Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications.

Background: Mitochondrial dysfunction in myocardium cells has been implicated in arrhythmogenesis, including ventricular tachycardia (VT). A carriage of point mitochondrial DNA (mtDNA) polymorphisms may contribute to the risk of certain arrhythmias. Therefore, it is hypothesized that mtDNA genotype could predict the risk of sustained VT (VT). We aimed to explore whether specific mtDNA polymorphisms of peripheral blood mononuclear cells (PBMC) can serve as biomarkers for predicting the risk of VT in patients with indications for an implantable cardioverter-defibrillator (ICD).

Methods: A total of 122 patients with ICD implantation indications who underwent transthoracic echocardiography (TTE) were enrolled in the study. Total DNA from PBMC was isolated using the phenol-chloroform extraction method. Genotyping of mtDNA polymorphisms A2706G, G3010A and G9055A was performed using restriction fragment length polymorphism analysis. Correlations between clinical parameters and mtDNA polymorphisms with VT registered prior to ICD implantation were evaluated. Based on our data, we developed a risk model for VT.

Results: Prior to ICD implantation, 70 (56.6%) patients had VT (1st group) and 52 (43.4%) patients did not have VT (2nd group). Patients with VT were significantly older than patients without VT (66.9 ± 9.9 year vs. 59.5 ± 10.6 year, < 0.001), had a lower value estimated glomerular filtration rate (GFR) (65.7 ± 19.7 mL/min/1.73 m vs. 77.9 ± 16.1 mL/min/1.73 m, < 0.001) and less frequently had A2706G mtDNA polymorphism (55.7% vs. 76.9%, = 0.015). According to the multivariable logistic regression, age (odds ratio (OR) = 1.055, 95% confidence interval (CI) 1.009-1.103, = 0.017), GFR (OR = 0.974, 95% CI 0.949-0.999, = 0.041) and absence of A2706G mtDNA polymorphism (OR = 0.335, 95% CI 0.141-0.797, = 0.013) were independently associated with the VT. We constructed a logistic equation with calculation of the cut-off value. The discriminative ability of the receiver operating characteristic curve (area under the curve) was 0.761 (95% confidence interval 0.675-0.833; sensitivity 65.71%; specificity 76.92%).

Conclusions: In patients with ICD implantation indications, a carriage of mtDNA polymorphism A2706G is associated with VT. Our risk model including age, GFR and absence of A2706G mtDNA substitution was able to distinguish patients with VT. Further investigations of their predictive significance are warranted.

Clinical Trial Registration: NCT03667989 (https://clinicaltrials.gov/study/NCT03667989).