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Ann Thorac Surg 1995;60:1406-1408
© 1995 The Society of Thoracic Surgeons

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Case Reports

Heart Transplantation for Chagas' Cardiomyopathy

Department of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California

Accepted for publication April 28, 1995.

	Abstract

Top Footnotes Abstract Introduction Case Reports Comment Acknowledgments References

 
We present 2 patients who underwent orthotopic heart transplantation for end-stage Chagas' cardiomyopathy. Despite immunosuppressive therapy, postoperative prophylaxis with nifurtimox appeared to prevent Trypanosoma cruzi reactivation. Neither patient has shown signs of Chagas' myocarditis, and both are clinically well 12 and 72 months after transplantation. The successful outcome of our patients suggests that heart transplantation is a reasonable therapeutic option in patients with end-stage Chagas' cardiomyopathy.

	Introduction

Top Footnotes Abstract Introduction Case Reports Comment Acknowledgments References

 
See also page 1408.

Chagas' disease represents a major public health problem in Latin America as it is endemic throughout most of Central and South America. It is estimated that between 16 and 18 million people worldwide are infected with Trypanosoma cruzi, and an additional 90 million are at risk. Approximately 50,000 people die of Chagas' disease every year [1–6]. During the last two decades, several million people have emigrated to the United States from areas where Chagas' disease is endemic. It is estimated that more than 100,000 infected persons now live in the United States [7]. Chagas' cardiomyopathy is a serious complication of Chagas' disease and represents a very rare indication for heart transplantation [1, 2]. We present our experience with 2 patients who underwent heart transplantation for end-stage Chagas' cardiomyopathy. In addition, a review of similar cases in the literature is presented.

	Case Reports

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Patient 1
A 44-year-old woman from Ecuador, who immigrated to the United States at 21 years of age, presented with a mild embolic cerebrovascular accident emanating from a left ventricular apical aneurysm 4 years ago. She had depressed left ventricular function (ejection fraction, 0.30) with marked cardiomegaly. Severe dyskinesia of the posterolateral and inferior walls was observed. Coronary angiogram demonstrated normal coronary arteries, and endomyocardial biopsy revealed diffuse myocardial fibrosis. No parasites were observed on microscopic examination. The diagnosis of Chagas' cardiomyopathy was confirmed by a positive immunoprecipitation and complement fixation test.

The patient experienced progressive deterioration of cardiac function, accompanied by severe mitral and tricuspid regurgitation. Refractory ventricular tachycardia and intractable congestive heart failure developed that necessitated orthotopic heart transplantation. Her postoperative recovery was uneventful, and the patient remains clinically well 72 months after transplantation.

Immunosuppression consisted of OKT3 induction therapy (5 mg/day for 14 days) with concomitant administration of cyclosporine (5 mg•kg^-1•day^-1 for a level of 150 to 200 ng/mL by fluorescence polarization immunoassay started postoperatively once the serum creatinine level was less than 2.0 mg/dL), azathioprine (4 mg/kg preoperatively and 2 mg•kg^-1•day^-1 postoperatively), and steroids (methylprednisolone sodium succinate, 1 g at removal of aortic cross-clamp intraoperatively, and then 125 mg intravenously every 8 hours for three doses postoperatively, followed by prednisone, 0.25 mg•kg^-1 •day^-1 during OKT3 therapy, increased to 0.5 mg•kg^-1 •day^-1, and then tapered in the subsequent 3 to 8 months). No preoperative therapy for Chagas' disease was used. Nifurtimox (Bayer, Buenos Aires, Argentina) (120 mg/day for 3 months followed by 150 mg on alternate days) was administered postoperatively and will be continued indefinitely. No reactivation of Chagas' disease has been observed at 6 years' follow-up.

Histologic examination of the explanted heart revealed diffuse endocardial interstitial fibrosis. Lymphocytic, plasmocytic, and eosinophilic infiltrates of endocardium, myocardium, and pericardium (pancarditis) were observed indicating acute and chronic myocarditis. No organisms were seen microscopically, and cultures were negative. An apical aneurysm was present.

Patient 2
A 59-year-old Honduran woman, who immigrated to the United States at age 39 years, had a left cerebrovascular accident, from which she fully recovered, 4 years ago. The patient was found to have severe cardiomegaly and a left anterior hemiblock and right bundle-branch block on electrocardiography. Two-dimensional echocardiography demonstrated inferior wall akinesis and severe hypokinesis in the posterolateral and anterior wall, moderate mitral regurgitation, and an estimated ejection fraction of 0.18. The coronary arteries were normal on cineangiography. Endomyocardial biopsy revealed interstitial fibrosis with no evidence of intracardiac parasites. The diagnosis of Chagas' cardiomyopathy was confirmed by an indirect fluorescent antibody titer of 1:128. Subsequently, multiple bouts of congestive heart failure developed, and a permanent pacemaker was implanted for a third-degree atrioventricular block. Her cardiac decompensation progressed to severe biventricular failure, and she underwent orthotopic heart transplantation, with an uneventful postoperative course. The patient remains clinically well 12 months after transplantation.

The same immunosuppressive regimen used for patient 1 was followed, except OKT3 induction therapy was given for only 7 days. No preoperative therapy for Chagas' disease was given. The patient was started on the same prophylactic nifurtimox protocol postoperatively, which will be continued indefinitely. No reactivation of Chagas' disease has been observed.

Microscopic examination of the explanted heart revealed extensive patchy fibrosis, multifocal pancarditis, and interstitial fibrosis with focal subendocardial myocytolysis. No parasites were observed and cultures were negative. A posterobasal aneurysm was observed.

	Comment

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Chagas' disease (american trypanosomiasis) is a chronic illness caused by the protozoan hemoflagellate T cruzi. It multiplies in the intestinal tract of insect vectors and transmission to humans occurs when parasites gain access via skin or mucous membranes through contaminated feces of the Triatoma [4, 5, 8]. After local intracellular multiplication disrupts the host cells, T cruzi is liberated into the bloodstream and persists in its host indefinitely. Spontaneous remission is not known to occur [8]. Transmission of the parasite can also occur by blood transfusion, congenitally, by laboratory accidents, and by organ transplantation [1, 4–6, 8]. Contaminated blood transfusion from asymptomatic donors is considered the most important mechanism of transmission in this country [3]; the prevalence of infected donors in the Los Angeles area is between 1:500 and 1:100 [4, 5]. Serologic testing for Chagas' disease in potential donors is not routinely performed.

The heart is the most commonly affected organ in the chronic phase. The pathology of Chagas' disease is characterized by chronic myocarditis, with the formation of a left ventricular aneurysm and mural thrombus, localized areas of akinesis or dyskinesis, fibrosis, and biventricular enlargement. Involvement of the conduction system produces right bundle-branch block, left anterior fascicular block, or complete atrioventricular block. When myocardial involvement is diffuse, a dilated cardiomyopathy develops [4–7]. Other manifestations of chronic infection include megaesophagus, megacolon, or both. They are usually associated with dysphagia, regurgitation, aspiration, severe constipation, and malnutrition. Less often, the duodenum, stomach, small intestine, and the biliary tract may be involved, with resultant hypotonia, stasis, hyposecretion, and malabsorption. The pathogenesis of the gastrointestinal and cardiac lesions associated with chronic Chagas' disease remains unclear, but it appears to be related to local organ denervation [4–6]. The neurologic manifestations associated with chronic T cruzi infection are secondary to lesions of the cerebellum, hypothalamus, spinal cord, and cerebral cortex, and result from destruction of central motor neurons and peripheral sensory nervous fibers [6]. The prognosis is poor for patients with heart failure, left ventricular aneurysm, or global systolic dysfunction [7]. Life expectancy from the onset of heart failure is 6 to 13 months [8], and death usually results from heart failure or arrhythmic events [4, 5].

In the United States, Chagas' cardiomyopathy commonly mimics coronary artery disease or idiopathic dilated cardiomyopathy [7]. There may be approximately 75,000 undiagnosed cases of chronic Chagas' cardiomyopathy in this country [3].

Organ transplantation is usually contraindicated in patients with chronic infection because immunosuppressive therapy can trigger reactivation. There is in vitro and in vivo evidence that T cruzi can replicate actively with immunosuppressive drugs [8], and Chagas' disease can have a fulminant course in an immunocompromised patient [8, 10]. However, clinical experience in patients with Chagas' disease who underwent kidney transplantation is favorable. Currently, Chagas' disease is not considered a contraindication to renal transplantation [4, 5, 9, 10].

Heart transplantation in patients with end-stage Chagas' cardiomyopathy has been performed in 55 patients in Brazil, although the rate of T cruzi reactivation is high [1, 2, 11; Stolf NA, personal communication]. The high incidence of posttransplantation allograft myocarditis has been viewed as a potential contraindication for transplantation [4, 5]. Postoperative prophylaxis with benzonidazole has been used [1, 2], although it may be responsible for an increased incidence of lymphoproliferative disorder. At the present time, these patients do not receive any prophylactic therapy because it seems it does not prevent reactivation [Stolf NA, Bocchi EA; personal communications]. Furthermore, it appears that a reduction of cyclosporine dose postoperatively may lead to a decrease in clinical reactivation of T cruzi infection after heart transplantation with improved survival [11]. A total of 7 patients with Chagas' cardiomyopathy, including the 2 presented in this report, have received transplants in the United States, although only 1 has been reported [8]. Four patients received prophylactic nifurtimox postoperatively and did not experience reactivation. Those patients without prophylaxis had T cruzi reactivation involving the skin (3) and myocardium (1), but responded well to nifurtimox therapy [4] (Table 1). Because of the lack of guidelines in postoperative prophylactic therapy after heart transplantation, we plan to continue nifurtimox therapy in our patients indefinitely. Neither one has shown signs of Chagas' disease reactivation at 12 and 72 months after transplantation.

The successful clinical outcome of our patients, as well as the experience of others, might indicate that heart transplantation is a reasonable therapeutic option for patients with end-stage Chagas' cardiomyopathy. However, due to the small number of patients, it is difficult to establish guidelines for postoperative prophylaxis, although it appears that the regimen used prevents reactivation of T cruzi in the posttransplantation period.

	Acknowledgments

Top Footnotes Abstract Introduction Case Reports Comment Acknowledgments References

 
We thank Kathleen Farrington and Marilyn Sanders for their expertise in the preparation of the manuscript.

Supported by the Deutsche Forschungsgemeinschaft (DFG, grant A1 381/1-1).

	Footnotes

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Address reprint requests to Dr Blanche, Heart Transplant Program, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 6215, Los Angeles, CA 90048.

	References

Top Footnotes Abstract Introduction Case Reports Comment Acknowledgments References

 

1. Stolf NA, Higushi L, Bocchi EA, et al. Heart transplantation in patients with Chagas' disease cardiomyopathy. J Heart Transplant 1987;6:307–12.[Medline]
2. Bocchi EA, Bellotti G, Uip D, et al. Long-term follow-up after heart transplantation in Chagas' disease. Transplant Proc 1993;25:1329–30.[Medline]
3. Milei J, Mautner B, Storino R, Sanchez JA, Ferrans VJ. Does Chagas' disease exist as an undiagnosed form of cardiomyopathy in the United States? Am Heart J 1992;123:1732–5.[Medline]
4. Kirchhoff LV. American trypanosomiasis (Chagas' disease). A tropical disease now in the United States. N Engl J Med 1993;329:639–44.[Free Full Text]
5. Kirchhoff LV. Chagas' disease. American trypanosomiasis. Infect Disease Clin North Am 1993;7:487–501.[Medline]
6. Prata A. Chagas' disease. Infect Disease Clin North Am 1994;8:61–76.[Medline]
7. Hagar JM, Rahimtoola SH. Chagas' heart disease in the United States. N Engl J Med 1991;325:763–8.[Abstract]
8. Libow LF, Beltrani VP, Silvers DN, Grossman ME. Post-cardiac transplant reactivation of Chagas' disease diagnosed by skin biopsy. Cutis 1991;48:37–40.[Medline]
9. Lopez Blanco OA, Cavalli NH, Jasovich A, Gotlieb D, Gonzalez-Cappa S. Chagas' disease and kidney transplantation. Follow-up of nine patients for 11 years. Transplant Proc 1992;24:3089–90.[Medline]
10. Luders C, Caetano MA, Ianhez LE, Fonseca JA, Sabbaga E. Renal transplantation in patients with Chagas' disease: a long-term follow-up. Transplant Proc 1992;24:1878–9.[Medline]
11. Bocchi EA, Belloti G, Wip D, et al. Improved results after heart transplantation for treatment of Chagas' heart disease with reduced doses of cyclosporine. Circulation 1994;90(Suppl 1):153.
12. Moreira LFP, Seferian P Jr, Bocchi EA, et al. Survival improvement with dynamic cardiomyoplasty in patients with dilated cardiomyopathy. Circulation 1991;84(Suppl 3):296–302.

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Carlos Blanche Ivan Aleksic Alfredo Trento Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blanche, C. Articles by Trento, A. Search for Related Content PubMed PubMed Citation Articles by Blanche, C. Articles by Trento, A. Related Collections Related Article