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Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with left ventricular assist device bridge to transplant.

ABSTRACT: BACKGROUND:Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation. OBJECTIVES:The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation. METHODS:Subjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to transplantation underwent bone marrow aspiration the day before surgery; the bone marrow was processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34-). At LVAD implantation, all fractions and a saline control were injected epicardially into predetermined areas and each injection site marked. At the time of transplantation, injected areas were collected. Data were analyzed by paired Student t test comparing the effect of cell fractions injected within each subject. RESULTS:Six subjects completed the study. There were no statistically significant differences in complications with the procedure versus control subjects. Histological analysis indicated that myocardium injected with CD34+ cells had decreased density of endothelial cells compared to saline-injected myocardium. There were no significant differences in fibrosis or inflammation between groups; however, density of activated fibroblasts was decreased in both CD34+ and CD34- injected areas. CONCLUSIONS:Tissue analysis does not support the hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection.

SUBMITTER: Stempien-Otero A

PROVIDER: S-EPMC4771180 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with left ventricular assist device bridge to transplant.

Stempien-Otero April A Helterline Deri D Plummer Tabitha T Farris Stephen S Prouse Andrew A Polissar Nayak N Stanford Derek D Mokadam Nahush A NA

Journal of the American College of Cardiology 20150401 14

<h4>Background</h4>Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation.<h4>Objectives</h4>The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in hum ...[more]

PMID: 25857908

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Project description:AimsThis study investigated outcomes after continuous flow left ventricular assist device (CF-LVAD) implantation as bridge to heart transplantation (BTT) in advanced heart failure patients stratified by race.Methods and resultsDe-identified data from the United Network for Organ Sharing database was obtained for all patients who had a CF-LVAD as BTT from 2008 to 2018. Patients were stratified into four groups on the basis of ethnicity [Caucasian, African American (AA), Hispanic, and others (Asian, Pacific Islanders, and American Indian)]. Outcomes investigated were waitlist mortality or delisting and post-transplant 5 year survival. Cox proportional hazards modelling was used to identify independent predictors of waitlist mortality or delisting and post-transplant survival. We used Kaplan-Meier survival curves and the log-rank test to estimate and compare survival among groups. A total of 14 234 patients who had CF-LVADs as BTT were identified. Of these, 64% (n = 9058) were Caucasians, 26% (n = 3677) were AA, 7% (n = 997) were Hispanic, and 3% (n = 502) had a different race. Compared with Caucasian, AA, and Hispanic patients had higher body mass indexes and a lower level of education and are more likely to be public health insurance beneficiaries. There was a significantly lower incidence of transplantation in AAs compared with Caucasians, Hispanics, and others at 12, 24, and 60 months, respectively (Gray's test, P < 0.001). The AA race was a significant predictor of waitlist mortality or delisting owing to worsening clinical status [hazard ratio, 95% confidence interval: 1.10 (1.01 to 1.16; P < 0.001)]. Among those who were successfully BTT, risk-adjusted post-transplant survival was similar among the four groups (log-rank test: P = 0.589).ConclusionsDisparities exist among different races that receive a CF-LVAD as a BTT. These disparities translate into increased waitlist morbidity and mortality but not long-term post-transplant survival among those who successfully reach transplant.

Dataset Information

Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with left ventricular assist device bridge to transplant.

Publications

Mechanisms of bone marrow-derived cell therapy in ischemic cardiomyopathy with left ventricular assist device bridge to transplant.

Similar Datasets

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