Targeting the Sarcomere: Myosin Inhibitors as the Revolutionary Game Changer in Hypertrophic Cardiomyopathy

Figures

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  Fig. 1.. Timeline of milestones in hypertrophic cardiomyopathy (HCM). Key advances are shown from the first clinical description (1869) and early surgical/interventional therapies (myectomy, 1964; alcohol septal ablation, 1994) to the modern era of cardiac myosin inhibitors, with landmark trials illustrating the paradigm shift from invasive to disease-specific pharmacological therapy. Created in Illustrae (https://illustrae.co/)

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  Fig. 2.. Mechanism of action of cardiac myosin inhibitors (CMIs). Balanced distribution of myosin heads between the super-relaxed (SRX) and disordered relaxed (DRX) states, permitting normal contractility and efficient relaxation (A). In hypertrophic cardiomyopathy (HCM), destabilization of the SRX state increases myosin head availability for cross-bridge formation, resulting in hypercontractility, diastolic dysfunction, and impaired energetics (B). CMIs such as mavacamten and aficamten stabilize the SRX state, reduce excessive cross-bridge cycling, and restore energetic efficiency (C). Schematic chemical structures of mavacamten and aficamten are shown (D). Created in Illustrae (https://illustrae.co/)