Background: The QT interval, an electrocardiogram (ECG) parameter, can be corrected for heart rate to obtain the QTc, an indicator of ventricular repolarization widely used as a predictor of ventricular arrhythmia. Although prolonged QTc and atrial fibrillation (AF) development are linked, there are few reports of QTc variability and AF development. Purpose: To identify a relationship between QTc prolongation and variability and new-onset AF in the general Japanese population. Methods: This retrospective study evaluated the annual health check-up data of 103,304 adults (50,438 males; age, 54±15 years) without AF at baseline, between April 2005 and October 2018. Most participants underwent annual health examinations as recommended by the Japanese health welfare policy. The QTc times were calculated with the Bazett formula (QTc=QT/√RR), using the mean QT and RR intervals. QTc variability was evaluated as the difference between the maximum and minimum QTc values at multiple checkups. AF was diagnosed using a 12-lead surface ECG. The strength of the association between QTc prolongation and variability and new-onset AF was determined using logistic regression analyses. Multivariate analyses were adjusted for clinical variables (age, sex, obesity, hypertension, dyslipidemia, diabetes, estimated glomerular filtration rate, and habitual drinking). Results: The median follow-up time was 6 years. During follow-up, 341 (0.3%) new AF cases were recorded. Univariate analysis revealed a significant increase in new-onset AF in the QTc prolongation (odds ratio [OR] per 10 ms, 1.08; 95% confidence interval [CI], 1.03-1.13; p<0.001) and the QTc variability (OR per 10 ms, 1.15; 95% CI, 1.07-1.23; p<0.001). After adjusting for clinical variables, multivariate analysis revealed that QTc prolongation and variability were significantly associated with new-onset AF (OR per 10 ms, 1.09; 95% CI, 1.04-1.14; p<0.001) (OR per 10 ms, 1.16; 95% CI, 1.09-1.24; p<0.001). Conclusions: QTc prolongation and variability are associated with an increased risk of new-onset AF in the general Japanese population. Although they have been reported to be involved with the autonomic nervous system, the mechanism of this causal relationship requires further investigation.
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