Study of the Efficacy of Autologous Cell Therapy in Dilated Cardiomyopathy

(Abstract) Background. Dilated cardiomyopathy (DCM) is one of the main causes of heart failure induction all over the world. In non-clinical trial many authors have demonstrated safety and effectiveness of autologous mesenchymal stem cells (MSCs). However, effectiveness of autologous MSCs in DCM with reduced ejection fraction (HFrEF) (≤40%) has been studied insufficiently.
Objective. To evaluate effectiveness of autologous cell therapy in patients with dilated cardiomyopathy and reduced left ventricular ejection fraction.                                                                                               
Material and methods. This single center randomized clinical study included 61 patients with DCM, class III-IV of heart failure according to New York Heart Association (NYHA), with HFrEF (≤40%) who made 2 visits every 3 months. Patients included in the study were randomized into two groups: the main group (32 patients) and the control group (29 patients). Patients of the main group received standard optimal medical therapy (OMT) and cell therapy, and patients of the second group received OMT. Data were analyzed using SPSS Statistica 10 and GraphPad Prism 7.
Results. The median patient age in control group was 57.0±12.0 and in the main group was 47.0±10.4 years.  On average ~2/3 of the total number of patients were male in both groups. Disease duration in control group was 4.9 ± 3.1, and in main group was 4.8 ± 2.8. Сomorbidities: type 2 diabetes mellitus (DM), arterial hypertension (AH) and cardiac arrhythmias (CA) did not differ between groups amounting to 17 to 44% of all patients. After 12 months of observation main group showed significant improvements associated with cell therapy: based on the results of laboratory test: statistically significant decrease in the level of eosinophils, normalization of coagulogram parameters, decrease in urea and increase in blood calcium, furthermore, there was a notable increase in anti-inflammatory cytokines CD73+ and IL-4, alongside reduction in pro-inflammatory CD8+ levels and brain natriuretic peptide (NT-proBNP). Echocardiographic (ECHO) data revealed significant increase in LVEF from 26.1 ± 8.4% to 37.6 ± 7.6% (p<0.0001) and reduction in end-systolic volume (ESV) from 146 ± 54   to 113 ± 42  p=0.0496) in the main group, whereas no such changes were observed in the control group.
Conclusion.  Combined therapy, including OMT and cell therapy, resulted in improved left ventricular function, reduced cardiac chamber dimensions (according to echocardiographic data), decreased pro-BNP levels, and improved routine laboratory parameters. However, these findings require confirmation in large-scale, multicenter randomized clinical trial
Keywords: heart failure, dilated cardiomyopathy, cell therapy, mesenchymal stem cells.