Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). This large, phase 3 trial is now fully enrolled (N = 282). Baseline characteristics reflect an ethnically diverse population with characteristics typical of patients encountered clinically with substantial functional and symptom burden. The study will assess the effect of aficamten vs placebo, in addition to standard-of-care medications, on functional capacity and symptoms over 24 weeks. Future clinical trials could model the approach in SEQUOIA-HCM to evaluate the effect of potential therapies on the burden of oHCM. (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM [SEQUOIA-HCM]; NCT05186818).

Beijing Anzhen Hospital Capital Medical University Beijing China

Charité Campus Virchow Klinikum Berlin Germany

Cytokinetics Incorporated South San Francisco California USA

Département de Cardiologie Assistance Publique Hôpitaux de Paris Hôpital Européen Georges Pompidou Paris France

Department of Cardiology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Erasmus University Medical Center Rotterdam the Netherlands

Hospital Da Luz Lisbon Portugal

Hospital Universitario Puerta de Hierro de Majadahonda IDIPHISA CIBERCV and Centro Nacional de Investigaciones Cardiovasculares Madrid Spain

Hypertrophic Cardiomyopathy Center at Lahey Medical Center Burlington Massachusetts USA

Leviev Heart Center Sheba Medical Center Israel

Massachusetts General Hospital Boston Masachusetts USA

Meyer Children's Hospital Istituto di Ricovero e Cura a Carattere Scientifico Florence Italy

Narodowy Instytut Kardiologii Warsaw Poland

Northwestern University Feinberg School of Medicine Chicago Illinois USA

Oregon Health and Science University Portland Oregon USA

Radcliffe Department of Medicine University of Oxford Oxford United Kingdom

School of Cardiovascular and Metabolic Health University of Glasgow Glasgow United Kingdom

Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark

Tel Aviv University Medical School Israel

UCSF Medical Center San Francisco California USA

University Hospital Motol and 2nd Medical School Charles University Prague Czech Republic

University of Pennsylvania Philadelphia Pennsylvania USA

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$a Coats, Caroline J $u School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom. Electronic address: caroline.coats@glasgow.ac.uk

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$a Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design / $c CJ. Coats, MS. Maron, TP. Abraham, I. Olivotto, MMY. Lee, M. Arad, N. Cardim, CS. Ma, L. Choudhury, HD. Düngen, P. Garcia-Pavia, AA. Hagège, GD. Lewis, M. Michels, A. Oreziak, AT. Owens, J. Tfelt-Hansen, J. Veselka, HC. Watkins, SB. Heitner, DL. Jacoby, S. Kupfer, FI. Malik, L. Meng, A. Wohltman, A. Masri, SEQUOIA-HCM Investigators

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$a Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). This large, phase 3 trial is now fully enrolled (N = 282). Baseline characteristics reflect an ethnically diverse population with characteristics typical of patients encountered clinically with substantial functional and symptom burden. The study will assess the effect of aficamten vs placebo, in addition to standard-of-care medications, on functional capacity and symptoms over 24 weeks. Future clinical trials could model the approach in SEQUOIA-HCM to evaluate the effect of potential therapies on the burden of oHCM. (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM [SEQUOIA-HCM]; NCT05186818).

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