Micro-RNA 150-5p predicts overt heart failure in patients with univentricular hearts

Background: In patients with left heart failure, microRNAs (miRNAs) have been shown to be of diagnostic and prognostic value. The present study aims to identify miRNAs in patients with univentricular heart (UVH) disease that may be predictive of overt heart failure. Methods: A large panel of human miRNA arrays were used to determine miRNA expression profiles in the blood of 48 UVH patients and 32 age and gender-matched healthy controls. For further selection, the most abundantly expressed miRNA arrays were related to clinical measures of heart failure and selected miRNAs validated by Reverse transcription quantitative polymerase chain reaction (RT-qPCR). These validated miRNAs were used for the prediction of overt heart failure and all-cause mortality. Results: According to microarray analysis, 50 miRNAs were found to be significantly abundant in UVH patients of which miR-150-5p was best related to heart failure parameters. According to ROC analysis, NT-proBNP levels (AUC 0.940, 95% CI 0.873-1.000; p=0.001), miR-150-5p expression levels (AUC 0.905, 95% CI 0.779-1.000; p=0.001) and a higher NYHA class ≥ III (AUC 0.893, 95% CI 0.713-1.000; p=0.002) were the 3 most significant predictors of overt heart failure. Using a combined biomarker model, AUC increased to 0.980 indicating an additive value of miR-150-5p. Moreover, in the multivariate analysis, a higher NYHA class ≥ III (p=0.005) and miR-150-5p (p=0.006) turned out to be independent predictors of overt heart failure. Conclusion: In patients with UVH, miR-150-5p has additive value to natriuretic peptides for the prediction of overt heart failure and thus may be used as additional biomarker for risk assessment in these patients. We profiled the miRNA in 48 patients with univentricular heart (UVH) disease that may be predictive of overt heart failure and 32 healthy controls

背景：左心衰竭患者中，微小核糖核酸（microRNAs, miRNAs）已被证实具备诊断与预后评估价值。本研究旨在探究单心室心脏（univentricular heart, UVH）疾病患者体内可预测显性心力衰竭的miRNA表达特征。
方法：本研究采用大规模人miRNA芯片检测技术，对48例UVH患者与32例年龄、性别匹配的健康对照者的血液样本开展miRNA表达谱分析。为进一步筛选差异miRNA，将高丰度表达的miRNA与心力衰竭临床指标进行关联分析，并通过逆转录定量聚合酶链反应（Reverse transcription quantitative polymerase chain reaction, RT-qPCR）对候选miRNA进行验证。后续将验证通过的miRNA用于显性心力衰竭及全因死亡率的预测建模。
结果：芯片分析显示，UVH患者体内共有50种miRNA表达显著异常，其中miR-150-5p与心力衰竭参数的相关性最为突出。受试者工作特征（Receiver Operating Characteristic, ROC）曲线分析表明，NT-末端脑钠肽前体（NT-proBNP）水平（曲线下面积AUC=0.940，95%置信区间CI：0.873~1.000；p=0.001）、miR-150-5p表达水平（AUC=0.905，95%CI：0.779~1.000；p=0.001）以及纽约心脏协会（New York Heart Association, NYHA）心功能分级≥III级（AUC=0.893，95%CI：0.713~1.000；p=0.002）是预测显性心力衰竭的三大核心指标。构建联合生物标志物模型后，AUC提升至0.980，证实miR-150-5p具备额外的预测价值。多因素回归分析进一步显示，NYHA心功能分级≥III级（p=0.005）与miR-150-5p表达水平（p=0.006）是显性心力衰竭的独立预测因子。
结论：在UVH患者中，miR-150-5p可与利钠肽类标志物联用，提升显性心力衰竭的预测效能，因此可作为此类患者风险评估的补充生物标志物。本研究对48例单心室心脏疾病患者及32例健康对照者的血液miRNA表达谱进行了检测，上述UVH患者的miRNA表达水平可能用于预测显性心力衰竭。