miR-1-3p Downregulation as a Consistent Biomarker for Atrial Fibrillation Burden in Patients with Sick Sinus Syndrome: A Multi-Sample Analysis.

Atrial fibrillation (AF) is a leading cause of stroke, heart failure, and cardiovascular morbidity, yet its pathophysiology remains incompletely understood. Among various molecular regulators, microRNAs (miRNAs) have emerged as promising biomarkers for AF detection and burden monitoring. However, the optimal sample type for miRNA analysis remains unclear, posing a challenge for biomarker standardization. This study aimed to assess whether miRNA expression profiles remain consistent across plasma and blood cells, with a focus on identifying miRNAs with a strong predictive potential for AF burden. This exploratory study recruited patients diagnosed with sick sinus syndrome who had undergone permanent pacemaker implantation. Participants were stratified into three groups based on AF status: no AF (n = 2), paroxysmal AF (PaAF; n = 2), and persistent AF (PerAF; n = 2) for white blood cell (WBC) samples, and pooled plasma samples from no AF (n = 3 pools) and PerAF (n = 3 pools). Using an miRNA microarray analysis, miR-1-3p was consistently downregulated in both WBC and plasma samples of patients with AF, showing significant decreases (fold-change in WBC: PaAF 0.22, PerAF 0.20; plasma PerAF 0.28) and highlighting its potential as a circulating biomarker for AF burden. Additional differentially expressed miRNAs, including miR-451a and miR-382-5p, exhibited sample-dependent variations, underscoring the importance of validating miRNA expression across multiple biological compartments. The study highlights the need for mechanistic investigations to determine whether miR-1-3p directly contributes to AF pathogenesis or serves as a downstream consequence of atrial remodeling. These findings reinforce the potential of miR-1-3p as a reliable circulating biomarker for AF, offering new avenues for non-invasive monitoring and risk stratification. Future research should explore the role of miR-1-3p in AF-related molecular pathways and its applicability as a therapeutic target.