Cardiac transplantation pathology

Abstract

Survival rates for heart transplants have risen to 88 % after 1 year, 75 % after 5 years, and about 56 % after 10 years. Patients have benefited from improvements in immunosuppressive therapy and from skilled clinicians' increased ability to recognize rejection. While immunosuppressive therapy has reduced the rate of acute cellular rejection (ACR), the incidence of antibody-mediated rejection (AMR) has remained largely unchanged over the years. AMR appears in about 10-20 % of heart transplant patients and is associated with poor outcomes such as hemodynamic instability and greater development of cardiac allograft vasculopathy (CAV). Risk factors for AMR include female gender, elevated pretransplant panel-reactive antibodies, development of de novo donor-specific antibodies (DSAs), positive donor-specific crossmatch, seropositivity for cytomegalovirus, retransplantation, and prior use of a ventricular assist device. Endomyocardial biopsies (EMBs) remain the mainstay for diagnosing both ACR and AMR and for monitoring rejection. This chapter describes the EMB procedure and its recommended timing and how to evaluate biopsy findings, including for indicators of AMR or more rare developments such as posttransplant lymphoproliferative disease. The pathophysiology of ACR and AMR is also detailed, as is the progression in standardized ACR grading systems developed by the International Society for Heart and Lung Transplantation. While progress is being made, research is needed for better ways to recognize and treat early signs of CAV and AMR. One area under investigation, for example, is using proteomic and genomic markers to predict cardiac transplant rejection and risk of graft failure.