What are the treatments for hypertrophic cardiomyopathy?

Treatment of Hypertrophic Cardiomyopathy

Beta-blockers are the first-line treatment for all symptomatic HCM patients, titrated to achieve a resting heart rate below 60-65 bpm, as they reduce left ventricular outflow tract obstruction through negative inotropic and chronotropic effects. 1, 2

Initial Pharmacologic Management

First-Line: Beta-Blockers

• Non-vasodilating beta-blockers (metoprolol, propranolol, or atenolol) should be initiated and pushed to maximum tolerated doses until physiologic beta-blockade is achieved, demonstrated by resting heart rate suppression below 60-65 bpm. 1, 3
• Beta-blockers work by slowing heart rate, improving diastolic filling time, reducing myocardial oxygen demand, and decreasing the dynamic outflow tract gradient. 1, 3
• Do not declare beta-blocker failure until adequate dosing achieves resting heart rate suppression—this is the physiologic evidence of beta-blockade. 1
• Use with caution in patients with sinus bradycardia or severe conduction disease. 2, 3

Second-Line: Non-Dihydropyridine Calcium Channel Blockers

• If beta-blockers are ineffective, not tolerated, or contraindicated, verapamil or diltiazem are reasonable alternatives. 4, 2, 3
• Verapamil should be started at low doses and titrated up to 480 mg/day, providing relief through negative inotropic and chronotropic effects. 1, 3
• Verapamil must be used with extreme caution in patients with high gradients (>50 mmHg at rest), advanced heart failure symptoms, or systemic hypotension, as it can precipitate pulmonary edema. 4, 5
• Never combine beta-blockers with verapamil or diltiazem due to risk of high-grade atrioventricular block. 1, 2, 3

Medications to Eliminate Immediately

Discontinue all vasodilators immediately, as they worsen outflow tract obstruction and symptoms:

• Dihydropyridine calcium channel blockers (nifedipine, amlodipine) are potentially harmful in patients with resting or provocable LVOT obstruction. 4, 2
• ACE inhibitors and ARBs are potentially harmful in patients with resting or provocable LVOT obstruction. 4
• Digitalis is potentially harmful in HCM patients without atrial fibrillation. 4, 2
• Avoid high-dose diuretics that promote obstruction through volume depletion. 1

Management of Refractory Symptoms

Third-Line: Add Disopyramide

• If symptoms persist despite optimal beta-blocker or verapamil therapy, add disopyramide (400-600 mg/day) combined with beta-blocker or verapamil—never as monotherapy. 1, 2, 6
• Disopyramide alone is potentially harmful in patients with atrial fibrillation because it may enhance atrioventricular conduction and increase ventricular rate. 4, 2
• In a prospective registry of 299 patients requiring advanced therapy, disopyramide added to beta-blockers or verapamil achieved pharmacological control of symptoms in 64% of patients. 6

Cautious Use of Diuretics

• Low-dose loop or thiazide diuretics may be cautiously added only if congestive symptoms persist despite first-line therapy, but must be used judiciously to avoid volume depletion that worsens obstruction. 4, 1, 3

Invasive Septal Reduction Therapy

Septal reduction therapy should be performed only by experienced operators at comprehensive HCM centers for patients with severe drug-refractory symptoms and LVOT obstruction. 4, 2

Patient Selection Criteria (All Must Be Met):

• Clinical: Severe dyspnea or chest pain (NYHA class III or IV) that interferes with everyday activity despite optimal medical therapy. 4
• Hemodynamic: Dynamic LVOT gradient ≥50 mmHg at rest or with physiologic provocation, associated with septal hypertrophy and systolic anterior motion of the mitral valve. 4
• Anatomic: Targeted anterior septal thickness sufficient to perform the procedure safely. 4

Surgical Myectomy vs. Alcohol Septal Ablation

• Surgical septal myectomy is the first consideration for the majority of eligible patients, particularly younger patients (<40 years), those with greater septal thickness, and those with concomitant cardiac disease requiring surgical correction. 4
• Alcohol septal ablation is beneficial when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age. 4
• Alcohol septal ablation should not be performed in patients <21 years of age and is discouraged in adults <40 years if myectomy is viable. 4
• In the prospective registry, 46% of advanced-care patients underwent surgical myectomy with 10-year survival of 88%, not different from nonobstructed patients. 6

Critical Pitfalls to Avoid

• Septal reduction therapy should not be performed in asymptomatic patients or those whose symptoms are medically controlled, regardless of gradient severity. 4, 2
• Permanent pacemaker implantation should not be performed as first-line therapy to relieve symptoms in medically refractory patients who are candidates for septal reduction. 4

Management of Systolic Dysfunction (End-Stage HCM)

Patients with nonobstructive HCM who develop systolic dysfunction with ejection fraction ≤50% should be treated according to evidence-based medical therapy for heart failure with reduced EF, including ACE inhibitors, ARBs, beta-blockers, and other indicated drugs. 4, 3

• Consider other concomitant causes of systolic dysfunction (such as CAD) as potential contributors. 4
• Reassess and consider discontinuing negative inotropic agents previously indicated (verapamil, diltiazem, disopyramide) in patients who develop systolic dysfunction. 4
• Patients with advanced heart failure (end-stage) and nonobstructive HCM with EF <50% not amenable to other interventions should be considered for heart transplantation. 4

Special Considerations for Atrial Fibrillation

Initiate anticoagulation immediately in all HCM patients with atrial fibrillation or flutter, regardless of CHA₂DS₂-VASc score. 1, 2

Acute Management of Hypotension in Obstructive HCM

• Administer cautious IV fluid boluses of 250-500 mL normal saline over 30-60 minutes if hypotension develops, avoiding aggressive fluid resuscitation. 2
• Use intravenous phenylephrine (alpha-adrenergic agent) for acute hypotension that doesn't respond to fluid administration. 2, 5
• Dopamine, dobutamine, norepinephrine, and other intravenous positive inotropic drugs are potentially harmful for acute hypotension in obstructive HCM. 4

Key Clinical Pitfalls

• Success is determined by symptom response, not measured gradient, as outflow tract obstruction varies remarkably throughout daily life. 1
• Never use combination beta-blocker plus calcium channel blocker for HCM treatment due to AV block risk. 1, 2
• Experienced operators are defined as an individual with ≥20 procedures or working in a dedicated HCM program with ≥50 procedures. 4