Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study.

Details

Serval ID
serval:BIB_D3F4AD7667C7
Type
Article: article from journal or magazin.
Collection
Publications
Title
Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study.
Journal
Circulation
Author(s)
Coronel R., Casini S., Koopmann T.T., Wilms-Schopman F.J., Verkerk A.O., de Groot J.R., Bhuiyan Z., Bezzina C.R., Veldkamp M.W., Linnenbank A.C., van der Wal A.C., Tan H.L., Brugada P., Wilde A.A., de Bakker J.M.
ISSN
1524-4539 (Electronic)
ISSN-L
0009-7322
Publication state
Published
Issued date
01/11/2005
Peer-reviewed
Oui
Volume
112
Number
18
Pages
2769-2777
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown.
A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient's explanted heart was studied electrophysiologically and histopathologically. Whole-cell currents were measured in HEK293 cells expressing wild-type or mutated sodium channels from the patient. The right ventricular outflow tract (RVOT) endocardium showed activation slowing and was the origin of ventricular fibrillation without a transmural repolarization gradient. Conduction restitution was abnormal in the RVOT but normal in the left ventricle. Right ventricular hypertrophy and fibrosis with epicardial fatty infiltration were present. HEK293 cells expressing a G1935S mutation in the gene encoding the cardiac sodium channel exhibited enhanced slow inactivation compared with wild-type channels. Computer simulations demonstrated that conduction slowing in the RVOT might have been the cause of the ECG changes.
In this patient with BS, conduction slowing based on interstitial fibrosis, but not transmural repolarization differences, caused the ECG signs and was the origin of ventricular fibrillation.

Keywords
Adult, Amino Acid Substitution, Cell Line, Electric Stimulation, Humans, Kidney, Male, Reference Values, Sodium Channels/genetics, Sodium Channels/physiology, Syndrome, Ventricular Fibrillation/genetics, Ventricular Fibrillation/pathology, Ventricular Fibrillation/physiopathology
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2018 16:37
Last modification date
20/08/2019 16:53
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