Circulating MicroRNAs and Clinical Parameters in Hypertrophic Cardiomyopathy: A Systematic Review and Correlation Meta-Analysis

Background: Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous and characterized by left ventricular hypertrophy, myocardial fibrosis, and diverse clinical manifestations. Although circulating microRNAs (miRNAs) are promising biomarkers of pathological cardiac remodeling, the correlation of these miRNAs with specific clinical characteristics of HCM remains unclear. Therefore, we systematically reviewed and quantified the correlation between circulating miRNAs and structural and functional cardiac parameters in HCM. Methods: This systematic review and meta-analysis of observational studies evaluated the association between circulating miRNA expression levels and Echocardiography, magnetic resonance imaging, and histological parameters for HCM. We comprehensively searched the PubMed, Embase, Scopus, and Web of Science databases, and extracted and transformed correlation coefficients into Fisher’s Z-scores. The study was registered with PROSPERO under registration number CRD420251058653. Meta-analyses were conducted using random-effects models, and heterogeneity was assessed using the I2 statistic. Sensitivity analyses, meta-regression, and publication bias were also assessed. Results: A total of 11 studies comprising 633 patients were included. Pooled analysis showed moderate-to-strong positive correlations between miRNAs (miR-21, miR-29a, miR-199a-5p, and miR-27a) and myocardial fibrosis, wall thickness, and left ventricular mass (r = 0.53; 95% confidence interval 0.40–0.64; I2 = 60.1%). Sensitivity and meta-regression analyses confirmed the robustness of the results, with no significant publication bias. The risk-of-bias assessment (Quality Assessment of Diagnostic Accuracy Studies 2) revealed moderate concerns, primarily related to patient selection and index-test blinding. Conclusion: Circulating miRNAs were significantly correlated with structural and functional cardiac changes in HCM, supporting the potential role of these miRNAs as noninvasive biomarkers. However, further high-quality studies are needed to validate their clinical applicability.