{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:50:53Z","timestamp":1785797453142,"version":"3.56.0"},"reference-count":30,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mem. Inst. Oswaldo Cruz"],"abstract":"<jats:p> BACKGROUND  Chronic Chagas cardiomyopathy (CCC) is the most severe clinical form of the Chagas disease. There is a strong correlation between soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) and cardiac and functional parameters in CCC, but their prognostic value remains unknown.  OBJECTIVE  To verify the prognostic value of sTNFR1 and sTNFR2 in CCC.  METHODS  A longitudinal study was conducted. Sixty-nine patients with CCC (53.70 \u00b1 9.66 years, NYHA I-II) were submitted to blood collection and echocardiography, and followed for 43.81 \u00b1 1.21 months. The outcome was determined by the combination of cardiac death, heart transplantation, or stroke.  FINDINGS  After the follow-up, 15 patients (22%) presented adverse cardiovascular events. Only left ventricular ejection fraction (LVEF) [heart rate at rest (HR): 0.935, 95% CI 0.878 to 0.994; p = 0.033] and sTNFR2 (HR: 1.002, 95% CI 1.001 to 1.003; p = 0.006) remained as independent predictors of adverse cardiovascular events. The optimal cutoff point to identify these patients was the value of 1784.00 pg\/mL. There was a significant difference between the groups with lower and higher sTNFR2 levels (long-rank &lt; 0.001).  MAIN CONCLUSIONS  High serum levels of sTNFR2, together with lower LVEF, are strong independent predictors of adverse cardiovascular events in CCC, making them valuable for risk stratification.<\/jats:p>","DOI":"10.1590\/0074-02760240107","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T20:33:18Z","timestamp":1744057998000},"source":"Crossref","is-referenced-by-count":2,"title":["Prognostic value of soluble TNF receptors in Chagas cardiomyopathy: observational study"],"prefix":"10.1590","volume":"120","author":[{"given":"Matheus Ribeiro","family":"\u00c1vila","sequence":"first","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Menezes","family":"de Souza","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Fr\u00f3is Fernandes","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Henrique Scheidt","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliany Mara Carvalho","family":"Silva","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whesley Tanor","family":"Silva","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Felippe Felix","family":"Mediano","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Augusto da Costa","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano Fonseca Lemos","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Alessandro","family":"de Alcantara","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanny Cristina de Castro","family":"Faria","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Nascimento","family":"Arrieiro","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Amaral","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Rodrigues","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1426-7246","authenticated-orcid":false,"given":"Henrique Silveira","family":"Costa","sequence":"additional","affiliation":[{"name":"Universidade Federal dos Vales do Jequitinhonha e Mucuri,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"key":"ref1","article-title":"Nova tripanozomiaze humana. Estudos sobre a morfologia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem","author":"Chagas C","year":"1909","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref2","year":"2024"},{"issue":"1-2","key":"ref3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.actatropica.2009.07.019","article-title":"Chagas disease in Spain, the United States and other non-endemic countries","volume":"115","author":"Gascon J","year":"2010","journal-title":"Acta Trop"},{"issue":"6","key":"ref4","article-title":"Diretriz da SBC sobre diagn\u00f3stico e tratamento de pacientes com cardiomiopatia da doen\u00e7a de Chagas - 2023","volume":"120","author":"Marin-Neto JA","year":"2023","journal-title":"Arq Bras Cardiol"},{"issue":"9723","key":"ref5","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/S0140-6736(10)60061-X","article-title":"Chagas disease","volume":"375","author":"Rassi Jr A","year":"2010","journal-title":"Lancet"},{"issue":"12","key":"ref6","first-page":"e169","article-title":"Chagas cardiomyopathy an update of current clinical knowledge and management: a scientific statement from the American Heart Association","volume":"138","author":"Nunes MCP","year":"2018","journal-title":"Circulation"},{"issue":"3","key":"ref7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0020-7519(02)00283-7","article-title":"Severity of chronic Chagas disease is associated with cytokine\/antioxidant imbalance in chronically infected individuals","volume":"33","author":"P\u00e9rez-Fuentes R","year":"2003","journal-title":"Int J Parasitol"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1590\/S0074-02762003000300021","article-title":"Increased plasma levels of tumor necrosis factor-a in asymptomatic\/\"indeterminate\" and Chagas disease cardiomyopathy patients","volume":"98","author":"Ferreira RC","year":"2003","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fcell.2019.00091","article-title":"TNFR1 and TNFR2 in the control of the life and death balance of macrophages","volume":"7","author":"Wajant H","year":"2019","journal-title":"Front Cell Dev Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"585880","DOI":"10.3389\/fimmu.2020.585880","article-title":"Tumor necrosis factor receptors pleiotropic signaling complexes and their differential effects","volume":"11","author":"Gough P","year":"2020","journal-title":"Front Immunol"},{"issue":"3","key":"ref11","doi-asserted-by":"crossref","first-page":"100033","DOI":"10.1016\/j.cytox.2020.100033","article-title":"Tumor necrosis factor-a, TNF receptor, and soluble TNF receptor responses to aerobic exercise in the heat","volume":"2","author":"Arroyo E","year":"2020","journal-title":"Cytokine X"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"683230","DOI":"10.1155\/2014\/683230","article-title":"Chagas disease cardiomyopathy immunopathology and genetics","volume":"2014","author":"Cunha-Neto E","year":"2014","journal-title":"Mediators Inflamm"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"798078","DOI":"10.1155\/2014\/798078","article-title":"Tumor necrosis factor is a therapeutic target for immunological unbalance and cardiac abnormalities in chronic experimental Chagas' heart disease","volume":"2014","author":"Pereira IR","year":"2014","journal-title":"Mediators Inflamm"},{"issue":"4","key":"ref14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines for reporting observational studies","volume":"61","author":"von Elm E","year":"2008","journal-title":"J Clin Epidemiol"},{"issue":"6","key":"ref15","first-page":"434","article-title":"I Latin American Guidelines for the diagnosis and treatment of Chagas' heart disease Executive summary","volume":"96","author":"Andrade JP","year":"2011","journal-title":"Arq Bras Cardiol"},{"key":"ref16","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","author":"Lang RM","year":"2015","journal-title":"J Am Soc Echocardiogr"},{"issue":"9","key":"ref17","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1586\/erc.12.111","article-title":"Mortality prediction in Chagas heart disease","volume":"10","author":"Nunes MC","year":"2012","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"ref18","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760210172","article-title":"Prognosis of chronic Chagas heart disease and other pending clinical challenges","volume":"117","author":"Torres RM","year":"2022","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1590\/S0074-02762008000400011","article-title":"TNF\/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection beneficial effects of TNF-a blockade","volume":"103","author":"Kroll-Palhares K","year":"2008","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"11","key":"ref20","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1073\/pnas.89.11.4845","article-title":"Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo","volume":"89","author":"Van Zee KJ","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0609.1995.tb01618.x","article-title":"Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis","volume":"54","author":"Diez-Ruiz A","year":"1995","journal-title":"Eur J Haematol"},{"issue":"5","key":"ref22","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1399-0039.2009.01332.x","article-title":"Plasma concentrations of TNF-alpha and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease","volume":"74","author":"Safranow K","year":"2009","journal-title":"Tissue Antigens"},{"issue":"16","key":"ref23","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1161\/01.CIR.103.16.2055","article-title":"Cytokines and cytokine receptors in advanced heart failure an analysis of the cytokine database from the Vesnarinone trial (VEST)","volume":"103","author":"Deswal A","year":"2001","journal-title":"Circulation"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"656928","DOI":"10.3389\/fphar.2021.656928","article-title":"Serum soluble tumor necrosis factor receptors 1 and 2 are early prognosis markers after ST-segment elevation myocardial infarction","volume":"12","author":"Paccalet A","year":"2021","journal-title":"Front Pharmacol"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"152166","DOI":"10.1016\/j.imbio.2021.152166","article-title":"Is a negative correlation between sTNFR1 and TNF in patients with chronic Chagas disease the key to clinical progression","volume":"227","author":"Torres DJL","year":"2022","journal-title":"Immunobiology"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"7245","DOI":"10.1038\/s41598-024-57265-x","article-title":"Circulating TNF receptor levels are associated with estimated glomerular filtration rate even in healthy individuals with normal kidney function","volume":"14","author":"Gohda T","year":"2024","journal-title":"Sci Rep"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijcard.2020.04.053","article-title":"Plasma levels of soluble TNF receptors are associated with cardiac function in patients with Chagas heart disease","volume":"316","author":"Silva WT","year":"2020","journal-title":"Int J Cardiol"},{"key":"ref28","first-page":"361730","article-title":"In situ expression of regulatory cytokines by heart inflammatory cells in Chagas' disease patients with heart failure","volume":"2012","author":"Rodrigues DBR","year":"2012","journal-title":"Clin Dev Immunol"},{"issue":"4","key":"ref29","first-page":"225","article-title":"Male sex Prognostic factor in Chagas' disease","volume":"60","author":"Barretto AC","year":"1993","journal-title":"Arq Bras Cardiol"},{"issue":"7","key":"ref30","first-page":"788","article-title":"Predictors of mortality in patients with dilated cardiomyopathy relevance of Chagas disease as an etiological factor","volume":"63","author":"Nunes MCP","year":"2010","journal-title":"Rev Esp Cardiol"}],"container-title":["Mem\u00f3rias do Instituto Oswaldo Cruz"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S0074-02762025000101115&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T20:34:10Z","timestamp":1744058050000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0074-02762025000101115&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":30,"alternative-id":["S0074-02762025000101115"],"URL":"https:\/\/doi.org\/10.1590\/0074-02760240107","relation":{},"ISSN":["1678-8060","0074-0276"],"issn-type":[{"value":"1678-8060","type":"electronic"},{"value":"0074-0276","type":"print"}],"subject":[],"published":{"date-parts":[[2025]]},"article-number":"e240107"}}