Resumo:
Background: Chagas disease (CD) is linked to an elevated stroke risk predominantly
through chronic cardiomyopathy; however, mounting evidence suggests that systemic
inflammatory processes also contribute to cerebrovascular events and cognitive
impairment even when myocardial injury is mild. Chronic inflammation plays a central
role in the pathogenesis of acute ischemic stroke and dementia, raising the hypothesis
that pro-inflammatory biomarkers would be higher in CD patients than in those with
other etiologies of heart failure (HF). Objective: To determine whether serum levels of
five pro-inflammatory biomarkers—interleukin-6 (IL-6), matrix metalloproteinase-9
(MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), orosomucoid, and
neprilysin—are higher in patients with Chagas-related HF compared to those with nonChagas HF. Methods: In this cross-sectional study, 173 HF patients (94 with CD and
79 with other causes) were consecutively recruited from specialty HF clinics at two
university hospitals. Mean age was 55 ± 12 years, and 49% were male. HF severity
was assessed by transthoracic echocardiography, and serum biomarker
concentrations were measured by ELISA in blood samples drawn on the day of
evaluation. Results: Although non-Chagas patients had worse ventricular function
(mean LVEF 38.2 ± 15.3% vs. 53.3 ± 18.0% in Chagas; p<0.001), serum TIMP-1 was
significantly higher in CD patients, with an adjusted mean difference of 2.2 ng/mL (95%
CI 0.1–4.5; p = 0.037). TIMP-1 levels also correlated positively with LVEF (r = 0.32; p
= 0.002), suggesting a link to subclinical myocardial remodeling. In contrast, IL-6,
MMP-9, orosomucoid, and neprilysin did not differ between groups. Exploratory
neuroimaging analyses further indicated that distinct patterns of MMP-9 and TIMP-1
were associated with silent infarcts and microembolic signals, pointing to different
profiles of cerebral vascular injury. Discussion and conclusion: In HF patients,
elevated TIMP-1 in those with CD occurs despite relatively preserved ventricular
function, underscoring its role as an early fibroproliferative mediator and potential
indicator of vascular risk. The dissociation between echocardiographic severity and
inflammatory activation suggests that TIMP-1 may serve as a sensitive marker of
subclinical myocardial and cerebral injury, with promise for guiding personalized
monitoring and therapeutic strategies in Chagas disease.
