Long-term impact of aficamten on patient-reported outcome measures in obstructive hypertrophic cardiomyopathy: results from FOREST-HCM

AIMS: Treatment with aficamten in patients with obstructive hypertrophic cardiomyopathy (oHCM) led to significant improvements in patient-reported outcomes (PROs) in the pivotal SEQUOIA-HCM trial over 24 weeks, but its longer-term impact has not been described. The aim of this study was to describe the long-term effects of aficamten across multiple PROs in FOREST-HCM, an open-label extension study. METHODS AND RESULTS: Participants with oHCM completing an aficamten trial were offered enrollment in FOREST-HCM. The Kansas City Cardiomyopathy Questionnaire (KCCQ), Seattle Angina Questionnaire 7-item (S), EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) index, and visual analogue scale (VAS) were administered at baseline and at weeks 12, 24, 36, and 48. Associations among PROs and clinical markers of oHCM severity were assessed with Spearman correlation coefficients.A total of 172 participants (mean age 60.4 [SD ±13.1] years; 45.3% female) completed 48 weeks of follow up as of August 31, 2024, and were included. Significant improvements in all PROs were observed by week 12 and sustained through week 48. At 48 weeks, mean KCCQ-OSS improved by 18.8 (16.9-20.6) points, (P < 0.001, with the largest gains in the KCCQ Quality of Life domain (25.8 points [23.2-28.5; P < 0.001]). S-Summary Scores increased by 17.2 (15.1-19.4; p < 0.001), and EQ-5D-5L index and VAS scores improved by 0.11 and 12.7 points, respectively (p < 0.001). Improvements in PROs were significantly correlated with important clinical measures of oHCM. CONCLUSIONS: Aficamten resulted in sustained improvements across multiple health status dimensions, which also correlated with clinical markers of oHCM severity.