Beta-blockers remain first-line therapy for obstructive HCM, yet newer myosin inhibitors may provide superior structural and functional benefits. The MAPLE-HCM randomized controlled trial, published in JACC, compared aficamten monotherapy with metoprolol in 175 patients with symptomatic obstructive HCM treated for 24 weeks 

Aficamten achieved significantly greater reductions in both resting (−30 mm Hg; 95% CI: −37 to −23) and Valsalva LVOT gradients (−35 mm Hg; 95% CI: −44 to −26) compared with metoprolol (both P<0.001). Improvements extended to diastolic function, with reductions in E/e′ of −2.8 at the lateral wall and −3.1 at the septal wall (both P<0.001).Left atrial volume index decreased by −7.0 mL/m² (95% CI: −9.1 to −4.8; P<0.001).

Additional benefits included reduced mitral valve systolic anterior motion, less mitral regurgitation, and modest reduction in maximal wall thickness (−1.0 mm; P=0.02). Treatment with aficamten, however, was associated with decreases in LVEF (−4%) and global strain indices, though resting cardiac output remained unchanged.

These exploratory findings suggest aficamten monotherapy confers broader structural and functional benefits than metoprolol in symptomatic obstructive HCM. Its long-term effects on systolic function remain uncertain and require further study.