Cardiac myosin inhibitors - a cutting-edge solution for the management of hypertrophic cardiomyopathy: a narrative review

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disorder characterized by unexplained left ventricular hypertrophy, affecting approximately 0.2% of the global population. Around 40% of HCM cases are linked to mutations in sarcomeric protein genes such as β-myosin heavy chain and myosin-binding protein C, which impair calcium signaling and myocardial contractility. Objective: This review aims to explore the therapeutic potential of cardiac myosin inhibitors (CMIs) by assessing their effects on the underlying pathophysiology of HCM, specifically targeting sarcomere function and hypercontractility. Methods: A literature search from 2013 to 2024 using PubMed and Google Scholar identified studies on CMIs in HCM. Relevant trials and reviews were selected based on strict criteria. Two reviewers screened studies, and findings on mechanisms, efficacy, safety, and outcomes were narratively synthesized for analysis. Results: Recent studies have highlighted the role of cardiac fibroblasts and transforming growth factor-β signaling in the development of myocardial fibrosis in HCM. CMIs have shown effectiveness in reducing left ventricular outflow tract gradients, improving exercise tolerance, and lowering biomarkers such as N-terminal pro-b-type natriuretic peptide, without significantly affecting left ventricular ejection fraction (LVEF). Compared to beta-blockers and calcium channel blockers, CMIs offer a targeted approach by modulating sarcomere activity. Conclusion: CMIs represent a promising and mechanism-based treatment for HCM. Their potential to reduce the need for invasive procedures and improve patient outcomes highlights the importance of their integration into clinical practice. Further large-scale trials are needed to establish long-term safety, cost-effectiveness, and broader clinical applicability.