Three-year follow up after pulsed-field and cryoballoon based pulmonary vein isolation supports a possible effect of autonomic modulation on atrial fibrillation recurrence

Abstract Background Changes in cardiac autonomic innervation can contribute to recurrent atrial fibrillation (AF) after ablation. Previous data showed that pulsed-field ablation (PFA) inflicts less neurocardiac damage than cryoballoon ablation (CBA) during PVI. To evaluate the contribution of autonomic denervation on AF ablation success, pulmonary vein (PV) reconnection rate and the impact of neurocardiac damage during PVI on autonomic functioning using biomarker (S100B) and heart rate (HR) measurements and their time-dependent changes during the first 6 months after PVI were collected and related to three-year follow-up for recurrent AF in patients undergoing a first PVI. Methods We prospectively included consecutive patients in sinus rhythm prior to first pulmonary vein isolations (PVIs) using either PFA (n=121) or CBA (n=183). S100B was measured via ELISA in blood samples obtained pre- and post-procedure. HR was assessed continuously using ECG and wearables (PPG). Recurrent AF was detected using Holter ECGs, wearables and telephone interviews. Results Baseline characteristics did not differ between PFA and CBA. PFA induced less S100B release (28 ng/dl) than CBA (68 ng/dl, p<0.001), as a surrogate parameter of neurocardiac damage. After CBA-based PVI, heart rate increased (pre: 62 vs. post: 70 bpm, p<0.001) reflecting vagal denervation. Continuous monitoring via PPG wearables confirmed the initial heart rate increase, followed by a decline in the first month and recovery of HR-increase after three months. In contrast, heart rate did not change after PFA (pre: 63 vs. post: 63 bpm) and without substantially change during the observation period of five months. After CBA-based PVI, HRV decreased (SDNN pre 54 vs. post 26 ms, p=0.007) but not for PFA (SDNN pre 37 vs. post 36 ms, p=0.890). In a direct comparison, the HRV-decrease after CBA-based PVI was significant compared to PFA (SDNN -1 vs. 29 ms, p=0.003) and remained significantly different at 3- and 6 month follow up. 3-year follow-up revealed freedom from AF in 63% after PFA and 70% after CBA (p=0.545). PV reconnection rates in repeat procedures were similar between PFA (37%) and CBA (36%). In an exploratory analysis, patients with vagal ablation, defined by a heart rate increase of more than 3 bpm after PVI (n=157), had a higher AF ablation success rate (75%) than patients without HR increase(n=133, freedom from AF 58%, p=0.038, Figure 1). The group of high HR increase (>3 bpm) was characterised by a lower baseline HR (56 vs. 68 bpm, p<0.001) and more CBA procedures (73% vs. 43%, p<0.001). Conclusion These hypothesis-generating data suggest that ablation-induced vagal denervation may contribute to long-term success after AF ablation, calling for further analyses of autonomic modulation after AF ablation.Figure 1- 3y FU after PVI - HR increase