Temporal changes in the clinical-epidemiological profile of patients with Chagas disease at a referral center in Brazil.

INTRODUCTION: We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS: This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS: A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients' levels of education. CONCLUSIONS: The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

Temporal changes in the clinical-epidemiological profile of patients with Chagas disease at a referral center in Brazil

Abstract INTRODUCTION We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients' levels of education. CONCLUSIONS The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

Associations between Cardiac Magnetic Resonance T1 Mapping Parameters and Ventricular Arrhythmia in Patients with Chagas Disease.

Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease (n = 47) and a control group (n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) was performed. There was an increase in myocardial fibrosis CMR parameters and ventricular arrhythmias among different stages of Chagas disease, combined with a decrease in the left ventricular ejection fraction (LVEF) by CMR and also in the right ventricular systolic function by S' wave on tissue Doppler. Fibrosis mass and ECV were associated with the Rassi score, ventricular extrasystole, and E/e' ratio in a logistic regression model adjusted for age and gender. The ECV maintained an association with the presence of NSVT, even after adjustments for fibrosis mass and LVEF assessed by CMR. The receiver-operating characteristic area under the curve for global ECV (0.85; 95% CI: 0.71-0.99) and NSVT was greater than that for fibrosis mass (0.75; 95% CI: 0.54-0.96), although this difference was not statistically significant. Extracellular volume could be an early marker of increased risk of ventricular arrhythmia in Chagas disease, presenting an independent association with NSVT in the initial stages of chronic Chagas cardiomyopathy, even after adjustment for fibrosis mass and LVEF.

Progression Rate from the Indeterminate Form to the Cardiac Form in Patients with Chronic Chagas Disease: Twenty-Two-Year Follow-Up in a Brazilian Urban Cohort.

Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. METHODS: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. RESULTS: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 4 8 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). CONCLUSION: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.

Adverse drug events and the associated factors in patients with chronic Chagas disease.

INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Adverse drug events and the associated factors in patients with chronic Chagas disease

Abstract INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity.

Chagas disease is one of the most important endemic infections in Latin America affecting around 6-7 million people. About 30-50% of patients develop the cardiac form of the disease, which can lead to severe cardiac dysfunction and death. In this scenario, the identification of immunological markers of disease progression would be a valuable tool for early treatment and reduction of death rates. In this observational study, the production of anti-Trypanosoma cruzi antibodies through a retrospective longitudinal follow-up in chronic Chagas disease patients´ cohort and its correlation with disease progression and heart commitment was evaluated. Strong inverse correlation (ρ = -0.6375, p = 0.0005) between anti-T. cruzi IgG1 titers and left ventricular ejection fraction (LVEF) in chronic Chagas cardiomyopathy (CCC) patients were observed after disease progression. Elevated levels of anti-T. cruzi IgG3 titers were detected in all T. cruzi-infected patients, indicating a lack of correlation of this IgG isotype with disease progression. Furthermore, low levels of anti-T. cruzi IgG2, IgG4, and IgA were detected in all patients through the follow-up. Although without statistical significance anti-T. cruzi IgE tends to be more reactive in patients with the indeterminate form (IND) of the disease (p = 0.0637). As this study was conducted in patients with many years of chronic disease no anti-T. cruzi IgM was detected. Taken together, these results indicate that the levels of anti-T. cruzi IgG1 could be considered to seek for promising biomarkers to predict the severity of chronic Chagas disease cardiomyopathy.

Benznidazole treatment safety: the Médecins Sans Frontières experience in a large cohort of Bolivian patients with Chagas' disease.

Background: Up to half of patients with Chagas' disease under benznidazole treatment present adverse drug reactions (ADRs) and up to one-third do not complete standard treatment. Objectives: To verify the incidence and possible factors associated with the suspension of benznidazole treatment in a large cohort of patients. Methods: We included 2075 patients treated with benznidazole during the projects managed by the medical humanitarian organization Doctors Without Borders (Médecins Sans Frontières) in Bolivia from 2009 to 2013. Benznidazole treatment was provided two or three times per day for ∼60 days at 5-7.5 mg/kg/day. A multiple logistic regression model was developed to evaluate the factors associated with permanent suspension of benznidazole treatment. Results: Permanent benznidazole treatment suspension occurred in 211 patients (10.2%) and the average time until permanent treatment suspension was 23 days. Multifactorial analysis revealed that female sex (adjusted OR = 1.70), moderate ADRs (adjusted OR = 10.57), mild ADRs (adjusted OR = 1.69) and skin disorders (adjusted OR = 4.18) were significantly associated with the permanent suspension of benznidazole treatment. Women with mild or moderate skin ADRs presented a probability of treatment interruption of 18.6% and 59.0%, respectively. Conclusions: Benznidazole treatment was safe and a large proportion of patients were able to complete a full course of benznidazole treatment under close treatment surveillance. Female sex, skin disorders and mild and moderate ADRs were independently associated with the permanent suspension of benznidazole treatment. In particular, women with moderate skin ADRs had the highest risk of benznidazole treatment interruption.

Mecanismo de morte e grau de acometimento miocárdico na fase crônica da doença de chagas / Death mechanisms and myocardial effect levels in the chronic phase of Chagas disease

Objetivo: Avaliar os mecanismos de morte, correlacionando-os com o grau de acometimento miocárdico na fase crônica da doença de Chagas (DC). Métodos: Foi analisada uma coorte de 1167 pacientes com DC recrutados entre 03/1990 e 12/2003. Todos foram submetidos a exame clínico, ECG, RX tórax e ECO. Na avaliação da gravidade do acometimento miocárdico, foi utilizada a classificação preconizada pelo Consenso Brasileiro em DC (2005) e a FE do VE estimada ao ECO. Resultados: Durante 67 mais ou menos 43 meses de seguimento ocorreram 106 óbitos, 82 de causa cardíaca, sendo 54 mortes súbitas (MS), 22 mortes por IC refratária e 6 mortes decorrentes de AVE embólico. O mecanismo de óbito variou de acordo com o estágio da cardiopatia (p menor 0,0001) e com o grau de disfunção ventricular (p menor 0,0001). MS foi o mecanismo mais frequente de óbito em todos os estágios, exceto no stágio D em que predominou a morte por IC. A maioria dos óbitos por AVE ocorreu em pacientes sem IC. A média da FE do VE foi diferente nos diversos mecanismos de morte: pacientes com morte não-cardíaca (p menor 0,0001). Conclusões: MS foi o mecanismo predominante de óbito, ocorrendo frequentemente em pacientes sem IC e/ou com FE maior 35 por cento. IC progressiva foi o principal mecanismo de óbito entre os pacientes no estágio D e foi associada à disfunção sistólica do VE mais avançada. AVE embólico foi uma causa de óbito minoritária nesta coorte, sendo associada a menor grau de acometimento miocárdio.

Mecanismos de morte e função ventricular na fase crônica da doença de Chagas / Death mechanisms and ventricular function in the chronic stage of Chagas disease

Objetivo: avaliar mecanismos de morte na doença de Chagas (DC) correlacionando com a função ventricular. Métodos: Estudo prospectivo, longitudinal em coorte de 1053 pacientes com DC no período de 03/1990 a 03/2003. Todos foram submetidos a exame clínico, ECG, RX tórax e ECO na admissão. Os óbitos de causa cardíaca decorreram de morte súbita (MS), insuficiência cardíaca (IC) ou evento cardiometabólico (AVE). Na análise estatística, utilizaram-se os testes qui-quadrado, t de Student e ANOVA (correção de Bonferroni). Resultados: O tempo médio de acompanhamento foi de 66 maior ou menor que 43 meses (seguimento completo de 84 por cento). Ocorreram 93 óbitos, 78 (83 por cento) de causa cardíaca: 53 MS, 20 IC e 5 AVE. Ocorreram 6 óbitos (causa não-cardíaca) quando o ECG foi normal e 87 quando foi anormal, 78 de causa cardíaca. MS foi o mecanismo mais freqüente de óbito em todas as faixas de fração de ejeção (FE). Morte por IC só ocorreu na FE menor que 35 por cento com 83 por cento dos óbitos na classe funcional III e IV com tratamento clínico otimizado. A FE média foi de 25 maior ou menor que 7 por cento nos que faleceram de IC, 38 maior ou menor que 16 por cento naqueles com MS; 51 maior ou menor que 19 por cento naqueles com AVE embólico e de 56 maior ou menor que 14 por cento nos pacientes com morte não cardíaca (p menor que 0,0001)...

Incidência e preditores de morte súbita na cardiopatia chagásica crônica com função sistólica preservada / Incidence predictors of sudden death in chronic chagas cardiopathy with preserved systolic function

Objetivos:Avaliar a incidência e os preditores de morte súbita em uma coorte de pacientes com cardiopatia chagásica crônica e função sistólica preservada (FE maior 45 por cento).Métodos: Estudo prospectivo, longitudinal de uma coorte de 1053 pacientes com doença de Chagas, recrutados no período de 03/1990 a 03/2002 e acompanhados até 03/2003.todos foram submetidos a exame clínico, ECG, RX tórax e ECO na admissão.Na análise da incidência, foram descritas a incidência cumulativa e a incidência dencidade.Foram utilizaod o teste qui-quadrado para a comparação de variáveis categóricas e o teste t de Student para a comparação de médias entre 2 grupos. Resultados:Não houve qualquer caso de morte súbita entre os pacientes com ECG inicial normal.Nos 539 pacientes com ECG alterado, 377 aparesentavam FE maior 45 por cento e constituem a coorte de interesse