Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome

Journal article


Chen, Gan-Xiao, Barajas-Martínez, Hector, Ciconte, Giuseppe, Wu, Cheng-I, Monasky, Michelle M, Xia, Hao, Li, Bian, Capra, John A, Guo, Kai, Zhang, Zhong-He, Chen, Xiu, Yang, Bo, Jiang, Hong, Tse, Gary, Mak, Chloe Miu, Aizawa, Yoshiyasu, Gollob, Michael H, Antzelevitch, Charles, Wilde, Arthur A M, Pappone, Carlo and Hu, Dan 2022. Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome. EBioMedicine. 87, p. 104388. https://doi.org/10.1016/j.ebiom.2022.104388
AuthorsChen, Gan-Xiao, Barajas-Martínez, Hector, Ciconte, Giuseppe, Wu, Cheng-I, Monasky, Michelle M, Xia, Hao, Li, Bian, Capra, John A, Guo, Kai, Zhang, Zhong-He, Chen, Xiu, Yang, Bo, Jiang, Hong, Tse, Gary, Mak, Chloe Miu, Aizawa, Yoshiyasu, Gollob, Michael H, Antzelevitch, Charles, Wilde, Arthur A M, Pappone, Carlo and Hu, Dan
AbstractBrugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever. A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively. In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5-81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS. In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever. None. [Abstract copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.]
KeywordsSudden cardiac death; Ventricular arrhythmias; Genetics; Fever; Brugada syndrome
Year2022
JournalEBioMedicine
Journal citation87, p. 104388
PublisherElsevier
ISSN2352-3964
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ebiom.2022.104388
Official URLhttps://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00570-9/fulltext
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Online12 Dec 2022
Publication process dates
Accepted15 Nov 2022
Deposited05 Jan 2023
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