Mavacamten Treatment in Obstructive Hypertrophic Cardiomyopathy: Results from the Multi-centric TranslatiOnal Registry for CardiomyopatHies-Plus (TORCH-Plus-DZHK21)

J. Kölemen (Heidelberg)¹, F. Sedaghat-Hamedani (Heidelberg)¹, C. Reich (Heidelberg)¹, J. Trebing (Heidelberg)², E. Kayvanpour (Heidelberg)¹, K. Becht (Heidelberg)³, A. Amr (Heidelberg)¹, A. Rieth (Bad Nauheim)⁴, U. Rauch-Kröhnert (Berlin)⁵, F. Edelmann (Berlin)⁶, S. Cremer (Frankfurt am Main)⁷, K. Lehnert (Greifswald)⁸, M. Schroeter (Wolfsburg)⁹, M. Lutz (Kiel)¹⁰, I. Eitel (Lübeck)¹¹, P. S. Wild (Mainz)¹², I. Akin (Mannheim)¹³, H. Schunkert (München)¹⁴, S. Kääb (München)¹⁵, K.-L. Laugwitz (München)¹⁶, W. Hoffmann (Greifswald)¹⁷, N. Frey (Heidelberg)¹, B. Meder (Heidelberg)^1
1Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland; ²University Hospital Heidelberg Institute for Cardiomyopathies Heidelberg Heidelberg, Deutschland; ³Universitätsklinikum Heidelberg Innere Medizin III: Klinik für Kardiologie, Angiologie und Pneumologie Heidelberg, Deutschland; ⁴Kerckhoff Klinik GmbH Abteilung für Kardiologie Bad Nauheim, Deutschland; ⁵Deutsches Herzzentrum der Charite (DHZC) Klinik für Kardiologie, Angiologie und Intensivmedizin Berlin, Deutschland; ⁶Charité - Universitätsmedizin Berlin Leiter des Clinical Study Center CVK Berlin, Deutschland; ⁷Universitätsklinikum Frankfurt Med. Klinik III - Kardiologie, Angiologie Frankfurt am Main, Deutschland; ⁸Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B Greifswald, Deutschland; ⁹Klinikum Wolfsburg Medizinische Klinik I Wolfsburg, Deutschland; ¹⁰Universitätsklinikum Schleswig-Holstein Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin Kiel, Deutschland; ¹¹Universitätsklinikum Schleswig-Holstein Medizinische Klinik II / Kardiologie, Angiologie, Intensivmedizin Lübeck, Deutschland; ¹²Universitätsmedizin der Johannes Gutenberg-Universität Mainz Präventive Kardiologie und Medizinische Prävention Mainz, Deutschland; ¹³Universitätsklinikum Mannheim GmbH I. Medizinische Klinik Mannheim, Deutschland; ¹⁴Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; ¹⁵LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; ¹⁶Klinikum rechts der Isar der Technischen Universität München Klinik und Poliklinik für Innere Medizin I München, Deutschland; ¹⁷Universität Greifswald Institut für Community Medicine Greifswald, Deutschland

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 (TranslatiOnal Registry for CardiomyopatHies-Plus) is a prospective, observational registry conducted at tertiary cardiomyopathy centers across Germany within the DZHK network (German Centre for Cardiovascular Research). Adult patients with symptomatic oHCM who initiated Mavacamten between 2023 and 2025 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
161 patients with symptomatic oHCM (NYHA II–III, baseline resting LVOT gradient: 39.6 ± 29.1 mmHg, baseline valsalva LVOT gradient: 82.3 ± 42.1 mmHg) were enrolled. At baseline, the mean age was 60.6 ± 11.3 years, with 54.7% of patients being male. Mavacamten led to a significant reduction in mean resting (Δ −28.6 ± 32.1 mmHg; p < 0.001) and valsalva LVOT gradients at 6 months (Δ −58.1 ± 43.5 mmHg; p < 0.001), accompanied by a decrease in mean NT-proBNP levels at 6 Months (Δ −972.5 ± 1771.4 pg/mL; p < 0.001). By month 6, 66% of patients had improved by ≥1 NYHA class, with 45% achieving NYHA I. In the imaging subgroup, echocardiography at follow-up showed no significant decline in ejection fraction. 1 case of LVEF <50% was observed after 6 months of treatment. Mavacamten was well tolerated; dose titration was guided by echocardiographic and biomarker monitoring. Temporary treatment discontinuation due to adverse effects or self-reported intolerance was observed in 3.9% of patients at 6 months.

Conclusions
In this large, prospective, real-world cohort from 15 expert centers, Mavacamten demonstrated robust and sustained reduction in LVOT gradients, functional improvement, and biomarker normalization in symptomatic oHCM. The favorable safety profile and echocardiographic response underscore its value as a disease-specific pharmacological strategy in specialized care settings.