J-shaped association between QTc interval duration and the risk of atrial fibrillation: results from the Copenhagen ECG study

Abstract

Objectives: The aim of this study was to investigate whether the heart rate-corrected QT (QTc) interval on the electrocardiogram (ECG) is associated with the onset of atrial fibrillation (AF).

Background: Patients with hereditary short-QT or long-QT syndromes, representing the very extremes of the QT interval, both seem to have a high prevalence of AF.

Methods: A total of 281,277 subjects were included, corresponding to one-third of the population of the greater region of Copenhagen. These subjects underwent digital ECG recordings in a general practitioner's core facility from 2001 to 2010. Data on drug use, comorbidities, and outcomes were collected from Danish registries.

Results: After a median follow-up period of 5.7 years, 10,766 subjects had developed AF, of whom 1,467 (14%) developed lone AF. Having a QTc interval lower than the first percentile (≤372 ms) was associated with a multivariate-adjusted hazard ratio of 1.45 (95% confidence interval: 1.14 to 1.84; p = 0.002) of AF, compared with the reference group (411 to 419 ms). From the reference group and upward, the risk of AF increased with QTc interval duration in a dose-response manner, reaching a hazard ratio of 1.44 (95% confidence interval: 1.24 to 1.66, p < 0.001) for those with QTc intervals ≥99th percentile (≥464 ms). The association with respect to longer QTc intervals was stronger for the outcome of lone AF, as evidenced by a hazard ratio of 2.32 (95% confidence interval: 1.52 to 3.54, p < 0.001) for having a QTc interval ≥99th percentile (≥458 ms).

Conclusions: In this large ECG study, a J-shaped association was found between QTc interval duration and risk of AF. This association was strongest with respect to the development of lone AF.