{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:47:40Z","timestamp":1753876060982,"version":"3.41.2"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Brugada Syndrome (BrS) is a cardiogenetic disease known for its association with sudden cardiac death (SCD) in individuals with structurally normal hearts. The prevalence of BrS is higher in males, who also face a greater risk of SCD. Its higher prevalence and worse outcome in male subjects may be due to testosterone effects on ion channels expression and function. The influence of testosterone on cardiac action potentials, both genomically and non-genomically, underscores its potential role in unmasking the syndrome and triggering life-threatening arrhythmias. Notably, testosterone replacement therapy (TRT), used for hypogonadism and gender reassignment, has been linked to BrS unmasking. The role of epicardial ablation in symptomatic BrS patients where hormonal therapy cannot be discontinued is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In this study we describe the first two cases of substrate mapping and ablation in BrS patients experiencing arrhythmic events while on TRT. In both cases, high-density epicardial mapping revealed abnormal areas of prolonged and fragmented electrograms in the right ventricular (RV) outflow tract and anterior wall. These abnormalities were completely abolished by radiofrequency ablation (RFA). After ablation, both patients showed a persistent normalization of the ECG and were free from ventricular arrhythmias at follow-up, despite ongoing TRT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>RFA can be considered as a therapeutic option in symptomatic BrS patients with a high-risk profile who cannot discontinue TRT, being essential for restoring their normal physiology or preserving their sexual identity. As testosterone use is increasing, further studies are warranted to define a standardized diagnostic and therapeutic strategy in this specific subset of BrS patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euad254","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T20:14:33Z","timestamp":1693426473000},"source":"Crossref","is-referenced-by-count":2,"title":["Arrhythmogenic substrate elimination for safe testosterone therapy in symptomatic Brugada syndrome patients"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1531-3504","authenticated-orcid":false,"given":"Gabriele","family":"Negro","sequence":"first","affiliation":[{"name":"Arrhythmia and Electrophysiology Center, IRCCS Policlinico San Donato , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-2675","authenticated-orcid":false,"given":"Antonio","family":"Boccellino","sequence":"additional","affiliation":[{"name":"Arrhythmia and Electrophysiology Center, IRCCS Policlinico San Donato , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Napolano","sequence":"additional","affiliation":[{"name":"Arrhythmia and Electrophysiology Center, IRCCS Policlinico San Donato , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8298-7800","authenticated-orcid":false,"given":"Emanuele","family":"Micaglio","sequence":"additional","affiliation":[{"name":"Arrhythmia and Electrophysiology Center, IRCCS Policlinico San Donato , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3267-9850","authenticated-orcid":false,"given":"Zarko","family":"Calovic","sequence":"additional","affiliation":[{"name":"Arrhythmia and Electrophysiology Center, IRCCS Policlinico San Donato , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0712-2161","authenticated-orcid":false,"given":"Luigi","family":"Anastasia","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University , Via Olgettina 58, 20132 Milan , Italy"},{"name":"Institute of Molecular and Translational Cardiology (IMTC) , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-5467","authenticated-orcid":false,"given":"Giuseppe","family":"Ciconte","sequence":"additional","affiliation":[{"name":"Arrhythmia and Electrophysiology Center, IRCCS Policlinico San Donato , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"},{"name":"Vita-Salute San Raffaele University , Via Olgettina 58, 20132 Milan , Italy"},{"name":"Institute of Molecular and Translational Cardiology (IMTC) , Piazza Malan 2, San Donato Milanese, 20097 Milan , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,9,1]]},"reference":[{"key":"2023090110111647600_euad254-B1","first-page":"665","article-title":"J-Wave syndromes expert consensus conference report: emerging concepts and gaps in 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electrocardiogram after surgical castration: a role for testosterone and an explanation for the male preponderance","volume":"26","author":"Matsuo","year":"2003","journal-title":"Pacing Clin Electrophysiol PACE"},{"key":"2023090110111647600_euad254-B8","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.19102\/icrm.2019.100202","article-title":"Brugada syndrome unmasked by use of testosterone in a transgender male: gender trumps sex as a risk factor","volume":"10","author":"Sichrovsky","year":"2019","journal-title":"J Innov Cardiac Rhythm Manag"},{"key":"2023090110111647600_euad254-B9","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1093\/eurheartj\/ehaa942","article-title":"Brugada syndrome genetics is associated with phenotype severity","volume":"42","author":"Ciconte","year":"2021","journal-title":"Eur Heart 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