Blocking activation of CD4-CD8- T cells modulates their cytotoxic potential and decreases the expression of inflammatory and chemotactic receptors.

CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.

Predictive factors for the progression of chronic Chagas cardiomyopathy in patients without left ventricular dysfunction.

The identification of predictors for the progression of chronic Chagas cardiomyopathy (CCC) is essential to ensure adequate patient management. This study looked into a non-concurrent cohort of 165 CCC patients between 1985 and 2010 for independent predictors for CCC progression. The outcomes were worsening of the CCC scores and the onset of left ventricular dysfunction assessed by means of echo-Doppler cardiography. Patients were analyzed for social, demographic, epidemiologic, clinical and workup-related variables. A descriptive analysis was conducted, followed by survival curves based on univariate (Kaplan-Meier and Cox's univariate model) and multivariate (Cox regression model) analysis. Patients were followed from two to 20 years (mean: 8.2). Their mean age was 44.8 years (20-77). Comparing both iterations of the study, in the second there was a statistically significant increase in the PR interval and in the QRS duration, despite a reduction in heart rates (Wilcoxon < 0.01). The predictors for CCC progression in the final regression model were male gender (HR = 2.81), Holter monitoring showing pauses equal to or greater than two seconds (HR = 3.02) increased cardiothoracic ratio (HR = 7.87) and time of use of digitalis (HR = 1.41). Patients with multiple predictive factors require stricter follow-up and treatment.

Predictive factrrs for the progression of chronc chagas cardiomyopathy in patiients without left ventricular dysfunction / Preditores da evolução da cardiopatia chagásica crônica em pacientes sem disfunção ventricular esquerda

The identification of predictors for the progression of chronic Chagas cardiomyopathy (CCC) is essential to ensure adequate patient management. This study looked into a non-concurrent cohort of 165 CCC patients between 1985 and 2010 for independent predictors for CCC progression. The outcomes were worsening of the CCC scores and the onset of left ventricular dysfunction assessed by means of echo-Doppler cardiography. Patients were analyzed for social, demographic, epidemiologic, clinical and workup-related variables. A descriptive analysis was conducted, followed by survival curves based on univariate (Kaplan-Meier and Cox’s univariate model) and multivariate (Cox regression model) analysis. Patients were followed from two to 20 years (mean: 8.2). Their mean age was 44.8 years (20-77). Comparing both iterations of the study, in the second there was a statistically significant increase in the PR interval and in the QRS duration, despite a reduction in heart rates (Wilcoxon < 0.01). The predictors for CCC progression in the final regression model were male gender (HR = 2.81), Holter monitoring showing pauses equal to or greater than two seconds (HR = 3.02) increased cardiothoracic ratio (HR = 7.87) and time of use of digitalis (HR = 1.41). Patients with multiple predictive factors require stricter follow-up and treatment.

A identificação de preditores da progressão da cardiopatia chagásica crônica (CCC) é essencial ao manejo adequado do paciente. Estudo coorte não concorrente de 165 pacientes portadores de CCC entre 1985-2010 quanto a preditores independentes da evolução da CCC. Os desfechos foram piora da classificação da CCC e surgimento de disfunção ventricular esquerda ao ecoDopplercardiograma. Variáveis sócio-demográficas, epidemiológicas, clínicas e propedêuticas foram estudadas e realizadas análise descritiva, análise de sobrevida com análise univariada (Kaplan-Meier e modelo univariado de Cox) e multivariada (modelo de regressão de Cox). O seguimento foi de dois a 20 anos, com média de 8,2 anos. A média de idade dos pacientes foi de 44,8 anos (20- 77 anos). Comparando ambos os tempos do estudo, no tempo 2 houve significância estatística do aumento do intervalo PR e da duração do QRS, além da redução da frequência cardíaca (Wilcoxon < 0,01). Os preditores da evolução da CCC no modelo final de regressão foram sexo masculino (HR = 2,81), pausas iguais ou maiores que dois segundos ao Holter (HR = 3,02), aumento do índice cardiotorácico (HR = 7,87) e tempo de uso de digital (HR = 1,41), destacando-se necessidade de seguimento e tratamento mais rigoroso para os chagásicos que cumulam estes fatores.

Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age.

A case-control study on chronic Chagas heart disease (CCHD) was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD). Fourty-six patients (51.1%) with Chagas heart disease (anomalous ECG) were assigned to the case group and 44 (48.9%) were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin), epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking), and clinical (systemic hypertension) variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age--presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%: 1.09-7.61)--and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11-7.23). Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.

Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

A case-control study on chronic Chagas heart disease (CCHD) was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD). Fourty-six patients (51.1 percent) with Chagas heart disease (anomalous ECG) were assigned to the case group and 44 (48.9 percent) were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin), epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking), and clinical (systemic hypertension) variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age - presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95 percent: 1.09-7.61) - and family history of Chagas heart disease (OR: 2.833, CI 95 percent: 1.11-7.23). Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.

Avaliação clínica do paciente idoso / Clinical evaluation of aged patient

Os autores descrevem as principais características das doenças na idade avançada (co-morbidades, doenças crônico-degenerativas, apresentação atípica e inespecífica, etiologia múltipla, resposta imprevisível ao tratamento), a sua forma mais freqüente de apresentação (gigantes da Geriatria), assim como a dificuldade de reconhecimento das enfermidades nesta faixa etária (fenômeno do iceberg). A avaliação do paciente idoso deve obrigatoriamente incluir as áreas psíquica, clínica, funcional, nutricional e social, além de uma descrição minuciosa das drogas em uso. A abordagem dos complexos e variados problemas médicos dos idosos usualmente requer a atuação de uma equipe intermultidisciplinar