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

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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.

Section snippets

Population

We studied 33 patients who underwent orthotopic heart transplantation over a period of 5 years. 18 patients were C and 15 NC. NC patients had dilated cardiomyopathy (n = 13), ischemic myocardiopathy (n = 1), and congenital heart disease (n = 1). 22 patients were male (11 C and 11 NC) and 11 were female (7 C and 4 NC) 14 to 63 years old, all of whom had NYHA functional class III or IV heart failure. The donors were serologically tested for Chagas’ disease (hemagglutination and indirect

General findings

In both groups there was a predominance of male patients (61.1% in the C and 73.3% in the NC group), with a similar distribution in both groups (p = 0.458). Moreover, there was no difference in the C and NC groups concerning patient age (mean age 37.6 years in the C group and 41.4 in the NC group, p = 0.238).

Endomyocardial biopsies

A total of 293 EMBs were analyzed, with a mean of 9 biopsies per patient (range 1 to 16).

Discussion

Chagas’ disease, particularly its pathogenesis, has been the subject of many investigations. Cardiac involvement frequently causes severe cardiac failure with a poorer prognosis compared to cardiomyopathy of other etiologies.18 Recently, heart transplantation has become a good therapeutic option for terminal patients, despite the possibility of recurrent infectious disease.5, 6

Experience accumulated over the years has led to improved survival, stimulating the increasing number of heart

Acknowledgements

This work was partially supported by a FAPESP and CNPq grants. The authors thank Dr. Maria de Lourdes Higuchi, Dr. Maria Regis Silva, Angela T. Paes, Dr. Venâncio Alves and Dr. Maria Teresa Seixas for help in the histopathological study and statistic analysis.

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