Hypertrophic cardiomyopathy (HCM) is frequently caused by pathogenic variants in genes encoding sarcomere proteins and is characterized by left ventricular (LV) hypertrophy, hypercontractility, and in many cases, LV outflow tract obstruction. Despite standard management, obstructive HCM (oHCM) can still cause substantial morbidity, highlighting the critical need for more effective disease-specific therapeutic approaches. Over the past decade, improved understanding of the molecular pathobiology of HCM has culminated in development of cardiac myosin inhibitors (CMI), a novel drug class that in recent randomized clinical trials have been shown to decrease LVOT obstruction, improve exercise capacity, and ameliorate symptom burden in patients with oHCM. Although promising, areas of uncertainty remain, including the long-term safety and efficacy of CMI and whether they have the potential to modify disease progression. Herein, we review key milestones in the clinical development of CMI, contextualize CMI with established oHCM therapies, and discuss future challenges and opportunities for the use of CMI across the HCM spectrum.

Editors

JACC Heart Failure Editor-in-Chief
Biykem Bozkurt, MD, PhD, FACC 

Deputy Editor
Akshay S. Desai, MD, MPH 

JACC Heart Failure CME/MOC Editor
Kenneth A. Ellenbogen, MD

Author
Yevgeniy Khariton, MD 

Important Dates

Date of Release: July 3, 2023
Term of Approval/Date of CME/MOC Expiration: July 2, 2024