First-year intravascular ultrasound results as a surrogate marker for outcomes after heart transplantation.

Heart transplantation is the therapy of choice for selected patients with end-stage heart disease. The half-life of heart transplant recipients is now slightly more than 9 years with one of the major causes of late death being cardiac allograft vasculopathy (CAV). The mechanisms of this complication appear to be due to immune-mediated factors although non-immune factors also play a role. It appears that the processes of this long-term complication begin in the donor even before transplantation. Peri-operative and early post-operative events continue to play a pivotal role in the upregulation of the immune system, which causes chronic vascular insults. It appears that the events of the first year after transplant may determine the recipient’s immune response to the donor heart and the subsequent development of CAV. As of yet, there is no clear surrogate marker for the development of CAV. However, recent work has suggested that the first-year intravascular ultrasound (IVUS) data might provide this information. Pre-transplant and peri-operative events may dictate the recipient’s immune response to the donor heart. It has been demonstrated that coronary artery endothelial cells in the donor may express major histocompatability complex Class I and II antigens in response to brain death. In addition, within hours of brain death, upregulation of the immune system can be seen with, for example, intercellular adhesion molecule (ICAM) being identified on cell surfaces. Clinically, it has been reported that the mode of death in the donor, such as explosive brain death (bleed, closed head trauma, gunshot wounds), has been associated with greater development of subsequent CAV. In a consecutive cohort of 61 heart transplant recipients, Mehra et al found that recipients whose donor died from explosive brain death were more likely to develop severe intimal thickness (0.59 mm vs 0.32 mm, p 0.02). Cardiac events (sudden death, myocardial infarction, re-vascularization) were also more frequent in the explosive brain-death group in a 5-year follow-up than those patients whose donors died from gradual brain death (37% vs 12%, p 0.01). It is likely that explosive brain death, which is accompanied by sudden elevations in intracranial pressure and surges of sympathetic outflow, may cause greater donor heart endothelial cell injury and thereby enhance the recipient’s immune response to the transplanted organ. Early post-operative events may also influence outcome. A multicenter study has demonstrated that increased cellular rejection in the first 3 months, as represented by high average biopsy score, correlates with greater intimal thickness by IVUS at 1 year post-transplant. The study suggested that recurrent lower grades of rejections or a smoldering rejection process was more influential in causing vascular damage. Donor-specific antibody found on immunoflourescence staining on endoFrom the Department of Cardiology, UCLA Medical Center, Los Angeles, California. Submitted and accepted May 8, 2003. Reprint requests: Jon A. Kobashigawa, MD, UCLA Medical Center, 100 UCLA Medical Plaza Building, Suite 630, Los Angeles, California 90095-6988. Telephone: 310-794-1200; Fax: 310-794-1211. E-mail: jonKmednet.ucla.edu J Heart Lung Transplant 2003;22:711–714. Copyright © 2003 by the International Society for Heart and Lung Transplantation. 1053-2498/03/$–see front matter doi:10.1016/S1053-2498(03)00210-9