Harling Leanne, Lambert Jonathan, Ashrafian Hutan, Darzi Ara, Gooderham Nigel J, Athanasiou Thanos
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.
Eur J Cardiothorac Surg. 2017 Jan;51(1):73-78. doi: 10.1093/ejcts/ezw245. Epub 2016 Jul 15.
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.
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.
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%.
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.
术后房颤(POAF)是最常见的术后心律失常,约三分之一接受冠状动脉旁路移植术(CABG)的患者会受到影响。尽管其病因复杂,但心房基质变化可能是其发病的诱因。本研究旨在确定POAF的心房微小RNA特征,并确定循环微小RNA作为这种心律失常术前生物标志物的潜力。
前瞻性招募了34例接受非急诊、体外循环CABG的患者。术中取右心房活检组织并速冻以提取RNA。在术前24小时以及术后2天和4天采集血浆。通过连续动态心电图记录定义POAF。根据需要使用学生t检验或方差分析进行组间比较。采用受试者工作特征(ROC)分析来确定术前血清微小RNA作为POAF生物标志物的诊断准确性。
与维持窦性心律的患者相比,POAF患者心房心肌中有16种微小RNA表达存在差异。miR-208a表达下调最为明显[倍数变化(FC)=2.458],miR-483-5p表达上调最为明显(FC = 1.804)。miR-483-5p在这些患者的术前血清中也有显著上调,ROC分析显示总体预测准确率为78%。
本研究首次描述了POAF患者心房心肌和循环血浆中的微小RNA情况。我们的研究结果表明,POAF可能与预先存在的易导致心律失常的心房基质差异有关。此外,本研究突出了miR-483-5p在生物标志物开发方面的潜力。现在必须开展进一步工作,在更大的患者队列中对这些结果进行前瞻性、针对性验证。