Combined measurement of N-terminal pro-B-type natriuretic peptide and highly sensitive cardiac troponin T for diagnosis and monitoring of heart injury in chronic Chagas' disease.

OBJECTIVE: Chronic Chagas disease afflicts millions of patients in Latin America of which 70% remain asymptomatic but 30% develop fatal heart injury. To evaluate the impact of laboratory medicine for diagnosis and guiding of patients with Chagas' heart disease, we measured N-terminal B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT). DESIGN AND METHODS: NT-proBNP and cTnT using the highly sensitive assay (hs-cTnT) were measured in 48 asymptomatic Chagas' patients (control group; (-) CM), and in symptomatic patients who suffered from mild/moderate (group (+/++) CM, n=62) or severe cardiomyopathy (group (+++) CM, n=27). RESULTS: Both markers were higher in (+/++) CM and (+++) CM vs. (-) CM and increased in the cardiomyopathy severity. Values of 3 ng/L cTnT and 160 ng/L NT-proBNP were calculated as optimal cut-offs to distinguish (-) CM vs. CM. The NT-proBNP cut-off of 125ng/L, as recommended by international guidelines, was additionally incorporated in the analysis. Cardiomyopathy was most successfully predicted by dual positivity of both markers (positive predictive value=1.0). Negativity of both markers effectively excluded cardiomyopathy (negative predictive value of 0.85). Positivity for at least one of the markers is the best for overall correct classification. CONCLUSIONS: Combined measurement of hs-cTnT and NT-proBNP can be used for diagnosis and monitoring of cardiomyopathy in chronic Chagas' patients. In this way, laboratory medicine increases the pre-test probability of the cardiologic diagnostics, which would reduce its time, cost, and logistical problems.

Chronic Chagas' heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine.

Chagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10-30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease.

Distinct patterns of autoantibodies against G-protein-coupled receptors in Chagas' cardiomyopathy and megacolon. Their potential impact for early risk assessment in asymptomatic Chagas' patients.

OBJECTIVES: Distinguishing the patterns of autoantibodies (AAB) against G-protein-coupled receptors in Chagas' cardiomyopathy and megacolon and the discovery of such a pattern in patients who are as yet asymptomatic could help to identify patients at high risk of developing the life-threatening complications of Chagas' disease. BACKGROUND: Such AAB against receptors as beta 1 (beta1-AAB), beta 2 (beta2-AAB), and muscarinergic 2 (M2-AAB) are thought to be involved in the pathogenesis of Chagas' cardiomyopathy and megacolon, the predominant manifestations of Chagas' disease, which is the most serious parasitic disease in Latin America. METHODS: Beta1-AAB, beta2-AAB, and M2-AAB were measured in the serum of asymptomatic Chagas' patients and in those with cardiomyopathy and/or megacolon. RESULTS: Nearly all Chagas' patients with cardiomyopathy and/or megacolon had AAB. Predominance of beta1-AAB combined with M2-AAB in Chagas' cardiomyopathy and beta2-AAB with M2-AAB in megacolon was found. Such patterns were also found in 34% of the asymptomatic patients, of whom 85% possessed a beta1-AAB level typical for Chagas' cardiomyopathy. CONCLUSIONS: The percentage of asymptomatic Chagas' patients who had a specific AAB pattern and had a beta1-AAB level above a defined cutoff point mirrors very well the epidemiological situation, which showed that clinical manifestations develop in nearly 30% of Chagas' patients and cardiomyopathy in nearly 90% of them. We hypothesize that beta1-, beta2-, and M2-AAB measurement might be a useful tool for risk assessment in the indeterminate state of Chagas' disease to select patients for earlier involvement in care programs. However, prospective studies are needed to further evaluate this hypothesis.