The microRNA Expression Profiling in Heart Failure: A Systematic Review and Meta-Analysis

Background: Heart failure (HF) is a main consequence of cardiovascular diseases worldwide. Abnormal expression levels of microRNAs (miRNAs) in HF are observed in current studies. Novel biomarkers miRNAs may play an important role in the development of HF. Nevertheless, the inconsistency of miRNA expression limits the clinical application. We thus perform this systematic review of the miRNAs expression profiling to identify potential HF biomarkers. Methods: The electronic databases of Embase, Medline, and Cochrane Library were systematically searched to identify the miRNA expression profiles between HF subjects and non-HF controls before May 26th, 2021. The pooled results were shown as log10 odds ratios (logORs) with 95% confidence intervals (CI) using random-effect models. Subgroup analyses were conducted according to species, region, and sample source. The quality assessment of included studies was independently conducted based on Diagnostic Accuracy Study 2 (QUADAS-2). The sensitivity analysis was conducted based on sample size. Results: A total of 55 miRNA expression articles reporting 276 miRNAs of HF were included. 47 consistently up-regulated and 10 down-regulated miRNAs were identified in the overall analysis, with the most up-regulated miR-21 (logOR 8.02; 95% CI: 6.76-9.27, P < 0.001) and the most down-regulated miR-30c (logOR 6.62; 95% CI: 3.04-10.20, P < 0.001). The subgroup analysis of sample source identified 35 up-regulated and 10 down-regulated miRNAs in blood sample, the most up-regulated and down-regulated miRNAs were miR-210-3p and miR-30c, respectively. In the region sub-groups, let-7i-5p and miR-129 were most up-regulated and down-regulated in Asian countries, while in non-Asian countries, let-7e-5p and miR-30c were the most dysregulated. It's worth noting that miR-622 was consistently up-regulated in both Asian and non-Asian countries. Sensitivity analysis showed that 46 out of 58 (79.31%) miRNAs were dysregulated. Conclusion: A total of 57 consistently dysregulated miRNAs related to HF were confirmed in this study. Seven dysregulated miRNAs (miR-21, miR-30c, miR-210-3p, let-7i-5p, miR-129, let-7e-5p, and miR-622) may be considered as potential non-invasive biomarkers for HF. However, further validation in larger-scale studies are needed to verify our conclusions.