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Thorac Cardiovasc Surg 2010; 58(1): 11-16
DOI: 10.1055/s-0029-1186199
Original Cardiovascular

© Georg Thieme Verlag KG Stuttgart · New York

Transmyocardial Laser Revascularization Combined with Intramyocardial Endothelial Progenitor Cell Transplantation in Patients with Intractable Ischemic Heart Disease Ineligible for Conventional Revascularization: Preliminary Results in a Highly Selected Small Patient Cohort

J. Babin-Ebell1 , H.-H. Sievers1 , E. I. Charitos1 , H. M. Klein2 , F. Jung3 , A.-K. Hellberg3 , R. Depping4 , H. A. Sier1 , J. Marxsen5 , S. Stoelting5 , E. G. Kraatz1 , K. F. Wagner6
  • 1Cardiac and Thoracic Vascular Surgery Clinic, University of Luebeck, Luebeck, Germany
  • 2Cardiac Surgery Clinic, University of Düsseldorf, Düsseldorf, Germany
  • 3Anesthesiology Clinic, University of Luebeck, Luebeck, Germany
  • 4Department of Physiology, University of Luebeck, Luebeck, Germany
  • 5Hematology and Oncology Clinic, University of Luebeck, Luebeck, Germany
  • 6Anesthesiology Clinic (KFW), Suedstadt Clinic Rostock, Rostock, Germany
Further Information

Publication History

received Nov. 5, 2008

Publication Date:
13 January 2010 (online)

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Abstract

Objective: Transmyocardial laser revascularization for angina relief and intramyocardial autologous endothelial progenitor cell injection for neoangiogenesis may offer a new treatment strategy for patients with intractable ischemic heart disease. Methods: Transmyocardial laser revascularization and intramyocardial injection of bone marrow-derived CD133+ cells was performed in six highly symptomatic patients. Transmyocardial laser channels were created and isolated CD133+ cells were injected intramyocardially. All patients were followed up for a minimum of 6 months postoperatively. Results: One patient died shortly after the operation due to refractory heart failure. In the five survivors, CCS class improved as well as left ventricular ejection fraction. Left ventricular end-diastolic volume and myocardial perfusion varied between the patients. All patients described a considerable improvement in quality of life postoperatively. Repeated 24-hour Holter monitoring revealed no significant arrhythmias. Conclusions: In this small patient cohort, intramyocardial CD 133+ cell injection combined with transmyocardial laser revascularization led to an improvement in clinical symptomatology in all patients and in left ventricular function in 4 out of 5 patients, with an unclear effect on myocardial perfusion. Caution is advised when employing this therapy in patients with severely depressed left ventricular function.

Key words

heart disease - cardiomyopathy - myocardial infarction

References

  • 1 Horvath K A. Mechanisms and results of transmyocardial laser revascularization.  Cardiology. 2004;  101 (1–3) 37-47
    CrossrefPubMedSearch in Google Scholar
  • 2 Huikeshoven M, van der Sloot J A, Tukkie R, Beek J F. Transmyocardial laser revascularisation and other treatment modalities for angina pectoris.  Lasers Med Sci. 2003;  18 (1) 2-11
    CrossrefPubMedSearch in Google Scholar
  • 3 Abbott J D, Huang Y, Liu D, Hickey R, Krause D S, Giordano F J. Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury.  Circulation. 2004;  110 (21) 3300-3305
    CrossrefPubMedSearch in Google Scholar
  • 4 Patel A N, Geffner L, Vina R F, Saslavsky J, Urschel Jr H C, Kormos R et al. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study.  J Thorac Cardiovasc Surg. 2005;  130 (6) 1631-1638
    CrossrefPubMedSearch in Google Scholar
  • 5 Stamm C, Kleine H D, Choi Y H, Dunkelmann S, Lauffs J A, Lorenzen B et al. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies.  J Thorac Cardiovasc Surg. 2007;  133 (3) 717-725
    CrossrefPubMedSearch in Google Scholar
  • 6 Ghodsizad A, Ruhparwar A, Marktanner R, Borowski A, Mohammad Hasani M R, Poll L et al. Autologous transplantation of CD133+ BM-derived stem cells as a therapeutic option for dilatative cardiomyopathy.  Cytotherapy. 2006;  8 (3) 308-310
    CrossrefPubMedSearch in Google Scholar
  • 7 Klein H M, Ghodsizad A, Borowski A, Saleh A, Draganov J, Poll L et al. Autologous bone marrow-derived stem cell therapy in combination with TMLR. A novel therapeutic option for endstage coronary heart disease: report on 2 cases.  Heart Surg Forum. 2004;  7 (5) E416-E419
    CrossrefPubMedSearch in Google Scholar
  • 8 Klein H M, Ghodsizad A, Marktanner R, Poll L, Voelkel T, Mohammad Hasani M R et al. Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery.  Heart Surg Forum. 2007;  10 (1) E66-E69
    CrossrefPubMedSearch in Google Scholar
  • 9 Eguchi M, Masuda H, Asahara T. Endothelial progenitor cells for postnatal vasculogenesis.  Clin Exp Nephrol. 2007;  11 (1) 18-25
    CrossrefPubMedSearch in Google Scholar
  • 10 Lyngbaek S, Schneider M, Hansen J L, Sheikh S P. Cardiac regeneration by resident stem and progenitor cells in the adult heart.  Basic Res Cardiol. 2007;  102 (2) 101-114
    CrossrefPubMedSearch in Google Scholar
  • 11 Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.  N Engl J Med. 2006;  355 (12) 1210-1221
    CrossrefPubMedSearch in Google Scholar
  • 12 Wollert K C, Drexler H. Clinical applications of stem cells for the heart.  Circ Res. 2005;  96 (2) 151-163
    CrossrefPubMedSearch in Google Scholar
  • 13 Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L et al. The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation.  Circulation. 2008;  117 (9) 1189-1200
    CrossrefPubMedSearch in Google Scholar
  • 14 Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N et al. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair.  Proc Natl Acad Sci USA. 2007;  104 (5) 1643-1648
    CrossrefPubMedSearch in Google Scholar
  • 15 Tang Y L, Zhao Q, Qin X, Shen L, Cheng L, Ge J et al. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction.  Ann Thorac Surg. 2005;  80 (1) 229-236
    CrossrefPubMedSearch in Google Scholar
  • 16 Tossios P, Muller-Ehmsen J, Schmidt M, Scheid C, Unal N, Moka D et al. No evidence of myocardial restoration following transplantation of mononuclear bone marrow cells in coronary bypass grafting surgery patients based upon cardiac SPECT and 18F-PET.  BMC Med Imaging. 2006;  6 7
    CrossrefPubMedSearch in Google Scholar
  • 17 Yaoita H, Takase S, Maruyama Y, Sato Y, Satokawa H, Hoshi N et al. Scintigraphic assessment of the effects of bone marrow-derived mononuclear cell transplantation combined with off-pump coronary artery bypass surgery in patients with ischemic heart disease.  J Nucl Med. 2005;  46 (10) 1610-1617
    PubMedSearch in Google Scholar
  • 18 Al-Sheikh T, Allen K B, Straka S P, Heimansohn D A, Fain R L, Hutchins G D et al. Cardiac sympathetic denervation after transmyocardial laser revascularization.  Circulation. 1999;  100 (2) 135-140
    PubMedSearch in Google Scholar
  • 19 Gassler N, Wintzer H O, Stubbe H M, Wullbrand A, Helmchen U. Transmyocardial laser revascularization. Histological features in human nonresponder myocardium.  Circulation. 1997;  95 (2) 371-375
    PubMedSearch in Google Scholar
  • 20 Lutter G, Schwarzkopf J, Lutz C, Martin J, Beyersdorf F. Histologic findings of transmyocardial laser channels after two hours.  Ann Thorac Surg. 1998;  65 (5) 1437-1439
    CrossrefPubMedSearch in Google Scholar
  • 21 Lutter G, Saurbier B, Nitzsche E, Kletzin F, Martin J, Schlensak C et al. Transmyocardial laser revascularization (TMLR) in patients with unstable angina and low ejection fraction.  Eur J Cardiothorac Surg. 1998;  13 (1) 21-26
    CrossrefPubMedSearch in Google Scholar
  • 22 Kraatz E G, Misfeld M, Jungbluth B, Sievers H H. Survival after transmyocardial laser revascularization in relation to nonlasered perfused myocardial zones.  Ann Thorac Surg. 2001;  71 (2) 532-536
    CrossrefPubMedSearch in Google Scholar
  • 23 Menasche P, Hagege A A, Vilquin J T, Desnos M, Abergel E, Pouzet B et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction.  J Am Coll Cardiol. 2003;  41 (7) 1078-1083
    CrossrefPubMedSearch in Google Scholar

MD Efstratios I. Charitos

Cardiac and Thoracic Vascular Surgery Clinic
University of Lübeck

Ratzeburger Allee 160

23538 Lübeck

Germany

Phone: + 49 45 15 00 47 63

Fax: + 49 45 15 00 20 51

Email: efstratios.charitos@gmail.com