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To address this gap, we generated engineered heart tissues (EHTs) using CRISPR-edited human induced pluripotent stem cell-derived cardiomyocytes that lack dystrophin. These dystrophic EHTs reproduced aspects of systolic and diastolic dysfunction seen in DMD-related DCM as they showed impaired contractile function and slower kinetics. Increased beat rate variability was also observed in dystrophic EHTs. Accompanying these facets of the DMD pathology were attenuated Ca2+ transients and delayed kinetics. Lastly, histological analysis of EHTs revealed that dystrophin-null cardiomyocytes had reduced size and shorter sarcomere lengths when compared to isogenic controls. Together, these findings demonstrate that EHTs provide a physiologically relevant human model of DMD-associated DCM and may serve as a valuable platform for mechanistic studies and therapeutic testing.<\/jats:p>","DOI":"10.1115\/1.4070408","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T11:18:26Z","timestamp":1763205506000},"update-policy":"https:\/\/doi.org\/10.1115\/crossmarkpolicy-asme","source":"Crossref","is-referenced-by-count":0,"title":["Dystrophin Loss in Engineered Heart Tissues Recapitulates Clinically Relevant Aspects of Dystrophic Cardiomyopathy"],"prefix":"10.1115","volume":"148","author":[{"given":"Alex J.","family":"Goldstein","sequence":"first","affiliation":[{"name":"Department of Lab Medicine and Pathology, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas P.","family":"Leahy","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan J.","family":"Sniadecki","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"33","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"issue":"7","key":"2025122309242696100_bib1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.4330\/wjc.v7.i7.410","article-title":"Cardiac Involvement in Duchenne and Becker Muscular Dystrophy","volume":"7","year":"2015","journal-title":"World J. 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