Aficamten in Obstructive Hypertrophic Cardiomyopathy: A Multidomain, Patient-Level Analysis of the MAPLE-HCM Trial
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Authors
Wang A.
GarciaPavia P.
Masri A.
Merkely B.
Nassif M.E.
PenaPena M.L.
BarrialesVilla R.
Bilen O.
Burroughs M.
Claggett B.L.
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2026
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Article
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BackgroundFor >60 years, beta-blockers have been first-line therapy for symptomatic obstructive hypertrophic cardiomyopathy (oHCM), although limited data support this recommendation. The MAPLE-HCM trial showed greater improvement in exercise capacity and secondary endpoints for aficamten monotherapy vs metoprolol monotherapy.ObjectivesThe purpose of this study was to evaluate the effects of aficamten vs metoprolol across multiple clinically relevant and patient-centric measures of disease burden in oHCM.MethodsPatients with oHCM and left ventricular outflow tract gradient (LVOT-G) >=30 mm Hg at rest and/or >=50 mm Hg with Valsalva were randomly assigned to aficamten (n = 88) or metoprolol (n = 87). Dose titration was based on vital signs and echocardiograms. Assessment of clinical response by treatment arm was based on improvement in multiple parameters reflecting oHCM disease burden: LVOT-G =1 class improvement in NYHA functional class and/or >=10-point improvement in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS); >=50% reduction in N-terminal pro-B-type natriuretic peptide; >=1.0 mL/kg/min increase in peak oxygen consumption (pVO2); and >=10% reduction in left atrial volume index. Clinical response was classified by number of efficacy outcomes achieved: nonresponder (none), limited (1 or 2), positive (3 or 4), or complete (all 5).ResultsBaseline characteristics were similar for both treatment groups. For the overall cohort, mean age was 58 +/- 13.2 years; 73 (42%) were women, 103 (70%) were in NYHA functional class II and 52 (30%) in class III, mean pVO2 was 19.9 +/- 5.1 mL/kg/min, and mean KCCQ-CSS score was 66 +/- 16. At 24 weeks, aficamten treatment was associated with greater benefits in all efficacy outcome measures, with numbers needed to treat ranging from 1.5 to 5.0 relative to metoprolol treatment. Patients treated with aficamten were more likely to be either positive or complete responders compared with patients treated with metoprolol (78% vs 3%, respectively; P < 0.001).ConclusionsIn patients with symptomatic oHCM, aficamten monotherapy led to superior and rapid treatment benefits across several clinically relevant outcome measures of disease burden compared with metoprolol. These observations support the emerging role of aficamten as monotherapy for oHCM. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM [MAPLE-HCM]; NCT05767346) Copyright © 2026 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
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Journal of the American College of Cardiology
Volume
87
Issue
8