Pulsed field vs cryoballoon ablation: A meta-analysis with Hartung–Knapp, subgroup, and meta-regression analyses

Abstract

BACKGROUND

Atrial fibrillation, affecting approximately 33 million people globally, is the most common sustained arrhythmia, increasing risks of stroke, heart failure, and mortality. Pulmonary vein isolation via catheter ablation is a key rhythm control strategy, with cryoballoon ablation (CBA) being a standard thermal method but associated with risks like phrenic nerve palsy (5%-10%), esophageal injury, and vein stenosis. Pulsed field ablation (PFA), a non-thermal technique using electrical pulses for selective electroporation, offers potential for shorter procedures and improved safety. Limited direct comparisons between PFA and CBA necessitate a systematic evaluation of their efficacy and safety.

AIM

To compare the procedural success, safety, and 1-year arrhythmia-free survival of PFA vs CBA for first-time pulmonary vein isolation in adults with paroxysmal or persistent atrial fibrillation.

METHODS

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review and meta-analysis was conducted, searching PubMed, EMBASE, Web of Science, and other databases up to August 2025 for comparative studies. Pooled mean difference for continuous outcomes and odds ratio (OR) for dichotomous outcomes were calculated using random-effects models. Study quality was assessed with the Newcastle-Ottawa Scale, heterogeneity with I², and publication bias with funnel plots.

RESULTS

Seven studies (six cohorts, one randomized controlled trial) were included, with a mean age of approximately 66 years, 59%-78% male, and high prevalence of hypertension and diabetes. PFA significantly reduced procedure time (mean difference = -15.24 minutes, 95%CI: -16.63 to -13.85, P < 0.00001; I² = 89%), improved arrhythmia-free survival (OR = 1.27, 95%CI: 1.04-1.55, P = 0.02; I² = 45%), and lowered phrenic nerve palsy risk (OR = 0.17, 95%CI: 0.04-0.63, P = 0.008; I² = 0%). No significant differences were found in fluoroscopy time, cardiac tamponade, repeat ablation, or vascular complications.

CONCLUSION

PFA demonstrates shorter procedure times, reduced phrenic nerve palsy, and better arrhythmia control compared to CBA, with comparable safety profiles. However, evidence is limited by observational study designs, heterogeneity, and potential bias. Large-scale randomized controlled trials with extended follow-up are needed to confirm these findings and guide clinical practice.

Keywords: Atrial fibrillation; Pulmonary vein isolation; Pulsed field ablation; Cryoballoon ablation; Meta-analysis; Catheter ablation

Core Tip: This meta-analysis synthesizes data from comparative studies to evaluate pulsed field ablation (PFA) vs cryoballoon ablation for atrial fibrillation. Beyond standard pooled estimates, advanced analyses including Hartung-Knapp adjustment, subgroup, and meta-regression techniques were applied to enhance robustness. PFA demonstrated significantly shorter procedure times and lower phrenic nerve palsy risk, with comparable efficacy and safety profiles to cryoballoon ablation. These findings highlight PFA’s procedural advantages and support its growing clinical adoption, while underscoring the need for large-scale randomized trials.