Comparative histopathology of endomyocardial biopsies in chagasic and non-chagasic heart transplant recipients

Abstract

Background: Heart transplantation has been an option for the treatment of chagasic (C) cardiomyopathy despite difficulties concerning the control of rejection and reactivation. The parasite-host interaction under the influence of immunosuppressive therapy may affect the immunological response to the graft in a pattern different from that in non-chagasic (NC) patients. The aim of this study was to compare the major histopathological features in heart: transplantation in C and NC patients.Methods: We studied 293 endomyocardial biopsies from two groups of heart transplanted patients, including 18 C and 15 NC. Both groups had identical surgical and clinical procedure except immunosuppressive therapy was lower in C patients. The histopathological parameters evaluated were the Quilty effect, rejection, C myocarditis reactivation, fibrosis, hypertrophy, and ischemia. In addition, lymphocytic cellular infiltration of myocarditis due to rejection or reactivation was immunophenotyped in the biopsies of both groups with rejection grades 3 to 4, in biopsies with signs of reactivation, and in fragments of the receptor heart with chronic C myocarditis. A search for Trypanosoma cruzi was performed in all biopsies in the C group in which lymphocyte immunophenotyping was done. We used immunofluorescence and confocal microscopy.Results: The Quilty effect was present in 23% of the biopsies, involving 69.7% of the patients without a significant difference between groups (p = 0.509). Rejection was frequently observed in biopsies with the Quilty effect and the effect often recurred in the same patient. Rejection grades 3 to 4 was more frequent in the C group (p = 0,023). There were 5 episodes of Chagas' disease reactivation with myocarditis in 2 cases. The mean numbers of CD8+ and CD4+ T cells, and the CD4+-to-CD8+ ratio were similar for rejection in both groups (p > 0.05), while the CD4+-to-CD8+ ratio was significantly lower in chronic C myocarditis compared to rejection in the C group (p = 0.043). There was no significant difference in ischemic damage or interstitial fibrosis in the groups but there was a higher frequency of hypertrophy in the NC group (p = 0.007).Conclusions: The histopathological features of heart transplantation in C patients did not differ from that in NC patients in regard to the Quilty effect, development of myocardial fibrosis and ischemia. However, the higher involvement of the C group for rejection grades 3 to 4 suggested higher susceptibility to this event. The similarity of the lymphocytic cellular composition for rejection in both groups indicates that C patients respond to immunological stimulus in a similar pattern as NC patients.