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      Treatment of Chagas Cardiomyopathy

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          Abstract

          Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi ( T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities.

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          Pathogenesis of chronic Chagas heart disease.

          José Marin-Neto, Edecio Cunha-Neto, Benedito Maciel … (2007)
          Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.
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            Development and validation of a risk score for predicting death in Chagas' heart disease.

            Anis Rassi, William C Little, Sérgio Xavier … (2006)
            Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death in patients with Chagas' heart disease. We retrospectively evaluated 424 outpatients from a regional Brazilian cohort. The association of potential risk factors with death was tested by Cox proportional-hazards analysis, and a risk score was created. The model was validated in 153 patients from a separate community hospital. During a mean follow-up of 7.9 years, 130 patients in the development cohort died. Six independent prognostic factors were identified, and each was assigned a number of points proportional to its regression coefficient: New York Heart Association class III or IV (5 points), evidence of cardiomegaly on radiography (5 points), left ventricular systolic dysfunction on echocardiography (3 points), nonsustained ventricular tachycardia on 24-hour Holter monitoring (3 points), low QRS voltage on electrocardiography (2 points), and male sex (2 points). We calculated risk scores for each patient and defined three risk groups: low risk (0 to 6 points), intermediate risk (7 to 11 points), and high risk (12 to 20 points). In the development cohort, the 10-year mortality rates for these three groups were 10 percent, 44 percent, and 84 percent, respectively. In the validation cohort, the corresponding mortality rates were 9 percent, 37 percent, and 85 percent. The C statistic for the point system was 0.84 in the development cohort and 0.81 in the validation cohort. A simple risk score was developed to predict death in Chagas' heart disease and was validated in an independent cohort. Copyright 2006 Massachusetts Medical Society.
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              Predictors of mortality in chronic Chagas disease: a systematic review of observational studies.

              Anis Rassi, G Rassi (2007)
              Chagas disease is a major cause of morbidity and mortality in Latin America. Knowledge of the predictors of prognosis can help clinical decision making by identifying patients' level of risk. We reviewed the published literature on prognostic factors in patients with Chagas disease by performing a PubMed search for articles published in any language between 1985 and February 2006 and hand searches of the reference lists of retrieved articles. Studies were selected if they included patients in the chronic phase of Chagas disease, analyzed a clearly defined outcome (all-cause mortality, sudden cardiac deaths, and/or cardiovascular deaths), and used multivariable regression models of prognosis. From 606 potentially relevant studies, 12 met the inclusion criteria: 8 clinic-based studies including 3928 patients and 4 hospital-based studies including 349 patients. Impaired left ventricular function by echocardiogram or cineventriculogram was found to be the most common and consistent independent predictor of death. New York Heart Association functional class III/IV and cardiomegaly on the chest radiography also were independently associated with higher mortality. More recently, strong evidence was found that nonsustained ventricular tachycardia on 24-hour Holter monitoring indicated an adverse prognosis. The typical ECG abnormalities showed limited additional prognostic value. Other often-mentioned risk factors, advanced age and male sex, showed inconsistent results. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic review of published studies indicates that impaired left ventricular function, New York Heart Association class III/IV, cardiomegaly, and nonsustained ventricular tachycardia indicate a poor prognosis in patients with chronic Chagas disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date (Print): 2013
                Publication date (Electronic): 24 November 2013
                Volume: 2013
                Electronic Location Identifier: 849504
                Affiliations
                1Postgraduate Course of Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, 30130 100 Belo Horizonte, MG, Brazil
                2Hospital das Clínicas, Universidade Federal de Minas Gerais, 30130 100 Belo Horizonte, MG, Brazil
                3Fundação Hospitalar do Estado de Minas Gerais, 30150 260 Belo Horizonte, MG, Brazil
                4School of Medicine, Universidade Federal de Ouro Preto, 35400 000 Ouro Preto, MG, Brazil
                5Departamento de Fisioterapia, Universidade Federal do Vale do Mucuri e Jequitinhonha, 39100 000 Diamantina, MG, Brazil
                Author notes

                Academic Editor: Christof Kolb

                Article
                DOI: 10.1155/2013/849504
                PMC ID: 3857751
                PubMed ID: 24350293
                SO-VID: 0039591b-be5f-4a36-b4d1-118383276530
                Copyright © Copyright © 2013 Fernando A. Botoni et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 April 2013
                Date revision received : 17 September 2013
                Date accepted : 17 September 2013
                Categories
                Subject: Review Article

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