Masri, AhmadSherrid, Mark VAbraham, Theodore PChoudhury, LubnaGarcia-Pavia, PabloKramer, Christopher MBarriales-Villa, RobertoOwens, Anjali TRader, FlorianNagueh, Sherif FOlivotto, IacopoSaberi, SaraTower-Rader, AlbreeWong, Timothy CCoats, Caroline JWatkins, HughFifer, Michael ASolomon, Scott DHeitner, Stephen BJacoby, Daniel LKupfer, StuartMalik, Fady IMeng, LisaSohn, Regina LWohltman, AmyMaron, Martin S2024-07-092024-07-092024-03-15J Card Fail. 2024 Mar 15:S1071-9164(24)00082-4.http://hdl.handle.net/20.500.12105/20368BACKGROUND This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). METHODS Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5-15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. RESULTS We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of -5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%-48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. CONCLUSIONS Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04219826.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/Atribución-NoComercial-CompartirIgual 4.0 Internacional3849383210.1016/j.cardfail.2024.02.0201532-8414Journal of cardiac failureopen access