Stimulated periodic repolarisation dynamics as a predictor of new-onset device-detected atrial fibrillation

Periodic Repolarisation Dynamics (PRD) is a novel ECG-based risk marker reflecting low-frequency oscillations in cardiac repolarisation, caused by efferent sympathetic nervous system activity. Elevated PRD (≥ 5.75 deg²) predicts malignant arrhythmias and sudden cardiac death in both ischaemic and non-ischaemic cardiomyopathy. The relationship between PRD and atrial arrhythmias, particularly atrial fibrillation (AF), remains unclear despite growing evidence of cardiac autonomic dysfunction (c-AD) in AF pathogenesis. This study examines the relationship between c-AD, as measured by PRD, and the incidence of device-detected atrial fibrillation (DDAF) in patients with implanted cardiac pacemakers.

In the observational ACasA study, patients with implanted cardiac pacemakers were prospectively enrolled. High-resolution ECG recordings under native (AAI) and stimulated (DDD) conditions were used to calculate PRD at the baseline visit. c-AD was defined by native PRD ≥ 5.75 deg² and stimulated PRD > 4.3 deg², as determined by the Youden index method. DDAF episodes (≥ 6 minutes) were identified via continuous telemedical pacemaker monitoring. The primary endpoint was time to first DDAF episode, analysed with Kaplan-Meier curves and Cox regression to assess the relationship between PRD and DDAF, adjusting for potential confounders.

Between November 2021 and January 2024, a total of 233 patients were prospectively enrolled. Patients with known clinical AF were excluded. Overall, 13,801 patient-days of 111 patients (median age 76 years, 44% female) were analysed. Of the 111 patients analysed, 60 had c-AD (median stimulated PRD: 7.7 [5.7–8.6] deg²) and 51 did not (median stimulated PRD: 3.8 [2.0–7.3] deg²). During a 120-day follow-up, DDAF occurred in 41.2% of patients with c-AD, compared to 21.7% in those without c-AD (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.3–8.5; p = 0.009). However, native PRD showed no significant effect on the incidence of DDAF (HR, 1.27; 95% CI, 0.4–4.0).

Elevated stimulated PRD predicts the occurrence of DDAF in pacemaker patients without prior clinical AF, highlighting cardiac autonomic dysfunction’s role in atrial arrhythmogenesis. Native PRD did not show a significant association with DDAF, suggesting stimulated PRD may offer better predictive value. Further research is needed to explore the relationship between pacing modalities, autonomic function, and arrhythmogenesis.