Decreased plasma cell-free mitochondrial DNA may be a new biomarker of tachycardia-induced cardiomyopathy in patients with atrial fibrillation

Objectives: To determine cell-free mitochondrial DNA (mt-cfDNA) levels in tachycardia-induced cardiomyopathy (TIC) and non-TIC among atrial fibrillation (AF) cases. Backgrounds: TIC is a reversible cardiomyopathy resulting from tachyarrhythmias, such as AF. The exact cause of TIC is not fully understood, but mitochondrial dysfunction has been reported in a variety of cardiomyopathies and may be involved in TIC as well. AF is recognized to be associated with systemic inflammation, and studies have shown that in patients with AF have elevated levels of mt-cfDNA increased, and this increase is linked to systemic inflammation. Methods: We enrolled 67 patients with TIC (TIC group) and 671 patients without TIC (non-TIC group), who underwent catheter ablation for AF at our hospital between November 2009 and September 2016 and did not meet the exclusion criteria. We performed quantitative PCR analysis of plasma mt-cfDNA and nuclear-cfDNA and compared clinical factors and these measurements between the two groups. Results: Levels of mt-cfDNA were significantly lower in the TIC group than in the non-TIC group (1110.01 vs. 1918.71 copies/mu g plasma, P = 0.027), while levels of nuclear-cfDNA were comparable between these two groups. In particular, mt-cfDNA (P P = 0.0003, odds ratio [OR] 2.54), non-paroxysmal AF (P P < 0.0001, OR 3.07), and diabetes mellitus (P P = 0.006, OR 2.36) were identified as independent factors associated with TIC. Conclusion: There are lower mt-cfDNA in TIC, and decreased plasma levels of circulating mt-cfDNA may be a new biomarker and involve in related mechanisms for AF associated TIC. Condensed abstract: Tachycardia-induced cardiomyopathy (TIC) is a reversible cardiomyopathy caused by tachyarrhythmias, such as atrial fibrillation (AF) tachycardia. The pathogenesis of TIC remains incompletely understood, and there is currently no method to predict its development in patients. In this study, we show that cell-free mitochondrial DNA (mt-cfDNA) levels were significantly lower in the TIC group than in the non-TIC group. Persistent AF, coexisting diabetes mellitus, and decreased mt-cfDNA levels were independently associated with TIC. Decreased mt-cfDNA levels may serve as a novel biomarker for predicting TIC in patients with AF.