Functional Epicardial Conduction Disturbances Due to a SCN5A Variant Associated With Brugada Syndrome.
Brugada syndrome
SCN5A variant
epicardial arrhythmogenic conduction substrate
right ventricle
sudden cardiac death
Journal
JACC. Clinical electrophysiology
ISSN: 2405-5018
Titre abrégé: JACC Clin Electrophysiol
Pays: United States
ID NLM: 101656995
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
03
02
2023
revised:
06
03
2023
accepted:
10
03
2023
medline:
11
8
2023
pubmed:
25
5
2023
entrez:
25
5
2023
Statut:
ppublish
Résumé
Brugada syndrome is a significant cause of sudden cardiac death (SCD), but the underlying mechanisms remain hypothetical. This study aimed to elucidate this knowledge gap through detailed ex vivo human heart studies. A heart was obtained from a 15-year-old adolescent boy with normal electrocardiogram who experienced SCD. Postmortem genotyping was performed, and clinical examinations were done on first-degree relatives. The right ventricle was optically mapped, followed by high-field magnetic resonance imaging and histology. Connexin-43 and Na A Brugada-related SCD diagnosis was established for the donor because of a SCN5A Brugada-related variant (p.D356N) inherited from his mother, together with a concomitant NKX2.5 variant of unknown significance. Optical mapping demonstrated a localized epicardial region of impaired conduction near the outflow tract, in the absence of repolarization alterations and microstructural defects, leading to conduction blocks and figure-of-8 patterns. Na This study demonstrates for the first time that SCD associated with a Brugada-SCN5A variant can be caused by localized functionally, not structurally, impaired conduction.
Sections du résumé
BACKGROUND
Brugada syndrome is a significant cause of sudden cardiac death (SCD), but the underlying mechanisms remain hypothetical.
OBJECTIVES
This study aimed to elucidate this knowledge gap through detailed ex vivo human heart studies.
METHODS
A heart was obtained from a 15-year-old adolescent boy with normal electrocardiogram who experienced SCD. Postmortem genotyping was performed, and clinical examinations were done on first-degree relatives. The right ventricle was optically mapped, followed by high-field magnetic resonance imaging and histology. Connexin-43 and Na
RESULTS
A Brugada-related SCD diagnosis was established for the donor because of a SCN5A Brugada-related variant (p.D356N) inherited from his mother, together with a concomitant NKX2.5 variant of unknown significance. Optical mapping demonstrated a localized epicardial region of impaired conduction near the outflow tract, in the absence of repolarization alterations and microstructural defects, leading to conduction blocks and figure-of-8 patterns. Na
CONCLUSIONS
This study demonstrates for the first time that SCD associated with a Brugada-SCN5A variant can be caused by localized functionally, not structurally, impaired conduction.
Identifiants
pubmed: 37227351
pii: S2405-500X(23)00207-4
doi: 10.1016/j.jacep.2023.03.009
pmc: PMC10406612
pii:
doi:
Substances chimiques
SCN5A protein, human
0
Connexins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1248-1261Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL148803
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures This work received financial support from the French Government as part of the “Investments of the Future” program managed by the National Research Agency (ANR-10-IAHU04-LIRYC), the Leducq-Foundation (RHYTHM network, 16CVD02), and the Fondation Coeur et Artères (FC17T2). Dr Barc is supported by the ANR JCJC LEARN (R21006NN, RPV21014NNA). Dr Schott is supported by IRP-, an I-SITE NExT health and engineering initiative (Ecole Centrale & Nantes University) and by the IRP- GAINES funded by INSERM and CNRS. Dr Marionneau is supported by the ANR-16-CE92-0013-01 and the National Institutes of Health (R01-HL148803). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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