Maria do Carmo Pereira Nunes

An evaluation of the cardiotoxicity of imatinib mesylate

We studied 103 consecutive patients with chronic myeloid leukaemia on treatment with imatinib (IM) and 57 patients with chronic myeloproliferative disorders not treated with IM in order to evaluate its cardiotoxicity. There was no statistical difference regarding cardiac symptoms and signs, BNP levels and echocardiographic measurements for IM and control groups, except for peripheral oedema, more frequent in the IM group. Four patients in the IM group presented a BNP level >100pg/ml, one of them with depressed LVEF. IM was not related to systematic deterioration of cardiac function, but there is still a possibility of isolated cases of cardiotoxicity.

Predictors of Mortality in Patients with Dilated Cardiomyopathy: Relevance of Chagas Disease as an Etiological Factor

INTRODUCTION AND OBJECTIVES Previous studies on the influence of Chagas disease on mortality in patients with heart failure were limited by the heterogeneity of the patient populations. Few data are available on the association between the underlying cause of dilated cardiomyopathy and long-term prognosis. The aims of this study were to identify risk factors for mortality in patients with dilated cardiomyopathy that was either secondary to Chagas disease or idiopathic and to determine the prognostic value of identifying Chagas disease as the underlying etiology of dilated cardiomyopathy. METHODS We investigated outcomes in 287 patients with heart failure secondary to dilated cardiomyopathy. Patients were divided into two groups according to the underlying etiology: Chagas cardiomyopathy (224 patients) and idiopathic dilated cardiomyopathy (63 patients). The study end-points were death and heart transplantation. RESULTS Over a median follow-up period of 39.5 months, 104 patients died and 9 underwent heart transplantation. Under multivariate Cox proportional hazards analysis, New York Heart Association functional class, left ventricular ejection fraction, right ventricular function and left atrial volume remained predictors of an adverse outcome. Chagas etiology was also independently associated with a poor prognosis (hazard ratio=2.48; 95% confidence interval, 1.28-4.78; P=.007) compared with idiopathic disease, after adjustment for other well-established predictive parameters in heart failure. CONCLUSIONS The identification of Chagas etiology in patients with dilated cardiomyopathy was of prognostic significance. Chagas cardiomyopathy was associated with poorer survival compared with idiopathic disease, irrespective of other clinical and echocardiographic parameters related to a poor prognosis in heart failure.

Prognostic Value of Signal-Averaged Electrocardiogram in Chagas Disease

Background: The value of signal‐averaged ECG (SAECG) in the risk stratification of Chagas disease (ChD), a potentially lethal illness prevalent in Latin America, remains controversial. The aim of this prospective longitudinal study was to determine the prognostic value of SAECG in ChD, using multivariate models with other established prognostic predictors, and to develop a simple prediction risk score.

Foxp3+CD25high CD4+ regulatory T cells from indeterminate patients with Chagas disease can suppress the effector cells and cytokines and reveal altered correlations with disease severity

Immunoregulatory mechanisms are important to control the intense immune activity induced in Chagas disease. We evaluated the phenotypic profile and the mechanisms by which Treg cells function in patients with the indeterminate (IND) and cardiac (CARD) clinical forms of Chagas disease. The frequency of Foxp3(+)CD25(high) CD4(+)-T cells is augmented and correlated with the maintenance of a better cardiac function in IND. Treg cells from IND present suppressive activity, although the mechanism is not IL-10 or CTLA-4 dependent and are able to produce augmented levels of IL-17, IL-10 and granzyme B being its frequency correlated with percentage of Annexin V(+) CD4(+)-cells. In contrast, CARD presents higher frequency of IL-6(+), IFN-gamma(+), TNF-alpha(+) and CTLA-4(+) Treg-cells than IND. Thus, our data suggest that Treg cells have an important role in controlling the exacerbated immune response and morbidity in Trypanosoma cruzi infection, probably modulating the cytokine environment and/or killing effector cells.

Assessing pre-clinical ventricular dysfunction in obese children and adolescents: the value of speckle tracking imaging

AIMS Obesity has become a major health problem worldwide. Cardiovascular abnormalities have been described not only in obese adults but also in obese children and adolescents. The aim of the present study was to investigate left and right, systolic and diastolic ventricular dysfunction in obese paediatric patients without comorbidities using 2D speckle tracking longitudinal strain. METHODS AND RESULTS Doppler echocardiogram was performed on 50 obese children and adolescents with body mass index (BMI) above the 95th percentile (OG) and 46 non-obese sex- and age-matched controls (CG). Systolic and diastolic functions of both ventricles were investigated through conventional Doppler echocardiography. Tissue Doppler imaging (TDI), colour Doppler myocardial imaging (CDMI), and two-dimensional (2D) speckle tracking were also used to analyse ventricular performance in both groups. Left-ventricular (LV) ejection fraction was similar between groups (68.2 ± 6.2 vs. 68.3 ± 5.3, P = 0.931). Left-ventricular diastolic parameters did not differ between groups, except for a lower mitral A wave (61.6 ± 13.0 vs. 51.9 ± 10.0 cm/s, P > 0.001) and higher E/A ratio (1.8 ± 0.5 vs. 2.1 ± 0.4, P = 0.007) in the controls. Left-ventricular global strain was lower in the OG by both methods (CDMI: 22.0 ± 2.8 vs. 24.6 ± 2.7%, P = 0.020; 2D speckle tracking: 18.4 ± 1.6 vs. 20.4 ± 1.7%, P < 0.001). In multivariate analysis, 2D longitudinal global strain correlated negatively with BMI, r = -0.433, p = 0.002. CONCLUSION Although EF was not different between the two groups, LV 2D speckle tracking longitudinal strain was lower in the obese group, even in the absence of other comorbidities, indicating that obesity effects on LV function is an early finding in obesity.

Strain imaging in morbid obesity: insights into subclinical ventricular dysfunction.

Obesity has become an important health problem throughout the world. Early detection of cardiovascular abnormalities may be useful in the future for patient management. This study aimed to identify subclinical ventricular dysfunction in obese patients.

Plasma cytokine expression is associated with cardiac morbidity in chagas disease.

The expression of immune response appears to be associated with morbidity in Chagas disease. However, the studies in this field have usually employed small samples of patients and statistical analyses that do not consider the wide dispersion of cytokine production observed in these patients. The aim of this study was to evaluate the plasma cytokine levels in well-defined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity. Patients infected with Trypanosoma cruzi (T. cruzi) were grouped as indeterminate (IND) and cardiac (CARD) forms ranging from 23 to 69 years of age (mean of 45.6±11.25). The IND group included 82 individuals, ranging from 24 to 66 years of age (mean of 39.6±10.3). The CARD group included 94 patients ranging from 23 to 69 years of age (mean of 48±12.52) presenting dilated cardiomyopathy. None of the patients have undergone chemotherapeutic treatment, nor had been previously treated for T. cruzi infection. Healthy non-chagasic individuals, ranging from 29 to 55 years of age (mean of 42.6±8.8) were included as a control group (NI). IND patients have a higher intensity of interleukin 10 (IL-10) expression when compared with individuals in the other groups. By contrast, inflammatory cytokine expression, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1β), proved to be the highest in the CARD group. Correlation analysis showed that higher IL-10 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Altogether, these findings reinforce the concept that a fine balance between regulatory and inflammatory cytokines represents a key element in the establishment of distinct forms of chronic Chagas disease.

Profile of infective endocarditis at a tertiary care center in Brazil during a seven-year period: prognostic factors and in-hospital outcome.

OBJECTIVES To describe the epidemiological, clinical, and laboratory profile of infective endocarditis (IE) at a Brazilian tertiary care center, and to identify the predictors of in-hospital mortality. METHODS Data from 62 patients who fulfilled the modified Dukes criteria for IE during a seven-year period were gathered prospectively. The Cox proportional hazards model was used to identify predictive factors for death. RESULTS The mean age of patients was 45 years, and 39 patients (63%) were male. The median time from admission to diagnosis was 15 days. Rheumatic heart disease was the predominant underlying heart condition (39%), followed by valvular prosthesis (31%). Neurological complications were observed in 12 patients (19%). Echocardiography demonstrated one or more vegetations in 84% of cases. The infective agent was identified in 65% of cases, and the most frequent causative agents were staphylococci (48%), followed by streptococci (20%). The median duration of hospitalization was 39 days. Surgery was performed during the acute phase of the IE in 53% of cases. The overall in-hospital mortality was 31%. On multivariate analysis, vegetation length >13mm remained the only independent predictor of in-hospital mortality (hazard ratio 1.05 per millimeter, 95% confidence interval 1.003-1.110, p=0.038). CONCLUSIONS IE remains a severe disease affecting the young population in Brazil, and rheumatic heart disease continues to be the most common underlying heart condition. Large vegetation size, assessed early in the course of IE by transesophageal echocardiography, along with the clinical and microbiological features, may predict in-hospital death.

Ischemic cerebrovascular events in patients with Chagas cardiomyopathy: A prospective follow-up study

BACKGROUND Chagas disease cardiomyopathy is a common form of dilated cardiomyopathy worldwide, and an important cause of stroke in Latin America. The long-term cumulative risk of ischemic cerebrovascular event (ICE) and its relation to left ventricular (LV) dysfunction have not been determined. The aims of this study were to describe the incidence and to evaluate the effect of LV ejection fraction on the risk for ICE in patients with Chagas cardiomyopathy. METHODS A total of 213 consecutive patients with Chagas disease and LV systolic dysfunction, 131 males, mean age 48+/-12 years, were prospectively enrolled. The use of anticoagulation was based on clinical indications. The end point was ICE, which included fatal or nonfatal stroke and transient ischemic attack. Risk factors for events were assessed by Cox proportional-hazards analysis. RESULTS Mean follow-up was 36 months; 69 patients died and seven underwent cardiac transplantation. The overall incidence of ICE was 2.67 events per 100 patient/years. Independent risk factors for ICE included LV ejection fraction (HR 0.95, 95% CI 0.91 to 0.99, p=0.009) and left atrial volume corrected for body surface area (HR 1.04, 95% CI 1.01 to 1.07, p=0.007), which persisted after adjustment for anticoagulation use. Patients with ejection fractions<or=35% had a relative risk of events of 3.41, as compared with the other patients. The presence of apical aneurysm or thrombus, age, and history of previous stroke were not an independent long-term risk for ICE. CONCLUSIONS In patients with Chagas cardiomyopathy, the annual incidence of ICE is low. Left ventricular ejection fraction and indexed left atrial volume appear to be independently associated with these events.

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

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.