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).

AIMS: 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) vs. thermal ablation (TA) in patients with atrial fibrillation (AF) through a pooled analysis.

METHODS AND

RESULTS

A systematic search of PubMed and Embase was conducted through 5 April 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).

CONCLUSION

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.