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Plasma MicroRNAs Relate to Atrial Fibrillation Recurrence after Catheter Ablation: Longitudinal Findings from the MiRhythm Study

Aditya Vaze, Kevin Donahue, Matthew Spring, Mayank Sardana, Kahraman Tanriverdi, Jane E. Freedman, John F. Keaney, Emelia J. Benjamin, Steven A. Lubitz MPH, Lawrence Rosenthal, Kevin Floyd and David D. McManus*

Introduction: Genetic and transcriptomic factors play important roles as mediators of new-onset and recurrent atrial fibrillation (AF). MicroRNAs (miRNAs) regulate expression of gene networks involved in key aspects of atrial remodeling. Associations between circulating miRNAs and AF recurrence are unknown. We tested the hypothesis that cardiac miRNAs associated with electrical and structural remodeling predict recurrent AF rhythm in post-ablation patients.

Methods: We quantified plasma expression of 86 cardiac miRNAs using RT-qPCR in 83 consenting participants undergoing ablation for AF. MiRNA expression was re-measured 1-month post-ablation in a subset of 43 of 83 study participants. Then all 83 patients were followed over a 12-month period for AF recurrence and plasma miRNA expression was compared between baseline and 1-month post-ablation and between those with and without an AF recurrence.

Results: The mean age of study participants was 59 years, 34% were female, and 63% had paroxysmal AF. Plasma levels of miRNAs 125a-5p and 10b were 3-fold lower after ablation compared to pre-ablation (p<0.01). Pre-ablation plasma expression of miRNAs 125a and 10b, as well as miRNAs 60, 30a-3p and 199b, were higher among patients with an AF recurrence compared to those without recurrence after ablation (p<0.05) even after adjustment for clinical risk factors.

Conclusion: The plasma miRnome is dynamic after AF ablation and associated with AF recurrence. Higher pre-ablation levels of circulating gene regulators implicated in atrial remodeling and AF, including miRNAs 125a-5p and 10b, were associated with AF recurrence and that these same miRNAs decreased post-ablation. Our investigation highlights dynamic gene regulatory networks in patients undergoing ablation and identifies potentially new AF treatment targets.