Pathophysiology and Therapeutic Needs in Nonobstructive Hypertrophic Cardiomyopathy

Affiliations

¹ HCM Center, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address: desaim2@ccf.org.
² Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy; Service of Cardiology, Lausanne University Hospital, Lausanne, Switzerland.
³ Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Bologna, Italy.
⁴ European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Bologna, Italy; Sorbonne University, AP-HP, IHU-ICAN, Department of Cardiology and Department of Genetics, Pitié-Salpêtrière University Hospital, Paris, France.
⁵ InCor, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
⁶ Puerta de Hierro Majadahonda University Hospital, Health Research Institute of the Puerta de Hierro Majadahonda-Segovia de Arana University Hospital (IDIPHISA), CIBERCV, Madrid, Spain.
⁷ Bristol Myers Squibb, Princeton, New Jersey, USA.
⁸ ProCardio Center for Research Based Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁹ Cardiovascular Division, Department of Medicine, University of Virginia Health, Charlottesville, Virginia, USA.
¹⁰ Department of Internal Medicine III, Institute for Cardiomyopathies, University of Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Heidelberg, Germany; Department of Genetics, Genome Technology Center, Stanford University, Stanford, California, USA.
¹¹ European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Bologna, Italy; Cardiovascular Institute, Thorax Center, Department of Cardiology, Erasmus Medical Center, Rotterdam, Netherlands.
¹² Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹³ Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
¹⁴ UCL Institute of Cardiovascular Science and St Bartholomew's Hospital, London, United Kingdom.

PMID: 40997544
DOI: 10.1016/j.jchf.2025.102658

Free article

Review

Pathophysiology and Therapeutic Needs in Nonobstructive Hypertrophic Cardiomyopathy

Milind Y Desai et al. JACC Heart Fail. 2025 Nov.

Free article

. 2025 Nov;13(11):102658.

doi: 10.1016/j.jchf.2025.102658. Epub 2025 Sep 24.

Authors

Affiliations

¹ HCM Center, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address: desaim2@ccf.org.
² Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy; Service of Cardiology, Lausanne University Hospital, Lausanne, Switzerland.
³ Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Bologna, Italy.
⁴ European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Bologna, Italy; Sorbonne University, AP-HP, IHU-ICAN, Department of Cardiology and Department of Genetics, Pitié-Salpêtrière University Hospital, Paris, France.
⁵ InCor, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
⁶ Puerta de Hierro Majadahonda University Hospital, Health Research Institute of the Puerta de Hierro Majadahonda-Segovia de Arana University Hospital (IDIPHISA), CIBERCV, Madrid, Spain.
⁷ Bristol Myers Squibb, Princeton, New Jersey, USA.
⁸ ProCardio Center for Research Based Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁹ Cardiovascular Division, Department of Medicine, University of Virginia Health, Charlottesville, Virginia, USA.
¹⁰ Department of Internal Medicine III, Institute for Cardiomyopathies, University of Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Heidelberg, Germany; Department of Genetics, Genome Technology Center, Stanford University, Stanford, California, USA.
¹¹ European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Bologna, Italy; Cardiovascular Institute, Thorax Center, Department of Cardiology, Erasmus Medical Center, Rotterdam, Netherlands.
¹² Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹³ Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
¹⁴ UCL Institute of Cardiovascular Science and St Bartholomew's Hospital, London, United Kingdom.

PMID: 40997544
DOI: 10.1016/j.jchf.2025.102658

Abstract

Hypertrophic cardiomyopathy (HCM) affects individuals worldwide with an estimated prevalence of over 1 in 500 individuals. Nonobstructive HCM accounts for approximately 30% to 70% of cases, is extremely heterogeneous, and is associated with a notable degree of morbidity, including daily life limitations, ventricular tachyarrhythmias, progression to heart failure, and atrial fibrillation. No approved pharmaceutical therapies target the pathophysiology of nonobstructive HCM, although several clinical trials are underway. This narrative review provides a comprehensive overview of nonobstructive HCM, focusing on epidemiology, natural history, genetics, pathophysiology, clinical manifestations, diagnosis, burden of disease, and current treatments and ongoing clinical trials.

Keywords: heart failure; hypertrophic cardiomyopathy; nonobstructive.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by Bristol Myers Squibb (Princeton, New Jersey, USA). Dr Desai has consultant and research agreements with Bristol Myers Squibb, Cytokinetics, Edgewise Therapeutics, Tenaya Therapeutics, and Viz.Ai. Dr Maurizi has received consulting fees and advisory board fees from Academic CME, Bristol Myers Squibb, and CardioLink. Dr Biagini has received consulting fees from Amicus, Bristol Myers Squibb, Chiesi, Sanofi-Genzyme, and Takeda. Dr Charron has received consulting fees from Amicus, Bristol Myers Squibb, Owkin, Pfizer, Sanofi, and Servier. Dr Fernandes has received consulting fees from Alnylam, AstraZeneca, Bristol Myers Squibb, and Pfizer. Dr González-López has received speaker fees from Alnylam, Bristol Myers Squibb, Eidos, and Pfizer; and consulting fees from Akcea, Bristol Myers Squibb, Novo Nordisk, Pfizer, and Proclara. Dr van Haelst is an employee of Bristol Myers Squibb and may own Bristol Myers Squibb stock or stock options. Dr Hermann Haugaa has received consulting fees from Bristol Myers Squibb and Solid BioSciences; and speaker fees from Boehringer Ingelheim and Novartis. Dr Kramer has received research grants from Bristol Myers Squibb, Cytokinetics, and Eli Lilly; and consulting fees from Eli Lilly. Dr Meder has received funding regarding hypertrophic cardiomyopathy research from the Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research), Informatics for Life (Klaus Tschira Foundation), and the Leducq Foundation; and honoraria for advising on HCM topics and/or travel support/speaker honoraria from Bristol Myers Squibb, Cytokinetics, Novo Nordisk, and Pfizer. Dr Michels has received research funding from Bristol Myers Squibb; and consulting fees from Alnylam, Bayer, Bristol Myers Squibb, Cytokinetics, Pfizer, and Sanofi. Dr Owens has received consulting and/or advisory board fees from Alexion, Avidity, Bayer, Biomarin, Bristol Myers Squibb, Corvista, Cytokinetics, Edgewise Therapeutics, Imbria, Lexeo, Pfizer, Stealth, and Tenaya Therapeutics. Dr Yuasa has received lecture fees from Amgen, Bristol Myers Squibb, Daiichi Sankyo, Kowa Company, Nippon Boehringer Ingelheim, Novartis, Pfizer Japan, and Toa Eiyo, Japan; research funding from Bayer Yakuhin; and equity ownership in Heartseed Inc. Dr Elliott has received consulting fees from Alnylam, Bristol Myers Squibb, Cardior, DiNAQOR, Freeline, Pfizer, Sanofi, and Sarepta.

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Pathophysiology and Therapeutic Needs in Nonobstructive Hypertrophic Cardiomyopathy

Affiliations

Pathophysiology and Therapeutic Needs in Nonobstructive Hypertrophic Cardiomyopathy

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources