The PR interval and risk of cardiac events and mortality: a nationwide study

Abstract Background The electrocardiographic PR-interval reflects the time from activation of the sinus node to the start of the ventricular depolarization. Studies of the PR-interval and its association with cardiac events have shown inconsistent results, often limited by small cohort sizes and availability of only one electrocardiogram (ECG) per individual. We aimed at investigating the association of the PR-interval – and its temporal changes – with cardiac endpoints and all-cause mortality in a large, nationwide cohort. Methods ECGs from Danish Nationwide Electrogram Cohort (11,952,349 ECGs, n=2,485,981) were linked with national registries and were excluded based on age <18 years, brady- and tachycardia, non-sinus rhythm, pre-excitation syndromes, congenital heart disease, inflammatory cardiomyopathy, preexisting cardiac device, and extreme outliers. The association between the first (index) PR-interval, and absolute changes in PR-interval over time (ΔPR), and cardiac events and all-cause mortality were studied using multivariable Cox proportional hazard models. Results A total of 9,022,066 ECGs (n= 2,234,660, median age 57 years; 53% female) remained after exclusion, 1,213,095 individuals had >1 ECG available, and the median follow-up was 6.1 years. The median index PR-interval was 158 ms (IQR 142-176); a short PR- (<120 ms) or long (>200 ms) PR-interval was found in 2.9% and 7.4% of the cohort, respectively. Prevalence of PR >200 ms increased with age and was more frequent in men. Cox modelling of the index PR-interval showed a U-shaped association in the hazard ratios (HR) of atrial fibrillation/flutter, heart failure, and ventricular arrhythmias with the highest HR observed in individuals with the shortest (HR range 1.04-1.16, P<0.05) and longest PR-interval (HR range 1.09-1.24, P<0.05) (Figure). In syncope, HR showed a stepwise increase above a PR threshold of ≥170 ms (HR range 1.08-1.36, P<0.001). In high-degree atrioventricular block or implantation of a cardiac device, HR showed a linear association with increasing PR values (HR range 0.8-2.11, P<0.05). The association with all-cause mortality was J-shaped (HR range 0.96-1.44, P<0.05). Cox modelling of temporal changes in the PR interval showed a stepwise increase in HR of all six endpoints with increasing ΔPR values. Conclusion Short, long, and temporal changes in the PR-interval, are all associated with increased rate of cardiac events and all-cause mortality.