Key result
LQT3 genotype linked to ~6.6-fold higher risk of early-onset AF vs genotype-negative controls.
Why the study?
Large-scale studies assessing the risk of atrial fibrillation among patients with long QT syndrome and its relationship to LQTS genotype and manifestations were lacking.
Does the specific LQTS genotype alter the lifetime risk of incident atrial fibrillation and predict subsequent cardiac events compared to genotype-negative controls?
Cohort (n=3,806)
Yes
Does the specific LQTS genotype alter the lifetime risk of incident atrial fibrillation and predict subsequent cardiac events compared to genotype-negative controls?
LQT3 mutations confer a significantly heightened risk of early-onset atrial fibrillation which predicts subsequent severe cardiac events, whereas LQT2 mutations appear to offer a protective effect against late-onset atrial fibrillation.
LQT3 patients may merit earlier AF monitoring; extends LQTS genotype-phenotype data but remains hypothesis-generating.
Background: Long QT syndrome (LQTS) is caused by the abnormal function of ion channels, which may also affect atrial electrophysiology and be associated with the risk of atrial fibrillation (AF). However, large-scale studies of AF risk among patients with LQTS and its relation to LQTS manifestations are lacking. We aimed to assess the risk of AF and its relationship to the LQTS genotype and the long-term prognosis in patients with LQTS. Methods: Genotype-positive patients with LQTS (784 LQT1, 746 LQT2, and 233 LQT3) were compared with 2043 genotype-negative family members. Information on the occurrence of AF was based on physician-reported ECG-verified events. Multivariate Cox proportional hazards regression analyses were performed for ages 0 to 60 and after 60 years (reflecting an early and late-onset of AF) to assess the risk of incident AF by genotype and the relationship of AF to the risk of cardiac events defined as syncope, documented torsades de pointes, and aborted cardiac arrest or sudden cardiac death. Results: In patients followed from birth to 60 years of age, patients with LQT3 had an increased risk of AF compared with genotype-negative family members (hazard ratio=6.62; 95% CI, 2.04–21.49; P <0.001), while neither LQT1 nor LQT2 demonstrated increased AF risk. After the age of 60 years, patients with LQT2 had significantly lower risk of AF compared with genotype-negative controls (hazard ratio=0.07; 95% CI, 0.01–0.53, P =0.011). AF was a significant predictor of cardiac events in patients with LQT3 through the age of 60 (hazard ratio=5.38; 95% CI, 1.17–24.82; P =0.031). Conclusions: Our data demonstrate an increased risk of early age AF in patients with LQT3 and also indicate a protective effect of the LQT2 genotype in it’s association with a decreased risk of AF after the age of 60.
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Platonov et al. (2019) conducted a cohort in Long QT syndrome (n=3,806). LQT3 Genotype vs. Genotype-negative family members was evaluated on Incident early-onset atrial fibrillation (from birth to 60 years of age) (HR 6.62, 95% CI 2.04-21.49, p=<0.001). The LQT3 genotype significantly increased the risk of early-onset atrial fibrillation compared with genotype-negative family members (HR 6.62), acting as a significant predictor of cardiac events.
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