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Hypertrophic cardiomyopathy

Nature Reviews Disease Primers volume 11, Article number: 58 (2025) Cite this article

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Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and represents a leading cause of morbidity and mortality. HCM is a sarcomeric disease characterized by genetically determined defects in sarcomere proteins, leading to left ventricular hypertrophy, hypercontractility and diastolic dysfunction. The phenotypic spectrum of the disease is heterogeneous, ranging from mild forms that can remain stable and asymptomatic for many years, through to childhood-onset, severe cases that can result in progressive heart failure and ventricular arrhythmias. Multi-imaging techniques including echocardiography and cardiac magnetic resonance are pivotal for diagnostic and prognostic assessment in HCM. For decades, therapeutic approaches were limited to invasive septal reduction therapies and nonspecific pharmacological treatment for heart failure. In the last 10 years, however, an in-depth understanding of the pathological mechanisms of HCM has led to the development of targeted therapies, such as myosin inhibitors, which have proven to be safe and effective in improving functional capacity and reducing symptoms. Innovative therapeutic approaches, such as gene therapies that aim to target the genetic variants underpinning the condition, are currently under investigation.

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Fig. 1: Left ventricular outflow tract obstruction.
Fig. 2: Pathophysiology of hypertrophic cardiomyopathy.
Fig. 3: Genes involved in HCM pathophysiology.
Fig. 4: Echocardiographic features of a 32-year-old patient with obstructive hypertrophic cardiomyopathy.
Fig. 5: Contrast-enhanced cardiac MRI in a 26-year-old carrier of a MYBPC3 variant.
Fig. 6: Diagnostic workflow for infant-onset HCM.
Fig. 7: Electrocardiogram and echocardiography of a child with Pompe disease.
Fig. 8: Summary of hypertrophic cardiomyopathy therapeutic options.

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Authors and Affiliations

  1. Cardiomyopathy Unit, University of Florence, Florence, Italy

    Alessia Argirò & Iacopo Olivotto

  2. Stanford Center for Inherited Cardiovascular Disease, Stanford University School of Medicine, Stanford, CA, USA

    Victoria Parikh

  3. Expert Center for Rare Genetic Cardiovascular Diseases, Prof. Dr. C.C. Iliescu Emergency Institute for Cardiovascular Diseases, Bucarest, Romania

    Ruxandra Jurcut

  4. Carol Davila University of Medicine and Pharmacy, Bucarest, Romania

    Ruxandra Jurcut

  5. Cardiovascular Sciences Research Centre, St George’s, University of London, London, UK

    Gherardo Finocchiaro

  6. Cardiology, University College London and Great Ormond Street Hospital for Children, London, UK

    Juan Pablo Kaski

  7. Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    Eric Adler

  8. Meyer Children’s Hospital IRCCS, Florence, Italy

    Iacopo Olivotto

Authors
  1. Alessia Argirò
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  2. Victoria Parikh
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  3. Ruxandra Jurcut
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  4. Gherardo Finocchiaro
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  6. Eric Adler
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  7. Iacopo Olivotto
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Contributions

Introduction (I.O. and A.A.); Epidemiology (I.O., A.A. and V.P.); Mechanisms/pathophysiology (I.O., A.A. and V.P.); Diagnosis, screening and prevention (I.O., A.A., R.J., G.F., J.P.K. and E.A); Management (I.O., A.A., G.F., J.P.K. and E.A.); Quality of life (I.O. and A.A.); Outlook (I.O. and A.A.); overview of the Primer (I.O.).

Corresponding author

Correspondence to Iacopo Olivotto.

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Competing interests

A.A. is a consultant for Lexeo Therapeutics. I.O. is a consultant and/or adviser for Amicus Therapeutics, Inc.; Boston Scientific Corporation; Bristol Myers Squibb; Cytokinetics, Inc.; and Tenaya Therapeutics, Inc., and has received grant and/or research support from Amicus Therapeutics, Inc.; Bayer AG; Boston Scientific Corporation; Bristol Myers Squibb; Genzyme Corporation; The Menarini Group; Sanofi; Shire plc; and Takeda Pharmaceuticals International, Inc. E.A. is the Chief Science Officer for Lexeo Therapeutics, a shareholder with Rocket Pharmaceuticals and is a founder of Papillion Therapeutics and a founder, on the scientific board of and a shareholder of Corstasis Therapeutics. The other authors declare no competing interests.

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Argirò, A., Parikh, V., Jurcut, R. et al. Hypertrophic cardiomyopathy. Nat Rev Dis Primers 11, 58 (2025). https://doi.org/10.1038/s41572-025-00643-0

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