{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:18:09Z","timestamp":1791670689608,"version":"4.3.4"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Valsartan has been shown to attenuate phenotypic progression among individuals with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Myocardial tissue characterization by cardiac magnetic resonance (CMR) imaging may enhance mechanistic insights, but whether valsartan influences these parameters remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the treatment effects of valsartan on myocardial structure, function, and tissue parameters in early-stage sarcomeric HCM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This prespecified CMR substudy of the VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) randomized clinical trial evaluated treatment effects of valsartan vs placebo on myocardial structure, function, and tissue parameters and was conducted from April 2014 through July 2019 at 17 international sites. Individuals aged 8 to 45 years with early-stage HCM aged between 8 and 45 years and with no or minimal symptoms were eligible for inclusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Treatment with placebo or valsartan (80 mg per day for children weighing &amp;amp;lt;35 kg, 160 mg per day for children weighing \u226535 kg, or 320 mg per day for adults aged 18 years or older).<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcome was mean change in CMR parameters between baseline and year 2, including indexed extracellular volume (iECV), indexed intracellular volume (iICV), and late gadolinium enhancement (LGE). Mean between-group differences in CMR parameters between baseline and year 2 were evaluated using multivariable mixed-effects linear regression models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 137 of 178 VANISH participants (77.0%) underwent CMR imaging at baseline and year 2. Among these participants, mean (SD) age was 23 (10) years, and 51 participants (37.2%) were female. Baseline characteristics and CMR parameters were well balanced between treatment groups. Higher LGE, iECV, and iICV at baseline were associated with higher cardiac biomarker levels and more pronounced cardiac remodeling. Between baseline and year 2, valsartan appeared to increase left ventricular (LV) end-diastolic volume index (mean difference [MD], 3.3 mL\/m<jats:sup>2<\/jats:sup>; 95% CI, 0.4-6.2; <jats:italic>P<\/jats:italic>\u2009=\u2009.03), suggesting treatment benefit, but did not significantly impact LV mass index (MD, \u22122.9 g\/m<jats:sup>2<\/jats:sup>; 95% CI, \u22126.1 to 0.2; <jats:italic>P<\/jats:italic>\u2009=\u2009.07) or LV ejection fraction. Similarly, valsartan appeared to reduce decline in right ventricular volumes. Valsartan appeared to significantly reduce iICV progression (MD, \u22125.0 mL\/m<jats:sup>2<\/jats:sup>; 95% CI, \u22129.7 to \u22120.4; <jats:italic>P<\/jats:italic>\u2009=\u2009.03), but did not impact iECV (MD, 0.0 mL\/m<jats:sup>2<\/jats:sup>; 95% CI, \u22121.4 to 1.3; <jats:italic>P<\/jats:italic>\u2009=\u2009.95) or LGE progression (MD, 0.5%; 95% CI, \u22120.4 to 1.3; <jats:italic>P<\/jats:italic>\u2009=\u2009.30).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>These findings enhance mechanistic insights into the effect of valsartan in early-stage HCM, showing potential benefits on biventricular remodeling and myocardial intracellular volume. Further research to identify cellular mechanisms of valsartan on HCM progression is needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34556856\/\">NCT01912534<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2024.5677","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T16:02:00Z","timestamp":1741190520000},"page":"617","source":"Crossref","is-referenced-by-count":2,"title":["Valsartan and Cardiac Remodeling in Early-Stage Hypertrophic Cardiomyopathy"],"prefix":"10.1001","volume":"10","author":[{"given":"John W.","family":"Ostrominski","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jerosch-Herold","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Axelsson","family":"Raja","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharlene M.","family":"Day","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Russell","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Zahka","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Colan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Canter","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Bach","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W.","family":"Rossano","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali T.","family":"Owens","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Mestroni","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R. 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