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


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.
Advanced Heart Failure and Transplantation Center, Department of Cardiology, Ljubljana University Medical Center, Zaloska 7, Ljubljana, MC SI-1000, Slovenia. bvrtovec@stanford.edu
Bojan
B
Vrtovec
Gregor
G
Poglajen
Luka
L
Lezaic
Matjaz
M
Sever
Dragoslav
D
Domanovic
Peter
P
Cernelc
Aljaz
A
Socan
Sonja
S
Schrepfer
Guillermo
G
Torre-Amione
François
F
Haddad
Joseph C
JC
Wu
D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002140:California; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002423:Cause of Death; D002465:Cell Movement; D058948:Cell Tracking; D016009:Chi-Square Distribution; D003326:Coronary Circulation; D004452:Echocardiography; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007269:Injections, Intra-Arterial; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D055414:Myocardial Perfusion Imaging; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D016016:Proportional Hazards Models; D020127:Recovery of Function; D017524:Slovenia; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D013234:Stem Cells / Q000276:immunology*; D013318:Stroke Volume; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D016277:Ventricular Function, Left
D018952:Antigens, CD34; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain