Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy SEQUOIA-HCM Baseline Characteristics and Study Design

被引：32

作者：

Coats, Caroline J. ^{[1
,24
]}

Maron, Martin S. ^{[2
]}

Abraham, Theodore P. ^{[3
]}

Olivotto, Iacopo ^{[4
]}

Lee, Matthew M. Y. ^{[1
]}

Arad, Michael ^{[5
,6
]}

Cardim, Nuno ^{[7
]}

Ma, Chang-Sheng ^{[8
]}

Choudhury, Lubna ^{[9
]}

Duengen, Hans-Dirk ^{[10
,11
]}

Garcia-Pavia, Pablo ^{[12
]}

Hagege, Albert A. ^{[13
]}

Lewis, Gregory D. ^{[14
]}

Michels, Michelle ^{[15
]}

Oreziak, Artur ^{[16
]}

Owens, Anjali T. ^{[17
]}

Tfelt-Hansen, Jacob ^{[18
,19
,20
]}

Veselka, Josef ^{[21
]}

Watkins, Hugh C. ^{[22
]}

Heitner, Stephen B. ^{[23
]}

Jacoby, Daniel L. ^{[23
]}

Kupfer, Stuart ^{[23
]}

Malik, Fady I. ^{[23
]}

Meng, Lisa ^{[23
]}

Wohltman, Amy ^{[23
]}

Masri, Ahmad

机构：

[1] Univ Glasgow, Sch Cardiovasc & Metab Hlth, Glasgow, Scotland

[2] Lahey Med Ctr, Hypertroph Cardiomyopathy Ctr, Burlington, MA USA

[3] UCSF Med Ctr, San Francisco, CA USA

[4] Ist Ricovero & Cura Carattere Sci IRCCS, Meyer Childrens Hosp, Florence, Italy

[5] Leviev Heart Ctr, Sheba Med Ctr, Tel Hashomer, Israel

[6] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[7] Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China

[8] Northwestern Univ, Feinberg Sch Med, Chicago, IL USA

[9] Charite Campus Virchow Klinikum, Berlin, Germany

[10] Hosp Univ Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, Madrid, Spain

[11] Ctr Nacl Invest Cardiovasc CN, Madrid, Spain

[12] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Dept Cardiol, F-75015 Paris, France

[13] Massachusetts Gen Hosp, Boston, MA USA

[14] Erasmus Univ, Med Ctr, Rotterdam, Netherlands

[15] Narodowy Inst Kardiologii, Warsaw, Poland

[16] Univ Penn, Philadelphia, PA USA

[17] Univ Copenhagen, Fac Hlth & Med Sci, Dept Forens Med, Sect Forens Genet, Copenhagen, Denmark

[18] Rigshosp, Rigshospitalet, Dept Cardiol, Copenhagen, Denmark

[19] Univ Hosp Motol, Charles Univ, Prague, Czech Republic

[20] Charles Univ Prague, Med Sch 2, Prague, Czech Republic

[21] Univ Oxford, Radcliffe Dept Med, Oxford, England

[22] Cytokinet Inc, San Francisco, CA USA

[23] Oregon Hlth & Sci Univ, Portland, OR USA

[24] Univ Glashow, Sch Cardiovasc & Metab Hlth, BHF Glasgow Cardiovasc Res Ctr, 126 Univ Pl, Glasgow G12 8TA, Scotland

来源：

JACC-HEART FAILURE | 2024年 / 12卷 / 01期

基金：

美国国家卫生研究院;

关键词：

aficamten; drug therapy; obstructive hypertrophic cardiomyopathy; randomized controlled trial; ALCOHOL SEPTAL ABLATION; NATRIURETIC PEPTIDE; MYOTOMY-MYECTOMY; HEART-FAILURE; MANAGEMENT; REDUCTION; AFICAMTEN; PREVALENCE; PREDICTORS; INHIBITOR;

D O I：

10.1016/j.jchf.2023.10.004

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 1/4 282). 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). (J Am Coll Cardiol HF 2024;12:199-215) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

引用

页码：199 / 215

页数：17

共 61 条

[21] A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice [J].

Green, Eric M. ;

Wakimoto, Hiroko ;

Anderson, Robert L. ;

Evanchik, Marc J. ;

Gorham, Joshua M. ;

Harrison, Brooke C. ;

Henze, Marcus ;

Kawas, Raja ;

Oslob, Johan D. ;

Rodriguez, Hector M. ;

Song, Yonghong ;

Wan, William ;

Leinwand, Leslie A. ;

Spudich, James A. ;

McDowell, Robert S. ;

Seidman, J. G. ;

Seidman, Christine E. .

SCIENCE, 2016, 351 (6273) :617-621

[22] Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy [J].

Harris, Kevin M. ;

Spirito, Paolo ;

Maron, Martin S. ;

Zenovich, Andrey G. ;

Formisano, Francesco ;

Lesser, John R. ;

Mackey-Bojack, Shannon ;

Manning, Warren J. ;

Udelson, James E. ;

Maron, Barry J. .

CIRCULATION, 2006, 114 (03) :216-225

[23] Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy A Clinical Trial [J].

Heitner, Stephen B. ;

Jacoby, Daniel ;

Lester, Steven J. ;

Owens, Anjali ;

Wang, Andrew ;

Zhang, David ;

Lambing, Joseph ;

Lee, June ;

Semigran, Marc ;

Sehnert, Amy J. .

ANNALS OF INTERNAL MEDICINE, 2019, 170 (11) :741-+

[24] Natriuretic Peptide Response and Outcomes in Chronic Heart Failure With Reduced Ejection Fraction [J].

Januzzi, James L., Jr. ;

Ahmad, Tariq ;

Mulder, Hillary ;

Coles, Adrian ;

Anstrom, Kevin J. ;

Adams, Kirkwood F. ;

Ezekowitz, Justin A. ;

Fiuzat, Mona ;

Houston-Miller, Nancy ;

Mark, Daniel B. ;

Pia, Ileana L. ;

Passmore, Gayle ;

Whellan, David J. ;

Cooper, Lawton S. ;

Leifer, Eric S. ;

Desvigne-Nickens, Patrice ;

Felker, G. Michael ;

O'Connor, Christopher M. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2019, 74 (09) :1205-1217

[25] MAPPING A GENE FOR FAMILIAL HYPERTROPHIC CARDIOMYOPATHY TO CHROMOSOME-14Q1 [J].

JARCHO, JA ;

MCKENNA, W ;

PARE, JAP ;

SOLOMON, SD ;

HOLCOMBE, RF ;

DICKIE, S ;

LEVI, T ;

DONISKELLER, H ;

SEIDMAN, JG ;

SEIDMAN, CE .

NEW ENGLAND JOURNAL OF MEDICINE, 1989, 321 (20) :1372-1378

[26] Hospital Volume Outcomes After Septal Myectomy and Alcohol Septal Ablation for Treatment of Obstructive Hypertrophic Cardiomyopathy US Nationwide Inpatient Database, 2003-2011 [J].

Kim, Luke K. ;

Swaminathan, Rajesh V. ;

Looser, Patrick ;

Minutello, Robert M. ;

Wong, S. Chiu ;

Bergman, Geoffrey ;

Naidu, Srihari S. ;

Gade, Christopher L. F. ;

Charitakis, Konstantinos ;

Singh, Harsimran S. ;

Feldman, Dmitriy N. .

JAMA CARDIOLOGY, 2016, 1 (03) :324-332

[27] Nonsurgical septal reduction for hypertrophic obstructive cardiomyopathy - Outcome in the first series of patients [J].

Knight, C ;

Kurbaan, AS ;

Seggewiss, H ;

Henein, M ;

Gunning, M ;

Harrington, D ;

Fassbender, D ;

Gleichmann, U ;

Sigwart, U .

CIRCULATION, 1997, 95 (08) :2075-2081

[28] EXERCISE CAPACITY IN HYPERTROPHIC CARDIOMYOPATHY - ROLE OF STROKE VOLUME LIMITATION, HEART-RATE, AND DIASTOLIC FILLING CHARACTERISTICS [J].

LELE, SS ;

THOMSON, HL ;

SEO, H ;

BELENKIE, I ;

MCKENNA, WJ ;

FRENNEAUX, MP .

CIRCULATION, 1995, 92 (10) :2886-2894

[29] Mortality Among Referral Patients With Hypertrophic Cardiomyopathy vs the General European Population [J].

Lorenzini, Massimiliano ;

Anastasiou, Zacharias ;

O'Mahony, Constantinos ;

Guttman, Oliver P. ;

Gimeno, Juan Ramon ;

Monserrat, Lorenzo ;

Anastasakis, Aristides ;

Rapezzi, Claudio ;

Biagini, Elena ;

Garcia-Pavia, Pablo ;

Limongelli, Giuseppe ;

Pavlou, Menelaos ;

Elliott, Perry M. ;

Tome-Esteban, Maite ;

Pantazis, Antonis ;

Dickie, Shaughan ;

Fernandez, Xusto ;

Lopez, Angela ;

Vlagkouli, Vasiliki ;

Romero, Antonio ;

Buono, Andrea ;

Pacileo, Giuseppe ;

Gallego-Delgado, Maria ;

Cobo-Marcos, Marta .

JAMA CARDIOLOGY, 2020, 5 (01) :73-80

[30] Clinical and prognostic impact of chronotropic incompetence in patients with hypertrophic cardiomyopathy [J].

Magri, Damiano ;

Agostoni, Piergiuseppe ;

Sinagra, Gianfranco ;

Re, Federica ;

Correale, Michele ;

Limongelli, Giuseppe ;

Zachara, Elisabetta ;

Mastromarino, Vittoria ;

Santolamazza, Caterina ;

Casenghi, Matteo ;

Pacileo, Giuseppe ;

Valente, Fabio ;

Morosin, Marco ;

Musumeci, Beatrice ;

Pagannone, Erika ;

Maruotti, Antonello ;

Uguccioni, Massimo ;

Volpe, Massimo ;

Autore, Camillo .

INTERNATIONAL JOURNAL OF CARDIOLOGY, 2018, 271 :125-131

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