What's the best route to treat hypertrophic cardiomyopathy?

Treatment of Hypertrophic Cardiomyopathy

Beta-blocking drugs are the first-line treatment for symptomatic patients with hypertrophic cardiomyopathy (HCM), whether obstructive or non-obstructive, due to their negative inotropic effects and ability to control symptoms such as angina and dyspnea. 1

First-Line Therapy

• Beta blockers should be initiated for symptomatic patients with HCM (both obstructive and non-obstructive forms) to reduce symptoms of angina and dyspnea 1
• If low doses are ineffective, titrate beta blockers to achieve a resting heart rate of less than 60-65 bpm (up to maximum recommended doses) 1
• Beta blockers work by reducing heart rate, prolonging diastolic filling period, and attenuating adrenergic-induced tachycardia 1
• Use beta blockers with caution in patients with sinus bradycardia or severe conduction disease 1

Second-Line Therapy

• Verapamil (starting at low doses and titrating up to 480 mg/day) is recommended for patients who don't respond to beta blockers or have contraindications/side effects to beta blockers 1
• Verapamil should be used with caution in patients with high gradients, advanced heart failure, or sinus bradycardia 1
• Recent data suggests verapamil therapy is not associated with higher adverse events compared to beta blockers in low-risk HCM patients 2
• FDA labeling warns about potential risks of verapamil in HCM patients with severe left ventricular outflow obstruction, including pulmonary edema and hypotension 3

Combination Therapy for Refractory Symptoms

• For obstructive HCM patients with persistent symptoms despite beta blockers or verapamil alone, combining disopyramide with either agent is reasonable 1
• For non-obstructive HCM patients with persistent dyspnea despite beta blockers or verapamil, adding oral diuretics is reasonable 1

Invasive Therapies for Obstructive HCM

• For patients with severe refractory symptoms attributable to LVOT obstruction (gradient ≥50 mmHg) despite optimal medical therapy, invasive therapies should be considered 1
• Surgical septal myectomy is the preferred treatment for most eligible patients with obstructive HCM and refractory symptoms 1
• Factors favoring surgical myectomy include younger age, greater septal thickness, and concomitant cardiac disease requiring surgical correction 1
• Alcohol septal ablation is an alternative for patients who are not optimal surgical candidates due to comorbidities, advanced age, or strong preference to avoid open-heart surgery 1

Management of Associated Conditions

• Atrial fibrillation is common in HCM and requires anticoagulation with direct-acting oral anticoagulants (first-line) or vitamin K antagonists (second-line), regardless of CHA₂DS₂-VASc score 1
• For rate control in HCM patients with atrial fibrillation, beta blockers, verapamil, or diltiazem are recommended 1
• Comorbidities that contribute to cardiovascular disease (hypertension, diabetes, hyperlipidemia, obesity) should be treated according to relevant guidelines 1

Emerging Therapies

• Cardiac myosin inhibitors (e.g., aficamten) have shown promise as a new class of medications developed specifically for HCM 4, 5
• Recent research demonstrates that aficamten monotherapy is superior to metoprolol monotherapy in improving peak oxygen uptake, hemodynamics, and symptoms in obstructive HCM 4

Important Considerations and Pitfalls

• Avoid dihydropyridine calcium channel blockers (e.g., nifedipine) in patients with obstructive HCM as their vasodilatory effects may worsen outflow obstruction 1
• Use verapamil with extreme caution in patients with severe outflow obstruction due to risk of pulmonary edema and hypotension 3
• Avoid using beta blockers with verapamil or diltiazem without careful monitoring due to potential for high-grade atrioventricular block 1
• Septal reduction therapy should not be performed for asymptomatic patients with HCM 1

The treatment approach should follow a stepwise algorithm: starting with beta blockers, moving to verapamil if beta blockers fail or are contraindicated, adding disopyramide or diuretics for persistent symptoms, and considering invasive therapies only when medical management fails to control symptoms.