Allograft vasculopathy: diagnosing the nemesis of heart transplantation.

Remarkable progress has been made with respect to cardiac transplantation over the past 3 decades.1 Few dramas are as compelling as a successful heart transplant in a patient who otherwise would die of cardiogenic shock. Improved outcomes relate to our greater (but yet incomplete) insight into the pathophysiology of allograft rejection. Still, the transplanted heart is not normal, and it is subjected to chronic immunologic assault. The long-term function of cardiac allografts is related primarily to the integrity of the organ at the time of transplantation and to rejection. More general systemic pathological processes, such as hypertension, lipid perturbation, diabetes, and infection, are also likely to take their toll.2 Although with contemporary immunomodulating strategies, cardiac allografts may perform satisfactorily for $20 years, a more reasonable expectation of the half-life of these organs is between 7 and 10 years. It is disturbing to note that the long-term survival of cardiac allografts has changed little over the past 2 decades. Obviously, there is a complicated interplay between immunologic and nonimmunologic factors that determine the long-term function of the transplanted heart, but so-called chronic rejection dictates outcome in large part. This process (at times rapid) is a diffuse, obliterative atherosclerosis, also referred to as allograft arteriopathy or vasculopathy (veins rarely can be involved as well). The pathophysiology of chronic cardiac allograft rejection is probably analogous to that of chronic nephrosclerosis of transplanted kidneys, biliary atresia of liver allografts, and bronchiolitis obliterans after lung transplantation. Interestingly, we still rather crudely separate rejection episodes into hyperacute, acute, and chronic classifications. Although these different categories probably have, at root, common intertwining immunologic themes, we believe that hyperacute rejection is mediated by a rapid humoral immune response, with complement activation noted immediately after organ reperfusion. Myocyte dysfunction occurs immediately in this setting, and allografts become nonfunctional over the course of minutes or, at the most, hours. Acute cardiac allograft rejection generally refers to T-cell lymphocyte–mediated processes manifested by cellular cardiac muscle infiltration over hours or days. Resultant ventricular dysfunction can be rapid and profound, particularly when effective immunosuppressive therapies have not been prescribed; but more commonly, acute rejection is slower to evolve and leads to cardiac dysfunction over a longer period of time. Acute cell-mediated rejection can often be treated effectively, with subsequent satisfactory ventricular performance.