natriuretic-peptide--brain and Chagas-Cardiomyopathy

In the present review we have summarized remarkable historical data on Chagas' disease studies putting special emphasis on histopathological findings and pathogenetic theories as well as recent discoveries based on the use of advanced modern technologies in pathology and immunology. A unified theory that links almost all of these findings is proposed. Chronic cardiac Chagas' disease represents the result of a close interaction between the host and the parasite, causing different clinical pictures: patients with an efficient immune response may adequately circumvent the parasitic infection and the individual will develop the indeterminate form. Deficient immune response of the host and/or a high initial parasitemia favor an immune imbalance that might lead to development of a permanent inadequate immunological response against the parasite. The inflammatory response, which is probably recurrent, undergoing periods of more accentuated exacerbation, is most likely responsible for progressive neuronal damage, microcirculatory alterations, heart matrix deformations and consequent organ failure.

Topics: Animals; Antigens, CD; Atrial Natriuretic Factor; Autoimmunity; CD8-Positive T-Lymphocytes; Cell Adhesion Molecules; Chagas Cardiomyopathy; Cytokines; Heart; Humans; Immune Tolerance; Natriuretic Peptide, Brain; Parasitemia; Trypanosoma cruzi

The assessment of the type-B natriuretic peptide (BNP) has shown utility as a diagnostic and prognostic tool of heart failure. The aim of this study was to evaluate the BNP levels and to know its association within the systolic dysfunction level on Chagas disease. During the period 2010-2011, 64 patients were evaluated in the Chagas clinic of the Cardiopulmonary Unit of the University Hospital Dr. Luis Razetti, Barcelona-Anzoátegui state, Venezuela. After confirming the seropositive state to antibodies anti-T. cruzi with three inmunoserological tests (ELISA, indirect inmunofluorescence and indirect hemaglutination), patients were classified into Groups I, II and III of cardiac disease, by the evaluation with electrocardiogram, echocardiogram and thorax radiography. Thirty three seronegative cardiological patients and eight healthy volunteers were included in the study as controls. BNP groups levels were as follow: Chagas I = 18.87 +/- 18.00 pg/mL (n=20), Chagas II = 99.88 +/- 171.52 pg/mL (n=24) y Chagas III = 365.80 +/- 280.54 pg/mL (n=20). The sensitivity and specificity of BNP were 85.0% and 93.2%, respectively, (p<0.0001; IC 95%), employing as parameter of reference the left ventricle fraction ejection (LVFE <40%), with a prognostic value of 89.0% (p=0.006). These results place the BNP in an equivalent position with the echocardiogram for the evaluation of cardiological patients, with the benefits of rapidity and simplicity, which makes the determination of this biochemical parameter a useful tool to perform field studies in endemic zones with limited access to the echocardiographic test.

Topics: Aged; Antibodies, Protozoan; Biomarkers; Chagas Cardiomyopathy; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Trypanosoma cruzi; Ultrasonography; Ventricular Dysfunction, Left

The effects of exercise training in chronic heart failure are well established, however, they have not been evaluated in Chagas cardiomyopathy (ChC). We sought to determine the effects of exercise training on functional capacity, health-related quality of life (HQoL), and brain natriuretic peptide (BNP) levels in patients with ChC.. This randomized, controlled, single-blind trial included 40 patients with ChC (age 49.5 +/- 7.8 years, 57.5% male) who did not practice regular exercise. All patients were assessed, at baseline and at the end of the study, by exercise test (VO(2) and exercise time), six-minute walk test (6MWT), Goldman Specific Activity Scale (SAS), HQoL, and BNP levels. Patients were randomized to inactive control group (ICG = 19) or exercise training group (ETG = 21). Exercise training group patients underwent 12 weeks of exercise training: walking for up to 30 min (intensity 50-70% HR reserve + HR at rest) and warm-up and cooling-down exercising, three times a week. The data were analysed for delta values (Delta= end - baseline). After intervention, compared with the ICG, the ETG had significant increases in functional parameters including, DeltaVO(2) (6.5 vs. 2.8 mL/kg/min, P = 0.001), Delta exercise time (2.9 vs.1.1 min, P < 0.001), Delta6MWT distance (83.5 vs. 2.0 m, P = 0.001) improved DeltaSAS (8 vs. 1 patient, P = 0.008), and HQoL: Delta domains vitality (7.5 vs. 0 points, P = 0.013), Delta emotional aspects (16.7 vs. 0 points, P = 0.012), and Delta mental health (16.1 vs. 0 points, P = 0.031). There was no difference in BNP levels.. In patients with ChC, exercise training was associated with a major improvement in functional capacity and HQoL without any adverse effects.

Topics: Adult; Chagas Cardiomyopathy; Exercise Test; Exercise Therapy; Exercise Tolerance; Female; Health Status Indicators; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Patient Compliance; Quality of Life; Single-Blind Method; Surveys and Questionnaires

To analyze the association of circulating dehydroepiandrosterone sulfate (DHEA-S) levels with cardiovascular outcomes in patients with chronic Chagas cardiomyopathy (CCM) diagnosis.. DHEA-S is among the main endogenous steroid hormones. Some studies have suggested a relevant role of this hormone in infections and the setting of CCM. Nevertheless, no study has evaluated the prognostic role of DHEA-S in CCM patients.. Prospective cohort study. Patients with CCM and reduced ejection fraction were included. We explored the association of DHEA-S levels with NT-proBNP levels and echocardiographic variables using linear regression models. Next, by using Cox Proportional Hazard models, we examined whether levels of DHEA-S could predict a composite outcome (CO) including all-cause mortality, cardiac transplantation, and implantation of a left ventricular assist device (LVAD).. Seventy-four patients were included (59% males, median age: 64 years). After adjustment for confounding factors, high DHEA-S levels were associated with better LVEF, lower left atrium volume, end-systolic volume of the left ventricle and lower NT-proBNP levels. 43% of patients experienced the CO during a median follow-up of 40 months. Increased levels of DHEA-S were associated with a lower risk of developing the CO (HR 0.43; 95%CI 0.21-0.86). Finally, adding DHEA-S to the multivariate model did not improve the prediction of the CO, but substituting NT-proBNP in the model with DHEA-S showed similar performance.. In patients with CCM, higher DHEA-S levels were associated with lower mortality, heart transplantation, and LVAD implantation. Further larger studies are required to confirm our results and assess causality.

Topics: Biomarkers; Cardiomyopathies; Chagas Cardiomyopathy; Chagas Disease; Dehydroepiandrosterone; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Stroke Volume

Topics: Biomarkers; Chagas Cardiomyopathy; Echocardiography; Humans; Natriuretic Peptide, Brain; Prognosis; Ventricular Dysfunction, Left

Chronic Chagas cardiomyopathy (CCM) is characterized by a unique type of cardiac involvement. Few studies have characterized echocardiographic (Echo) transitions from the indeterminate Chagas disease (ChD) form to CCM. The objective of this study was to identify the best cutoffs in multiple Echo parameters, speckle tracking, and N-terminal pro B-type natriuretic peptide (NT-proBNP) to distinguish patients without CCM (stage A) vs patients with myocardial involvement (stages B, C, or D).. Cross-sectional study conducted in 273 consecutive patients with different CCM stages. Echo parameters, NT-proBNP, and other clinical variables were measured. Logistic regression models (dichotomized in stage A versus B, C, and D) adjusted for age, sex, body mass index, and NT-proBNP were performed.. Left ventricular global longitudinal strain (LV-GLS), mitral flow E velocity, LV mass index, and NT-proBNP identified early changes that differentiated stages A vs B, C, and D. The LV-GLS with a cutoff -20.5% showed the highest performance (AUC 92.99%; accuracy 84.56% and negative predictive value (NPV) 88.82%), which improved when it was additionally adjusted by NT-proBNP with a cutoff -20.0% (AUC 94.30%; accuracy 88.42% and NPV 93.55%).. Our findings suggest that Echo parameters and NT-proBNP may be used as diagnostic variables in detecting the onset of myocardial alterations in patients with the indeterminate stage of ChD. LV-GLS was the more accurate measurement regarding stage A differentiation from the stages B, C, and D. Prospective longitudinal studies are needed to validate these findings.

Topics: Biomarkers; Chagas Cardiomyopathy; Cross-Sectional Studies; Echocardiography; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ventricular Dysfunction, Left

Background Risk stratification of Chagas disease patients in the limited-resource setting would be helpful in crafting management strategies. We developed a score to predict 2-year mortality in patients with Chagas cardiomyopathy from remote endemic areas. Methods and Results This study enrolled 1551 patients with Chagas cardiomyopathy from Minas Gerais State, Brazil, from the SaMi-Trop cohort (The São Paulo-Minas Gerais Tropical Medicine Research Center). Clinical evaluation, ECG, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were performed. A Cox proportional hazards model was used to develop a prediction model based on the key predictors. The end point was all-cause mortality. The patients were classified into 3 risk categories at baseline (low, <2%; intermediate, ≥2% to 10%; high, ≥10%). External validation was performed by applying the score to an independent population with Chagas disease. After 2 years of follow-up, 110 patients died, with an overall mortality rate of 3.505 deaths per 100 person-years. Based on the nomogram, the independent predictors of mortality were assigned points: age (10 points per decade), New York Heart Association functional class higher than I (15 points), heart rate ≥80 beats/min (20 points), QRS duration ≥150 ms (15 points), and abnormal NT-proBNP adjusted by age (55 points). The observed mortality rates in the low-, intermediate-, and high-risk groups were 0%, 3.6%, and 32.7%, respectively, in the derivation cohort and 3.2%, 8.7%, and 19.1%, respectively, in the validation cohort. The discrimination of the score was good in the development cohort (C statistic: 0.82), and validation cohort (C statistic: 0.71). Conclusions In a large population of patients with Chagas cardiomyopathy, a combination of risk factors accurately predicted early mortality. This helpful simple score could be used in remote areas with limited technological resources.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Brazil; Chagas Cardiomyopathy; Clinical Decision-Making; Decision Support Techniques; Electrocardiography; Endemic Diseases; Female; Health Status; Health Status Indicators; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Reproducibility of Results; Risk Assessment; Risk Factors; Young Adult

Up 30 to 40% of Chagas patients exhibit cardiomyopathy with different degrees of cardiac involvement. Biomarkers may help in differentiation of the severity of Chagas cardiomyopathy (CCM). This study sought to examine the diagnostic value of a panel of biomarkers to distinguish the severity of (CCM).. 100 patients with CCM were included in this cross-sectional study. Based on electrocardiogram and echocardiogram, CCM patients were classified in three stages according to disease's severity. Levels of high-sensitivity cardiac troponin T (Hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), soluble ST2 (sST2) and cystatin-c (Cys-c) were measured. Logistic regression models were used to assess the association between levels of natural log-transformed values of biomarkers and stages C/D versus B. We also calculated the area under curve (AUC) for each of the models.. In models adjusted for age, sex, body mass index, kidney function and medication use, increased levels of NT-proBNP (per 1 unit natural log-transformed values, odds ratio (OR)=5.55; 95CI%:1.65-18.72) and Hs-cTnT (per 1 unit natural log-transformed values, OR=7.11; 95CI%:1.41-35.90) showed significant association with the severity of CCM per 1 unit increase of biomarkers. The accuracy of NT-proBNP and Hs-cTnT for diagnosis of the severity of CCM was high: AUC of 0.968 and 0.956 respectively. No significant difference was found in the AUC between NT-proBNP and Hs-cTnT. No association was found between Gal-3, NGAL, sST2 and Cys-C and severity of CCM.. NT-proBNP and Hs-cTnT have both same diagnostic value in distinguishing severity of CCM.

Topics: Adult; Age Factors; Aged; Area Under Curve; Biomarkers; Chagas Cardiomyopathy; Cross-Sectional Studies; Cystatin C; Disease Progression; Electrocardiography; Female; Galectin 3; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Prognosis; Risk Assessment; ROC Curve; Severity of Illness Index; Sex Factors; Survival Rate; Troponin T

Topics: Adolescent; Adult; Biomarkers; Chagas Cardiomyopathy; Female; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Spain; Young Adult

We have established a prospective cohort of 1959 patients with chronic Chagas cardiomyopathy to evaluate if a clinical prediction rule based on ECG, brain natriuretic peptide (BNP) levels, and other biomarkers can be useful in clinical practice. This paper outlines the study and baseline characteristics of the participants.. The study is being conducted in 21 municipalities of the northern part of Minas Gerais State in Brazil, and includes a follow-up of 2 years. The baseline evaluation included collection of sociodemographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas disease, functional class, quality of life, blood sample collection, and ECG. Patients were mostly female, aged 50-74 years, with low family income and educational level, with known Chagas disease for >10 years; 46% presented with functional class >II. Previous use of benznidazole was reported by 25.2% and permanent use of pacemaker by 6.2%. Almost half of the patients presented with high blood cholesterol and hypertension, and one-third of them had diabetes mellitus. N-terminal of the prohormone BNP (NT-ProBNP) level was >300 pg/mL in 30% of the sample.. Clinical and laboratory markers predictive of severe and progressive Chagas disease were identified as high NT-ProBNP levels, as well as symptoms of advanced heart failure. These results confirm the important residual morbidity of Chagas disease in the remote areas, thus supporting political decisions that should prioritise in addition to epidemiological surveillance the medical treatment of chronic Chagas cardiomyopathy in the coming years. The São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) represents a major challenge for focused research in neglected diseases, with knowledge that can be applied in primary healthcare.. We will continue following this patients' cohort to provide relevant information about the development and progression of Chagas disease in remotes areas, with social and economic inequalities.. NCT02646943; Pre-results.

Topics: Aged; Biomarkers; Brazil; Chagas Cardiomyopathy; Chronic Disease; Disease Progression; Female; Follow-Up Studies; Heart Failure; Humans; Immunosuppressive Agents; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Nitroimidazoles; Peptide Fragments; Population Surveillance; Predictive Value of Tests; Prognosis; Prospective Studies; Quality of Life; Socioeconomic Factors

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.. This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) who 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 patients (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.. 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 the most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Donors; Case-Control Studies; Chagas Cardiomyopathy; Chemokines; Child; Child, Preschool; Cross-Sectional Studies; Cytokines; Female; Humans; Infant; Infant, Newborn; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Plasminogen Activator Inhibitor 1; Retrospective Studies; Trypanosoma cruzi; Young Adult

Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival.. This study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital.. The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, electrocardiogram findings, medications, and serum cardiac biomarker levels (B-type natriuretic peptide [BNP], N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatine kinase-myocardial band [CK-MB], troponin I, matrix metalloproteinase [MMP]-2, MMP-9, tissue inhibitor of metalloproteinases [TIMP] 1 and 2, transforming growth factor [TGF] beta 1 and 2) were ascertained. Echocardiograms were performed on those with cardiac symptoms or electrocardiogram abnormalities at baseline. Participants were contacted approximately 1 year after initial evaluation; deaths were reported by family members. Receiver-operating characteristic curves (ROC) were used to optimize cutoff values for each marker. For markers with area under the curve (AUC) >0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality.. The median follow-up time was 14.1 months (interquartile range 12.5, 16.7). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy at baseline, 20 (40%) had died. Higher baseline levels of BNP (HR: 3.1, 95% CI: 1.2 to 8.4), NT-proBNP (HR: 4.4, 95% CI: 1.8 to 11.0), CK-MB (HR: 3.3, 95% CI: 1.3 to 8.0), and MMP-2 (HR: 4.2, 95% CI: 1.5 to 11.8) were significantly associated with subsequent mortality.. Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NT-proBNP, CK-MB, and MMP-2 have added predictive value for mortality, even in the presence of decreased ejection fraction and other clinical signs of congestive heart failure.

Topics: Adult; Aged; Biomarkers; Body Mass Index; Bolivia; Chagas Cardiomyopathy; Cohort Studies; Creatine Kinase, MB Form; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Prognosis; Proportional Hazards Models; Protective Factors; Severity of Illness Index; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Transforming Growth Factor beta1; Transforming Growth Factor beta2; Troponin I

Trypanosoma cruzi (Tc), the etiological agent of Chagas disease, triggers multiple responses in the myocardium, a central organ of infection and pathology in the host. Parasite-driven induction of diverse regulators of cardiovascular function, including the vasoconstrictor endothelin-1 (ET-1), the inducible form of nitric oxide synthase (iNOS) and the B-type natriuretic peptide (BNP), has been linked to the development of severe chagasic cardiomyopathy. Our current goal was to analyze the participation of the zinc finger transcription factor GATA4, critically implicated in pathological cardiac hypertrophic response, in the generation of key mediators involved in the pathogenesis of Tc-elicited heart dysfunction. In this study, we found that the combined effects of Tc and ET-1 on atrial myocytes promoted the protein expression, phosphorylation and DNA-binding activity of GATA4, leading to augmented protein levels of iNOS and increased nitric oxide release. Moreover, Tc- and ET-1-co-activation of cardiomyocytes resulted in enhanced GATA4-dependent secretion of BNP. Accordingly, mice with chronic chagasic cardiomyopathy showed increased expression of GATA4, iNOS and BNP at inflammatory lesions in cardiac muscle. Our findings support a role for the GATA4 signaling pathway in the myocardial production of pathogenic mediators associated with Chagas heart disease, and may help define novel therapeutic targets.

Topics: Animals; Cells, Cultured; Chagas Cardiomyopathy; Disease Models, Animal; Endothelin-1; GATA4 Transcription Factor; Mice, Inbred BALB C; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase Type II; Signal Transduction; Trypanosoma cruzi

Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc-) individuals.. Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc- groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed.. Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities.. BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.

Topics: Adult; Aged; Biomarkers; Bolivia; Cardiomyopathies; Chagas Cardiomyopathy; Electrocardiography; Female; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

Heart failure (HF) is a condition with poor outcome, especially in advanced cases. Determination of B-type natriuretic peptide (BNP) levels is useful in the diagnosis of cardiac decompensation and has also been proving useful in the prognostic evaluation.. To verify whether BNP levels are able to identify patients with a poorer outcome and whether it is an independent prognostic factor considering age, gender, cardiac and renal functions, as well as the cause of heart disease.. 189 patients in functional class III/IV advanced HF were studied. All had systolic dysfunction and had their BNP levels determined during hospitalization. Variables related to mortality were studied using univariate and multivariate analyses.. BNP levels were higher in patients who died in the first year of follow-up (1,861.9 versus 1,408.1 pg/dL; p = 0.044) and in chagasic patients (1,985 versus 1,452 pg/mL; p = 0.001); the latter had a higher mortality rate in the first year of follow-up (56% versus 35%; p = 0.010). The ROC curve analysis showed that the BNP level of 1,400 pg/mL was the best predictor of events; high levels were associated with lower LVEF (0.23 versus 0.28; p = 0.002) and more severe degree of renal dysfunction (mean urea 92 versus 74.5 mg/dL; p = 0.002).. In advanced HF, high BNP levels identified patients at higher risk of a poorer outcome. Chagasic patients showed higher BNP levels than those with heart diseases of other causes, and have poorer prognosis.

Topics: Biomarkers; Chagas Cardiomyopathy; Epidemiologic Methods; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Urea

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).. 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).. 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.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Chagas Cardiomyopathy; Chronic Disease; Disease Progression; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Severity of Illness Index; Troponin T

B-type natriuretic peptide (BNP) is a diagnostic and prognostic tool in heart failure and also in Chagas disease, which is caused by the protozoan Trypanosoma cruzi and has cardiomyopathy as a main feature. BNP lipolytic actions and T. cruzi infection in the adipose tissue have been recently described. We aim to investigate the relationship between BNP and anthropometric measures and whether it is influenced by T. cruzi infection. We measured BNP, body mass index (BMI), waist circumference (WC), triceps skin-fold thickness (TSF) and performed serological, biochemical and electrocardiographic exams in 1398 subjects (37.5% infected with T. cruzi) in a community-dwelling elderly population in Bambui city, Brazil. Linear multivariate regression analysis was performed to investigate determinants of BNP levels. BNP levels were significantly (p<0.05) higher in T. cruzi-infected subjects than in the non-infected group (median=121 and 64pg/mL, respectively). BMI, WC and TSF in infected subjects were significantly lower than those in non-infected subjects (24.3 vs. 25.5kg/m2; 89.2 vs. 92.4cm; and 14.5 vs. 16.0mm, respectively). There was an inverse relationship between BNP levels and BMI (b=-0.018), WC (b=-0.005) and TSF (b=-0.193) levels. Infected and non-infected groups showed similar inverse relationships between BNP and BMI (b=-0.021 and b=-0.015, respectively). In conclusion, there was an inverse relationship between BNP levels and the anthropometric measures. Despite the actions in the adipose tissue, T. cruzi infection did not modify the associations between BNP and BMI, suggesting that body mass does not modify the accuracy of BNP in Chagas disease.

Topics: Aged; Biomarkers; Blood Pressure; Body Mass Index; Brazil; Chagas Cardiomyopathy; Chagas Disease; Cohort Studies; Creatine; Cross-Sectional Studies; Female; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Skinfold Thickness; Trypanosoma cruzi; Waist Circumference

Parameters of diastolic function have been shown to correlate with exercise capacity (EC) in individuals with impaired left ventricular (LV) systolic function. However, the role of LV diastolic function in predicting EC in Chagas cardiomyopathy has not been reported.. This study aimed to determine the relationship between LV diastolic parameters assessed by echocardiography and EC in patients with Chagas cardiomyopathy.. We studied 40 patients (23 men; 49 + or - 8 years), with diagnosis of Chagas disease and dilated cardiomyopathy. Medical therapy was individually adjusted according to standardized guidelines. Methods of acquiring two-dimensional Doppler, tissue Doppler imaging (TDI), and their measurements were described. Exercise testing was performed by a Bruce protocol. Brain natriuretic peptide (BNP) levels were also determined.. Most patients (63%) were in NYHA functional class I. Mean peak oxygen consumption estimated (peakVO(2)) was 31.7 + or - 10.2 mL/kg per minute, and mean left ventricular ejection fraction (LVEF) was 36.3 + or - 7.8%. Univariate analysis showed that various echocardiographic parameters of diastolic function were correlated with peakVO(2). There was no correlation between BNP levels or LVEF and EC. Multivariate analysis, after adjustment for age and gender, revealed that E/E' ratio and left atrial volume (LAV), emerged as independent predictors of EC, as demonstrated in the model: peakVO(2)= 60.825 + (0.439 x LAV) - (1.620 x E/E' ratio) - (0.483 x age) - (4.821 x female gender). The R(2) of this model was 0.52.. Functional capacity assessed by peakVO(2) was related to increase LV filling pressures, independently on systolic function in patients with Chagas cardiomyopathy. (Echocardiography 2010;27:519-524).

Topics: Chagas Cardiomyopathy; Diastole; Echocardiography; Enzyme-Linked Immunosorbent Assay; Exercise Test; Female; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Statistics, Nonparametric; Systole; Ventricular Dysfunction, Left

Topics: Atrial Fibrillation; Biomedical Research; Chagas Cardiomyopathy; Chagas Disease; Humans; Incidence; Latin America; Natriuretic Peptide, Brain; Stroke; Survival Rate; Trypanosoma cruzi

Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP) in the early identification of cardiac involvement in Chagas disease.. Fifty-four patients divided into 3 groups--group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32), group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14), and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction <50% on echocardiography; N = 8)--and 44 control subjects were studied. Patients with significant non-cardiac diseases, other heart diseases and previous treatment with benznidazol were excluded. The median age was 37 (20-58) years; 40% were men. BNP levels, longitudinal and radial myocardial strain and LV diastolic dysfunction increased progressively from group 1 to 3 (p for trend <0.01). Abnormal BNP levels (>37 pg/ml) were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27 ± 26 vs. 11 ± 8 pg/ml, p = 0.03).. In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

Topics: Adult; Biomarkers; Chagas Cardiomyopathy; Diastole; Early Diagnosis; Echocardiography; Female; Humans; Latin America; Male; Middle Aged; Natriuretic Peptide, Brain; Sensitivity and Specificity

Cardiomyopathy is the most important manifestation of Chagas' disease. Brain natriuretic peptide (BNP) level and Doppler echocardiographic parameters for diastolic dysfunction have shown correlation with left ventricle (LV) filling pressures.. The purpose of this study is to compare BNP levels with Doppler echocardiographic parameters in patients with chagasic cardiomyopathy.. Forty-three patients (69.8% men; mean age 41.0 +/- 10.4 years) were submitted to an echocardiographic study and 39 had their BNP levels measured.. BNP levels increased with the deterioration of the diastolic function (P=0.025). Pulmonary venous flow parameters were correlated with BNP levels, but E/E'ratio (E'measured at the inferior mitral annulus) was the only diastolic parameter that remained an independent predictor of elevated BNP levels in the multivariate analysis. The area under the receiver-operating curve for BNP to detect E/E' >15 was 0.875. A BNP value of 280.4 pg/ml had a sensitivity of 96% and a specificity of 75% for predicting E/E' >15.. In a group of patients with chagasic cardiomyopathy, BNP levels correlated with diastolic function patterns regardless of systolic function. The E/E'ratio (inferior wall) was the only isolated parameter of diastolic function that was independently associated with BNP levels.

Topics: Adult; Chagas Cardiomyopathy; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left; Ventricular Pressure

NT pro-BNP is a marker of systolic and diastolic dysfunction.. To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction.. A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD)--14 patients; 2) hypertrophic cardiomyopathy (HCM)--71 patients; 3) endomyocardial fibrosis (EMF)--26 patients; 4) pericardial effusion (PE)--18 patients; and 5) constrictive pericarditis (CP)--16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay.. NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06).. NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction.

Topics: Adult; Biomarkers; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; Case-Control Studies; Chagas Cardiomyopathy; Diastole; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pericardial Effusion; Pericarditis, Constrictive; Pericardium; Prospective Studies; Systole; Ultrasonography; Ventricular Dysfunction

We studied systematically, for the first time, the utility of the six-minute walk test (6MWT) in Chagas disease. The walked distance at 6MWT correlated negatively with the increased circulating levels of monocyte chemoattractant protein (MCP-1, r=-0.358, p=0.04) and natriuretic peptide type B (BNP, r=-0.349, p=0.04), as well as positively with ejection fraction deterioration (r=0.451, p=0.004), indicating that submaximal functional capacity of chagasic patients is related to the severity of the cardiopathy. 6MWT may constitute an auxiliary tool in the evaluation of the clinical status of Chagas disease patients.

Topics: Chagas Cardiomyopathy; Chemokine CCL2; Exercise Test; Exercise Tolerance; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Stroke Volume; Time Factors

Leptin is produced primarily by adipocytes. Although originally associated with the central regulation of satiety and energy metabolism, increasing evidence indicates that leptin may be an important mediator in cardiovascular pathophysiology. The aim of the present study was to investigate plasma leptin levels in patient with Chagas' heart disease and their relation to different forms of the disease. We studied 52 chagasic patients and 30 controls matched for age and body mass index. All subjects underwent anthropometric, leptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements and were evaluated by echocardiography, 12-lead electrocardiogram (ECG), and chest X-ray. All patients had fasting blood samples taken between 8:00 and 9:00 am. Chagasic patients were divided into 3 groups: group I (indeterminate form, IF group) consisted of 24 subjects with 2 positive serologic reactions for Chagas' disease and no cardiac involvement as evaluated by chest X-rays, ECG and two-dimensional echocardiography; group II (showing ECG abnormalities and normal left ventricular systolic function, ECG group) consisted of 14 patients; group III consisted of 14 patients with congestive heart failure (CHF group) and left ventricular dysfunction. Serum leptin levels were significantly lower (P < 0.001) in the CHF group (1.4 +/- 0.8 ng/mL) when compared to the IF group (5.3 +/- 5.3 ng/mL), ECG group (9.7 +/- 10.7 ng/mL), and control group (8.1 +/- 7.8 ng/mL). NT-proBNP levels were significantly higher (P < 0.001) in the CHF group (831.8 +/- 800.1 pg/mL) when compared to the IF group (53.2 +/- 33.3 pg/mL), ECG group (83.3 +/- 57.4 pg/mL), and control group (32 +/- 22.7 pg/mL). Patients with Chagas' disease and an advanced stage of CHF have high levels of NT-ProBNP andlow plasma levels of leptin. One or more leptin-suppressing mechanisms may operate in chagasic patients.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Chagas Cardiomyopathy; Chagas Disease; Echocardiography; Electrocardiography; Female; Fluoroimmunoassay; Heart Failure; Humans; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

To evaluate asymptomatic patients with chronic Chagas disease to determine prevalence of ventricular arrhythmias, left ventricular dysfunction, and B-type natriuretic peptide (BNP) plasma levels.. One hundred and six patients from the Chagas disease outpatient clinic underwent clinical evaluation, electrocardiogram (ECG), cardiothoracic index (CTI), ambulatory electrocardiogram (Holter monitoring), echocardiogram, and BNP measurement and then were distributed into three groups: GI, with normal ECG (n = 50); GIIA, with ECG changes characteristic of Chagas disease (n = 31); and GIIB, with other ECG changes (n = 25).. The most common electrocardiographic changes were the following. GIIA: complete right bundle branch block (35%), left anterior hemiblock (35%), and electrically inactive areas (32%); GIIB: inferolateral repolarization change (28%), and left ventricular overload (24%). Mean CTI index values were similar (p = 0.383). Ventricular arrhythmia prevalence was higher in the GIIA (77%) and GIIB (75%) groups than in the GI group (46%) (p = 0.002). Ventricular dysfunction was more prevalent in the GIIA (52%) and GIIB (32%) groups than in the GI group (14%) (p = 0.001). Systolic dysfunction was more prevalent in the GIIA group (29%) than in the GIIB (20%) and GI groups (2%) (p < 0.001). Diastolic dysfunction was more prevalent in the GIIA (42%) and GIIB (28%) groups than in the GI group (12%) (p = 0.005). Mean B-type natriuretic peptide levels were 30 +/- 88 pg/mL in the GI group, 66 +/- 194 in the GIIA group and 24 +/- 82 for the GIIB group (p = 0.121), respectively.. Arrhythmias and left ventricular dysfunction are more prevalent in asymptomatic patients with chronic Chagas disease and abnormal ECG than in patients with normal ECG. Plasma BNP levels were similar among the groups.

Topics: Adult; Arrhythmias, Cardiac; Biomarkers; Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Cross-Sectional Studies; Echocardiography; Electrocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Prevalence; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Chagas Cardiomyopathy; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

To measure the serum levels of brain natriuretic peptide (BNP) in patients with chronic chagasic heart disease and in individuals with positive serology for Chagas' disease and no heart impairment, and to correlate the serum BNP levels with the degree of cardiac impairment, cardiac dimensions, presence of a pacemaker, and ejection fraction.. Serum BNP concentrations were determined by use of the Triage-BNP Test produced by BIOSITE. Serum BNP was assessed in 25 patients from the Chagas' disease outpatient clinic of the Hospital Universitario Oswaldo Cruz, who were divided into 2 groups as follows: 1) G1--comprising 13 asymptomatic patients with positive serology for Chagas' disease and no heart disease detectable on electrocardiography, chest X-ray, and echocardiography; and 2) G2--comprising 12 patients with Chagas' disease and heart impairment.. Significantly more elevated BNP levels were detected in the chagasic patients with cardiac impairment: (G1=4.4 +/-4.4 pg/ml, G2=293.0+/-460.2 pg/ml); (P<0.01). In the 2 groups, the serum levels of BNP correlated neither with age nor with sex. The levels were directly proportional to functional class and cardiac area on chest X-ray. Although a trend towards an increment in systolic function impairment was observed, no linear correlation with the ejection fraction on echocardiography occurred. The presence of definitive pacemaker and electrocardiographic alterations did not change the serum BNP levels.. Asymptomatic individuals with a positive serology for Chagas' disease and no evidence of ventricular dysfunction have serum BNP levels similar to those of the general population.

Topics: Adult; Aged; Biomarkers; Chagas Cardiomyopathy; Chagas Disease; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index

Topics: Biomarkers; Chagas Cardiomyopathy; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Patients with Chagas' cardiomyopathy have the worst prognosis when compared to other aetiologies. It has been suggested that a more intense inflammatory activation could be responsible for this excessive mortality. We studied 35 patients with idiopathic dilated cardiomyopathy (IDC group) and 28 patients with Chagas' heart disease (Chagas' group) and 12 control subjects. We compared plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptor type 1 (sTNF-R1), soluble Fas (sFas), interleukin 6 (IL-6), and brain natriuretic peptide type B (BNP) concentrations between the groups. TNF-alpha and IL-6 concentrations were higher in the IDC and Chagas groups as compared to controls (p<0.001 and p=0.001, respectively). sTNF-R1 concentration was higher in IDC after stratification for functional class (p=0.039), and there was a trend toward higher plasma TNF-alpha concentration in the Chagas' group (p=0.092). IL-6 concentration was higher in Chagas than in IDC (p=0.005). Higher IL-6 levels were associated with worse outcome (p=0.03 for Chagas; p=0.003 for IDC). sFas concentration was similar among groups. BNP concentrations were higher in IDC (350 pg/ml) and in Chagas (444.6 pg/ml) as compared to the controls (20.3 pg/ml; p<0.01). Higher BNP levels were associated with death and heart transplantation in both aetiologies. Inflammatory activation in Chagas heart disease differs from IDC and is associated with heart failure severity.

Topics: Adult; Cardiomyopathy, Dilated; Chagas Cardiomyopathy; fas Receptor; Female; Humans; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Prospective Studies; Receptors, Tumor Necrosis Factor; Survival Analysis; Tumor Necrosis Factor-alpha

Topics: Chagas Cardiomyopathy; Heart Rate; Humans; Natriuretic Peptide, Brain; Stroke Volume; Vagus Nerve; Ventricular Dysfunction, Left

Chronic myocarditis is the main pathological finding associated with Chagas disease-related morbidity. Concentrations of CCL2, CCL3, tumor necrosis factor (TNF)-alpha, and brain natriuretic peptide (BNP) were evaluated in plasma samples obtained from patients with different clinical forms of chronic chagasic cardiomyopathy. Patients with more-severe Chagas disease had elevated plasma concentrations of TNF-alpha, CCL2, and BNP, and there was a good correlation between levels of these proteins (especially TNF-alpha ) and the degree of heart dysfunction. Indeed, TNF-alpha level was an excellent predictor of heart failure. Peripheral blood mononuclear cell samples obtained from patients with mild or severe chagasic cardiomyopathy produced greater amounts of TNF-alpha and CCL2 than did those obtained from noninfected individuals. The elevation of TNF-alpha and CCL2 levels in the plasma of patients appears to be secondary to the degree of heart dysfunction, whereas spontaneous production of TNF-alpha and CCL2 by mononuclear cells is secondary not only to heart dysfunction, but also to the underlying inflammation in the heart of chagasic patients. Measurement of the TNF-alpha level could be a useful tool in the identification of patients with heart dysfunction who may benefit from further investigation and treatment.

Topics: Adult; Biomarkers; Chagas Cardiomyopathy; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Humans; Macrophage Inflammatory Proteins; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Tumor Necrosis Factor-alpha

Global left ventricular (LV) systolic dysfunction is the strongest predictor of morbidity and mortality in Chagas disease. Echocardiography is considered the gold standard for the detection of LV dysfunction, but not always available in endemic areas where chagasic cardiomyopathy is most common. Brain natriuretic peptide (BNP) is a neurohormone that has been recently described as a simple and inexpensive diagnostic and prognostic marker for patients with congestive heart failure. Chagasic patients (n = 63) and non-infected healthy individuals (n = 18) were recruited prospectively and underwent complete clinical examination, echocardiography and 24-h Holter monitoring. BNP was measured from thawed plasma samples using the Triage BNP test. We observed high levels of BNP in association with depression of LV ejection fraction, with increase of LV end-diastolic diameter and with LV premature complexes. An elevated concentration of BNP, defined as a concentration of 60 pg/ml or more, had a sensitivity of 91.7%, specificity of 82.8%, positive predictive value of 52.4%, and negative predictive value of 98% for detecting LV dysfunction (LV ejection fraction < 40%).BNP measurement using a simple, relatively inexpensive and rapid test has a promising role in identifying LV dysfunction associated with chagasic cardiomyopathy. Equally important, patients with Trypanosoma cruzi infection who have low levels of BNP level in plasma have a very low likelihood of severe cardiac involvement, and echocardiography is probably not necessary.

Topics: Adult; Biomarkers; Chagas Cardiomyopathy; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity; Severity of Illness Index; Ventricular Dysfunction, Left

Topics: Biomarkers; Chagas Cardiomyopathy; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left