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.

Exercise training improves microvascular function in patients with Chagas heart disease: Data from the PEACH study.

BACKGROUND: Chagas heart disease (CHD) impairs the systemic microvascular function. We investigated the effects of exercise training on cutaneous microvascular function among patients with CHD. METHODS: Patients from the PEACH study were randomly assigned to a supervised exercise training 3 times/week for 6 months (Trained; n = 10) or a control group (Untrained; n = 8). Both groups underwent evaluation of microvascular function before, and at 3- and 6-months of follow-up. Cutaneous vascular conductance (CVC) was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh), sodium nitroprusside (SNP) and during post-occlusive reactive hyperemia (PORH). RESULTS: At 3-months of follow-up, no difference was detected between groups in CVC responses to ACh (p = 0.50), SNP (p = 0.26) and HRPO (p = 0.65). However, at 6-months of follow-up, trained vs. untrained patients improved CVC induced by SNP-iontophoresis (0.19 ± 0.10 vs. 0.14 ± 0.15 APU.mmHg-1; p = 0.05) and PORH (0.63 ± 0.15 vs. 0.48 ± 0.18 APU.mmHg-1; p = 0.05). CVC response to ACh-iontophoresis was similar between groups (0.19 ± 0.11 vs. 0.22 ± 0.17 APU.mmHg-1; p = 0.38). CONCLUSION: Exercise training performed during 6 months improved the cutaneous microvascular function of CHD patients. Further studies evaluating the mechanism involved in this response are warranted.

Factors related to the discontinuation and mortality rates of a cardiac rehabilitation programme in patients with Chagas disease: a 6-year experience in a Brazilian tertiary centre.

OBJECTIVES: To describe the clinical and sociodemographic characteristics of participants as well as discontinuation and mortality rates in a cardiac rehabilitation programme (CRP) tailored to Chagas disease (CD). METHODS: Participants underwent functional capacity, anthropometry and cardiac function evaluations before beginning a CRP. Univariate and multivariate Cox proportional hazards models were performed to investigate the associations between clinical and sociodemographic characteristics at baseline with discontinuation rates and deaths. RESULTS: Forty-two patients were enrolled in the CRP (61.9% men, mean age of 58.1 ± 11.8 years). During a median follow-up period of 10.8 months, 74% discontinued and 14% died while enrolled in CRP. 34% of the patients who discontinued CRP died during follow-up. White race (HR = 0.09; 95% CI 0.01-1.00), right ventricular systolic dysfunction (HR = 10.54; 95% CI 1.24-89.50) and oxygen pulse (HR = 0.69; 95% CI 0.48-0.99) were independently associated with death while enrolled in CRP. Married status (HR = 0.44; 95% CI 0.21-0.95) was independently associated with discontinuation rates from CRP. VO2 peak (HR = 0.85; 95% CI 0.74-0.98) and CRP discontinuation due to CD-related reasons (HR = 8.33; 95% CI 1.91-36.27) were the variables independently associated with death after discontinuation of CRP. CONCLUSION: In this population, sociodemographic aspects and severity of CD were important determinants of CRP discontinuation and mortality.

OBJECTIFS: Décrire les caractéristiques cliniques et sociodémographiques des participants ainsi que les taux d'abandon et de décès dans un programme de réadaptation cardiaque (PRC) adapté à la maladie de Chagas (MC). MÉTHODES: Les participants ont subi des évaluations de la capacité fonctionnelle, de l'anthropométrie et de la fonction cardiaque avant de commencer un PRC. Des modèles de risques proportionnels de Cox univariés et multivariés ont été appliqués pour étudier les associations entre les caractéristiques cliniques et sociodémographiques au départ avec les taux d'abandon et les décès. RÉSULTATS: 42 patients ont été enrôlés dans le PRC (61,9% d'hommes, âge moyen de 58,1 ± 11,8 ans). Au cours d'une période médiane de suivi de 10,8 mois, 74% ont abandonné et 14% sont décédés durant leur enrôlement au PRC. 34% des patients qui ont arrêté le PRC sont décédés au cours du suivi. La race blanche (HR = 0,09; IC95%: 0,01-1,00), le dysfonctionnement systolique ventriculaire droite (HR = 10,54; IC95%: 1,24-89,50) et le pouls d'oxygène (HR = 0,69; IC95%: 0,48-0,99) étaient indépendamment associés avec le décès lors de l'enrôlement au PRC. Le statut marié (HR = 0,44; IC95%: 0,21-0,95) était indépendamment associé aux taux d'abandon de la CRP. Le pic de VO2 (HR = 0,85; IC95%: 0,74-0,98) et l'arrêt du PRC pour des raisons liées à la MC (HR = 8,33; IC95%: 1,91 à 36,27) étaient les variables indépendamment associées au décès après l'arrêt du PRC. CONCLUSION: Dans cette population, les aspects sociodémographiques et la sévérité de la MC étaient des déterminants importants de l'arrêt du PRC et du décès.

Impact of pharmaceutical care on the quality of life of patients with heart failure due to chronic Chagas disease: Randomized clinical trial.

AIMS: Chronic Chagas disease (ChD) has high morbimortality and loss in quality of life due to heart failure (HF). Pharmaceutical care (PC) optimizes clinical treatment and can improve quality of life in HF. We evaluated if PC improves quality of life of patients with ChD and HF. METHODS: Single-blinded, randomized, controlled trial that assigned adult patients with ChD and HF (81 patients; 61 ± 11 years; 48% male) to PC (n = 40) or standard care (n = 41). Quality of life according to SF-36 and Minnesota living with HF questionnaires, incidence of drug-related problems (DRPs), and adherence to medical treatment were determined at baseline and at every 3 months for 1 year. Intention-to-treat analyses were performed by mixed linear model to verify the treatment effect on the changes of these variables throughout the intervention period. RESULTS: Relative changes from baseline to 1 year of follow-up of the domains physical functioning (+16.6 vs -8.5; P < .001), role-physical (+34.0 vs +5.2; P = .01), general health (+19.4 vs -6.1; P < .001), vitality (+11.5 vs. -5.8; P = .003), social functioning (+7.5 vs -13.3; P = .002), and mental health (+9.0 vs -3.7; P = .006) of the SF-36 questionnaire and the Minnesota living with HF questionnaire score (-12.7 vs +4.8; P < .001) were superior in the PC group than in the standard care group. Adherence to medical treatment increased as early as after 3 months of follow-up and DRPs incidence decreased after 6 months of follow-up only in the PC group. CONCLUSIONS: Patients with ChD and HF who received PC presented improved quality of life, decrease in DRP frequency, and increase in medication adherence.

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.

Autochthonous transmission of Chagas disease in Rio de Janeiro State, Brazil: a clinical and eco-epidemiological study.

BACKGROUND: After the control of the main modes of Chagas disease (CD) transmission in most endemic countries, it is important to identify the participation of native sylvatic vectors in CD transmission. Although CD is not considered endemic in Rio de Janeiro State (RJ), Brazil, we identified patients with CD born in RJ and investigated the possible autochthonous transmission in the state. METHODS: Patients born in RJ and followed in our institution between 1986 and 2011 were retrospectively analyzed. The cases identified as autochthonous transmission were submitted to epidemiological, clinical, serological, parasitological and molecular studies. Sectional field study with serological survey, research of sylvatic reservoirs and vectors was conducted in rural areas where patients were born. RESULTS: Among 1963 patients, 69 (3.5%) were born in RJ. From these, 15 (21.7%) were considered to have acquired the infection by autochthonous transmission. Cardiac form was the commonest form of presentation (60%). In rural areas in RJ northern region, sylvatic cycles of Trypanosoma cruzi and domestic invasion by Triatoma vitticeps were identified, and CD prevalence among inhabitants was 0.74%.TcI genotype was identified in sylvatic reservoirs and vectors. The genotype (mixed infection TcI/TcVI) could be identified in one of the autochthonous cases. CONCLUSIONS: The autochthonous vectorial transmission of CD occurs in RJ, probably due to wild cycles of T. cruzi and sylvatic vectors, such as T. vitticeps. Therefore, the health authorities should evaluate if RJ should be included in the original endemic area of CD and CD should be included in the diagnostic work out of cardiomyopathy of patients born in RJ. Moreover, control and educational measures should be put into place in the risk areas.

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.

Matrix metalloproteinases 2 and 9 are differentially expressed in patients with indeterminate and cardiac clinical forms of Chagas disease.

Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8(+) T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.

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.

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.

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.

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.

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

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.

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.

Acute and subacute hemodynamic responses and perception of effort in subjects with chronic Chagas cardiomyopathy submitted to different protocols of inspiratory muscle training: a cross-over trial.

PURPOSE: This study aimed to evaluate acute and subacute hemodynamic responses and perception of effort in individuals with CCC submitted to different IMT protocols. MATERIALS AND METHODS: This was a randomized cross-over trial conducted on CCC subjects with systolic left ventricular dysfunction (<45% left ventricular ejection fraction) without or with heart failure (stages B2 and C, respectively). Twenty-one participants performed two IMT protocols, one targeting 60% maximal inspiratory pressure with 3 × 10 repetitions (MIP60) and the other targeting 30% maximal inspiratory pressure (MIP30) with 3 × 20 repetitions with a 2 min recovery between sets for both. MIP60 and MIP30 were performed on the same day with a 2 h washout period. Measurements were taken at baseline, during and 60 min after IMT. RESULTS: No differences in hemodynamic variables were observed across protocols. The perception of effort increased in both protocols, with higher scores for the MIP30 protocol (ß = +1.6, p = 0.01; ß = +1.1, p = 0.02; ß = +0.9, p = 0.08 for the 1st, 2nd and 3rd sets, respectively). CONCLUSIONS: There were no differences in hemodynamic responses comparing MIP60 and MIP30 protocols in subjects with CCC. Despite the higher perception of effort during endurance protocol, both protocols can be considered a safe therapeutic strategy.IMPLICATIONS FOR REHABILITATIONDespite inspiratory muscle training may result in functional capacity improvements, no previous study evaluated the hemodynamic acute and subacute responses to inspiratory muscle training in chronic Chagas cardiomyopathy.The two inspiratory muscle training protocols (30% and 60% of maximal inspiratory pressure) did not cause significant hemodynamic repercussions in subjects with chronic Chagas cardiomyopathy.Inspiratory muscle training seems to be an effective strategy to improve functional capacity and can be implemented in the rehabilitation programs for patients with Chagas cardiomyopathy.Since no significant adverse responses were observed in any of the hemodynamic parameters during the inspiratory muscle training sessions, these two protocols of inspiratory muscle training (30% and 60% of maximal inspiratory pressure) seems to be safe in subjects with Chagas cardiomyopathy.

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.

Impact of COVID-19 In-hospital Mortality in Chagas Disease Patients.

The COVID-19 virus infection caused by the new SARS-CoV-2 was first identified in Rio de Janeiro (RJ), Brazil, in March 2020. Until the end of 2021, 504,399 COVID-19 cases were confirmed in RJ, and the total death toll reached 68,347. The Evandro Chagas National Institute of Infectious Diseases from Oswaldo Cruz Foundation (INI-Fiocruz) is a referral center for treatment and research of several infectious diseases, including COVID-19 and Chagas disease (CD). The present study aimed to evaluate the impact of COVID-19 on in-hospital mortality of patients with CD during the COVID-19 pandemic period. This observational, retrospective, longitudinal study evaluated all patients with CD hospitalized at INI-Fiocruz from May 1, 2020, to November 30, 2021. One hundred ten hospitalizations from 81 patients with CD (58% women; 68 ± 11 years) were evaluated. Death was the study's main outcome, which occurred in 20 cases. The mixed-effects logistic regression was performed with the following variables to test whether patients admitted to the hospital with a COVID-19 diagnosis would be more likely to die than those admitted with other diagnoses: admission diagnosis, sex, age, COVID-19 vaccination status, CD clinical classification, and the number of comorbidities. Results from multiple logistic regression analysis showed a higher risk of in-hospital mortality in patients diagnosed with COVID-19 (OR 6.37; 95% CI 1.78-22.86) compared to other causes of admissions. In conclusion, COVID-19 infection had a significant impact on the mortality risk of INI-Fiocruz CD patients, accounting for one-third of deaths overall. COVID-19 presented the highest percentage of death significantly higher than those admitted due to other causes during the COVID-19 pandemic.