title: Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation.
abstract: OBJECTIVE
  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.
authors.affiliation: National Heart & Lung Institute, Hammersmith Hospital, Imperial College London, London, UK leanne.harling@imperial.ac.uk.|Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK.|Department of Biomolecular Medicine, South Kensington Campus, Imperial College London, London, UK.
authors.forename: Leanne
authors.initials: L
authors.lastname: Harling
authors.affiliation: Department of Biomolecular Medicine, South Kensington Campus, Imperial College London, London, UK.|Institute for Child Health, University College London, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lambert
authors.affiliation: Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK.|Department of Biomolecular Medicine, South Kensington Campus, Imperial College London, London, UK.
authors.forename: Hutan
authors.initials: H
authors.lastname: Ashrafian
authors.affiliation: Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK.
authors.forename: Ara
authors.initials: A
authors.lastname: Darzi
authors.affiliation: Department of Biomolecular Medicine, South Kensington Campus, Imperial College London, London, UK.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Gooderham
authors.affiliation: National Heart & Lung Institute, Hammersmith Hospital, Imperial College London, London, UK.|Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK.|Department of Biomolecular Medicine, South Kensington Campus, Imperial College London, London, UK.
authors.forename: Thanos
authors.initials: T
authors.lastname: Athanasiou
mesh_terms: D001281:Atrial Fibrillation / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D046228:Microarray Analysis; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011183:Postoperative Complications; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C548912:MIRN483 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Post-operative atrial fibrillation; Surgery; microRNA