Pathology and etiology of chronic rejection of the heart

Abstract

As there are other lesions in the cardiac allografts of long-term survivors, it is best to refer to the vascular lesion as "graft vascular disease". Graft vascular disease may be evident as early as 3 months after cardiac transplantation and may cause death in the recipient as late as 22 years post-transplant. The disease affects infants, children, and adults as well as the recipients of combined heart-lung transplants. It is one of the most discouraging aspects of long-term survival in combined heart-lung and heart transplantation, accounting for 18% of the deaths among the 201 cardiac transplants performed at Stanford during the cyclosporine era. The pathology of graft vascular disease is that of a concentric intimal proliferation with minimal damage to the elastic lamina and minimal or no change in the media of the coronary vessel wall. The lesion may affect the entire length of the vessel wall as well as the branches and small branches that penetrate into the myocardium of the coronary system. These changes differ from that of naturally occurring atherosclerosis in that, instead of focal lesions developing, the whole length of the vessel is affected, including the small branches. This precludes optimal treatment with angioplasty and other therapies. Because small vessels are involved, the resulting myocardial infarcts may be patchy and small. Presently, no strong correlation has been made with usual risk factors or transplantation for end-stage coronary atherosclerosis, cardiomyopathy or congenital heart disease. The etiology of graft coronary disease remains unclear. Studies have suggested vascular cell activation of various kinds, including cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)