Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI).
BACKGROUND
Experimental studies suggest that transplantation of blood-derived or bone marrow-derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown.


RESULTS
We randomly allocated 20 patients with reperfused acute myocardial infarction (AMI) to receive intracoronary infusion of either bone marrow-derived (n=9) or circulating blood-derived progenitor cells (n=11) into the infarct artery 4.3+/-1.5 days after AMI. Transplantation of progenitor cells was associated with a significant increase in global left ventricular ejection fraction from 51.6+/-9.6% to 60.1+/-8.6% (P=0.003), improved regional wall motion in the infarct zone (-1.5+/-0.2 to -0.5+/-0.7 SD/chord; P<0.001), and profoundly reduced end-systolic left ventricular volumes (56.1+/-20 mL to 42.2+/-15.1 mL; P=0.01) at 4-month follow-up. In contrast, in a nonrandomized matched reference group, left ventricular ejection fraction only slightly increased from 51+/-10% to 53.5+/-7.9%, and end-systolic volumes remained unchanged. Echocardiography revealed a profound enhancement of regional contractile function (wall motion score index 1.4+/-0.2 at baseline versus 1.19+/-0.2 at follow-up; P<0.001). At 4 months, coronary blood flow reserve was significantly (P<0.001) increased in the infarct artery. Quantitative F-18-fluorodeoxyglucose-positron emission tomography analysis revealed a significant (P<0.01) increase in myocardial viability in the infarct zone. There were no differences for any measured parameter between blood-derived or bone marrow-derived progenitor cells. No signs of an inflammatory response or malignant arrhythmias were observed.


CONCLUSIONS
In patients with AMI, intracoronary infusion of autologous progenitor cells appears to be feasible and safe and may beneficially affect postinfarction remodeling processes.
Assmus
Birgit
B
Department of Molecular Cardiology, University of Frankfurt, Frankfurt, Germany.
Schächinger
Volker
V
Teupe
Claudius
C
Britten
Martina
M
Lehmann
Ralf
R
Döbert
Natascha
N
Grünwald
Frank
F
Aicher
Alexandra
A
Urbich
Carmen
C
Martin
Hans
H
Hoelzer
Dieter
D
Dimmeler
Stefanie
S
Zeiher
Andreas M
AM
D002478:Cells, Cultured; D017023:Coronary Angiography; D003326:Coronary Circulation; D004452:Echocardiography; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000379:methods*; D011877:Radionuclide Imaging; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D013318:Stroke Volume; D035703:Therapies, Investigational / Q000009:adverse effects / Q000379:methods; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology
D019788:Fluorodeoxyglucose F18