Clinical and Genetic Features of Japanese Patient with Congenital Long QT Syndrome

Abstract

Backgrounds: Genotype-phenotype aspects in Japanese patients (pts) with congenital long QT syndrome (LQTS) have not been fully elucidated. Methods and Results: Genotyped LQTS patients from Japanese multicenter registry (402 LQT1, 381 LQT2, and 113 LQT3 pts) were investigated. Age at first cardiac event (CE) was significantly lower and corrected QT (QTc) interval was significantly shorter in LQT1 than in LQT2 and LQT3 (13±14, 19±15, 17±20 yo; P=0.0004, 475±46, 489±46, 482±58 ms; P=0.0003). Notched T wave (NTW) was more frequently observed in LQT2 (77%) than in LQT1 (9%) and LQT3 (10%). T wave alternance (TWA) was more frequently found in LQT3 (13%) compared with LQT1 (4%) and LQT2 (6%). Multivariate Cox-regression demonstrated that LQT1 and LQT2 pts with pore-site mutation and LQT3 pts with transmembrane mutation had significantly higher CE rate than those without (HR=1.52, 1.63, and 4.67, respectively). TWA (HR=2.37) in LQT1, longer QTc (HR=1.06 for QTc/10 ms) and NTW (HR=1.51) in LQT2, and longer QTc (HR=1.11), NTW (HR=3.26), and TWA (HR=2.51) in LQT3 were independent risk factors of CE. Conclusions: In addition to mutations located in transmembrane region, some electrocardiographic parameters can be available as predictors of cardiac events in 3 genotypes of Japanese LQTS.