Effects of a Mycophenolate Mofetil-Based Immunosuppressive Regimen in Chagas′ Heart Transplant Recipients

Abstract

Mycophenolate Mofetil (MMF) has increasingly been used in the immunosuppressive protocol of cardiac transplant recipients worldwide because of its superiority in comparison to azathioprine, not only for decreasing the incidence of posttransplant coronary artery disease, but also for improving survival (1). Cardiac transplantation has been recommended for patients with end-stage heart failure secondary to Chagas’ cardiomyopathy (2), the leading cause of chronic heart failure in areas where the disease is endemic (3). Little is known about the impact of a MMF-based immunosuppressive regimen on posttransplantation morbidities as well as on the incidence of side-effects in Chagas′ heart transplant recipients. Thirty-one consecutive heart transplant recipients who survived the perioperative period (30 days after heart transplantation) at our Institution from September 2000 to December 2005 were given MMF as immunosuppressant along with a calcineurin inhibitor and prednisone. We have not analyzed data of the perioperative period because of the potential for confounding factors related to the cardiac procedure itself and MMF use. Ten (32%) patients who had a positive indirect immunofluorescence test for Chagas′ disease were compared to 21 (68%) non- Chagas’ disease patients regarding number of rejection and infection episodes, cardiac allograft vasculopathy, malignancy, and bone marrow and gastrointestinal side effects. Median follow up was 917 days (489 to 1607) in Chagas′ disease and 798 days (495 to 1636) in non-Chagas′ disease patients (P>0.05). One patient in the Chagas’ disease group and three patients in the non-Chagas’ disease group died during the study period (P>0.05). Table 1 lists posttransplant morbidities in Chagas’ disease and non- Chagas’ disease patients. Trypanosoma cruzi (T. cruzi) infection reactivation (treated with benznidazole, 5 mg/kg, bid, for 60 days) was detected in biopsy samples from the heart or subcutaneous tissue in 9 (90%) out of 10 Chagas′ heart transplant recipients.TABLE 1: Comparison of posttransplant morbidities in Chagas’ disease (n=10) and in non-Chagas’ disease (n=21) patientsThis study clearly shows that a MMF-based immunosuppressive regimen is associated with an incidence of posttransplant morbidities in Chagas’ disease patients similar to that found in non-Chagas’ disease patients. Importantly, infection episodes were less frequently found in Chagas’ disease than in non-Chagas’ disease patients, and the incidence of rejection episodes graded 3A or more (4) was similar in both groups. However, since the sample size was small, our encouraging results about efficacy and safety of a MMF-based immunosuppressive regimen in Chagas’ disease patients need to be confirmed in larger, prospective studies. A high incidence of T. cruzi infection reactivation was observed in Chagas’ disease patients. This is in accordance with the study by Bacal et al. (5) who found a high incidence of parasite infection reactivation in Chagas’ disease patients on a MMF-based immunosuppressive regimen. Since we have not measured mycophenolic acid plasma levels (6), it is conceivable that over-immunosuppression caused by a fixed daily dose of MMF has allowed T. cruzi infection reactivation to ensue. Nevertheless, a double-blinded, randomized, controlled trial comparing the effects of MMF and azathioprine is necessary to establish the role of MMF in the immunosuppressive protocol of Chagas’ heart tranplant recipients. Reinaldo B. Bestetti Tatiana R. Souza Milena F. Lima Tatiana A. D. Theodoropoulos Division of Cardiology, Hospital de Base, São José do Rio Preto, Brazil José A. Cordeiro Division of Statistics, FAMERP, São José do Rio Preto, Brazil Emmanuel A. Burdmann Division of Nephrology, Hospital de Base, São José do Rio Preto, Brazil