{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:11:53Z","timestamp":1778080313905,"version":"3.51.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Innovation Council of the European Union"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Loss-of-function (LOF) variants in SCN5A are associated with Brugada syndrome (BrS), progressive conduction slowing, and other arrhythmias. While the prognosis of SCN5A carriers with a positive sodium channel blocker challenge (SCBC) is established, data on those with negative SCBC are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the clinical presentation and prognosis of SCN5A variant carriers with negative SCBC, and compare them to relatives with positive SCBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We retrospectively included patients from five university hospitals (2000\u20132024) carrying a pathogenic or likely pathogenic SCN5A variant and negative SCBC. Relatives with the same variant and positive SCBC were also analysed. Patients with spontaneous type 1 ECG, gain-of-function variants, double variants, or ACMG class 1\u20133 variants were excluded. Clinical, ECG, genetic, and follow-up data were collected. Conduction slowing was evaluated using the PR interval and QRS duration. The cohort included 162 patients from 43 families (median age 37 \u00b1 19 years, 46% male), of whom 69 (43%) had negative SCBC. Among these 69 patients, 25 (36%) had baseline intraventricular conduction defects, and 19 (28%) had first-degree AV block. After a median follow-up of 75 [40\u2013168] months, 52% of patients developed progressive conduction slowing. Negative SCBC patients had fewer conduction defects (36% vs. 70%, p = 0.002) and ICD implantations (1% vs. 23%, P &amp;lt; 0.001). Non-missense variants were associated with more conduction slowing (71% vs. 42%, P = 0.04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This multicentre study provides the largest analysis of SCN5A carriers with negative SCBC, showing excellent arrhythmic prognosis despite frequent progressive conduction slowing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/europace\/euag014","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T12:41:57Z","timestamp":1772196117000},"source":"Crossref","is-referenced-by-count":1,"title":["Clinical profile and prognosis of brugada syndrome\n                    <i>SCN5A<\/i>\n                    variant carriers with negative sodium channel blocker challenge"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0362-6351","authenticated-orcid":false,"given":"Elodie","family":"Surget","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology, Centre Hospitalier Universitaire Robert Debr\u00e9, Universit\u00e9 Paris Cit\u00e9 , 48 boulevard S\u00e9rurier, 75019 Paris ,","place":["France"]},{"name":"Department of Cardiology, Reference Center for Inherited Arrhythmic Syndromes, Centre Hospitalier Universitaire Bichat\u2013Claude Bernard , AP-HP, Universit\u00e9 Paris Cit\u00e9, 46 rue Henri Huchard, 75018 Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4631-6196","authenticated-orcid":false,"given":"Gael","family":"Clerici","sequence":"additional","affiliation":[{"name":"Department of Cardiology, CHR La R\u00e9union , Saint-Pierre ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-9320","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Sacher","sequence":"additional","affiliation":[{"name":"Department of Cardiology, CHU Bordeaux, H\u00f4pital Cardiologique du Haut-L\u00e9v\u00eaque , Bordeaux ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5716-6712","authenticated-orcid":false,"given":"Raphael","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Cardiology , CHU Rennes, Rennes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-1841","authenticated-orcid":false,"given":"Philippe","family":"Maury","sequence":"additional","affiliation":[{"name":"Department of Cardiology, CHU Toulouse , Toulouse ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-9461","authenticated-orcid":false,"given":"Isabelle","family":"Denjoy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Centre Hospitalier Universitaire Robert Debr\u00e9, Universit\u00e9 Paris Cit\u00e9 , 48 boulevard S\u00e9rurier, 75019 Paris ,","place":["France"]},{"name":"Department of Cardiology, Reference Center for Inherited Arrhythmic Syndromes, Centre Hospitalier Universitaire Bichat\u2013Claude Bernard, AP-HP, Universit\u00e9 Paris Cit\u00e9 , 46 rue Henri Huchard, 75018 Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3776-6072","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Thollet","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Genetics, Institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes, CHU Nantes, Nantes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4106-5946","authenticated-orcid":false,"given":"Julien","family":"Barc","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes , CHU Nantes, Nantes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-8310","authenticated-orcid":false,"given":"Jean Jacques","family":"Schott","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Genetics, Institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes, CHU Nantes, Nantes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Drapier","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Genetics, Institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes, CHU Nantes, Nantes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7751-2280","authenticated-orcid":false,"given":"Richard","family":"Redon","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Genetics, Institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes, CHU Nantes, Nantes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6961-2131","authenticated-orcid":false,"given":"Jean Baptiste","family":"Gourraud","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Medical Genetics, Institut du Thorax, INSERM, CNRS, Universit\u00e9 de Nantes, CHU Nantes, Nantes 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