What are the treatment options for hypertrophic cardiomyopathy?

Treatment Options for Hypertrophic Cardiomyopathy

Beta-blockers are the first-line pharmacologic therapy for symptomatic HCM, followed by non-dihydropyridine calcium channel blockers (verapamil or diltiazem) if beta-blockers are ineffective or not tolerated, with surgical myectomy being the preferred invasive option for refractory obstructive disease. 1, 2

Pharmacologic Management

First-Line Therapy: Beta-Blockers

• Non-vasodilating beta-blockers should be initiated as first-line therapy for symptomatic patients with obstructive HCM, titrated to maximum tolerated doses to reduce heart rate, decrease contractility, and prolong diastolic filling time 1, 2
• Beta-blockers provide negative inotropic effects and attenuate adrenergic-induced tachycardia, which improves symptoms of dyspnea, chest pain, and palpitations 1

Second-Line Therapy: Calcium Channel Blockers

• Verapamil (320-720 mg/day) is reasonable for patients who cannot tolerate or do not respond to beta-blockers, with demonstrated subjective improvement in 85% of symptomatic patients 1, 2, 3
• Diltiazem is an alternative non-dihydropyridine calcium channel blocker that improves diastolic performance and reduces myocardial ischemia 1
• Critical contraindication: Verapamil must be avoided in patients with severe outflow obstruction (gradient >100 mmHg), severe symptoms at rest, hypotension, or elevated pulmonary wedge pressure due to risk of precipitating pulmonary edema 1, 4
• Dihydropyridine calcium channel blockers (e.g., nifedipine) are contraindicated in obstructive HCM as their vasodilatory effects worsen outflow obstruction 1

Third-Line Therapy: Disopyramide

• Disopyramide can be added to beta-blockers or calcium channel blockers for patients with persistent symptoms despite monotherapy, particularly in obstructive HCM 1, 2

Novel Therapy: Mavacamten

• Mavacamten (cardiac myosin inhibitor) is recommended for adult patients with obstructive HCM who do not respond adequately to conventional therapy, representing a disease-modifying approach 2, 5
• Mavacamten is contraindicated during pregnancy due to potential teratogenic effects 2

Adjunctive Medications

• Diuretics should be used cautiously at low doses only in patients with clinical evidence of volume overload, as aggressive diuresis can worsen outflow obstruction 1, 2
• High-dose diuretics and pure vasodilators must be avoided as they exacerbate LVOT obstruction 1

Invasive Septal Reduction Therapy

Indications for Invasive Treatment

• Invasive therapy is indicated for patients with NYHA class III-IV symptoms refractory to optimal medical therapy AND resting or provoked LVOT gradient ≥50 mmHg 1, 2

Surgical Myectomy

• Surgical septal myectomy is the preferred invasive approach, particularly for younger patients, those with septal thickness >30mm, concomitant cardiac disease requiring surgery, or unfavorable septal anatomy for ablation 1, 2
• Myectomy provides durable symptom relief with low mortality (<1%) at experienced centers and allows concurrent mitral valve repair if needed 1

Alcohol Septal Ablation

• Alcohol septal ablation is a reasonable alternative for older patients (typically >65 years), those with significant comorbidities, or strong preference to avoid surgery 1, 2
• Transesophageal or transthoracic echocardiography with intracoronary contrast injection is required for intraprocedural guidance 1

Management of Atrial Fibrillation

Anticoagulation

• Warfarin (INR 2.0-3.0) or direct oral anticoagulants are mandatory for all patients with paroxysmal, persistent, or chronic AF, regardless of symptom severity, due to high thromboembolic risk 1, 2

Rate and Rhythm Control

• High-dose beta-blockers and non-dihydropyridine calcium channel blockers are required for ventricular rate control in AF, often exceeding typical doses 1
• Amiodarone and disopyramide are reasonable options for rhythm control, with amiodarone demonstrating safety and efficacy in HCM 1, 2
• Catheter ablation (pulmonary vein isolation) or surgical maze procedure can be considered for refractory AF 1

Sudden Cardiac Death Prevention

ICD Implantation

• ICD placement is recommended (Class I) for patients with prior cardiac arrest or sustained ventricular tachycardia 1
• ICD is reasonable (Class IIa) for patients with ≥1 major risk factors: family history of sudden death in first-degree relative, unexplained syncope, LV wall thickness ≥30mm, non-sustained VT on Holter monitoring, or abnormal blood pressure response to exercise 1
• Dual-chamber ICDs are reasonable for patients with sinus bradycardia, paroxysmal AF, or elevated resting gradients >50 mmHg who may benefit from pacing 1

Advanced Heart Failure Management

Systolic Dysfunction (LVEF <50%)

• Guideline-directed medical therapy for heart failure with reduced ejection fraction should be initiated, including ACE inhibitors/ARBs/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists 1
• Discontinue negative inotropic agents (verapamil, diltiazem, disopyramide) when systolic dysfunction develops 1
• Cardiac resynchronization therapy is reasonable for patients with LVEF <50%, NYHA class II-IV symptoms, and left bundle branch block 1

End-Stage Disease

• Heart transplantation evaluation is recommended for patients with NYHA class III-IV symptoms despite optimal therapy or life-threatening refractory arrhythmias 1
• Continuous-flow left ventricular assist devices are reasonable as bridge to transplantation 1

Activity and Sports Participation

Competitive Sports

• Patients with HCM should not participate in high-intensity competitive sports regardless of age, sex, or presence of obstruction, due to increased sudden death risk during intense exertion 1
• Low-intensity competitive sports (golf, bowling) are reasonable for most patients 1
• Genotype-positive, phenotype-negative individuals can reasonably participate in competitive athletics of any intensity 1

Recreational Exercise

• Mild to moderate-intensity recreational exercise is beneficial for cardiorespiratory fitness and quality of life, following general population physical activity guidelines 1
• Aerobic exercise is preferable to isometric exercise; avoid burst exertion activities (e.g., sprinting, full-court basketball) 1
• Patients should avoid extreme environmental conditions (heat, cold, high humidity) and maintain adequate hydration 1

Asymptomatic Patient Management

• All asymptomatic patients require sudden death risk stratification, family screening counseling, and education about activity restrictions 1
• Aggressive treatment of atherosclerotic risk factors is recommended as concomitant CAD significantly impacts survival 1
• Annual ECG monitoring is reasonable to detect asymptomatic conduction changes or AF 1
• Transthoracic echocardiography every 12-18 months is reasonable for stable patients to assess disease progression 1

Critical Pitfalls to Avoid

• Never use dihydropyridine calcium channel blockers in obstructive HCM - they worsen obstruction through vasodilation 1
• Do not combine beta-blockers with verapamil or diltiazem without extreme caution due to risk of high-grade AV block 1, 4
• Avoid aggressive diuresis in obstructive disease - volume depletion exacerbates LVOT gradients 1
• Refer complex cases to specialized HCM centers for invasive therapy decisions and advanced management 2