Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial.
OBJECTIVE
The Transplantation of Progenitor Cells And Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) trial investigates both safety, feasibility, and potential effects on parameters of myocardial function of intracoronary infusion of either circulating progenitor cells (CPC) or bone marrow-derived progenitor cells (BMC) in patients with acute myocardial infarction (AMI).


BACKGROUND
In animal experiments, therapy with adult progenitor cells was shown to improve vascularization, left ventricular (LV) remodeling, and contractility after AMI.


METHODS
A total of 59 patients with AMI were randomly assigned to receive either CPC (n = 30) or BMC (n = 29) into the infarct artery at 4.9 +/- 1.5 days after AMI.


RESULTS
Intracoronary progenitor cell application did not incur any measurable ischemic myocardial damage, but one patient experienced distal embolization before cell therapy. During hospital follow-up, one patient in each cell group developed myocardial infarction; one of these patients died of cardiogenic shock. No further cardiovascular events, including ventricular arrhythmias or syncope, occurred during one-year follow-up. By quantitative LV angiography at four months, LV ejection fraction (EF) significantly increased (50 +/- 10% to 58 +/- 10%; p < 0.001), and end-systolic volumes significantly decreased (54 +/- 19 ml to 44 +/- 20 ml; p < 0.001), without differences between the two cell groups. Contrast-enhanced magnetic resonance imaging after one year revealed an increased EF (p < 0.001), reduced infarct size (p < 0.001), and absence of reactive hypertrophy, suggesting functional regeneration of the infarcted ventricles.


CONCLUSIONS
Intracoronary infusion of progenitor cells (either BMC or CPC) is safe and feasible in patients after AMI successfully revascularized by stent implantation. Both the excellent safety profile and the observed favorable effects on LV remodeling, provide the rationale for larger randomized double-blind trials.
Department of Cardiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Volker
V
Schächinger
Birgit
B
Assmus
Martina B
MB
Britten
Jörg
J
Honold
Ralf
R
Lehmann
Claudius
C
Teupe
Nasreddin D
ND
Abolmaali
Thomas J
TJ
Vogl
Wolf-Karsten
WK
Hofmann
Hans
H
Martin
Stefanie
S
Dimmeler
Andreas M
AM
Zeiher
D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D003326:Coronary Circulation / Q000502:physiology; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000503:physiopathology; D018380:Hematopoietic Stem Cell Transplantation; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D010865:Pilot Projects; D011183:Postoperative Complications / Q000401:mortality; D012038:Regeneration / Q000502:physiology; D012770:Shock, Cardiogenic / Q000401:mortality; D020257:Ventricular Remodeling / Q000502:physiology