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  • Clinical Research
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Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study

Nature Clinical Practice Cardiovascular Medicine volume 6, pages 70–81 (2009)Cite this article

Abstract

Background Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction (AMI). We compared the safety and feasibility of early and late delivery of stem cells with combined therapy approaches.

Methods Patients with left ventricular ejection fraction less than 45% after AMI were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3–6 weeks or 3–4 months after AMI. Primary end points were changes in infarct size and left ventricular ejection fraction 3 months after therapy.

Results A total of 60 patients were treated. The mean changes in infarct size at 3 months were −3.5 ± 5.1% (95% CI −5.5% to −1.5%, P = 0.001) in the early group and −3.9 ± 5.6% (95% CI −6.1% to −1.6%, P = 0.002) in the late group, and changes in ejection fraction were 3.5 ± 5.6% (95% CI 1.3–5.6%, P = 0.003) and 3.4 ± 7.0% (95% CI 0.7–6.1%, P = 0.017), respectively. At 9–12 months after AMI, ejection fraction remained significantly higher than at baseline in both groups. In the early and late groups, a mean of 200.3 ± 68.7 × 106 and 194.8 ± 60.4 × 106 stem cells, respectively, were delivered to the myocardium, and 1.30 ± 0.68 × 109 and 1.29 ± 0.41 × 109 cells, respectively, were delivered into the artery. A high number of cells was required for significant improvements in the primary end points.

Conclusions Combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.

Key Points

  • The combined (intramyocardial followed by intracoronary) application of cardiac BM-MNC therapy is safe and feasible in patients with recent AMI and severely depressed left ventricular function

  • Both early (mean 32 days post-AMI) and late (mean 93 days post-AMI) treatment resulted in an improvement in infarct size and global ejection fraction, with temporary significant benefit of the early therapy

  • The 9–12 months control revealed a sustained beneficial effect of the combined delivery of the BM-MNC on left ventricular function

  • A reduction of infarct size was achieved in 76.6% and 70% of patients in Early and Late groups respectively, with 66.7% of patients in both groups showing improvement in global ejection fraction 3 months after cardiac delivery of BM-MNC

  • The total number of intramyocardially injected BM-MNC proved to be a statistically significant predictor of the reduction of infarct size

  • For a 5% decrease in infarct size, at least 219 × 106 intramyocardially injected BM-MNC and 4.29 × 106 CD34+ cells are required

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Figure 1: Selection and enrollment of patients.
Figure 2: Changes in infarct size and ejection fraction after therapy with bone-marrow-derived mononuclear cells.
Figure 3: NOGA® (Cordis Corp., Miami Lakes, FL) mapping and 99m-technetium-labeled sestamibi single-photon emission CT assessment of infarct size before and after administration of bone-marrow-derived stem cells.
Figure 4: Frequency of improvement and worsening of infarct size and ejection fraction after administration of bone-marrow-derived stem cells.
Figure 5: Correlations between the absolute numbers of intramyocardially injected unselected bone-marrow-derived (mononuclear) stem cells and CD34+ cells and the improvements in infarct size.

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Acknowledgements

This study was supported by the Österreichischer Herzfond (project number 05/059), an educational grant from the OMAA (Austrian-Hungarian Action Foundation, project number 60öu7), and the Austrian Society of Cardiology.

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Authors and Affiliations

  1. Department of Cardiology, Medical University of Vienna, Austria

    Mariann Gyöngyösi, Irene Lang, Gilbert Beran, Senta Graf, Heinz Sochor, Silvia Charwat, Rayyan Hemetsberger, Günter Christ, Sholeh Zamini, Aliasghar Khorsand, Gerald Maurer & Dietmar Glogar

  2. Department of Transfusion Medicine, Medical University of Vienna, Austria

    Markus Dettke

  3. Department of Cardiology and Internal Medicine, National Health Service Center, Budapest, Hungary

    Noémi Nyolczas, Róbert Kiss & István Préda

  4. Department of Cardiology, University of Debrecen, Hungary

    István Édes & László Balogh

  5. Cardiology, AK St. Georg, Hamburg, Germany

    Korff Thomas Krause, Kai Jaquet & Karl-Heinz Kuck

  6. Department of Cardiology, University of Targu Mures, Romania

    Imre Benedek & Theodora Hintea

  7. Uni-Clinic-Center, University “St. Cyril and Methodius”, Skopje, Macedonia

    Vladimir Kotevski & Hristo Pejkov

  8. Department of Emergency Medicine, Medical University of Vienna, Austria

    Gottfried Sodeck

  9. Institute of Clinical Biometrics, Medical University of Vienna, Austria

    Alexandra Kaider

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  1. Mariann Gyöngyösi
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Correspondence to Mariann Gyöngyösi.

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Gyöngyösi, M., Lang, I., Dettke, M. et al. Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study. Nat Rev Cardiol 6, 70–81 (2009). https://doi.org/10.1038/ncpcardio1388

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