Circulating MicroRNAs as Specific Biomarkers in Atrial Fibrillation: A Meta-Analysis

Atrial fibrillation (AF) is the most frequently occurring supraventricular arrhythmia. Although microRNAs (miRNAs) have been associated with AF pathogenesis, standard protocols for quantifying and selecting specific miRNAs for clinical use as biomarkers should be optimized. In this study, we evaluated the clinical application of miRNAs as biomarkers for the prognosis and diagnosis of AF. Literature searches were conducted on PubMed, Cochrane Library, and EMBASE. We included prospective or retrospective observational studies that had been published as of 14 February 2022; our main objective was to analyze the relationship between circulating miRNAs and AF. The data were extracted using the descriptors “Atrial fibrillation AND miRNA”, “Atrial fibrillation AND diagnostic AND miRNA”, and “Atrial fibrillation AND prognosis AND miRNA”. No filters were applied for period delimitation, type of publication, or language. Studies using samples isolated from blood plasma and TaqMan and RT-qPCR for detecting and quantifying miRNAs were selected, and those that used atrial tissue samples were excluded. We identified 272 articles and excluded 102 duplicated articles. Two authors independently read the titles and abstracts of 170 out of 272 articles and selected 56 potential articles, 6 of which were selected for final review. Our analysis revealed a significant association between AF and miR-4798 [OR = 1.90 (95% CI 1.45–2.47)], AF and miRNA-133a [2.77 (2.73–2.82)], AF and miRNA-150 [3.77 (1.50–9.46); I2 = 70%], AF and miRNA-21 [2.23 (1.20–4.17); I2 = 99%], AF and hsa-miRNA4443 [2.32 (2.20–2.44)], and AF and miR-20a-5p [3.67 (1.42–9.49)]. The association between miRNAs and AF showed an OR of 2.51 [95% CI 1.99–3.16; I2 = 99%]. Our meta-analysis demonstrated that circulating miRNAs are potential biomarkers of AF, as they exhibit stable expression post–sample collection. In addition to regulating cellular processes, such as proliferation, differentiation, development, and cell death, miRNAs were found to be linked to arrhythmia development.