Orthotopic Heart Transplant Rejection and Immunosuppression

Abstract

This chapter focuses on orthotopic heart transplant rejection. Hyperacute rejection is a catastrophic complication that occurs early post-transplantation. This type of rejection is most often due to pre-formed donor-specific anti–human leukocyte antigen antibodies or an ABO blood type mismatch and is rarely seen in the current era because pre-transplant virtual and prospective crossmatch has become routine practice. Meanwhile, immune activation of recipient T cells against the cardiac allograft causes acute cellular rejection (ACR). Treatment of ACR will vary depending on the grade of rejection, symptoms, and hemodynamic significance. On the other hand, antibody-mediated rejection (AMR), previously known as humoral or vascular rejection, is primarily mediated by antibodies and not T cells, as in ACR. AMR is difficult to treat because it may persist or be recurrent and is associated with an increased risk of cardiac allograft vasculopathy and mortality. The chapter then discusses the management of acute rejection. Induction therapy is augmented immunosuppression in the early period following heart transplantation, when the recipient is at the greatest risk of rejection. Maintenance immunosuppression includes calcineurin inhibitors, anti-metabolites, glucocorticoids, and proliferation signal inhibitors.