Circulating miR-20b-5p and miR-330-3p are novel biomarkers for progression of atrial fibrillation: Intracardiac/extracardiac plasma sample analysis by small RNA sequencing

Abstract

Background Circulating microRNAs (miRNAs, miR) have been considered as biomarkers reflecting the underlying pathophysiology in atrial fibrillation (AF). Nevertheless, miRNA expression in the peripheral blood samples might not reflect a cardiac phenomenon since most miRNAs are expressed in numerous organs. This study aimed to identify the cardiac-specific circulating miRNAs as biomarkers for AF. Methods Plasma samples were obtained from a luminal coronary sinus catheter (CS, cardiac-specific samples) and femoral venous sheath (FV, peripheral samples) in patients with AF and paroxysmal supraventricular tachycardia (control, CTL) undergoing catheter ablation. The circulating miRNA profiles were analyzed by small RNA sequencing. Differently expressed miRNAs between AF and CTL were identified in each sample of the CS and FV; miRNAs exhibiting similar expression patterns in the CS and FV samples were selected as candidates for cardiac-specific biomarkers. The selected miRNAs were related to the outcome of catheter ablation of AF. Results Small RNA sequencing detected 849 miRNAs. Among the top 30 most differently expressed miRNAs between AF and CTL, circulating hsa-miR-20b-5p, hsa-miR-330-3p, and hsa-miR-204-5p had a similar pattern in the CS and FV samples. Another set of peripheral blood samples was obtained from AF patients undergoing catheter ablation (n = 141). The expression of the miR-20b-5p and miR-330-3p, but not the miR-204-5p, negatively correlated with the echocardiographic left-atrial dimension and was decreased in patients with AF recurrence as compared to those without AF recurrence during a 1-year follow-up. Conclusion Circulating miR-20b-5p and miR-330-3p can be cardiac-specific biomarkers for atrial remodeling progression and arrhythmia recurrence after catheter ablation in AF patients.

Circulating microRNAs and DNA Methylation as Regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation and Key Elements for the Identification of the Mechanism of Action (miR-CRAFT): Study Design and Patient Enrolment

“…In AF, miRs have drawn great attention as potential noninvasive biomarkers of disease. Evidence has been emerging that differences in circulating miRs expression are associated with AF development and progression [ 17 , 18 , 19 , 20 ]. In anticoagulation, the role of miRs has not yet been elucidated.…”

Comment on Polak et al. Principles and Limitations of miRNA Purification and Analysis in Whole Blood Collected during Ablation Procedure from Patients with Atrial Fibrillation. J. Clin. Med. 2024, 13, 1898

“…In the current issue of the journal, the paper by Polak et al [1] focuses on evaluating and optimising methods for the extraction of microRNAs (miRNA) from blood samples taken from atrial fibrillation (AF) patients. In the context of AF, circulating miRNAs have been profiled in both paroxysmal and persistent AF, from early work linking reduced plasma miR-150-5p levels to some aspects of AF pathogenesis [2] to a recent study that uncovered miR-20b-5p and miR-330-3p as putative cardiac-specific biomarkers that may predict AF recurrence one year after catheter ablation [3]. What makes the work of Polak and colleagues stand out is the use of left atrium blood taken during pulmonary vein isolation for both paroxysmal and persistent AF.…”