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Therapeutic Angiogenesis and Myocardial Regeneration

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Interventional Cardiology

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Ischemic heart disease is the leading cause of morbidity and mortality in the Western world. The term “ischemic heart disease” covers a broad spectrum of manifestations ranging from effort-induced angina without myocardial damage, through stages of chronic myocardial ischemia with associated reversible impairment in ventricular function, to states of irreversible myocardial injury and necrosis resulting in congestive heart failure (CHF). Ischemic heart disease, therefore, is the leading cause of CHF, a disease process that affects approx 1% of adults in the United States, with 550,00 new cases diagnosed annually and an incidence of 10 cases per 1000 population after age 65 (1). With the aging of the population, the incidence of this problem is increasing, as evidenced by the number of discharges for CHF, which rose from 377,00 in 1979 to 999,000 in 2000 (165% increase) (1) . In addition, >50,000 deaths per year in the United States are directly attributable to CHF (1). Likewise, the costs of caring for these patients is enormous, with $3.6 billion ($5471 per discharge) paid to Medicare beneficiaries for CHF-related treatment based on the most recently available data from 1998 (1). Currently, median survival after diagnosis of CHF is 1.7 yr for men and 3.2 yr for women (1), indicating a general inadequacy of presently available treatment options for the majority of these patients. Consequently, novel therapies are needed to improve the outlook for this patient population.

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References

  1. American Heart Association. Heart disease and stroke statistics—2003 update. Dallas, TX: American Heart Association, 2002.

    Google Scholar 

  2. Hughes GC, Post MJ, Simons M, Annex BH. Porcine models of human coronary artery disease: implications for pre-clinical trials of therapeutic angiogenesis. J Appl Physiol 2003;94:1689–1701.

    PubMed  Google Scholar 

  3. Schoebel FC, Frazier OH, Jessurun GAJ, et al. Refractory angina pectoris in end-stage coronary artery disease: evolving therapeutic concepts. Am Heart J 1997;134:587–602.

    Article  PubMed  CAS  Google Scholar 

  4. Mukherjee D, Bhatt DL, Roe MT, et al. Direct myocardial revascularization and angiogenesis-how many patients might be eligible? Am J Cardiol 1999;84:598–600.

    Article  PubMed  CAS  Google Scholar 

  5. Hughes GC, Abdel-aleem S, Biswas SS, et al. Transmyocardial laser revascularization: experimental and clinical results. Can J Cardiol 1999;15:797–806.

    PubMed  CAS  Google Scholar 

  6. Sen PK, Udwadia TE, Kinare SG, Parulkar GB. Transmyocardial acupuncture. A new approach to myocardial revascularization. J Thorac Cardiovasc Surg 1965;50:181–189.

    PubMed  CAS  Google Scholar 

  7. Yamamoto N, Kohmoto T, Gu A, et al. Angiogenesis is enhanced in ischemic canine myocardium by transmyocardial laser revascularization. J Am Coll Cardiol 1998;31:1426–1433.

    Article  PubMed  CAS  Google Scholar 

  8. Ozaki S, Meyns B, Racz R, et al. Effect of transmyocardial laser revascularization on chronic ischemic hearts in sheep. Eur J Cardio-thorac Surg 2000;18:404–410.

    Article  CAS  Google Scholar 

  9. Horvath KA, Greene R, Belkind N, et al. Left ventricular functional improvement after transmyocardial laser revascularization. Ann Thorac Surg 1998;66:721–725.

    Article  PubMed  CAS  Google Scholar 

  10. Horvath KA, Belkind N, Wu I, et al. Functional comparison of transmyocardial revascularization by mechanical and laser means. Ann Thorac Surg 2001;72:1997–2002.

    Article  PubMed  CAS  Google Scholar 

  11. Martin JS, Sayeed-Shah U, Byrne JG, et al. Excimer versus carbon dioxide transmyocardial laser revascularization: effects on regional left ventricular function and perfusion. Ann Thorac Surg 2000;69: 1811–1816.

    Article  PubMed  CAS  Google Scholar 

  12. Hamawy AH, Lee LY, Samy SA, et al. Transmyocardial laser revascularization dose response: enhanced perfusion in a porcine ischemia model as a function of channel density. Ann Thorac Surg 2001;72:817–822.

    Article  PubMed  CAS  Google Scholar 

  13. Mühling OM, Wang Y, Panse P, et al. Transmyocardial laser revascularization preserves regional myocardial perfusion: an MRI first pass perfusion study. Cardiovasc Res 2003;57:63–70.

    Article  PubMed  Google Scholar 

  14. Hughes GC, Kypson AP, St Louis JD, et al. Improved perfusion and contractile reserve after transmyocardial laser revascularization in a model of hibernating myocardium. Ann Thorac Surg 1999;67:1714–1720.

    Article  PubMed  CAS  Google Scholar 

  15. Hughes GC, Kypson AP, Annex BH, et al. Induction of angiogenesis after TMR: a comparison of holmium: YAG, CO2, and excimer lasers. Ann Thorac Surg 2000;70:504–509.

    Article  PubMed  CAS  Google Scholar 

  16. Hughes GC, Biswas SS, Yin B, et al. A comparison of mechanical and laser transmyocardial revascularization for induction of angiogenesis and arteriogenesis in chronically ischemic myocardium. J Am Coll Cardiol 2002;39: 1220–1228.

    Article  PubMed  Google Scholar 

  17. Nahrendorf M, Hiller K-H, Theisen D, et al. Effect of transmyocardial laser revascularization on myocardial perfusion and left ventricular remodeling after myocardial infarction in rats. Radiology 2002;225: 487–493.

    Article  PubMed  Google Scholar 

  18. Kwong KF, Kanellopoulos GK, Nickols JC, et al. Transmyocardial laser treatment denervates canine myocardium. J Thorac Cardiovasc Surg 1997;114:883–890.

    Article  PubMed  CAS  Google Scholar 

  19. Kwong KF, Schuessler RB, Kanellopoulos GK, et al. Nontransmural laser treatment incompletely denervates canine myocardium. Circulation 1998;98(19 Suppl)II-67–II-71.

    CAS  Google Scholar 

  20. Hirsch GM, Thompson GW, Arora RC, et al. Transmyocardial laser revascularization does not denervate the canine heart. Ann Thorac Surg 1999;68:460–468.

    Article  PubMed  CAS  Google Scholar 

  21. Minisi AJ, Topaz O, Quinn MS, Mohanty LB. Cardiac nociceptive reflexes after transmyocardial laser revascularization: implications for the neural hypothesis of angina relief. J Thorac Cardiovasc Surg 2001; 122: 712–719.

    Article  PubMed  CAS  Google Scholar 

  22. Arora RC, Hirsch GM, Hirsch K, Armour JA. Transmyocardial laser revascularization remodels the intrinsic cardiac nervous system in a chronic setting. Circulation 2001;104:I-115–I-120.

    Article  CAS  Google Scholar 

  23. Al-Sheikh T, Allen KB, Straka SP, et al. Cardiac sympathetic denervation after transmyocardial laser revascularization. Circulation 1999;100:135–140.

    PubMed  CAS  Google Scholar 

  24. Hughes GC, Landolfo KP, Lowe JE, et al. Diagnosis, incidence, and clinical significance of early postoperative ischemia after transmyocardial laser revascularization. Am Heart J 1999;137:1163–1168.

    Article  PubMed  CAS  Google Scholar 

  25. Myers J, Oesterle SN, Jones J, Burkhoff D. Do transmyocardial and percutaneous laser revascularization induce silent ischemia? An assessment by exercise testing. Am Heart J 2002;143:1052–1057.

    Article  PubMed  Google Scholar 

  26. Hughes GC, Baklanov DV, Biswas SS, et al. Regional cardiac sympathetic innervation early and late after transmyocardial laser revascularization. J Cardiac Surg 2004;19:1–7.

    Article  Google Scholar 

  27. Mack CA, Magovern CJ, Hahn RT, et al. Channel patency and neovascularization after transmyocardial revascularization using an excimer laser. Results and comparisons to nonlased channels. Circulation 1997; 96(Suppl II):II-65–II-69.

    Google Scholar 

  28. Fisher PE, Kohmoto T, DeRosa CM, et al. Histologic analysis of transmyocardial channels: comparison of CO2 and homium: YAG lasers. Ann Thorac Surg 1997;64:466–472.

    Article  PubMed  CAS  Google Scholar 

  29. Hughes GC, Lowe JE, Kypson AP, et al. Neovascularization after transmyocardial laser revascularization in a model of chronic ischemia. Ann Thorac Surg 1998;66:2029–2036.

    Article  PubMed  CAS  Google Scholar 

  30. Saririan M, Eisenberg MJ. Myocardial laser revascularization for the treatment of end-stage coronary artery disease. J Am Coll Cardiol 2003;41:173–183.

    Article  PubMed  Google Scholar 

  31. Peterson ED, Kaul P, Kaczmarek RG, et al. From controlled trials to clinical practice: monitoring transmyocardial revascularization use and outcomes. J Am Coll Cardiol 2003;42:1611–1616.

    Article  PubMed  Google Scholar 

  32. Frazier OH, March RJ, Horvath KA. Transmyocardial revascularization with carbon dioxide laser in patients with end-stage coronary artery disease. N Engl J Med 1999;341:1021–1028.

    Article  PubMed  CAS  Google Scholar 

  33. Allen KB, Dowling RD, Fudge TL, et al. Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina. N Engl J Med 1999;341:1029–1036.

    Article  PubMed  CAS  Google Scholar 

  34. Schofield PM, Sharples LD, Caine N, et al. Transmyocardial laser revascularization in patients with refractory angina: a randomized controlled trial. Lancet 1999;353:519–524.

    Article  PubMed  CAS  Google Scholar 

  35. Burkhoff D, Schmidt S, Schulman SP, et al. Transmyocardial laser revascularization compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomized trial. ATLANTIC investigators: angina treatments—lasers and normal therapies in comparison. Lancet 1999;354:885–890.

    Article  PubMed  CAS  Google Scholar 

  36. Jones JW, Schmidt SE, Richman BW, et al. Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status. Ann Thorac Surg 1999;67:1596–1602.

    Article  PubMed  CAS  Google Scholar 

  37. Aaberge L, Nordstrand K, Dragsund M, et al. Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris: clinical results from the Norwegian randomized trial. J Am Coll Cardiol 2000; 35:1170–1177.

    Article  PubMed  CAS  Google Scholar 

  38. Oesterle SN, Sanborn TA, Ali N, et al. Percutaneous transmyocardial laser revascularization for severe angina: the PACIFIC randomised trial. Lancet 2000;356:1705–1710.

    Article  PubMed  CAS  Google Scholar 

  39. Stone GW, Teirstein PS, Rubenstein R, et al. A prospective, multicenter, randomized trial of percutaneous transmyocardial laser revascularization in patients with nonrecanalizable chronic total occlusions. J Am Coll Cardiol 2002;39:1581–1587.

    Article  PubMed  Google Scholar 

  40. Gray TJ, Burns SM, Clarke SC, et al. Percutaneous myocardial laser revascularization in patients with refractory angina pectoris. Am J Cardiol 2003;91:661–666.

    Article  PubMed  Google Scholar 

  41. Leon MB. DIRECT (DMR In Regeneration of Endomyocardial Channels Trial). Presented at Late-Breaking Trials, Transcatheter Cardiovascular Therapeutics, 2000.

    Google Scholar 

  42. Burkhoff D, Jones JW, Becker LC. Variability of myocardial perfusion defects assessed by thallium 201 scintigraphy in patients with coronary artery disease not amenable to angioplasty or bypass surgery. J Am Coll Cardiol 2001;38:1033–1039.

    Article  PubMed  CAS  Google Scholar 

  43. Laham RJ, Simons M, Pearlman J, et al. Magnetic resonance imaging demonstrates improved regional systolic wall motion and thickening and myocardial perfusion of myocardial territories treated by laser myocardial revascularization. J Am Coll Cardiol 2002;39:1–8.

    Article  PubMed  Google Scholar 

  44. Schaper W, Buschmann I. Arteriogenesis, the good and bad of it. Cardiovasc Res 1999;43:835–837.

    Article  PubMed  CAS  Google Scholar 

  45. Freedman SB, Isner JM. Therapeutic angiogenesis for coronary artery disease. Ann Intern Med 2002; 136:54–71.

    PubMed  Google Scholar 

  46. Schaper W, Ito WD. Molecular mechanisms of coronary collateral vessel growth. Circ Res 1996;79: 911–919.

    PubMed  CAS  Google Scholar 

  47. Schaper W. Quo vadis collateral blood flow? A commentary on a highly cited paper. Cardiovasc Res 2000; 45:220–223.

    Article  PubMed  CAS  Google Scholar 

  48. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964–967.

    Article  PubMed  CAS  Google Scholar 

  49. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.

    PubMed  CAS  Google Scholar 

  50. Papetti M, Herman IM. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 2002;282:C947–C970.

    PubMed  CAS  Google Scholar 

  51. Luttun A, Carmeliet P. De novo vasculogenesis in the heart. Cardiovasc Res 2003;58:378–389.

    Article  PubMed  CAS  Google Scholar 

  52. St.Louis JD, Hughes GC, Kypson AP, et al. An experimental model of chronic myocardial hibernation. Ann Thorac Surg 2000;69:1351–1357.

    Article  PubMed  CAS  Google Scholar 

  53. Hughes GC. Cellular models of hibernating myocardium: implications for future research. Cardiovasc Res 2001;51:191–193.

    Article  PubMed  CAS  Google Scholar 

  54. Carmelit P, Ng YS, Nuyens D, et al. Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nature Med 1999;5:495–502.

    Article  Google Scholar 

  55. Detillieux KA, Sheikh F, Kardami E, Cattini PA. Biological activities of fibroblast growth factor-2 in the adult myocardium. Cardiovasc Res 2003;57:8–19.

    Article  PubMed  CAS  Google Scholar 

  56. Post MJ, Laham R, Sellke FW, Simons M. Therapeutic angiogenesis in cardiology using protein formulations. Cardiovasc Res 2001;49:522–531.

    Article  PubMed  CAS  Google Scholar 

  57. Simons M, Annex BH, Laham RJ, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2. Double-blind, randomized, controlled clinical trial. Circulation 2002;105: 788–793.

    Article  PubMed  CAS  Google Scholar 

  58. Grines CL, Watkins MW, Helmer G, et al. Angiogenic gene therapy (AGENT) trial in patients with stable angina pectoris. Circulation 2002;105:1291–1297.

    Article  PubMed  CAS  Google Scholar 

  59. Losordo DW, Vale PR, Hendel RC, et al. Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia. Circulation 2002;105:2012–2018.

    Article  PubMed  CAS  Google Scholar 

  60. Henry TD, Annex BH, McKendall GR, et al. The VIVA trial. Vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation 2003;107:1359–1365.

    Article  PubMed  CAS  Google Scholar 

  61. Grines CL, Watkins MW, Mahmarian JJ, et al. A randomized, double-blind, placebo-controlled trials of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J Am Coll Cardiol 2003; 42: 1339–1347.

    Article  PubMed  CAS  Google Scholar 

  62. Dimmeler S, Vasa-Nicotera M. Aging of progenitor cells: limitation for regenerative capacity? J Am Coll Cardiol 2003;42:2081–2082.

    Article  PubMed  Google Scholar 

  63. Rupp S, Badorff C, Koyanagi M, et al. Statin therapy in patients with coronary artery disease improves the impaired endothelial progenitor cell differentiation into cardiomyogenic cells. Basic Res Cardiol 2004;99: 61–68.

    Article  PubMed  CAS  Google Scholar 

  64. Abbott JD, Giordano FJ. Stem cells and cardiovascular disease. J Nucl Cardiol 2003;10:403–412.

    Article  PubMed  Google Scholar 

  65. Perin EC, Geng Y-J, Willerson JT. Adult stem cell therapy in perspective. Circulation 2003;107: 935–938.

    Article  PubMed  Google Scholar 

  66. Körbling M, Estrov Z. Adult stem cells for tissue repair-a new therapeutic concept? N Engl J Med 2003;349:570–582.

    Article  PubMed  Google Scholar 

  67. van der Heyden MAG, Hescheler J, Mummery CL. Spotlight on stem cells-makes old hearts fresh. Cardiovasc Res 2003;58:241–245.

    Article  PubMed  Google Scholar 

  68. Smits PC, van Geuns R-JM, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure. J Am Coll Cardiol 2003;42: 2063–2069.

    Article  PubMed  Google Scholar 

  69. Atkins BZ, Lewis CW, Kraus WE, et al. Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ. Ann Thorac Surg 1999;67:124–129.

    Article  PubMed  CAS  Google Scholar 

  70. Makkar RR, Lill M, Chen P-S. Stem cell therapy for myocardial repair. Is it arrhythmogenic? J Am Coll Cardiol 2003;42:2070–2072.

    Article  PubMed  Google Scholar 

  71. Tse H-F, Kwong Y-L, Chan JKF, et al. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003;361:47–49.

    Article  PubMed  Google Scholar 

  72. Perin EC, Dohmann HFR, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003;107:2294–2302.

    Article  PubMed  Google Scholar 

  73. Fuchs S, Satler LF, Kornowski R, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease. J Am Coll Cardiol 2003;41:1721–1724.

    Article  PubMed  Google Scholar 

  74. Assmus B, Schächinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002;106:3009–3017.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC

    G. Chad Hughes MD

  2. Division of Cardiology, Department of Medicine, Durham Veterans Administration and Duke University Medical Center, Durham, NC

    Brian H. Annex MD

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  1. G. Chad Hughes MD
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Editors and Affiliations

  1. Cardiovascular Division, Department of Medicine, University of Pennsylvania School of Medicine, USA

    Howard C. Herrmann MD (Professor of Medicine, Director) (Professor of Medicine, Director)

  2. Interventional Cardiology and Cardiac Catheterization Laboratories, Hospital of the University of Pennsylvania, Philadelphia, PA

    Howard C. Herrmann MD (Professor of Medicine, Director) (Professor of Medicine, Director)

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© 2005 Humana Press Inc., Totowa, NJ

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Hughes, G.C., Annex, B.H. (2005). Therapeutic Angiogenesis and Myocardial Regeneration. In: Herrmann, H.C. (eds) Interventional Cardiology. Contemporary Cardiology. Humana Press. https://doi.org/10.1385/1-59259-898-6:271

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  • DOI: https://doi.org/10.1385/1-59259-898-6:271

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-367-1

  • Online ISBN: 978-1-59259-898-4

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