Effect of Aficamten on Cardiac Structure and Function in Patients with Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

BACKGROUND: Aficamten significantly improved both functional capacity and patient-reported health status in patients with symptomatic nonobstructive hypertrophic cardiomyopathy in the phase 3 randomized, placebo-controlled ACACIA-HCM trial (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints in Adults with Non-Obstructive HCM; NCT06081894). Serial echocardiographic examinations may provide insights into the mechanisms underlying the therapeutic effect of aficamten in this prespecified exploratory analysis. METHODS: Symptomatic patients with nonobstructive hypertrophic cardiomyopathy were randomized 1:1 to receive aficamten (range, 5–20 mg, titration based on left ventricular [LV] ejection fraction) or placebo for up to 72 weeks (end of treatment). The effect of aficamten on echocardiographic measures at 36 weeks (time of primary end point) and end of treatment was assessed with linear regression models adjusted for baseline values, intracavity obstruction, and baseline atrial fibrillation. RESULTS: Among 517 participants (mean±SD: age, 55±16 years; 54% female, 75% White, 13% Asian), mean baseline LV ejection fraction was 68±4% with abnormal measures of diastolic function. Compared with placebo, aficamten decreased LV ejection fraction (−4.6% [−5.5, −3.6]; P