{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:36:22Z","timestamp":1787960182799,"version":"build-2784847793"},"reference-count":117,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2016-02362316"],"award-info":[{"award-number":["GR-2016-02362316"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Brugada syndrome (BrS) is an inherited autosomal dominant genetic disorder responsible for sudden cardiac death from malignant ventricular arrhythmia. The term \u201cchannelopathy\u201d is nowadays used to classify BrS as a purely electrical disease, mainly occurring secondarily to loss-of-function mutations in the \u03b1 subunit of the cardiac sodium channel protein Nav1.5. In this setting, arrhythmic manifestations of the disease have been reported in the absence of any apparent structural heart disease or cardiomyopathy. Over the last few years, however, a consistent amount of evidence has grown in support of myocardial structural and functional abnormalities in patients with BrS. In detail, abnormal ventricular dimensions, either systolic or diastolic dysfunctions, regional wall motion abnormalities, myocardial fibrosis, and active inflammatory foci have been frequently described, pointing to alternative mechanisms of arrhythmogenesis which challenge the definition of channelopathy. The present review aims to depict the status of the art of concealed arrhythmogenic substrates in BrS, often resulting from an advanced and multimodal diagnostic workup, to foster future preclinical and clinical research in support of the cardiomyopathic nature of the disease.<\/jats:p>","DOI":"10.3390\/genes13101755","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T20:58:47Z","timestamp":1664398727000},"page":"1755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Concealed Substrates in Brugada Syndrome: Isolated Channelopathy or Associated Cardiomyopathy?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2880-6631","authenticated-orcid":false,"given":"Chiara","family":"Di Resta","sequence":"first","affiliation":[{"name":"Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-1404","authenticated-orcid":false,"given":"Andrea","family":"Villatore","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4282-7095","authenticated-orcid":false,"given":"Marianna","family":"Maia","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Pili","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fioravanti","sequence":"additional","affiliation":[{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-782X","authenticated-orcid":false,"given":"Rossella","family":"Tomaiuolo","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-8892","authenticated-orcid":false,"given":"Simone","family":"Sala","sequence":"additional","affiliation":[{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Benedetti","sequence":"additional","affiliation":[{"name":"UOC Screening Neonatale e Malattie Metaboliche, ASST Fatebenefratelli Sacco Ospedale dei Bambini \u201cVittore Buzzi\u201d, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-4000","authenticated-orcid":false,"given":"Giovanni","family":"Peretto","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jacc.2018.06.037","article-title":"Present Status of Brugada Syndrome","volume":"72","author":"Brugada","year":"2018","journal-title":"J. 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