CYTOCHROME C IS A MITOCHONDRIAL DAMAGE MARKER: ASSOCIATIONS WITH CLINICAL PARAMETERS AND QUALITY OF LIFE OF HEART FAILURE PATIENTS WITH CORONARY ARTERY DISEASE

Highlights The association of cytochrome C concentration, a marker of mitochondrial damage, with the left ventricular ejection fraction (LVEF), exercise tolerance and quality of life in heart failure (HF) patients with reduced and mildly reduced LVEF of ischemic etiology has been shown. The obtained results emphasize the importance of mitochondrial dysfunction in the pathogenesis of HF. Abstract Background . A feature of the pathogenesis of chronic heart failure (HF) in patients with coronary artery disease (CAD) is the development of myocardial dysfunction against the background of repeated episodes of ischemia/reperfusion. Damage to the mitochondria of cardiomyocytes leads to stimulation of cell death and the release of mitochondrial DNA and mitochondrial enzymes into the interstitium and blood. Cytochrome C is one of the mitochondrial proteins released into the systemic circulation, but the clinical significance of cytochrome C in HF remains poorly understood. Aim . The aim of this study was to search for associations between cytochrome C concentration and clinical characteristics of HF of ischemic etiology, including quality of life, as well as to analyze the dynamics of cytochrome C in the postoperative period after coronary artery bypass grafting (CABG). Methods . The study included 30 patients aged 67 (58; 71) years with HF with reduced (HFrEF) and mildly reduced (HFmrEF) left ventricular ejection fraction (LVEF), who were scheduled for CABG. All patients underwent collection of complaints, anamnesis, standard laboratory and instrumental dates. Quality of life was assessed using the Kansas Cardiomyopathy Questionnaire (KCCQ). Blood samples for determination of cytochrome C concentration were taken before CABG and on days 3 and 10 after surgery. Statistical processing of the results was performed using IBM SPSS 21.0. Results . The cytochrome C concentration before CABG in the study cohort was 24.1 (17.1; 31.1) ng/ml. Patients were divided into two equal groups (n = 15) depending on the cytochrome C level: group 1 included patients with cytochrome C concentration less than or equal to the median value, group 2 – with cytochrome C concentration values ​​greater than the median. Patients in group 2 had lower values ​​of distance in the six-minute walk test: 341 (232; 370) m, compared with group 1 – 400 (310; 440) m (p = 0.048). Lower values ​​of quality of life were recorded in patients of group 2 (p = 0.046). The value of LVEF was also statistically significantly different in the analyzed groups: 44.5 (36.5; 48.3) % and 30 (28; 44) %, respectively, in groups 1 and 2 (p = 0.029). In addition, it was shown that in group 1, on the third day after CABG, a statistically significant increase in the concentration of cytochrome C was recorded (p = 0.05), while in group 2, no pronounced dynamics of this indicator in the perioperative period were revealed. Conclusion . Elevated blood cytochrome C concentrations in patients with HFrEF and HFmrEF and coronary artery disease are associated with lower LVEF values, a shorter six-minute walk distance, and worse quality of life. Cytochrome C dynamics after CABG depended on the initial concentration of this marker.