Treatment of Hypertrophic Obstructive Cardiomyopathy (HOCM)
Beta-blockers are the first-line treatment for symptomatic HOCM, titrated to achieve a resting heart rate below 60-65 bpm to reduce left ventricular outflow tract obstruction through negative inotropic and chronotropic effects. 1
First-Line Pharmacologic Therapy: Beta-Blockers
Non-vasodilating beta-blockers (metoprolol, propranolol, or atenolol) should be initiated and pushed to maximum tolerated doses, targeting a resting heart rate <60-65 bpm. 2, 1
Beta-blockers work by slowing heart rate (prolonging diastolic filling time), reducing myocardial oxygen demand, and decreasing the dynamic outflow tract gradient through negative inotropic effects. 2, 1
Do not declare beta-blocker failure until adequate dosing achieves physiologic beta-blockade (demonstrated by resting heart rate suppression below 60-65 bpm). 1 This is a critical pitfall—many patients are undertreated.
Second-Line Therapy: Non-Dihydropyridine Calcium Channel Blockers
If beta-blockers are ineffective, not tolerated, or contraindicated, verapamil or diltiazem are reasonable alternatives. 2, 1
Verapamil should be started at low doses and titrated up to 480 mg/day, providing relief through negative inotropic and chronotropic effects similar to beta-blockers. 1
Use verapamil with extreme caution in patients with severe outflow tract obstruction, elevated pulmonary artery wedge pressure, or low systemic blood pressure—a decrease in blood pressure may trigger increased outflow obstruction and precipitate pulmonary edema. 2, 3 The FDA label warns that 3 of 120 HOCM patients died in pulmonary edema when treated with verapamil, all with severe LVOT obstruction and prior left ventricular dysfunction. 3
Never combine beta-blockers with verapamil or diltiazem due to risk of high-grade atrioventricular block. 2, 1, 4
Third-Line Therapy: Disopyramide
For patients with obstructive HCM who remain symptomatic despite beta-blockers and calcium channel blockers (alone or in combination), add disopyramide (400-600 mg/day) combined with beta-blocker or verapamil. 2, 1, 4
Never use disopyramide as monotherapy—it may enhance AV conduction in atrial fibrillation, leading to dangerously rapid ventricular rates. 1, 4
Medications to Eliminate Immediately
Discontinue all vasodilators immediately: dihydropyridine calcium channel blockers (nifedipine), ACE inhibitors, and ARBs—they worsen outflow tract obstruction by decreasing systemic vascular resistance. 2, 1, 5
Avoid high-dose diuretics that promote obstruction through volume depletion; low-dose diuretics may be cautiously added only if congestive symptoms persist despite first-line therapy. 2, 1
Digitalis is potentially harmful in HOCM patients without atrial fibrillation. 1, 4
Novel Pharmacotherapy: Mavacamten
Consider mavacamten (cardiac myosin inhibitor) in adults with symptomatic HOCM, which improves gradients and symptoms in 30-60% of patients. 1, 6
Monitor closely: 7-10% may develop reversible LVEF reduction <50% requiring temporary discontinuation. 1, 6
Invasive Therapies for Refractory Symptoms
Septal reduction therapy should be reserved for severely symptomatic patients despite optimal medical therapy, with LVOT gradients ≥50 mm Hg at rest or with provocation. 2, 4
Patient Selection Criteria
- Symptoms attributable to LVOT obstruction refractory to optimal pharmacologic therapy 2
- Maximal instantaneous gradients ≥50 mm Hg at rest or with physiologic provocation 2
- Obstruction caused by apposition of mitral valve with hypertrophied septum 2
Surgical Myectomy vs. Alcohol Septal Ablation
Surgical septal myectomy is the preferred treatment for most patients given its duration of experience, documented long-term results, and safety data in experienced centers. 2
Considerations favoring surgical intervention: younger age, greater septal thickness, concomitant cardiac disease requiring surgical correction. 2
Alcohol septal ablation is appropriate for older patients, those with significant comorbidities, or strong desire to avoid surgery. 2, 7
Both procedures must be performed only by experienced operators in comprehensive HCM clinical programs. 4, 7
Critical Pitfalls to Avoid
Never perform septal reduction therapy in asymptomatic patients regardless of gradient severity—there is no benefit and potential harm. 1, 4
Success is determined by symptom response, not measured gradient, as outflow tract obstruction varies remarkably throughout daily life. 1
Do not use combination beta-blocker plus calcium channel blocker for HOCM treatment due to AV block risk. 1, 4
Special Considerations
Atrial Fibrillation/Flutter Management
- Initiate anticoagulation immediately regardless of CHA₂DS₂-VASc score—all HOCM patients with atrial fibrillation require anticoagulation. 1, 4