Pilot study to evaluate the safety and feasibility of intracoronary CD133(+) and CD133(-) CD34(+) cell therapy in patients with nonviable anterior myocardial infarction.
OBJECTIVE
The long-term effect of intracoronary infusion of progenitor cells in patients with chronic ischemic cardiomyopathy.


BACKGROUND
Bone marrow stem-cell administration in patients with myocardial infarction improved myocardial performance and in some studies contributed to favorable left ventricular remodeling.


METHODS
We report on the results of a pilot, single center, controlled safety, and feasibility study, including 24 patients with old, nonviable anterior myocardial infarction. Twelve patients underwent intracoronary administration of selected CD133(+) and CD133(-)CD34(+) progenitor cells and 12 were followed up on medical therapy. Left ventricular volumes and ejection fraction, at rest and during low-dose dobutamine, and myocardial viability, using TL-201 reinjection scintigraphy, were analyzed at baseline and long-term follow-up.


RESULTS
Patients in the treatment group experienced a sustained decrease in left ventricular end-diastolic and end-systolic resting volumes (P = 0.008 and P = 0.002, respectively), as well as an improvement in global ejection fraction at rest [from (27.2 +/- 6.8)% to (29.7 +/- 7.3)%, P = 0.016]. Segmental anterior and apical wall perfusion, during TL-201 reinjection, were similarly improved (P = 0.005 and P < 0.001, respectively). One patient developed restenosis at the cell delivery site and one progression of atherosclerosis. During 28.0 +/- 8.7 months of clinical follow-up, only one patient experienced deterioration of heart failure. In the control group, we observed stability in the perfusion defect and deterioration in end-diastolic and end-systolic volumes (P= 0.002 and P = 0.003, respectively) and a nonsignificant decrease in ejection fraction (P = 0.11).


CONCLUSIONS
Intracoronary infusion of selected CD133(+) and CD133(-)CD34(+) progenitor cells to a previously infarcted and nonviable anterior wall is safe, and results in sustained improvement in segmental myocardial perfusion and in favorable left ventricular remodeling.
Manginas
Athanassios
A
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. nassoseft@yahoo.com
Goussetis
Evgenios
E
Koutelou
Maria
M
Karatasakis
George
G
Peristeri
Ioulia
I
Theodorakos
Athanassios
A
Leontiadis
Evangelos
E
Plessas
Nikolaos
N
Theodosaki
Maria
M
Graphakos
Stelios
S
Cokkinos
Dennis V
DV
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D003326:Coronary Circulation; D004452:Echocardiography / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D010455:Peptides / Q000032:analysis*; D010865:Pilot Projects; D011446:Prospective Studies; D012107:Research Design; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013234:Stem Cells / Q000276:immunology*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides