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.

A cardiac rehabilitation exercise program potentially inhibits progressive inflammation in patients with severe Chagas cardiomyopathy: A pilot single-arm clinical trial.

BACKGROUND: Cardiac rehabilitation exerts anti-inflammatory effect on several cardiovascular diseases; however, these effects were not described for Chagas cardiomyopathy, which is associated with pro-inflammatory imbalance. MATERIALS AND METHODS: Ten patients with severe Chagas cardiomyopathy performed 8 months of exercise training in a cardiac rehabilitation program. Interleukin-1 beta (IL-1ß), IL-8, IL-10, interferon gamma (IF-γ), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) serum levels were measured using enzyme-linked immunosorbent assay at baseline, 4, and 8 months. The influence of exercise on cytokine levels was evaluated using the one-way analysis of variance for repeated measurements, with Bonferroni posttest for multiple comparisons. RESULTS: Levels of pro-inflammatory (TNF-α, IL-1ß, IL-8, IF-γ, and (MCP-1) and anti-inflammatory (IL-10) cytokines did not vary significantly during the observation period. CONCLUSION: Exercise may benefit patients with severe Chagas cardiomyopathy by curbing the production of pro-inflammatory cytokines in this disease characterized by a continuous state of inflammation.

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.

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.

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.

Chagas heart disease: An overview of diagnosis, manifestations, treatment, and care.

Chagas heart disease (CHD) affects approximately 30% of patients chronically infected with the protozoa Trypanosoma cruzi. CHD is classified into four stages of increasing severity according to electrocardiographic, echocardiographic, and clinical criteria. CHD presents with a myriad of clinical manifestations, but its main complications are sudden cardiac death, heart failure, and stroke. Importantly, CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies, and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies. Among patients with CHD, approximately 90% of deaths can be attributed to complications of Chagas disease. Sudden cardiac death is the most common cause of death (55%-60%), followed by heart failure (25%-30%) and stroke (10%-15%). The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with. Therefore, the management of CHD is challenging, and in this review, we present the most updated available data to help clinicians and cardiologists in the care of these patients. We describe the clinical manifestations, diagnosis and classification criteria, risk stratification, and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.

Relationship between Dietary Fatty Acid Intake with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in People with HIV.

We aimed to evaluate the relationship between food intake of lipids with nonalcoholic fatty liver disease (NAFLD) and/or liver fibrosis in people living with HIV/AIDS (PLWHA). In this cross-sectional study, transient elastography was used to detect the presence of NAFLD and/or liver fibrosis. The dietary intake of fats and fatty acids (FA) were assessed by two 24 h dietary recalls (24-HDR) (n = 451). Multivariate logistic regression models were performed. Participants with higher intake of total fat were associated with higher odds for NAFLD compared to those with lower consumption [adjusted odds ratio (aOR) = 1.91 (95% confidence interval (95% CI) 1.06-3.44)]. Furthermore, participants with intermediate intake of n6-PUFA (n6-poly-unsaturated FA) and lauric FA had lower odds for NAFLD, respectively aOR = 0.54 (95% CI 0.3-0.98) and aOR = 0.42 (95% CI 0.22-0.78). Additionally, a higher intake of myristoleic FA (fourth quartile) was a significant protective factor for NAFLD [aOR = 0.56 (95% CI 0.32-0.99)]. Participants with higher intake of lauric FA [0.38 (95% CI 0.18-0.80)], myristic FA [0.38 (0.17-0.89)], palmitoleic FA [0.40 (0.19-0.82)] and oleic FA [0.35 (0.16-0.79)] had positively less odds of having liver fibrosis. On the other hand, higher intake of n-6 PUFA was significantly associated with fibrosis [aOR = 2.45 (95% CI 1.12-5.32)]. Dietary assessment of total fat and FA should be incorporated into HIV care as a tool for preventing NAFLD and fibrosis in PLWHA.

Prevalence of metabolic syndrome and associated factors among patients with chronic Chagas disease.

The increase in life expectancy and the migration of individuals with Chagas disease (ChD) from rural to urban centers exposes them to the development of chronic-degenerative abnormalities that may increase the prevalence of metabolic syndrome (MetS). The present study aimed to identify the prevalence of MetS and its components in individuals with chronic ChD. This is a cross-sectional study with 361 patients of both sexes, aging >18 years, followed at a national reference center (Rio de Janeiro, Brazil). MetS diagnosis followed the International Diabetes Federation 2005 criteria. The association between the variables was determined through logistic regression models. The mean age was and 60.7±10.8 years. About half (56.2%) were female and the majority self-reported their race as mulatto (59.8%). The percentage of individuals with MetS was 40.4%. The variables independently associated with MetS were age (OR 1.06; 95%CI 1.04-1.09), high education levels (OR 0.36; 95%CI 0.17-0.79) and cardiac form with heart failure (OR 0.34; 95%CI 0.17-0.68). Therefore, a high prevalence of MetS was found in this Brazilian chronic ChD cohort. The identification of the associated factors can facilitate the development of effective approaches for preventing and managing MetS in ChD patients.

Effect of Physical Exercise Training in Patients With Chagas Heart Disease (from the PEACH STUDY).

Chagas heart disease (HD) is a chronic fibrosing myocarditis with high mortality. The PEACH study aimed to evaluate if exercise training can improve the functional capacity of Chagas HD patients with left ventricular dysfunction and/or heart failure. The PEACH study was a single center, parallel-group, clinical trial that randomized 30 clinical stable Chagas HD patients with left ventricular ejection fraction <45% or heart failure symptoms to either supervised exercise training 3 times/week for 6 months or a control group. Both groups had the same monthly pharmaceutical and nutritional counseling and usual care. Primary end point was functional capacity assessed by peak exercise oxygen consumption (peak VO2) obtained by cardiopulmonary exercise test. Secondary end points included other cardiopulmonary exercise test variables, cardiac function by echocardiography, body composition, muscle respiratory strength, and metabolic biomarkers. Peak VO2 increased among patients in exercise group from 17.60 ± 4.65 mlO2 kg-1 min-1 to 19.40 ± 5.51 mlO2 kg-1 min-1 while decreased in controls from 15.40 ± 6.30 mlO2 kg-1 min-1 to 12.96 ± 4.50 mlO2 kg-1 min-1, resulting in significant difference in change in peak VO2 between groups after 6 months (ß = +4.6, p = 0.004). There were significant differences between groups in changes in anaerobic threshold (ß = 3.7, p = 0.05), peak oxygen pulse (ß = +2.7, p = 0.032) and maximum minute ventilation (ß = +13.9, p < 0.0001) after 6 months of intervention. In conclusion, exercise training improved functional capacity of chronic Chagas HD patients with left ventricular dysfunction and/or heart failure.

Predictive factors associated with liver fibrosis and steatosis by transient elastography in patients with HIV mono-infection under long-term combined antiretroviral therapy.

INTRODUCTION: Non-alcoholic fatty liver disease is characterized by the presence of hepatic steatosis and can be associated with fibrosis progression, development of cirrhosis and liver-related complications. Data on the prevalence of liver fibrosis and steatosis in HIV patients remain contradictory in resource-limited settings. We aimed to describe the prevalence and factors associated with liver fibrosis and steatosis in patients with HIV mono-infection under long-term antiretroviral therapy (ART) in Rio de Janeiro, Brazil. METHODS: Clinical assessment, fasting blood collection and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by transient elastography were performed on the same day for this cross-sectional study (PROSPEC-HIV study; NCT02542020). Patients with viral hepatitis co-infection, ART-naïve or missing data were excluded. Liver fibrosis and steatosis were defined by LSM ≥ 8.0 kPa and CAP ≥ 248 dB/m respectively. HIV history, cumulative and current ART regimens were evaluated. Multivariate logistic regression models adjusted for age and gender were performed. RESULTS: In total, 395 patients (60% female; median age of 45 (IQR, 35 to 52) years, body mass index = 25.7 (23.2 to 29.4) kg/m2 , alanine aminotransferase = 30 (23 to 42) IU/L, duration of ART for 7 (4 to 14) years) were included. LSM and CAP were reliable in 93% (n = 367) and 87% (n = 344) respectively. The prevalence of fibrosis and steatosis were 9% (95% confidence interval (CI), 7 to 13) and 35% (95% CI, 30 to 40) respectively. The following factors were associated with fibrosis (odds ratio (OR) (95% CI)): older age (per 10 years; 1.80 (1.27 to 2.55); p = 0.001) and CD4+ count <200 cells/mm3 (7.80 (2.09 to 29.09), p = 0.002). Type 2 diabetes had a trend towards the presence of liver fibrosis (2.67 (0.96 to 7.46), p = 0.061). Central obesity (10.74 (4.40 to 26.20), p < 0.001), type 2 diabetes (9.74 (3.15 to 30.10), p < 0.001), dyslipidaemia (2.61 (1.35 to 5.05), p = 0.003) and metabolic syndrome (4.28 (2.45 to 7.46), p < 0.001) were associated with steatosis. A dominant backbone ART regimen of zidovudine (AZT), d4T, ddI or ddC was associated with steatosis (1.90 (1.07 to 3.38), p = 0.028) independently of metabolic features. CONCLUSION: Integrated strategies for preventing non-communicable diseases in people with HIV mono-infection are necessary to decrease the burden of liver diseases. Clinical Trial Number: NCT02542020.

A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC) trial.

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.