Efficacy and Safety of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

Abstract Obstructive hypertrophic cardiomyopathy (oHCM) is driven by hypercontractility and systolic anterior motion (SAM) of the mitral valve, causing dynamic left ventricular outflow tract obstruction (LVOTO) and symptoms (dyspnea, angina, reduced exercise tolerance). Traditional therapies (β–blockers, non–dihydropyridine calcium–channel blockers ± disopyramide) mainly relieve symptoms; septal reduction therapy (SRT) is considered in refractory cases. Myosin modulators offer a disease–specific approach: mavacamten reduces sarcomeric force and LVOT gradients, requiring serial echocardiographic monitoring of left ventricular ejection fraction (LVEF) per label. Case A 58–year–old hypertensive man, no family history, presented with exertional dyspnea, palpitations, and atypical angina (NYHA II–III). Examination revealed a mid–systolic ejection murmur that increased with Valsalva; BP 120/70 mmHg, HR 72 bpm. Assessment/strategy: Despite optimized β–blocker therapy and lifestyle measures, symptoms and obstruction persisted. Baseline: SAM with moderate mitral regurgitation (MR); LVOT gradient 66 mmHg at rest and 180 mmHg with Valsalva; LVEF 65%; hypertrophy (septum 22 mm, posterior wall 13 mm) with increased LV mass index (LVMi 140 g/m²). ECG showed high voltages (Sokolow–Lyon 48 mm; Cornell 33 mm). Mavacamten was initiated on a compassionate–use basis at 5 mg/day with serial LVEF and gradient monitoring; due to insufficient response, the dose was titrated to 10 mg/day while maintaining LVEF ≥60%. 6–month follow–up: Functional status improved to NYHA I, palpitations resolved, and normal activities were resumed; the murmur became minimal and no longer increased with Valsalva. Echocardiography showed LVOT gradients of 10 mmHg at rest and 30 mmHg with Valsalva, with SAM resolution and MR improving to mild/trivial. Favorable remodeling was observed (septum 17 mm; posterior wall 11 mm; LVMi 110 g/m²) with preserved LVEF (60–65%). ECG voltages decreased (Sokolow–Lyon 36 mm; Cornell 28 mm). Conclusion In symptomatic oHCM despite optimized therapy, mavacamten provided substantial clinical and echocardiographic benefit at 6 months—marked gradient reduction, SAM resolution, and functional improvement—while maintaining safe LVEF through echo–guided titration, consistent with EXPLORER–HCM and VALOR–HCM.