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J Am Coll Cardiol, 2007; 50:1761-1767, doi:10.1016/j.jacc.2007.07.041 (Published online 12 October 2007).
© 2007 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: MYOCARDIAL INFARCTION

Impact of Intracoronary Cell Therapy on Left Ventricular Function in the Setting of Acute Myocardial Infarction

A Collaborative Systematic Review and Meta-Analysis of Controlled Clinical Trials

Michael J. Lipinski, MD*,{dagger},2, Giuseppe G.L. Biondi-Zoccai, MD{ddagger},2,*, Antonio Abbate, MD{dagger}, Reena Khianey, MD{dagger}, Imad Sheiban, MD{ddagger}, Jozef Bartunek, MD, PhD§,1, Marc Vanderheyden, MD§,1, Hyo-Soo Kim, MD||, Hyun-Jae Kang, MD||, Bodo E. Strauer, MD# and George W. Vetrovec, MD{dagger}

* Department of Internal Medicine, University of Virginia, Charlottesville, Virginia
{dagger} Virginia Commonwealth University, Pauley Heart Center, Richmond, Virginia
{ddagger} Interventional Cardiology, Division of Cardiology, University of Turin, Turin, Italy
§ Cardiovascular Center and Cardiovascular Research Center, Aalst, Belgium
|| Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
# Department of Internal Medicine, Division of Cardiology, Pneumology, and Angiology, Heinrich Heine University, Duesseldorf, Germany.

Manuscript received May 21, 2007; revised manuscript received July 16, 2007, accepted July 17, 2007.

* Reprint requests and correspondence: Dr. Giuseppe Biondi-Zoccai, Interventional Cardiology, Division of Cardiology, University of Turin, S. Giovanni Battista "Molinette" Hospital, Corso Bramante 88-90, 10126 Turin, Italy. (Email: gbiondizoccai{at}gmail.com).

Objectives: We aimed to perform a meta-analysis of clinical trials on intracoronary cell therapy after acute myocardial infarction (AMI).

Background: Intracoronary cell therapy continues to be evaluated in the setting of AMI with variable impact on left ventricular ejection fraction (LVEF).

Methods: We searched the CENTRAL, mRCT, and PubMed databases for controlled trials reporting on intracoronary cell therapy performed in patients with a recent AMI (≤14 days), revascularized percutaneously, with follow-up of ≥3 months. The primary end point was change in LVEF, and secondary end points were changes in infarct size, cardiac dimensions, and dichotomous clinical outcomes.

Results: Ten studies were retrieved (698 patients, median follow-up 6 months), and pooling was performed with random effect. Subjects that received intracoronary cell therapy had a significant improvement in LVEF (3.0% increase [95% confidence interval (CI) 1.9 to 4.1]; p < 0.001), as well as a reduction in infarct size (–5.6% [95% CI –8.7 to –2.5]; p < 0.001) and end-systolic volume (–7.4 ml [95% CI –12.2 to –2.7]; p = 0.002), and a trend toward reduced end-diastolic volume (–4.6 ml [95% CI –10.4 to 1.1]; p = 0.11). Intracoronary cell therapy was also associated with a nominally significant reduction in recurrent AMI (p = 0.04) and with trends toward reduced death, rehospitalization for heart failure, and repeat revascularization. Meta-regression suggested the existence of a dose-response association between injected cell volume and LVEF change (p = 0.066).

Conclusions: Intracoronary cell therapy following percutaneous coronary intervention for AMI appears to provide statistically and clinically relevant benefits on cardiac function and remodeling. These data confirm the beneficial impact of this novel therapy and support further multicenter randomized trials targeted to address the impact of intracoronary cell therapy on overall and event-free long-term survival.

Abbreviations and Acronyms
  AMI = acute myocardial infarction
  BMC = bone marrow cell
  CI = confidence interval
  G-CSF = granulocyte colony-stimulating factor
  LV = left ventricular
  LVEDV = left ventricular end-diastolic volume
  LVEF = left ventricular ejection fraction
  LVESV = left ventricular end-systolic volume
  OR = odds ratio
  PMC = peripheral mononuclear cell
  TVR = target vessel revascularization


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M. C. van Oostrom, O. van Oostrom, P. H. A. Quax, M. C. Verhaar, and I. E. Hoefer
Insights into mechanisms behind arteriogenesis: what does the future hold?
J. Leukoc. Biol., December 1, 2008; 84(6): 1379 - 1391.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
T. Ziebart, C.-H. Yoon, T. Trepels, A. Wietelmann, T. Braun, F. Kiessling, S. Stein, M. Grez, C. Ihling, M. Muhly-Reinholz, et al.
Sustained Persistence of Transplanted Proangiogenic Cells Contributes to Neovascularization and Cardiac Function After Ischemia
Circ. Res., November 21, 2008; 103(11): 1327 - 1334.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
M. Ruel, A. F.R. Stewart, and E. J. Suuronen
From Genes to Regenerative Medicine: Approaches in Development
Circ. Res., November 7, 2008; 103(10): 1050 - 1052.
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 Eur Heart JHome page
H. V. Huikuri, K. Kervinen, M. Niemela, K. Ylitalo, M. Saily, P. Koistinen, E.-R. Savolainen, H. Ukkonen, M. Pietila, J. K.E. Airaksinen, et al.
Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction
Eur. Heart J., November 2, 2008; 29(22): 2723 - 2732.
[Abstract] [Full Text] [PDF]

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 HeartHome page
S. L M A Beeres, D. E Atsma, J. van Ramshorst, M. J Schalij, and J. J Bax
Cell therapy for ischaemic heart disease
Heart, September 1, 2008; 94(9): 1214 - 1226.
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 Eur Heart JHome page
P. Tossios, B. Krausgrill, M. Schmidt, T. Fischer, M. Halbach, J. W.U. Fries, S. Fahnenstich, P. Frommolt, I. Heppelmann, A. Schmidt, et al.
Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction
Eur. Heart J., August 1, 2008; 29(15): 1911 - 1921.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
P. Menasche
Towards the second generation of skeletal myoblasts?
Cardiovasc Res, August 1, 2008; 79(3): 355 - 356.
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 Cardiovasc ResHome page
M. R. Ward and D. J. Stewart
Erythropoietin and mesenchymal stromal cells in angiogenesis and myocardial regeneration: one plus one equals three?
Cardiovasc Res, August 1, 2008; 79(3): 357 - 359.
[Full Text] [PDF]

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 Eur J Heart FailHome page
A. C.P. Diederichsen, J. E. Moller, P. Thayssen, A. B. Junker, L. Videbaek, S. G. Saekmose, T. Barington, M. Kristiansen, and M. Kassem
Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure The Danish Stem Cell study--Congestive Heart Failure trial (DanCell-CHF)
Eur J Heart Fail, July 1, 2008; 10(7): 661 - 667.
[Abstract] [Full Text] [PDF]

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 Ther Adv Cardiovasc DisHome page
T. J. Povsic and P. J. Goldschmidt-Clermont
Review: Endothelial progenitor cells: markers of vascular reparative capacity
Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 199 - 213.
[Abstract] [PDF]

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 J Am Coll CardiolHome page
A. Abbate, G. G.L. Biondi-Zoccai, D. L. Appleton, P. Erne, A. W. Schoenenberger, M. J. Lipinski, P. Agostoni, I. Sheiban, and G. W. Vetrovec
Survival and Cardiac Remodeling Benefits in Patients Undergoing Late Percutaneous Coronary Intervention of the Infarct-Related Artery: Evidence From a Meta-Analysis of Randomized Controlled Trials
J. Am. Coll. Cardiol., March 4, 2008; 51(9): 956 - 964.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
R. K. Burt, Y. Loh, W. Pearce, N. Beohar, W. G. Barr, R. Craig, Y. Wen, J. A. Rapp, and J. Kessler
Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases
JAMA, February 27, 2008; 299(8): 925 - 936.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, P. Clopton, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, J. D. Knoke, W. Y.W. Lew, J. A.C. Lima, et al.
Highlights of the Year in JACC 2007
J. Am. Coll. Cardiol., January 29, 2008; 51(4): 490 - 512.
[Full Text] [PDF]


 
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