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Long-term effects of autologous bone marrow stem cell treatment in acute myocardial infarction: factors that may influence outcomes.

ABSTRACT: AIMS: To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. METHODS AND RESULTS: MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005-2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 10(8) cells and to patients with more severe heart dysfunction. CONCLUSIONS: Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials.

SUBMITTER: Clifford DM

PROVIDER: S-EPMC3360027 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Long-term effects of autologous bone marrow stem cell treatment in acute myocardial infarction: factors that may influence outcomes.

Clifford David M DM Fisher Sheila A SA Brunskill Susan J SJ Doree Carolyn C Mathur Anthony A Clarke Mike J MJ Watt Suzanne M SM Martin-Rendon Enca E

PloS one 20120524 5

<h4>Aims</h4>To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment.<h4>Methods and results</h4>MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searche ...[more]

PMID: 22655042

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Project description:The study examined the long-term outcome of cardiac stem cell transplantation in hearts with postinfarction left ventricular (LV) remodeling. Myocardial infarction (MI) was created by ligating the first and second diagonal branches of the left anterior descending coronary artery in miniature swine. Intramyocardial injections of 50 million LacZ-labeled bone marrow-derived multipotent progenitor cells (MPC) were performed in the periscar region (Cell, n = 7) immediately after MI, whereas, in control animals (Cont, n = 7), saline was injected. Functional outcome was assessed monthly for 4 mo with MRI and (31)P-magnetic resonance spectroscopy. Engraftment was studied on histology, and gene chip (Affymetrix) array analysis was used to study differential expression of genes in the two groups. MPC treatment resulted in improvement of ejection fraction as early as 10 days after MI (Cell, 43.4 +/- 5.1% vs. Cont, 32.2 +/- 5.5%; P < 0.05). This improvement was seen each month and persisted to 4 mo (Cell, 51.2 +/- 4.8% vs. Cont, 35.7 +/- 5.0%; P < 0.05). PCr-to-ATP ratio (PCr/ATP) improved with MPC transplantation, which was most pronounced at high cardiac work states (subendocardial PCr/ATP was 1.70 +/- 0.10 vs. 1.34 +/- 0.14, P < 0.05). There was no significant difference in scar size (scar/LV area * 100) at 10 days postinfarction. However, at 4 mo, there was a significant decrease in scar size in the Cell group (Cell, 4.6 +/- 1.0% vs. Cont, 8.6 +/- 2.4%; P < 0.05). No significant engraftment of MPC was observed. MPC transplantation was associated with a downregulation of mitochondrial oxidative enzymes and increased levels of myocyte enhancer factor 2a and zinc finger protein 91. In conclusion, MPC transplantation leads to long-term functional and bioenergetic improvement in a porcine model of postinfarction LV remodeling, despite no significant engraftment of stem cells in the heart. MPC transplantation reduces regional wall stresses and infarct size and mitigates the adverse effects of LV remodeling, as seen by a reduction in LV hypertrophy and LV dilatation, and is associated with differential expression of genes relating to metabolism and apoptosis.

Project description:ObjectivesThis study sought to determine the association of chronic stress with long-term adverse outcomes after acute myocardial infarction (AMI).BackgroundChronic stress has been shown to be associated with the development of cardiovascular disease and, in the case of particular types of stress such as job and marital strain, with recurrent adverse events after AMI. Little is known, however, about the association of chronic stress with mortality and adverse health status outcomes in a general AMI population.MethodsIn a cohort of 4,204 AMI patients from 24 U.S. hospitals completing the Perceived Stress Scale-4 (sum scores ranging from 0 to 16) during hospitalization, moderate/high stress over the previous month was defined as scores in the top 2 quintiles (scores of 6 to 16). Detailed data on sociodemographics, psychosocial status, and clinical characteristics were collected at baseline. Outcomes included patients' 1-year health status, assessed with the Seattle Angina Questionnaire, Short Form-12, and EuroQol Visual Analog Scale, and 2-year mortality.ResultsAMI patients with moderate/high stress had increased 2-year mortality compared with those having low levels of stress (12.9% vs. 8.6%; p < 0.001). This association persisted after adjusting for sociodemographics, clinical factors (including depressive symptoms), revascularization status, and GRACE (Global Registry of Acute Coronary Events) discharge risk scores (hazard ratio: 1.42: 95% confidence interval: 1.15 to 1.76). Furthermore, moderate/high stress was independently associated with poor 1-year health status, including a greater likelihood of angina, worse disease-specific and generic health status, and worse perceived health (p < 0.01 for all).ConclusionsModerate/high perceived stress at the time of an AMI is associated with adverse long-term outcomes, even after adjustment for important confounding factors. Future studies need to examine whether stress mediates observed racial and socioeconomic disparities and whether novel interventions targeting chronic stress and coping skills can improve post-AMI outcomes.

Dataset Information

Long-term effects of autologous bone marrow stem cell treatment in acute myocardial infarction: factors that may influence outcomes.

Publications

Long-term effects of autologous bone marrow stem cell treatment in acute myocardial infarction: factors that may influence outcomes.

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