Efficiency of Intramyocardial Injections of Autologous Bone Marrow Mononuclear Cells in Patients with Ischemic Heart Failure: A Randomized Study

Abstract

Intramyocardial transplantation of autologous bone marrow mononuclear cells (BMMC) is believed to be a promising method for the treatment of patients with chronic ischemic heart disease. The aim of this study was to evaluate long-term results of intramyocardial bone marrow cell transplantation in patients with severe ischemic heart failure. One hundred nine patients with chronic myocardial infarction and end-stage chronic heart failure were randomized into two groups: 55 patients received intramyocardial BMMC injection and 54 received optimal medical therapy. The NOGA system (Biosense-Webster) was used to administer 41 +/- 16 x 106 BMMC into the border zone of myocardial infarction. None of the patients developed periprocedural complications following BMMC injections. The injections led to improvement of CCS class (3.1 +/- 0.4 to 1.6 +/- 0.6 after 6 months and 1.6 +/- 0.4 after 12 months; p = 0.001) and NYHA functional class (3.3 +/- 0.2 to 2.3 +/- 0.2 after 6 months and 2.5 +/- 0.1 after 12 months; p = 0.006). Left ventricular ejection fraction increased significantly in the BMMC group (27.8 +/- 3.4% vs 32.3 +/- 4.1%; p = 0.04) while it tended to decrease in the control group (26.8 +/- 3.8% to 25.2 +/- 4.1%; p = 0.61). Summed rest score improved in the BMMC group after 12 months (30.2 +/- 5.6 to 27.8 +/- 5.1; p = 0.032). The improvement of stress score was more noticeable (34.5 +/- 5.4 to 28.1 +/- 5.2; p = 0.016). Neither stress nor rest score changed in patients numbers on medical therapy. In BMMC group 6 (10.9%) patients died at 12-month follow-up compared with 21 (38.9%) in control group (log-rank test, p = 0.0007). Intramyocardial bone marrow cell transplantation to patients with ischemic heart failure is safe and improved survival, clinical symptoms, and has beneficial effect on LV function.

Meta-Analysis of Cell Therapy Trials for Patients With Heart Failure

“…The primary outcomes of this Where multiple times of follow-up were reported, data were extracted for the longest possible duration of shortterm and long-term follow-up. The authors of 18 trials were contacted for clarification of data, including apparent discrepancies and insufficient detail in the reporting of methods or results 19,[22][23][24][25][26][27][28][29] or for mean and standard deviation values of outcomes where not explicitly reported 11,19,25,[30][31][32][33][34][35][36] or where reported graphically. 9,10,[37][38][39] Responses were obtained from authors of 7 trials (see Acknowledgments section).…”

“…16 This conclusion was mainly drawn from a combination of low number of events (deaths) from the contributing RCTs and discordant results from one particular study. 19 During the last year, new clinical evidence has become available in the form of new trials of stem cells treatment for HF patients, which have been completed and reported. 9,20,21 In addition, previous meta-analyses have not included trials of cell therapy for DCM.…”

Stem Cell Therapy in Myocardial Infarction Clinical Point of View and the Results of the REANIMA Study (REgenerAtion of Myocardium with boNe Marrow Mononuclear Cells in MyocArdial Infarction)

“…Four relatively larger randomized studies with trans-endocardial application of bone marrow derived MNC or myoblasts have been recently published. Pokushalov's group (Pokushalov et al, 2010) The extremely valuable study comes from Ramshort group. They examined a role of trans-endocardial injections of bone marrow derived MNC into the electrically alive but functionally inactive myocardium in patients with severe, refractory angina and without additional option of revascularization (Ramshort et al, 2009).…”

“…Finaly, and probably the most important aspect of stem cell therapy is a clinical benefit. REPEAR-AMI (Schächinger et al, 2010), studies of Strauer's group in AMI (Yousef et al, 2009) and CMI (Strauer et al, 2010) and the largest study with endocardial implantation of bone marrow derived stem cells in CMI (Pokushalov et al, 2010) have showed clear clinical benefit with hard end points during the relatively long period of follow-up. In our study, we have not a sufficient number of patients to show the difference of major adverse cardiac events in several groups of our patients.…”

Safety and Feasibility for Pediatric Cardiac Regeneration Using Epicardial Delivery of Autologous Umbilical Cord Blood-Derived Mononuclear Cells Established in a Porcine Model System

“…The study of stem cell strategies to address heart failure has advanced steadily over the last decade, predominantly in the adult population. There is expanding clinical experience with first generation cell-based therapies to mitigate the effects of ischemic and nonischemic heart diseases in adults that involve the administration of both autologous and allogeneic bone marrow-derived stem cells (BMSCs) [1][2][3][4][5][6]. These studies have provided evidence that validates the overall safety and feasibility of direct injection into the left heart muscle in adult cardiac disease.…”