What medications are recommended for patients with hypertrophic cardiomyopathy (HCM) and a normal ejection fraction?

Medication Management for Hypertrophic Cardiomyopathy with Normal Ejection Fraction

Beta-blockers are the first-line medication therapy for patients with hypertrophic cardiomyopathy (HCM) with normal ejection fraction, followed by non-dihydropyridine calcium channel blockers if beta-blockers are ineffective or not tolerated. 1

First-Line Therapy

Beta-Blockers

• Indications: First-line therapy for symptomatic patients with both obstructive and non-obstructive HCM 1
• Mechanism: Improve diastolic function by lengthening diastole, reducing outflow obstruction, and inducing beneficial remodeling 2
• Dosing:
  • Titrate to effectiveness or maximally tolerated doses 1
  • Target resting heart rate of <60-65 bpm 1
  • Non-vasodilating beta-blockers (e.g., propranolol) are preferred 3
  • Higher doses may be required in pediatric patients (up to 4.5-8 mg/kg/day of propranolol) 2
• Caution: Use with care in patients with sinus bradycardia or severe conduction disease 1

Second-Line Therapy

Non-Dihydropyridine Calcium Channel Blockers

• Indications: For patients who do not respond to beta-blockers or who have side effects/contraindications to beta-blockers 1
• Options:
  • Verapamil: Start at 40 mg TID, titrate up to 480 mg/day 1, 3
  • Diltiazem: Start at 60 mg TID, titrate up to 360 mg/day 3
• Contraindications:
  • Verapamil is potentially harmful in patients with obstructive HCM with systemic hypotension, severe dyspnea at rest, very high resting gradients (>100 mm Hg), or in children <6 weeks of age 1
  • Use with caution in patients with high gradients, advanced heart failure, or sinus bradycardia 1

Additional Therapies for Persistent Symptoms

Disopyramide

• Indication: For patients with obstructive HCM who have persistent severe symptoms despite beta-blockers or calcium channel blockers 1
• Dosing: Combine with beta-blockers or verapamil; titrate to maximum tolerated dose (usually 400-600 mg/day) 1, 3
• Monitoring: Requires QTc interval monitoring 3

Diuretics

• Indication: For patients with non-obstructive HCM when dyspnea persists despite beta-blockers or calcium channel blockers 1
• Caution: Use cautiously and in low doses to avoid excessive diuresis, which can worsen symptoms in obstructive HCM 1, 3

Medications to Avoid or Use with Caution

1. Dihydropyridine calcium channel blockers (e.g., nifedipine): Potentially harmful in patients with resting or provocable LVOT obstruction 1
2. Digitalis: Potentially harmful in the absence of atrial fibrillation 1
3. Vasodilators (ACE inhibitors, ARBs): Not well established for HCM with preserved EF and potentially harmful in obstructive HCM 1

Special Considerations

Atrial Fibrillation Management

• Beta-blockers, verapamil, or diltiazem are recommended for rate control 1
• Anticoagulation with direct-acting oral anticoagulants (first-line) or vitamin K antagonists (second-line) is recommended regardless of CHA₂DS₂-VASc score 1

Ventricular Arrhythmias

• Beta-blockers are first-line therapy 1
• For symptomatic ventricular arrhythmias or recurrent ICD shocks despite beta-blocker use, consider antiarrhythmic drugs 1

Monitoring and Follow-up

• Regular assessment of symptom status
• Monitor for bradycardia when using calcium channel blockers and beta-blockers in combination 3
• Periodic echocardiography to evaluate LVOT obstruction and ventricular function
• Avoid excessive diuresis to prevent symptomatic hypotension and hypovolemia 3

Comparative Effectiveness

Recent evidence suggests that in low-risk HCM patients with normal ejection fraction, verapamil therapy is not associated with a higher incidence of adverse events compared to beta-blocker therapy, challenging the traditional hierarchy of these medications 4. However, current guidelines still recommend beta-blockers as first-line therapy.