Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk

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

●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 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.

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 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), 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 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 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'.)

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".)

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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'.)

•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 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.