Abstract

Introduction: Chagas disease (CD) is a neglected disease caused by Trypanosoma cruzi ( T. cruzi ), and benznidazole (BZN) is the most prescribed trypanocidal drug in Brazil in function of its best tolerability profile. While treatment with this drug is effective in acute disease, there is no consensus on its effectiveness in adults with chronic infection. Although it is now accepted that treatment directed against T. cruzi is necessary to avoid the long-term sequelae of the disease, the lack of reliable markers for assessment of treatment efficacy is a major obstacle to evaluating new drugs. Hypothesis: the objective of this study is to determine if BZN treatment reduces cardiac inflammation/fibrosis as assessed by magnetic resonance imaging (MRI), using parametric mapping techniques. Methods: Prospective, multi-center study of chronic CD patients underwent MRI T1 and T2 mapping and extracellular volume measurement (ECV) using the modified Look-Locker inversion recovery (MOLLI) sequence, undergoing treatment with BZN, at a dose of 300 mg/kg daily divided into two doses and taken for 60 days. Absolute change T1 and T2 mapping, ECV, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricle ejection fraction (LVEF) were analyzed from baseline to 6-month follow-up. Results: 53 patients (females 83%, 53.9 ± 11.9 years old) were studied. LVEDV (149 ± 27ml vs 147 ± 29ml, p = 0.52), LVESV (66 ± 29 vs 64 ± 15, p = 0.65) and LVEF (55 ± 11% vs 57 ± 8%, p = 0,28) did not change between baseline and post treatment. Native T1 time showed reduced values among anterior (1030 ± 41ms vs 1011 ± 52ms, p = 0.011), septal (1052 ± 53ms vs 1006 ± 38ms, p = 0.000) and lateral (1042 ± 55ms vs 1019 ± 44ms, p = 0.003) LV walls. T2 mapping showed reduction in LV septal wall (53 ± 4ms vs 52 ± 3ms, p = 0.005). ECV showed significant reduction from baseline to 6-month follow-up (29.9 ± 3,3% vs 28.2 ± 3.5%, p = 0.0001). Conclusions: For the first time, we observe favorable changes in CMR ECV, T1 and T2 mapping induced by benznidazole therapy in chronic Chagas disease patients. These findings suggest that there may be an opportunity to decrease fibrosis/inflammation in chronic CD patients with the use of this therapeutic approach.

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