Evaluation of the effectiveness of combined treatment of coronary heart disease – coronary artery bypass grafting, transplantation of autologous bone marrow mononuclear cells: a randomized, double-blind, placebo-controlled study

Abstract

Introduction . Despite resounding success in treatment of patients with coronary heart disease (CHD), researchers are yet unable to significantly reduce mortality in this disease. With this in mind, there are ongoing studies everywhere, which are aimed at investigating new techniques in order to boost the efficiency of existing standards. One of such promising techniques is cell/regenerative therapy with autologous bone marrow mononuclear cells (ABMMCs). However, even though ABMMCs have been studied for more than 10 years, there are no unambiguous data yet on several issues. Objective : to evaluate the outcome of ABMMC transplantation during coronary artery bypass grafting (CABG) surgery in combined treatment of CHD. Materials and methods . The data of 408 patients admitted to the clinic from 2013 to 2016 for planned surgical treatment of CHD were analyzed. The work included 117 people based on the design of the study. Patients were randomized in 3 groups: Group 0 (control group) – CABG surgery and intramyocardial injection of 0.9% NaCl solution, Group 1 – CABG surgery and intramyocardial injection of ABMMCs, Group 2 – CABG surgery, intramyocardial and intra-graft injection of ABMMCs. The dynamics was assessed 12 months later – functional class of angina pectoris and heart failure, echocardiography, speckle tracking (assessment of the degree of myocardial deformation), treadmill test, 6-minute walk test, daily ECG monitoring, quality of life questionnaires, coronary angiography. Qualitative indicators were calculated using the Pearson’s chi-squared test and Fisher criteria. Quantitative indicators were calculated using the Kruskal–Wallis and Wilcoxon tests. Factor analysis was used to identify certain severity factors and to study data homogeneity. Discriminant analysis was performed to investigate the leading characteristics that determine differentiation between the groups. For analysis of variance, taking into account various factors, the model of variance analysis for dependent samples – Repeated Measures ANOVA – was used. Results . In the observation groups, an improvement in both systolic and diastolic myocardial function was universally noted. A six-minute walk test showed statistically significant increase in Groups 1 and 2 compared with the control Group 0 – 315.06 ± 17.6 (433.54 ± 20.6), Group 1 – 319.8 ± 24.5 (524.4 ± 28.7), Group 2 – 329.9 ± 25.3 (452.7 ± 29.7) meters. A significant decrease in the functional class of exertional angina pectoris in Groups 1 and 2 was noted unlike in the control group. The percentage of functioning coronary shunts after a 12-month follow-up period was 87.6% in Group 0. In Groups 1 and 2, this ratio was 96.2% and 97.3%, respectively. Predictors of overall effectiveness were identified: smoking, initial diastolic myocardial dysfunction, left ventricular ejection fraction. Conclusion . In addition to surgical treatment of coronary heart disease, ABMMC transplantation can improve myocardial contractility, boost exercise tolerance, and increase the duration of the functioning of coronary shunts at the follow-up period of 12 months. The study showed the need for stage-by-stage analytical calculations with the aim of possible correction of further work.