Exploring the Historical Background and Clinical Implications of Electrocardiogram in the Context of Chagas Disease Research

ABSTRACT Chagas disease (CD) remains one of the most significant endemic diseases in Latin America. Approximately 30% of individuals with CD develop the cardiac form, the main determinant of morbidity and mortality, which is characterized by typical electrocardiogram (ECG) changes caused by chronic chagasic cardiopathy (CCC). This review accentuates to how crucial it is for research teams and reference centers that treat patients with CD to standardize ECG in CCC. This was a non-systematic review of the literature. ECG is the most widely used examination in the diagnosis and evaluation of CCC, and it is also employed in epidemiological surveys, risk stratification for cardiovascular events and death, and monitoring the clinical progression of the disease. Carlos Chagas and Eurico Villela published the first work addressing CCC in 1922. Other works followed, including the study by Evandro Chagas' which was the first to perform ECG in CD, culminating in Francisco Laranja's seminal work in 1956. Since the 1980s, standardizations and ECG reading codes for CD have been established. This standardization aimed to code complex arrhythmias and characteristic ventricular conduction disorders and standardize ECG readings for clinical and epidemiological studies in CD. Nearly all existing electrocardiographic abnormalities can be found in CD, with a predominance of abnormalities in the formation and conduction of cardiac stimuli. The complex and heterogeneous substrate of CD with varied electrocardiographic manifestations poses a significant challenge when comparing studies involving patients with CCC, emphasizing the need for ECG standardization in CD.

Inspiratory Muscle Strength in Chagas Cardiomyopathy: A Systematic Scoping Review

ABSTRACT The increase in inflammatory markers associated with persistent chronic fibrosing myocarditis, a characteristic of chronic Chagas disease, can result in a reduction in inspiratory muscle strength (IMS) in Chagas cardiomyopathy (CC). However, literature in this field is still scarce. This review aimed to map and summarize the evidence regarding IMS in patients with CC. The inclusion criteria included reports with adult participants with a CC diagnosis, with or without heart failure (HF). The core concept examined was the maximum inspiratory pressure evaluated in the untrained and trained groups in the pre-training period. The context was open, including but not limited to hospitals and health centers. Two authors independently identified eligible studies and extracted the data. Descriptive synthesis was used as the primary strategy for analyzing the results. Nine studies (five clinical trials, three cross-sectional, and one cohort) were included. The CC classification differed among the studies, with no mention of HF in five and no CC staging specification in six. IMS was assessed using a manovacuometer, and only six studies analyzed and interpreted the data concerning the predicted values. The CC population with HF appeared to have impaired IMS. All studies involved only Brazilian volunteers. In conclusion, randomized clinical trials evaluating IMS and the effects of inspiratory muscle training need to be conducted to better understand the prevalence and risk of inspiratory muscle weakness in the CC population, as well as the effects of training. Such studies should be conducted at different stages of CC in different populations and countries.

The CUIDA Chagas Project: towards the elimination of congenital transmission of Chagas disease in Bolivia, Brazil, Colombia, and Paraguay

ABSTRACT Background: Mother-to-child transmission of Chagas disease (CD) has become a relevant problem in both endemic and non-endemic areas. Methods: Description of the CUIDA Chagas Project - Communities United for Innovation, Development and Attention for Chagas disease'. Results: Through innovative and strategic research, this project will provide improved diagnostic and treatment options as well as replicable implementation models that are adaptable to different contexts. Conclusions: By integrating test, treat and care actions for CD into primary health care practices, the burden of CD on people and health systems may be significantly reduced.

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience

ABSTRACT Background We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. Methods: This was an observational retrospective study with clinical data retrieved from medical records. Results: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. Conclusions: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Epidemiological-clinical profile and mortality in patients coinfected with Trypanosoma cruzi/HIV: experience from a Brazilian reference center

ABSTRACT Background: The recent urbanization of Chagas disease (CD) has contributed to a greater risk of coexistence with human immunodeficiency virus (HIV) and AIDS. Methods: This retrospective observational study included patients who were followed at INI-Fiocruz between July 1986 and October 2021. All patients underwent an assessment protocol that included sociodemographic profile, epidemiological history, and clinical evaluation. Descriptive data analyses included reports of the medians and frequencies of variables of interest. Differences in medians between groups were tested using the Mann-Whitney U test. Differences in frequency were tested using Fisher's exact test. Results: Among 2201 patients, 11 (0.5%) were identified with Trypanosoma cruzi/HIV coinfection. Of these, 63.6% were women with a median age of 51.0 years old. Two patients had the indeterminate form of CD, six had the cardiac form, two had the digestive form and one had the cardio-digestive form. Half of the patients were undergoing antiretroviral treatment at the time of coinfection diagnosis with a median CD4+ count of 350 cells/μL and a viral load of 1500 copies/μL. Four patients underwent a xenodiagnosis test at coinfection diagnosis, which all yielded positive results; two of them presented high parasitemia under the risk of reactivation. Prophylaxis for CD reactivation was administered to four patients; two with ketoconazole and two with benznidazole. Six patients died after a median follow-up of 22.5 months, with AIDS being the most common cause of death. Only one case of reactivation was observed. Conclusions: Early diagnosis and prompt treatment of CD reactivation dramatically reduced mortality. Identification of Trypanosoma cruzi/HIV co-infection is crucial to planning a close follow-up of coinfected patients.

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.

Indeterminate form of Chagas disease: historical, conceptual, clinical, and prognostic aspects

Abstract Chagas disease (CD) remains a serious endemic disease in Latin America and a major public health problem. Because of globalization, the disease has spread to non-endemic areas in the northern hemisphere. In the chronic phase of the disease, most patients present with the indeterminate form (IF), characterized by positive serology for Trypanosoma cruzi, absence of clinical findings, and normal findings in electrocardiogram (ECG). IF was not recognized as a clinical entity until decades after the discovery of the disease, and only in the 1940-50s, it was categorized as a form of CD, and its conceptual definition was ratified in the 1980s. Children, adolescents, and young adults with the IF benefit from etiological treatment and tend to have less progression to heart disease in the long term than the untreated ones. IF patients have an essentially benign clinical condition, and their prognosis can be compared to that of healthy individuals with normal ECG findings. Currently, because of aging, patients with the IF have comorbidities that require attention in health services.

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.

Agreement between upper endoscopy and esophagography in the diagnosis of megaesophagus in Chagas disease

Abstract INTRODUCTION The diagnosis and classification of megaesophagus can be challenging in patients with Chagas disease. The present study aimed to evaluate the agreement between upper endoscopies and esophagographies for the diagnosis and classification of megaesophagus in Chagas disease. METHODS: A cross-sectional study of 50 patients with Chagas disease with upper digestive symptoms was undertaken. Esophagography and upper endoscopy exams were performed to compare diagnoses. Statistical analysis included sensitivity and specificity used to evaluate the diagnostic accuracy of upper endoscopies, and measures of agreement: linearly weighted Kappa (κw) and Cohen`s classical Kappa (κ) coefficients with 95% confidence intervals (95% CI). RESULTS: Twenty-three patients (46%) were diagnosed with megaesophagus by esophagography. The upper endoscopy sensitivity and specificity for megaesophagus diagnosis were 100% and 33.3%, respectively. Regarding megaesophagus classifications, there was a substantial agreement between the two exams (κw = 0.622; 95% CI: 0.498 to 0.746). Within megaesophagus groups, agreement for group I was slight (κ = 0.096; 95% CI: 0.000 to 0.403); for group II, substantial (κ = 0.703; 95% CI: 0.456 to 0.950); and for groups III and IV, inconclusive (κ = 0.457; 95% CI: 0.000 to 0.967; κ = 0.540; 95% CI: 0.035 to 1.000, respectively). CONCLUSIONS Upper endoscopy has a high sensitivity, but a low specificity to diagnose megaesophagus. Agreement between the two exams varies depending on the megaesophagus grade. Thus, upper endoscopy can be used in the diagnostic workup of a possible Chagas disease megaesophagus, but all identified cases should undergo esophagography.

Global Longitudinal Strain Accuracy for Cardiotoxicity Prediction in a Cohort of Breast Cancer Patients During Anthracycline and/or Trastuzumab Treatment / Acurácia do Strain Longitudinal Global na Predição de Cardiotoxicidade em uma Coorte de Pacientes com Câncer de Mama em Tratamento com Antracíclicos e/ou Trastuzumab

Abstract Background: The high cardiotoxicity morbidity and mortality rates associated with the antineoplastic therapy for breast cancer could be reduced with the early use of cardioprotective drugs. However, the low sensitivity of left ventricular ejection fraction limits its use in that preventive strategy. New parameters, such as global longitudinal strain, are being used in the early detection of contractile function changes. Objectives: To assess the incidence of cardiotoxicity in patients treated for breast cancer, the independent factors associated with that event, and the ability of strain to identify it early. Methods: Prospective observational study of consecutive outpatients diagnosed with breast cancer, with no previous antineoplastic treatment and no ventricular dysfunction, who underwent anthracycline and/or trastuzumab therapy. The patients were quarterly evaluated on a 6- to 12-month follow-up by an observer blind to therapy. Cox regression was used to evaluate the association of cardiotoxicity with clinical, therapeutic and echocardiographic variables. A ROC curve was built to identify the strain cutoff point on the third month that could predict the ejection fraction reduction on the sixth month. For all tests, the statistical significance level adopted was p ≤ 0.05. Results: Of 49 women (mean age, 49.7 ± 12.2 years), cardiotoxicity was identified in 5 (10%) on the third (n = 2) and sixth (n = 3) months of follow-up. Strain was independently associated with the event (p = 0.004; HR = 2.77; 95%CI: 1.39-5.54), with a cutoff point for absolute value of -16.6 (AUC = 0.95; 95%CI: 0.87-1.0) or a cutoff point for percentage reduction of 14% (AUC = 0.97; 95%CI: 0.9-1.0). Conclusion: The 14% reduction in strain (absolute value of -16.6) allowed the early identification of patients who could develop anthracycline and/or trastuzumab-induced cardiotoxicity.

Resumo Fundamentos: A elevada morbimortalidade da cardiotoxicidade associada à terapia antineoplásica para o câncer de mama poderia ser reduzida com uso precoce de drogas cardioprotetoras. No entanto, a baixa sensibilidade da fração de ejeção limita sua utilização nessa estratégia preventiva. Novos parâmetros, como o strain longitudinal global, estão sendo utilizados na detecção precoce das alterações da função contrátil. Objetivos: Avaliar a incidência de cardiotoxicidade entre pacientes tratados para câncer de mama, os fatores independentes associados a esse evento e a capacidade do strain em identificá-la precocemente. Métodos: Estudo prospectivo observacional de pacientes ambulatoriais consecutivos com diagnóstico de câncer de mama, sem tratamento antineoplásico prévio, sem disfunção ventricular, submetidos ao uso de antracíclicos e/ou trastuzumab, avaliados trimestralmente de forma cega em relação à terapia, seguidos por 6 a 12 meses. Regressão de Cox foi utilizada para avaliar a associação de variáveis clínicas, terapêuticas e ecocardiográficas com cardiotoxicidade. Curva ROC foi construída para identificar o ponto de corte do strain capaz de prever redução da fração de ejeção. Para todos os testes, o nível de significância estatística foi definido com p ≤ 0,05. Resultados: Dentre 49 mulheres com idade média de 49,7 ± 12,2 anos, identificamos 5 casos de cardiotoxicidade (10%), aos 3 (n = 2) e 6 (n = 3) meses de seguimento. Strain foi associado de forma independente ao evento (p = 0,004; HR = 2,77; IC95%: 1,39-5,54), tendo como ponto de corte o valor absoluto de -16,6 (ASC = 0,95; IC95%: 0,87-1,0) ou redução de 14% (ASC = 0,97; IC95%: 0,9-1,0). Conclusão: A redução de 14% do strain (ou valor absoluto de -16,6) foi capaz de identificar precocemente pacientes que podem evoluir com cardiotoxicidade associada ao antracíclico e/ou trastuzumab.

Reassessment of quality of life domains in patients with compensated Chagas heart failure after participating in a cardiac rehabilitation program

Abstract INTRODUCTION: We evaluated the effects of a cardiac rehabilitation program on quality of life. METHODS This secondary analysis of a single-arm study included 12 patients with Chagas heart failure. The cardiac rehabilitation program comprised exercise training and nutritional and pharmaceutical counseling. Quality of life was assessed using the SF-36 questionnaire. RESULTS: The program promoted improved physical functioning (β= +5.7; p=0.003), role-physical (β= +1.9; p=0.03), and bodily pain (β= +3.5; p=0.02) scores. Moreover, the summary physical health score (β= +1.4; p=0.001) improved. CONCLUSION: The cardiac rehabilitation program significantly improved the physical quality of life of patients with Chagas heart failure.

II Consenso Brasileiro em Doença de Chagas, 2015 / Brazilian Consensus on Chagas Disease, 2015

A doença de Chagas é uma condição crônica negligenciada com elevada carga de morbimortalidade e impacto dos pontos de vista psicológico, social e econômico. Representa um importante problema de saúde pública no Brasil, com diferentes cenários regionais. Este documento traduz a sistematização das evidências que compõe o Consenso Brasileiro de Doença de Chagas. O objetivo foi sistematizar estratégias de diagnóstico, tratamento, prevenção e controle da doença de Chagas no país, de modo a refletir as evidências científicas disponíveis. Sua construção fundamentou-se na articulação e contribuição estratégica de especialistas brasileiros com conhecimento, experiência e atualização sobre diferentes aspectos da doença. Representa o resultado da estreita colaboração entre a Sociedade Brasileira de Medicina Tropical e o Ministério da Saúde. Espera-se com este documento fortalecer o desenvolvimento de ações integradas para enfrentamento da doença no país com foco em epidemiologia, gestão, atenção integral (incluindo famílias e comunidades), comunicação, informação, educação e pesquisas.

Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.

Cardiac rehabilitation program in patients with Chagas heart failure: a single-arm pilot study

Abstract: INTRODUCTION: The benefit of a cardiac rehabilitation (CR) program for patients with Chagas heart failure (CHF) remains unclear. Therefore, we aimed to investigate the effects of CR for CHF patients. METHODS: A single-arm pilot study, including 12 patients with CHF, was performed. Patients participated in an 8-month physical exercise intervention, comprising aerobic, strength, and stretching exercises (3 times per week, 60 minutes per session). Nutritional and pharmaceutical counseling were also performed. Functional capacity (cardiopulmonary exercise test), muscle respiratory strength (manovacuometry), and body composition (anthropometry and skinfolds) were evaluated at baseline, and after 4 and 8 months of intervention. Cardiac function (echocardiography), biomarkers (lipid profile, glucose, and glycated hemoglobin) and quality of life (Minnesota Living with Heart Failure Questionnaire) were assessed at baseline and at the end of the intervention. RESULTS: Seven of 12 patients included in the study completed the 8-month follow-up period. Only 2 moderate adverse events occurred during the exercise training. Functional capacity improved after 4 months of CR, while left ventricular ejection fraction (LVEF) and respiratory strength improved after 8 months. Patients with right ventricular (RV) dysfunction at baseline exhibited an improvement in functional capacity after 4 months, and improvements in left ventricular (LV) diastolic pressure, respiratory strength, and quality of life at the end of follow-up. Conversely, those with normal baseline RV function demonstrated LVEF increases that were not observed in patients with RV dysfunction. CONCLUSIONS: CR was feasible, safe, and has important clinical benefits for patients with CHF, specifically for cardiac function and muscle respiratory strength.

Atrial Fibrillation in Decompensated Heart Failure: Associated Factors and In-Hospital Outcome / Fibrilação Atrial em Insuficiência Cardíaca Descompensada: Fatores Associados e Evolução Hospitalar

Background: Studies on atrial fibrillation (AF) in decompensated heart failure (DHF) are scarce in Brazil. Objectives: To determine AF prevalence, its types and associated factors in patients hospitalized due to DHF; to assess their thromboembolic risk profile and anticoagulation rate; and to assess the impact of AF on in-hospital mortality and hospital length of stay. Methods: Retrospective, observational, cross-sectional study of incident cases including 659 consecutive hospitalizations due to DHF, from 01/01/2006 to 12/31/2011. The thromboembolic risk was assessed by using CHADSVASc score. On univariate analysis, the chi-square, Student t and Mann Whitney tests were used. On multivariate analysis, logistic regression was used. Results: The prevalence of AF was 40%, and the permanent type predominated (73.5%). On multivariate model, AF associated with advanced age (p < 0.0001), non-ischemic etiology (p = 0.02), right ventricular dysfunction (p = 0.03), lower systolic blood pressure (SBP) (p = 0.02), higher ejection fraction (EF) (p < 0.0001) and enlarged left atrium (LA) (p < 0.0001). The median CHADSVASc score was 4, and 90% of the cases had it ≥ 2. The anticoagulation rate was 52.8% on admission and 66.8% on discharge, being lower for higher scores. The group with AF had higher in-hospital mortality (11.0% versus 8.1%, p = 0.21) and longer hospital length of stay (20.5 ± 16 versus 16.3 ± 12, p = 0.001). Conclusions: Atrial fibrillation is frequent in DHF, the most prevalent type being permanent AF. Atrial fibrillation is associated with more advanced age, non-ischemic etiology, right ventricular dysfunction, lower SBP, higher EF and enlarged LA. Despite the high thromboembolic risk profile, anticoagulation is underutilized. The presence of AF is associated with longer hospital length of stay and high mortality. .

Fundamento: Estudos sobre fibrilação atrial (FA) na insuficiência cardíaca descompensada (ICD) são muito escassos no Brasil. Objetivos: Determinar a prevalência, os tipos e os fatores associados à FA em pacientes hospitalizados por ICD; analisar perfil de risco embólico e taxa de anticoagulação; e avaliar o impacto da FA na mortalidade hospitalar e no tempo de internação. Métodos: Estudo seccional de casos incidentes, retrospectivo, observacional. Analisaram-se 659 internações consecutivas por ICD entre 01/01/2006 a 31/12/2011. Risco embólico foi avaliado pelo acrônimo CHADSVASc. Na análise univariada, foram utilizados o qui-quadrado, teste t de Student ou Mann Whitney. Na análise multivariada, utilizou-se a regressão logística. Resultados: A prevalência de FA foi de 40%, predominando o tipo permanente (73,5%). No modelo multivariado, a FA se associou à idade avançada (p < 0,0001), etiologia não isquêmica (p = 0,02), disfunção ventricular direita (VD) (p = 0,03), menor pressão arterial sistólica (PAS) (p = 0,02), maior fração de ejeção (FE) (p < 0,0001) e aumento atrial esquerdo (AE) (p < 0,0001). A mediana do CHADSVASc foi quatro e 90% tinham escore ≥ 2. A taxa de anticoagulação foi de 52,8% na admissão e 66,8% na alta, sendo menor em escores mais elevados. O grupo com FA apresentou maior mortalidade hospitalar (11,0% versus 8,1%, p = 0,21) e internação mais prolongada (20,5 ± 16 versus 16,3 ± 12, p = 0,001). Conclusões: A FA é frequente na ICD, predominando o tipo permanente. Associa-se com idade avançada, etiologia não isquêmica, disfunção de VD, menor PAS, maior FE e aumento AE. O perfil de risco embólico é elevado e a anticoagulação é subutilizada. ...