ArticleEuropean heart journal supplements : journal of the European Society of Cardiology2026
The ODYSSEY-HCM and MAPLE-HCM studies: the role of cardiac myosin inhibitors in hypertrophic cardiomyopathy (obstructive and non-obstructive).
Article in European heart journal supplements : journal of the European Society of Cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Hypertrophic cardiomyopathy (HCM) is an inherited heart disease characterized by unexplained left ventricular hypertrophy with or without outflow tract obstruction. Conventional therapies may relieve symptoms associated with left ventricular outflow tract (LVOT) obstruction; however, they do not act directly on the contractile cell, and refractory patients may require septal reduction therapy. Allosteric cardiac myosin inhibitors (CMIs) represent a novel therapeutic approach directly targeting sarcomeric hypercontractility. Mavacamten and aficamten have demonstrated significant clinical and haemodynamic benefits in obstructive HCM (oHCM). The MAPLE-HCM trial revealed that aficamten significantly improved peak oxygen uptake, NYHA functional class, quality of life, and reduced LVOT gradients compared with metoprolol, with a favourable safety profile. Encouraged by these findings, CMIs have been investigated in non-obstructive HCM (nHCM). The ODYSSEY-HCM trial evaluated mavacamten in patients with symptomatic nHCM. While the primary endpoints of exercise capacity and patient-reported health status were not met, secondary analyses showed favourable effects on NT-proBNP, high-sensitivity troponin I, left ventricular diastolic function, and hypertrophy parameters. In conclusion, CMIs offer substantial benefits in oHCM, improving symptoms and cardiac haemodynamics. In nHCM, despite limited impact on functional capacity, CMIs demonstrate biological activity and favourable cardiac remodelling, supporting further research into their potential role in modulating disease pathophysiology.
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