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

Abstract

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 (_SVT). We aimed to explore whether specific mtDNA polymorphisms of peripheral blood mononuclear cells (PBMC) can serve as biomarkers for predicting the risk of _SVT 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 _SVT registered prior to ICD implantation were evaluated. Based on our data, we developed a risk model for _SVT.

Results: Prior to ICD implantation, 70 (56.6%) patients had _SVT (1st group) and 52 (43.4%) patients did not have _SVT (2nd group). Patients with _SVT were significantly older than patients without _SVT (66.9 ± 9.9 year vs. 59.5 ± 10.6 year, p < 0.001), had a lower value estimated glomerular filtration rate (_eGFR) (65.7 ± 19.7 mL/min/1.73 m² vs. 77.9 ± 16.1 mL/min/1.73 m², p < 0.001) and less frequently had A2706G mtDNA polymorphism (55.7% vs. 76.9%, p = 0.015). According to the multivariable logistic regression, age (odds ratio (OR) = 1.055, 95% confidence interval (CI) 1.009-1.103, p = 0.017), _eGFR (OR = 0.974, 95% CI 0.949-0.999, p = 0.041) and absence of A2706G mtDNA polymorphism (OR = 0.335, 95% CI 0.141-0.797, p = 0.013) were independently associated with the _SVT. 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 _SVT. Our risk model including age, _eGFR and absence of A2706G mtDNA substitution was able to distinguish patients with _SVT. Further investigations of their predictive significance are warranted.

Clinical trial registration: NCT03667989 (https://clinicaltrials.gov/study/NCT03667989).