Scientific Sessions 2025  /  Biological and Pragmatic Interventions in Heart Failure: From Present to Future  /  Effect of Aficamten versus Metoprolol Monotherapy on Biomarkers in Obstructive Hypertrophic Cardiomyopathy: The MAPLE-HCM Trial
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Effect of Aficamten versus Metoprolol Monotherapy on Biomarkers in Obstructive Hypertrophic Cardiomyopathy: The MAPLE-HCM Trial

Abstract Body (Do not enter title and authors here): Introduction/Background: Circulating biomarkers of myocardial stress and injury are associated with exercise capacity, health status, and clinical outcomes in obstructive hypertrophic cardiomyopathy (oHCM) and may change with therapeutic intervention. It is unclear if differences exist in biomarker response to aficamten vs beta-adrenergic blockade as first-line medical therapy and how changes in biomarkers parallel treatment effects. MAPLE-HCM (NCT05767346) compared aficamten vs metoprolol succinate as monotherapy/first-line treatment on peak oxygen uptake (pVO2), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), and echocardiographic measures in symptomatic oHCM.
Methods/Approach: Differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were studied in MAPLE-HCM. Biomarkers were measured at baseline and serially throughout the study. Changes in biomarkers from baseline to end of therapy were compared by treatment.
Results/Data: Participants were randomized to aficamten (n=88) vs metoprolol (n=87) and were well-matched for baseline characteristics, including mean rest/Valsalva LVOT-G (49 ± 30 vs 46 ± 27 mmHg; 75 ± 34 vs 72 ± 31 mmHg), median [IQR] NT-proBNP (510 [213, 993] vs 439 [171, 907] ng/L), and hs-cTnI (14.2 [7.3, 34.0] vs 11.6 [6.3, 25.1] ng/L). After 24-wk treatment, mean NT-proBNP decreased by 73% with aficamten and increased by 42% with metoprolol (treatment effect at 24 wk −81% [−85%, −76%], P<0.001; change from baseline shown in Figure 1) and mean hs-cTnI decreased by 43% with aficamten and 17% with metoprolol (treatment effect -28% [−41%, −13%], P=0.001; change from baseline shown in Figure 2). The correlation between changes in NT-proBNP vs Valsalva LVOT-G, rest LVOT-G, and KCCQ-CSS over 24 wk were +0.44, +0.48, and −0.26 (all P<0.05). The correlation between change in biomarkers and change in pVO2 over 24 wk was significant for NT-proBNP (−0.42, P<0.001), but not hs-cTnI (−0.11, P=0.22). Biomarkers reverted to baseline values after washout in both treatment groups.
Conclusions: As monotherapy for oHCM, aficamten significantly reduced NT-proBNP and hs-cTnI compared with metoprolol as monotherapy. Reduction in NT-proBNP concentrations correlated significantly with improved exercise capacity, LVOT-G, and health status. These results provide insights regarding the mechanism of clinical benefit of aficamten compared to metoprolol in MAPLE-HCM.
  • Lakdawala, Neal  ( Brigham and Womens Hospital , Boston , Massachusetts , United States )
  • Burroughs, Melissa  ( WellStar Medical Group , Hiram , Georgia , United States )
  • Claggett, Brian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Costabel, Juan  ( Instituto Cardiovascular de Buenos Aires , Buenos Aires , Argentina )
  • Correia, Edileide  ( Instituto Dante Pazzanese de Cardio , Sao Paulo , Brazil )
  • Dybro, Anne  ( Aarhus University Hospital , Aarhus , Denmark )
  • Elliott, Perry  ( University College London , London , United Kingdom )
  • Kulac, Ian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Lewis, Gregory  ( Massachusetts General Hospital , Boston , Massachusetts , United States )
  • Mann, Amy  ( Patient Advocate , Colorado Springs , Colorado , United States )
  • Nair, Ajith  ( Baylor College of Medicine , Houston , Texas , United States )
  • Garcia-pavia, Pablo  ( Hospital Puerta de Hierro , Majadahonda , Spain )
  • Poulsen, Steen  ( Aarhus Hospital University , Aarhus , Denmark )
  • Reant, Patricia  ( Hopital Cardiologique Haut-Leveque , Bordeaux-Pessac , France )
  • Schulze, Christian  ( UNIVERSITY HOSPITAL JENA , Jena , Germany )
  • Solomon, Scott  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Wang, Andrew  ( Duke University Hospital , Durham , North Carolina , United States )
  • Sohn, Regina  ( Cytokinetics, Incorporated , San Francisco , California , United States )
  • Berhane, Indrias  ( Cytokinetics Inc. , Portland , Oregon , United States )
  • Heitner, Stephen  ( Cytokinetics Inc. , Portland , Oregon , United States )
  • Jacoby, Daniel  ( Cytokinetics Inc. , Portland , Oregon , United States )
  • Kupfer, Stuart  ( Cytokinetics Inc. , Portland , Oregon , United States )
  • Maron, Martin  ( Lahey Hospital and Medical Center , Burlington , Massachusetts , United States )
  • Malik, Fady  ( Cytokinetics Inc. , Portland , Oregon , United States )
  • Wohltman, Amy  ( Cytokinetics Inc. , Portland , Oregon , United States )
  • Fifer, Michael  ( MASSACHUSETTS GEN HOSP , Brookline , Massachusetts , United States )
  • Januzzi, James  ( Baim Institute for Clinical Research, Massachusetts General Hospital , Boston , Massachusetts , United States )
  • Masri, Ahmad  ( OHSU , Portland , Oregon , United States )
  • Merkely, Béla  ( Semmelweis University , Budapest , Hungary )
  • Nassif, Michael  ( University of Missouri Kansas City Healthcare Institute for Innovations in Quality and Saint Luke’s Mid America Heart Institute , Kansas City , Missouri , United States )
  • Pena Pena, Maria Luisa  ( GENERAL HOSPITAL OF H.U. VIRGEN DEL ROCIO , Seville , Spain )
  • Barriales-villa, Roberto  ( Complexo Hospitalario Universitario , A Coruna , Spain )
  • Bilen, Ozlem  ( Emory University , Decatur , Georgia , United States )
    • Author Disclosures:
    Neal Lakdawala: DO have relevant financial relationships ; Consultant:BMS:Active (exists now) ; Advisor:Neuvocore:Active (exists now) ; Consultant:Gemma:Active (exists now) ; Advisor:Kardigan:Active (exists now) ; Consultant:Tenaya:Active (exists now) ; Consultant:Cytokinetics:Active (exists now) ; Consultant:Pfizer:Past (completed) ; Consultant:Alexion:Active (exists now) | Melissa Burroughs: DO have relevant financial relationships ; Consultant:Cytokinetics :Active (exists now) ; Consultant:Novartis:Active (exists now) ; Speaker:Bristol Myers Squibb:Active (exists now) ; Speaker:AstraZeneca:Active (exists now) ; Consultant:Alnylam:Active (exists now) | Brian Claggett: No Answer | Juan Costabel: No Answer | Edileide Correia: DO NOT have relevant financial relationships | Anne Dybro: DO have relevant financial relationships ; Advisor:Cytokinetics:Active (exists now) ; Speaker:Bristol myers squibb:Past (completed) | Perry Elliott: DO have relevant financial relationships ; Consultant:Pfizer:Active (exists now) ; Consultant:Amicus:Active (exists now) ; Speaker:Chiesi:Active (exists now) ; Speaker:Amicus:Active (exists now) ; Advisor:Solid:Active (exists now) ; Consultant:Forbion:Active (exists now) ; Consultant:Affinia:Active (exists now) ; Consultant:Astra Zeneca:Past (completed) ; Consultant:BMS:Past (completed) | Ian Kulac: No Answer | Gregory Lewis: No Answer | Amy Mann: DO have relevant financial relationships ; Independent Contractor:CytoKinetics:Active (exists now) ; Independent Contractor:Bristol-Myers Squibb:Past (completed) ; Employee:hypertrophic cardiomyopathy association:Past (completed) ; Independent Contractor:Lumanity:Past (completed) ; Speaker:American Heart Association Northern California:Past (completed) | Ajith Nair: DO have relevant financial relationships ; Speaker:Johnson & Johnson:Past (completed) ; Speaker:Natera:Past (completed) ; Speaker:Impulse Dynamics:Past (completed) | Pablo Garcia-Pavia: DO have relevant financial relationships ; Speaker:Pfizer:Active (exists now) ; Consultant:Life Molecular Imaging:Active (exists now) ; Consultant:Kardigan:Active (exists now) ; Consultant:Ionis Pharmaceuticals:Active (exists now) ; Consultant:Edgewise:Active (exists now) ; Consultant:Cytokinetics:Active (exists now) ; Consultant:Intellia:Active (exists now) ; Consultant:Bridgebio:Active (exists now) ; Consultant:BMS:Active (exists now) ; Consultant:Bayer:Active (exists now) ; Speaker:AstraZeneca:Active (exists now) ; Speaker:Alnylam:Active (exists now) ; Consultant:Biomarin:Active (exists now) ; Consultant:Rocket:Active (exists now) ; Consultant:Lexeo:Active (exists now) | Steen Poulsen: No Answer | Patricia Reant: DO NOT have relevant financial relationships | Christian Schulze: DO NOT have relevant financial relationships | Scott Solomon: DO have relevant financial relationships ; Research Funding (PI or named investigator):Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly,NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, US2.AI:Active (exists now) ; Consultant:Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, Askbio, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo, Synhale, Recordati:Active (exists now) | Andrew Wang: DO have relevant financial relationships ; Consultant:Bristol Myers Squibb:Past (completed) ; Independent Contractor:ICON:Active (exists now) ; Research Funding (PI or named investigator):Abbott Vascular:Active (exists now) ; Research Funding (PI or named investigator):Edgewise:Expected (by end of conference) ; Research Funding (PI or named investigator):Lexicon:Expected (by end of conference) ; Speaker:Bristol Myers Squibb:Past (completed) ; Research Funding (PI or named investigator):Cytokinetics:Active (exists now) ; Research Funding (PI or named investigator):Bristol Myers Squibb:Active (exists now) | Regina Sohn: DO have relevant financial relationships ; Employee:Cytokinetics:Active (exists now) ; Individual Stocks/Stock Options:Cytokinetics:Active (exists now) | Indrias Berhane: No Answer | Stephen Heitner: DO have relevant financial relationships ; Employee:Cytokinetics Inc.:Active (exists now) ; Individual Stocks/Stock Options:Cytokinetics Inc.:Active (exists now) | Daniel Jacoby: DO have relevant financial relationships ; Employee:Cytokinetics:Active (exists now) ; Individual Stocks/Stock Options:Cytokinetics:Active (exists now) | Stuart Kupfer: DO have relevant financial relationships ; Employee:Cytokinetics:Active (exists now) ; Individual Stocks/Stock Options:Cytokinetics:Active (exists now) | Martin maron: DO NOT have relevant financial relationships | Fady Malik: DO have relevant financial relationships ; Executive Role:Cytokinetics, Inc.:Active (exists now) ; Individual Stocks/Stock Options:Cytokinetics, Inc:Active (exists now) | Amy Wohltman: No Answer | Michael Fifer: DO have relevant financial relationships ; Consultant:Cytokinetics:Active (exists now) ; Consultant:Imbria:Past (completed) ; Consultant:Edgewise:Active (exists now) ; Consultant:Bristol-Myers Squibb:Past (completed) ; Research Funding (PI or named investigator):Cytokinetics:Past (completed) | James Januzzi: No Answer | Ahmad Masri: DO have relevant financial relationships ; Consultant: Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, AstraZeneca, Avidity, Neurimmune, and Tenaya.:Active (exists now) ; Research Funding (PI or named investigator): Pfizer, Ionis, Attralus, Cytokinetics and Janssen. :Active (exists now) | Béla Merkely: No Answer | Michael Nassif: No Answer Roberto Barriales-Villa: No Answer | Ozlem Bilen: DO have relevant financial relationships ; Consultant:Cytokinetics:Active (exists now) ; Consultant:BMS:Active (exists now)
Meeting Info:

Scientific Sessions 2025

2025

New Orleans, Louisiana

Session Info:

Biological and Pragmatic Interventions in Heart Failure: From Present to Future

Sunday, 11/09/2025 , 08:00AM - 09:15AM

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Clinical Responses to Aficamten Monotherapy Compared with Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy Outcomes and Disease Burden: MAPLE-HCM Responder Analysis

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