Chagas heart disease is associated with decreased physical activity levels: A cross-sectional analysis.

Background: Studies evaluating physical activity (PA) levels in individuals with Chagas disease (CD) are still scarce. The present study aimed to evaluate PA levels in CD individuals and examine their association with Chagas heart disease (ChHD). Methods: We included patients with CD regularly followed in a reference center for treatment of infectious diseases. PA levels were assessed using the short version of the International Physical Activity Questionnaire (IPAQ). ChHD was determined following the Brazilian Consensus on Chagas Disease. The association between ChHD and levels of PA (total, walking, moderate, and vigorous) as a continuous variable was fitted using generalized linear models. Logistic regression models were fitted to evaluate the association between ChHD and meeting WHO's PA recommendations. Results: Among the 361 participants included in the analysis (60.7 ± 10.7 years; 56.2 % women), 58.1 % (n = 210) complied with the WHO's PA recommendations. After adjustments for potential confounders, regression analyses revealed that ChHD without heart failure was significantly associated with reduced vigorous PA (Exp ß 0.32 95 % CI 0.10 to 0.98). ChHD with heart failure had significantly lower levels of total (Exp ß 0.61 95 % CI 0.44 to 0.84) and moderate (Exp ß 0.59 95 % CI 0.39 to 0.89) PA. ChHD with heart failure had a lower odd of meeting the PA recommendation in comparison to those with no cardiac involvement (OR 0.48 95 % CI 0.24 to 0.97). Conclusions: We found low levels of PA among individuals with CD. Presence of ChHD (mainly with HF) was associated with decreased levels of PA.

Effect of an exercise-based cardiac rehabilitation program on quality of life of patients with chronic Chagas cardiomyopathy: results from the PEACH randomized clinical trial.

To investigate the effect of an exercise-based cardiac rehabilitation program on the quality of life (QoL) of patients with chronic Chagas cardiomyopathy (CCC). PEACH study was a single-center, superiority randomized clinical trial of exercise training versus no exercise (control). The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction < 45%, without or with HF symptoms (CCC stages B2 or C, respectively). QoL was assessed at baseline, after three months, and at the end of six months of follow-up using the SF-36 questionnaire. Patients randomized for the exercise group (n = 15) performed exercise training (aerobic, strength and stretching exercises) for 60 min, three times a week, during six months. Patients in the control group (n = 15) were not provided with a formal exercise prescription. Both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of exercise training on QoL, considering the interaction term (group × time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using linear mixed models. Models were fitted adjusting for each respective baseline QoL value. There were significant improvements in physical functioning (ß = + 10.7; p = 0.02), role limitations due to physical problems (ß = + 25.0; p = 0.01), and social functioning (ß = + 19.2; p < 0.01) scales during the first three months in the exercise compared to the control group. No significant differences were observed between groups after six months. Exercise-based cardiac rehabilitation provided short-term improvements in the physical and mental aspects of QoL of patients with CCC.Trial registration: ClinicalTrials.gov Identifier: NCT02517632; August 7, 2015.

Inspiratory Muscle Strength in Chagas Cardiomyopathy: A Systematic Scoping Review.

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.

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

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.

Valores de referência de parâmetros ecocardiográficos estruturais e funcionais para a população brasileira: avaliação de câmaras direitas - estudo de normais - DIC / Reference values ​​of structural and functional echocardiographic parameters for the Brazilian population: evaluation of right chambers - study of normals - DIC

INTRODUÇÃO: A avaliação e quantificação das dimensões e função das câmaras cardíacas direitas pelo ecocardiograma auxilia no diagnóstico e prognóstico de várias situações clinicas; seus valores de referência, no entanto, refletem as características antropométricas da população estudada. OBJETIVO: analisar prospectivamente exames ecocardiográficos bidimensionais de indivíduos normais das diversas regiões brasileiras para a determinação de valores de referência de câmaras direitas. MÉTODO: Ecocardiogramas de indivíduos de ambos sexos, > 18 anos, sem doença cardíaca, sistêmica ou fatores de risco cardiovascular foram obtidos em centros das 5 regiões do Brasil e analisados offline (Ultrasound Workspace- Tomtec- Phillips) para avaliação de medidas das câmaras cardíacas direitas e função ventricular direita (VD): variação fracional da área (FAC) do VD, TAPSE, s­ do VD e strain longitudinal (SL) do VD (global e parede livre) por speckle tracking. Foram analisadas as diferenças entre os sexos pelo teste t não pareado de Student. RESULTADOS: Foram incluídos 445 indivíduos, com idade de 42+ 15 anos, 56% do sexo feminino, sendo excluídos 40 por imagem/dados inadequados; As medidas ecocardiográficas foram realizadas em 147 indivíduos e mostraram maiores dimensões de câmaras direitas para o sexo masculino (p<0.001); para parâmetros funcionais, apenas o FAC mostrou diferença significativa entre os grupos, sendo maior para o sexo feminino (p = 0.04); os demais parâmetros funcionais ( TAPSE, S­ VD, e SGL e de parede livre do VD) foram similares para ambos os sexos . CONCLUSÃO: Resultados preliminares da população brasileira sugerem parâmetros estruturais com maiores dimensões de câmaras direitas para o sexo masculino, o que infere que esses dados devam ser indexados para a superfície corpórea. Parâmetros funcionais, por outro lado, parecem sofrer pouca influência do sexo.

Comparative effects of a cardiovascular rehabilitation program on functional capacity in patients with chronic chagasic cardiomyopathy with or without heart failure.

PURPOSE: The aim of the present study was to evaluate the effects of cardiovascular rehabilitation (CR) on functional capacity of patients with chronic chagasic cardiomyopathy (CCC) and to compare the responses between CCC patients without and with heart failure (HF). MATERIALS AND METHODS: A longitudinal observational retrospective study was carried out including 36 patients with CCC without HF (stage B2 [n = 7]) and with HF (stage C [n = 29]), who participated in a CR program. Functional capacity was assessed by a maximal progressive cardiopulmonary exercise test performed on a treadmill. The longitudinal effects of the CR on functional capacity were determined by linear mixed models that included an interaction term to evaluate the differential responses between patients without and with HF. RESULTS: Significant improvements in peak oxygen consumption, resting heart rate and blood pressure, and maximum pulmonary ventilation were observed for the overall study sample, with no apparent differential effects according to the presence of HF. CONCLUSIONS: CR significantly improved functional capacity of patients with CCC. The responses to CR appear to be similar among patients without and with HF, reinforcing the need for its inclusion as a standard treatment strategy of CCC.Implications for rehabilitationExercise-based cardiovascular rehabilitation (CR) is a safe strategy that improves functional capacity, cardiac function, and quality of life in patients with several cardiovascular diseases, and recent studies also suggested a potential beneficial effect of CR in chronic chagasic cardiomyopathy (CCC).In this observational study, CR seems to equally improve exercise capacity, resting heart rate, resting blood pressure, and maximum pulmonary ventilation in patients with CCC without (stage B2) and with heart failure (stage C).Cardiovascular rehabilitation should be included as a standard treatment strategy for patients with CCC, regardless the severity of cardiomyopathy.

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.

Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023. / Posicionamento do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia sobre o Uso do Strain Miocárdico na Rotina do Cardiologista ­ 2023.

Central Illustration : Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023 Proposal for including strain in the integrated diastolic function assessment algorithm, adapted from Nagueh et al.67 Am: mitral A-wave duration; Ap: reverse pulmonary A-wave duration; DD: diastolic dysfunction; LA: left atrium; LASr: LA strain reserve; LVGLS: left ventricular global longitudinal strain; TI: tricuspid insufficiency. Confirm concentric remodeling with LVGLS. In LVEF, mitral E wave deceleration time < 160 ms and pulmonary S-wave < D-wave are also parameters of increased filling pressure. This algorithm does not apply to patients with atrial fibrillation (AF), mitral annulus calcification, > mild mitral valve disease, left bundle branch block, paced rhythm, prosthetic valves, or severe primary pulmonary hypertension.

Figura Central : Posicionamento do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia sobre o Uso do Strain Miocárdico na Rotina do Cardiologista ­ 2023 Proposta de inclusão do strain no algoritmo integrado de avaliação da função diastólica, adaptado e traduzido de Nagueh et al. 67 AE: átrio esquerdo; Ap: duração da onda A reversa pulmonar; Am: duração da onda A mitral; DD: disfunção diastólica; FEVEr: fração de ejeção do ventrículo esquerdo reduzida; IT: insuficiência tricúspide; SAEr: strain do AE de reservatório; SLGVE: strain longitudinal global do ventrículo esquerdo. Se remodelamento concêntrico, confirmar com SLGVE. Na presença de FEVEr, tempo de desaceleração da onda E mitral (TDE) < 160 ms e onda S < D pulmonar também são parâmetros de pressão de enchimento aumentada. Esse algoritmo não se aplica a pacientes com fibrilação atrial (FA), calcificação do anel mitral ou valvopatia mitral maior que discreta, bloqueio de ramo esquerdo (BRE), ritmo de marca-passo, próteses valvares ou hipertensão pulmonar (HP) primária grave.

The association between variables of cardiopulmonary exercise test and quality of life in patients with chronic Chagas cardiomyopathy (Insights from the PEACH STUDY).

Studies investigating the association between functional capacity and quality of life (QoL) in individuals with chronic Chagas cardiomyopathy (CCC) usually do not include a gold-standard evaluation of functional capacity, limiting the validity and the interpretation of the results. The present study is a cross-section analysis aiming to evaluate the association between functional capacity (quantified by cardiopulmonary exercise test [CPET]) and QoL in individuals with CCC. QoL was assessed using the SF-36 questionnaire. Sociodemographic, anthropometric, clinical, cardiac function and maximal progressive CPET variables were obtained from PEACH study. Generalized linear models adjusted for age, sex, and left ventricular ejection fraction were performed to evaluate the association between CPET variables and QoL. After adjustments, VO2 peak and VO2 AT were both associated with physical functioning (ß = +0.05 and ß = +0.05, respectively) and physical component summary (ß = +0.03 and ß = +0.03, respectively). Double product was associated with physical functioning (ß = +0.003), general health perceptions (ß = +0.003), physical component summary (ß = +0.002), and vitality (ß = +0.004). HRR≤12bpm was associated with physical functioning (ß = -0.32), role limitations due to physical problems (ß = -0.87), bodily pain (ß = -0.26), physical component summary (ß = -0.21), vitality (ß = -0.38), and mental health (ß = -0.19). VE/VCO2 slope presented association with all mental scales of SF-36: vitality (ß = -0.028), social functioning (ß = -0.024), role limitations due to emotional problems (ß = -0.06), mental health (ß = -0.04), and mental component summary (ß = -0.02). The associations between CPET variables and QoL demonstrate the importance of CPET inclusion for a more comprehensive evaluation of individuals with CCC. In this setting, intervention strategies aiming to improve functional capacity may also promote additional benefits on QoL and should be incorporated as a treatment strategy for patients with CCC.

Analysis of Three-Dimensional Scar Architecture and Conducting Channels by High-Resolution Contrast-Enhanced Cardiac Magnetic Resonance Imaging in Chagas Heart Disease.

BACKGROUND: We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events. METHODS: Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range). RESULTS: A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60). CONCLUSIONS: High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events.

Corrigendum: Impact of COVID-19 in-hospital mortality in chagas disease patients.

[This corrects the article DOI: 10.3389/fmed.2022.880796.].

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.

Chagas disease (CD) affects at least 6 million people in 21 South American countries besides several thousand in other nations all over the world. It is estimated that at least 14,000 people die every year of CD. Since vaccines are not available, chemotherapy remains of pivotal relevance. About 30% of the treated patients cannot complete the therapy because of severe adverse reactions. Thus, the search for novel drugs is required. Here we tested the benznidazole (BZ) combination with the repositioned drug disulfiram (DSF) and its derivative diethyldithiocarbamate (DETC) upon Trypanosoma cruzi in vitro and in vivo. DETC-BZ combination was synergistic diminishing epimastigote proliferation and enhancing selective indexes up to over 10-fold. DETC was effective upon amastigotes of the BZ- partially resistant Y and the BZ-resistant Colombiana strains. The combination reduced proliferation even using low concentrations (e.g., 2.5 µM). Scanning electron microscopy revealed membrane discontinuities and cell body volume reduction. Transmission electron microscopy revealed remarkable enlargement of endoplasmic reticulum cisternae besides, dilated mitochondria with decreased electron density and disorganized kinetoplast DNA. At advanced stages, the cytoplasm vacuolation apparently impaired compartmentation. The fluorescent probe H2-DCFDA indicates the increased production of reactive oxygen species associated with enhanced lipid peroxidation in parasites incubated with DETC. The biochemical measurement indicates the downmodulation of thiol expression. DETC inhibited superoxide dismutase activity on parasites was more pronounced than in infected mice. In order to approach the DETC effects on intracellular infection, peritoneal macrophages were infected with Colombiana trypomastigotes. DETC addition diminished parasite numbers and the DETC-BZ combination was effective, despite the low concentrations used. In the murine infection, the combination significantly enhanced animal survival, decreasing parasitemia over BZ. Histopathology revealed that low doses of BZ-treated animals presented myocardial amastigote, not observed in combination-treated animals. The picrosirius collagen staining showed reduced myocardial fibrosis. Aminotransferase de aspartate, Aminotransferase de alanine, Creatine kinase, and urea plasma levels demonstrated that the combination was non-toxic. As DSF and DETC can reduce the toxicity of other drugs and resistance phenotypes, such a combination may be safe and effective.

Cost-effectiveness of an exercise-based cardiovascular rehabilitation program in patients with chronic Chagas cardiomyopathy in Brazil: An analysis from the PEACH study.

OBJECTIVES: The present study aimed to perform a cost-effectiveness analysis of an exercise-based cardiovascular rehabilitation (CR) program in patients with chronic Chagas cardiomyopathy (CCC). METHODS: Cost-effectiveness analysis alongside a randomised clinical trial evaluating the effects of a 6-month exercise-based CR program. The intervention group underwent 3 weekly exercise sessions. The variation of peak oxygen consumption (VO2peak ) was used as a measurement of clinical outcome. Cost information from all healthcare expenses (examinations, healthcare visits, medication and hospitalisation) were obtained from the medical records in Brazilian reais (R$) and transformed into dollars using the purchasing power parity ($PPP). The longitudinal costs variation was evaluated through linear mixed models, represented by ß coefficient, adjusted for the baseline values of the dependent variable. The cost-effectiveness evaluation was determined through an incremental cost-effectiveness ratio using the HEABS package (Stata 15.0). RESULTS: The intervention group presented higher costs with healthcare visits (ß = +3317.3; p < 0.001), hospitalisation (ß = +2810.4; p = 0.02) and total cost (ß = +6407.9; p < 0.001) after 3 months of follow-up. Costs related to healthcare visits (ß = +2455.8; p < 0.001) and total cost (ß = +4711.4; p < 0.001) remained higher in the intervention group after 6 months. The CR program showed an incremental cost-effectiveness ratio (ICER) of $PPP 1874.3 for each increase of 1.0 ml kg-1  min-1 of VO2peak . CONCLUSIONS: The CR program can be considered a cost-effective alternative and should be included as an intervention strategy in the care of patients with CCC.