Effects of Intracoronary Stem Cell Transplantation in Patients With Dilated Cardiomyopathy

doi:10.1016/j.cardfail.2010.11.007

Journal of Cardiac Failure

Volume 17, Issue 4, April 2011, Pages 272-281

https://doi.org/10.1016/j.cardfail.2010.11.007 Get rights and content

Abstract

Background

We investigated clinical effects of intracoronary transplantation of CD34+ cells in patients with dilated cardiomyopathy (DCM).

Methods

Of 55 patients with DCM, 28 were randomized to CD34+ transplantation (SC group), and 27 patients did not receive stem cell therapy (controls). In the SC group, peripheral blood CD34+ cells were mobilized by granulocyte-colony stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and CD34+ cells were injected in the coronary artery supplying the segments with reduced viability.

Results

At baseline, the 2 groups did not differ in age, gender, left ventricular ejection fraction (LVEF), or NT-proBNP levels. At 1 year, stem cell therapy was associated with an increase in LVEF (from 25.5 ± 7.5% to 30.1 ± 6.7%; P = .03), an increase in 6-minute walk distance (from 359 ± 104 m to 485 ± 127 m; P = .001), and a decrease in NT-proBNP (from 2069 ± 1996 pg/mL to 1037 ± 950 pg/mL; P = .01). The secondary endpoint of 1-year mortality or heart transplantation was lower in patients receiving SC therapy (2/28, 7%) than in controls (8/27, 30%) (P = .03), and SC therapy was the only independent predictor of outcome on multivariable analysis (P = .04).

Conclusions

Intracoronary stem cell transplantation could lead to improved ventricular remodeling, better exercise tolerance and potentially improved survival in patients with DCM.

Section snippets

Patient Population

This study consists of an open-label randomized study design conducted at the Advanced Heart Failure and Transplantation Center at University Medical Center Ljubljana between January 1, 2008, and September 1, 2008, in collaboration with the Methodist DeBakey Heart Center and Stanford University.

Patients with heart failure referred to Advanced Heart Failure and Transplantation Center at University Medical Center Ljubljana were considered for inclusion in the study. Inclusion criteria consisted

Patient Characteristics

Of 61 patients entering Phase 1, we excluded 1 patient because of improvement of cardiac function and 5 patients with inadequate neutrophil rise after G-CSF stimulation. The remaining 55 patients were randomly allocated into SC group (n = 28) and control group (n = 27). A flowchart of the study design is presented in Figure 1. In either Phase I or Phase 1 or Phase 2, there have been no G-CSF-related cardiovascular adverse events, and the troponin levels remained normal throughout the

Discussion

In this pilot, open-label randomized study, we investigated the clinical effects of intracoronary administration of autologous bone marrow-derived stem cells in patients with dilated cardiomyopathy. Although our sample size was small, we were able to demonstrate successful engraftment of transplanted stem cells and improvement in left ventricular systolic function (LVEF) and exercise capacity at 12 months. The potential beneficial effects of SC therapy in patients with DCM were also supported

Conclusions

The results of this pilot randomized trial suggest that intracoronary delivery of autologous CD34+ cells represents a safe and effective technique that improves left ventricular function and clinical status of patients with dilated cardiomyopathy, which may be associated with better 1-year outcome. Further, larger studies are warranted to better define the underlying mechanisms and to investigate whether or not these findings may also translate into improved long-term survival of patients with

Disclosures

None.

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Twelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93–6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62–157.35, P = 0.0004) and reduced BNP level (–294.94 pg/mL, 95% CI, –383.97 to –205.90, P < 0.00001) and NYHA classification (–0.70, 95% CI, –0.98 to –0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, –0.09 cm, 95% CI, –0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52–1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23–0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27–0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive.
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Heart failure is a global epidemic that drastically cuts short longevity and compromises quality of life. Approximately 6 million Americans ≥20 years of age carry a diagnosis of heart failure. Worldwide, about 40 million adults are affected. The treatment of HF depends on the etiology. If left untreated it rapidly progresses and compromises quality of life. One of the newer technologies still in its infancy is stem cell therapy for heart failure. This review attempts to highlight the clinical studies done in ischemic cardiomyopathy, dilated cardiomyopathy and restrictive cardiomyopathy. A combined approach of simultaneous revascularization and stem cell therapy appears to produce maximum benefit in ischemic cardiomyopathy. Treatment of dilated cardiomyopathy with stem cells also holds promise but needs more definition with regards to timing, route of cell delivery and type of cell used to achieve reproducible results. The variability noted in response to stem cell therapy in patients could also be secondary to their co-morbidities. Abnormalities of glucose metabolism and diabetes in particular impair stem cell and angiogenic cell mobilization. This opens up a whole new area of investigation into exploring the biochemical microenvironment which could influence the efficacy of stem cell therapy. This article is part of a Special Issue entitled: Stem Cells and Their Applications to Human Diseases edited by Hemachandra Reddy.
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View all citing articles on Scopus

: Clinical Trial Registration Information: Clinicaltrials.gov identifier: NCT00629018.

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Clinical TrialEffects of Intracoronary Stem Cell Transplantation in Patients With Dilated Cardiomyopathy

Abstract

Background

Methods

Results

Conclusions

Section snippets

Patient Population

Patient Characteristics

Discussion

Conclusions

Disclosures

Cardiovasc Revasc Med

J Elecardiol

Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis

Arch Intern Med

Transcoronary transplantation of progenitor cells after myocardial infarction

N Engl J Med

Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy

Circulation

Simultaneous autologous transplantation of cocultured mesenchymal stem cells and skeletal myoblasts improves ventricular function in a murine model of Chagas disease

Circulation

ESC Working Group. The classification concept of the ESC Working Group on myocardial and pericardial diseases for dilated cardiomyopathy

Herz

Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review

Eur Heart J

Beat-to-beat QT interval variability: novel evidence for repolarization lability in ischemic and nonischemic dilated cardiomyopathy

Circulation

G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation: safety, kinetics of mobilization, and composition of the graft

Br J Haematol

Feasibility and safety of autologous intracoronary stem cell transplantation in patients of non ischemic dilated cardiomyopathy

Indian Heart J

Transendocardial injection of autologous bone marrow mononuclear cells may enhance myocardial viability around cell injection site

J Am Coll Cardiol

Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure

Circulation

Clinical Trial
Effects of Intracoronary Stem Cell Transplantation in Patients With Dilated Cardiomyopathy