EXPEDITED REVIEW
Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction
Final one-year results of the TOPCARE-AMI Trial
Volker Schächinger, MD*,
Birgit Assmus, MD*,
Martina B. Britten, MD*,
Jörg Honold, MD*,
Ralf Lehmann, MD*,
Claudius Teupe, MD*,
Nasreddin D. Abolmaali, MD ,
Thomas J. Vogl, MD,
Wolf-Karsten Hofmann, MD ,
Hans Martin, MD,
Stefanie Dimmeler, PhD* and
Andreas M. Zeiher, MD*,*
* Department of Cardiology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany
Department of Radiology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany
Department of Hematology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany
Manuscript received June 8, 2004;
revised manuscript received June 24, 2004,
accepted August 2, 2004.
* Reprint requests and correspondence: Dr. Andreas M. Zeiher, Department of Internal Medicine IV, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
(Email: zeiher{at}em.uni-frankfurt.de).
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | AMI = acute myocardial infarction | | BMC = bone marrow-derived progenitor cells | | CPC = circulating progenitor cells | | EF = ejection fraction | | LAD = left anterior descending | | LV = left ventricular | | MI = myocardial infarction | | MRI = magnetic resonance imaging | | TOPCARE-AMI = Transplantation of Progenitor Cells And Regeneration Enhancement in Acute Myocardial Infarction trial |
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