Assessment of functional performance in Chagas heart disease by Human Activity Profile questionnaire.

PURPOSE: To verify the association between Human Activity Profile and functional capacity, functional class and systolic function of the patients with Chagas heart disease (CHD). METHODS: Sixty-two patients with CHD were evaluated by echocardiography, maximal exercise testing and Human Activity Profile questionnaire. The sample was stratified, according to the values of peak oxygen uptake (low or normal), functional class (symptomatic or asymptomatic), and left ventricular ejection fraction (preserved or systolic dysfunction). Linear regression and two-group comparisons analyses were used. Receiver-operating characteristic analysis was used to determine different cutoff values of the Human Activity Profile for low peak oxygen uptake prediction. RESULTS: Peak oxygen uptake was an independent predictor of Human Activity Profile (R2-adjusted = 0.27). Patients with low peak oxygen uptake had lower scores in Human Activity Profile [difference of 6.9 (95%CI 2.5-11.4)] than those with normal peak oxygen uptake. Symptomatic patients also showed lower scores when compared to the asymptomatic [difference of 6.2 (95%CI 1.7-10.8)]. There was no difference between left ventricular ejection fraction classes. The Human Activity Profile score of 76.5 was the optimal cut point value in predicting low peak oxygen uptake (sensitivity = 66.0% and specificity = 71.8%). CONCLUSION: The Human Activity Profile questionnaire is associated with functional capacity of patients with CHD and is able to identify individuals with low peak oxygen uptake.Implications for rehabilitationFunctional impairment is one of the most common clinical findings in all stages and is an important predictor of poor prognosis of the Chagas heart disease;A patient-derived measure of functional capacity is potentially useful in the setting of the Chagas heart disease;The Human Activity Profile questionnaire is effective in the identification of patients with Chagas heart disease with functional impairment and may be a valid method for functional evaluation.

Non-genetic factors and polymorphisms in genes CYP2C9 and VKORC1: predictive algorithms for TTR in Brazilian patients on warfarin.

PURPOSE: This study was designed to evaluate the association of non-genetic factors and polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) with time in therapeutic range (TTR), and to build a regression model to predict the quality of oral anticoagulation control in a sample of Brazilian patients. METHODS: This is a retrospective cohort study developed at an anticoagulation clinic of a university hospital. Overall, 312 patients were included. The quality of oral anticoagulation control was evaluated by TTR. TTR was dichotomized for analysis, using two cutoff points for classification as inadequate (TTR ≤ 60.0%) and optimal (TTR ≥ 75.0%) control. RESULTS: The average age was 60.4 ± 13.5 years, with a predominance of women (187; 59.9%). The -G1639A polymorphism of the VKORC1 gene, when evaluated, based on the recessive inheritance pattern [AA × (GA + GG)], patients with AA genotype exhibited a higher TTR (68.2% versus 62.8%, p = 0.017). TTR ≤ 60.0% was associated with number of drugs in chronic use, assistance for warfarin administration, reports of not taking warfarin, absenteeism, sex (female), and target INR (International Normalized Ratio; 2.00-3.00). TTR ≥ 75.0% was associated with sex (male), target INR (2.00-3.00), assistance for warfarin administration, reports of not taking warfarin, and absenteeism. The two algorithms proposed showed adequate ability to predict TTR presenting good sensitivity and specificity. CONCLUSIONS: Our findings provided useful information for risk stratification depending on TTR level and for future investigations on the quality of oral anticoagulation control in Brazilian anticoagulation clinics.

Prognostic value of serum brain-derived neurotrophic factor levels in patients with Chagas cardiomyopathy.

BACKGROUND: Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC. METHODS: Forty-nine patients with ChC (50 ± 7 years, New York Heart Association "NYHA" I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression. RESULTS: After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval (CI) 1.1-1.4; p = 0.001), peak oxygen uptake (HR 1.2, 95% CI 1.0-1.3; p = 0.009), and left ventricular ejection fraction (HR 0.8, 95% CI 0.7-0.9; p = 0.001) were the independent predictors of survival. The combination of low serum BDNF levels and reduced left ventricular ejection fraction were highly predictive of death (HR 5.6, 95% CI: 1.2-9.7; p = 0.026). CONCLUSION: In patients with ChC, reduced serum BDNF levels, especially if associated with systolic function, may provide useful prognostic information.

Prognostic value of serum brain-derived neurotrophic factor levels in patients with Chagas cardiomyopathy

BACKGROUND Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC. METHODS Forty-nine patients with ChC (50 ± 7 years, New York Heart Association "NYHA" I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression. RESULTS After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval (CI) 1.1-1.4; p = 0.001), peak oxygen uptake (HR 1.2, 95% CI 1.0-1.3; p = 0.009), and left ventricular ejection fraction (HR 0.8, 95% CI 0.7-0.9; p = 0.001) were the independent predictors of survival. The combination of low serum BDNF levels and reduced left ventricular ejection fraction were highly predictive of death (HR 5.6, 95% CI: 1.2-9.7; p = 0.026). CONCLUSION In patients with ChC, reduced serum BDNF levels, especially if associated with systolic function, may provide useful prognostic information.

Annexin A1 Is Involved in the Resolution of Inflammatory Responses during Leishmania braziliensis Infection.

Leishmaniases are diseases caused by several Leishmania species. Leishmania (Viannia) braziliensis can cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated in L. braziliensis-infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also after L. braziliensis infection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1-/- mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1-/- mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-γ, IL-4, and IL-10. AnxA1-/- mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-κB) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed during L. braziliensis infection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size.

The role of interleukin 17-mediated immune response in Chagas disease: High level is correlated with better left ventricular function.

Interleukin 17A (IL-17A) has been associated with protective rather than pathogenic response in Chagas disease (ChD). However, it is not established whether or not IL-17A-mediated immune response is correlated with patient's left ventricular (LV) function in ChD. To address this question we have gathered cardiac functional parameters from ChD patients and analysed the possible relationship between their plasma IL-17A levels and LV function. Plasma IL-17A levels were measured by BD Cytometric Bead Array (CBA) in 240 patients with positive specific serology for Trypanosoma cruzi (T. cruzi) grouped as indeterminate (IND) and Chagas cardiomyopathy (CARD) forms. The levels of IL-17A in ChD patients were compared with 32 healthy individuals, mean age of 39 years, 50% male, that were also included as a control group (non-infected [NI]). The overall mean age of ChD patients was 46 years and 52% were male. The IND group included 95 asymptomatic patients, with ages ranging from 27 to 69 years (mean of 43 years), and 42.1% of them were male. The CARD group included 145 patients, which 58.6% were male, with ages ranging from 23 to 67 years (mean of 49). The IND group presented substantially higher levels of IL-17A, median of 26.16 (3.66-48.33) as compared to both the CARD group, median of 13.89 (3.87-34.54) (P <0.0001), and the NI group, median of 10.78 (6.23-22.26) (P <0.0001). The data analysis demonstrated that the IND group comprises a significantly greater proportion (P <0.001) of high IL-17A producers (52.6%, 50 of 95 subjects) than do the other groups. A significant direct correlation was verified between IL-17A levels and cardiac function expressed by LV ejection fraction (LVEF), LV diastolic diameter (LVDd), and body surface area (BSA)-indexed LVDd as well as ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') in both groups. We demonstrated that plasma IL-17A levels has an accurate sensitivity and specificity to predict heart failure in serology-positive patients and might be a useful parameter to distinguish patients with or without cardiac impairment. This study indicates a consistent relationship between high expression of IL-17A and better LV in human chronic ChD. Our data raise the possibility that IL-17A plays an important immunomodulatory role in the chronic phase of ChD and might be involved in protection against myocardial damage.

Is atrial function in Chagas dilated cardiomyopathy more impaired than in idiopathic dilated cardiomyopathy?

AIMS: Atrial function is an important component in overall cardiovascular performance. However, information on atrial function in dilated cardiomyopathy is limited. This study aimed to assess atrial function in dilated cardiomyopathy and to investigate if parameters of atrial function are more impaired in Chagas dilated cardiomyopathy (CDC) than in idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Seventy-two patients with dilated cardiomyopathy (36 with CDC and 36 with IDC) and 32 healthy controls were evaluated by tissue Doppler, Doppler-based strain and strain rate (SR) imaging of the left atrium (LA) and right atrium (RA). Peak atrial strain during systole and SR during systole, early and late diastolic SR, were measured at the interatrial septum, LA inferior wall and at the lateral wall of the RA. The clinical characteristics and the parameters of LV function were similar between patients with CDC and IDC. Myocardial deformation indices during the reservoir phase of both RA and LA were lower in patients with dilated cardiomyopathy than in controls, suggesting atrial dysfunction in cardiomyopathies. However, LA and RA deformation parameters did not differ between CDC and IDC patients (interatrial septal strain during the reservoir phase: -25.2 ± 14.8 vs. -24.9 ± 16.0%, P = NS; strain rate during the reservoir phase: -1.3 ± 0.7 vs. -1.5 ± 0.9/s, P = NS). CONCLUSIONS: Atrial myocardial deformation properties are abnormal in patients with dilated cardiomyopathy. CDC does not seem to have more atrial involvement than IDC.

Effect of pacing-induced ventricular dyssynchrony on right ventricular function.

BACKGROUND: Asynchronous electrical activation induced by right ventricular (RV) pacing can cause several abnormalities in left ventricular (LV) function. However, the effect of ventricular pacing on RV function has not been well established. We evaluated RV function in patients undergoing long-term RV pacing. METHODS: Eighty-five patients and 24 healthy controls were included. After pacemaker implantation, conventional echocardiography and strain imaging were used to analyze RV function. Strain imaging measurements included peak systolic strain and strain rate. LV function and ventricular dyssynchrony by tissue Doppler imaging (TDI) were assessed. Intra- and interobserver variabilities of TDI parameters were tested on 15 randomly selected cases. RESULTS: All patients were in New York Heart Association functional class I or II and percentage of ventricular pacing was 96 ± 4%. RV apical induced interventricular dyssynchrony in 49 patients (60%). LV dyssynchrony was found in 51 patients (60%), when the parameter examined was the standard deviation of the time to peak myocardial systolic velocity of all 12 segments greater than 34 ms. Likewise, septal-to-lateral delay ≥ 65 ms was found in 31 patients (36%). All echocardiographic indexes of RV function were similar between patients and controls (strain: -22.8 ± 5.8% vs -22.1 ± 5.6%, P = 0.630; strain rate: -1.47 ± 0.91 s(-1) vs -1.42 ± 0.39 s(-1) , P = 0.702). Intra- and interobserver variability for RV strain was 3.1% and 5.3%, and strain rate was 1.3% and 2.1%, respectively. CONCLUSIONS: In patients with standard pacing indications, RV apical pacing did not seem to affect RV systolic function, despite induction of electromechanical dyssynchrony.

A randomized trial of the effects of exercise training in Chagas cardiomyopathy.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: In patients with ChC, exercise training was associated with a major improvement in functional capacity and HQoL without any adverse effects.

Morbidity and prognostic factors in chronic chagasic cardiopathy.

Chagas disease is a pleomorphic clinical entity that has several unique features. The aim of this study is to summarise some of the recent contributions from our research group to knowledge of the morbidity and prognostic factors in Chagas heart disease. A retrospective study suggested that ischaemic stroke associated with left ventricular (LV) apical thrombi is the first clinical manifestation of Chagas disease observed in a large proportion of patients. LV function and left atrial volume (LAV) are independent risk factors for ischaemic cerebrovascular events during follow-up of Chagas heart disease patients. Pulmonary congestion in Chagas-related dilated cardiomyopathy is common but usually mild. Although early right ventricular (RV) involvement has been described, we have shown by Doppler echocardiography that RV dysfunction is evident almost exclusively when it is associated with left ventricle dilatation and functional impairment. In addition, RV dysfunction is a powerful predictor of survival in patients with heart failure secondary to Chagas disease. We have also demonstrated that LAV provides incremental prognostic information independent of clinical data and conventional echocardiographic parameters that predict survival.

Morbidity and prognostic factors in chronic chagasic cardiopathy

Chagas disease is a pleomorphic clinical entity that has several unique features. The aim of this study is to summarise some of the recent contributions from our research group to knowledge of the morbidity and prognostic factors in Chagas heart disease. A retrospective study suggested that ischaemic stroke associated with left ventricular (LV) apical thrombi is the first clinical manifestation of Chagas disease observed in a large proportion of patients. LV function and left atrial volume (LAV) are independent risk factors for ischaemic cerebrovascular events during follow-up of Chagas heart disease patients. Pulmonary congestion in Chagas-related dilated cardiomyopathy is common but usually mild. Although early right ventricular (RV) involvement has been described, we have shown by Doppler echocardiography that RV dysfunction is evident almost exclusively when it is associated with left ventricle dilatation and functional impairment. In addition, RV dysfunction is a powerful predictor of survival in patients with heart failure secondary to Chagas disease. We have also demonstrated that LAV provides incremental prognostic information independent of clinical data and conventional echocardiographic parameters that predict survival.

The influence of HCV coinfection on clinical, immunological and virological responses to HAART in HIV-patients.

The potential impact of the hepatitis C virus (HCV) on clinical, immunological and virological responses to initial highly active antiretroviral therapy (HAART) of patients infected with human immunodeficiency virus (HIV) is important to evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort study was conducted among 824 HIV-infected patients starting HAART at a public referral service in Belo Horizonte, Brazil, to assess the impact of HCV seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS-related death, suppression of viral load, and an increase in CD4-cell count. A total of 76 patients (9.2%) had a positive HCV test, 26 of whom (34.2%) had a history of intravenous drug use. In multivariate analysis, HCV seropositivity was associated with a smaller CD4-cell recovery (RH=0.68; 95% CI [0.49-0.92], but not with progression to a new AIDS-defining opportunistic illness or to AIDS-related death (RH=1.08; 95% CI [0.66-1.77]), nor to suppression of HIV-1 viral load (RH=0.81; 95% CI [0.56-1.17]) after starting HAART. These results indicate that although associated with a blunted CD4-cell recovery, HCV coinfection did not affect the morbidity or mortality related to AIDS or the virological response to initial HAART.

The influence of HCV coinfection on clinical, immunological and virological responses to HAART in HIV-patients

The potential impact of the hepatitis C virus (HCV) on clinical, immunological and virological responses to initial highly active antiretroviral therapy (HAART) of patients infected with human immunodeficiency virus (HIV) is important to evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort study was conducted among 824 HIV-infected patients starting HAART at a public referral service in Belo Horizonte, Brazil, to assess the impact of HCV seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS-related death, suppression of viral load, and an increase in CD4-cell count. A total of 76 patients (9.2 percent) had a positive HCV test, 26 of whom (34.2 percent) had a history of intravenous drug use. In multivariate analysis, HCV seropositivity was associated with a smaller CD4-cell recovery (RH=0.68; 95 percent CI [0.49-0.92], but not with progression to a new AIDS-defining opportunistic illness or to AIDS-related death (RH=1.08; 95 percent CI [0.66-1.77]), nor to suppression of HIV-1 viral load (RH=0.81; 95 percent CI [0.56-1.17]) after starting HAART. These results indicate that although associated with a blunted CD4-cell recovery, HCV coinfection did not affect the morbidity or mortality related to AIDS or the virological response to initial HAART.

Right ventricular dysfunction is an independent predictor of survival in patients with dilated chronic Chagas' cardiomyopathy.

BACKGROUND: Right ventricular (RV) involvement is a typical feature of Chagas' disease. In patients with congestive heart failure of other etiologies, RV dysfunction is a strong indicator of poor prognosis. However, the prognostic value of RV dysfunction in patients with Chagas' cardiomyopathy has not been reported. This study sought to investigate the prognostic value of RV dysfunction, apart from other well established risk factors, in patients with Chagas' cardiomyopathy. METHODS: The study enrolled 158 patients (99 men; mean age of 48+/-12 years) from a tertiary center for Chagas' disease. Patients were selected if found to have both the diagnosis of Chagas' disease and cardiomyopathy. All patients underwent a comprehensive Doppler echocardiogram and the global RV function was quantitatively assessed using the RV index of myocardial performance (Tei index). RESULTS: Most of the patients were in NYHA classes I and II (79%). During a mean follow up of 34+/-23 months, 44 patients (28%) died: 24 (55%) patients died of progressive heart failure and 16 (36%) of sudden death. RV Tei index emerged as an independent predictor of survival (hazard ratio 5.75, 95% confidence interval 1.69 to 19.51). Kaplan-Meier survival curves showed a higher cumulative mortality among patients in the highest quartile of RV Tei index, compared with other 3 quartiles (log-rank statistic 21.87, p<0.001). After adjustment for clinical data and LV ejection fraction, RV Tei index in the highest quartile (>0.56) remained a significant predictor of death (hazard ratio 5.29, 95% confidence interval 2.43 to 11.52). CONCLUSIONS: RV function assessed by the Tei index added significant prognostic information, incremental to the NYHA clinical classification and to the standard echocardiographic evaluation of LV systolic function. A simple measure of a Doppler index, which allows analysis of both systolic and diastolic function of the RV, appears to be a useful non-invasive tool for risk stratification in patients with dilated chronic Chagas' cardiomyopathy.

A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy.

OBJECTIVE: The objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy. BACKGROUND: Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials. METHODS: We conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points. RESULTS: Optimization of RAS inhibition was safe, hemodynamically well tolerated, and associated with improvements in Framingham score (P = .001) and quality of life as well as reductions in the cardiothoracic index (P = .002), brain natriuretic peptide level (P = .032), and RANTES (regulated on activation, normal T expressed and secreted) level (P = .001). Left ventricular ejection fraction increased by 2.3% (P = .25); in patients with an LVEF < or = 45% at baseline, it increased by 2.8% (P = .017). Treatment with carvedilol was associated with a trend toward an increase in LVEF (absolute difference between groups, 2.3%; P = .094). The addition of carvedilol was safe, hemodynamically well tolerated, and not associated with symptomatic bradycardia. CONCLUSIONS: In patients with chronic Chagas cardiomyopathy, optimization of treatment with enalapril and spironolactone and subsequent addition of carvedilol were safe and associated with benefits in cardiac function and clinical status. Larger trials are needed to show effects on mortality and/or hospitalization.

N-terminal proBNP levels in patients with Chagas disease: a marker of systolic and diastolic dysfunction of the left ventricle.

AIMS: NT-proBNP levels are known to be elevated in systolic and diastolic dysfunction. Doppler indices of diastolic dysfunction (DD) have been shown to have prognostic value in patients with Chagas' cardiomyopathy (CC). However, the additional value of NT-proBNP levels in further stratifying these patients according to DD has not been established. This study analyzed the correlation of N-terminal proBNP (NT-proBNP) levels with systolic and diastolic function in patients with CC. METHODS AND RESULTS: NT-proBNP levels were measured in 59 patients with dilated cardiomyopathy due to Chagas disease without other systemic illness that were studied by Doppler echocardiography, including left atrial volume (LAV) calculation and tissue Doppler evaluation of LV longitudinal function. Univariate analysis showed a strong correlation of NT-proBNP values with LVEF (r=-0.733, p<0.001) and a weak correlation with most Doppler echocardiographic parameters of diastolic function. On a multivariate analysis, LVEF and LAV volume emerged as correlating with elevated levels of the NT-proBNP. Patients with restrictive filling pattern (n=10), when compared to other patterns of DD, (n=49), showed a lower LVEF (25.4+/-6.4% vs. 39.8+/-9.4, p<0.001), a larger LAV (50.1+/-17.2 vs. 37.7+/-15.6 ml/m(2), p=0.004) and higher NT-proBNP levels (median+/-IQR: 3488+/-3056 vs. 492+/-700 pg/dl, p<0.001). A marked elevated concentration of NT-proBNP (> or =800 pg/ml) had a sensitivity of 90.0%, specificity of 70.5%, positive predictive value of 40.9% and negative predictive value of 96.9% for detecting a restrictive filling pattern. CONCLUSION: In patients with CC, NT-proBNP augmentation is a marker of LV dysfunction, with higher levels correlating with the more severe forms of both systolic and diastolic dysfunction.

Brain natriuretic peptide based strategy to detect left ventricular dysfunction in Chagas disease: a comparison with the conventional approach.

BACKGROUND: Left ventricular dysfunction (LVd) is the main predictor of mortality in Chagas disease (ChD). AIMS: To compare the diagnostic performance of the conventional approach (ECG and chest X-ray) in the recognition of LVd in ChD, with a new strategy, in which BNP is measured in patients with an abnormal ECG. METHODS: Consecutive ChD patients recruited at an Outpatient Reference Center in Belo Horizonte, Brazil, without other systemic diseases, in 1998-99 (sample 1, n = 165) and in 2001-02 (sample 2, n = 62) underwent ECG, chest X-ray, BNP measurement and echocardiography. RESULTS: The prevalence of LVd (ejection fraction

Type 1 chemokine receptor expression in Chagas' disease correlates with morbidity in cardiac patients.

Chemokines and chemokine receptors (CKRs) control the migration of leukocytes during the inflammatory process and are important immunological markers of type 1 (CCR5 and CXCR3) and type 2 (CCR3 and CCR4) responses. The coexpression of CKRs (CCR2, CCR3, CCR5, CXCR3, and CXCR4) and intracellular cytokines (interleukin-10 [IL-10], IL-4, tumor necrosis factor alpha [TNF-alpha], and gamma interferon [IFN-gamma]) on T CD4+ and CD8+ peripheral cells from individuals with indeterminate (IND) or cardiac (CARD) clinical forms of Chagas' disease after in vitro stimulation with Trypanosoma cruzi antigens, were evaluated in this study. The percentage of T CD4+ and CD8+ cells coexpressing CCR5 and IFN-gamma, CXCR3 and IFN-gamma, and CXCR3 and TNF-alpha were higher in CARD than in IND individuals; on the other hand, the percentage of T CD4+ or CD8+ cells coexpressing CCR3 and IL-10 or coexpressing CCR3 and IL-4 were lower in CARD individuals than in IND individuals. In addition, a significant positive correlation between the expression of CCR5 or CXCR3 and IFN-gamma was observed in CARD individuals contrasting with a significant positive correlation between the expression of CCR3 and IL-4 and of CCR3 and IL-10 in IND patients. These results reinforce the hypothesis that a T. cruzi-exacerbated specific type 1 immune response developed by CARD chagasic patients is associated with the development of heart pathology.

The clinical immunology of human Chagas disease.

Human infection with the protozoan parasite Trypanosoma cruzi leads to Chagas disease, which affects approximately 17 million people in Latin America. A significant percentage of the infected population will develop clinical symptoms or present changes in laboratory and/or image evaluation. The existence of a large spectrum of clinical manifestations--with patients ranging from asymptomatic to severe cardiac involvement--emphasizes the need to use standardized and well-defined clinical criteria among different research groups. In this article, we carry out a systematic review of the immunology in human Chagas disease, discussing recent findings in the context of a clinical perspective.