Predictors of Higher Mavacamten Maintenance Dose in Obstructive Hypertrophic Cardiomyopathy

Mavacamten has emerged as an effective therapy for obstructive hypertrophic cardiomyopathy (oHCM); however, interindividual variability in maintenance dosing remains a practical challenge in clinical practice. We conducted a multicenter retrospective study of adults with oHCM treated with mavacamten across 3 tertiary sites to identify baseline predictors of higher maintenance dose requirements. Patients with at least 1-year follow-up and stable dosing for 6 months or more were included and categorized into low-dose (2.5-5 mg) and high-dose (10-15 mg) maintenance groups. Among 77 patients (mean age, 60 years; 50.6% men), 28 required high-dose maintenance therapy. Baseline medial ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e') was significantly higher in the high-dose group than that in the low-dose group (20.0 vs 16.1; P=.018). On multivariable logistic regression adjusting for left ventricular outflow tract gradient, left ventricular ejection fraction, and global longitudinal strain, medial E/e' remained independently associated with higher maintenance dose requirement (odds ratio, 1.20; 95% CI, 1.10-1.30; P=.04), whereas other echocardiographic, biomarker, and electrocardiographic parameters were not predictive. These findings suggest that baseline diastolic dysfunction, as reflected by medial E/e', plays a central role in mavacamten dose trajectory and may help inform individualized titration strategies in patients with oHCM.