Clinical, histologic, and molecular associations of early and late recurrence after thoracoscopic ablation for atrial fibrillation.

BACKGROUND

Early recurrence (ER) of atrial fibrillation (AF) is common after ablation. However, its mechanism remains unclear.

OBJECTIVE

This study aimed to investigate the variability in the timing of ER and its relation to late recurrence (LR) and explore potential underlying substrate.

METHODS

We prospectively enrolled 449 patients (62 ± 9 years; 26.7% female) undergoing thoracoscopic ablation of advanced AF with concomitant left atrial appendage excision. Rhythm surveillance was performed for 2 years. ER was defined as any atrial tachyarrhythmia lasting >30 seconds within 90 days after ablation; LR as recurrence after 90 days. Patients were categorized as having no ER, ER at 0-30 days, or ER at 31-90 days. We performed histologic and bulk RNA-sequencing analyses of the excised left atrial appendage to explore different mechanisms of ER.

RESULTS

ER occurred in 176 of 449 patients (39.2%), of whom 152 (86.4%) experienced their first ER episode within 30 days. Compared with no ER, ER at 0-30 days and 31-90 days was associated with higher LR risk (hazard ratio 1.52 and 2.01; log-rank P = .002). Higher proteoglycan content was associated with an increased risk of LR. Bulk RNA sequencing showed that fibroinflammatory pathways were enriched in patients with ER + LR vs patients without any recurrence.

CONCLUSION

After thoracoscopic AF ablation, ER was associated with an increased risk of LR. ER occurring at 31-90 days was associated with a higher observed risk of LR than ER occurring at 0-30 days. Exploratory findings suggested differences in extracellular matrix remodeling and inflammatory signaling across recurrence patterns.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier for AFACT study: NCT01091389, NL30199.018.10; MARK-AF registry: NL50069.018.14.