Rejection after cardiac transplantation is a lifelong risk, although the incidence of rejection decreases with time. Rejection can be divided into three types, based on mechanism of rejection and time after transplantation. Hyperacute rejection is mediated by preformed anti-HLA antibodies directed against the donor tissue. Hyperacute rejection results in immediate and irreversible donor heart failure and is a fatal complication unless the patient can be maintained with a mechanical assist device until a new donor heart is located. With the use of ABO blood group-compatible donors and screening of transplant candidates for elevated levels of preformed anti-HLA antibodies, hyperacute rejection is very rare in cardiac transplantation.

Acute rejection, the most common type of rejection encountered, occurs in approximately 75 percent of all patients at some time after transplantation. The incidence of acute rejection is greatest within the first 6 weeks posttransplantation as immunosuppressive medications are weaned to chronic maintenance levels. Rejection can occur at any time after transplantation. Late episodes can usually be correlated with some change in the patient's immunosuppressive status, such as an acute illness or noncompliance with medications. Acute rejection is a cellular phenomenon resulting in the infiltration of lymphocytes into the myocardium, with subsequent destruction of individual myocytes. Because most episodes of rejection do not cause clinically detectable graft dysfunction, surveillance endomyocardial biopsies are performed on a routine basis after transplantation. Biopsy specimens are examined histologically and graded according to a grading system ( T§bl§,56:4) developed by a working group of the ISHLT.7 Mild to moderate episodes of rejection (grades 0 to 2) are generally not accompanied by clinical symptoms or hemodynamic changes. Severe rejection (grade 4) can result in profound myocardial dysfunction and death. Patients with grade 2 or higher rejection are treated with augmented steroids or cytotoxic therapy, as outlined below.

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