What is the treatment approach for Hypertrophic Obstructive Cardiomyopathy (HoCM)?

Treatment of Hypertrophic Obstructive Cardiomyopathy (HoCM)

Start with beta-blockers as first-line therapy, titrated to achieve a resting heart rate below 60-65 bpm, as they are the mainstay of treatment for symptomatic HoCM through negative inotropic and chronotropic effects that reduce left ventricular outflow tract obstruction. 1, 2

First-Line Pharmacologic Therapy: Beta-Blockers

• Initiate non-vasodilating beta-blockers (metoprolol, propranolol, or atenolol) and push doses to maximum tolerated levels until you achieve physiologic beta-blockade, demonstrated by resting heart rate suppression below 60-65 bpm. 1, 3

• Beta-blockers work through multiple mechanisms: slowing heart rate to prolong diastolic filling time, reducing myocardial oxygen demand, attenuating adrenergic-induced tachycardia, and decreasing the dynamic outflow tract gradient. 4, 1

• Critical pitfall: Do not declare beta-blocker failure until adequate dosing achieves resting heart rate suppression—this is the physiologic evidence that you've reached therapeutic beta-blockade. 1

• Use caution in patients with sinus bradycardia or severe conduction disease. 3

Second-Line Therapy: Calcium Channel Blockers

• If beta-blockers are ineffective, not tolerated, or contraindicated, switch to verapamil starting at low doses and titrating up to 480 mg/day. 1, 2

• Verapamil provides symptomatic relief through negative inotropic and rate-lowering effects similar to beta-blockers. 4

• Major warning: Use verapamil with extreme caution in patients with high gradients (≥50 mmHg), advanced heart failure symptoms, elevated pulmonary artery wedge pressure, or systemic hypotension, as it can trigger increased outflow obstruction and precipitate pulmonary edema. 4, 5

• Never combine beta-blockers with verapamil or diltiazem due to risk of high-grade atrioventricular block. 4, 1, 5

• Diltiazem is an alternative non-dihydropyridine calcium channel blocker that has shown benefit in improving diastolic performance. 4

Medications to Eliminate Immediately

• Discontinue all vasodilators including dihydropyridine calcium channel blockers (nifedipine), ACE inhibitors, and ARBs, as they worsen outflow tract obstruction through peripheral vasodilation. 4, 1, 2

• Avoid high-dose diuretics that promote obstruction through volume depletion. 1

• Digitalis is potentially harmful in HoCM patients without atrial fibrillation. 1, 3

Third-Line Therapy: Disopyramide

• For patients with persistent symptoms despite optimal beta-blocker or verapamil therapy, add disopyramide 400-600 mg/day combined with the beta-blocker or verapamil—never as monotherapy. 1, 2

• Disopyramide should never be used alone in patients with atrial fibrillation, as it may enhance atrioventricular conduction and increase ventricular rate. 1, 2

• Monitor QTc interval during dose titration and reduce dose if it exceeds 480 ms. 2

• Avoid disopyramide in patients with glaucoma, prostatism, or those taking other QT-prolonging medications (amiodarone, sotalol). 2

Adjunctive Medical Therapy

• Use low-dose diuretics cautiously only if congestive symptoms persist despite first-line therapy—avoid aggressive diuresis that can worsen obstruction. 4, 1

Novel Pharmacologic Option: Mavacamten

• Consider mavacamten (cardiac myosin inhibitor) in adults with symptomatic HoCM, which improves gradients and symptoms in 30-60% of patients. 1

• Monitor closely as 7-10% may develop reversible LVEF reduction <50% requiring temporary discontinuation. 1, 6

Invasive Septal Reduction Therapy

Indications for septal reduction therapy require ALL of the following criteria: 4, 2

• Severe symptoms (NYHA class III-IV) refractory to optimal pharmacologic therapy
• LVOT obstruction with maximal instantaneous gradients ≥50 mmHg at rest or with physiologic provocation
• Obstruction caused by apposition of the mitral valve with the hypertrophied septum
• Performed only at experienced comprehensive HCM centers

Surgical Septal Myectomy vs. Alcohol Septal Ablation

• Surgical septal myectomy is the preferred treatment for most patients meeting invasive therapy criteria, with >90% relief of obstruction, <1% perioperative mortality at experienced centers, and excellent long-term outcomes. 4, 7, 8

• Considerations favoring surgical myectomy: younger age, greater septal thickness (extreme hypertrophy), concomitant cardiac disease requiring surgery. 4, 7

• Alcohol septal ablation is appropriate for older patients, those with significant comorbidities, or strong desire to avoid surgery—results are comparable to myectomy in many patients but depend on septal perforator anatomy. 4, 7

• Critical contraindication: Never perform septal reduction therapy in asymptomatic patients regardless of gradient severity—there is no benefit and potential harm. 1, 2

Special Considerations

Atrial Fibrillation Management

• Initiate anticoagulation immediately in all HoCM patients with atrial fibrillation or flutter, regardless of CHA₂DS₂-VASc score—all require anticoagulation. 1, 3

Acute Hypotension Management

• For acute hypotension not responding to fluid administration, use intravenous phenylephrine (alpha-adrenergic agent) to maintain blood pressure. 3, 5

• In HoCM patients, alpha-adrenergic agents (phenylephrine, metaraminol, methoxamine) should be used rather than isoproterenol or norepinephrine. 5

Activity Recommendations

• Low-intensity aerobic exercise is reasonable as part of a healthy lifestyle for HoCM patients. 2, 3

• Avoid volume depletion and activities that provoke obstruction. 9

Treatment Algorithm Summary

1. Start beta-blocker → titrate to HR <60-65 bpm
2. If inadequate response or intolerance → switch to verapamil (up to 480 mg/day)
3. If still symptomatic → add disopyramide (400-600 mg/day) to beta-blocker or verapamil
4. Consider mavacamten as alternative pharmacologic option
5. If severe refractory symptoms with gradient ≥50 mmHg → septal reduction therapy at experienced center

Success is determined by symptom response, not measured gradient, as outflow tract obstruction varies remarkably throughout daily life. 1