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

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 1,327 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.