidly descending than ascending limb of the T wave [44]. SQT4, 5, 6, 7, and 8 show variable T wave heights but are usually symmetrical. In most cases, a distinct ST segment is short or absent, with the T wave originating from the S wave. Electrophysiological study Although electrophysiological study (EPS) has a role in confirming the diagnosis by revealing short ventricular refractory periods, its role in risk stratification remains unclear. As such, EPS is not routinely performed unless the diagnosis of SQTS remains unclear based on the available ECG data. (See "Invasive diagnostic cardiac electrophysiology studies".) During invasive EPS, patients with SQTS characteristically show extremely short atrial and ventricular effective refractory periods (ERP), regardless of genotype [8,20,28,43,44]. The ventricular ERP measured at the right ventricular apex varies between 140 and 180 milliseconds at a cycle length of 500 to 600 milliseconds and 130 to 180 milliseconds at pacing cycle length of 400 to 430 milliseconds. Atrial ERP measured in the high lateral right atrium varies between 120 and 180 milliseconds at a cycle length of 600 milliseconds. The programmed electrical stimulation with two to three premature stimuli down to refractoriness induced both atrial fibrillation and VF in many patients. The inducibility of VF at EPS in SQTS patients is approximately 60 percent. Moreover, in one case series, VF was inducible at EPS in only three of six patients with clinically documented VF, suggesting that the sensitivity of EPS for the inducibility of VF is low [20]. https://www.uptodate.com/contents/short-qt-syndrome/print 10/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Genetic testing In patients where SQTS is suspected as the diagnosis, based on ECG findings and clinical history, genetic testing of the patient should be considered. Given the relative scarcity of this clinical entity, decisions regarding genotyping should be performed in collaboration with an electrophysiologist or other clinician with expertise in the evaluation and diagnosis of patients with suspected SQTS. (See 'Genetic basis' above and 'Diagnosis and diagnostic criteria' below.) Screening family members First-degree relatives of those diagnosed with SQTS should undergo clinical screening with an ECG and genetic testing. Mutation-specific genetic testing is recommended for all family members and relatives suspected of SQTS following the identification of the SQTS-causative mutation in an index case [65]. Family members who test positive for the familial mutation should consult a cardiologist with expertise in SQTS to discuss further management. Conversely, a negative genetic test for the familial mutation obviates the need for repeated follow-up. DIAGNOSIS AND DIAGNOSTIC CRITERIA While ECG findings in SQTS can be suggestive of the diagnosis, the solitary presence of a shorter than normal QT interval is not always diagnostic. Clinical history, family history of sudden death, and genotype results can all contribute to the diagnostic certainty. While there is ongoing debate on the optimal diagnostic strategy for SQTS, the authors and editors of this topic agree with and recommend following the proposed diagnostic criteria for SQTS. The 2013 HRS/EHRA/APHRS Expert Consensus Statement and the 2015 ESC Guidelines indicate that a QTc of 330 or 340 milliseconds alone may be diagnostic of SQTS, but that SQTS should be considered in the presence of a QTc of <360 milliseconds when accompanied by a confirmed pathogenic mutation, family history of SQTS, family history of sudden death at age <40 years, or survival from a VT/VF episode in the absence of heart disease [66,67]. Based on a comprehensive review of 61 reported cases of SQTS, proposed diagnostic criteria were developed to facilitate the evaluation of individuals suspected to have SQTS [10]. A scoring system was developed based on ECG characteristics, clinical presentation, family history, and genetic findings ( table 2). The most controversial aspect of the differential diagnosis of SQTS involves the QT interval cutoff, as shown by the increasing number of points assigned to shorter QT intervals in the proposed diagnostic criteria. DIFFERENTIAL DIAGNOSIS https://www.uptodate.com/contents/short-qt-syndrome/print 11/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Before arriving at a diagnosis of SQTS, other potential causes for QT shortening should be excluded. Normal variant The sole presence of a shorter-than-normal QT interval does not appear to be diagnostic for SQTS and, in fact, may represent a normal variant in many people. Up to 2 percent of the population has QT intervals 360 milliseconds, highlighting the importance of utilizing the diagnostic criteria for the diagnosis of SQTS. (See 'Prevalence of a short QT interval' above and 'Diagnosis and diagnostic criteria' above.) Acquired causes of short QT interval Secondary causes of short QT interval are reviewed in ( table 3). Briefly, these include: Metabolic and electrolyte abnormalities such as hyperkalemia, acidosis, and hypercalcemia. Hyperthermia. Drug effects from digitalis, acetylcholine, or catecholamines. Myocardial ischemia. Vagal tone. Combination of genetic and secondary causes, including hyperkalemia, hypercalcemia, acidosis, myocardial ischemia, and increased vagal tone (QTc prolongation is similar in having potential genetic and secondary causes). Deceleration-dependent shortening of the QT interval A rare but interesting paradoxical ECG phenomenon called deceleration-dependent shortening of QT interval (DDSQTI) should also be considered in the differential diagnosis of SQTS [6]. Strong parasympathetic stimulation can + lead to bradycardia and concurrent activation of myocardial acetylcholine-sensitive K channels (K ). In such cases, the QT interval abbreviates paradoxically with a decrease in heart rate ACh instead of lengthening. Such shortening of the QT interval may be transient and should resolve as parasympathetic tone decreases. MANAGEMENT OF PATIENTS WITH A SHORT QT INTERVAL As discussed previously, the sole presence of a shorter-than-normal QT interval on an ECG does not appear to be diagnostic for the short QT syndrome and, in isolation, may not be associated with an increased risk of sudden cardiac death (SCD). Because the rate of serious complications of implantable cardioverter-defibrillator (ICD) therapy is not trivial, particularly over the life of a young patient, it is important to discriminate between patients with an isolated short QT interval and those who meet the criteria for SQTS ( table 2). Prior to making a final decision regarding https://www.uptodate.com/contents/short-qt-syndrome/print 12/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate the management of these patients, acquired causes of a shortened QT interval should be excluded. (See 'Acquired causes of short QT interval' above.) Patients with low/intermediate probability of SQTS There are no randomized trials and few observational studies of patients assessing the prognosis of patients with isolated short QT intervals who have no apparent clinical history, family history, or genetic criteria suggestive of SQTS [68]. As such, the following management strategies for such patients are based on expert opinion [7]: Patients with a short QT interval (330 to 360 milliseconds) who have none of the clinical history, family history, or genotype criteria proposed for the diagnosis of SQTS are classified as low probability for the diagnosis of SQTS. For these low-probability patients, we suggest no specific pharmacologic or device-based therapy. This approach is consistent with the published recommendations in the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of SCD [69]. Patients with a markedly shortened QT interval (<330 milliseconds) are classified as intermediate-probability for the diagnosis of SQTS despite having none of the clinical history, family history, or genotype criteria proposed for the diagnosis of SQTS. For these intermediate-probability patients, there are limited data available to guide management. However, we suggest no specific pharmacologic or device-based therapy. We do suggest referral to an electrophysiologist for comprehensive testing, including genetic screening, if this has not yet been completed. Patients with a high probability of SQTS Most patients with a QT interval <350 milliseconds and at least one criterion from the list of clinical history, family history, or genotype criteria will be classified as high-probability for the SQTS. Because of the association between SQTS and sudden cardiac death due to arrhythmias, therapy with an ICD is recommended in these patients, along with consideration of antiarrhythmic therapy if appropriate shocks are frequent. Implantable cardioverter-defibrillator Patients with SQTS are at a very high risk for SCD [15]. As such, we recommend ICD implantation for both primary and secondary prevention of SCD in patients with SQTS unless absolutely contraindicated or refused by the patient. Because the sensitivity of inducibility of ventricular fibrillation (VF) is only 50 percent, failure to induce VF during EP study does not preclude future risk of SCD [20,49]. Accordingly, a negative EP study should not defer a clinician's decision to implant an ICD. Professional society guidelines recommend ICD implantation as a class I indication in symptomatic patients with a diagnosis of https://www.uptodate.com/contents/short-qt-syndrome/print 13/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate SQTS who are survivors of a cardiac arrest and/or have documented spontaneous sustained ventricular tachycardia with or without syncope [67,69]. ICD implantation may be considered (class IIb) in asymptomatic patients with a diagnosis of SQTS and a family history of SCD [67]. Oversensing of the T wave is a frequent clinical problem encountered in patients with SQTS who receive an ICD [70]. The tall, peaked, and closely coupled T waves are often mistakenly sensed as R waves, leading to inappropriate ICD shocks. Reprogramming the decay delay, the sensitivity, or both generally prevents such inappropriate discharges. Caution must be exercised to avoid programming modifications that prevent the detection of lethal ventricular tachyarrhythmia. (See "Cardiac implantable electronic devices: Long-term complications".) Ablation therapy There is limited evidence regarding the use of ablation therapy in SQTS. In a single case report, radiofrequency ablation of PVCs appeared to be successful in controlling ventricular arrhythmic events [71]. Further studies are needed. Pharmacologic therapy Pharmacologic therapy is primarily used as an adjunct to ICD placement, with a goal of reducing the likelihood of additional ICD shocks. However, pharmacologic therapy may be the primary treatment modality in patients who refuse ICD placement, patients with an absolute contraindication to ICD placement, or in very young patients in whom ICD implantation is problematic. For patients with SQTS who have refused or are not candidates for ICD therapy, or in those with recurrent ventricular arrhythmias resulting in frequent ICD therapy, we recommend adjunctive pharmacologic therapy with QT-prolonging drugs. In the case of SQT1, we recommend quinidine rather than a class IC or class III ( table 4) antiarrhythmic drug [69]. In other forms of SQTS, data are too limited to permit specific suggestions or recommendations. Data regarding pharmacologic therapy in SQTS are very limited, with much of the data pertaining to patients with SQT1: Four different antiarrhythmic drugs, flecainide, sotalol, ibutilide, and hydroquinidine, were tested in six patients with SQT1 to determine their effects on various electrophysiologic properties [72]. Only hydroquinidine, a class IA antiarrhythmic drug ( table 4), normalized the QT interval, increased ventricular ERP, and rendered VF noninducible. In a one-year follow-up, patients treated with hydroquinidine remained asymptomatic, and no further episodes of ventricular arrhythmia were detected [57]. Long-term treatment with hydroquinidine (hydroquinidine 584 53 mg/day) was evaluated in a cohort of 17 patients with SQTS (82 percent male, mean age 29 years, mean QTc pretreatment 331 milliseconds [QTc <320 milliseconds in four patients], previous aborted SCD in six patients), among whom 15 patients continued treatment for an average of six https://www.uptodate.com/contents/short-qt-syndrome/print 14/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate years (two discontinued treatment due to gastrointestinal intolerance) [73]. The QTc increased by an average of 60 milliseconds with treatment, and no life-threatening ventricular arrhythmias were seen during the six years of treatment. The annual rate of life-threatening arrhythmic events in patients with a previous cardiac arrest dropped from 12 to 0 percent on hydroquinidine therapy. Similarly, disopyramide has proved to be effective in prolonging the QT interval and restoring the ventricular effective refractory period towards normal [74]. The combination of disopyramide and nifekalant, a class III agent available primarily in Japan, was reported in one patient to increase QTc to >410 milliseconds [75]. Amiodarone has been shown to prolong the QT interval in two patients with SQTS of unknown genotype [48]. The failure of class IC and pure class III antiarrhythmic drugs in SQT1 caused by the N588K mutation in KCNH2 is due to the fact that this mutation by removing inactivation of the I Kr channel results in a desensitization of the channel to these agents. Class III agents such as sotalol, E-4031, and dofetilide have a greater affinity for the inactivated state of the channel. Quinidine, by virtue of its effect to block the activated state of the I channel, was reasoned to Kr be more effective in this setting in which the inactivated state of the channel is lost. |
not appear to be diagnostic for the short QT syndrome and, in isolation, may not be associated with an increased risk of sudden cardiac death (SCD). Because the rate of serious complications of implantable cardioverter-defibrillator (ICD) therapy is not trivial, particularly over the life of a young patient, it is important to discriminate between patients with an isolated short QT interval and those who meet the criteria for SQTS ( table 2). Prior to making a final decision regarding https://www.uptodate.com/contents/short-qt-syndrome/print 12/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate the management of these patients, acquired causes of a shortened QT interval should be excluded. (See 'Acquired causes of short QT interval' above.) Patients with low/intermediate probability of SQTS There are no randomized trials and few observational studies of patients assessing the prognosis of patients with isolated short QT intervals who have no apparent clinical history, family history, or genetic criteria suggestive of SQTS [68]. As such, the following management strategies for such patients are based on expert opinion [7]: Patients with a short QT interval (330 to 360 milliseconds) who have none of the clinical history, family history, or genotype criteria proposed for the diagnosis of SQTS are classified as low probability for the diagnosis of SQTS. For these low-probability patients, we suggest no specific pharmacologic or device-based therapy. This approach is consistent with the published recommendations in the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of SCD [69]. Patients with a markedly shortened QT interval (<330 milliseconds) are classified as intermediate-probability for the diagnosis of SQTS despite having none of the clinical history, family history, or genotype criteria proposed for the diagnosis of SQTS. For these intermediate-probability patients, there are limited data available to guide management. However, we suggest no specific pharmacologic or device-based therapy. We do suggest referral to an electrophysiologist for comprehensive testing, including genetic screening, if this has not yet been completed. Patients with a high probability of SQTS Most patients with a QT interval <350 milliseconds and at least one criterion from the list of clinical history, family history, or genotype criteria will be classified as high-probability for the SQTS. Because of the association between SQTS and sudden cardiac death due to arrhythmias, therapy with an ICD is recommended in these patients, along with consideration of antiarrhythmic therapy if appropriate shocks are frequent. Implantable cardioverter-defibrillator Patients with SQTS are at a very high risk for SCD [15]. As such, we recommend ICD implantation for both primary and secondary prevention of SCD in patients with SQTS unless absolutely contraindicated or refused by the patient. Because the sensitivity of inducibility of ventricular fibrillation (VF) is only 50 percent, failure to induce VF during EP study does not preclude future risk of SCD [20,49]. Accordingly, a negative EP study should not defer a clinician's decision to implant an ICD. Professional society guidelines recommend ICD implantation as a class I indication in symptomatic patients with a diagnosis of https://www.uptodate.com/contents/short-qt-syndrome/print 13/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate SQTS who are survivors of a cardiac arrest and/or have documented spontaneous sustained ventricular tachycardia with or without syncope [67,69]. ICD implantation may be considered (class IIb) in asymptomatic patients with a diagnosis of SQTS and a family history of SCD [67]. Oversensing of the T wave is a frequent clinical problem encountered in patients with SQTS who receive an ICD [70]. The tall, peaked, and closely coupled T waves are often mistakenly sensed as R waves, leading to inappropriate ICD shocks. Reprogramming the decay delay, the sensitivity, or both generally prevents such inappropriate discharges. Caution must be exercised to avoid programming modifications that prevent the detection of lethal ventricular tachyarrhythmia. (See "Cardiac implantable electronic devices: Long-term complications".) Ablation therapy There is limited evidence regarding the use of ablation therapy in SQTS. In a single case report, radiofrequency ablation of PVCs appeared to be successful in controlling ventricular arrhythmic events [71]. Further studies are needed. Pharmacologic therapy Pharmacologic therapy is primarily used as an adjunct to ICD placement, with a goal of reducing the likelihood of additional ICD shocks. However, pharmacologic therapy may be the primary treatment modality in patients who refuse ICD placement, patients with an absolute contraindication to ICD placement, or in very young patients in whom ICD implantation is problematic. For patients with SQTS who have refused or are not candidates for ICD therapy, or in those with recurrent ventricular arrhythmias resulting in frequent ICD therapy, we recommend adjunctive pharmacologic therapy with QT-prolonging drugs. In the case of SQT1, we recommend quinidine rather than a class IC or class III ( table 4) antiarrhythmic drug [69]. In other forms of SQTS, data are too limited to permit specific suggestions or recommendations. Data regarding pharmacologic therapy in SQTS are very limited, with much of the data pertaining to patients with SQT1: Four different antiarrhythmic drugs, flecainide, sotalol, ibutilide, and hydroquinidine, were tested in six patients with SQT1 to determine their effects on various electrophysiologic properties [72]. Only hydroquinidine, a class IA antiarrhythmic drug ( table 4), normalized the QT interval, increased ventricular ERP, and rendered VF noninducible. In a one-year follow-up, patients treated with hydroquinidine remained asymptomatic, and no further episodes of ventricular arrhythmia were detected [57]. Long-term treatment with hydroquinidine (hydroquinidine 584 53 mg/day) was evaluated in a cohort of 17 patients with SQTS (82 percent male, mean age 29 years, mean QTc pretreatment 331 milliseconds [QTc <320 milliseconds in four patients], previous aborted SCD in six patients), among whom 15 patients continued treatment for an average of six https://www.uptodate.com/contents/short-qt-syndrome/print 14/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate years (two discontinued treatment due to gastrointestinal intolerance) [73]. The QTc increased by an average of 60 milliseconds with treatment, and no life-threatening ventricular arrhythmias were seen during the six years of treatment. The annual rate of life-threatening arrhythmic events in patients with a previous cardiac arrest dropped from 12 to 0 percent on hydroquinidine therapy. Similarly, disopyramide has proved to be effective in prolonging the QT interval and restoring the ventricular effective refractory period towards normal [74]. The combination of disopyramide and nifekalant, a class III agent available primarily in Japan, was reported in one patient to increase QTc to >410 milliseconds [75]. Amiodarone has been shown to prolong the QT interval in two patients with SQTS of unknown genotype [48]. The failure of class IC and pure class III antiarrhythmic drugs in SQT1 caused by the N588K mutation in KCNH2 is due to the fact that this mutation by removing inactivation of the I Kr channel results in a desensitization of the channel to these agents. Class III agents such as sotalol, E-4031, and dofetilide have a greater affinity for the inactivated state of the channel. Quinidine, by virtue of its effect to block the activated state of the I channel, was reasoned to Kr be more effective in this setting in which the inactivated state of the channel is lost. It is thought that the efficacy of quinidine in SQT1 is due to its ability to inhibit the N588K channel at pharmacologically relevant concentrations, presumably due not only to its ability to block the activated state of the I channel, but also its ability to block other outward currents, Kr particularly I Quinidine's multi-ion channel inhibition may underlie its effectiveness in other Ks. forms of SQTS, particularly SQT4-SQT6 where its I blocking action may provide a therapeutic to edge over other antiarrhythmic drugs by reducing the substrate and trigger for Brugada syndrome. Prolongation of the QT interval by quinidine has been reported in one patient with SQT4 [28]. One study has identified another missense mutation in hERG (T618I), which produces a more modest increase in I than reported for the N588K-hERG variant. Interestingly, all drugs studied, Kr including quinidine and D-sotalol, retained their ability to inhibit the I current recorded with Kr this genetic variant [76]. The 2013 HRS/EHRA/APHRS guidelines indicate that quinidine and sotalol may be considered (class II) in asymptomatic patients with a diagnosis of SQTS and a family history of SCD [67]. The available data, both experimental and clinical, suggest that all agents with Class III (QT prolonging) actions should be effective in all SQTS types with the exception of SQT1. This https://www.uptodate.com/contents/short-qt-syndrome/print 15/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate hypothesis remains to be more fully tested in clinical experience. In the case of SQT3-6, representing an overlap between SQTS and BrS, the combination of quinidine and isoproterenol has been shown to be effective, particularly in patients presenting with a VT/VF storm [77]. Atrial fibrillation (AF) is another common clinical problem in SQTS. Some patient with SQTS exhibit only AF [78]. Propafenone as well as quinidine have been shown to be therapeutically effective is a small case series [14]. (See 'Clinical presentation' above.) PROGNOSIS Timely diagnosis and optimal treatment improve the prognosis of patients with SQTS, although an accurate long-term prognosis in these patients remains difficult to assess. In contrast to the long QT syndrome, there is a paucity of data regarding SQTS in terms of its clinical presentation, diagnosis, genotype-phenotype correlation, risk-stratification, and treatment. In a cohort of 25 pediatric patients (84 percent male, median age 15 years) who were followed for an average of six years, 14 patients (56 percent) experienced symptoms during follow-up, including aborted SCD and syncope [79]. Patients with a higher clinical risk score ( table 2) were more likely to be symptomatic. In an analysis of 34 patients (from a larger 73 patient cohort) who had all the required data available to assess the performance of the proposed prognostic SQTS score ( table 2), 21 patients had a score of 3, corresponding to a relatively "good" prognosis, with the remaining 13 patients having a score of 4 or greater, indicating a "poor" prognosis [52]. Among the eight patients who experienced a cardiac event, five of whom had a SQTS score 3, there was no significant difference in risk based on SQTS score, with an incidence of cardiac events of 4.6 percent per year in the "good" prognosis group and 4.2 percent per year in the "poor" prognosis group. Markedly shortened QTc values 300 ms have been shown to be associated with increased risk of SCD, especially during sleep or rest, in young individuals, in whom the median QTc was 285 ms [79,80]. There is a scarcity of information concerning the long-term effectiveness of pharmacologic therapy. As such, pharmacologic therapy remains, for most patients, an adjunct to ICD treatment. (See 'Pharmacologic therapy' above.) https://www.uptodate.com/contents/short-qt-syndrome/print 16/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Definition Short QT Syndrome (SQTS) is an inherited channelopathy associated with marked shortening of QT intervals and sudden cardiac death (SCD) in individuals with structurally normal hearts. (See 'Introduction' above.) In SQTS, typical electrocardiogram (ECG) features include a QT interval <360 milliseconds (range 220 to 360 milliseconds), absence of the ST segment, tall and peaked T waves in the precordial leads, and poor rate adaptation of the QT interval. (See 'Electrocardiographic findings' above.) Genetic basis SQTS is a genetically heterogeneous disease with pathogenic variants in eight different genes (three gain-of-function and five loss-of-function) that encode different cardiac ion channels, a carnitine transporter, and chloride-bicarbonate anion exchanger ( table 1). (See 'Genetic basis' above.) Clinical presentation and diagnosis Whereas many patients are asymptomatic, the majority present with one or more of the following: SCD, palpitations, syncope, and atrial fibrillation. (See 'Clinical presentation' above.) The sole presence of a shorter-than-normal QT interval is not always diagnostic of SQTS and may represent a normal variant. Diagnostic criteria have been developed to facilitate the evaluation of individuals suspected to have SQTS with a scoring system based on ECG characteristics, clinical presentation, family history, and genetic findings ( table 2). (See 'Diagnosis and diagnostic criteria' above.) Variant-specific genetic evaluation This is recommended for all family members and relatives suspected of SQTS following the identification of the SQTS-causative mutation in an index case. Family members who test positive for the familial mutation should be seen by a cardiologist with expertise in SQTS for further management. (See 'Screening family members' above.) https://www.uptodate.com/contents/short-qt-syndrome/print 17/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Acquired causes These include hyperkalemia, acidosis, hypercalcemia, hyperthermia, effect of drugs like digitalis, increased vagal tone, and deceleration-dependent shortening of QT interval. (See 'Differential diagnosis' above.) Management This depends on whether the short QT interval occurs in isolation or is associated with other clinical history, family history, or genetic criteria ( table 2) that increase the probability of SQTS. Patients with a short QT interval (330 to 360 milliseconds) who have none of the clinical history, family history, or genotype criteria proposed for the diagnosis of SQTS are classified as low probability for the diagnosis of SQTS. For these low-probability patients, we suggest no specific pharmacologic or device-based therapy (Grade 2C). Patients with a markedly shortened QT interval (<330 milliseconds) are classified as intermediate probability for the diagnosis of SQTS, despite having none of the clinical history, family history, or genotype criteria proposed for the diagnosis of SQTS. For these intermediate-probability patients, we suggest no specific pharmacologic or device-based therapy (Grade 2C). We do refer to an electrophysiologist for comprehensive testing, including genetic screening, if this has not yet been completed. Patients with SQTS are at a very high risk for SCD. As such, we recommend implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention of SCD (Grade 1B). (See 'Implantable cardioverter-defibrillator' above.) Pharmacologic therapy in patients with SQTS is primarily used as an adjunct to ICD placement. However, it may also be the primary treatment modality in patients who refuse or have contraindications to ICD placement or very young patients in whom ICD implantation is problematic. For patients with SQTS who have refused or are not candidates for ICD therapy, or in those with recurrent ventricular arrhythmias resulting in frequent ICD therapy, antiarrhythmic treatment is required. In the case of SQT1, we recommend quinidine rather than a class IC or class III ( table 4) antiarrhythmic drug (Grade 1C). This recommendation is based on the positive electrophysiologic effects of quinidine (eg, QT prolongation to the normal range) in patients with SQTS studied thus far. (See 'Pharmacologic therapy' above.) ACKNOWLEDGMENT https://www.uptodate.com/contents/short-qt-syndrome/print 18/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate The UpToDate editorial staff thank Dr. Jonathan M. Cordeiro for his contributions as an author to prior versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Algra A, Tijssen JG, Roelandt JR, et al. QT interval variables from 24 hour electrocardiography and the two year risk of sudden death. Br Heart J 1993; 70:43. 2. Fei L, Camm AJ. Shortening of the QT interval immediately preceding the onset of idiopathic spontaneous ventricular tachycardia. Am Heart J 1995; 130:915. 3. Kontny F, Dale J. Self-terminating idiopathic ventricular fibrillation presenting as syncope: a 40-year follow-up report. J Intern Med 1990; 227:211. 4. Campbell TJ. Characteristics of cardiac action potentials in marsupials. J Comp Physiol B 1989; 158:759. 5. Rezakhani A, Webster JD, Atwell RB. The electrocardiogram of the eastern grey kangaroo (Macropus giganteus). Aust Vet J 1986; 63:310. 6. Gussak I, Brugada P, Brugada J, et al. Idiopathic short QT interval: a new clinical syndrome? Cardiology 2000; 94:99. 7. Bjerregaard P. Diagnosis and management of short QT syndrome. Heart Rhythm 2018; 15:1261. 8. Gaita F, Giustetto C, Bianchi F, et al. Short QT Syndrome: a familial cause of sudden death. Circulation 2003; 108:965. 9. Cross B, Homoud M, Link M, et al. The short QT syndrome. J Interv Card Electrophysiol 2011; 31:25. 10. Gollob MH, Redpath CJ, Roberts JD. The short QT syndrome: proposed diagnostic criteria. J Am Coll Cardiol 2011; 57:802. 11. Rautaharju PM, Zhou SH, Wong S, et al. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol 1992; 8:690. 12. Gussak I, Antzelevitch C, Goodman D, Bjerregaard P. Short QT interval: ECG phenomenon an d clinical syndrome. In: Cardiac Repolarization. Bridging Basic and Clinical Sciences, Gussak I, Antzelevitch C (Eds), Humana Press, Totowa, NJ 2003. p.497. 13. Gussak I, Bjerregaard P. Short QT syndrome 5 years of progress. J Electrocardiol 2005; 38:375. 14. Bjerregaard P, Gussak I. Short QT syndrome. Ann Noninvasive Electrocardiol 2005; 10:436. https://www.uptodate.com/contents/short-qt-syndrome/print 19/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate 15. Bjerregaard P, Gussak I. Short QT syndrome: mechanisms, diagnosis and treatment. Nat Clin Pract Cardiovasc Med 2005; 2:84. 16. Anttonen O, Junttila MJ, Rissanen H, et al. Prevalence and prognostic significance of short QT interval in a middle-aged Finnish population. Circulation 2007; 116:714. 17. Kobza R, Roos M, Niggli B, et al. Prevalence of long and short QT in a young population of 41,767 predominantly male Swiss conscripts. Heart Rhythm 2009; 6:652. 18. Miyamoto A, Hayashi H, Yoshino T, et al. Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population. Heart Rhythm 2012; 9:66. 19. Mason JW, Ramseth DJ, Chanter DO, et al. Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 2007; 40:228. 20. Giustetto C, Di Monte F, Wolpert C, et al. Short QT syndrome: clinical findings and diagnostic-therapeutic implications. Eur Heart J 2006; 27:2440. 21. Hu D, Li Y, Zhang J, et al. The Phenotypic Spectrum of a Mutation Hotspot Responsible for the Short QT Syndrome. JACC Clin Electrophysiol 2017; 3:727. 22. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004; 109:30. 23. Cordeiro JM, Brugada R, Wu YS, et al. Modulation of I(Kr) inactivation by mutation N588K in KCNH2: a link to arrhythmogenesis in short QT syndrome. Cardiovasc Res 2005; 67:498. 24. McPate MJ, Duncan RS, Milnes JT, et al. The N588K-HERG K+ channel mutation in the 'short QT syndrome': mechanism of gain-in-function determined at 37 degrees C. Biochem Biophys Res Commun 2005; 334:441. 25. Sun Y, Quan XQ, Fromme S, et al. A novel mutation in the KCNH2 gene associated with short QT syndrome. J Mol Cell Cardiol 2011; 50:433. 26. Thorsen K, Dam VS, Kjaer-Sorensen K, et al. Loss-of-activity-mutation in the cardiac chloride- bicarbonate exchanger AE3 causes short QT syndrome. Nat Commun 2017; 8:1696. 27. Templin C, Ghadri JR, Rougier JS, et al. Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J 2011; 32:1077. 28. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442. 29. Burashnikov E, Pfeiffer R, Barajas-Martinez H, et al. Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm 2010; 7:1872. https://www.uptodate.com/contents/short-qt-syndrome/print 20/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate 30. Roussel J, Labarthe F, Thireau J, et al. Carnitine deficiency induces a short QT syndrome. Heart Rhythm 2016; 13:165. 31. Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci 2004; 1033:42. 32. Tein I. Role of carnitine and fatty acid oxidation and its defects in infantile epilepsy. J Child Neurol 2002; 17 Suppl 3:3S57. 33. Ferro F, Ouill A, Tran TA, et al. Long-chain acylcarnitines regulate the hERG channel. PLoS One 2012; 7:e41686. 34. Campuzano O, Fernandez-Falgueras A, Lemus X, et al. Short QT Syndrome: A Comprehensive Genetic Interpretation and Clinical Translation of Rare Variants. J Clin Med 2019; 8. 35. Walsh R, Adler A, Amin AS, et al. Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death. Eur Heart J 2022; 43:1500. 36. Patel C, Antzelevitch C. Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome. Heart Rhythm 2008; 5:585. 37. Extramiana F, Antzelevitch C. Amplified transmural dispersion of repolarization as the basis for arrhythmogenesis in a canine ventricular-wedge model of short-QT syndrome. Circulation 2004; 110:3661. 38. Burashnikov A, Antzelevitch C. Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation. Pacing Clin Electrophysiol 2006; 29:290. 39. McPate MJ, Zhang H, Adeniran I, et al. Comparative effects of the short QT N588K mutation at 37 degrees C on hERG K+ channel current during ventricular, Purkinje fibre and atrial action potentials: an action potential clamp study. J Physiol Pharmacol 2009; 60:23. 40. Cordeiro JM, Greene L, Heilmann C, et al. Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle. Am J Physiol Heart Circ Physiol 2004; 286:H1471. 41. Sah R, Ramirez RJ, Oudit GY, et al. Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (I(to)). J Physiol 2003; 546:5. 42. Schimpf R, Antzelevitch C, Haghi D, et al. Electromechanical coupling in patients with the short QT syndrome: further insights into the mechanoelectrical hypothesis of the U wave. Heart Rhythm 2008; 5:241. 43. Bellocq C, van Ginneken AC, Bezzina CR, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 2004; 109:2394. https://www.uptodate.com/contents/short-qt-syndrome/print 21/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate 44. Priori SG, Pandit SV, Rivolta I, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 2005; 96:800. 45. Anttonen O, V n nen H, Junttila J, et al. Electrocardiographic transmural dispersion of repolarization in patients with inherited short QT syndrome. Ann Noninvasive Electrocardiol 2008; 13:295. 46. Gupta P, Patel C, Patel H, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 2008; 41:567. 47. Anttonen O, Junttila MJ, Maury P, et al. Differences in twelve-lead electrocardiogram between symptomatic and asymptomatic subjects with short QT interval. Heart Rhythm 2009; 6:267. 48. Lu LX, Zhou W, Zhang X, et al. Short QT syndrome: a case report and review of literature. Resuscitation 2006; 71:115. 49. Schimpf R, Bauersfeld U, Gaita F, Wolpert C. Short QT syndrome: successful prevention of sudden cardiac death in an adolescent by implantable cardioverter-defibrillator treatment for primary prophylaxis. Heart Rhythm 2005; 2:416. 50. Fan X, Yang G, Kowitz J, et al. Preclinical short QT syndrome models: studying the phenotype and drug-screening. Europace 2022; 24:481. 51. Odening KE, Bodi I, Franke G, et al. Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility. Eur Heart J 2019; 40:842. 52. Mazzanti A, Kanthan A, Monteforte N, et al. Novel insight into the natural history of short QT syndrome. J Am Coll Cardiol 2014; 63:1300. 53. Ferrero-Miliani L, Holst AG, Pehrson S, et al. Strategy for clinical evaluation and screening of sudden cardiac death relatives. Fundam Clin Pharmacol 2010; 24:619. 54. J rgensen IN, Skakkebaek A, Andersen NH, et al. Short QTc interval in males with klinefelter syndrome-influence of CAG repeat length, body composition, and testosterone replacement therapy. Pacing Clin Electrophysiol 2015; 38:472. 55. El-Battrawy I, Schlentrich K, Besler J, et al. Sex-differences in short QT syndrome: A systematic literature review and pooled analysis. Eur J Prev Cardiol 2020; 27:1335. 56. Fish JM, Antzelevitch C. Cellular and ionic basis for the sex-related difference in the manifestation of the Brugada syndrome and progressive conduction disease phenotypes. J Electrocardiol 2003; 36 Suppl:173. https://www.uptodate.com/contents/short-qt-syndrome/print 22/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate 57. Giustetto C, Schimpf R, Mazzanti A, et al. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol 2011; 58:587. 58. Harrell DT, Ashihara T, Ishikawa T, et al. Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome. Int J Cardiol 2015; 190:393. 59. Frea S, Giustetto C, Capriolo M, et al. New echocardiographic insights in short QT syndrome: More than a channelopathy? Heart Rhythm 2015; 12:2096. 60. Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol 2010; 3:401. 61. Wolpert C, Schimpf R, Giustetto C, et al. Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol 2005; 16:54. 62. T l men E, Giustetto C, Wolpert C, et al. PQ segment depression in patients with short QT syndrome: a novel marker for diagnosing short QT syndrome? Heart Rhythm 2014; 11:1024. 63. Watanabe H, Makiyama T, Koyama T, et al. High prevalence of early repolarization in short QT syndrome. Heart Rhythm 2010; 7:647. 64. Antzelevitch C, Yan GX. J wave syndromes. Heart Rhythm 2010; 7:549. 65. Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm 2011; 8:1308. 66. Priori SG, Blomstr m-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Europace 2015; 17:1601. 67. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932. 68. Zhang Y, Post WS, Dalal D, et al. QT-interval duration and mortality rate: results from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2011; 171:1727. 69. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden https://www.uptodate.com/contents/short-qt-syndrome/print 23/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 70. Schimpf R, Wolpert C, Bianchi F, et al. Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery. J Cardiovasc Electrophysiol 2003; 14:1273. 71. Morimoto Y, Watanabe A, Morita H, et al. Successful radiofrequency catheter ablation of a premature ventricular contraction triggering ventricular fibrillation in a patient with short QT syndrome. HeartRhythm Case Rep 2019; 5:262. 72. Gaita F, Giustetto C, Bianchi F, et al. Short QT syndrome: pharmacological treatment. J Am Coll Cardiol 2004; 43:1494. 73. Mazzanti A, Maragna R, Vacanti G, et al. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. J Am Coll Cardiol 2017; 70:3010. 74. McPate MJ, Duncan RS, Witchel HJ, Hancox JC. Disopyramide is an effective inhibitor of mutant HERG K+ channels involved in variant 1 short QT syndrome. J Mol Cell Cardiol 2006; 41:563. 75. Mizobuchi M, Enjoji Y, Yamamoto R, et al. Nifekalant and disopyramide in a patient with short QT syndrome: evaluation of pharmacological effects and electrophysiological properties. Pacing Clin Electrophysiol 2008; 31:1229. 76. El Harchi A, Melgari D, Zhang YH, et al. Action potential clamp and pharmacology of the variant 1 Short QT Syndrome T618I hERG K channel. PLoS One 2012; 7:e52451. 77. Antzelevitch C, Yan GX, Ackerman MJ, et al. J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 2016; 13:e295. 78. Hong K, Bjerregaard P, Gussak I, Brugada R. Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. J Cardiovasc Electrophysiol 2005; 16:394. 79. Villafa e J, Atallah J, Gollob MH, et al. Long-term follow-up of a pediatric cohort with short QT syndrome. J Am Coll Cardiol 2013; 61:1183. 80. Iribarren C, Round AD, Peng JA, et al. Short QT in a cohort of 1.7 million persons: prevalence, correlates, and prognosis. Ann Noninvasive Electrocardiol 2014; 19:490. Topic 16697 Version 32.0 https://www.uptodate.com/contents/short-qt-syndrome/print 24/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate GRAPHICS Ventricular action potential and QRS-T cycle The QRS-T cycle on the electrocardiogram corresponds to different phases of the ventricular action potential. Graphic 78354 Version 1.0 https://www.uptodate.com/contents/short-qt-syndrome/print 25/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Genetic basis of SQTS QTc (milliseconds) Gene (cardiac ion channel) [1] ) SQT1 286 6 KCNH2 (I Kr [2] ) SQT2 302 KCNQ1 (I Ks [3] ) SQT3 315-330 KCNJ2 (I K1 [4] ) SQT4 331-370 CACNB2b (I Ca [4] ) SQT5 346-360 CACNA1C (I Ca [5] ) SQT6 330 CACNA2D1 (I Ca [6] SLC22A5 ( carnitine - I SQT7 282-340 ) Kr [7] SQT8 340 18 SLC4A3 (pHi-[Cl-]) References: 1. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004; 109:30. 2. Bellocq C, van Ginneken AC, Bezzina CR, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 2004; 109:2394. 3. Priori SG, Pandit SV, Rivolta I, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 2005; 96:800. 4. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442. 5. Templin C, Ghadri JR, Rougier JS, et al. Identi cation of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J 2011; 32:1077. 6. Roussel J, Labarthe F, Thireau J, et al. Carnitine de ciency induces a short QT syndrome. Heart Rhythm 2016; 13:165. 7. Thorsen K, Dam VS, Kjaer-Sorensen K, et al. Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nature communications 2017; 8:1696. Graphic 72304 Version 6.0 https://www.uptodate.com/contents/short-qt-syndrome/print 26/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Action potential currents Major cardiac ion currents and channels responsible for a ventricular action potential are shown with their common name, abbreviation, and the gene and protein for the alpha subunit that forms the pore or transporter. The diagram on the left shows the time course of amplitude of each current during the action potential, but does not accurately reflect amplitudes relative to each of the other currents. This summary represents a ventricular myocyte, and lists only the major ion channels. The currents and their molecular nature vary within regions of the ventricles, and in atria, and other specialized cells such as nodal and Purkinje. Ion channels exist as part of multi-molecular complexes including beta subunits and other associated regulatory proteins which are also not shown. Courtesy of Jonathan C Makielski, MD, FACC. Graphic 70771 Version 4.0 https://www.uptodate.com/contents/short-qt-syndrome/print 27/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Electrocardiographic characteristics of the short QT syndrome (A) A 12-lead ECG showing ECG characteristic of SQT1. (B) A 12-lead ECG showing ECG characteristic of SQT4 displaying combined ECG phenotype of Brugada and short QT syndromes. Note that ECG shows Brugada type ST elevation in V1 and V2 after administration of ajmaline in addition to short QT intervals. Reproduced with permission from: Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol 2010; 3:401. Copyright 2010 Lippincott Williams & Wilkins. Graphic 51616 Version 6.0 https://www.uptodate.com/contents/short-qt-syndrome/print 28/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Proposed diagnostic criteria for short QT syndrome Criteria Points QTc, milliseconds <370 1 <350 2 <330 3 J T point peak interval <120 milliseconds 1 Clinical history* History of sudden cardiac arrest 2 Documented polymorphic VT or VF 2 Unexplained syncope 1 Atrial fibrillation 1 Family history* First- or second-degree relative with high probability of SQTS 2 First- or second-degree relative with autopsy-negative sudden cardiac death 1 Sudden infant death syndrome 1 Genotype* Genotype positive 2 Mutation of undetermined significance in a culprit gene 1 Total High-probability SQTS: 4 points. Intermediate-probability SQTS: 3 points. Low-probability SQTS: 2 points. VF: ventricular fibrillation; VT: ventricular tachycardia; SQTS: short QT syndrome; QT: Bazett corrected QT interval. A minimum of 1 point must be obtained in the electrocardiographic section in order to obtain additional points. Original table modi ed for this publication. Gollob MH, Redpath CJ, Roberts JD: The short QT syndrome: proposed diagnostic criteria. J Am Coll Cardiol 2011; 57:802. Table used with the permission of Elsevier Inc. All rights reserved. https://www.uptodate.com/contents/short-qt-syndrome/print 29/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Graphic 65743 Version 5.0 https://www.uptodate.com/contents/short-qt-syndrome/print 30/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Secondary causes of short QT interval on ECG Hyperkalemia Hypercalcemia Hyperthermia Acidosis Effect of catecholamine Activation of ATP-sensitive potassium current Activation of acetylcholine-sensitive potassium current Effects of drugs like digitalis Myocardial ischemia Increased vagal tone Bufatolin (toad extract and antineoplastic, traditional Chinese medicine) Graphic 59159 Version 2.0 https://www.uptodate.com/contents/short-qt-syndrome/print 31/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/short-qt-syndrome/print 32/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/short-qt-syndrome/print 33/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Contributor Disclosures |
correlates, and prognosis. Ann Noninvasive Electrocardiol 2014; 19:490. Topic 16697 Version 32.0 https://www.uptodate.com/contents/short-qt-syndrome/print 24/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate GRAPHICS Ventricular action potential and QRS-T cycle The QRS-T cycle on the electrocardiogram corresponds to different phases of the ventricular action potential. Graphic 78354 Version 1.0 https://www.uptodate.com/contents/short-qt-syndrome/print 25/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Genetic basis of SQTS QTc (milliseconds) Gene (cardiac ion channel) [1] ) SQT1 286 6 KCNH2 (I Kr [2] ) SQT2 302 KCNQ1 (I Ks [3] ) SQT3 315-330 KCNJ2 (I K1 [4] ) SQT4 331-370 CACNB2b (I Ca [4] ) SQT5 346-360 CACNA1C (I Ca [5] ) SQT6 330 CACNA2D1 (I Ca [6] SLC22A5 ( carnitine - I SQT7 282-340 ) Kr [7] SQT8 340 18 SLC4A3 (pHi-[Cl-]) References: 1. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004; 109:30. 2. Bellocq C, van Ginneken AC, Bezzina CR, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 2004; 109:2394. 3. Priori SG, Pandit SV, Rivolta I, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 2005; 96:800. 4. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442. 5. Templin C, Ghadri JR, Rougier JS, et al. Identi cation of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J 2011; 32:1077. 6. Roussel J, Labarthe F, Thireau J, et al. Carnitine de ciency induces a short QT syndrome. Heart Rhythm 2016; 13:165. 7. Thorsen K, Dam VS, Kjaer-Sorensen K, et al. Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nature communications 2017; 8:1696. Graphic 72304 Version 6.0 https://www.uptodate.com/contents/short-qt-syndrome/print 26/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Action potential currents Major cardiac ion currents and channels responsible for a ventricular action potential are shown with their common name, abbreviation, and the gene and protein for the alpha subunit that forms the pore or transporter. The diagram on the left shows the time course of amplitude of each current during the action potential, but does not accurately reflect amplitudes relative to each of the other currents. This summary represents a ventricular myocyte, and lists only the major ion channels. The currents and their molecular nature vary within regions of the ventricles, and in atria, and other specialized cells such as nodal and Purkinje. Ion channels exist as part of multi-molecular complexes including beta subunits and other associated regulatory proteins which are also not shown. Courtesy of Jonathan C Makielski, MD, FACC. Graphic 70771 Version 4.0 https://www.uptodate.com/contents/short-qt-syndrome/print 27/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Electrocardiographic characteristics of the short QT syndrome (A) A 12-lead ECG showing ECG characteristic of SQT1. (B) A 12-lead ECG showing ECG characteristic of SQT4 displaying combined ECG phenotype of Brugada and short QT syndromes. Note that ECG shows Brugada type ST elevation in V1 and V2 after administration of ajmaline in addition to short QT intervals. Reproduced with permission from: Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol 2010; 3:401. Copyright 2010 Lippincott Williams & Wilkins. Graphic 51616 Version 6.0 https://www.uptodate.com/contents/short-qt-syndrome/print 28/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Proposed diagnostic criteria for short QT syndrome Criteria Points QTc, milliseconds <370 1 <350 2 <330 3 J T point peak interval <120 milliseconds 1 Clinical history* History of sudden cardiac arrest 2 Documented polymorphic VT or VF 2 Unexplained syncope 1 Atrial fibrillation 1 Family history* First- or second-degree relative with high probability of SQTS 2 First- or second-degree relative with autopsy-negative sudden cardiac death 1 Sudden infant death syndrome 1 Genotype* Genotype positive 2 Mutation of undetermined significance in a culprit gene 1 Total High-probability SQTS: 4 points. Intermediate-probability SQTS: 3 points. Low-probability SQTS: 2 points. VF: ventricular fibrillation; VT: ventricular tachycardia; SQTS: short QT syndrome; QT: Bazett corrected QT interval. A minimum of 1 point must be obtained in the electrocardiographic section in order to obtain additional points. Original table modi ed for this publication. Gollob MH, Redpath CJ, Roberts JD: The short QT syndrome: proposed diagnostic criteria. J Am Coll Cardiol 2011; 57:802. Table used with the permission of Elsevier Inc. All rights reserved. https://www.uptodate.com/contents/short-qt-syndrome/print 29/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Graphic 65743 Version 5.0 https://www.uptodate.com/contents/short-qt-syndrome/print 30/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Secondary causes of short QT interval on ECG Hyperkalemia Hypercalcemia Hyperthermia Acidosis Effect of catecholamine Activation of ATP-sensitive potassium current Activation of acetylcholine-sensitive potassium current Effects of drugs like digitalis Myocardial ischemia Increased vagal tone Bufatolin (toad extract and antineoplastic, traditional Chinese medicine) Graphic 59159 Version 2.0 https://www.uptodate.com/contents/short-qt-syndrome/print 31/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/short-qt-syndrome/print 32/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/short-qt-syndrome/print 33/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Contributor Disclosures Charles Antzelevitch, PhD, FACC, FAHA, FHRS Grant/Research/Clinical Trial Support: InCarda Pharmaceuticals [Atrial fibrillation]; Kymera Pharmaceuticals [Safety pharmacology]; NHLBI of the NIH [WW Smith Trust]; Novartis [Atrial fibrillation]; Trevena Inc [Electrophysiology of oliceridine]. Consultant/Advisory Boards: Novartis [Atrial fibrillation]; Trevena Inc [Electrophysiology of oliceridine]. Speaker's Bureau: Invitae [Mechanisms underlying the J wave syndromes as a cause of SCD]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/short-qt-syndrome/print 34/34 |
7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Supportive data for advanced cardiac life support in adults with sudden cardiac arrest : Mark S Link, MD : Richard L Page, MD, Ron M Walls, MD, FRCPC, FAAEM : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 09, 2021. INTRODUCTION Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity with hemodynamic collapse, often due to sustained ventricular tachycardia/ventricular fibrillation. Other causes of SCA and SCD are asystole and pulseless electrical activity. These events most commonly occur in patients with structural heart disease (that may not have been previously diagnosed), particularly coronary heart disease. (See "Pathophysiology and etiology of sudden cardiac arrest".) The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation) results in the return of spontaneous circulation (ROSC) and restored circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.) The treatment of SCA consists of emergency resuscitation followed, in survivors, by immediate post-resuscitative care and attempted long-term prevention of recurrence using pharmacologic and nonpharmacologic interventions. Over time, the frequency of cardiopulmonary resuscitation (CPR) performed by bystanders has increased, and the interval between collapse and defibrillation has decreased, both of which are particularly important in survival [1,2]. Despite these improvements as well as advances in the treatment of heart disease, the outcome https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 1/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate of patients experiencing SCA remains poor. (See "Prognosis and outcomes following sudden cardiac arrest in adults".) In reality, there are only two out of hospital therapies of resuscitation that have been shown to be associated with improved survival: excellent, prompt chest compressions and early defibrillation. Resuscitation should focus on providing these two elements with the highest quality. This is not to say that advanced cardiac life support (ACLS) therapies should be withheld if indicated; however, shockable rhythms should first be defibrillated, and excellent CPR (either compressions only, or compressions and mouth to mouth breathing) should be performed. Any other interventions should be delayed until these first-line therapies are implemented. In general, the performance of the second-line interventions (as part of ACLS) should rarely interfere with defibrillation and excellent CPR. The only other therapy has shown to be associated with a neurologically favorable survival advantage is targeted temperature management (TTM) in the post-arrest care. This is discussed in greater detail separately. (See 'Targeted temperature management' below and "Initial assessment and management of the adult post-cardiac arrest patient", section on 'Temperature management'.) The data supporting advanced cardiac life support (ACLS) recommendations for the management of SCA will be reviewed here. The performance of ACLS, controversies surrounding cardiopulmonary resuscitation, and issues related to the prevention of recurrent SCA in survivors are discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Adult basic life support (BLS) for health care providers" and "Therapies of uncertain benefit in basic and advanced cardiac life support" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Pharmacologic therapy in survivors of sudden cardiac arrest".) VF AND PULSELESS VT The management of ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) is the same ( algorithm 1) [3]. Survival depends upon prompt, high-quality cardiopulmonary resuscitation (CPR) with chest compressions and the earliest defibrillation possible to reestablish organized electrical activity with a stable sinus or supraventricular rhythm. Excellent CPR is a priority and should be maintained throughout the resuscitative effort; pauses should only occur during rhythm analysis and defibrillation (as soon as possible for the first defibrillation and then at two-minute intervals, and when required to deliver ventilations in an un-intubated patient by bag-mask ventilation at a ratio of 30:2). Other procedures, such as vascular access, vasopressor https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 2/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate administration, and intubation, should not be performed in the initial resuscitation efforts (ie, first few minutes) unless they can be performed without interrupting CPR and defibrillation. Multiple studies have reported that intubation should not be attempted in adults until return of spontaneous circulation (ROSC) unless bag-mask ventilation is ineffective or there has been a prolonged period of resuscitation [4-6]. Any adjunctive procedure requiring discontinuation of CPR should occur during rhythm checks, as this minimizes interruptions in perfusion and the build-up necessary to reach threshold perfusion pressures once compressions are restarted. Interruptions should be brief and should never create prolonged delays in resumption of CPR. (See "Advanced cardiac life support (ACLS) in adults".) Specific issues relating to the management of VF and pVT, including technical aspects of defibrillation, are discussed below. The use of automated external defibrillators (AED) for the treatment of cardiac arrest is presented separately. (See "Automated external defibrillators".) Defibrillation The only effective approach for the treatment of VF and pVT is defibrillation, with earlier efforts yielding better outcomes. VF rarely, if ever, terminates spontaneously or after delivery of an antiarrhythmic drug. (See "Cardioversion for specific arrhythmias", section on 'Ventricular fibrillation'.) Timing The success of defibrillation and patient survival depends upon the duration of the arrhythmia and the promptness of defibrillation [2,7-9]: When VF has been present for seconds to a few minutes and the fibrillatory waves are coarse, the success rate for terminating VF with defibrillation is high. As VF continues, the fibrillatory waves become finer ( waveform 1) [10]. When VF continues for more than four minutes, especially if not accompanied by excellent CPR, irreversible damage to the central nervous system and other organs begins, which can reduce survival even if defibrillation is successful [11-13]. There is strong evidence that longer interruptions in chest compressions reduce the likelihood of successful defibrillation and lower the odds of survival [14-18]. In a prospective observational cohort of 506 adult patients with out-of-hospital cardiac arrest, patients with the highest chest compression fractions (61 to 80 percent and 81 to 100 percent), defined as the proportion of time in cardiac arrest without spontaneous circulation during which chest compressions were being performed, had the greatest chance of survival to hospital discharge (adjusted odds ratios [OR] 3.01, 95% CI 1.37-6.58 and 2.33, 95% CI 0.96-5.63, respectively). As there are data indicating that shortening the duration between stopping compressions and delivering the defibrillatory shock has a survival advantage, defibrillators should be fully charged prior to cessation of https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 3/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate compressions, after which immediate rhythm identification and shock delivery is performed as indicated (this should typically occur in no more than three to five seconds) [18,19]. In a series of over 12,000 patients treated by Emergency Medical Services, 4546 had witnessed VF [2]. For these patients with witnessed VF, a shorter defibrillation response interval was significantly correlated with an increased chance of survival to hospital discharge. The analysis yielded an odds ratio for survival of 0.88 for every one-minute increase in response time, which corresponds to a 3 to 5 percent drop in survival for each minute of delay to defibrillation [2]. There is debate about whether CPR should be performed prior to defibrillation. Outcomes may be improved by performing CPR before defibrillation, in particular if the patient has been in SCA for a longer time period. This was illustrated in a retrospective report that compared outcomes in patients with out-of-hospital VF in two time periods: when an initial shock was given as soon as possible; and when the initial shock was delayed until 90 seconds of CPR had been performed [20]. Survival to hospital discharge was significantly increased with routine CPR before defibrillation (30 versus 24 percent without prior CPR); this benefit was primarily seen in patients in whom the initial response interval was four minutes or longer (27 versus 17 percent without prior CPR). Yet in a randomized controlled trial, there was no difference in outcome. In this RCT, in which 200 patients presenting with out-of-hospital VF were assigned to immediate defibrillation or CPR for three minutes prior to the first defibrillation attempt, there was no difference in outcome between the two groups for patients with an EMS response time 5 minutes [21]. For those with response times >5 minutes, patients undergoing CPR first were significantly more likely to survive to hospital discharge (22 versus 4 percent). Subsequent larger randomized controlled studies, however, have not confirmed that performing CPR prior to defibrillation improves survival to hospital discharge [22-24]. As one example, in a randomized trial of 9933 patients with out-of-hospital cardiac arrest who were assigned to either 30 to 60 seconds of CPR versus 180 seconds of CPR prior to initial cardiac rhythm analysis, there was no significant difference in survival to hospital discharge [24]. Practically, however, in nearly all cardiac arrest, rescuers should perform excellent compressions before the arrival and deployment of an AED or while a monitor/defibrillator is being placed and charged. Thus, CPR should generally be performed prior to defibrillation in these situations. Early defibrillation of VT/VF in patients with in-hospital cardiac arrest has also been shown to improve survival, in both the short term and long term. Among a cohort of 8119 with in-hospital cardiac arrest with VT/VF, patients who were defibrillated within two minutes of cardiac arrest had significantly better survival (compared with initial defibrillation at >2 minutes) at one year https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 4/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate (26 versus 16 percent), three years (19 versus 11 percent), and five years (15 versus 9 percent) [25]. Based upon the above studies, the 2020 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation and emergency cardiovascular care suggest the initiation of CPR while awaiting the arrival of a defibrillator [26-29]. Once the defibrillator is attached to the patient, CPR should be briefly stopped to allow for a rhythm check and shock, if indicated (cessation of compressions should not occur until the defibrillator is fully charged), followed by immediate resumption of CPR for two minutes prior to any additional rhythm checks. Defibrillatory waveforms Defibrillators manufactured prior to 2000 deliver a monophasic wave of direct electrical current. Since then, "biphasic" devices have been developed, which reverse current polarity 5 to 10 milliseconds after discharge begins ( figure 1). Biphasic waveforms defibrillate more effectively and at lower energies than monophasic waveforms. They have a much higher likelihood of first shock efficacy, which is the basis for the current recommendation to deliver a single shock compared with earlier recommendations that three shocks be delivered in rapid succession [3]. Data comparing the use of monophasic and biphasic waveforms in the treatment of VF are presented separately. (See "Basic principles and technique of external electrical cardioversion and defibrillation", section on 'Monophasic versus biphasic waveforms'.) There have been case reports in the literature on the successful use of double sequence defibrillation for VF not terminated by maximal energy from a single defibrillator [30,31]. Importantly, this procedure is not warranted for those whose VF terminates with shock and then reinitiates. This procedure employs two external defibrillators used simultaneously or sequentially (one right after the other) to deliver higher energy with the intent to convert VF to a perfusing rhythm. Despite these case reports, two retrospective studies with small patient populations of OHCA showed disparate results; one reported no difference [30,31]. More and better research is needed on the efficacy of this therapy prior to making any recommendations. VF or VT arrest and vasopressors Despite conflicting data on survival, the 2020 guidelines concluded that it is appropriate to administer epinephrine (1 mg IV/IO every three to five minutes) for patients presenting with cardiac arrest [3,29,32]. Routine use of high-dose epinephrine is not supported by data and is not recommended. Additionally, the 2020 guidelines state that vasopressin alone or in combination with epinephrine may be considered during resuscitation from cardiac arrest but offers no advantage over epinephrine alone. Accordingly, we recommend that epinephrine be used as the sole vasopressor during resuscitation from cardiac arrest and that vasopressin no longer be used [3]. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 5/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate The totality of the evidence assessing the efficacy of epinephrine for out-of-hospital cardiac arrest suggest that, although ROSC and even overall survival may be increased with the use of epinephrine, meaningful survival with favorable neurologic outcome is not improved [33-36]. Whether improvement in post-ROSC care will be able to transform those without meaningful neurologic outcome is not clear. Thus, as the data are quite mixed in outcome, they do not support the routine use of epinephrine in the treatment of all patients, but should serve as an impetus for additional randomized controlled trials of this issue targeting subgroups who are more likely to benefit. Pending review and updating of ACLS protocols, it is reasonable to include epinephrine in resuscitation protocols as an option for resuscitation personnel, and the decision whether to administer it can occur on a case-by-case basis. Epinephrine has been studied in two randomized, double-blind, placebo-controlled trials, with mixed survival results [33,34]. In the trial of 8014 patients in the United Kingdom with out-of-hospital cardiac arrest (PARAMEDIC-2) who were randomized to either epinephrine (1 mg doses, mean total dose 4.9 mg) or placebo, the primary outcome (30-day survival) was significantly higher in the group who received epinephrine (130 patients [3.2 percent] versus 94 patients [2.4 percent]; adjusted OR 1.47; 95% CI 1.09-1.97) [33]. Subgroup analysis showed a significant survival benefit for patients with a nonshockable initial rhythm (OR 2.10; 95% CI 1.11-3.98) that was not seen in patients with an initial shockable rhythm. However, patients receiving epinephrine had no significant improvement in survival with favorable neurologic outcome (score between 0 and 3 on modified Rankin scale) but among survivors were more likely to have severe neurologic impairment (modified Rankin scale score 4 or 5; 31 versus 18 percent of survivors). In a trial of 601 patients with out-of-hospital cardiac arrest who were randomized to either epinephrine (1 mg doses, mean total dose 5 mg) or placebo, patients who received epinephrine were more likely to have ROSC (24 versus 8 percent, OR 3.4, 95% CI 2.0-5.6) and survival to hospital admission, but there was no significant improvement in survival to hospital discharge (4 versus 1.9 percent, OR 2.2, 95% CI 0.7-6.3) [34]. A 2019 meta-analysis, which combined the data from these two randomized trials, reported increased survival to hospital discharge for patients with nonshockable initial rhythms receiving epinephrine, with the results largely driven by the PARAMEDIC-2 data [35]. No significant improvement in survival to hospital discharge was seen in patients with an initial shockable rhythm. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 6/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate The benefits of epinephrine (and other vasopressors) in the treatment of cardiac arrest have been questioned in numerous nonrandomized studies: In a prospective observational study of 417,188 adults with out-of-hospital cardiac arrest, investigators compared ROSC, survival, and neurologic outcome in patients who received epinephrine (15,030 patients, 3.6 percent) with those who did not receive epinephrine (402,158 patients, 96.4 percent) [37]. While there was a significantly greater ROSC in the epinephrine group (18.5 versus 5.7 percent using raw data, 18.3 versus 10.5 percent using propensity analysis), this did not translate into improved outcomes. In fact, using propensity analysis, patients receiving epinephrine had significantly lower rates of survival at one month (5.1 versus 7.0 percent); survival with moderate or good cerebral performance (1.3 versus 3.1 percent); and survival with no, mild, or moderate neurological disability (1.3 versus 3.1 percent). Similar results were reported from a study of 1646 patients presenting to a single center between 2000 and 2012 following out-of-hospital cardiac arrest with ROSC, in which the chance of survival was significantly lower among patients who received epinephrine and decreased further as the cumulative dose of epinephrine during resuscitation increased [38]. The early administration of epinephrine within two minutes following the initial defibrillation for VF/VT may be detrimental. In a prospective cohort study of 2978 patients with in-hospital cardiac arrest and a shockable rhythm (1510 patients with epinephrine administered within two minutes of defibrillation and 1468 propensity score matched patients without early epinephrine administration), patients who received early epinephrine had a significantly decreased likelihood of survival (OR 0.70, 95% CI 0.59-0.82) [39]. (See "Advanced cardiac life support (ACLS) in adults", section on 'Pulseless ventricular tachycardia and ventricular fibrillation'.) In a 2019 Cochrane Database systematic review which looked only at randomized controlled trials (26 trials with 21,704 patients) in which standard-dose epinephrine was compared to placebo, high-dose epinephrine, or vasopressin (alone or in combination with epinephrine), the following findings were reported among patients receiving epinephrine compared with placebo [40]: Moderate quality evidence of ROSC (relative risk [RR] 2.86; 95% CI 2.21-3.71) Moderate quality evidence of survival to hospital discharge (RR 1.44; 95% CI 1.11-1.86) No significant difference in survival with favorable neurologic outcomes (RR 1.21; 95% CI 0.90-1.62) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 7/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Although the 2020 guidelines still allow vasopressin to be "considered" (ie, 2b) alone or in combination with epinephrine, we recommend that vasopressin no longer be used for SCA29. Although a single randomized controlled trial found higher rates of successful resuscitation and 24-hour survival with vasopressin compared with epinephrine, subsequent randomized trials and a meta-analysis failed to show an improvement in initial ROSC or survival to hospital discharge [41-44]. Furthermore, in a multicenter trial of 1442 patients, treatment of out-of- hospital cardiac arrest with a combination of epinephrine and vasopressin did not improve outcomes compared with treatment with epinephrine alone [45]. Because of this lack of benefit of vasopressin over epinephrine, the 2015 AHA guidelines removed vasopressin from the treatment protocol (allowing for EMS and hospitals to remove it from resuscitation supplies) for patients with VF or pVT [3]. Because vasopressors given in the setting of ROSC may be detrimental, it is now strongly suggested that resuscitation be performed using quantitative waveform capnography so that ROSC may be more readily identified during ongoing compressions [46-48]. As soon as ROSC is obtained, no further vasopressors should generally be administered. (See "Advanced cardiac life support (ACLS) in adults", section on 'Airway management' and "Carbon dioxide monitoring (capnography)".) Antiarrhythmic drugs VF or VT may persist despite electrical countershock or recur after successful electrical countershock. The 2020 AHA guidelines state that IV/IO antiarrhythmic drug therapy may be considered in such cases, in particular for witnessed cardiac arrest in which the time to drug administration is shorter, although benefit from this therapy remains uncertain [3,29,49-51]. Antiarrhythmic drugs that may be used include amiodarone and lidocaine, with no guideline-based preference of a preferred agent. Some post-hoc nonrandomized data suggest that outcomes are better for both amiodarone and lidocaine administered intravenously (compared with intraosseously), but this has not been assessed in an RCT [52,53]. The performance of ACLS, including the details of antiarrhythmic drug therapy, is discussed elsewhere. (See "Advanced cardiac life support (ACLS) in adults".) Amiodarone Intravenous amiodarone increases ROSC and survival to hospital admission compared with lidocaine in patients with refractory VF and pVT, However, there is no significant difference between amiodarone and lidocaine in terms of the patient-important outcomes of survival to hospital discharge and neurologically intact survival [49,54]. In the ALIVE trial of 347 patients with out-of-hospital sudden cardiac arrest (SCA) and persistent or recurrent VF despite three defibrillation shocks, IV/IO epinephrine, and a further attempt at defibrillation, survival to hospital admission was significantly higher in https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 8/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate patients receiving amiodarone (23 versus 12 percent for lidocaine, OR 2.17, 95% CI 1.21- 3.83) [55]. Among patients who had the ROSC prior to antiarrhythmic administration, amiodarone led to an even higher rate of survival to admission (42 versus 27 percent with lidocaine). Despite these benefits, the in-hospital death rates in the two groups were 78 and 75 percent, similar to those in other studies, and there was no significant difference in survival to hospital discharge (nine and five patients in the amiodarone and lidocaine groups, respectively). In the ARREST trial of 504 patients with SCA due to VF or pVT who were not resuscitated after at least three defibrillation shocks, patients were randomly assigned to intravenous bolus amiodarone (300 mg) or placebo [56]. While the mean time to resuscitation and the total number of shocks delivered were similar in the two groups, survival to hospital admission was significantly greater in the amiodarone group (44 versus 34 percent with placebo), especially in patients who had the ROSC during defibrillation prior to receiving amiodarone (64 versus 41 percent placebo). Amiodarone, however, was associated with more adverse effects, including hypotension (59 versus 48 percent) and bradycardia requiring therapy (41 versus 25 percent). (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) The ARREST trial was not sufficiently powered to detect differences in survival to hospital discharge, which did not differ significantly between the two groups, similar to the findings in the ALIVE trial. Intravenous amiodarone is also effective for the acute suppression of life-threatening, hemodynamically significant ventricular tachyarrhythmias that recur despite therapy with other agents. Amiodarone can prevent recurrence of sustained spontaneous VT or VF in more than 50 percent of patients, and it has been approved for the acute treatment and prevention of VF and for hemodynamically significant VT that is refractory to other agents [57,58]. Lidocaine There is no significant difference between lidocaine and amiodarone in terms of the patient-important outcomes of survival to hospital discharge and neurologically intact survival. The 2020 AHA guidelines state that either lidocaine or amiodarone can be administered during cardiac arrest for VT/VF refractory to shocks and epinephrine [29,50,51]. (See 'Amiodarone' above and "Advanced cardiac life support (ACLS) in adults", section on 'Pulseless patient in sudden cardiac arrest'.) Comparison of amiodarone and lidocaine In 2016, the first randomized trial (the ALPS study) was published that compared amiodarone, lidocaine, and placebo in patients with pVT or https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 9/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate VF refractory to defibrillation and initial vasopressor therapy [59]. This study was the first to evaluate the effect of a new preparation of amiodarone that employs a solvent that is not associated with hypotension. In this trial of 3026 patients, there was no significant difference in the primary outcome (survival to hospital discharge) among the three groups, with no statistically significant improvement in survival for either the amiodarone or lidocaine groups compared with placebo (24.4 versus 23.7 versus 21.0 percent, respectively). Similarly, there was no significant improvement in the prespecified secondary outcome of favorable neurologic function at discharge among those who received amiodarone or lidocaine. Subgroup analysis identified a nonsignificant mortality decrease of 5 percent for either drug therapy in patients with bystander-witnessed arrest (in whom CPR and activation of emergency medical systems likely occur earlier than in non-witnessed patients). A prespecified analysis from the ALPS study was performed on a cohort of 1063 patients with cardiac arrest initially due to a nonshockable rhythm (ie, pulseless electrical activity or asystole) that subsequently evolved to a shockable rhythm during resuscitation efforts [60]. As with the primary cohort from the ALPS study (patients presenting with cardiac arrest due to pVT or VF), patients were randomized to amiodarone, lidocaine, or placebo. Similar to the findings among patients presenting with an initial shockable rhythm, for patients who evolved from a nonshockable to a shockable rhythm during resuscitation, there was no significant difference in the primary outcome (survival to hospital discharge) among the amiodarone, lidocaine, and placebo groups (4.1 versus 3.1 versus 1.9 percent, respectively). These randomized trial data further support the approach as stated in the 2018 AHA focused update to the 2015 AHA guidelines, in which amiodarone and lidocaine "may be considered" for patients with VF or pVT which is refractory to initial treatments, especially when arrest is witnessed [50,51]. Magnesium sulfate Data from randomized trials do NOT support the routine use of magnesium sulfate for the treatment of cardiac arrest [50,51]. However, observational data from a small number of patients suggest that intravenous magnesium sulfate is beneficial for the treatment of a VF or pVT arrest due to drug-induced prolonged QT interval associated with torsades de pointes [61]. Magnesium's primary benefit is in the prevention of recurrent episodes of VF, not in the termination of such. Defibrillation is generally necessary for termination. The 2020 AHA guidelines state that torsades de pointes is the only arrhythmia for which administration of magnesium sulfate should be considered [29,50,51]. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) Targeted temperature management The induction of mild to moderate hypothermia (target temperature 32 to 34 C for 24 hours) has been shown to improve survival in patients https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 10/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate successfully resuscitated after a cardiac arrest who are comatose. Improved neurologic outcome and reduced mortality have been demonstrated in multiple series of patients with VF arrest in whom spontaneous circulation was restored, even when the patient remained comatose after resuscitation. More recently, a large randomized controlled trial, which involved 939 patients with ROSC following cardiac arrest and compared target temperatures of 32 to 34 degrees with targeted temperatures of 34 to 36 degrees, showed no significant difference in survival between the groups [62]. It is still unclear whether the benefits of targeted temperature management are related to actual cooling or the prevention of post-ROSC fever. Targeted temperature management is discussed in greater detail elsewhere. (See "Advanced cardiac life support (ACLS) in adults", section on 'Post-resuscitation care' and "Initial assessment and management of the adult post-cardiac arrest patient", section on 'Temperature management'.) PULSELESS ELECTRICAL ACTIVITY In contrast to ventricular fibrillation or pulseless ventricular tachycardia, there is no role for defibrillation in the management of pulseless electrical activity (PEA) or asystole ( algorithm 1). Excellent cardiopulmonary resuscitation (CPR), vasopressor therapy, and rapid treatment of reversible causes are the mainstays of PEA management. However, because CPR is ineffective in cardiac arrest due to cardiac tamponade and tension pneumothorax, the rapid identification and treatment of these eminently reversible causes must be of primary importance. Reversible causes include the five H's and T's (hypoxia, hypovolemia, hydrogen ion (acidosis), hypo-/hyperkalemia, hypothermia, toxins [especially narcotics and benzodiazepines], tamponade [cardiac], tension pneumothorax, thrombosis [pulmonary], thrombosis [coronary]) as defined by the 2015 AHA guidelines ( table 1) [3]. While CPR with excellent chest compressions is performed, other rescuers should not be afraid to perform "heroic" procedures, even if no definitive confirmatory studies are available, for plausibly suspected causes of PEA. CPR should be provided throughout the resuscitative effort, except during brief pauses at two- minute intervals to analyze the rhythm and assess for return of spontaneous circulation (ROSC). In a cohort of 3960 patients with out-of-hospital cardiac arrest and a nonshockable cardiac rhythm, 1774 patients were treated with ACLS before and 2186 patients were treated with ACLS after the revised 2005 guidelines, which increased the emphasis on chest compressions during resuscitation [63]. Patients treated after 2005 with an increased emphasis on chest compressions had significantly greater ROSC (34 versus 27 percent), one month survival (6.2 versus 4.1 percent), and favorable neurologic outcomes (5.1 versus 3.4 percent). (See "Advanced cardiac life support (ACLS) in adults", section on 'Asystole and pulseless electrical activity'.) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 11/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate PEA and vasopressors The efficacy of epinephrine (1 mg IV/IO push every three to five minutes) for PEA remains uncertain, but it remains a part of the 2015 AHA guidelines for the treatment of cardiac arrest with PEA [3,37]. In a secondary analysis of a cardiac arrest registry, among a cohort of 32,101 patients with out-of-hospital cardiac arrest and a nonshockable initial rhythm (published after the 2015 AHA guidelines), earlier administration of epinephrine was associated with improved survival, with a 4 percent decreased likelihood of survival for each additional minute of delay in epinephrine administration [64]. Improvements in one-year survival following in-hospital cardiac arrest have also been reported with early administration of epinephrine [25]. (See 'VF or VT arrest and vasopressors' above.) PEA and atropine Atropine is not recommended in the 2020 guidelines for PEA because of its lack of therapeutic benefit [3,29]. The administration of atropine (1 mg IV/IO every three to five minutes) may be considered for PEA when the rate is slow, ie, absolute bradycardia with a rate <50 beats/minute or a relative bradycardia (rate less than expected relative to the underlying condition) [26,27]. Atropine's effect is on vagally-mediated bradycardia, which is rarely a cause of cardiac arrest, and treatment successes are reportable. In a cohort study of 1029 patients with PEA published after the 2010 AHA guidelines, 30-day neurologic outcomes were no different in the groups treated with epinephrine and atropine versus epinephrine alone [65]. In addition, survival was significantly lower in the group treated with epinephrine and atropine (3.2 percent versus 7.1 percent in epinephrine only group; OR 0.43, 95% CI 0.19 to 0.91), suggesting that atropine may actually be harmful when used to treat PEA. Registry data on over 20,000 in-hospital cardiac arrests with a non-shockable rhythm, collected between 2006 and 2015, showed no difference in survival before and after atropine was removed from the treatment protocol in the 2010 AHA guidelines [66]. ASYSTOLE Sudden cardiac arrest in which asystole is the initial rhythm is associated with an extremely poor prognosis (0 to 2 percent survival to hospital discharge). Asystole is usually a secondary event, resulting from prolonged ventricular fibrillation or pulseless electrical activity (PEA) with subsequent loss of all electrical activity. It may also occur as a result of prolonged hypoxia, acidosis, and death of myocardial tissue ( waveform 1). (See "Prognosis and outcomes following sudden cardiac arrest in adults", section on 'Asystole'.) True asystole should be confirmed by checking the ECG and defibrillator cable connections, making certain that the gain is turned up and the monitor is working. Confirmation of asystole in another lead is recommended. The 2015 AHA guidelines recommend that asystole be treated https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 12/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate in the same manner as PEA, with excellent cardiopulmonary resuscitation (CPR), vasopressors, and the consideration of possible reversible causes ( table 1) [3]. Atropine is no longer recommended as therapy in asystole. CPR, with an emphasis on excellent chest compressions, should be provided throughout the resuscitative effort, stopping only at two-minute intervals during which brief rhythm analysis and defibrillation is provided if the patient has reverted to a shockable rhythm [63]. There is no benefit to defibrillation in patients with asystole. (See 'Pulseless electrical activity' above and "Advanced cardiac life support (ACLS) in adults", section on 'Asystole and pulseless electrical activity'.) Because randomized controlled trials and other data have not shown a survival benefit with the use of temporary pacing in asystole, its routine use is not recommended by the 2020 AHA guidelines [3,29,67-71]. Prolonged resuscitative efforts of patients in asystole are generally futile. Termination of resuscitation is discussed elsewhere. (See "Advanced cardiac life support (ACLS) in adults", section on 'Termination of resuscitative efforts'.) Asystole and vasopressors Epinephrine Epinephrine (1 mg IV/IO push every three to five minutes) is recommended in patients with asystole, although its benefit has not been clearly demonstrated in prospective trials [3,37]. In a secondary analysis of a cardiac arrest registry, among a cohort of 32,101 patients with out-of-hospital cardiac arrest and a nonshockable initial rhythm (published after the 2015 AHA guidelines), earlier administration of epinephrine was associated with improved survival, with a 4 percent decreased likelihood of survival for each additional minute of delay in epinephrine administration [64]. Improvements in one-year survival following in-hospital cardiac arrest have also been reported with early administration of epinephrine [25]. In a separate registry study that included more than 41,000 patients (not all of whom were in asystole), delay to epinephrine administration was also associated reduced survival [72]. (See 'VF or VT arrest and vasopressors' above.) Routine use of high-dose epinephrine is not supported by data and is not recommended [73,74]. In a randomized trial comparing repeated high doses and standard doses of epinephrine for out-of-hospital cardiac arrest, survival to hospital discharge was similar with high-dose and standard dose epinephrine [74]. Although high-dose epinephrine improved the rate of successful resuscitation in patients with asystole, it did not improve survival to hospital discharge. Vasopressin Vasopressin has been studied as a potential alternative to epinephrine. In one trial comparing vasopressin with epinephrine in 1186 patients with out-of-hospital arrest, the |
reversible causes are the mainstays of PEA management. However, because CPR is ineffective in cardiac arrest due to cardiac tamponade and tension pneumothorax, the rapid identification and treatment of these eminently reversible causes must be of primary importance. Reversible causes include the five H's and T's (hypoxia, hypovolemia, hydrogen ion (acidosis), hypo-/hyperkalemia, hypothermia, toxins [especially narcotics and benzodiazepines], tamponade [cardiac], tension pneumothorax, thrombosis [pulmonary], thrombosis [coronary]) as defined by the 2015 AHA guidelines ( table 1) [3]. While CPR with excellent chest compressions is performed, other rescuers should not be afraid to perform "heroic" procedures, even if no definitive confirmatory studies are available, for plausibly suspected causes of PEA. CPR should be provided throughout the resuscitative effort, except during brief pauses at two- minute intervals to analyze the rhythm and assess for return of spontaneous circulation (ROSC). In a cohort of 3960 patients with out-of-hospital cardiac arrest and a nonshockable cardiac rhythm, 1774 patients were treated with ACLS before and 2186 patients were treated with ACLS after the revised 2005 guidelines, which increased the emphasis on chest compressions during resuscitation [63]. Patients treated after 2005 with an increased emphasis on chest compressions had significantly greater ROSC (34 versus 27 percent), one month survival (6.2 versus 4.1 percent), and favorable neurologic outcomes (5.1 versus 3.4 percent). (See "Advanced cardiac life support (ACLS) in adults", section on 'Asystole and pulseless electrical activity'.) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 11/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate PEA and vasopressors The efficacy of epinephrine (1 mg IV/IO push every three to five minutes) for PEA remains uncertain, but it remains a part of the 2015 AHA guidelines for the treatment of cardiac arrest with PEA [3,37]. In a secondary analysis of a cardiac arrest registry, among a cohort of 32,101 patients with out-of-hospital cardiac arrest and a nonshockable initial rhythm (published after the 2015 AHA guidelines), earlier administration of epinephrine was associated with improved survival, with a 4 percent decreased likelihood of survival for each additional minute of delay in epinephrine administration [64]. Improvements in one-year survival following in-hospital cardiac arrest have also been reported with early administration of epinephrine [25]. (See 'VF or VT arrest and vasopressors' above.) PEA and atropine Atropine is not recommended in the 2020 guidelines for PEA because of its lack of therapeutic benefit [3,29]. The administration of atropine (1 mg IV/IO every three to five minutes) may be considered for PEA when the rate is slow, ie, absolute bradycardia with a rate <50 beats/minute or a relative bradycardia (rate less than expected relative to the underlying condition) [26,27]. Atropine's effect is on vagally-mediated bradycardia, which is rarely a cause of cardiac arrest, and treatment successes are reportable. In a cohort study of 1029 patients with PEA published after the 2010 AHA guidelines, 30-day neurologic outcomes were no different in the groups treated with epinephrine and atropine versus epinephrine alone [65]. In addition, survival was significantly lower in the group treated with epinephrine and atropine (3.2 percent versus 7.1 percent in epinephrine only group; OR 0.43, 95% CI 0.19 to 0.91), suggesting that atropine may actually be harmful when used to treat PEA. Registry data on over 20,000 in-hospital cardiac arrests with a non-shockable rhythm, collected between 2006 and 2015, showed no difference in survival before and after atropine was removed from the treatment protocol in the 2010 AHA guidelines [66]. ASYSTOLE Sudden cardiac arrest in which asystole is the initial rhythm is associated with an extremely poor prognosis (0 to 2 percent survival to hospital discharge). Asystole is usually a secondary event, resulting from prolonged ventricular fibrillation or pulseless electrical activity (PEA) with subsequent loss of all electrical activity. It may also occur as a result of prolonged hypoxia, acidosis, and death of myocardial tissue ( waveform 1). (See "Prognosis and outcomes following sudden cardiac arrest in adults", section on 'Asystole'.) True asystole should be confirmed by checking the ECG and defibrillator cable connections, making certain that the gain is turned up and the monitor is working. Confirmation of asystole in another lead is recommended. The 2015 AHA guidelines recommend that asystole be treated https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 12/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate in the same manner as PEA, with excellent cardiopulmonary resuscitation (CPR), vasopressors, and the consideration of possible reversible causes ( table 1) [3]. Atropine is no longer recommended as therapy in asystole. CPR, with an emphasis on excellent chest compressions, should be provided throughout the resuscitative effort, stopping only at two-minute intervals during which brief rhythm analysis and defibrillation is provided if the patient has reverted to a shockable rhythm [63]. There is no benefit to defibrillation in patients with asystole. (See 'Pulseless electrical activity' above and "Advanced cardiac life support (ACLS) in adults", section on 'Asystole and pulseless electrical activity'.) Because randomized controlled trials and other data have not shown a survival benefit with the use of temporary pacing in asystole, its routine use is not recommended by the 2020 AHA guidelines [3,29,67-71]. Prolonged resuscitative efforts of patients in asystole are generally futile. Termination of resuscitation is discussed elsewhere. (See "Advanced cardiac life support (ACLS) in adults", section on 'Termination of resuscitative efforts'.) Asystole and vasopressors Epinephrine Epinephrine (1 mg IV/IO push every three to five minutes) is recommended in patients with asystole, although its benefit has not been clearly demonstrated in prospective trials [3,37]. In a secondary analysis of a cardiac arrest registry, among a cohort of 32,101 patients with out-of-hospital cardiac arrest and a nonshockable initial rhythm (published after the 2015 AHA guidelines), earlier administration of epinephrine was associated with improved survival, with a 4 percent decreased likelihood of survival for each additional minute of delay in epinephrine administration [64]. Improvements in one-year survival following in-hospital cardiac arrest have also been reported with early administration of epinephrine [25]. In a separate registry study that included more than 41,000 patients (not all of whom were in asystole), delay to epinephrine administration was also associated reduced survival [72]. (See 'VF or VT arrest and vasopressors' above.) Routine use of high-dose epinephrine is not supported by data and is not recommended [73,74]. In a randomized trial comparing repeated high doses and standard doses of epinephrine for out-of-hospital cardiac arrest, survival to hospital discharge was similar with high-dose and standard dose epinephrine [74]. Although high-dose epinephrine improved the rate of successful resuscitation in patients with asystole, it did not improve survival to hospital discharge. Vasopressin Vasopressin has been studied as a potential alternative to epinephrine. In one trial comparing vasopressin with epinephrine in 1186 patients with out-of-hospital arrest, the https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 13/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 528 patients with asystole who received vasopressin were significantly more likely to survive until hospital admission (29 versus 20 percent with epinephrine, odds ratio [OR] 0.6, 95% CI 0.4- 0.9) and hospital discharge (4.7 versus 1.5 percent, OR 0.3, 95% CI 0.1-1.0) [43]. However, a subsequent meta-analysis, which included data from this and four smaller studies (1519 patients overall), found no significant benefit of vasopressin compared with epinephrine among patients with asystole, or any other initial cardiac rhythm [44]. Based upon these data, the 2020 AHA guidelines removed vasopressin as an option for the treatment of patients with asystole [3,29]. A more recent placebo-controlled randomized trial of 501 patients with in-hospital cardiac arrest showed that vasopressin given with methylprednisolone after epinephrine administration was associated with a higher rate of return of spontaneous circulation (42 versus 33 percent) but no difference in 30-day mortality or neurologic recovery [75]. These new data are unlikely to modify the 2020 guideline recommendation regarding vasopressin. Asystole and atropine Due to a paucity of data supporting the use of atropine for asystole, the 2020 AHA guidelines no longer recommend the routine use of atropine for the management of asystole [3,29]. In a cohort study of 6419 patients with asystole, return of spontaneous circulation was significantly greater in patients receiving epinephrine and atropine (33 versus 19 percent with epinephrine alone) [65]. However, overall survival and 30-day neurologic outcomes were no different in the two groups. Registry data on over 20,000 in-hospital cardiac arrests with a non-shockable rhythm, collected between 2006 and 2015, showed no difference in survival before and after atropine was removed from the treatment protocol in the 2010 AHA guidelines [66]. INEFFECTIVE THERAPIES A number of therapies have been shown to be generally ineffective in patients who present with sudden cardiac arrest, and therefore are not part of routine management: Sodium bicarbonate, except in patients with hyperkalemia (calcium is first-line therapy) or tricyclic antidepressant overdose Fibrinolytic therapy Cardiac pacing for asystole or pulseless electrical activity (PEA) Magnesium sulfate, except in patients who have drug-induced QT prolongation and develop torsades de pointes (see 'Magnesium sulfate' above) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 14/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Vasopressin for SCA of any cause Atropine for PEA The relevant data regarding these therapies are presented separately. (See "Therapies of uncertain benefit in basic and advanced cardiac life support".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Basic and advanced cardiac life support in adults".) SUMMARY AND RECOMMENDATIONS In patients with sudden cardiac arrest (SCA), survival depends upon prompt resuscitative efforts, including excellent cardiopulmonary resuscitation (CPR) with chest compressions and, when indicated, defibrillation to reestablish organized electrical activity with a stable rhythm. Chest compressions should not be stopped until the defibrillator is fully charged and the patient is ready for defibrillation. (See 'Introduction' above.) Excellent CPR should be provided throughout the resuscitative effort until return of spontaneous circulation or termination of resuscitative efforts. Brief (10 second) pauses in CPR should only occur at two-minute intervals for rhythm analysis and defibrillation, if indicated. (See "Advanced cardiac life support (ACLS) in adults" and 'Introduction' above.) The only definitively effective treatment of ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) is defibrillation, as VF and VT rarely, if ever, terminate spontaneously or after delivery of an antiarrhythmic drug. The chances of successful defibrillation, and survival, are greatest when defibrillation is performed early after the onset of VF or VT. However, while awaiting the arrival and setup of a defibrillator, CPR should be performed. (See "Advanced cardiac life support (ACLS) in adults" and 'VF and pulseless VT' above and 'Defibrillation' above.) In shockable rhythms, the priority remains early defibrillation and excellent CPR. If return of spontaneous circulation is not achieved after the second defibrillation, epinephrine 1 mg IV/IO should be administered every three to five minutes while excellent CPR and defibrillation are continued. (See "Advanced cardiac life support (ACLS) in adults" and 'VF or VT arrest and vasopressors' above.) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 15/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate VF and VT often persist despite defibrillation, or recur promptly after successful defibrillation. In such cases, intravenous antiarrhythmic drug therapy should be used, with amiodarone or lidocaine being the preferred antiarrhythmic drugs. Notably in the management of cardiac arrest, amiodarone did not provide any benefit when assessing the clinically relevant outcome of neurologically favorable survival as compared with lidocaine or placebo. (See "Advanced cardiac life support (ACLS) in adults" and 'Antiarrhythmic drugs' above.) In patients with recurrent VF or pVT thought to be due to torsades de pointes with a prolonged QT interval, the administration of intravenous magnesium sulfate should be considered. (See 'Magnesium sulfate' above.) In contrast to SCA caused by VF or pVT, there is no role for defibrillation in the management of pulseless electrical activity (PEA) or asystole. While CPR is ongoing, epinephrine should be administered as soon as possible (and repeated every three to five minutes). However, before vascular access and epinephrine administration are considered, excellent CPR must be in progress, and epinephrine should only administered after early identification and management of other etiologies of non-shockable rhythms ( table 1). (See "Advanced cardiac life support (ACLS) in adults" and 'Pulseless electrical activity' above and 'Asystole' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Charles Pozner, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Herlitz J, Andersson E, B ng A, et al. Experiences from treatment of out-of-hospital cardiac arrest during 17 years in G teborg. Eur Heart J 2000; 21:1251. 2. Rea TD, Eisenberg MS, Becker LJ, et al. Temporal trends in sudden cardiac arrest: a 25-year emergency medical services perspective. Circulation 2003; 107:2780. 3. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S444. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 16/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 4. McMullan J, Gerecht R, Bonomo J, et al. Airway management and out-of-hospital cardiac arrest outcome in the CARES registry. Resuscitation 2014; 85:617. 5. Hasegawa K, Hiraide A, Chang Y, Brown DF. Association of prehospital advanced airway management with neurologic outcome and survival in patients with out-of-hospital cardiac arrest. JAMA 2013; 309:257. 6. Benoit JL, Gerecht RB, Steuerwald MT, McMullan JT. Endotracheal intubation versus supraglottic airway placement in out-of-hospital cardiac arrest: A meta-analysis. Resuscitation 2015; 93:20. 7. Winkle RA, Mead RH, Ruder MA, et al. Effect of duration of ventricular fibrillation on defibrillation efficacy in humans. Circulation 1990; 81:1477. 8. De Maio VJ, Stiell IG, Wells GA, et al. Optimal defibrillation response intervals for maximum out-of-hospital cardiac arrest survival rates. Ann Emerg Med 2003; 42:242. 9. Larsen MP, Eisenberg MS, Cummins RO, Hallstrom AP. Predicting survival from out-of- hospital cardiac arrest: a graphic model. Ann Emerg Med 1993; 22:1652. 10. Niemann JT, Cairns CB, Sharma J, Lewis RJ. Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock. Circulation 1992; 85:281. 11. Baum RS, Alvarez H 3rd, Cobb LA. Survival after resuscitation from out-of-hospital ventricular fibrillation. Circulation 1974; 50:1231. 12. Callans DJ. Out-of-hospital cardiac arrest the solution is shocking. N Engl J Med 2004; 351:632. 13. Thompson RJ, McCullough PA, Kahn JK, O'Neill WW. Prediction of death and neurologic outcome in the emergency department in out-of-hospital cardiac arrest survivors. Am J Cardiol 1998; 81:17. 14. Eftest l T, Sunde K, Steen PA. Effects of interrupting precordial compressions on the calculated probability of defibrillation success during out-of-hospital cardiac arrest. Circulation 2002; 105:2270. 15. Eftestol T, Sunde K, Ole Aase S, et al. Predicting outcome of defibrillation by spectral characterization and nonparametric classification of ventricular fibrillation in patients with out-of-hospital cardiac arrest. Circulation 2000; 102:1523. 16. Eftest l T, Wik L, Sunde K, Steen PA. Effects of cardiopulmonary resuscitation on predictors of ventricular fibrillation defibrillation success during out-of-hospital cardiac arrest. Circulation 2004; 110:10. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 17/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 17. Christenson J, Andrusiek D, Everson-Stewart S, et al. Chest compression fraction determines survival in patients with out-of-hospital ventricular fibrillation. Circulation 2009; 120:1241. 18. Yu T, Weil MH, Tang W, et al. Adverse outcomes of interrupted precordial compression during automated defibrillation. Circulation 2002; 106:368. 19. Steen S, Liao Q, Pierre L, et al. The critical importance of minimal delay between chest compressions and subsequent defibrillation: a haemodynamic explanation. Resuscitation 2003; 58:249. 20. Cobb LA, Fahrenbruch CE, Walsh TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999; 281:1182. 21. Wik L, Hansen TB, Fylling F, et al. Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation: a randomized trial. JAMA 2003; 289:1389. 22. Baker PW, Conway J, Cotton C, et al. Defibrillation or cardiopulmonary resuscitation first for patients with out-of-hospital cardiac arrests found by paramedics to be in ventricular fibrillation? A randomised control trial. Resuscitation 2008; 79:424. 23. Jacobs IG, Finn JC, Oxer HF, Jelinek GA. CPR before defibrillation in out-of-hospital cardiac arrest: a randomized trial. Emerg Med Australas 2005; 17:39. 24. Stiell IG, Nichol G, Leroux BG, et al. Early versus later rhythm analysis in patients with out- of-hospital cardiac arrest. N Engl J Med 2011; 365:787. 25. Patel KK, Spertus JA, Khariton Y, et al. Association Between Prompt Defibrillation and Epinephrine Treatment With Long-Term Survival After In-Hospital Cardiac Arrest. Circulation 2018; 137:2041. 26. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S729. 27. Field JM, Hazinski MF, Sayre MR, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S640. 28. Neumar RW, Shuster M, Callaway CW, et al. Part 1: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S315. 29. Panchal AR, Bartos JA, Caba as JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2020; 142:S366. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 18/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 30. Emmerson AC, Whitbread M, Fothergill RT. Double sequential defibrillation therapy for out- of-hospital cardiac arrests: The London experience. Resuscitation 2017; 117:97. 31. Cortez E, Krebs W, Davis J, et al. Use of double sequential external defibrillation for refractory ventricular fibrillation during out-of-hospital cardiac arrest. Resuscitation 2016; 108:82. 32. Soar J, Maconochie I, Wyckoff MH, et al. 2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces. Circulation 2019; 140:e826. 33. Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med 2018; 379:711. 34. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation 2011; 82:1138. 35. Perkins GD, Kenna C, Ji C, et al. The effects of adrenaline in out of hospital cardiac arrest with shockable and non-shockable rhythms: Findings from the PACA and PARAMEDIC-2 randomised controlled trials. Resuscitation 2019; 140:55. 36. Vargas M, Buonanno P, Iacovazzo C, Servillo G. Epinephrine for out of hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials. Resuscitation 2019; 136:54. 37. Hagihara A, Hasegawa M, Abe T, et al. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA 2012; 307:1161. 38. Dumas F, Bougouin W, Geri G, et al. Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol 2014; 64:2360. 39. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ 2016; 353:i1577. 40. Finn J, Jacobs I, Williams TA, et al. Adrenaline and vasopressin for cardiac arrest. Cochrane Database Syst Rev 2019; 1:CD003179. 41. Lindner KH, Dirks B, Strohmenger HU, et al. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997; 349:535. 42. Stiell IG, H bert PC, Wells GA, et al. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet 2001; 358:105. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 19/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 43. Wenzel V, Krismer AC, Arntz HR, et al. A comparison of vasopressin and epinephrine for out- of-hospital cardiopulmonary resuscitation. N Engl J Med 2004; 350:105. 44. Aung K, Htay T. Vasopressin for cardiac arrest: a systematic review and meta-analysis. Arch Intern Med 2005; 165:17. 45. Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med 2008; 359:21. 46. Grmec S, Lah K, Tusek-Bunc K. Difference in end-tidal CO2 between asphyxia cardiac arrest and ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest in the prehospital setting. Crit Care 2003; 7:R139. 47. Grmec S, Klemen P. Does the end-tidal carbon dioxide (EtCO2) concentration have prognostic value during out-of-hospital cardiac arrest? Eur J Emerg Med 2001; 8:263. 48. Kolar M, Krizmaric M, Klemen P, Grmec S. Partial pressure of end-tidal carbon dioxide successful predicts cardiopulmonary resuscitation in the field: a prospective observational study. Crit Care 2008; 12:R115. 49. Ali MU, Fitzpatrick-Lewis D, Kenny M, et al. Effectiveness of antiarrhythmic drugs for shockable cardiac arrest: A systematic review. Resuscitation 2018; 132:63. 50. Panchal AR, Berg KM, Kudenchuk PJ, et al. 2018 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Antiarrhythmic Drugs During and Immediately After Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2018; 138:e740. 51. Soar J, Donnino MW, Maconochie I, et al. 2018 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary. Resuscitation 2018; 133:194. 52. Daya MR, Leroux BG, Dorian P, et al. Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest. Circulation 2020; 141:188. 53. Mody P, Brown SP, Kudenchuk PJ, et al. Intraosseous versus intravenous access in patients with out-of-hospital cardiac arrest: Insights from the resuscitation outcomes consortium continuous chest compression trial. Resuscitation 2019; 134:69. 54. McLeod SL, Brignardello-Petersen R, Worster A, et al. Comparative effectiveness of antiarrhythmics for out-of-hospital cardiac arrest: A systematic review and network meta- analysis. Resuscitation 2017; 121:90. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 20/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 55. Dorian P, Cass D, Schwartz B, et al. Amiodarone as compared with lidocaine for shock- resistant ventricular fibrillation. N Engl J Med 2002; 346:884. 56. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999; 341:871. 57. Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. The Intravenous Amiodarone Multicenter Investigators Group. Circulation 1995; 92:3264. 58. Kowey PR, Levine JH, Herre JM, et al. Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter Investigators Group. Circulation 1995; 92:3255. 59. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, Lidocaine, or Placebo in Out-of- Hospital Cardiac Arrest. N Engl J Med 2016; 374:1711. 60. Kudenchuk PJ, Leroux BG, Daya M, et al. Antiarrhythmic Drugs for Nonshockable-Turned- Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo). Circulation 2017; 136:2119. 61. Tzivoni D, Banai S, Schuger C, et al. Treatment of torsade de pointes with magnesium sulfate. Circulation 1988; 77:392. 62. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 C versus 36 C after cardiac arrest. N Engl J Med 2013; 369:2197. 63. Kudenchuk PJ, Redshaw JD, Stubbs BA, et al. Impact of changes in resuscitation practice on survival and neurological outcome after out-of-hospital cardiac arrest resulting from nonshockable arrhythmias. Circulation 2012; 125:1787. 64. Hansen M, Schmicker RH, Newgard CD, et al. Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults. Circulation 2018; 137:2032. 65. Survey of Survivors After Out-of-hospital Cardiac Arrest in KANTO Area, Japan (SOS-KANTO) Study Group. Atropine sulfate for patients with out-of-hospital cardiac arrest due to asystole and pulseless electrical activity. Circ J 2011; 75:580. 66. Holmberg MJ, Moskowitz A, Wiberg S, et al. Guideline removal of atropine and survival after adult in-hospital cardiac arrest with a non-shockable rhythm. Resuscitation 2019; 137:69. 67. Hedges JR, Syverud SA, Dalsey WC, et al. Prehospital trial of emergency transcutaneous cardiac pacing. Circulation 1987; 76:1337. https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 21/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 68. Barthell E, Troiano P, Olson D, et al. Prehospital external cardiac pacing: a prospective, controlled clinical trial. Ann Emerg Med 1988; 17:1221. 69. Cummins RO, Graves JR, Larsen MP, et al. Out-of-hospital transcutaneous pacing by emergency medical technicians in patients with asystolic cardiac arrest. N Engl J Med 1993; 328:1377. 70. Ornato JP, Peberdy MA. The mystery of bradyasystole during cardiac arrest. Ann Emerg Med 1996; 27:576. 71. Quan L, Graves JR, Kinder DR, et al. Transcutaneous cardiac pacing in the treatment of out- of-hospital pediatric cardiac arrests. Ann Emerg Med 1992; 21:905. 72. Okubo M, Komukai S, Callaway CW, Izawa J. Association of Timing of Epinephrine Administration With Outcomes in Adults With Out-of-Hospital Cardiac Arrest. JAMA Netw Open 2021; 4:e2120176. 73. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. N Engl J Med 1992; 327:1051. 74. Gueugniaud PY, Mols P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group. N Engl J Med 1998; 339:1595. 75. Andersen LW, Isbye D, Kj rgaard J, et al. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2021; 326:1586. Topic 1028 Version 43.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 22/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate GRAPHICS Adult cardiac arrest algorithm https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 23/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 24/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 25/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Continuous electrocardigraphic (ECG) strip during an episode of ventricular fibrillation (VF) that progresses to fine VF and then asystole At the onset of ventricular fibrillation (VF), the QRS complexes are regular, widened, and of tall amplitude, suggesting a more organized ventricular tachyarrhythmia. Over a brief period of time, the rhythm becomes more disorganized with high amplitude fibrillatory waves; this is coarse VF. After a longer period of time, the fibrillatory waves become fine, culminating in asystole. Graphic 67777 Version 3.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 26/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Defibrillation waveforms in implantable cardioverter- defibrillators Figure A shows the monophasic, exponentially decaying pulse was the waveform used in the first generation of ICDs. Figure B shows the biphasic waveform, which is generated with a single capacitor by switching the output polarity during discharge. Each division is 2 milliseconds. ICD: implantable cardioverter-defibrillator. Graphic 51842 Version 3.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 27/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Treatable conditions associated with cardiac arrest Condition Common associated clinical settings Acidosis Diabetes, diarrhea, drug overdose, renal dysfunction, sepsis, shock Anemia Gastrointestinal bleeding, nutritional deficiencies, recent trauma Cardiac Post-cardiac surgery, malignancy, post-myocardial infarction, pericarditis, trauma tamponade Hyperkalemia Drug overdose, renal dysfunction, hemolysis, excessive potassium intake, rhabdomyolysis, major soft tissue injury, tumor lysis syndrome Hypokalemia* Alcohol abuse, diabetes mellitus, diuretics, drug overdose, profound gastrointestinal losses Hypothermia Alcohol intoxication, significant burns, drowning, drug overdose, elder patient, endocrine disease, environmental exposure, spinal cord disease, trauma Hypovolemia Significant burns, diabetes, gastrointestinal losses, hemorrhage, malignancy, sepsis, trauma Hypoxia Upper airway obstruction, hypoventilation (CNS dysfunction, neuromuscular disease), pulmonary disease Myocardial infarction Cardiac arrest Poisoning History of alcohol or drug abuse, altered mental status, classic toxidrome (eg, sympathomimetic), occupational exposure, psychiatric disease Pulmonary embolism Immobilized patient, recent surgical procedure (eg, orthopedic), peripartum, risk factors for thromboembolic disease, recent trauma, presentation consistent with acute pulmonary embolism Tension Central venous catheter, mechanical ventilation, pulmonary disease (eg, asthma, pneumothorax chronic obstructive pulmonary disease), thoracentesis, thoracic trauma CNS: central nervous system. Hypomagnesemia should be assumed in the setting of hypokalemia, and both should be treated. Adapted from: Eisenberg MS, Mengert TJ. Cardiac resuscitation. N Engl J Med 2001; 344:1304. Graphic 52416 Version 8.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 28/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Contributor Disclosures Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Richard L Page, MD No relevant financial relationship(s) with ineligible companies to disclose. Ron M Walls, MD, FRCPC, FAAEM Other Financial Interest: Airway Management Education Center [Health care provider education and resources]; First Airway [Health care provider education and resources]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 29/29 |
7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. The benefits and risks of aerobic exercise : Douglas M Peterson, MD, MBA, FACP, FACSM : Mark D Aronson, MD, Francis G O'Connor, MD, MPH, FACSM, FAMSSM : Sara Swenson, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 26, 2023. INTRODUCTION Physical inactivity is a major health problem worldwide, particularly in developed countries. The medical literature clearly demonstrates beneficial effects of physical activity on several health outcomes, including cardiovascular disease and all-cause mortality [1]. Although there are risks associated with exercise in some patients, the benefits outweigh the risks in most patients. This topic will provide an overview of the benefits and risks of aerobic exercise in adults. The benefits and risks of strength training in adults, exercise physiology and exercise recommendations for children and adolescents, as well as for specific conditions, are discussed in detail elsewhere. (See "Strength training for health in adults: Terminology, principles, benefits, and risks" and "Exercise physiology" and "Physical activity and strength training in children and adolescents: An overview" and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "Obesity in adults: Role of physical activity and exercise" and "Exercise in the treatment and prevention of hypertension" and "Exercise guidance in adults with diabetes mellitus" and "Exercise during pregnancy and the postpartum period".) The medical evaluation of adults prior to beginning an exercise program and the exercise prescription are presented separately. (See "Exercise for adults: Terminology, patient assessment, and medical clearance", section on 'Medical assessment and clearance for exercise' and "Exercise prescription and guidance for adults", section on 'Prescribing an exercise program'.) https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 1/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate DEFINITIONS Physical activity and exercise are not interchangeable terms [2]. Physical activity is defined as bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above the basal level. Any type of physical activity can be included (occupational, household, leisure time, and transportation) and categorized by level of intensity. (See "Exercise for adults: Terminology, patient assessment, and medical clearance", section on 'Determining exercise intensity'.) The term "exercise" refers to a form of physical activity that is planned, structured, repetitive, and purposeful with a main objective of improvement or maintenance of one or more components of physical fitness. PHYSICAL INACTIVITY AND HEALTH Physical inactivity is prevalent and associated with poor health outcomes. Despite the widespread prevalence of physical inactivity, its associated health risks, and the potential of increasing physical activity to improve health outcomes, clinicians do not routinely screen patients for physical inactivity or provide adequate counseling. In developed countries, only 13 to 34 percent of primary care patients reported receiving advice on physical activity from their primary care clinician [3-5]. Prevalence Worldwide, one out of every four adults is physically inactive, a proportion that is increasing [6,7]. Physical inactivity is particularly prevalent in more developed countries and among females, older persons, and those with lower incomes. In addition to lack of regular exercise, the percentage of time spent in sedentary behaviors (watching television or in front of a computer) is increasing [8-11]. In the United States, approximately one quarter of adults are sedentary, sitting for more than eight hours per day [12]. In addition, the majority of American adults do not meet national guidelines, with only 19 percent of females and 26 percent of males meeting criteria for sufficient physical activity [13,14]. Health effects of physical inactivity/sedentary behavior In large prospective cohort studies from several countries, sedentary behavior is associated with a variety of poor health outcomes, including increased mortality [8,15-19]. One study calculated the global attributable risk for premature mortality and estimated that physical inactivity caused 9 percent of premature deaths worldwide in 2008 [20]. A 10 percent reduction in inactivity https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 2/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate could avert 533,000 deaths every year. Independent of physical activity levels, sedentary behavior is associated with negative health outcomes. As an example, in a 2015 meta- analysis, prolonged sedentary time was independently correlated with an increase in all- cause mortality, cardiovascular disease incidence and mortality, diabetes incidence, and cancer incidence and mortality at all levels of physical activity [21]. (See 'Mortality' below.) Health effects of extended sitting time Extended sitting time appears to be an independent risk factor for mortality [21-26]. In addition to the total daily duration of sitting, the risk of mortality may be higher among those who sit for prolonged, uninterrupted periods as compared with those who sit for shorter, interrupted periods [22]. Prolonged sitting/sedentary time has also been associated with an increased risk for diabetes, cardiovascular disease, and cancer [21,23]. Replacing sitting time with physical activity has health benefits. As examples: In a prospective study including over 150,000 adults aged 59 to 82 years, replacing sitting time with exercise was associated with a decrease in all-cause mortality [27]. For inactive adults, replacing one hour of sitting time with a variety of nonexercise activities (eg, household chores, lawn and garden work, and daily walking outside of exercise) was also associated with decreased all-cause mortality. In a 2016 meta-analysis of 16 studies involving over one million individuals, daily sitting time of over eight hours per day was associated with increased all-cause mortality [26]. However, this increased risk was no longer evident among those individuals who engaged in moderate-intensity activity (35.5 metabolic equivalents [MET] for task hours per week), approximately 60 to 75 minutes per day or more. In a prospective study of 150,000 Australian adults aged 45 and older, an association between greater sitting time and increased mortality was found among inactive individuals. However, even among individuals with the most sitting time, the association with increased mortality was eliminated with the addition of 300 minutes per week of moderate- to high-intensity physical activity [28]. Studies evaluating interventions to reduce sitting time have reported mixed results. A 2016 systematic review concluded that there was some evidence that sit-stand desks decrease sitting time but found inconsistent evidence for interventions such as counseling or computer prompts [29]. BENEFITS OF EXERCISE https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 3/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Exercise favorably impacts multiple systems and health outcomes ( table 1). A graded relationship between exercise and the development of common chronic conditions (including cardiovascular disease, diabetes mellitus, chronic lung disease, chronic kidney disease, and some cancers) has been observed, such that greater exercise in midlife was associated with compression of morbidity in later years with a decreased risk of multiple chronic conditions in the last five years of life [30]. Mortality Most data on the benefits of exercise come from observational studies. There are no high-quality, long-term, randomized trials of exercise for prevention of cardiovascular disease or death in a healthy population. Large observational studies suggest that regular exercise reduces risk of all-cause and disease-specific mortality for most individuals, including males and females, younger and older populations, and those with hypertension [1,13,31-42]. This risk reduction is seen with recreational and non-recreational physical activity and in countries with low, middle, and high incomes. The beneficial effects of exercise appear to be dose-dependent [43,44]. However, persons who engage in as little as one to two 75-minute sessions of exercise per week ( weekend warriors ) appear to have decreased all-cause, cardiovascular, and cancer-related mortality compared with sedentary individuals [45]. The evidence also suggests that the benefits of exercise on reducing mortality may plateau after a certain activity level [46]. Doses above 100 minutes/day for moderate-intensity physical activity in healthy individuals do not appear to be associated with additional reductions in mortality rates [47]. Representative studies include: In a retrospective cohort study, physical activity habits were analyzed in 10,269 Harvard College alumni over 12 years [33]. Males who engaged in moderately vigorous sports activity had a 23 percent lower risk of death than those who were less active. The improvement in survival with exercise was equivalent and additive to other lifestyle measures such as smoking cessation, control of hypertension, and avoidance of obesity ( figure 1). This highlights the importance of exercise given that the specific benefits of regular exercise persist despite individuals attempting to improve multiple lifestyle habits concurrently. Moderate levels of physical activity appear to confer a significant health benefit, although greater amounts of activity afford greater protection from premature death ( figure 2) [36,43]. Progressing from lower to higher levels of physical activity has been shown to reduce overall mortality [33,35,37,39]. Vigorous exercise (at least 20 minutes three times a week) combined with regular exercise (at least 30 minutes of moderate activity most days https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 4/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate of the week) was associated with a 50 percent decreased mortality risk in an observational study involving over 250,000 adults aged 50 to 71 years [35]. Data from the Framingham Heart Study show that moderate and high, compared with low, physical activity levels increase life expectancy for males at age 50 by 1.3 and 3.7 years, respectively; results were similar for females (1.5 and 3.5 years) [37]. Total daily activity energy expenditure may correlate more strongly with mortality benefit than self-reported exercise intensity. Comparing mortality among individuals in the highest versus lowest tertile for activity energy expenditure in a study of 302 high-functioning volunteers (age 70 to 82 years), the hazard ratio (HR) for mortality over six years was 0.31 (95% CI 0.14-0.69); self-reported exercise intensity did not differ significantly across the energy tertiles, although frequency of paid employment and stair climbing was greater in the higher-energy groups [38]. In an observational cohort study involving 336,560 participants stratified by high-sensitivity C-reactive protein (CRP) level, patients with regular vigorous physical activity had lower mortality compared with those who had no regular physical activity (HR 0.75; 95% CI 0.60- 0.93) [40]. The reduction in mortality was less pronounced among patients with regular but less vigorous physical activity (HR 0.85; 95% CI 0.72-0.99). Similar trends were noted for cardiovascular and cancer-related mortality in these groups. In a longitudinal study of almost 4000 cognitively frail older adults aged 60 and older, those who were physically active had a 36 percent reduction in mortality compared with those who were inactive (95% CI 21-47) [48]. Cardiovascular disease A number of studies have shown a strong inverse relationship between habitual exercise and the risk of coronary disease, cardiac events, and cardiovascular death for both primary and secondary prevention ( figure 3) [1,49-52]. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease".) Observational studies suggest that exercise may also have the following beneficial effects: Aerobic training induces beneficial effects on lipoproteins (eg, decrease in very low-density lipoprotein, increase in high-density lipoprotein), body composition, and aerobic capacity, as well as improves hemostatic factors associated with thrombosis. (See "Effects of exercise on lipoproteins and hemostatic factors".) Regular physical activity is associated with decreased levels of markers of inflammation (CRP and interleukin [IL]-6) [53,54]. (See "C-reactive protein in cardiovascular disease" and https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 5/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate "Overview of established risk factors for cardiovascular disease", section on 'Inflammation'.) Long-term aerobic exercise has a beneficial effect upon systemic blood pressure [55,56]. (See "Exercise in the treatment and prevention of hypertension".) Exercise may reduce the risk of stroke [57-59]. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "Overview of secondary prevention of ischemic stroke".) Diabetes Aerobic exercise may improve glycemic control and insulin sensitivity and may prevent the development of type 2 diabetes in high-risk groups. (See "Exercise guidance in adults with diabetes mellitus" and "Prevention of type 2 diabetes mellitus", section on 'Exercise'.) Cancer prevention and treatment Exercise may provide modest protection against breast, intestinal, bladder, kidney, lung, stomach, esophageal, prostate, endometrial, and pancreatic cancers [13,52,60,61]. Substantial observational data suggest that regular physical activity appears to be associated with protection from both proximal and distal colorectal cancer [62-64]. In a meta-analysis of 21 studies, there was a significant 27 percent reduced risk of proximal colon cancer when comparing the most versus the least active individuals (RR 0.73, 95% CI 0.66- 0.81) [63]. An almost identical result was found for distal colon cancer (RR 0.74, 95% CI 0.68- 0.80). (See "Overview of cancer prevention", section on 'Physical activity'.) For patients treated for cancer, observational studies have reported a link between survival and exercise, with most of the data coming from survivors with breast, colorectal, or prostate cancers. In addition, interventional studies have shown a direct effect of exercise on other outcomes, including fatigue and quality of life. (See "The roles of diet, physical activity, and body weight in cancer survivors" and "Cancer-related fatigue: Treatment", section on 'Exercise'.) Obesity Preventing or treating obesity may lead to significant health benefits over the course of a lifetime. Compared with a weight loss diet alone, diet coupled with either exercise or exercise and resistance training is associated with a greater reduction in body fat and enhanced preservation of body lean mass, compared with weight loss diet alone. Aerobic exercise and resistance training, even in the absence of caloric restriction, may result in weight loss and a reduction in body fat [65-67]. Long-term (20-year) follow-up of participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study found that habitual activity was associated with less weight gain at middle age, especially in females [68]. However, a 15-year longitudinal study in postmenopausal females found that a minimum of 60 minutes a day of moderate intensity activity, sustained over years, was necessary to prevent weight gain https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 6/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 2 and was effective only in those whose initial body mass index (BMI) was <25 kg/m (normal or underweight) [69]. (See "Obesity in adults: Role of physical activity and exercise".) Other health outcomes Osteoporosis Weightbearing exercise is associated with an increase in bone mineral density in males and females. In addition, among patients with osteoporosis, exercise is associated with a decreased risk of hip fractures. (See "Prevention of osteoporosis", section on 'Physical activity' and "Overview of the management of osteoporosis in postmenopausal women", section on 'Exercise'.) Smoking cessation Vigorous exercise modestly facilitates short- and long-term smoking cessation in females when combined with a cognitive-behavioral smoking cessation program [70]. Vigorous exercise also delays weight gain following smoking cessation. (See "Behavioral approaches to smoking cessation".) Gallstones Physical activity is associated with a decreased risk of symptomatic cholelithiasis. (See "Gallstones: Epidemiology, risk factors and prevention", section on 'Physical activity'.) Cognition Exercise has been associated with improved cognitive function in both young and older adults [71-73]. However, it is unclear whether physical activity prevents dementia and cognitive decline [74]. (See "Risk factors for cognitive decline and dementia", section on 'Lifestyle and activity' and "Prevention of dementia", section on 'Lifestyle and activity'.) Psychological Regular exercise is associated with improved sleep, reduced stress and anxiety, and a lower risk of depression [13,75-77]. In one randomized trial, higher exercise energy expenditure led to greater improvement in measures of both physical and psychological quality of life [78]. (See "Insufficient sleep: Evaluation and management", section on 'Management' and "Complementary and alternative treatments for anxiety symptoms and disorders: Physical, cognitive, and spiritual interventions", section on 'Physical exercise'.) Kidney function Regular exercise may reduce the decline in kidney function seen with normal aging (see "The aging kidney", section on 'GFR declines with normal aging'). In a randomized trial including over 1600 sedentary older adults, participation in a regular, moderate-intensity exercise program reduced the degree of decline in kidney function, 2 measured by eGFR (0.96 mL/min/1.73 m , 95% CI 0.02-1.91), as well the risk of rapid cystatin C decline in kidney function (odds ratio [OR] 0.79, 95% CI, 0.65-0.97) at two years compared with receiving only an education intervention [79]. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 7/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Additionally, regular physical activity is associated with fewer falls and fall-related injuries in older adults and, in pregnant individuals, a reduced risk of excessive weight gain, gestational diabetes, and post-partum depression [13]. (See "Falls: Prevention in community-dwelling older persons", section on 'Exercise' and "Gestational weight gain" and "Gestational diabetes mellitus: Glucose management and maternal prognosis", section on 'Exercise' and "Exercise during pregnancy and the postpartum period".) RISKS OF EXERCISE The benefits of physical activity far outweigh the possible associated risks in the majority of patients [2]. Musculoskeletal injury is the most common risk of exercise. More serious but much less common risks include arrhythmia, sudden cardiac arrest, and myocardial infarction (MI). One study analyzed available data from several exercise trials in diverse patient populations (mostly sedentary at baseline and some with identified cardiovascular risk factors) and found that exercise was associated with an adverse change in one or more metabolic risk factors for cardiovascular disease in 8 to 13 percent of participants, while a similar proportion of participants experienced an unusually strong positive change in these risk factors [80]. Based upon measurements in a small sample of controls, the authors felt that these changes were larger than would be expected just with random variation; however, random variation still appears to be a likely explanation for the results. The study did not look at actual cardiovascular event rates. Any potential risks of routine exercise do not outweigh its benefits, in the absence of a contraindication to exercise. (See "Exercise prescription and guidance for adults", section on 'Contraindications to exercise'.) Musculoskeletal injury Those who engage in sports activities run a higher risk of incurring minor injury; however, people who do not participate in regular exercise are more likely to incur more severe injuries when engaging in such activity [81]. Acute strains and tears, inflammation of various types, chronic strain, stress fractures, traumatic fractures, nerve palsies, tendonitis, and bursitis all may occur during or as result of physical activity [82,83]. Musculoskeletal injuries vary based on a variety of factors, including age (child, adolescent, adult, older adult), type of activity (eg, contact sports, high-impact exercises, walking), and intensity. Many of the musculoskeletal injuries are secondary to overuse [84,85]. Two of the most common risk factors for injury among runners, for example, are longer running distances and history of https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 8/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate previous injury [85]. (See "Musculoskeletal injury in children and skeletally immature adolescents: Overview of treatment principles for nonoperative injuries" and "Overview of running injuries of the lower extremity".) Arrhythmia There is an increased risk of arrhythmia during exercise in patients with underlying heart disease or a prior history of arrhythmia. Exercise training may reduce atrial and ventricular arrhythmia risk by increasing myocardial oxygen supply and reducing sympathetic nervous system activity. (See "Athletes with arrhythmias: Clinical manifestations and diagnostic evaluation" and "Athletes: Overview of sudden cardiac death risk and sport participation".) A separate issue, ventricular and atrial arrhythmias occurring during exercise testing, is discussed elsewhere. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Ventricular arrhythmias' and "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Atrial arrhythmias'.) Sudden cardiac death Sudden cardiac death (SCD) is rare but may occur during physical or sexual activity [86,87]. The risk of SCD in athletes is discussed separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation".) The increase in risk is seen in both males and females. In the Physicians' Health Study of 21,481 males followed for 12 years, the absolute risk of SCD during any one episode of vigorous exercise was low (one death per 1.51 million episodes of exercise) [88]. In the Nurses' Health Study of 69,693 females, the absolute risk was even lower, with one death per 36.5 million hours of exertion [89]. The risk of cardiac arrest is less or may not be increased at all if there is habitual, heavy leisure-time physical activity, as noted in both the Physicians' Health Study and the Nurses' Health Study [88,89]. Mechanisms of SCD in those who exercise include coronary artery disease, arrhythmias (especially ventricular tachycardia and ventricular fibrillation), structural heart disease, and myocarditis [90]. Causes of SCD in people who exercise can be divided according to age [86]. Among those over age 35 years, SCD is generally a result of atherosclerotic coronary artery disease; among younger individuals, it is more likely due to congenital abnormalities such as hypertrophic cardiomyopathy, coronary anomalies, or myocarditis. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Exercise'.) Because the increase in risk of SCD during or just after activity is low, the long-term health benefits of exercise outweigh the risks in patient with and without established heart disease [91]. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 9/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Myocardial infarction Physical or sexual activity is associated with a temporary increase in the risk of having an MI, particularly among those who exercise infrequently and have multiple cardiac risk factors [87,91,92]. In a study of 1194 patients who completed a survey within two weeks of having an MI, physical exertion at the onset of infarction was reported in 7.1 percent of the case patients compared with 3.9 percent of matched controls prior to the onset of the control event [92]. The adjusted relative risk (RR) of having engaged in strenuous physical activity at the onset of the MI was 2.1; the RR was much higher in patients who performed regular exercise less than four times per week and compared with those who exercised four or more times per week (RR 6.9 versus 1.3). Although patients with coronary disease are more likely to have an MI at the time they are participating in strenuous exercise than when they are not, patients with coronary disease who exercise are overall less likely to have an MI than those with coronary disease who do not exercise. A 12-year prospective study of 2400 males found that those who were in the highest third of vigorous physical activity, compared with the lowest third, experienced a decreased risk of MI, regardless of the presence of symptomatic, asymptomatic (electrocardiogram [ECG] changes consistent with ischemia), or no coronary heart disease at baseline (hazard ratio [HR] 0.71, 0.42, and 0.60, respectively) [93]. Rhabdomyolysis Subclinical myoglobinemia, myoglobinuria, and elevation of creatine kinase (CK) are common following physical exertion [94]. The CK level can rise several-fold, particularly after intense exercise for extended periods of time (eg, marathon running). Rhabdomyolysis may occur following extreme exertion in individuals with normal muscles when the energy supply to muscle is insufficient to meet demands. Severe complications of rhabdomyolysis include renal failure, electrolyte abnormalities (eg, hyperkalemia, metabolic acidosis), and compartment syndrome. (See "Rhabdomyolysis: Clinical manifestations and diagnosis".) Massive rhabdomyolysis may arise with marked physical exertion, particularly when the following risk factors are present [95,96]: The individual is physically untrained. Exertion occurs in extremely hot, humid conditions. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults".) Normal heat loss through sweating is impaired, such as via the use of anticholinergic medications or heavy football equipment. An individual with a sickle cell syndrome exercises at high altitude, a setting in which the decreased partial pressure of oxygen causes erythrocyte sickling with subsequent vascular https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 10/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate occlusion and muscle ischemia. (See "Overview of compound sickle cell syndromes".) Electrolytes abnormalities are present, particularly hypokalemia, which can be partly caused by potassium loss from sweating. (See "Rhabdomyolysis: Epidemiology and etiology", section on 'Electrolyte disorders'.) Metabolic or inflammatory myopathies are present. (See "Approach to the metabolic myopathies" and "Clinical manifestations of dermatomyositis and polymyositis in adults".) However, rhabdomyolysis can also occur in trained individuals following physical exertion in the absence of these risk factors [97,98]. Bronchoconstriction Exercise-induced bronchoconstriction occurs in the majority of patients with current symptomatic asthma [99]. The magnitude of exercise-induced bronchoconstriction is correlated with the degree of airway hyperresponsiveness. Improving a patient's cardiovascular fitness reduces the minute ventilation required for a given level of exercise, thereby decreasing the stimulus for bronchoconstriction. Thus, regular, long- term exercise may be helpful in preventing the onset of exercise-induced bronchoconstriction. (See "Exercise-induced bronchoconstriction".) Other effects Hyperthermia, hypothermia, and dehydration are potential preventable risks of physical activity. Heat-related risks range from mild fatigue to death [100]. Dehydration may be a problem itself or can be related to hyperthermia. Intense exercise can lead to amenorrhea and infertility, particularly in females with low body weight. The "female athlete triad" consists of disordered eating, amenorrhea, and osteoporosis. This is commonly seen in younger individuals, especially those who exercise regularly and intensely. (See "Functional hypothalamic amenorrhea: Pathophysiology and clinical manifestations".) Urticaria and anaphylaxis can rarely occur with exercise. (See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis".) Exercise-associated hyponatremia primarily occurs in athletes participating in aerobic (endurance) events, such as marathons (42.2 km), triathlons (3.8 km swim, 180 km cycling, and 42.2 km running), and ultra-distance (100 km) races. (See "Exercise-associated hyponatremia".) Exercise has acute and chronic effects on drug pharmacokinetics [101], but the clinical implications of these changes are unclear. Pending additional information, these observations should not be used to dissuade patients from exercising. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 11/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Exercise in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Exercise and movement (The Basics)" and "Patient education: Physical activity for people with arthritis (The Basics)" and "Patient education: Rhabdomyolysis (The Basics)") Beyond the Basics topics (See "Patient education: Exercise (Beyond the Basics)" and "Patient education: Arthritis and exercise (Beyond the Basics)".) SUMMARY AND RECOMMENDATIONS Health effects of physical inactivity and sedentary behavior Physical inactivity is a major health problem worldwide, particularly in developed countries and among females, older persons, and those with lower incomes. (See 'Physical inactivity and health' above.) Sedentary behavior is prevalent and is also associated with a variety of poor health outcomes, including increased mortality and increased risk for diabetes and cardiovascular disease. Some of these risks do not appear to be mitigated by participation in physical activity, although adding moderate- to vigorous-intensity physical activity may reduce the association with increased all-cause mortality. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 12/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Health benefits of exercise Moderate and/or vigorous exercise is associated with several beneficial health outcomes, including improved bone health and decreased risk of obesity, coronary heart disease, stroke, certain types of cancer, and all-cause mortality ( table 1 and figure 1 and figure 2). Exercise may also increase the likelihood of stopping tobacco use, improve cognitive function, decrease the risk of falls and fall related injuries in older adults, and reduce stress, anxiety, and depression. (See 'Benefits of exercise' above.) Potential risks of exercise Musculoskeletal injury is the most common risk of exercise. More serious, but less common, risks include arrhythmia, sudden cardiac arrest, and myocardial infarction (MI). However, the benefits of exercise outweigh the potential risks. (See 'Risks of exercise' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kodama S, Saito K, Tanaka S, et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA 2009; 301:2024. 2. US Department of Health and Human Services. 2008 physical activity guidelines for America ns. Hyattsville, MD: US Department of Health and Human Services 2008. Available at: www.h ealth.gov/PAGuidelines/guidelines/default.aspx (Accessed on October 17, 2011). 3. Wee CC, McCarthy EP, Davis RB, Phillips RS. Physician counseling about exercise. JAMA 1999; 282:1583. 4. Eakin E, Brown W, Schofield G, et al. General practitioner advice on physical activity who gets it? Am J Health Promot 2007; 21:225. 5. Croteau K, Schofield G, McLean G. Physical activity advice in the primary care setting: results of a population study in New Zealand. Aust N Z J Public Health 2006; 30:262. 6. Guthold R, Stevens GA, Riley LM, Bull FC. Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled analysis of 358 population-based surveys with 1 9 million participants. Lancet Glob Health 2018; 6:e1077. 7. Dumith SC, Hallal PC, Reis RS, Kohl HW 3rd. Worldwide prevalence of physical inactivity and its association with human development index in 76 countries. Prev Med 2011; 53:24. 8. Owen N, Sparling PB, Healy GN, et al. Sedentary behavior: emerging evidence for a new health risk. Mayo Clin Proc 2010; 85:1138. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 13/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 9. Rey-L pez JP, Vicente-Rodriguez G, Ortega FB, et al. Sedentary patterns and media availability in European adolescents: The HELENA study. Prev Med 2010; 51:50. 10. Yang L, Cao C, Kantor ED, et al. Trends in Sedentary Behavior Among the US Population, 2001-2016. JAMA 2019; 321:1587. 11. Du Y, Liu B, Sun Y, et al. Trends in Adherence to the Physical Activity Guidelines for Americans for Aerobic Activity and Time Spent on Sedentary Behavior Among US Adults, 2007 to 2016. JAMA Netw Open 2019; 2:e197597. 12. Ussery EN, Fulton JE, Galuska DA, et al. Joint Prevalence of Sitting Time and Leisure-Time Physical Activity Among US Adults, 2015-2016. JAMA 2018; 320:2036. 13. Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA 2018; 320:2020. 14. Bull FC, Al-Ansari SS, Biddle S, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 2020; 54:1451. 15. Proper KI, Singh AS, van Mechelen W, Chinapaw MJ. Sedentary behaviors and health outcomes among adults: a systematic review of prospective studies. Am J Prev Med 2011; 40:174. 16. Pavey TG, Peeters GG, Brown WJ. Sitting-time and 9-year all-cause mortality in older women. Br J Sports Med 2015; 49:95. 17. Le n-Mu oz LM, Mart nez-G mez D, Balboa-Castillo T, et al. Continued sedentariness, change in sitting time, and mortality in older adults. Med Sci Sports Exerc 2013; 45:1501. 18. Matthews CE, Cohen SS, Fowke JH, et al. Physical activity, sedentary behavior, and cause- specific mortality in black and white adults in the Southern Community Cohort Study. Am J Epidemiol 2014; 180:394. 19. Patel AV, Maliniak ML, Rees-Punia E, et al. Prolonged Leisure Time Spent Sitting in Relation to Cause-Specific Mortality in a Large US Cohort. Am J Epidemiol 2018; 187:2151. 20. Lee IM, Shiroma EJ, Lobelo F, et al. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012; 380:219. 21. Biswas A, Oh PI, Faulkner GE, et al. Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis. Ann Intern Med 2015; 162:123. 22. Diaz KM, Howard VJ, Hutto B, et al. Patterns of Sedentary Behavior and Mortality in U.S. Middle-Aged and Older Adults: A National Cohort Study. Ann Intern Med 2017; 167:465. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 14/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 23. van der Ploeg HP, Chey T, Korda RJ, et al. Sitting time and all-cause mortality risk in 222 497 Australian adults. Arch Intern Med 2012; 172:494. 24. Gennuso KP, Gangnon RE, Matthews CE, et al. Sedentary behavior, physical activity, and markers of health in older adults. Med Sci Sports Exerc 2013; 45:1493. 25. Chau JY, Grunseit A, Midthjell K, et al. Sedentary behaviour and risk of mortality from all- causes and cardiometabolic diseases in adults: evidence from the HUNT3 population cohort. Br J Sports Med 2015; 49:737. 26. Ekelund U, Steene-Johannessen J, Brown WJ, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta- analysis of data from more than 1 million men and women. Lancet 2016; 388:1302. 27. Matthews CE, Moore SC, Sampson J, et al. Mortality Benefits for Replacing Sitting Time with Different Physical Activities. Med Sci Sports Exerc 2015; 47:1833. 28. Stamatakis E, Gale J, Bauman A, et al. Sitting Time, Physical Activity, and Risk of Mortality in Adults. J Am Coll Cardiol 2019; 73:2062. 29. Shrestha N, Kukkonen-Harjula KT, Verbeek JH, et al. Workplace interventions for reducing sitting at work. Cochrane Database Syst Rev 2016; 3:CD010912. 30. Willis BL, Gao A, Leonard D, et al. Midlife fitness and the development of chronic conditions in later life. Arch Intern Med 2012; 172:1333. 31. Lear SA, Hu W, Rangarajan S, et al. The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low- |
Basics topics (see "Patient education: Exercise and movement (The Basics)" and "Patient education: Physical activity for people with arthritis (The Basics)" and "Patient education: Rhabdomyolysis (The Basics)") Beyond the Basics topics (See "Patient education: Exercise (Beyond the Basics)" and "Patient education: Arthritis and exercise (Beyond the Basics)".) SUMMARY AND RECOMMENDATIONS Health effects of physical inactivity and sedentary behavior Physical inactivity is a major health problem worldwide, particularly in developed countries and among females, older persons, and those with lower incomes. (See 'Physical inactivity and health' above.) Sedentary behavior is prevalent and is also associated with a variety of poor health outcomes, including increased mortality and increased risk for diabetes and cardiovascular disease. Some of these risks do not appear to be mitigated by participation in physical activity, although adding moderate- to vigorous-intensity physical activity may reduce the association with increased all-cause mortality. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 12/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Health benefits of exercise Moderate and/or vigorous exercise is associated with several beneficial health outcomes, including improved bone health and decreased risk of obesity, coronary heart disease, stroke, certain types of cancer, and all-cause mortality ( table 1 and figure 1 and figure 2). Exercise may also increase the likelihood of stopping tobacco use, improve cognitive function, decrease the risk of falls and fall related injuries in older adults, and reduce stress, anxiety, and depression. (See 'Benefits of exercise' above.) Potential risks of exercise Musculoskeletal injury is the most common risk of exercise. More serious, but less common, risks include arrhythmia, sudden cardiac arrest, and myocardial infarction (MI). However, the benefits of exercise outweigh the potential risks. (See 'Risks of exercise' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kodama S, Saito K, Tanaka S, et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA 2009; 301:2024. 2. US Department of Health and Human Services. 2008 physical activity guidelines for America ns. Hyattsville, MD: US Department of Health and Human Services 2008. Available at: www.h ealth.gov/PAGuidelines/guidelines/default.aspx (Accessed on October 17, 2011). 3. Wee CC, McCarthy EP, Davis RB, Phillips RS. Physician counseling about exercise. JAMA 1999; 282:1583. 4. Eakin E, Brown W, Schofield G, et al. General practitioner advice on physical activity who gets it? Am J Health Promot 2007; 21:225. 5. Croteau K, Schofield G, McLean G. Physical activity advice in the primary care setting: results of a population study in New Zealand. Aust N Z J Public Health 2006; 30:262. 6. Guthold R, Stevens GA, Riley LM, Bull FC. Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled analysis of 358 population-based surveys with 1 9 million participants. Lancet Glob Health 2018; 6:e1077. 7. Dumith SC, Hallal PC, Reis RS, Kohl HW 3rd. Worldwide prevalence of physical inactivity and its association with human development index in 76 countries. Prev Med 2011; 53:24. 8. Owen N, Sparling PB, Healy GN, et al. Sedentary behavior: emerging evidence for a new health risk. Mayo Clin Proc 2010; 85:1138. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 13/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 9. Rey-L pez JP, Vicente-Rodriguez G, Ortega FB, et al. Sedentary patterns and media availability in European adolescents: The HELENA study. Prev Med 2010; 51:50. 10. Yang L, Cao C, Kantor ED, et al. Trends in Sedentary Behavior Among the US Population, 2001-2016. JAMA 2019; 321:1587. 11. Du Y, Liu B, Sun Y, et al. Trends in Adherence to the Physical Activity Guidelines for Americans for Aerobic Activity and Time Spent on Sedentary Behavior Among US Adults, 2007 to 2016. JAMA Netw Open 2019; 2:e197597. 12. Ussery EN, Fulton JE, Galuska DA, et al. Joint Prevalence of Sitting Time and Leisure-Time Physical Activity Among US Adults, 2015-2016. JAMA 2018; 320:2036. 13. Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA 2018; 320:2020. 14. Bull FC, Al-Ansari SS, Biddle S, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 2020; 54:1451. 15. Proper KI, Singh AS, van Mechelen W, Chinapaw MJ. Sedentary behaviors and health outcomes among adults: a systematic review of prospective studies. Am J Prev Med 2011; 40:174. 16. Pavey TG, Peeters GG, Brown WJ. Sitting-time and 9-year all-cause mortality in older women. Br J Sports Med 2015; 49:95. 17. Le n-Mu oz LM, Mart nez-G mez D, Balboa-Castillo T, et al. Continued sedentariness, change in sitting time, and mortality in older adults. Med Sci Sports Exerc 2013; 45:1501. 18. Matthews CE, Cohen SS, Fowke JH, et al. Physical activity, sedentary behavior, and cause- specific mortality in black and white adults in the Southern Community Cohort Study. Am J Epidemiol 2014; 180:394. 19. Patel AV, Maliniak ML, Rees-Punia E, et al. Prolonged Leisure Time Spent Sitting in Relation to Cause-Specific Mortality in a Large US Cohort. Am J Epidemiol 2018; 187:2151. 20. Lee IM, Shiroma EJ, Lobelo F, et al. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012; 380:219. 21. Biswas A, Oh PI, Faulkner GE, et al. Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis. Ann Intern Med 2015; 162:123. 22. Diaz KM, Howard VJ, Hutto B, et al. Patterns of Sedentary Behavior and Mortality in U.S. Middle-Aged and Older Adults: A National Cohort Study. Ann Intern Med 2017; 167:465. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 14/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 23. van der Ploeg HP, Chey T, Korda RJ, et al. Sitting time and all-cause mortality risk in 222 497 Australian adults. Arch Intern Med 2012; 172:494. 24. Gennuso KP, Gangnon RE, Matthews CE, et al. Sedentary behavior, physical activity, and markers of health in older adults. Med Sci Sports Exerc 2013; 45:1493. 25. Chau JY, Grunseit A, Midthjell K, et al. Sedentary behaviour and risk of mortality from all- causes and cardiometabolic diseases in adults: evidence from the HUNT3 population cohort. Br J Sports Med 2015; 49:737. 26. Ekelund U, Steene-Johannessen J, Brown WJ, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta- analysis of data from more than 1 million men and women. Lancet 2016; 388:1302. 27. Matthews CE, Moore SC, Sampson J, et al. Mortality Benefits for Replacing Sitting Time with Different Physical Activities. Med Sci Sports Exerc 2015; 47:1833. 28. Stamatakis E, Gale J, Bauman A, et al. Sitting Time, Physical Activity, and Risk of Mortality in Adults. J Am Coll Cardiol 2019; 73:2062. 29. Shrestha N, Kukkonen-Harjula KT, Verbeek JH, et al. Workplace interventions for reducing sitting at work. Cochrane Database Syst Rev 2016; 3:CD010912. 30. Willis BL, Gao A, Leonard D, et al. Midlife fitness and the development of chronic conditions in later life. Arch Intern Med 2012; 172:1333. 31. Lear SA, Hu W, Rangarajan S, et al. The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low- income countries: the PURE study. Lancet 2017; 390:2643. 32. Andersen LB, Schnohr P, Schroll M, Hein HO. All-cause mortality associated with physical activity during leisure time, work, sports, and cycling to work. Arch Intern Med 2000; 160:1621. 33. Paffenbarger RS Jr, Hyde RT, Wing AL, et al. The association of changes in physical-activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993; 328:538. 34. Gregg EW, Cauley JA, Stone K, et al. Relationship of changes in physical activity and mortality among older women. JAMA 2003; 289:2379. 35. Leitzmann MF, Park Y, Blair A, et al. Physical activity recommendations and decreased risk of mortality. Arch Intern Med 2007; 167:2453. 36. Manson JE, Hu FB, Rich-Edwards JW, et al. A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women. N Engl J Med 1999; 341:650. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 15/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 37. Franco OH, de Laet C, Peeters A, et al. Effects of physical activity on life expectancy with cardiovascular disease. Arch Intern Med 2005; 165:2355. 38. Manini TM, Everhart JE, Patel KV, et al. Daily activity energy expenditure and mortality among older adults. JAMA 2006; 296:171. 39. Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011; 378:1244. 40. Lee JY, Ryu S, Cheong E, Sung KC. Association of Physical Activity and Inflammation With All- Cause, Cardiovascular-Related, and Cancer-Related Mortality. Mayo Clin Proc 2016; 91:1706. 41. Garatachea N, Santos-Lozano A, Sanchis-Gomar F, et al. Elite athletes live longer than the general population: a meta-analysis. Mayo Clin Proc 2014; 89:1195. 42. Joseph G, Marott JL, Torp-Pedersen C, et al. Dose-Response Association Between Level of Physical Activity and Mortality in Normal, Elevated, and High Blood Pressure. Hypertension 2019; 74:1307. 43. Ekelund U, Tarp J, Steene-Johannessen J, et al. Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis. BMJ 2019; 366:l4570. 44. Saint-Maurice PF, Troiano RP, Bassett DR Jr, et al. Association of Daily Step Count and Step Intensity With Mortality Among US Adults. JAMA 2020; 323:1151. 45. O'Donovan G, Lee IM, Hamer M, Stamatakis E. Association of "Weekend Warrior" and Other Leisure Time Physical Activity Patterns With Risks for All-Cause, Cardiovascular Disease, and Cancer Mortality. JAMA Intern Med 2017; 177:335. 46. Eijsvogels TM, Thompson PD. Exercise Is Medicine: At Any Dose? JAMA 2015; 314:1915. 47. Arem H, Moore SC, Patel A, et al. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern Med 2015; 175:959. 48. Esteban-Cornejo I, Cabanas-S nchez V, Higueras-Fresnillo S, et al. Cognitive Frailty and Mortality in a National Cohort of Older Adults: the Role of Physical Activity. Mayo Clin Proc 2019; 94:1180. 49. Wessel TR, Arant CB, Olson MB, et al. Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women. JAMA 2004; 292:1179. 50. Myers J, Kaykha A, George S, et al. Fitness versus physical activity patterns in predicting mortality in men. Am J Med 2004; 117:912. 51. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364:937. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 16/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 52. Kyu HH, Bachman VF, Alexander LT, et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ 2016; 354:i3857. 53. Hamer M, Sabia S, Batty GD, et al. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation 2012; 126:928. 54. Aggio D, Papachristou E, Papacosta O, et al. Association Between 20-Year Trajectories of Nonoccupational Physical Activity From Midlife to Old Age and Biomarkers of Cardiovascular Disease: A 20-Year Longitudinal Study of British Men. Am J Epidemiol 2018; 187:2315. 55. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med 2002; 136:493. 56. Fagard RH, Cornelissen VA. Effect of exercise on blood pressure control in hypertensive patients. Eur J Cardiovasc Prev Rehabil 2007; 14:12. 57. Wendel-Vos GC, Schuit AJ, Feskens EJ, et al. Physical activity and stroke. A meta-analysis of observational data. Int J Epidemiol 2004; 33:787. 58. Armstrong ME, Green J, Reeves GK, et al. Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective study of women in the United Kingdom. Circulation 2015; 131:721. 59. Howard VJ, McDonnell MN. Physical activity in primary stroke prevention: just do it! Stroke 2015; 46:1735. 60. Michaud DS, Giovannucci E, Willett WC, et al. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 2001; 286:921. 61. Kushi LH, Doyle C, McCullough M, et al. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 2012; 62:30. 62. Wolin KY, Yan Y, Colditz GA, Lee IM. Physical activity and colon cancer prevention: a meta- analysis. Br J Cancer 2009; 100:611. 63. Boyle T, Keegel T, Bull F, et al. Physical activity and risks of proximal and distal colon cancers: a systematic review and meta-analysis. J Natl Cancer Inst 2012; 104:1548. 64. Rezende LFM, S TH, Markozannes G, et al. Physical activity and cancer: an umbrella review of the literature including 22 major anatomical sites and 770 000 cancer cases. Br J Sports Med 2018; 52:826. 65. Irwin ML, Yasui Y, Ulrich CM, et al. Effect of exercise on total and intra-abdominal body fat in postmenopausal women: a randomized controlled trial. JAMA 2003; 289:323. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 17/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 66. Slentz CA, Duscha BD, Johnson JL, et al. Effects of the amount of exercise on body weight, body composition, and measures of central obesity: STRRIDE a randomized controlled study. Arch Intern Med 2004; 164:31. 67. Strasser B, Siebert U, Schobersberger W. Resistance training in the treatment of the metabolic syndrome: a systematic review and meta-analysis of the effect of resistance training on metabolic clustering in patients with abnormal glucose metabolism. Sports Med 2010; 40:397. 68. Hankinson AL, Daviglus ML, Bouchard C, et al. Maintaining a high physical activity level over 20 years and weight gain. JAMA 2010; 304:2603. 69. Lee IM, Djouss L, Sesso HD, et al. Physical activity and weight gain prevention. JAMA 2010; 303:1173. 70. Marcus BH, Albrecht AE, King TK, et al. The efficacy of exercise as an aid for smoking cessation in women: a randomized controlled trial. Arch Intern Med 1999; 159:1229. 71. Loprinzi PD, Kane CJ. Exercise and cognitive function: a randomized controlled trial examining acute exercise and free-living physical activity and sedentary effects. Mayo Clin Proc 2015; 90:450. 72. Northey JM, Cherbuin N, Pumpa KL, et al. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med 2018; 52:154. 73. Stern Y, MacKay-Brandt A, Lee S, et al. Effect of aerobic exercise on cognition in younger adults: A randomized clinical trial. Neurology 2019; 92:e905. 74. Brasure M, Desai P, Davila H, et al. Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med 2018; 168:30. 75. Herring MP, O'Connor PJ, Dishman RK. The effect of exercise training on anxiety symptoms among patients: a systematic review. Arch Intern Med 2010; 170:321. 76. Schuch FB, Vancampfort D, Firth J, et al. Physical Activity and Incident Depression: A Meta- Analysis of Prospective Cohort Studies. Am J Psychiatry 2018; 175:631. 77. Gordon BR, MCDowell CP, Hallgren M et. Association of Efficacy of Resistance Exercise Training with Depressive Symptoms. JAMA Psychiatry 2018. 78. Martin CK, Church TS, Thompson AM, et al. Exercise dose and quality of life: a randomized controlled trial. Arch Intern Med 2009; 169:269. 79. Shlipak MG, Sheshadri A, Hsu FC, et al. Effect of Structured, Moderate Exercise on Kidney Function Decline in Sedentary Older Adults: An Ancillary Analysis of the LIFE Study Randomized Clinical Trial. JAMA Intern Med 2022; 182:650. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 18/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 80. Bouchard C, Blair SN, Church TS, et al. Adverse metabolic response to regular exercise: is it a rare or common occurrence? PLoS One 2012; 7:e37887. 81. Diener-Martin E, Bruegger O, Martin B. Physical activity promotion and safety prevention: what is the relationship in different population groups? Br J Sports Med 2011; 45:332. 82. Conn JM, Annest JL, Gilchrist J. Sports and recreation related injury episodes in the US population, 1997-99. Inj Prev 2003; 9:117. 83. Falvey EC, Eustace J, Whelan B, et al. Sport and recreation-related injuries and fracture occurrence among emergency department attendees: implications for exercise prescription and injury prevention. Emerg Med J 2009; 26:590. 84. Burns J, Keenan AM, Redmond AC. Factors associated with triathlon-related overuse injuries. J Orthop Sports Phys Ther 2003; 33:177. 85. Wen DY. Risk factors for overuse injuries in runners. Curr Sports Med Rep 2007; 6:307. 86. Corrado D, Migliore F, Basso C, Thiene G. Exercise and the risk of sudden cardiac death. Herz 2006; 31:553. 87. Dahabreh IJ, Paulus JK. Association of episodic physical and sexual activity with triggering of acute cardiac events: systematic review and meta-analysis. JAMA 2011; 305:1225. 88. Albert CM, Mittleman MA, Chae CU, et al. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 2000; 343:1355. 89. Whang W, Manson JE, Hu FB, et al. Physical exertion, exercise, and sudden cardiac death in women. JAMA 2006; 295:1399. 90. Cheitlin MD, MacGregor J. Congenital anomalies of coronary arteries: role in the pathogenesis of sudden cardiac death. Herz 2009; 34:268. 91. Franklin BA, Thompson PD, Al-Zaiti SS, et al. Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training: Placing the Risks Into Perspective-An Update: A Scientific Statement From the American Heart Association. Circulation 2020; 141:e705. 92. Willich SN, Lewis M, L wel H, et al. Physical exertion as a trigger of acute myocardial infarction. Triggers and Mechanisms of Myocardial Infarction Study Group. N Engl J Med 1993; 329:1684. 93. Yu S, Patterson CC, Yarnell JW. Is vigorous physical activity contraindicated in subjects with coronary heart disease? Evidence from the Caerphilly study. Eur Heart J 2008; 29:602. 94. Sayers SP, Clarkson PM. Exercise-induced rhabdomyolysis. Curr Sports Med Rep 2002; 1:59. 95. Santos J Jr. Exertional rhabdomyolysis. Potentially life-threatening consequence of intense exercise. JAAPA 1999; 12:46. https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 19/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate 96. Guron G, Marcussen N, Friberg P. Urinary acidification and net acid excretion in adult rats treated neonatally with enalapril. Am J Physiol 1998; 274:R1718. 97. Lonka L, Pedersen RS. Fatal rhabdomyolysis in marathon runner. Lancet 1987; 1:857. 98. Alpers JP, Jones LK Jr. Natural history of exertional rhabdomyolysis: a population-based analysis. Muscle Nerve 2010; 42:487. 99. Randolph C. An update on exercise-induced bronchoconstriction with and without asthma. Curr Allergy Asthma Rep 2009; 9:433. 100. P riard JD, Caillaud C, Thompson MW. Central and peripheral fatigue during passive and exercise-induced hyperthermia. Med Sci Sports Exerc 2011; 43:1657. 101. McLaughlin M, Jacobs I. Exercise Is Medicine, But Does It Interfere With Medicine? Exerc Sport Sci Rev 2017; 45:127. Topic 2786 Version 105.0 https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 20/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate GRAPHICS Health benefits of regular physical activity Lower risk of all-cause mortality Lower risk of cardiovascular disease mortality Lower risk of cardiovascular disease (including heart disease and stroke) Lower risk of hypertension Lower risk of type 2 diabetes Lower risk of adverse blood lipid profile Lower risk of cancers of the bladder, breast, colon, endometrium, esophagus, kidney, lung, and stomach Improved cognition Reduced risk of dementia (including Alzheimer disease) Improved quality of life Reduced anxiety Reduced risk of depression Improved sleep Slowed or reduced weight gain Weight loss, particularly when combined with reduced calorie intake Prevention of weight regain following initial weight loss Improved bone health Improved physical function Lower risk of falls (older adults) Lower risk of fall-related injuries (older adults) For pregnant women, reduced risk of excessive weight gain, gestational diabetes, and postpartum depression For people with various chronic medical conditions, reduced risk of all-cause and disease-specific mortality, improved physical function, and improved quality of life Reproduced from: US Department of Health and Human Services. Physical Activity Guidelines for Americans, 2nd edition, US Department of Health and Human Services, Washington, DC 2018. Graphic 59285 Version 2.0 https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 21/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Lifestyle factors and survival Additional years of life according to age associated with adoption or maintenance of a favorable physical-activity ( 4.5 metabolic equivalents, or METS) level and other characteristics between 1962 or 1966 and 1977, as estimated from mortality rates among 10,269 male Harvard alumni from 1977 through 1985. Prolongation of life was greater in younger men and with cessation of smoking, alone or particularly with exercise. The effect of each individual factor was adjusted for differences in other factors. HTN: hypertension. Data from Pa enberger RS Jr, Hyde RT, Wing AL, et al. The association of changes in physical- activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993; 328:538. Graphic 56864 Version 3.0 https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 22/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate The risk of dying prematurely declines as people become physically active Reproduced from: Physical Activity Guidelines for Americans. US Department of Heath and Human Services. Available at https://health.gov/sites/default/ les/2019- 09/paguide.pdf. Graphic 74679 Version 4.0 https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 23/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Beneficial effects of any physical activity on coronary heart disease Coronary events are less frequent among those who exercise. In a study of 5159 men, aged 40 to 49 years, followed for an average of almost 19 years, the age-adjusted coronary heart disease event rate per 1000 person-years is lower in those who perform any physical activity compared with inactive subjects. Data from: Wannamethee SG, Shaper AG, Alberti KG. Arch Intern Med 2000; 160:2108. Graphic 81608 Version 4.0 https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 24/25 7/6/23, 1:46 PM The benefits and risks of aerobic exercise - UpToDate Contributor Disclosures Douglas M Peterson, MD, MBA, FACP, FACSM No relevant financial relationship(s) with ineligible companies to disclose. Mark D Aronson, MD No relevant financial relationship(s) with ineligible companies to disclose. Francis G O'Connor, MD, MPH, FACSM, FAMSSM No relevant financial relationship(s) with ineligible companies to disclose. Sara Swenson, MD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/the-benefits-and-risks-of-aerobic-exercise/print 25/25 |
7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wearable cardioverter-defibrillator : Mina K Chung, MD : Richard L Page, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 22, 2023. INTRODUCTION The implantable cardioverter-defibrillator (ICD) has been shown to improve survival from sudden cardiac arrest and to improve overall survival in several populations at high risk for sudden cardiac death (SCD). However, there remain situations in which implantation of an ICD is immediately not feasible (eg, patients with an active infection), may be of uncertain benefit, may not be covered by third-party payers (eg, early post-myocardial infarction, patients with limited life expectancy or new onset systolic heart failure), or when an ICD must be removed (eg, infection). In cases where ICD implantation must be deferred, a wearable cardioverter-defibrillator (WCD) offers an alternative approach for the prevention of SCD. The WCD (LifeVest [Zoll Medical Corporation] or Assure [Kestra Medical Technologies, Inc]) is an external device capable of automatic detection and defibrillation of ventricular tachycardia and ventricular fibrillation ( picture 1 and figure 1). While the WCD can be worn for years, typically the device is used for several months as temporary protection against SCD. The indications, efficacy, and limitations of the wearable cardioverter-defibrillator will be discussed here. Detailed discussions of the roles of the ICD are presented separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 1/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate DESCRIPTION AND FUNCTIONS OF THE WCD The WCD is an external device capable of automatic detection and defibrillation of ventricular tachycardia (VT) or ventricular fibrillation (VF) [1]. The approved devices do not have pacing capabilities and therefore are unable to provide therapy for bradycardic events or antitachycardic pacing. Wearing the WCD The WCD is composed of dry, nonadhesive monitoring electrodes, defibrillation electrodes incorporated into a chest strap or vest assembly, and a defibrillation battery and monitor unit ( picture 1). The Assure WCD garment has two styles designed for female and male body habitus and different sizes. The monitoring electrodes are positioned circumferentially around the chest and provide two to four surface electrocardiogram (ECG) leads. The defibrillation electrodes are positioned in a vest assembly for apex-posterior defibrillation. Proper fitting is required to achieve adequate skin contact to avoid noise and frequent alarms. Detection and delivery of shocks Arrhythmia detection by the WCD is programmed using ECG rate and morphology criteria. The system is programmed to define ventricular arrhythmias when the ventricular heart rate exceeds a preprogrammed rate threshold with an ECG morphology that does not match a baseline electrocardiographic template. Typical programming is reflected in default device settings: VT detection 150 beats per minute (LifeVest) or 170 beats per minute (Assure). Programmable ranges for LifeVest are 120 to 250 beats per minute, not to exceed the VF detection rate; for Assure they are, 130 to the programmed VF threshold minus 10 beats per minute. VF detection 200 beats per minute. Programmable ranges are 120 to 250 beats per minute (LifeVest) or 180 to 220 beats per minute (Assure). Treatment with 150 joules (LifeVest) or 170 joules (Assure) shocks for up to five shocks. For the Zoll LifeVest WCD, the tachycardia detection rate is programmable for VF between 120 and 250 beats per minute, and the VF shock delay can be programmed from 25 to 55 seconds. The VT detection rate is programmable between 120 bpm to the VF setting with a VT shock delay https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 2/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate of 60 to 180 seconds. VT signals can allow synchronized shock delivery on the R wave, but if the R wave cannot be identified, unsynchronized shocks will be delivered. For the Kestra Assure WCD, the tachycardia detection rate is programmable for VF between 180 and 220 beats per minute, and for VT detection programmable from 130 beats per minute up to the programmed VF rate: 10 beats per minute. Detection utilizes a segment-based analysis of 4.8-second segments that continuously overlap by 2.4 seconds. VF confirmation requires two out of two segments (approximately 5 seconds), and VT confirmation requires 15 out of 19 segments (approximately 45 seconds). The first and last segments must be in the programmed treatment zone. If an arrhythmia is detected, vibration and audible alarms are initiated. A flashing red light and shock icon are activated on the Assure monitor. Although shocks may be transmitted to bystanders in physical contact with the patient being shocked by a WCD, a voice cautions the patient and bystanders to the impending shock. Patients are trained to hold a pair of response buttons on the LifeVest device or press the alert button on the Assure device during these alarms to avoid receiving a shock while awake. A patient's response serves as a test of consciousness; if no response occurs and a shock is indicated, the device charges, extrudes gel from the defibrillation electrodes, and delivers up to five biphasic shocks at preprogrammed energy levels (ranging from 75 to 150 joules for the LifeVest device and 170 joules for the Assure device). The LifeVest device includes a default sleep time from 11 PM to 6 AM, programmable in one-hour increments, which allows additional time for deep sleepers, if they awaken, to abort shocks. Efficacy in terminating VT/VF Shock efficacy with the WCD appears to be similar to that reported with implantable cardioverter-defibrillators (ICDs). However, sudden cardiac death may still occur in those not wearing the device, those with improper positioning of the device, due to bystander interference, due to the inability of the WCD to detect the ECG signal, or due to bradyarrhythmias. These results highlight the importance of patient education and promotion of compliance while using the WCD. The efficacy of the WCD has been tested for induced ventricular tachyarrhythmias as well as for spontaneous events during clinical trials and postmarket studies. When worn properly, the WCD appears to be as effective as an ICD for the termination of VT and VF, with successful shocks occurring in up to 100 percent of cases [1-7]. In a study of induced VT/VF in the electrophysiology laboratory, the WCD successfully detected and terminated VT/VF with 100 percent first-shock success [2]. The following large registry studies of patients with WCDs showed high shock success rates: https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 3/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate In a US postmarket study of 8453 patients who wore a WCD after myocardial infarction, 146 VT/VF events occurred in 133 patients, and the overall shock success rate for terminating VT/VF was 82 percent, with 91 percent immediate survival [6]. In this study, shock success resulting in survival was 95 percent in revascularized and 84 percent in non-revascularized patients, suggesting that lower efficacy rates may be related to ischemic events. In the WEARIT-II registry of 2000 patients who wore a WCD for a median of 90 days, 120 episodes of sustained VT/VF were seen in 41 patients [7]. For 90 of the episodes, patients pressed the response buttons to abort shock delivery, with the majority of sustained VT episodes terminating spontaneously following use of the response button. All of the remaining 30 VT/VF episodes in 22 different patients were successfully terminated with a single shock. Among 6043 German patients who wore the device between April 2010 and October 2013, 94 patients were shocked for sustained VT/VF, with the WCD successfully terminating VT/VF in 88 patients (94 percent) [8]. The WCD appears equally efficacious among patients with and without myocardial ischemia immediately prior to VT/VF detection and shock (as defined by 0.1 mV ST-segment changes on ECG), with first shock termination rates of 96 percent in both groups [9]. Avoiding inappropriate shocks When electronic noise occurs, which may potentially be interpreted at VT or VF, the WCD emits a noise alarm. This electronic noise can often be minimized or eliminated by changing body position or tightening of the electrode belt, and shocks can be avoided by pushing the response buttons. While a dual-chamber ICD with an atrial lead would seemingly have greater ability to discriminate between supraventricular tachycardia (SVT) and VT, the incidence of inappropriate shocks due to atrial fibrillation, sinus tachycardia, or other supraventricular arrhythmias in clinical studies of WCDs has been low. The LifeVest WCD uses a two-channel proprietary vectorcardiogram morphology matching algorithm to prevent shocks during SVT if the QRS is unchanged, and inappropriate shocks can also be averted when the patient presses the response buttons. The Assure WCD uses a four-channel ECG with a single noise-free channel required for analysis and an algorithm that excludes noisy and low amplitude channels ( figure 2). (See 'Inappropriate shocks' below.) In a small study of the 60 patients with a permanent pacemaker, in which a variety of pacing modes (AAI, VVI, DDD) and configurations (unipolar, bipolar) were tested, unipolar DDD pacing triggered VT/VF detection in six patients (10 percent), while no other pacing modes or configurations triggered arrhythmia detection [10]. As such, patients whose pacemaker is https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 4/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate programmed to unipolar DDD pacing should be evaluated for pacemaker reprogramming to a bipolar mode prior to WCD usage. In a study of 130 patients with an ICD and fitted with an ASSURE WCD programmed for detection only and followed for 30 days, of 163 WCD-detected episodes, four were VT/VF and 159 were non-VT/VF with three false-positive shock alarm markers recorded, corresponding to a very low rate of inappropriate detection [11]. No ICD-recorded VT/VF episodes meeting WCD programmed criteria were missed. Median daily use was high at 23 hours. Bradycardia/asystole Neither of the approved WCDs deliver antibradycardic pacing, but they do record the ventricular rate when the heart rate decreases or asystole occurs: For the LifeVest device, asystole recordings are triggered when ventricular heart rates drop below 10 beats per minute or 16 seconds of asystole, and the device automatically records the event with 120 seconds preceding the onset. If using the secure website in conjunction with the WCD, alerts can be configured to prompt the healthcare provider that a patient is experiencing bradycardia or an asystole. For the Assure device, asystole is detected when there is no detected heart rate for >20 seconds (five of seven segments with heart rate 0 beats per minute or amplitude <100 uV); prolonged heart rates below 30 beats per minute may be detected as bradycardia. When asystole or bradycardia is detected, a loud alarm is triggered to attract bystanders and instruct them to call 911 and begin CPR if the patient is unconscious. The alert can be silenced by pressing the alert button or it resolves when a heart rate >30 bpm is detected for >30 seconds. Storage of ECGs and compliance data In addition to delivering therapeutic shocks for life- threatening ventricular arrhythmias, the WCD stores data regarding tachyarrhythmias, bradycardia/asystole (see 'Bradycardia/asystole' above), patient compliance with the device, and noise or interference with its proper functioning. Arrhythmia recordings from the WCD are available for clinician review once stored data are transmitted via a modem to the manufacturer's network. Treatments, patient compliance, ECG records, and system performance can be viewed using a secure website. The WCD stores ECGs from arrhythmia detections, usage, and compliance trends: For the LifeVest system: The system is programmed to define ventricular arrhythmias when the ventricular heart rate exceeds a preprogrammed rate threshold with an ECG morphology that does not match a baseline ECG template. The monitoring software captures 30 seconds of ECG https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 5/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate signal prior to the determination of VT or VF and continuously records until 15 seconds after the alarms stop. Patients can perform manual recordings by pressing response buttons for three seconds, which records the prior 30 seconds plus the next 15 seconds. Data on patient compliance, ECG signal quality, alarm history, and noise occurrence are recorded, including time/date stamps for device on/off switching, monitor connection to the electrodes, and electrode-to-skin contact. Compliance may be determined by assessing the time that the user had the device turned on, the belt connected, and at least one monitoring electrode contacting the skin. For the Assure system: Up to 120 seconds of data are recorded prior to arrhythmia onset detection, confirmation, and therapy are detected, and up to 60 seconds are detected after rate recovery or conversion. Patient activity is also stored, utilizing an accelerometer located in the hub component in the middle of the patient's back. Daily usage is recorded in one-minute increments when the sensors are in contact with the patient's skin. INDICATIONS The WCD is indicated as temporary therapy for patients with a high risk for sudden cardiac death (SCD) [1,12-16]. Our recommended approach is consistent with that of the 2016 science advisory from the American Heart Association (also endorsed by the Heart Rhythm Society) and the 2017 AHA/ACC/HRS guideline [16,17]. Examples of persons who may benefit from the temporary use of a WCD include: Patients with a permanent implantable cardioverter-defibrillator (ICD) that must be explanted, or those with a delay in implanting a newly indicated ICD (eg, due to systemic infection). (See 'Bridge to indicated or interrupted ICD therapy' below.) Patients with reduced left ventricular (LV) systolic function (LVEF 35 percent) who have had a myocardial infarction (MI) within the past 40 days. (See 'Early post-MI patients with LV dysfunction' below.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 6/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Patients with reduced LV systolic function (LVEF 35 percent) who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery in the past three months. (See 'Patients with LV dysfunction early after coronary revascularization' below.) Patients with newly diagnosed nonischemic cardiomyopathy with severely reduced LV systolic function (LVEF 35 percent) that is potentially reversible. (See 'Newly diagnosed nonischemic cardiomyopathy' below.) Patients with severe heart failure who are awaiting heart transplantation. (See 'Bridge to heart transplant' below.) A 2019 systematic review and meta-analysis, which included 33,242 WCD users from 28 studies (the randomized VEST trial and 27 nonrandomized studies), assessed the likelihood of WCD therapy in a broad range of patient populations, including both primary/secondary prevention and ischemic/nonischemic cardiomyopathy patients. The incidence of appropriate shocks was 5 per 100 persons over three months (1.67 percent per month) with mortality while wearing the device noted to be 0.7 per 100 persons over three months [18]. Bridge to indicated or interrupted ICD therapy In some patients with an indication for ICD placement, implantation of the device may be delayed due to comorbid conditions, including [16,17]: Infection Recovery from surgery Lack of vascular access In addition, patients with a preexisting ICD who develop device infection or endocarditis usually require system extraction to effectively treat the infection. Unless the patient is pacemaker dependent, reimplantation in many patients is deferred until the infection is completely cleared after an appropriate course of antibiotics. The WCD may provide protection against ventricular tachyarrhythmias during these periods until an ICD can be implanted [4,5,16]. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis".) In a review of 8058 patients who were prescribed the WCD after ICD removal because of infection, median time to reimplantation was 50 days, and 334 (4 percent) experienced 406 ventricular tachycardia/ventricular fibrillation (VT/VF) events, with 348 events treated by the WCD and 54 treatments averted by conscious patients [19]. The one-year cumulative event rate was 10 percent. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 7/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Early post-MI patients with LV dysfunction Among patients with LV ejection fraction (LVEF) 35 percent who are less than 40 days post-MI, there are conflicting data on the benefits of a WCD for primary prevention against SCD. Following discussion of the potential benefits and risks, use of the WCD within this 40-day window could be considered among motivated patients who have LVEF 35 percent and in New York Heart Association (NYHA) functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for ICD implantation after 40 days [16,17]. Patients should be reminded of the importance of compliance with the WCD in order to optimize any potential benefits on prevention of arrhythmic death. Reevaluation of LVEF should occur one to three months after the MI. If LVEF remains 35 percent on follow-up assessment, while the patient is taking appropriate medical therapy, ICD implantation is indicated [16]. After ICD implantation, use of the WCD would be discontinued. Despite advances in the treatment of acute coronary syndromes with early revascularization and effective medical therapies that have reduced mortality, some residual risk of SCD remains in the early period following an MI, especially in the setting of severely reduced LVEF (2.3 percent/month for patients with LVEF 30 percent) [4,20]. However, there are conflicting data on the utility of an ICD in the early post-MI period. In an analysis of 712 patients with a history of MI who were enrolled in the SCD-HeFT trial, there was no evidence of differential mortality benefit with ICDs as a function of time after MI, indicating that the potential benefit of ICD therapy is not restricted only to remote MIs [21]. In the DINAMIT (674 patients) and IRIS (898 patients) trials, which randomized patients with LVEF 35 percent to either early ICD implantation 6 to 40 days after acute MI or medical therapy alone, there was no significant improvement in overall mortality [22,23]. Despite a reduction in arrhythmic deaths among patients with an ICD, there was a higher risk of nonarrhythmic deaths during this early period, resulting in similar overall mortality rates. Professional society guidelines do not recommend ICD implantation for primary prevention of SCD within 40 days of acute MI [16]. However, due to the risk of SCD in some patients early post- MI, the WCD has been studied in this patient population. In the VEST trial, 2302 patients with an acute MI and LVEF 35 percent were randomly assigned (within seven days of hospital discharge) in a 2:1 ratio to wear the WCD in addition to usual medical treatment (1524 patients) or to receive standard medical treatment alone (778 patients) [24]. Over an average follow-up of 84 days, patients in the https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 8/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate WCD group had no significant improvement in the primary outcome of arrhythmic death (25 patients [1.6 percent] versus 19 patients [2.4 percent] with medical therapy alone; relative risk [RR] 0.67; 95% CI 0.37-1.21). Compliance with medical therapy was excellent in both groups, likely contributing to fewer than expected events and the trial possibly being underpowered. However, compliance with WCD usage was markedly lower than expected (median and mean daily wear times of 18 and 14 hours, respectively), with over half of patients assigned to the WCD not wearing it by the end of the 90-day study. Among 48 total deaths in the WCD group, only 12 patients (25 percent) were wearing the WCD at the time of death. Asystolic events not treated by the WCD likely also contributed to the nonsignificant primary outcome results of the trial. A subsequent as-treated and per- protocol analysis of VEST (censoring participants at the time they stopped wearing the WCD) reported a significant reduction in total and arrhythmic mortality among participants wearing the WCD compared with control participants (total mortality hazard ratio 0.25; CI 0.13-0.43; arrhythmic death hazard ratio 0.09; CI 0.02-0.39) [25]. The VEST study also demonstrates the challenges in trying to improve mortality in the post- MI population. Not all patients will survive despite initial appropriate and successful shocks for VT or VF. Of nine patients wearing the WCD with arrhythmic death in the VEST trial, four had been initially successfully treated but subsequently died. Of six patients who had an appropriate shock from the WCD but died during the study, two developed post-VT/VF asystole. Similar WCD shock rates (between 1.5 and 2 percent within 90 days post-MI) have been reported in observational studies [3,5,6]. In registry data from two large registries (involving 3569 and 8453 patients, respectively), similar rates of WCD shocks have been seen (1.7 and 1.6 percent of patients, respectively) [5,6]. Patients with LV dysfunction early after coronary revascularization Among patients with LVEF 35 percent who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) in the past three months, we offer a WCD to highly motivated patients for primary prevention against SCD [16]. LVEF should be reassessed three months following CABG or PCI. If a sustained ventricular tachyarrhythmia has occurred, or if the LVEF remains 35 percent three months after CABG or PCI, implantation of an ICD is usually indicated [16]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) While professional society guidelines do not specifically exclude ICD implantation for patients with LV dysfunction within three months of revascularization, reimbursement in some countries https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 9/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate may be denied. As an example, in the United States the national coverage decision for the Centers for Medicare & Medicaid Service (CMS) excludes coverage for primary prevention ICDs if patients have had CABG surgery or PCI within the past three months. This is based upon the clinical profile of subjects included in the major ICD trials for primary prevention of SCD in ischemic cardiomyopathy [12,13,26,27]. Despite this exclusion period, patients with LV dysfunction (eg, LVEF 30 percent) have been shown to have significantly higher rates of mortality early after PCI or CABG based on large National Cardiovascular Data Registry (NCDR) and Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database studies, respectively [28,29]. Patients with significant LV dysfunction have higher 30-day mortality rates after coronary artery bypass graft (CABG) surgery than patients with normal LV function. While these persons have an increased risk of SCD due to ventricular arrhythmias, they are also at risk for nonarrhythmic causes of death. There are limited data on the utility of an ICD in the early post-CABG period, as several ICD studies of primary prevention have excluded patients within one to three months after coronary revascularization [12-14]. However, the CABG Patch trial did not report a survival benefit from epicardial ICD implantation at the time of CABG in patients with LVEF 35 percent [27]. (See "Early cardiac complications of coronary artery bypass graft surgery" and "Early noncardiac complications of coronary artery bypass graft surgery".) Professional society guidelines do not recommend ICD implantation for primary prevention of SCD within three months of CABG [16]. However, due to the risk of SCD in some patients early post-CABG, the WCD has been studied in this patient population, in whom wearing the WCD may provide protection from SCD during healing and potential recovery of LV function [3,16,17]. The potential utility for a WCD in this setting is illustrated by the following studies: In a nonrandomized comparison of nearly 5000 patients with LVEF 35 percent from two separate cohorts who underwent revascularization with CABG or percutaneous coronary intervention (PCI) (809 patients discharged with a WCD from a national registry and 4149 patients discharged without WCD from Cleveland Clinic CABG and PCI registries), patients discharged with the WCD had significantly lower 90-day mortality rates (3 versus 7 percent) [30]. While patients using a WCD appear to have improved outcomes, only 1.3 percent of the WCD group received an appropriate therapy while wearing the device, thereby indicating that the majority of the mortality benefit was not attributable to life-saving therapies from the WCD. In a German cohort of 354 patients who wore the WCD, including approximately 90 patients in the early post-CABG period, 7 percent received a shock for a ventricular tachyarrhythmia during the three months of WCD use [4]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 10/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate In a study of 3569 patients in the United States using the WCD, among which 9 percent of WCD use was early post-CABG, appropriate shocks for a ventricular tachyarrhythmia occurred in 0.8 percent of these patients over a mean follow-up of 47 days [5,31]. Newly diagnosed nonischemic cardiomyopathy In selected patients with newly diagnosed nonischemic cardiomyopathy with severely reduced LV systolic function that is potentially reversible, such as tachycardia- or myocarditis-associated cardiomyopathy, the WCD may be useful for the prevention of SCD due to ventricular arrhythmias while awaiting improvement in LV function [16,17]. While a benefit from ICD implantation has long been recognized in patients with significant LV systolic dysfunction related to underlying ischemic heart disease, an increase in SCD risk and potential benefit from an ICD has also been demonstrated in patients with a nonischemic cardiomyopathy in several studies [14,32]: In SCD-HeFT, which compared ICD implantation with amiodarone treatment alone or placebo for primary prevention of SCD in patients with ischemic or nonischemic heart failure and LVEF 35 percent, patients who received an ICD had significantly improved survival [14]. However, patients within three months of their initial heart failure diagnosis were excluded from this study. In DEFINITE, which compared ICD implantation with standard medical therapy to standard medical therapy alone for primary prevention of SCD in patients with a nonischemic cardiomyopathy, nonsustained VT, and LVEF 35 percent, there was a trend toward improved mortality in patients who received an ICD, regardless of duration since diagnosis [32]. Following DEFINITE, another study reported similar occurrences of lethal arrhythmias irrespective of diagnosis duration in patients with a nonischemic cardiomyopathy and LVEF 35 percent [33]. Major society guidelines recommend implantation of an ICD for nonischemic cardiomyopathy with LVEF 35 percent, provided that a reversible cause of transient LV dysfunction has been excluded and that response to optimal medical therapy has been assessed [16]. The guidelines do not specify a waiting period prior to reassessing LVEF. In the United States, however, the Center for Medicare Services (CMS) requires a three-month period of optimal medical therapy prior to reimbursement for ICD placement for primary prevention (if repeat LVEF assessment continues to show LVEF 35 percent). (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Nonischemic dilated cardiomyopathy'.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 11/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate In patients felt to be at high risk of SCD while undergoing a trial of optimal medical therapy, the WCD may provide protection against SCD while awaiting improvement in LV function, although the event rates in this population appear to be lower than patients with ischemic cardiomyopathy [16]. In a post-approval study of the WCD, 0.7 percent of patients prescribed a WCD for recently diagnosed nonischemic cardiomyopathy required shocks for a ventricular tachyarrhythmia over a mean follow-up period of 57 days [5,31]. Among a single-center cohort of 254 patients with newly diagnosed nonischemic cardiomyopathy treated with the WCD between 2004 and 2015 (median duration of treatment 61 days, total follow-up 56.7 patient-years) who were highly compliant with using the WCD (median wear time 22 hours per day), no patients received an appropriate shock, and only three patients (1.2 percent) received an inappropriate shock [34]. This was compared with 6 of 271 patients (2.2 percent) with newly diagnosed ischemic cardiomyopathy who received an appropriate shock; in this group, two (0.7 percent) received inappropriate shocks. Of interest, 39 percent of nonischemic and 32 percent of ischemic cardiomyopathy patients experienced improvement in LVEF to >35 percent, obviating the need for an ICD. In a prospective study of the WCD in advanced heart failure patients (SWIFT), 75 patients hospitalized with heart failure (66 percent nonischemic cardiomyopathy) were prescribed a WCD for three months. Among the nonischemic cardiomyopathy patients, one had recurrent supraventricular tachycardia and another had multiple ventricular premature beats detected, but no WCD therapies were delivered [35]. In the WEARIT II registry, which included 927 patients with nonischemic cardiomyopathy, over a median wear time of 90 days, the treated event rate was 1 percent, compared with 3 percent for the 805 patients with ischemic cardiomyopathy [7]. Special populations include those with alcoholic cardiomyopathy, postpartum cardiomyopathy, or myocarditis, all of which may or may not be associated with improvement in ventricular function with optimal medical therapy and reversal or treatment of causative factors. In a study of 127 patients with alcoholic cardiomyopathy wearing the WCD a median of 51 days, 5.5 percent had appropriate shocks for VT/VF [36]. Improved LVEF occurred in 33 percent, and 23.6 percent received an ICD. In the PROLONG study of 156 patients (111 with nonischemic cardiomyopathy) with newly diagnosed LVEF 35 percent wearing a WCD for an average of 101 days, WCD shocks for VT/VF were experienced by 7.2 percent, compared with 6.7 percent in the 45 patients with https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 12/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate ischemic cardiomyopathy [37]. The event rates were 21.1 percent in the 19 patients with postpartum cardiomyopathy, 0 percent in the six patients with myocarditis, and 4.7 percent in patients with other forms of nonischemic cardiomyopathy. In a separate study of 107 women with peripartum cardiomyopathy, who were matched to 159 nonpregnant women with nonischemic dilated cardiomyopathy, the event rate was 0 in the peripartum cardiomyopathy over an average WCD use of 124 days, compared with two shocks in one patient with nonperipartum nonischemic cardiomyopathy [38]. With such low event rates, the utility of the WCD for newly-diagnosed nonischemic cardiomyopathy has been debated. However, from the WEARIT II registry, the number of VT/VF events per 100 patient-years was 1.5 for treated events versus 12 for untreated events [7]. Presumably, some of the untreated events led to earlier ICD implantation and may represent a nontreatment yield from the WCD monitoring functions. As data remain limited for such patients, the decision on whether to use a WCD remains based on clinical judgment for patients assessed to have high-risk severe newly diagnosed nonischemic cardiomyopathy while undergoing optimization of medical therapy, awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See "Treatment and prognosis of myocarditis in adults", section on 'Therapy for arrhythmias'.) Bridge to heart transplant Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD [17]. ICD implantation is often recommended for such patients, particularly those discharged to home while awaiting transplantation. The WCD may be a reasonable noninvasive alternative approach, though data on its use in patients awaiting heart transplantation are limited: In one study of 91 cardiac transplant candidates discharged to home (UNOS Status 1B patients receiving home inotrope infusion), among whom 25 had an ICD and 13 used a WCD, two patients died suddenly at home, one who was not wearing his WCD and another who declined use of a WCD [39]. In the 13 patients wearing the WCD, three asymptomatic events occurred with one shock delivered for rapid atrial fibrillation. In a German study of 354 WCD patients, 6 percent wore the WCD while awaiting heart transplantation, with an incidence of ventricular arrhythmias of 11 percent [4]. In the WEARIT study of WCD use in 177 patients with NYHA functional class III or IV heart failure (not listed for heart transplant but with similar functional status to patients who might be listed for heart transplant), one patient received two successful defibrillations [3]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 13/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate In a registry of 121 patients prescribed a WCD as a bridge to heart transplantation, seven patients (6 percent) received appropriate shocks over an average use of 127 days (median 39 days) [40]. The International Society for Heart and Lung Transplantation Guidelines state as a class I recommendation that an ICD or WCD should be provided for status 1B patients who are discharged home given that the wait for transplantation remains significant [41]. The WCD may also be appropriate in patients whose anticipated waiting time to transplant is short (ie, blood types A and B) if an ICD is not already present [41]. WCD in patients with VADs The role for ICD and WCD therapy remains unclear in patients with ventricular assist devices (VADs). With VADs, circulatory support is often adequate even in the event of a ventricular tachyarrhythmia. However, one study reported the presence of an ICD was associated with improved survival in patients undergoing VAD support [42]. Whether the WCD could impart similar survival benefits in patients awaiting transplantation with VAD support has yet to be studied. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".) WCD use in hemodialysis patients Patients with end-stage kidney disease on hemodialysis are at high risk for SCD, but they are also at higher risk for infection, bleeding, and other complications of implantable device therapies, which may lead to underutilization of ICDs. Although the arrhythmia event rates for patients on hemodialysis wearing a WCD are not published, a study of 75 hemodialysis patients who experienced sudden cardiac arrest events while wearing a WCD reported that 78.6 percent of events were due to VT/VF and 21.4 percent were due to asystole [43]. Survival was 71, 51, and 31 percent at 24 hours, 30 days, and one year, respectively, which was reported to be improved compared with historical controls. LIMITATIONS AND PRECAUTIONS In spite of its overall efficacy for terminating life-threatening ventricular arrhythmias, the WCD does have some limitations. The device must be fitted to each patient, and some patients may not have a good fit due to body habitus. Its external nature does not allow for pacemaker functionality and introduces a component of patient interaction and compliance as well as the potential for external noise leading to inappropriate shocks. The device must be removed for bathing, but no protection is afforded while the device is off. Therefore, it is advisable that caregivers or other persons be nearby during these periods when the WCD is not worn. Comfort may also be an issue for some patients due to the size and weight of the device. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 14/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Patient size The WCD can only be fitted on patients with a chest circumference less than 57 inches (144 cm); therefore, it may not be an option for morbidly obese patients. However, among 574 patients from the WCD registry, which included normal weight (body mass index [BMI] between 18 and 24.9; n = 157), overweight (BMI between 25 and 29.9; n = 186), and obese (BMI 30; n = 231, including 55 with BMI 40) patients who experienced 623 ventricular tachycardia/ventricular fibrillation (VT/VF) events while wearing the WCD, the median daily wear time (21 hours), first shock success rate (93 to 94 percent), and 24-hour post-shock survival (92 to 94 percent) were similar across all BMI groups [44]. There are also limited data on WCD use in children, in whom the device may not fit properly if the child is small. (See 'Use of the WCD in children' below.) Lack of pacemaker functionality Because of its external nature, the WCD is not able to function as a pacemaker, which limits the possible therapies it can deliver in two ways: The WCD cannot deliver pacing therapies to treat bradycardia or asystole. In the German study, two patients developed asystole while wearing the WCD, and both patients died [4]. |
percent for the 805 patients with ischemic cardiomyopathy [7]. Special populations include those with alcoholic cardiomyopathy, postpartum cardiomyopathy, or myocarditis, all of which may or may not be associated with improvement in ventricular function with optimal medical therapy and reversal or treatment of causative factors. In a study of 127 patients with alcoholic cardiomyopathy wearing the WCD a median of 51 days, 5.5 percent had appropriate shocks for VT/VF [36]. Improved LVEF occurred in 33 percent, and 23.6 percent received an ICD. In the PROLONG study of 156 patients (111 with nonischemic cardiomyopathy) with newly diagnosed LVEF 35 percent wearing a WCD for an average of 101 days, WCD shocks for VT/VF were experienced by 7.2 percent, compared with 6.7 percent in the 45 patients with https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 12/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate ischemic cardiomyopathy [37]. The event rates were 21.1 percent in the 19 patients with postpartum cardiomyopathy, 0 percent in the six patients with myocarditis, and 4.7 percent in patients with other forms of nonischemic cardiomyopathy. In a separate study of 107 women with peripartum cardiomyopathy, who were matched to 159 nonpregnant women with nonischemic dilated cardiomyopathy, the event rate was 0 in the peripartum cardiomyopathy over an average WCD use of 124 days, compared with two shocks in one patient with nonperipartum nonischemic cardiomyopathy [38]. With such low event rates, the utility of the WCD for newly-diagnosed nonischemic cardiomyopathy has been debated. However, from the WEARIT II registry, the number of VT/VF events per 100 patient-years was 1.5 for treated events versus 12 for untreated events [7]. Presumably, some of the untreated events led to earlier ICD implantation and may represent a nontreatment yield from the WCD monitoring functions. As data remain limited for such patients, the decision on whether to use a WCD remains based on clinical judgment for patients assessed to have high-risk severe newly diagnosed nonischemic cardiomyopathy while undergoing optimization of medical therapy, awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See "Treatment and prognosis of myocarditis in adults", section on 'Therapy for arrhythmias'.) Bridge to heart transplant Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD [17]. ICD implantation is often recommended for such patients, particularly those discharged to home while awaiting transplantation. The WCD may be a reasonable noninvasive alternative approach, though data on its use in patients awaiting heart transplantation are limited: In one study of 91 cardiac transplant candidates discharged to home (UNOS Status 1B patients receiving home inotrope infusion), among whom 25 had an ICD and 13 used a WCD, two patients died suddenly at home, one who was not wearing his WCD and another who declined use of a WCD [39]. In the 13 patients wearing the WCD, three asymptomatic events occurred with one shock delivered for rapid atrial fibrillation. In a German study of 354 WCD patients, 6 percent wore the WCD while awaiting heart transplantation, with an incidence of ventricular arrhythmias of 11 percent [4]. In the WEARIT study of WCD use in 177 patients with NYHA functional class III or IV heart failure (not listed for heart transplant but with similar functional status to patients who might be listed for heart transplant), one patient received two successful defibrillations [3]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 13/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate In a registry of 121 patients prescribed a WCD as a bridge to heart transplantation, seven patients (6 percent) received appropriate shocks over an average use of 127 days (median 39 days) [40]. The International Society for Heart and Lung Transplantation Guidelines state as a class I recommendation that an ICD or WCD should be provided for status 1B patients who are discharged home given that the wait for transplantation remains significant [41]. The WCD may also be appropriate in patients whose anticipated waiting time to transplant is short (ie, blood types A and B) if an ICD is not already present [41]. WCD in patients with VADs The role for ICD and WCD therapy remains unclear in patients with ventricular assist devices (VADs). With VADs, circulatory support is often adequate even in the event of a ventricular tachyarrhythmia. However, one study reported the presence of an ICD was associated with improved survival in patients undergoing VAD support [42]. Whether the WCD could impart similar survival benefits in patients awaiting transplantation with VAD support has yet to be studied. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".) WCD use in hemodialysis patients Patients with end-stage kidney disease on hemodialysis are at high risk for SCD, but they are also at higher risk for infection, bleeding, and other complications of implantable device therapies, which may lead to underutilization of ICDs. Although the arrhythmia event rates for patients on hemodialysis wearing a WCD are not published, a study of 75 hemodialysis patients who experienced sudden cardiac arrest events while wearing a WCD reported that 78.6 percent of events were due to VT/VF and 21.4 percent were due to asystole [43]. Survival was 71, 51, and 31 percent at 24 hours, 30 days, and one year, respectively, which was reported to be improved compared with historical controls. LIMITATIONS AND PRECAUTIONS In spite of its overall efficacy for terminating life-threatening ventricular arrhythmias, the WCD does have some limitations. The device must be fitted to each patient, and some patients may not have a good fit due to body habitus. Its external nature does not allow for pacemaker functionality and introduces a component of patient interaction and compliance as well as the potential for external noise leading to inappropriate shocks. The device must be removed for bathing, but no protection is afforded while the device is off. Therefore, it is advisable that caregivers or other persons be nearby during these periods when the WCD is not worn. Comfort may also be an issue for some patients due to the size and weight of the device. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 14/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Patient size The WCD can only be fitted on patients with a chest circumference less than 57 inches (144 cm); therefore, it may not be an option for morbidly obese patients. However, among 574 patients from the WCD registry, which included normal weight (body mass index [BMI] between 18 and 24.9; n = 157), overweight (BMI between 25 and 29.9; n = 186), and obese (BMI 30; n = 231, including 55 with BMI 40) patients who experienced 623 ventricular tachycardia/ventricular fibrillation (VT/VF) events while wearing the WCD, the median daily wear time (21 hours), first shock success rate (93 to 94 percent), and 24-hour post-shock survival (92 to 94 percent) were similar across all BMI groups [44]. There are also limited data on WCD use in children, in whom the device may not fit properly if the child is small. (See 'Use of the WCD in children' below.) Lack of pacemaker functionality Because of its external nature, the WCD is not able to function as a pacemaker, which limits the possible therapies it can deliver in two ways: The WCD cannot deliver pacing therapies to treat bradycardia or asystole. In the German study, two patients developed asystole while wearing the WCD, and both patients died [4]. In the US post-approval registry study, 23 of 3569 patients (0.6 percent) experienced asystole, with an associated mortality of 74 percent [5]. In the post-myocardial infarction (MI) registry of 8453 patients, 34 died (0.4 percent) with bradycardia-asystole events [6]. In the WEARIT-II registry, 6 of 2000 patients (0.3 percent) had asystole, and all three of the deaths that occurred while wearing the WCD during the study (0.2 percent) occurred following an asystole event [7]. The WCD cannot provide antitachycardia pacing for VT, which can reduce patient shocks, when effective. When considering these limitations, an implantable cardioverter-defibrillator (ICD) would be preferred, if indicated, in a patient who is pacemaker-dependent or in whom antitachycardia pacing is desired as the initial therapy for VT. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) Use in patients with a preexisting permanent pacemaker With certain precautions, the WCD can be used in patients with a preexisting permanent pacemaker. The manufacturer recommends that the device not be worn if the pacemaker stimulus artifact exceeds 0.5 millivolts, as this may mask underlying ventricular fibrillation and prevent appropriate device therapy. Conversely, the VT threshold of the WCD should be set higher than the maximal pacing rate to avoid an inappropriate WCD shock due to oversensing paced beats. Following any WCD shock, the patient's pacemaker should be interrogated to ensure that there has been no damage to the pacemaker or any changes in the pacemaker setting. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 15/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Inappropriate shocks Both the WCD and the ICD may inappropriately deliver shocks due to electronic noise, device malfunction, or detection of supraventricular tachycardia above the preprogrammed rate criteria. Studies of ICDs have reported an incidence of inappropriate shock of 0.2 to 2.3 percent of patients per month [32,45-51]. Comparable rates of inappropriate shocks have been reported among users of the WCD, with rates ranging from 0.5 to 1.4 percent per month [3-7]. In a systematic review and meta-analysis which included 33,242 patients from 28 studies (the randomized VEST trial and 27 nonrandomized studies), inappropriate shocks occurred at a rate of 2 per 100 persons over three months (0.67 percent per month) [18]. Inappropriate shocks with a WCD can be potentially reduced due to the ability to abort shocks while awake by pressing response buttons. (See 'Avoiding inappropriate shocks' above.) Patient compliance and complaints Patients may not comply with wearing the WCD for a variety of reasons, chief among them device size and weight, skin rash, itching, and problems sleeping. However, efficacy of the WCD in the prevention of sudden cardiac death is highly dependent on patient compliance and appropriate use of the device [3-5,7]. In the WEARIT/BIROAD study, 23 percent of the 289 subjects withdrew before reaching a study endpoint, with size and weight of the monitor being the most frequent reason for withdrawal [3]. Skin rash and/or itching were also reported by 6 percent of patients. In the US postmarket study, median and mean daily use were 21.7 hours and 19.9 hours, respectively [5]. Daily use was >90 percent (>21.6 hours) in 52 percent of patients and >80 percent (>19.2 hours) in 71 percent of patients. Longer duration of monitoring correlated with higher compliance rates. WCD use was stopped prematurely in 14 percent, primarily because of comfort issues related to the size and weight of the WCD. In the WEARIT-II registry, median daily use was 22.5 hours [7]. Similar to the US postmarket study, longer duration of monitoring (15 or more days) was associated with higher rates of compliance. In the nationwide German cohort, median daily use among 6043 patients was 23.1 hours for a median of 59 days [8]. Lower rates of compliance were reported in a study of 147 patients from two academic medical centers in Boston, in which median daily use was 21 hours for a median of 50 days [52]. In an international registry of 708 patients, appropriate WCD shock was documented in 2.2 percent, inappropriate shock in 0.5 percent, and mean wear time was 21.2 4.3 hours/day (and was lower in younger patients) [53]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 16/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate In the WEARIT-France cohort study of 1157 patients, median daily wear time was 23.4 hours, with younger age associated with lower compliance [54]. In the VEST randomized trial after MI, median and mean daily wear times were only 18 and 14 hours, respectively, with over half of patients assigned to the WCD not wearing it by the end of the 90-day study [24]. Among 48 total deaths in the WCD group, only 12 patients (25 percent) were wearing the WCD at the time of death. In the as-treated and per-protocol analysis of VEST [25], better WCD compliance was predicted by cardiac arrest during index MI, higher creatinine, diabetes, prior heart failure, ejection fraction 25 percent, Polish enrolling center, and number of WCD alarms. Worse compliance was associated with being divorced, Asian race, higher body mass index, prior PCI, or any WCD shock. In a study of 130 patients with an ICD and fitted with an ASSURE WCD programmed for detection only and followed for 30 days, median daily use was high at 23 hours [11]. Rates of WCD discontinuation appear similar to reported rates of compliance with other prescribed therapies. One study reported that 15 percent of patients stop using aspirin, ACE inhibitors and beta-blockers within 30 days of a MI [55]. Improved compliance and acceptance of the WCD may be seen with newer devices, which are 40 percent smaller in size and weight or which offer multiple sizes and gender-specific fitting. USE OF THE WCD IN CHILDREN In December 2015, the US Food and Drug Administration (FDA) approved the WCD for use in children, although the WCD was used off-label prior to FDA approval [56]. As such, there are relatively few peer-reviewed publications documenting experience with the WCD in children [57- 59]. In a retrospective review of all patients <18 years of age who were prescribed the WCD between 2009 and 2016 (n = 455 patients), median duration of use was 33 days and wear time 20.6 hours [59]. Eight patients received at least one shock (seven episodes of ventricular tachycardia/ventricular fibrillation [VT/VF] in six patients, two inappropriate shocks due to oversensing), with four of the seven episodes of VT/VF terminated with a single shock and all seven episodes successfully terminated by the WCD. There were seven deaths (1.5 percent); none were wearing the WCD at the time of death. Children require special attention to assure compliance and correct fitting for optimal use. A variety of device harness sizes are available, but the smallest option may still be too large for https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 17/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate smaller children. Additional data on clinical efficacy, compliance, and complications should be collected in children as WCD use increases. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Introduction The wearable cardioverter-defibrillator (WCD) is an external device capable of automatic detection and defibrillation of ventricular tachycardia (VT) or ventricular fibrillation (VF) ( picture 1). In cases where the need for an implantable cardioverter- defibrillator (ICD) is felt to be temporary or implantation of the ICD must be deferred, a WCD may be an acceptable alternative approach for the prevention of sudden cardiac death (SCD). (See 'Description and functions of the WCD' above.) Device functions In addition to delivering therapeutic shocks for life-threatening ventricular arrhythmias, the WCD stores data regarding arrhythmias, patient compliance with the device, and noise or interference with its proper functioning. Arrhythmia recordings from the WCD are available for clinician review once stored data are transmitted to the manufacturer's network. (See 'Storage of ECGs and compliance data' above.) Efficacy When worn properly, the WCD appears to be as effective as an ICD for the termination of VT and VF, with successful shocks occurring in nearly 100 percent of cases. In addition, inappropriate shock rates from the WCD appear to be comparable to and in some studies lower than those reported for ICDs. (See 'Efficacy in terminating VT/VF' above and 'Inappropriate shocks' above.) Indications The WCD is an option as temporary therapy for select patients with a high risk for SCD: Among patients with left ventricular ejection fraction (LVEF) 35 percent who are less than 40 days post-myocardial infarction (MI), we discuss the potential benefits and risks of WCD use and offer it to highly motivated patients with NYHA functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for ICD https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 18/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate implantation after 40 days. Reevaluation of LVEF should occur one to three months after the MI. If LVEF remains 35 percent on follow-up assessment, despite appropriate medical therapy, ICD implantation is indicated and should be considered. (See 'Early post-MI patients with LV dysfunction' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Among patients with LVEF 35 percent who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery in the past three months, we offer a WCD to highly motivated patients for primary prevention against SCD. LVEF should be reassessed three months following CABG. If a sustained ventricular tachyarrhythmia has occurred, or if the LVEF remains 35 percent three months after CABG, implantation of an ICD is usually indicated. (See 'Patients with LV dysfunction early after coronary revascularization' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) In selected patients with severe but potentially reversible cardiomyopathy, such as tachycardia- or myocarditis-associated cardiomyopathy, the WCD may be useful for the prevention of SCD due to ventricular arrhythmias while awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See 'Newly diagnosed nonischemic cardiomyopathy' above.) Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD in whom ICD implantation is often recommended. The WCD may be a reasonable noninvasive alternative approach, particularly for patients whose anticipated waiting time to transplant is short if an ICD is not already present. (See 'Bridge to heart transplant' above.) Some patients with an indication for an ICD may require a delay in ICD implantation due to comorbid conditions (ie, infection, recovery from surgery, lack of vascular access). Additionally, some patients who have an ICD need it removed due to infection. In such patients, the WCD may provide protection against ventricular tachyarrhythmias until an ICD can be implanted or reimplanted. (See 'Bridge to indicated or interrupted ICD therapy' above.) Device limitations Limitations of the WCD (compared with a traditional ICD) include the lack of pacemaker functionality, the requirement for patient interaction and compliance, and potential discomfort due to the size and weight of the device. (See 'Limitations and precautions' above.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 19/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Sharma PS, Bordachar P, Ellenbogen KA. Indications and use of the wearable cardiac defibrillator. Eur Heart J 2016. 2. Reek S, Geller JC, Meltendorf U, et al. Clinical efficacy of a wearable defibrillator in acutely terminating episodes of ventricular fibrillation using biphasic shocks. Pacing Clin Electrophysiol 2003; 26:2016. 3. Feldman AM, Klein H, Tchou P, et al. Use of a wearable defibrillator in terminating tachyarrhythmias in patients at high risk for sudden death: results of the WEARIT/BIROAD. Pacing Clin Electrophysiol 2004; 27:4. 4. Klein HU, Meltendorf U, Reek S, et al. Bridging a temporary high risk of sudden arrhythmic death. Experience with the wearable cardioverter defibrillator (WCD). Pacing Clin Electrophysiol 2010; 33:353. 5. Chung MK, Szymkiewicz SJ, Shao M, et al. Aggregate national experience with the wearable cardioverter-defibrillator: event rates, compliance, and survival. J Am Coll Cardiol 2010; 56:194. 6. Epstein AE, Abraham WT, Bianco NR, et al. Wearable cardioverter-defibrillator use in patients perceived to be at high risk early post-myocardial infarction. J Am Coll Cardiol 2013; 62:2000. 7. Kutyifa V, Moss AJ, Klein H, et al. Use of the wearable cardioverter defibrillator in high-risk cardiac patients: data from the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II Registry). Circulation 2015; 132:1613. 8. W nig NK, G nther M, Quick S, et al. Experience With the Wearable Cardioverter- Defibrillator in Patients at High Risk for Sudden Cardiac Death. Circulation 2016; 134:635. 9. Kandzari DE, Perumal R, Bhatt DL. Frequency and Implications of Ischemia Prior to Ventricular Tachyarrhythmia in Patients Treated With a Wearable Cardioverter Defibrillator Following Myocardial Infarction. Clin Cardiol 2016; 39:399. 10. Schmitt J, Abaci G, Johnson V, et al. Safety of the Wearable Cardioverter Defibrillator (WCD) in Patients with Implanted Pacemakers. Pacing Clin Electrophysiol 2017; 40:271. 11. Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter defibrillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. 12. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 20/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335:1933. 13. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346:877. 14. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225. 15. Al-Khatib SM, Friedman P, Ellenbogen KA. Defibrillators: Selecting the Right Device for the Right Patient. Circulation 2016; 134:1390. 16. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 17. Piccini JP Sr, Allen LA, Kudenchuk PJ, et al. Wearable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac Death: A Science Advisory From the American Heart Association. Circulation 2016; 133:1715. 18. Masri A, Altibi AM, Erqou S, et al. Wearable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac Death: A Systematic Review and Meta-Analysis. JACC Clin Electrophysiol 2019; 5:152. 19. Ellenbogen KA, Koneru JN, Sharma PS, et al. Benefit of the Wearable Cardioverter- Defibrillator in Protecting Patients After Implantable-Cardioverter Defibrillator Explant: Results From the National Registry. JACC Clin Electrophysiol 2017; 3:243. 20. Solomon SD, Zelenkofske S, McMurray JJ, et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 2005; 352:2581. 21. Piccini JP, Al-Khatib SM, Hellkamp AS, et al. Mortality benefits from implantable cardioverter- defibrillator therapy are not restricted to patients with remote myocardial infarction: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Heart Rhythm 2011; 8:393. 22. Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter- defibrillator after acute myocardial infarction. N Engl J Med 2004; 351:2481. 23. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med 2009; 361:1427. 24. Olgin JE, Pletcher MJ, Vittinghoff E, et al. Wearable Cardioverter-Defibrillator after Myocardial Infarction. N Engl J Med 2018; 379:1205. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 21/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate 25. Olgin JE, Lee BK, Vittinghoff E, et al. Impact of wearable cardioverter-defibrillator compliance on outcomes in the VEST trial: As-treated and per-protocol analyses. J Cardiovasc Electrophysiol 2020; 31:1009. 26. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882. 27. Bigger JT Jr. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med 1997; 337:1569. 28. Weintraub WS, Grau-Sepulveda MV, Weiss JM, et al. Prediction of long-term mortality after percutaneous coronary intervention in older adults: results from the National Cardiovascular Data Registry. Circulation 2012; 125:1501. 29. Shahian DM, O'Brien SM, Sheng S, et al. Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study). Circulation 2012; 125:1491. 30. Zishiri ET, Williams S, Cronin EM, et al. Early risk of mortality after coronary artery revascularization in patients with left ventricular dysfunction and potential role of the wearable cardioverter defibrillator. Circ Arrhythm Electrophysiol 2013; 6:117. 31. Verdino RJ. The wearable cardioverter-defibrillator: lifesaving attire or "fashion faux pas?". J Am Coll Cardiol 2010; 56:204. 32. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004; 350:2151. 33. Makati KJ, Fish AE, England HH, et al. Equivalent arrhythmic risk in patients recently diagnosed with dilated cardiomyopathy compared with patients diagnosed for 9 months or more. Heart Rhythm 2006; 3:397. 34. Singh M, Wang NC, Jain S, et al. Utility of the Wearable Cardioverter-Defibrillator in Patients With Newly Diagnosed Cardiomyopathy: A Decade-Long Single-Center Experience. J Am Coll Cardiol 2015; 66:2607. 35. Barsheshet A, Kutyifa V, Vamvouris T, et al. Study of the wearable cardioverter defibrillator in advanced heart-failure patients (SWIFT). J Cardiovasc Electrophysiol 2017; 28:778. 36. Salehi N, Nasiri M, Bianco NR, et al. The Wearable Cardioverter Defibrillator in Nonischemic Cardiomyopathy: A US National Database Analysis. Can J Cardiol 2016; 32:1247.e1. 37. Duncker D, K nig T, Hohmann S, et al. Avoiding Untimely Implantable Cardioverter/Defibrillator Implantation by Intensified Heart Failure Therapy Optimization https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 22/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Supported by the Wearable Cardioverter/Defibrillator-The PROLONG Study. J Am Heart Assoc 2017; 6. 38. Saltzberg MT, Szymkiewicz S, Bianco NR. Characteristics and outcomes of peripartum versus nonperipartum cardiomyopathy in women using a wearable cardiac defibrillator. J Card Fail 2012; 18:21. 39. Lang CC, Hankins S, Hauff H, et al. Morbidity and mortality of UNOS status 1B cardiac transplant candidates at home. J Heart Lung Transplant 2003; 22:419. 40. Opreanu M, Wan C, Singh V, et al. Wearable cardioverter-defibrillator as a bridge to cardiac transplantation: A national database analysis. J Heart Lung Transplant 2015; 34:1305. 41. Gronda E, Bourge RC, Costanzo MR, et al. Heart rhythm considerations in heart transplant candidates and considerations for ventricular assist devices: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates 2006. J Heart Lung Transplant 2006; 25:1043. 42. Cantillon DJ, Tarakji KG, Kumbhani DJ, et al. Improved survival among ventricular assist device recipients with a concomitant implantable cardioverter-defibrillator. Heart Rhythm 2010; 7:466. 43. Wan C, Herzog CA, Zareba W, Szymkiewicz SJ. Sudden cardiac arrest in hemodialysis patients with wearable cardioverter defibrillator. Ann Noninvasive Electrocardiol 2014; 19:247. 44. Wan C, Szymkiewicz SJ, Klein HU. The impact of body mass index on the wearable cardioverter defibrillator shock efficacy and patient wear time. Am Heart J 2017; 186:111. 45. Sweeney MO, Wathen MS, Volosin K, et al. Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial. Circulation 2005; 111:2898. 46. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008; 359:1009. 47. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008; 51:1357. 48. Klein RC, Raitt MH, Wilkoff BL, et al. Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. J Cardiovasc Electrophysiol 2003; 14:940. 49. Wilkoff BL, Ousdigian KT, Sterns LD, et al. A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators: results from the prospective https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 23/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate randomized multicenter EMPIRIC trial. J Am Coll Cardiol 2006; 48:330. 50. Wilkoff BL, Williamson BD, Stern RS, et al. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol 2008; 52:541. 51. Wilkoff BL, Hess M, Young J, Abraham WT. Differences in tachyarrhythmia detection and implantable cardioverter defibrillator therapy by primary or secondary prevention indication in cardiac resynchronization therapy patients. J Cardiovasc Electrophysiol 2004; 15:1002. 52. Leyton-Mange JS, Hucker WJ, Mihatov N, et al. Experience With Wearable Cardioverter- Defibrillators at 2 Academic Medical Centers. JACC Clin Electrophysiol 2018; 4:231. 53. El-Battrawy I, Kovacs B, Dreher TC, et al. Real life experience with the wearable cardioverter- defibrillator in an international multicenter Registry. Sci Rep 2022; 12:3203. 54. Garcia R, Combes N, Defaye P, et al. Wearable cardioverter-defibrillator in patients with a transient risk of sudden cardiac death: the WEARIT-France cohort study. Europace 2021; 23:73. 55. Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med 2006; 166:1842. 56. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm466852.htm (Access ed on December 21, 2015). 57. Everitt MD, Saarel EV. Use of the wearable external cardiac defibrillator in children. Pacing Clin Electrophysiol 2010; 33:742. 58. Collins KK, Silva JN, Rhee EK, Schaffer MS. Use of a wearable automated defibrillator in children compared to young adults. Pacing Clin Electrophysiol 2010; 33:1119. 59. Spar DS, Bianco NR, Knilans TK, et al. The US Experience of the Wearable Cardioverter- Defibrillator in Pediatric Patients. Circ Arrhythm Electrophysiol 2018; 11:e006163. Topic 15824 Version 35.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 24/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate GRAPHICS Wearable cardioverter-defibrillator The wearable cardioverter-defibrillator consists of a vest incorporating two defibrillation electrodes and four sensing electrocardiographic electrodes connected to a waist unit containing the monitoring and defibrillation electronics. Reproduced with permission from: ZOLL Medical Corporation. Copyright 2012. All rights reserved. Graphic 60103 Version 3.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 25/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Electrocardiogram sensing (A) Five ECG electrodes are positioned circumferentially around the torso at the level of the subxiphoid process, labelled left front (LF), right front (RF), left back (LB), right back (RB), and right leg drive (RLD). Red dashed arrows represent the four differential ECG vectors derived using RLD as a ground reference. (B) Garment interior depicting five embedded, cushioned ECG electrodes and defibrillation pads (two posterior and one anterior). ECG: electrocardiogram. From: Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter de brillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. https://onlinelibrary.wiley.com/doi/10.1111/jce.15417. Copyright 2022 Wiley Periodicals, LLC. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/). Graphic 140856 Version 1.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 26/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate ASSURE WCD System noise management The A WCD employs three levels of protection to achieve a low false alarm rate due to noise. Level 1 (blue) minimize noise. Level 2 (red) detect and remove noise that does occur. Level 3 (yellow) allow time for remaining noise to subside before alarming. A-WCD: ASSURE WCD System; VT: ventricular tachycardia; VF: ventricular fibrillation; ECG: electrocardiogram. From: Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter de brillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. https://onlinelibrary.wiley.com/doi/10.1111/jce.15417. Copyright 2022 Wiley Periodicals, LLC. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/). Graphic 140843 Version 1.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 27/28 7/6/23, 1:46 PM Wearable cardioverter-defibrillator - UpToDate Contributor Disclosures Mina K Chung, MD No relevant financial relationship(s) with ineligible companies to disclose. Richard L Page, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 28/28 |
7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Atrial arrhythmias (including AV block) in congenital heart disease : Samuel Asirvatham, MD, Heidi M Connolly, MD, FACC, FASE, Christopher J McLeod, MB, ChB, PhD : Hugh Calkins, MD, Charles I Berul, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 08, 2022. INTRODUCTION One of the striking successes in caring for patients with congenital heart disease (CHD) over the last few decades is the improved longevity. Over one million adults with CHD are now living in the United States [1-4]; up to half having undergone at least one open heart surgical procedure resulting in one or more residual atrial scars [5,6]. For the purposes of this topic, CHD does not include bicuspid valves. As a consequence of both the added longevity and the atrial scarring from surgical procedures, atrial arrhythmias are increasingly recognized in this group. They are a major cause of hospital admission and morbidity in patients with CHD [7-9]. These rhythm abnormalities may be poorly tolerated and are associated with an almost 50 percent increase in mortality compared with those patients without atrial arrhythmias [9]. Although all forms of atrial bradycardia and tachycardia can adversely affect patients with CHD, there are particular considerations in this group because of the anatomy and prior surgical repairs. Although some arrhythmias are intrinsic to the cardiac maldevelopment itself, most are secondary to surgical scars and chronic hemodynamic burden. This review will focus on the management of these arrhythmias ( table 1), which should involve a comprehensive multidisciplinary approach. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 1/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate PREVALENCE AND INCIDENCE Excluding bicuspid aortic valve, around 1 percent of infants are born with congenital heart disease (CHD) ( table 2), with minor reported racial differences in the United States [10]. Many of the congenital cardiac lesions (45 percent) are classified as simple forms, such as atrial septal defects (ASD) and ventricular septal defects (VSD); moderate forms of CHD such as tetralogy of Fallot occur less commonly, and complex CHD occurs infrequently [11]. The epidemiology of CHD is discussed in detail elsewhere. (See "Identifying newborns with critical congenital heart disease", section on 'Epidemiology'.) The abnormal hemodynamics associated with CHD (through atrial stretch and concomitant fibrosis) exaggerates an arrhythmogenic milieu and increases the likelihood of atrial arrhythmias over time. (See "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis" and "Isolated atrial septal defects (ASDs) in children: Management and outcome" and "Management and outcome of tetralogy of Fallot" and "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".) Longitudinal studies suggest that atrial tachyarrhythmias afflict between 20 and 50 percent of individuals with CHD over their lifetime [9]. Approximately half of patients who have ASD repair over age 25 years [12] and nearly one-third of patients with tetralogy of Fallot develop atrial tachyarrhythmias [13]. (See "Clinical manifestations and diagnosis of atrial septal defects in adults" and "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults" and "Stroke associated with patent foramen ovale (PFO): Evaluation".) The development of atrial tachyarrhythmias is associated with higher morbidity, mortality, and hospitalization rates in patients with CHD and a worse functional class. Atrial tachyarrhythmias are independently associated with a higher risk of death in patients with single-ventricle anatomy, pulmonary hypertension, and valvular heart disease [14]. Atrial arrhythmias are seen in more than half of patients with the more complex repairs such as the classical atriopulmonary Fontan operation [15,16], and in response to this, alternate surgical approaches such as the extracardiac Fontan, which excludes the right atrium and the nidus for atrial arrhythmias, have evolved [17,18]. The frequency of congenital heart disease as a cause of atrial arrhythmias in the fetal heart is discussed separately. (See "Fetal arrhythmias".) PATHOPHYSIOLOGY https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 2/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Tachycardias in this group of patients most commonly have a reentrant mechanism and are facilitated by abnormal atrial substrate adjacent to valves, patches, or suture lines. In addition, cellular injury from longstanding hypoxia and atrial stretch conceivably also engenders inhomogeneity in myocardial conduction and refractoriness and hence adds to the arrhythmogenic milieu ( table 1) [19]. (See "Approach to the child with tachycardia".) Bradycardia can be inherent to the congenital anomaly, such as abnormalities of the sinus node or atrioventricular (AV) node in the heterotaxy (isomerism) syndromes, L-transposition of great arteries, or AV septal defects [20,21]. However, bradycardia is most commonly seen secondary to iatrogenic disruption of these structures and can occur in both the early postoperative period and/or many years after the operation, presumably driven by fibrosis [15,22-25] ( table 1). (See "Bradycardia in children".) Bradycardias Symptomatic bradycardia can cause considerable morbidity in patients with congenital heart disease (CHD). Pacemaker implantation is required for bradyarrhythmias in up to 3 to 4 percent of patients after surgical repair of Ebstein anomaly [26]; in approximately 7 percent of Fontan patients [15,27]; in over 80 percent of patients who have undergone atrial switch procedures for d-transposition of the great arteries; and around half of those patients with congenitally corrected transposition [28] of the great arteries (ccTGA) [22]. (See "Clinical manifestations and diagnosis of Ebstein anomaly".) Congenital sinus node dysfunction Superior sinus venosus ASDs (occurring in the septum between the superior vena cava and right-sided pulmonary veins) account for around 5 to 10 percent of all ASDs [29,30]. Due to the location of this defect, congenital sinus node dysfunction is commonly found [31]. This is also the case in the other rare CHD lesions that involve the heterotaxy syndromes or juxtaposed atrial appendages [32]. (See "Clinical manifestations and diagnosis of atrial septal defects in adults", section on 'Sinus venosus defect' and "Fetal arrhythmias".) Acquired sinus node dysfunction Any procedure involving an atriotomy such as cannulation for cardiopulmonary bypass potentially risks injury to the sinus node by virtue of its location. More extensive congenital operations involving atrial repair pose substantial risk to the sinus node. These include the atrial switch (Mustard/Senning), Glenn, Fontan, and Ebstein repairs [15,22,23,33]. Patients may present with an overt loss of sinus rhythm or a poor chronotropic response to exercise [22,23]. (See "Management of complications in patients with Fontan circulation", section on 'Arrhythmias'.) Congenital AV block While familial congenital AV block is reported, the majority of congenital AV block is secondary to maternal auto-antibodies in the settings of diseases like https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 3/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate systemic lupus erythematosus and Sj gren's disease [34,35]. The AV node is a right atrial structure, whereas the His bundle, the electrical continuation of the AV node, is a ventricular structure. Therefore, anatomical defects, which include misalignment of these two contiguous chambers, frequently result in interruption of AV conduction. These anomalies include ccTGA, large primum ASDs, and large AV septal defects (AV canal defects) [21,36]. These malformations can result in either complete heart block or progressive AV conduction disease [37]. (See "Pregnancy in women with congenital heart disease: Specific lesions", section on 'Congenitally corrected transposition of the great arteries' and "Management and outcome of atrioventricular (AV) canal defects", section on 'Arrhythmias'.) Acquired AV node dysfunction Surgical trauma in the region of the AV conduction axis occurs most commonly with operations that involve this region, such as aortic valve, left ventricular outflow tract, or AV valve repair/replacement [24]. Tachycardias Intraatrial reentrant tachycardia Atrial scars in repaired CHD patients provide a fundamental element for the development of intraatrial reentrant tachycardia (IART), which is the most common atrial tachyarrhythmia [33] in this population (see "Intraatrial reentrant tachycardia"). Mechanistically, IART is similar to atrial flutter, with a macro-reentrant circuit requiring a zone of slow conduction that develops in diseased tissue and is bordered by scars/valve or vena cava. Found primarily in patients where the atrial tissue is damaged through chronic stretch or operative scars, these circuits usually develop many years after the original intervention [38,39]. Classical intracardiac Fontan repairs, which utilize atrial tissue and the Mustard/Senning procedures, are most commonly associated with this arrhythmia. They can occur also with simple atriotomy scars ( figure 1). Concomitant sinus node dysfunction and older age at first surgical repair appear to increase the incidence [15]. The atrial rate may vary between 150 and 250 beats per minute, and in the presence of preserved AV nodal function, the ensuing ventricular response may be 1:1, with rapid clinical deterioration. Atrial fibrillation The pulmonary venous origins of paroxysmal atrial fibrillation in CHD do not appear to differ markedly from acquired heart disease [40]. Left heart lesions with subsequent left atrial stretch and fibrosis are most commonly associated with this rhythm abnormality. Associated coronary disease or lesions involving the left ventricular outflow tract and/or mitral valve are the more commonly related lesions [41]. The presence of CHD does not preclude other conditions contributing to atrial arrhythmias such as obstructive sleep apnea and thyroid disease, and these should be sought. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 4/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Ectopic/focal atrial tachycardia The precise etiology and prevalence of this arrhythmia in CHD is less clear (see "Focal atrial tachycardia"). It is far less common than IART and appears to be more prevalent in children than in adults with CHD [42]. It may originate from atrial tissue within the Fontan circuit, from the atrial appendages, or adjacent to the pulmonary veins. On the surface electrocardiogram, this arrhythmia can be identified by the unusual p-wave axis and often a progressive increase in the rate. Catheter ablation of the focus, however, is associated with much higher rates of success than IART and provides an excellent chance of cure [43]. EVALUATION Cardiac referral and further evaluation The management and treatment of patients with congenital heart disease (CHD) and atrial arrhythmias are often more complex than more typical arrhythmia patients. These patients should be referred to centers that routinely follow this population [44-46]. Importantly, atrial arrhythmias can be a harbinger of underlying hemodynamic deterioration, and a comprehensive congenital clinical and hemodynamic assessment is vital for all congenital cardiac patients. History A thorough surgical history, including operative reports, is necessary. This information is critical not only in the diagnostic work-up of the patient and atrial arrhythmia, but also in identifying whether venous access for catheters or permanent pacing is feasible. Similarly, during pacing or ablation procedures, inadvertent injury to the AV conduction system may occur. In these instances, it is critical to know whether a transvenous route to rapidly pace the ventricle is available. Physical examination The physical examination is important in order to identify evidence for concomitant cardiovascular lesions, which may be integral to the arrhythmia development. For example, the presence of peripheral edema, ascites, and an enlarged liver might identify Fontan obstruction or failure, and revision of this conduit may prove to be the most appropriate ultimate intervention for worsening atrial arrhythmias. Electrocardiogram The 12-lead electrocardiogram (ECG) is instrumental in clarifying the underlying rhythm disturbance in CHD patients [47]. However, the ECG can be misleading in this patient population, reemphasizing the importance of specialty care ( waveform 1). Patients with intraatrial reentrant tachycardia (IART) often have atrial rates that are slower than typical cavotricuspid isthmus dependent flutter, with discrete p-waves and an isoelectric interval. This rhythm is often mistaken for sinus tachycardia, as the p-wave can be buried in the preceding QRS complex or in the setting of 1:1 conduction through a healthy AV node ( waveform 2). Patients who have undergone modified Maze surgeries often have very little evidence of atrial https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 5/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate activity on the ECG, making electrocardiographic diagnosis challenging [48]. (See "Atrial fibrillation: Surgical ablation" and "Atrial fibrillation: Surgical ablation", section on 'Maze procedure'.) An underlying IART may be missed in this instance and running a longer rhythm strip can be helpful to identify grouped beating occurring in the context of variable AV block. The T wave should also be scrutinized for any sharp deflections not usually associated with repolarization, and hence indicative of atrial depolarization. Echocardiogram The transthoracic echocardiogram is invaluable in identifying structural and hemodynamic cardiac lesions that may have precipitated the rhythm disturbance. Conduit or valvular dysfunction may lead to secondary effects on the atrial muscle and thus a CHD specialist should interpret the echocardiograms in these patients. The echo examination may also provide the first clue to an atrial rhythm disturbance or demonstrate reduction in ventricular function from tachycardia. Fetal echocardiography has allowed identification of congenital cardiac anomalies, and this should be considered in fetuses at increased risk. (See "Congenital heart disease: Prenatal screening, diagnosis, and management".) Ambulatory ECG/Holter monitoring/prolonged cardiac monitoring device Twenty-four- hour Holter recordings or prolonged device monitoring (such as wireless patch cardiac monitors) are important tools to identify the underlying rhythm abnormality when the patient's ECG is unrevealing and there is a history of presyncope, syncope, or palpitations [49]. In addition, this can be a useful adjunctive investigation when chronotropic incompetence is suspected, due to underlying sinus, AV node, or medication-related bradycardia. (See "Ambulatory ECG monitoring".) Event monitor The event monitor is used to identify the etiology of short-lived symptoms that cannot be characterized by the ECG, Holter recordings, or prolonged device monitoring. One- to three-month periods of transient cardiac event monitors or looping recorders are frequently employed diagnostically, and insertable cardiac monitors (ICM; also sometimes referred to as implantable cardiac monitor or implantable loop recorder) can be considered for patients with infrequent symptoms. (See "Ambulatory ECG monitoring".) Exercise testing Exercise testing is vital in demonstrating chronotropic incompetence in the setting of symptomatic sinus node dysfunction and also for exposing infranodal AV conduction block in those patients with 2:1 AV block or exertional dyspnea. Catecholaminergic surges that develop during maximal effort can also precipitate tachyarrhythmias by influencing conduction velocity and refractoriness. In addition, faster AV node function during exercise may allow 1:1 https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 6/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate conduction in the context of a previously undiagnosed atrial tachycardia with 2:1 AV block. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".) Electrophysiology study It is recommended to proceed with an electrophysiology study in the evaluation of the patient with CHD following an unexplained cardiac arrest or syncopal event, and for those who present with sustained ventricular tachycardia. This is aimed at identifying potential lethal sinus or AV nodal disease and can identify whether a ventricular arrhythmia was likely causative. Electrophysiology study is also recommended in select CHD patients prior to cardiac surgical intervention such as those with Ebstein anomaly with a history of arrhythmias [50]. It should also be considered for this group of patients with palpitations where a standard workup has been unrevealing [50]. (See "Invasive diagnostic cardiac electrophysiology studies".) MANAGEMENT It is important to recognize that in the management of atrial tachyarrhythmias in patients with congenital heart disease (CHD), rhythm versus rate control has not been studied. (See "Management of atrial fibrillation: Rhythm control versus rate control".) The AFFIRM and HOT- CAF studies [51,52] did not include patients with CHD with or without prior repair, and as such we do not have any long-term data comparing the outcomes with these strategies. In addition, the most common atrial arrhythmia encountered in clinical practice is that of intraatrial reentrant tachycardia [41], an arrhythmia that is unlikely to respond to rate-control because of the fixed circuit and slower atrial cycle length. For this reason, antiarrhythmic medications and ablation provide the cornerstone of therapy [50]. Acute termination For any atrial tachyarrhythmia that is associated with hemodynamic instability, synchronized direct current (DC) cardioversion should be utilized without delay. (See "Basic principles and technique of external electrical cardioversion and defibrillation".) DC cardioversion can also be reserved for the initial management of hemodynamically stable yet symptomatic arrhythmias if a more definitive strategy has not yet been chosen, and the patient has fairly infrequent episodes. In this context, transesophageal echocardiography (TEE) to identify intracardiac clot is strongly recommended, especially in Fontan circulations, irrespective of the anticoagulation status [53,54]. The classical Fontan often entails sluggish blood flow, and atrial thrombus formation is common. Embolism of the thrombus into the pulmonary bed through DC cardioversion can be fatal in these patients. Cardioversion in the patient with CHD with appropriate precautions including anticoagulation and pre- or periprocedure TEE is proven to be safe and effective and should not be withheld [54,55]. TEE-guided cardioversions for https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 7/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Fontan and other high-risk congenital patients are commonly done in conjunction with anesthesia staff due to tenuous hemodynamics and the risk of complications related to sedation. Symptomatic bradyarrhythmias may require acute temporary pacing, and preprocedure knowledge of intracardiac and vena caval anatomy is critical. Anticoagulation is recommended for any CHD patient with an intracardiac shunt receiving a temporary pacemaker to avoid systemic thromboembolism from the pacing lead, until a permanent epicardial or alternate percutaneous system can be placed. (See "Temporary cardiac pacing".) Permanent pacemaker implantation In general, the indications for permanent pacing in CHD are similar to those in acquired heart disease. All symptomatic sinus or AV node disease requires pacemaker intervention [56]. (See "Permanent cardiac pacing: Overview of devices and indications" and "Congenital third-degree (complete) atrioventricular block".) Several special considerations apply to patients with CHD who require pacemaker implantation: Planning of lead access Lead access frequently poses difficulties in this group, and a detailed surgical history is necessary, often with adjunctive review of cross-sectional imaging (eg, computerized tomography, magnetic resonance imaging) or venography. In complex CHD patients with prior operative intervention in whom surgical reports are not available and urgent pacemaker placement is needed, imaging of venous anatomy with cross-sectional imaging or venography is crucial. Avoid thromboembolic stroke To avoid paradoxical thromboembolic stroke from transvenous lead thrombus, the clinician should image the heart and vessels (TEE with bubble study or venography) to exclude intracardiac shunting/baffle-leaks. If these are present and not amenable to closure, epicardial pacemaker lead placement may be indicated, depending on the patient-specific comorbid conditions [57-59]. No lead across mechanical tricuspid valve In patients with a mechanical tricuspid (non- systemic AV) valve, a pacemaker lead should not be positioned crossing the valve. Options in this setting include a coronary sinus lead [60] or an epicardial lead. Antiarrhythmic drug therapy Antiarrhythmic drugs remain a cornerstone in the management of atrial arrhythmias in CHD patients. Class I agents (such as propafenone or flecainide) should be avoided in any patient with ventricular scar given the potential for life- threatening ventricular arrhythmias [61-63]. (See "Arrhythmia management for the primary care clinician".) These medications slow cardiac electrical conduction, can also result in slower, more sustained atrial flutters, and hence are not the medications of choice in this group. Dofetilide https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 8/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate [64] and sotalol [65] delay repolarization and therefore are the most suitable for reentrant atrial arrhythmias (such as intraatrial reentrant tachycardia), with dofetilide having the added benefit of avoiding any impact on the sinus or AV nodes in the bradycardic patient [66]. (See "Clinical uses of sotalol" and "Clinical use of dofetilide".) The most effective drug is amiodarone [67], although significant side effects may be problematic leading to noncompliance or discontinuation [68]. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring" and "Amiodarone: Clinical uses".) Long-term use of amiodarone requires close monitoring of eye, thyroid, pulmonary, and hepatic function [64], and this should rarely be considered as lifelong suppressive therapy in the younger adult CHD patient with atrial arrhythmias [50]. Ablation Radiofrequency catheter ablation (RFA) is now utilized early in the course of many adult congenital patients with atrial tachyarrhythmias. Atrial arrhythmia ablation should be considered in symptomatic patients refractory to or unsuitable for long-term antiarrhythmic therapy. Minimally symptomatic atrial tachyarrhythmias can also be targeted with this approach to avoid a tachycardia-mediated decline in ventricular function. RFA can be complex in patients with CHD, and it is recommended these procedures be performed at centers experienced with RFA in this patient population [50]. Although early success rates are excellent even in the most complex defects [69,70], long-term recurrence rates remain suboptimal, especially when multiple circuits coexist and atrial scars are abundant [71]. The clinical tachycardia can most often be eradicated to reduce symptomatic recurrence and improve antiarrhythmic drug therapy or pacing efficacy [72-74], yet other arrhythmias can subsequently develop. Older age at time of ablation and complexity of the atrial repair (Fontan or atrial-switch) both predict worse procedural success [75]. It is also important to recognize that the electrophysiological study often unmasks underlying sinus node dysfunction, and a role for permanent pacing may be identified [75]. For this reason, we recommend discussing this antecedently with patients. Atrial antitachycardia devices Pacemakers with atrial antitachycardia pacing capability have been used to treat reentrant atrial tachycardias in patients with CHD. As a sole therapy, long- term efficacy for this approach is poor, but can be considered in patients with symptomatic bradycardia and/or other clear indications for pacing. In this setting, and often in conjunction with ablation, Maze, or anti-arrhythmic drug therapy, this pacing strategy can be effective in limiting symptomatic exacerbations [76,77]. Maze surgery CHD patients undergoing operative repair of a cardiac defect should be considered for Maze surgery if there is a background of atrial arrhythmias [78]. Cut-and-sew https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 9/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate techniques have higher rates of freedom from atrial arrhythmia when compared with alternative energy sources such as radio-frequency ablation or cryoablation [79,80]. No data currently exist on preemptive Maze surgery in CHD patients at high risk for, but without, prior documented arrhythmias. (See "Atrial fibrillation: Surgical ablation" and "Atrial fibrillation: Surgical ablation", section on 'Maze procedure'.) Anticoagulation therapy Anticoagulation therapy should be considered in CHD patients as soon as an atrial rhythm disturbance is identified. Patients with Fontan circulations have low flow states [81] and are at high risk of thrombus formation within the atria or Fontan circuit. Patients with repaired atrial septal defects also appear to be at high risk for thromboembolic complications in the setting of atrial arrhythmias, accounting for around one-fifth of late deaths in one series [12]. The use of conventional thromboembolic and hemorrhagic risk-assessment scores, such as CHA DS -VASc and CHADS2, 2 2 has not been rigorously evaluated in these patient groups. National and international societal recommendations [50] do, however, recommend using the CHA DS -VASc risk schema for simple 2 2 CHD syndromes (such as repaired atrial septal defect or ventricular septal defect) and then prescription of either warfarin or a direct oral anticoagulant is permissible. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) For all other patients with atrial arrhythmias (those with CHD of moderate or severe complexity), warfarin is generally recommended without the need for thromboembolic risk stratification [50]. Limited data regarding the non-vitamin K oral anticoagulant agents suggest efficacy in CHD patients [82-84]. SPECIFIC CONSIDERATIONS ASD Atrial septal defect (ASD) is one of the most common congenital cardiac anomalies and is associated with a high incidence of atrial arrhythmias, which increase in frequency as affected patients age [9,12]. (See "Management of atrial septal defects in adults".) The later in life the ASD is repaired, the more likely atrial arrhythmias are to develop. Surgical and device closure do not appear to mitigate the development of this problem [12]. In addition, significant thromboembolic complications have been observed in patients who had surgical ASD closure performed at 24 years of age or older, affecting around 22 percent of these patients [12]. For this reason, anticoagulation is recommended for all patients with atrial arrhythmias following surgical ASD closure with a CHA DS -VASc 2 [50]. Atrial arrhythmias should be actively 2 2 identified using routine ambulatory ECG monitoring. Intraatrial reentrant tachycardia circuits https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 10/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate around a patch or suture lines also occur frequently, and ablative therapy should be considered early in their management [85]. Prior Maze Modified Maze operations are a common, safe, and highly effective surgical method of restoring sinus rhythm in patients with CHD and atrial fibrillation/flutter. (See "Atrial fibrillation: Surgical ablation".) These interventions, which are often performed at the time of CHD operations, can be effective in preventing atrial arrhythmia recurrence approximately 70 to 80 percent at 10 years [86]. Maze procedures present potential electrical and mechanical complications subsequent to the extensive transmural lesions that not only potentially interfere with sinus and intraatrial conduction but which can also disrupt atrial mechanical compliance and transport. Sinus node dysfunction, atrial bradyarrhythmias and tachyarrhythmias, and development of an indication for permanent pacemaker implantation are among the sequelae of the Maze procedure. New atrial tachyarrhythmias can develop around Maze lesions, and ablation of these is commonly subsequently necessary. Antiarrhythmic drug therapy is frequently used in this setting, and atrial antitachycardia pacemakers can be of added utility [87]. (See "Atrial fibrillation: Surgical ablation", section on 'Limitations and complications'.) Tetralogy of Fallot Bradyarrhythmias requiring permanent pacing in patients with tetralogy of Fallot are uncommon. However, atrial tachyarrhythmias are a frequent cause of morbidity and may be seen in up to 25 percent of patients with tetralogy of Fallot [13] (see "Management and outcome of tetralogy of Fallot"). The prevalence of atrial arrhythmias markedly increases after 45 years of age in this group and in those with reduced left ventricular function [88]. Fontan procedure The "classic" Fontan procedure that fashions an atriopulmonary conduit from right atrial tissue is more frequently associated with the development of atrial arrhythmias [89] compared with contemporary "extracardiac" Fontan procedures [90]. In a retrospective analysis of adult patients with prior Fontan procedure (mean follow-up of 18.6 years), 42 percent sustained at least one tachyarrhythmia [74,91]. The most common arrhythmia was intraatrial reentrant tachycardia. These are commonly recurrent issues and are associated with important morbidity [70]. Anticoagulation is recommended in all Fontan patients with atrial arrhythmias [81], and empiric anticoagulation is often recommended for all patients with the classical atriopulmonary connection, since these patients are at the highest risk of thromboembolic events and atrial arrhythmias [90]. Conversion to an extracardiac conduit or total cavopulmonary connection may provide hemodynamic relief and reduce the arrhythmia burden, but it comes with substantial inherent operative risk, and candidates for this procedure should be carefully selected [92]. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 11/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Injury to the sinus node is also common following the Fontan procedure [93], and permanent pacing may be necessary. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient education: Heart block in adults (The Basics)" and "Patient education: Heart block in children (The Basics)") SUMMARY AND RECOMMENDATIONS Atrial arrhythmias are common in congenital heart disease (CHD), affecting at least 20 percent of CHD patients over their lifetime. (See 'Prevalence and incidence' above.) Atrial arrhythmias are a major cause of morbidity in patients with CHD and can be precipitated by cardiac residua. They can also cause hemodynamic deterioration. For this reason, it is imperative that a comprehensive clinical and hemodynamic assessment be undertaken as part of the initial arrhythmia work-up. (See 'Prevalence and incidence' above and 'Evaluation' above.) https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 12/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate CHD patients with atrial arrhythmias should be referred to centers that routinely care for CHD patients. Bradycardia can be inherent to the CHD anomaly; however, it is more commonly seen secondary to operative disruption of the conduction system. This can occur in both the early postoperative period or later due to fibrosis. (See 'Bradycardias' above.) Stroke is common in adult CHD patients, and atrial arrhythmias such as atrial fibrillation and intraatrial reentrant tachycardia (IART) should prompt the clinician to consider long- term oral anticoagulation. (See 'Anticoagulation therapy' above.) Indications for permanent pacing in CHD are similar to those in acquired heart disease. All symptomatic sinus or atrioventricular (AV) node disease requires pacemaker intervention with preemptive delineation of venous anatomy and intracardiac shunting being fundamental. (See 'Permanent pacemaker implantation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Marelli AJ, Mackie AS, Ionescu-Ittu R, et al. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation 2007; 115:163. 2. Brickner ME, Hillis LD, Lange RA. Congenital heart disease in adults. Second of two parts. N Engl J Med 2000; 342:334. 3. Brickner ME, Hillis LD, Lange RA. Congenital heart disease in adults. First of two parts. N Engl J Med 2000; 342:256. 4. Gilboa SM, Devine OJ, Kucik JE, et al. Congenital Heart Defects in the United States: Estimating the Magnitude of the Affected Population in 2010. Circulation 2016; 134:101. 5. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39:1890. 6. Waldmann V, Laredo M, Abadir S, et al. Atrial fibrillation in adults with congenital heart disease. Int J Cardiol 2019; 287:148. 7. Engelfriet P, Boersma E, Oechslin E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. Eur Heart J 2005; 26:2325. 8. Kanter RJ, Garson A Jr. Atrial arrhythmias during chronic follow-up of surgery for complex congenital heart disease. Pacing Clin Electrophysiol 1997; 20:502. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 13/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate 9. Bouchardy J, Therrien J, Pilote L, et al. Atrial arrhythmias in adults with congenital heart disease. Circulation 2009; 120:1679. 10. Botto LD, Correa A, Erickson JD. Racial and temporal variations in the prevalence of heart defects. Pediatrics 2001; 107:E32. 11. Walsh EP, Cecchin F. Arrhythmias in adult patients with congenital heart disease. Circulation 2007; 115:534. 12. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome after surgical repair of isolated atrial septal defect. Follow-up at 27 to 32 years. N Engl J Med 1990; 323:1645. 13. Roos-Hesselink J, Perlroth MG, McGhie J, Spitaels S. Atrial arrhythmias in adults after repair of tetralogy of Fallot. Correlations with clinical, exercise, and echocardiographic findings. Circulation 1995; 91:2214. 14. Yap SC, Harris L, Chauhan VS, et al. Identifying high risk in adults with congenital heart disease and atrial arrhythmias. Am J Cardiol 2011; 108:723. 15. Fishberger SB, Wernovsky G, Gentles TL, et al. Factors that influence the development of atrial flutter after the Fontan operation. J Thorac Cardiovasc Surg 1997; 113:80. 16. Stephenson EA, Lu M, Berul CI, et al. Arrhythmias in a contemporary fontan cohort: prevalence and clinical associations in a multicenter cross-sectional study. J Am Coll Cardiol 2010; 56:890. 17. Cecchin F, Johnsrude CL, Perry JC, Friedman RA. Effect of age and surgical technique on symptomatic arrhythmias after the Fontan procedure. Am J Cardiol 1995; 76:386. 18. Stamm C, Friehs I, Mayer JE Jr, et al. Long-term results of the lateral tunnel Fontan operation. J Thorac Cardiovasc Surg 2001; 121:28. 19. Walsh EP. Interventional electrophysiology in patients with congenital heart disease. Circulation 2007; 115:3224. 20. Momma K, Takao A, Shibata T. Characteristics and natural history of abnormal atrial rhythms in left isomerism. Am J Cardiol 1990; 65:231. 21. Anderson RH, Ho SY. The morphology of the specialized atrioventricular junctional area: the evolution of understanding. Pacing Clin Electrophysiol 2002; 25:957. 22. Flinn CJ, Wolff GS, Dick M 2nd, et al. Cardiac rhythm after the Mustard operation for complete transposition of the great arteries. N Engl J Med 1984; 310:1635. 23. Manning PB, Mayer JE Jr, Wernovsky G, et al. Staged operation to Fontan increases the |
sustained at least one tachyarrhythmia [74,91]. The most common arrhythmia was intraatrial reentrant tachycardia. These are commonly recurrent issues and are associated with important morbidity [70]. Anticoagulation is recommended in all Fontan patients with atrial arrhythmias [81], and empiric anticoagulation is often recommended for all patients with the classical atriopulmonary connection, since these patients are at the highest risk of thromboembolic events and atrial arrhythmias [90]. Conversion to an extracardiac conduit or total cavopulmonary connection may provide hemodynamic relief and reduce the arrhythmia burden, but it comes with substantial inherent operative risk, and candidates for this procedure should be carefully selected [92]. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 11/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Injury to the sinus node is also common following the Fontan procedure [93], and permanent pacing may be necessary. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient education: Heart block in adults (The Basics)" and "Patient education: Heart block in children (The Basics)") SUMMARY AND RECOMMENDATIONS Atrial arrhythmias are common in congenital heart disease (CHD), affecting at least 20 percent of CHD patients over their lifetime. (See 'Prevalence and incidence' above.) Atrial arrhythmias are a major cause of morbidity in patients with CHD and can be precipitated by cardiac residua. They can also cause hemodynamic deterioration. For this reason, it is imperative that a comprehensive clinical and hemodynamic assessment be undertaken as part of the initial arrhythmia work-up. (See 'Prevalence and incidence' above and 'Evaluation' above.) https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 12/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate CHD patients with atrial arrhythmias should be referred to centers that routinely care for CHD patients. Bradycardia can be inherent to the CHD anomaly; however, it is more commonly seen secondary to operative disruption of the conduction system. This can occur in both the early postoperative period or later due to fibrosis. (See 'Bradycardias' above.) Stroke is common in adult CHD patients, and atrial arrhythmias such as atrial fibrillation and intraatrial reentrant tachycardia (IART) should prompt the clinician to consider long- term oral anticoagulation. (See 'Anticoagulation therapy' above.) Indications for permanent pacing in CHD are similar to those in acquired heart disease. All symptomatic sinus or atrioventricular (AV) node disease requires pacemaker intervention with preemptive delineation of venous anatomy and intracardiac shunting being fundamental. (See 'Permanent pacemaker implantation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Marelli AJ, Mackie AS, Ionescu-Ittu R, et al. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation 2007; 115:163. 2. Brickner ME, Hillis LD, Lange RA. Congenital heart disease in adults. Second of two parts. N Engl J Med 2000; 342:334. 3. Brickner ME, Hillis LD, Lange RA. Congenital heart disease in adults. First of two parts. N Engl J Med 2000; 342:256. 4. Gilboa SM, Devine OJ, Kucik JE, et al. Congenital Heart Defects in the United States: Estimating the Magnitude of the Affected Population in 2010. Circulation 2016; 134:101. 5. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39:1890. 6. Waldmann V, Laredo M, Abadir S, et al. Atrial fibrillation in adults with congenital heart disease. Int J Cardiol 2019; 287:148. 7. Engelfriet P, Boersma E, Oechslin E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. Eur Heart J 2005; 26:2325. 8. Kanter RJ, Garson A Jr. Atrial arrhythmias during chronic follow-up of surgery for complex congenital heart disease. Pacing Clin Electrophysiol 1997; 20:502. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 13/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate 9. Bouchardy J, Therrien J, Pilote L, et al. Atrial arrhythmias in adults with congenital heart disease. Circulation 2009; 120:1679. 10. Botto LD, Correa A, Erickson JD. Racial and temporal variations in the prevalence of heart defects. Pediatrics 2001; 107:E32. 11. Walsh EP, Cecchin F. Arrhythmias in adult patients with congenital heart disease. Circulation 2007; 115:534. 12. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome after surgical repair of isolated atrial septal defect. Follow-up at 27 to 32 years. N Engl J Med 1990; 323:1645. 13. Roos-Hesselink J, Perlroth MG, McGhie J, Spitaels S. Atrial arrhythmias in adults after repair of tetralogy of Fallot. Correlations with clinical, exercise, and echocardiographic findings. Circulation 1995; 91:2214. 14. Yap SC, Harris L, Chauhan VS, et al. Identifying high risk in adults with congenital heart disease and atrial arrhythmias. Am J Cardiol 2011; 108:723. 15. Fishberger SB, Wernovsky G, Gentles TL, et al. Factors that influence the development of atrial flutter after the Fontan operation. J Thorac Cardiovasc Surg 1997; 113:80. 16. Stephenson EA, Lu M, Berul CI, et al. Arrhythmias in a contemporary fontan cohort: prevalence and clinical associations in a multicenter cross-sectional study. J Am Coll Cardiol 2010; 56:890. 17. Cecchin F, Johnsrude CL, Perry JC, Friedman RA. Effect of age and surgical technique on symptomatic arrhythmias after the Fontan procedure. Am J Cardiol 1995; 76:386. 18. Stamm C, Friehs I, Mayer JE Jr, et al. Long-term results of the lateral tunnel Fontan operation. J Thorac Cardiovasc Surg 2001; 121:28. 19. Walsh EP. Interventional electrophysiology in patients with congenital heart disease. Circulation 2007; 115:3224. 20. Momma K, Takao A, Shibata T. Characteristics and natural history of abnormal atrial rhythms in left isomerism. Am J Cardiol 1990; 65:231. 21. Anderson RH, Ho SY. The morphology of the specialized atrioventricular junctional area: the evolution of understanding. Pacing Clin Electrophysiol 2002; 25:957. 22. Flinn CJ, Wolff GS, Dick M 2nd, et al. Cardiac rhythm after the Mustard operation for complete transposition of the great arteries. N Engl J Med 1984; 310:1635. 23. Manning PB, Mayer JE Jr, Wernovsky G, et al. Staged operation to Fontan increases the incidence of sinoatrial node dysfunction. J Thorac Cardiovasc Surg 1996; 111:833. 24. Weindling SN, Saul JP, Gamble WJ, et al. Duration of complete atrioventricular block after congenital heart disease surgery. Am J Cardiol 1998; 82:525. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 14/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate 25. Bruckheimer E, Berul CI, Kopf GS, et al. Late recovery of surgically-induced atrioventricular block in patients with congenital heart disease. J Interv Card Electrophysiol 2002; 6:191. 26. Allen MR, Hayes DL, Warnes CA, Danielson GK. Permanent pacing in Ebstein's anomaly. Pacing Clin Electrophysiol 1997; 20:1243. 27. Cohen MI, Wernovsky G, Vetter VL, et al. Sinus node function after a systematically staged Fontan procedure. Circulation 1998; 98:II352. 28. Graham TP Jr, Bernard YD, Mellen BG, et al. Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study. J Am Coll Cardiol 2000; 36:255. 29. Oliver JM, Gallego P, Gonzalez A, et al. Sinus venosus syndrome: atrial septal defect or anomalous venous connection? A multiplane transoesophageal approach. Heart 2002; 88:634. 30. Peacock, TB. Malformations of the heart. In: On Malformations of the Human Heart: With Or iginal Cases, Peacock, TB (Eds), John Churchill, London 1858. p.11. 31. Attenhofer Jost CH, Connolly HM, Danielson GK, et al. Sinus venosus atrial septal defect: long-term postoperative outcome for 115 patients. Circulation 2005; 112:1953. 32. Anjos RT, Ho SY, Anderson RH. Surgical implications of juxtaposition of the atrial appendages. A review of forty-nine autopsied hearts. J Thorac Cardiovasc Surg 1990; 99:897. 33. Ghai A, Harris L, Harrison DA, et al. Outcomes of late atrial tachyarrhythmias in adults after the Fontan operation. J Am Coll Cardiol 2001; 37:585. 34. Jaeggi ET, Hamilton RM, Silverman ED, et al. Outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block. A single institution's experience of 30 years. J Am Coll Cardiol 2002; 39:130. 35. Baruteau AE, Fouchard S, Behaghel A, et al. Characteristics and long-term outcome of non- immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study. Eur Heart J 2012; 33:622. 36. Anderson RH, Shinebourne EA, Gerlis LM. Criss-cross atrioventricular relationships producing paradoxical atrioventricular concordance or discordance. Their significance to nomenclature of congenital heart disease. Circulation 1974; 50:176. 37. Connelly MS, Liu PP, Williams WG, et al. Congenitally corrected transposition of the great arteries in the adult: functional status and complications. J Am Coll Cardiol 1996; 27:1238. 38. Li W, Somerville J. Atrial flutter in grown-up congenital heart (GUCH) patients. Clinical characteristics of affected population. Int J Cardiol 2000; 75:129. 39. Wong T, Davlouros PA, Li W, et al. Mechano-electrical interaction late after Fontan operation: relation between P-wave duration and dispersion, right atrial size, and atrial arrhythmias. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 15/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Circulation 2004; 109:2319. 40. Ha ssaguerre M, Ja s P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339:659. 41. Kirsh JA, Walsh EP, Triedman JK. Prevalence of and risk factors for atrial fibrillation and intra- atrial reentrant tachycardia among patients with congenital heart disease. Am J Cardiol 2002; 90:338. 42. Walsh, EP, Walsh, et al. Cardiac arrhythmias in children and young adults with congenital he art disease, Lippincott Williams & Wilkins, Philadelphia 2001. 43. Tracy CM, Swartz JF, Fletcher RD, et al. Radiofrequency catheter ablation of ectopic atrial tachycardia using paced activation sequence mapping. J Am Coll Cardiol 1993; 21:910. 44. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019; 73:1494. 45. Bhatt AB, Foster E, Kuehl K, et al. Congenital heart disease in the older adult: a scientific statement from the American Heart Association. Circulation 2015; 131:1884. 46. Baumgartner H, De Backer J, Babu-Narayan SV, et al. 2020 ESC Guidelines for the management of adult congenital heart disease. Eur Heart J 2021; 42:563. 47. Akar JG, Kok LC, Haines DE, et al. Coexistence of type I atrial flutter and intra-atrial re- entrant tachycardia in patients with surgically corrected congenital heart disease. J Am Coll Cardiol 2001; 38:377. 48. Park HE, Kim KH, Kim KB, et al. Characteristics of P wave in patients with sinus rhythm after maze operation. J Korean Med Sci 2010; 25:712. 49. Dewey RC, Capeless MA, Levy AM. Use of ambulatory electrocardiographic monitoring to identify high-risk patients with congenital complete heart block. N Engl J Med 1987; 316:835. 50. Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD). Heart Rhythm 2014; 11:e102. 51. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 16/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate patients with atrial fibrillation. N Engl J Med 2002; 347:1825. 52. Opolski G, Torbicki A, Kosior DA, et al. Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Chest 2004; 126:476. 53. Egbe AC, Asirvatham SJ, Connolly HM, et al. Outcomes of Direct Current Cardioversion in Adults With Congenital Heart Disease. Am J Cardiol 2017; 119:1468. 54. Egbe AC, Connolly HM, Niaz T, McLeod CJ. Outcome of direct current cardioversion for atrial arrhythmia in adult Fontan patients. Int J Cardiol 2016; 208:115. 55. Ammash NM, Phillips SD, Hodge DO, et al. Outcome of direct current cardioversion for atrial arrhythmias in adults with congenital heart disease. Int J Cardiol 2012; 154:270. 56. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 57. Khairy P, Landzberg MJ, Gatzoulis MA, et al. Transvenous pacing leads and systemic thromboemboli in patients with intracardiac shunts: a multicenter study. Circulation 2006; 113:2391. 58. Cohen MI, Bush DM, Vetter VL, et al. Permanent epicardial pacing in pediatric patients: seventeen years of experience and 1200 outpatient visits. Circulation 2001; 103:2585. 59. Odim J, Suckow B, Saedi B, et al. Equivalent performance of epicardial versus endocardial permanent pacing in children: a single institution and manufacturer experience. Ann Thorac Surg 2008; 85:1412. 60. Noheria A, van Zyl M, Scott LR, et al. Single-site ventricular pacing via the coronary sinus in patients with tricuspid valve disease. Europace 2018; 20:636. 61. Perry JC, Garson A Jr. Flecainide acetate for treatment of tachyarrhythmias in children: review of world literature on efficacy, safety, and dosing. Am Heart J 1992; 124:1614. 62. Pfammatter JP, Paul T, Lehmann C, Kallfelz HC. Efficacy and proarrhythmia of oral sotalol in pediatric patients. J Am Coll Cardiol 1995; 26:1002. 63. Anastasiou-Nana MI, Anderson JL, Stewart JR, et al. Occurrence of exercise-induced and spontaneous wide complex tachycardia during therapy with flecainide for complex ventricular arrhythmias: a probable proarrhythmic effect. Am Heart J 1987; 113:1071. 64. Wells R, Khairy P, Harris L, et al. Dofetilide for atrial arrhythmias in congenital heart disease: a multicenter study. Pacing Clin Electrophysiol 2009; 32:1313. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 17/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate 65. Moore BM, Cordina RL, McGuire MA, Celermajer DS. Efficacy and adverse effects of sotalol in adults with congenital heart disease. Int J Cardiol 2019; 274:74. 66. Miyazaki A, Ohuchi H, Kurosaki K, et al. Efficacy and safety of sotalol for refractory tachyarrhythmias in congenital heart disease. Circ J 2008; 72:1998. 67. Moore BM, Cordina RL, McGuire MA, Celermajer DS. Adverse effects of amiodarone therapy in adults with congenital heart disease. Congenit Heart Dis 2018; 13:944. 68. Thorne SA, Barnes I, Cullinan P, Somerville J. Amiodarone-associated thyroid dysfunction: risk factors in adults with congenital heart disease. Circulation 1999; 100:149. 69. Kanter RJ, Papagiannis J, Carboni MP, et al. Radiofrequency catheter ablation of supraventricular tachycardia substrates after mustard and senning operations for d- transposition of the great arteries. J Am Coll Cardiol 2000; 35:428. 70. Egbe AC, Connolly HM, Khan AR, et al. Outcomes in adult Fontan patients with atrial tachyarrhythmias. Am Heart J 2017; 186:12. 71. de Groot NM, Atary JZ, Blom NA, Schalij MJ. Long-term outcome after ablative therapy of postoperative atrial tachyarrhythmia in patients with congenital heart disease and characteristics of atrial tachyarrhythmia recurrences. Circ Arrhythm Electrophysiol 2010; 3:148. 72. Triedman JK, Alexander ME, Love BA, et al. Influence of patient factors and ablative technologies on outcomes of radiofrequency ablation of intra-atrial re-entrant tachycardia in patients with congenital heart disease. J Am Coll Cardiol 2002; 39:1827. 73. Ja s P, Shah DC, Ha ssaguerre M, et al. Prospective randomized comparison of irrigated-tip versus conventional-tip catheters for ablation of common flutter. Circulation 2000; 101:772. 74. Triedman JK, DeLucca JM, Alexander ME, et al. Prospective trial of electroanatomically guided, irrigated catheter ablation of atrial tachycardia in patients with congenital heart disease. Heart Rhythm 2005; 2:700. 75. Yap SC, Harris L, Silversides CK, et al. Outcome of intra-atrial re-entrant tachycardia catheter ablation in adults with congenital heart disease: negative impact of age and complex atrial surgery. J Am Coll Cardiol 2010; 56:1589. 76. Rhodes LA, Walsh EP, Gamble WJ, et al. Benefits and potential risks of atrial antitachycardia pacing after repair of congenital heart disease. Pacing Clin Electrophysiol 1995; 18:1005. 77. Stephenson EA, Casavant D, Tuzi J, et al. Efficacy of atrial antitachycardia pacing using the Medtronic AT500 pacemaker in patients with congenital heart disease. Am J Cardiol 2003; 92:871. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 18/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate 78. Fuster V, Ryd n LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114:e257. 79. Stulak JM, Dearani JA, Sundt TM 3rd, et al. Superiority of cut-and-sew technique for the Cox maze procedure: comparison with radiofrequency ablation. J Thorac Cardiovasc Surg 2007; 133:1022. 80. Stulak JM, Dearani JA, Puga FJ, et al. Right-sided Maze procedure for atrial tachyarrhythmias in congenital heart disease. Ann Thorac Surg 2006; 81:1780. 81. Egbe AC, Connolly HM, McLeod CJ, et al. Thrombotic and Embolic Complications Associated With Atrial Arrhythmia After Fontan Operation: Role of Prophylactic Therapy. J Am Coll Cardiol 2016; 68:1312. 82. Yang H, Bouma BJ, Dimopoulos K, et al. Non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prevention, are they safe in congenital heart disease? Results of a worldwide study. Int J Cardiol 2020; 299:123. 83. Pujol C, M ssigmann M, Schiele S, et al. Direct oral anticoagulants in adults with congenital heart disease - a single centre study. Int J Cardiol 2020; 300:127. 84. Kawamatsu N, Ishizu T, Machino-Ohtsuka T, et al. Direct oral anticoagulant use and outcomes in adult patients with Fontan circulation: A multicenter retrospective cohort study. Int J Cardiol 2021; 327:74. 85. Kalman JM, VanHare GF, Olgin JE, et al. Ablation of 'incisional' reentrant atrial tachycardia complicating surgery for congenital heart disease. Use of entrainment to define a critical isthmus of conduction. Circulation 1996; 93:502. 86. Mavroudis C, Deal BJ, Backer CL, Tsao S. Arrhythmia surgery in patients with and without congenital heart disease. Ann Thorac Surg 2008; 86:857. 87. Drago F, Silvetti MS, Grutter G, De Santis A. Long term management of atrial arrhythmias in young patients with sick sinus syndrome undergoing early operation to correct congenital heart disease. Europace 2006; 8:488. 88. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010; 122:868. 89. Gelatt M, Hamilton RM, McCrindle BW, et al. Risk factors for atrial tachyarrhythmias after the Fontan operation. J Am Coll Cardiol 1994; 24:1735. https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 19/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate 90. Deshaies C, Hamilton RM, Shohoudi A, et al. Thromboembolic Risk After Atriopulmonary, Lateral Tunnel, and Extracardiac Conduit Fontan Surgery. J Am Coll Cardiol 2019; 74:1071. 91. Quinton E, Nightingale P, Hudsmith L, et al. Prevalence of atrial tachyarrhythmia in adults after Fontan operation. Heart 2015; 101:1672. 92. Mavroudis C, Backer CL, Deal BJ. Late reoperations for Fontan patients: state of the art invited review. Eur J Cardiothorac Surg 2008; 34:1034. 93. Takahashi K, Cecchin F, Fortescue E, et al. Permanent atrial pacing lead implant route after Fontan operation. Pacing Clin Electrophysiol 2009; 32:779. Topic 13599 Version 24.0 https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 20/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate GRAPHICS Etiology of arrhythmias in congenital heart disease Bradycardia Examples Congenital Congenital sinus node Situs inversus dysfunction Congenital AV block AV canal defects; cc-TGA Acquired Acquired sinus node dysfunction s/p repair of Mustand/Senning, Fontan, Glenn or sinus venosus ASD Acquired AV node dysfunction s/p VSD/LVOT/aortic valve operation Tachycardia Examples Congenital Twin AV nodes Heterotaxy syndrome Acquired Atrial tachycardia/flutter Atrial baffles; post-MAZE Atrial fibrillation ASD's, mitral valve disease Ectopic atrial tachycardia Fontan AV: atrioventricular; cc-TGA: congenitally corrected transposition of the great arteries; ASD: atrial septal defect; VSD: ventricular septal defect; LVOT: left ventricular outflow tract. Graphic 64292 Version 3.0 https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 21/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Common congenital anomalies per 10,000 live births Lesion Average Ventricular septal defect 36 Patent ductus arteriosus 8 Atrial septal defect 9 Atrioventricular septal defect 4 Pulmonary stenosis 7 Aortic stenosis 4 Coarctation of the aorta 4 Tetralogy of Fallot 4 d-Transposition of the great arteries 3 Bicuspid aortic valve 136 Data from: Ho man JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 32:1890. Graphic 78627 Version 2.0 https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 22/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Atriotomy scars The majority of atrial arrhythmias in congenital heart disease are driven by a scar-related reentrant mechanism. As evidenced in this diagram, the scars and postsurgical fibrotic tissue provide boundaries as well as a substrate for slow conduction, which allows for propagation of electrical reentry and intraatrial reentrant tachycardia (IART). The arrows delineate potential routes for electrical reentry during the propagation of IART. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; TV: tricuspid valve. By permission of the Mayo Foundation for Medical Education and Research. All rights reserved. Graphic 75779 Version 10.0 https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 23/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Atrial versus sinus rhythm on electocardiogram An ECG demonstrating an intraatrial reentrant tachycardia/atrial flutter in a patient with congenital heart dis Viewing lead V1, only a single p-wave is visible (arrows), and it is slightly positive with a negative terminal component, consistent with sinus rhythm/sinus tachycardia and potentially misleading. Lead II, however, rev notching of the T-wave (a second p-wave, dashed arrows), and the third p-wave is entirely hidden within the Q complex (not shown) in a 3:1 atrioventricular ratio. ECG: electrocardiogram. Graphic 114371 Version 2.0 https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 24/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Intraatrial reentrant tachycardia An electrocardiogram from a patient with a Fontan repair, demonstrating an intra-atrial reentrant tachycardia. The periods of higher grade AV block allow for easy identification of the P waves. Without these pauses, the atrial rhythm can be difficult to identify, as the P waves are frequently buried within the preceding QRS complex. This is most evident on the paced beats. Graphic 52478 Version 3.0 https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 25/26 7/6/23, 1:47 PM Atrial arrhythmias (including AV block) in congenital heart disease - UpToDate Contributor Disclosures Samuel Asirvatham, MD Grant/Research/Clinical Trial Support: Medtronic [Defibrillators]; St Jude's [Sudden Cardiac Death]. Consultant/Advisory Boards: BioTronik [Defibrillators]; Boston Scientific [Sudden Cardiac Death]. All of the relevant financial relationships listed have been mitigated. Heidi M Connolly, MD, FACC, FASE No relevant financial relationship(s) with ineligible companies to disclose. Christopher J McLeod, MB, ChB, PhD Consultant/Advisory Boards: BioSig Technologies [Signal processing module for cardiac mapping]. All of the relevant financial relationships listed have been mitigated. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Charles I Berul, MD Patent Holder: PeriCor LLC [Pacemakers/defibrillators]. Grant/Research/Clinical Trial Support: Medtronic Inc [Pacemakers/defibrillators]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atrial-arrhythmias-including-av-block-in-congenital-heart-disease/print 26/26 |
7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Atrioventricular nodal reentrant tachycardia : Bradley P Knight, MD, FACC : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 30, 2023. INTRODUCTION Atrioventricular nodal reentrant tachycardia (AVNRT) is a regular supraventricular tachycardia (SVT) that results from the formation of a reentry circuit confined to the AV node and perinodal atrial tissue. Because of its abrupt onset and termination, AVNRT is categorized as a paroxysmal SVT (PSVT). As with the majority of SVTs, the QRS complex in AVNRT is usually narrow (ie, 120 milliseconds), reflecting normal ventricular activation through the His-Purkinje system. However, rate-related aberrant conduction during SVT or an underlying bundle branch block can result in a wide QRS complex tachycardia. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Paroxysmal and incessant SVT'.) This topic will review the mechanisms, clinical manifestations, diagnosis, and the management of AVNRT. A detailed discussion of the broader approach to narrow QRS complex tachycardias is presented separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) EPIDEMIOLOGY AVNRT is the most common form of regular, sustained, paroxysmal supraventricular tachycardia (PSVT), accounting for nearly two-thirds of all PSVTs, and is more common in women compared with men [1-3]. AVNRT can present at any age, but as with AV reentrant tachycardia (AVRT) that involves an accessory pathway, it is more likely to begin in young adults. In a series of 231 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 1/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate patients with AVNRT, the mean age of symptom onset was 32 years, with two-thirds of cases beginning after the age of 20 [4]. ANATOMY AND PATHOPHYSIOLOGY The physiologic substrate for AVNRT involves dual electrical pathways that lead to the compact AV node ( table 1) [5,6]. The arrhythmia usually develops in hearts that are otherwise normal, although it can also occur in the presence of underlying structural heart disease [7,8]. A more detailed discussion of the electrophysiology of AVNRT can be found in published reviews [5,6,9,10]. (See 'Dual AV nodal physiology' below.) Anatomy The exact anatomic distribution of these pathways is uncertain. Koch's triangle is bounded by the tricuspid ring and the tendon of Todoro, which bracket the coronary sinus at the base of the triangle and are in close proximity forming the apex near the His bundle at the membranous septum ( figure 1 and figure 2) [5,11]. As an approximation, Koch's triangle can be divided into thirds: The anterior third, which contains the AV node and fast pathways The middle third The posterior third, the usual site of slow pathways Dual AV nodal physiology The simplest concept of AV nodal physiology that allows for reentry involves separate electrical pathways proximal to the AV node ( figure 3). This model is supported by clinical observations as well as animal and human mapping studies [5,12,13]. These pathways may be distinct anatomic structures, or they may be functionally separate (ie, regions that appear anatomically continuous but have different electrical properties). It is possible that some cases of AVNRT are acquired when there is right atrial pressure overload leading to changes in the electrophysiologic properties of the AV nodal inputs. Rare cases of familial AVNRT have also been reported [14]. Whether the dual pathways are anatomic or functional, in order for reentry to occur, they must have different conduction velocities and refractory periods [15]: One pathway conducts rapidly and has a relatively long refractory period. This is called the fast pathway. The second pathway conducts relatively slowly and has a shorter refractory period. This is called the slow pathway. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 2/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate The origins of the fast and slow pathways are probably in perinodal atrial tissue. These pathways join and enter a final common pathway in the compact AV node. While atrial tissue above the AV node appears to be part of the reentrant circuit, the bundle of His below the node is not a necessary part of the circuit. This can be illustrated by the following observations: AVNRT is associated with 2:1 AV block in approximately 10 percent of patients [16]. The AV block in this setting is probably a functional infranodal block within the bundle of His [16]. His bundle electrograms indicate that reentry is proximal to the recording site [17,18]. Not all patients with AVNRT have evidence of dual pathways during electrophysiology (EP) studies. Conversely, not all patients with dual AV nodal pathways have clinical AVNRT ( waveform 1A-B). The imperfect association between dual AV nodal physiology and clinical AVNRT was illustrated in a series of 180 patients undergoing EP studies for a variety of indications [19]. Among the 87 patients with AVNRT, 39 percent did not have clear evidence of dual AV nodal physiology. In contrast, 30 percent of the 66 patients with documented dual AV nodal physiology did not have AVNRT. A concealed atrio-Hisian tract that bypasses the AV node may constitute the retrograde fast pathway in up to a third of all apparently "typical" AVNRT cases [20]. Thus, the anatomic and electrophysiologic mechanism of AVNRT may be more complex than the dual AV nodal physiology model suggests [21,22]. Dual AV nodal pathways during normal sinus rhythm During normal sinus rhythm, AV conduction occurs as follows ( figure 3): The normal sinus beat enters the AV node and the impulse travels down both the fast and slow pathways. The impulse traveling down the fast pathway reaches the His bundle first, creating a refractory wake. The impulse traveling down the slow pathway is extinguished when, in the area of the final common pathway, it runs into the refractory wake of the impulse that had traveled down the fast pathway. Typical AVNRT Approximately 80 to 90 percent of patients with AVNRT present with what is called the common form of the arrhythmia. The common form is also called "typical AVNRT" or "slow-fast" AVNRT. Typical AVNRT usually initiates as follows ( figure 3): https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 3/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate A premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) (or less commonly, a premature junctional or ventricular beat with retrograde conduction) arrives at the AV node when the fast pathway is in its refractory period. Thus, antegrade conduction down the fast pathway is blocked. If the premature beat arrives in a specific time window (ie, a "critically timed" premature beat), the slow pathway, with a shorter refractory period than the fast pathway, is available for conduction to the ventricle. The premature beat conducts via the slow pathway, through the final common pathway, to the bundle of His. As a result, the PR interval of the premature beat will be longer than those of normal beats conducted through the fast pathway. If the fast pathway has recovered its excitability by the time the slow pathway impulse reaches the distal junction of the two pathways, the impulse can conduct retrograde up the fast pathway. The circuit may then become repetitive with antegrade conduction back down the slow pathway and retrograde conduction up the fast pathway resulting in a sustained tachycardia ( figure 3 and figure 4). This proposed mechanism explains a number of clinical observations in AVNRT: A single PAC (or retrograde penetration of the AV node from a junctional or premature ventricular complex/contraction [PVC; also referred to a premature ventricular beats or premature ventricular depolarizations]) can initiate the arrhythmia. Penetration of the reentrant circuit by a premature beat can abruptly terminate the arrhythmia. Atypical AVNRT Up to 20 percent of patients with AVNRT have uncommon forms of the arrhythmia, referred to as "atypical AVNRT." As examples: Antegrade conduction can occur down the fast pathway with retrograde conduction up the slow pathway ( figure 5 and figure 6 and waveform 2) [23]. This is referred to as "fast-slow" AVNRT. Some patients have multiple slow pathways, resulting in "slow-slow AVNRT" variants in which both the antegrade and retrograde limbs of the circuit utilize slow AV nodal pathways. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 4/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Rarely during AVNRT, conduction through the reentrant circuit is so slow that the heart rate is less than 100 beats per minute, by definition not a tachycardia. Despite the absence of tachycardia, patients can be symptomatic and may be treated with a slow pathway ablation. This arrhythmia, sometimes referred to as AV nodal reentrant arrhythmia (AVNRA), has been mistaken for a junctional rhythm. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Undetectable P waves'.) Typical and atypical AVNRT have rarely been found to coexist in the same patient during electrophysiology studies [24]. CLINICAL MANIFESTATIONS Symptoms Patients with AVNRT most commonly report palpitations, dizziness or lightheadedness, and dyspnea. Because of the paroxysmal nature of the arrhythmia, the onset and termination of the symptoms are usually sudden. Those with significant heart disease may have additional symptoms such as dyspnea and chest pain. Because atrial activation occurs coincident with ventricular activation during typical AVNRT, atrial contraction occurs when the tricuspid valve is closed, causing rhythmic abrupt rises in venous pressure, and can result in a sensation of neck pounding. Some patients with AVNRT have a feeling of polyuria and experience a diuresis during or after AVNRT; the mechanism probably is related to an elevated mean right atrial pressure and plasma level of atrial natriuretic peptide, which are present during the arrhythmia [25]. In a series of 167 supraventricular tachycardia (SVT) patients referred for radiofrequency ablation, the 64 patients with AVNRT reported the following symptoms [26]: Palpitations 98 percent Dizziness 78 percent Dyspnea 47 percent Chest pain 38 percent Fatigue 19 percent Syncope 16 percent Syncope is an uncommon feature of AVNRT and appears to be more likely with high heart rates (eg, heart rate 170 beats per minute). However, factors other than heart rate also contribute to syncope. As an example, abnormal vasomotor adaptation during AVNRT has been reported, suggesting a role for neurally mediated (neurocardiogenic) responses [27,28]. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 5/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate In very rare cases, AVNRT can result in cardiac arrest [29]. Triggers Most often there is no apparent precipitating cause for episodes of AVNRT. In some patients, nicotine, alcohol, stimulants, and exercise can initiate episodes. A 2020 scientific statement from the American Heart Association details drugs associated with AVNRT [30]. Some patients experience the onset of AVNRT during sleep or after sudden bending forward or squatting, all of which can enhance vagal tone. In contrast to using vagal maneuvers to terminate AVNRT, increased vagal tone may facilitate the induction of AVNRT in some circumstances. In one series of 10 patients with AVNRT, electrophysiologic data were measured before and during continuous enhancement of vagal tone induced by infusing phenylephrine [31]. Vagal enhancement markedly prolonged the effective refractory period and functional refractory period of antegrade conduction in the fast pathway. However, the refractoriness of antegrade conduction in the slow pathway and retrograde conduction in the fast pathway were unchanged. Electrocardiographic characteristics All patients with palpitations should undergo 12-lead electrocardiography (ECG), ideally while symptomatic. There are several ECG features that are helpful in confirming the diagnosis of AVNRT. Ventricular rate The ventricular rate is generally between 120 and 220 beats per minute. Abrupt onset following PAC If the initiation of the tachycardia is captured on a tracing, the tachycardia often begins with a PAC with sudden prolongation of the PR interval ( figure 4). (See 'Typical AVNRT' above.) Relationship between QRS complexes and P waves Because of the relationships between the QRS complex and the following P wave, typical AVNRT is referred to as a "short RP tachycardia," while atypical AVNRT is a "long RP tachycardia" [10]. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'RP relationship'.) In typical AVNRT, retrograde atrial activation and antegrade ventricular activation occur almost simultaneously ( figure 4). The P wave, therefore, is usually buried within or fused with the QRS complex. A component of the P wave is often evident slightly after, or less commonly before, the QRS ( figure 7 and waveform 3). When the P wave occurs shortly after the QRS https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 6/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate complex, the fused waveform can produce a pseudo-R' (a second R wave) in lead V1 and a pseudo-S wave in the inferior leads. (See 'Typical AVNRT' above.) In atypical AVNRT, retrograde atrial activation occurs long after ventricular activation, resulting in a P wave so late after the QRS complex that it appears to be occurring shortly before the next QRS complex ( figure 5 and figure 6 and waveform 2). This pattern resembles that seen in atrial tachycardias. In such cases, an electrophysiology (EP) study may be required to define the arrhythmogenic mechanism. (See 'Atypical AVNRT' above and "Invasive diagnostic cardiac electrophysiology studies".) P wave morphology The P wave axis, when P waves can be clearly identified, is abnormal due to retrograde atrial activation. This is usually manifested on the electrocardiogram as a negative P wave axis with inverted P waves in leads II, III and aVF [32]. ST segment depression Significant ST segment depression during tachycardia has been observed in 25 to 50 percent of patients with AVNRT, although it is more commonly seen in those with an AV reentrant tachycardia associated with an accessory pathway [33-35]. The ST segment depression does not represent myocardial ischemia in most patients (although it may in patients with significantly underlying coronary heart disease), but rather represents abnormalities of repolarization [36]. T wave inversions following termination After acute termination of AVNRT and other paroxysmal SVTs, T wave inversions may be seen in the anterior or inferior leads in approximately 40 percent of patients [37]. Inverted T waves may be seen immediately upon termination or may develop within the first six hours, and can persist for hours to days. The occurrence of negative T waves is not predicted by clinical parameters, tachycardia rate or duration, or the presence and extent of ST segment depression during the tachycardia. They are not the result of coronary artery disease, but are repolarization abnormalities, likely due to ionic current alterations resulting from the rapid rate. DIAGNOSIS The diagnosis of AVNRT should be suspected in a patient with the abrupt onset and offset of rapid sustained palpitations, often associated with lightheadedness or dyspnea. The ability for a patient to terminate the symptoms with a vagal maneuver is also suggestive of AVNRT as a potential etiology of symptoms. (See 'Symptoms' above and 'Vagal maneuvers' below.) The diagnosis of AVNRT is typically confirmed following the review of an ECG acquired during the arrhythmia. When possible, review of the ECG at the onset or termination of the arrhythmia https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 7/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate should be performed as this frequently provides additional information (ie, initiation following an PAC with sudden prolongation of the PR interval ( figure 4)). When there is sudden termination of a regular paroxysmal supraventricular tachycardia (PSVT) that has 1:1AV conduction associated with AV block but not due to a PAC (last beat of the tachycardia is a P wave rather than a QRS complex that occurs at the expected timing), then an atrial tachycardia is very unlikely. In typical AVNRT, the P wave is usually buried within or fused with the QRS complex, resulting in a pseudo-R' (a second R wave) in lead V1 and a pseudo-S wave in the inferior leads. In atypical AVNRT, the P wave occurs late after the QRS complex, often appearing shortly before the next QRS complex, resulting in a pattern that resembles atrial tachycardia. If the diagnosis cannot be confirmed following review of the surface ECG, invasive electrophysiology studies can be performed in an effort to confirm the diagnosis. (See "Invasive diagnostic cardiac electrophysiology studies".) DIFFERENTIAL DIAGNOSIS The differential diagnosis of palpitations is extensive ( table 2), and the etiology varies depending upon the population studied. The approach to palpitations is discussed separately. (See "Evaluation of palpitations in adults".) Once a tachycardia with a narrow QRS complex has been identified, the differential diagnosis is generally limited to SVTs, although on rare occasions idiopathic left ventricular tachycardia (a ventricular tachycardia arising from septum) can present as a narrow complex tachycardia. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Idiopathic left ventricular tachycardia'.) Sustained narrow QRS complex tachycardias are generally divided according to whether the QRS complexes occur regularly or irregularly: Irregular QRS complexes Atrial fibrillation, atrial flutter with variable conduction, multifocal atrial tachycardia. Regular QRS complexes Sinus tachycardia, atrial flutter, AVNRT, atrioventricular reentrant tachycardia (AVRT), atrial tachycardia (AT), and junctional ectopic tachycardia (JET). The term PSVT generally refers to AVNRT, AVRT, AT, and JET. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 8/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Because AVNRT is a regular tachycardia, the tachycardias with irregular QRS complex can be excluded immediately. The remainder of the differential diagnosis discussion will focus on the other regular narrow QRS complex tachycardias. Sinus tachycardia Sinus tachycardia is the most common narrow QRS complex tachycardia. Typically, sinus tachycardia is a response to another condition in which catecholamine release is physiologically enhanced or, less commonly, the parasympathetic nervous system withdrawn. In contrast to the abrupt onset and termination of AVNRT, sinus tachycardia has a gradual onset and offset, which typically occurs over 30 seconds to several minutes. Additionally, for the vast majority of patients, sinus tachycardia does not result in symptoms. (See "Sinus tachycardia: Evaluation and management".) Atrioventricular reentrant tachycardia Patients with AVRT can present in a similar fashion to patients with AVNRT. Both arrhythmias are associated with the abrupt onset of palpitations, and the surface ECG may appear very similar with regular QRS complexes and inverted P waves and a short RP interval that is less than one-half of the RR interval. AVNRT is most easily distinguished from AVRT when evidence of pre-excitation (short PR interval and delta wave) can be identified on prior ECGs during normal sinus rhythm (when available) consistent with an accessory pathway and the potential for AVRT. In the event of concealed pre-excitation, invasive electrophysiology studies may be required to distinguish AVNRT from AVRT. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Atrial tachycardia As with AVNRT and AVRT, most patients with focal atrial tachycardia report an abrupt onset of palpitations associated with their episodes of tachycardia. In contrast to AVNRT, the P wave morphology during atrial tachycardia can appear normal or abnormal, depending upon the site of origin of the tachycardia, and the P waves tend to occur prior to the QRS complex, resulting in a long RP tachycardia. (See "Focal atrial tachycardia".) Junctional ectopic tachycardia Junctional ectopic tachycardia (JET) is a focal ectopic arrhythmia arising from the AV node region itself. It is a rare arrhythmia most often seen in young children as a congenital arrhythmia or after surgery for congenital heart disease [38]. JET can be difficult to differentiate from typical AVNRT. However, JET should be suspected when there is ventriculoatrial block during tachycardia and when the tachycardia is initiated by a premature junctional beat. Because the substrate related to JET is near the compact AV node, there is a greater concern for AV block during catheter ablation of JET compared with AVNRT [39]. Other SVTs Other than sinus tachycardia, AVRT, and atrial tachycardia, the remaining SVTs occur far less commonly. Inappropriate sinus tachycardia and sinoatrial nodal reentrant https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 9/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate tachycardia have an identical appearance to sinus tachycardia. In contrast to sinus tachycardia, sinoatrial nodal reentrant tachycardia can have an abrupt onset (making it look identical to atrial tachycardia) and requires invasive electrophysiology studies to diagnose. Inappropriate sinus tachycardia tends to persist for days to weeks without the typical associations seen with sinus tachycardia (eg, pain, fever, hypovolemia, etc) and is relatively refractory to rate-slowing medications. Intraatrial tachycardia is a type of reentrant tachycardia seen almost exclusively in patients with underlying structural heart disease and prior cardiac procedures resulting in scar formation (eg, repair of congenital heart disease, catheter ablation for atrial fibrillation, etc). (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia' and "Sinoatrial nodal reentrant tachycardia (SANRT)" and "Intraatrial reentrant tachycardia".) INITIAL MANAGEMENT The initial management of a patient presenting with a narrow QRS tachycardia and suspected AVNRT is guided by whether or not the patient is experiencing signs and symptoms of hemodynamic instability ( algorithm 1) related to the rapid heart rate (eg, hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness). Unstable patients require urgent electrical cardioversion. However, it is very rare that a patient with paroxysmal supraventricular tachycardia (PSVT) requires electrical cardioversion. There are several effective therapies for the acute termination of AVNRT, but few data regarding the optimal sequence of therapies for the acute termination of AVNRT [40,41]. These treatment options include: Vagal maneuvers (see "Vagal maneuvers") Intravenous (IV) adenosine IV calcium channel blockers or beta blockers Management recommendations are based upon an understanding of the properties and risks of the treatment options. Almost all patients, including those who are severely symptomatic, can be treated first with several attempts at vagal maneuvers or IV adenosine [40,41]. Our recommendations are in general agreement with published professional society recommendations [40,41]. Electrical cardioversion AVNRT almost always terminates with vagal maneuvers or intravenous antiarrhythmic therapy with adenosine, calcium channel blockers, or beta blockers. However, if the patient is hemodynamically unstable, or if AVNRT persists in spite of vagal https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 10/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate maneuvers or AV nodal blocking medications, electrical cardioversion should be considered ( algorithm 1). Electrical cardioversion is usually successful but may require relatively high energy levels, probably due to the deep location of the reentrant pathway. If sinus rhythm is not restored following an initial 50 to 100 joule shock, subsequent shocks should be at higher energy levels ( algorithm 2). Although energy requirements with biphasic waveforms have not been reported, they are likely to be lower than for monophasic waveforms based upon experience with other arrhythmias. (See "Cardioversion for specific arrhythmias".) Vagal maneuvers Vagal maneuvers (eg, Valsalva maneuver or carotid sinus massage) are safe, easily performed, and effective first-line therapies for patients with AVNRT ( algorithm 1). For patients who are hemodynamically stable and able to effectively perform the vagal maneuvers, we recommend at least one or two attempts at a standard Valsalva maneuver, followed by at least one or two attempts using the modified Valsalva maneuver (if AVNRT persists), as the initial treatment for AVNRT rather than another vagal maneuver or adenosine. Vagal maneuvers increase parasympathetic tone, which produces a gradual slowing of conduction in the antegrade slow pathway. Slowing and eventual block in the antegrade slow pathway are the usual cause for arrhythmia termination with these interventions [42], although they can also produce abrupt block in the retrograde fast pathway. In one systematic review, which included 316 patients with a total of 965 episodes of supraventricular tachycardia (SVT; which included both AVNRT and atrioventricular reciprocating tachycardia), the standard Valsalva maneuver (exhaling forcefully against a closed glottis for 10 to 15 seconds) successfully terminated 45 percent of SVT episodes and was more successful than carotid sinus massage [43]. To perform a standard Valsalva maneuver, the patient is placed in a supine or semi-recumbent position and instructed inhale normally and then to exhale forcefully against a closed glottis for 10 to 15 seconds. A modified Valsalva maneuver (which begins with the standard Valsalva maneuver and is followed by supine positioning and passive leg raising) has been proposed as an improvement on the standard Valsalva maneuver. In the largest randomized trial of vagal maneuvers for the treatment of SVT, 428 patients with hemodynamically stable SVT were randomly assigned to perform the standard Valsalva maneuver (strain generating 40 mmHg pressure for 15 seconds while in a semi-recumbent position) or to perform the standard Valsalva maneuver followed by supine repositioning (placing the patient supine from the upright or semi- recumbent position) and passive leg raise for 15 seconds (214 patients per group) [44]. Patients performing the modified Valsalva maneuver with supine repositioning and passive leg raise were significantly more likely to have restoration of sinus rhythm at one minute (43 versus 17 percent in the standard Valsalva group; adjusted odds ratio 3.7; 95% CI 2.3-5.8). When feasible, https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 11/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate we recommend the modified Valsalva maneuver given the greater likelihood of successful restoration of sinus rhythm. Additional information on the performance and use of vagal maneuvers is presented separately. (See "Vagal maneuvers".) Adenosine If vagal maneuvers cannot be performed or if they fail to terminate the arrhythmia, IV medical therapy that blocks AV nodal conduction is indicated as the next step ( algorithm 1). For patients with AVNRT that persists following vagal maneuvers (or in whom vagal maneuvers cannot be adequately performed), we recommend IV adenosine rather than a calcium channel blocker or a beta blocker. The protocol for administration of adenosine is described in the algorithm ( algorithm 3). The advantages of adenosine over other agents include rapid onset and a short half-life. Adenosine terminates AVNRT in over 80 percent of cases [45-47]. It is well tolerated in most patients, with the exception of those with severe bronchospastic asthma or severe coronary artery disease. The use of adenosine for the evaluation and termination of SVTs is presented separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Intravenous adenosine'.) Other AV nodal blocking drugs If vagal maneuvers and adenosine have been ineffective or terminate the tachycardia followed by an immediate recurrence, IV nondihydropyridine calcium channel blockers (eg, verapamil and diltiazem) or IV beta blockers (eg, metoprolol, esmolol) can be used ( algorithm 1) to terminate AVNRT [48,49]. A phase 2 trial of an intranasally administered calcium channel blocker, etripamil, terminated SVT in up to 95 percent of patients [50], and a phase 3 placebo-controlled trial of etripamil has been undertaken [51]. The choice between these drugs is usually based on familiarity with and availability of the particular agents, although a calcium channel blocker would be preferred for a patient with reactive airway disease and active wheezing. Calcium channel and beta blockers are generally well tolerated, although potential adverse effects include hypotension (due to both negative inotropic and vasodilatory effects) and bradycardia [52-54]. Initial IV dosing options include: Verapamil 5 to 10 mg IV bolus over two minutes; if no response, an additional 10 mg IV bolus may be administered 15 to 30 minutes following the initial dose. Diltiazem 0.25 mg/kg (average dose 20 mg) IV bolus over two minutes; if no response, an additional 0.35 mg/kg (average dose 25 mg) IV bolus may be administered 15 to 30 minutes following the initial dose. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 12/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Metoprolol 2.5 to 5 mg IV bolus over two to five minutes; if no response, an additional 2.5 to 5 mg IV bolus may be administered every 10 minutes to a total dose of 15 mg. Esmolol 500 mcg/kg IV bolus over one minute, followed by a 50 to 150 mcg/kg/minute infusion, if necessary. Infusion rate can be adjusted as needed to maintain desired heart rate (up to 300 mcg/kg/minute). Because of their longer half-lives, verapamil, diltiazem, and beta blockers have the potential to suppress arrhythmia recurrence. Thus, these drugs should be used in patients who have early arrhythmia recurrence after termination with adenosine. SUBSEQUENT MANAGEMENT The approach to the management of subsequent AVNRT episodes is based around acute management of recurrent episodes and/or preventive therapy to reduce or eliminate recurrences. Because AVNRT is usually well tolerated in the majority of patients, with a variety of safe and effective treatment options, and there are no compelling data favoring one therapy over another, the choice of long-term management strategies is largely influenced by patient preference. When working with a patient to select a treatment strategy, the following issues should be considered: Frequency of episodes Severity of symptoms Comorbid conditions Medication compliance Medication side effects Patients who have had syncope in the setting of AVNRT may be subject to driving restrictions, which vary between municipalities. (See "Syncope in adults: Management and prognosis", section on 'Driving restrictions'.) Acute management of recurrent episodes For the initial management of recurrent AVNRT, we generally work with the patient to develop a patient-directed treatment approach using either vagal maneuvers or an oral medication ("pill-in-the-pocket" approach). For most patients, we suggest a combination of one or more vagal maneuvers rather than the pill-in-the-pocket approach. Patients who have experienced prior episodes and who have been educated on the proper performance of vagal maneuvers are frequently able to terminate subsequent episodes by https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 13/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate performing vagal maneuvers on their own. If one or more vagal maneuvers successfully terminate the arrhythmia, patients generally do not need to seek urgent medical attention. Conversely, patients should be instructed to consult with their clinician or seek medical attention if the arrhythmia persists in spite of several attempts at patient-directed vagal maneuvers. (See 'Vagal maneuvers' above.) An alternative patient-directed approach to the management of recurrent AVNRT is the pill-in- the-pocket approach. For selected patients with infrequent, well-tolerated, and long-lasting episodes of AVNRT, a single dose of an antiarrhythmic agent that was previously evaluated under observation can be effective for acute termination of the arrhythmia [40,55,56]. This strategy can both reduce the need for emergency department visits and avoid chronic medical therapy or invasive procedures. This approach has been evaluated with the nondihydropyridine calcium channel blockers, beta blockers, and the class IC antiarrhythmic drug flecainide [56]. However, based upon the efficacy of alternative, lower-risk therapies, and the efficacy of catheter ablation, flecainide is rarely used in the management of AVNRT. The choice of a particular agent will vary from patient to patient depending on comorbidities and patient preference. Preventive therapy The decision to treat with long-term preventive therapy is based upon the following factors: The frequency of the arrhythmia The severity of the symptoms Patient tolerance of medications Patient preference Many patients with infrequent episodes of AVNRT, or those with minimal or well-tolerated symptoms, may prefer a more conservative management approach with either no specific therapy or pharmacologic suppression. If pharmacologic therapy fails or if the side effects result from chronic medical therapy, catheter ablation remains an option. Conversely, for patients with significant symptoms, or for patients who prefer definitive therapy, even for rare, well-tolerated episodes, catheter ablation may be considered early in the patient's management [40,41]. No treatment Patients with infrequent and well-tolerated episodes of AVNRT may choose no chronic therapy. For these patients, we emphasize the patient-directed approach to the termination of recurrent episodes using one or more vagal maneuvers, with the ability to reassess long-term management options at any time should there be a change in the frequency or severity of recurrences. (See 'Acute management of recurrent episodes' above and "Vagal maneuvers".) https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 14/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Catheter ablation For patients with episodes of AVNRT that are either frequently occurring, refractory to medical therapy, poorly tolerated (eg, associated with near-syncope or syncope, angina, or severe dyspnea), or result in presentation to the emergency department or admission to the hospital, we recommend catheter ablation rather than chronic medical therapy as initial long-term management strategy. In such cases, the risks associated with recurrent arrhythmic events (eg, syncope with associated trauma) outweigh the procedural risks. In addition, the potential for definitive therapy makes ablation preferable to medical therapy in this setting. Catheter ablation offers the opportunity for definitive cure of AVNRT in greater than 95 percent of patients, with high rates of success in both the typical and atypical forms [57-59]. However, ablation is associated with a small but non-trivial rate of procedural complications. The most significant potential complication of radiofrequency ablation for AVNRT is AV block (approximately 1 percent). Historically, the risk of AV block requiring permanent pacing following ablation ranged from 1 to 3 percent, but in multiple contemporary cohorts, the need for permanent pacing following the procedure has consistently been <1 percent [58,60,61]. Older age and baseline PR interval prolongation are predictors of an increased risk of post-ablation AV block [62-65]. However, due to its high success rate in curing AVNRT by successful slow pathway ablation and low complication rate, catheter ablation is increasingly favored among patients with recurrent AVNRT [40,41]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) The general approach to the catheter ablation of AVNRT is based upon the concept of dual AV nodal pathways. The most common AVNRT circuit (80 to 90 percent) involves antegrade conduction down the slow pathway and retrograde conduction up the fast pathway. The ablation target is the posterior slow pathway ( figure 8) since ablation here carries the lowest risk of AV block, preserves fast pathway function (and a normal PR interval post-ablation), and is facilitated by reliable anatomic and electrophysiologic landmarks. The anterior fast pathway can also be ablated, but this approach is now limited to a few special circumstances since fast pathway ablation results in a long PR interval during sinus rhythm and is associated with a higher risk of heart block. During ablation for atypical "fast-slow" AVNRT, the slow pathway is the usual target. The slow pathway in these patients tends to be posteriorly located near the coronary sinus ostium as with patients who have typical AVNRT. However, there are reports of rare cases of atypical AV nodal reentry where the slow retrograde limb of the circuit is located more superiorly near the compact AV node [66]. The relative efficacy and costs of catheter ablation and medical therapy were compared in a series of 79 patients with newly documented supraventricular tachycardia (SVT) who were treated with either ablation or pharmacologic therapy, based upon patient preference [67]. After a follow-up period of 12 months, both medication and ablation decreased the frequency of |
rate (up to 300 mcg/kg/minute). Because of their longer half-lives, verapamil, diltiazem, and beta blockers have the potential to suppress arrhythmia recurrence. Thus, these drugs should be used in patients who have early arrhythmia recurrence after termination with adenosine. SUBSEQUENT MANAGEMENT The approach to the management of subsequent AVNRT episodes is based around acute management of recurrent episodes and/or preventive therapy to reduce or eliminate recurrences. Because AVNRT is usually well tolerated in the majority of patients, with a variety of safe and effective treatment options, and there are no compelling data favoring one therapy over another, the choice of long-term management strategies is largely influenced by patient preference. When working with a patient to select a treatment strategy, the following issues should be considered: Frequency of episodes Severity of symptoms Comorbid conditions Medication compliance Medication side effects Patients who have had syncope in the setting of AVNRT may be subject to driving restrictions, which vary between municipalities. (See "Syncope in adults: Management and prognosis", section on 'Driving restrictions'.) Acute management of recurrent episodes For the initial management of recurrent AVNRT, we generally work with the patient to develop a patient-directed treatment approach using either vagal maneuvers or an oral medication ("pill-in-the-pocket" approach). For most patients, we suggest a combination of one or more vagal maneuvers rather than the pill-in-the-pocket approach. Patients who have experienced prior episodes and who have been educated on the proper performance of vagal maneuvers are frequently able to terminate subsequent episodes by https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 13/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate performing vagal maneuvers on their own. If one or more vagal maneuvers successfully terminate the arrhythmia, patients generally do not need to seek urgent medical attention. Conversely, patients should be instructed to consult with their clinician or seek medical attention if the arrhythmia persists in spite of several attempts at patient-directed vagal maneuvers. (See 'Vagal maneuvers' above.) An alternative patient-directed approach to the management of recurrent AVNRT is the pill-in- the-pocket approach. For selected patients with infrequent, well-tolerated, and long-lasting episodes of AVNRT, a single dose of an antiarrhythmic agent that was previously evaluated under observation can be effective for acute termination of the arrhythmia [40,55,56]. This strategy can both reduce the need for emergency department visits and avoid chronic medical therapy or invasive procedures. This approach has been evaluated with the nondihydropyridine calcium channel blockers, beta blockers, and the class IC antiarrhythmic drug flecainide [56]. However, based upon the efficacy of alternative, lower-risk therapies, and the efficacy of catheter ablation, flecainide is rarely used in the management of AVNRT. The choice of a particular agent will vary from patient to patient depending on comorbidities and patient preference. Preventive therapy The decision to treat with long-term preventive therapy is based upon the following factors: The frequency of the arrhythmia The severity of the symptoms Patient tolerance of medications Patient preference Many patients with infrequent episodes of AVNRT, or those with minimal or well-tolerated symptoms, may prefer a more conservative management approach with either no specific therapy or pharmacologic suppression. If pharmacologic therapy fails or if the side effects result from chronic medical therapy, catheter ablation remains an option. Conversely, for patients with significant symptoms, or for patients who prefer definitive therapy, even for rare, well-tolerated episodes, catheter ablation may be considered early in the patient's management [40,41]. No treatment Patients with infrequent and well-tolerated episodes of AVNRT may choose no chronic therapy. For these patients, we emphasize the patient-directed approach to the termination of recurrent episodes using one or more vagal maneuvers, with the ability to reassess long-term management options at any time should there be a change in the frequency or severity of recurrences. (See 'Acute management of recurrent episodes' above and "Vagal maneuvers".) https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 14/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Catheter ablation For patients with episodes of AVNRT that are either frequently occurring, refractory to medical therapy, poorly tolerated (eg, associated with near-syncope or syncope, angina, or severe dyspnea), or result in presentation to the emergency department or admission to the hospital, we recommend catheter ablation rather than chronic medical therapy as initial long-term management strategy. In such cases, the risks associated with recurrent arrhythmic events (eg, syncope with associated trauma) outweigh the procedural risks. In addition, the potential for definitive therapy makes ablation preferable to medical therapy in this setting. Catheter ablation offers the opportunity for definitive cure of AVNRT in greater than 95 percent of patients, with high rates of success in both the typical and atypical forms [57-59]. However, ablation is associated with a small but non-trivial rate of procedural complications. The most significant potential complication of radiofrequency ablation for AVNRT is AV block (approximately 1 percent). Historically, the risk of AV block requiring permanent pacing following ablation ranged from 1 to 3 percent, but in multiple contemporary cohorts, the need for permanent pacing following the procedure has consistently been <1 percent [58,60,61]. Older age and baseline PR interval prolongation are predictors of an increased risk of post-ablation AV block [62-65]. However, due to its high success rate in curing AVNRT by successful slow pathway ablation and low complication rate, catheter ablation is increasingly favored among patients with recurrent AVNRT [40,41]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) The general approach to the catheter ablation of AVNRT is based upon the concept of dual AV nodal pathways. The most common AVNRT circuit (80 to 90 percent) involves antegrade conduction down the slow pathway and retrograde conduction up the fast pathway. The ablation target is the posterior slow pathway ( figure 8) since ablation here carries the lowest risk of AV block, preserves fast pathway function (and a normal PR interval post-ablation), and is facilitated by reliable anatomic and electrophysiologic landmarks. The anterior fast pathway can also be ablated, but this approach is now limited to a few special circumstances since fast pathway ablation results in a long PR interval during sinus rhythm and is associated with a higher risk of heart block. During ablation for atypical "fast-slow" AVNRT, the slow pathway is the usual target. The slow pathway in these patients tends to be posteriorly located near the coronary sinus ostium as with patients who have typical AVNRT. However, there are reports of rare cases of atypical AV nodal reentry where the slow retrograde limb of the circuit is located more superiorly near the compact AV node [66]. The relative efficacy and costs of catheter ablation and medical therapy were compared in a series of 79 patients with newly documented supraventricular tachycardia (SVT) who were treated with either ablation or pharmacologic therapy, based upon patient preference [67]. After a follow-up period of 12 months, both medication and ablation decreased the frequency of https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 15/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate arrhythmia-related symptoms, but ablation was more likely to result in complete abolition of symptoms (74 versus 33 percent). (See 'Chronic suppressive therapy' below.) Chronic suppressive therapy For patients with symptomatic episodes of AVNRT who are not candidates for or who have declined catheter ablation, chronic medical therapy using beta blockers, nondihydropyridine calcium channel blockers, or antiarrhythmic drugs can be initiated in an effort to suppress recurrent arrhythmias. There are few data comparing the relative efficacy of various agents used for chronic suppressive therapy of AVNRT. Because they are effective and well tolerated, the medications that are most commonly used for the chronic suppression of AVNRT are beta blockers (eg, metoprolol) and nondihydropyridine calcium channel blockers (eg, verapamil and diltiazem). Traditionally, beta blockers were preferred rather than calcium channel blockers unless the patient has reactive airway disease or another contraindication, although calcium channel blockers may have fewer side effects. The choice of a starting dose for chronic suppressive medication will vary depending upon the baseline heart rate and blood pressure. The dose of beta blocker or calcium channel blocker is titrated as tolerated with the dose limited to avoid hypotension (symptomatic hypotension or asymptomatic systolic blood pressure <100 mmHg) and bradycardia (heart rate <55 beats per minute). Among patients who do not respond to optimally titrated diltiazem, verapamil, or beta blockers and who do not want to pursue ablation, the following antiarrhythmic drugs may be considered: Flecainide (class IC) Propafenone (class IC) Sotalol (class III) Dofetilide (class III) Amiodarone (class III) The choice of a particular agent will need to be individualized in each patient based on other comorbidities. However, due to the potential for significant toxicities, including proarrhythmia, the use of class I and class III antiarrhythmic drugs for the management of AVNRT should be reserved for rare cases and should be administered in consultation with an electrophysiologist. In particular, because of the risk of toxicities with long-term use, amiodarone is usually avoided in young patients. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 16/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Catheter ablation of arrhythmias" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Supraventricular tachycardia (SVT) (The Basics)") SUMMARY AND RECOMMENDATIONS Definition and prevalence Atrioventricular nodal reentrant tachycardia (AVNRT) is a regular tachycardia that results from the formation of a reentry circuit confined to the AV node and perinodal atrial tissue. The physiologic substrate for AVNRT involves dual electrical pathways in or near the AV node. It is the most common form of regular, sustained, paroxysmal supraventricular tachycardia (PSVT), and it accounts for nearly two- thirds of all PSVTs. (See 'Introduction' above and 'Epidemiology' above.) Pathophysiology The simplest concept of AV nodal physiology that allows for reentry involves separate electrical pathways within or proximal to the AV node ( figure 3). The fast pathway conducts rapidly and has a relatively long refractory period, while the slow pathway conducts relatively slowly and has a shorter refractory period. Both typical and atypical forms of AVNRT can result from reentry involving the fast and slow pathways. Tachycardia is initiated by a premature beat. (See 'Anatomy and pathophysiology' above.) https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 17/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Symptoms Patients with AVNRT most commonly report palpitations, dizziness or lightheadedness, and dyspnea. Because of the paroxysmal nature of the arrhythmia, the onset and termination of the symptoms are usually sudden. Those with significant heart disease may have additional symptoms such as dyspnea and chest pain. (See 'Symptoms' above.) ECG features There are several features seen on an ECG that are helpful in confirming the diagnosis of AVNRT, including the ventricular rate, abrupt onset following a PAC, the relationship between QRS complexes and P waves, and spontaneous termination with AV block in the absence of a PAC. (See 'Electrocardiographic characteristics' above.) Initial management The initial management ( algorithm 1) of a patient presenting with a narrow QRS tachycardia and suspected AVNRT is guided by whether or not the patient is experiencing signs and symptoms of hemodynamic instability related to the rapid heart rate (eg, hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness). Hemodynamically unstable Rare patients who are severely hemodynamically unstable should undergo urgent cardioversion. (See 'Electrical cardioversion' above.) Hemodynamically stable For patients who are hemodynamically stable and able to effectively perform the vagal maneuvers, we recommend at least one or two attempts of a standard Valsalva maneuver, followed by at least one or two attempts using the modified Valsalva maneuver (if AVNRT persists), as the initial treatment for AVNRT rather than another vagal maneuver or adenosine (Grade 1B). (See 'Vagal maneuvers' above.) If vagal maneuvers cannot be performed or if they fail to terminate the arrhythmia, intravenous (IV) medical therapy that blocks AV nodal conduction is indicated as the next step. For patients with AVNRT that persists following vagal maneuvers (or in whom vagal maneuvers cannot be adequately performed), we recommend IV adenosine ( algorithm 3) rather than a calcium channel blocker or a beta blocker (Grade 1B). (See 'Adenosine' above.) If both vagal maneuvers and adenosine are ineffective, or when these options are followed by an immediate recurrence of the tachycardia, IV verapamil, diltiazem, or a beta blocker can be used to terminate or prevent recurrent AVNRT. (See 'Other AV nodal blocking drugs' above.) https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 18/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Management of recurrent episodes The approach to the management of subsequent AVNRT episodes is based around acute management of recurrent episodes and/or preventive therapy to reduce or eliminate recurrences. Because AVNRT is usually well- tolerated in the majority of patients, with a variety of safe and effective treatment options, and there are no compelling data favoring one therapy over another, the choice of long- term management strategies is largely influenced by patient preference. Initial management For the initial management of recurrent AVNRT, we generally work with the patient to develop a patient-directed treatment approach using either vagal maneuvers or an oral medication ("pill-in-the-pocket" approach). For most patients, we suggest a combination of one or more vagal maneuvers rather than the pill-in-the-pocket approach (Grade 2C). (See 'Acute management of recurrent episodes' above.) Infrequent and well-tolerated episodes Patients with infrequent and well-tolerated episodes of AVNRT may choose no chronic therapy. For these patients, we emphasize the patient-directed approach to the termination of recurrent episodes using one or more vagal maneuvers. (See 'No treatment' above.) Frequent or poorly tolerated episodes For patients with episodes of AVNRT that are either frequently occurring or poorly tolerated (eg, associated with near-syncope or syncope, angina, or severe dyspnea), we recommend catheter ablation rather than chronic medical therapy as initial long-term management strategy (Grade 1B). In such cases, the risks associated with recurrent arrhythmic events (eg, syncope with associated trauma) outweigh the procedural risks. In addition, the potential for definitive therapy makes ablation preferable to medical therapy in this setting. (See 'Catheter ablation' above.) For patients with poorly tolerated symptomatic episodes of AVNRT who are not candidates for or who have declined catheter ablation, chronic medical therapy using beta blockers, nondihydropyridine calcium channel blockers, or antiarrhythmic drugs can be initiated in an effort to suppress recurrent arrhythmias. Our experts typical prefer beta blockers rather than calcium channel blockers or antiarrhythmic drugs as the initial option for chronic medical therapy. (See 'Chronic suppressive therapy' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 19/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 1. Liuba I, J nsson A, S fstr m K, Walfridsson H. Gender-related differences in patients with atrioventricular nodal reentry tachycardia. Am J Cardiol 2006; 97:384. 2. Ferguson JD, DiMarco JP. Contemporary management of paroxysmal supraventricular tachycardia. Circulation 2003; 107:1096. 3. Ganz LI, Friedman PL. Supraventricular tachycardia. N Engl J Med 1995; 332:162. 4. Goyal R, Zivin A, Souza J, et al. Comparison of the ages of tachycardia onset in patients with atrioventricular nodal reentrant tachycardia and accessory pathway-mediated tachycardia. Am Heart J 1996; 132:765. 5. McGuire MA, Bourke JP, Robotin MC, et al. High resolution mapping of Koch's triangle using sixty electrodes in humans with atrioventricular junctional (AV nodal) reentrant tachycardia. Circulation 1993; 88:2315. 6. McGuire MA, Janse MJ, Ross DL. "AV nodal" reentry: Part II: AV nodal, AV junctional, or atrionodal reentry? J Cardiovasc Electrophysiol 1993; 4:573. 7. Meiltz A, Zimmermann M. Atrioventricular nodal reentrant tachycardia in the elderly: efficacy and safety of radiofrequency catheter ablation. Pacing Clin Electrophysiol 2007; 30 Suppl 1:S103. 8. Grecu M, Floria M, Georgescu CA. Abnormal atrioventricular node conduction and atrioventricular nodal reentrant tachycardia in patients older versus younger than 65 years of age. Pacing Clin Electrophysiol 2009; 32 Suppl 1:S98. 9. Janse MJ, Anderson RH, McGuire MA, Ho SY. "AV nodal" reentry: Part I: "AV nodal" reentry revisited. J Cardiovasc Electrophysiol 1993; 4:561. 10. Pieper SJ, Stanton MS. Narrow QRS complex tachycardias. Mayo Clin Proc 1995; 70:371. 11. Yamabe H, Shimasaki Y, Honda O, et al. Demonstration of the exact anatomic tachycardia circuit in the fast-slow form of atrioventricular nodal reentrant tachycardia. Circulation 2001; 104:1268. 12. Mazgalev TN, Tchou PJ. Surface potentials from the region of the atrioventricular node and their relation to dual pathway electrophysiology. Circulation 2000; 101:2110. 13. Sung RJ, Waxman HL, Saksena S, Juma Z. Sequence of retrograde atrial activation in patients with dual atrioventricular nodal pathways. Circulation 1981; 64:1059. 14. Hayes JJ, Sharma PP, Smith PN, Vidaillet HJ. Familial atrioventricular nodal reentry tachycardia. Pacing Clin Electrophysiol 2004; 27:73. 15. MOE GK, PRESTON JB, BURLINGTON H. Physiologic evidence for a dual A-V transmission system. Circ Res 1956; 4:357. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 20/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 16. Man KC, Brinkman K, Bogun F, et al. 2:1 atrioventricular block during atrioventricular node reentrant tachycardia. J Am Coll Cardiol 1996; 28:1770. 17. Schmitt C, Miller JM, Josephson ME. Atrioventricular nodal supraventricular tachycardia with 2:1 block above the bundle of His. Pacing Clin Electrophysiol 1988; 11:1018. 18. Yeh SJ, Yamamoto T, Lin FC, Wu D. Atrioventricular block in the atypical form of junctional reciprocating tachycardia: evidence supporting the atrioventricular node as the site of reentry. J Am Coll Cardiol 1990; 15:385. 19. Bogun F, Daoud E, Goyal R, et al. Comparison of atrial-His intervals in patients with and without dual atrioventricular nodal physiology and atrioventricular nodal reentrant tachycardia. Am Heart J 1996; 132:758. 20. Otomo K, Suyama K, Okamura H, et al. Participation of a concealed atriohisian tract in the reentrant circuit of the slow-fast type of atrioventricular nodal reentrant tachycardia. Heart Rhythm 2007; 4:703. 21. Wu J, Zipes DP. Mechanisms underlying atrioventricular nodal conduction and the reentrant circuit of atrioventricular nodal reentrant tachycardia using optical mapping. J Cardiovasc Electrophysiol 2002; 13:831. 22. Kwaku KF, Josephson ME. Typical AVNRT an update on mechanisms and therapy. Card Electrophysiol Rev 2002; 6:414. 23. Otomo K, Nagata Y, Uno K, et al. Atypical atrioventricular nodal reentrant tachycardia with eccentric coronary sinus activation: electrophysiological characteristics and essential effects of left-sided ablation inside the coronary sinus. Heart Rhythm 2007; 4:421. 24. Katritsis DG, Marine JE, Latchamsetty R, et al. Coexistent Types of Atrioventricular Nodal Re- Entrant Tachycardia: Implications for the Tachycardia Circuit. Circ Arrhythm Electrophysiol 2015; 8:1189. 25. Abe H, Nagatomo T, Kobayashi H, et al. Neurohumoral and hemodynamic mechanisms of diuresis during atrioventricular nodal reentrant tachycardia. Pacing Clin Electrophysiol 1997; 20:2783. 26. Wood KA, Drew BJ, Scheinman MM. Frequency of disabling symptoms in supraventricular tachycardia. Am J Cardiol 1997; 79:145. 27. Doi A, Miyamoto K, Uno K, et al. Studies on hemodynamic instability in paroxysmal supraventricular tachycardia: noninvasive evaluations by head-up tilt testing and power spectrum analysis on electrocardiographic RR variation. Pacing Clin Electrophysiol 2000; 23:1623. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 21/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 28. Leitch JW, Klein GJ, Yee R, et al. Syncope associated with supraventricular tachycardia. An expression of tachycardia rate or vasomotor response? Circulation 1992; 85:1064. 29. Wang YS, Scheinman MM, Chien WW, et al. Patients with supraventricular tachycardia presenting with aborted sudden death: incidence, mechanism and long-term follow-up. J Am Coll Cardiol 1991; 18:1711. 30. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 31. Chiou CW, Chen SA, Kung MH, et al. Effects of continuous enhanced vagal tone on dual atrioventricular node and accessory pathways. Circulation 2003; 107:2583. 32. Ng KS, Lauer MR, Young C, et al. Correlation of P-wave polarity with underlying electrophysiologic mechanisms of long RP' tachycardia. Am J Cardiol 1996; 77:1129. 33. Riva SI, Della Bella P, Fassini G, et al. Value of analysis of ST segment changes during tachycardia in determining type of narrow QRS complex tachycardia. J Am Coll Cardiol 1996; 27:1480. 34. G le S, Erta F, Karao uz R, et al. Value of ST-segment depression during paroxysmal supraventricular tachycardia in the diagnosis of coronary artery disease. Am J Cardiol 1999; 83:458. 35. Imrie JR, Yee R, Klein GJ, Sharma AD. Incidence and clinical significance of ST segment depression in supraventricular tachycardia. Can J Cardiol 1990; 6:323. 36. Petsas AA, Anastassiades LC, Antonopoulos AG. Exercise testing for assessment of the significance of ST segment depression observed during episodes of paroxysmal supraventricular tachycardia. Eur Heart J 1990; 11:974. 37. Paparella N, Ouyang F, Fuc G, et al. Significance of newly acquired negative T waves after interruption of paroxysmal reentrant supraventricular tachycardia with narrow QRS complex. Am J Cardiol 2000; 85:261. 38. Villain E, Vetter VL, Garcia JM, et al. Evolving concepts in the management of congenital junctional ectopic tachycardia. A multicenter study. Circulation 1990; 81:1544. 39. Fishberger SB, Rossi AF, Messina JJ, Saul JP. Successful radiofrequency catheter ablation of congenital junctional ectopic tachycardia with preservation of atrioventricular conduction in a 9-month-old infant. Pacing Clin Electrophysiol 1998; 21:2132. 40. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 22/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 41. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 42. Belz MK, Stambler BS, Wood MA, et al. Effects of enhanced parasympathetic tone on atrioventricular nodal conduction during atrioventricular nodal reentrant tachycardia. Am J Cardiol 1997; 80:878. 43. Pandya A, Lang E. Valsalva maneuver for termination of supraventricular tachycardia. Ann Emerg Med 2015; 65:27. 44. Appelboam A, Reuben A, Mann C, et al. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. Lancet 2015; 386:1747. 45. Glatter KA, Cheng J, Dorostkar P, et al. Electrophysiologic effects of adenosine in patients with supraventricular tachycardia. Circulation 1999; 99:1034. 46. Cairns CB, Niemann JT. Intravenous adenosine in the emergency department management of paroxysmal supraventricular tachycardia. Ann Emerg Med 1991; 20:717. 47. Rankin AC, Brooks R, Ruskin JN, McGovern BA. Adenosine and the treatment of supraventricular tachycardia. Am J Med 1992; 92:655. 48. Waxman HL, Myerburg RJ, Appel R, Sung RJ. Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atrial fibrillation or flutter: a double-blind randomized cross-over study. Ann Intern Med 1981; 94:1. 49. Das G, Tschida V, Gray R, et al. Efficacy of esmolol in the treatment and transfer of patients with supraventricular tachyarrhythmias to alternate oral antiarrhythmic agents. J Clin Pharmacol 1988; 28:746. 50. Stambler BS, Dorian P, Sager PT, et al. Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm. J Am Coll Cardiol 2018; 72:489. 51. https://clinicaltrials.gov/ct2/show/NCT03464019 (Accessed on July 26, 2018). 52. Sung RJ, Elser B, McAllister RG Jr. Intravenous verapamil for termination of re-entrant supraventricular tachycardias: intracardiac studies correlated with plasma verapamil concentrations. Ann Intern Med 1980; 93:682. 53. DiMarco JP, Sellers TD, Berne RM, et al. Adenosine: electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983; 68:1254. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 23/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 54. Dougherty AH, Jackman WM, Naccarelli GV, et al. Acute conversion of paroxysmal supraventricular tachycardia with intravenous diltiazem. IV Diltiazem Study Group. Am J Cardiol 1992; 70:587. 55. Margolis B, DeSilva RA, Lown B. Episodic drug treatment in the management of paroxysmal arrhythmias. Am J Cardiol 1980; 45:621. 56. Alboni P, Tomasi C, Menozzi C, et al. Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia. J Am Coll Cardiol 2001; 37:548. 57. Spector P, Reynolds MR, Calkins H, et al. Meta-analysis of ablation of atrial flutter and supraventricular tachycardia. Am J Cardiol 2009; 104:671. 58. Chrispin J, Misra S, Marine JE, et al. Current management and clinical outcomes for catheter ablation of atrioventricular nodal re-entrant tachycardia. Europace 2018; 20:e51. 59. Katritsis DG, Marine JE, Contreras FM, et al. Catheter Ablation of Atypical Atrioventricular Nodal Reentrant Tachycardia. Circulation 2016; 134:1655. 60. Hosseini SM, Rozen G, Saleh A, et al. Catheter ablation for cardiac arrhythmias: utilization and in-hospital complications, 2000 to 2013. J Am Coll Cardiol EP 2017; 3:1240. 61. Katritsis DG, Zografos T, Siontis KC, et al. Endpoints for Successful Slow Pathway Catheter Ablation in Typical and Atypical Atrioventricular Nodal Re-Entrant Tachycardia: A Contemporary, Multicenter Study. J Am Coll Cardiol EP 2019; 5:113. 62. Boulos M, Hoch D, Schecter S, et al. Age dependence of complete heart block complicating radiofrequency ablation of the atrioventricular nodal slow pathway. Am J Cardiol 1998; 82:390. 63. Li YG, Gr nefeld G, Bender B, et al. Risk of development of delayed atrioventricular block after slow pathway modification in patients with atrioventricular nodal reentrant tachycardia and a pre-existing prolonged PR interval. Eur Heart J 2001; 22:89. 64. Natale A, Greenfield RA, Geiger MJ, et al. Safety of slow pathway ablation in patients with long PR interval: further evidence of fast and slow pathway interaction. Pacing Clin Electrophysiol 1997; 20:1698. 65. Reithmann C, Hoffmann E, Gr newald A, et al. Fast pathway ablation in patients with common atrioventricular nodal reentrant tachycardia and prolonged PR interval during sinus rhythm. Eur Heart J 1998; 19:929. 66. Kaneko Y, Naito S, Okishige K, et al. Atypical Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Incorporating a "Superior" Slow Pathway: A Distinct Supraventricular Tachyarrhythmia. Circulation 2016; 133:114. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 24/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 67. Bathina MN, Mickelsen S, Brooks C, et al. Radiofrequency catheter ablation versus medical therapy for initial treatment of supraventricular tachycardia and its impact on quality of life and healthcare costs. Am J Cardiol 1998; 82:589. Topic 902 Version 46.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 25/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate GRAPHICS Electrophysiologic characteristics of the different types of supraventricular tachycardia (SVT) Characteristic Reentrant Triggered Automatic Initiation by extrastimuli and/or continuous pacing Yes Yes No Initiation by continuous pacing depends upon the rate No Yes No and number of stimuli Termination by extrastimuli Yes No No Termination by continuous pacing (overdrive) Yes Yes No Overdrive suppression of tachycardia No No Yes Overdrive enhancement of tachycardia Yes Yes No Entrainment possible Yes No No First P wave identical to P waves in arrhythmia No Sometimes Yes Warm-up or acceleration of pacemaker after onset No Sometimes Yes Graphic 53347 Version 2.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 26/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Schematic representation of Koch's triangle and environment Around the compact atrioventricular (AV) node is an extended zone with transitional cells. LBB: left bundle branch; RBB: right bundle branch. Graphic 69647 Version 2.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 27/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Koch's triangle and fast and slow pathways Schematic representation of Koch's triangle which is bounded by the tricuspid ring and the tendon of Todoro. The tendon of Todoro and the tricuspid ring are in close proximity forming the apex of the triangle near the His bundle at the membranous septum. Koch's triangle can be divided into thirds: the anterior contains the compact AV node; the posterior contains the coronary sinus; and the middle or mid-septal third is between the anterior and posterior portions. The anterior third is associated with fast pathways, and the middle and posterior thirds with slow pathways. Graphic 52196 Version 2.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 28/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Slow-fast form of atrioventricular nodal reentrant tachycardia (AVNRT) Representation of dual pathway physiology involving the atrioventricular (AV) node and perinodal atrial tissue in the common form of AVNRT. Left panel: A normal sinus beat (A ) is conducted through the fast pathway (F) to the final common pathway (fcp) in the AV node and into the Bundle of His. The conduction through the slow pathway (S) runs into the refractory period of the impulse through the fast pathway and is extinguished. 1 Middle panel: A critically timed atrial premature beat (A ) finds the fast pathway refractory in the antegrade direction but is able to conduct antegrade through the slow pathway, which has a shorter refractory period. If excitability in the fast pathway has recovered by 2 the time the impulse reaches the fcp, there may be retrograde activation of the fast pathway. Right panel: The retrograde impulse throws off an echo to the atrium (A*), and, if the slow pathway has recovered its excitability, the impulse reenters the slow pathway and produces ventricular depolarization (V*). If the mechanism persists, a repetitive circuit is established that creates a sustained reentrant tachycardia. The sequence of antegrade (S) and retrograde (F) conduction is called the slow-fast form of AVNRT. Graphic 79760 Version 6.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 29/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Electrophysiologic study (EPS) in a patient with atrioventricular nodal reentrant tachycardia and dual AV nodal pathways The tracing shows three surface ECG leads (I, II, V1) and intracardiac recordings from the high right atrium (HRA), bundle of His (HIS), right ventricular apex (RVA), and coronary sinus (CS). During atrial pacing (S1) at a cycle length of 600 milliseconds (100 beats per minute), the AH interval is 120 milliseconds. An atrial premature beat (S2) is added at a coupling cyle of 420 milliseconds; this results in a prolongation of the PR interval and increase in the AH interval to 184 milliseconds. Courtesy of Martin Burke, DO. Graphic 60369 Version 4.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 30/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Electrophysiologic study (EPS) in a patient with atrioventricular nodal reentrant tachycardia and dual AV nodal pathways The tracing shows three surface ECG leads (I, II, V1) and intracardiac recordings from the high right atrium (HRA), bundle of His (HIS), right ventricular apex (RVA), and coronary sinus (CS). During atrial pacing (S1) at a cycle length of 600 milliseconds (100 beats per minute), the AH interval is 120 milliseconds. An atrial premature beat (S2) is added at a coupling cyle of 410 milliseconds; this results in a prolongation of the PR interval and increase in the AH interval to 242 milliseconds, which represents a 60-millisecond increase compared with the AH when a premature beat was added with a coupling interval of 420 milliseconds. This represents a "jump" due to a shift of AV nodal conduction from the fast to slow AV nodal pathway. Since the fast pathway has time to recover, there is retrograde VA conduction via the fast pathway, resulting in the occurrence of a retrograde His depolarization (HIS "A") and an atrial echo beat at the CS os area (CS 10-9). Courtesy of Martin Burke, DO. Graphic 72161 Version 4.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 31/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Generation of ECG in common form of atrioventricular nodal reentrant tachycardia (AVNRT) Ladder diagram of the common (slow-fast) form of AVNRT showing transmission of the impulse in atrial, atrioventricular (AV) nodal, and ventricular tissue and the resultant ECG. The first two cycles show the normal sinus beat (A ) conducting through the fast pathway (F) to the ventricle (V ) with the impulse blocked in the slow pathway. The premature atrial beat (A on ladder diagram, P on ECG) is timed critically; it finds the fast pathway refractory but is able to conduct through slow pathway, resulting in a long PR interval, and a ventricular depolarization (V ). It is also able to reenter and conduct 1 1 2 2 retrogradely up the now recovered fast pathway, resulting in an inverted P wave (A*) that is buried in the QRS complex. This atrial echo beat (A*) then reenters the now recovered slow pathway, which conducts anterogradely and results in ventricular depolarization (V*). The cycle repeats, and AV nodal reentry is established. ECG: electrocardiogram. Graphic 50122 Version 6.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 32/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Uncommon fast-slow variant of atrioventricular nodal reentrant tachycardia (AVNRT) Diagrammatic representation in the circuit (left panel) and the ladder diagram (right panel) of the uncommon form of AVNRT (fast-slow variant). Antegrade conduction is through the fast (F) pathway and retrograde conduction is through the slow (S) pathway. Because of slow retrograde activation of the atrium, the P wave occurs after the QRS complex with a long RP interval and relatively short PR interval before the next QRS complex. ECG: electrocardiogram. Graphic 56806 Version 4.0 |
therapy for initial treatment of supraventricular tachycardia and its impact on quality of life and healthcare costs. Am J Cardiol 1998; 82:589. Topic 902 Version 46.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 25/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate GRAPHICS Electrophysiologic characteristics of the different types of supraventricular tachycardia (SVT) Characteristic Reentrant Triggered Automatic Initiation by extrastimuli and/or continuous pacing Yes Yes No Initiation by continuous pacing depends upon the rate No Yes No and number of stimuli Termination by extrastimuli Yes No No Termination by continuous pacing (overdrive) Yes Yes No Overdrive suppression of tachycardia No No Yes Overdrive enhancement of tachycardia Yes Yes No Entrainment possible Yes No No First P wave identical to P waves in arrhythmia No Sometimes Yes Warm-up or acceleration of pacemaker after onset No Sometimes Yes Graphic 53347 Version 2.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 26/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Schematic representation of Koch's triangle and environment Around the compact atrioventricular (AV) node is an extended zone with transitional cells. LBB: left bundle branch; RBB: right bundle branch. Graphic 69647 Version 2.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 27/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Koch's triangle and fast and slow pathways Schematic representation of Koch's triangle which is bounded by the tricuspid ring and the tendon of Todoro. The tendon of Todoro and the tricuspid ring are in close proximity forming the apex of the triangle near the His bundle at the membranous septum. Koch's triangle can be divided into thirds: the anterior contains the compact AV node; the posterior contains the coronary sinus; and the middle or mid-septal third is between the anterior and posterior portions. The anterior third is associated with fast pathways, and the middle and posterior thirds with slow pathways. Graphic 52196 Version 2.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 28/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Slow-fast form of atrioventricular nodal reentrant tachycardia (AVNRT) Representation of dual pathway physiology involving the atrioventricular (AV) node and perinodal atrial tissue in the common form of AVNRT. Left panel: A normal sinus beat (A ) is conducted through the fast pathway (F) to the final common pathway (fcp) in the AV node and into the Bundle of His. The conduction through the slow pathway (S) runs into the refractory period of the impulse through the fast pathway and is extinguished. 1 Middle panel: A critically timed atrial premature beat (A ) finds the fast pathway refractory in the antegrade direction but is able to conduct antegrade through the slow pathway, which has a shorter refractory period. If excitability in the fast pathway has recovered by 2 the time the impulse reaches the fcp, there may be retrograde activation of the fast pathway. Right panel: The retrograde impulse throws off an echo to the atrium (A*), and, if the slow pathway has recovered its excitability, the impulse reenters the slow pathway and produces ventricular depolarization (V*). If the mechanism persists, a repetitive circuit is established that creates a sustained reentrant tachycardia. The sequence of antegrade (S) and retrograde (F) conduction is called the slow-fast form of AVNRT. Graphic 79760 Version 6.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 29/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Electrophysiologic study (EPS) in a patient with atrioventricular nodal reentrant tachycardia and dual AV nodal pathways The tracing shows three surface ECG leads (I, II, V1) and intracardiac recordings from the high right atrium (HRA), bundle of His (HIS), right ventricular apex (RVA), and coronary sinus (CS). During atrial pacing (S1) at a cycle length of 600 milliseconds (100 beats per minute), the AH interval is 120 milliseconds. An atrial premature beat (S2) is added at a coupling cyle of 420 milliseconds; this results in a prolongation of the PR interval and increase in the AH interval to 184 milliseconds. Courtesy of Martin Burke, DO. Graphic 60369 Version 4.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 30/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Electrophysiologic study (EPS) in a patient with atrioventricular nodal reentrant tachycardia and dual AV nodal pathways The tracing shows three surface ECG leads (I, II, V1) and intracardiac recordings from the high right atrium (HRA), bundle of His (HIS), right ventricular apex (RVA), and coronary sinus (CS). During atrial pacing (S1) at a cycle length of 600 milliseconds (100 beats per minute), the AH interval is 120 milliseconds. An atrial premature beat (S2) is added at a coupling cyle of 410 milliseconds; this results in a prolongation of the PR interval and increase in the AH interval to 242 milliseconds, which represents a 60-millisecond increase compared with the AH when a premature beat was added with a coupling interval of 420 milliseconds. This represents a "jump" due to a shift of AV nodal conduction from the fast to slow AV nodal pathway. Since the fast pathway has time to recover, there is retrograde VA conduction via the fast pathway, resulting in the occurrence of a retrograde His depolarization (HIS "A") and an atrial echo beat at the CS os area (CS 10-9). Courtesy of Martin Burke, DO. Graphic 72161 Version 4.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 31/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Generation of ECG in common form of atrioventricular nodal reentrant tachycardia (AVNRT) Ladder diagram of the common (slow-fast) form of AVNRT showing transmission of the impulse in atrial, atrioventricular (AV) nodal, and ventricular tissue and the resultant ECG. The first two cycles show the normal sinus beat (A ) conducting through the fast pathway (F) to the ventricle (V ) with the impulse blocked in the slow pathway. The premature atrial beat (A on ladder diagram, P on ECG) is timed critically; it finds the fast pathway refractory but is able to conduct through slow pathway, resulting in a long PR interval, and a ventricular depolarization (V ). It is also able to reenter and conduct 1 1 2 2 retrogradely up the now recovered fast pathway, resulting in an inverted P wave (A*) that is buried in the QRS complex. This atrial echo beat (A*) then reenters the now recovered slow pathway, which conducts anterogradely and results in ventricular depolarization (V*). The cycle repeats, and AV nodal reentry is established. ECG: electrocardiogram. Graphic 50122 Version 6.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 32/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Uncommon fast-slow variant of atrioventricular nodal reentrant tachycardia (AVNRT) Diagrammatic representation in the circuit (left panel) and the ladder diagram (right panel) of the uncommon form of AVNRT (fast-slow variant). Antegrade conduction is through the fast (F) pathway and retrograde conduction is through the slow (S) pathway. Because of slow retrograde activation of the atrium, the P wave occurs after the QRS complex with a long RP interval and relatively short PR interval before the next QRS complex. ECG: electrocardiogram. Graphic 56806 Version 4.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 33/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Atypical atrioventricular nodal reentrant tachycardia Shown are three simultaneous ECG leads (I, II, and III) during an uncommon or atypical form of an atrioventricular nodal reentrant tachycardia (AVNRT) in which antegrade conduction to the ventricle is via the fast pathway and retrograde atrial activation is by the slow pathway. As a result of delayed atrial activation, there is a long RP and short PR interval and a negative P wave in the inferior leads II and III. Graphic 66828 Version 2.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 34/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 12 lead ECG of an uncommon form of an atrioventricular nodal reentrant tachycardia The 12 lead ECG shows a regular, narrow complex tachycardia at a rate of 130 beats per minute. The QRS complexes are normal. There is an abnormal "notching" within the ST segment, representing a retrograde P wave (*). The interval from the proceeding R wave (RP interval) is longer than the PR interval; this is a "long RP tachycardia," due to an atypical atrioventricular nodal reentrant tachycardia. Courtesy of Martin Burke, DO. Graphic 81639 Version 4.0 Normal ECG https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 35/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 36/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Typical atrioventricular nodal reentrant tachycardia The first two complexes are normal sinus beats with a normal P wave followed by a QRS complex. The third complex, an atrial premature beat (APB), has a prolonged PR interval; it initiates a common or typical atrioventricular nodal reentrant tachycardia (AVNRT) in which antegrade conduction to the ventricle is via the slow pathway and retrograde atrial activation is by the fast pathway. Although no distinct P wave is seen, the QRS complex has a small terminal deflection, known as a pseudo r', which is the P wave superimposed upon the terminal portion of the QRS complex. Graphic 54290 Version 3.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 37/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate 12 lead ECG of the common form of an atrioventricular nodal reentrant tachycardia The 12 lead ECG shows a regular narrow complex tachycardia with a rate of 135 beats per minute; no P waves can be seen. The QRS morphology is identical to that seen during sinus rhythm. Courtesy of Martin Burke, DO. Graphic 57001 Version 2.0 Normal ECG https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 38/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 39/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Causes of palpitations Cardiac Arrhythmias (tachyarrhythmias, bradyarrhythmias, and ectopic beats) due to: Structural heart disease Underlying conduction system abnormality Medical comorbidity (eg, COPD, pulmonary embolism) Idiopathic Mitral valve prolapse Pacemaker syndrome Atrial myxoma Intra-cardiac shunt High output states Normal pregnancy Anemia Paget disease of bone Fever Metabolic and endocrine Hypoglycemia Hyperthyroidism Pheochromocytoma Catecholamine excess Stress Exercise Substance use Cocaine Caffeine Alcohol Amphetamines Nicotine Medications Sympathomimetic agents Vasodilators Anticholinergics Beta blocker withdrawal https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 40/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Psychiatric disorders Generalized anxiety Panic disorder Somatization disorder COPD: chronic obstructive pulmonary disease. Graphic 64306 Version 3.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 41/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Algorithm for the acute treatment of atrioventricular nodal reentrant tachycar AVNRT: atrioventricular nodal reentrant tachycardia; IV: intravenous; ECG: electrocardiogram; CCB: calcium channel blocker; ACLS: advanced cardiac life support; BB: beta blocker. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 42/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Evidence of hemodynamic instability may include hypotension, altered mental status, or signs and symptom of chest pain or heart failure. If patient becomes hemodynamically unstable at any point, proceed with electrical cardioversion. If initial low-energy shock is unsuccessful, subsequent shocks should be attempted using higher energy levels. The exact energy level varies depending upon the type of defibrillator (ie, biphasic versus monophasic Patients should be sedated and monitored when undergoing electrical cardioversion. Most patients who remain hemodynamically stable and who are able to participate in vagal maneuvers should perform several attempts prior to pharmacologic therapy. Adenosine is administered by rapid IV injection over one to two seconds at a peripheral site, followed by a normal saline flush. The rapid administration of both the drug and the saline flush is most easily accomplishe through a three-way stopcock. The usual initial dose is 6 mg, which can be followed by a dose of 12 mg if not successful. A dose of 18 mg can be used if 12 mg fails to convert the patient to sinus rhythm. Repeated dosin beyond the 18 mg bolus is not usually effective. Adenosine can be readministered immediately, for up to three doses, if AVNRT reoccurs. If AVNRT continue to recur following successful termination(s) with adenosine, a second drug should be administered (eg, BB o CCB) in an attempt to suppress the arrhythmia. The choice between BB and CCB is usually based on familiarity with and availability of the particular agents Typical options and doses include: Verapamil 5 to 10 mg IV bolus over two minutes; if no response, an additional 10 mg IV bolus may be administered 15 to 30 minutes following the initial dose. Diltiazem 0.25 mg/kg (average dose 20 mg) IV bolus over two minutes; if no response, an additional 0. mg/kg (average dose 25 mg) IV bolus may be administered 15 to 30 minutes following the initial dose. Metoprolol 2.5 to 5 mg IV bolus over two to five minutes; if no response, an additional 2.5 to 5 mg IV bolus may be administered every 10 minutes to a total dose of 15 mg. Refer to UpToDate content on advanced cardiac life support. Diagnostic testing is usually indicated following the initial presentation with AVNRT or in patients with signs/symptoms of concurrent angina or heart failure. Stable patients can undergo diagnostic testing in an outpatient environment. Refer to UpToDate topics for diagnostic approach. * Preventive therapy may include no specific treatment, pharmacologic suppression, or catheter ablation depending upon the frequency of AVNRT, severity of associated symptoms, and patient preference. Graphic 126471 Version 1.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 43/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Adult tachycardia with a pulse algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130747 Version 10.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 44/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 45/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par When a third dose is indicated, an alternative approach is to administer 12 mg (in those weighing >110 kg. [1] mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 46/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Radiofrequency ablation sites in Koch's triangle Schematic representation of Koch's triangle which is bounded by the tricuspid ring and the tendon of Todoro. Koch's triangle can be divided into thirds: the anterior contains the compact AV node; the posterior contains the coronary sinus; and the middle or mid-septal third is between the anterior and posterior portions. The anterior third is associated with fast pathways, and the middle and posterior thirds with slow pathways. The anterior and posterior approaches to ablate the fast and slow pathways, respectively, are indicated by the position of the catheters (shown in green). Graphic 62108 Version 1.0 https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 47/48 7/6/23, 1:48 PM Atrioventricular nodal reentrant tachycardia - UpToDate Contributor Disclosures Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atrioventricular-nodal-reentrant-tachycardia/print 48/48 |
7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Maternal conduction disorders and bradycardia during pregnancy : Louise Harris, MBChB, Sing-Chien Yap, MD, PhD, Candice Silversides, MD, MS, FRCPC : Hugh Calkins, MD, N A Mark Estes, III, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 13, 2022. INTRODUCTION Arrhythmias and conduction disorders are the most common cardiac complications encountered during pregnancy in women with and without structural heart disease [1-3]. They may manifest for the first time during pregnancy, and in other cases, pregnancy can trigger exacerbations in women with pre-existing arrhythmias [1,4-6]. Women with established arrhythmias or structural heart disease are at highest risk of developing arrhythmias during pregnancy. Due to surgical advances, there has been an increase in the number of women of childbearing age with congenital heart disease and this group of women is at particularly high risk for arrhythmias ( figure 1) [1,2,7-11]. Because of these associations, any woman who presents with an arrhythmia should have a clinical work up (including an electrocardiogram and a transthoracic echocardiogram) for evidence of structural heart disease. In general, the approach to the treatment of conduction disturbances and bradycardia in pregnant women is similar to that in the nonpregnant patient. Treatment strategies during pregnancy are hampered by the lack of randomized trials in this cohort of women. Choice of therapy, for the most part, is based on limited data from case reports, observational studies, and clinical experience. The prevalence, clinical presentation, and management of conduction disorders and bradycardia during pregnancy will be reviewed here. Electrocardiographic characteristics of sinus https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 1/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate bradycardia and conduction disorders are discussed in detail elsewhere. (See "ECG tutorial: Rhythms and arrhythmias of the sinus node" and "ECG tutorial: Atrioventricular block".) Issues relating to supraventricular and ventricular arrhythmias, as well as cardiac arrest during pregnancy, are discussed separately. (See "Sudden cardiac arrest and death in pregnancy" and "Supraventricular arrhythmias during pregnancy" and "Ventricular arrhythmias during pregnancy".) PALPITATIONS Palpitations occur frequently during pregnancy and are a common indication for cardiac evaluation during pregnancy. The differential diagnosis of palpitations is extensive and the diagnostic evaluation of pregnant women with palpitations does not differ from nonpregnant women. (See "Evaluation of palpitations in adults".) In one study of 110 pregnant women with arrhythmia-related symptoms (palpitations: 87 percent; dizziness: 13 percent; syncope/presyncope: 6 percent) who were evaluated with 24-hour Holter ambulatory monitoring, bradycardia was identified as a cause only 1 percent of the time [12]. SINUS BRADYCARDIA Sinus bradycardia is a rhythm in which fewer than the normal number of impulses arises from the sinoatrial (SA) node. The normal heart rate has been considered historically to range from 60 to 100 beats/min, with sinus bradycardia being defined as a sinus rhythm with a rate below 60 beats/min. Sinus bradycardia is not common during the antepartum period. Normally, there is a pregnancy-related physiologic increase in heart rate of 10 to 20 beats/min above baseline [13]. Mild sinus bradycardia may occur transiently after normal delivery and may persist for a few days in the postpartum period [13]. In the absence of structural heart disease, sinus bradycardia is seldom associated with symptoms and requires no intervention. (See "Sinus bradycardia".) FIRST DEGREE AV BLOCK First-degree atrioventricular (AV) block may be seen in women with structural heart disease such as rheumatic or congenital heart disease [13]. Transient first degree AV block may be seen in settings of increased vagal tone. It is not uncommon for sinus bradycardia with first degree AV block to occur in healthy individuals while sleeping. This is a physiologic rather than a pathologic https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 2/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate condition. Transient AV block resulting from increased vagal tone would be expected to occur less frequently in pregnant women than nonpregnant women. The exact prevalence of first- degree AV block is unknown [13]. The site of AV delay is usually located in the atrioventricular node, above the bundle of His, and it rarely progresses to advanced heart block. (See "First- degree atrioventricular block".) SECOND DEGREE AV BLOCK Second-degree AV block is sometimes seen in pregnancy. Mobitz type I (Wenckebach) AV block is more commonly encountered and generally has a benign outcome [14-16]. Typical Mobitz Type I (Wenckebach) block occurs at the level of the atrioventricular node, and, like first degree AV block, it rarely progresses to more advanced heart block. Accordingly, a conservative clinical strategy of monitoring is appropriate. Mobitz type II block (usually below the AV node) may precede the development of complete infra His AV block. It is uncommon during pregnancy. It is more likely to occur in women with structural heart disease. AV block at a level below the His bundle is usually associated with a very slow or absent ventricular escape rhythm, and therefore commonly results in hemodynamic compromise and/or syncope. Because of the risk of progression of Mobitz II block to complete infra His block, a permanent pacemaker is usually recommended even in an asymptomatic patient. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II".) COMPLETE HEART BLOCK Complete heart block may be congenital or acquired. The prevalence of new onset of complete heart block during pregnancy is unknown, but is likely quite rare. There is no obvious association between pregnancy and new onset complete heart block [17], although some experts have suggested that the atrial stretch associated with pregnancy may provoke conduction disorders [18,19]. Newly acquired complete heart block is rarely first detected during pregnancy [13,18]. The development of complete heart block may be associated with prior cardiac surgery, congenital heart disease, acute myocardial infarction, cardiomyopathy, drug intoxication, metabolic disturbances, systemic lupus erythematosus, or acute infection [20-22]. Progressive conduction disturbances during pregnancy that resolve in the postpartum period have been reported [18]. https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 3/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate Because placement of a pacemaker during pregnancy usually requires radiation exposure, women with complete heart block contemplating pregnancy should be evaluated by a cardiologist prior to becoming pregnant so a decision can be made regarding pacemaker implantation. Clinical presentation Many women with congenital complete heart block present before pregnancy, often in childhood [23]. Congenital heart block is sometimes identified in adulthood or, rarely, during pregnancy. Women may present with presyncope, syncope, or the heart block may be an incidental finding on an ECG. Typically, there is an escape rhythm with a narrow QRS complex. Many women with symptomatic congenital complete heart block will have a permanent pacemaker implanted before pregnancy. The role of prophylactic pacemaker implantation in asymptomatic women with congenital complete heart block to prevent sudden death is not known. There is an emerging body of evidence to suggest that pacemaker implantation should be carefully considered in the asymptomatic adult with congenital complete heart block, as it may prevent development of cardiomyopathy, mitral regurgitation, and lower the risk of ventricular arrhythmias. In one study of pregnancy outcomes in women with congenital complete heart block (n = 32), 24 women without a pacemaker gave birth to 45 children [24]. Thirteen percent (3 of 24) of the pregnancies were complicated by syncope, and a pacemaker was implanted in two women. The eight women with a pacemaker before pregnancy had 14 uneventful pregnancies. MANAGEMENT DURING PREGNANCY There are no guidelines that address monitoring during pregnancy in women with conduction disorders. Approach to monitoring Women with first degree AV block should have an electrocardiogram (ECG) at the time of clinic visits. They do not require ambulatory ECG monitoring during pregnancy or telemetry at the time of labor and delivery. In the asymptomatic patient, we perform an ambulatory ECG monitor to examine the extent of heart block and an exercise stress test to confirm robust AV nodal conduction with exercise. Management of Mobitz type II and complete heart block with narrow QRS must be individualized. Management is dependent on the presence of structural heart disease and the symptom status of the patient. All women should have ECG at the time of clinic visits to assess any changes in conduction. Serial ambulatory ECG monitoring is useful to assess the burden of conduction disease. The frequency of ambulatory ECG monitoring is dependent on the symptom https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 4/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate status of the women and the underlying cardiac condition. Women with syncope and high degree AV block should be admitted to hospital for monitoring and assessment for pacemaker implantation. At the time of labor and delivery, women with Mobitz type II block or complete heart block should have continuous telemetry monitoring. Some women may develop postpartum bradycardia and therefore monitoring should continue in the immediate postpartum period while in hospital. After hospital discharge, ambulatory ECG monitoring is recommended as some women with newly identified conduction block in pregnancy may have resolution of conduction block postpartum. Pacemaker therapy Pacemaker implantation is recommended for almost all patients with complete heart block who are symptomatic. For women with complete heart block first detected during pregnancy who have a stable narrow complex junctional escape rhythm, pacemaker implantation can be deferred until after delivery [24-28]. However, women with complete heart block who exhibit a slow wide QRS complex escape rhythm (suggestive of block below the His bundle) should undergo pacemaker implantation during pregnancy [28,29]. In women with a pacemaker who undergo cesarean delivery, the interference generated by monopolar surgical diathermy/electrocautery can be sufficient to temporarily inhibit pacemaker output, or may give rise to a temporary increase in pacing rate. Therefore, the pacemaker should be programmed to avoid inappropriate inhibition or high-rate pacing. All patients with permanent pacemakers should be on continuous cardiac monitoring during labor and following delivery. Pacemaker implantation is recommended for all patients with complete heart block who are symptomatic, and also in patients with asymptomatic complete heart block below the bundle of His. Perhaps the only exception to these indications for pacemaker implantation is patients with congenital complete heart block who are completely asymptomatic and have a stable junctional escape rhythm. Because placement of a pacemaker during pregnancy requires radiation exposure, women with complete heart block contemplating pregnancy should be evaluated by a cardiologist prior to becoming pregnant so a decision can be made regarding pacemaker implantation. Although rare, women with complete heart block who develop symptomatic bradycardia, including syncope and presyncope, may need to have a pacemaker implantation during pregnancy [18,30-33], but there is no consensus among experts on the best location for a pacemaker placement [29]. Radiation exposure due to the use of fluoroscopy during pacemaker https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 5/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate implantation is the most frequent concern for pregnant women and clinicians. (See "Diagnostic imaging in pregnant and lactating patients".) Fetal risks of anomalies, growth restriction, or abortions are not increased with radiation exposure of less than 50 mGy (5 rads) [34]. One study estimated that the average radiation dose to the fetus was <1 mGy during catheter ablation of supraventricular tachycardia (much longer fluoroscopy times compared with pacemaker implantation) [35]. Other precautions can be used to minimize radiation exposure. During fluoroscopy for pacemaker implantation, the uterus is positioned outside the field of view and therefore, the fetus is exposed to internal and external scattered radiation only. It may be possible to use a lead shield to protect the uterus from external scattered radiation; however, because the dose from external scattered radiation is minimal, the use of lead shielding is left to the discretion of the operator. Modifying the exposure time, number of films obtained, beam size, and imaging area can further reduce the amount of radiation exposure. If necessary, pacemaker implantation can be safely performed with minimal radiation exposure by a skilled operator in a cath lab with pulse fluoroscopy. Although some have advocated echocardiographic guidance during the first trimester, the amount of fluoroscopy received is sufficiently low, that it is our opinion that an echocardiographic guided approach should not be advised [30,31,33]. Three-dimensional (3D) electro-anatomic mapping systems can be used to implant permanent pacemakers without using fluoroscopy [36]. With an experienced implanting clinician and appropriate fluoroscopy equipment and shielding of the fetus, temporary and permanent pacemaker leads can be safely placed during all stages of pregnancy [37-39]. (See "Diagnostic imaging in pregnant and lactating patients".) Prophylactic temporary pacing for labor The Valsalva maneuver during labor can be associated with a vasovagal reaction, resulting in slowing of the heart rate and potentially syncope. Thus, some centers advocate prophylactic temporary transvenous pacing for labor and delivery in asymptomatic women [23,40,41]. Other centers do not prophylactically insert pacemakers in all women with complete heart block [18,42-44]. In one small case series of six asymptomatic, non-paced women with complete heart block, there was no significant change in heart rate before, during, or after labor and delivery [42]. Only one woman developed hypotension secondary to postpartum hemorrhage. In general, the indications for temporary pacing during labor are identical to those for nonpregnant adults. In emergency situations, temporary transcutaneous pacing can be used. However, this is painful and generally poorly tolerated by patients. Transcutaneous pacing generally is used for a short period of time while a transvenous pacing is placed or the bradycardia resolves. (See "Temporary cardiac pacing".) https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 6/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient education: Bradycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Sinus bradycardia This can occur transiently after normal delivery and may persist for a few days in the postpartum period. (See 'Sinus bradycardia' above.) Conduction disorders These can be associated with structural heart disease such as rheumatic heart disease or ischemia heart disease. (See 'First degree AV block' above.) Complete heart block during pregnancy This may be acquired or congenital. Because placement of a pacemaker during pregnancy usually requires radiation exposure, women with complete heart block contemplating pregnancy should be evaluated by a cardiologist prior to becoming pregnant so a decision can be made regarding pacemaker implantation. (See 'Complete heart block' above.) Indications for pacing In general, the indications for temporary and permanent pacing during pregnancy are similar to those in the general population. (See 'Complete heart block' above.) Safety of undergoing pregnancy in women with pacemakers Pregnancies in women with pacemakers are safe. Women with pacemakers who undergo cesarean delivery may https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 7/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate require pacemaker reprogramming to avoid interference caused by electrocautery. (See 'Pacemaker therapy' above.) Prophylactic temporary pacing for labor There is no consensus with regard to prophylactic temporary pacing for labor in asymptomatic women with congenital complete heart block. (See 'Prophylactic temporary pacing for labor' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001; 104:515. 2. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007; 49:2303. 3. Drenthen W, Boersma E, Balci A, et al. Predictors of pregnancy complications in women with congenital heart disease. Eur Heart J 2010; 31:2124. 4. Lee SH, Chen SA, Wu TJ, et al. Effects of pregnancy on first onset and symptoms of paroxysmal supraventricular tachycardia. Am J Cardiol 1995; 76:675. 5. Doig JC, McComb JM, Reid DS. Incessant atrial tachycardia accelerated by pregnancy. Br Heart J 1992; 67:266. 6. Silversides CK, Harris L, Haberer K, et al. Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes. Am J Cardiol 2006; 97:1206. 7. Siu SC, Sermer M, Harrison DA, et al. Risk and predictors for pregnancy-related complications in women with heart disease. Circulation 1997; 96:2789. 8. Drenthen W, Pieper PG, Ploeg M, et al. Risk of complications during pregnancy after Senning or Mustard (atrial) repair of complete transposition of the great arteries. Eur Heart J 2005; 26:2588. 9. Drenthen W, Pieper PG, van der Tuuk K, et al. Cardiac complications relating to pregnancy and recurrence of disease in the offspring of women with atrioventricular septal defects. Eur Heart J 2005; 26:2581. 10. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Pregnancy and delivery in women after Fontan palliation. Heart 2006; 92:1290. 11. Blomstr m-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias executive summary: a report of https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 8/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias). Circulation 2003; 108:1871. 12. Shotan A, Ostrzega E, Mehra A, et al. Incidence of arrhythmias in normal pregnancy and relation to palpitations, dizziness, and syncope. Am J Cardiol 1997; 79:1061. 13. MENDELSON CL. Disorders of the heartbeat during pregnancy. Am J Obstet Gynecol 1956; 72:1268. 14. COPELAND GD, STERN TN. Wenckebach periods in pregnancy and puerperium. Am Heart J 1958; 56:291. 15. Sherer DM, Nawrocki MN, Thompson HO, Woods JR Jr. Type I second-degree AV block (Mobitz type I, Wenckebach AV block) during ritodrine therapy for preterm labor. Am J Perinatol 1991; 8:150. 16. Matta BF, Magee P. Wenckebach type heart block following spinal anaesthesia for caesarean section. Can J Anaesth 1992; 39:1067. 17. Eddy WA, Frankenfeld RH. Congenital complete heart block in pregnancy. Am J Obstet Gynecol 1977; 128:223. 18. Thaman R, Curtis S, Faganello G, et al. Cardiac outcome of pregnancy in women with a pacemaker and women with untreated atrioventricular conduction block. Europace 2011; 13:859. 19. Young D, Shravan Turaga NS, Amisha FNU, et al. Recurrence of complete heart block in pregnancy. HeartRhythm Case Rep 2021; 7:679. 20. Tateno S, Niwa K, Nakazawa M, et al. Arrhythmia and conduction disturbances in patients with congenital heart disease during pregnancy: multicenter study. Circ J 2003; 67:992. 21. Suri V, Keepanasseril A, Aggarwal N, et al. Maternal complete heart block in pregnancy: analysis of four cases and review of management. J Obstet Gynaecol Res 2009; 35:434. 22. Lo CH, Wei JCC, Tsai CF, et al. Syncope caused by complete heart block and ventricular arrhythmia as early manifestation of systemic lupus erythematosus in a pregnant patient: a case report. Lupus 2018; 27:1729. 23. Dalvi BV, Chaudhuri A, Kulkarni HL, Kale PA. Therapeutic guidelines for congenital complete heart block presenting in pregnancy. Obstet Gynecol 1992; 79:802. 24. Micha lsson M, Jonzon A, Riesenfeld T. Isolated congenital complete atrioventricular block in adult life. A prospective study. Circulation 1995; 92:442. https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 9/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate 25. Kenmure AC, Cameron AJ. Congenital complete heart block in pregnancy. Br Heart J 1967; 29:910. 26. Avasthi K, Gupta S, Avasthi G. An unusual case of complete heart block with triplet pregnancy. Indian Heart J 2003; 55:641. 27. European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011; 32:3147. 28. Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J 2021; 42:3427. 29. Jaffe R, Gruber A, Fejgin M, et al. Pregnancy with an artificial pacemaker. Obstet Gynecol Surv 1987; 42:137. 30. Jordaens LJ, Vandenbogaerde JF, Van de Bruaene P, De Buyzere M. Transesophageal echocardiography for insertion of a physiological pacemaker in early pregnancy. Pacing Clin Electrophysiol 1990; 13:955. 31. Lau CP, Lee CP, Wong CK, et al. Rate responsive pacing with a minute ventilation sensing pacemaker during pregnancy and delivery. Pacing Clin Electrophysiol 1990; 13:158. 32. Amikam S, Abramovici H, Brandes JM, et al. Pregnancy in the presence of an implanted pacemaker. Int Surg 1981; 66:369. 33. G dal M, Kervancio lu C, Oral D, et al. Permanent pacemaker implantation in a pregnant woman with the guidance of ECG and two-dimensional echocardiography. Pacing Clin Electrophysiol 1987; 10:543. 34. ACOG Committee on Obstetric Practice. ACOG Committee Opinion. Number 299, September 2004 (replaces No. 158, September 1995). Guidelines for diagnostic imaging during pregnancy. Obstet Gynecol 2004; 104:647. 35. Damilakis J, Theocharopoulos N, Perisinakis K, et al. Conceptus radiation dose and risk from cardiac catheter ablation procedures. Circulation 2001; 104:893. 36. K hne M, Schaer B, Reichlin T, et al. X-ray-free implantation of a permanent pacemaker during pregnancy using a 3D electro-anatomic mapping system. Eur Heart J 2015; 36:2790. 37. Velasco A, Velasco VM, Rosas F, et al. Utility of the NavX Electroanatomic Mapping System for Permanent Pacemaker Implantation in a Pregnant Patient with Chagas Disease. Indian Pacing Electrophysiol J 2013; 13:34. https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 10/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate 38. Ruiz-Granell R, Ferrero A, Morell-Cabedo S, et al. Implantation of single-lead atrioventricular permanent pacemakers guided by electroanatomic navigation without the use of fluoroscopy. Europace 2008; 10:1048. 39. Tuzcu V, Gul EE, Erdem A, et al. Cardiac Interventions in Pregnant Patients without Fluoroscopy. Pediatr Cardiol 2015; 36:1304. 40. Sharma JB, Malhotra M, Pundir P. Successful pregnancy outcome with cardiac pacemaker after complete heart block. Int J Gynaecol Obstet 2000; 68:145. 41. Ramsewak S, Persad P, Perkins S, Narayansingh G. Twin pregnancy in a patient with complete heart block. A case report. Clin Exp Obstet Gynecol 1992; 19:166. 42. Hidaka N, Chiba Y, Kurita T, et al. Is intrapartum temporary pacing required for women with complete atrioventricular block? An analysis of seven cases. BJOG 2006; 113:605. 43. Hidaka N, Chiba Y, Fukushima K, Wake N. Pregnant women with complete atrioventricular block: perinatal risks and review of management. Pacing Clin Electrophysiol 2011; 34:1161. 44. Keepanasseril A, Maurya DK, Suriya Y, Selvaraj R. Complete atrioventricular block in pregnancy: report of seven pregnancies in a patient without pacemaker. BMJ Case Rep 2015; 2015. Topic 15252 Version 18.0 https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 11/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate GRAPHICS Prevalence of arrhythmias during pregnancy in women with congenital heart disease AOS: aortic stenosis; ASD: atrial septal defect; AVSD: atrioventricular septal defect; CC-TGA: congenital corrected transposition of the great arteries; CHD: congenital heart disease; PAVSD: pulmonary atresia with ventricular septal defect; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Data from: Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007; 49:2303. Graphic 61986 Version 4.0 https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 12/13 7/6/23, 1:48 PM Maternal conduction disorders and bradycardia during pregnancy - UpToDate Contributor Disclosures Louise Harris, MBChB No relevant financial relationship(s) with ineligible companies to disclose. Sing- Chien Yap, MD, PhD Grant/Research/Clinical Trial Support: Medtronic [Ventricular arrhythmias]. Consultant/Advisory Boards: Boston Scientific [Ventricular arrhythmias]. All of the relevant financial relationships listed have been mitigated. Candice Silversides, MD, MS, FRCPC No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/maternal-conduction-disorders-and-bradycardia-during-pregnancy/print 13/13 |
7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of the acute management of tachyarrhythmias : Jordan M Prutkin, MD, MHS, FHRS : James Hoekstra, MD, Hugh Calkins, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 03, 2023. INTRODUCTION Tachyarrhythmias, defined as abnormal heart rhythms with a ventricular rate of 100 or more beats per minute, are frequently symptomatic and often result in patients seeking care at their provider's office or the emergency department. Signs and symptoms related to the tachyarrhythmia may include shock, hypotension, heart failure, shortness of breath, chest pain, acute myocardial infarction, palpitations, and/or decreased level of consciousness. An overview of the management of these various arrhythmias will be presented here. More complete reviews of the individual arrhythmias are discussed separately. INITIAL DIAGNOSTIC AND TREATMENT DECISIONS In patients who present with a symptomatic tachyarrhythmia, a 12-lead electrocardiogram (ECG) should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient. Is the patient clinically (or hemodynamically) unstable? The most important clinical determination in a patient presenting with a tachyarrhythmia is whether or not the patient is experiencing signs and symptoms related to the rapid heart rate. These can include hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 1/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Determining whether a patient's symptoms are related to the tachycardia depends upon several factors, including age and the presence of underlying cardiac disease. Hemodynamically unstable and not sinus rhythm If a patient has clinically significant hemodynamic instability potentially due to the tachyarrhythmia, an attempt should be made as quickly as possible to determine whether the rhythm is sinus tachycardia ( algorithm 1). If the rhythm is not sinus tachycardia, or if there is any doubt that the rhythm is sinus tachycardia, urgent conversion to sinus rhythm is recommended. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Similar to sinus rhythm' and "Basic principles and technique of external electrical cardioversion and defibrillation" and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Assessment of hemodynamic stability'.) Hemodynamically stable If the patient is not experiencing hemodynamic instability, a nonemergent approach to the diagnosis of the patient's rhythm can be undertaken [1-3]. A close examination of the 12-lead ECG should permit the correct identification of the arrhythmia in 80 percent of cases [4]. (See 'Is the QRS complex narrow or wide? Regular or irregular?' below and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Evaluation' and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'.) Is the QRS complex narrow or wide? Regular or irregular? Treatment of any tachyarrhythmia depends on a variety of clinical factors. However, most treatment decisions are made based on the width, morphology, and regularity of the QRS complex ( algorithm 2). In most patients, the differentiation between narrow and wide QRS complex tachyarrhythmias requires only a surface ECG. Narrow QRS complex tachyarrhythmias have a QRS complex <120 milliseconds in duration Wide QRS complex tachyarrhythmias have a QRS complex 120 milliseconds in duration The various types of narrow and wide QRS complex tachyarrhythmias are discussed below. (See 'Narrow QRS complex tachyarrhythmias' below and 'Wide QRS complex tachyarrhythmias' below.) NARROW QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of narrow QRS complex tachycardias will be divided into those with a regular ventricular response and those with an irregular ventricular response ( algorithm 3 and algorithm 1). https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 2/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Regular narrow QRS complex tachyarrhythmias The regular narrow QRS complex tachycardias include ( algorithm 2) [3]: Sinus tachycardia (see "Sinus tachycardia: Evaluation and management") Inappropriate sinus tachycardia (see "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia') Sinoatrial nodal reentrant tachycardia (SANRT) (see "Sinoatrial nodal reentrant tachycardia (SANRT)") Atrioventricular nodal reentrant tachycardia (AVNRT) (see "Atrioventricular nodal reentrant tachycardia") Atrioventricular reentrant (or reciprocating) tachycardia (AVRT) (see "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway") Atrial tachycardia (AT) (see "Focal atrial tachycardia") Atrial flutter (see "Overview of atrial flutter") Intraatrial reentrant tachycardia (IART) (see "Intraatrial reentrant tachycardia") Junctional ectopic tachycardia Nonparoxysmal junctional tachycardia Because the vast majority of regular narrow QRS complex tachycardias are due to sinus tachycardia, AVNRT, AVRT, AT, and atrial flutter, these conditions will be presented here. Discussions regarding the treatment of the other less common types of regular narrow QRS complex tachycardias are presented separately. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia' and "Sinoatrial nodal reentrant tachycardia (SANRT)", section on 'Treatment' and "Intraatrial reentrant tachycardia", section on 'Treatment' and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Permanent junctional reciprocating tachycardia'.) Sinus tachycardia The most common tachycardia is sinus tachycardia. If it is certain that the patient's rhythm is sinus tachycardia and clinically significant cardiac symptoms are present, management should be focused on the underlying disorder and on treating any contributing cause of the rapid heart rate (eg, coronary ischemia, pulmonary embolism, respiratory or cardiac failure, hypovolemia, anemia, hyperthyroidism, fever, pain, or anxiety). This may include volume replacement or diuresis, antibiotics, anti-pyretics, oxygen, pain control, or other treatments as appropriate. In patients with sinus tachycardia and certain forms of heart disease, such as coronary disease or aortic stenosis, treatment may need to be directed at the heart rate itself. In such cases, cautious use of an intravenous beta blocker is appropriate. (See "Sinus tachycardia: Evaluation and management" and "Acute myocardial infarction: Role of beta blocker therapy" and "Medical management of symptomatic aortic stenosis".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 3/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Atrioventricular nodal reentrant tachycardia (AVNRT) Patients with AVNRT associated with hemodynamic compromise or severe symptoms due to the tachycardia (eg, angina, hypotension, or heart failure) require rapid termination of the arrhythmia. (See "Atrioventricular nodal reentrant tachycardia", section on 'Initial management'.) For patients with AVNRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers (Valsalva maneuver or carotid sinus massage) is also reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with AVNRT associated with severe symptoms due to the tachycardia (eg, angina, hypotension, heart failure, or mental status changes) in whom intravenous access is available, we suggest an initial attempt at termination with adenosine ( algorithm 4) rather than cardioversion. If adenosine cannot be administered or is ineffective, patients should undergo immediate DC cardioversion. For patients with AVNRT that is not associated with severe symptoms or hemodynamic collapse, including patients without symptoms, we suggest the following sequential approach to acute termination: Vagal maneuvers (see "Vagal maneuvers") IV adenosine ( algorithm 4) IV non-dihydropyridine calcium channel blocker or an IV beta blocker Atrioventricular reentrant tachycardia (AVRT) Patients with any arrhythmia (ie, orthodromic AVRT, antidromic AVRT, atrial fibrillation/flutter) involving an accessory pathway should have a prompt initial assessment of hemodynamic status. AVRT may result in either a narrow QRS complex tachycardia or a wide QRS complex tachycardia depending on the direction of conduction across the accessory pathway and also the presence of aberrant conduction. (See 'Antidromic AVRT' below and "Treatment of arrhythmias associated with the Wolff-Parkinson- White syndrome", section on 'Acute treatment of symptomatic arrhythmias'.) For patients with AVRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers is reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with acute symptomatic orthodromic AVRT (usually narrow QRS complex in the absence of an underlying conduction delay) who are hemodynamically stable, our approach is as follows ( table 1): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 4/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate We recommend initial treatment with one or more vagal maneuvers rather than pharmacologic therapy. (See "Vagal maneuvers".) If vagal maneuvers are ineffective, pharmacologic therapy with an AV nodal blocking agent (ie, adenosine, verapamil, beta blockers) should be instituted. We suggest intravenous adenosine ( algorithm 4) rather than intravenous verapamil as the initial choice based on its high efficacy and short half-life. If adenosine is ineffective, we proceed with intravenous verapamil as the second-line agent. If orthodromic AVRT persists, intravenous procainamide and beta blockers approved for intravenous administration (propranolol, metoprolol, and esmolol) are additional therapeutic options. Amiodarone may also be considered. Because most patients with acute symptomatic antidromic AVRT have a wide QRS complex, the approach to this arrhythmia is discussed below. (See 'Antidromic AVRT' below.) Atrial tachycardia Focal atrial tachycardias (AT), usually paroxysmal and self-limited, arise from a single site or area of microreentry or enhanced automaticity outside of the sinus node. (See "Focal atrial tachycardia", section on 'Acute treatment'.) For patients with AT who are felt to be hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. For a hemodynamically stable patient with symptomatic AT, we suggest acute treatment with an oral or intravenous beta blocker or non-dihydropyridine calcium channel blocker (ie, diltiazem or verapamil). Such treatment may slow the ventricular response and/or terminate the arrhythmia. Intravenous amiodarone is an acceptable alternative that may be preferred in a patient with borderline hypotension as amiodarone may slow the rate or convert the rhythm back to normal sinus. Atrial flutter Atrial flutter usually presents as a regular narrow complex tachycardia, though it occasionally may have an irregular ventricular response. Atrial flutter should always be considered high on the differential diagnosis when a patient presents with a regular narrow complex tachycardia with a ventricular response of approximately 150 beats per minute. As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' below.) Irregular narrow QRS complex tachyarrhythmias The irregular narrow QRS complex tachycardias include ( algorithm 2): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 5/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Atrial fibrillation (AF) (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation") Atrial flutter with variable conduction (see "Overview of atrial flutter") Focal atrial tachycardia with variable conduction (see "Focal atrial tachycardia") Multifocal atrial tachycardia (MAT) (see "Multifocal atrial tachycardia") Atrial fibrillation Most patients with new onset (ie, first detected or diagnosed) AF with a rapid rate present with symptoms related to the arrhythmia. Except for embolization, the symptoms associated with new onset AF are primarily due to a rapid and/or irregular ventricular response. The early steps in the management of a patient with new onset rapid AF involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Urgent or emergent cardioversion should be considered for patients with active ischemia, significant hypotension, severe heart failure, or the presence of a preexcitation syndrome associated with rapid conduction using the accessory pathway. (See 'Atrioventricular reentrant tachycardia (AVRT)' above.) For all patients who do not require urgent or emergent cardioversion, we recommend rate control to improve symptoms and to reduce the risk of tachycardia-mediated cardiomyopathy. We believe a goal of less than 110 beats per minute is reasonable for an asymptomatic patient with a normal ejection fraction. Beta blockers and non- dihydropyridine calcium channel blockers are preferred as first-line agents in most patients, and digoxin should only rarely be used. Intravenous preparations are preferred to oral preparations when rapid control of rate is necessary. For patients with AF less than 48 hours in duration in whom cardioversion is planned, the use of antithrombotic therapy pre-cardioversion to reduce the risk of embolization can be considered. For patients with AF longer than 48 hours in duration (or of unknown duration), we recommend four weeks of therapeutic oral anticoagulation prior to cardioversion, as opposed to immediate cardioversion. Transesophageal echocardiography-based (TEE) screening for the presence of atrial thrombi is recommended if cardioversion is desired earlier than four weeks. Anticoagulation must be continued for a minimum of four weeks after cardioversion. Whether long-term anticoagulation is indicated depends on assessment of the patient's thromboembolic risk profile. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 6/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Atrial flutter As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' above.) Multifocal atrial tachycardia Multifocal atrial tachycardia (MAT) is an arrhythmia with organized atrial activity yielding P waves with three or more different morphologies. MAT is commonly associated with significant underlying pulmonary or cardiac illness. (See "Multifocal atrial tachycardia", section on 'Treatment'.) Most episodes of MAT do not precipitate hemodynamic compromise or limiting symptoms. Thus, therapy in patients with MAT should be aimed at the inciting underlying disease. Patients with MAT and associated hypokalemia or hypomagnesemia should undergo electrolyte repletion prior to the initiation of additional medical therapy for MAT. Medical therapy for MAT is indicated only if MAT causes a sustained rapid ventricular response that causes or worsens myocardial ischemia, heart failure, peripheral perfusion, or oxygenation. Options for medical therapy for patients with symptomatic MAT requiring ventricular rate control include non-dihydropyridine calcium channel blockers and beta blockers. For patients without heart failure or bronchospasm, we suggest initial therapy with a beta blocker, usually metoprolol, before calcium channel blockers. Conversely, for patients with severe bronchospasm, we suggest initial therapy with a non-dihydropyridine calcium channel blocker, usually verapamil, rather than a beta blocker. Beta blockers may be used cautiously in patients with stable heart failure. Rate control therapy is typically unsuccessful, however, without treating the underlying disorder. WIDE QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of wide QRS complex tachycardias, similar to narrow QRS complex tachycardias, can be divided into those with a regular or irregular ventricular rate. Regular wide QRS complex tachyarrhythmias The regular wide QRS complex tachycardias include ( algorithm 2): Monomorphic ventricular tachycardia (VT). (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Ventricular tachycardia in the absence of apparent structural heart disease".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 7/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Supraventricular tachycardia with aberrant conduction, underlying conduction delay, conduction over an accessory pathway (eg, AVNRT with right bundle branch block), or a paced ventricular response. Supraventricular tachycardia in a patient on certain antiarrhythmic medications or with significant electrolyte abnormalities. Antidromic AVRT. The most concerning potential cause of a wide QRS complex tachycardia is VT, and, in the majority of patients, the arrhythmia should be assumed to be VT until proven otherwise. Immediate assessment of patient stability takes precedence over any further diagnostic evaluation. (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'.) A patient who is unresponsive or pulseless should be treated according to standard advance cardiac life support (ACLS) algorithms ( algorithm 5). In a patient who is unstable but conscious, we recommend immediate synchronized cardioversion with appropriate sedation when possible. In a stable patient, a focused diagnostic evaluation may proceed to determine the etiology of the arrhythmia and guide specific therapy. Ventricular tachycardia In stable patients with known or presumed VT, we recommend the following approach (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'): We recommend synchronized external cardioversion, following appropriate sedation, as the initial therapy for most patients with stable VT. If the patient has an implantable cardioverter-defibrillator, it may be possible to terminate the arrhythmia by antitachycardia pacing prior to an attempted cardioversion. In patients with refractory or recurrent wide complex tachycardia (WCT), we suggest an intravenous class I or III antiarrhythmic drug ( table 2), such as amiodarone, lidocaine, or procainamide. In selected patients known to have one of the syndromes of VT in the setting of a structurally normal heart, we suggest calcium channel blockers or beta blockers be used for arrhythmia termination or suppression. However, the decision to use these drugs in this https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 8/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate setting should be made in consultation with a cardiologist experienced in arrhythmia management. Supraventricular tachycardia with aberrant conduction The narrow complex supraventricular tachycardia (SVT) rhythms may present with a wide complex in the setting of aberrant conduction or conduction over an accessory pathway (not including AVRT). In stable patients with a WCT that is known to be an SVT, initial management is similar to that of an SVT with a narrow QRS complex. A continuous rhythm strip should be obtained during any intervention that is intended to slow or terminate the arrhythmia. (See 'Regular narrow QRS complex tachyarrhythmias' above.) For AVNRT or AVRT, or an SVT in which the specific arrhythmia is unknown, we suggest the following sequence of interventions in order to terminate the arrhythmia or to slow ventricular response and facilitate diagnosis in stable patients: Vagotonic maneuvers (eg, valsalva or carotid sinus pressure) Intravenous adenosine ( algorithm 4) Intravenous calcium channel blockers or beta blockers Cardioversion in selected persistent cases, or if the patient is unstable Supraventricular tachycardia with a pacemaker Regular wide QRS complex tachycardias in patients with a pacemaker may be due to tracking of one of the typical supraventricular tachycardias (eg, sinus tachycardia, atrial flutter, etc) or may be due to endless loop tachycardia (ELT, also referred to as pacemaker-mediated tachycardia [PMT]). (See "Unexpected rhythms with normally functioning dual-chamber pacing systems", section on 'Pacemaker-mediated tachycardia'.) In patients with tracking of a native supraventricular tachyarrhythmia, the pacemaker usually should automatically mode switch to a non-tracking mode. If it does not, placing a magnet on the pacemaker will lead to asynchronous pacing at a fixed and lower rate, and the pacemaker settings can be adjusted to prevent rapid pacing. If the rhythm is due to ELT, retrograde conduction from the ventricle to the atrium is sensed by the pacemaker and serves as a trigger to pace the ventricle, which again conducts back to the atrium and perpetuates the tachycardia. Placing a magnet on the pacemaker leads to asynchronous pacing and will stop the tachycardia. Most pacemakers have algorithms to prevent or treat ELT, but pacemaker settings can usually be reprogrammed if they are ineffective. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 9/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Antidromic AVRT For patients with acute symptomatic antidromic AVRT (regular and wide QRS complex) who are hemodynamically stable, our approach is as follows (see "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Antidromic AVRT'): We treat with intravenous procainamide in an effort to terminate the tachycardia or, if the tachycardia persists, slow the ventricular response. This is because it is often difficult to correctly determine that the rhythm is due to antidromic AVRT and not ventricular tachycardia. If the rhythm is definitely known to be antidromic AVRT, then adenosine ( algorithm 4), verapamil, or IV beta blockers may be considered, but monitoring should be continued to ensure that there is not a rapid ventricular rate if atrial fibrillation (AF) subsequently develops after SVT termination. Irregular wide QRS complex tachyarrhythmias The irregular wide QRS complex tachycardias include ( algorithm 2): Polymorphic VT, including torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Irregular narrow complex tachycardias with aberrant conduction, antegrade conduction over an accessory pathway (eg, preexcited AF), or underlying conduction delay (eg, AF with right bundle branch block). Ventricular fibrillation. Polymorphic ventricular tachycardia Polymorphic (or polymorphous) ventricular tachycardia (VT) is defined as an unstable rhythm with a continuously varying QRS complex morphology in any recorded electrocardiographic (ECG) lead. Polymorphic VT is generally a rapid and hemodynamically unstable rhythm, and urgent defibrillation is usually necessary. In addition to immediate defibrillation, further therapy is intended to treat underlying disorders and to prevent recurrences. The specific approach depends upon whether or not the QT interval on the baseline ECG is prolonged. Polymorphic VT that occurs in the setting of QT prolongation in sinus rhythm is considered as a distinct arrhythmia, called torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Prompt defibrillation is indicated in patients with hemodynamically unstable torsades de pointes. In the conscious patient with recurrent episodes of torsades de pointes: https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 10/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Intravenous magnesium sulfate (initial dose of 1 to 2 grams IV over 15 minutes, may be followed by an infusion) is first-line therapy, as it is highly effective for both treatment and prevention of recurrence of long QT-related ventricular ectopic beats that trigger torsades de pointes. The benefit is seen even in patients with normal serum magnesium concentrations at baseline. Temporary transvenous overdrive pacing (atrial or ventricular) at about 100 beats per minute is generally reserved for patients who do not respond to intravenous magnesium. In those with congenital long QT syndrome, beta blockers may be used to reduce the frequency of premature ventricular contractions and shorten the QT interval. For patients with polymorphic VT triggered by pauses or bradycardia, isoproterenol (initial dose 0.05 to 0.1 mcg/kg per minute in children and 2 mcg/minute in adults, then titrated to achieve a heart rate of 100 beats per minute) can be used as a temporizing measure to achieve a heart rate of 100 beats per minute prior to pacing. For patients with polymorphic VT and a normal baseline QT interval, the most likely cause is myocardial ischemia. Treatments may include: Prompt defibrillation in the hemodynamically unstable patient. Beta-blockers if blood pressure tolerates. Metoprolol 5 mg intravenously every five minutes, to a total of 15 mg, may be given. IV amiodarone may prevent a recurrent episode. Urgent coronary angiography and possible revascularization. Short-term mechanical circulatory support. Magnesium is less likely to be effective for polymorphic VT if the baseline QT interval is normal. If the polymorphic VT is due to catecholaminergic polymorphic ventricular tachycardia (CPVT), beta blockers should be used. If it is due to Brugada syndrome, isoproterenol should be initiated. (See "Catecholaminergic polymorphic ventricular tachycardia", section on 'Acute management' and "Brugada syndrome or pattern: Management and approach to screening of relatives".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 11/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Preexcited atrial fibrillation For patients with acute symptomatic preexcited AF who are hemodynamically stable, our approach is as follows: We suggest initial medical therapy with rhythm control versus rate control. While there is no clear first-line medication for rhythm control, options include ibutilide and procainamide. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Atrial fibrillation with preexcitation'.) For all patients with preexcited AF, we recommend not using standard AV nodal blocking medications (ie, beta blockers, non-dihydropyridine calcium channel blockers [verapamil and diltiazem], digoxin, adenosine). Blocking the AV node may result in increased conduction of atrial impulses to the ventricle by way of the accessory pathway, increasing the ventricular rate and potentially resulting in hemodynamic instability and development of ventricular fibrillation. While preexcited AF conducts down a bypass pathway, in contrast to AVRT, the rhythm is irregularly irregular and wide complex. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Basic and advanced cardiac life support in adults" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 12/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Tachycardia (The Basics)" and "Patient education: Ventricular tachycardia (The Basics)" and "Patient education: Supraventricular tachycardia (SVT) (The Basics)") SUMMARY AND RECOMMENDATIONS Initial diagnostic and treatment decisions In patients who present with a symptomatic tachyarrhythmia, a 12-lead ECG should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or |
crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone Antidromic AV reentrant tachycardia Acute termination* Unstable patients: Adenosine, verapamil, diltiazem, Synchronized cardioversion beta blockers, digoxin should all be avoided if NOT certain of diagnosis Stable patients (if CERTAIN of the diagnosis): Same progression of therapies as acute termination of orthodromic AVRT Stable patients (if NOT certain of the diagnosis): IV procainamide, synchronized cardioversion if procainamide is ineffective or not available https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 20/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Chronic prevention First line: Catheter ablation of the accessory pathway Digoxin Beta blockers Second line: Oral flecainide or propafenone in the absence of Verapamil, diltiazem structural or ischemic heart disease Other therapies: Oral IA antiarrhythmic agent OR oral amiodarone Pre-excited atrial fibrillation Acute termination* Unstable patients: Amiodarone Synchronized cardioversion Stable patients: Digoxin Beta blockers First line: IV ibutilide or IV procainamide Adenosine Other therapies: IC antiarrhythmic agent or dofetilide; synchronized cardioversion if other therapies are ineffective or not available Verapamil, diltiazem Chronic prevention First line: Catheter ablation or the accessory pathway Oral digoxin Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone AVRT: atrioventricular reciprocating tachycardia; IV: intravenous; class IC: flecainide, propafenone; class IA: quinidine, procainamide, disopyramide. Cardioversion is indicated if hemodynamically unstable or drugs are ineffective. Ablation of the accessory pathway is generally preferred to cure the arrhythmia. Procainamide is the intravenous drug of choice for acute termination of suspected antidromic AVRT. If the tachycardia is definitely known to be antidromic AVRT, and it has been verified that the AV node (rather than a second accessory pathway) is acting as the retrograde limb of the circuit, one could consider treatment with an agent such as adenosine similar to therapy for orthodromic AVRT, https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 21/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate but it is rare to have all of the necessary data in the acute setting to justify use of AV nodal blocking agents. Graphic 62762 Version 7.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 22/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 23/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 24/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 25/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 26/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 27/28 7/6/23, 1:49 PM Overview of the acute management of tachyarrhythmias - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 28/28 |
7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinoatrial nodal reentrant tachycardia (SANRT) : Munther K Homoud, MD : Samuel L vy, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 18, 2021. INTRODUCTION Atrial tachycardias have traditionally been characterized as automatic, triggered, or reentrant. However, the European Society of Cardiology and the North American Society of Pacing and Electrophysiology in 2001 proposed a classification that takes into consideration both anatomic features and electrophysiologic mechanisms [1]. In 2015, the joint American College of Cardiology, American Heart Association, and Heart Rhythm Society guidelines further defined sinus node reentrant tachycardia as "a specific type of focal atrial tachycardia that is due to microreentry arising from the sinus node complex, characterized by abrupt onset and termination, resulting in a P-wave morphology that is indistinguishable from sinus rhythm" [2]. Atrial tachycardia is the overriding term that includes two major categories: Focal atrial tachycardia due to an automatic, triggered, or microreentrant mechanism Macroreentrant atrial tachycardia, including typical atrial flutter and other well- characterized macroreentrant circuits in the right and left atrium Sinoatrial nodal reentrant tachycardia (SANRT), also called sinus node reentry or sinus node reentrant tachycardia, falls into the latter group of reentrant arrhythmias. This topic will discuss the mechanisms, clinical manifestations, and treatment of SANRT. Discussions of other specific atrial arrhythmias are presented separately. (See "Focal atrial tachycardia" and "Intraatrial reentrant tachycardia" and "Overview of atrial flutter".) DEFINITION AND MECHANISMS https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 1/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Initially described in the 1940s [3], SANRT has often been considered a form of atrial tachycardia. However, SANRT has an activation sequence similar to that of normal sinus rhythm so that the P waves on the surface ECG appear to be normal. In comparison, intraatrial reentry has a different activation sequence of atrial depolarization, leading to a P wave morphology that differs from that of normal sinus rhythm. (See "Intraatrial reentrant tachycardia".) Some of the electrophysiologic features that distinguish SA nodal reentrant tachycardia and other reentrant atrial rhythms ( figure 1) from automatic and triggered atrial tachycardias are summarized ( table 1). The exact mechanism of SA nodal reentry is not known; however, three possibilities have been suggested [4] (see "Reentry and the development of cardiac arrhythmias"): Reentry occurring entirely within the SA node, based primarily on one animal study in which the reentrant pathway was localized within the SA node [5]. Reentry involving the SA node and perinodal tissue, based on a number of studies that have suggested the reentrant loop involves more than the SA node [4,6-8]. What we call the SA node is actually the integrated activity of pacemaker cells in the compact region of the SA node [9]. These several thousand cells depolarize and produce action potentials almost synchronously and seem to influence each other through cell-to-cell coupling, a process that has been called "mutual entrainment" [10,11]. Reentry using the SA node as the refractory center around which reentry occurs, although there is limited evidence for this potential mechanism [4]. Using high resolution optical mapping, both micro- and macro- reentry have been demonstrated as mechanisms of SANRT in a post-myocardial infarction model. Additionally, SANRT was not seen in structurally normal hearts, as it required functional and/or structural abnormalities to support reentry [12]. Reentry with the SA node only or the SA node and perinodal tissue is the most likely mechanism of SANRT [13,14]. INCIDENCE SANRT, an uncommon arrhythmia that rarely causes symptoms, occurs most commonly in adults and children who have structural heart disease [15-18]. In patients with supraventricular tachycardia referred for electrophysiologic study, estimates of the frequency of SANRT have ranged from 2 to 17 percent [16,19]. However, approximately 10 to 15 percent of patients who https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 2/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate undergo electrophysiologic studies for symptomatic atrial tachycardia have sinus nodal echoes (single or multiple reentrant beats that utilize the SA node), indicating the presence of a substrate for SA nodal tachycardia [16,19]. In addition, the actual incidence of this arrhythmia may be higher than appreciated since many patients are asymptomatic and do not come to electrophysiologic study. CLINICAL MANIFESTATIONS In most cases, the clinical manifestations and significance of SANRT are minimal. Most patients are asymptomatic, while others have symptoms that range from palpitations and lightheadedness to, in rare cases, syncope. Symptoms, when present, tend to start and stop abruptly. If a patient is examined during an episode of arrhythmia, he or she will have a regular heart rate greater than 100 beats per minute. Most episodes of SANRT do not precipitate hemodynamic compromise or limiting symptoms. However, on rare occasions, SANRT can be sufficiently recurrent, rapid, and/or sustained to be symptomatic. Higher ventricular rates associated with SANRT in a patient with underlying advanced cardiac or pulmonary disease can sometimes exacerbate their disease, leading to signs and symptoms of angina, heart failure, or worsening systemic oxygenation. In the face of persistently elevated ventricular rates (eg, for weeks to months), particularly if baseline ventricular dysfunction exists, heart failure (tachycardia-mediated cardiomyopathy) may ensue [20,21]. (See "Arrhythmia-induced cardiomyopathy".) DIAGNOSIS The diagnosis of SANRT should be considered in the presence of a regular but rapid pulse and heartbeat on physical examination. The electrocardiogram (ECG) will show P waves with a rate between 100 and 150 beats per minute. Given that the P waves are virtually identical to those observed in sinus rhythm, patients may often be thought to have inappropriate sinus tachycardia. In most cases, the diagnosis of SANRT cannot be confirmed without invasive electrophysiologic studies. Vagal maneuvers and adenosine can sometimes help as either will slow the tachycardia before the arrhythmia is abruptly terminated. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia'.) While pursuing invasive testing to make the diagnosis is not generally necessary, when symptoms are present clinically or the arrhythmia appears incessant, it is important to distinguish SANRT from other supraventricular tachycardias (SVT). In a patient with sustained https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 3/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate tachycardia and reduced left ventricular function in whom tachycardia-mediated cardiomyopathy is a consideration, we would suggest more aggressive efforts at confirming or excluding SANRT as the diagnosis. (See "Arrhythmia-induced cardiomyopathy".) Electrocardiographic findings As mentioned above, SANRT has an activation sequence similar to that of normal sinus rhythm (see 'Definition and mechanisms' above). Thus, the surface ECG has P waves that are virtually identical to those observed in sinus rhythm and often will be interpreted as a sinus tachycardia. The abrupt onset and termination of the arrhythmias can aid clinically in differentiating SANRT from sinus tachycardia. Conduction through the AV node, the specialized infranodal conduction system (His bundle, fascicles and bundle branches, terminal Purkinje fibers), and the ventricles also should be similar to normal AV conduction unless the rapid rate causes some type of functional conduction disturbance (ie, rate-related bundle branch block). The rate in SANRT is usually between 100 and 150 beats per minute. Episodes vary in length, lasting anywhere from seconds to hours. The response to vagal maneuvers can aid in differentiating sinus tachycardia (gradual slowing in response to vagal stimulus) from SANRT (abrupt termination of the arrhythmia). Patients should undergo continuous ECG monitoring during the vagal maneuvers. (See 'Autonomic maneuvers' below.) Electrophysiologic features Clinically, when symptoms are present or the arrhythmia appears incessant, it is important to distinguish SANRT from other supraventricular tachycardias (SVT), particularly focal atrial tachycardia. Since the surface electrocardiogram alone is not reliable in distinguishing SANRT from other types of SVT, invasive electrophysiological studies (EPS) can be employed to help make this distinction. Since macroreentrant atrial arrhythmias, including SANRT, are reentrant, they can be entrained during EPS with manifest and concealed fusion, and upon cessation of atrial pacing, the post pacing interval should be within 30 milliseconds of the tachycardia cycle length if pacing is performed within the reentrant pathway. The use of newer mapping techniques such as electroanatomical mapping further helps to make this distinction where focal mechanisms display centrifugal activation patterns, reentry displays an "early meets late," and the entire cycle length of the tachycardia can be mapped to the chamber containing the tachycardia. The initiation with premature atrial complexes (PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) independent of intraatrial or AV nodal conduction delays or, better yet, in the presence of AV block, helps confirm the diagnosis. The P wave morphology is identical to sinus node P wave morphology. (See "Invasive diagnostic cardiac electrophysiology studies".) https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 4/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate SA nodal reentrant tachycardia can be initiated by PACs, atrial pacing, and, unlike intraatrial reentry, by premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) and ventricular pacing with retrograde VA conduction. The rarity of induction of intraatrial reentry by a PVC is due to the delay in retrograde VA conduction which limits the prematurity with which the premature beat can depolarize the atrium. Neither the AV node nor a bypass tract is a necessary part of the circuit. The reentrant circuit can be penetrated and reentry aborted by premature atrial depolarizations or atrial pacing. Differential diagnosis The differential diagnosis for sinoatrial nodal reentrant tachycardia (SANRT) is similar to that for other narrow QRS complex tachycardias (assuming there is normal AV conduction without bundle branch block) and includes: Atrial flutter Atrioventricular reciprocating tachycardia Focal atrial tachycardia Intraatrial reentrant tachycardia Sinus tachycardia, including inappropriate sinus tachycardia Atrioventricular nodal reentrant tachycardia Only the abrupt onset and termination of the arrhythmia aids clinically in differentiating SANRT from sinus tachycardia, which is not a paroxysmal condition but manifests a gradual increase and decrease in rate ( waveform 1). Other arrhythmias included in the differential diagnosis, however, typically have a P wave morphology that is different from normal, although the difference may be subtle. In addition, other reentrant tachycardias are usually, but not always, more rapid than SANRT (rate up to 240 beats per minute versus 100 to 150 beats per minute). A more in-depth discussion of the differential diagnosis of narrow QRS complex tachycardias is presented separately. TREATMENT Most episodes of SA nodal reentrant tachycardia require no specific therapy since the usual rates (100 to 150 beats/min) rarely produce symptoms or hemodynamic compromise. However, persistent and/or symptomatic SANRT requires treatment to relieve symptoms and to prevent long-term sequelae such as tachycardia-mediated cardiomyopathy [22]. (See "Arrhythmia- induced cardiomyopathy".) https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 5/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Efforts to acutely terminate SANRT should begin with vagal maneuvers. If vagal maneuvers are unsuccessful, intravenous adenosine can be administered for the acute termination of SANRT. Chronic suppressive therapy, when necessary, is usually with verapamil, although digoxin and amiodarone have been tried with some success. Catheter ablation of SANRT is generally the treatment of choice for chronic management of this arrhythmia given its efficacy. Autonomic maneuvers For the acute termination of symptomatic SANRT, we suggest carotid sinus massage or another vagal maneuver as the initial therapy. (See "Vagal maneuvers".) The SA node has extensive autonomic innervation. As a result, carotid sinus massage and other vagal maneuvers (such as the Valsalva maneuver) generally terminate SA nodal reentrant arrhythmias abruptly [13,19,21]. This is in contrast to the effect of vagal maneuvers on sinus tachycardia and reentrant intraatrial rhythms. The response to sinus tachycardia is characterized by gradual slowing and then gradual acceleration upon cessation of the maneuver. The atria are less well innervated than the sinus node. As a result, vagal stimulation has a variable and often negligible effect on reentrant intraatrial rhythms. Enhancement of vagal tone may, however, result in AV nodal blockade, which will result in a reduction in the ventricular rate without altering the atrial rate. Pharmacologic therapy There are no large studies of pharmacologic therapy in SA nodal reentrant tachycardia because of the rarity of the arrhythmia and its general lack of clinical consequence. Several drugs have been evaluated for both acute termination and chronic suppression of SANRT in small nonrandomized studies: Adenosine acutely terminated SANRT in six of six patients in a single-center cohort [23]. Verapamil (two of two) and amiodarone (four of four) effectively prevented induction of SANRT during electrophysiologic testing in a single-center cohort [21]. Beta blockers have not been extensively studied but failed to prevent induction of SANRT in two of two patients during electrophysiologic testing in a single-center cohort [21]. Ouabain, an analog of digoxin, successfully prevented induction of SANRT during electrophysiologic testing in a single-center cohort. In addition, digoxin has been reported to successfully suppress recurrent SANRT for 18 months in an infant [21,24]. Radiofrequency catheter ablation SANRT is on occasion sufficiently symptomatic or persistent to warrant specific intervention. Increasing experience is being gained with https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 6/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate radiofrequency ablation of a portion of the reentrant circuit [16,20,25-28]. Of approximately 45 patients in these reports, the arrhythmia recurred in only one patient who then underwent a second successful ablation. Evaluation in a larger number of patients with longer follow-up is required to more accurately determine the role of ablation in this disorder. However, we feel that catheter ablation should be considered as first-line therapy for symptomatic patients or in patients with persistent tachycardia who are at risk for or who have developed tachycardia- mediated cardiomyopathy. (See "Arrhythmia-induced cardiomyopathy".) Our approach to treatment Based on the limited available evidence, we take the following approach to treatment: For acute termination of symptomatic SANRT that persists despite the use of vagal maneuvers, we suggest intravenous adenosine. Synchronized cardioversion can be used in an unstable patient. For chronic suppression of recurrent SANRT, we suggest catheter ablation rather than pharmacologic therapy. This choice is based upon the high success rates of catheter ablation in conjunction with fewer potential long-term medication side effects. For chronic therapy of SANRT when ablation is not an option or has been unsuccessful in preventing recurrent SANRT, we suggest verapamil or beta adrenergic receptor blockers as the first choice, followed by the combination of both if SANRT recurs. If SANRT recurs despite the combination of verapamil and beta adrenergic receptor blockers, amiodarone can be considered. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Sinoatrial nodal reentrant tachycardia (SANRT), also called "sinus node reentry" or "sinus node reentrant tachycardia," is a reentrant tachyarrhythmias involving the SA node and/or perinodal tissue. (See 'Definition and mechanisms' above.) SANRT occurs most commonly in adults and children who have structural heart disease and is estimated to be responsible for anywhere from 2 to 17 percent of supraventricular https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 7/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate tachycardias. (See 'Incidence' above.) In most cases, the clinical manifestations and significance of SANRT are minimal. Most patients are asymptomatic, while others have symptoms that range from palpitations and lightheadedness to, in rare cases, syncope. (See 'Clinical manifestations' above.) The diagnosis of SANRT should be considered in the presence of a regular but rapid pulse and heartbeat on physical examination. The electrocardiogram (ECG) will show P waves with a rate between 100 and 150 beats per minute. Given that the P waves are virtually identical to those observed in sinus rhythm, in most cases the diagnosis cannot be confirmed without invasive electrophysiologic studies. (See 'Diagnosis' above.) The differential diagnosis for SANRT is similar to that for other narrow QRS complex tachycardias (assuming there is normal AV conduction without bundle branch block). Only the abrupt onset and termination of the arrhythmia aids clinically in differentiating SANRT from sinus tachycardia, which is not a paroxysmal condition but manifests a gradual increase and decrease in rate. (See 'Differential diagnosis' above.) While SANRT is most often transient and asymptomatic, persistent and/or symptomatic SANRT requires treatment to relieve symptoms and to prevent long-term sequelae such as tachycardia-mediated cardiomyopathy. We take the following approach to treatment (see 'Our approach to treatment' above): For acute termination of symptomatic SANRT that persists despite the use of vagal maneuvers, we suggest intravenous adenosine (Grade 2C). For chronic suppression of recurrent SANRT, we suggest catheter ablation rather than pharmacologic therapy (Grade 2C). This choice is based upon the high success rates of catheter ablation in conjunction with fewer potential long-term medication side effects. For chronic therapy of SANRT when ablation is not an option or has been unsuccessful in preventing recurrent SANRT, we suggest verapamil or beta adrenergic receptor blockers as the first choice (Grade 2C), followed by the combination of both if SANRT recurs. If SANRT recurs despite the combination of verapamil and beta adrenergic receptor blockers, amiodarone is another option. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 8/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate 1. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2016; 13:e136. 3. Barker PS, Wilson FN, Johnson FD. The mechanism of auricular paroxysmal tachycardia. Am Heart J 1943; 26:435. 4. Kirchhoff CJ, Bonke FI, Allessie MA. Sinus node reentry: Fact or fiction?. In: Cardiac Arrhythmi as: Where to Go from Here?, Brugade P, Wellens HJ (Eds), Martinus Nijhoff, The Hague 1987. p.53. 5. Allessie MA, Bonke FI. Direct demonstration of sinus node reentry in the rabbit heart. Circ Res 1979; 44:557. 6. Childers RW, Arnsdorf MF, De la Fuente DJ, et al. Sinus nodal echoes. Clinical case report and canine studies. Am J Cardiol 1973; 31:220. 7. Paulay KL, Varghese PJ, Damato AN. Sinus node reentry. An in vivo demonstration in the dog. Circ Res 1973; 32:455. 8. Strauss HC, Bigger JT Jr. Electrophysiological properties of the rabbit sinoatrial perinodal fibers. Circ Res 1972; 31:490. 9. Bleeker WK, Mackaay AJ, Masson-P vet M, et al. Functional and morphological organization of the rabbit sinus node. Circ Res 1980; 46:11. 10. Jalife J. Mutual entrainment and electrical coupling as mechanisms for synchronous firing of rabbit sino-atrial pace-maker cells. J Physiol 1984; 356:221. 11. Jalife J. Synchronization of pacemaker cells in the sinus node. In: Atrial Arrhythmias: Current Concepts and Management, Touboul P, Waldo AL (Eds), Mosby Year Book, St. Louis 1990. p.6 9. 12. Glukhov AV, Hage LT, Hansen BJ, et al. Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness. Circ Arrhythm Electrophysiol 2013; 6:984. 13. Coss SF, Steinberg JS. Supraventricular tachyarrhythmias involving the sinus node: clinical and electrophysiologic characteristics. Prog Cardiovasc Dis 1998; 41:51. https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 9/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate 14. Narula OS. Sinus node re-entry: a mechanism for supraventricular tachycardia. Circulation 1974; 50:1114. 15. Pahlajani DB, Miller RA, Serratto M. Sinus node re-entry and sinus node tachycardia. Am Heart J 1975; 90:305. 16. Gomes JA, Mehta D, Langan MN. Sinus node reentrant tachycardia. Pacing Clin Electrophysiol 1995; 18:1045. 17. Garson A Jr, Gillette PC. Electrophysiologic studies of supraventricular tachycardia in children. I. Clinical-electrophysiologic correlations. Am Heart J 1981; 102:233. 18. Blaufox AD, Numan M, Knick BJ, Saul JP. Sinoatrial node reentrant tachycardia in infants with congenital heart disease. Am J Cardiol 2001; 88:1050. 19. Josephson ME. Supraventricular Tachycardias. In: Clinical Cardiac Electrophysiology: Techniq ues and Interpretations, 4th, Lippincott, Williams, and Wilkins, Philadelphia 2008. 20. Kay GN, Chong F, Epstein AE, et al. Radiofrequency ablation for treatment of primary atrial tachycardias. J Am Coll Cardiol 1993; 21:901. 21. Gomes JA, Hariman RJ, Kang PS, Chowdry IH. Sustained symptomatic sinus node reentrant tachycardia: incidence, clinical significance, electrophysiologic observations and the effects of antiarrhythmic agents. J Am Coll Cardiol 1985; 5:45. 22. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 23. Engelstein ED, Lippman N, Stein KM, Lerman BB. Mechanism-specific effects of adenosine on atrial tachycardia. Circulation 1994; 89:2645. 24. Ozer S, Schaffer M. Sinus node reentrant tachycardia in a neonate. Pacing Clin Electrophysiol 2001; 24:1038. 25. Lesh MD, Van Hare GF, Epstein LM, et al. Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms. Circulation 1994; 89:1074. 26. Sanders WE Jr, Sorrentino RA, Greenfield RA, et al. Catheter ablation of sinoatrial node reentrant tachycardia. J Am Coll Cardiol 1994; 23:926. 27. Ivanov MY, Evdokimov VP, Vlasenco VV. Predictors of successful radiofrequency catheter ablation of sinoatrial tachycardia. Pacing Clin Electrophysiol 1998; 21:311. 28. Goya M, Iesaka Y, Takahashi A, et al. Radiofrequency catheter ablation for sinoatrial node reentrant tachycardia: electrophysiologic features of ablation sites. Jpn Circ J 1999; 63:177. https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 10/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Topic 918 Version 29.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 11/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate GRAPHICS Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 12/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Electrophysiologic characteristics of the different types of supraventricular tachycardia (SVT) Characteristic Reentrant Triggered Automatic Initiation by extrastimuli and/or continuous pacing Yes Yes No Initiation by continuous pacing depends upon the rate and number of stimuli No Yes No Termination by extrastimuli Yes No No Termination by continuous pacing (overdrive) Yes Yes No Overdrive suppression of tachycardia No No Yes Overdrive enhancement of tachycardia Yes Yes No Entrainment possible Yes No No First P wave identical to P waves in arrhythmia No Sometimes Yes Warm-up or acceleration of pacemaker after onset No Sometimes Yes Graphic 53347 Version 2.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 13/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Single-lead electrocardiogram (ECG) showing sinoatrial (SA) nodal reentrant tachycardia Electrocardiogram showing SA nodal reentrant tachycardia. The first three beats are normal sinus beats at a rate of about 107 beats/min; the fourth beat is an atrial premature beat that is followed by a return to sinus rhythm. The eighth beat (arrow) represents the sudden onset of SA nodal reentrant tachycardia at a rate of about 145 beats/min. Since the P waves are similar to the sinus beats, the diagnosis is suggested only by the abrupt onset of the tachycardia. Courtesy of Morton F Arnsdorf, MD. Graphic 76364 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 14/15 7/6/23, 1:49 PM Sinoatrial nodal reentrant tachycardia (SANRT) - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinoatrial-nodal-reentrant-tachycardia-sanrt/print 15/15 |
7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Supraventricular arrhythmias during pregnancy : Candice Silversides, MD, MS, FRCPC, Louise Harris, MBChB, Sing-Chien Yap, MD, PhD : Hugh Calkins, MD, N A Mark Estes, III, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jan 31, 2022. INTRODUCTION Arrhythmias are the most common cardiac complication encountered during pregnancy in females with and without structural heart disease [1-3]. In the United States, the incidence of pregnancy-related hospitalizations with arrhythmias has increased between 2000 and 2012 primarily due to increases in the incidence of atrial fibrillation and ventricular tachycardia [4]. Arrhythmias may manifest for the first time during pregnancy, and in other cases, pregnancy can trigger exacerbations in those with pre-existing arrhythmias [1,5,6]. Females with established arrhythmias or structural heart disease are at highest risk of developing arrhythmias during pregnancy. In addition, there has been an increase in the number of female patients of childbearing age with congenital heart disease due to surgical advances and improvements in the care of adults with congenital heart disease, and these are at particularly high risk for arrhythmias ( figure 1) [1,2,7-11]. Because of these associations, any pregnant person who presents with an arrhythmia should have a clinical evaluation with a complete history and cardiac examination, an electrocardiogram, and a transthoracic echocardiogram to evaluate for evidence of structural heart disease. In general, the approach to the treatment of arrhythmias in pregnancy is similar to that in the nonpregnant patient. However, due to the theoretical or known adverse effects of antiarrhythmic drugs on the fetus, antiarrhythmic drugs are often reserved for the treatment of arrhythmias associated with clinically significant symptoms or hemodynamic compromise [12- 14]. Treatment recommendations are hampered by the lack of randomized trials and very little or no data on efficacy or safety of antiarrhythmic drugs during pregnancy. Choice of therapy, for https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 1/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate the most part, is based on limited data from animal studies, case reports, and observational studies, as well as clinical experience. The prevalence, clinical presentation, and management of supraventricular arrhythmias during pregnancy will be reviewed. Electrocardiographic characteristics of supraventricular arrhythmias, as well as issues relating to conduction disorders, ventricular arrhythmias, and cardiac arrest during pregnancy, are discussed separately. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias" and "Maternal conduction disorders and bradycardia during pregnancy" and "Ventricular arrhythmias during pregnancy".) MECHANISM OF ARRHYTHMOGENESIS IN PREGNANCY The exact mechanism of increased arrhythmia burden during pregnancy is unclear, but has been attributed to hemodynamic, hormonal, and autonomic changes related to pregnancy. The hemodynamic changes of pregnancy have been well studied, and a number of these changes likely contributes to the development of arrhythmias during pregnancy [15,16]. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".) Intravascular volume increases, augmenting the preload on the ventricles and increasing both atrial and ventricular size [15,17-20]. Atrial and ventricular myocardial stretch may contribute to arrhythmogenesis, due to stretch-activated ion channel activity causing membrane depolarization, shortened refractoriness, slowed conduction, and spatial dispersion of refractoriness and conduction [21-24]. There is also an increase in resting heart rate, which has been associated with markers of arrhythmogenesis such as late potentials, premature ventricular contractions, and depressed heart rate variability [25]. Few studies have been published on the influence of hormonal and autonomic changes on arrhythmogenesis in pregnancy. Although catecholamine levels do not appear to change during pregnancy, there is an increase in adrenergic responsiveness during pregnancy [26-30]. Estrogen has been shown to increase the number of myocardial alpha-adrenergic receptors [31]. This increased adrenergic activity may contribute to enhanced automaticity and triggered activity [32]. SYMPTOM-RHYTHM CORRELATION Palpitations occur frequently during pregnancy and are a common indication for cardiac evaluation during pregnancy. The differential diagnosis of palpitations is extensive and the https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 2/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate diagnostic evaluation of pregnant individuals with palpitations does not differ from nonpregnant individuals. (See "Evaluation of palpitations in adults".) One study compared 110 pregnant females with symptoms suggestive of possible arrhythmia (palpitations: 87 percent; dizziness: 13 percent; syncope/presyncope: 6 percent) with 52 pregnant females evaluated for a functional murmur [33]. Prevalence of supraventricular and ventricular ectopic activity on 24-hour Holter ambulatory monitoring was similar in the symptomatic and control groups. Only 10 percent of symptomatic episodes were accompanied by the presence of arrhythmias. A sensation of palpitations during pregnancy, in the absence of concomitant cardiac arrhythmias, may be related to the high output state, including increased heart rate, decreased peripheral resistance, and increased stroke volumes. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".) ATRIAL PREMATURE BEATS Premature atrial complexes (PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) are very frequent in pregnant patients and the prevalence is dependent on the duration of observation. (See "Supraventricular premature beats".) In one study of 162 pregnancies in patients with structurally normal hearts evaluated with 24- hour Holter monitoring, the prevalence of PACs was 57 percent and frequent PACs (>100 PACs per 24 hours) occurred in six percent of pregnancies [33]. There was a significant reduction in the frequency of atrial and ventricular ectopic activity in nine patients in whom Holter monitoring was repeated postpartum. Clinical presentation PACs produce few or no symptoms in the majority of pregnant patients, although some people may have symptoms of palpitations. Management No therapy is required for PACs in the asymptomatic woman. Pregnant persons with symptomatic PACs should be reassured of the benign nature of PACs and be advised to discontinue potential precipitant factors such as smoking, coffee intake, alcohol intake, or other stimulants. If ectopic activity continues and is associated with intolerable symptoms, treatment with cardioselective beta blockers such as metoprolol can be effective. (See 'Issues regarding antiarrhythmic drug treatment' below.) https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 3/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA Paroxysmal supraventricular tachycardia (PSVT) describes a tachycardia that is caused, in the vast majority of patients, either by reentry within the atrioventricular (AV) node or by use of an accessory pathway, either manifest or concealed. (See "Atrioventricular nodal reentrant tachycardia".) In pregnant patients with structurally normal hearts, AV nodal reentrant tachycardia (AVNRT) is the most common PSVT, followed by AV reciprocating tachycardia (AVRT) [5]. The prevalence of PSVT has been estimated at 22 to 24 per 100,000 hospital admissions in pregnant patients [4,34]. A population-based cohort study of pregnancies in Taiwan between 2001 and 2012 demonstrated that PSVT in pregnant patients was associated with severe maternal morbidity, cesarean deliveries, low birth weight babies, preterm labor, and obvious fetal abnormalities in comparison with females without PSVT [35]. These data should be interpreted with caution, however, as there are a number of possible explanations for this association: while PSVT in pregnancy may be directly detrimental to the developing fetus, PSVT may also be associated with other maternal factors that impact maternal and fetal health, and patients presenting with PSVT may have had more intensive fetal monitoring as a consequence of their presentation with PSVT, with possible earlier delivery and lower birth weight. There are discrepancies between studies as to whether pregnancy increases the risk of first onset of PSVT [5,36]. One study of 38 patients with PSVT and a previous pregnancy found that the initial onset of PSVT occurred during pregnancy in 13 patients (34 percent). The estimated relative risk of first onset of PSVT during pregnancy was 5.1 (95 percent confidence interval 2.8 to 9.2) [36]. In contrast, another study of 173 patients with symptomatic PSVT and a history of pregnancy referred for electrophysiologic testing and radiofrequency catheter ablation, reported that only 4.6 percent had initial onset of PSVT during pregnancy [5]. In that series, pregnancy was not associated with first onset of PSVT. Furthermore, in patients with AVNRT there was a decreased risk of first onset of AVNRT during pregnancy (relative risk 0.11, 95% CI 0.02-0.56). The same study found that among patients with a first onset of PSVT before pregnancy, the majority (85 percent) of patients had an exacerbation of PSVT during pregnancy [5]. Exacerbations of PSVT during pregnancy were more symptomatic (assessed by a semiquantitative questionnaire) when compared with arrhythmias during nonpregnant periods. Clinical presentation The presentation of PSVT during pregnancy is the same as in the nonpregnant state and includes symptoms of palpitations that may be associated with presyncope, syncope, dyspnea, and/or chest pain. Patients with PSVT typically describe a regular https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 4/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate and rapid tachycardia of abrupt onset, with or without abrupt termination. The clinical and hemodynamic consequences of the arrhythmia depend on many variables including the presence or absence of structural heart disease. For example, in women with Ebstein s anomaly of the tricuspid valve, symptomatic AVRT episodes can result in serious hemodynamic deterioration [13,37]. PSVT is usually well tolerated in pregnant patients without structural heart disease [38-42]. Management Our management approach is in general agreement with the recommendations for pregnant patients made by professional society guidelines for the management of patients with supraventricular tachycardia [11,13,43]. Management of acute episodes If hemodynamic compromise is evident, direct-current cardioversion should be performed [11,43]. (See "Cardioversion for specific arrhythmias" and "Basic principles and technique of external electrical cardioversion and defibrillation" and "Cardioversion for specific arrhythmias", section on 'Cardioversion during pregnancy'.) When the patient is hemodynamically stable, acute episodes of PSVT may be terminated by transiently blocking AV nodal conduction [11]. If vagal maneuvers (eg, Valsalva maneuver or carotid sinus massage) fail, intravenous adenosine (6 to 18 mg) is an appropriate choice in pregnancy, terminating approximately 90 percent of PSVT [44]. Case reports have demonstrated the effectiveness of adenosine in pregnant patients, although in most of the reports adenosine was administrated in the second and third trimester [45]. (See "Atrioventricular nodal reentrant tachycardia", section on 'Initial management'.) Adenosine has a very short half-life (<10 seconds), reducing the placental exposure to adenosine. Despite reduced adenosine deaminase activity during pregnancy (25 percent) [46], the adenosine dose required for PSVT termination during pregnancy is not reduced, possibly due to the increased volume of distribution [47]. (See 'Issues regarding antiarrhythmic drug treatment' below.) Recommended second-line drugs are intravenous beta-1 selective blockers [11,43,45]. The experience with intravenous verapamil is limited [48], and the longer half-life (5.3 hours) of verapamil can cause significant hypotension, especially when given as a rapid intravenous bolus injection. (See 'Issues regarding antiarrhythmic drug treatment' below.) Prophylactic pharmacologic therapy Prevention of PSVT in patients without WPW syndrome can be accomplished with a number of AV nodal blocking agents (ie, beta-1 selective blockers [except atenolol] or verapamil, in order of preference) [11,13,49,50]. In pregnant patients without structural heart disease who have PSVT not controlled with AV nodal blocking agents, flecainide, propafenone, or sotalol can be considered for the prevention of PSVT https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 5/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate [11,13,49]. In pregnant patients with WPW syndrome and without ischemic or structural heart disease, flecainide or propafenone are options for the prevention of PSVT [11,13]. (See 'Issues regarding antiarrhythmic drug treatment' below and "Atrioventricular nodal reentrant tachycardia", section on 'Preventive therapy'.) Experience with digoxin is extensive and it is considered safe during pregnancy [51]. However, the efficacy of digoxin for prophylaxis has not been demonstrated. One small, randomized, cross-over study of 11 nonpregnant patients showed that there was similar efficacy between digoxin, propranolol, and verapamil with respect to the frequency or duration of PSVT [52]. Propranolol and metoprolol are often used, but the potential fetal risks of beta blockers need to be discussed with the mother, in particular the risk of intra-uterine growth restriction [50] (see 'Issues regarding antiarrhythmic drug treatment' below). Atenolol should not be used for treatment of arrhythmias. Because pregnancy may exacerbate PSVT, radiofrequency catheter ablation is recommended in symptomatic patients with recurrent PSVT who plan to become pregnant [11]. In patients with malignant, drug-resistant arrhythmias, radiofrequency catheter ablation during pregnancy may be an option in selected cases [11,13,53]. (See 'Radiofrequency catheter ablation' below and "Atrioventricular nodal reentrant tachycardia".) In general, anticoagulation therapy is not indicated for SVT such as AVNRT, AVRT over a bypass tract, or ectopic atrial tachycardia. FOCAL ATRIAL TACHYCARDIA Focal atrial tachycardia is relatively rare during pregnancy. (See "Focal atrial tachycardia".) Although this arrhythmia is often associated with structural heart disease in nonpregnant patients, most reports of atrial tachycardia during pregnancy have been reported in patients without apparent structural heart disease [41,42]. Clinical presentation As in the nonpregnant state, this arrhythmia is often persistent and can be refractory to treatment, including direct current (DC) cardioversion [41,42]. Because many atrial tachycardias are caused by enhanced automaticity, vagal maneuvers or the use of antiarrhythmic agents that decrease atrioventricular nodal conduction (eg, adenosine, digoxin, beta blockers, calcium channel blockers), will usually not terminate the arrhythmia [41,42]. In most reported cases, the arrhythmia subsides and terminates shortly after delivery, suggesting that pregnancy may contribute to the initiation and maintenance of this https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 6/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate tachyarrhythmia [41,42]. Diagnosis and management The differentiation between atrial tachycardia and other supraventricular tachyarrhythmias may be difficult. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) The administration of adenosine may be useful as a therapeutic and diagnostic tool. Because atrial tachycardia is difficult to treat and is generally well tolerated by the mother and the fetus, urgent DC cardioversion or administration of multiple intravenous drugs is not recommended when pregnant patients are hemodynamically stable. The goal of therapy should be to achieve adequate rate control. The risk of not treating an incessant atrial tachycardia is the development of a tachycardia-induced cardiomyopathy [54]. (See "Arrhythmia-induced cardiomyopathy".) Rate control can be achieved with digoxin, beta blockers, or verapamil [11,41-43,49], with reservation of sotalol, flecainide, or amiodarone (in very rare cases due to potential toxicity) for refractory cases ( table 1) [42,55]. Decisions regarding the use of other antiarrhythmic drugs should be made with the assistance of an electrophysiologist. For patients with hemodynamically significant atrial tachycardia with a rapid ventricular response who do not respond to medical therapy and do not have a reversible precipitating cause, DC cardioversion may be required. However, as noted above, atrial tachycardias may be particularly resistant to cardioversion. (See "Cardioversion for specific arrhythmias", section on 'Cardioversion during pregnancy' and 'Electrical cardioversion' below.) In some pregnant patients with incessant atrial tachycardia, radiofrequency catheter ablation may need to be considered [11,13,53,56]. (See 'Radiofrequency catheter ablation' below and "Focal atrial tachycardia".) ATRIAL FIBRILLATION AND FLUTTER The management of atrial fibrillation is often similar in pregnancy compared with the non- pregnant state. Unique considerations include: Choice of specific pharmacotherapy to maximize safety and minimize adverse effects during pregnancy and lactation. Hemodynamic changes across pregnancy and labor and delivery, particularly in pregnant patients with structural heart disease. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 7/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate Recognition of pregnancy as a hypercoagulable, prothrombotic state. Early and frequent labor and delivery planning throughout pregnancy. This includes shared decision-making between the patient and multidisciplinary care team. Epidemiology and risk factors Atrial fibrillation and flutter during pregnancy are relatively uncommon. In an Agency for Healthcare Research Quality database of >1200 hospitals across the United States, the prevalence of atrial fibrillation was 27 per 100,000 pregnancy-related hospital admissions, and atrial flutter was 4 per 100,000 [4]. This study found that atrial fibrillation rates nearly doubled from 2000 to 2012 (18 to 35 per 100,000 hospital admissions). Advancing maternal age and higher burden of AF risk factors (hypertension, diabetes mellitus, obesity, and congenital heart disease) over this time period likely explain increased atrial fibrillation rates. Although atrial fibrillation and flutter can occur in pregnant patients with structurally normal hearts [57,58], they are more common in pregnant patients with structural heart disease, such as rheumatic heart disease, valvular heart disease, hypertrophic cardiomyopathy [59], peripartum cardiomyopathy, and congenital heart disease [6,60-62]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation" and "Overview of atrial flutter".) Metabolic disturbances such as hyperthyroidism, electrolyte imbalances, and alcohol use can also contribute to the development of atrial fibrillation during pregnancy. Clinical presentation The clinical presentation and hemodynamic consequences of atrial fibrillation and flutter depend on many variables, including the underlying heart condition and the associated ventricular response rate. In addition to hemodynamic consequences, pregnant patients with atrial fibrillation are at increased risk of systemic embolism both from hemostatic changes seen in normal pregnancy [63] and from atrial fibrillation. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Common presenting symptoms of atrial fibrillation in pregnancy are palpitations, feeling of rapid heart beating, heart fluttering, lightheadedness, syncope, or dyspnea. Atrial fibrillation is less well tolerated in persons with preexisting structural heart disease. Symptoms may be further exacerbated by pregnancy-related physiologic changes, such as increased blood volume, increased heart rate, shunting of blood to the uteroplacental system, and anemia. Symptoms include concomitant pulmonary edema, dyspnea at rest and on exertion, dizziness, and syncope due to rise in left atrial pressure and lower stroke volume. Structural heart conditions that predispose to atrial fibrillation and flutter, and are seen in pregnant patients, include mitral stenosis, congenital heart disease, and other conditions https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 8/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate causing heart failure. These conditions are described in detail separately: Mitral stenosis. (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis".) Congenital heart disease [61] or preexisting heart failure. (See "Pregnancy in women with congenital heart disease: General principles".) Another scenario that can present for the first time in pregnancy is conduction down an antegrade accessory pathway that produces rapid atrial fibrillation. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Atrial fibrillation'.) Diagnostic testing As with the nonpregnant patient, atrial fibrillation and flutter can be associated with structural heart disease in females of childbearing age; thus, all pregnant patients presenting with these arrhythmias should have a thorough clinical investigation. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) The evaluation includes: History and physical examination. Electrocardiogram. Transthoracic echocardiogram. Continuous cardiac rhythm monitoring to assess arrhythmia burden and average heart rate. Search for any obvious provoking factor (eg, hyperthyroidism, electrolyte imbalances, pulmonary embolism, alcohol abuse) with treatment of the precipitant as necessary. Management Management, as with the nonpregnant patient, includes treatment of acute episodes, prevention of systemic embolization, and deciding on a rate versus rhythm control strategy. In the pregnant patient, it is important to discuss the labor and delivery plan as early as possible in pregnancy using a multidisciplinary team-based, shared decision-making approach. We agree with the recommendations for pregnant patients made in the 2020 European Society of Cardiology (ESC) guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery [14] and the 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy [13,14]. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 9/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate Management of acute episodes Much of the management of acute atrial fibrillation is similar in pregnant and nonpregnant persons. Hemodynamic instability Episodes of atrial fibrillation and flutter that cause hemodynamic instability require emergent direct current (DC) cardioversion [13,14]. Atrial fibrillation with rapid ventricular rates in pregnant patients with preexcitation is also best treated with DC cardioversion. (See 'Electrical cardioversion' below.) Some patients may require concomitant initiation of anticoagulation. No hemodynamic instability For pregnant patients who are hemodynamically stable, either electrical or pharmacological cardioversion can be attempted. The choice of approach is discussed separately. (See "Atrial fibrillation: Cardioversion", section on 'Electrical versus pharmacologic cardioversion'.) Prevention of embolization For patients in whom immediate cardioversion is not needed, it is important to recognize that if an episode of AF lasts more than 48 hours, or is of unknown duration, a transesophageal echocardiogram should be performed to rule out left atrial appendage thrombus, or systemic anticoagulation should be maintained for three weeks prior to electrical or pharmacologic cardioversion. Systemic anticoagulation is needed for at least four weeks following cardioversion [14]. This is discussed in detail separately. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'AF duration uncertain or 48 or more hours'.) Pharmacological cardioversion In pregnant patients, flecainide ( table 1) is used to achieve cardioversion [13,14]. In the pregnant patient, ibutilide is avoided after the first trimester, as there is little experience with its use [14]. Amiodarone is also avoided due to potential fetotoxicity [64,65]. Obstetric care For the pregnant patient with atrial fibrillation or flutter, decisions about hospitalization for an acute atrial fibrillation episode and whether to perform fetal monitoring should be coordinated with the obstetrics care providers. Rhythm control versus rate control During pregnancy, we prefer a rhythm control strategy for newly diagnosed atrial fibrillation and for patients who remain symptomatic with a rate- control strategy. This approach differs from nonpregnant patients, where more consideration is given to pursuing rate control, particularly in patients without structural heart disease. This is discussed separately. (See "Management of atrial fibrillation: Rhythm control versus rate control".) https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 10/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate Rhythm control Flecainide, propafenone, or sotalol should be considered to prevent atrial fibrillation if AV nodal-blocking drugs fail [13,14]. Amiodarone is not typically used in pregnancy due to its potential fetal teratogenic effects. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".) Rate control If rhythm control cannot be achieved or is unlikely to be successful, then ventricular rate control can be instituted. In pregnant patients, beta-selective blockers are recommended for rate control [13,14]. If beta blockers fail, digoxin or verapamil should be considered. These are used alone or in combination to control the ventricular response rate [66]. Amiodarone is not typically used in pregnancy due to its potential fetal teratogenic effects. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Anticoagulation Pregnancy is associated with a prothrombotic state and increased thromboembolic risk. However, risk stratification for stroke in atrial fibrillation has not been extensively studied in regard to pregnant patients; only one small retrospective study demonstrated that the CHA DS -VASc score may underestimate the risk of stroke in pregnant 2 2 patients [67]. Given the lack of specific data, we follow the same recommendations as in nonpregnant patients [13,14]. Women with nonvalvular atrial fibrillation at low stroke risk (CHA DS -VASc score 1) may 2 2 not require anticoagulation. Anticoagulation is recommended for stroke prevention in nonpregnant patients with nonvalvular atrial fibrillation and CHA DS -VASc score of 3. 2 2 Anticoagulation may be considered in females with nonvalvular atrial fibrillation and CHA DS - 2 2 VASc score of 2 or less where treatment should be individualized based on net clinical benefit and consideration of patient values and preferences. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'CHA2DS2-VASc score' and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.) Preferred anticoagulant The preferred anticoagulant for most patients is low molecular weight heparin. Heparin can be used throughout all stages of pregnancy but should be discontinued prior to delivery. (See "Use of anticoagulants during pregnancy and postpartum" and "Use of anticoagulants during pregnancy and postpartum", section on 'LMW heparins' and "Use of anticoagulants during pregnancy and postpartum", section on 'Timing for starting LMW heparin'.) Management of antithrombotic therapy for pregnant patients with prosthetic heart valves is discussed in detail separately. (See "Management of antithrombotic therapy for a https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 11/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate prosthetic heart valve during pregnancy".) Warfarin is often not used in pregnancy because of the risk of embryopathy and fetopathy. Similarly, novel oral anticoagulants are not recommended during pregnancy because of the lack of safety data and the potential fetal toxicity at high doses [13,14]. (See "Use of anticoagulants during pregnancy and postpartum".) Labor and delivery plan If a patient is on anticoagulation, it should be held at the time of labor and delivery. It is reasonable to obtain a 12-lead electrocardiogram upon arrival to labor and delivery. If the patient is in atrial fibrillation, they have had a high burden of atrial fibrillation, they have had problems with rate control, or there is structural heart disease, the use of telemetry is reasonable in order to monitor heart rate and rhythm. Close coordination between the patient and multidisciplinary cardio-obstetrics team (including cardiology, high-risk obstetrics, maternal fetal medicine, neonatology, social work, and anesthesia providers) to develop the labor and delivery plan for patients with atrial fibrillation and flutter is important [68,69]. (See "Acquired heart disease and pregnancy", section on 'Management of labor and delivery'.) ISSUES REGARDING ANTIARRHYTHMIC DRUG TREATMENT The rate of placental passage of any drug is dependent on lipid solubility, molecular weight, protein binding, ionization, fetal and placental blood flow, and pH of maternal and fetal fluids. Nonionized, nonprotein bound, lipid soluble drugs with molecular weight below 600 Daltons freely cross the placenta [70], while high molecular weight drugs are not transported in significant amounts. Almost all antiarrhythmic drugs cross the placenta. Fetal tissues begin to differentiate during the period of organogenesis (gestational weeks 5 to 10) and are most susceptible to the effects of teratogens at that time. The major concern with antiarrhythmic drugs taken during the second and third trimesters are potential adverse effects on fetal growth and development, drug-related side effects in the neonate, risk of proarrhythmia, and possible effects on uterine contractility. Safety during pregnancy Safety profiles of antiarrhythmic drugs are drawn from case reports, case series, registry data, and case control and cohort studies of pregnant patients treated with these drugs, alone or with other agents, and for a variety of indications, including hypertension, maternal or fetal arrhythmias, and a wide spectrum of underlying medical disorders, which could confound findings. There are no data from large well-designed https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 12/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate randomized trials on which to base a recommendation for use of one drug over another. Data regarding both comparative efficacy in improving maternal outcome and fetal safety are inadequate for almost all antiarrhythmic drugs. Information related to the toxicity and teratogenicity of medications in pregnant patients must be interpreted in light of the background risk of adverse pregnancy outcomes in any pregnant woman. Major birth defects are defined as events of medical, surgical, or cosmetic significance. It is estimated that the prevalence of major birth defects is 2 to 4 percent among live born infants, and in utero growth restriction occurs in 3 to 10 percent of pregnancies, depending on the definition used. Intrauterine growth restriction can be related to in utero drug exposure, the mother's disease, other drug therapy, or a combination of these and other factors (eg, intrinsic fetal or placental factors). Since 1975, the United States Food and Drug Administration (FDA) has assigned pregnancy risk factors to all drugs available in the United States. Information on the use of specific drugs in pregnancy, including the FDA risk category and pregnancy implications, is available in the UpToDate drug database. Specific information on the fetal and neonatal risks of maternal drug ingestion during pregnancy and lactation are also available from the following website: www.perinatology.com/exposures/druglist.htm. The following table provides a brief synopsis of pregnancy and breastfeeding implications for the drugs discussed in this topic ( table 1). Pharmacokinetic changes during pregnancy Physiological changes during pregnancy may alter the absorption, excretion and effective plasma concentration of all antiarrhythmic drugs. Increased intravascular volumes during pregnancy may require an increase in loading dose. Gastrointestinal absorption of drugs may be altered by changes in gastric secretion and intestinal motility. Increase in renal blood flow and progesterone-induced increase of hepatic metabolism may augment drug clearance [71]. Finally, decreased serum protein concentrations may reduce protein binding, decreasing the total drug concentration and leading to greater fluctuation in unbound drug concentration. These pharmacokinetic changes may explain why pregnant patients previously stable on antiarrhythmic therapy have breakthrough arrhythmias. Because of intra-individual variability in the above-mentioned factors, drug dose should be optimized on an individual basis with monitoring of clinical response. Breast feeding In general, drugs that are most likely to be transferred from maternal plasma to milk have the following characteristics: nonionized, nonprotein bound, low molecular weight, high lipid solubility, and high pH. In addition to drug transfer, drug clearance in the setting of a https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 13/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate neonate's immature renal and hepatic function also determines whether a drug and/or its metabolites reach therapeutic or toxic levels in the infant. The LactMed database, produced by the National Library of Medicine, provides monographs on many prescription and over-the-counter medications. The database is available free of charge. The UpToDate drug database also provides information on lactation and breastfeeding implications for all drugs in the database. The following table provides a brief synopsis of pregnancy and breastfeeding implications for drugs discussed in this topic ( table 1). ISSUES REGARDING NON-PHARMACOLOGIC TREATMENT Electrical cardioversion Emergent or elective electrical cardioversion can be performed at all stages of pregnancy [13,14,72], and should be used for any sustained arrhythmia with hemodynamic compromise and can be considered for drug-refractory arrhythmias. Electrical cardioversion does not result in compromise of blood flow to the fetus [72]. While there is a theoretical risk of inducing an arrhythmia in the fetus, this risk is very small due to the high fibrillation threshold and small amount of energy reaching the fetus. Nonetheless, fetal rhythm monitoring is recommended because of reported cases of emergency cesarean delivery due to fetal arrhythmias [73]. In the third trimester, some physicians prefer to perform electrical cardioversion under general anesthesia and intubation, considering the more difficult airway and increased risk of gastric aspiration during pregnancy. Radiofrequency catheter ablation In nonpregnant patients, more definitive treatment of atrial fibrillation, atrial flutter, and other arrhythmias can be accomplished with catheter ablation. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Introduction'.) Catheter ablation prior to pregnancy is recommended in patients with symptomatic arrhythmias [11]. Ablation of atrial flutter and other arrhythmias is generally avoided during pregnancy given the need for fluoroscopy. For those experiencing new onset of arrhythmias suitable for radiofrequency ablation, or worsening of existing arrhythmias during pregnancy, ablation is generally delayed until after delivery. Experience with radiofrequency catheter ablation during pregnancy has been limited to cases of supraventricular tachycardia [53,56,74-81]. These procedures are generally not performed during pregnancy, mainly due to concerns of ionizing radiation exposure to the fetus. However, in rare cases, patients with severe and drug-resistant arrhythmias during pregnancy may be considered for an ablation procedure [11,13]. The risk of radiation exposure for the fetus during https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 14/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate a typical ablation is small (<1 mGy at all periods of gestation), and is mainly attributable to scatter from the thorax of the mother [82]. (See "Diagnostic imaging in pregnant and lactating patients".) Cases of successful ablation of atrial tachycardia using intracardiac echocardiography and electro-anatomic mapping without fluoroscopy have been reported [83,84]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) SUMMARY AND RECOMMENDATIONS Symptoms Palpitations occur frequently during pregnancy and are a common indication for cardiac evaluation during pregnancy. (See 'Symptom-rhythm correlation' above.) Evaluation for structural heart disease Since cardiac arrhythmias are frequently associated with structural heart disease, any woman who presents with an arrhythmia |
differentiate during the period of organogenesis (gestational weeks 5 to 10) and are most susceptible to the effects of teratogens at that time. The major concern with antiarrhythmic drugs taken during the second and third trimesters are potential adverse effects on fetal growth and development, drug-related side effects in the neonate, risk of proarrhythmia, and possible effects on uterine contractility. Safety during pregnancy Safety profiles of antiarrhythmic drugs are drawn from case reports, case series, registry data, and case control and cohort studies of pregnant patients treated with these drugs, alone or with other agents, and for a variety of indications, including hypertension, maternal or fetal arrhythmias, and a wide spectrum of underlying medical disorders, which could confound findings. There are no data from large well-designed https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 12/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate randomized trials on which to base a recommendation for use of one drug over another. Data regarding both comparative efficacy in improving maternal outcome and fetal safety are inadequate for almost all antiarrhythmic drugs. Information related to the toxicity and teratogenicity of medications in pregnant patients must be interpreted in light of the background risk of adverse pregnancy outcomes in any pregnant woman. Major birth defects are defined as events of medical, surgical, or cosmetic significance. It is estimated that the prevalence of major birth defects is 2 to 4 percent among live born infants, and in utero growth restriction occurs in 3 to 10 percent of pregnancies, depending on the definition used. Intrauterine growth restriction can be related to in utero drug exposure, the mother's disease, other drug therapy, or a combination of these and other factors (eg, intrinsic fetal or placental factors). Since 1975, the United States Food and Drug Administration (FDA) has assigned pregnancy risk factors to all drugs available in the United States. Information on the use of specific drugs in pregnancy, including the FDA risk category and pregnancy implications, is available in the UpToDate drug database. Specific information on the fetal and neonatal risks of maternal drug ingestion during pregnancy and lactation are also available from the following website: www.perinatology.com/exposures/druglist.htm. The following table provides a brief synopsis of pregnancy and breastfeeding implications for the drugs discussed in this topic ( table 1). Pharmacokinetic changes during pregnancy Physiological changes during pregnancy may alter the absorption, excretion and effective plasma concentration of all antiarrhythmic drugs. Increased intravascular volumes during pregnancy may require an increase in loading dose. Gastrointestinal absorption of drugs may be altered by changes in gastric secretion and intestinal motility. Increase in renal blood flow and progesterone-induced increase of hepatic metabolism may augment drug clearance [71]. Finally, decreased serum protein concentrations may reduce protein binding, decreasing the total drug concentration and leading to greater fluctuation in unbound drug concentration. These pharmacokinetic changes may explain why pregnant patients previously stable on antiarrhythmic therapy have breakthrough arrhythmias. Because of intra-individual variability in the above-mentioned factors, drug dose should be optimized on an individual basis with monitoring of clinical response. Breast feeding In general, drugs that are most likely to be transferred from maternal plasma to milk have the following characteristics: nonionized, nonprotein bound, low molecular weight, high lipid solubility, and high pH. In addition to drug transfer, drug clearance in the setting of a https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 13/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate neonate's immature renal and hepatic function also determines whether a drug and/or its metabolites reach therapeutic or toxic levels in the infant. The LactMed database, produced by the National Library of Medicine, provides monographs on many prescription and over-the-counter medications. The database is available free of charge. The UpToDate drug database also provides information on lactation and breastfeeding implications for all drugs in the database. The following table provides a brief synopsis of pregnancy and breastfeeding implications for drugs discussed in this topic ( table 1). ISSUES REGARDING NON-PHARMACOLOGIC TREATMENT Electrical cardioversion Emergent or elective electrical cardioversion can be performed at all stages of pregnancy [13,14,72], and should be used for any sustained arrhythmia with hemodynamic compromise and can be considered for drug-refractory arrhythmias. Electrical cardioversion does not result in compromise of blood flow to the fetus [72]. While there is a theoretical risk of inducing an arrhythmia in the fetus, this risk is very small due to the high fibrillation threshold and small amount of energy reaching the fetus. Nonetheless, fetal rhythm monitoring is recommended because of reported cases of emergency cesarean delivery due to fetal arrhythmias [73]. In the third trimester, some physicians prefer to perform electrical cardioversion under general anesthesia and intubation, considering the more difficult airway and increased risk of gastric aspiration during pregnancy. Radiofrequency catheter ablation In nonpregnant patients, more definitive treatment of atrial fibrillation, atrial flutter, and other arrhythmias can be accomplished with catheter ablation. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Introduction'.) Catheter ablation prior to pregnancy is recommended in patients with symptomatic arrhythmias [11]. Ablation of atrial flutter and other arrhythmias is generally avoided during pregnancy given the need for fluoroscopy. For those experiencing new onset of arrhythmias suitable for radiofrequency ablation, or worsening of existing arrhythmias during pregnancy, ablation is generally delayed until after delivery. Experience with radiofrequency catheter ablation during pregnancy has been limited to cases of supraventricular tachycardia [53,56,74-81]. These procedures are generally not performed during pregnancy, mainly due to concerns of ionizing radiation exposure to the fetus. However, in rare cases, patients with severe and drug-resistant arrhythmias during pregnancy may be considered for an ablation procedure [11,13]. The risk of radiation exposure for the fetus during https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 14/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate a typical ablation is small (<1 mGy at all periods of gestation), and is mainly attributable to scatter from the thorax of the mother [82]. (See "Diagnostic imaging in pregnant and lactating patients".) Cases of successful ablation of atrial tachycardia using intracardiac echocardiography and electro-anatomic mapping without fluoroscopy have been reported [83,84]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) SUMMARY AND RECOMMENDATIONS Symptoms Palpitations occur frequently during pregnancy and are a common indication for cardiac evaluation during pregnancy. (See 'Symptom-rhythm correlation' above.) Evaluation for structural heart disease Since cardiac arrhythmias are frequently associated with structural heart disease, any woman who presents with an arrhythmia during pregnancy should undergo clinical evaluation for structural heart disease. including an electrocardiogram and a transthoracic echocardiogram. (See 'Diagnostic testing' above.) Paroxysmal supraventricular tachycardia In pregnant patients with structurally normal hearts, paroxysmal supraventricular tachycardia (PSVT), including atrioventricular (AV)- nodal reentrant tachycardia and AV-reciprocating tachycardia, is the most common arrhythmia. Management of PSVT is performed with AV-nodal blocking agents. If hemodynamic compromise is evident, direct current (DC) cardioversion should be performed. (See 'Paroxysmal supraventricular tachycardia' above.) Atrial fibrillation and flutter These arrhythmias occur less frequently than PSVT and are more common in patients with structural heart disease. (See 'Atrial fibrillation and flutter' above.) Hemodynamically unstable pregnant patients require urgent cardioversion. (See 'Electrical cardioversion' above.) We suggest a rhythm control over a rate control strategy in pregnancy (Grade 2C). In pregnant patients, we use flecainide, propafenone, or sotalol ( table 1). (See 'Rhythm https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 15/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate control versus rate control' above.) If rhythm control cannot be achieved or is unlikely to be successful, then ventricular rate control can be instituted. Rate-control agents in pregnancy include beta-selective blockers, verapamil, and digoxin ( table 1), either alone or in combination. Although pregnancy is a prothrombotic state, given the lack of extensive data on risk stratification during pregnancy, similar recommendations for stroke risk assessment should be used as those in nonpregnant patients. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) The preferred anticoagulant for most pregnant patients is low molecular weight heparin. Heparin can be used throughout all stages of pregnancy but should be discontinued prior to delivery. (See 'Anticoagulation' above.) The labor and delivery plan Pregnant patients with arrhythmia should develop an early birth/labor plan with their multidisciplinary team including cardiology, OB-GYN, and anesthesia. A 12-lead electrocardiogram upon arrival to labor and delivery and telemetry may be indicated. (See 'Labor and delivery plan' above.) Information on the use of specific antiarrhythmic drugs in pregnancy is available in the UpToDate drug database. (See 'Issues regarding antiarrhythmic drug treatment' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001; 104:515. 2. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007; 49:2303. 3. Drenthen W, Boersma E, Balci A, et al. Predictors of pregnancy complications in women with congenital heart disease. Eur Heart J 2010; 31:2124. 4. Vaidya VR, Arora S, Patel N, et al. Burden of Arrhythmia in Pregnancy. Circulation 2017; 135:619. 5. Lee SH, Chen SA, Wu TJ, et al. Effects of pregnancy on first onset and symptoms of paroxysmal supraventricular tachycardia. Am J Cardiol 1995; 76:675. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 16/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate 6. Silversides CK, Harris L, Haberer K, et al. Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes. Am J Cardiol 2006; 97:1206. 7. Siu SC, Sermer M, Harrison DA, et al. Risk and predictors for pregnancy-related complications in women with heart disease. Circulation 1997; 96:2789. 8. Drenthen W, Pieper PG, Ploeg M, et al. Risk of complications during pregnancy after Senning or Mustard (atrial) repair of complete transposition of the great arteries. Eur Heart J 2005; 26:2588. 9. Drenthen W, Pieper PG, van der Tuuk K, et al. Cardiac complications relating to pregnancy and recurrence of disease in the offspring of women with atrioventricular septal defects. Eur Heart J 2005; 26:2581. 10. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Pregnancy and delivery in women after Fontan palliation. Heart 2006; 92:1290. 11. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 12. Joglar JA, Page RL. Treatment of cardiac arrhythmias during pregnancy: safety considerations. Drug Saf 1999; 20:85. 13. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018; 39:3165. 14. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373. 15. Silversides CK, Colman JM. Physiological changes in pregnancy. In: Heart disease in pregnan cy, 2nd ed, Oakley C, Warnes CA (Eds), Blackwell Publishing, Malden 2007. p.6. 16. Elkayam U, Gleicher N. Hemodynamics and cardiac function during normal pregnancy and p uerperium. In: Cardiac problems in pregnancy, 3rd ed, Elkayam U, Gleicher N (Eds), Wiley-Lis s, New York 1998. p.3. 17. Katz R, Karliner JS, Resnik R. Effects of a natural volume overload state (pregnancy) on left ventricular performance in normal human subjects. Circulation 1978; 58:434. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 17/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate 18. Rubler S, Damani PM, Pinto ER. Cardiac size and performance during pregnancy estimated with echocardiography. Am J Cardiol 1977; 40:534. 19. Liebson PR, Mann LI, Evans MI, et al. Cardiac performance during pregnancy: serial evaluation using external systolic time intervals. Am J Obstet Gynecol 1975; 122:1. 20. Campos O. Doppler Echocardiography During Pregnancy: Physiological and Abnormal Findings. Echocardiography 1996; 13:135. 21. Franz MR, Cima R, Wang D, et al. Electrophysiological effects of myocardial stretch and mechanical determinants of stretch-activated arrhythmias. Circulation 1992; 86:968. 22. Wang Y, Joyner RW, Wagner MB, et al. Stretch-activated channel activation promotes early afterdepolarizations in rat ventricular myocytes under oxidative stress. Am J Physiol Heart Circ Physiol 2009; 296:H1227. 23. Ninio DM, Saint DA. The role of stretch-activated channels in atrial fibrillation and the impact of intracellular acidosis. Prog Biophys Mol Biol 2008; 97:401. 24. Kamkin A, Kiseleva I, Isenberg G. Stretch-activated currents in ventricular myocytes: amplitude and arrhythmogenic effects increase with hypertrophy. Cardiovasc Res 2000; 48:409. 25. Soliman EZ, Elsalam MA, Li Y. The relationship between high resting heart rate and ventricular arrhythmogenesis in patients referred to ambulatory 24 h electrocardiographic recording. Europace 2010; 12:261. 26. Zuspan FP. Catecholamines. Their role in pregnancy and the development of pregnancy- induced hypertension. J Reprod Med 1979; 23:143. 27. Natrajan PG, McGarrigle HH, Lawrence DM, Lachelin GC. Plasma noradrenaline and adrenaline levels in normal pregnancy and in pregnancy-induced hypertension. Br J Obstet Gynaecol 1982; 89:1041. 28. Whittaker PG, Gerrard J, Lind T. Catecholamine responses to changes in posture during human pregnancy. Br J Obstet Gynaecol 1985; 92:586. 29. Barron WM, Mujais SK, Zinaman M, et al. Plasma catecholamine responses to physiologic stimuli in normal human pregnancy. Am J Obstet Gynecol 1986; 154:80. 30. Ramsay MM, Broughton Pipkin F, Rubin PC. Pressor, heart rate and plasma catecholamine responses to noradrenaline in pregnant and nonpregnant women. Br J Obstet Gynaecol 1993; 100:170. 31. Roberts JM, Insel PA, Goldfien A. Regulation of myometrial adrenoreceptors and adrenergic response by sex steroids. Mol Pharmacol 1981; 20:52. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 18/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate 32. Priori SG, Mantica M, Schwartz PJ. Delayed afterdepolarizations elicited in vivo by left stellate ganglion stimulation. Circulation 1988; 78:178. 33. Shotan A, Ostrzega E, Mehra A, et al. Incidence of arrhythmias in normal pregnancy and relation to palpitations, dizziness, and syncope. Am J Cardiol 1997; 79:1061. 34. Li JM, Nguyen C, Joglar JA, et al. Frequency and outcome of arrhythmias complicating admission during pregnancy: experience from a high-volume and ethnically-diverse obstetric service. Clin Cardiol 2008; 31:538. 35. Chang SH, Kuo CF, Chou IJ, et al. Outcomes Associated With Paroxysmal Supraventricular Tachycardia During Pregnancy. Circulation 2017; 135:616. 36. Tawam M, Levine J, Mendelson M, et al. Effect of pregnancy on paroxysmal supraventricular tachycardia. Am J Cardiol 1993; 72:838. 37. Smith WM, Gallagher JJ, Kerr CR, et al. The electrophysiologic basis and management of symptomatic recurrent tachycardia in patients with Ebstein's anomaly of the tricuspid valve. Am J Cardiol 1982; 49:1223. 38. Gleicher N, Meller J, Sandler RZ, Sullum S. Wolff-Parkinson-White syndrome in pregnancy. Obstet Gynecol 1981; 58:748. 39. Widerhorn J, Widerhorn AL, Rahimtoola SH, Elkayam U. WPW syndrome during pregnancy: increased incidence of supraventricular arrhythmias. Am Heart J 1992; 123:796. 40. Kounis NG, Zavras GM, Papadaki PJ, et al. Pregnancy-induced increase of supraventricular arrhythmias in Wolff-Parkinson-White syndrome. Clin Cardiol 1995; 18:137. 41. Murphy JJ, Hutchon DJ. Incessant atrial tachycardia accelerated by pregnancy. Br Heart J 1992; 68:342. 42. Treakle K, Kostic B, Hulkower S. Supraventricular tachycardia resistant to treatment in a pregnant woman. J Fam Pract 1992; 35:581. 43. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 44. Elkayam U, Goodwin TM. Adenosine therapy for supraventricular tachycardia during pregnancy. Am J Cardiol 1995; 75:521. 45. Ghosh N, Luk A, Derzko C, et al. The acute treatment of maternal supraventricular tachycardias during pregnancy: a review of the literature. J Obstet Gynaecol Can 2011; 33:17. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 19/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate 46. Jaqueti J, Martinez-Hern ndez D, Hern ndez-Garcia R, et al. Adenosine deaminase in pregnancy serum. Clin Chem 1990; 36:2144. 47. Mariani PJ. Pharmacotherapy of pregnancy related SVT. Ann Emerg Med 1992; 21:229. 48. Byerly WG, Hartmann A, Foster DE, Tannenbaum AK. Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia. Ann Emerg Med 1991; 20:552. 49. Halpern DG, Weinberg CR, Pinnelas R, et al. Use of Medication for Cardiovascular Disease During Pregnancy: JACC State-of-the-Art Review. J Am Coll Cardiol 2019; 73:457. 50. Bateman BT, Heide-J rgensen U, Einarsd ttir K, et al. -Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study. Ann Intern Med 2018; 169:665. 51. Briggs GC, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation, 8th ed, Lippincott Willia ms & Wilkins, Philadelphia 2008. 52. Winniford MD, Fulton KL, Hillis LD. Long-term therapy of paroxysmal supraventricular tachycardia: a randomized, double-blind comparison of digoxin, propranolol and verapamil. Am J Cardiol 1984; 54:1138. 53. Szumowski L, Szufladowicz E, Orczykowski M, et al. Ablation of severe drug-resistant tachyarrhythmia during pregnancy. J Cardiovasc Electrophysiol 2010; 21:877. 54. Cruz FE, Cheriex EC, Smeets JL, et al. Reversibility of tachycardia-induced cardiomyopathy after cure of incessant supraventricular tachycardia. J Am Coll Cardiol 1990; 16:739. 55. Haines DE, DiMarco JP. Sustained intraatrial reentrant tachycardia: clinical, electrocardiographic and electrophysiologic characteristics and long-term follow-up. J Am Coll Cardiol 1990; 15:1345. 56. Pagad SV, Barmade AB, Toal SC, et al. 'Rescue' radiofrequency ablation for atrial tachycardia presenting as cardiomyopathy in pregnancy. Indian Heart J 2004; 56:245. 57. Gowda RM, Punukollu G, Khan IA, et al. Lone atrial fibrillation during pregnancy. Int J Cardiol 2003; 88:123. 58. Kuczkowski KM. New onset transient lone atrial fibrillation in a healthy parturient: d j vu. Int J Cardiol 2004; 97:339. 59. Autore C, Conte MR, Piccininno M, et al. Risk associated with pregnancy in hypertrophic cardiomyopathy. J Am Coll Cardiol 2002; 40:1864. 60. Walsh EP, Cecchin F. Arrhythmias in adult patients with congenital heart disease. Circulation 2007; 115:534. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 20/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate 61. Tateno S, Niwa K, Nakazawa M, et al. Arrhythmia and conduction disturbances in patients with congenital heart disease during pregnancy: multicenter study. Circ J 2003; 67:992. 62. Balci A, Drenthen W, Mulder BJ, et al. Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events. Am Heart J 2011; 161:307. 63. O'Riordan MN, Higgins JR. Haemostasis in normal and abnormal pregnancy. Best Pract Res Clin Obstet Gynaecol 2003; 17:385. 64. Kockova R, Kocka V, Kiernan T, Fahy GJ. Ibutilide-induced cardioversion of atrial fibrillation during pregnancy. J Cardiovasc Electrophysiol 2007; 18:545. 65. Burkart TA, Kron J, Miles WM, et al. Successful termination of atrial flutter by ibutilide during pregnancy. Pacing Clin Electrophysiol 2007; 30:283. 66. Tan HL, Lie KI. Treatment of tachyarrhythmias during pregnancy and lactation. Eur Heart J 2001; 22:458. 67. Giehm-Reese M, Kronborg MB, Lukac P, et al. Recurrent atrial flutter ablation and incidence of atrial fibrillation ablation after first-time ablation for typical atrial flutter: A nation-wide Danish cohort study. Int J Cardiol 2020; 298:44. 68. Davis MB, Walsh MN. Cardio-Obstetrics. Circ Cardiovasc Qual Outcomes 2019; 12:e005417. 69. Sharma G, Zakaria S, Michos ED, et al. Improving Cardiovascular Workforce Competencies in Cardio-Obstetrics: Current Challenges and Future Directions. J Am Heart Assoc 2020; 9:e015569. 70. Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet 2004; 43:487. 71. Dunlop W. Serial changes in renal haemodynamics during normal human pregnancy. Br J Obstet Gynaecol 1981; 88:1. 72. Wang YC, Chen CH, Su HY, Yu MH. The impact of maternal cardioversion on fetal haemodynamics. Eur J Obstet Gynecol Reprod Biol 2006; 126:268. 73. Barnes EJ, Eben F, Patterson D. Direct current cardioversion during pregnancy should be performed with facilities available for fetal monitoring and emergency caesarean section. BJOG 2002; 109:1406. 74. Bongiorni MG, Di Cori A, Soldati E, et al. Radiofrequency catheter ablation of atrioventricular nodal reciprocating tachycardia using intracardiac echocardiography in pregnancy. Europace 2008; 10:1018. 75. Risius T, Mortensen K, Meinertz T, Willems S. Cluster of multiple atrial tachycardias limited to pregnancy after radiofrequency ablation following senning operation. Int J Cardiol 2008; 123:e48. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 21/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate 76. Kanjwal Y, Kosinski D, Kanj M, et al. Successful radiofrequency catheter ablation of left lateral accessory pathway using transseptal approach during pregnancy. J Interv Card Electrophysiol 2005; 13:239. 77. Bombelli F, Lagona F, Salvati A, et al. Radiofrequency catheter ablation in drug refractory maternal supraventricular tachycardias in advanced pregnancy. Obstet Gynecol 2003; 102:1171. 78. Dom nguez A, Iturralde P, Hermosillo AG, et al. Successful radiofrequency ablation of an accessory pathway during pregnancy. Pacing Clin Electrophysiol 1999; 22:131. 79. Berruezo A, D ez GR, Berne P, et al. Low exposure radiation with conventional guided radiofrequency catheter ablation in pregnant women. Pacing Clin Electrophysiol 2007; 30:1299. 80. Driver K, Chisholm CA, Darby AE, et al. Catheter Ablation of Arrhythmia During Pregnancy. J Cardiovasc Electrophysiol 2015; 26:698. 81. Chen G, Sun G, Xu R, et al. Zero-fluoroscopy catheter ablation of severe drug-resistant arrhythmia guided by Ensite NavX system during pregnancy: Two case reports and literature review. Medicine (Baltimore) 2016; 95:e4487. 82. Damilakis J, Theocharopoulos N, Perisinakis K, et al. Conceptus radiation dose and risk from cardiac catheter ablation procedures. Circulation 2001; 104:893. 83. Ferguson JD, Helms A, Mangrum JM, DiMarco JP. Ablation of incessant left atrial tachycardia without fluoroscopy in a pregnant woman. J Cardiovasc Electrophysiol 2011; 22:346. 84. Szumowski L, Szufladowicz E, Orczykowski M, et al. Ablation of severe drug-resistant tachyarrhythmia during pregnancy. J Cardiovasc Electrophysiol 2010; 21:877. Topic 13600 Version 31.0 https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 22/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate GRAPHICS Prevalence of arrhythmias during pregnancy in women with congenital heart disease AOS: aortic stenosis; ASD: atrial septal defect; AVSD: atrioventricular septal defect; CC-TGA: congenital corrected transposition of the great arteries; CHD: congenital heart disease; PAVSD: pulmonary atresia with ventricular septal defect; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Data from: Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007; 49:2303. Graphic 61986 Version 4.0 https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 23/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate Antiarrhythmic drugs in pregnancy Drug Pregnancy Breastfeeding Amiodarone Has been associated with serious adverse effects. Congenital Not recommended because of potential risk of hypothyroidism in goiter/hypothyroidism and hyperthyroidism can occur after in neonate. utero exposure. Other potential risks include prolonged QT interval in neonates. Beta blockers No evidence of increased risk of The AAP considers these agents teratogenesis, but some (particularly atenolol) may impair fetal growth when compatible with breastfeeding, but newborns should be observed for signs used for a prolonged duration in the second and third trimesters. Use only of beta blockade. Atenolol is a weak base that will accumulate in milk. Accumulation is in the third trimester is associated with reduced placental weight. enhanced by its water-soluble, low Newborns of patients taking these drugs near delivery are at risk of protein binding, little or no hepatic metabolism, and renal excretion bradycardia, hypoglycemia, and other symptoms of beta blockade. properties. Because it has been associated with beta-blocking effects and cyanosis in nursing infants, it is best avoided during breastfeeding. Among this class of drugs, atenolol appears to have the most unfavorable effect on birthweight. Sotalol Sotalol, which has both beta blocker Sotalol is concentrated in breast milk, and type III antiarrhythmic properties, with milk levels several-fold higher is not teratogenic, and its use has not been associated with fetal growth than those in maternal plasma, so close monitoring for bradycardia, restriction. Its use near birth has been associated with newborn bradycardia. hypotension, respiratory distress, and hypoglycemia is advised. Adenosine No evidence of increased risk of No information. Because of very short teratogenesis or increased risk of adverse fetal/neonatal effects. half-life, it is unlikely to have any adverse effects on the neonate. Digoxin No evidence of increased risk of The AAP considers digoxin compatible teratogenesis or increased risk of with breastfeeding. adverse fetal/neonatal effects. Verapamil No evidence of increased risk of teratogenesis or increased risk of The AAP considers verapamil compatible with breastfeeding. adverse fetal/neonatal effects. Procainamide No evidence of increased risk of teratogenesis or increased risk of The AAP classifies procainamide as compatible with breastfeeding. https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 24/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate adverse fetal/neonatal effects. However, the long-term effects of exposure in the nursing infant are unknown, particularly with respect to potential drug toxicity (eg, development of antinuclear antibodies and lupus-like syndrome). Quinidine No evidence of increased risk of teratogenesis. In therapeutic doses, The AAP considers quinidine compatible with breastfeeding. the oxytocic properties of quinidine have been rarely observed, but high doses can produce this effect and may result in preterm labor or abortion. Flecainide Developmental toxicity has been noted The AAP considers flecainide in animals, but there is limited compatible with breastfeeding. information on human risk from early pregnancy exposure. This risk appears to be low when used for refractory fetal arrhythmia. It may be the treatment of choice for tachycardia in hydropic fetuses. AAP: American Academy of Pediatrics. Adapted from: Briggs GG, Freeman RK, Ya e SJ. Drugs in Pregnancy and Lactation, 8th edition. Philadelphia: Lippincott Williams & Wilkins. Graphic 50716 Version 8.0 https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 25/26 7/6/23, 1:50 PM Supraventricular arrhythmias during pregnancy - UpToDate Contributor Disclosures Candice Silversides, MD, MS, FRCPC No relevant financial relationship(s) with ineligible companies to disclose. Louise Harris, MBChB No relevant financial relationship(s) with ineligible companies to disclose. Sing-Chien Yap, MD, PhD Grant/Research/Clinical Trial Support: Medtronic [Ventricular arrhythmias]. Consultant/Advisory Boards: Boston Scientific [Ventricular arrhythmias]. All of the relevant financial relationships listed have been mitigated. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/supraventricular-arrhythmias-during-pregnancy/print 26/26 |
7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Supraventricular premature beats : Antonis S Manolis, MD : Hugh Calkins, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 27, 2022. INTRODUCTION Supraventricular premature beats represent premature activation of the atria from a site other than the sinus node and can originate from the atria (premature atrial complexes [PACs]; also referred to as premature atrial beats, premature supraventricular complexes, or premature supraventricular beats) or the atrioventricular node (called junctional premature beats [JPBs]), though the vast majority are atrial in origin. PACs are triggered from the atrial myocardium in a variety of situations and occur in a broad spectrum of the population. This includes patients without structural heart disease and those with any form of cardiac disease, independent of severity. The prevalence, mechanisms, clinical manifestations, diagnosis, and treatment of PACs will be presented here. A discussion of premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) is presented separately. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation".) PREVALENCE PACs are fairly ubiquitous, occurring commonly in both young and older adult subjects and in those with and without significant heart disease. The prevalence of PACs is highly dependent upon the technique used for evaluation. PACs are less commonly seen on standard 10-second electrocardiogram (ECG) compared with 24-hour or longer duration Holter monitoring. In a cross-sectional analysis of 1742 Swiss adults (50 years of https://www.uptodate.com/contents/supraventricular-premature-beats/print 1/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate age or older) from the general population who underwent Holter monitoring for 24 hours, 99 percent had at least one PAC during the monitoring period [1]. In this Swiss cohort, the frequency of PACs steadily increased with age, with rates of 0.8, 1.4, and 2.6 PACs per hour among participants aged 50 to 55 years, 60 to 65 years, and 70 or more years, respectively [1]. Similar findings of greater PAC frequency with advancing age have been reported in other cohorts as well [2-4]. The presence and frequency of PACs is dependent upon the presence of structural heart disease. PACs are particularly frequent in patients with mitral valve disease and in those with left ventricular dysfunction regardless of etiology. However, the high prevalence of PACs in the normal population makes such associations uncertain. (See 'Etiology' below.) The wide range in the reported prevalence of PACs in different populations may be related to the day-to-day variability in their prevalence and frequency. Circadian variation in the frequency of PACs may also occur, but there is significant interpatient variation. In the Copenhagen Holter Study cohort, in which 638 persons (ages 55 to 75 years) underwent up to 48-hour Holter recording and were followed for a median of 14 years, a circadian variation was observed in the group with frequent PACs ( 720/day; n = 66 persons), with the fewest PACs/h observed during the night with a nadir at 6 AM and then reaching a peak value in the afternoon at 3 PM. Runs of PACs in all subjects showed a similar circadian variation, while the risk of atrial fibrillation (AF) was equal in all time intervals throughout the day [5]. Junctional premature beats (JPBs) occur less commonly than both PACs and PVCs and are rarely seen in clinical practice. Their prevalence has not been well studied due in part to their scarcity as well as difficulty in making the correct diagnosis. In addition, many studies combine JPBs and PACs into one category of supraventricular premature beats. MECHANISMS Since invasive testing is rarely performed in patients with only simple PACs, there is little information about the mechanisms of PACs in humans. Although the mechanisms responsible for spontaneous PACs are not clear or well investigated, it seems likely that multiple mechanisms are responsible for PACs in different patients, depending upon the clinical situation. Possible mechanisms, which are discussed in greater detail elsewhere, include: Reentry within the atrium [6] (see "Reentry and the development of cardiac arrhythmias") Abnormal automaticity [7] (see "Enhanced cardiac automaticity") Triggered activity [8] (see "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Mechanisms for PVCs') https://www.uptodate.com/contents/supraventricular-premature-beats/print 2/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Although the mechanisms responsible for JPBs are not clear or well investigated, they are most likely due to abnormal automaticity. (See "Enhanced cardiac automaticity".) ETIOLOGY PACs Because PACs occur frequently in subjects with normal hearts as well as in persons with known cardiovascular disease, it is difficult to establish a definite relationship to other disorders or to delineate the factors that predispose to these extra beats. Furthermore, the incidence of PACs is variable in different forms of structural heart disease. Idiopathic PACs In patients without structural heart disease, PACs frequently originate from the pulmonary veins. PACs have long been observed to precede the degeneration of sinus rhythm into AF and are thus considered the main triggers of this common arrhythmia [9,10]. Lifestyle risk factors Smoking, alcohol, and coffee are widely considered as potential precipitants of PACs [11-13]. Smoking and alcohol are known to increase sympathetic tone, which may affect the frequency of PACs [11,12]. Although there is a widespread belief that caffeine, particularly at high doses, is associated with palpitations and a number of arrhythmias, there is no evidence that it is proarrhythmic [14,15]. Caffeine has clear electrophysiologic effects on the atria, although the association with PACs is uncertain [13]. In a study of 1388 participants in the Cardiovascular Health Study, in which caffeine consumption was self-reported and patients underwent 24-hour ambulatory monitoring, there was no significant differences in the frequency of PACs between users and non-users of caffeine [16]. Nevertheless, there are patients who may be more sensitive to caffeine and note a relationship of palpitations to caffeine intake. Theophylline, another methylxanthine compound, also may increase PAC frequency [17,18]. Obesity and poor physical activity in midlife have been associated with a higher frequency of PACs in late life [19]. Acute myocardial infarction Patients with an acute myocardial infarction (MI) have an early increase in the frequency of PACs, with an incidence ranging from 25 to 81 percent [1,20,21]. One study noted a mean of 9 to 14 PACs per hour on day 1 post-MI, which decreased to one to two PACs per hour on day 10 post-MI [20]. Paroxysmal https://www.uptodate.com/contents/supraventricular-premature-beats/print 3/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate supraventricular tachycardia (PSVT) is discussed separately. (See "Supraventricular arrhythmias after myocardial infarction".) Coronary heart disease Among patients with known or suspected coronary heart disease, PACs can be induced during exercise testing, but the prognostic importance of PACs during exercise testing remains unknown [22]. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Atrial arrhythmias'.) Other heart diseases The frequency of PACs appears to be increased in mitral stenosis, hypertrophic cardiomyopathy, and any condition that results in an elevation in pressure or dilatation of the right or left atrium including cardiomyopathy and valvular heart disease [23,24]. Some studies have suggested the existence of an atrial myopathy as the underlying disease in patients with and without AF. The concept is that aging, atrial stretching, and/or inflammation may produce atrial remodeling, which may lead to left atrial thrombogenesis in some patients even in the absence of AF [25,26]. Apart from echocardiographic indices and possible biomarkers of inflammation, fibrosis, and endothelial dysfunction, recordings of frequent or excessive burden of PACs ( 30 PACs/h daily or 200 PACs/24 h, or any runs of 20 PACs) might constitute an ECG marker of such myopathy [26-29]. On the other hand, some investigators have suggested that frequent PACs impair left atrial contractile function and promote adverse atrial remodeling and may thus be responsible for the development of atrial myopathy [30]. In addition, cardiac amyloidosis, particularly atrial amyloidosis, a form of senile amyloidosis, may be another type of atrial myopathy causing frequent PACs that may lead to AF, mostly in older individuals [29]. (See "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis".) Chronic obstructive pulmonary disease (COPD) In patients with COPD, bronchodilator use has been identified as a significant risk factor for increased PACs [31]. JPBs JPBs may occur in subjects with normal or abnormal hearts. Their presence may be increased by hypokalemia, digitalis toxicity, chronic lung disease, acute ischemia or myocardial infarction, excessive caffeine, nicotine or alcohol use, amphetamine use, stress, valvular heart disease, pericarditis, heart failure (HF), hyperthyroidism, or inflammatory changes in the AV junction following heart surgery. https://www.uptodate.com/contents/supraventricular-premature-beats/print 4/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate CLINICAL MANIFESTATIONS The presence of PACs is associated with several characteristic findings on history, physical examination, and ECG. PACs may be asymptomatic or cause symptoms such as a sensation of "skipping" or palpitations. PACs are often single and isolated, but they may be frequent and may occur in a bigeminal pattern. Although PACs have a wide array of manifestations, they are not life-threatening by themselves. In predisposed individuals, PACs may initiate supraventricular and, less commonly, ventricular arrhythmias, with AF being the most common arrhythmia induced by PACs [32-35]. Symptoms PACs produce few or no symptoms in the vast majority of patients (as is also the case in most persons with PVCs), although some individuals may experience palpitations or dizziness. PACs rarely cause true hemodynamic compromise, except when they are associated with an underlying bradycardia. PACs may lead to palpitations (when there is a pause and increased left ventricular inotropy resulting from an increase in stroke volume) or the sensation of skipped beats which may be due to nonconducted PACs or ineffective contraction resulting from poor filling of the left ventricle during the premature beat. Atrial bigeminy with nonconducted PACs may lead to ventricular rates approaching 40 beats/min, possibly leading to symptoms (ie, lightheadedness, dizziness, presyncope) related to the bradyarrhythmia ( waveform 1). Frequent PACs have been associated with a reversible cardiomyopathy in animal models, with rare case reports in humans, wherein patients with incessant PACs may present with symptoms of HF [36]. This is discussed in more detail separately. (See "Arrhythmia-induced cardiomyopathy", section on 'Frequent atrial ectopy'.) Most subjects with junctional premature beats (JPBs), like most subjects with PACs, are asymptomatic. However, JPBs may lead to symptoms of palpitations or the sensation of skipped beats. Concealed JPBs that lead to second degree AV block may be associated with symptoms of lightheadedness or near syncope, particularly if they occur in a bigeminal pattern. Physical examination The most characteristic finding on physical exam is the presence of an irregular pulse resulting from the presence of PACs or JPBs during the examination. Palpation of the peripheral pulse will demonstrate either premature pulse waves or pauses. Early PACs may lead to cannon A waves on the jugular venous pulsations as they may occur while the AV valves are still closed from the previous ventricular systole. This finding may be particularly helpful in differentiating early nonconducted PACs from sinus pauses. Auscultation of the heart may detect https://www.uptodate.com/contents/supraventricular-premature-beats/print 5/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate early heart sounds or pauses. PACs and JPBs may also lead to changes in the intensity or timing of a variety of cardiac murmurs (such as those due to mitral valve prolapse) due to the reduction in diastolic filling time and a reduction in ventricular volumes. These changes may be reversed with the post extrasystolic beat since there is an increase in ventricular volume due to the pause. (See "Auscultation of cardiac murmurs in adults".) Electrocardiography An ECG should be part of the standard evaluation for any patient with suspected PACs or JPBs. ECG findings with APBs PACs are observed on the surface ECG as a P wave that occurs relatively early in the cardiac cycle (ie, prematurely before the next sinus P wave should occur) and has a different morphology and axis from the sinus P wave. Often the PR interval is different from that during sinus rhythm; it may be longer or shorter, depending upon the site of origin of the PAC. With faster baseline heart rates, the abnormal P wave may be hidden within the preceding T wave, producing a "peaked" or "camel hump" type of T wave. If this is not apparent to the interpreting clinician, the PAC may be mistaken for a JPB. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Premature atrial complex'.) PACs may have a variety of manifestations on the ECG ( waveform 2), including: A normal QRS complex and a normal or short PR interval. A normal QRS complex and a prolonged PR interval. A conducted but aberrant (widened) QRS complex. In general, right bundle branch block aberrancy is more common than left bundle branch block aberrancy because of the longer refractory period of the right bundle branch [37]. No QRS complex (nonconducted PAC) ( waveform 3). The site of origin of an PAC can affect its conduction through the AV node and its P wave morphology: An PAC originating in the low right atrium near the AV node may result in a short PR interval (<120 ms) and may even be mistaken for a junctional premature depolarization. A negative P wave in the inferior leads, particularly aVF, suggests a low atrial focus, while a negative P wave in lead I and aVL suggests a left atrial origin. The AV nodal conduction time, and therefore the PR interval, may also differ depending on the input pathway to the AV node. PACs that originate from the left atrium typically have shorter conduction times than those originating from the right atrium [38]. https://www.uptodate.com/contents/supraventricular-premature-beats/print 6/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate An incomplete compensatory pause follows an PAC due to resetting of the sinus node by the PAC, with the subsequent sinus beat occurring slightly earlier than would be expected in sinus rhythm (less than twice the sinus P-P interval). This is in contrast to the fully compensatory pause which is observed after a ventricular premature beat. Rarely, one may encounter interpolated PACs without a compensatory pause [39]. A nonconducted PAC, especially one that may be obscured by the T wave, may give the false appearance of a sinus pause or sinoatrial exit block ( waveform 3). Evaluation of multiple leads may be required to detect the PAC, since it may cause a discernible deflection, seen as a deformity of the normal T wave, in only one or a few ECG leads. (See "Sinoatrial nodal pause, arrest, and exit block".) ECG findings with JPBs JPBs may have a variety of manifestations on the surface ECG. They are most often detected when there is a premature beat with a normal QRS complex and: A P wave with a PR interval that is too short to be considered to be conducted through the AV node ( waveform 4). Although the upper limits of the conduction times (PR interval) consistent with JPBs have not been defined, a premature complex with a PR interval less than 90 ms is unlikely to reflect a conducted PAC. No P wave. The absence of a P wave may be due to burial of the wave within the QRS complex or the lack of retrograde atrial activation. A P wave that occurs at the terminal portion of the QRS complex, within the ST segment, or on the T wave, depending upon the rate of retrograde conduction. The location of the P wave relative to the QRS complex provides no definitive information regarding the site of origin within the AV junction; it is simply a manifestation of the relative anterograde and retrograde conduction velocities. Like PACs, JPBs may conduct anterogradely with a functional or rate-related bundle branch block. In this setting, they may be indistinguishable on the ECG from premature ventricular depolarizations. In this setting, only intracardiac recording of His bundle activation will differentiate between these two possibilities. (See "Invasive diagnostic cardiac electrophysiology studies".) JPBs may also conduct retrogradely to the atrium and demonstrate conduction block to the ventricles. In this setting, they are similar to PACs and are indistinguishable from nonconducted PACs on the surface ECG. https://www.uptodate.com/contents/supraventricular-premature-beats/print 7/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Ambulatory monitoring Patients with palpitations or other symptoms suggesting PACs, but an unrevealing physical examination and ECG, should undergo ambulatory monitoring. In evaluating patients with suspected PACs, 24 to 48 hours of ambulatory ECG monitoring significantly increases the likelihood of making the diagnosis, given the sporadic nature of PACs in most patients. In addition, 24-hour Holter monitoring is also the best accepted approach to quantifying the frequency of PACs as a percentage of total heart beats. (See "Ambulatory ECG monitoring", section on 'Indications'.) DIAGNOSIS The diagnosis of an PAC is made when a P wave with a morphology different from that of the sinus P wave (inverted or biphasic) occurs earlier than the anticipated sinus P wave ( waveform 5). If the ectopic focus is near the sinus node, the P wave may be similar to that of the sinus P. However, every lead should be examined as subtle differences in morphology may be present. EVALUATION The evaluation of patients with symptoms suggesting PACs (or JPBs) should focus on documenting their presence or absence with an ECG or some form of ambulatory cardiac monitoring. (See 'Electrocardiography' above.) Once PACs (or JPBs) have been identified, an additional evaluation should be performed focusing on the presence or absence of underlying structural heart disease. For patients in whom PACs have been identified, the following evaluation should be performed: 24-hour ambulatory (Holter) monitor to quantify the frequency of PACs and determine if they are monomorphic or multimorphic Echocardiography to assess cardiac structure and function Further testing is indicated only when this initial evaluation identifies significant structural cardiac abnormalities that require further evaluation. EP testing There are no indications for performing electrophysiology (EP) studies in patients with PACs. JPBs generally do not require invasive electrophysiologic investigation unless there is a question of infra-His conduction disease, as in the patient with "pseudo AV block" who may possibly have Mobitz II second-degree AV block. (See "Second-degree atrioventricular block: Mobitz type II".) https://www.uptodate.com/contents/supraventricular-premature-beats/print 8/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate However, when PACs occur in a patient undergoing EP study for another reason, EP findings include an atrial activation sequence that is different from the sinus activation sequence, and normal conduction through the AV node and His-Purkinje system ( waveform 6). Additionally, functional bundle branch block may be seen, leading to HV interval prolongation. Nonconducted PACs typically demonstrate block at the AV node. (See "Invasive diagnostic cardiac electrophysiology studies".) TREATMENT In persons found to have frequent PACs or JPBs, further evaluation and management is based on the presence or absence of underlying structural heart disease and/or symptoms. The presence of frequent PACs should prompt a diagnostic evaluation for the possible presence of underlying structural heart disease, which has prognostic significance and may require specific therapy. No therapy is required for PACs or JPBs in the asymptomatic individual. For patients with symptomatic PACs, simple reassurance regarding the benign nature of PACs is frequently adequate to alleviate symptoms. In addition, patients should be counselled to avoid or minimize potential PAC precipitants (ie, smoking, alcohol intake, stress, caffeine intake in patients whose symptoms are temporally related). Options for therapy in patients with symptomatic PACs include medical therapy and, in patients with persistent symptoms, catheter ablation. However, there are few direct data to guide the choice of medical therapies, with most of the available data derived from case reports or small case series. Much of the rationale for the use of certain medications is drawn from their use in the treatment of other arrhythmias (eg, supraventricular tachyarrhythmias, PVCs). In addition, there are no studies that directly compare medical therapies with each other or with catheter ablation. Due to their low frequency of JPBs and even rarer incidence of significant symptoms, the appropriate treatment of symptomatic JPBs has not been evaluated. Reassurance of the benign nature of this rhythm abnormality may alleviate symptoms. For patients with persistent, limiting symptoms due to JPBs, therapy is similar to that for PACs, with beta blockers as the primary option. Medical therapy For patients with ongoing symptomatic PACs following efforts to minimize potential PAC precipitants (ie, smoking, caffeine intake, alcohol intake, stress), medical therapy with a beta blocker is recommended if no contraindication exists for its use (eg, oral metoprolol 25 mg twice daily with uptitration as needed for effect). Beta blockers can reduce the symptoms https://www.uptodate.com/contents/supraventricular-premature-beats/print 9/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate related to PACs and may reduce their frequency, particularly if they are due to enhanced automaticity related to enhanced sympathetic output. Beta blockers do not suppress PACs but may be useful to reduce symptoms by reducing the increased inotropy seen with the post extrasystolic beat (ie, post extrasystolic potentiation). The response to beta blockers is inconsistent and variable, with some patients having complete or near complete symptom resolution and others showing minimal benefit. A cohort study examined whether beta blockers at low doses may improve long-term outcomes in individuals with PACs, stratified into high-burden ( 100 PACs/24 h) and low-burden (<100 PACs/24 h) subcohorts [40]. In the high-burden subcohort, after propensity score matching, the treatment group (n = 208) had significantly lower mortality rates during mean follow-up of about three years than the nontreatment group (n = 832; hazard ratio [HR] 0.52, 95% CI 0.294-0.923), but rates of new stroke and of new AF were similar in the two groups. Similarly, in the low- burden subcohort, the treatment group (n = 614) had a 40 percent mortality reduction (HR 0.60, 95% CI 0.396-0.913) compared with the nontreatment group (n = 1228), but rates of new stroke and new AF were similar in the two groups. These findings suggest that beta blockers may decrease the mortality rate in patients with high or low burden of PACs, but this effect was not related to the risk of new stroke or new AF. Type IA, type IC, and type III antiarrhythmic agents ( table 1) can diminish the frequency of PACs in the symptomatic patient. These drugs may also suppress PACs that precipitate or trigger other supraventricular arrhythmias including AF, atrial flutter, atrioventricular nodal reentrant tachycardia, or atrioventricular reentrant tachycardia. Although controlled studies have not been performed with many of these agents, several reports describe their successful use [41-43]. However, administration of these agents must be balanced with the risk of proarrhythmia. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations", section on 'Proarrhythmia' and "Major side effects of class I antiarrhythmic drugs".) By comparison, digoxin, calcium channel blockers, and type IB antiarrhythmic agents have not been clearly shown to be beneficial in patients with symptomatic PACs. Catheter ablation When PACs are symptomatic and documented to trigger AF, they may be a target for catheter ablation, particularly in patients with concern for cardiomyopathy due to frequent PACs or those with persistent PACs and symptoms in spite of medical therapy. (See "Atrial fibrillation: Catheter ablation".) https://www.uptodate.com/contents/supraventricular-premature-beats/print 10/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate PACs arising from the pulmonary veins may be treated by pulmonary vein isolation. PACs of non- pulmonary vein origin may also be managed by ablation guided by electroanatomic mapping techniques [44-47]. Successful pulmonary vein isolation procedures in patients with paroxysmal AF and high trigger burden (approximately 500 PACs/h) not only reduce the trigger burden but also increase the PAC coupling interval, suggesting that shorter coupled PACs originate preferentially from the pulmonary veins, which has been considered a reflection of the pulmonary veins' abbreviated refractoriness in patients with AF [48-50]. PROGNOSIS The prognosis related to PACs depends on the presence of any underlying cardiovascular pathology. However, the presence of PACs in populations of apparently healthy persons appears to be associated with a greater risk of cardiovascular morbidity and mortality. Cardiovascular mortality Frequent PACs have been associated with greater risk of cardiovascular mortality [51-55]. Among 7692 healthy participants with no history of myocardial infarction, stroke, AF, or atrial flutter enrolled in the prospective Japanese NIPPON DATA 90 cohort and followed for an average of 14 years, only 64 persons (0.8 percent) had one or more PACs on a screening 12-lead ECG at enrollment [53]. However, the presence of PACs was an independent predictor for cardiovascular (CV) deaths (hazard ratio [HR] 2.03, 95% CI 1.12-3.66). Among 7504 healthy participants in the NHANES study without known CVD who were followed for up to 18 years, 89 persons (1.2 percent) had one or more PACs on a screening 12-lead ECG [54]. As seen in the Japanese study, the presence of PACs was associated with higher CV mortality (HR 1.78, 95% CI 1.26-2.44) as well as higher total mortality (HR 1.41, 95% CI 1.08-1.80). Among 5371 consecutive Taiwanese patients without AF or a permanent pacemaker (PPM) at baseline who underwent 24-hour Holter monitoring, an PAC burden >76 beats per day was an independent predictor of mortality (HR 1.4, 95% CI 1.2-1.6), cardiovascular hospitalization (HR 1.3; 95% CI 1.1-1.5), new-onset AF (HR 1.8, 95% CI 1.4- 2.2), and PPM implantation (HR 2.8, 95% CI 1.9-4.2) over a mean follow-up of 10 years [55]. A cohort study examined the distribution of PAC burden and its relationship to all-cause mortality and CV death in 15,893 persons [56]. PAC burden increased with age with no https://www.uptodate.com/contents/supraventricular-premature-beats/print 11/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate apparent sex difference. Multivariate analysis found that PAC burden was associated th st with the risk of all-cause mortality (4 versus 1 quartile, adjusted HR 1.67) and CV death (HR 1.12 per ln PAC increase). In subgroup analyses, the risk of high PAC burden ( 100 PACs/24 h) was consistent across the overall cohort and prespecified subgroups. Similar findings, though with a less magnitude of risk, have been seen in other smaller cohorts of patients who were evaluated with 24-hour Holter monitoring and who were stratified based on total numbers of PACs in 24 hours [51,52]. AF Frequent PACs or increased PAC burden may predict new or undiagnosed AF and adverse cardiovascular events [51,52,55,57-65]. As examples: In a single-center cohort of 428 patients without AF or structural heart disease who were referred for 24-hour Holter monitoring to evaluate palpitations, dizziness, or syncope, 107 (25 percent) had frequent PACs (number of PACs at the top quartile, ie, >100 PACs/day) [51]. After a mean of 6.1 years of follow-up, significantly more patients with frequent PACs developed AF (31 patients [29 percent] compared with 29 patients [9 percent] with less frequent PACs). In a subset of the prospective Cardiovascular Health Study, 1260 adults without prevalent AF who enrolled between 1989 and 1990 underwent 24-hour Holter monitoring and were followed for 15 years. Using the Framingham AF risk algorithm, doubling of the hourly PAC count was associated with a significant increase in AF risk (HR 1.17, 95% CI 1.13-1.22) [52]. In a Japanese cohort of 63,197 persons without known CVD at baseline who were followed for an average of 14 years, the presence of PACs on baseline ECG was associated with a significantly higher likelihood of developing AF in both men (HR 4.9, 95% CI 3.6-6.6) and women (HR 3.9, 95% CI 2.7-5.6) [59]. In a retrospective cohort, which analyzed Holter recordings from 1357 veterans free of AF at baseline (mean age 64 years; 93 percent men), with a median follow-up of 7.5 years, AF was significantly more common in patients with frequent ( 100/day) PACs compared with patients with infrequent (<100/day) PACs (22 versus 6 percent, adjusted HR 3.0, 95% CI 1.9-4.8) [60]. In the STROKESTOP I mass-screening study for AF in 75- and 76-year-old persons in Sweden, over a median follow-up of 4.2 years, of the 6100 participants, 15 percent (n = 894) had arrhythmia, with frequent PACs being the most common (11.6 percent; n = 709) and irregular supraventricular tachycardias being more common than regular [66]. https://www.uptodate.com/contents/supraventricular-premature-beats/print 12/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Persons with the most AF-similar supraventricular tachycardias, irregular and lacking p waves (1.6 percent; n = 97), had the highest risk of developing AF (HR 4.3) and an increased risk of death (HR 2.0). Thus, progression of atrial arrhythmias from PACs to more AF-like episodes was associated with development of AF, suggesting a possible role for screening for AF in individuals with frequent supraventricular activity. Frequent PACs during exercise (>5 beats per stage) provided prognostic information with a higher incidence (5.5 percent) of new-onset AF/atrial flutter at follow-up (approximately one year) in 128 patients compared with 870 patients with no frequent PACs (0.6 percent AF/atrial flutter incidence) [67]. Treadmill-induced frequent PACs, chronotropic incompetence, and palpitation as a reason for treadmill testing were independent risk factors that predicted new-onset AF/atrial flutter. Higher numbers of PACs have also been shown to be a predictor of subclinical AF in patients with cryptogenic stroke as well as a predictor of late AF recurrence following pulmonary vein isolation for AF [62,63]. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)" and "Atrial fibrillation: Catheter ablation".) In a meta-analysis of 12 studies with a total of 109,689 subjects with frequent (n = 9217) and non-frequent (n = 100,472) PACs, patients with frequent PACs, however variably defined, had an increased risk of new onset AF (pooled risk ratio 2.8, 95% CI 2.1-3.7) [68]. In a study of 4331 participants with hypertension and receiving treatment, AF risk associated with PACs could potentially be decreased by treatment with angiotensin- II receptor blockers (ARBs) and statins, along with lowering blood pressure and managing diabetes [69]. Stroke There are mixed data on the risk of stroke in patients with PACs, with some studies suggesting a higher risk of stroke in patients with frequent PACs [27,28,70,71] while others have found no such increase in risk [72]. Because not all of the studies presented data on the development of AF during follow-up, and AF is definitively associated with an increased risk of stroke, the impact of frequent PACs on stroke risk remains uncertain. However, in patients with acute stroke, the presence of numerous PACs and short runs of supraventricular tachycardia have been associated with a greater risk for subsequently developing AF, which might potentially explain the etiology of the stroke [73-75]. Furthermore, the concept that atrial myopathy might play a role and be responsible for a stroke in some patients independently from AF has also been advanced, and frequent or an https://www.uptodate.com/contents/supraventricular-premature-beats/print 13/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate excessive burden of PACs ( 30 PACs/h daily or any runs of 20 PACs) might constitute an ECG marker for such a myopathy [26,27]. A meta-analysis of 12 studies examining whether PACs can predict AF in 2340 ischemic stroke patients (mean age 66 years) indicated that PACs were highly associated with AF occurrence in stroke (pooled odds ratio [OR] 4.16, 95% CI 3.06-5.65) and cryptogenic stroke patients (pooled OR 3.72, 95% CI 2.66-5.20) [76]. Subgroup analysis showed that PAC presence (pooled OR 3.72, 95% 1.65-8.36) and frequent PACs (pooled OR 5.12, 95% CI 3.12- 8.41) were correlated with stroke in AF patients. Frequent PACs were identified as the risks for asymptomatic AF (OR 6.18, 95% CI 3.23-11.83) and future AF occurrence (OR 3.71, 95% CI 2.62-5.26) in stroke patients. Sudden cardiac death Isolated PACs have not been associated with sudden death (SCD). Among 14,574 patients in the ARIC study who had a 12-lead ECG and a two-minute 3-lead rhythm strip at baseline, there was no significant increase in the risk of SCD among persons with PACs (HR 1.15, 95% CI 0.56-2.39), although when PACs occur concurrently in individuals with VPBs, the risk of SCD was higher (HR 6.39 compared with patients with neither PACs nor VPBs; 95% CI 2.58-15.84) [77]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Catheter ablation of arrhythmias" and "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Definition Supraventricular premature beats represent premature activation of the atria from a site other than the sinus node. The vast majority originate from the atria (premature atrial complexes [PACs]) though some originate from the atrioventricular node (called junctional premature beats [JPBs]). (See 'Introduction' above.) Prevalence PACs are fairly ubiquitous, occurring commonly in both young and older adult subjects and in those with and without significant heart disease. JPBs occur less commonly than both PACs and premature ventricular complexes/contractions (PVCs) and are rarely seen in clinical practice. (See 'Prevalence' above.) https://www.uptodate.com/contents/supraventricular-premature-beats/print 14/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Symptoms and signs PACs and JPBs are asymptomatic in the vast majority of patients but can cause symptoms such as a sensation of "skipping" or palpitations. The most characteristic physical exam finding is an irregular pulse. (See 'Clinical manifestations' above.) Diagnostic evaluation The evaluation of patients with suspected PACs (or JPBs) should focus on documenting their presence or absence with an ECG or ambulatory cardiac monitoring. PACs These are observed on the surface ECG as a P wave that occurs earlier than the anticipated next sinus P wave and has a different morphology (eg, inverted or biphasic) from the sinus P wave ( waveform 1 and waveform 2 and waveform 3 and waveform 5). Every lead should be examined as subtle differences in morphology may be present. Often the PR interval is different from that during sinus rhythm. (See 'ECG findings with APBs' above.) JPBs These are observed on the ECG as a QRS complex with no preceding P wave or with a P wave occurring too soon before the QRS to be considered to be conducted through the AV node ( waveform 4). (See 'ECG findings with JPBs' above.) Once PACs (or JPBs ( waveform 4)) have been identified, additional evaluation should be performed to identify any underlying structural heart disease. (See 'Evaluation' above.) Management In persons with frequent PACs or JPBs, management is based on the presence or absence of symptoms and/or underlying structural heart disease. (See 'Treatment' above.) Asymptomatic PACs or JPBs No therapy is required for PACs or JPBs in the asymptomatic individual. Symptomatic PACs For patients with symptomatic PACs, reassurance regarding the benign nature of PACs is frequently adequate to alleviate symptoms. In addition, patients should be counseled to avoid or minimize potential PAC precipitants (eg, smoking, alcohol intake, stress, caffeine intake, obesity, poor physical activity). For patients with persistent symptomatic PACs despite efforts to minimize potential PAC precipitants we suggest a trial of medical therapy with a beta blocker (eg, oral metoprolol 25 mg twice daily with uptitration as needed for effect) (Grade 2C). When PACs are symptomatic and documented to trigger atrial fibrillation (AF) or persist despite medical therapy, they may be a target for catheter ablation, particularly in https://www.uptodate.com/contents/supraventricular-premature-beats/print 15/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate patients with concern for cardiomyopathy due to frequent PACs. (See 'Catheter ablation' above.) Symptomatic JPBs Reassurance of the benign nature of this rhythm abnormality may alleviate symptoms. For patients with persistent, limiting symptoms due to JPBs, therapy is similar to that for PACs, with beta blockers as the primary option. ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Bernard Gersh, MB, |
more AF-like episodes was associated with development of AF, suggesting a possible role for screening for AF in individuals with frequent supraventricular activity. Frequent PACs during exercise (>5 beats per stage) provided prognostic information with a higher incidence (5.5 percent) of new-onset AF/atrial flutter at follow-up (approximately one year) in 128 patients compared with 870 patients with no frequent PACs (0.6 percent AF/atrial flutter incidence) [67]. Treadmill-induced frequent PACs, chronotropic incompetence, and palpitation as a reason for treadmill testing were independent risk factors that predicted new-onset AF/atrial flutter. Higher numbers of PACs have also been shown to be a predictor of subclinical AF in patients with cryptogenic stroke as well as a predictor of late AF recurrence following pulmonary vein isolation for AF [62,63]. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)" and "Atrial fibrillation: Catheter ablation".) In a meta-analysis of 12 studies with a total of 109,689 subjects with frequent (n = 9217) and non-frequent (n = 100,472) PACs, patients with frequent PACs, however variably defined, had an increased risk of new onset AF (pooled risk ratio 2.8, 95% CI 2.1-3.7) [68]. In a study of 4331 participants with hypertension and receiving treatment, AF risk associated with PACs could potentially be decreased by treatment with angiotensin- II receptor blockers (ARBs) and statins, along with lowering blood pressure and managing diabetes [69]. Stroke There are mixed data on the risk of stroke in patients with PACs, with some studies suggesting a higher risk of stroke in patients with frequent PACs [27,28,70,71] while others have found no such increase in risk [72]. Because not all of the studies presented data on the development of AF during follow-up, and AF is definitively associated with an increased risk of stroke, the impact of frequent PACs on stroke risk remains uncertain. However, in patients with acute stroke, the presence of numerous PACs and short runs of supraventricular tachycardia have been associated with a greater risk for subsequently developing AF, which might potentially explain the etiology of the stroke [73-75]. Furthermore, the concept that atrial myopathy might play a role and be responsible for a stroke in some patients independently from AF has also been advanced, and frequent or an https://www.uptodate.com/contents/supraventricular-premature-beats/print 13/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate excessive burden of PACs ( 30 PACs/h daily or any runs of 20 PACs) might constitute an ECG marker for such a myopathy [26,27]. A meta-analysis of 12 studies examining whether PACs can predict AF in 2340 ischemic stroke patients (mean age 66 years) indicated that PACs were highly associated with AF occurrence in stroke (pooled odds ratio [OR] 4.16, 95% CI 3.06-5.65) and cryptogenic stroke patients (pooled OR 3.72, 95% CI 2.66-5.20) [76]. Subgroup analysis showed that PAC presence (pooled OR 3.72, 95% 1.65-8.36) and frequent PACs (pooled OR 5.12, 95% CI 3.12- 8.41) were correlated with stroke in AF patients. Frequent PACs were identified as the risks for asymptomatic AF (OR 6.18, 95% CI 3.23-11.83) and future AF occurrence (OR 3.71, 95% CI 2.62-5.26) in stroke patients. Sudden cardiac death Isolated PACs have not been associated with sudden death (SCD). Among 14,574 patients in the ARIC study who had a 12-lead ECG and a two-minute 3-lead rhythm strip at baseline, there was no significant increase in the risk of SCD among persons with PACs (HR 1.15, 95% CI 0.56-2.39), although when PACs occur concurrently in individuals with VPBs, the risk of SCD was higher (HR 6.39 compared with patients with neither PACs nor VPBs; 95% CI 2.58-15.84) [77]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Catheter ablation of arrhythmias" and "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Definition Supraventricular premature beats represent premature activation of the atria from a site other than the sinus node. The vast majority originate from the atria (premature atrial complexes [PACs]) though some originate from the atrioventricular node (called junctional premature beats [JPBs]). (See 'Introduction' above.) Prevalence PACs are fairly ubiquitous, occurring commonly in both young and older adult subjects and in those with and without significant heart disease. JPBs occur less commonly than both PACs and premature ventricular complexes/contractions (PVCs) and are rarely seen in clinical practice. (See 'Prevalence' above.) https://www.uptodate.com/contents/supraventricular-premature-beats/print 14/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Symptoms and signs PACs and JPBs are asymptomatic in the vast majority of patients but can cause symptoms such as a sensation of "skipping" or palpitations. The most characteristic physical exam finding is an irregular pulse. (See 'Clinical manifestations' above.) Diagnostic evaluation The evaluation of patients with suspected PACs (or JPBs) should focus on documenting their presence or absence with an ECG or ambulatory cardiac monitoring. PACs These are observed on the surface ECG as a P wave that occurs earlier than the anticipated next sinus P wave and has a different morphology (eg, inverted or biphasic) from the sinus P wave ( waveform 1 and waveform 2 and waveform 3 and waveform 5). Every lead should be examined as subtle differences in morphology may be present. Often the PR interval is different from that during sinus rhythm. (See 'ECG findings with APBs' above.) JPBs These are observed on the ECG as a QRS complex with no preceding P wave or with a P wave occurring too soon before the QRS to be considered to be conducted through the AV node ( waveform 4). (See 'ECG findings with JPBs' above.) Once PACs (or JPBs ( waveform 4)) have been identified, additional evaluation should be performed to identify any underlying structural heart disease. (See 'Evaluation' above.) Management In persons with frequent PACs or JPBs, management is based on the presence or absence of symptoms and/or underlying structural heart disease. (See 'Treatment' above.) Asymptomatic PACs or JPBs No therapy is required for PACs or JPBs in the asymptomatic individual. Symptomatic PACs For patients with symptomatic PACs, reassurance regarding the benign nature of PACs is frequently adequate to alleviate symptoms. In addition, patients should be counseled to avoid or minimize potential PAC precipitants (eg, smoking, alcohol intake, stress, caffeine intake, obesity, poor physical activity). For patients with persistent symptomatic PACs despite efforts to minimize potential PAC precipitants we suggest a trial of medical therapy with a beta blocker (eg, oral metoprolol 25 mg twice daily with uptitration as needed for effect) (Grade 2C). When PACs are symptomatic and documented to trigger atrial fibrillation (AF) or persist despite medical therapy, they may be a target for catheter ablation, particularly in https://www.uptodate.com/contents/supraventricular-premature-beats/print 15/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate patients with concern for cardiomyopathy due to frequent PACs. (See 'Catheter ablation' above.) Symptomatic JPBs Reassurance of the benign nature of this rhythm abnormality may alleviate symptoms. For patients with persistent, limiting symptoms due to JPBs, therapy is similar to that for PACs, with beta blockers as the primary option. ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Bernard Gersh, MB, ChB, DPhil, FRCP, MACC, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Conen D, Adam M, Roche F, et al. Premature atrial contractions in the general population: frequency and risk factors. Circulation 2012; 126:2302. 2. Southall DP, Richards J, Mitchell P, et al. Study of cardiac rhythm in healthy newborn infants. Br Heart J 1980; 43:14. 3. Folarin VA, Fitzsimmons PJ, Kruyer WB. Holter monitor findings in asymptomatic male military aviators without structural heart disease. Aviat Space Environ Med 2001; 72:836. 4. Rossi A. Twenty-four-hour electrocardiographic study in the active very elderly. Cardiology 1987; 74:159. 5. Larsen BS, Kumarathurai P, Nielsen OW, Sajadieh A. The circadian variation of premature atrial contractions. Europace 2016; 18:1573. 6. WALLACE AG, DAGGETT WM. RE-EXCITATION OF THE ATRIUM. "THE ECHO PHENOMENON". Am Heart J 1964; 68:661. 7. DE CARVALHO AP, DE MELLO WC, HOFFMAN BF. Electrophysiological evidence for specialized fiber types in rabbit atrium. Am J Physiol 1959; 196:483. 8. Wit AL, Cranefield PF. Triggered and automatic activity in the canine coronary sinus. Circ Res 1977; 41:434. 9. KILLIP T, GAULT JH. MODE OF ONSET OF ATRIAL FIBRILLATION IN MAN. Am Heart J 1965; 70:172. 10. Vincenti A, Brambilla R, Fumagalli MG, et al. Onset mechanism of paroxysmal atrial fibrillation detected by ambulatory Holter monitoring. Europace 2006; 8:204. https://www.uptodate.com/contents/supraventricular-premature-beats/print 16/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate 11. Davis MJ, Hockings BE, el Dessouky MA, et al. Cigarette smoking and ventricular arrhythmia in coronary heart disease. Am J Cardiol 1984; 54:282. 12. Ettinger PO, Wu CF, De La Cruz C Jr, et al. Arrhythmias and the "Holiday Heart": alcohol- associated cardiac rhythm disorders. Am Heart J 1978; 95:555. 13. Dobmeyer DJ, Stine RA, Leier CV, et al. The arrhythmogenic effects of caffeine in human beings. N Engl J Med 1983; 308:814. 14. Enriquez A, Frankel DS. Arrhythmogenic effects of energy drinks. J Cardiovasc Electrophysiol 2017; 28:711. 15. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and Arrhythmias: Time to Grind the Data. JACC Clin Electrophysiol 2018; 4:425. 16. Dixit S, Stein PK, Dewland TA, et al. Consumption of Caffeinated Products and Cardiac Ectopy. J Am Heart Assoc 2016; 5. 17. Bittar G, Friedman HS. The arrhythmogenicity of theophylline. A multivariate analysis of clinical determinants. Chest 1991; 99:1415. 18. Sessler CN, Cohen MD. Cardiac arrhythmias during theophylline toxicity. A prospective continuous electrocardiographic study. Chest 1990; 98:672. 19. Krishnappa D, Wang W, Rooney MR, et al. Life's Simple 7 cardiovascular health score and premature atrial contractions: The atherosclerosis risk in communities (ARIC) study. Int J Cardiol 2021; 332:70. 20. Rechavia E, Strasberg B, Mager A, et al. The incidence of atrial arrhythmias during inferior wall myocardial infarction with and without right ventricular involvement. Am Heart J 1992; 124:387. 21. Zoni Berisso M, Ferroni A, De Caro E, et al. Clinical significance of supraventricular tachyarrhythmias after acute myocardial infarction. Eur Heart J 1986; 7:743. 22. Bunch TJ, Chandrasekaran K, Gersh BJ, et al. The prognostic significance of exercise-induced atrial arrhythmias. J Am Coll Cardiol 2004; 43:1236. 23. Ramsdale DR, Arumugam N, Singh SS, et al. Holter monitoring in patients with mitral stenosis and sinus rhythm. Eur Heart J 1987; 8:164. 24. Lazzeroni E, Domenicucci S, Finardi A, et al. Severity of arrhythmias and extent of hypertrophy in hypertrophic cardiomyopathy. Am Heart J 1989; 118:734. 25. Shen MJ, Arora R, Jalife J. Atrial Myopathy. JACC Basic Transl Sci 2019; 4:640. 26. Sajeev JK, Kalman JM, Dewey H, et al. The Atrium and Embolic Stroke: Myopathy Not Atrial Fibrillation as the Requisite Determinant? JACC Clin Electrophysiol 2020; 6:251. https://www.uptodate.com/contents/supraventricular-premature-beats/print 17/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate 27. Larsen BS, Kumarathurai P, Falkenberg J, et al. Excessive Atrial Ectopy and Short Atrial Runs Increase the Risk of Stroke Beyond Incident Atrial Fibrillation. J Am Coll Cardiol 2015; 66:232. 28. Sajeev JK, Koshy AN, Dewey H, et al. Association between excessive premature atrial complexes and cryptogenic stroke: results of a case-control study. BMJ Open 2019; 9:e029164. 29. Manolis AS, Manolis AA, Manolis TA, Melita H. Cardiac amyloidosis: An underdiagnosed/underappreciated disease. Eur J Intern Med 2019; 67:1. 30. John AG, Hirsch GA, Stoddard MF. Frequent premature atrial contractions impair left atrial contractile function and promote adverse left atrial remodeling. Echocardiography 2018; 35:1310. 31. Kusunoki Y, Nakamura T, Hattori K, et al. Atrial and Ventricular Arrhythmia-Associated Factors in Stable Patients with Chronic Obstructive Pulmonary Disease. Respiration 2016; 91:34. 32. Bennett MA, Pentecost BL. The pattern of onset and spontaneous cessation of atrial fibrillation in man. Circulation 1970; 41:981. 33. Durrer D, Schoo L, Schuilenburg RM, Wellens HJ. The role of premature beats in the initiation and the termination of supraventricular tachycardia in the Wolff-Parkinson-White syndrome. Circulation 1967; 36:644. 34. Nallasivan M, Appel RA, Welch WJ, Bauernfeind RA. Ventricular tachycardia due to bundle branch reentry: induction by spontaneous atrial premature beats. Am Heart J 1988; 116:552. 35. Berman ND. Ventricular tachycardia initiated by both normally and aberrantly conducted atrial premature beats. Pacing Clin Electrophysiol 1980; 3:519. 36. Vervueren PL, Delmas C, Berry M, et al. Reversal of Dilated Cardiomyopathy After Successful Radio-Frequency Ablation of Frequent Atrial Premature Beats, a New Cause for Arrhythmia- Induced Cardiomyopathy. J Atr Fibrillation 2012; 5:627. 37. MOE GK, MENDEZ C, HAN J. ABERRANT A-V IMPULSE PROPAGATION IN THE DOG HEART: A STUDY OF FUNCTIONAL BUNDLE BRANCH BLOCK. Circ Res 1965; 16:261. 38. Batsford WP, Akhtar M, Caracta AR, et al. Effect of atrial stimulation site on the electrophysiological properties of the atrioventricular node in man. Circulation 1974; 50:283. 39. Carbone V, Marafioti V, Oreto G. An unusual narrow QRS complex tachycardia: what is the mechanism? Ann Noninvasive Electrocardiol 2015; 20:94. 40. Huang TC, Lee PT, Huang MS, et al. The Beneficial Effects of Beta Blockers on the Long-Term Prognosis of Patients With Premature Atrial Complexes. Front Cardiovasc Med 2022; https://www.uptodate.com/contents/supraventricular-premature-beats/print 18/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate 9:806743. 41. Arif M, Laidlaw JC, Oshrain C, et al. A randomized, double-blind, parallel group comparison of disopyramide phosphate and quinidine in patients with cardiac arrhythmias. Angiology 1983; 34:393. 42. Carrasco HA, Vicu a AV, Molina C, et al. Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage. Int J Cardiol 1985; 9:425. 43. Coumel P, Leclercq JF, Assayag P. European experience with the antiarrhythmic efficacy of propafenone for supraventricular and ventricular arrhythmias. Am J Cardiol 1984; 54:60D. 44. Ha ssaguerre M, Ja s P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339:659. 45. Ha ssaguerre M, Shah DC, Ja s P, et al. Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation 2000; 102:2463. 46. Oral H, Knight BP, Tada H, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation 2002; 105:1077. 47. Yamada T, Murakami Y, Okada T, et al. Electroanatomic mapping in the catheter ablation of premature atrial contractions with a non-pulmonary vein origin. Europace 2008; 10:1320. 48. Yamane T, Date T, Kanzaki Y, et al. Behavior of atrial ectopic beats before and after pulmonary vein isolation in patients with atrial fibrillation: a reduction in the number and arrhythmogenicity of ectopic firings. Heart Rhythm 2006; 3:1421. 49. Brooks AG, Rangnekar G, Ganesan AN, et al. Characteristics of ectopic triggers associated with paroxysmal and persistent atrial fibrillation: evidence for a changing role. Heart Rhythm 2012; 9:1367. 50. Ja s P, Hocini M, Macle L, et al. Distinctive electrophysiological properties of pulmonary veins in patients with atrial fibrillation. Circulation 2002; 106:2479. 51. Chong BH, Pong V, Lam KF, et al. Frequent premature atrial complexes predict new occurrence of atrial fibrillation and adverse cardiovascular events. Europace 2012; 14:942. 52. Dewland TA, Vittinghoff E, Mandyam MC, et al. Atrial ectopy as a predictor of incident atrial fibrillation: a cohort study. Ann Intern Med 2013; 159:721. 53. Inohara T, Kohsaka S, Okamura T, et al. Long-term outcome of healthy participants with atrial premature complex: a 15-year follow-up of the NIPPON DATA 90 cohort. PLoS One 2013; 8:e80853. 54. Qureshi W, Shah AJ, Salahuddin T, Soliman EZ. Long-term mortality risk in individuals with atrial or ventricular premature complexes (results from the Third National Health and https://www.uptodate.com/contents/supraventricular-premature-beats/print 19/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Nutrition Examination Survey). Am J Cardiol 2014; 114:59. 55. Lin CY, Lin YJ, Chen YY, et al. Prognostic Significance of Premature Atrial Complexes Burden in Prediction of Long-Term Outcome. J Am Heart Assoc 2015; 4:e002192. 56. Huang TC, Lee PT, Huang MS, et al. Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome. Sci Rep 2021; 11:12198. 57. Suzuki S, Sagara K, Otsuka T, et al. Usefulness of frequent supraventricular extrasystoles and a high CHADS2 score to predict first-time appearance of atrial fibrillation. Am J Cardiol 2013; 111:1602. 58. Hashimoto M, Yamauchi A, Inoue S. Premature atrial contraction as a predictor of postoperative atrial fibrillation. Asian Cardiovasc Thorac Ann 2015; 23:153. 59. Murakoshi N, Xu D, Sairenchi T, et al. Prognostic impact of supraventricular premature complexes in community-based health checkups: the Ibaraki Prefectural Health Study. Eur Heart J 2015; 36:170. 60. Acharya T, Tringali S, Bhullar M, et al. Frequent Atrial Premature Complexes and Their Association With Risk of Atrial Fibrillation. Am J Cardiol 2015; 116:1852. 61. Alhede C, Lauridsen TK, Johannessen A, et al. The impact of supraventricular ectopic complexes in different age groups and risk of recurrent atrial fibrillation after antiarrhythmic medication or catheter ablation. Int J Cardiol 2018; 250:122. 62. Gladstone DJ, Dorian P, Spring M, et al. Atrial premature beats predict atrial fibrillation in cryptogenic stroke: results from the EMBRACE trial. Stroke 2015; 46:936. 63. Gang UJ, Nalliah CJ, Lim TW, et al. Atrial ectopy predicts late recurrence of atrial fibrillation after pulmonary vein isolation. Circ Arrhythm Electrophysiol 2015; 8:569. 64. O'Neal WT, Kamel H, Judd SE, et al. Usefulness of Atrial Premature Complexes on Routine Electrocardiogram to Determine the Risk of Atrial Fibrillation (from the REGARDS Study). Am J Cardiol 2017; 120:782. 65. Sasaki K, Nakajima I, Higuma T, et al. Revisit to the Prognostic Value of Premature Atrial Contraction Burden in 24-h Holter Electrocardiography for Predicting Undiagnosed Atrial Fibrillation - A Propensity Score-Matched Study. Circ J 2021; 85:1265. 66. Hygrell T, Stridh M, Friberg L, Svennberg E. Prognostic Implications of Supraventricular Arrhythmias. Am J Cardiol 2021; 151:57. 67. Hwang JK, Gwag HB, Park SJ, et al. Frequent atrial premature complexes during exercise: A potent predictor of atrial fibrillation. Clin Cardiol 2018; 41:458. 68. Prasitlumkum N, Rattanawong P, Limpruttidham N, et al. Frequent premature atrial complexes as a predictor of atrial fibrillation: Systematic review and meta-analysis. J https://www.uptodate.com/contents/supraventricular-premature-beats/print 20/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Electrocardiol 2018; 51:760. 69. Soliman EZ, Howard G, Judd S, et al. Factors Modifying the Risk of Atrial Fibrillation Associated With Atrial Premature Complexes in Patients With Hypertension. Am J Cardiol 2020; 125:1324. 70. Engstrom G, Hedblad B, Juul-Moller S, et al. Cardiac arrhythmias and stroke: increased risk in men with high frequency of atrial ectopic beats. Stroke 2001; 31:2925. 71. Pinho J, Braga CG, Rocha S, et al. Atrial ectopic activity in cryptogenic ischemic stroke and TIA: a risk factor for recurrence. J Stroke Cerebrovasc Dis 2015; 24:507. 72. Ofoma U, He F, Shaffer ML, et al. Premature cardiac contractions and risk of incident ischemic stroke. J Am Heart Assoc 2012; 1:e002519. 73. Kochh user S, Dechering DG, Dittrich R, et al. Supraventricular premature beats and short atrial runs predict atrial fibrillation in continuously monitored patients with cryptogenic stroke. Stroke 2014; 45:884. 74. Weber-Kr ger M, Gr schel K, Mende M, et al. Excessive supraventricular ectopic activity is indicative of paroxysmal atrial fibrillation in patients with cerebral ischemia. PLoS One 2013; 8:e67602. 75. Wallmann D, T ller D, Wustmann K, et al. Frequent atrial premature beats predict paroxysmal atrial fibrillation in stroke patients: an opportunity for a new diagnostic strategy. Stroke 2007; 38:2292. 76. Tao Y, Xu J, Gong X, et al. Premature atrial complexes can predict atrial fibrillation in ischemic stroke patients: A systematic review and meta-analysis. Pacing Clin Electrophysiol 2021; 44:1599. 77. Cheriyath P, He F, Peters I, et al. Relation of atrial and/or ventricular premature complexes on a two-minute rhythm strip to the risk of sudden cardiac death (the Atherosclerosis Risk in Communities [ARIC] study). Am J Cardiol 2011; 107:151. Topic 932 Version 36.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 21/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate GRAPHICS Single-lead electrocardiogram (ECG) showing atrial bigeminy and blocked atrial premature beats (APBs) The single channel electrocardiographic recording shows a sinus P wave (P) followed by an atrial premature beat (P') in a repeating pattern, termed atrial bigeminy. The P' does not result in ventricular activation since conduction is blocked within the atrioventricular node (blocked atrial premature beat). Graphic 72122 Version 3.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 22/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Electrocardiogram (ECG) showing atrial premature beats (APBs) that are norma conducted and aberrantly conducted APBs may be normally (asterisk) or aberrantly conducted (double asterisk; usually RBBB aberrancy), and may different P wave morphology and axis and variable PR intervals. APBs: atrial premature beats; RBBB: right bundle branch block. Graphic 96438 Version 2.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 23/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Electrocardiogram (ECG) strips showing a blocked atrial premature beat (APB) Simultaneous electrocardiographic leads V1, II, and V5 show an atrial premature beat (red arrow) that is blocked within the atrioventricular node and not conducted to the ventricle. The P wave of the atrial premature beats alters the terminal portion of preceding T wave, seen in leads V1 and II, but not in lead V5. Graphic 77154 Version 3.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 24/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Electrocardiogram (ECG) strips showing junctional premature beats Three simultaneous electrocardiographic surface leads V1, II, and V5 show a junctional premature beat (asterisk). In panel A, there is a sinus P wave seen in lead II just prior to the junctional premature beat, which alters its initial deflection (arrow). The junctional premature beat has a QRS morphology that is identical to that of the sinus beat. In panel B, a sinus P wave is seen immediately after the junctional premature beat in lead II (arrow). The junctional premature beat has a QRS morphology which is slightly different from the sinus QRS complex. Graphic 62336 Version 3.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 25/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Electrocardiogram strips showing an atrial premature beat, followed by a noncompensatory pause Simultaneous electrocardiographic recording from surface leads V1, II, and V5 shows an atrial premature beat (P'), which is conducted with aberration. The P wave is different from that of the sinus beat and the PR interval is longer,due to delayed conduction in the atrioventricular node. A noncompensatory pause is present (ie, the interval measured from the sinus beat before and after the atrial premature beat is less than 2 sinus RR intervals). Graphic 66489 Version 5.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 26/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Electrophysiology (EP) study showing surface and intracardiac electrocardiogram tracings of an atrial premature beat (APB) Simultaneous surface electrocardiographic leads I, II, V1 and intracardiac recordings from the high right atrium (HRA), His bundle (HBE), proximal (CSp) and distal (CSd) coronary sinus, and right ventricular apex (RVA). During sinus rhythm, the impulse originates in the HRA and is then conducted through the HBE, CSp, CSd, and ultimately the RVA (blue line 1). An atrial premature beat (APB), denoted by the red asterisk, originates in the CSp (blue line 2) and is conducted retrogradely to the HRA and antegradely to the CSd and RVA. The APB has a longer AH interval compared with sinus rhythm and is associated with a full compensatory pause. Graphic 70505 Version 4.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 27/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/supraventricular-premature-beats/print 28/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/supraventricular-premature-beats/print 29/30 7/6/23, 1:51 PM Supraventricular premature beats - UpToDate Contributor Disclosures Antonis S Manolis, MD No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/supraventricular-premature-beats/print 30/30 |
7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Carotid sinus hypersensitivity and carotid sinus syndrome : David Benditt, MD : Peter Kowey, MD, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 13, 2022. INTRODUCTION Carotid sinus hypersensitivity (CSH) manifests as a greater than normal fall in heart rate and/or blood pressure in response to stimulation of the carotid artery baroreceptors. Carotid sinus syndrome (CSS) is a type of reflex syncope or near-syncope in which symptoms (eg, syncope, lightheadedness) are caused by CSH manifesting during daily activities. CSH and CSS will be reviewed here. Other types of reflex syncope, including vasovagal syncope, as well as the pathogenesis, etiology, and evaluation of syncope, are discussed separately. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation" and "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".) DEFINITIONS Carotid sinus hypersensitivity CSH is a clinical finding of a greater than normal fall in heart rate (HR) and/or systemic blood pressure (BP) in response to stimulation of the carotid baroreceptors, as tested by carotid sinus massage (CSM). Criteria for CSH vary and are discussed below. (See 'Test interpretation' below.) CSH itself is not a clinical syndrome. It commonly occurs in individuals with no history of symptoms such as syncope (most often in older males). In individuals with a prior history of syncope or presyncope, identifying CSH by CSM is a key element in the diagnosis of CSS but CSH alone is not diagnostic of CSS. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 1/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Carotid sinus syndrome CSS is a type of reflex syncope or near-syncope with symptoms (eg, syncope, lightheadedness) caused by CSH manifesting during activities of daily life that put pressure on the carotid sinus (eg, turning the neck, looking upward). When CSS manifests as syncope it is called carotid sinus syncope. (See 'Clinical manifestations' below.) PREVALENCE CSH is a commonly observed physical finding, but CSS is an uncommon cause of symptoms, accounting for approximately 1 percent of syncope cases [1]. CSS is almost entirely restricted to older (>65 year old) male patients. Older individuals and males are more likely to have an abnormal CSH response even if they do not have CSS [2-5]. The prevalence of CSH depends upon the diagnostic criteria utilized. CSH, identified by commonly used sensitive but nonspecific criteria (eg, asystole of 3 s), is commonly observed in older adults (39 percent in an unselected sample of older adults [mean age 71 years]) in a community practice [2]. CSH is commonly observed in individuals with no prior presyncope or syncope (eg, 20 percent [6] and 35 percent [2]), in unselected syncope patients (eg, 14 percent), and in patients with syncope unexplained by initial screening (eg, 49 percent [7]) [6-9]. PATHOPHYSIOLOGY The carotid baroreceptors, specialized tissues sensitive to mechanical pressure, are located bilaterally in the carotid sinuses at the base of the internal carotid arteries just above the bifurcation of the internal and external carotid arteries ( figure 1). These baroreceptors are physiologically important for blood pressure (BP) control and, to a lesser extent, heart rate (HR) control, acting through a reflex arc. The carotid sinus reflex arc is composed of: An afferent limb arising from mechanoreceptors in the internal carotid artery and terminating in the cardiovascular control centers in the vagal nucleus and the vasomotor center in the medulla. and An efferent limb with two components: Innervation of the sinoatrial and atrioventricular (AV) nodes via the vagus nerve and the parasympathetic ganglia. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 2/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Inhibition of sympathetic nervous tone to the heart and blood vessels. The site of the abnormality that causes the hypersensitive response in patients with CSH has not been definitively established. Several possible causes have been postulated, and several factors may be operative in any patient, such as: Increased responsiveness of the peripheral receptors. Increased responsiveness of the baroreceptor region due to comorbidities such as atherosclerotic vascular disease, nearby neck surgery, or irradiation that alters the receptor milieu. Abnormal proprioception responses in nearby neck muscles that modify the manner in which central sites interpret baroreceptor afferent signals. Increased responsiveness of midbrain reflex sites. CSS symptoms are deemed to result from CSH-induced excessive and inappropriate cardioinhibition (ie, slowing of HR) and/or vasodilation, yielding a drop in BP. Both cardioinhibition and vasodilation transiently diminish brain perfusion. (See 'Types of abnormal responses' below.) CLINICAL MANIFESTATIONS Patients with CSS may present with a variety of symptoms following carotid baroreceptor stimulation, but one or more of the following presentations are most common: Lightheadedness/presyncope Syncope Otherwise unexplained falls in older patients A careful medical history is required to develop a clinical suspicion of CSS. Although a clear relationship between neck movements and symptom episodes is rarely established, a history of syncope following accidental manipulation of the carotid sinuses should be sought. The index of suspicion for CSH is increased by a history of syncope in the setting of activities associated with possible pressure on the carotid sinus (eg, neck movement, fitting a tie, or shaving) and by presence of any of the following risk factors: older age, male sex, atherosclerotic disease, abnormalities of the structure of the neck (eg, prior neck surgery and/or irradiation), or tumors in the region of the carotid sinuses. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 3/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate DIAGNOSTIC EVALUATION Approach to diagnosis In a patient with possible or suspected CSS, the first step of the diagnostic evaluation is to perform an initial evaluation including a careful history to determine the circumstances (including any pressure on the neck) and characteristics associated with the presenting symptoms (eg, syncope, lightheadedness, or collapse). As CSS is one of many potential causes for syncope, near-syncope, or an unexplained fall, this initial evaluation enables exclusion of other possible causes of syncopal or nonsyncopal symptoms ( algorithm 1). An overview of the diagnostic approach to lightheadedness, near-syncope, and syncope in general is provided separately. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".) Along with careful exclusion of other possible causes of symptoms, the primary test for CSS is carotid sinus massage (CSM). When to perform CSM In patients over age 50 with syncope or presyncope of unknown etiology despite an initial evaluation ( algorithm 1) (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation"), we recommend performing CSM to evaluate for possible CSS. This recommendation is similar to those in major society guidelines that recommend CSM in patients with syncope with uncertain cause after the initial evaluation [10,11]. Although history of pressure in the region of the carotid sinuses prior to syncope or risk factors for CSS raises the index of suspicion for CSS, absence of these features does not exclude CSS, so the indication for CSM to assess for CSS is broad. CSS is diagnosed by the combination of reproducing appropriate spontaneous symptoms with documented CSH following CSM (best performed with the patient upright but protected from falling). When CSH is documented following CSM, concurrent symptoms provide the most convincing evidence for CSS. An asymptomatic "positive" response for CSH is less specific than CSH with reproduction of symptoms, particularly if a full evaluation for other causes of syncope has not yet been performed. By history, spontaneous syncope symptoms can be reasonably attributed to mechanical manipulation of the carotid sinuses resulting in CSH. CSS is one of many potential causes for syncope, near-syncope, or unexplained fall symptoms. Careful history taking is crucial to establishing the diagnosis. The finding of CSH in older adult patients should not be construed as diagnostic for the presenting symptoms (ie, lightheadedness, syncope, falls) unless other causes https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 4/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate of the symptoms have been eliminated or the history clearly relates symptoms to neck movement or mechanical distortion. Contraindications to CSM CSM should be avoided in patients at risk for stroke due to carotid artery disease, including those with one or more of the following clinical features, although data are lacking on the risk of stroke with CSM [10,11]: Prior transient ischemic attack (TIA) or stroke within the past three months. Clinically significant carotid stenosis (eg, 70 percent carotid artery stenosis). Prior complication (eg, TIA or stroke) from CSM. Carotid bruit (unless carotid Doppler ultrasound studies have excluded significant stenosis). Since a carotid bruit is not a sensitive indicator of carotid artery disease, some have suggested performing carotid Doppler ultrasound studies in patients with coronary artery disease or peripheral artery disease, since such patients are at high risk for stroke [12]. CSM procedure CSM methodology varies among laboratories, but one recommended method for evaluation of CSH/CSS follows: Monitoring Beat-to-beat blood pressure (BP) monitoring (preferably not by sphygmomanometer) and continuous heart rate (HR) monitoring by electrocardiogram (ECG; single-lead telemetry is adequate) are performed throughout the CSM procedure. The recordings are best achieved with a beat-to-beat noninvasive HR/BP monitor system (eg, Finapres). Patient position The patient may be studied first while supine, but upright posture is usually needed to reproduce symptoms. Symptom reproduction is the best method to secure a diagnosis of CSS. If supine study is done first, then the subject is initially placed in a horizontal supine position with the neck extended (ie, chin raised away from the chest) to maximize access to the carotid artery. However, symptoms associated with CSH are rarely induced unless CSM is carried out with the patient upright. The carotid sinus is usually located near the arterial impulse inferior to the angle of the mandible at the level of the thyroid cartilage ( figure 1). If the response in a horizontal supine position is nondiagnostic and symptoms are not reproduced, the procedure should be repeated with the patient seated upright or positioned head-up on a tilt table at 70 to 80 degrees (but gently secured to prevent a fall) [10,11]. The https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 5/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate diagnostic yield is likely to increase by performing CSM during head-up tilt, as this is likely to induce a greater degree of hypotension and is thus more likely to reproduce symptoms [13,14]. In a report of 1149 patients over 55 years of age presenting with unexplained syncope, CSH provoked by CSM was observed in 223 patients (19 percent); in one-third of these patients, a response to CSM was elicited during upright tilt after a negative response to supine massage [14]. Technique Firm, steady massage (with a vertical up and down movement) is applied at the region of the carotid baroreceptors (at the carotid artery just below the angle of the mandible and medial to the sternocleidomastoid muscle) ( figure 1) [12]. Pressure is applied to only one carotid sinus at a time (generally, first on the right and then on the left with patient upright either seated or on a tilt table), usually for 10 to 12 s; the carotid artery should not be occluded. Up and down motion may be more effective, but some argue that steady pressure may be more reproducible [10,15]. For older patients, some clinicians start CSM with 3 s of gentle pressure and, if no response, then apply firmer pressure. Reproduction of syncope symptoms is the best endpoint [11]. If the initial response is nondiagnostic, the procedure should be repeated on the contralateral side (unless contraindicated) following a one- to two-minute delay. In some patients, it may be useful to repeat the CSM after atropine administration in order to differentiate the hypotensive contributions of the cardioinhibitory and vasodepressor components of the reflex. However, in terms of assessing if a pacemaker may be useful in a given patient, the reproducibility of the atropine intervention is not fully established. Further, it is important to be aware that the reflex fatigues with multiple massage attempts over a short time, and, consequently, repetitive tests may inherently result in a diminished response. A rest period of approximately 15 to 20 min should be included between baseline tests and drug testing [16]. Test interpretation Criteria for and types of abnormal responses are discussed below. (See 'Criteria for abnormal responses' below and 'Types of abnormal responses' below.) Criteria for abnormal responses Experts disagree on what constitutes a "positive" (ie, abnormal) response to CSM suggesting CSH (and CSS if the patient s clinical symptoms are reproduced). The disagreement mainly focuses on the length of the HR pause that is considered abnormal. Stringent criteria Reproduction of the patient s symptoms (eg, syncope or presyncope) with an HR (ventricular) pause of 6 s or a fall in mean arterial BP to <60 mmHg lasting for 6 s is the most diagnostic finding for CSS [5]. If these HR and BP criteria are met without https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 6/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate symptoms, the test may still be considered positive but is less specific. These criteria are based upon observational studies suggesting that at least 6 s of asystole may be required to cause syncope or presyncope [17,18]. Less specific criteria Less specific criteria (sensitive but nonspecific) are included in the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society syncope guideline (a HR [ventricular] pause >3 seconds and/or a fall in systolic BP 50 mmHg) [10] and in the 2018 European Society of Cardiology syncope guidelines (a ventricular pause >3 s and/or a drop in systolic BP >50 mmHg) [11]. Types of abnormal responses Abnormal responses to CSM (as defined above) (see 'Criteria for abnormal responses' above) are classified as: Cardioinhibitory There is an abnormal decline in HR without an abnormal decline in BP. Vasodepressor There is an abnormal decline in BP without an abnormal decline in HR. or Mixed There are abnormal declines in HR and BP. In most cases with an abnormal response (including responses associated with reproduction of clinical symptoms consistent with CSS), the response is "mixed," indicating that symptoms in patients with CSS are commonly a combination of HR slowing and vasodilation. A combination of HR and BP responses is a typical feature of all reflex faints, including vasovagal syncope. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies", section on 'Reflex syncope'.) CSM may unmask CSH in older adult patients, but this should not be automatically deemed a diagnostic finding of CSS in patients with lightheadedness, syncope, or falls [3]. Thus, alternative causes should be explored before attributing syncope to CSH in older adult patients. Given the limited sensitivity and specificity of CSM for diagnosing CSS, some have advocated using stricter criteria for identification of CSH [5]. DIAGNOSIS CSS is diagnosed when all three of following conditions are met: The patient has a clinical history of syncope (or presyncope). Causes of syncope/collapse ( algorithm 1) other than CCS have been reasonably excluded by history and laboratory testing. (See "Syncope in adults: Clinical manifestations and initial https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 7/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate diagnostic evaluation".) The patient s response to carotid sinus massage (CSM) is abnormal (showing CSH) and reproduces the patients clinical symptoms. As noted above, stringent or less specific criteria may be used to identify an abnormal response. (See 'Criteria for abnormal responses' above.) An abnormal response to CSM without reproducing the patient s presenting symptoms is a less specific finding, particularly in older adults. Such as response suggests a diagnosis of CSS only if other causes of the symptoms have been excluded, particularly if the patient s history clearly relates symptoms to pressure on or movement of the neck movement. A positive (abnormal) response to CSM suggests CSH, but itself does not establish CSH as a cause of syncope. Thus, CSS is diagnosed when spontaneous syncope symptoms can be reasonably attributed to mechanical manipulation of the carotid sinuses. Unfortunately, obtaining a clear history of carotid sinus stimulation is challenging and uncommon. DIFFERENTIAL DIAGNOSIS As for other types of syncope (or presyncope), suspected CSS should be distinguished from other causes of syncope and/or collapse ( algorithm 1). From a pathophysiologic standpoint, carotid sinus syncope is similar to other forms of reflex syncope such as vasovagal syncope in involving cardioinhibitory and vasodilatory components. However, precipitating factors for these two types of reflex syncope differ. CSS is attributed to mechanical stress on hypersensitive carotid baroreceptors whereas vasovagal syncope is most often triggered by emotional events, painful stimuli, or prolonged upright posture. Other reflex faints (eg, defecation syncope, swallow syncope, trumpet blowers syncope) may also need to be considered depending on the specific circumstances of the patient presentation. (See 'Clinical manifestations' above and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".) A full discussion of the differential diagnosis of syncope in adults is presented separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".) MANAGEMENT https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 8/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Approach to management The management of patients with CSH depends upon whether symptoms are present or absent. Asymptomatic patients (isolated CSH) Patients with isolated CSH who remain asymptomatic require no specific therapy other than counselling to avoid movements or positions that may accidentally stimulate the carotid baroreceptors. CSS (symptomatic CSH) CSS is a multifaceted syndrome in terms of symptoms (type and frequency) as well as pathophysiology. Consequently, it is important to consider the risks associated with treating the patient every day for prevention of events which may be infrequent. Treatment of patients with CSS depends upon the type of abnormal response to carotid stimulation (cardioinhibitory and/or vasodilatory response), as described below. (See 'Permanent pacing' below and 'Pharmacologic therapy' below.) General management Education General treatment measures for CSS include education regarding the nature, risks, and prognosis of the condition [10]. The patient should be advised to avoid accidental mechanical manipulation of the carotid sinuses such as might occur if they receive medical or chiropractic treatments to the neck area or wear tight collars. Risks of CSS to the patient and bystanders should be discussed in detail. Lightheadedness and near-syncope may not cause frank loss of consciousness but can cause inattention and slow reaction times during operation of vehicles and machinery. The latter promotes the chances of accidents and falls with potential for major injury. Syncope may occur with a similar or greater potential for hazard to the patient and others if the patient loses control of a vehicle or other machine or simply falls in a crowded environment. (See 'Driving restrictions' below.) Driving restrictions Our approach to driving restriction recommendations for patients with CSS is generally consistent with the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society syncope guidelines ( table 1) [10], though supporting evidence is limited. It is also important to consult relevant local laws and regulations. Patients with CSH alone but without symptoms No restriction. Patients with untreated CSS (ie, known or suspected [by history] relation of symptoms to CSH in the absence of alternative cause) Not fit to drive. Patients with CSS treated with a permanent pacemaker to overcome a predominant cardioinhibitory component May drive after one week of observation to ensure stable pacing system is in place. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 9/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Patients with CSS (known or suspected) in whom the vasodepressor component is dominant (a relatively rare condition) who are treated to diminish vasodilation May drive after a reasonable observation period to demonstrate treatment effectiveness. Recommendations for commercial drivers are linked to local and/or federal government department of transportation or comparable regulatory body regulations [19]. Generally, a symptom-free period of six months is required, but regulations differ among geographic regions. Practitioners must be aware of local laws and regulations in their region, which may differ from professional society guidelines. (See "Syncope in adults: Management and prognosis", section on 'Driving restrictions'.) Pharmacologic therapy Pharmacologic therapy is a component of therapy for patients with CCS with a predominantly vasodilatory response to carotid sinus massage (CSM), but relatively little is known of the optimal treatment of such patients, as these cases seem to be rare (or at least rarely recognized) and therefore difficult to study. As an initial step, drugs such as vasodilators or diuretics that may exacerbate the condition should be reduced or discontinued, if feasible. Although some therapies for vasovagal syncope (such as salt loading and vasoconstrictors) may be expected to be helpful, such treatments may cause supine hypertension and are usually undesirable in the older patient population with CSS [10]. Vasoconstrictive drugs such as midodrine or droxidopa may be used (as prescribed for orthostatic hypotension (see "Treatment of orthostatic and postprandial hypotension", section on 'Sympathomimetic agents')), but limited data are available to support their use for CSS [11,20]. Additionally, vasoconstrictive drugs must be used cautiously to minimize the risk of hypertension. In individuals with CSS and essential hypertension (a common combination), it is necessary to use vasoconstrictors during waking hours and short-acting antihypertensives at bedtime to diminish supine hypertension. Permanent pacing Indication For patients with recurrent syncope diagnosed with CSS (see 'Diagnosis' above) (whether by stringent criteria or by less specific criteria (see 'Criteria for abnormal responses' above)) with either a cardioinhibitory or "mixed" response to CSM resulting in asystole for more than three to six seconds, we suggest referral for permanent cardiac pacemaker implantation. The certainty of a beneficial response is highest for patients meeting stringent criteria for CSS including reproduction of symptoms with CSM. (See 'Permanent pacing' above.) This recommendation is in broad agreement with major society guidelines [10,11]. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 10/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Most patients with CSS have a cardioinhibitory or mixed response and thus are candidates for pacemaker therapy, although residual vasodepressor response may diminish overall pacing effectiveness. Patients with CSS with a dominant vasodilatory response (drop in systolic blood pressure >50 mmHg) without associated cardioinhibition are unlikely to respond to pacemaker therapy [21]. Consequently, each patient must be carefully evaluated for cardioinhibitory versus vasodepressor contributions to hypotension before a pacemaker intervention is advised. If cardioinhibition predominates, then pacing may be helpful, as discussed below. Permanent pacing is not indicated for a cardioinhibitory response to carotid sinus stimulation in patients with no history of symptoms (such as syncope or presyncope) or with only vague symptoms (ie, pacing is not indicated for CSH). A positive cardioinhibitory response (asystole >3 to 6 s) during CSM is thought to be predictive of an asystolic mechanism of spontaneous syncope, but only limited evidence is available to support this approach [17,22]. As an example, in a study of 18 patients with recurrent syncope and cardioinhibitory response to CSM and 36 patients with recurrent syncope and negative response to CSM, insertable cardiac monitors (also sometimes referred to as implantable cardiac monitors or implantable loop recorders) identified the following [22]: Asystole with syncope in 16 of 18 (89 percent) patients with a positive cardioinhibitory response to CSM. Asystole with syncope in 18 of 36 (50 percent) patients with a negative cardioinhibitory response to CSM. In CSS, most studies suggest a benefit from pacing despite the concern that both cardioinhibitory and vasodepressor mechanisms may be operating. This observation differs from observations of other reflex conditions such as the vasovagal faint in which a predominant vasodepressor component may undermine the value of pacing therapy. Why these two forms of reflex syncope respond differently to pacemaker therapy is unknown, but may be due to a higher frequency of cardioinhibitory response in patients with CSS than with other types of reflex syncope. Two small randomized trials found that pacing reduced the rate of syncope recurrence in patients with CSS [23,24]. Dual-chamber pacing is beneficial in patients with CSS who have a cardioinhibitory response, but not in those with a pure vasodilatory response [21]. Pacing may prevent nonmechanical falls as well as syncope in some patients populations. This was suggested by the SAFE PACE trial, in which 175 patients seen in an emergency facility https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 11/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate because of a nonmechanical fall without loss of consciousness were randomly assigned to a dual-chamber pacemaker or no therapy [25], but not confirmed in SAFE PACE 2 [26]. Choice of pacemaker When a pacemaker is placed, dual-chamber pacing is generally favored [10,11]. Single-chamber AAI (atrial demand) pacing is not recommended for patients with CSS, as transient AV block may occur during an episode and eliminate any potential pacing benefit. This approach is in general agreement with published society guidelines [10]. (See "Permanent cardiac pacing: Overview of devices and indications" and "Modes of cardiac pacing: Nomenclature and selection".) In a study of 21 patients with CSS and syncope or near-syncope, patients were randomized to VVI (ventricular demand), DDDR (dual-chamber with rate modulation), or DDDR pacing with sudden bradycardia response (SBR) in a double-blinded sequential crossover basis with six months in each mode [27]. There were 29 syncopal and 258 presyncopal events among 21 patients during the preceding six months. Following pacing, there were two syncopal events in two patients and 17 presyncopal events in 12 patients in six months, and these events were not related to the three pacing methods. While these data do not support one specific mode of pacing, some patients have a better hemodynamic response to AV sequential pacing, and, if this is known a priori, we suggest a dual-chamber pacemaker be implanted from the start. Failure of pacing most likely would be due to the patient having a prominent vasodepressor component of the CSS reflex, similar to what may happen in patients with vasovagal syncope. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Vagal maneuvers and their responses (The Basics)") https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 12/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate SUMMARY AND RECOMMENDATIONS Definitions (See 'Definitions' above.) Carotid sinus hypersensitivity (CSH) CSH is a clinical finding of greater than normal fall in heart rate (HR) and/or systemic blood pressure (BP) in response to carotid sinus massage (CSM). Criteria for an abnormal response to CSM vary (see 'Test interpretation' above). CSH itself is not a clinical syndrome. It occurs in individuals with and without a history of symptoms such as syncope. Carotid sinus syndrome (CSS) CSS is a type of reflex syncope with symptoms (eg, syncope, lightheadedness) caused by CSH manifesting during activities of daily life that put pressure on the carotid sinus (eg, turning the neck, looking upward). When CSS manifests as syncope it is called carotid sinus syncope. (See 'Clinical manifestations' above.) Prevalence CSH is a commonly observed physical finding but an uncommon cause of symptoms (as in CSS). CSS is a relative rare cause of syncope, accounting for approximately 1 percent of syncope cases. Older individuals and males are more likely to have an abnormal CSH response even if they do not have CSS. Clinical presentation The most common presenting symptoms of CSS are lightheadedness/presyncope, syncope, and otherwise unexplained falls. Although a clear relationship between neck movements and symptom episodes is rarely established, a history of syncope following accidental manipulation of the carotid sinuses should be sought. (See 'Clinical manifestations' above.) When to perform CSM to diagnose CSS In patients over age 50 with syncope or presyncope of unknown etiology despite an initial evaluation (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation"), we recommend performing CSM to evaluate for possible CSS. However, false positive results are common in older adults, so other potential causes of syncope or collapse should be excluded ( algorithm 1). (See 'Diagnostic evaluation' above and 'When to perform CSM' above.) Although a history of pressure in the region of the carotid sinuses prior to syncope or presence of a risk factor for CSS raises the index of suspicion, absence of these features does not exclude CSS, so the indication for CSM to assess for CSS is broad. Contraindications to CSM CSM should be avoided in patients at risk for stroke due to carotid artery disease, including those with prior transient ischemic attack (TIA) or stroke https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 13/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate within the past three months, clinically significant carotid stenosis, or carotid bruit. (See 'Contraindications to CSM' above.) Abnormal responses to CSM Criteria for a positive (ie, abnormal) response to CSM are controversial, ranging from stringent criteria that are more specific to less specific criteria that are more sensitive. The test is most diagnostic for CSS when stringent criteria are met with reproduction of symptoms (see 'Criteria for abnormal responses' above): Stringent criteria A HR pause of 6 s or a fall in systolic BP to <60 mmHg lasting for 6 s. Less specific criteria a HR pause >3 s or a fall in systolic BP of 50 mmHg. Types of abnormal responses An abnormal response to CSM may be cardioinhibitory (greater than normal decline in HR), vasodilatory (greater than normal fall in BP) or mixed (greater than normal fall in HR and BP). (See 'Types of abnormal responses' above.) General management (See 'Approach to management' above and 'General management' above.) For CSH Patients with isolated CSH who remain asymptomatic require no specific therapy other than counselling to avoid movements or positions that may accidentally stimulate the carotid baroreceptors. For CSS General measures include education regarding CSS risks, applicable driving restrictions, and treatment options. Pharmacologic therapy is an option for patients with a vasodilatory response to CSM. (See 'General management' above.) Permanent pacing For patients with recurrent syncope diagnosed with CSS (by either stringent or less specific criteria) with a cardioinhibitory or "mixed" response to CSM resulting in asystole for more than three to six seconds, we suggest permanent cardiac pacemaker implantation (Grade 2C). The certainty of a beneficial response is highest for patients meeting stringent criteria for CSS, including reproduction of symptoms with CSM. (See 'Permanent pacing' above.) ACKNOWLEDGMENT The editorial staff at UpToDate acknowledges Brian Olshansky, MD, who contributed to earlier versions of this topic review. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 14/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Thomas JE. Hyperactive carotid sinus reflex and carotid sinus syncope. Mayo Clin Proc 1969; 44:127. 2. Kerr SR, Pearce MS, Brayne C, et al. Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls. Arch Intern Med 2006; 166:515. 3. Sullivan RM, Olshansky B. Carotid sinus hypersensitivity: disease state or clinical sign of ageing? The need for hard endpoints. Europace 2010; 12:1516. 4. Tan MP, Kenny RA, Chadwick TJ, et al. Carotid sinus hypersensitivity: disease state or clinical sign of ageing? Insights from a controlled study of autonomic function in symptomatic and asymptomatic subjects. Europace 2010; 12:1630. 5. Krediet CT, Parry SW, Jardine DL, et al. The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive? Europace 2011; 13:14. 6. Volkmann H, Schnerch B, K hnert H. Diagnostic value of carotid sinus hypersensitivity. Pacing Clin Electrophysiol 1990; 13:2065. 7. Brignole M, Menozzi C, Gianfranchi L, et al. Carotid sinus massage, eyeball compression, and head-up tilt test in patients with syncope of uncertain origin and in healthy control subjects. Am Heart J 1991; 122:1644. 8. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol 2001; 37:1921. 9. McIntosh SJ, Lawson J, Kenny RA. Clinical characteristics of vasodepressor, cardioinhibitory, and mixed carotid sinus syndrome in the elderly. Am J Med 1993; 95:203. 10. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 11. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 12. Pasquier M, Clair M, Pruvot E, et al. Carotid Sinus Massage. N Engl J Med 2017; 377:e21. 13. Morillo CA, Camacho ME, Wood MA, et al. Diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in patients with unexplained syncope. J Am Coll Cardiol 1999; 34:1587. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 15/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate 14. Parry SW, Richardson DA, O'Shea D, et al. Diagnosis of carotid sinus hypersensitivity in older adults: carotid sinus massage in the upright position is essential. Heart 2000; 83:22. 15. Waxman MB, Wald RW, Sharma AD, et al. Vagal techniques for termination of paroxysmal supraventricular tachycardia. Am J Cardiol 1980; 46:655. 16. Sutton R. Carotid sinus syndrome: Progress in understanding and management. Glob Cardiol Sci Pract 2014; 2014:1. 17. Menozzi C, Brignole M, Lolli G, et al. Follow-up of asystolic episodes in patients with cardioinhibitory, neurally mediated syncope and VVI pacemaker. Am J Cardiol 1993; 72:1152. 18. Wieling W, Thijs RD, van Dijk N, et al. Symptoms and signs of syncope: a review of the link between physiology and clinical clues. Brain 2009; 132:2630. 19. Epstein AE, Miles WM, Benditt DG, et al. Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations. A medical/scientific statement from the American Heart Association and |
syncope, lightheadedness) caused by CSH manifesting during activities of daily life that put pressure on the carotid sinus (eg, turning the neck, looking upward). When CSS manifests as syncope it is called carotid sinus syncope. (See 'Clinical manifestations' above.) Prevalence CSH is a commonly observed physical finding but an uncommon cause of symptoms (as in CSS). CSS is a relative rare cause of syncope, accounting for approximately 1 percent of syncope cases. Older individuals and males are more likely to have an abnormal CSH response even if they do not have CSS. Clinical presentation The most common presenting symptoms of CSS are lightheadedness/presyncope, syncope, and otherwise unexplained falls. Although a clear relationship between neck movements and symptom episodes is rarely established, a history of syncope following accidental manipulation of the carotid sinuses should be sought. (See 'Clinical manifestations' above.) When to perform CSM to diagnose CSS In patients over age 50 with syncope or presyncope of unknown etiology despite an initial evaluation (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation"), we recommend performing CSM to evaluate for possible CSS. However, false positive results are common in older adults, so other potential causes of syncope or collapse should be excluded ( algorithm 1). (See 'Diagnostic evaluation' above and 'When to perform CSM' above.) Although a history of pressure in the region of the carotid sinuses prior to syncope or presence of a risk factor for CSS raises the index of suspicion, absence of these features does not exclude CSS, so the indication for CSM to assess for CSS is broad. Contraindications to CSM CSM should be avoided in patients at risk for stroke due to carotid artery disease, including those with prior transient ischemic attack (TIA) or stroke https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 13/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate within the past three months, clinically significant carotid stenosis, or carotid bruit. (See 'Contraindications to CSM' above.) Abnormal responses to CSM Criteria for a positive (ie, abnormal) response to CSM are controversial, ranging from stringent criteria that are more specific to less specific criteria that are more sensitive. The test is most diagnostic for CSS when stringent criteria are met with reproduction of symptoms (see 'Criteria for abnormal responses' above): Stringent criteria A HR pause of 6 s or a fall in systolic BP to <60 mmHg lasting for 6 s. Less specific criteria a HR pause >3 s or a fall in systolic BP of 50 mmHg. Types of abnormal responses An abnormal response to CSM may be cardioinhibitory (greater than normal decline in HR), vasodilatory (greater than normal fall in BP) or mixed (greater than normal fall in HR and BP). (See 'Types of abnormal responses' above.) General management (See 'Approach to management' above and 'General management' above.) For CSH Patients with isolated CSH who remain asymptomatic require no specific therapy other than counselling to avoid movements or positions that may accidentally stimulate the carotid baroreceptors. For CSS General measures include education regarding CSS risks, applicable driving restrictions, and treatment options. Pharmacologic therapy is an option for patients with a vasodilatory response to CSM. (See 'General management' above.) Permanent pacing For patients with recurrent syncope diagnosed with CSS (by either stringent or less specific criteria) with a cardioinhibitory or "mixed" response to CSM resulting in asystole for more than three to six seconds, we suggest permanent cardiac pacemaker implantation (Grade 2C). The certainty of a beneficial response is highest for patients meeting stringent criteria for CSS, including reproduction of symptoms with CSM. (See 'Permanent pacing' above.) ACKNOWLEDGMENT The editorial staff at UpToDate acknowledges Brian Olshansky, MD, who contributed to earlier versions of this topic review. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 14/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Thomas JE. Hyperactive carotid sinus reflex and carotid sinus syncope. Mayo Clin Proc 1969; 44:127. 2. Kerr SR, Pearce MS, Brayne C, et al. Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls. Arch Intern Med 2006; 166:515. 3. Sullivan RM, Olshansky B. Carotid sinus hypersensitivity: disease state or clinical sign of ageing? The need for hard endpoints. Europace 2010; 12:1516. 4. Tan MP, Kenny RA, Chadwick TJ, et al. Carotid sinus hypersensitivity: disease state or clinical sign of ageing? Insights from a controlled study of autonomic function in symptomatic and asymptomatic subjects. Europace 2010; 12:1630. 5. Krediet CT, Parry SW, Jardine DL, et al. The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive? Europace 2011; 13:14. 6. Volkmann H, Schnerch B, K hnert H. Diagnostic value of carotid sinus hypersensitivity. Pacing Clin Electrophysiol 1990; 13:2065. 7. Brignole M, Menozzi C, Gianfranchi L, et al. Carotid sinus massage, eyeball compression, and head-up tilt test in patients with syncope of uncertain origin and in healthy control subjects. Am Heart J 1991; 122:1644. 8. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol 2001; 37:1921. 9. McIntosh SJ, Lawson J, Kenny RA. Clinical characteristics of vasodepressor, cardioinhibitory, and mixed carotid sinus syndrome in the elderly. Am J Med 1993; 95:203. 10. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 11. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 12. Pasquier M, Clair M, Pruvot E, et al. Carotid Sinus Massage. N Engl J Med 2017; 377:e21. 13. Morillo CA, Camacho ME, Wood MA, et al. Diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in patients with unexplained syncope. J Am Coll Cardiol 1999; 34:1587. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 15/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate 14. Parry SW, Richardson DA, O'Shea D, et al. Diagnosis of carotid sinus hypersensitivity in older adults: carotid sinus massage in the upright position is essential. Heart 2000; 83:22. 15. Waxman MB, Wald RW, Sharma AD, et al. Vagal techniques for termination of paroxysmal supraventricular tachycardia. Am J Cardiol 1980; 46:655. 16. Sutton R. Carotid sinus syndrome: Progress in understanding and management. Glob Cardiol Sci Pract 2014; 2014:1. 17. Menozzi C, Brignole M, Lolli G, et al. Follow-up of asystolic episodes in patients with cardioinhibitory, neurally mediated syncope and VVI pacemaker. Am J Cardiol 1993; 72:1152. 18. Wieling W, Thijs RD, van Dijk N, et al. Symptoms and signs of syncope: a review of the link between physiology and clinical clues. Brain 2009; 132:2630. 19. Epstein AE, Miles WM, Benditt DG, et al. Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations. A medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology. Circulation 1996; 94:1147. 20. Moore A, Watts M, Sheehy T, et al. Treatment of vasodepressor carotid sinus syndrome with midodrine: a randomized, controlled pilot study. J Am Geriatr Soc 2005; 53:114. 21. Almquist A, Gornick C, Benson W Jr, et al. Carotid sinus hypersensitivity: evaluation of the vasodepressor component. Circulation 1985; 71:927. 22. Maggi R, Menozzi C, Brignole M, et al. Cardioinhibitory carotid sinus hypersensitivity predicts an asystolic mechanism of spontaneous neurally mediated syncope. Europace 2007; 9:563. 23. Brignole M, Menozzi C, Lolli G, et al. Long-term outcome of paced and nonpaced patients with severe carotid sinus syndrome. Am J Cardiol 1992; 69:1039. 24. Claesson JE, Kristensson BE, Edvardsson N, W hrborg P. Less syncope and milder symptoms in patients treated with pacing for induced cardioinhibitory carotid sinus syndrome: a randomized study. Europace 2007; 9:932. 25. Kenny RA, Richardson DA, Steen N, et al. Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE). J Am Coll Cardiol 2001; 38:1491. 26. Ryan DJ, Nick S, Colette SM, Roseanne K. Carotid sinus syndrome, should we pace? A multicentre, randomised control trial (Safepace 2). Heart 2010; 96:347. 27. McLeod CJ, Trusty JM, Jenkins SM, et al. Method of pacing does not affect the recurrence of syncope in carotid sinus syndrome. Pacing Clin Electrophysiol 2012; 35:827. Topic 1071 Version 30.0 https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 16/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate GRAPHICS Anatomy of the carotid sinus The carotid sinus is located at the base of the internal carotid artery just superior to its bifurcation from the external carotid artery. Graphic 139405 Version 1.0 https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 17/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Algorithm for syncope/collapse This algorithm poses key questions about a collapse episode, including whether and when LOC occurred. However, in the absence of a credible witness, information about such episodes is often limited, as the affected individual may not have accurate recall of the event. Some causes have more than one possible type of presentation. LOC: loss of consciousness; BLS: basic life support; ACLS: advanced cardiac life support; SAH: subarachnoid hemorrhage; TIA: transient ischemic attack. This includes actual LOC as well as apparent LOC. Accidental falls without LOC often have multiple causes, including gait, posture, or balance impairment, environmental hazard, vertigo, focal seizure, TIA, stroke, and presyncope. These conditions result in apparent transient LOC, although consciousness may be preserved. https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 18/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Other causes of collapse may cause secondary head trauma. Most TIAs and strokes are not associated with LOC. An SAH may cause transient or prolonged LOC. A rare cause of LOC is a brainstem stroke. Graphic 131146 Version 1.0 https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 19/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Recommendations for resuming driving after syncope Condition Symptom-free waiting time* OH 1 month [1] VVS, no syncope in prior year No restriction [2] VVS, 1 to 6 syncope per year 1 month [1,2] VVS, >6 syncope per year Not fit to drive until symptoms resolved Situational syncope other than cough syncope 1 month Cough syncope, untreated Not fit to drive Cough syncope, treated with cough suppression 1 month [1] Carotid sinus syncope, untreated Not fit to drive Carotid sinus syncope, treated with permanent 1 week [1] pacemaker [1] Syncope due to nonreflex bradycardia, untreated Not fit to drive Syncope due to nonreflex bradycardia, treated with [1,3] permanent pacemaker 1 week [1] Syncope due to SVT, untreated Not fit to drive [1] Syncope due to SVT, pharmacologically suppressed 1 month [1] Syncope due to SVT, treated with ablation 1 week Syncope with LVEF <35% and a presumed arrhythmic [4,5] etiology without an ICD Not fit to drive Syncope with LVEF <35% and presumed arrhythmic etiology with an ICD 3 months [6,7] Syncope presumed due to VT/VF, structural heart disease, and LVEF 35%, untreated Not fit to drive Syncope presumed due to VT/VF, structural heart disease, and LVEF 35%, treated with an ICD and guideline-directed drug therapy 3 months [6,7] Syncope presumed due to VT with a genetic cause, Not fit to drive untreated Syncope presumed due to VT with a genetic cause, treated 3 months with an ICD or guideline-directed drug therapy Syncope presumed due to a nonstructural heart disease VT, Not fit to drive such as RVOT or LVOT, untreated https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 20/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Syncope presumed due to a nonstructural heart disease VT, 3 months such as RVOT or LVOT, treated successfully with ablation or suppressed pharmacologically [1] Syncope of undetermined etiology 1 month OH: orthostatic hypotension; VVS: vasovagal syncope; SVT: supraventricular tachycardia; LVEF: left ventricular ejection fraction; ICD: implantable cardioverter-defibrillator; VT: ventricular tachycardia; VF: ventricular fibrillation; RVOT: right ventricular outflow tract; LVOT: left ventricular outflow tract. It may be prudent to wait and observe for this time without a syncope spell before resuming driving. References: 1. Epstein AE, Miles WM, Benditt DG, et al. Personal and public safety issues related to arrhythmias that may a ect consciousness: implications for regulation and physician recommendations. A medical/scienti c statement from the American Heart Association and the North American Society of Pacing and Electrophysiology. Circulation 1996; 94:1147-66. 2. Tan VH, Ritchie D, Maxey C, et al. Prospective assessment of the risk of vasovagal syncope during driving. JACC Clin Electrophysiol 2016; 2:203. 3. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013; 61:e6. 4. B nsch D, Brunn J, Castrucci M, et al. Syncope in patients with an implantable cardioverter-de brillator: incidence, prediction and implications for driving restrictions. J Am Coll Cardiol 1998; 31:608. 5. Antonelli D, Peres D, Freedberg NA, et al. Incidence of postdischarge symptomatic paroxysmal atrial brillation in patients who underwent coronary artery bypass graft: long-term follow-up. Pacing Clin Electrophysiol 2004; 27:365. 6. Thijssen J, Borle s CJ, van Rees JB, et al. Driving restrictions after implantable cardioverter de brillator implantation: an evidence-based approach. Eur Heart J 2011; 32:2678. 7. Vijgen J, Botto G, Camm J, et al. Consensus statement of the European Heart Rhythm Association: updated recommendations for driving by patients with implantable cardioverter de brillators. Europace 2009; 11:1097. Reproduced from: Shen W-K, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope. J Am Coll Cardiol 2017. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 113080 Version 2.0 https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 21/22 7/6/23, 2:38 PM Carotid sinus hypersensitivity and carotid sinus syndrome - UpToDate Contributor Disclosures David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and defibrillators]; St Jude Medical [Pacemakers/event recorders and defibrillators]. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced CPR Solutions [Outside director]. All of the relevant financial relationships listed have been mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias]. Consultant/Advisory Boards: Abbvie [Arrhythmias]; Acesion Pharma [Arrhythmias]; Allergan [Arrhythmias, cardiac safety of non-cardiac drugs]; Anthos [Anticoagulants]; Boehringer-Ingelheim [Arrhythmias]; Bristol-Meyers-Squibb [Arrhythmias]; Daiichi Sankyo [Arrhythmias]; Gilead [Arrhythmias]; Huya [Arrhythmias]; InCarda Therapeutics [Arrhythmias]; INSTA [Arrhythmias]; Johnson & Johnson [Arrhythmias]; Medtronic [Arrhythmias]; Milestone [Arrhythmias]; Novartis [Arrhythmias, cardiac safety of non-cardiac drugs]; Pfizer [Arrhythmias]; Sanofi [Arrhythmias]; Takeda [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/carotid-sinus-hypersensitivity-and-carotid-sinus-syndrome/print 22/22 |
7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation : David Benditt, MD : Peter Kowey, MD, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 18, 2022. INTRODUCTION Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often the result of an abrupt drop of systemic blood pressure. Unfortunately, the term "syncope" is often misapplied by clinicians to encompass any form of abrupt collapse that may or may not be accompanied by TLOC, including seizures and concussions; this latter broad and less-specific usage should be avoided. Reflex syncope (previously termed neurally-mediated syncope) is TLOC due to a reflex response that encompasses vasodilatation and/or bradycardia, leading to systemic hypotension and cerebral hypoperfusion [1,2]. Types of reflex syncope include vasovagal syncope, situational reflex syncope (eg, micturition syncope), carotid sinus syncope, and some cases without apparent triggers ( table 1). In these cases, the syncope is due to hypotension, which may be caused by severe bradycardia, vascular dilation (vasodepressor effect), or both. Vasovagal syncope is the most common cause of syncope in patients of all ages [3,4], and its diagnosis may usually be made by taking a careful history detailing the features of symptomatic events and identifying well-known triggers; however, a classic history is not always present, especially in older individuals. Acute vasovagal reactions leading to syncope or presyncope are also common in a number of potentially stressful settings, such as blood donation or emotional upset. Even among patients with structural heart disease, if electrophysiology testing is nondiagnostic, approximately 60 percent of syncope recurrences are reflex in origin [5]. The https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 1/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate diagnosis can also be suggested by exclusion of other causes of syncope and by a characteristic response to upright tilt table testing, during which the patient may become syncopal. (See "Blood donor screening: Overview of recipient and donor protections", section on 'Vasovagal and hypovolemic reactions'.) The clinical presentation and diagnostic evaluation of patients with vasovagal syncope and situational reflex syncope will be reviewed here. Discussions of the treatment of patients with reflex syncope, as well as the pathogenesis, etiology, evaluation and management of syncope in general, are discussed separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Syncope in adults: Management and prognosis" and "Reflex syncope in adults and adolescents: Treatment".) PATHOGENESIS OF REFLEX SYNCOPE Understanding the pathophysiology involved in reflex syncope is essential to understanding its clinical manifestations and prevention strategies. Both neural (arterial and cardiac baroreceptor, including carotid sinus reflexes) and endogenous chemical pathways are thought to be involved ( figure 1) [6]. The potential neurohumoral events that participate in vasovagal reactions are complex but remain poorly understood; better understanding may be expected to lead to more specific therapeutic strategies in the future [7]. The most frequent mechanism for reflex syncope is a mixed hemodynamic response combining cardioinhibitory (ie, heart slowing, usually to <30 beats per minute and/or pauses >5 sec) and vasodepressor features (ie, a drop of systemic blood pressure independent of change of heart rate). An individual patient may have syncopal events caused by varying mechanisms, with vasodepressor, cardioinhibitory, or mixed responses at different times. Infrequently, an individual patient may have syncopal events characterized entirely by vasodepressor or cardioinhibitory responses. Cardioinhibitory and vasodepressor responses Alterations in autonomic activation are responsible for reflex syncope. Vasovagal syncope may be caused by autonomic cardioinhibitory and/or vasodilator responses. Three types of responses are seen [8]: Cardioinhibitory response The cardioinhibitory response (ie, marked sinus bradycardia or pauses) results principally from increased parasympathetic activation and may be manifested by any or all of the following: sinus bradycardia, PR interval prolongation, advanced atrioventricular (AV) block, or asystole. The simultaneous presence of sinus bradycardia and AV block on a heart rhythm tracing strongly favors a reflex mechanism. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 2/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Vasodepressor response The vasodepressor response is principally due to inhibition of (decreased) peripheral sympathetic activity and can lead to symptomatic hypotension even in the absence of severe bradycardia. In one report, for example, the final trigger for symptomatic hypotension appeared to be the abrupt disappearance of muscle sympathetic nerve activity, but this has not been a consistent observation [9]. Reduced cardiopulmonary baroreceptor sensitivity may be a contributing factor [10]. Paradoxically, circulating epinephrine may be quite high [11]. Mixed response The mixed response contains components of both the cardioinhibitory response and the vasodepressor response. In one cohort of 111 patients with presumed vasovagal syncope who received an insertable cardiac monitor (sometimes referred to as an implantable loop recorder) and were followed for 3 to 15 months, 34 percent experienced recurrent syncope [12]. A correlation between syncope and electrocardiographic changes was found in 84 percent, with the most frequent abnormality (seen in 50 percent) being one or more prolonged asystolic pauses, primarily due to sinus arrest. Bradycardia (<40 beats per minute) without pauses was seen in 9 percent, while the remaining patients had normal sinus rhythm or sinus tachycardia and probably had a vasodepressor response. Although wearable ambulatory electrocardiogram (ECG) recorders and insertable cardiac monitors have proved valuable in improving understanding of bradycardias as potential contributors to syncope/collapse, they do not offer insight into possible concomitant vasodepressor activity. Merely observing a slow heart rate is insufficient to conclude that the faint was solely cardioinhibitory in nature. Autonomic dysfunction Underlying autonomic dysfunction only infrequently contributes to reflex syncope, but may be relevant in those whose presentation does not include the usual premonitory symptoms (ie, feeling hot or cold, nausea, sweating, etc); the latter are often associated with cardiovascular or neurologic disorders, which may include orthostatic or postprandial hypotension [1,2]. Reflexes initiated in various arterial and cardiac baroreceptors and carotid sinus reflexes may be involved (in the past, the term Bezold-Jarisch reflex has been used, but it is now best abandoned as it does not fully express the complex pathophysiology) [6]. Patients may have increased muscle sympathetic nerve activity at rest and a blunted response to orthostatic stress [13]. Baroreceptor reflexes Receptors in the atria, great veins, aorta, and left ventricle exist whose activation results in reflex bradycardia and vasodilation. Activation of these mechanoreceptors (including those in the left ventricle and stretch receptors in the great https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 3/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate vessels) with pressure or volume changes (as may occur with sympathetic stimulation) activate afferent C fibers to the midbrain; such stimulation may result in activation of vagal afferents and then vagal efferents. However, the neural pathways are not well established. In particular, the role of epicardial atrial cardiac ganglia as a trigger site is of increased interest, as cardioneuroablation has been proposed as a means to diminish susceptibility to vasovagal reflex events [14]. Carotid sinus reflex Blood pressure and heart rate are normally controlled in part by input from baroreceptors located within the carotid sinus and aortic arch. An increase in blood pressure or pressure applied to the carotid sinus enhances the baroreceptor firing rate and activates vagal activity, thereby slowing the heart rate and reducing the blood pressure. Central serotonergic pathways It has been argued that central serotonergic pathways may participate in the pathogenesis of vasovagal syncope, but the evidence is weak, and serotonin re-uptake inhibition is not routinely very helpful for prevention of attacks. Adenosine Adenosine has a variety of actions, including negative chronotropic and inotropic activity and vasodepression [15]. Adenosine release, perhaps mediated by mechanoreceptors in the heart, may be involved in the triggering mechanism of syncope, at least during tilt testing. The observation that adenosine administration can provoke reflex syncope raises the possibility that endogenous adenosine plays a role in the pathogenesis of vasovagal syncope. Recently, a low-adenosine phenotype has been described with low expression of A2A receptors. These individuals are thought to be particularly susceptible to endogenous adenosine and manifest reflex syncope with sinus arrest and/or paroxysmal AV block [16]. This topic remains to be more fully explored. TYPES OF REFLEX SYNCOPE Vasovagal syncope Vasovagal syncope (also known as the "common faint") refers to a variety of clinical scenarios in which a neural reflex results in usually self-limited systemic hypotension characterized by bradycardia and/or peripheral vasodilation/venodilation. It is the most common cause of syncope (approximately 35 to 70 percent of cases depending on the age group being evaluated), particularly in patients without apparent cardiovascular or neurologic disease [4,17- 23]. However, vasovagal syncope remains the most common cause of syncope even among patients with heart disease and should be considered as a potential cause in such patients after more worrisome causes ( table 2) have been excluded [5,20]. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".) https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 4/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Vasovagal syncope is a common cause of syncope in athletes. However, other potential causes of syncope should be considered, particularly if the syncope occurs during exertion (ie, during "full flight" not during the post exercise cooling down period). Athletes with syncope during physical activity should be evaluated for underlying structural heart disease, which, if present, increases potential risk of sudden death. (See "Athletes with arrhythmias: Clinical manifestations and diagnostic evaluation".) Situational syncope Situational syncope refers to syncope associated with specific scenarios. Some situations (eg, micturition, defecation, posttussive, etc) appear to trigger a neural reflex; others (eg, straining, squatting) may cause syncope via additional mechanisms unrelated to neural reflexes. Avoidance of trigger situations is the first step in prevention of recurrences. Glossopharyngeal neuralgia (GN) is an uncommon cause of reflex syncope. Episodes of GN pain are frequently triggered by activities such as swallowing, coughing, or yawning. Episodes of GN pain are rarely associated with syncope. (See "Glossopharyngeal neuralgia", section on 'Clinical features'.) CLINICAL PRESENTATION The clinical features associated with a syncopal event may be diagnostic ( table 1) [1,2,24,25]. Patients with vasovagal syncope are often young and otherwise healthy. In younger persons, vasovagal syncope is usually associated with a prodrome of nausea, pallor, and diaphoresis, consistent with increased vagal tone. Typical triggers and premonitory symptoms are strongly suggestive of vasovagal syncope, although these may be absent or difficult to correlate to the syncopal episode in some individuals, particularly in older adults. However, as noted earlier, vasovagal syncope is the most common form of syncope in all age groups and, consequently, should not be overlooked as a possibility in older individuals. The history may not be classical in older patients. Symptoms The classic prodromal symptoms associated with imminent syncope and presyncope, particularly in the case of the vasovagal form of reflex syncope, include: Lightheadedness A feeling of being warm or cold Sweating Palpitations Nausea or non-specific abdominal discomfort Visual "blurring" occasionally proceeding to temporary darkening or "white-out" of vision https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 5/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Diminution of hearing and/or occurrence of unusual sounds (particularly a "whooshing" noise) Pallor reported by onlookers Fatigue after recovery Vasovagal syncope typically occurs in the sitting or standing position, as the supine position helps to maintain adequate blood flow to the brain. Typically, reflex syncope is short in duration (one to two minutes), but full recovery may be delayed as the patient may feel fatigued for an extended period following the event. This course may help distinguish vasovagal syncope from syncope associated with arrhythmia, which is typically of abrupt onset and of short duration but without autonomic-mediated prodrome or post-episode fatigue. Loss of consciousness may be prolonged with some other causes of TLOC, such as seizures, but rarely with vasovagal syncope. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".) Older patients, unlike younger patients, may not only experience vasovagal syncope, but also be at increased risk of carotid sinus hypersensitivity and/or orthostatic hypotension [26,27]. They are also more likely to have coexisting cardiovascular disease and to be taking hypotension- provoking medications. Consequently, in older patients, patients with syncope during exertion, and other patients who may have structural heart disease, potential causes of syncope other than reflex syncope must be considered. (See 'Medical history' below and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Approach to initial evaluation' and "Carotid sinus hypersensitivity and carotid sinus syndrome".) Triggers Women and patients younger than 40 years are more likely to have typical symptoms and triggers for vasovagal syncope [28]. However, older patients may also be diagnosed with vasovagal syncope but, as emphasized earlier, may not have typical premonitory symptoms [29]. The "classical" of "typical" presentation of vasovagal syncope refers to syncope triggered by emotional or orthostatic stress, painful or noxious stimuli, fear of bodily injury, prolonged standing, heat exposure, or after physical exertion. The "atypical" (also referred to as "nonclassical") presentation of vasovagal syncope occurs in some patients, especially those who are older, who have recurrent episodes of syncope without an identifiable cause or trigger. Situation syncope may be triggered by a variety of scenarios, including micturition, coughing, defecating, swallowing, etc. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 6/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Recurrence Reflex syncope can be a recurrent problem, depending on the particular individual and triggers. However, a significant proportion of patients will do well without any further episodes. A study of self-reported symptom burden in 418 patients diagnosed with vasovagal syncope indicated that 35 percent were symptom free at median five-year follow-up, regardless of presenting symptom or treatment received [30]. Evaluation of vasovagal syncope recurrence has demonstrated the randomness of recurrence, but events often occur in clusters [31]. Consequently, evaluating treatment efficacy is complex both for individual patients and in the setting of clinical trials. INITIAL EVALUATION The initial evaluation of suspected reflex syncope should include obtaining a comprehensive history detailing the nature of and circumstances surrounding spontaneous events, performance of a physical examination (which may include careful carotid sinus massage in patients over age 55 years), and review of resting and ambulatory ECG recordings. Additional diagnostic evaluation, if indicated, should be individualized based upon the suspected etiology of syncope, but is rarely needed in patients with suspected reflex syncope in whom the story and associated symptoms are often adequate to establish the diagnosis. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Approach to initial evaluation'.) Medical history Obtaining a detailed medical history is the first step in determining whether syncope is reflex syncope or due to some other cause. If the history obtained is thorough, the story provided by the patient (and witnesses, if any) will often reveal that the collapse was due to syncope of reflex origin and will provide a means of guiding subsequent testing and treatment. However, history taking is highly dependent upon the experience of the clinician, and in addition depends on the whether the patient and witnesses can give an accurate account of events (which may be limited in patients who are very young, very elderly, uncomfortable [eg, experiencing pain], intoxicated, or in whom a language barrier exists). Key points from the medical history include (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Clinical features'): Number, frequency, and duration of episodes (true syncope is usually brief unless complicated by head injury due to a fall) Associated symptoms preceding syncope (ie, prodromal symptoms) Patient position at the time of syncope Triggers or provocative factors https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 7/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Associated symptoms following syncope Witnessed signs Preexisting medical conditions, medications, and family history Symptoms after recovery Syncope precipitated by emotional distress or orthostatic stress and associated with typical prodrome is suggestive but not diagnostic of vasovagal syncope. Further evaluation with tilt table test is not usually indicated if diagnostic vasovagal features are identified and further testing will not alter treatment. However, reproduction of symptoms during tilt table testing may help reassure patients that the clinician has observed a spell and therefore is better positioned to care for the patient. Recent history may be more helpful than lifetime history in predicting vasovagal syncope recurrence. In a study of 208 subjects with a positive tilt test and 3 lifetime syncope spells, the number of vasovagal syncope spells in the preceding year better predicted syncope recurrence than total number of historical spells (likelihood ratio statistic 28.4 versus 20.4) [32]. However, as noted earlier, randomness is also a feature of vasovagal recurrences. Physical examination A number of findings on physical examination can aid in the identification of some of the common causes of syncope, including abnormalities in the vital signs, cardiovascular abnormalities, and less frequently neurological signs. Typically, patients with reflex syncope will have a normal physical examination, or non-specific findings on physical examination which do not relate to the syncopal episode. Electrocardiogram An ECG should be obtained in all patients with syncope, including patients with suspected reflex syncope. The 12-lead ECG is usually normal or nonspecific in patients with vasovagal and most other forms of reflex syncope. Certain ECG findings (eg, conduction system abnormalities, prolonged QT interval, Brugada pattern) may suggest underlying cardiac disease that would potentially require additional evaluation and monitoring. Risk stratification As part of the initial syncope evaluation, clinicians must determine whether the affected individual needs in-hospital care for further evaluation and/or initiation of treatment. The primary factor determining whether the patient with presumed syncope should be hospitalized is the individual's immediate mortality, falls/injury risk, and, to a lesser extent, the issue of whether the patient has adequate home care and whether certain treatments require hospital monitoring for safe initiation. The risk stratification of patients with syncope is discussed in detail separately. In most cases, when the collapse is thought to be reflex syncope, patients are considered to be at low risk of near-term mortality or recurrent syncope resulting in injury. Patients with reflex https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 8/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate syncope most often have no evidence of structural heart disease and have a normal baseline ECG, although patients with these conditions can also experience reflex syncope. Reflex syncope is considered relatively benign with regard to the risk of early mortality, but not necessarily with regard to recurrent syncope with risk of falls resulting in injury. Most patients can be treated and discharged home for further outpatient evaluation as needed if their home care situation is appropriate to prevent injury should there be a recurrence. SELECTED ADDITIONAL TESTING Patients with a certain diagnosis of reflex syncope (ie, a classic history) generally do not require further diagnostic evaluation, although on occasion a confirmatory test may be warranted [1,2]. For patients with an uncertain diagnosis after the initial evaluation, particularly for patients with an atypical presentation, specific confirmatory testing utilizing upright tilt table testing or ambulatory ECG monitoring is warranted in order to solidify or refute the diagnosis of reflex syncope. Such testing may help reassure the patient that the correct diagnosis has been established and that the physician has now witnessed the patient's symptom event. Upright tilt table test Tilt-table testing is an example of a "confirmatory" test, which can be used when the diagnosis of a reflex vasovagal syncope is suspected, but the presentation is not classical [33,34]. However, the tilt table test has limited specificity. The test result must be interpreted by an experienced clinician in light of other history and physical finding data. A detailed discussion of the tilt table test is found elsewhere. (See "Upright tilt table testing in the evaluation of syncope".) We proceed with tilt table testing in the following situations: Patients with unexplained single syncopal episodes in high-risk settings (eg, collapse while driving, using machinery, or working in an occupation that may result in injury). Patients with recurrent syncopal episodes in the absence of organic heart disease, or in the presence of organic heart disease after cardiac causes have been excluded. Patients in whom it is of clinical value to demonstrate susceptibility to reflex syncope. Patients in whom both reflex syncope and orthostatic hypotension syncope are being considered. Patients who express skepticism regarding the proposed diagnosis or in whom job requirements necessitate such testing to confirm the proposed diagnosis. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 9/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Electrocardiographic monitoring Ambulatory ECG monitoring is most commonly used when there is suspicion that a cardiac arrhythmia may be the cause of syncope, but may also be used in patients with suspected reflex syncope in an attempt to document the heart rhythm during an event and to exclude primary cardiac causes (eg, high grade atrioventricular block, ventricular tachycardia, etc). In patients with more frequent reflex syncope, relatively short-term (one month) non-invasive electrocardiographic monitoring (eg, an event [loop] recorder) may suffice (bearing in mind the limitations of such testing due to the randomness and clustering of recurrences discussed earlier). Since syncopal episodes often occur less frequently (eg, less than once per month), longer-term monitoring options may be required and can significantly improve the diagnostic yield over shorter-term monitoring [35]. The insertable cardiac monitor (ICM) is a subcutaneous monitoring device for the detection of cardiac arrhythmias [35,36]. ICMs are most commonly utilized in the evaluation of palpitations or syncope of undetermined etiology, particularly when symptoms are infrequent (eg, less than once per month) and/or other ambulatory monitoring has been unrevealing or inconclusive ( table 3). The use of ICMs and other electrocardiographic monitoring in the diagnosis of otherwise unexplained syncope is discussed separately. (See "Ambulatory ECG monitoring".) DIAGNOSIS The diagnosis of reflex syncope is made primarily based on the clinical features of the event ( table 4). Laboratory testing is used mainly to support a clinical suspicion. There are no testing procedures that are sensitive or specific enough to definitively establish a diagnosis on their own; laboratory findings must be compatible with the history in order to be diagnostically useful. Diagnostic criteria have been proposed, but these are primarily based on the clinical features of the event. Patients with vasovagal syncope usually experience a prodrome of nausea, pallor, and diaphoresis, consistent with increased vagal tone. Typical triggers and premonitory symptoms are strongly suggestive of vasovagal syncope. Situational syncope is usually diagnosed with the same prodromal symptoms as are seen in vasovagal syncope based on the setting of a specific scenario or trigger, such as micturition, coughing, defecating, or swallowing. Situational faints often do not have prodromal symptoms. DIFFERENTIAL DIAGNOSIS https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 10/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate The differential diagnosis of vasovagal syncope includes other causes of syncope ( table 1), as well as non-syncopal conditions that produce apparent or real transient loss of consciousness (eg, falls, transient ischemic attacks, seizures) ( table 5). The major causes of syncope are discussed in greater detail separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".) Vasovagal syncope may be considered in some cases a cause of acute postural hypotension. Other causes of postural hypotension are discussed separately. (See "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Postural tachycardia syndrome".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definitions Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often the result of https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 11/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate an abrupt drop of systemic blood pressure. Reflex syncope (previously termed neurally- mediated syncope) is TLOC due to a reflex response that encompasses vasodilatation and/or bradycardia (rarely tachycardia), leading to systemic hypotension and cerebral hypoperfusion. Types of reflex syncope include vasovagal syncope, situational syncope, carotid sinus syncope, and some cases without apparent triggers ( table 1). (See 'Introduction' above and "Carotid sinus hypersensitivity and carotid sinus syndrome".) Pathogenesis The most frequent mechanism for reflex syncope is a mixed cardioinhibitory and vasodepressor hemodynamic response. An individual patient may have syncopal events caused by varying mechanisms, with vasodepressor, cardioinhibitory, or mixed responses at different times. Cardioinhibitory response This response results primarily from increased parasympathetic activation and may be manifested by sinus bradycardia, PR interval prolongation, advanced atrioventricular block, and/or asystole. Vasodepressor response This response is due to decreased sympathetic activity and can lead to symptomatic hypotension even in the absence of severe bradycardia. Mixed response This response contains components of both the cardioinhibitory and vasodepressor responses. (See 'Pathogenesis of reflex syncope' above.) Clinical presentation The clinical features associated with a syncopal event may be diagnostic ( table 4). In younger individuals, vasovagal syncope is usually associated with a prodrome of nausea, pallor, and diaphoresis, consistent with increased vagal tone. These symptoms may be absent or difficult to correlate to the syncopal episode in some individuals, particularly in older adults. (See 'Clinical presentation' above.) Initial evaluation The initial evaluation of patients with suspected TLOC due to reflex syncope serves both diagnostic and prognostic purposes. For nearly all patients, the initial evaluation of suspected reflex syncope should include obtaining a comprehensive history, performance of a physical examination (which may include careful carotid sinus massage in older patients), and review of an electrocardiogram (ECG). Additional diagnostic evaluation is rarely needed in patients with suspected reflex syncope. (See 'Initial evaluation' above.) Risk stratification The initial syncope evaluation includes a determination of whether the affected individual requires hospitalization. In most cases of suspected reflex syncope, patients are considered to be at low risk of near-term mortality, but not necessarily with regard to recurrent syncope with risk of falls resulting in injury. Most patients can be https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 12/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate treated and discharged home for further outpatient evaluation as needed. (See 'Risk stratification' above.) Additional testing Patients with a certain diagnosis of reflex syncope generally do not require further diagnostic evaluation, although on occasion a confirmatory test may be warranted. Such a test may reassure the patient that the physician has witnessed the patient's symptoms. For patients with an uncertain diagnosis after the initial evaluation, particularly for patients with an atypical presentation, specific confirmatory testing utilizing upright tilt table testing or ambulatory ECG monitoring is warranted in order to solidify or exclude the diagnosis of reflex syncope. (See 'Selected additional testing' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Brian Olshansky, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 2. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 3. Chen-Scarabelli C, Scarabelli TM. Neurocardiogenic syncope. BMJ 2004; 329:336. 4. Parry SW, Tan MP. An approach to the evaluation and management of syncope in adults. BMJ 2010; 340:c880. 5. Shenthar J, Prabhu MA, Banavalikar B, et al. Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study. JACC Clin Electrophysiol 2019; 5:608. 6. Mosqueda-Garcia R, Furlan R, Tank J, Fernandez-Violante R. The elusive pathophysiology of neurally mediated syncope. Circulation 2000; 102:2898. 7. Benditt DG, van Dijk JG, Krishnappa D, et al. Neurohormones in the Pathophysiology of Vasovagal Syncope in Adults. Front Cardiovasc Med 2020; 7:76. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 13/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate 8. Chen MY, Goldenberg IF, Milstein S, et al. Cardiac electrophysiologic and hemodynamic correlates of neurally mediated syncope. Am J Cardiol 1989; 63:66. 9. Morillo CA, Eckberg DL, Ellenbogen KA, et al. Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation 1997; 96:2509. 10. Thomson HL, Wright K, Frenneaux M. Baroreflex sensitivity in patients with vasovagal syncope. Circulation 1997; 95:395. 11. Kohno R, Detloff BLS, Chen LY, et al. Greater early epinephrine rise with head-up posture: A marker of increased syncope susceptibility in vasovagal fainters. J Cardiovasc Electrophysiol 2019; 30:289. 12. Moya A, Brignole M, Menozzi C, et al. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope. Circulation 2001; 104:1261. 13. B chir M, Binggeli C, Corti R, et al. Dysfunctional baroreflex regulation of sympathetic nerve activity in patients with vasovagal syncope. Circulation 2003; 107:1620. 14. Yao Y, Shi R, Wong T, et al. Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol 2012; 5:279. 15. Saadjian AY, L vy S, Franceschi F, et al. Role of endogenous adenosine as a modulator of syncope induced during tilt testing. Circulation 2002; 106:569. 16. Brignole M, Groppelli A, Brambilla R, et al. Plasma adenosine and neurally mediated syncope: ready for clinical use. Europace 2020; 22:847. 17. WAYNE HH. Syncope. Physiological considerations and an analysis of the clinical characteristics in 510 patients. Am J Med 1961; 30:418. 18. Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet 2001; 357:348. 19. Engelstein, ED, Hutchins, et al. Normal cardiac sympathetic innervation in patients with neurocardiac syncope (abstract). J Am Coll Cardiol 1998; 31:165A. 20. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol 2001; 37:1921. 21. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. 22. Colivicchi F, Ammirati F, Biffi A, et al. Exercise-related syncope in young competitive athletes without evidence of structural heart disease. Clinical presentation and long-term outcome. Eur Heart J 2002; 23:1125. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 14/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate 23. Sakaguchi S, Shultz JJ, Remole SC, et al. Syncope associated with exercise, a manifestation of neurally mediated syncope. Am J Cardiol 1995; 75:476. 24. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997; 126:989. 25. Calkins H, Shyr Y, Frumin H, et al. The value of the clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block, and neurocardiogenic syncope. Am J Med 1995; 98:365. 26. McIntosh S, Da Costa D, Kenny RA. Outcome of an integrated approach to the investigation of dizziness, falls and syncope in elderly patients referred to a 'syncope' clinic. Age Ageing 1993; 22:53. 27. Alboni P, Brignole M, Menozzi C, et al. Clinical spectrum of neurally mediated reflex syncopes. Europace 2004; 6:55. |
prolongation, advanced atrioventricular block, and/or asystole. Vasodepressor response This response is due to decreased sympathetic activity and can lead to symptomatic hypotension even in the absence of severe bradycardia. Mixed response This response contains components of both the cardioinhibitory and vasodepressor responses. (See 'Pathogenesis of reflex syncope' above.) Clinical presentation The clinical features associated with a syncopal event may be diagnostic ( table 4). In younger individuals, vasovagal syncope is usually associated with a prodrome of nausea, pallor, and diaphoresis, consistent with increased vagal tone. These symptoms may be absent or difficult to correlate to the syncopal episode in some individuals, particularly in older adults. (See 'Clinical presentation' above.) Initial evaluation The initial evaluation of patients with suspected TLOC due to reflex syncope serves both diagnostic and prognostic purposes. For nearly all patients, the initial evaluation of suspected reflex syncope should include obtaining a comprehensive history, performance of a physical examination (which may include careful carotid sinus massage in older patients), and review of an electrocardiogram (ECG). Additional diagnostic evaluation is rarely needed in patients with suspected reflex syncope. (See 'Initial evaluation' above.) Risk stratification The initial syncope evaluation includes a determination of whether the affected individual requires hospitalization. In most cases of suspected reflex syncope, patients are considered to be at low risk of near-term mortality, but not necessarily with regard to recurrent syncope with risk of falls resulting in injury. Most patients can be https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 12/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate treated and discharged home for further outpatient evaluation as needed. (See 'Risk stratification' above.) Additional testing Patients with a certain diagnosis of reflex syncope generally do not require further diagnostic evaluation, although on occasion a confirmatory test may be warranted. Such a test may reassure the patient that the physician has witnessed the patient's symptoms. For patients with an uncertain diagnosis after the initial evaluation, particularly for patients with an atypical presentation, specific confirmatory testing utilizing upright tilt table testing or ambulatory ECG monitoring is warranted in order to solidify or exclude the diagnosis of reflex syncope. (See 'Selected additional testing' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Brian Olshansky, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 2. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 3. Chen-Scarabelli C, Scarabelli TM. Neurocardiogenic syncope. BMJ 2004; 329:336. 4. Parry SW, Tan MP. An approach to the evaluation and management of syncope in adults. BMJ 2010; 340:c880. 5. Shenthar J, Prabhu MA, Banavalikar B, et al. Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study. JACC Clin Electrophysiol 2019; 5:608. 6. Mosqueda-Garcia R, Furlan R, Tank J, Fernandez-Violante R. The elusive pathophysiology of neurally mediated syncope. Circulation 2000; 102:2898. 7. Benditt DG, van Dijk JG, Krishnappa D, et al. Neurohormones in the Pathophysiology of Vasovagal Syncope in Adults. Front Cardiovasc Med 2020; 7:76. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 13/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate 8. Chen MY, Goldenberg IF, Milstein S, et al. Cardiac electrophysiologic and hemodynamic correlates of neurally mediated syncope. Am J Cardiol 1989; 63:66. 9. Morillo CA, Eckberg DL, Ellenbogen KA, et al. Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation 1997; 96:2509. 10. Thomson HL, Wright K, Frenneaux M. Baroreflex sensitivity in patients with vasovagal syncope. Circulation 1997; 95:395. 11. Kohno R, Detloff BLS, Chen LY, et al. Greater early epinephrine rise with head-up posture: A marker of increased syncope susceptibility in vasovagal fainters. J Cardiovasc Electrophysiol 2019; 30:289. 12. Moya A, Brignole M, Menozzi C, et al. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope. Circulation 2001; 104:1261. 13. B chir M, Binggeli C, Corti R, et al. Dysfunctional baroreflex regulation of sympathetic nerve activity in patients with vasovagal syncope. Circulation 2003; 107:1620. 14. Yao Y, Shi R, Wong T, et al. Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol 2012; 5:279. 15. Saadjian AY, L vy S, Franceschi F, et al. Role of endogenous adenosine as a modulator of syncope induced during tilt testing. Circulation 2002; 106:569. 16. Brignole M, Groppelli A, Brambilla R, et al. Plasma adenosine and neurally mediated syncope: ready for clinical use. Europace 2020; 22:847. 17. WAYNE HH. Syncope. Physiological considerations and an analysis of the clinical characteristics in 510 patients. Am J Med 1961; 30:418. 18. Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet 2001; 357:348. 19. Engelstein, ED, Hutchins, et al. Normal cardiac sympathetic innervation in patients with neurocardiac syncope (abstract). J Am Coll Cardiol 1998; 31:165A. 20. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol 2001; 37:1921. 21. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. 22. Colivicchi F, Ammirati F, Biffi A, et al. Exercise-related syncope in young competitive athletes without evidence of structural heart disease. Clinical presentation and long-term outcome. Eur Heart J 2002; 23:1125. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 14/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate 23. Sakaguchi S, Shultz JJ, Remole SC, et al. Syncope associated with exercise, a manifestation of neurally mediated syncope. Am J Cardiol 1995; 75:476. 24. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997; 126:989. 25. Calkins H, Shyr Y, Frumin H, et al. The value of the clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block, and neurocardiogenic syncope. Am J Med 1995; 98:365. 26. McIntosh S, Da Costa D, Kenny RA. Outcome of an integrated approach to the investigation of dizziness, falls and syncope in elderly patients referred to a 'syncope' clinic. Age Ageing 1993; 22:53. 27. Alboni P, Brignole M, Menozzi C, et al. Clinical spectrum of neurally mediated reflex syncopes. Europace 2004; 6:55. 28. Romme JJ, van Dijk N, Boer KR, et al. Influence of age and gender on the occurrence and presentation of reflex syncope. Clin Auton Res 2008; 18:127. 29. Tan MP, Parry SW. Vasovagal syncope in the older patient. J Am Coll Cardiol 2008; 51:599. 30. Ross R, Parry S, Norton M, Newton JL. Self-reported symptom burden; outcome in 418 patients from the Newcastle Vasovagal (Neurocardiogenic) cohort. QJM 2008; 101:127. 31. Sahota IS, Maxey C, Pournazari P, Sheldon RS. Clusters, Gaps, and Randomness: Vasovagal Syncope Recurrence Patterns. JACC Clin Electrophysiol 2017; 3:1046. 32. Sumner GL, Rose MS, Koshman ML, et al. Recent history of vasovagal syncope in a young, referral-based population is a stronger predictor of recurrent syncope than lifetime syncope burden. J Cardiovasc Electrophysiol 2010; 21:1375. 33. Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001; 22:1256. 34. Oribe E, Caro S, Perera R, et al. Syncope: the diagnostic value of head-up tilt testing. Pacing Clin Electrophysiol 1997; 20:874. 35. Benditt DG, Adkisson WO, Sutton R, et al. Ambulatory diagnostic ECG monitoring for syncope and collapse: An assessment of clinical practice in the United States. Pacing Clin Electrophysiol 2018; 41:203. 36. Krahn AD, Klein GJ, Skanes AC, Yee R. Insertable loop recorder use for detection of intermittent arrhythmias. Pacing Clin Electrophysiol 2004; 27:657. Topic 1050 Version 40.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 15/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate GRAPHICS Major cardiovascular causes of syncope Reflex-mediated* Vasovagal Orthostatic vasovagal syncope: usually after prolonged standing, frequently in a warm environment, etc Emotional vasovagal syncope: secondary to fear, pain, medical procedure, etc Unknown trigger Situational Micturition, defecation Swallowing Coughing/sneezing Carotid sinus syndrome Orthostatic hypotension* Medication-related Diuretics (eg, thiazide or loop diuretics) Vasodilators (eg, dihydropyridine calcium channel blockers, nitrates, alpha blockers, etc) Antidepressants (eg, tricyclic drugs, SSRIs, etc) Volume depletion Hemorrhage Gastrointestinal losses (ie, vomiting or diarrhea) Diminished thirst drive (primarily in older patients) Autonomic failure Primary: pure autonomic failure, Parkinson disease, multiple system atrophy, Lewy body dementia Secondary: diabetes mellitus, amyloidosis, spinal cord injuries, autoimmune neuropathy (eg, Guillain-Barr ), paraneoplastic neuropathy Cardiac Tachyarrhythmias Ventricular tachycardia Supraventricular tachycardias Bradyarrhythmias (with inadequate ventricular response) Sinus node dysfunction https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 16/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Atrioventricular block Structural disease Severe aortic stenosis Hypertrophic cardiomyopathy Cardiac tamponade Prosthetic valve dysfunction Congenital coronary anomalies Cardiac masses and tumors (eg, atrial myxoma) Cardiopulmonary/vascular Pulmonary embolus Severe pulmonary hypertension Aortic dissection SSRI: selective serotonin reuptake inhibitor. Reflex-mediated syncope and syncope due to orthostatic hypotension are more likely to occur, or are more severe, when other factors may also be contributing, such as medication(s) causing low blood pressure, volume depletion, pulmonary diseases causing reduction in brain oxygen supply, alcohol use, and/or environmental factors (excessive heat or humidity). Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. Graphic 118175 Version 4.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 17/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Pathways in neurally mediated syncope Schematic representation of the specific syndromes, the suspected peripheral receptors (triggers), the afferent neural pathways, and the efferent pathways responsible for the clinical manifestations of bradycardia and hypotension in specific syncopal syndromes. GI: gastrointestinal; GU: genitourinary; NTS: nucleus tractus solitarius; V, VII, VIII, IX, and X: cranial nerves. Graphic 80233 Version 4.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 18/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Major life threatening causes of syncope Cardiovascular syncope Arrhythmia Ventricular tachycardia Long QT syndrome Brugada syndrome Bradycardia: Mobitz type II or 3rd degree heart block Significant sinus pause >3 seconds Ischemia Acute coronary syndrome, myocardial infarction Structural Abnormalities Valvular heart disease: aortic stenosis, mitral stenosis Cardiomyopathy (ischemic, dilated, hypertrophic) Atrial myxoma Cardiac tamponade Aortic dissection Significant hemorrhage Trauma with significant blood loss Gastrointestinal bleeding Tissue rupture: aortic aneurysm, spleen, ovarian cyst, ectopic pregnancy, retroperitoneal hemorrhage Pulmonary embolism Saddle embolus resulting in outflow tract obstruction or severe hypoxia Subarachnoid hemorrhage Graphic 81820 Version 1.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 19/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Electrocardiographic monitoring for syncope Recommendations Class* Level Indications ECG monitoring is indicated in patients who have clinical or ECG features I B suggesting arrhythmic syncope (listed in the "Risk stratification for syncope" table). The duration (and technology) of monitoring should be selected according to the risk and the predicted recurrence rate of syncope: Immediate in-hospital monitoring (in bed or telemetric) is indicated in high risk patients (as defined in the "Risk stratification for syncope" table) I C Holter monitoring is indicated in patients who have very frequent syncope or pre-syncope ( one per week) I B ILR is indicated in: An early phase of evaluation in patients with recurrent syncope of uncertain origin, absence of high risk criteria, and a high likelihood of recurrence within battery longevity of the device I B High risk patients (as defined in the "Risk stratification for syncope" table) in whom a comprehensive evaluation did not demonstrate a cause of syncope or lead to a specific treatment I B ILR should be considered to assess the contribution of bradycardia before embarking on cardiac pacing in patients with suspected or certain reflex IIa B syncope presenting with frequent or traumatic syncopal episodes External loop recorders should be considered in patients who have an inter-symptom interval four weeks IIa B Diagnostic criteria ECG monitoring is diagnostic when a correlation between syncope and an arrhythmia (brady- or tachyarrhythmia) is detected I B In the absence of such correlation, ECG monitoring is diagnostic when periods of Mobitz II or III degree AV block or a ventricular pause >3 s (with the possible exception of young trained persons, during sleep, medicated I C patients, or rate-controlled atrial fibrillation), or rapid prolonged paroxysmal SVT or VT are detected. The absence of arrhythmia during syncope excludes arrhythmic syncope. The ECG documentation of pre-syncope without any relevant arrhythmia is not an accurate surrogate for syncope III C Asymptomatic arrhythmias (other than those listed above) are not an accurate surrogate for syncope III C https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 20/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Sinus bradycardia (in the absence of syncope) is not an accurate surrogate for III C syncope AV: atrioventricular; ECG: electrocardiogram; ILR: implantable loop recorder; SVT: supraventricular tachyradia; VT: ventricular tachycardia. Class of recommendation. Level of evidence. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 57636 Version 11.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 21/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Clinical features of syncope that suggest a cause Neurally mediated syncope: Absence of heart disease Long history of recurrent syncope After sudden unexpected unpleasant sight, sound, smell, or pain Prolonged standing or crowded, hot places Nausea, vomiting associated with syncope During a meal or postprandial With head rotation or pressure on carotid sinus (as in tumors, shaving, tight collars) After exertion Syncope due to OH: After standing up Temporal relationship with start or changes of dose of vasodepressive drugs leading to hypotension Prolonged standing, especially in crowded, hot places Presence of autonomic neuropathy or Parkinsonism Standing after exertion Cardiovascular syncope: Presence of definite structural heart disease Family history of unexplained sudden death or channelopathy During exertion or supine Abnormal ECG Sudden onset palpitation immediately followed by syncope ECG findings suggesting arrhythmic syncope: Bifascicular block (defined as either LBBB or RBBB combined with left anterior or left posterior fascicular block) Other intraventricluar conduction abnormalities (QRS duration 0.12 s) Mobitz I second-degree AV block Asymptomatic inappropriate sinus bradycardia (<50 bpm), sinoatrial block or sinus pause 3 s in the absence of negatively chronotropic medications Nonsustained VT https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 22/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Preexcited QRS complexes Long or short QT intervals Early repolarization RBBB pattern with ST elevation in leads V1 to V3 (Brugada syndrome) Negative T waves in right precordial leads, epsilon waves and ventricular late potentials suggestive of ARVC Q waves suggesting myocardial infarction OH: orthostatic hypotension; ECG: electrocardiogram; LBBB: left bundle branch block; RBBB: right bundle branch block; AV: atrioventricular; bpm: beats per minute; VT: ventricular tachycardia; ARVC: arrhythmogenic right ventricular cardiomyopathy. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 66884 Version 10.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 23/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Conditions incorrectly diagnosed as syncope Disorders with partial or complete LOC but without global cerebral hypoperfusion Epilepsy Metabolic disorders including hypoglycaemia, hypoxia, hyperventilation with hypocapnia Intoxication Vertebrobasilar TIA Disorders without impairment of consciousness Cataplexy Drop attacks Falls Functional (psychogenic pseudosyncope) TIA or carotid origin LOC: loss of consciousness; TIA: transient ischaemic attack. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 76023 Version 6.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 24/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Contributor Disclosures David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and defibrillators]; St Jude Medical [Pacemakers/event recorders and defibrillators]. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced CPR Solutions [Outside director]. All of the relevant financial relationships listed have been mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias]. Consultant/Advisory Boards: Abbvie [Arrhythmias]; Acesion Pharma [Arrhythmias]; Allergan [Arrhythmias, cardiac safety of non-cardiac drugs]; Anthos [Anticoagulants]; Boehringer-Ingelheim [Arrhythmias]; Bristol-Meyers-Squibb [Arrhythmias]; Daiichi Sankyo [Arrhythmias]; Gilead [Arrhythmias]; Huya [Arrhythmias]; InCarda Therapeutics [Arrhythmias]; INSTA [Arrhythmias]; Johnson & Johnson [Arrhythmias]; Medtronic [Arrhythmias]; Milestone [Arrhythmias]; Novartis [Arrhythmias, cardiac safety of non-cardiac drugs]; Pfizer [Arrhythmias]; Sanofi [Arrhythmias]; Takeda [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 25/25 |
7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Reflex syncope in adults and adolescents: Treatment : David Benditt, MD : Peter Kowey, MD, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 29, 2022. INTRODUCTION Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral blood flow, caused most often by an abrupt drop of systemic blood pressure. Reflex syncope (previously termed neurally mediated syncope) is a condition in which a reflex response causes vasodilatation and/or bradycardia. The heart rate slowing may or may not be profound but results in a heart rate that is slower than appropriate for the falling blood pressure, leading to systemic hypotension and cerebral hypoperfusion with TLOC. Types of reflex syncope include vasovagal syncope (eg, cough syncope, deglutition syncope, and others), situational syncope, carotid sinus syncope, and some cases without apparent triggers ( table 1). Vasovagal syncope is by far the most common type of syncope across all age groups. The treatment of patients with reflex syncope is reviewed here, focusing on preventive measures. Related issues are discussed separately: (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Syncope in adults: Management and prognosis".) (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".) https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 1/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate IMMEDIATE MANAGEMENT The immediate management of syncope to minimize the duration of loss of consciousness and reduce the risk of injury is discussed separately. (See "Syncope in adults: Management and prognosis", section on 'Immediate (emergency) treatment of syncopal patients'.) GENERAL MEASURES Therapy for patients with reflex syncope is primarily aimed at patients with recurrent episodes. These are primarily vasovagal faints (eg, with venipuncture) but may also be due to recurrent situational reflex faints, especially cough syncope. No therapy has been proven consistently effective for preventing vasovagal syncope recurrences. However, the measures discussed herein are undertaken to reduce the risk of syncope and/or the risk of injury from syncope. Treat predisposing conditions Medical conditions that may increase the risk of syncope (eg, volume depletion that predisposes to vasovagal syncope, pulmonary disease for cough syncope, or esophageal disease in deglutition syncope) should be identified and treated. Of particular importance, medications that may induce volume depletion (eg, vasodilators, diuretics) should be minimized or avoided to the extent that alternative therapies are available [1,2]. Patient education Patients should be provided with education regarding the nature, risks, and prognosis of reflex syncope [1,2]. Trigger avoidance Patients should be advised to take steps to avoid known trigger events. Preventive steps include assuming a protected posture (eg, sitting to avoid prolonged standing), smoking cessation and cough suppression to avoid cough syncope, stool softeners to avoid defecation syncope, avoidance of excessive fluid intake (especially alcohol) prior to bedtime to diminish risk of postmicturition syncope, and avoidance of large gulps of cold drinks or boluses of food to avoid swallow syncope. Other steps that may be helpful include consuming small meals and reducing carbohydrates in the diet. (See "Treatment of orthostatic and postprandial hypotension".) Recognizing symptoms and taking action Patients should be educated to recognize early symptoms and take action to avert syncope and reduce the risk of injury. If the symptoms are mild, the patient may perform a physical counterpressure maneuver while moving safely to a seated or supine position, which should terminate the episode. If the symptoms are severe, the patient should move directly to a supine position. In either case, they should remain in a safe, https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 2/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate gravitationally neutral position long enough to be sure that all of the warning symptoms have subsided. Arising too soon may trigger a symptom recurrence. Counterpressure maneuvers Patients with vasovagal syncope and prodromal symptoms should be taught how to perform physical counterpressure maneuvers. The rationale for these maneuvers is to reduce venous pooling and thus improve cardiac output. The patient should undertake these maneuvers upon first recognition of premonitory symptoms [1-3] and then assume a supine position. These maneuvers may abort a syncope episode or at least delay it long enough for the patient to move to a safe protected position [4]. While isometric activity may offset a syncopal response, release of this activity may be associated with precipitous decline in heart rate and blood pressure. Examples of counterpressure maneuvers include: Leg-crossing with simultaneous tensing of leg, abdominal, and buttock muscles (very effective). Handgrip, which consists of maximum grip on a rubber ball or similar object (effectiveness is limited by hand strength). Arm tensing, which involves gripping one hand with the other while simultaneously abducting both arms (effectiveness is limited by arm strength). The efficacy of these maneuvers was evaluated in a randomized trial of 223 patients with recurrent vasovagal syncope and recognizable prodromal symptoms [5]. Patients were randomly assigned to lifestyle modification (eg, avoidance of triggers, increasing fluid and salt intake, lying down at the onset of prodromal symptoms), or lifestyle modification plus physical counterpressure maneuvers. Over a mean follow-up of 14 months, patients assigned to counterpressure maneuvers were significantly less likely to have recurrent syncope compared with those assigned to lifestyle modification alone (32 versus 51 percent). Supine position Patients should be advised to assume the supine position with legs raised at the onset of severe symptoms or immediately after performing a counterpressure maneuver, whenever feasible. Assuming a seated or squatting position may also prove effective. Volume support Patients with recurrent reflex syncope should receive counseling on steps to optimize and maintain intravascular volume, similar to the regimens for orthostatic hypotension (see "Treatment of orthostatic and postprandial hypotension") [1,2,6]. These include: https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 3/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate Increase fluid intake A reasonable regimen is ingesting 500 mL of fluid upon waking with a daily target of 1.5 to 3 L. The fluid may be a low-carbohydrate electrolyte-containing drink or water. Patients can conserve resources by adding electrolyte powder to water. Liberalizing salt intake Unless there is a contraindication, a typical target dose is 6 to 10 g of sodium daily. This may be achieved by high sodium-containing food, drink, or salt tablets. Salt tablets are often poorly tolerated from a gastrointestinal perspective, and electrolyte caplets (available on various websites) may be preferred. Compression stockings and binders Compression undergarments may help support intravascular volume. Many options may be found on the internet. Compression type "bicycling" shorts are relatively easy to put on and focus on the major muscle groups in the buttocks, thighs, and, to some extent, the abdomen. Compression vests or abdominal binders that compress the splanchnic may be helpful as the splanchnic bed is a large, highly compliant vascular bed that can sequester large volumes of blood, but use of these garments may be limited by discomfort. They are only infrequently needed. Compression (or support) stockings should extend to the waist as the leg muscles have limited blood volume. However, these stockings are poorly tolerated by many patients. Many individuals find these stockings difficult to put on and take off (especially for older patients) and too hot to wear on warm days. They may be contraindicated for patients with evidence of leg ischemia due to peripheral vascular disease or with extensive lower extremity skin lesions. (See "Compression therapy for the treatment of chronic venous insufficiency", section on 'Contraindications'.) Counseling on risk Patients should be reassured about the benign nature of reflex syncope but, nevertheless, warned about potential for injury due to collapse. While mortality risk is very low, injury and accidents are a concern. The risk of injury is highest in patients who have recurrent syncope, are older adults/frail and at risk of fall-induced injury, or who are active in high-risk settings (eg, commercial vehicle driver, pilot, individuals working on ladders) and wish to continue these activities. Patients with recurrent episodes may require restriction of activities until therapy is shown to be effective. Practitioners should consult local regulations advising patients regarding driving or flying. (See 'Driving restrictions' below.) Driving restrictions Although vasovagal syncope generally has a benign prognosis from a mortality perspective, a frequent concern is the potential for accidents and injury, particularly during certain activities such as driving. Clinicians should be familiar with local driving https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 4/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate restrictions and reporting requirements for patients with conditions that could impair safe motor vehicle operation. The applicable local laws and regulations vary widely [7,8]. Insurance companies may decline accident coverage for individuals who are restricted from driving. Nonetheless, given the demands of daily life, it is recognized that adherence to clinician-advised driving restrictions may be low for patients who have been counseled to abstain from driving because of concerns about recurrent syncope [9]. Whether clinicians are legally obligated to report such patients to local authorities varies from region to region. Yoga training Some studies suggest that yoga training may reduce susceptibility to vasovagal syncope [10,11]. An open-label trial randomly assigned 49 patients with recurrent episodes to standard measures and 51 to guided yoga training. The mean number of syncopal episodes before the study was 6.36. There were fewer recurrent episodes in Group 2 compared with Group 1 at the third month (0.8 versus 1.8), at the sixth month (1.0 versus 3.4), and at the twelfth month (1.1 versus 3.8). ADDITIONAL MEASURES Approach to refractory recurrent syncope For patients with recurrent syncope despite the general measures described above (see 'General measures' above), treatment is based upon the results of tilt testing and other clinical characteristics. For patients 40 years of age with recurrent syncope despite general measures, bradycardic or asystolic episodes ( 3 seconds if with syncope, 6 seconds if asymptomatic) documented by electrocardiographic monitoring and no major vasodepressor component on tilt testing [12,13], we suggest permanent cardiac pacing [1,2,14,15]. (See 'Pacemaker therapy' below and "Permanent cardiac pacing: Overview of devices and indications".) For patients with recurrent syncope despite general measures who do not have an indication for permanent cardiac pacing, we suggest treatment with fludrocortisone or midodrine. The choice of drug is based upon the patient s clinical characteristics and preferences. Based on limited evidence, fludrocortisone may be preferred for patients with baseline systolic blood pressure <120 mmHg. Pacemaker therapy Rationale and limitations Although there is usually a significant bradycardic response in vasovagal syncope, there has been uncertainty about the role of pacemakers because of the severe vasodepressor reactions often found in most episodes of reflex syncope. This is true even https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 5/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate for those patients who have asystole during a tilt-table test [16]. Only in carotid sinus hypersensitivity does pacing seem to be consistently effective. In vasovagal syncope, pacing may be useful if the patient does not exhibit a prominent vasodepressor response on tilt-table testing [13]. This finding suggests that recurrent vasovagal syncope is predominantly cardioinhibitory in nature and may thereby respond to pacing treatment. (See "Permanent cardiac pacing: Overview of devices and indications".) In a patient with a mixed response (significant cardioinhibitory and vasodepressor components), dual-chamber permanent pacing may blunt the symptoms. However, many patients with recurrent vasovagal syncope experience a significant fall in blood pressure prior to any significant decline in heart rate, so pacemakers that sense only changes in heart rate cannot provide pacing in a timely manner [17]. Several algorithms (eg, rate-drop response, closed-loop stimulation [CLS]) have been included in pacemakers in an attempt to prevent vasovagal syncope: CLS Dual-chamber permanent pacing with CLS has been the best-studied approach [18- 20]. CLS uses a specialized assessment of cardiac contraction changes to intervene with pacing at an early stage of the evolving faint, thereby potentially interrupting its development. Pacemakers that offer CLS should eliminate most if not all symptoms in patients with a pure cardioinhibitory response [18,20]. Rate-drop response The rate-drop response provides a high pacing rate temporarily during a detected vasovagal event to help support the circulation; it is less well-studied than is CLS [21]. Efficacy of pacemaker therapy Evidence from clinical trials suggests a limited role for pacemaker therapy in patients with vasovagal syncope [20-24]. Pacemaker therapy is not helpful as a routine treatment for all patients with vasovagal syncope, but some evidence suggests that pacemakers may be helpful in selected patients with recurrent syncope who have documented asystole 3 seconds with syncope or asystole 6 seconds without syncope [14]. Pacing effectiveness is limited if the hypotension is predominantly of vasodepressor origin or if bradycardia occurs only late during evolution of the vasovagal event when the hypotension is already severe. A 2018 meta-analysis suggested that an insertable cardiac monitor (ICM; also referred to as implantable cardiac monitor or implantable loop recorder (see "Ambulatory ECG monitoring", section on 'Insertable cardiac monitor')) may be helpful in identifying patients with recurrent vasovagal syncope who have asystole and are likely to respond to pacemaker therapy [24]. Of https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 6/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate 1046 patients with recurrent syncope who were studied by ICM, 201 patients were documented as having an asystolic event (mean duration 12.8 sec) and underwent pacemaker implantation. Follow-up was available in 60 percent of patients with asystolic events. Syncope recurred after pacing in 14.9 percent of patients with an actuarial rate of 13 percent at one year, 21 percent at two years, and 24 percent at three years. On multivariable analysis, positive tilt-test response was the only significant predictor of syncope recurrence (hazard ratio [HR] 4.3, 95% CI 1.4-13). A possible reason for the difference in results between this meta-analysis and earlier studies [22] is the use of ICM to identify candidates for pacing, in contrast to use of tilt testing as a criterion in earlier trials [23]. The above cited meta-analysis included the ISSUE-3 trial in which 511 patients aged 40 years with 3 syncopal episodes within the prior two years received an ICM [21]. Eighty-nine patients were identified with 3 seconds of asystole with syncope or 6 seconds of asystole without syncope; of these 89 patients, 77 received a dual-chamber pacemaker and were randomly assigned to having the pacing function programmed ON or OFF. The two-year estimated syncope recurrence rate was 25 percent (95% CI 13-45) with the pacing function ON and 57 percent (95% CI 40-74) with the pacing function OFF. The later Biosync CLS trial found that pacemakers with a closed loop stimulation (CLS) function (see 'Rationale and limitations' above) reduced the risk of recurrence in selected individuals with reflex syncope identified by tilt test [20]. Patients aged 40 years or older with two or more episodes of unpredictable reflex syncope during the last year and tilt-induced syncope with an asystolic pause longer than 3 sec were randomly assigned to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with CLS. After a median follow-up of 11.2 months, syncope occurred in fewer patients in the pacing group than in the control group (16 versus 53 percent; HR 0.23). Minor device-related adverse events were reported in 4 percent. Drug therapy Fludrocortisone Fludrocortisone is a mineralocorticoid that retains salt in the body and thereby enhances fluid retention. It may be helpful when used along with augmented fluid and salt intake as a means of reducing susceptibility to reflex faints. The drug is typically administered as 0.1 to 0.2 mg daily and is well tolerated. It may, however, cause loss of potassium from the body, and this effect should be monitored, with dietary replacement provided as needed. Fludrocortisone should generally be avoided in patients with hypertension or heart failure. Fludrocortisone may also aggravate migraine susceptibility. In terms of dose, 0.2 mg daily is often needed, but over time (and especially if hypertension evolves) the dose can be reduced to 0.1 mg daily or even lower to 0.1 mg two to four times weekly. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 7/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate In the POST2 Trial, fludrocortisone provided only modest benefit versus placebo [6]. In this trial, 210 patients (median age 30 years, median 15 syncopal spells over a median of 9 years) were randomly assigned to fludrocortisone or placebo. The baseline median systolic blood pressure was 112.5 mmHg. Ninety-six patients had one or more syncope recurrences, and 14 patients were lost to follow-up before syncope recurrence. The frequency of syncope in the fludrocortisone group was nominally but not significantly reduced (HR 0.69, 95% CI 0.46-1.03). In a multivariable model that adjusted for lifetime frequency of spells, fludrocortisone significantly reduced the likelihood of syncope (HR 0.63, 95% CI 0.42-0.94). Fludrocortisone was not helpful in a small trial in children [25]. Midodrine Midodrine is a prodrug; the active metabolite is an alpha-1-adrenergic agonist. Contraindications to midodrine therapy include hypertension and urinary retention. The usual starting dose for midodrine is 5 mg three times daily (morning, noon, and late afternoon). The dose range is 2.5 mg, twice daily, four hours apart to 10 mg, three times daily, four hours apart. Dosing within three to four hours of bedtime should be avoided due to potential detrimental impact on sleep. In some patients, 5 mg twice daily is adequate if the patient has had a more positive response to lifestyle-based therapies. In general, therapy with midodrine should not be considered as a lifelong therapy; patients should be evaluated every three to six months with the goal of reducing or discontinuing the medication if reflex syncope has resolved. Midodrine is used off-label in the management of reflex syncope, as a beneficial effect was suggested by two small randomized trials and a number of observational studies [26-30]. However, the efficacy of midodrine in reflex syncope is limited, and side effects (including supine hypertension) necessitate termination in a substantial number of cases [31]. The largest randomized trial included 133 patients (mean age 32 years; 73 percent female) with a median of six syncope episodes in the prior year [30]. The median baseline systolic blood pressure was 117 mmHg. The participants were randomly assigned to take midodrine or placebo with 12 months of follow-up. The recurrence of syncope was less frequent in the group receiving midodrine (42 versus 61 percent; relative risk 0.69, 95% CI 0.49-0.97). The number needed to treat to prevent syncope in one patient was 5.3. A subgroup analysis suggested that most of the benefit from midodrine was associated with a baseline systolic blood pressure >120 mmHg. Adverse effects were similar in the two groups. TREATMENTS WITH UNCERTAIN BENEFIT https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 8/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate Orthostatic training The efficacy of orthostatic training has not been established [15]. Four randomized controlled trials found that home orthostatic training in patients with syncope and positive tilt-table tests did not reduce tilt-positive responses or spontaneous syncopal events [32-35]. One of these studies suggested a possible benefit in the subset of patients with vasodepressor-type syncope [35]. Unproven drug therapies A variety of medications other than midodrine and fludrocortisone have been used (sometimes in an off-label fashion) in the management of patients with vasovagal syncope [1,2]. None of these drugs are deemed to be consistently effective, and they should be used as a last resort. These medications, including serotonin reuptake inhibitors, anticholinergics (eg, disopyramide, scopolamine), theophylline, desmopressin, and erythropoietin, should only be used in patients who have ongoing issues in spite of reassurance, physical counterpressure maneuvers, and volume support with liberal sodium and fluid intake. The limited available evidence for these supplemental medications in all cases is largely based on small and/or uncontrolled series. Beta blockers The available evidence does not support efficacy of beta blockers for treatment of reflex syncope [2], although these drugs have been commonly used to treat this condition based on a proposed role of a catecholamine trigger for vasovagal events [36]. At least four randomized trials have failed to show a benefit compared with placebo [1,37-40] despite observational data that suggested a benefit [41-43]. The best data come from the POST trial, which enrolled 208 patients with recurrent syncope and an abnormal tilt-table test [39]. The patients were randomly assigned to treatment with placebo or metoprolol (titrated to 200 mg daily or the highest tolerated dose; average dose 122 mg daily). At one year, the rate of recurrent syncope was 36 percent in both groups, with no benefit in any prespecified subgroups. Vasoconstrictors other than midodrine There is insufficient evidence to support the use of vasoconstrictors other than midodrine to treat reflex syncope: Etilefrine The alpha agonist etilefrine was ineffective in a placebo-controlled study of 126 patients [2,44]. Droxidopa This synthetic amino acid is converted in the body to norepinephrine and is approved by the US Food and Drug Administration for short-term use in adults with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure. This agent may be an alternative to midodrine, but supportive evidence for use to treat reflex syncope is lacking [45]. (See "Treatment of orthostatic and postprandial hypotension".) https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 9/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate A preliminary report of seven patients refractory to all other medical therapies suggested benefit from methylphenidate [46]. This agent shares some properties with the amphetamines. It is a peripheral vasoconstrictor and stimulates the central nervous system. Other drugs SSRIs Small studies have suggested that selective serotonin reuptake inhibitors (SSRIs) such as sertraline, fluoxetine, or paroxetine may reduce symptoms in patients with vasovagal syncope [40,47,48]. However, a study found that paroxetine did not prevent a vasovagal reaction to carotid sinus massage and/or lower body negative pressure in healthy volunteers [49]. Disopyramide Disopyramide may be useful due to its negative inotropic (inhibition of myocardial mechanoreceptors) and anticholinergic properties [50]. However, despite apparent benefit in observational studies [50,51], a small controlled trial showed that the rate of recurrent syncope at 29 months was similar with disopyramide and placebo (27 versus 30 percent) [52]. Overall, the potential risks of disopyramide (a Class 1 antiarrhythmic drug that causes QT prolongation) outweigh a possible benefit. Theophylline Small studies have suggested that theophylline may reduce the risk of recurrent reflex syncope [53]. Theophylline may helpful for patients with a mixed vasodepressor and bradycardic response with associated fatigue during the episodes, but data are lacking to support this clinical observation. Ganglionic ablation Radiofrequency ablation has been proposed as a means of reducing vagal inputs to the heart and diminishing susceptibility to reflex vasovagal faints. The methodologies and overall clinical experience remain in their infancy, although there has been increasing interest [54-56]. Use of this procedure should be restricted to prospective clinical trials [12]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) INFORMATION FOR PATIENTS https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 10/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definition Reflex syncope is a condition in which a reflex response causes vasodilatation and/or bradycardia (which may not be profound but is nevertheless slower than appropriate for the falling blood pressure), leading to systemic hypotension and cerebral hypoperfusion with transient loss of consciousness (TLOC). Types of reflex syncope include vasovagal syncope, situational syncope, carotid sinus syncope, and some cases without apparent triggers ( table 1). Vasovagal syncope is the most common type of syncope. (See 'Introduction' above.) General measures General measures for patients with recurrent reflex syncope include (see 'General measures' above): Treatment of predisposing conditions This includes treatment of pulmonary disease for cough syncope. (See 'Treat predisposing conditions' above.) Patient education This includes education on trigger avoidance, need for volume support with high daily fluid and salt intake (if not contraindicated), symptom recognition and appropriate action to avoid risk of injury, and applicable driving restrictions. Patients with vasovagal syncope and prodromal symptoms are counseled to use counterpressure maneuvers (eg, leg crossing) upon first recognition of https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 11/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate premonitory symptoms and to move to a supine position as soon as feasible when symptoms develop. (See 'Patient education' above.) Driving restrictions As the regulations and restrictions on driving differ widely depending upon local law, clinicians should become familiar with the pertinent local regulations. (See 'Driving restrictions' above.) Management of refractory recurrent syncope For patients with recurrent syncope despite the general measures described above, treatment is based upon the results of tilt testing and other clinical characteristics. (See 'Approach to refractory recurrent syncope' above.) For bradycardic or asystolic episodes For patients 40 years of age with recurrent syncope despite general measures, spontaneous bradycardic or asystolic episodes ( 3 seconds if with syncope, 6 seconds if asymptomatic) documented by ambulatory electrocardiographic monitoring and no major vasodepressor component (documented by tilt test), we suggest permanent cardiac pacing (Grade 2C). (See 'Pacemaker therapy' above.) For other types of episodes For patients with recurrent syncope despite general measures who do not have an indication for permanent cardiac pacing, we suggest treatment with fludrocortisone or midodrine (Grade 2C). The choice of drug is based upon the patient s clinical characteristics and preferences. Based on limited evidence, fludrocortisone may be preferred for patients with baseline systolic blood pressure <120 mmHg. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Brian Olshansky, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 12/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate 2. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 3. Soar J, Maconochie I, Wyckoff MH, et al. 2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces. Circulation 2019; 140:e826. 4. Brignole M, Croci F, Menozzi C, et al. Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope. J Am Coll Cardiol 2002; 40:2053. 5. van Dijk N, Quartieri F, Blanc JJ, et al. Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: the Physical Counterpressure Manoeuvres Trial (PC-Trial). J Am Coll Cardiol 2006; 48:1652. 6. Sheldon R, Raj SR, Rose MS, et al. Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial. J Am Coll Cardiol 2016; 68:1. 7. Epstein AE, Miles WM, Benditt DG, et al. Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations. A medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology. Circulation 1996; 94:1147. 8. Epstein AE, Baessler CA, Curtis AB, et al. Addendum to "Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations: a medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology": public safety issues in patients with implantable defibrillators: a scientific statement from the American Heart Association and the Heart Rhythm Society. Circulation 2007; 115:1170. 9. Maas R, Ventura R, Kretzschmar C, et al. Syncope, driving recommendations, and clinical reality: survey of patients. BMJ 2003; 326:21. 10. Shenthar J, Gangwar RS, Banavalikar B, et al. A randomized study of yoga therapy for the prevention of recurrent reflex vasovagal syncope. Europace 2021; 23:1479. 11. Gunda S, Kanmanthareddy A, Atkins D, et al. Role of yoga as an adjunctive therapy in patients with neurocardiogenic syncope: a pilot study. J Interv Card Electrophysiol 2015; 43:105. 12. Brignole M, Moya A, de Lange FJ, et al. Practical Instructions for the 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:e43. 13. Brignole M, Arabia F, Ammirati F, et al. Standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncope: 3-year insights from the Syncope https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 13/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate Unit Project 2 (SUP 2) study. Europace 2016; 18:1427. 14. Sutton R, de Jong JSY, Stewart JM, et al. Pacing in vasovagal syncope: Physiology, pacemaker sensors, and recent clinical trials-Precise patient selection and measurable benefit. Heart Rhythm 2020; 17:821. 15. Sheldon RS, Grubb BP 2nd, Olshansky B, et al. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm 2015; 12:e41. 16. Lacroix D, Kouakam C, Klug D, et al. Asystolic cardiac arrest during head-up tilt test: incidence and therapeutic implications. Pacing Clin Electrophysiol 1997; 20:2746. 17. Kosinski DJ, Grubb BP, Wolfe DA. Permanent cardiac pacing as primary therapy for neurocardiogenic (reflex) syncope. Clin Auton Res 2004; 14 Suppl 1:76. 18. Palmisano P, Dell'Era G, Russo V, et al. Effects of closed-loop stimulation vs. DDD pacing on haemodynamic variations and occurrence of syncope induced by head-up tilt test in older patients with refractory cardioinhibitory vasovagal syncope: the Tilt test-Induced REsponse in Closed-loop Stimulation multicentre, prospective, single blind, randomized study. Europace 2018; 20:859. 19. Baron-Esquivias G, Morillo CA, Moya-Mitjans A, et al. Dual-Chamber Pacing With Closed Loop Stimulation in Recurrent Reflex Vasovagal Syncope: The SPAIN Study. J Am Coll Cardiol 2017; 70:1720. 20. Brignole M, Russo V, Arabia F, et al. Cardiac pacing in severe recurrent reflex syncope and tilt-induced asystole. Eur Heart J 2021; 42:508. 21. Brignole M, Menozzi C, Moya A, et al. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation 2012; 125:2566. 22. Evidence Review Committee Members, Varosy PD, Chen LY, et al. Pacing as a treatment for reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope: A systematic review for the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2017; 14:e255. 23. Benditt DG. Cardiac pacing for prevention of vasovagal syncope. J Am Coll Cardiol 1999; 33:21. 24. Brignole M, Deharo JC, Menozzi C, et al. The benefit of pacemaker therapy in patients with neurally mediated syncope and documented asystole: a meta-analysis of implantable loop recorder studies. Europace 2018; 20:1362. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 14/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate 25. Salim MA, Di Sessa TG. Effectiveness of fludrocortisone and salt in preventing syncope recurrence in children: a double-blind, placebo-controlled, randomized trial. J Am Coll Cardiol 2005; 45:484. 26. Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998; 79:45. 27. Mitro P, Trejbal D, Ryb r AR. Midodrine hydrochloride in the treatment of vasovagal syncope. Pacing Clin Electrophysiol 1999; 22:1620. 28. Klingenheben T, Credner S, Hohnloser SH. Prospective evaluation of a two-step therapeutic strategy in neurocardiogenic syncope: midodrine as second line treatment in patients refractory to beta-blockers. Pacing Clin Electrophysiol 1999; 22:276. 29. Samniah N, Sakaguchi S, Lurie KG, et al. Efficacy and safety of midodrine hydrochloride in patients with refractory vasovagal syncope. Am J Cardiol 2001; 88:A7, 80. 30. Sheldon R, Faris P, Tang A, et al. Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial. Ann Intern Med 2021; 174:1349. 31. Izcovich A, Gonz lez Malla C, Manzotti M, et al. Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review. Neurology 2014; 83:1170. 32. Foglia-Manzillo G, Giada F, Gaggioli G, et al. Efficacy of tilt training in the treatment of neurally mediated syncope. A randomized study. Europace 2004; 6:199. 33. On YK, Park J, Huh J, Kim JS. Is home orthostatic self-training effective in preventing neurally mediated syncope? Pacing Clin Electrophysiol 2007; 30:638. 34. Gurevitz O, Barsheshet A, Bar-Lev D, et al. Tilt training: does it have a role in preventing vasovagal syncope? Pacing Clin Electrophysiol 2007; 30:1499. 35. Duygu H, Zoghi M, Turk U, et al. The role of tilt training in preventing recurrent syncope in patients with vasovagal syncope: a prospective and randomized study. Pacing Clin Electrophysiol 2008; 31:592. 36. Kohno R, Detloff BL, Chen LY, et al. Epinephrine rise concept. J Cardiovasc Electrophysiol 2019; 30:1396. |
12/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate 2. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 3. Soar J, Maconochie I, Wyckoff MH, et al. 2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces. Circulation 2019; 140:e826. 4. Brignole M, Croci F, Menozzi C, et al. Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope. J Am Coll Cardiol 2002; 40:2053. 5. van Dijk N, Quartieri F, Blanc JJ, et al. Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: the Physical Counterpressure Manoeuvres Trial (PC-Trial). J Am Coll Cardiol 2006; 48:1652. 6. Sheldon R, Raj SR, Rose MS, et al. Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial. J Am Coll Cardiol 2016; 68:1. 7. Epstein AE, Miles WM, Benditt DG, et al. Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations. A medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology. Circulation 1996; 94:1147. 8. Epstein AE, Baessler CA, Curtis AB, et al. Addendum to "Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations: a medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology": public safety issues in patients with implantable defibrillators: a scientific statement from the American Heart Association and the Heart Rhythm Society. Circulation 2007; 115:1170. 9. Maas R, Ventura R, Kretzschmar C, et al. Syncope, driving recommendations, and clinical reality: survey of patients. BMJ 2003; 326:21. 10. Shenthar J, Gangwar RS, Banavalikar B, et al. A randomized study of yoga therapy for the prevention of recurrent reflex vasovagal syncope. Europace 2021; 23:1479. 11. Gunda S, Kanmanthareddy A, Atkins D, et al. Role of yoga as an adjunctive therapy in patients with neurocardiogenic syncope: a pilot study. J Interv Card Electrophysiol 2015; 43:105. 12. Brignole M, Moya A, de Lange FJ, et al. Practical Instructions for the 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:e43. 13. Brignole M, Arabia F, Ammirati F, et al. Standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncope: 3-year insights from the Syncope https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 13/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate Unit Project 2 (SUP 2) study. Europace 2016; 18:1427. 14. Sutton R, de Jong JSY, Stewart JM, et al. Pacing in vasovagal syncope: Physiology, pacemaker sensors, and recent clinical trials-Precise patient selection and measurable benefit. Heart Rhythm 2020; 17:821. 15. Sheldon RS, Grubb BP 2nd, Olshansky B, et al. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm 2015; 12:e41. 16. Lacroix D, Kouakam C, Klug D, et al. Asystolic cardiac arrest during head-up tilt test: incidence and therapeutic implications. Pacing Clin Electrophysiol 1997; 20:2746. 17. Kosinski DJ, Grubb BP, Wolfe DA. Permanent cardiac pacing as primary therapy for neurocardiogenic (reflex) syncope. Clin Auton Res 2004; 14 Suppl 1:76. 18. Palmisano P, Dell'Era G, Russo V, et al. Effects of closed-loop stimulation vs. DDD pacing on haemodynamic variations and occurrence of syncope induced by head-up tilt test in older patients with refractory cardioinhibitory vasovagal syncope: the Tilt test-Induced REsponse in Closed-loop Stimulation multicentre, prospective, single blind, randomized study. Europace 2018; 20:859. 19. Baron-Esquivias G, Morillo CA, Moya-Mitjans A, et al. Dual-Chamber Pacing With Closed Loop Stimulation in Recurrent Reflex Vasovagal Syncope: The SPAIN Study. J Am Coll Cardiol 2017; 70:1720. 20. Brignole M, Russo V, Arabia F, et al. Cardiac pacing in severe recurrent reflex syncope and tilt-induced asystole. Eur Heart J 2021; 42:508. 21. Brignole M, Menozzi C, Moya A, et al. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation 2012; 125:2566. 22. Evidence Review Committee Members, Varosy PD, Chen LY, et al. Pacing as a treatment for reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope: A systematic review for the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2017; 14:e255. 23. Benditt DG. Cardiac pacing for prevention of vasovagal syncope. J Am Coll Cardiol 1999; 33:21. 24. Brignole M, Deharo JC, Menozzi C, et al. The benefit of pacemaker therapy in patients with neurally mediated syncope and documented asystole: a meta-analysis of implantable loop recorder studies. Europace 2018; 20:1362. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 14/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate 25. Salim MA, Di Sessa TG. Effectiveness of fludrocortisone and salt in preventing syncope recurrence in children: a double-blind, placebo-controlled, randomized trial. J Am Coll Cardiol 2005; 45:484. 26. Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998; 79:45. 27. Mitro P, Trejbal D, Ryb r AR. Midodrine hydrochloride in the treatment of vasovagal syncope. Pacing Clin Electrophysiol 1999; 22:1620. 28. Klingenheben T, Credner S, Hohnloser SH. Prospective evaluation of a two-step therapeutic strategy in neurocardiogenic syncope: midodrine as second line treatment in patients refractory to beta-blockers. Pacing Clin Electrophysiol 1999; 22:276. 29. Samniah N, Sakaguchi S, Lurie KG, et al. Efficacy and safety of midodrine hydrochloride in patients with refractory vasovagal syncope. Am J Cardiol 2001; 88:A7, 80. 30. Sheldon R, Faris P, Tang A, et al. Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial. Ann Intern Med 2021; 174:1349. 31. Izcovich A, Gonz lez Malla C, Manzotti M, et al. Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review. Neurology 2014; 83:1170. 32. Foglia-Manzillo G, Giada F, Gaggioli G, et al. Efficacy of tilt training in the treatment of neurally mediated syncope. A randomized study. Europace 2004; 6:199. 33. On YK, Park J, Huh J, Kim JS. Is home orthostatic self-training effective in preventing neurally mediated syncope? Pacing Clin Electrophysiol 2007; 30:638. 34. Gurevitz O, Barsheshet A, Bar-Lev D, et al. Tilt training: does it have a role in preventing vasovagal syncope? Pacing Clin Electrophysiol 2007; 30:1499. 35. Duygu H, Zoghi M, Turk U, et al. The role of tilt training in preventing recurrent syncope in patients with vasovagal syncope: a prospective and randomized study. Pacing Clin Electrophysiol 2008; 31:592. 36. Kohno R, Detloff BL, Chen LY, et al. Epinephrine rise concept. J Cardiovasc Electrophysiol 2019; 30:1396. 37. Madrid AH, Ortega J, Rebollo JG, et al. Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study. J Am Coll Cardiol 2001; 37:554. 38. Flevari P, Livanis EG, Theodorakis GN, et al. Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients' well-being. J Am Coll Cardiol 2002; 40:499. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 15/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate 39. Sheldon R, Connolly S, Rose S, et al. Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope. Circulation 2006; 113:1164. 40. Theodorakis GN, Leftheriotis D, Livanis EG, et al. Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study. Europace 2006; 8:193. 41. Cox MM, Perlman BA, Mayor MR, et al. Acute and long-term beta-adrenergic blockade for patients with neurocardiogenic syncope. J Am Coll Cardiol 1995; 26:1293. 42. Natale A, Sra J, Dhala A, et al. Efficacy of different treatment strategies for neurocardiogenic syncope. Pacing Clin Electrophysiol 1995; 18:655. 43. Ventura R, Maas R, Zeidler D, et al. A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. Pacing Clin Electrophysiol 2002; 25:816. 44. Raviele A, Brignole M, Sutton R, et al. Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal syncope: a double-blind, randomized, placebo-controlled trial. The Vasovagal Syncope International Study. Circulation 1999; 99:1452. 45. Podoleanu C, Deharo JC. Novel Therapeutic Options in the Management of Reflex Syncope. Am J Ther 2019; 26:e268. 46. Grubb BP, Kosinski D, Mouhaffel A, Pothoulakis A. The use of methylphenidate in the treatment of refractory neurocardiogenic syncope. Pacing Clin Electrophysiol 1996; 19:836. 47. Di Girolamo E, Di Iorio C, Sabatini P, et al. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 1999; 33:1227. 48. Grubb BP, Samoil D, Kosinski D, et al. Use of sertraline hydrochloride in the treatment of refractory neurocardiogenic syncope in children and adolescents. J Am Coll Cardiol 1994; 24:490. 49. Takata TS, Wasmund SL, Smith ML, et al. Serotonin reuptake inhibitor (Paxil) does not prevent the vasovagal reaction associated with carotid sinus massage and/or lower body negative pressure in healthy volunteers. Circulation 2002; 106:1500. 50. Milstein S, Buetikofer J, Dunnigan A, et al. Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia. Am J Cardiol 1990; 65:1339. 51. Kelly PA, Mann DE, Adler SW, et al. Low dose disopyramide often fails to prevent neurogenic syncope during head-up tilt testing. Pacing Clin Electrophysiol 1994; 17:573. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 16/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate 52. Morillo CA, Leitch JW, Yee R, Klein GJ. A placebo-controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by head-up tilt. J Am Coll Cardiol 1993; 22:1843. 53. Nelson SD, Stanley M, Love CJ, et al. The autonomic and hemodynamic effects of oral theophylline in patients with vasodepressor syncope. Arch Intern Med 1991; 151:2425. 54. Pachon JC, Pachon EI, Pachon JC, et al. "Cardioneuroablation" new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF- ablation. Europace 2005; 7:1. 55. Pachon JC, Pachon EI, Cunha Pachon MZ, et al. Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace 2011; 13:1231. 56. Aksu T, Golcuk E, Yalin K, et al. Simplified Cardioneuroablation in the Treatment of Reflex Syncope, Functional AV Block, and Sinus Node Dysfunction. Pacing Clin Electrophysiol 2016; 39:42. Topic 111958 Version 20.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 17/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate GRAPHICS Major cardiovascular causes of syncope Reflex-mediated* Vasovagal Orthostatic vasovagal syncope: usually after prolonged standing, frequently in a warm environment, etc Emotional vasovagal syncope: secondary to fear, pain, medical procedure, etc Unknown trigger Situational Micturition, defecation Swallowing Coughing/sneezing Carotid sinus syndrome Orthostatic hypotension* Medication-related Diuretics (eg, thiazide or loop diuretics) Vasodilators (eg, dihydropyridine calcium channel blockers, nitrates, alpha blockers, etc) Antidepressants (eg, tricyclic drugs, SSRIs, etc) Volume depletion Hemorrhage Gastrointestinal losses (ie, vomiting or diarrhea) Diminished thirst drive (primarily in older patients) Autonomic failure Primary: pure autonomic failure, Parkinson disease, multiple system atrophy, Lewy body dementia Secondary: diabetes mellitus, amyloidosis, spinal cord injuries, autoimmune neuropathy (eg, Guillain-Barr ), paraneoplastic neuropathy Cardiac Tachyarrhythmias Ventricular tachycardia Supraventricular tachycardias Bradyarrhythmias (with inadequate ventricular response) Sinus node dysfunction https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 18/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate Atrioventricular block Structural disease Severe aortic stenosis Hypertrophic cardiomyopathy Cardiac tamponade Prosthetic valve dysfunction Congenital coronary anomalies Cardiac masses and tumors (eg, atrial myxoma) Cardiopulmonary/vascular Pulmonary embolus Severe pulmonary hypertension Aortic dissection SSRI: selective serotonin reuptake inhibitor. Reflex-mediated syncope and syncope due to orthostatic hypotension are more likely to occur, or are more severe, when other factors may also be contributing, such as medication(s) causing low blood pressure, volume depletion, pulmonary diseases causing reduction in brain oxygen supply, alcohol use, and/or environmental factors (excessive heat or humidity). Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. Graphic 118175 Version 4.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 19/20 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Treatment - UpToDate Contributor Disclosures David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and defibrillators]; St Jude Medical [Pacemakers/event recorders and defibrillators]. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced CPR Solutions [Outside director]. All of the relevant financial relationships listed have been mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias]. Consultant/Advisory Boards: Abbvie [Arrhythmias]; Acesion Pharma [Arrhythmias]; Allergan [Arrhythmias, cardiac safety of non-cardiac drugs]; Anthos [Anticoagulants]; Boehringer-Ingelheim [Arrhythmias]; Bristol-Meyers-Squibb [Arrhythmias]; Daiichi Sankyo [Arrhythmias]; Gilead [Arrhythmias]; Huya [Arrhythmias]; InCarda Therapeutics [Arrhythmias]; INSTA [Arrhythmias]; Johnson & Johnson [Arrhythmias]; Medtronic [Arrhythmias]; Milestone [Arrhythmias]; Novartis [Arrhythmias, cardiac safety of non-cardiac drugs]; Pfizer [Arrhythmias]; Sanofi [Arrhythmias]; Takeda [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-treatment/print 20/20 |
7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Syncope in adults: Clinical manifestations and initial diagnostic evaluation : David Benditt, MD : Peter Kowey, MD, FACC, FAHA, FHRS, Korilyn S Zachrison, MD, MSc : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jul 05, 2022. INTRODUCTION Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral blood flow and oxygenation, most often the result of an abrupt drop of systemic blood pressure. Typically, the inadequate cerebral nutrient flow is of relatively brief duration, and, by definition, syncope is self-limited. Unfortunately, the term "syncope" is often misapplied to encompass other forms of abrupt collapse such as seizures or accidents, which may or may not be accompanied by TLOC. Such broader, less-specific usage of the term "syncope" should be avoided, as imprecise usage impairs accurate diagnosis and undermines comparison of clinical study outcomes. [1]. (See 'Differential diagnosis' below.) Issues relating to the clinical presentation and diagnosis of syncope in adults will be reviewed here. Related issues are discussed separately: (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".) (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".) (See "Approach to the adult patient with syncope in the emergency department".) (See "Syncope in adults: Management and prognosis".) (See "Syncope in adults: Risk assessment and additional diagnostic evaluation".) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 1/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate DEFINITIONS Patients may present with syncopal or presyncopal episodes, or both types of episodes on different occasions. Syncope is a transient, self-limited loss of consciousness caused by transient, self- terminating, inadequate nutrient flow to the brain. Syncopal episodes may or may not be preceded by prodromal symptoms, which are described below. (See 'Onset/prodrome' below.) Presyncope (or near-syncope) is a clinical manifestation that is suggestive of an impending syncope often occurring in conjunction with a similar set of prodromal symptoms (see 'Onset/prodrome' below) reflecting the same conditions that might lead to syncope in the same individual at other times. APPROACH TO INITIAL EVALUATION The initial evaluation of patients with transient loss of consciousness (TLOC), some with suspected true syncope, serves both diagnostic and prognostic purposes ( algorithm 1). This evaluation enables the clinician to ascertain whether the episode was true syncope or another type of event, determine whether the affected patient should be admitted to the hospital or can be safely managed in the outpatient environment (ie, risk stratification) ( table 1), and assess potential causes ( table 2). Establishing the likely etiology guides appropriate diagnostic and treatment strategies to assess prognosis and prevent future events. For nearly all patients, the initial evaluation of suspected syncope should include: Obtaining a comprehensive history, including information about the episode(s) and past medical history. (See 'Clinical features' below and 'Medical history' below.) Performance of a physical examination (which may include careful carotid sinus massage in older patients). (See 'Physical examination' below.) Review of an electrocardiogram (ECG) and any available rhythm strips. A transthoracic echocardiogram is performed if structural heart disease is suspected or cannot be otherwise excluded after the above evaluation is completed. The efficacy of initial clinical evaluation has been summarized in professional society practice guidelines [2,3]. Overall, various reports suggest that an etiology for syncope may be obtained https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 2/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate by an experienced clinician after thorough evaluation in 45 to 65 percent of patients. CLINICAL FEATURES Obtaining a detailed medical history is the first step in determining whether apparent transient loss of consciousness (TLOC) episodes are true syncope or the result of some other cause of collapse. If the history obtained is thorough, the story provided by the patient (and witnesses, if any) will often reveal the most likely cause(s) of syncope and will provide a means of focusing subsequent testing and treatment. Identifying any common threads with regard to associated symptoms, "downtime," or circumstances of onset can be helpful in suggesting an etiology. However, history taking is highly dependent on the experience of and time available to the clinician and whether the patient and witnesses can convey an accurate account of events, which may be limited due to communication barriers (eg, language barrier or cognitive dysfunction) or patient discomfort or intoxication. Also, in stressful circumstances, time periods (ie, duration of the event) may be difficult to accurately estimate. Even under ideal circumstances, the sensitivity of the history taking alone has not been well established. Consequently, confirmatory testing (with focus based upon the clinical evaluation) may be required to establish a diagnosis. Frequency and duration The number, frequency, duration of episodes, and span of time (eg, days, months, or years) over which the patient has experienced presumed syncope events are important. Number and frequency of episodes The frequency of episodes due to benign causes (such as vasovagal faint) is variable; many patients may experience only single or very rare episodes, but others will have multiple episodes over many years, leading to an impaired quality of life and predisposing to injury. Of note, the patient with multiple episodes occurring over a short period of time (ie, several days or weeks) is more likely to be suffering from a serious underlying disorder (eg, intermittent high-grade atrioventricular [AV] block, paroxysmal ventricular tachycardia [VT], etc) and requires aggressive evaluation. However, it is unusual for multiple syncope episodes to occur in a single day. In particular, while reflex vasovagal faints may recur immediately if the affected individual tries to stand up prematurely, it is unusual for multiple vasovagal events to occur on the same day. Individuals having many episodes of apparent "syncope" each day and/or episodes lasting many minutes in duration may be suffering from nonsyncope psychogenic disorders https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 3/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate ("psychogenic pseudosyncope" or "psychogenic pseudoseizures") which are considered to be conversion reactions rather than true syncope. (See 'Differential diagnosis' below.) Span of time marked by episodes In general, the longer the period of time over which episodes have occurred (eg, many years versus very recent onset) and the younger the patient s age at onset (particularly when less than 35 years), the less likely that the cause of syncope is life-threatening, unless the individual has identifiable structural heart disease (assessed by clinical evaluation and testing) or a suspected channelopathy (which may be suggested by family history and ECG findings) [4]. Triggers and circumstances A detailed history should assess circumstances at the time of syncope, as this information may identify possible triggers. Triggers Reflex syncope may be triggered by emotional or orthostatic stress, fear, or intense pain, or by a warm and/or crowded environment. However, in many instances, it may not be possible to confidently identify the trigger. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Triggers'.) Situational syncope (a type of reflex syncope) occurs during or immediately after certain apparent triggers such as urination, defecation, coughing, swallowing, or after eating a meal [2,3]. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Situational syncope'.) Carotid sinus syndrome (CSS) is suggested by syncope occurring immediately following abrupt neck movements. Carotid sinus hypersensitivity triggered during carotid sinus massage (CSM) may suggest this susceptibility, but should not be relied on to establish the diagnosis of CSS unless other possible causes have been considered and excluded and CSM reproduces syncope symptoms. Carotid sinus syncope is usually a condition of older patients (generally >60 years of age with male predominance) or patients with prior head and neck surgery or irradiation. (See "Carotid sinus hypersensitivity and carotid sinus syndrome".) Patient position Assessing the patient's position (ie, supine, sitting, or standing) at the time of syncope, along with any recent changes in position during the preceding few minutes prior to syncope, provides clues to the etiology. While in an unprotected position (eg, prolonged standing) Reflex syncope most commonly occurs when the patient is upright (standing or seated) and almost never when supine. Syncope resulting from orthostatic hypotension is frequently associated https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 4/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate with a change from a supine to erect posture, although several minutes may pass between the patient arising and the subsequent collapse. While supine Syncope that occurs when the patient is supine or recumbent suggests a cardiac arrhythmia and is therefore worrisome. Even if the arrhythmia persists, the TLOC is often brief given the body's adaptive hemodynamic compensatory responses (eg, vascular constriction). Relation to exercise The timing of syncope in relation to exercise is very important, as syncope during full-flight exercise may be indicative of a serious condition (eg, exercise- triggered tachyarrhythmia or hypotension), while syncope immediately after exercise tends to be more innocent and reflex in origin. Syncope that occurs during exertion suggests a potentially life-threatening etiology (eg, aortic stenosis, hypertrophic cardiomyopathy, catecholaminergic polymorphic ventricular tachycardia or other channelopathy) and should be taken very seriously. On the other hand, syncope occurring soon after termination of exertion (eg, during cooling-off period) is more likely reflex in origin, similar to the vasovagal faint. Onset/prodrome Symptoms preceding syncope can point toward a specific cause ( table 2) [2,3]. Most patients who experience syncope have a warning premonition period of at least a few seconds or longer prior to losing consciousness. This is particularly the case for reflex faints. On the other hand, some patients will suddenly lose consciousness without apparent warning or, due to retrograde amnesia, may not recollect a warning symptom. Extended symptoms with a classic prodrome are more commonly associated with the vasovagal form of reflex syncope, while sudden onset of syncope with minimal or no prodrome is more common among patients with cardiac syncope. However, some patients with impaired memory may be amnestic following the event and unable to recall any prodrome, and may therefore report sudden TLOC without warning. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".) The following are classic prodromal (presyncopal) symptoms associated with imminent syncope and presyncope. These are particularly common in younger patients with the vasovagal form of reflex syncope but less so in older vasovagal fainters or those with syncope from other causes: Lightheadedness. Feeling unstable in the upright position. A feeling of being warm or cold/clammy. https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 5/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Sweating. Palpitations The sudden onset of palpitations immediately followed by syncope suggests a cardiac arrhythmia, but palpitations due to sinus tachycardia may also precede reflex syncope. Nausea, vomiting, or nonspecific abdominal discomfort. Visual "blurring" occasionally proceeding to temporary darkening or "white-out" of vision. Diminution of hearing and/or occurrence of unusual sounds (particularly a "whooshing" noise). Pallor reported by onlookers. Prodromal symptoms may be very disconcerting and are often described by patients as "nearly blacking out" or "nearly fainting." Distinguishing true presyncope from more nonspecific complaints such as "lightheadedness," "brain fog," or other conditions such as "vertigo" may be difficult but is important. (See 'Differential diagnosis' below.) Witnessed signs If the syncopal event was observed, the witness should be asked to provide as much information as possible in addition to the history obtained from the patient. A mobile phone video can be very helpful if the witness is capable of obtaining one. Witnesses should be asked to describe the following features: The manner in which the collapse occurred (eg, was there an abrupt fall with possibility of injury or was there purposeful avoidance of injury?). Loss of postural stability is inevitable with TLOC, and, consequently, syncope is generally associated with physical collapse. Physical collapse may cause injury due to a fall (such as may occur if the person is standing) or other type of accident (eg, if syncope occurs while driving or while in a high-risk environment such as working on a ladder or with machinery). The injury risk, of course, applies not only to the "fainter" but may affect others who are injured secondarily (eg, motor vehicle accident) [2,3]. The appearance of the patient (eg, was the skin pale or clammy, or were the eyelids open or closed?). The duration of the loss of consciousness True syncope of any etiology is usually brief since the loss of postural tone (and the subsequent gravitationally neutral position) generally restores brain blood flow. https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 6/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Longer periods of real or apparent loss of consciousness (especially if >5 minutes) suggest that the event is not syncope or is not syncope alone. A prolonged event could be syncope resulting in a fall complicated by head injury (concussion may prolong TLOC), a seizure, or psychogenic pseudosyncope (a collapse deemed secondary to a conversion reaction or dissociative episode [2,5]). Estimates of the duration of a TLOC episode by patients or witnesses are generally imprecise. Determining the duration of spontaneous TLOC events is further complicated when retrograde amnesia occurs, which is more common in older patients with or without head trauma. Nonetheless, an estimate from witnesses should be sought and may be helpful from a diagnostic perspective. Alterations in the patient's breathing pattern. Any physical movements (eg, tonic-clonic or myoclonic movements, tongue biting, incontinence, etc). Did these movements begin before the collapse (favors seizure) or after (favors syncope)? Clinical features after the event Recovery from true syncope is usually complete, with episodes rarely lasting more than a minute. (See 'Frequency and duration' above.) Symptoms following syncope reported by patients and findings observed by witnesses after the episode can help point toward a specific cause ( table 2) [2,3]. Patients should be asked about experiencing any of the following during the event or shortly after recovery: Confusion Fatigue Injury Nausea Vomiting Feeling cold or clammy Palpitations Shortness of breath Chest pain Bladder or bowel incontinence Persistence of nausea, pallor, and diaphoresis in addition to prolonged fatigue (lasting minutes to hours) after a syncope episode suggest a reflex event (particularly a vasovagal episode). These findings are helpful in distinguishing reflex syncope from syncope due to an arrhythmia. https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 7/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Neurologic changes or confusion during the recovery period may suggest a stroke or seizure. However, postevent confusion may also occur with syncope and may complicate accuracy of recall of the event, including time estimates. MEDICAL HISTORY Preexisting conditions A variety of preexisting medical conditions can suggest but not definitively prove an etiology for the patient's transient loss of consciousness (TLOC)/collapse. Patients should be questioned about personal history of the following: Structural heart disease (eg, coronary artery disease with or without prior myocardial infarction, valvular heart disease, congenital heart disease, cardiomyopathies, prior cardiac surgery, etc). Among patients with structural heart disease, there is an increased risk of cardiac arrhythmias that may cause syncope. Also, some types of structural heart disease (eg, severe aortic stenosis) are associated with other mechanisms for syncope. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".) Neurologic conditions (eg, seizure disorders, migraine headaches, Parkinson disease, autonomic failure, stroke, etc). Diabetes mellitus. Patients with diabetes mellitus may develop true syncope resulting from orthostatic hypotension (OH) secondary to autonomic neuropathy or exhibit an apparent "syncope" due to hypoglycemia. Intoxications (eg, alcohol, illicit drug use, or prescription narcotics). Psychiatric disorders may be associated with episodes of apparent TLOC secondary to hyperventilation, panic attacks, conversion reactions, or medications. Medications A variety of prescription and over-the-counter medications can predispose patients to syncope through a number of different mechanisms. Patients should be asked to provide a comprehensive list of prescription and over-the-counter medications, and should be queried specifically about the recent addition of any new agents or recent dose adjustments. Some examples of mechanisms and potential offending medications include: Hypovolemia Diuretics or excessively strict salt avoidance. Electrolyte disturbances (eg, hypokalemia) Diuretics. https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 8/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Hypotension (primarily OH) All classes of antihypertensive agents, but particularly vasodilators, may induce or worsen hypotension, particularly OH. Bradyarrhythmias Numerous medications ( table 3), including beta blockers and calcium channel blockers. Torsades de pointes (polymorphic VT with associated QT interval prolongation) Drugs include antiarrhythmic agents, antiinfective drugs (eg, azole antifungals, fluoroquinolones, macrolides, etc), antipsychotic drugs, and antidepressants. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Family history Important elements of the family history include the following: Sudden death, particularly if unexpected and/or at a young age (less than 40 years of age). Familial cardiomyopathy (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) or channelopathy (eg, long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, familial conduction system disease). Familial predisposition to syncope. Familial associations have been observed for reflex syncope [6] and for the above cardiac conditions. Seizure disorders or migraine headaches. (See "Evaluation and management of the first seizure in adults", section on 'Family history' and "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Genetic basis'.) PHYSICAL EXAMINATION A number of findings on physical examination can aid in the identification of some of the common causes of syncope, including abnormalities in vital signs, cardiovascular disturbances, and, less frequently, neurologic signs [2]. Vital signs Orthostatic vital signs Pulse and blood pressure should be obtained with the patient supine, seated, and standing (the last immediately upon standing as well as after standing at least five minutes). These measurements may detect susceptibility to orthostatic hypotension (OH). A drop of 20 mmHg (>30 mmHg in hypertensive patients) in systolic pressure and/or a drop of 10 mmHg in diastolic pressure is considered diagnostic of OH. However, such numbers should only be used as touchstones, and should not be considered https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 9/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate definitive proof of the etiology of syncope unless it is consistent with the patient's clinical presentation, such as syncope triggered immediately (immediate form) or three to five minutes (delayed or classic form) after standing or occurring after prolonged upright posture in absence of other explanation. A noninvasive system for continuous beat-by-beat blood pressure and heart rate monitoring (eg, Nexfin) that avoids multiple inflations of a sphygmomanometer cuff is preferred. Conventional blood pressure cuff pressures may not be taken rapidly enough to avoid missing the transient blood pressure fall often associated with immediate OH during change of posture. (See "Mechanisms, causes, and evaluation of orthostatic hypotension", section on 'Diagnosis'.) Heart rate and rhythm The heart rate may be slow or rapid due to a number of possible rhythm disturbances, or irregular due to atrial fibrillation, atrial flutter, or frequent ectopy. Irregularities suspected based on evaluation of the pulse should be confirmed by ECG. (See 'Electrocardiogram' below.) Respiratory rate Hyperventilation with an elevated respiratory rate can be seen with pulmonary embolism or psychiatric causes of apparent transient loss of consciousness (TLOC; eg, anxiety, etc). (See "Hyperventilation syndrome in adults", section on 'Somatic symptoms'.) Cardiovascular findings Important cardiovascular findings on physical examination include differences in blood pressure in each arm (suggesting possible aortic dissection or, very rarely, aortic coarctation), pathologic cardiac murmurs (suggesting aortic stenosis, hypertrophic cardiomyopathy, myxoma, etc), and signs of pulmonary embolism (tachypnea and tachycardia being most common but, alone, lack specificity). (See "Auscultation of cardiac murmurs in adults" and "Physiologic and pharmacologic maneuvers in the differential diagnosis of heart murmurs and sounds".) Careful carotid sinus massage with gentle initial pressure is performed in selected older patients (usually over age 40 years) with syncope of unknown etiology without contraindication, as discussed separately . (See "Carotid sinus hypersensitivity and carotid sinus syndrome", section on 'Diagnostic evaluation'.) Neurologic findings Most focal neurologic conditions do not cause true syncope. Exceptions are those with major autonomic dysfunction components, such as pure autonomic failure, Parkinson disease, or, occasionally, temporal lobe seizures that may trigger "ictal asystole." Signs of focal neurologic disease, such as hemiparesis, dysarthria, diplopia, vertigo, or signs of Parkinsonism, are suggestive of (but not diagnostic of) a neurologic cause of impairment of consciousness, warranting a full neurologic evaluation. In general, however, while neurologic https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 10/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate disease may be responsible for other forms of TLOC, such as generalized epilepsy, true syncope is not indicative of a primary neurologic condition. On the other hand, syncope or accidental falls with secondary head trauma leading to concussion may necessitate neurologic evaluation. INITIAL TESTING Electrocardiogram An ECG should be obtained in all patients with suspected syncope [2,3]. The 12-lead ECG only rarely identifies a specific arrhythmic cause of syncope, although certain findings may be very helpful ( table 1). In many instances, prolonged ambulatory ECG monitoring for weeks to months is necessary [7]. The 2018 European Society of Cardiology guidelines list the following as probable causes of arrhythmia-related syncope, but careful confirmative evaluation remains essential [3]: Persistent sinus bradycardia <40 beats per minute or sinus pauses >3 seconds in an awake patient. These findings are deemed suggestive of a bradycardic etiology, as it requires >8 to 10 seconds of hypotension to trigger syncope. (See "Sinus bradycardia".) Mobitz II second-degree AV block. (See "Second-degree atrioventricular block: Mobitz type II".) Third-degree (complete) AV block. (See "Third-degree (complete) atrioventricular block".) Alternating left and right bundle branch block. (See "Chronic bifascicular blocks", section on 'Definitions'.) VT or paroxysmal supraventricular tachycardia with rapid ventricular rate and/or in the setting of substantial left ventricular dysfunction. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) Nonsustained polymorphic VT with long or short QT interval. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease" and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management" and "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Short QT syndrome" and "Catecholaminergic polymorphic ventricular tachycardia".) Pacemaker or implantable cardioverter-defibrillator malfunction with cardiac pauses. (See "Pacing system malfunction: Evaluation and management".) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 11/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate In addition, a variety of abnormal ECG findings ( table 2) may indicate the presence of heart disease and thereby provide a basis for proceeding with further testing [3]: Bifascicular block (defined as left or right bundle branch block combined with left anterior or left posterior fascicular block), especially with concomitant first-degree AV block. (See "Chronic bifascicular blocks".) Other intraventricular conduction abnormalities (QRS duration 0.12 seconds). (See "Basic approach to delayed intraventricular conduction".) Mobitz I second-degree AV block. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)".) Sinus bradycardia ( 40 beats per minute) or atrial fibrillation with a slow ventricular rate ( 40 beats per minute) in the absence of negatively chronotropic medications. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation".) Nonsustained VT. (See "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management".) Preexcited QRS complexes, suggesting Wolff-Parkinson-White syndrome. (See "Wolff- Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) Long or short QT intervals. (See "Congenital long QT syndrome: Diagnosis" and "Short QT syndrome".) Early repolarization. (See "Early repolarization".) Right bundle branch block pattern with ST elevation in leads V1 to V3 (Brugada syndrome). (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Negative T waves in right precordial leads or epsilon waves suggestive of arrhythmogenic right ventricular cardiomyopathy. (See "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations".) Left ventricular hypertrophy, suggesting hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".) Presence of an epsilon wave in V1 and V2, suggesting arrhythmogenic right ventricular cardiomyopathy. https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 12/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Echocardiography When structural heart disease is known or is suspected based on the results of the history, physical examination, and ECG, a transthoracic echocardiogram should be performed to evaluate for structural heart disease [2]. This approach is consistent with professional society guidelines, which recommend echocardiography in patients with syncope when structural cardiac disease is suspected ( table 2) [3]. In general, echocardiographic findings are used to identify the presence of structural heart disease, but they do not usually provide a specific causal diagnosis in syncope patients, as more than one potential diagnosis may be contributing. However, certain findings are highly suggestive of a cause of syncope, including left atrial myxoma, severe aortic valvular stenosis, hypertrophic cardiomyopathy with significant left ventricular outflow tract obstruction, marked pulmonary arterial hypertension, certain forms of congenital heart disease, such as abnormal aortic origin of a coronary artery, and pericardial tamponade [8]. The clinical features associated with the episode must be carefully considered, and other tests may be warranted to confirm the cause of syncope. Additional diagnostic evaluation may include other cardiac imaging modalities (eg, to evaluate for cardiomyopathy); these additional tests should be individualized based on the suspected etiology of syncope. (See "Syncope in adults: Risk assessment and additional diagnostic evaluation" and "Determining the etiology and severity of heart failure or cardiomyopathy".) DIFFERENTIAL DIAGNOSIS Syncope should be distinguished from other causes of abrupt collapse which may or may not be accompanied by transient loss of consciousness (TLOC) ( algorithm 1) [1]. Syncope is only one of the many causes of TLOC or apparent TLOC, including seizure disorders, traumatic brain injury (ie, concussion), intoxications, metabolic disturbances, mechanical falls, and conversion disorders (ie, psychogenic "pseudosyncope" or "pseudoseizures") [9-12]. Distinguishing these conditions from true syncope can be challenging, but is crucial to appropriate management and assessment of prognosis. When caring for patients who present with TLOC/collapse, it is also important to consider causes that are not syncope ( algorithm 1). Examples of nonsyncopal causes of TLOC or apparent TLOC include: Seizures. (See "Evaluation and management of the first seizure in adults".) Cardiac arrest, which requires resuscitation. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Adult basic life support (BLS) for health care providers" and https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 13/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate "Advanced cardiac life support (ACLS) in adults".) Sleep disturbances, including narcolepsy and cataplexy. (See "Clinical features and diagnosis of narcolepsy in adults".) Accidental falls or other incidents resulting in traumatic brain injury (ie, concussion). Intoxications and metabolic disturbances (including hypoglycemia). Some psychiatric conditions (eg, conversion reactions resulting in psychogenic pseudosyncope or pseudoseizures, with the latter termed "nonepileptic seizures" by some neurologists). (See "Nonepileptic paroxysmal disorders in adolescents and adults".) ADDITIONAL EVALUATION Additional diagnostic evaluation is individualized based on the suspected etiology of syncope ( table 4 and table 2) [2]. The major causes of syncope and their evaluation are discussed separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Risk assessment and additional diagnostic evaluation".) Of note, many patients have multiple comorbidities that can contribute to TLOC, and, consequently, there may be multiple plausible causes of syncope that require careful assessment. An observed abnormality should not be assumed to be the cause of collapse without first giving careful consideration to alternative diagnoses and interactions among various coexisting conditions. For example, orthostatic hypotension is common among older patients, but susceptibility to syncope may be the result of medications that the patient has been prescribed, an intercurrent illness, a previously unrecognized neurologic disease (eg, Parkinson disease), or even a previously unsuspected arrhythmia that undermines the individual's hemodynamic stability. Similarly, carotid sinus hypersensitivity (CSH) is a common finding in older patients, but only infrequently is CSH the cause of syncope (in which case the condition is termed carotid sinus syndrome). (See "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Carotid sinus hypersensitivity and carotid sinus syndrome".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 14/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definition Syncope is a transient, self-limited loss of consciousness caused by transient, self-terminating, inadequate nutrient flow to the brain; episodes may or may not be preceded by prodromal symptoms. Presyncope (or near-syncope) is a manifestation of prodromal symptoms reflecting the same conditions that might lead to syncope in the same individual at other times. (See 'Definitions' above.) Initial evaluation The initial evaluation of patients with transient loss of consciousness (TLOC) and suspected syncope should focus on differentiation of true syncope from other events ( algorithm 1), risk stratification ( table 1), and assessment of potential causes ( table 2). The evaluation should generally include a comprehensive history (including information about events, preexisting conditions, medications, and family history), witness observations if available, a physical examination (which may include careful carotid sinus massage in older patients), and review of ECGs. Documentation of medications that the patient is taking is an important element of the initial evaluation. A transthoracic echocardiogram is useful to evaluate for structural heart disease if this is suspected. (See 'Approach to initial evaluation' above.) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 15/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Clinical features The clinical features associated with a syncopal event may be diagnostic ( table 1 and table 2). Key features of events include the frequency and duration of events, triggers and circumstances, presence and types of prodromal symptoms, witnessed signs during episodes, and features of recovery. (See 'Clinical features' above.) Classic prodromal symptoms associated with syncope and presyncope, particularly the vasovagal form of reflex syncope, include lightheadedness, a feeling of being warm or cold, sweating, palpitations, pallor, nausea, visual blurring, and diminution of hearing and/or occurrence of unusual (often "whooshing") sounds. (See 'Onset/prodrome' above.) Physical examination A number of findings on physical examination can aid in the identification of some of the common causes of syncope, including abnormalities in the vital signs, orthostatic blood pressure changes, cardiovascular abnormalities, and, less frequently, neurologic signs. (See 'Physical examination' above.) Electrocardiogram A 12-lead ECG should be obtained in all patients with suspected syncope, and an ambulatory ECG is warranted in many cases. The 12-lead ECG only rarely identifies a specific arrhythmic cause of syncope, although certain findings (eg, persistent bradycardia <40 beats per minute, high-grade atrioventricular (AV) block, ventricular or supraventricular tachycardia with rapid ventricular rate, pacemaker malfunction, etc) are considered diagnostic. (See 'Electrocardiogram' above.) Differential diagnosis Distinguishing syncope from other conditions with or without TLOC requires careful diagnostic assessment ( algorithm 1). Nonsyncopal causes of TLOC |
of the many causes of TLOC or apparent TLOC, including seizure disorders, traumatic brain injury (ie, concussion), intoxications, metabolic disturbances, mechanical falls, and conversion disorders (ie, psychogenic "pseudosyncope" or "pseudoseizures") [9-12]. Distinguishing these conditions from true syncope can be challenging, but is crucial to appropriate management and assessment of prognosis. When caring for patients who present with TLOC/collapse, it is also important to consider causes that are not syncope ( algorithm 1). Examples of nonsyncopal causes of TLOC or apparent TLOC include: Seizures. (See "Evaluation and management of the first seizure in adults".) Cardiac arrest, which requires resuscitation. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Adult basic life support (BLS) for health care providers" and https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 13/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate "Advanced cardiac life support (ACLS) in adults".) Sleep disturbances, including narcolepsy and cataplexy. (See "Clinical features and diagnosis of narcolepsy in adults".) Accidental falls or other incidents resulting in traumatic brain injury (ie, concussion). Intoxications and metabolic disturbances (including hypoglycemia). Some psychiatric conditions (eg, conversion reactions resulting in psychogenic pseudosyncope or pseudoseizures, with the latter termed "nonepileptic seizures" by some neurologists). (See "Nonepileptic paroxysmal disorders in adolescents and adults".) ADDITIONAL EVALUATION Additional diagnostic evaluation is individualized based on the suspected etiology of syncope ( table 4 and table 2) [2]. The major causes of syncope and their evaluation are discussed separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Risk assessment and additional diagnostic evaluation".) Of note, many patients have multiple comorbidities that can contribute to TLOC, and, consequently, there may be multiple plausible causes of syncope that require careful assessment. An observed abnormality should not be assumed to be the cause of collapse without first giving careful consideration to alternative diagnoses and interactions among various coexisting conditions. For example, orthostatic hypotension is common among older patients, but susceptibility to syncope may be the result of medications that the patient has been prescribed, an intercurrent illness, a previously unrecognized neurologic disease (eg, Parkinson disease), or even a previously unsuspected arrhythmia that undermines the individual's hemodynamic stability. Similarly, carotid sinus hypersensitivity (CSH) is a common finding in older patients, but only infrequently is CSH the cause of syncope (in which case the condition is termed carotid sinus syndrome). (See "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Carotid sinus hypersensitivity and carotid sinus syndrome".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 14/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definition Syncope is a transient, self-limited loss of consciousness caused by transient, self-terminating, inadequate nutrient flow to the brain; episodes may or may not be preceded by prodromal symptoms. Presyncope (or near-syncope) is a manifestation of prodromal symptoms reflecting the same conditions that might lead to syncope in the same individual at other times. (See 'Definitions' above.) Initial evaluation The initial evaluation of patients with transient loss of consciousness (TLOC) and suspected syncope should focus on differentiation of true syncope from other events ( algorithm 1), risk stratification ( table 1), and assessment of potential causes ( table 2). The evaluation should generally include a comprehensive history (including information about events, preexisting conditions, medications, and family history), witness observations if available, a physical examination (which may include careful carotid sinus massage in older patients), and review of ECGs. Documentation of medications that the patient is taking is an important element of the initial evaluation. A transthoracic echocardiogram is useful to evaluate for structural heart disease if this is suspected. (See 'Approach to initial evaluation' above.) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 15/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Clinical features The clinical features associated with a syncopal event may be diagnostic ( table 1 and table 2). Key features of events include the frequency and duration of events, triggers and circumstances, presence and types of prodromal symptoms, witnessed signs during episodes, and features of recovery. (See 'Clinical features' above.) Classic prodromal symptoms associated with syncope and presyncope, particularly the vasovagal form of reflex syncope, include lightheadedness, a feeling of being warm or cold, sweating, palpitations, pallor, nausea, visual blurring, and diminution of hearing and/or occurrence of unusual (often "whooshing") sounds. (See 'Onset/prodrome' above.) Physical examination A number of findings on physical examination can aid in the identification of some of the common causes of syncope, including abnormalities in the vital signs, orthostatic blood pressure changes, cardiovascular abnormalities, and, less frequently, neurologic signs. (See 'Physical examination' above.) Electrocardiogram A 12-lead ECG should be obtained in all patients with suspected syncope, and an ambulatory ECG is warranted in many cases. The 12-lead ECG only rarely identifies a specific arrhythmic cause of syncope, although certain findings (eg, persistent bradycardia <40 beats per minute, high-grade atrioventricular (AV) block, ventricular or supraventricular tachycardia with rapid ventricular rate, pacemaker malfunction, etc) are considered diagnostic. (See 'Electrocardiogram' above.) Differential diagnosis Distinguishing syncope from other conditions with or without TLOC requires careful diagnostic assessment ( algorithm 1). Nonsyncopal causes of TLOC or apparent TLOC include accidental falls, cardiac arrest, seizures, sleep disturbances, intoxications, metabolic disorders, and some psychiatric conditions. (See 'Differential diagnosis' above.) Additional testing Additional diagnostic evaluation is individualized based on the suspected etiology of syncope ( table 2 and table 4). Many patients have multiple comorbidities that can contribute to TLOC, and thus multiple plausible causes of syncope may require careful assessment. (See 'Additional evaluation' above and "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Risk assessment and additional diagnostic evaluation".) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 16/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate 1. Thijs RD, Benditt DG, Mathias CJ, et al. Unconscious confusion a literature search for definitions of syncope and related disorders. Clin Auton Res 2005; 15:35. 2. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 3. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 4. Albassam OT, Redelmeier RJ, Shadowitz S, et al. Did This Patient Have Cardiac Syncope?: The Rational Clinical Examination Systematic Review. JAMA 2019; 321:2448. 5. Furlan R, Alciati A. Psychogenic pseudosyncope and pseudoseizure: Approach and treatmen t. In: Syncope: An Evidence-Based Approach, 2nd ed, Brignole M, Benditt DG (Eds), Springer Nature 2020. p.135. 6. Fedorowski A, Pirouzifard M, Sundquist J, et al. Risk Factors for Syncope Associated With Multigenerational Relatives With a History of Syncope. JAMA Netw Open 2021; 4:e212521. 7. Altinsoy M, Sutton R, Kohno R, et al. Ambulatory ECG monitoring for syncope and collapse in United States, Europe, and Japan: The patients' viewpoint. J Arrhythm 2021; 37:1023. 8. Sarasin FP, Junod AF, Carballo D, et al. Role of echocardiography in the evaluation of syncope: a prospective study. Heart 2002; 88:363. 9. van Dijk JG, Thijs RD, Benditt DG, Wieling W. A guide to disorders causing transient loss of consciousness: focus on syncope. Nat Rev Neurol 2009; 5:438. 10. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine (Baltimore) 1990; 69:160. 11. Blanc JJ, L'Her C, Touiza A, et al. Prospective evaluation and outcome of patients admitted for syncope over a 1 year period. Eur Heart J 2002; 23:815. 12. Ungar A, Morrione A, Rafanelli M, et al. The management of syncope in older adults. Minerva Med 2009; 100:247. Topic 969 Version 46.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 17/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate GRAPHICS Algorithm for syncope/collapse This algorithm poses key questions about a collapse episode, including whether and when LOC occurred. However, in the absence of a credible witness, information about such episodes is often limited, as the affected individual may not have accurate recall of the event. Some causes have more than one possible type of presentation. LOC: loss of consciousness; BLS: basic life support; ACLS: advanced cardiac life support; SAH: subarachnoid hemorrhage; TIA: transient ischemic attack. This includes actual LOC as well as apparent LOC. Accidental falls without LOC often have multiple causes, including gait, posture, or balance impairment, environmental hazard, vertigo, focal seizure, TIA, stroke, and presyncope. https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 18/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate These conditions result in apparent transient LOC, although consciousness may be preserved. Other causes of collapse may cause secondary head trauma. Most TIAs and strokes are not associated with LOC. An SAH may cause transient or prolonged LOC. A rare cause of LOC is a brainstem stroke. Graphic 131146 Version 1.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 19/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Clinical and electrocardiographic (ECG) features of patients with syncope at high risk of an arrhythmic cause Significant structural heart disease or CAD (including reduced LVEF, heart failure, CAD with prior MI, severe aortic or mitral stenosis, hypertrophic cardiomyopathy) Persistent sinus bradycardia <40 beats per minute or sinus pauses >3 seconds in an awake patient Third-degree (complete) AV block Mobitz II second-degree AV block Preexcited QRS complexes, suggesting Wolff-Parkinson-White syndrome Alternating left and right bundle branch block VT or paroxysmal supraventricular tachycardia with rapid ventricular rate Nonsustained polymorphic VT with long or short QT interval Long or short QT intervals Right bundle branch block pattern with ST elevation in leads V1 to V3 (Brugada syndrome) Negative T waves in right precordial leads and epsilon waves suggestive of arrhythmogenic right ventricular cardiomyopathy Pacemaker or implantable cardioverter-defibrillator malfunction with cardiac pauses CAD: coronary artery disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; AV: atrioventricular; VT: ventricular tachycardia. Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. Graphic 118883 Version 3.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 20/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Clinical features of syncope that suggest a cause Neurally mediated syncope: Absence of heart disease Long history of recurrent syncope After sudden unexpected unpleasant sight, sound, smell, or pain Prolonged standing or crowded, hot places Nausea, vomiting associated with syncope During a meal or postprandial With head rotation or pressure on carotid sinus (as in tumors, shaving, tight collars) After exertion Syncope due to OH: After standing up Temporal relationship with start or changes of dose of vasodepressive drugs leading to hypotension Prolonged standing, especially in crowded, hot places Presence of autonomic neuropathy or Parkinsonism Standing after exertion Cardiovascular syncope: Presence of definite structural heart disease Family history of unexplained sudden death or channelopathy During exertion or supine Abnormal ECG Sudden onset palpitation immediately followed by syncope ECG findings suggesting arrhythmic syncope: Bifascicular block (defined as either LBBB or RBBB combined with left anterior or left posterior fascicular block) Other intraventricluar conduction abnormalities (QRS duration 0.12 s) Mobitz I second-degree AV block Asymptomatic inappropriate sinus bradycardia (<50 bpm), sinoatrial block or sinus pause 3 s in the absence of negatively chronotropic medications Nonsustained VT https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 21/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Preexcited QRS complexes Long or short QT intervals Early repolarization RBBB pattern with ST elevation in leads V1 to V3 (Brugada syndrome) Negative T waves in right precordial leads, epsilon waves and ventricular late potentials suggestive of ARVC Q waves suggesting myocardial infarction OH: orthostatic hypotension; ECG: electrocardiogram; LBBB: left bundle branch block; RBBB: right bundle branch block; AV: atrioventricular; bpm: beats per minute; VT: ventricular tachycardia; ARVC: arrhythmogenic right ventricular cardiomyopathy. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 66884 Version 10.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 22/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Causes of bradycardia Intrinsic Extrinsic Idiopathic degenerative disorder Drugs Ischemic heart disease Antiarrhythmic agents Chronic ischemia Class IA - quinidine, procainamide Acute myocardial infarction Class IC - propafenone, flecainide Hypertensive heart disease Class II - -blockers Cardiomyopathy Class III - sotalol, amiodarone, dronedarone Trauma Class IV - diltiazem, verapamil Surgery for congenital heart disease Cardiac glycosides Heart transplant Antihypertensive agents Inflammation Clonidine, reserpine, methyldopa Collagen vascular disease Antipsychotic agents Rheumatic fever Lithium, phenothiazines, amitriptyline Pericarditis Autonomically mediated Infection Vasovagal syncope (cardioinhibitory) Viral myocarditis Carotid sinus hypersensitivity Lyme disease (Borrelia burgdorfer I) Hypothyroidism Neuromuscular disorder Intracranial hypertension Friedreich ataxia Hypothermia X-linked muscular dystrophy Hyperkalemia Familial disorder Hypoxia Anorexia nervosa Reproduced with permission from: Fuster V, Walsh R, Harrington R. Hurst's the Heart, 13th ed, McGraw-Hill Professional, New York 2010. Copyright 2010 The McGraw-Hill Companies, Inc. Graphic 65521 Version 11.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 23/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Major cardiovascular causes of syncope Reflex-mediated* Vasovagal Orthostatic vasovagal syncope: usually after prolonged standing, frequently in a warm environment, etc Emotional vasovagal syncope: secondary to fear, pain, medical procedure, etc Unknown trigger Situational Micturition, defecation Swallowing Coughing/sneezing Carotid sinus syndrome Orthostatic hypotension* Medication-related Diuretics (eg, thiazide or loop diuretics) Vasodilators (eg, dihydropyridine calcium channel blockers, nitrates, alpha blockers, etc) Antidepressants (eg, tricyclic drugs, SSRIs, etc) Volume depletion Hemorrhage Gastrointestinal losses (ie, vomiting or diarrhea) Diminished thirst drive (primarily in older patients) Autonomic failure Primary: pure autonomic failure, Parkinson disease, multiple system atrophy, Lewy body dementia Secondary: diabetes mellitus, amyloidosis, spinal cord injuries, autoimmune neuropathy (eg, Guillain-Barr ), paraneoplastic neuropathy Cardiac Tachyarrhythmias Ventricular tachycardia Supraventricular tachycardias Bradyarrhythmias (with inadequate ventricular response) Sinus node dysfunction Atrioventricular block Structural disease https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 24/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Severe aortic stenosis Hypertrophic cardiomyopathy Cardiac tamponade Prosthetic valve dysfunction Congenital coronary anomalies Cardiac masses and tumors (eg, atrial myxoma) Cardiopulmonary/vascular Pulmonary embolus Severe pulmonary hypertension Aortic dissection SSRI: selective serotonin reuptake inhibitor. Reflex-mediated syncope and syncope due to orthostatic hypotension are more likely to occur, or are more severe, when other factors may also be contributing, such as medication(s) causing low blood pressure, volume depletion, pulmonary diseases causing reduction in brain oxygen supply, alcohol use, and/or environmental factors (excessive heat or humidity). Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. Graphic 118175 Version 4.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 25/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Contributor Disclosures David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and defibrillators]; St Jude Medical [Pacemakers/event recorders and defibrillators]. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced CPR Solutions [Outside director]. All of the relevant financial relationships listed have been mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias]. Consultant/Advisory Boards: Abbvie [Arrhythmias]; Acesion Pharma [Arrhythmias]; Allergan [Arrhythmias, cardiac safety of non-cardiac drugs]; Anthos [Anticoagulants]; Boehringer-Ingelheim [Arrhythmias]; Bristol-Meyers-Squibb [Arrhythmias]; Daiichi Sankyo [Arrhythmias]; Gilead [Arrhythmias]; Huya [Arrhythmias]; InCarda Therapeutics [Arrhythmias]; INSTA [Arrhythmias]; Johnson & Johnson [Arrhythmias]; Medtronic [Arrhythmias]; Milestone [Arrhythmias]; Novartis [Arrhythmias, cardiac safety of non-cardiac drugs]; Pfizer [Arrhythmias]; Sanofi [Arrhythmias]; Takeda [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Korilyn S Zachrison, MD, MSc Grant/Research/Clinical Trial Support: American College of Emergency Physicians [Stroke quality improvement]; CRICO [Headache management]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [Telestroke, telehealth, prehospital stroke care, COVID and thromboembolic risk]. Speaker's Bureau: Efficient CME [Honorarium]. Other Financial Interest: Journal of the American Heart Association [Associate Editor]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 26/26 |
7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Syncope in adults: Epidemiology, pathogenesis, and etiologies : David Benditt, MD : Peter Kowey, MD, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 25, 2022. INTRODUCTION Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often due to diminished blood flow resulting from an abrupt drop of systemic blood pressure. Typically, the hypotensive event is of relatively brief duration (8 to 10 seconds) and, in syncope, is by definition spontaneously self-limited. Loss of postural tone is an expected outcome with loss of consciousness, and, consequently, syncope usually is associated with collapse, which can trigger injury due to a fall (such as may occur if the person is standing) or other type of accident (eg, if syncope occurs while driving or during use of factory machinery). Recovery from true syncope is usually complete and rapid, with episodes rarely lasting more than a minute or two. Longer periods of real or apparent loss of consciousness suggest that the event is not syncope or is not syncope alone (eg, syncope resulting in a head injury [concussion], thereby prolonging the event). True syncope has many possible causes ( table 1), but is only one of the many potential causes of TLOC. Examples of nonsyncopal causes of TLOC, or apparent TLOC, include seizure disorders, traumatic brain injury (eg, concussion), intoxications, metabolic disturbances, and conversion disorders (eg, psychogenic "pseudosyncope" or "pseudoseizures"). Distinguishing these other conditions from true syncope may be challenging, but is crucial in order to determine appropriate management. Unfortunately, and inappropriately, true syncope and other TLOC https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 1/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate events are often considered as one category both in clinical practice and in some published literature, thereby undermining the determination of an accurate diagnosis. The epidemiology, pathogenesis, and etiologies of syncope will be reviewed here. The clinical manifestations, diagnostic evaluation, and management of syncope is discussed in detail separately. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Syncope in adults: Management and prognosis".) EPIDEMIOLOGY Syncope/collapse is a common clinical problem, with a lifetime prevalence in the population as a whole of approximately 20 percent [1,2]. In the Framingham Heart study, 822 of 7814 individuals (11 percent) who were followed for an average of 17 years reported an apparent syncopal episode [3]. However, given advances in the evaluation of patients with suspected syncope, the applicability of the Framingham data requires reevaluation given the manner in which syncope and the causal "diagnosis" was established. The study did not use the current definition of syncope (ie, self-limited inadequate cerebral perfusion). As a result, the report inevitably combined syncope and nonsyncopal collapse, and some seizures may also have been included. Also, the cause of syncope in the Framingham population was, at best, inferential. As an example, a diagnosis of "cardiac syncope" was based on the presence of cardiac disease, not a documented connection to the symptoms as currently required. Despite these limitations, the Framingham data provide a useful population estimate of syncope/collapse, and are largely consistent with a later study [1]. In a retrospective community-based study of more than 1900 adults from Olmsted county, Minnesota, aged 45 years (47 percent male, mean age 62 years), 364 individuals (19 percent) reported having experienced syncope [1]. Nearly 50 percent of these individuals had subsequent recurrences of syncope, which may have been related to their mean age of 62. The occurrence of syncope versus age has been reported as roughly bimodal, with a peak in late adolescence to early adulthood (mostly vasovagal in origin) and a second peak later in older age, with a sharp rise after age 70 years ( figure 1). In younger patients, reflex syncope (particularly vasovagal faints) overwhelmingly predominates in terms of cause. Reflex faints also remain common as patients age, but, in older adult patients, disease-related abnormalities may not only predispose to transient hypotensive events (eg, arrhythmias, orthostatic hypotension) but may also impair the ability to respond to physiologic stresses that would ordinarily not cause syncope [4]. https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 2/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Syncope/collapse appears to be slightly more common among females depending upon the population studied [1,3]. Variation in the reported rates of syncope in different studies is due to varying study populations, definitions of syncope, and diagnostic methods and criteria. Males, however, are more likely than females to have a cardiac cause of syncope, presumably due to greater risk of cardiovascular disease in males [3,5]. Syncope/collapse is also a common clinical complaint of patients treated in the emergency department and is the source for a significant number of hospital admissions. Between 1 and 3 percent of all emergency department visits, and 1 percent of all hospital admissions, are related to syncope [6-8]. In general, approximately 35 percent of patients who present to the emergency department with syncope/collapse are admitted to hospital. This later proportion is substantially greater than is essential, and efforts have been directed to reducing admission rates. In particular, emergency department-based scoring systems are evolving to facilitate decisions regarding hospital admission versus outpatient evaluation of patients presenting with apparent transient loss of consciousness (TLOC). The OESIL score and the Canadian Syncope Risk Score are typical well-studied examples of tools that physicians may use to help facilitate the decision- making process [9,10]. (See "Approach to the adult patient with syncope in the emergency department", section on 'Risk stratification'.) In regard to reducing hospital admission rates, a 2018 report shows a trend reduction of hospital admission for syncope in the United States, possibly due to greater use of short-term observation or outpatient care; nonetheless, the overall cost of care continues to rise [11]. Among 282,311 United States patients (54 percent female; median age 72 years) with a primary diagnosis of syncope identified from the 2013 to 2014 Nationwide Readmissions Database, 9.3 percent were re-admitted within 30 days; predictors of readmission primarily centered around medical co-morbidities (eg, heart failure [HF], atrial fibrillation, COPD, diabetes) and longer initial hospital stays (>3 days) [12]. (See "Approach to the adult patient with syncope in the emergency department".) Determining the cause of syncope is important for both prognostic and therapeutic reasons. Several large studies have assessed the causes for syncope [3,13-16]. In general, vasovagal attacks are the most common cause of syncope in all age groups, followed by orthostatic syncope and then cardiac arrhythmias. Vasovagal syncope (also known as the "common" or "innocent" faint), a type of reflex (neurally-mediated) syncope, is the most common cause of TLOC in all age groups, particularly in patients without apparent cardiac or neurologic disease. In contrast to vasovagal syncope, carotid sinus hypersensitivity is much more common in older patients (mostly males), especially those with atherosclerotic vascular disease. https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 3/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate A pooled analysis of five population-based studies including 1002 patients with presumed syncope between 1984 and 1990 found that arrhythmias were responsible for 14 percent of syncope cases (range 4 to 38 percent in different studies) [15]. Orthostatic hypotension accounted for 8.6 and 9.9 percent of syncope cases among individuals in the Framingham cohort, respectively, and for 8 percent of cases in the five pooled cohort studies ( table 2 and table 3) [3,15]. However, the frequency of orthostatic hypotension increases substantially in older populations in whom treatment with antihypertensive drugs and diuretics is common. The cause of syncope/collapse is unknown in approximately one-fifth to one-third of cases ( table 2 and table 3), but the number of cases with undetermined causes is falling as more physicians are developing expertise in the syncope/collapse evaluation and diagnostic tools are improving. As an example, arrhythmias that may be the etiology of a significant proportion of unexplained syncopal events are now more readily detected by a variety of wearable and insertable ambulatory electrocardiogram (ECG) recorders [17,18]. (See 'Causes of syncope' below.) Cardiovascular disease is a major risk factor for syncope. The age-adjusted incidence rate for apparent syncope among participants with cardiovascular disease was almost twice that of participants without cardiovascular disease in the Framingham cohort (10.6 versus 6.4 per 1000 person-years) [3]. Nonetheless, reflex syncope (particularly vasovagal syncope) is the most common cause of syncope overall. (See 'Reflex syncope' below.) CAUSES OF SYNCOPE In the evaluation of a patient with transient loss of consciousness (TLOC) in whom syncope is suspected, the clinician must necessarily consider and exclude conditions that mimic TLOC/syncope but are not true syncope. The most common of these conditions are seizures, sleep disturbances, accidental falls, and some psychiatric conditions (eg, conversion reactions resulting in psychogenic pseudo-syncope, or as preferred by many neurologists, nonepileptic seizures, also called psychogenic pseudoseizures). These conditions are discussed in detail separately. (See "Classification of sleep disorders" and "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis" and "Evaluation and management of the first seizure in adults".) The possible causes of TLOC resulting in true syncope are generally grouped into several major categories ( table 1): https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 4/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Reflex syncope (neurally-mediated) Orthostatic syncope Cardiac (arrhythmias and structural cardiopulmonary disease) Reflex syncope accounts for the vast majority of cases in younger individuals, and approximately 50 percent of cases in older patients. As individuals age, orthostatic and cardiac causes increase in frequency. Reflex syncope Reflex syncope comprises a number of related conditions in which neural reflexes modify heart rate and blood pressure inappropriately, resulting in syncope or near- syncope. The most well-known of these conditions is vasovagal syncope, otherwise known as the common faint. Other types of neurally-mediated reflex syncope include carotid sinus syncope as well as syncope triggered by micturition, defecation, swallowing, or coughing. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Types of reflex syncope' and "Carotid sinus hypersensitivity and carotid sinus syndrome".) Orthostatic (postural) hypotension Orthostatic (postural) hypotension, defined as a decrease in systolic blood pressure of at least 20 mmHg, or in diastolic blood pressure of at least 10 mmHg upon assuming upright posture, is another common cause of near-syncope and syncope. Orthostatic syncope occurs most often following movement from lying or sitting to a standing position. Orthostatic (postural) hypotension is often considered as being either immediate or delayed. Immediate orthostatic hypotension Many healthy individuals experience a minor form of orthostatic change in blood pressure when rising abruptly from a supine or seated position, and need to support themselves momentarily, a condition referred to as immediate orthostatic hypotension (OH). Immediate OH usually occurs within 10 seconds of movement to standing and is fully resolved 10 to 20 seconds later. Delayed orthostatic hypotension Delayed or "classic" orthostatic hypotension refers to episodes of near-syncope or syncope that occur after the affected individual has been upright for some period of time (usually one to several minutes). Such episodes are generally more worrisome, as the patient may be unprepared to protect themselves from the hazards of a fall and risk of injury. The major causes of orthostatic hypotension associated with syncope include (see "Mechanisms, causes, and evaluation of orthostatic hypotension"): Decreased intravascular volume, as may occur with inadequate fluid intake, excessive fluid loss in hot, dry environments or with exercise, or the result of diuretics or as a https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 5/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate consequence of losses associated with certain gastrointestinal disorders. Drug effects, especially antidepressants (tricyclics, phenothiazine) and antihypertensive agents (beta and alpha blockers, hydralazine, angiotensin converting enzyme inhibitors, ganglionic blockers), particularly vasodilators, including calcium channel blockers and nitrates (more commonly observed in older adults). Other drugs that may cause orthostatic hypotension include opiates and bromocriptine. Primary autonomic insufficiency or failure (including pure autonomic failure, multiple system atrophy, Parkinson disease, and others). Secondary autonomic insufficiency (eg, diabetes mellitus and amyloidosis). Alcohol consumption which impairs vasoconstriction [19]. Aging is associated with an increased prevalence of orthostatic hypotension [20]. One contributory mechanism may be attenuation of the vestibulo-sympathetic reflex [21]. The greatest risk of orthostatic hypotension resulting in syncope is in older frail individuals, patients on multiple vasodilating and/or diuretic drugs, those who have underlying medical problems causing autonomic failure (eg, diabetes, certain nervous system diseases), and persons who are dehydrated (eg, hot environments, inadequate fluid intake). (See "Mechanisms, causes, and evaluation of orthostatic hypotension".) Cardiac arrhythmias Cardiac arrhythmias may cause syncope or near-syncope if the heart rate is either too slow or too fast to permit maintenance of an adequate cardiac output and systemic arterial pressure. Bradycardia resulting from prolonged sinus pauses, high grade atrioventricular (AV) block, or at the termination of an atrial tachyarrhythmia may cause syncope and near-syncope. Similarly, syncope or near-syncope may occur at the onset of an episode of tachycardia in which a fall in cardiac output cannot be adequately compensated for by vascular constriction. Although an arrhythmic etiology for syncope is often suspected clinically, the culprit arrhythmia frequently may be difficult to diagnose since most are paroxysmal and infrequent. Long-term ambulatory ECG monitoring is often essential. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Ambulatory ECG monitoring".) The most common arrhythmic causes of syncope include: AV block High grade (ie, complete or Mobitz type II second degree) AV block may trigger syncope (an event previously termed a Stokes-Adams attack). Conversely, Mobitz type I (Wenckebach) second degree AV block is usually benign and not associated with syncope. When Mobitz type II second degree or third degree AV block is present in conjunction with https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 6/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate syncope, a permanent pacemaker is indicated. (See "Syncope in adults: Management and prognosis", section on 'Arrhythmias' and "Second-degree atrioventricular block: Mobitz type II" and "Third-degree (complete) atrioventricular block".) Cardiac pauses Cardiac pauses may be caused by intrinsic or drug-induced sinus pauses or prolonged recovery times after spontaneous termination of an episode of atrial fibrillation or flutter or other supraventricular tachycardia. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation".) Ventricular tachyarrhythmias Syncope resulting from ventricular tachycardia (VT) occurs most commonly in the setting of structural heart disease, particularly coronary heart disease. Patients with dilated cardiomyopathy and some congenital myopathic processes (eg, hypertrophic cardiomyopathy [HCM], arrhythmogenic right ventricular cardiomyopathy) are also prone to have VT presenting with syncope. In addition, an unusual form of VT, torsades de pointes, may cause syncope in patients with either the congenital or acquired forms of long QT syndrome. In addition, there has been substantial expansion of knowledge into other genetic cardiac ion channel diseases. While relatively rare, conditions such as Brugada syndrome, catecholaminergic polymorphic VT (CPVT), and others need to be considered as part of the syncope/collapse differential diagnosis. Finally, ventricular fibrillation is not often a cause of syncope as it only rarely is self-terminating [22]. In nearly all cases, this rhythm disturbance causes cardiac arrest and death. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy" and "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Ventricular bigeminy Ventricular bigeminy, with ventricular premature beats occurring every other beat, may occasionally be associated with hypotension, bradycardia, and near syncope, though full syncope with loss of consciousness is exceedingly rare. Syncope occurs primarily in patients with an underlying sinus bradycardia or those with advanced heart disease and significant left ventricular dysfunction. Ventricular bigeminy typically is associated with in ineffective cardiac output of the premature beats, thereby diminishing overall cardiac output. Supraventricular tachyarrhythmias Supraventricular tachyarrhythmias are only rarely associated with syncope [23]. Syncope may occur at the onset of the arrhythmia as impaired vasomotor function may be responsible for syncope due to delayed vasoconstrictive compensation. In some cases, the cause may be due to neurally-mediated (neurocardiogenic) responses rather than a direct result of the tachycardia [24-26]. In https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 7/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate others, concomitant drug therapy (eg, vasodilators) may undermine compensatory vascular response. Individuals with underlying heart disease (eg, previous myocardial infarction [MI], valvular heart disease), a channelopathy (eg, long QT syndrome, Brugada syndrome), HCM, congenital heart disease, or significant vascular disease are at greatest risk for syncope due to a tachyarrhythmia (usually VT). In contrast to patients who have vasovagal or other causes of syncope, an arrhythmic cause of syncope often occurs without warning. This is particularly true of the bradyarrhythmias and, in addition to reporting no warning symptoms, the patient may also suffer an injury with the event. Patients with a tachyarrhythmia may report having palpitations but may also have syncope without warning symptoms. An abrupt change in heart rate, as occurs during the initiation of many arrhythmias, can cause TLOC. The blood pressure may precipitously decline, especially in an upright position, causing TLOC if a prompt compensatory vasopressor response (which may be blunted by antihypertensive or HF medications) does not occur. Then, gradually, with augmentation in sympathetic nervous system activation and elevation of catecholamine levels triggered by systemic hypotension, vasoconstriction and increased ventricular contractility restores adequate cerebral blood flow. The hemodynamic stability resulting from any arrhythmia is also influenced by other factors including rate, ventricular function or presence of coronary or valvular heart disease, body position, medications, and baroreceptor sensitivity [27,28]. Structural cardiac or cardiopulmonary disease The presence of heart disease has been shown to be an independent predictor of cardiac cause of syncope, with a sensitivity of 95 percent and a specificity of 45 percent; by contrast, the absence of heart disease excludes a cardiac cause of syncope in 97 percent of patients [29]. Structural cardiac or cardiopulmonary diseases that may lead to syncope due to inadequate cardiac output include cardiac valvular disease (particularly aortic stenosis), HCM, atrial myxoma, pulmonary embolus, pulmonary hypertension, pericardial tamponade, acute MI/ischemia, and acute aortic dissection. Channelopathies such as long QT syndrome, Brugada syndrome, CPVT, and others that are less frequent should also be included here, although the "structural" disease is at the cellular level. Patients with an underlying cardiovascular cause of syncope have higher rates of sudden cardiac death (SCD) and all-cause mortality than those with a noncardiovascular cause of syncope. The mortality rate in patients with cardiovascular disease after five years of follow-up has been reported to approach 50 percent, with a 30 percent incidence of death in the first year https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 8/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate ( figure 2) [3,6,30,31]. Mortality in these patients is in large part due to the severity of the underlying cardiovascular disease. Syncope may be caused by obstruction to blood flow due to cardiovascular abnormalities, the most frequent being aortic stenosis and HCM. Less common conditions include pulmonic stenosis, idiopathic pulmonary arterial hypertension, atrial myxomas, and pulmonary embolism. Aortic stenosis Aortic stenosis rarely presents with syncope unless the valve is critically stenotic. Syncope in patients with aortic stenosis is often associated with exertion. In most such cases, syncope results from an inability to produce a compensatory increase in cardiac output (due to the obstruction), which normally occurs in response to exercise- induced peripheral vasodilation [32,33]. Patients with syncope and severe aortic stenosis have a high mortality if untreated; aortic valve replacement is generally indicated in such patients. (See "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Dizziness and syncope' and "Natural history, epidemiology, and prognosis of aortic stenosis" and "Indications for valve replacement for high gradient aortic stenosis in adults".) Hypertrophic cardiomyopathy Syncope may occur in up to 25 percent of patients who have HCM and may be due to dynamic left ventricular outflow tract (LVOT) obstruction or other causes. LVOT obstruction can intensify with postural changes, hypovolemia, or drugs. Multiple mechanisms may lead to syncope in patients with HCM and LVOT obstruction, notably including the LVOT obstruction itself (leading to reduced cardiac output) and VT. Syncope in patients with HCM is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Syncope'.) Myocardial ischemia VT and bradyarrhythmias secondary to myocardial ischemia are infrequent causes of syncope, accounting for only 1 percent of cases [34]. Although patients who are admitted to the hospital with syncope are commonly evaluated for acute coronary syndrome (myocardial infarction or unstable angina), generally, only a limited evaluation for acute coronary syndrome is required, as discussed separately. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Approach to initial evaluation'.) Other causes Pulmonary embolism, severe pulmonic stenosis, idiopathic pulmonary arterial hypertension, and atrial myxomas are all rare causes of syncope due to obstruction of blood flow [35]. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'History and examination'.) https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 9/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Cerebrovascular disease Atherosclerotic disease of the cerebral arteries is almost never the cause of true syncope, as the brain has a very redundant blood supply. Instead, stroke and transient ischemia attacks cause focal neurologic deficits that do not recover rapidly or, in most cases, completely. As examples: If the posterior cerebral circulation is impaired (vertebrobasilar artery insufficiency), symptoms such as dizziness are more apt to occur than syncope. Other causes of syncope should be excluded in patients with syncope and suspected vertebrobasilar ischemia. If the anterior circulation is compromised, a focal neurologic deficit and not a global decrease in consciousness will occur. The rare exception in which syncope can occur is with severe obstructive four vessel cerebrovascular disease; however, other neurologic findings are likely to occur prior to the loss of consciousness in these patients. (See "Vertebral artery revascularization".) A vascular steal syndrome occurs when the arterial circulation to the arm is blocked proximally, resulting in a shunt of blood through the cerebrovascular system that supplies both parts of the brain and the arm. Impairment in brain perfusion during arm exercise may cause loss of consciousness. Vertebrobasilar steal is typically associated with vertigo, diplopia, blurred vision, cranial nerve dysfunction, drop attacks (sudden fall without loss of consciousness), and syncope. (See "Overview of upper extremity peripheral artery disease" and "Subclavian steal syndrome", section on 'Clinical features' and "Subclavian steal syndrome", section on 'Definition and physiology'.) SYNCOPE OF UNKNOWN ORIGIN When the initial evaluation, including history, physical examination, and ECG, are completely nondiagnostic, the patient is considered to have syncope/collapse of unknown origin/cause. Importantly, as was noted above, in many instances, apart from not knowing the cause, it may not be clear that the patient has experienced true syncope. The published literature often misses this point and syncope and nonsyncope collapse are, as a result, inappropriately combined; as noted earlier, lumping these conditions together complicates our understanding of the epidemiology and prognosis associated with such patients. (See 'Epidemiology' above.) Leaving aside the uncertainty regarding combining true syncope and nonsyncopal causes of collapse (eg, accidents, seizures), approximately one-fifth to one-third of cases in the literature have been identified as having syncope from "unknown causes." However, identification of this group is problematic given limitations in diagnostic discrimination of causes. As an example, in https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 10/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate the Framingham Heart Study cited above, the group identified as having syncope of "unknown" origin likely included individuals with a mixed group of conditions in which benign and not-so- benign diagnoses could not be sorted out given the limited diagnostic data available to Framingham investigators [3]. In more contemporary practice, however, with the increasingly broader availability of specialized syncope/collapse clinics, the frequency of "unexplained" transient loss of consciousness is diminishing and may be closer to 10 percent [36,37]. CAUSES OF NONSYNCOPAL ATTACKS Episodes that may be confused with syncope include disorders without impairment of consciousness and disorders with partial or complete loss of consciousness ( table 4). These disorders should be considered and excluded as part of the initial evaluation of the transient loss of consciousness (TLOC)/collapse patient (which includes a thorough history, physical examination, ECG, and selected additional testing on a case by case basis) ( algorithm 1). Seizures Seizures are the probable cause in 5 to 15 percent of apparent TLOC/collapse episodes [3,15,34,38]. They can mimic syncope, especially when the seizure is atypical and not associated with tonic-clonic movements, the seizure is not observed, or a complete/detailed history cannot be obtained ( table 5). Another potentially confounding factor is that loss of cerebral blood flow due to any cause of syncope can result in a myoclonic jerking that nonexpert witnesses may conclude is an epileptic state. As an example, the initiation of a rapid ventricular tachycardia may be associated with impaired cerebral blood flow, followed within seconds by movements that might (although only rarely) appear to the lay bystander or inexperienced medical practitioner to be tonic-clonic activity. This apparent seizure activity is associated with brain wave slowing, not epileptiform spikes, on the electroencephalogram. One distinguishing feature is that patients with seizures rarely have an abrupt complete recovery. Instead, the postictal state is characterized by a slow complete recovery. Other important clues, if present, are evidence of soft tissue injury at multiple sites due to tonic-clonic movements during the seizure. (See "Evaluation and management of the first seizure in adults".) Psychogenic pseudo-syncope and nonepileptic "seizures" Conversion disorders can mimic syncope or seizures and have been termed in some literature as psychogenic nonepileptic seizures (but are better called psychogenic pseudosyncope or psychogenic pseudoseizures, the distinction being whether the patient manifests jerky movements suggesting a seizure to untrained bystanders). These conditions, diagnosed in approximately 1 percent of patients referred to a syncope/collapse clinic, are usually distinguished by having multiple recurrences of apparent collapse, prolonged duration of https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 11/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate apparent TLOC (often many minutes), absence of physical injury, and absence of evidence pointing toward a cause for syncope or evidence of seizure activity [39-41]. (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".) Metabolic and/or toxic abnormalities Metabolic or toxic abnormalities are rarely associated with an abrupt onset or complete brisk recovery; syncope is therefore rare in this setting. Hypoglycemia and encephalitis can cause coma, stupor, and confusion, but rarely the transient loss of consciousness characteristic of syncope. Although metabolic abnormalities (such as hypoglycemia or hypoxia) infrequently cause syncope, they can cause impaired consciousness that may be difficult to distinguish from syncope. Metabolic abnormalities, anemia, and hypovolemia can be effectively managed by specific therapy to correct these abnormalities. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 12/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Epidemiology Syncope is a common clinical problem, which is one of the many causes of transient loss of consciousness (TLOC). Syncope has a lifetime prevalence in the population as a whole of approximately 20 percent. Syncope is responsible for between 1 and 3 percent of all emergency department visits and 1 percent of all hospital admissions. (See 'Epidemiology' above.) Causes The possible causes of TLOC resulting in true syncope are generally grouped into four major categories ( table 1): reflex syncope (neurally-mediated), orthostatic syncope, cardiac arrhythmias, and structural cardiopulmonary disease. (See 'Causes of syncope' above.) Causes of nonsyncopal attacks In the evaluation of a patient with TLOC in whom syncope is suspected, the clinician must necessarily consider and exclude conditions that mimic TLOC/syncope but are not true syncope ( algorithm 1). The most common of these conditions are seizures, sleep disturbances, accidental falls, and some psychiatric conditions (eg, conversion reactions resulting in psychogenic nonepileptic seizures, previously called psychogenic pseudoseizures). (See 'Causes of nonsyncopal attacks' above and "Evaluation and management of the first seizure in adults" and "Classification of sleep disorders" and "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".) Atherosclerotic disease of the cerebral arteries is almost never the cause of true syncopal symptoms, as the brain has a very redundant blood supply. Instead, stroke and transient ischemia attacks cause focal neurologic deficits that do not recover rapidly or completely. (See 'Cerebrovascular disease' above.) Syncope of unknown origin When the initial evaluation, including history, physical examination, and ECG, is nondiagnostic in a patient with suspected syncope, the patient is considered to have syncope with an unexplained diagnosis (ie, syncope of unknown origin). The frequency of an "unknown" cause was previously approximately one-third of cases, but is now closer to 10 percent as syncope experts and specialized syncope diagnostic clinics have become more widely available. As a rule, syncope of unknown cause is generally associated with a good prognosis, suggesting that most are likely "reflex" in origin. (See 'Syncope of unknown origin' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 13/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate 1. Chen LY, Shen WK, Mahoney DW, et al. Prevalence of syncope in a population aged more than 45 years. Am J Med 2006; 119:1088.e1. 2. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 3. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. 4. Lipsitz LA. Syncope in the elderly. Ann Intern Med 1983; 99:92. 5. Freed LA, Eagle KA, Mahjoub ZA, et al. Gender differences in presentation, management, and cardiac event-free survival in patients with syncope. Am J Cardiol 1997; 80:1183. 6. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine (Baltimore) 1990; 69:160. 7. Manolis AS, Linzer M, Salem D, Estes NA 3rd. Syncope: current diagnostic evaluation and management. Ann Intern Med 1990; 112:850. 8. Costantino G, Sun BC, Barbic F, et al. Syncope clinical management in the emergency department: a consensus from the first international workshop on syncope risk stratification in the emergency department. Eur Heart J 2016; 37:1493. 9. Colivicchi F, Ammirati F, Melina D, et al. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score. Eur Heart J 2003; 24:811. 10. Zimmermann T, du Fay de Lavallaz J, Nestelberger T, et al. International Validation of the Canadian Syncope Risk Score : A Cohort Study. Ann Intern Med 2022; 175:783. 11. Anand V, Benditt DG, Adkisson WO, et al. Trends of hospitalizations for syncope/collapse in the United States from 2004 to 2013-An analysis of national inpatient sample. J Cardiovasc Electrophysiol 2018; 29:916. 12. Kadri AN, Abuamsha H, Nusairat L, et al. Causes and Predictors of 30-Day Readmission in Patients With Syncope/Collapse: A Nationwide Cohort Study. J Am Heart Assoc 2018; 7:e009746. 13. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol 2001; 37:1921. 14. Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet 2001; 357:348. https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 14/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate 15. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American |
11/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate apparent TLOC (often many minutes), absence of physical injury, and absence of evidence pointing toward a cause for syncope or evidence of seizure activity [39-41]. (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".) Metabolic and/or toxic abnormalities Metabolic or toxic abnormalities are rarely associated with an abrupt onset or complete brisk recovery; syncope is therefore rare in this setting. Hypoglycemia and encephalitis can cause coma, stupor, and confusion, but rarely the transient loss of consciousness characteristic of syncope. Although metabolic abnormalities (such as hypoglycemia or hypoxia) infrequently cause syncope, they can cause impaired consciousness that may be difficult to distinguish from syncope. Metabolic abnormalities, anemia, and hypovolemia can be effectively managed by specific therapy to correct these abnormalities. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 12/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Epidemiology Syncope is a common clinical problem, which is one of the many causes of transient loss of consciousness (TLOC). Syncope has a lifetime prevalence in the population as a whole of approximately 20 percent. Syncope is responsible for between 1 and 3 percent of all emergency department visits and 1 percent of all hospital admissions. (See 'Epidemiology' above.) Causes The possible causes of TLOC resulting in true syncope are generally grouped into four major categories ( table 1): reflex syncope (neurally-mediated), orthostatic syncope, cardiac arrhythmias, and structural cardiopulmonary disease. (See 'Causes of syncope' above.) Causes of nonsyncopal attacks In the evaluation of a patient with TLOC in whom syncope is suspected, the clinician must necessarily consider and exclude conditions that mimic TLOC/syncope but are not true syncope ( algorithm 1). The most common of these conditions are seizures, sleep disturbances, accidental falls, and some psychiatric conditions (eg, conversion reactions resulting in psychogenic nonepileptic seizures, previously called psychogenic pseudoseizures). (See 'Causes of nonsyncopal attacks' above and "Evaluation and management of the first seizure in adults" and "Classification of sleep disorders" and "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".) Atherosclerotic disease of the cerebral arteries is almost never the cause of true syncopal symptoms, as the brain has a very redundant blood supply. Instead, stroke and transient ischemia attacks cause focal neurologic deficits that do not recover rapidly or completely. (See 'Cerebrovascular disease' above.) Syncope of unknown origin When the initial evaluation, including history, physical examination, and ECG, is nondiagnostic in a patient with suspected syncope, the patient is considered to have syncope with an unexplained diagnosis (ie, syncope of unknown origin). The frequency of an "unknown" cause was previously approximately one-third of cases, but is now closer to 10 percent as syncope experts and specialized syncope diagnostic clinics have become more widely available. As a rule, syncope of unknown cause is generally associated with a good prognosis, suggesting that most are likely "reflex" in origin. (See 'Syncope of unknown origin' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 13/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate 1. Chen LY, Shen WK, Mahoney DW, et al. Prevalence of syncope in a population aged more than 45 years. Am J Med 2006; 119:1088.e1. 2. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 3. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. 4. Lipsitz LA. Syncope in the elderly. Ann Intern Med 1983; 99:92. 5. Freed LA, Eagle KA, Mahjoub ZA, et al. Gender differences in presentation, management, and cardiac event-free survival in patients with syncope. Am J Cardiol 1997; 80:1183. 6. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine (Baltimore) 1990; 69:160. 7. Manolis AS, Linzer M, Salem D, Estes NA 3rd. Syncope: current diagnostic evaluation and management. Ann Intern Med 1990; 112:850. 8. Costantino G, Sun BC, Barbic F, et al. Syncope clinical management in the emergency department: a consensus from the first international workshop on syncope risk stratification in the emergency department. Eur Heart J 2016; 37:1493. 9. Colivicchi F, Ammirati F, Melina D, et al. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score. Eur Heart J 2003; 24:811. 10. Zimmermann T, du Fay de Lavallaz J, Nestelberger T, et al. International Validation of the Canadian Syncope Risk Score : A Cohort Study. Ann Intern Med 2022; 175:783. 11. Anand V, Benditt DG, Adkisson WO, et al. Trends of hospitalizations for syncope/collapse in the United States from 2004 to 2013-An analysis of national inpatient sample. J Cardiovasc Electrophysiol 2018; 29:916. 12. Kadri AN, Abuamsha H, Nusairat L, et al. Causes and Predictors of 30-Day Readmission in Patients With Syncope/Collapse: A Nationwide Cohort Study. J Am Heart Assoc 2018; 7:e009746. 13. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol 2001; 37:1921. 14. Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet 2001; 357:348. https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 14/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate 15. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997; 126:989. 16. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 2: Unexplained syncope. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997; 127:76. 17. Olshansky B, Mazuz M, Martins JB. Significance of inducible tachycardia in patients with syncope of unknown origin: a long-term follow-up. J Am Coll Cardiol 1985; 5:216. 18. Benditt DG, Adkisson WO, Sutton R, et al. Ambulatory diagnostic ECG monitoring for syncope and collapse: An assessment of clinical practice in the United States. Pacing Clin Electrophysiol 2018; 41:203. 19. Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension : implications for alcohol-related syncope. Circulation 2000; 101:398. 20. Rutan GH, Hermanson B, Bild DE, et al. Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension 1992; 19:508. 21. Ray CA, Monahan KD. Aging attenuates the vestibulosympathetic reflex in humans. Circulation 2002; 105:956. 22. Kontny F, Dale J. Self-terminating idiopathic ventricular fibrillation presenting as syncope: a 40-year follow-up report. J Intern Med 1990; 227:211. 23. Benditt DG. Syncope risk assessment in the emergency department and clinic. Prog Cardiovasc Dis 2013; 55:376. 24. Leitch JW, Klein GJ, Yee R, et al. Syncope associated with supraventricular tachycardia. An expression of tachycardia rate or vasomotor response? Circulation 1992; 85:1064. 25. Doi A, Miyamoto K, Uno K, et al. Studies on hemodynamic instability in paroxysmal supraventricular tachycardia: noninvasive evaluations by head-up tilt testing and power spectrum analysis on electrocardiographic RR variation. Pacing Clin Electrophysiol 2000; 23:1623. 26. Brembilla-Perrot B, Beurrier D, Houriez P, et al. Incidence and mechanism of presyncope and/or syncope associated with paroxysmal junctional tachycardia. Am J Cardiol 2001; 88:134. 27. Hamer AW, Rubin SA, Peter T, Mandel WJ. Factors that predict syncope during ventricular tachycardia in patients. Am Heart J 1984; 107:997. 28. Landolina M, Mantica M, Pessano P, et al. Impaired baroreflex sensitivity is correlated with hemodynamic deterioration of sustained ventricular tachycardia. J Am Coll Cardiol 1997; https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 15/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate 29:568. 29. Menozzi C, Brignole M, Garcia-Civera R, et al. Mechanism of syncope in patients with heart disease and negative electrophysiologic test. Circulation 2002; 105:2741. 30. Kapoor W, Karpf M, Levey GS. Issues in evaluating patients with syncope. Ann Intern Med 1984; 100:755. 31. Krahn AD, Andrade JG, Deyell MW. Selecting appropriate diagnostic tools for evaluating the patient with syncope/collapse. Prog Cardiovasc Dis 2013; 55:402. 32. Grech ED, Ramsdale DR. Exertional syncope in aortic stenosis: evidence to support inappropriate left ventricular baroreceptor response. Am Heart J 1991; 121:603. 33. Goliasch G, Kammerlander AA, Nitsche C, et al. Syncope: The Underestimated Threat in Severe Aortic Stenosis. JACC Cardiovasc Imaging 2019; 12:225. 34. WAYNE HH. Syncope. Physiological considerations and an analysis of the clinical characteristics in 510 patients. Am J Med 1961; 30:418. 35. Badertscher P, du Fay de Lavallaz J, Hammerer-Lercher A, et al. Prevalence of Pulmonary Embolism in Patients With Syncope. J Am Coll Cardiol 2019; 74:744. 36. Kenny RA, Brignole M, Dan GA, et al. Syncope Unit: rationale and requirement the European Heart Rhythm Association position statement endorsed by the Heart Rhythm Society. Europace 2015; 17:1325. 37. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 38. Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol 2002; 40:142. 39. Heyer GL, Harvey RA, Islam MP. Comparison of Specific Fainting Characteristics Between Youth With Tilt-Induced Psychogenic Nonsyncopal Collapse Versus Reflex Syncope. Am J Cardiol 2017; 119:1116. 40. Walsh KE, Baneck T, Page RL, et al. Psychogenic pseudosyncope: Not always a diagnosis of exclusion. Pacing Clin Electrophysiol 2018; 41:480. 41. Tannemaat MR, van Niekerk J, Reijntjes RH, et al. The semiology of tilt-induced psychogenic pseudosyncope. Neurology 2013; 81:752. Topic 1049 Version 37.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 16/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate GRAPHICS Major cardiovascular causes of syncope Reflex-mediated* Vasovagal Orthostatic vasovagal syncope: usually after prolonged standing, frequently in a warm environment, etc Emotional vasovagal syncope: secondary to fear, pain, medical procedure, etc Unknown trigger Situational Micturition, defecation Swallowing Coughing/sneezing Carotid sinus syndrome Orthostatic hypotension* Medication-related Diuretics (eg, thiazide or loop diuretics) Vasodilators (eg, dihydropyridine calcium channel blockers, nitrates, alpha blockers, etc) Antidepressants (eg, tricyclic drugs, SSRIs, etc) Volume depletion Hemorrhage Gastrointestinal losses (ie, vomiting or diarrhea) Diminished thirst drive (primarily in older patients) Autonomic failure Primary: pure autonomic failure, Parkinson disease, multiple system atrophy, Lewy body dementia Secondary: diabetes mellitus, amyloidosis, spinal cord injuries, autoimmune neuropathy (eg, Guillain-Barr ), paraneoplastic neuropathy Cardiac Tachyarrhythmias Ventricular tachycardia Supraventricular tachycardias Bradyarrhythmias (with inadequate ventricular response) Sinus node dysfunction https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 17/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Atrioventricular block Structural disease Severe aortic stenosis Hypertrophic cardiomyopathy Cardiac tamponade Prosthetic valve dysfunction Congenital coronary anomalies Cardiac masses and tumors (eg, atrial myxoma) Cardiopulmonary/vascular Pulmonary embolus Severe pulmonary hypertension Aortic dissection SSRI: selective serotonin reuptake inhibitor. Reflex-mediated syncope and syncope due to orthostatic hypotension are more likely to occur, or are more severe, when other factors may also be contributing, such as medication(s) causing low blood pressure, volume depletion, pulmonary diseases causing reduction in brain oxygen supply, alcohol use, and/or environmental factors (excessive heat or humidity). Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. Graphic 118175 Version 4.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 18/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Incidence rates of syncope according to age and sex The incidence rates of syncope per 1000 person-years of follow-up increased with age among both men and women. The increase in the incidence rate was steeper starting at the age of 70 years. Syncope rates were similar among men and women. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. Graphic 82449 Version 2.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 19/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Causes of syncope in pooled data from five population-based studies Cause Mean prevalence, percent Neurally mediated Vasovagal 18 Situational (eg, cough, micturition, defecation, swallow) 5 Carotid sinus syncope 1 Orthostatic hypotension 8 Medications 3 Psychiatric 2 Neurologic 10 Cardiac Organic heart disease 4 Arrhythmia 14 Unknown 34 Data from Linzer M, Yang EH, Estes M, et al. Ann Intern Med 1997; 126:989. Includes 1002 unselected patients with syncope, including those from hospital-based referrals, emergency departements, and outpatient clinics between 1984 and 1990. Graphic 55289 Version 2.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 20/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Causes of syncope in Framingham cohort Prevalence, percent Cause Men Women Cardiac 13.2 6.7 Stroke or transient ischemic attack 4.3 4.0 Seizure disorder 7.2 3.2 Vasovagal 19.8 22.2 Orthostatic hypotension 8.6 9.9 Medication 6.3 7.2 Other 9.5 6.1 Unknown 31.0 40.7 Includes data from 727 patients. Data from Soteriades ES, Evans JC, Larson MG, et al. N Engl J Med 2002; 347:878. Graphic 68080 Version 2.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 21/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Overall survival of patients with syncope Survival was worst for patients with a cardiovascular cause of syncope. p<0.001 for the comparison between participants with and those without syncope. The category "Vasovagal and other causes" includes vasovagal, orthostatic, medication-induced, and other, infrequent cause of syncope. Sorteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. Graphic 53302 Version 4.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 22/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Conditions incorrectly diagnosed as syncope Disorders with partial or complete LOC but without global cerebral hypoperfusion Epilepsy Metabolic disorders including hypoglycaemia, hypoxia, hyperventilation with hypocapnia Intoxication Vertebrobasilar TIA Disorders without impairment of consciousness Cataplexy Drop attacks Falls Functional (psychogenic pseudosyncope) TIA or carotid origin LOC: loss of consciousness; TIA: transient ischaemic attack. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 76023 Version 6.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 23/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Algorithm for syncope/collapse This algorithm poses key questions about a collapse episode, including whether and when LOC occurred. However, in the absence of a credible witness, information about such episodes is often limited, as the affected individual may not have accurate recall of the event. Some causes have more than one possible type of presentation. LOC: loss of consciousness; BLS: basic life support; ACLS: advanced cardiac life support; SAH: subarachnoid hemorrhage; TIA: transient ischemic attack. This includes actual LOC as well as apparent LOC. Accidental falls without LOC often have multiple causes, including gait, posture, or balance impairment, environmental hazard, vertigo, focal seizure, TIA, stroke, and presyncope. These conditions result in apparent transient LOC, although consciousness may be preserved. https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 24/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Other causes of collapse may cause secondary head trauma. Most TIAs and strokes are not associated with LOC. An SAH may cause transient or prolonged LOC. A rare cause of LOC is a brainstem stroke. Graphic 131146 Version 1.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 25/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Differentiation of generalized tonic-clonic seizures from pseudoseizures and syncope Generalized Characteristic seizure tonic- Pseudoseizure Syncope clonic Circumstances Situation Awake or sleep Awake Usually upright; any position if cardiogenic Precipitating Sleep loss, alcohol Emotion Emotion, injury, heat, factors withdrawal, flashing crowds; none if lights cardiogenic Presence of others Variable Usual Variable Motor phenomena Vocalization At onset, if any During course None Location of motor component (if present) Proximal limb Proximal limb None Generalized motor Tonic, then clonic Tonic; flailing; struggling or thrashing, or both Usually atonic; if syncope lasts >20 seconds: tonic, then clonic Tonic posture Partial flexion or straight Opisthotonic Head movements To one side or none Side to side Clonus/limb jerks Bilaterally Asynchronous Bilaterally synchronous synchronous Purposeful movements Absent Occasional, including avoidance Absent Biting Tongue, inside Lips, arms, other people Tongue biting rare mouth Babinski's sign Present Absent Absent Autonomic features Micturition Frequent Rare Occasional Eyes Open Closed Open Pupils Dilated or hippus during attacks Normal Dilated https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 26/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Colour Cyanotic or grey Rubor or normal Pale Pulse Rapid, strong Normal Slow if vasovagal, weak if vasodepressor; that of arrhythmias if cardiogenic Timing Usual duration 1 to 5 min 5 to 60 min 1 to 2 min Onset Sudden Gradual Gradual; possibly sudden if cardiogenic Sequence of Stereotyped Variable Stereotyped symptoms Termination Spontaneous Spontaneous or induced Rapid by supraorbital pressure, suggestion Sequelae Injury Frequent, mild; scalp, face, common Rare, but multiple bruises possible; scalp, face, rare If sudden onset Postictal Tired, confused, sleepy Alert, emotional outburst Regains consciousness in 2 to 3 min; alert but tired Reproduced with permission from: Blume WT. Diagnosis and management of epilepsy. CMAJ 2003; 168:441. Copyright 2003 Canadian Medical Association. Graphic 73515 Version 2.0 https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 27/28 7/6/23, 2:38 PM Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate Contributor Disclosures David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and defibrillators]; St Jude Medical [Pacemakers/event recorders and defibrillators]. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced CPR Solutions [Outside director]. All of the relevant financial relationships listed have been mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias]. Consultant/Advisory Boards: Abbvie [Arrhythmias]; Acesion Pharma [Arrhythmias]; Allergan [Arrhythmias, cardiac safety of non-cardiac drugs]; Anthos [Anticoagulants]; Boehringer-Ingelheim [Arrhythmias]; Bristol-Meyers-Squibb [Arrhythmias]; Daiichi Sankyo [Arrhythmias]; Gilead [Arrhythmias]; Huya [Arrhythmias]; InCarda Therapeutics [Arrhythmias]; INSTA [Arrhythmias]; Johnson & Johnson [Arrhythmias]; Medtronic [Arrhythmias]; Milestone [Arrhythmias]; Novartis [Arrhythmias, cardiac safety of non-cardiac drugs]; Pfizer [Arrhythmias]; Sanofi [Arrhythmias]; Takeda [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print 28/28 |
7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Syncope in adults: Management and prognosis : David Benditt, MD : Peter Kowey, MD, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Nov 29, 2022. INTRODUCTION Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often the result of an abrupt drop of systemic blood pressure [1-4]. Typically, the inadequate cerebral nutrient flow is of relatively brief duration (8 to 10 seconds) and, by definition, syncope is self-limited. Unfortunately, the term "syncope" is often misapplied to encompass any form of abrupt collapse which may or may not be accompanied by TLOC, including seizures and concussions; such overbroad usage should be avoided as it deflects diagnostic focus from causes of cerebral hypoperfusion ( algorithm 1) [5]. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".) Issues relating to the treatment and prognosis of syncope in adults will be reviewed here. The pathogenesis and etiology of syncope, and the clinical manifestations and diagnostic evaluation of patients with syncope, are discussed elsewhere. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".) TREATMENT Treatment is based upon the underlying cause of syncope ( table 1 and table 2) and is directed at preventing recurrence and/or, in some cases, death. A brief review of the available treatment options for each of the possible underlying disorders is presented below. https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 1/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate Responding to prodromal symptoms Syncope may or may not be preceded by prodromal symptoms warning of an imminent faint, depending on the cause of syncope [6,7]. Certain symptoms may evolve during a short period before an imminent collapse, and recognition of these prodromal symptoms may permit the affected individual to react and both prevent evolution of the episode into a full faint and avoid TLOC hazards such as accidents and injury. Appropriate reactions may include pulling off to the side of the road if driving, lying down or sitting down if standing to avoid a fall, and lowering the head if feeling near faint. Prodromes are common in young patients with reflex syncope, but seem to occur less often, or are less well recollected, in older individuals. Typical prodromes warning of imminent vasovagal faints include feeling hot or cold, feeling sweaty, pallor, nausea, and palpitations. Prodromes may also provide warning with certain cardiac syncope events (eg, chest pain with ischemia, palpitations with tachycardias), but not with others (eg, abrupt atrioventricular [AV] block or prolonged pauses). It may be helpful to ask bystanders if the affected individual expressed any symptoms before the collapse occurred; such symptoms may not be recalled by the "fainter" (particularly the older fainter) after the fact. Patients with reflex (ie, vasovagal) syncope who experience prodromal symptoms are advised immediately respond to the warning by moving to a safe position (seated or ideally supine) and if possible, initiating physical isometric counterpressure maneuvers such as leg-crossing and/or lower body muscle tensing. The pathophysiology of these faints includes an abrupt initial drop of venous return leading to diminished stroke volume and cardiac output [8]. Counterpressure maneuvers reduce translocation of blood to dependent parts of the body and thus help maintain stroke volume and cardiac output [9,10]. Examples of physical counterpressure maneuvers include: Leg-crossing with simultaneous tensing of leg, abdominal, and buttock muscles Handgrip, which consists of maximum grip on a rubber ball or similar object Arm tensing, which involves gripping one hand with the other while simultaneously abducting both arms Physical counterpressure maneuvers may also be helpful for patients with symptomatic orthostatic hypotension. An important risk of undertaking these maneuvers (particularly standing with legs crossed and muscles tensed) is postural instability, particularly for individuals who are frail or older. These maneuvers are discussed in detail separately. (See "Reflex syncope in adults and adolescents: Treatment", section on 'Recognizing symptoms and taking action'.) Immediate (emergency) treatment of syncopal patients For witnessed syncope, the immediate treatment of a patient with syncope or presyncope includes the following: https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 2/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate Assist the patient to the ground, chair, or stretcher to avoid traumatic injury. When necessary, remove the patient from any potential external dangers (eg, high places, water, electrical wires, etc). Lay the patient supine, with legs elevated if possible to enhance venous return to the heart and thereby restore adequate cerebral perfusion. Assess vital signs, namely a pulse and evidence of respiration, to distinguish cardiac arrest from syncope. Observe for other signs (eg, pallor, diaphoresis, seizure-like or jerky muscular movements, etc) that may assist in establishing the etiology. Note whether eyelids are open, closed, or fluttering. Call for additional assistance if needed. Attempt to arouse the patient. Do not try to raise the patient up until the patient indicates readiness to do so. Raising the patient too soon may trigger a recurrence of the transient loss of consciousness. For patients who are identified to be hypotensive not directly caused by excessive bradycardia or asystole, raising the legs and providing fluid resuscitation (eg, intravenous saline infusion) are the first steps for treatment. Orthostatic hypotension associated with evidence of volume depletion should improve following volume expansion. Orthostatic hypotension due to an autonomic neuropathy may not be entirely reversed with fluids, but in most cases some benefit will be achieved and, consequently, a trial of fluid resuscitation is appropriate. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock", section on 'Intravenous fluids' and "Treatment of orthostatic and postprandial hypotension".) Patients who are identified to have symptomatic bradycardia or high-grade AV block (ie, Mobitz type II second-degree AV block or third-degree [complete] AV block) may or may not be hypotensive when medical care is initiated. For hypotensive patients, atropine followed by temporary cardiac pacing are usually the initial treatments. If these steps are not available or effective, and depending on the severity of hypotension, isoproterenol or dobutamine infusion may help to increase heart rate. Severe hypotension may require treatment with parenteral vasoconstrictors. (See "Advanced cardiac life support (ACLS) in adults", section on 'Bradycardia' and "Third-degree (complete) atrioventricular block", section on 'Unstable patients' and "Second- degree atrioventricular block: Mobitz type II", section on 'Unstable patients'.) Therapies to prevent syncope recurrences Therapies directed toward prevention of syncope recurrences are highly variable depending upon the suspected etiology of the syncope https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 3/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate [1,2,11,12]. Reflex syncope Vasovagal syncope is the most common condition in this category in all age groups and, if recurrent, may necessitate attempts at reducing susceptibility. Unfortunately, vasovagal events are unpredictable, and no therapy has been proven consistently effective for recurrent vasovagal syncope. The treatment of reflex syncope is presented in detail separately. (See "Reflex syncope in adults and adolescents: Treatment".) Carotid sinus syncope Carotid sinus hypersensitivity is a physical finding in which carotid massage results in a marked pause (generally 5 seconds or greater) and/or vasodepressor hypotensive effect [1,2]. Carotid sinus hypersensitivity is a common finding, especially in older men, and does not warrant treatment if asymptomatic. If carotid sinus hypersensitivity is found to cause syncope or near-syncope, then the condition is deemed to be a particular subtype of reflex syncope known as carotid sinus syndrome (CSS). As with reflex syncope in general, initial treatment measures include reassurance and education regarding the nature, risks, and prognosis of the condition. The patient should be advised to avoid accidental mechanical manipulation of the carotid sinuses (eg, abrupt turning of the neck, tight collars). In CSS patients, medications that may induce hypotension (such as vasodilator therapy) should be discontinued or reduced when feasible. Pacemakers are helpful in many patients with CSS in whom the cardioinhibitory response (ie, bradycardia or asystole) is prominent, but are not as beneficial in individuals with a predominant vasodepressor response. The treatment of CSS is discussed in detail separately. (See "Carotid sinus hypersensitivity and carotid sinus syndrome".) Situational syncope Situational syncope, as the name suggests, comprises a group of reflex syncope conditions that occur in or are triggered by particular circumstances. For example, cough syncope, micturition syncope, and swallow syncope are examples in which the trigger is apparent. Treatment, however, may be difficult as it entails minimizing the impact that these common circumstances have on susceptible individuals. Orthostatic hypotension Orthostatic hypotension (OH) is a very common cause of lightheadedness or syncope accompanying movement to upright posture. It may be the result of volume depletion, neurologic disorders, or the effects of drugs (eg, vasodilators, diuretics). OH may be considered to comprise two clinical forms [13,14]. The "immediate" (sometimes also referred to as the "initial") form occurs momentarily after arising and may occur in all age groups, including healthy individuals. https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 4/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate The "delayed" or "classic" form tends to occur in older patients and/or those with neurologic disorders (eg, Parkinson disease, autonomic failure, diabetic neuropathy). The classic form may be more hazardous, as TLOC may not begin until the patient is sufficiently far from support (such as a chair or sofa) that they have nothing to hold on to in order to diminish the severity of the collapse. Injury is far more prevalent in the classic form. Causes and evaluation of orthostatic hypotension are discussed further separately. (See "Mechanisms, causes, and evaluation of orthostatic hypotension".) Identifying the underlying cause of OH is crucial to determine appropriate preventive treatment. OH associated with evidence of volume depletion should be treated with volume expansion and avoidance of precipitating factors (such as diuretic use). In the absence of volume depletion, OH is most often due to administration of vasodilator or negative chronotropic drugs; other cases may be due to autonomic neuropathy, with causes including diabetes mellitus, alcohol abuse, and other toxins. In the latter group (ie, autonomic dysfunction), supine hypertension is a common limiting factor. Long-term management of OH is complicated by the associated risk of supine hypertension in many of these patients, and is discussed in detail separately. (See "Treatment of orthostatic and postprandial hypotension".) Medication-induced syncope Recurrent syncope resulting as a side effect of therapy with certain medications is often preventable. Most, but not all, of medication-induced syncope are orthostatic. Effective interventions should, if possible, include the elimination of the offending medication, substitution of an alternative agent, dose adjustment, or altering the timing of drug administration. As examples: Orthostatic complications: Patients with OH, particularly if taking one or more medications (eg, antihypertensives, vasodilators) that may exacerbate orthostasis ( table 3). Patients with volume depletion who are taking diuretics. Nonorthostatic complications: Patients with bradyarrhythmias and/or heart block who are taking beta blockers, calcium channel blockers, other antiarrhythmic drugs and/or digoxin. Patients with tendency to long QT syndrome who are prescribed QT-prolonging drugs may develop collapse due to torsades de pointes. (See "Congenital long QT syndrome: https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 5/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate Treatment" and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) Cardiac syncope Syncope of cardiac origin is most often due to tachy- and bradyarrhythmias (with causes including genetically determined channelopathies and various types of structural cardiac diseases). Less commonly, "mechanical" disturbances may trigger hypotension and syncope (eg, severe aortic stenosis with inadequate cardiac output on exertion). Arrhythmias Patients with syncope and documented ventricular tachyarrhythmias are often candidates for drug or device therapy aimed at both preventing recurrences and addressing concerns regarding sudden cardiac death (SCD). Documented, suspected, or induced ventricular tachycardia Syncope in patients with ventricular tachycardia (VT) may reflect an increased risk of SCD or hemodynamic collapse in the setting of structural heart disease. Patients with structural cardiac disease, syncope, and documented ventricular arrhythmias are at high risk for recurrent VT and/or SCD. Therapy with ablation and/or an implantable cardioverter-defibrillator (ICD) is indicated in most such patients [1]. Additionally, ICD therapy is an option for some patients who have syncope due to an unknown cause but have underlying structural heart disease that places them at risk of SCD. While ICD therapy plays an important role in preventing sudden death, it may not protect against syncope recurrences. A full discussion of the secondary prevention of SCD due to VT is presented separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Supraventricular arrhythmias While many patients with a supraventricular tachycardia (SVT) will develop symptoms, usually palpitations, chest discomfort, or dyspnea, syncope is much less often encountered, as most SVTs are hemodynamically well tolerated. However, syncope may occur at the onset of SVT when the vascular compensatory mechanisms to maintain blood pressure take time to become active. In some patients, usually older adults, syncope may occur when SVT terminates and a pause ensues, since return to an adequate rhythm may be delayed due to overdrive suppression. Patients with severe underlying cardiac disease (eg, decompensated heart failure, etc) in whom there is insufficient cardiac reserve to tolerate the increase in heart rate may be at particular risk of collapse with tachyarrhythmias. When possible, patients with syncope due to SVT and an accessory pathway should be treated with catheter ablation. A full discussion of the treatment of SVT in patients with an accessory pathway is presented separately. (See "Treatment of https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 6/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Treatment to prevent recurrent arrhythmias'.) Bradyarrhythmias In some patients with syncope, a bradyarrhythmia will be recorded at presentation. These may be due to a wide range of underlying conduction system problems, such as sinus node dysfunction, progressive disease of the specialized conduction system, and genetically determined disorders such as the muscular dystrophies. In any case, bradyarrhythmias of sufficient severity to cause syncope (eg, sinus pause, pause after SVT termination) can be infrequent and difficult to document. In such cases, it is essential to extend periods of ambulatory electrocardiogram (ECG) monitoring to capture infrequent events [14]. In general, if no reversible causes are present, definitive treatment of high-grade AV block (ie, Mobitz type II second degree AV block or third degree [complete] AV block) or prolonged pauses in a patient with documented correlation between symptoms and bradycardia necessitates permanent pacemaker placement [1]. (See "Third-degree (complete) atrioventricular block", section on 'Stable patients' and "Second-degree atrioventricular block: Mobitz type II", section on 'Stable patients' and "Sinus node dysfunction: Treatment", section on 'Symptomatic patients'.) Rarely, a permanent pacemaker is used empirically when baseline ECG or invasive electrophysiology studies (EPS) strongly suggest a conduction abnormality as the cause for syncope as illustrated by the following examples [1]: Pacemaker therapy is reasonable in patients with syncope when clinically significant sinus node dysfunction is observed or provoked during EPS. However, it is unusual for EPS to be particularly useful in this setting. Pacemaker therapy is reasonable in patients with syncope and bifascicular or trifascicular disease on the baseline ECG if other causes have been excluded, specifically VT. Electrophysiologic study to assess severity and anatomic level of the block may be warranted. However, some studies have raised concern that empiric pacing in these settings may not prevent syncope [15,16]. In some older adult patients, severe bradycardia is recorded (occasionally as low as 20 to 30 beats per minute), but symptoms are not reported. The appropriate role for pacemakers in this situation remains controversial. Obstruction to left ventricular outflow Syncope in a patient with severe aortic stenosis may be directly related to the valve disease; however, patients with severe aortic stenosis and syncope may also have syncope from another cause (eg, reflex-mediated, orthostatic hypotension, conduction system disturbance, etc) which is only indirectly attributable to the aortic valve disease itself. As with all patients who experience syncope, a thorough history https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 7/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate and physical examination are critical in determining the etiology and subsequent management. For patients with severe aortic stenosis in whom no other etiology of syncope is identified, aortic valve replacement may be indicated, but thorough discussion with the patient and family (ie, shared decision making) is crucial. The approach to symptomatic severe aortic stenosis is discussed in detail separately. (See "Clinical manifestations and diagnosis of aortic stenosis in adults" and "Indications for valve replacement for high gradient aortic stenosis in adults".) Syncope may also occur in patients with dynamic outflow obstruction resulting from hypertrophic cardiomyopathy (HCM). Unexplained syncope (ie, not related to neurocardiogenic/vasovagal causes) is considered a marker for increased risk of sudden death. The approach to patients with HCM and syncope is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Syncope' and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk stratification'.) DRIVING RESTRICTIONS Rules regarding driving may vary from region to region within some countries and certainly between countries. Driving restrictions are indicated for some patients at risk for recurrent syncope for the safety of themselves and others. In general, patients with untreated syncope should not drive until appropriate preventive treatment has been instituted ( table 4) [1,17]. Following the institution of therapy for syncope, the duration of time patients should avoid driving varies significantly depending upon the underlying condition as well as the legal restrictions of the local, state, or national government. Because of the significant variability in legal restrictions worldwide, providers should be familiar with their local driving laws and restrictions and advise patients accordingly. The assessment of motor vehicle accident risk among patients with a history of syncope, or, as is more often the case, a diagnosis of "syncope/collapse," is difficult in practical terms due to the rarity of events, and especially of repeat events in the same individual. Consequently, the topic remains controversial. The likelihood of a motor vehicle crash has been estimated to be between 1.5 and 4 times higher for patients with a history of syncope compared with the general population [17-21]. In a Danish cohort of 41,039 patients with first episodes of syncope between 2008 and 2012 with a median follow-up of two years, 1791 patients (4.4 percent) experienced a motor vehicle crash at a rate that was significantly higher than the general population (20.6 compared with 12.1 per 1000 patient-years in the general population; rate ratio 1.83, 95% CI 1.74-1.91) [17,18]. https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 8/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate While the risk of motor vehicle crash may be higher in patients with history of syncope than in the general population, a British Columbia study suggested that the crash risk in patients with presumed syncope may be similar to that for other patients presenting to emergency departments [21]. In this study of 43,589 patients visiting emergency departments (9223 with syncope and 34,366 with other conditions), the baseline motor vehicle crash rates for "syncope and collapse" and control groups were similar and higher than in the general population (12.2, 13.2, and 8.2 crashes per 100 driver-years, respectively) [21]. During the year after the index emergency department visit, crashes occurred at similar rates in the "syncope and collapse" and control groups (9.2 versus 10.1 percent; adjusted hazard ratio 0.93, 95% CI 0.87-1.01). A major limitation of the interpretation of this study and similar emergency department-based studies is that emergency department clinicians often of necessity combine "syncope and collapse" rather than restrict observations to "syncope" alone. The take-away lesson may then be that motor vehicle accidents are likely to be similarly increased in frequency among patients with an acute illness of sufficient severity to cause them to seek emergency department evaluation. PROGNOSIS The prognosis of the patient with syncope is in most cases directly related to the underlying etiology of the syncope and the underlying comorbidities, not the syncope itself [22-25]. As a result, patients can be categorized into different risk categories based upon cause ( figure 1). Those with an underlying cardiovascular cause are at higher risk for sudden death and all-cause total mortality rates than those with a noncardiovascular cause. Overall mortality in the cardiovascular group after five years of follow-up has been reported to approach 50 percent, with a 30 percent incidence of death in the first year. However, a major problem in determining the true mortality rate in patients with syncope is that most individuals with transient loss of consciousness do not seek medical advice. It is suspected that most individuals have a low recurrence rate of syncope and an excellent long-term survival in the absence of underlying cardiac disease or channelopathy (eg, long QT syndrome, Brugada syndrome). Underlying cardiac disease substantially increases mortality risk. Outpatients never admitted for their episodes may be at lesser risk for recurrence and have a more benign long- term prognosis than those requiring hospitalization. Improvements in diagnostic capability have altered understanding of the prognosis associated with syncope/collapse of unknown cause. In considering syncope/collapse prognosis, it is important to differentiate studies derived from the emergency department (ED) from those obtained in presumably lower-risk, community-based studies. The ED studies have resulted in development of several risk stratification schemes mainly focused on short-term risk, as https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 9/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate discussed separately. (See "Approach to the adult patient with syncope in the emergency department", section on 'Risk stratification'.) In evaluation of longer-term prognostic implications of syncope of unknown cause, the Framingham study indicated that syncope/collapse of unexplained cause is accompanied by a mortality risk profile that is about halfway between low-risk vasovagal syncope patients (who had mortality rates no different than the normal population) and high-risk cardiac syncope patients (who had a much more worrisome mortality) ( figure 1). However, as discussed above, given the important limitations associated with its diagnostic methodologies, the Framingham conclusions in this regard need to be reconsidered. Contemporary evidence, while still in need of refinement, suggests that with a few exceptions (eg, channelopathies), mortality in patients with syncope/collapse of unknown cause is related less to having experienced a syncope event than to the presence and severity of underlying cardiovascular disease. For instance, a study of nationwide Danish registries identified 37,000 first hospitalizations with syncope which were compared with 185,000 nonsyncope controls [26]. Presence or absence of syncope had minimal effect on mortality over 10 years in older patients (>75 years) or younger individuals (<25 years) but did have an impact in middle-aged patients. The age-related differences are not readily explained, but tend to favor the interpretation that evolving underlying disease in middle-aged patients may be important. These data suggest that a hospitalization for syncope is a signal that warrants careful assessment of underlying cause. The Malmo (Sweden) population-based study found no major differences in outcomes during the first 12 years of follow-up between an index unexplained syncope versus orthostatic hypotension without syncope [27]. After 12 years, mortality was higher in the syncope group, but the cause of this observation is uncertain. A report in patients with syncope and moderate left ventricular dysfunction found no mortality difference over 30 months follow-up compared with previously reported nonsyncope patients with similar severity of heart disease [28]. A meta- analysis of observational cohort studies compared mortality in a control population without syncope with that in a population with noncardiac/unexplained syncope [29]. A noncardiac/unexplained syncope history was associated with a 13 percent greater all-cause mortality (pooled adjusted hazard ratio 1.13, 95% CI 1.05-1.23) in older individuals or those with a diabetic or hypertensive history. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 10/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain th th language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at th th the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (See "Patient education: Syncope (fainting) (The Basics)" and "Patient education: Bradycardia (The Basics)".) Beyond the Basics topic (See "Patient education: Syncope (fainting) (Beyond the Basics)".) SUMMARY AND RECOMMENDATIONS Patients with vasovagal syncope (the most common cause of syncope) and prodromal symptoms are instructed to move safely to a seated or supine position and perform physical isometric counterpressure maneuvers such as leg-crossing and/or lower body muscle tensing upon first recognition of premonitory symptoms. (See 'Responding to prodromal symptoms' above.) For witnessed syncope, the immediate treatment of a patient with syncope or presyncope includes assisting the patient to the ground or another location to avoid traumatic injury, laying the patient supine with legs elevated (if possible), assessing for vital signs, and calling for assistance. (See 'Immediate (emergency) treatment of syncopal patients' above.) Therapies directed toward prevention of recurrent syncope is selected based upon the suspected etiology of the syncope. (See 'Therapies to prevent syncope recurrences' above.) Recurrent syncope resulting as a side effect of therapy with certain medications is often preventable following elimination of the offending medication, substitution of an alternative agent, dose adjustment, or altering the timing of drug administration. (See 'Orthostatic hypotension' above.) https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 11/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate No therapy has been proven consistently effective for recurrent vasovagal syncope. However, patients should be reassured about the generally benign nature of reflex syncope (while noting the risk of injury), educated to avoid potential triggers and identify warning symptoms, and instructed on how to perform physical counterpressure maneuvers at the onset of symptoms. (See 'Reflex syncope' above and "Reflex syncope in adults and adolescents: Treatment".) Patients with syncope and documented ventricular tachyarrhythmias are often candidates for drug or device therapy aimed at preventing sudden cardiac death (SCD). Patients with syncope and high-grade atrioventricular (AV) block (ie, Mobitz type II second degree AV block or third degree [complete] AV block) or prolonged pauses are treated with permanent pacemaker placement. (See 'Arrhythmias' above.) For patients with severe aortic stenosis in whom no other etiology of syncope is identified, and the syncope is suspected to be due to the severe aortic stenosis, aortic valve replacement is indicated. Similarly, unexplained syncope (ie, not related to neurocardiogenic/vasovagal causes) in patients with hypertrophic cardiomyopathy is considered a marker for increased risk of sudden death. (See 'Obstruction to left ventricular outflow' above and "Indications for valve replacement for high gradient aortic stenosis in adults" and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) Driving restrictions are indicated for some patients at risk for recurrent syncope for the safety of themselves and others. In general, patients with untreated syncope should not drive until appropriate preventive treatment has been instituted. Following the institution of therapy for syncope, the duration of time patients should avoid driving varies significantly depending upon the underlying condition as well as the legal restrictions of the local, state, or national government ( table 4). (See 'Driving restrictions' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Brian Olshansky, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 12/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate 1. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 2. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 3. Parry SW, Tan MP. An approach to the evaluation and management of syncope in adults. BMJ 2010; 340:c880. 4. Thijs RD, Wieling W, Kaufmann H, van Dijk G. Defining and classifying syncope. Clin Auton Res 2004; 14 Suppl 1:4. 5. Thijs RD, Benditt DG, Mathias CJ, et al. Unconscious confusion a literature search for definitions of syncope and related disorders. Clin Auton Res 2005; 15:35. 6. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine (Baltimore) 1990; 69:160. 7. Blanc JJ, L'Her C, Touiza A, et al. Prospective evaluation and outcome of patients admitted for syncope over a 1 year period. Eur Heart J 2002; 23:815. 8. van Dijk JG, Ghariq M, Kerkhof FI, et al. Novel Methods for Quantification of Vasodepression and Cardioinhibition During Tilt-Induced Vasovagal Syncope. Circ Res 2020; 127:e126. 9. van Dijk N, Quartieri F, Blanc JJ, et al. Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: the Physical Counterpressure Manoeuvres Trial (PC-Trial). J Am Coll Cardiol 2006; 48:1652. 10. Krediet CT, van Dijk N, Linzer M, et al. Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing. Circulation 2002; 106:1684. 11. Anand V, Benditt DG, Adkisson WO, et al. Trends of hospitalizations for syncope/collapse in the United States from 2004 to 2013-An analysis of national inpatient sample. J Cardiovasc Electrophysiol 2018; 29:916. 12. Benditt DG, Adkisson WO, Sutton R, et al. Ambulatory diagnostic ECG monitoring for syncope and collapse: An assessment of clinical practice in the United States. Pacing Clin Electrophysiol 2018; 41:203. 13. Wieling W, Dambrink JH, Borst C. Cardiovascular effects of arising suddenly. N Engl J Med 1984; 310:1189. 14. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011; 21:69. https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 13/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate 15. Sheldon R, Talajic M, Tang A, et al. Randomized Pragmatic Trial of Pacemaker Versus Implantable Cardiac Monitor in Syncope and Bifascicular Block. JACC Clin Electrophysiol 2022; 8:239. 16. Santini M, Castro A, Giada F, et al. Prevention of syncope through permanent cardiac pacing in patients with bifascicular block and syncope of unexplained origin: the PRESS study. Circ Arrhythm Electrophysiol 2013; 6:101. 17. Sakaguchi S, Adkisson WO. Driving and flying: US and European recommendations. In: Sync ope: An Evidence-Based Approach, 2nd ed, Brignole M, Benditt DG (Eds), Springer Nature 20 20. p.319. 18. Num AK, Gislason G, Christiansen CB, et al. Syncope and Motor Vehicle Crash Risk: A Danish Nationwide Study. JAMA Intern Med 2016; 176:503. 19. Dischinger PC, Ho SM, Kufera JA. Medical conditions and car crashes. Annu Proc Assoc Adv Automot Med 2000; 44:335. 20. Redelmeier DA, Yarnell CJ, Thiruchelvam D, Tibshirani RJ. Physicians' warnings for unfit drivers and the risk of trauma from road crashes. N Engl J Med 2012; 367:1228. 21. Staples JA, Erdelyi S, Merchant K, et al. Syncope and the Risk of Subsequent Motor Vehicle Crash: A Population-Based Retrospective Cohort Study. JAMA Intern Med 2022; 182:934. 22. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. 23. Saklani P, Krahn A, Klein G. Syncope. Circulation 2013; 127:1330. 24. Kenny RA, O'Shea D, Walker HF. Impact of a dedicated syncope and falls facility for older adults on emergency beds. Age Ageing 2002; 31:272. 25. Shenthar J, Prabhu MA, Banavalikar B, et al. Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study. JACC Clin Electrophysiol 2019; 5:608. 26. Ruwald MH, Hansen ML, Lamberts M, et al. Prognosis among healthy individuals discharged with a primary diagnosis of syncope. J Am Coll Cardiol 2013; 61:325. 27. Yasa E, Ricci F, Magnusson M, et al. Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension. Heart 2018; 104:487. 28. Francisco-Pascual J, Rodenas-Alesina E, Rivas-G ndara N, et al. Etiology and prognosis of patients with unexplained syncope and mid-range left ventricular dysfunction. Heart Rhythm 2021; 18:597. 29. Ricci F, Sutton R, Palermi S, et al. Prognostic significance of noncardiac syncope in the general population: A systematic review and meta-analysis. J Cardiovasc Electrophysiol https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 14/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate 2018; 29:1641. Topic 1032 Version 39.0 https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 15/26 7/6/23, 2:38 PM Syncope in adults: Management and prognosis - UpToDate GRAPHICS Algorithm for syncope/collapse This algorithm poses key questions about a collapse episode, including whether and when LOC occurred. However, in the absence of a credible witness, information about such episodes is often limited, as the affected individual may not have accurate recall of the event. Some causes have more than one possible type of presentation. LOC: loss of consciousness; BLS: basic life support; ACLS: advanced cardiac life support; SAH: subarachnoid hemorrhage; TIA: transient ischemic attack. This includes actual LOC as well as apparent LOC. Accidental falls without LOC often have multiple causes, including gait, posture, or balance impairment, environmental hazard, vertigo, focal seizure, TIA, stroke, and presyncope. https://www.uptodate.com/contents/syncope-in-adults-management-and-prognosis/print 16/26 |