Gli studi Odyssey–HCM e MAPLE-HCM: ruolo dei modulatori della miosina nella cardiomiopatia ipertrofica (ostruttiva e non)

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 to left ventricular outflow tract (LVOT) obstruction, however do not act directly to 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 hemodynamic 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 favorable 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 favorable 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 hemodynamics. In nHCM, despite limited impact on functional capacity, CMIs demonstrate biological activity and favorable cardiac remodeling, supporting further research into their potential role in modulating disease pathophysiology.