Prognostic Value of Soluble TNF Receptors in Chagas Cardiomyopathy

Background on Chagas Disease and Cardiomyopathy

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a significant public health issue, especially in Latin America. With approximately 6 to 7 million people infected worldwide, CD can lead to various manifestations, notably chronic Chagas cardiomyopathy (CCC), which affects 20-30% of infected individuals (Ávila et al., 2025). CCC is characterized by progressive heart failure, arrhythmias, and increased mortality rates, making it imperative to identify reliable prognostic indicators for better management (Ávila et al., 2025).

The intricate relationship between inflammation and the progression of CCC highlights the potential role of soluble tumor necrosis factor receptors (sTNFRs) as biomarkers. Elevated levels of sTNFRs, particularly sTNFR2, have been associated with adverse cardiovascular events in various cardiac conditions. Understanding the prognostic value of these biomarkers can enhance risk stratification in patients with CCC, ultimately leading to improved clinical outcomes.

Role of sTNFRs in Cardiovascular Disease Prognosis

Soluble TNF receptors, including sTNFR1 and sTNFR2, are involved in the inflammatory response and have emerged as potential biomarkers for cardiovascular disease. TNF-α, a pro-inflammatory cytokine, binds to these receptors, which can be found in a soluble form in the circulation. The presence of sTNFRs can indicate the degree of systemic inflammation and has been linked to various cardiovascular events, including heart failure and myocardial infarction (Ávila et al., 2025).

In patients with CCC, the levels of sTNFRs provide valuable insights into the underlying pathophysiology. They reflect the immune response to T. cruzi and may correlate with cardiac function. Clinical studies have shown that increased sTNFR levels can predict adverse events, making them critical for monitoring and managing patients with CCC (Ávila et al., 2025).

Study Design and Patient Characteristics

A prospective observational study conducted by Ávila et al. involved 69 patients diagnosed with CCC, aged 53.70 ± 9.66 years, who were followed for an average of 43.81 months. The study aimed to assess the relationship between serum levels of sTNFR1 and sTNFR2 and clinical outcomes, such as cardiac death, heart transplantation, or stroke. Patients with CCC were selected based on the confirmation of T. cruzi infection through serological tests and evidence of cardiac involvement via echocardiographic findings (Ávila et al., 2025).

Table 1: Demographic and Clinical Characteristics of Study Participants

Key Findings on sTNFR2 as a Predictor of Adverse Events

The study revealed that 22% of the patients experienced adverse cardiovascular events during the follow-up period. Notably, only sTNFR2 and left ventricular ejection fraction (LVEF) remained independent predictors of these events. The optimal cutoff point for sTNFR2 was established at 1784 pg/mL, with sensitivity and specificity values indicating its potential utility in risk stratification.

Table 2: Predictors of Adverse Cardiovascular Events

Implications for Risk Stratification in Chagas Cardiomyopathy

The findings underscore the importance of sTNFR2 in predicting adverse cardiovascular outcomes in patients with CCC. High levels of sTNFR2, in conjunction with reduced LVEF, could serve as critical indicators for clinicians to identify patients at elevated risk for heart failure or other cardiovascular complications. By integrating sTNFR2 measurements into clinical practice, healthcare providers can enhance patient management strategies and tailor therapeutic interventions more effectively.

Key Clinical Takeaways:

1. sTNFR2 as a Biomarker: Elevated sTNFR2 levels are associated with a higher risk of adverse cardiovascular events in CCC.
2. LVEF Correlation: Reduced LVEF remains a significant predictor of clinical outcomes, reinforcing the need for regular echocardiographic assessments in this patient population.
3. Risk Stratification: Implementing sTNFR2 screening can aid in the risk stratification of patients with CCC, guiding treatment decisions and follow-up care.

FAQ

What is Chagas disease? Chagas disease is an infectious disease caused by the parasite Trypanosoma cruzi, primarily transmitted by triatomine bugs. It can lead to serious cardiac and gastrointestinal complications.

What is Chagas cardiomyopathy? Chagas cardiomyopathy is the most severe form of Chagas disease, characterized by heart failure, arrhythmias, and increased mortality risk.

What are soluble TNF receptors? Soluble TNF receptors (sTNFR1 and sTNFR2) are circulating forms of TNF receptors that can indicate systemic inflammation and have prognostic implications in various diseases, including cardiovascular conditions.

How does sTNFR2 relate to Chagas cardiomyopathy? Elevated levels of sTNFR2 have been associated with adverse cardiovascular events in patients with Chagas cardiomyopathy, making it a potential biomarker for risk stratification.

What is the significance of left ventricular ejection fraction (LVEF)? LVEF measures the percentage of blood pumped out of the heart’s left ventricle with each contraction. A reduced LVEF is indicative of heart dysfunction and is a key predictor of adverse outcomes in heart disease.

References

1. Ávila, M. R., de Souza, D. M., de Oliveira, L. F. F., Figueiredo, P. H. S., Silva, L. M. C., Silva, W. T., Mediano, M. F. F., Teixeira, L. A. C., de Oliveira, L. F. L., de Alcantara, M. A., Faria, S. C. de C., Arrieiro, A. N., Mendonça, V. A. (2025). Prognostic value of soluble TNF receptors in Chagas cardiomyopathy: observational study. Memórias do Instituto Oswaldo Cruz. https://doi.org/10.1590/0074-02760240107

2. Cheng, J., Wang, H.-Y., Song, C., Qiao, Z., Bian, X., Yin, D., Feng, L., Zhu, C., Yang, M., Gao, G., Dou, K. (2025). Optimizing Long-term Cardiovascular Risk Stratification: Integrating Biomarkers into the Very High-Risk ASCVD Definition in Asian Patients. American Journal of Preventive Cardiology. https://doi.org/10.1016/j.ajpc.2025.100965

3. Dong, W., Li, Y., Fei, Q., Li, S., He, X., Chai, Y., Zhou, J., Zong, Y., Geng, J., Li, Z. (2025). Targeted spleen modulation: a novel strategy for next-generation disease immunotherapy. Theranostics. https://doi.org/10.7150/thno.111116

4. Aoyagi, Y., Schwartz, A. W. B., Li, Z., Bai, H., Gonzalez, L., Lazcano Etchebarne, C., Ohashi, Y., Kano, M., Ho, B., Martin, K. (2025). Changes in vascular identity during vascular remodeling. JVS Vasc Sci. https://doi.org/10.1016/j.jvssci.2025.100282

5. Avendaño, J.A., et al. (2025). Sex differences in kidney and lung status in an animal model of brain death. Clin Sci. https://doi.org/10.1016/j.clinsp.2025.100623

6. Li, Y., et al. (2025). Decoding prognostic factors in SARS-CoV-2 complications among patients with hematological disorders. Clin Sci. https://doi.org/10.1016/j.clinsp.2025.100625