Management of Hypertrophic Cardiomyopathy with Cardiac Myosin Inhibitors

Introduction to Cardiac Myosin Inhibitors

• The American College of Cardiology recommends mavacamten, a cardiac myosin inhibitor, for adults with symptomatic NYHA class II-III obstructive HCM to improve functional capacity and symptoms, with a Class 1 recommendation for adding a myosin inhibitor for persistent symptoms despite first-line therapy 1, 2, 3

Clinical Positioning in Treatment Algorithm

• The American Heart Association, American College of Cardiology, and other societies recommend using mavacamten when first-line therapy fails, with beta-blockers or nondihydropyridine calcium channel blockers providing inadequate symptom relief, and in adult patients only, as it is not approved for pediatric use 4, 6, 7
• The treatment hierarchy is now: beta-blockers or calcium channel blockers → mavacamten, disopyramide, or septal reduction therapy, with a Class 1 recommendation for adding a myosin inhibitor for persistent symptoms despite first-line therapy 4, 6

Efficacy Data

• Mavacamten improves LVOT gradients, symptoms, and functional capacity in 30-60% of patients with obstructive HCM, with significant reduction in both resting and post-exercise LVOT gradients, improvement in peak oxygen consumption, reduction in NYHA functional class, and enhanced quality of life scores 4, 5

Critical Safety Considerations

• Mandatory monitoring is required due to Risk Evaluation and Mitigation Strategy (REMS) program, with LVEF reduction <50% occurring in 5.7% of patients attributable to the drug alone, but up to 7-10% when considering other clinical conditions, and must discontinue if persistent systolic dysfunction (LVEF <50%) develops 4, 5, 9, 10
• Mavacamten is contraindicated in pregnancy due to teratogenic effects, and regular echocardiographic monitoring is essential 9, 10, 8, 7