The efficacy of bone marrow mononuclear stem cell transplantation in patients with non-ischemic dilated cardiomyopathy-a meta analysis

Abstract

Cardiomyopathy refers to a wide spectrum of heart pathologies that interfere with normal heart function. Management options of patients with cardiomyopathy depended mainly on the severity of the condition. Lifestyle modifications and regular exercise together with a healthy diet is compatible for mild conditions. Severe conditions, however, rely on medications or surgery. Here, we aim to investigate the efficacy of bone marrow mononuclear stem cell transplantation in patients with dilated cardiomyopathy. We searched PubMed, Scopus, and Cochrane CENTRAL for relevant clinical trials and excluded observational studies. We performed the quality assessment of this study following GRADE guidelines. The assessment of the risk of bias was performed by the Cochrane's risk of bias tool. We present an analysis of the following outcomes: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and six minutes walking test. Data were pooled as mean differences (MD) and relative confidence intervals (CI). The analysis of 667 patients from 11 studies receiving autologous bone marrow cell therapy for non-ischemic dilated cardiomyopathy is presented. A total of 338 patients were allocated to the treatment group, and 329 participants entered the control group. The mean age of the patients in the treatment group is 52.4 ± 4.3 years, while that of the control is 53.7 ± 3.7 years. Seven studies (14.18-23) reported transplantation through the intracoronary route. Table 1 shows a summary of the baseline characteristics of the included studies and participants, the number of injected cells, and the type of injected cells in each trial. Table 2 summarizes and illustrates the previous treatment history of included patients in each trial, as well as the baseline values of different scores used as outcome measures in this analysis. We found that bone marrow mononuclear stem cell therapy leads to significantly increased LVEF (MD = 4.54%, 95% CI [3.52, 5.56], P < 0.0001). Patients in the transplant group experienced less left ventricular end-diastolic diameter (millimeter) than the control arm (MD = -1.86 mm, 95% CI [-4.01, 0.29], P = 0.09). Additionally, Patients in the transplant group could walk 28.53 m more than the controls (MD = 28.53 m, 95% CI [2.51, 54.55], P = 0.03). Transplantation of bone marrow stem cells yields acceptable results regarding left ventricular ejection fraction and lowers the left ventricular end-diastolic diameter. Additionally, the six minutes walking test is improved in the transplant group. Table 1 Demographic data about the included participants Study Year Sample size Age, years Males, n (%) Diabetics, n (%) Route of administration Number of injected cells Type of injected cells TTT Control TTT Control TTT Control TTT Control Bartolucci 2015 12 11 58 ± 14 57 ± 11 8 (66.7) 9 (81.8) 2 (16.7) 1 (9.1) Intracoronary 1.94 × 10^6 CD34 + Bocchi 2010 8 15 51 ± 15 NR NR NR NR Intracoronary NR NR Frljak 2018 30 30 56 ± 9 54 ± 11 27 (90) 26 (87) 3 (10) 2 (6) Trans-endocardial NR CD34 + Hamshere 2015 15 14 57.67 ± 12.32 56.79 ± 9.8 10 12 9(59.9%) 8(57.1%) Intracoronary 4.91 × 10^6 CD34 + Hu 2011 31 29 56.61 ± 9.72 58.27 ± 8.86 NR NR NR NR NR NR NR Matrino 2015 82 78 51 ± 11.1 49.6 ± 11.1 73.1 68.3 NR NR Intracoronary 10^8 TTT, CD45, CD105, and CD133 Sant'Anna 2014 20 10 48.3 ± 8.71 51.6 ± 7.79 13(65) 5 (50%) NR NR Intra-myocardial 1.06 × 108 CD3, CD4, CD14, CD34, CD38, and CD45 Seth 2010 41 40 45 ± 15 49 ± 9 33 35 NR NR NR 168 × 10^6 Bone marrow mononuclear cells Vrtovec 2011 28 27 52 ± 8 54 ± 7 26 (93) 23 (85) NR NR Intracoronary 123 × 10^6 CD34 + Vrtovec 2013 55 55 53 ± 8 55 ± 7 45 (82) 44 (80) NR NR Intracoronary NR NR Xiao 2017 16 20 49.5 ± 11.6 54.4 ± 11.6 9 (56.3) 14 (70.0) 6 (37.5) 5 (29.4) Intracoronary infusion (4.9 ± 1.7) × 108 (CD29, CD34, CD44, CD45, and CD166) Data are reported as mean ± SD or n (%) unless proved otherwise TTT treatment group, NR not reported Table 2 Previous history of treatment and drug intake by the patients Study Year Medical therapy, n (%) Baseline scores, mean (SD) Beta blockers ACE inhibitors Digoxin Diuretics LVEF, % LVEDD, mm Six minutes-walk test^* TTT Control TTT Control TTT Control TTT Control TTT Control TTT Control TTT Control Bartolucci 2015 10 (83.3) 8 (72.7) NR NR 3 (25) 3 (27.3) 11 (91.6) 10 (90.9) 26.8 ± 4.9 30.3 ± 6.3 NR NR NR NR Bocchi 2010 NR NR NR NR NR NR NR NR 21.8 ± 3.8 30.6 ± 7.3 79 (10) 78 (12) NR NR Frljak 2018 30 (100) 30 (100) 31 (100) 32 (100) 2 (7) 3 (10) 32 (100) 33 (100) 32.2 ± 9.3 31.1 ± 7.8 NR NR NR NR Hamshere 2015 13 14 15 13 6 2 9 8 32.93 ± 16.46 29.75 ± 9.2 NR NR NR NR Hu* 2011 NR NR NR NR NR NR NR NR NR NR NR NR 466 (402, 495) 448 (383, 497) Matrino 2015 9 (11) 8 (10.2) 53 (64.1) 48 (61.1) 63 (77) 62 (79) 74 (89.7) 69 (88.9) 23.8 ± 7.2 24.7 ± 7.0 NR NR 347.3(146.7) 349.8(139.7) Sant'Anna 2014 NR NR NR NR NR NR NR NR NR NR NR NR 358.5 (88.69) 353 (86.67) Seth 2010 29 (70) 29 (72) 41 (100) 40 (100) NR NR NR NR NR NR NR NR NR NR Vrtovec 2011 21 (75) 22 (81) NR NR 5 (18) 6 (22) 26 (93) 24 (88) 25.6 ± 5.1 26.7 ± 3.9 69 ± 10 70 ± 7 NR NR Vrtovec 2013 43 (79) 46 (84) 51 (93) 54 (98) 9 (16) 11 (20) 51 (93) 20 (91) 24.3 ± 6.5 25.7 ± 4.1 69 ± 10 70 ± 7 NR NR Xiao 2017 16 (100) 20 (100) 16 (100) 19 (95) 4 (25.0) 8 (40.0) 5 (31.3) 6 (30.0) 33.1 ± 3.9 33.7 ± 4.0 NR NR 355.0 ± 91.2 323.3 ± 89.4 Data are reported as mean ± SD or n (%) unless proved otherwise TTT treatment group, NR not reported ^*Data are reported as median (IQR).

Keywords: Bone marrow transplant; Cardiac treatment; Cardiomyopathy; Non-ischemic disease; Stem cell.