TOPLINE:

Patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) who received aficamten for 24 weeks showed significant improvements in exercise capacity, postexercise recovery, and overall exercise performance compared with those who received metoprolol.

METHODOLOGY:

• Researchers conducted a secondary analysis of a phase 3 randomized trial (MAPLE-HCM) comparing the effects of aficamten and metoprolol on exercise measures in patients with symptomatic obstructive HCM.
• They included 175 patients across 71 international sites between June 2023 and March 2025. The mean age of patients was 57.7 years, and 58.3% were male.
• Patients were randomly assigned to receive titrated aficamten (5-20 mg/d) or titrated metoprolol (50-200 mg/d) for 24 weeks.
• Cardiopulmonary exercise testing captured measures including the minute ventilation to carbon dioxide output ratio (VE/VCO₂ slope), anaerobic threshold, peak oxygen uptake (VO₂), exercise workload, heart rate reserve, postexercise VO₂ recovery times, and composite metrics such as circulatory power.
• Cardiopulmonary exercise testing was performed at baseline and at week 24. Validated exercise tests were available for 165 patients.

TAKEAWAY:

• Aficamten recipients had a 2.8‑unit greater reduction in the submaximal VE/VCO₂ slope than metoprolol recipients (P < .001).
• Aficamten recipients had greater gains in peak exercise measures than metoprolol recipients: Peak VO₂ was higher by 2.3 mL/kg/min, peak workload by 8 watts, peak heart rate by 28 beats/min, exercise duration by 0.6 minutes, and heart rate reserve by 12 beats/min (P < .01 for all).
• Aficamten recipients were 6.8-fold more likely to gain at least 3.0 mL/kg/min in peak VO₂ than metoprolol recipients (P < .001). They also experienced faster recovery of VO₂ after exercise and had a higher composite score for exercise performance.
• Circulatory power was significantly higher among aficamten recipients than among metoprolol recipients (P < .001).

IN PRACTICE:

“Findings provide compelling justification for aficamten treatment as an appropriate alternative to current first-line treatment with metoprolol to treat exercise intolerance in oHCM [obstructive HCM],” the researchers of the study wrote.

SOURCE:

The study was led by Gregory D. Lewis, MD, Mass General Brigham Heart and Vascular Institute, Boston. It was published online on June 17 in JAMA Cardiology.

LIMITATIONS:

Data were unavailable for 10 patients because of technical problems, deviation from protocol, or adverse events. Researchers could not assess long-term outcomes in a 24-week study. They did not evaluate the effects of aficamten in asymptomatic patients.

DISCLOSURES:

The MAPLE-HCM trial received funding from Cytokinetics. Several authors reported receiving consulting fees, honoraria, speaker or advisory payments, and/or research institutional grants from multiple sources including the funding company. Some authors reported being employees of or holding stocks in the sponsor company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.