Predictors of cardiomyopathy progression in a Chagas disease cohort in Bolivia

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DESCRIPTION (provided by applicant): Despite progress in the control of the triatomine vectors, Bolivia remains the country with the highest Trypanosoma cruzi infection prevalence in the world. The major clinical manifestation is Chagas cardiomyopathy, characterized by a chronic inflammatory process leading to conduction system abnormalities, ventricular arrhythmias, sinus node dysfunction and progressive dilated cardiomyopathy with congestive heart failure. National programs have historically only treated children with Chagas disease, but the impetus for adult treatment has grown significantly in the last 10 years, based on growing patient demand and observational data suggesting that treatment, even in patients with early cardiac morbidity decreases the progression of Chagas heart disease and possibly also mortality. Nevertheless, adult treatment will remain beyond the resources of countries like Bolivia, without an effective algorithm to target those at high risk of heart disease. A reliable early indicator of cardiac risk would allow treatment to be targeted to the 20 to 30% of infected individuals with the highest likelihood of future morbidity and mortality. Biomarkers to detect early Chagas heart disease may reflect early changes in cardiac structure and function, substances such as B-type natriuretic peptide released in response to cardiac disease or a substance such as transforming growth factor- beta1 involved in cardiac pathogenesis at the cellular level. We propose to examine biomarkers in multiple categories simultaneously to allow a comprehensive assessment of their relative utility, individually and in combination, in a cohort study recruited from (1) hyperendemic villages where >95% of adults have T. cruzi infection and 17% of infected individuals > 30 years have electrocardiographic abnormalities characteristic of Chagas cardiomyopathy, (2) a large public hospital in the city of Santa Cruz where we expect >50% of cardiac patients to have Chagas heart disease and (3) a district hospital in the same hyperendemic zone as the communities mentioned above. The major outcome measure will be progression of Chagas cardiomyopathy over a 4-year follow-up period. Because of the extraordinarily high prevalence of infection, this population will be ideal for assessing associations between biomarkers and early Chagas cardiomyopathy.