Aficamten in Obstructive Hypertrophic Cardiomyopathy: A Multidomain, Patient-Level Analysis of the MAPLE-HCM Trial.

Summary

In a randomized, active-comparator phase 3 trial, aficamten monotherapy achieved superior, rapid improvements versus metoprolol across multiple clinically relevant endpoints in obstructive HCM, including LVOT gradients, symptoms (NYHA), quality of life (KCCQ-CSS), NT-proBNP, and peak VO2. These patient-level, multidomain gains support aficamten as a potential monotherapy standard for symptomatic oHCM.

Key Findings

• Aficamten achieved greater rates of target LVOT gradient reduction at rest and with Valsalva than metoprolol.
• Patient-centric outcomes improved more with aficamten, including ≥1 NYHA class improvement and ≥10-point KCCQ-CSS gains.
• Biomarker and exercise capacity gains favored aficamten, including ≥50% NT-proBNP reduction and ≥1.0 mL/kg/min increase in peak VO2.
• Benefits were rapid and observed across baseline subgroups.

Clinical Implications

Aficamten may be considered as frontline monotherapy for symptomatic oHCM, with titration guided by vitals and echocardiography to reduce LVOT obstruction and improve functional status and quality of life.

Limitations

• Follow-up duration and detailed safety outcomes are not specified in the abstract; long-term durability is unknown
• Comparison limited to metoprolol; broader comparisons to other standard therapies are needed

Future Directions

Longer-term outcomes, safety profiling, and head-to-head comparisons with other pharmacologic options (e.g., mavacamten, disopyramide) and device or surgical strategies will clarify positioning in oHCM care.