Effects of Pulsed-Field Ablation (PFA) and Second-Generation Cryoballoon Ablation on Endothelium Damage in Paroxysmal Atrial Fibrillation Ablation: A Single Center Prospective Observational Study

Thromboembolic events, though infrequent, remain a significant complication of atrial fibrillation (AF) ablation, largely related to endothelial damage. Cryoballoon (CB) and radiofrequency ablation can induce pro-coagulant responses, whereas pulsed-field ablation (PFA), a novel non-thermal electroporation-based technique, has shown tissue selectivity with potential endothelial-sparing effects. We aimed to compare PFA and second-generation CB ablation regarding endothelial injury in patients with paroxysmal AF. In this single-center prospective observational study, 25 patients with paroxysmal drug-refractory AF underwent pulmonary vein isolation using either a pentaspline PFA catheter (n=14) or a second-generation CB catheter (n=11). Circulating von Willebrand factor antigen (vWF) levels were assessed before and after ablation as a biomarker of endothelial damage, alongside routine laboratory and echocardiographic parameters. Procedural characteristics were also analyzed. Baseline demographic, clinical, and echocardiographic data were comparable between groups. PFA was associated with significantly shorter skin-to-skin procedure time (59 vs. 94 min, p=0.005) and left atrial dwell time (44 vs. 79 min, p<0.001) compared with CB ablation. Importantly, vWF levels decreased significantly after PFA (−7.6%, p=0.007), while CB ablation showed a non-significant increase (+9.5%, p=0.155). The between-group difference in percent change of vWF was statistically significant (−5.6% vs. +8.3%, p=0.006). PFA was associated with reduced endothelial injury and shorter procedural times compared with CB ablation, suggesting a potential advantage in lowering thromboembolic risk. These findings support the concept of PFA as an “endothelial-sparing” ablation modality. Larger, randomized studies are warranted to confirm these results and evaluate long-term clinical outcomes.