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Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy

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Abstract

Background

Limited data is available for investigating the long-term safety and effects of intracoronary progenitor cell therapy in patients with acute myocardial infarction (AMI).

Objective

To assess the clinical course, NT-proBNP and MRI data as objective markers of cardiac function of the TOPCARE-AMI patients at 5-year follow-up.

Design

The TOPCARE-AMI trial was the first randomized study investigating the effects of intracoronary infusion of circulating (CPC) or bone marrow-derived progenitor cells (BMC) in 59 patients with successfully reperfused AMI.

Results

Five-year follow-up data were completed in 55 patients, 3 patients were lost to follow-up. None of the patients showed any signs of intramyocardial calcification or tumors at 5 years. One patient died during the initial hospitalization, no patient was rehospitalized for heart failure and 16 patients underwent target vessel revascularization (TVR). Only two TVRs occurred later than 1 year after cell administration making it very unlikely that the infused cells accelerate atherosclerotic disease progression.

Serum levels of NT-proBNP remained significantly reduced at the 5-year follow-up indicating the absence of heart failure. MRI subgroup analysis in 31 patients documented a persistent improvement of LV ejection fraction (from 46 ± 10% at baseline to 57 ± 10% at 5 years, p < 0.001)). Simultaneously, there was a reduction (p < 0.001) in functional infarct size measured as late enhancement volume normalized to LV mass. However, whereas LV end-systolic volume remained stable, LV end-diastolic volume increased significantly.

Conclusions

The 5-year follow-up of the TOPCARE-AMI trial provides reassurance with respect to the long-term safety of intracoronary cell therapy and suggests favorable effects on LV function.

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Abbreviations

AMI:

Acute myocardial infarction

BMC:

Bone marrow-derived mononuclear cells

BSA:

Body surface area

CPC:

Circulating progenitor cells

LVEF:

Left-ventricular ejection fraction

LAD:

Left anterior descending coronary artery

LV:

Left ventricular

LVEDV:

Left-ventricular end-diastolic volume

LVESV:

Left-ventricular end-systolic volume

MRI:

Magnetic resonance imaging

STEMI:

ST-segment elevation myocardial infarction

TOPCARE-AMI:

Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction trial

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Acknowledgments

We greatly appreciate the enthusiastic support of the staff of our catheterization laboratories and of our technicians Isabel Geweyer and Tabea Kretschmer (study nurses), Tina Rasper, and Nadine Sorg (biological technicians).

Conflict of interest

Drs. Dimmeler and Zeiher are cofounders of t2cure, a for-profit company focused on regenerative therapies for cardiovascular disease, and serve as scientific advisors and shareholders. Dr. Schächinger has received grant support from Guidant. Drs. Assmus and Schächinger report being scientific advisors of t2cure.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt, Germany

    David M. Leistner, Ulrich Fischer-Rasokat, Jörg Honold, Florian H. Seeger, Volker Schächinger, Ralf Lehmann, Andreas M. Zeiher & Birgit Assmus

  2. Division of Hematology, Department of Medicine II, Goethe University Frankfurt, Frankfurt, Germany

    Hans Martin

  3. Department of Radiology, Goethe University Frankfurt, Frankfurt, Germany

    Iris Burck

  4. Institute of Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany

    Carmen Urbich & Stefanie Dimmeler

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  1. David M. Leistner
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Correspondence to Birgit Assmus.

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Leistner, D.M., Fischer-Rasokat, U., Honold, J. et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy. Clin Res Cardiol 100, 925–934 (2011). https://doi.org/10.1007/s00392-011-0327-y

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