Abstract 10441: Latent Genetic Backgrounds and Molecular Pathogenesis in Acquired Long QT Syndrome with Distinct Arrhythmic Triggers
Introduction: A part of patients with acquired long QT syndrome (aLQTS) has been shown to carry mutations in cardiac ion channel genes similar to those identified in congenital long QT syndrome (cLQTS). Drugs and bradycardia are typical triggers for aLQTS, but it remains unknown whether these 2 subtypes of aLQTS have distinct genetic backgrounds.
Methods: Genetic testing was carried out for cLQTS-related genes (KCNQ1 , KCNH2 , SCN5A , KCNE1 , and KCNE2 ) in 34 subjects (20 drug-induced aLQTS and 14 bradycardia-induced aLQTS). Biophysical characteristics of the identified aLQTS-associated mutations were analyzed using a heterologous expression system (CHO cell line) and a computer simulation model.
Results: Bradycardia-induced aLQTS displayed significantly longer QTc interval than those with drug-induced aLQTS when without ventricular arrhythmias (495±42 vs. 446±29 ms, p<0.05). On the other hand, the positive-mutation rates were similar between the 2 groups (drug-induced aLQTS vs. bradycardia-induced aLQTS, 8 of 20 [40%] vs. 4 of 14 [29%], p=0.49). In experimental studies, KCNQ1 and KCNH2 mutant channels showed complex gating defects and a decreased current density. With the Luo-Rudy simulation model of action potentials, action potential durations of drug-induced aLQTS were between those of WT and cLQTS with representative mutations while those of bradycardia-induced aLQTS were similar to cLQTS.
Conclusions: The patients with aLQTS had similar positive-LQTS-related gene mutation rates irrespective of its triggers, but functional defects induced by the mutations differed depending on triggers of aLQTS.
- © 2010 by American Heart Association, Inc.