# Diagnostic and prognostic value of circulating microRNA-21 in heart failure: A systematic review and meta-analysis

## TL;DR

This study finds that microRNA-21 in the blood could help diagnose and predict outcomes in heart failure patients, though more research is needed.

## Contribution

The study provides a meta-analysis of miR-21's diagnostic and prognostic value in heart failure, revealing its potential as a biomarker.

## Key findings

- Circulating miR-21 levels are significantly higher in heart failure patients compared to controls.
- Elevated miR-21 is associated with increased risk of worsening heart failure severity and cardiovascular death.
- Diagnostic accuracy of miR-21 is high, with strong sensitivity and specificity.

## Abstract

Heart failure (HF) remains a leading cause of global mortality, underscoring the urgent need for reliable, minimally invasive biomarkers to facilitate early diagnosis and risk stratification. MicroRNA-21 (miR-21) has been implicated in cardiac fibrosis, hypertrophy, and the progression of HF; however, its clinical utility remains uncertain. This study presents a systematic review and diagnostic test accuracy (DTA) meta-analysis aimed at assessing the diagnostic and prognostic performance of circulating miR-21 in HF. We estimated pooled sensitivity, specificity, and area under the curve (AUC) for the DTA analysis, and synthesized hazard ratios (HRs) with 95% confidence intervals (CIs) for prognostic outcomes. Additionally, univariate meta-regression was conducted to explore demographic and clinical moderators. Our analysis included fourteen studies with a total of 1327 participants. Results demonstrated that circulating miR-21 levels were significantly elevated in HF patients compared to controls (fold change 1.61; 95% CI 1.46–1.78; P < 0.001). The diagnostic accuracy was notably high, with a sensitivity of 0.94 (95% CI 82.0–98.0), specificity of 0.90 (95% CI 79.0–96.0), and AUC of 0.97 (95% CI 96.0–98.0). Elevated levels of miR-21 were associated with an increased risk of worsening HF severity (HR 1.84; 95% CI 1.14–2.97; P ═ 0.01) and HF-related cardiovascular death (HR 2.00; 95% CI 1.30–3.03; P ═ 0.001). However, no significant association was found with HF-related hospitalization (HR 0.97; 95% CI 0.61–1.52; P ═ 0.88). Variability in sample type and differing clinical thresholds contributed to heterogeneity across studies. These findings support the potential of circulating miR-21 as a diagnostic and prognostic biomarker for HF. Nevertheless, further research with standardized sample sizes and clinical thresholds is necessary to establish robust evidence for its clinical application.