From evidence to practice: Mavacamten in obstructive Hypertrophic Cardiomyopathy - data from the multicenter TORCH-Plus-DZHK21 registry

Background Mavacamten, a first-in-class cardiac myosin inhibitor, has been shown to reduce left ventricular outflow tract (LVOT) gradients and improve symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). While randomized trials established its efficacy and safety in selected cohorts, real-world multicenter data across specialized cardiomyopathy networks remain limited. Methods TORCH-Plus-DZHK21 (TranslatiOnal Registry for CardiomyopatHies-Plus) is a prospective, observational registry conducted at tertiary cardiomyopathy centers across Germany. Adult patients with symptomatic oHCM who initiated Mavacamten between 2023 and 2026 were included from 15 expert centers. Clinical assessments, echocardiography (at rest and provoked LVOT gradients), NT-proBNP, and safety parameters were systematically collected at baseline and predefined follow-up intervals (3, 6, and 12 months). Adverse events and treatment modifications were documented. Results 240 patients with symptomatic oHCM (NYHA II–III, median (IQR) baseline resting LVOT gradient: 33 (16; 58.8) mmHg, baseline valsalva LVOT gradient: 84 (52; 115) mmHg) were enrolled. At baseline, the mean age was 60.3 ± 11.2 years, with 54.4% of patients being male. Mavacamten led to a significant reduction in median resting (Δ -20 (-40; -7) mmHg; p < 0.001) and valsalva LVOT gradients at 12 months (Δ -60 (-96.5; -34.5) mmHg; p < 0.001), accompanied by a decrease in median NT-proBNP levels at 12 months (Δ -353 (-1049; -128) pg/mL; p < 0.001). By month 12, 64% of patients had improved by ≥1 NYHA class, with 45% achieving NYHA I. Mavacamten was well tolerated; dose titration was guided by echocardiographic and biomarker monitoring. Echocardiography at follow-up demonstrated no clinically relevant overall decline in left ventricular ejection fraction (LVEF). 3 patients developed LVEF reduction to <50% after 12 months of therapy, prompting temporary treatment interruption and subsequent re-initiation at a lower dose. 1 patient underwent invasive septal reduction therapy, resulting in permanent discontinuation of Mavacamten. Conclusions In this large, prospective, real-world cohort from 15 expert centers, Mavacamten demonstrated robust and sustained reduction in LVOT gradients, functional improvement, and NT-proBNP reductions in symptomatic oHCM. The favorable safety profile and echocardiographic response underscore its value as a disease-specific pharmacological strategy in specialized care settings.