Mavacamten Mechanism and Monitoring — EECC MCQ

Correct answer: E — Mavacamten is a first-in-class cardiac myosin inhibitor that reduces excessive actin-myosin cross-bridge formation in HCM — it reduces LVOT gradient, MR severity, and symptoms; LVEF must be monitored (risk of excessive myocardial suppression if LVEF drops <50%)

Mavacamten (Camzyos) is a selective allosteric inhibitor of cardiac beta-myosin ATPase — it reduces the number of actin-myosin cross-bridges formed during contraction, directly targeting the hypercontractile state that causes LVOT obstruction in HCM. The EXPLORER-HCM trial: mavacamten reduced LVOT gradient by ~50 mmHg, improved NYHA class, exercise capacity, and biomarkers vs placebo. The VALOR-HCM trial: mavacamten reduced the need for septal reduction therapy. The 2023 ESC Cardiomyopathy Guidelines include mavacamten for symptomatic obstructive HCM refractory to beta-blocker/CCB (Class IIa). Critical monitoring: LVEF must be assessed regularly (every 12 weeks) — if LVEF drops <50%, dose reduction or interruption is required (excessive cross-bridge reduction can cause systolic impairment). Drug interactions: CYP2C19 and CYP3A4 metabolism; strong inhibitors increase mavacamten levels.

Reference: ESC (2023): Cardiomyopathies; EXPLORER-HCM/VALOR-HCM