Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation

Abstract

Objectives: Post-operative atrial fibrillation (POAF) is the commonest post-operative cardiac arrhythmia, affecting ∼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: Thirty-four 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 h pre-operatively and at 2 and 4 days post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using Student's t-test or analysis of variance as required. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of pre-operative serum miRNA as a POAF biomarker.

Results: Sixteen microRNAs were differentially expressed in the atrial myocardium of POAF patients when compared with those maintaining sinus rhythm. miR-208a was the most underexpressed [fold change (FC) = 2.458] and miR-483-5p the most overexpressed (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.

Keywords: Biomarker; Post-operative atrial fibrillation; Surgery; microRNA.

Figure 1:

Expression of hsa-miR-483-5p in pre-operative serum (Group 1: n = 23; Group 2: n = 10).

Figure 2:

Scatter plot demonstrating expression levels of microRNA-483-5p at three different time points: pre-operatively, 48-h post-operatively and 96-h post-operatively. Large crosses and trend line demonstrate mean ΔΔC_t values over time separated according to the presence or absence of POAF. P-values denote results of significance testing (Mann–Whitney) between AF and non-AF groups at each time point. AF: atrial fibrillation; POAF: post-operative atrial fibrillation.

Figure 3:

Receiver operating characteristic (ROC) curve of pre-operative hsa-miR-483-5p as a biomarker for post-operative atrial fibrillation (AF).