Mavacamten in Symptomatic Patients Resistant to Previous Advanced Therapy for Obstructive Hypertrophic Cardiomyopathy

The clinical benefits of mavacamten in patients with obstructive hypertrophic cardiomyopathy previously treated with advanced therapies are not established. Clinical and echocardiographic outcomes of patients treated with mavacamten for left ventricular outflow obstruction for at least 8 weeks were assessed based on prior treatment with one or more advanced therapies: disopyramide, septal myectomy, alcohol septal ablation, dual-chamber ventricular pacing with short atrioventricular delay; we also evaluated patients with left ventricular outflow obstruction that emerged as major driver of symptoms after aortic valve replacement. We included 115 consecutive patients (mean age 66±12 years, 57% women, wall thickness 17±4 mm) on mavacamten for a median 45 (interquartile range, 22-61) weeks, of whom 53 (46%) patients were previously on disopyramide (n=45); underwent septal myectomy (n=8), alcohol septal ablation (n=6), or forced ventricular pacing (n=11); and 5 had previous aortic valve replacement. New York Heart Association class improved from 2.6±0.5 to 1.8±0.6 (P<0.0001) in those with and without prior advanced therapy. Left ventricular systolic dysfunction (ejection fraction <50%) occurred in 12 (10%) patients, 8 (15%) in the advanced treatment group and 4 (7%) in those without (P=0.13). Maximal provoked peak left ventricular outflow gradients decreased from 103 (77-130) mm Hg to 11 (8-21) mm Hg in patients with prior advanced therapy and from 101 (81-130) mm Hg to 13 (8-25) mm Hg in those without (P=0.31). Mavacamten is a safe and effective treatment for symptomatic left ventricular outflow obstruction in patients with obstructive hypertrophic cardiomyopathy resistant to previous advanced pharmacologic therapy, surgery, or alcohol septal ablation or who develop manifest left ventricular outflow obstruction after aortic valve replacement.