Recurrence of giant cell myocarditis in cardiac allograft

Background: Giant cell myocarditis causes essentially irreversible fulminan t left ventricular dysfunction with associated conduction abnormalities and congestive failure. Response to immunosuppressive therapy is poor and card iac transplantation is the only viable treatment option. The histologic hal lmarks of giant cell myocarditis include a polymorphous inflammatory respon se with numerous multinucleated giant cells and extensive myocyte necrosis in a geographic pattern. There were 38 patients who received a cardiac tran splant for giant cell myocarditis in the Giant Cell Myocarditis Registry, A mong these patients, there were 9 recurrences of disease in the allograft, Concern has been expressed that recurrence of giant cell myocarditis in the allograft might be a contraindication for cardiac transplantation in the f uture. Methods: In our single-center analysis we describe the clinical and histolo gic findings of 5 patients transplanted for giant cell myocarditis at the C leveland Clinic. Results: All but 1 of the patients were New York Heart Association (NYHA) c lass 4 with an average cardiac index (CI) of 1.52 liters/min . m(2). Of the 5 patients transplanted, 1 developed recurrent giant cell myocarditis. Rou tine right ventricular endomyocardial biopsy at 1 week exhibited severe mul tifocal myocardial fibrosis in addition to mild acute vascular rejection an d mild grade 1A cellular rejection. Followup biopsy in this patient indicat ed grade IIIA moderate acute rejection in addition to multinucleated giant cells. Two distinct inflammatory processes were noted consisting of foci of T-cell inflammation identified by immunohistochemistry to be consistent wi th rejection, and a second inflammatory process with few mononuclear cells staining for macrophage or T-cell markers with eosinophils and myocyte necr osis consistent with giant cell myocarditis, Follow-up right ventricular en domyocardial biopsies (RVBXs) in this patient have subsequently demonstrate d improvement in the degree of inflammatory infiltrate without vascular or significant cellular rejection. Vascular rejection was noted in 1 of the re maining 4 patients and was treated successfully with muramab-CD3 and plasma pheresis. Conclusions: Giant cell myocarditis should be expected to recur in the allo graft and often does so concurrently with rejection, However, the disease i n the allograft responds to therapy in a favorable manner, which differs dr amatically from that in the native heart, This might be the result of detec tion of the disease at an earlier stage than in the native heart, or the im munosuppression milieu in the allograft, The favorable response to therapy suggests that the likelihood of recurrence of giant cell myocarditis should not be considered a barrier to transplantation.