Randomized Controlled Trial

. 2025 Dec;18(12):1300-1311.

doi: 10.1016/j.jcmg.2025.07.019. Epub 2025 Sep 16.

Long-Term Favorable Cardiac Remodeling in Obstructive Hypertrophic Cardiomyopathy Patients Treated With Mavacamten for Up to 128 Weeks: Insights From the VALOR-HCM Trial

Milind Y Desai¹, Yuichiro Okushi², Kathy Wolski³, Jeffrey B Geske⁴, Anjali Tiku Owens⁵, Qiuqing Wang³, Sara Saberi⁶, Andrew Wang⁷, Paul Cremer⁸, Neal K Lakdawala⁹, Mark V Sherrid¹⁰, Albree Tower-Rader¹¹, David R Fermin¹², Mark A Zenker¹³, Srihari S Naidu¹⁴, Kathy Lampl¹⁵, Steven E Nissen³, Zoran Popovic¹⁶; VALOR-HCM investigators

Collaborators, Affiliations

Collaborators

VALOR-HCM investigators:
Steven E Nissen, Milind Y Desai, Kathy Wolski, Christina Sewell, Ellen McErlean, Tammy Gamble, Srihari Naidu, Nick Smedira, Hartzell Schaff, Anjali Owens, Jeffrey Geske, Amy Sehnert, Jean Rouleau, Gary S Francis, Kenneth Mahaffey, A A Afifi, David Kerr, M Desai, J Geske, M Sherrid, A T Owens, S Saberi, A Wang, A Tower-Rader, D Fermin, N Lakdawala, A Masri, M Zenker, J Stendahl, M Wheeler, R Bach, J Orford, S Naidu, F Rader, P Bajona, M Desai, Paul Cremer, Wael A Jaber, Serge C Harb, Annitta Flinn, Allen Borowski, Jeanne Drinko, Amy Kanta, Maureen Martin, Margaret Park, Jill Odabashian, Cathy McDowell, Michelle Baksar, Eva Balazs, Kathy Wolski, Qiuqing Wang, Craig Balog, Richard Lee, Brian Knauf

Affiliations

¹ Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address: desaim2@ccf.org.
² Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
³ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁴ Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁷ Department of Cardiology, Duke University, Durham, North Carolina, USA.
⁸ Department of Cardiology, Northwestern University, Chicago, Illinois, USA.
⁹ Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁰ Department of Cardiology, New York University, New York, New York, USA.
¹¹ Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹² Department of Cardiology, Corewell Health, Grand Rapids, Michigan, USA.
¹³ Department of Cardiology, St Thomas, Nashville, Tennessee, USA.
¹⁴ Department of Cardiology, Westchester Medical Center, Valhalla, New York, USA.
¹⁵ Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USA.
¹⁶ Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.

PMID: 40956275
DOI: 10.1016/j.jcmg.2025.07.019

Randomized Controlled Trial

Long-Term Favorable Cardiac Remodeling in Obstructive Hypertrophic Cardiomyopathy Patients Treated With Mavacamten for Up to 128 Weeks: Insights From the VALOR-HCM Trial

Milind Y Desai et al. JACC Cardiovasc Imaging. 2025 Dec.

. 2025 Dec;18(12):1300-1311.

doi: 10.1016/j.jcmg.2025.07.019. Epub 2025 Sep 16.

Authors

Collaborators

VALOR-HCM investigators:
Steven E Nissen, Milind Y Desai, Kathy Wolski, Christina Sewell, Ellen McErlean, Tammy Gamble, Srihari Naidu, Nick Smedira, Hartzell Schaff, Anjali Owens, Jeffrey Geske, Amy Sehnert, Jean Rouleau, Gary S Francis, Kenneth Mahaffey, A A Afifi, David Kerr, M Desai, J Geske, M Sherrid, A T Owens, S Saberi, A Wang, A Tower-Rader, D Fermin, N Lakdawala, A Masri, M Zenker, J Stendahl, M Wheeler, R Bach, J Orford, S Naidu, F Rader, P Bajona, M Desai, Paul Cremer, Wael A Jaber, Serge C Harb, Annitta Flinn, Allen Borowski, Jeanne Drinko, Amy Kanta, Maureen Martin, Margaret Park, Jill Odabashian, Cathy McDowell, Michelle Baksar, Eva Balazs, Kathy Wolski, Qiuqing Wang, Craig Balog, Richard Lee, Brian Knauf

Affiliations

¹ Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address: desaim2@ccf.org.
² Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
³ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁴ Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁷ Department of Cardiology, Duke University, Durham, North Carolina, USA.
⁸ Department of Cardiology, Northwestern University, Chicago, Illinois, USA.
⁹ Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁰ Department of Cardiology, New York University, New York, New York, USA.
¹¹ Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹² Department of Cardiology, Corewell Health, Grand Rapids, Michigan, USA.
¹³ Department of Cardiology, St Thomas, Nashville, Tennessee, USA.
¹⁴ Department of Cardiology, Westchester Medical Center, Valhalla, New York, USA.
¹⁵ Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USA.
¹⁶ Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.

PMID: 40956275
DOI: 10.1016/j.jcmg.2025.07.019

Abstract

Background: In the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy; NCT04349072) trial, patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM) treated with mavacamten demonstrated significant improvement in left ventricular outflow tract (LVOT) gradients and echocardiographic indices of cardiac remodeling in the short term.

Objectives: The authors sought to assess whether mavacamten results in sustained favorable long-term cardiac remodeling at 128 weeks (end of trial).

Methods: A total of 112 adult symptomatic obstructive HCM patients (mean age: 60.3 years; 50% men; and 94% NYHA functional class III/IV) who were referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo for 16 weeks. Subsequently, placebo patients transitioned to and received 112 weeks of mavacamten, and the original mavacamten group received 128 weeks of mavacamten. All patients had comprehensive echocardiographic assessments (including LV and left atrial [LA] global longitudinal strain measurements using vendor neutral software [TOMTEC-ARENA TTA2, Philips Healthcare]) at baseline and 128-week follow-up.

Results: At week 128, there was a sustained improvement (mean percentage of change from baseline, all P < 0.05) in LVOT gradients (resting [-61%], post-Valsalva [-72%], and postexercise [-53%]), LV mass index (-11%), septal E/e' (-18%), LV global longitudinal strain (4.5%), LA volume index (-6%), and LA strain (conduit strain [16%], contraction [35%], and reservoir [32%]). In 71 patients with ≥5 point improvement in the Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score (KCCQ-23-CSS), there was a significant and sustained improvement (all P < 0.05), whereas in 25 patients with <5 point improvement in the KCCQ-23-CSS, there was no significant improvement in various LA and LV strain values.

Conclusions: In the VALOR-HCM trial, treatment with mavacamten resulted in sustained favorable cardiac remodeling, including improvement in LVOT gradients, cardiac volumes, cardiac hypertrophy, diastolic function, and markers of LA and LV strain from baseline through week 128, suggesting disease modification. These favorable changes also occurred in association with meaningful improvement in quality of life.

Keywords: cardiac remodeling; mavacamten; obstructive HCM.

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Conflict of interest statement

Funding Support and Author Disclosures VALOR-HCM was funded by Bristol Myers Squibb (Princeton, New Jersey, USA). Dr Desai has consulted for Bristol Myers Squibb, Cytokinetics, Tenaya, and Medtronic; and has received research support to Cleveland Clinic from Bristol Myers Squibb, Cytokinetics, and Tenaya. Dr Owens has consulted for Alexion, Bayer, Bristol Myers Squibb, Cytokinetics, Edgewise, Lexeo, Pfizer, Biomarin, Tenaya, Stealth, Imbria, and Corvista; and has received grant support for research from Bristol Myers Squibb. Dr Saberi has consulted for Bristol Myers Squibb and Cytokinetics. Dr Lakdawala has received consulting income from Bristol Myers Squibb, Pfizer, Tenaya, Cytokinetics, and Akros; and has received research support from Bristol Myers Squibb and Pfizer. Drs Naidu, Wang, Sherrid, and Tower-Rader have consulted for Bristol Myers Squibb and Cytokinetics. Dr Geske has consulted with Bristol Myers Squibb. Dr Fermin has consulted for Bristol Myers Squibb, Pfizer, and BridgeBio; and has received speaker fees from Bristol Myers Squibb and BridgeBio. Dr Zenker is a consultant for Bristol Myers Squibb, Cytokinetics, Tenaya, and Pfizer. Dr Lampl is an employee of Bristol Myers Squibb. Drs Nissen, Popovic, and Okushi and Ms Wang are employees of Cleveland Clinic, which received payments for current research from Bristol Myers Squibb. Dr Cremer was employed by Cleveland Clinic during the conduct of the trial, which received payments for current research from Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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Long-Term Favorable Cardiac Remodeling in Obstructive Hypertrophic Cardiomyopathy Patients Treated With Mavacamten for Up to 128 Weeks: Insights From the VALOR-HCM Trial

Collaborators

Affiliations

Long-Term Favorable Cardiac Remodeling in Obstructive Hypertrophic Cardiomyopathy Patients Treated With Mavacamten for Up to 128 Weeks: Insights From the VALOR-HCM Trial

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

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