Sustained Cardiac Remodeling with Long-Term Aficamten Therapy in Obstructive Hypertrophic Cardiomyopathy

By Sheila Hegde, M.D., M.P.H.

Assistant Professor of Internal Medicine

Obstructive hypertrophic cardiomyopathy (oHCM) remains a challenging condition in clinical practice, driven by dynamic LV outflow tract (LVOT) obstruction, diastolic dysfunction, and structural remodeling that contribute to symptoms, exercise limitation, and reduced quality of life. Aficamten, an investigational next-in-class cardiac myosin inhibitor, has shown early improvements in cardiac structure and function, but whether longer-term therapy leads to further cardiac remodeling remains an important clinical question for clinicians managing symptomatic patients.

At #AHA25, we presented new 48-week data from FOREST-HCM (NCT04848506), an open-label extension study enrolling patients who completed a prior aficamten parent trial. Participants received aficamten 5-20 mg daily, titrated to achieve Valsalva LVOT gradient < 30 mmHg while maintaining LV ejection fraction (LVEF) ≥ 50%. Serial echocardiographic assessments were performed to monitor changes in LV structure, function, and diastolic indices throughout the study.

Long-term aficamten therapy produced sustained reductions in both resting and Valsalva LVOT gradients, accompanied by sustained improvement in left atrial volume index. Notably, there was continued, progressive improvement in LV wall thickness, suggesting ongoing reverse remodeling over extended exposure. LVEF declined modestly (-7±8%) but remained within the normal range throughout treatment.

These findings, developed in collaboration with the Cardiovascular Imaging Core Laboratory team at Brigham and Women’s Hospital, extend observations from SEQUOIA-HCM and MAPLE-HCM in supporting the potential remodeling benefit of aficamten in the chronic treatment of symptomatic oHCM. The expanding therapeutic landscape for oHCM represents an important step forward in improving care for patients with this complex disease.