0012 : Antiarrhythmic action of flecainide in polymorphic ventricular arrhythmias caused by a gain-of-function mutation in the Nav1.5 sodium channel

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• 作者：Mohamed Yassine Amarouch¹ ; ^{mohamed.amarouch@usmba.ac.ma" class="auth_mail" title="E-mail the corresponding author} ; Jaakko Leinonen² ; Annukka Marjamaa³ ; Annukka M. Lahtinen⁴ ; Kimmo Kontula⁴ ; Lauri Toivonen³ ; Elisabeth Widen² ; Heikki Swan³ ; Hugues Abriel⁵
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：232
• 全文大小：49 K

文摘

The cardiac sodium channel Nav1.5, encoded by the gene SCN5A, is associated with several hereditary arrhythmias. The gain-of-function mutation p.I141V in SCN5A was identified in a large family with exercise-induced polymorphic ventricular arrhythmias. The aim of this study was to evaluate the clinical and molecular effect of flecanide therapy on patients with this syndrome. First, the functional alterations caused by the p.I141V mutation were confirmed to lead to an increase in the sodium window current. Next, eleven p.I141V carriers who exhibited frequent multiformic premature ventricular complexes (PVCs) during exercise were subjected to exercise stress tests, both before and after intravenous infusion of 2 mg/kg flecainide. This treatment significantly reduced the frequency of PVCs during and after exercise. The in vitro effects of flecainide were evaluated using the patch-clamp technique. The sensitivity of the p.I141V mutant channel to flecainide was compared to that of the wild type channel. Perfusion of flecainide inhibited the peak and window currents in both groups.

Altogether, these data demonstrates that flecainide may serve as an effective treatment for the defect in Nav1.5 that leads to an increased sodium window current.

The author hereby declares no conflict of interest