Atrioventricular Block-Induced Torsades de Pointes With Clinical and Molecular Backgrounds Similar to Congenital Long QT Syndrome

作者：Oka Yuko; Itoh Hideki; Ding Wei Guang; Shimizu Wataru; Makiyama Takeru; Ohno Seiko; Nishio Yukiko; Sakaguchi Tomoko; Miyamoto Akashi; Kawamura Mihoko; Matsuura Hiroshi; Horie Minoru^*

来源：Circulation Journal, 2010, 74(12): 2562-2571.

DOI：10.1253/circj.CJ-10-0498

• Atrioventricular block
• Ion channels
• Long QT syndrome
• Torsades de pointes

Background: Atrioventricular block (AVB) sometimes complicates QT prolongation and torsades de pointes (TdP).
Methods and Results: 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+/-76 ms in the presence of AVB, but shortened to 495+/-42 ms 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.
Conclusions: Incidental AVB, as a trigger of TdP, can manifest as clinical phenotypes of long QT syndrome (LOTS), and that some patients with AVB-induced TdP share a genetic background with those with congenital LQTS. (Circ J 2010; 74: 2562-2571)

• 出版日期2010-12