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(Circulation. 1997;96:2069-2077.)
© 1997 American Heart Association, Inc.


Articles

Cardiac Allograft Vasculopathy

A Review

Michael Weis, MD; ; Wolfgang von Scheidt, MD

From Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, University of Munich, Germany.

Correspondence to Dr Michael Weis, Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, University of Munich, Marchioninistraße 15, 81377 Munich, Germany. E-mail Micha.Weis{at}t-online.de

Abstract Cardiac allograft vasculopathy (CAV) remains a troublesome long-term complication of heart transplantation. It is manifested by a unique and unusually accelerated form of coronary disease affecting both intramural and epicardial coronary arteries and veins. CAV is characterized by vascular injury induced by a variety of noxious stimuli, including the immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classic risk factors such as hyperlipidemia, insulin resistance, and hypertension. The obstructive vascular lesions are thought to progress through repetitive endothelial injury followed by repair response. The role of major histocompatibility complex donor-recipient differences in the pathogenesis of CAV has not yet been completely elucidated. Intracoronary ultrasound studies reveal a dual morphology with donor-transmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern observed in distal segments. A lack of correlation between microvascular and epicardial vessel disease suggests discordant manifestations and progression of CAV. Apoptosis and loss of functional vascular remodeling have to be considered as important mediators of clinically relevant CAV. Strategies for blocking T-cell costimulation and expression of adhesion molecules may help prevent chronic rejection in clinical transplantation. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and antiproliferative drugs may slow progression of CAV by various effects. Methods to augment endogenous nitric oxide bioavailability as well as newer immunosuppressive regimens may be protective. Balloon angioplasty has a limited role in the treatment of focal lesions. Experiences with coronary stenting, coronary artery bypass grafting, and transmyocardial laser revascularization are limited. Retransplantation has a worse outcome than initial transplantation.


Key Words: transplantation • vasculopathy • coronary disease • endothelium




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H. Holschermann, R. M. Bohle, H. Zeller, H. Schmidt, U. Stahl, L. Fink, H. Grimm, H. Tillmanns, and W. Haberbosch
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Clin. Chem.Home page
D. W. Jacobsen
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Clin. Chem., November 1, 1998; 44(11): 2238 - 2239.
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D. E.C. Cole, H. J. Ross, J. Evrovski, L. J. Langman, S. E.S. Miner, P. A. Daly, and P.-Y. Wong
Correlation between total homocysteine and cyclosporine concentrations in cardiac transplant recipients
Clin. Chem., November 1, 1998; 44(11): 2307 - 2312.
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CirculationHome page
M. D. Rekhter, N. Shah, R. D. Simari, C. Work, J.-S. Kim, G. J. Nabel, E. G. Nabel, and D. Gordon
Graft Permeabilization Facilitates Gene Therapy of Transplant Arteriosclerosis in a Rabbit Model
Circulation, September 29, 1998; 98(13): 1335 - 1341.
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Cardiovasc ResHome page
B. Geny, F. Piquard, J. Lonsdorfer, and P. Haberey
Endothelin and heart transplantation
Cardiovasc Res, September 1, 1998; 39(3): 556 - 562.
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M. Cattaruzza, I. Eberhardt, and M. Hecker
Mechanosensitive Transcription Factors Involved in Endothelin B Receptor Expression
J. Biol. Chem., September 28, 2001; 276(40): 36999 - 37003.
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