Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up.

Abstract

RATIONALE:

CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance.

OBJECTIVE:

We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response.

METHODS AND RESULTS:

Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39).

CONCLUSIONS:

Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

• Authors: Bojan Vrtovec, Gregor Poglajen, Luka Lezaic, Matjaz Sever, Dragoslav Domanovic, Peter Cernelc, Aljaz Socan, Sonja Schrepfer, Guillermo Torre-Amione, François Haddad, Joseph C Wu
• Journal: Circulation research (Circ Res) Vol. 112 Issue 1 Pg. 165-73 (Jan 04 2013) ISSN: 1524-4571 [Electronic] United States
• PMID: 23065358 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD34
• Biomarkers
• IL6 protein, human
• Interleukin-6
• Peptide Fragments
• Tumor Necrosis Factor-alpha
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain

Topics

• Antigens, CD34 (metabolism)
• Biomarkers (metabolism)
• California
• Cardiomyopathy, Dilated (blood, diagnosis, immunology, mortality, pathology, physiopathology, surgery)
• Cause of Death
• Cell Movement
• Cell Tracking
• Chi-Square Distribution
• Coronary Circulation
• Echocardiography
• Exercise Test
• Exercise Tolerance
• Female
• Follow-Up Studies
• Humans
• Injections, Intra-Arterial
• Interleukin-6 (blood)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Myocardial Perfusion Imaging
• Myocardium (immunology, pathology)
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Proportional Hazards Models
• Recovery of Function
• Slovenia
• Stem Cell Transplantation (adverse effects, mortality)
• Stem Cells (immunology)
• Stroke Volume
• Texas
• Time Factors
• Treatment Outcome
• Tumor Necrosis Factor-alpha (blood)
• Ventricular Function, Left