Stem Cells Improve Left Ventricular Function in Acute Myocardial Infarction (original) (raw)
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Circulation Research, 2016
Rationale: Cardiac stem cells (CSC) therapy has been clinically introduced for cardiac repair after myocardial infarction (MI). To date, there has been no systematic overview and meta-analysis of studies using CSC therapy for MI. Objective: Here, we used meta-analysis to establish the overall effect of CSCs in preclinical studies and assessed translational differences between and within large and small animals in the CSC therapy field. In addition, we explored the effect of CSC type and other clinically relevant parameters on functional outcome to better predict and design future (pre)clinical studies using CSCs for MI. Methods and Results: A systematic search was performed, yielding 80 studies. We determined the overall effect of CSC therapy on left ventricular ejection fraction and performed meta-regression to investigate clinically relevant parameters. We also assessed the quality of included studies and possible bias. The overall effect observed in CSC-treated animals was 10.7% ...
The Indian journal of medical research, 2015
Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. In this phase III prospective, multicentric trial 250 patient...
Circulation: Cardiovascular Interventions, 2014
Background-Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the benefits still remain controversial. This meta-analysis aims to evaluate the efficacy of bone marrow-derived mononuclear cell (BMMNC) therapy in patients with acute myocardial infarction, but also explores the effect of newer generations of stem cells. Methods and Results-A random-effects meta-analysis was performed on randomized controlled trials investigating the effects of stem cell therapy in patients with acute myocardial infarction that were published between January 2002 and September 2013. The defined end points were left ventricular (LV) ejection fraction, LV end-systolic and end-diastolic volumes, infarct size, and major adverse cardiac and cerebrovascular event rates. Also, several subgroup analyses were performed on BMMNC trials. Overall, combining the results of 22 randomized controlled trials (RCTs), LV ejection fraction increased by +2.10% (95% confidence interval [CI], 0.68-3.52; P=0.004) in the BMMNC group as compared with controls, evoked by a preservation of LV end-systolic volume (−4.05 mL; 95% CI, −6.91 to −1.18; P=0.006) and a reduction in infarct size (−2.69%; 95% CI, −4.83 to −0.56; P=0.01). However, there is no effect on cardiac function, volumes, or infarct size, when only RCTs (n=9) that used MRI-derived end points were analyzed. Moreover, no beneficial effect could be detected on major adverse cardiac and cerebrovascular event rates after BMMNC infusion after a median follow-up duration of 6 months. Conclusions-Intracoronary infusion of BMMNC is safe, but does not enhance cardiac function on MRI-derived parameters, nor does it improve clinical outcome. New and possibly more potent stem cells are emerging in the field, but their clinical efficacy still needs to be defined in future trials.
Stem cell research & therapy, 2016
Bone marrow-derived cell therapy has been used to treat acute myocardial infarction. However, the therapeutic efficacy of this approach remains controversial. Here, we performed a systematic review and meta-analysis to evaluate short-term and long-term effectiveness of bone marrow-derived therapy. We searched eight databases (Ovid-Medline, Ovid-EMBASE, Cochrane Library, KoreaMed, KMBASE, KISS, RISS, and KisTi) up to December 2014. Demographic characteristics, clinical outcomes, and adverse events were analyzed. We identified 5534 potentially relevant studies; 405 were subjected to a full-text review. Forty-three studies with 2635 patients were included in this review. No safety issues related to cell injection were reported during follow-up. At 6 months, cell-injected patients showed modest improvements in left ventricular ejection fraction (LVEF) compared with the control group. However, there were no differences between groups at other time points. In the cardiac MRI analysis, the...
Interactive cardiovascular and thoracic surgery, 2011
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Can intracoronary stem cell injection permanently improve cardiac function after myocardial infarction?'. Altogether 314 papers were found using the reported search, of which five represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that stem cells may have controversial effects on cardiac function in long-term follow-up of more than two years as they improved the left ventricular ejection fraction and end systolic volume index just in two studies in which none of them utilized cardiac magnetic resonance imaging (MRI), as the most reliable method, to quantify cardiac function. However, all remaining three trials which reported negative results used cardiac MRI for assessment of cardiac inde...
Factors Affecting Outcomes of Bone Marrow Stem Cell Therapy for Acute Myocardial Infarction
Georgetown Medical Review
Myocardial infarction (MI) poses a significant burden to both patients and the health care system. The irreversible loss of functional cardiomyocytes due to ischemia threatens both patients’ immediate survival and quality of life over their lifespan. Stem cell therapy has been proposed as a solution to salvage cardiac contractility through the regeneration of cardiomyocytes, and bone marrow–derived stem cells (BMSc) are among the category of stem cells most extensively studied. Despite the promising theoretical potential of BMSc in tissue regeneration, several key aspects remain to be better understood to enable large-scale clinical application, including safety and efficacy. Our current work in synthesizing and evaluating both preclinical and clinical studies using stem cell applications in acute MI has demonstrated that BMSc transplantation is a safe therapy for MI. Although this therapy’s efficacy is not consistently proven, we have significantly improved our understanding of fac...
2009
To investigate the effect of intracoronary injection of autologous mononuclear bone marrow stem cells (BMSCs) in patients with ST-elevation myocardial infarction (STEMI) on left ventricular (LV) systolic and diastolic function using standard echocardiography and 2-dimensional systolic strain. A total of 60 patients with first anterior wall STEMI and LV ejection fraction of <40%, treated with successful primary percutaneous coronary intervention were randomly assigned to the treatment group (BMSC group) or the control group in a 2:1 ratio. Transcatheter intracoronary injection of BMSCs into the infarct-related artery was performed 7 days after STEMI. Standard echocardiography and speckle tracking analysis was performed at baseline and 6 months after STEMI. No differences were found in the baseline echocardiographic parameters of LV systolic and diastolic dysfunction--the LV ejection fraction was 35 +/- 6% in the BMSC group, similar to that in the control group (33 +/- 7%, p = 0.42). After 6 months, the absolute change in the LV ejection fraction was significantly greater in the BMSC group than in the control group (10 +/- 9% versus 5 +/- 8%, p = 0.04). Significant improvement was seen in 2-dimensional systolic strain in all segments (12 +/- 4 vs 14 +/- 4; p = 0.0009) and in the infarcted area (5 +/- 2 vs 6 +/- 2; p = 0.0038) only in the BMSC group. Of the diastolic function parameters, we observed improvement in the early filling propagation velocity (30 +/- 8 cm/s vs 37 +/- 13 cm/s; p = 0.0008), early diastolic velocity - E' (4.5 +/- 1.5 vs 5.0 +/- 1.3, p = 0.02), and the E/E' ratio (17 +/- 7 vs 14 +/- 5; p = 0.03) in the BMSC group. In conclusion, intracoronary injection of unselected BMSCs in patients with STEMI improved both LV systolic and diastolic function at 6 months of follow-up.