Abstract Body (Do not enter title and authors here): Background: Aficamten treatment over 24 weeks in SEQUOIA-HCM (NCT05186818) improved left ventricular (LV) outflow tract gradients (LVOT-G), showed evidence of favorable cardiac remodeling, and improved measures of LV diastolic function in patients with obstructive hypertrophic cardiomyopathy (oHCM). Whether longer-term treatment over 48 weeks results in further cardiac remodeling is unknown.

Research Question: This study evaluates the effect of chronic treatment with aficamten on echocardiographic measures of cardiac structure and function in FOREST-HCM (NCT04848506), an open-label extension study that enrolled patients who completed a parent study with aficamten.

Methods: Serial echocardiograms were performed in patients receiving open-label aficamten (5–20 mg daily) titrated to relieve LVOT obstruction (Valsalva LVOT <30 mmHg) while maintaining LV ejection fraction (LVEF) 50%.

Results: As of August 31, 2024, 169 patients (mean±SD age 60±13 years; 45.6% female, 95.6% White, 2.4% Black, 1.2% Asian) completed 48 weeks of follow-up. Aficamten treatment resulted in sustained improvement in Valsalva and resting LVOT-G, LV wall thickness, left atrial volume index, and lateral and septal E/e' (Figure 1). LVEF decreased mildly (-7±8%) and remained stable within a normal range between weeks 24 and 48. After 48 weeks, 74 patients demonstrated improvement in the total number of normal LV diastolic function measures (Figure 2).

Conclusion: Treatment with aficamten for 48 weeks in patients with oHCM resulted in significant improvement in important measures of cardiac structure and function, with continued benefit after 24 weeks and no meaningful adverse effects on LV systolic function, indicating sustained and favorable long-term cardiac remodeling.