Circulating miR-10b-5p as a Candidate Biomarker of Atrial Fibrillation Recurrence After Catheter Ablation: A Two-Phase Translational Study

BACKGROUND: The identification of reliable biomarkers for atrial fibrillation (AF) recurrence post-catheter ablation remains a clinical challenge. This study aimed to identify circulating microRNAs (miRNAs) associated with post-ablation AF recurrence and examine their underlying molecular pathways using an integrative translational approach. METHODS: This two-phase study included a discovery case-control phase (n=29) followed by a prospective validation cohort (n=126). In the discovery phase, 84 miRNAs were quantified via real-time PCR and candidates were selected using differential expression analysis and machine learning. In the validation phase, five candidate miRNAs (hsa-miR-342-3p, hsa-miR-424-5p, hsa-miR-486-5p, hsa-miR-10b-5p, and hsa-let-7d-5p) were further evaluated to assess their prognostic performance. Pathway enrichment analysis was performed for the most predictive miRNA. RESULTS: Differential expression analysis identified 14 miRNAs to be significantly associated with AF recurrence. In the validation cohort, hsa-miR-10b-5p showed the highest discriminative performance (AUC=0.96, p<0.001). Multivariable logistic regression confirmed that lower expression of hsa-miR-10b-5p was an independent predictor of recurrence (OR=0.06, p<0.001), significantly improving the baseline clinical model (ΔR²=63.3%). Pathway analysis linked hsa-miR-10b-5p to FOXO signaling, p53 signaling, circadian rhythm and cellular senescence, pathophysiologic mechanisms that are critical to atrial remodeling and fibrotic persistence. CONCLUSION: Downregulation of circulating hsa-miR-10b-5p was independently associated with AF recurrence after catheter ablation and improved risk discrimination beyond clinical variables. These findings support its potential role as a prognostic biomarker, although further multicenter validation is required before clinical application.