Predictors of development of cardiac and digestive disorders among patients with indeterminate chronic Chagas Disease

Abstract

American trypanosomiasis (Chagas disease, CD) affects circa 7 million persons worldwide. While of those persons present the asymptomatic, indeterminate chronic form (ICF), many will eventually progress to cardiac or digestive disorders. We studied a nonconcurrent (retrospective) cohort of patients attending an outpatient CD clinic in Southeastern Brazil, who were admitted while presenting the ICF in the period from 1998 through 2018 and followed until 2019. The outcomes of interest were the progression to cardiac or digestive CD forms. We were also interested in analyzing the impact of Benznidazole therapy on the progression of the disease. Extensive review of medical charts and laboratory files was conducted, collecting data up to year 2019. Demographics (upon inclusion), body mass index, comorbidities (including the Charlson index) and use of Benznidazole were recorded. The outcomes were defined by abnormalities in those test that could not be attributed to other causes. Statistical analysis included univariate and multivariable Cox regression models. Among 379 subjects included in the study, 87 (22.9%) and 100 (26.4%) progressed to cardiac and digestive forms, respectively. In the final multivariable model, cardiac disorders were positively associated with previous coronary syndrome (Hazzard Ratio [HR], 2.42; 95% Confidence Interval [CI], 1.53–3.81) and negatively associated with Benznidazole therapy (HR, 0.26; 95%CI, 0.11–0.60). On the other hand, female gender was the only independent predictor of progression to digestive forms (HR, 1.56; 95%CI, 1.03–2.38). Our results point to the impact of comorbidities on progression do cardiac CD, with possible benefit of the use of Benznidazole.

Author summary

Chagas Disease (CD) is a chronic, neglected infectious disease that affects several low-to-middle income countries. Besides its usual vector transmission, the etiological agent ( Trypanosoma cruzi) can be transmitted through blood transfusion, so that migration from individuals with CD to Europe and North America. The scarcity and lack of evidence for therapeutic options is a major challenge for clinical approach of CD patients. Most of those patients are diagnosed while in asymptomatic, indeterminate chronic form (ICF). Our study aimed at identifying factors associated with progression from ICF to cardiac or digestive disorders. We studied a cohort of 379 IFC patients in inner Brazil, of which 87 and 100 developed cardiac and digestive disorders. In univariate and multivariable analyses, the use of Benznidazole (one of the few drugs used for CD therapy) was statistically protective for progression to cardiac, but not to digestive CD forms. These findings emphasize the importance of novel research aimed at developing more effective therapeutic options.