Circulating miR-1254 predicts ventricular remodeling in patients with ST-Segment-Elevation Myocardial Infarction: A cardiovascular magnetic resonance study

David De Gonzalo-Calvo,Thomas Thum,Vicente Bodí,Elena Revuelta-Lopez,Vicenta Llorente-Cortes,Julio Núñez,Christian Bär,Josep Gavara,Antoni Bayes-Genis,César Ríos-Navarro,Germán Cediel

doi:10.1038/s41598-018-33491-y

Abstract

Reliable noninvasive prognostic biomarkers for left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) are needed. This study aimed to evaluate a panel of circulating microRNAs (miRNAs) as biomarkers of LV remodeling using cardiovascular magnetic resonance (CMR). We prospectively evaluated patients with a first STEMI treated with primary percutaneous coronary intervention who underwent CMR imaging at 1 week and 6 months after STEMI (n = 70). miRNAs were measured using PCR-based technologies in plasma samples collected at admission. The associations between miRNAs and LV diastolic and systolic volumes, and ejection fraction at 6-months were estimated in adjusted models. Median age was 60 years, 71.4% were male. miR-1254 was significantly associated in univariate analyses. Patients in the highest tertile of miR-1254 exhibited lower values of LVEDVI and LVESVI and higher values of LVEF at 1 week. After comprehensive multivariate adjustment including clinical, CMR variables, hs-troponin-T and NT-proBNP, miRNA-1254 was associated with decreasing LVESVI (P = 0.006), and borderline negative associated with LVEDVI (P = 0.063) at 6-months. miR-1254 also exhibited a significant positive association with increasing LVEF during follow-up (P < 0.001). Plasma miRNA-1254 predicted changes in LV volumes and LVEF at 6 months after STEMI. The value of miR-1254 to inform tailored treatment selection and monitor ongoing efficacy deserves further investigation.

Highlights

The incidence and extent of left ventricular (LV) remodeling after acute myocardial infarction (MI) have declined in the era of primary percutaneous coronary intervention (PPCI)[1]
We prospectively examined the prognostic performance of miR-132-3p, miR-423-5p, miR-1254 and miR-1306-5p as biomarkers of LV remodeling assessed by changes in cardiac magnetic resonance (CMR) parameters in a well-characterized cohort of patients with a first ST-segment elevation MI (STEMI)
Two KEGG pathways were enriched with the predicted targets of miR1254 (P < 0.050). Both pathways were related to ventricular remodeling: other types of O-glycan biosynthesis and TGF-beta signaling pathway. In this well-characterized cohort of patients with a first STEMI, and after adjusting for clinical, analytical and CMR parameters, we demonstrate for the first time that plasma levels of miR-1254 at admission predict the change in LV geometry and systolic function

Summary

Introduction

The incidence and extent of left ventricular (LV) remodeling after acute myocardial infarction (MI) have declined in the era of primary percutaneous coronary intervention (PPCI)[1] MiRNAs are small molecules (19–22 nucleotides) that participate in gene expression regulation at the post-transcriptional level and are key molecular players in virtually all cellular processes[6], including the cellular mechanisms implicated in cardiovascular disease[7]. They are crucial mediators for both physiological and pathological adaptations in heart structure and function[8,9]. We prospectively examined the prognostic performance of miR-132-3p, miR-423-5p, miR-1254 and miR-1306-5p as biomarkers of LV remodeling assessed by changes in cardiac magnetic resonance (CMR) parameters in a well-characterized cohort of patients with a first ST-segment elevation MI (STEMI)

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