Circulating MicroRNAs as Molecular Biomarkers of Atrial Fibrillation Recurrence After Catheter Ablation: A Systematic Review and Candidate-Centered Evidence Map

Abstract

Background: Recurrence after atrial fibrillation (AF) ablation remains difficult to predict. Circulating microRNAs may reflect molecular substrates not captured by established predictors. We mapped recurrence-specific evidence and identified priorities for prospective validation. Methods: Six databases were searched from inception through 29 August 2026 for adult AF ablation cohorts measuring circulating microRNAs before or around ablation and reporting atrial tachyarrhythmia recurrence. Recurrence-specific reports were assessed with the Quality in Prognosis Studies (QUIPS) tool. A post hoc candidate-centered framework required direct recurrence evidence in at least two analytically distinct samples and support in at least one additional clinical, mechanistic, or analytical domain. Candidate-specific certainty was evaluated with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Results: Thirty-five publications represented 29 linked programs; 26 recurrence-specific reports represented 25 independent cohorts (3309 enrolled; 3205 analyzed), and nine publications provided longitudinal context. Six microRNAs were identified as priorities for prospective validation: miR-21-5p, miR-150-5p, miR-29b-3p, miR-451a, miR-10b-5p, and miR-320a. Their evidence differed in mature-arm identity, matrix, sampling compartment, assay scale, biological source, and mechanistic support. Candidate-specific certainty was very low. Conclusions: The evidence supports candidate-specific prospective validation rather than a uniform circulating-microRNA class effect. Standardized preanalytics, mature-arm and carrier attribution, locked assays, and multicenter incremental-prediction studies are required before clinical utility can be established.