Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study) (original) (raw)
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Journal of Cardiovascular Translational Research, 2009
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±16×106 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
JAMA : the journal of the American Medical Association, 2012
Context Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy.Objective To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina.Design, Setting, and Patients A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Ce...
Revista Española de Cardiología (English Edition), 2013
Introduction and objectives: Different studies have shown improvement in patients with idiopathic nonischemic dilated cardiomyopathy treated with cell-therapy. However, factors influencing responsiveness are not well known. This trial investigates functional changes and factors influencing the 6-month gain in ejection fraction in 27 patients with dilated cardiomiopathy treated with intracoronary cell-therapy. Methods: Patients received intracoronary infusion of autologous bone-marrow mononuclear cells (mean infused, 10.2 [2.9]Â10 8). Flow cytometry and functional analyses of the cells were also performed. Results: The 6-month angiographic gain in ejection fraction ranged from À9% to 34% (mean, 9%). These changes were distinguished into 2 groups: 21 patients (78%) with a significant improvement at the 6-month evaluation (mean gain, 14 [7]%), and 6 patients who had no response (mean gain, À5 [3]%). The responders were younger as compared to the nonresponders (50 [12] years vs 62 [9] years; P<.04). There was an inverse correlation (r=À0.41; P<.003) between the gain in ejection fraction and the high density lipoprotein level, suggesting higher functional gain with low high density lipoprotein levels. The 24 h migratory capability of the infused cells was significantly reduced in the responders' group (5.4 [1.7]Â10 8 vs 8.1 [2.3]Â10 8 ; P<.009 for vascular endothelial growth factor and 5.8 [1.7]Â10 8 vs 8.4 [2.9]Â10 8 ; P<.002 for stromal cell-derived factor-1). Conclusions: Younger patients with dilated cardiomiopathy and lower plasma high density lipoprotein levels gain greater benefit from intracoronary cell-therapy. Functional improvement also seems to be enhanced by a lower migratory capacity of the infused cells.
The Journal of Heart and Lung Transplantation, 2014
BACKGROUND: Bone marrow mononuclear cell (BMMC) transplantation for heart failure has shown inconsistent therapeutic efficacy. METHODS: We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery (CABG). After 4-to 12-week pharmacotherapy optimization, 39 patients with left ventricular ejection fraction (LVEF) of r45% received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized, double-blind manner. RESULTS: The median number of cells injected was 8.4 Â 10 8 (interquartile range [IQR]: 5.2 Â 10 8 to 13.5 Â 10 8 ). We measured LV function and myocardial scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and single-photon emission computed tomography (SPECT), pre-operatively and after 1-year follow-up. LVEF, the pre-defined primary end-point measure, improved by a median of 5.6% in the control group (IQR 0.2 to 10.1) and by 4.8% in the BMMC group (IQR À0.5 to 8.2) (p ¼ 0.59). Wall thickening in injected segments rose by a median of 4.5% among controls (IQR À18.1 to 23.9) and by 5.5% in the BMMC group (IQR À6.6 to 26.5) (p ¼ 0.68). Changes in viability by PET and SPECT did not differ between groups. Myocardial scar size by MRI in injected segments rose by a median of 5.1% among controls (IQR À3.3 to 10.8), but fell by 13.1% in the BMMC group (IQR À21.4 to À6.5) (p ¼ 0.0002). CONCLUSIONS: BMMC therapy combined with CABG failed to improve LV systolic function, or viability, despite reducing myocardial scar size.
Transendocardial Autologous Bone Marrow Mononuclear Cell Injection in Ischemic Heart Failure
Circulation, 2005
Background— Cell-based therapies for treatment of ischemic heart disease are currently under investigation. We previously reported the results of a phase I trial of transendocardial injection of autologous bone marrow mononuclear (ABMM) cells in patients with end-stage ischemic heart disease. The current report focuses on postmortem cardiac findings from one of the treated patients, who died 11 months after cell therapy. Methods and Results— Anatomicopathologic, morphometric, and immunocytochemical findings from the anterolateral ventricular wall (with cell therapy) were compared with findings from the interventricular septum (normal perfusion and no cell therapy) and from the inferoposterior ventricular wall (extensive scar tissue and no cell therapy). No signs of adverse events were found in the cell-injected areas. Capillary density was significantly higher ( P <0.001) in the anterolateral wall than in the previously infarcted tissue in the posterior wall. The prominent vascul...
2010
Background-This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility. Methods and Results-Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage Ն6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (Pϭ0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (Pϭ0.003) and a reduction in end-systolic volume (Pϭ0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (PϽ0.0005) at 4 months after treatment. Conclusions-Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrowderived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function. (Circulation. 2003;107:2294-2302.)
The Journal of Heart and Lung Transplantation, 2015
BACKGROUND: Long-term results regarding treatment of chronic ischemic heart failure with bone marrow mononuclear cells (BMMCs) have been few. We received encouraging results at the 1-year follow-up of patients treated with combined coronary artery bypass grafting (CABG) and BMMCs, so we decided to extend the follow-up. METHODS: The study patients had received injections of BMMCs or vehicle into the myocardial infarction border area during CABG in a randomized and double-blind manner. We could contact 36 of the 39 patients recruited for the original study. Pre-operatively and after an extended follow-up period, we performed magnetic resonance imaging, measured pro-B-type amino-terminal natriuretic peptide, reviewed patient records from the follow-up period, and determined current quality of life with the Medical Outcomes Study Short-Form 36 (SF-36) Health Survey. RESULTS: The median follow-up time was 60.7 months (interquartile range [IQR], 45.1-72.6 months). No statistically significant difference was detected in change of pro-B-type amino-terminal natriuretic peptide values or in quality of life between groups. The median change in left ventricular ejection fraction was 4.9% (IQR,-2.1% to 12.3%) for controls and 3.9% (IQR,-5.2% to 10.2%) for the BMMC group (p ¼ 0.647). Wall thickening in injected segments increased by a median of 17% (IQR,-5% to 30%) for controls and 15% (IQR,-12% to 19%) for BMMC patients (p ¼ 0.434). Scar size in injected segments increased by a median of 2% (IQR,-7% to 19%) for controls but diminished for BMMC patients, with a median change of-17% (IQR,-30% to-6%; p ¼ 0.011). CONCLUSIONS: In the treatment of chronic ischemic heart failure, combining intramyocardial BMMC therapy with CABG fails to affect cardiac function but can sustainably reduce scar size, even in the longterm.
Critical Care, 2003
Introduction Cardiac surgery with cardiopulmonary bypass (CPB) is a recognized trigger of systemic inflammatory response, usually related to postoperative acute lung injury (ALI). As an attempt to dampen inflammatory response, steroids have been perioperatively administered to patients. Macrophage migration inhibitory factor (MIF), a regulator of the endotoxin receptor, is implicated in the pathogenesis of ALI. We have previously detected peak circulating levels of MIF, 6 hours post CPB. Experimental data have shown that steroids may induce MIF secretion by mononuclear cells. This study aims to correlate levels of MIF assayed 6 hours post CPB to the intensity of postoperative pulmonary dysfunction, analysing the impact of perioperative steroid administration.
European Journal of Cardio-Thoracic Surgery, 2009
Objective: Cell therapy for patients with ischaemic cardiomyopathy (IC) is still an open issue. We aimed to assess the long-term safety and therapeutic potency of autologous bone marrow mononuclear cell (ABMMNC) implantation into ungraftable coronary artery (UCA) territories in patients with IC. Methods: Bone marrow was aspirated from the iliac crest, and transepicardial ABMMNC implantation (n = 25, 24 men, aged 57 AE 7 years) as an adjunct to coronary artery bypass grafting (CABG) was performed into an area of reversible ischaemia within the territory of UCA (1.29 AE 0.09 Â 10 9 ABMMNCs). Control group (n = 25, 23 men, aged 59 AE 7 years) underwent incomplete CABG due to poor target vessel graftability. The study protocol consisted of coronary angiography, stress echocardiography, nuclear imaging and Holter monitoring at baseline and follow-up. The mean follow-up time was 988 AE 423 days. Results: There was no difference between the groups regarding postoperative complications and outcome. Overall 5-year survival for the ABMMNC group was 79 AE 10%, and 71 AE 12% for the controls (p = 0.48). Left ventricular ejection fraction (LVEF) at baseline was 24.8 AE 3.7 versus 25.9 AE 3.1 in the ABMMNC group and the controls, respectively. After 6 months, mean global LVEF increased to 36.3 AE 7.4 (p < 0.001) versus 31.4 AE 4.1 (p = 0.001), respectively. A significant difference was noted in delta LVEF between the groups (p < 0.001, 95% confidence interval (CI): 3.4-8.9) at 6 months, and (p = 0.001, 95% CI: 2.0-7.4) at 1 year. Accordingly, perfusion scores in UCA segments detected by single-photon emission computed tomography (SPECT) improved with ABMMNC therapy to 18.0 AE 24.4 from 7.1 AE 25.7 (p = 0.001 vs control UCA segments). Conclusion: Cellular therapy for IC within UCA could augment myocardial perfusion and contractility but does not improve overall survival. No adverse events were detected after cell therapy at mid-term follow-up.