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

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Title: Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation
Authors: Harling, L
Lambert, J
Ashrafian, H
Darzi, A
Gooderham, N
Athanasiou, T
Item Type: Journal Article
Abstract: 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.
Issue Date: 15-Jul-2016
Date of Acceptance: 8-Jun-2016
URI: http://hdl.handle.net/10044/1/34349
DOI: https://dx.doi.org/10.1093/ejcts/ezw245
ISSN: 1873-734X
Publisher: Oxford University Press (OUP)
Start Page: 73
End Page: 78
Journal / Book Title: European Journal of Cardio-thoracic Surgery
Volume: 51
Issue: 1
Copyright Statement: © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Imperial College Healthcare Charity
Wellcome Trust
Funder's Grant Number: 5117/R20R
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Respiratory System
Cardiovascular System & Cardiology
Post-operative atrial fibrillation
Atrial Fibrillation
Coronary Artery Bypass
Follow-Up Studies
Heart Atria
Microarray Analysis
Middle Aged
Postoperative Complications
Prospective Studies
ROC Curve
Risk Factors
Coronary Artery Bypass Grafting
1102 Cardiovascular Medicine And Haematology
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer
Institute of Global Health Innovation