Managing a mavacamten non-responder in obstructive hypertrophic cardiomyopathy: A case report

We report the case of a woman in her 40s with obstructive hypertrophic cardiomyopathy who remained symptomatic despite optimal medical therapy. A prior attempt of alcohol septal ablation was not performed due to unsuitable septal branch anatomy. Echocardiography demonstrated severe left ventricular outflow tract (LVOT) obstruction, systolic anterior motion (SAM) of the mitral valve (MV), and moderate-to-severe mitral regurgitation. Biomarkers indicated significant hemodynamic stress, and magnetic resonance imaging revealed myocardial fibrosis. Treatment with the cardiac myosin inhibitor mavacamten was initiated and despite stepwise escalation to 15 mg/day, LVOT gradients and symptoms persisted, classifying her as a treatment non-responder. Genetic testing detected a MYH7 variant of uncertain significance, potentially associated with reduced drug effectiveness. Given refractory obstruction, the multidisciplinary heart team recommended surgical septal myectomy. Intraoperative inspection of the mitral valve revealed not only SAM-related mitral regurgitation, but degenerative MV pathology requiring MV replacement. Postoperatively, LVOT obstruction resolved, and the patient became asymptomatic. Learning objective This case underscores the clinical importance of recognition of non-response to mavacamten therapy. It highlights the need for careful evaluation of concomitant mitral valve pathology, which may significantly contribute to persistent symptoms beside left ventricular outflow tract obstruction. In selected patients, timely consideration of surgical intervention remains essential to achieve optimal hemodynamic improvement and symptomatic relief when pharmacological treatment alone is insufficient.