Vascular rejection in heart transplantation: clinical correlation, treatment options, and future considerations

Vascular rejection injures the vascular endothelium in cardiac allografts in the absence of significant intramyocardial lymphocytic infiltration. When compared with cellular rejection, vascular rejection occurs earlier after transplantation, is more resistant to immunosuppressive augmentation, causes more allograft dysfunction, and is associated with a higher frequency of allograft loss. Between January 1990 and October 1992, acute hemodynamically significant vascular rejection developed in 13 of 170 patients (8%). Endomyocardial biopsy specimens revealed the typical findings of endothelial cell activation, immune complex deposition, and interstitial fibrin deposition in the absence of significant lymphocytic infiltration. All patients had clinical evidence of allograft dysfunction. In addition to high-dose corticosteroids, all patients received cyclophosphamide as an oral pulse for 4 days and underwent plasmapheresis for 3 consecutive days. Eight patients received OKT3 (n = 6) or antilymphoblast globulin (n = 2), and nine patients underwent systemic anticoagulation. Six patients required inotropic therapy for hemodynamic instability. Although one patient died during the initial episode, rejection resolved and left ventricular function returned to normal in 12 of 13 patients. However, vascular rejection recurred in three patients, two of whom subsequently died. Two other patients died during late follow-up because of noncompliance. Eight patients remain alive with normal allograft function and angiographically normal coronary arteries. Whereas the addition of cyclophosphamide and plasmapheresis may improve the outcome of vascular rejection, the results of treatment with currently available treatment modalities remain unacceptably poor.