• Milind Y Desai, Kathy Wolski, Anjali Owens, Srihari S Naidu, Jeffrey B Geske, Nicholas G Smedira, Hartzell Schaff, Kathy Lampl, Ellen McErlean, Christina Sewell, David Zhang, Jay M Edelberg, Amy J Sehnert, and Steven E Nissen.
• Hypertrophic Cardiomyopathy Center, Heart and Vascular Institute, Cleveland CLinic, Cleveland OH; Department of cardiovascular medicine, Heart and Vascular Institute, Cleveland CLinic, Cleveland OH; Cleveland Clinic Coordinating Center for Clinical Research, Heart and Vascular Institute, Cleveland CLinic, Cleveland OH. Electronic address: desaim2@ccf.org.
• Am. Heart J. 2021 Sep 1; 239: 80-89.

BackgroundHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder which frequently leads to symptoms such as dyspnea and exercise intolerance, often due to severe dynamic left ventricular outflow tract obstruction (LVOTO). Current guideline-recommended pharmacotherapies have variable therapeutic responses to relieve LVOTO. In recent phases 2 and 3, clinical trials for symptomatic obstructive HCM (oHCM), mavacamten, a small molecule inhibitor of β-cardiac myosin has been shown to improve symptoms, exercise capacity, health status, reduce LVOTO, along with having a beneficial impact on cardiac structure and function.MethodsVALOR-HCM is designed as a multicenter (approximately 20 centers in United States) phase 3, double-blind, placebo-controlled, randomized study. The study population consists of approximately 100 patients (≥18 years old) with symptomatic oHCM who meet 2011 American College of Cardiology/American Heart Association and/or 2014 European Society of Cardiology HCM-guideline criteria and are eligible and willing to undergo septal reduction therapy (SRT). The study duration will be up to 138 weeks, including an initial 2-week screening period, followed by16 weeks of placebo-controlled treatment, 16 weeks of active blinded treatment, 96 weeks of long-term extension, and an 8-week posttreatment follow-up visit. The primary endpoint will be a composite of the decision to proceed with SRT prior to or at Week 16 or remain guideline eligible for SRT at Week 16. Secondary efficacy endpoints will include change (from baseline to Week 16 in the mavacamten group vs placebo) in postexercise LVOT gradient, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire clinical summary score, NT-proBNP, and cardiac troponin. Exploratory endpoints aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology.ConclusionsIn severely symptomatic drug-refractory oHCM patients meeting guideline criteria of eligibility for SRT, VALOR-HCM will primarily study if a 16-week course of mavacamten reduces or obviates the need for SRT using clinically driven endpoints.Copyright © 2021. Published by Elsevier Inc.

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