Pathophysiology and Therapeutic Needs in Nonobstructive Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) affects individuals worldwide with an estimated prevalence of over 1 in 500 individuals. Nonobstructive HCM accounts for approximately 30% to 70% of cases, is extremely heterogeneous, and is associated with a notable degree of morbidity, including daily life limitations, ventricular tachyarrhythmias, progression to heart failure, and atrial fibrillation. No approved pharmaceutical therapies target the pathophysiology of nonobstructive HCM, although several clinical trials are underway. This narrative review provides a comprehensive overview of nonobstructive HCM, focusing on epidemiology, natural history, genetics, pathophysiology, clinical manifestations, diagnosis, burden of disease, and current treatments and ongoing clinical trials. (JACC Heart Fail. 2025;13:102658) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)