Referenced in: none

Automatically associated channels: Kv11.1 , Kv7.1 , Nav1.5

Title: Atrioventricular block-induced Torsades de Pointes with clinical and molecular backgrounds similar to congenital long QT syndrome.

Authors: Yuko Oka, Hideki Itoh, Wei-Guang Ding, Wataru Shimizu, Takeru Makiyama, Seiko Ohno, Yukiko Nishio, Tomoko Sakaguchi, Akashi Miyamoto, Mihoko Kawamura, Hiroshi Matsuura, Minoru Horie

Journal, date & volume: Circ. J., 2010 Nov 25 , 74, 2562-71

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20975234

Abstract
Atrioventricular block (AVB) sometimes complicates QT prolongation and torsades de pointes (TdP).The clinical and genetic background of 14 AVB patients (57±21 years, 13 females) who developed QT prolongation and TdP was analyzed. Electrophysiological characteristics of mutations were analyzed using heterologous expression in Chinese hamster ovary cells, together with computer simulation models. Every patient received a pacemaker or implantable cardioverter defibrillator; 3 patients had recurrence of TdP during follow-up because of pacing failure. Among the ECG parameters, QTc interval was prolonged to 561±76ms in the presence of AVB, but shortened to 495±42ms in the absence of AVB. Genetic screening for KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 revealed four heterozygous missense mutations of KCNQ1 or KCNH2 in 4 patients (28.6%). Functional analyses showed that all mutations had loss of functions and various gating dysfunctions of I(Ks) or I(Kr). Finally, action potential simulation based on the Luo-Rudy model demonstrated that most mutant channels induced bradycardia-related early afterdepolarizations.Incidental AVB, as a trigger of TdP, can manifest as clinical phenotypes of long QT syndrome (LQTS), and that some patients with AVB-induced TdP share a genetic background with those with congenital LQTS.