Atabekov Tariel, Korepanov Viacheslav, Krivolapov Sergey, Khlynin Mikhail, Afanasiev Sergey, Golubenko Maria, Batalov Roman, Popov Sergey
Department of Surgical Arrhythmology and Cardiac Pacing, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, Russia.
Laboratory of Molecular and Cellular Pathology and Gene Diagnostics, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, Russia.
Rev Cardiovasc Med. 2025 Mar 17;26(3):26744. doi: 10.31083/RCM26744. eCollection 2025 Mar.
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).
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.
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%).
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.
NCT03667989 (https://clinicaltrials.gov/study/NCT03667989).
心肌细胞中的线粒体功能障碍与心律失常的发生有关，包括室性心动过速（VT）。线粒体DNA（mtDNA）点多态性的携带可能会增加某些心律失常的风险。因此，推测mtDNA基因型可以预测持续性VT（VT）的风险。我们旨在探讨外周血单核细胞（PBMC）的特定mtDNA多态性是否可以作为预测植入式心脏复律除颤器（ICD）适应症患者VT风险的生物标志物。
共有122例有ICD植入适应症且接受经胸超声心动图（TTE）检查的患者纳入本研究。采用酚-氯仿提取法从PBMC中分离总DNA。使用限制性片段长度多态性分析对mtDNA多态性A2706G、G3010A和G9055A进行基因分型。评估临床参数与ICD植入前记录的VT的mtDNA多态性之间的相关性。基于我们的数据，我们建立了VT的风险模型。
在ICD植入前，70例（56.6%）患者发生VT（第1组），52例（43.4%）患者未发生VT（第2组）。发生VT的患者明显比未发生VT的患者年龄大（66.9±9.9岁对59.5±10.6岁，P<0.001），估计肾小球滤过率（GFR）值较低（65.7±19.7 mL/min/1.73 m对77.9±16.1 mL/min/1.73 m，P<0.001），且A2706G mtDNA多态性的携带频率较低（55.7%对76.9%，P=0.015）。根据多变量逻辑回归分析，年龄（优势比（OR）=1.055，95%置信区间（CI）1.009-1.103，P=0.017）、GFR（OR=0.974，95%CI 0.949-0.999，P=0.041）和不存在A2706G mtDNA多态性（OR=0.335，95%CI 0.141-0.797，P=0.013）与VT独立相关。我们构建了一个逻辑方程并计算了临界值。受试者工作特征曲线（曲线下面积）的判别能力为0.761（95%置信区间0.
