{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:22:04Z","timestamp":1788484924653,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hypertrophic cardiomyopathy (HCM) is the most prevalent hereditary cardiovascular disorder characterized by unexplained left ventricular hypertrophy, sarcomeric hypercontractility, and dynamic left ventricular outflow tract (LVOT) obstruction in approximately 70% of patients. Current therapies predominantly offer symptomatic relief through indirect modulation of cardiac function, leaving the underlying molecular pathophysiology unaddressed. Mavacamten, a first-in-class, selective allosteric inhibitor of \u03b2-cardiac myosin ATPase, exemplifies a precision pharmacological approach by directly targeting the sarcomeric hypercontractility fundamental to obstructive HCM (oHCM). This review synthesizes extensive clinical and preclinical evidence delineating mavacamten\u2019s mechanism of action, pharmacokinetics influenced by CYP2C19 genotype variability, and its demonstrated efficacy and long-term safety in improving functional capacity, symptom burden, and cardiac remodeling. Landmark trials, including EXPLORER-HCM and MAVERICK-HCM, underscore mavacamten\u2019s ability to reduce LVOT gradients, enhance diastolic function, and lower cardiac biomarkers, heralding a paradigm shift from symptomatic management to disease-modifying therapy. Despite current knowledge gaps in long-term outcomes and diverse population responses, mavacamten establishes a critical foundation for molecularly targeted therapeutics in HCM and broader cardiomyopathies.<\/jats:p>","DOI":"10.3390\/jcm14238594","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:20:29Z","timestamp":1765210829000},"page":"8594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Targeting Sarcomeric Hypercontractility with Demonstrated Long-Term Safety and Efficacy\u2014A Narrative Review"],"prefix":"10.3390","volume":"14","author":[{"given":"Ghaith K.","family":"Mansour","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7862-5778","authenticated-orcid":false,"given":"Ali F.","family":"Altebainawi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail 81422, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad W.","family":"Hajjar","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3496-5158","authenticated-orcid":false,"given":"Sabry Babiker H.","family":"Sayed","sequence":"additional","affiliation":[{"name":"General Medicine Practice Program, Batterjee Medical College, Dammam 32313, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fares A.","family":"Alazem","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-3928","authenticated-orcid":false,"given":"Muhammad Raihan","family":"Sajid","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liew, A.C., Vassiliou, V.S., Cooper, R., and Raphael, C.E. 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