Objective: Atrial fibrillation (POAF) is the commonest post-operative cardiac arrhythmia, affecting approximately 1 in 3 patients undergoing coronary artery bypass grafting (CABG). Although its aetiology is complex, atrial substrate changes may pre-dispose to its onset. This study aims to ascertain the atrial microRNA signature of POAF and determine the potential for circulating microRNA as a pre-operative biomarker for this arrhythmia.
Methods: 34 patients undergoing non-emergent, on-pump CABG were prospectively recruited. Right atrial biopsies were taken intra-operatively and snap frozen for RNA extraction. Plasma was obtained at 24 hours pre-operatively and at 2 and 4-days post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using student t-test or ANOVA as required. Receiver operating characteristics (ROC) analysis was used to determine the diagnostic accuracy of pre-operative serum miRNA as a POAF biomarker.
Results: 16 microRNA were differentially expressed in the atrial myocardium of POAF patients when compared to those maintaining sinus rhythm (SR). MiR-208a was the most under-expressed (FC:2.458) and miR-483-5p the most over-expressed (FC:1.804). Mir-483-5p also demonstrated significant overexpression in the pre-operative serum of these patients, with ROC analysis demonstrating an overall predictive accuracy of 78%.
Conclusions: This study provides the first description of atrial myocardial and circulating plasma microRNA in POAF patients. Our findings suggest POAF may be associated with pre-existing atrial substrate differences predisposing to arrhythmogenesis. Moreover, this study highlights the potential for miR-483-5p in biomarker development. Further work must now perform prospective, targeted validation of these results in a larger patient cohort.