{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:38:01Z","timestamp":1787855881742,"version":"build-2784847793"},"reference-count":100,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2025 Grant Program for Biomedical Engineering Research from the Nakatani Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by unexplained left ventricular hypertrophy, often resulting from pathogenic variants of sarcomeric protein genes. Conventional treatments, such as the use of beta blockers or calcium channel blockers, focus on symptomatic control but do not address the underlying hypercontractility at the sarcomere level. Recent advances in molecular understanding have led to the development of cardiac myosin inhibitors that directly modulate sarcomeric function by reducing myosin\u2013actin cross-bridge formation and adenosine triphosphatase (ATPase) activity. Mavacamten and aficamten have shown promising results in phase 2 and 3 clinical trials, improving symptoms, exercise capacity, and left ventricular outflow tract gradients in patients with obstructive HCM. This review summarizes the current understanding of HCM pathophysiology, diagnostic strategies, and conventional treatments with a focus on the mechanisms of action of myosin inhibitors, clinical evidence supporting their use, and future directions for improvement. We also discuss their potential applications in non-obstructive HCM and the importance of precision medicine guided by genetic profiling.<\/jats:p>","DOI":"10.3390\/ijms26199347","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:56:44Z","timestamp":1758790604000},"page":"9347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: From Sarcomere to Clinic"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8845-3626","authenticated-orcid":false,"given":"Kazufumi","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"},{"name":"Center for Advanced Heart Failure, Okayama University Hospital, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-2052","authenticated-orcid":false,"given":"Takahiro","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"},{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Pathology, Saiseikai Fukuoka General Hospital, Fukuoka 810-0001, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Onoue","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nara Medical University, Kashihara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5681-8854","authenticated-orcid":false,"given":"Toru","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-1464","authenticated-orcid":false,"given":"Hidemichi","family":"Kouzu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-3985","authenticated-orcid":false,"given":"Toshiyuki","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4009-2359","authenticated-orcid":false,"given":"Takayuki","family":"Inomata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/hrt.20.1.1","article-title":"Asymmetrical hypertrophy of the heart in young adults","volume":"20","author":"Teare","year":"1958","journal-title":"Br. 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