{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:54:43Z","timestamp":1788850483568,"version":"build-2803163510"},"reference-count":188,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"US Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-21-1-0424"],"award-info":[{"award-number":["W81XWH-21-1-0424"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biomedical Laboratory Research and Development Service of Veterans Affairs Office of Research and Development","award":["I01 BX002137"],"award-info":[{"award-number":["I01 BX002137"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL164415"],"award-info":[{"award-number":["1R01HL164415"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Defense","award":["USAMRAA W81XWH-21-1-0426"],"award-info":[{"award-number":["USAMRAA W81XWH-21-1-0426"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-111072"],"award-info":[{"award-number":["MOP-111072"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-130373"],"award-info":[{"award-number":["MOP-130373"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myotonic Dystrophy Type 1 (DM1) is a complex multisystemic genetic disorder caused by CTG repeat expansions in the DMPK gene, leading to RNA toxicity and widespread splicing defects. These splicing abnormalities affect multiple systems, including the respiratory, skeletal, cardiac, nervous, and endocrine systems, resulting in aggressive symptoms that significantly impact quality of life and survival. Cardiac complications are the second leading cause of deaths in DM1, after respiratory insufficiency. Current research is largely focused on understanding cardiac pathology in DM1. This review highlights recent advancements in the clinical and pathological characterization of DM1 cardiac involvement, preclinical models used to study cardiac dysfunction, and emerging therapeutic strategies that target the molecular basis of DM1. Promising approaches include RNA-targeting strategies such as antisense oligonucleotides (ASOs), gene-editing tools like CRISPR-Cas9, and small molecules that modulate RNA splicing. ASOs aim to reduce toxic RNA accumulation, CRISPR-based approaches aim to excise or correct the expanded CTG repeats, and repurposed small-molecule drugs, such as vorinostat, tideglusib, and metformin, could serve as potential therapeutic agents for DM1 patients with cardiac complications. Despite this progress, several challenges remain: the heterogeneity of cardiac manifestations, unpredictable and often silent progression of arrhythmias, limited therapeutic options beyond implantable cardioverter-defibrillator (ICD)\/pacemaker implantations, and complex interplay with the multisystemic nature of DM1. More research and well-designed clinical trials are urgently needed to translate these promising strategies into effective treatments for DM1-associated cardiac disease. Here, we discuss the current knowledge in DM1 cardiac pathology and preclinical models as well as the benefits and pitfalls of the available therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms262210992","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:57:13Z","timestamp":1763038633000},"page":"10992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5022-1683","authenticated-orcid":false,"given":"Vamsi Krishna Murthy","family":"Ginjupalli","sequence":"first","affiliation":[{"name":"Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY 11209, USA"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Baptiste","family":"Reisqs","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY 11209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cupelli","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY 11209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9500-2839","authenticated-orcid":false,"given":"Mohamed","family":"Chahine","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"},{"name":"CERVO Research Center, Institut Universitaire en Sant\u00e9 Mentale de Qu\u00e9bec, Quebec City, QC G1J 2G3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Boutjdir","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY 11209, USA"},{"name":"Departments of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Sciences University, New York, NY 11203, USA"},{"name":"Department of Medicine, Cardiology Division, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/0092-8674(92)90154-5","article-title":"Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3\u2032 end of a transcript encoding a protein kinase family member","volume":"68","author":"Brook","year":"1992","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.neurol.2016.08.003","article-title":"Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification","volume":"172","author":"Dogan","year":"2016","journal-title":"Rev. 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