1209Atrial fibrillation in long QT syndrome as a risk indicator of cardiac events

Abstract

Background: Long QT syndrome (LQTS) is caused by abnormal function of ion channels, which are not confined to ventricular myocardium but may also affect atrial electrophysiology and the risk of atrial fibrillation (AF). However, large-scale studies of AF risk among LQTS patients and its relation to LQTS manifestations are lacking. Objective(s): To assess the risk of AF and its relationship the long-term prognosis in patients with the most common LQTS variants. Material: Genotype-positive patients with LQTS (784 LQT1, 746 LQT2 and 233 LQT3) were compared with 2043 genotype-negative family members. Information on AF included physician-reported, ECG-verified or AF documented by device interrogations. Cox regression analysis adjusted for gender, QTc and timedependent beta-blocker therapy was performed to assess the risk of incident AF and its relationship to cardiac events defined as syncope, documented torsades de pointes, appropriate ICD therapy, aborted cardiac arrest or sudden cardiac death. Result(s): Kaplan-Meier curve analysis for AF risk is presented in the Figure. In the age interval 20-60 years, LQT3 patients had increased risk of AF compared to genotype-negative family members (HR=4.7, 95% CI 2.38-9.49, p<0.001), while neither LQT1 or LQT2 demonstrated increased AF risk. In the multivariable analysis that included adjustments for LQTS genotype, time-dependent AF remained significant predictor of cardiac events (HR=4.64, 95% CI 1.66-13.02, p=0.0035), which was mainly driven by incident AF in the LQT3 group, in which risk estimates for cardiac events (HR=4.22, 95% CI 0.91-19.55, p=0.065) and aborted cardiac arrest/sudden cardiac death (HR=7.09, 95% CI 0.76-66.03, p=0.085) demonstrated similar hazard even though subgroup analysis was underpowered for the clinical outcome endpoints. Conclusion(s): Our data support earlier suggested AF hazard associated with LQT3 genotype and for the first time indicate the association between AF and arrhythmic manifestations of LQTS, mainly confined to the LQT3 genotype. (Figure Presented).