Introduction to Chagas Cardiomyopathy and Its Importance

Chagas cardiomyopathy (CC) represents a significant public health challenge, particularly in regions endemic to Trypanosoma cruzi infection. This chronic condition, affecting approximately 20% to 30% of those infected, leads to serious cardiac complications, including heart failure, arrhythmias, and sudden cardiac death (Ávila et al., 2025). The pathophysiology of Chagas disease involves a complex interplay of inflammatory responses and immune dysregulation, which ultimately contribute to myocardial damage and dysfunction.

A deeper understanding of prognostic indicators in CC is crucial for effective patient management and risk stratification. Soluble tumor necrosis factor receptors (sTNFRs), specifically sTNFR1 and sTNFR2, have emerged as potential biomarkers in various cardiovascular diseases, including Chagas cardiomyopathy. These receptors play a pivotal role in the inflammatory response, and their elevated levels have been implicated in adverse cardiovascular outcomes. Identifying the prognostic value of sTNFRs in CC could enhance clinical decision-making and therapeutic strategies for affected patients.

The Role of Soluble TNF Receptors in Heart Disease

Soluble TNF receptors (sTNFRs) are the cleaved extracellular domains of the membrane-bound TNF receptors, TNFR1 and TNFR2. They are released into circulation and can bind to tumor necrosis factor (TNF), thus modulating its bioavailability and activity (Ávila et al., 2025). Elevated levels of sTNFRs have been associated with increased inflammation and poor outcomes in heart diseases, suggesting their potential as biomarkers for risk stratification in patients with Chagas cardiomyopathy.

In the context of heart disease, TNF is known to contribute to myocardial inflammation and remodeling. Increased levels of TNF and its receptors have been linked to cardiac dysfunction, fibrosis, and adverse outcomes. Studies indicate that patients with heart failure exhibit elevated sTNFR levels, correlating with disease severity and prognosis (Ávila et al., 2025). Thus, understanding the dynamics of sTNFR levels in Chagas cardiomyopathy could provide insights into the disease’s progression and potential therapeutic targets.

Key Findings on Soluble TNF Receptors and Adverse Events

Recent studies have demonstrated that high serum levels of sTNFR2, alongside lower left ventricular ejection fraction (LVEF), serve as independent predictors of adverse cardiovascular events in patients with Chagas cardiomyopathy. In a cohort study comprising 69 patients, a significant correlation was observed between elevated sTNFR2 levels and increased rates of cardiac death, heart transplantation, or stroke (Ávila et al., 2025). The optimal cut-off point for sTNFR2 was determined to be 1784 pg/mL, providing a reliable threshold for identifying patients at risk for adverse outcomes.

The prognostic implications of these findings suggest that monitoring sTNFR levels may facilitate early intervention strategies and improve clinical management for patients with Chagas cardiomyopathy. Moreover, these biomarkers could aid in the identification of individuals who may benefit from closer monitoring and aggressive therapeutic measures.

Correlation Between Left Ventricular Function and sTNFR Levels

The relationship between left ventricular function and sTNFR levels is a critical aspect of Chagas cardiomyopathy. In patients with diminished LVEF, elevated sTNFR levels reflect the underlying myocardial damage and inflammatory milieu. A study found that sTNFR2 was significantly higher in patients with systolic dysfunction compared to those with preserved LVEF (Ávila et al., 2025). This correlation underscores the importance of assessing both LVEF and sTNFR levels in evaluating disease severity and predicting outcomes.

Parameter	Without Adverse Event (n=54)	With Adverse Event (n=15)	p-value
Age (years)	55.09 ± 9.64	48.67 ± 8.20	0.022
LVEF (%)	51.73 ± 16.69	35.13 ± 7.55	<0.001
sTNFR2 (pg/mL)	359.29 (253.26 - 2237.20)	2668.23 (2060.55 - 3687.95)	<0.001

This table illustrates the significant differences in age, LVEF, and sTNFR2 levels between patients who experienced adverse events and those who did not. The findings reinforce the utility of sTNFR2 as a prognostic biomarker in Chagas cardiomyopathy.

Implications for Risk Stratification in Chagas Cardiomyopathy

The integration of sTNFR levels into clinical practice can significantly enhance risk stratification in patients with Chagas cardiomyopathy. Given the strong association between elevated sTNFR2 levels, low LVEF, and adverse outcomes, clinicians can utilize these biomarkers to identify high-risk individuals who may require more intensive monitoring and management strategies.

Furthermore, understanding the role of inflammation in Chagas cardiomyopathy can inform therapeutic approaches aimed at modulating the immune response. Targeting the TNF pathway may offer a potential therapeutic strategy to mitigate myocardial damage and improve outcomes in affected patients. Future research should focus on validating the prognostic utility of sTNFRs in larger cohorts and exploring the mechanistic pathways linking inflammation to cardiac dysfunction in Chagas disease.

FAQ Section

What is Chagas cardiomyopathy?
Chagas cardiomyopathy is a chronic heart condition caused by the parasitic infection with Trypanosoma cruzi, leading to heart failure, arrhythmias, and other serious complications.

What are soluble TNF receptors?
Soluble TNF receptors are the cleaved forms of membrane-bound TNF receptors, which can bind to tumor necrosis factor (TNF) in circulation, modulating its inflammatory effects.

How do sTNFR levels relate to cardiovascular events in Chagas cardiomyopathy?
Higher levels of sTNFR2, particularly in conjunction with lower left ventricular ejection fraction, are associated with an increased risk of adverse cardiovascular events such as cardiac death and heart transplantation.

What is the significance of monitoring sTNFR levels in Chagas patients?
Monitoring sTNFR levels can help identify patients at higher risk for adverse outcomes, enabling more aggressive management and potentially improving prognosis.

What further research is needed in this area?
Further studies are needed to validate the prognostic value of sTNFRs in larger populations and to investigate the underlying mechanisms linking inflammation to cardiac dysfunction in Chagas disease.

References

Ávila, M. R., de Souza, D. M., de Oliveira, L. F., Figueiredo, P. H. S., Silva, L. M. C., Silva, W. T., Mediano, M. F. F., Teixeira, L. A. C., de Oliveira, L. F., de Alcantara, M. A., Faria, S. C. de C., Arrieiro, A. N., Mendonça, V. A., Lacerda, A. C. R. (2025). Prognostic value of soluble TNF receptors in Chagas cardiomyopathy: observational study. Memórias do Instituto Oswaldo Cruz
Other relevant references can be added here as per the continued research and findings.