What are the treatment options for Hypertrophic Cardiomyopathy (HCM)?

Treatment of Hypertrophic Cardiomyopathy (HCM)

Beta-blockers are the first-line treatment for all symptomatic patients with HCM, whether obstructive or nonobstructive, and should be titrated aggressively to achieve a resting heart rate below 60-65 bpm before considering treatment failure. 1, 2

First-Line Pharmacotherapy: Beta-Blockers

• Non-vasodilating beta-blockers (metoprolol, propranolol, or atenolol) should be initiated and pushed to maximum tolerated doses, targeting physiologic beta-blockade demonstrated by resting heart rate suppression below 60-65 bpm 1, 2, 3

• Beta-blockers work through negative inotropic and chronotropic effects, reducing left ventricular outflow tract (LVOT) obstruction, improving diastolic filling time, and decreasing myocardial oxygen demand 4, 3

• Do not declare beta-blocker failure until you have documented physiologic evidence of beta-blockade (suppressed resting heart rate), as inadequate dosing is a common pitfall 1, 3

• Use caution in patients with sinus bradycardia or severe conduction disease 1, 2

Second-Line Therapy: Calcium Channel Blockers

• If beta-blockers are ineffective, not tolerated, or contraindicated, switch to verapamil or diltiazem (not in addition to beta-blockers) 1, 2

• Verapamil should be started at low doses and titrated up to 480 mg/day, providing symptom relief through negative inotropic and chronotropic effects 1, 4, 3

• Verapamil must be used with extreme caution in patients with high gradients (>50 mmHg), advanced heart failure, or sinus bradycardia, as it can cause severe hypotension and pulmonary edema in these settings 1, 4, 5

• Never combine beta-blockers with verapamil or diltiazem for HCM treatment due to risk of high-grade atrioventricular block 1, 2, 4, 3

Recent evidence from the MAPLE-HCM trial suggests that newer cardiac myosin inhibitors (aficamten) may be superior to metoprolol monotherapy, but beta-blockers remain guideline-recommended first-line therapy pending broader adoption of these agents 6

Advanced Therapy for Refractory Symptoms

For patients failing first-line therapy, escalate to one of three options: mavacamten, disopyramide, or septal reduction therapy. 1

Cardiac Myosin Inhibitors (Adults Only)

• Mavacamten improves LVOT gradients, symptoms, and functional capacity in 30-60% of patients with obstructive HCM 1

• Be aware that 7-10% of patients may develop reversible LVEF reduction <50% requiring temporary discontinuation, necessitating a risk evaluation and mitigation strategy in the United States 1

Disopyramide

• Disopyramide (400-600 mg/day) should be combined with a beta-blocker or verapamil, never used as monotherapy, because it enhances atrioventricular conduction and can cause rapid ventricular response if atrial fibrillation develops 1, 2, 3

• This agent provides symptomatic benefit in patients with obstructive HCM who have failed first-line therapy 1

Septal Reduction Therapy

• Septal reduction therapy (surgical myectomy or alcohol septal ablation) should only be performed by experienced operators at comprehensive HCM centers for patients with severe drug-refractory symptoms and LVOT gradients ≥50 mmHg 1, 2, 4

• Never perform septal reduction therapy in asymptomatic patients regardless of gradient severity, as there is no benefit and potential harm 1, 3

• Surgical myectomy is very effective for relieving LVOTO when performed at experienced centers 1

Medications to Eliminate Immediately

Stop all vasodilators and minimize diuretics, as these worsen LVOT obstruction. 1, 2, 4, 3

• Discontinue dihydropyridine calcium channel blockers (nifedipine, amlodipine), ACE inhibitors, and ARBs, as these promote outflow tract obstruction through vasodilation 1, 2, 4, 3

• Avoid high-dose diuretics that decrease preload and augment LVOTO 1, 2

• Low-dose diuretics may be cautiously added only if congestive symptoms persist despite optimal first-line therapy 1, 2

• Digitalis is potentially harmful in HCM patients without atrial fibrillation 1, 4

Special Clinical Scenarios

Acute Hypotension in Obstructive HCM

• Administer intravenous phenylephrine (pure vasoconstrictor) for acute hypotension that does not respond to fluid administration 1, 2

• Maximize preload and afterload while avoiding increases in contractility or heart rate 1

• Beta-blockade can be useful in combination with vasoconstrictors as it dampens contractility and improves preload by prolonging diastolic filling 1

Atrial Fibrillation Management

• Initiate anticoagulation immediately in all HCM patients with atrial fibrillation (paroxysmal, persistent, or chronic), regardless of CHA₂DS₂-VASc score 1, 3

• Direct-acting oral anticoagulants are first-line, with vitamin K antagonists as second-line 1

• For rate control, use beta-blockers, verapamil, or diltiazem based on patient comorbidities 1

Advanced Heart Failure

• In patients with HCM who develop systolic dysfunction with LVEF <50%, transition to guideline-directed therapy for heart failure with reduced ejection fraction 4

• Consider heart transplantation assessment for patients with recurrent life-threatening ventricular arrhythmias refractory to maximal therapy 1

Ventricular Arrhythmias

• For recurrent ventricular arrhythmias despite beta-blocker use, add amiodarone (most effective but with increased adverse effects), dofetilide, mexiletine, or sotalol 1

• Program antitachycardia pacing in patients with pacing-capable ICDs to minimize shocks 1

• Consider catheter ablation for recurrent symptomatic sustained monomorphic VT or recurrent ICD shocks despite optimal medical therapy 1

Lifestyle Modifications

• Low-intensity aerobic exercise is reasonable as part of a healthy lifestyle 1, 2

• Patients should avoid intense competitive sports regardless of symptoms or obstruction 1

• Treat comorbidities (hypertension, diabetes, hyperlipidemia, obesity) according to relevant guidelines 1

Critical Pitfalls to Avoid

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

• Do not use combination beta-blocker plus calcium channel blocker for HCM treatment (though this may have a role in managing concomitant hypertension) 1, 2

• Avoid aggressive diuresis, as decreasing preload can worsen LVOTO 1

• Exercise caution when introducing therapies for coexisting conditions, as some medications (diuretics, vasodilators) can worsen LVOTO symptoms 1