Peri-procedure and Mid-Long Term Effects of Pulsed Field Ablation vs. Thermal Ablation (Cryo- or Radiofrequency) on Autonomic Nervous System Function in Atrial Fibrillation: A Systematic and Quantitative Pooled-Analysis with Potential Implications for Patient Selection (The PULSE-COLD-HEAT-ANS Collaboration)

Ablation modalities differ in their mechanisms of action, tissue specificity, and collateral effects-particularly on the cardiac-autonomic-nervous-system. This study aimed to compare the autonomic effects of pulsed field ablation (PFA) versus thermal ablation (TA) in patients with atrial fibrillation (AF) through a pooled-analysis. A systematic search of PubMed and Embase was conducted through April 5, 2025, to identify comparative studies. The primary outcome was increase-in-heart-rate (IHR) after ablation, and the secondary outcome was increase in serum S100B (IS100B), a marker of neural injury. Eight studies involving 1007 AF patients were included (mean age: 63,39 ± 10,75 years; 36.3% female; maximum follow-up: 12 months). Baseline characteristics, including the use of antiarrhythmic drugs, were similar between the PFA and TA groups. Pooled-analysis showed that PFA was associated with a significantly lower IHR compared to TA (PFA: 4.41 ± 8.86 bpm vs. TA: 10.81 ± 10.46 bpm; p < 0.00001). This difference persisted at midterm (3-6 months) and long-term (12 months) follow-up and remained consistent across age, sex, and different TA modalities (cryoballoon vs. radiofrequency). Correspondingly, the IS100B was significantly less pronounced after PFA (PFA: 33.27 ± 9.46 pg/ml vs. TA: 97.53 ± 31.88 pg/ml; p < 0.00001). PFA-based pulmonary-vein-isolation in patients with AF results in a smaller post-procedural IHR and less S100B release, suggesting reduced neural damage and less disruption of the autonomic nervous system compared to TA. These effects are sustained through mid- to long-term follow-up and may have potential implications for patient selection and individualized ablation strategies.