# Evaluation of the autonomic nervous system in autochthonous patients from Amazon with acute Chagas disease treated with benznidazole

## TL;DR

This study evaluates autonomic nervous system function in Amazonian patients with acute Chagas disease before and after benznidazole treatment, finding persistent autonomic imbalances that could lead to long-term cardiac issues.

## Contribution

The study provides new empirical evidence on autonomic nervous system dysfunction in acute Chagas disease patients from the Amazon region.

## Key findings

- Acute Chagas disease patients showed significant reductions in heart rate variability indicators, indicating sympathovagal imbalance and reduced parasympathetic tone.
- Persistent autonomic modulation alterations were observed even after benznidazole treatment, suggesting a need for continued monitoring.
- These autonomic dysfunctions may predispose patients to structural cardiac changes and arrhythmias in the long term.

## Abstract

Chagas disease, a neglected tropical disease, is endemic in the Amazon region, where oral transmission predominates. Autonomic nervous system (ANS) impairment is a recognized pathophysiological mechanism contributing to disease progression, including Chagas cardiomyopathy. This study aimed to assess ANS function in patients with acute Chagas disease from the Amazon, evaluating responses pre- and post-benznidazole treatment. We included 28 acute-phase patients and 20 healthy controls. Participants underwent comprehensive cardiac evaluations, including 12-lead ECG, echocardiogram, 24-hour Holter monitoring, treadmill stress testing, and 5-minute heart rate variability (HRV) assessment. HRV was analyzed across time, frequency, and nonlinear domains, with statistical comparisons performed between groups and within the patient cohort. The study population predominantly comprised individuals from rural Amazonian municipalities (89.3%), with oral transmission accounting for 85.7% of infections. While resting ECGs were normal in 60.7%, diffuse ventricular repolarization was the most common abnormality (21.4%). Before treatment, 24-hour HRV showed significant reductions in SDANN and SDNN, indicating sympathovagal imbalance. For 5-minute HRV, significant alterations were observed across time (rMSSD, SDNN), frequency (LF, HF, LF/HF ratio), and nonlinear domains, reflecting reduced parasympathetic tone. Intragroup comparisons (pre- vs. post-treatment) further reinforced the sustained sympathovagal imbalance and parasympathetic inhibition. These findings highlight persistent autonomic modulation alterations, characterized by sympathovagal imbalance and reduced parasympathetic activity, in acute Chagas disease patients from the Amazon. Such dysfunction may predispose individuals to long-term structural cardiac changes and arrhythmias, underscoring the critical need for continued monitoring and potential targeted interventions to address autonomic imbalance in this vulnerable population.

Chagas disease is a neglected tropical disease, globally prevalent, with the potential for progression to severe forms. It is endemic to the Amazon region, presenting in both acute and chronic forms, with oral transmission being one of the most frequent modes of Chagas disease acquisition in this area. The primary pathogenic mechanisms proposed to explain disease progression include direct tissue damage, an immune response against the parasite with the potential for autoimmunity, and autonomic nervous system dysfunction. The aim of this study was to evaluate the autonomic nervous system response in patients diagnosed with acute Chagas disease, residing in the Amazon region and receiving care at the outpatient clinic of the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado.