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The utility of magnetic resonance imaging in cardiac tissue regeneration trials

Abstract

The past decade has seen the emergence of paradigm shifts in concepts involving cardiovascular tissue regeneration, including the idea that adult stem cells originate in hematopoietic or bone marrow cells, the belief that even adult organs, such as the heart and nervous system, are capable of post-mitotic regeneration, and the concept of inherent plasticity in cells that have undergone limited lineage differentiation. There has consequently been a flurry of proposed regenerative strategies, and safety and limited efficacy data from both animal and limited human trials have been presented. The drive to push these advances from the bench to the bedside has created a unique environment where the therapeutic agents, delivery approaches, and methods of measuring efficacy (often imaging technology) are evolving practically in parallel. The encouraging results of recent cell-therapy trials should therefore be assessed cautiously and in consonance with an understanding of the advantages and limitations of delivery strategies and end points. Arguably, the use of imaging technologies to evaluate surrogate end points might help overcome the difficulty posed by large sample sizes required for hard end point trials in cardiovascular therapeutics. Cardiac magnetic resonance imaging is one of the most sensitive techniques available to assess spatial and temporal changes following local or systemic therapies, and the availability of a bevy of complementary techniques enables interrogation of physiology, morphology, and metabolism in one setting. We contend that cardiac magnetic resonance imaging is ideally suited to assess response to myocardial regeneration therapy and can be exploited to yield valuable insights into the mechanism of action of myocardial regeneration therapies.

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Figure 1: Surrogate end points in cell-therapy trials guided by therapeutic strategy and target

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References

  1. Balsam LB et al. (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428: 668–673

    Article  CAS  Google Scholar 

  2. Murry CE et al. (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428: 664–668

    Article  CAS  Google Scholar 

  3. Rector TS and Cohn JN (1994) Prognosis in congestive heart failure. Annu Rev Med 45: 341–350

    Article  CAS  Google Scholar 

  4. Lima JA et al. (1995) Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI. Potential mechanisms. Circulation 92: 1117–1125

    Article  CAS  Google Scholar 

  5. Wagner A et al. (2003) Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet 361: 374–379

    Article  Google Scholar 

  6. Klein C et al. (2002) Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: comparison with positron emission tomography. Circulation 105: 162–167

    Article  Google Scholar 

  7. Kim RJ et al. (2000) The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 343: 1445–1453

    Article  CAS  Google Scholar 

  8. Selvanayagam JB et al. (2004) Value of delayed-enhancement cardiovascular magnetic resonance imaging in predicting myocardial viability after surgical revascularization. Circulation 110: 1535–1541

    Article  Google Scholar 

  9. Bello D et al. (2003) Gadolinium cardiovascular magnetic resonance predicts reversible myocardial dysfunction and remodeling in patients with heart failure undergoing β-blocker therapy. Circulation 108: 1945–1953

    Article  CAS  Google Scholar 

  10. Britten MB et al. (2003) Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 108: 2212–2218

    Article  CAS  Google Scholar 

  11. Cwajg JM et al. (2000) End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol 35: 1152–1161

    Article  CAS  Google Scholar 

  12. Kim RJ and Shah DJ (2004) Fundamental concepts in myocardial viability assessment revisited: when knowing how much is “alive” is not enough. Heart 90: 137–140

    Article  CAS  Google Scholar 

  13. Baumgartner H et al. (1998) Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts. J Am Coll Cardiol 32: 1701–1708

    Article  CAS  Google Scholar 

  14. Hombach V et al. (2005) Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 26: 549–557

    Article  Google Scholar 

  15. Kim RJ and Manning WJ (2004) Viability assessment by delayed enhancement cardiovascular magnetic resonance: will low-dose dobutamine dull the shine? Circulation 109: 2476–1479

    Article  Google Scholar 

  16. Vallee JP et al. (1999) Quantification of myocardial perfusion with FAST sequence and Gd bolus in patients with normal cardiac function. J Magn Reson Imaging 9: 197–203

    Article  CAS  Google Scholar 

  17. Simons M et al. (2000) Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary. Circulation 102: E73–E86

    Article  CAS  Google Scholar 

  18. Neubauer S et al. (1997) Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96: 2190–2196

    Article  CAS  Google Scholar 

  19. Wacker CM et al. (2003) Susceptibility-sensitive magnetic resonance imaging detects human myocardium supplied by a stenotic coronary artery without a contrast agent. J Am Coll Cardiol 41: 834–840

    Article  Google Scholar 

  20. Assmus B et al. (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106: 3009–3017

    Article  Google Scholar 

  21. Strauer BE et al. (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106: 1913–1918

    Article  Google Scholar 

  22. Perin EC et al. (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107: 2294–2302

    Article  Google Scholar 

  23. Kang HJ et al. (2004) Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 363: 751–756

    Article  CAS  Google Scholar 

  24. Wollert KC et al. (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364: 141–148

    Article  Google Scholar 

  25. Fernández-Avilés F et al. (2004) Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 95: 742–748

    Article  Google Scholar 

  26. Smits PC et al. (2003) Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol 42: 2063–2069

    Article  Google Scholar 

  27. Menasché P et al. (2003) Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 41: 1078–1083

    Article  Google Scholar 

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Correspondence to Valentin Fuster or Sanjay Rajagopalan.

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Fuster, V., Sanz, J., Viles-Gonzalez, J. et al. The utility of magnetic resonance imaging in cardiac tissue regeneration trials. Nat Rev Cardiol 3 (Suppl 1), S2–S7 (2006). https://doi.org/10.1038/ncpcardio0418

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