Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease

Abstract

Background Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups. Methods This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) that were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS. Results A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-γ IL-6, IL-10 and TNF-α and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status. Conclusions Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments.

Cardiac rehabilitation program in patients with Chagas heart failure: a single-arm pilot study

“…CHF presents with greater myocardial damage, abnormal autonomic regulation, low-grade chronic inflammation, and microvascular disturbance than other cardiomyopathies (42) (43) , which may have contributed to the poorer long-term effects of exercise on functional capacity observed in the present study.…”

Combined analysis of cross‐reacting antibodies anti‐β1AR and anti‐B13 in advanced stages of Chagas heart disease

“…In addition, it would be interesting to include them in more complex models employing other independent inflammation and cardiac damage markers reported recently (i.e. T. cruzi parasitemia by RT‐ PCR, NT‐proBNP) .…”

Measurement of Troponin in Cardiomyopathies

“…Cardiac Tn levels correlate with the severity of the cardiomyopathy and may be useful for monitoring chronic Chagas myocarditis, but are less sensitive than other biomarkers for predicting early disease development in seropositive individuals. 92,93 Peripartum cardiomyopathy Peripartum cardiomyopathy (PPCM) is a form of DCM that presents with signs of cardiac failure during the last month of pregnancy or within five months of delivery. 94 In a prospective multi-centre study of 106 patients with newly diagnosed PPCM surviving over 6 months 31% patients had elevated TnT levels which negatively correlated with left ventricular ejection fraction (LVEF) at follow-up.…”