Prognostic Utility of Circulating Inflammatory MicroRNA Signatures in Predicting Adverse Ventricular Remodeling Post-Infarction Heart Failure

Abstract

Background: Accurate prediction of adverse left ventricular (LV) remodeling following acute myocardial infarction (MI) remains a significant clinical challenge despite advances in cardiac imaging. Early identification of high-risk patients is critical for initiating aggressive cardioprotective therapies and improving long-term outcomes. MicroRNAs (miRNAs) regulating inflammatory pathways present as promising, non-invasive prognostic biomarkers for post-MI progression to chronic Heart Failure (HF). This study sought to validate a novel circulating miRNA signature panel as a robust predictive tool.

Methods: This prospective cohort study enrolled 412 patients presenting with first-time ST-elevation MI. Patients underwent comprehensive two-dimensional echocardiography at baseline and six months to define the primary endpoint: significant adverse LV remodeling (defined as an increase in LV end-systolic volume index >15%). Quantification of a targeted panel of four inflammatory-associated circulating microRNAs (miR-21, miR-133a, miR-146a, miR-499) was performed by quantitative reverse transcription PCR (qRT-PCR) at 48 hours post-event. Multivariate Cox Proportional Hazards regression was the primary statistical analysis for risk association.  

Results: At six months, 108 patients (26.2%) developed adverse LV remodeling. Univariate analysis confirmed that elevated levels of both miR-21 and miR-146a were independently associated with the primary endpoint (p<0.01 for both). In the final multivariate model, the integrated four-miRNA signature demonstrated superior prognostic stratification compared to baseline clinical factors (C-statistic: 0.82 vs. 0.70; p<0.001). Specifically, patients in the highest quartile of the composite miRNA score faced a significantly increased risk of remodeling, exhibiting an adjusted Hazard Ratio (HR) of 2.95 (95% CI: 1.88-4.10; p=0.001). This biomarker panel allows for accurate identification of vulnerable individuals who are not detected by traditional cardiac imaging metrics.

Conclusion: Circulating inflammatory microRNA signatures represent a robust, non-invasive prognostic tool for post-MI adverse LV remodeling. Early utilization of this biomarker panel enables targeted interventions to prevent progression to chronic HF, supporting precision medicine and advancing cost-effective, high-quality cardiovascular care.