Emerging treatments in hypertrophic cardiomyopathy: a focus on cardiac myosin inhibitors

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is commonly driven by sarcomeric hypercontractility and may cause dynamic left ventricular outflow tract obstruction (LVOTO). Conventional therapies reduce symptoms and hemodynamics but do not directly target sarcomeric force generation. AREAS COVERED: We reviewed translational and clinical evidence for cardiac myosin inhibitors (CMIs), which shift myosin toward energy-conserving relaxed states - disordered relaxed (DRX) 'on' and super-relaxed (SRX) 'off,' to reduce excessive cross-bridge cycling. A structured search of PubMed/MEDLINE, Embase, and ClinicalTrials.gov (January 2000-December 2025) was performed using terms related to HCM, mavacamten, aficamten, cardiac myosin inhibition, and major trial names. We summarize pivotal data in obstructive HCM for mavacamten and aficamten, discuss safety/monitoring and drug-drug interactions, and outline emerging investigational sarcomere modulators. Evidence in nonobstructive HCM is reviewed, including recent neutral phase 3 results and ongoing trials. EXPERT OPINION: CMIs establish a mechanism-based paradigm in obstructive HCM with consistent improvements in gradients and health status in randomized trials. Their future impact will depend on long-term outcomes, real-world implementation (monitoring, interactions, access), and identifying nonobstructive phenotypes most likely to benefit.