Predictive value of a novel 4-miRNAs diagnostic panel after acute myocardial infarction: independent validation from the MITOCARE study

Abstract

Following acute myocardial infarction (AMI), a significant proportion of patients develops heart failure (HF) due to left ventricular remodelling (LVR). The early identification of patients developing LVR is essential for evidence‐based intervention and pharmacological therapy. Novel biomarkers might pave the way for improved prediction approaches. Since the discovery of their stability in the bloodstream, miRNAs, short oligonucleotides which down‐regulate gene expression, have been extensively studied for their potential to diagnose AMI. We previously identified a panel of 4 circulating miRNAs (miR‐16‐5p/27a‐3p/101‐3p/150‐5p) able to significantly improve the prediction of post‐AMI LVR by a multivariable clinical model including N‐terminal pro‐brain natriuretic peptide (Nt‐pro‐BNP). In the present study, we aimed to confirm the predictive value of the 4‐miRNA panel in an independent cohort obtained from the MITOCARE study, a prospective randomized clinical trial conducted from 2011 to 2013. We enrolled 90 patients with STEMI treated by primary PCI. The HTG EdgeSeq targeting sequencing platform was used to assess the levels of miRNAs in plasma samples collected 3 days after AMI. Cardiac function was assessed by echocardiography at discharge and after 1 month. Left ventricular ejection fraction (LVEF) at 1 month was used to classify patients into 3 categories: LVEF 50 (n=41). Random forest model was used for predictive modelling and individual AUC, and confidence intervals (CI) were calculated for each miRNA. miR‐16‐5p/27a‐3p/101‐3p/150‐5p individual AUC were 0.81, 0.75, 0,84 and 0,61, respectively. The combination of the set of 4 miRNAs showed an average AUC of 0.83 (CI 0.80‐0.85). Combining the 4 miRNAs with NT‐pro‐BNP resulted in an AUC of 0.87 (CI 0.75 and 0.99). In conclusion, we here confirm the independent predictive value of the 4 miRNAs (miR‐16‐5p/27a‐3p/101‐3p/150‐5p) for the prediction of HF development after AMI. HTG EdgeSeq technology proves to be an efficient and clinically‐applicable tool to measure circulating miRNAs. These results motivate the development of molecular diagnostic kits based on miRNAs to aid in outcome prediction after AMI. (Figure Presented).