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Background Circulating microRNAs are emerging biomarkers for heart failure (HF). Our study aimed to assess the prognostic value of microRNA signature that is differentially expressed in patients with acute HF. Methods and Results Our study comprised a screening cohort of 15 patients with AHF and 5 controls, a PCR-discovery cohort of 50 patients with AHF and 26 controls and a validation cohort of 564 patients with AHF from registered study DRAGON-HF (Diagnostic, Risk Stratification and Prognostic Value of Novel Biomarkers in Patients With Heart Failure). Through screening by RNA-sequencing and verification by reverse-transcription quantitative polymerase chain reaction, 9 differentially expressed microRNAs were verified (miR-939-5p, miR-1908-5p, miR-7706, miR-101-3p, miR-144-3p, miR-4732-3p, miR-3615, miR-484 and miR-19b-3p). Among them, miR-19b-3p was identified as the microRNA signature with the highest fold-change of 8.4 and the strongest prognostic potential (area under curve with 95% CI, 0.791, 0.654-0.927). To further validate its prognostic value, in the validation cohort, the baseline level of miR-19b-3p was measured. During a follow-up period of 19.1 (17.7, 20.7) months, primary end point comprising of all-cause mortality or readmission due to HF occurred in 48.9% patients, while patients in the highest quartile of miR-19b-3p level presented the worst survival (Log-rank <0.001). Multivariate Cox model showed that the level of miR-19b-3p could independently predict the occurrence of primary end point (adjusted hazard ratio,1.39; 95% CI, 1.18-1.64). In addition, miR-19b-3p positively correlated with soluble suppression of tumorigenicity 2 and echocardiographic indexes of left ventricular hypertrophy. Conclusions Circulating miR-19b-3p could be a valuable prognostic biomarker for AHF. In addition, a high level of circulating miR-19b-3p might indicate ventricular hypertrophy in AHF subjects. Registration URL: https://www.clinicaltrials.gov. Unique Identifier: NCT03727828.

背景

循环 microRNAs 是心力衰竭 (HF) 的新兴生物标志物。我们的研究旨在评估在急性 HF 患者中差异表达的 microRNA 特征的预后价值。

方法和结果

我们的研究包括一个筛选队列，其中包括 15 名急性 HF 患者和 5 名对照者，一个由 50 名急性 HF 患者和 26 名对照者组成的 PCR 发现队列，以及来自注册研究 DRAGON-HF（心力衰竭患者新型生物标志物的诊断、风险分层和预后价值）的 564 名急性 HF 患者的验证队列。通过 RNA-seq 筛选和逆转录定量聚合酶链反应验证，验证了 9 个差异表达的 microRNAs（miR-939-5p、miR-1908-5p、miR-7706、miR-101-3p、miR-144-3p、miR-4732-3p、miR-3615、miR-484 和 miR-19b-3p）。其中，miR-19b-3p 被确定为具有最高 8.4 倍变化倍数和最强预后潜力的 microRNA 特征（95%CI 曲线下面积为 0.791，0.654-0.927）。为了进一步验证其预后价值，在验证队列中测量了 miR-19b-3p 的基线水平。在 19.1（17.7，20.7）个月的随访期间，主要终点包括所有原因死亡率或因 HF 再次入院，在 48.9%的患者中发生，而 miR-19b-3p 水平最高四分位数的患者生存最差（对数秩检验<0.001）。多变量 Cox 模型显示，miR-19b-3p 水平可独立预测主要终点的发生（调整后的危险比，1.39；95%CI，1.18-1.64）。此外，miR-19b-3p 与可溶性肿瘤抑制因子 2 和左心室肥厚的超声心动图指标呈正相关。