Avaliação de biomarcadores inflamatórios na cardiomiopatia chagásica

Abstract

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.