Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study.
AP, action potential
DAD, delayed afterdepolarization
EAD, early afterdepolarization
ECG, electrocardiography
HCM, hypertrophic cardiomyopathy
ICa-L, L-type Ca current
IK, delayed-rectifier K current
INaL, late Na current
LVOT, left ventricular outflow tract
NCX, Na+/Ca2+ exchanger
QT interval
RyR, ryanodine receptor
SR, sarcoplasmic reticulum
action potentials
arrhythmias
diastolic dysfunction
hERG, human ether-à-go-go-related gene
hypertrophic cardiomyopathy
pCa, Ca activation level
safety
Journal
JACC. Basic to translational science
ISSN: 2452-302X
Titre abrégé: JACC Basic Transl Sci
Pays: United States
ID NLM: 101677259
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
15
04
2019
revised:
07
06
2019
accepted:
07
06
2019
entrez:
31
1
2020
pubmed:
31
1
2020
medline:
31
1
2020
Statut:
epublish
Résumé
Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular and molecular mechanisms of action are unknown. We tested disopyramide in cardiomyocytes from the septum of surgical myectomy patients: disopyramide inhibits multiple ion channels, leading to lower Ca transients and force, and shortens action potentials, thus reducing cellular arrhythmias. The electrophysiological profile of disopyramide explains the efficient reduction of outflow gradients but also the limited prolongation of the QT interval and the absence of arrhythmic side effects observed in 39 disopyramide-treated patients. In conclusion, our results support the idea that disopyramide is safe for outpatient use in obstructive patients.
Identifiants
pubmed: 31998849
doi: 10.1016/j.jacbts.2019.06.004
pii: S2452-302X(19)30187-1
pmc: PMC6978554
doi:
Types de publication
Journal Article
Langues
eng
Pagination
795-813Subventions
Organisme : British Heart Foundation
ID : FS/17/22/32644
Pays : United Kingdom
Informations de copyright
© 2019 The Authors.
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