Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Pulsed field vs cryoballoon ablation: A meta-analysis with Hartung–Knapp, subgroup, and meta-regression analyses
Mirza Muhammad Hadeed Khawar, Sanjar Odilov, Uzer Memon, Huijing Sun, Sulaiman Samee, Prasansa Dhakal, Anwita Mishra, Sumaiya Khan, Moosa Feroze Tarar, Muhammad Iqbal, Asraf Hussain
Mirza Muhammad Hadeed Khawar, Department of Cardiology, Services Institute of Medical Sciences, Lahore 54000, Punjab, Pakistan
Sanjar Odilov, Department of Cardiology, Tashkent Medical Academy, Tashkent 100109, Uzbekistan
Uzer Memon, Department of Cardiology, Smt. N.H.L. Municipal Medical College, Ahmedabad 380006, Gujarat, India
Huijing Sun, Windsor University School of Medicine, Oak Brook, IL 60523, United States
Sulaiman Samee, Hinsdale Central High School, Hinsdale, IL 60521, United States
Prasansa Dhakal, Department of Cardiology, Nepalgunj Medical College, Kathmandu 21904, Nepal
Anwita Mishra, Department of Cardiology, All India Institute of Medical Sciences, Delhi 110029, India
Sumaiya Khan, Department of Internal Medicine, Khaja Bandanawaz Institute of Medical Sciences, Karnataka 585105, India
Moosa Feroze Tarar, Department of Internal Medicine, Services Institute of Medical Sciences, Lahore 54000, Punjab, Pakistan
Muhammad Iqbal, Dow Medical University, Karachi 74200, Pakistan
Asraf Hussain, Department of Cardiology, Chitwan Medical College, Bharatpur 33915, Nepal
Author contributions: Khawar MMH and Odilov S were responsible for conceptualization, methodology, data curation, formal analysis, investigation, writing original draft preparation, writing review and editing, and visualization; Memon U was responsible for data curation, formal analysis, investigation, writing original draft preparation, writing review and editing; Sun H, Samee S, Dhakal P, Mishra A, Khan S, and Tarar MF were responsible for data curation, investigation, writing original draft preparation, writing review and editing; Iqbal M was responsible for data curation, investigation, writing original draft preparation; Hussain A was responsible for conceptualization, methodology, formal analysis, supervision, project administration, writing review and editing; all of the authors read and approved the final version of the manuscript to be published.
Conflict-of-interest statement: The authors disclose that they have no conflict of interest related to the subject of this study.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Asraf Hussain, DM, MD, Associate Professor, Department of Cardio
logy, Chitwan Medical College, Bharatpur-10, Chitwan, Bharatpur 33915, Nepal.
drasrafcardiology@gmail.com
Received: October 14, 2025
Revised: October 26, 2025
Accepted: December 12, 2025
Published online: December 18, 2025
Processing time: 69 Days and 0.9 Hours
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.
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.
