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.

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

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 (ß= +5.7; p=0.003), role-physical (ß= +1.9; p=0.03), and bodily pain (ß= +3.5; p=0.02) scores. Moreover, the summary physical health score (ß= +1.4; p=0.001) improved. CONCLUSION:: The cardiac rehabilitation program significantly improved the physical quality of life of patients with Chagas heart failure.

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.

Effect of physical exercise training in patients with Chagas heart disease: study protocol for a randomized controlled trial (PEACH study).

BACKGROUND: The effects of exercise training on Chagas heart disease are still unclear. This study aimed to evaluate the effect of exercise training over functional capacity, cardiac function, quality of life, and biomarkers in Chagas heart disease. METHODS: The PEACH study is a superiority randomized clinical trial which will include subjects who meet the following criteria: Chagas heart disease with a left ventricular ejection fraction below 45 % with or without heart failure symptoms; clinical stability in the last 3 months; adherence to clinical treatment; and age above 18 years. The exclusion criteria are: pregnancy; neuromuscular limitations; smoking; evidence of non-chagasic heart disease; systemic conditions that limit exercise practice or cardiopulmonary exercise test; unavailability to attend the center three times a week during the intervention period; and practitioners of regular exercise. The intervention group will perform an exercise training intervention three times per week during 6 months and will be compared to the control group without exercise. Both groups will undergo the same monthly pharmaceutical and nutritional counseling as well as standard medical treatment according to the Brazilian consensus on Chagas disease. The primary outcome is functional capacity based on peak exercise oxygen consumption during cardiopulmonary exercise testing. Secondary outcomes are: cardiac function; body composition; muscle respiratory strength; microvascular reactivity; cardiac rhythm abnormalities; autonomic function; biochemical; oxidative stress and inflammatory biomarkers; and quality of life. Subjects will be evaluated at baseline, and at 3 and 6 months after randomization. Thirty patients will be randomly assigned into exercise or control groups at a ratio of 1:1. DISCUSSION: Findings of the present study will be useful to determine if physical exercise programs should be included as an important additional therapy in the treatment of patients with Chagas heart disease. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02517632 (registered on 6 August 2015).

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

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.

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.

Defective nitric oxide-cyclic guanosine monophosphate signaling in patients with bipolar disorder: a potential role for platelet dysfunction.

OBJECTIVE: Bipolar disorder (BD) is associated with elevated cardiovascular mortality rates. We investigated the modulation of l-arginine-nitric oxide (NO) signaling in platelets from patients with BD at different phases. METHODS: Platelets obtained from 28 patients with BD and 10 healthy volunteers were analyzed for l-arginine transport, NO synthase (NOS) activity, cyclic guanosine monophosphate content, and biomarkers of oxidative stress. Expressions of NOS isoforms, soluble guanylyl cyclase, and arginase were also measured in platelets. Amino acid and C-reactive protein levels in plasma were assessed. RESULTS: Plasma concentrations of l-arginine (mean [M] ± standard error of the mean [SEM] = 97 ± 10 versus 121 ± 10 µM) and its transport into platelets (median [interquartile range] = 26.0 [28.6] versus 26.5 [43.9] pmol/10(9) cells per minute) did not differ between patients with BD and controls (p > .05). Patients with BD showed reduced NOS activity (M ± SEM = 0.037 ± 0.003 versus 0.135 ± 0.022 pmol/10(8) cells, p < .001), but not endothelial NOS, inducible NOS, and arginase expression, compared with controls (p > .05). Cyclic guanosine monophosphate content was reduced (M ± SEM = 0.022 ± 0.003 versus 0.086 ± 0.020 pmol/10(8) cells, p < .05) despite the absence of changes in soluble guanylyl cyclase expression (median [interquartile range] = 21.6 [15.5] versus 9.5 [9.4] arbitrary units, p > .05) in patients with BD. Superoxide dismutase activity, but not catalase activity, was increased in patients with BD in the manic phase (M ± SEM = 2094 ± 335 versus 172 ± 17 U/mg protein, p < .001). C-reactive protein was elevated only in manic episodes (M ± SEM = 0.8 ± 0.2 versus 0.1 ± 0.02 mg/L, p < .001). CONCLUSIONS: Impaired NO generation from platelets, inflammation, and oxidative stress may play pivotal roles in the multifaceted process of cardiovascular events in BD.

Low plasma levels of L-arginine, impaired intraplatelet nitric oxide and platelet hyperaggregability: implications for cardiovascular disease in depressive patients.

BACKGROUND: Major depression (MD) is an independent cardiovascular risk factor, but the exact mechanisms are not clear. In this study we have investigated the intraplatelet L-arginine-nitric oxide (NO) pathway and platelet function in depressive patients. METHODS: Nineteen unmedicated patients with MD (34±4years) and 19 control subjects (CS, 34±3years) were included. L-[(3)H]-arginine influx, NO synthase (NOS) activity and intracellular cGMP levels were evaluated in platelets, as well as the expression of eNOS, iNOS, arginase and soluble guanylate cyclase (sGC), platelet aggregation and the systemic amino acid profile in MD patients and CS. RESULTS: L-arginine influx (pmol/10(9)cells/min) in platelets was reduced from 46.2±9.5 to 20.02±2.12 in depression. NOS activity (pmol/10(8) cells) was diminished in MD patients (0.09±0.01) compared to CS (0.17±0.01). Intracellular cGMP levels were also impaired in MD patients associated with hyperaggregability. Moreover, the concentration of plasma L-arginine was reduced by 20% in MD patients. The expression of eNOS, iNOS, arginase II and sGC in platelet lysates was not affected by MD. LIMITATIONS: Small number of patients in the study. CONCLUSIONS: This study has demonstrated an impairment of L-arginine-NO signaling in platelets from MD patients, suggesting a role in platelet activation and cardiovascular events.

A via L-arginina-óxido nítrico no transtorno depressivo e sua associação com a função plaquetária e o estresse oxidativo / L-arginine-nitric oxide pathway in depressive disorder associate with platelet function and oxidative stress

O transtorno depressivo (TD) é um fator de risco cardiovascular independente que apresenta elevada morbi-mortalidade. Recentes evidências sugerem a participação do óxido nítrico (NO), potente vasodilatador e anti-agregante plaquetário, na patogênese de doenças cardiovasculares e psiquiátricas. A síntese do NO ocorre através da conversão do aminoácido L-arginina em L-citrulina e NO, pela ação da enzima NO sintase (NOS). Esta tese aborda o papel da via L-arginina-NO em plaquetas de pacientes com TD e sua associação com a função plaquetária e estresse oxidativo. Para análise comportamental da depressão em modelo animal, foi utilizado o modelo de estresse pós-natal de separação única (SMU). Os animais foram divididos em quatro grupos para a realização do estudo: Grupo Controle Sedentário (GCS), Grupo Controle Exercício (GCE), Grupo SMU Sedentário (SMUS) e Grupo SMU Exercício (SMUE). O treinamento físico (TF) dos animais englobou 8 semanas, com duração de 30 minutos e uma velocidade de treinamento estabelecida pelo teste máximo (TE). Para o estudo em humanos, 10 pacientes com TD com score Hamilton: 20+-1, (média de idade: 38+-4anos), foram pareados com 10 indivíduos saudáveis (média de idade: 38+-3anos). Os estudos em humanos e animais foram aprovados pelos Comitês de Ética: 1436 - CEP/HUPE e CEUA/047/2010, respectivamente. Foi mensurado em humanos e em animais: transporte de L-arginina, concentração GMPc, atividade das enzimas NOS e superóxido dismutase (SOD) em plaquetas e cortisol sistêmico. Experimentos realizados somente em humanos: expressão das enzimas NOS, arginase e guanilato ciclase através de Western Blotting. A agregação plaquetária foi induzida por colágeno e foi realizada análise sistêmica de proteína C-reativa, fibrinogênio e L-arginina. Para o tratamento estatístico utilizou-se três testes estatísticos para avaliar as diferenças das curvas de sobrevida: Kaplan-Meier, e os testes de Tarone-Ware e Peto-Prentice. Em humanos, houve uma redução...

Major depressive disorder (MDD) is an independent cardiovascular risk factor that presents high morbimortality. Recent evidence suggests the involvement of nitric oxide (NO), a potent vasodilator and anti-aggregating effect, in the pathogenesis of cardiovascular and psychiatric diseases. Nitric oxide (NO) is synthesized through conversion of the amino acid L-arginine into L-citrulline and NO by the enzyme NO synthase (NOS). This thesis addresses the role of the L-arginine-NO pathway in platelets from patients with MDD and its association with platelet function and oxidative stress. For a behavioural analysis of depression in an animal model, we used the single maternal separation (SMS) model, where the offspring was separated from its mother for eight minutes. The animals were divided into four groups for the study: Sedentary Control Group (SCG), Exercise Control Group (ECG), SMS Sedentary Group (SSMS) and SMS Exercise Group (ESMS). Physical training (PT) of the animals took 8 weeks, with a duration of 30 minutes and a training speed established by the maximum test (ET) of 14m/min. For the human study, there were ten MDD patients with Hamilton score: 20+-1 (mean age: 38+-4 years) and 10 healthy subjects (mean age: 38+-3 years). The human and animal studies were approved by the Ethics Committee: 1436 - CEP/HUPE and CEUA/047/2010 respectively. The following were measured in human and animal models: L-arginine transport, NOS and superoxide dismutase (SOD) activities, cGMP concentration and analysis of systemic cortisol. Experiments performed only in humans: NOS, arginase and guanylate cyclae expression evaluated by Western Blotting. Platelet aggregation was induced by collagen, and C-reactive protein, fibrinogen, and L-arginine were systemically analyzed. For statistical treatment, three statistical tests were used to evaluate the differences in survival curves: Kaplan-Meier, and the Tarone-Ware and Peto-Prentice tests. In humans, there was a reduction...

[Maximal heart rate in exercise tests on treadmill and in a cycloergometer of lower limbs]. / Freqüência cardíaca máxima em testes de exercício em esteira rolante e em cicloergômetro de membros inferiores.

OBJECTIVE: To compare, retrospectively, the values of maximum heart rate (MHR) and the decrease of the heart rate at the first minute of recovery, which were obtained in an exercise test (ET) performed in two different ergometers and at different moments. METHODS: Sixty individuals (from 29 to 80 years old), submitted to cardiopulmonary ET in a cycle of lower limbs (CLL) in our laboratory and who had previous ET (up to 36 months) in a treadmill (TRM) in other laboratories, under identical conditions of medications of negative chronotropic action. RESULTS: MHR was similar in CLL: 156 +/- 3 and TRM: 154 +/- 2 bpm (p=0.125), whereas dHR was higher in CLL: 33 +/- 2, EST: 26 +/- 3 bpm (mean +/- standard error of the mean) (p<0.001). In hemodynamic variables studied, the systolic blood pressure and the double product were higher in the ET-CLL (p<0.001). The electrocardiogram (ECG) was similar in both ETs, except due to more frequent supraventricular arrhythmias in CLL. CONCLUSION: a) With some diligence from the examiner and previous knowledge of MHR in a previous ET it is possible to obtain high levels of MHR in an ET-CLL; b) interrupting the MHR-based ET forecast through equations tends to lead to sub-maximum efforts; c) dHR differs in active and passive recoveries; d) new ways to analyze the HR behavior under exercise, which is not only the value of MHR, are necessary to characterize an ET as maximum.

[Home exercise program: short term effects on physical aptitude and blood pressure in hypertensive individuals]. / Programa domiciliar de exercícios: efeitos de curto prazo sobre a aptidão física e pressão arterial de indivíduos hipertensos.

OBJECTIVE: To observe the influence of a four-month-unsupervised-exercise program performed at home on the blood pressure (BP) and physical performance in hypertensive adults. METHODS: A target group with 26 men and 52 women, and a control group with 9 men and 7 women were observed, with ages ranging from 25 to 77 years old. The target group underwent a home exercise program, basically with aerobic activity (60-80% of the estimated maximum heart rate for the age, 30 min of walking at least 3 times a week), in addition to the flexibility exercises. Guidelines on the control chart and variables that could influence the treatment were given at each assessment. Patients were followed-up for four months, with assessments every 2 months observing: BP at rest; body weight, waist-hip ratio (W/HR), body fat percentage (%F), sum of skinfold measurements (SM) and central-peripheral skinfold ratio (C/P); trunk flexibility (TF); heart rate and workload ratio during submaximal test in cycle ergometer (HR/W), represented by the regression curve inclination between both (a). RESULTS: The target group demonstrated significant alterations in weight (-3.7 kg), WHR (-0.03), SM (-12 mm), %F (-4.4%), TF (+2.3 cm), HR/W (-0.02) and BP (-6 and -9 mmHg for systolic and diastolic pressure respectively). The control group presented small weight alterations (+1.3 Kg) and %F (+1.7%). CONCLUSION: Unsupervised exercise home programs, even in short term, may present positive effects on the blood pressure and physical performance in hypertensive individuals.

Freqüência cardíaca máxima em testes de exercício em esteira rolante e em cicloergômetro de membros inferiores / Maximal heart rate in exercise tests on treadmill and in a cycloergometer of lower limbs

OBJETIVO: Comparar, retrospectivamente, os valores de freqüência cardíaca máxima (FCM) e o descenso da freqüência cardíaca no primeiro minuto da recuperacão (dFC), obtidos em teste de exercício (TE) realizados em dois ergômetros e momentos distintos. MÉTODOS: Sessenta indivíduos (29 a 80 anos de idade), submetidos a TE cardiopulmonar em ciclo de membros inferiores (CMI) em nosso laboratório e que possuíam TE prévio (até 36 meses) em esteira (EST) em outros laboratórios, nas condicões idênticas de medicacões de acão cronotrópica negativa. RESULTADOS: FCM foi semelhante no CMI: 156n3 e EST: 154n2 bpm (p=0,125), enquanto o dFC foi maior em CMI: 33n2, EST: 26n3 bpm (média n erro padrão da média) (p<0,001). Nas variáveis hemodinâmicas estudadas, a pressão arterial sistólica e o duplo produto foram maiores no TE-CMI (p<0,001). O eletrocardiograma (ECG) foi semelhante nos dois TEs, exceto por arritmias supraventriculares mais freqüentes no CMI. CONCLUSAO: a) É possível, com empenho do examinador e conhecimento prévio do resultado de FCM em um TE anterior, obter níveis altos de FCM em um TE-CMI; b) interromper o TE baseado em FCM prevista por equacões tende a levar a esforcos submáximos; c) o dFC difere nas recuperacões ativa e passiva; d) novas formas de analisar o comportamento da FC no exercício, que não apenas o valor da FCM, são necessárias para caracterizar um TE como máximo.

Programa domiciliar de exercícios: efeitos de curto prazo sobre a aptidão física e pressão arterial de indivíduos hipertensos / Home exercise program: short term effects on physical aptitude and blood pressure in hypertensive individuals

OBJETIVO: Observar a influência de quatro meses de um programa domiciliar não-supervisionado de exercícios sobre a pressão arterial (PA) e aptidão física em hipertensos. MÉTODOS: Foram observados um grupo experimental com 26 homens e 52 mulheres e um grupo controle, com 9 homens e 7 mulheres, com idades entre 25 e 77 anos. O grupo experimental submeteu-se a um programa domiciliar de exercícios, com atividades aeróbias (60-80 por cento da FC máxima para a idade, 30min de caminhadas no mínimo três vezes por semana), exercícios de flexibilidade. Orientacões sobre a ficha de controle e o treinamento eram dadas a cada reavaliacão. Foram acompanhados por quatro meses, com reavaliacões a cada dois meses, observando-se: PA em repouso; peso corporal, relacão cintura-quadril (RCQ), percentual de gordura ( por centoG), somatório de dobras cutâneas (SOMD) e relacão central e periférica de dobras (P/C); flexibilidade de tronco (FX); relacão entre freqüência cardíaca e carga de trabalho durante teste submáximo em ciclo-ergômetro (FC/W), traduzida pela inclinacão da curva de regressão entre ambas (a). RESULTADOS: O grupo experimental exibiu alteracões significativas para o peso (-3,7 kg), RCQ (-0,03), SOMD (-12 mm), por centoG (-4,4 por cento), FX (+2,3 cm), FC/W (-0,02) e PA (-6 e -9 mmHg para pressão sistólica e diastólica, respectivamente). O grupo controle teve pequenas alteracões no peso (+1,3 Kg) e por centoG (+1,7 por cento). CONCLUSAO: Programas domiciliares não supervisionados de exercícios, podem exercer efeito positivo sobre a PA e aptidão física de hipertensos.