Effectiveness and Adverse Event Profiles of Catheter Ablation in Persistent Atrial Fibrillation: A Meta–Analysis of Randomized and Single–Arm Clinical Trials
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
BACKGROUND
Catheter ablation is an established rhythm-control strategy for atrial fibrillation, but outcomes in persistent atrial fibrillation (PsAF) remain heterogeneous across evolving strategies and energy modalities. An updated synthesis is needed to define current effectiveness and adverse-event profiles in the modern ablation era.
METHODS
We conducted a systematic review and meta-analysis of prospective clinical trials of catheter ablation for PsAF published from 2010 through December 2025. We included randomized and nonrandomized prospective interventional studies reporting effectiveness and adverse events, and pooled outcomes using random-effects models. Prespecified subgroup analyses evaluated ablation strategy (pulmonary vein isolation [PVI] vs PVI with adjunctive lesion sets [PVI+]), ablation modality (radiofrequency [RF], cryoballoon [CRYO], and pulsed field [PF]), and endpoint definition (recurrence-only vs composite measures).
RESULTS
Thirty-two studies (9,194 patients) met inclusion criteria; 28 (7,948 patients) contributed to effectiveness analyses. The pooled 12-month arrhythmia-free proportion was 0.65 (95% CI, 0.61–0.68), with substantial heterogeneity. Effectiveness was numerically higher with PVI+ than PVI-only (0.66 [0.60–0.72] vs 0.63 [0.59–0.67]), similar for PF (0.65 [0.57–0.72]) and RF (0.65 [0.61–0.69]), and slightly lower for CRYO (0.64 [0.54–0.74]). Recurrence-only endpoints yielded higher effectiveness than composite endpoints (0.67 [0.63–0.71] vs 0.60 [0.55–0.64]). Safety analyses included 32 studies (9,002 patients). Adverse events were low but heterogeneous (0%–14.56%); pooled vascular access and pericardial complication incidences were each 1%, while thromboembolic events, accessory organ injury, and mortality were rare (pooled 0%). PF ablation showed numerically lower overall complication incidences than RF and CRYO.
CONCLUSION
In contemporary trials, catheter ablation for PsAF shows moderate effectiveness and low overall adverse-event risk. Adjunctive strategies and PF ablation are promising, but no approach is consistently superior. These findings support tailored, patient-specific ablation selection in PsAF.
Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/prospero/ , identifier 1322250.
CLINICAL RELEVANCE
What Is New?
-
This meta-analysis provides an updated synthesis of catheter ablation outcomes in persistent atrial fibrillation, including contemporary technologies and strategies such as pulsed field ablation and adjunctive lesion sets beyond pulmonary vein isolation.
-
Contemporary trials demonstrated moderate effectiveness, with an overall 12-month arrhythmia-free proportion of approximately 65% and substantial heterogeneity across studies.
-
Adverse events were uncommon, with vascular access and pericardial complications each occurring in about 1% of patients and other major complications remaining rare.
What Are the Clinical Implications?
-
Catheter ablation is a safe, effective rhythm-control option for persistent atrial fibrillation and should be considered in patient-centered care.
-
Clinicians should interpret outcomes within the context of significant variability across studies and tailor procedural strategies based on individual patient characteristics and operator expertise.
-
Further randomized studies with standardized endpoints and monitoring are needed to define optimal approaches and improve long-term outcomes.
