Circulating microRNAs in Atrial Fibrillation: Clinical Significance and Future Perspectives

Atrial fibrillation (AF) remains one of the most clinically demanding arrhythmias in contemporary cardiology—not because its mechanisms are unknown, but because what we know does not yet translate into precise, individualized management. Existing risk scores predict adverse outcomes reasonably well at the population level but perform inadequately for individual patients, and the molecular substrate driving disease progression remains largely invisible at the bedside. MicroRNAs (miRNAs), small non-coding RNA molecules of 20–25 nucleotides found stably in peripheral blood, have attracted considerable attention as potential biomarkers capable of bridging this gap. Their involvement in atrial fibrosis, electrical remodeling, and inflammatory signaling is mechanistically well-grounded. Whether this mechanistic plausibility can be translated into clinical utility is the central question this review addresses. We summarize the biological rationale for circulating miRNAs as AF biomarkers, review the most consistently replicated miRNA expression findings across clinical studies and meta-analyses, and appraise what the evidence supports—and what it does not—regarding diagnostic accuracy, prognostic value, and clinical decision-making applications. We also outline what the field needs to accomplish to move from promising findings to routine clinical use.