{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:13:28Z","timestamp":1787375608500,"version":"build-2736575974"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medtronic and Abbott"},{"name":"AFM-telethon and Fond Marion Elisabeth Brancher"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Ventricular fibrillation (VF) occurring in the acute phase of ST-elevation myocardial infarction (STEMI) is the leading cause of sudden cardiac death worldwide. Several studies showed that reduced connexin 43 (Cx43) expression and reduced conduction velocity increase the risk of VF in acute myocardial infarction (MI). Furthermore, genetic background might predispose individuals to primary VF (PVF). The primary objective was to evaluate the presence of GJA1 variants in STEMI patients. The secondary objective was to evaluate the arrhythmogenic impact of GJA1 variants in STEMI patients with VF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The MAP-IDM prospective cohort study included 966 STEMI patients and was designed to identify genetic predisposition to VF. A total of 483 (50.0%) STEMI patients with PVF were included. The presence of GJA1 variants increased the risk of VF in STEMI patients [from 49.1 to 70.8%, P = 0.0423; odds ratio (OR): 0.40; 95% confidence interval: 0.16\u20130.97; P = 0.04]. The risk of PVF decreased with beta-blocker intake (from 53.5 to 44.8%, P = 0.0085), atrial fibrillation (from 50.7 to 26.4%, P = 0.0022), and with left ventricular ejection fraction &amp;gt;50% (from 60.2 to 41.4%, P &amp;lt; 0.0001). Among 16 GJA1 variants, three novel heterozygous missense variants were identified in three patients: V236I, H248R, and I327M. In vitro studies of these variants showed altered Cx43 localization and decreased cellular communication, mainly during acidosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Connexin 43 variants are associated with increased VF susceptibility in STEMI patients. Restoring Cx43 function may be a potential therapeutic target to prevent PVF in patients with acute MI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>Clinical Trial Registration: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00859300<\/jats:p><\/jats:sec>","DOI":"10.1093\/europace\/euac128","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T07:49:59Z","timestamp":1660031399000},"page":"101-111","source":"Crossref","is-referenced-by-count":9,"title":["Identification of Cx43 variants predisposing to ventricular fibrillation in the acute phase of ST-elevation myocardial infarction"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-2229","authenticated-orcid":false,"given":"Philippe","family":"Chevalier","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lyon, universit\u00e9 Lyon 1, Inserm, CNRS, INMG , Lyon F-69008 , France"},{"name":"Hospices Civils de Lyon, 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Boulevard Pinel, 69677 Bron Cedex , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Do\u00f1ate","family":"Puertas","sequence":"additional","affiliation":[{"name":"Signaling and Cardiovascular Pathophysiology\u2014UMR-S 1180, Inserm, Universit\u00e9 Paris-Saclay , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babken","family":"Asatryan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Inselspital, Bern University Hospital , Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-9674","authenticated-orcid":false,"given":"Antoine","family":"Delini\u00e8re","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, universit\u00e9 Lyon 1, Inserm, CNRS, INMG , Lyon F-69008 , France"},{"name":"Hospices Civils de Lyon, Groupement Hospitalier Est, Service de Rythmologie, Ho\u0302pital Cardiologique Louis Pradel , 59 Boulevard 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