Clinical and genetic relationships between the QTc interval and risk of a stroke among atrial fibrillation patients undergoing catheter ablation

Background and objectives A prolonged QTc interval is associated with an increased risk of a stroke or atrial fibrillation (AF). However, its direct causal relationship with AF associated a stroke has not been proven yet. To examine whether QTc interval is causally linked with risk of stroke in AF patients, we used the Mendelian randomization analysis. Subjects and methods Among 2742 patients (73.6% male; 58.2 ± 11.0 years old; 69.5% with paroxysmal AF) who underwent AF catheter ablation, we analyzed 1766 patients who had preablation sinus rhythm electrocardiograms off antiarrhythmic drugs after excluding amiodarone users. Among them, 1213 subjects had genome-wide association study dataset analyzable for the Mendelian randomization. We explored the mechanistic relationships between QTc interval (ms) and the risk of a stroke by analyzing the Mendelian randomization (1213 subjects) after reviewing 35 genetic polymorphisms associated with the QTc in 31 European descent studies. Results Among the patients in the higher quartile with a higher QTc, CHA2DS2-VASc score (p < 0.001), and age (p < 0.001), the proportions of a prior stroke (p < 0.001), females, heart failure, and persistent AF were significantly higher than in those in the lower quartile. The QTc was independently associated with the CHA2DS2-VASc score (β, 4.63E−5; 95% confidence interval, 3.57E−6–8.90E−5; p = 0.034) and ischemic strokes (odds ratio, 1.01; 95% confidence interval, 1.00–1.01; p = 0.027). However, there was no direct causal relationship between the QTc and CHA2DS2-VASc score or a prior stroke in either the one-sample or two-sample Mendelian randomizations. Conclusion The QTc was independently associated with the CHA2DS2-VASc score and strokes among the patients with AF who underwent catheter ablation, despite no genetically direct causal relationship.