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.

The Association Between Physical Performance and Health-Related Quality of Life Based on the EQ-5D-3L Questionnaire in Patients With Chagas Disease.

OBJECTIVES: Chagas disease (CD) is a chronic disease to millions worldwide, and many patients develop heart disease. In addition, they are part of an aging population. These characteristics can be associated with a reduction in physical performance and health-related quality of life (HRQoL). This study evaluated HRQoL, and the relationship between physical performance and HRQoL in patients with chronic CD. METHODS: We used the 3-level version of EuroQol 5-dimensional questionnaire (EQ-5D-3L), with the visual analog scale (VAS). Physical performance was measured with 30-s chair-stand test (30sCST) and timed up and go test (TUGT). RESULTS: Sixty-three patients were evaluated. The majority were women (68.2%) aged 67.7 ± 9.7 years. Overall EQ-5D-3L utility index was 0.65 ± 0.28, and VAS score was 68.4 ± 25.1. Most patients with intermediate and high performance in 30sCST referred no problems in the domains "mobility," "usual activities," and "pain/feeling ill" (P < .001, P = .01, and P = .025, respectively). In a similar way, most patients with intermediate and high performance in TUGT referred no problems in "mobility" (P < .0001) and "usual activities" (P = .001). Higher performance in both tests was associated with higher overall EQ-5D-3L utility and VAS scores. HRQoL measured by EQ-5D-3L was associated with physical status in a cohort of patients with chronic CD. The results underscore the contribution of physical performance, measured by 2 inexpensive and safe physical tests, to HRQoL in these patients. CONCLUSION: Strategies aiming the improvement of HRQoL in patients with CD may focus on mobility skills and force. Future studies evaluating interventions in physical performance should be a priority in these patients.

The Association Between Physical Performance and Health-Related Quality of Life Based on the EuroQol 5-Dimensional Questionnaire in Patients With Chagas Disease.

OBJECTIVES: Chagas disease (CD) is a chronic disease to millions worldwide, and many patients develop heart disease. In addition, they are part of an aging population. These characteristics can be associated with a reduction in physical performance and health-related quality of life (HRQoL). This study evaluated HRQoL, and the relationship between physical performance and HRQoL in patients with chronic CD. METHODS: We used the 3-level version of EuroQol 5-dimensional questionnaire (EQ-5D-3L), with the visual analog scale (VAS). Physical performance was measured with 30-s chair-stand test (30sCST) and timed up and go test (TUGT). RESULTS: Sixty-three patients were evaluated. The majority were women (68.2%) aged 67.7 ± 9.7 years. Overall EQ-5D-3L utility index was 0.65 ± 0.28, and VAS score was 68.4 ± 25.1. Most patients with intermediate and high performance in 30sCST referred no problems in the domains "mobility," "usual activities," and "pain/feeling ill" (P < .001, P = .01, and P = .025, respectively). In a similar way, most patients with intermediate and high performance in TUGT referred no problems in "mobility" (P < .0001) and "usual activities" (P = .001). Higher performance in both tests was associated with higher overall EQ-5D-3L utility and VAS scores. HRQoL measured by EQ-5D-3L was associated with physical status in a cohort of patients with chronic CD. The results underscore the contribution of physical performance, measured by 2 inexpensive and safe physical tests, to HRQoL in these patients. CONCLUSION: Strategies aiming the improvement of HRQoL in patients with CD may focus on mobility skills and force. Future studies evaluating interventions in physical performance should be a priority in these patients.

Systemic microvascular endothelial dysfunction is associated with left ventricular ejection fraction reduction in chronic Chagas disease patients.

OBJECTIVE: This study compares microvascular reactivity (MR) in chronic Chagas disease (CD) patients with healthy individuals, matched for sex and age. In addition, we evaluated the association between MR and left ventricular ejection fraction (LVEF) in patients. METHODS: Acetylcholine iontophoresis was performed on the forearm skin, using laser speckle contrast imaging, to evaluate endothelium-dependent vasodilation. Clinical data were obtained from medical records. RESULTS: Thirty-six patients were compared to 25 healthy individuals (controls). Vasodilation was higher in controls, when compared to patients (p < .0001). There was a significant association between LVEF, stratified into quartiles, and MR (p-value for linear trend = .002). In addition, there was no difference in MR between patients with normal LVEF and the control group. In patients, MR was independent of the presence of arterial hypertension or diabetes. CONCLUSIONS: We have shown for the first time that the reduction of MR is associated with a decrease of LVEF in a cohort of chronic CD patients. The results were not affected by comorbidities, such as hypertension or diabetes. The evaluation of systemic endothelial function may be useful to tailor therapeutic and preventive approaches, targeted at systolic left ventricular failure associated with chronic CD cardiomyopathy.

COVID-19 and Microvascular Disease: Pathophysiology of SARS-CoV-2 Infection With Focus on the Renin-Angiotensin System.

The recently described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people, with thousands of fatalities. It has prompted global efforts in research, with focus on the pathophysiology of coronavirus disease-19 (COVID-19), and a rapid surge of publications. COVID-19 has been associated with a myriad of clinical manifestations, including the lungs, heart, kidneys, central nervous system, gastrointestinal system, skin, and blood coagulation abnormalities. The endothelium plays a key role in organ dysfunction associated with severe infection, and current data suggest that it is also involved in SARS-CoV-2-induced sepsis. This critical review aimed to address a possible unifying mechanism underlying the diverse complications of COVID-19: microvascular dysfunction, with emphasis on the renin-angiotensin system. In addition, research perspectives are suggested in order to expand understanding of the pathophysiology of the infection.

Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients.

BACKGROUND: Diabetes mellitus patients (DM) have more severe progression of atherosclerotic disease than non-diabetic (NDM) individuals. In situ inflammation and oxidative stress are key points in the pathophysiology of atherosclerosis, a concept largely based on animal model research. There are few studies comparing inflammation and oxidative stress parameters in medium-sized arteries between DM and NDM patients. A fragment of the internal mammary artery used in coronary artery bypass grafting (CABG) will be employed for this purpose OBJECTIVE: To assess the expression of inflammatory markers tumor necrosis factor-α, transforming growth factor-ß1, nuclear factor kappa B, the enzymes superoxide dismutase, and catalase in the vascular wall of the arterial graft used in CABG, comparing DM and NDM patients RESULTS: The present study will add information to the vascular degenerative processes occurring in diabetic patients.

Transcatheter Aortic Valve Replacement: The Experience of One Brazilian Health Care Center.

OBJECTIVE: Transcatheter aortic valve replacement has been an alternative to invasive treatment for symptomatic severe aortic stenosis in high risk patients. The primary endpoint was 30-day and 1-year mortality from any cause. Secondary endpoints were to compare the clinical and echocardiographic variation pre-and post- transcatheter aortic valve replacement, and the occurrence of complications throughout a 4-year follow-up period. METHODS: This prospective cohort, nestled to a multicenter study (Registro Brasileiro de Implante de Bioprótese por Cateter), describes the experience of a public tertiary center in transcatheter aortic valve replacement. All patients who underwent this procedure between October 2011 and February 2016 were included. RESULTS: Fifty-eight patients underwent transcatheter aortic valve replacement. The 30-day all-cause mortality was 5.2% (n=3) and after 1 year was 17.2% (n=10). A significant improvement in New York Heart Association functional classification was observed when comparing pre-and post- transcatheter aortic valve replacement (III or IV 84.4% versus 5.8%; P<0.001). A decline in peak was observed (P<0.001) and mean (P<0.001) systolic transaortic gradient. The results of peak and mean post-implant transaortic gradient were sustained after one year (P=0.29 and P=0.36, respectively). Left ventricular ejection fraction did not change significantly during follow-up (P=0.41). The most frequent complications were bleeding (28.9%), the need for permanent pacemaker (27.6%) and acute renal injury (20.6%). CONCLUSION: Mortality and complications in this study were consistent with worldwide experience. Transcatheter aortic valve replacement had positive clinical and hemodynamic results, when comparing pre-and post-procedure, and the hemodynamic profile of the prosthesis was sustained throughout follow-up.

Transcatheter aortic valve replacement: the experience of one brazilian health care center

Abstract Objective: Transcatheter aortic valve replacement has been an alternative to invasive treatment for symptomatic severe aortic stenosis in high risk patients. The primary endpoint was 30-day and 1-year mortality from any cause. Secondary endpoints were to compare the clinical and echocardiographic variation pre-and post- transcatheter aortic valve replacement, and the occurrence of complications throughout a 4-year follow-up period. Methods: This prospective cohort, nestled to a multicenter study (Registro Brasileiro de Implante de Bioprótese por Cateter), describes the experience of a public tertiary center in transcatheter aortic valve replacement. All patients who underwent this procedure between October 2011 and February 2016 were included. Results: Fifty-eight patients underwent transcatheter aortic valve replacement. The 30-day all-cause mortality was 5.2% (n=3) and after 1 year was 17.2% (n=10). A significant improvement in New York Heart Association functional classification was observed when comparing pre-and post- transcatheter aortic valve replacement (III or IV 84.4% versus 5.8%; P<0.001). A decline in peak was observed (P<0.001) and mean (P<0.001) systolic transaortic gradient. The results of peak and mean post-implant transaortic gradient were sustained after one year (P=0.29 and P=0.36, respectively). Left ventricular ejection fraction did not change significantly during follow-up (P=0.41). The most frequent complications were bleeding (28.9%), the need for permanent pacemaker (27.6%) and acute renal injury (20.6%). Conclusion: Mortality and complications in this study were consistent with worldwide experience. Transcatheter aortic valve replacement had positive clinical and hemodynamic results, when comparing pre-and post-procedure, and the hemodynamic profile of the prosthesis was sustained throughout follow-up.

Angiotensin II, Aldosterone, and Anti-Inflammatory Lymphocytes: Interplay and Therapeutic Opportunities.

Inflammation is recognized as an important factor in the pathophysiology of hypertension, with the renin-angiotensin-aldosterone system (RAAS) playing a key role in the disease. Initially described because of its contribution to extracellular fluid and electrolyte homeostasis, the RAAS has been implicated in endothelial dysfunction, vascular remodeling, oxidative stress, proinflammatory cytokine production, and adhesion molecule synthesis by the vascular wall. Both angiotensin II and aldosterone are involved in these systemic effects, activating innate and adaptive immune responses. This paper highlights some aspects connecting RAAS to the hypertensive phenotype, based on experimental and clinical studies, with emphasis on new findings regarding the contribution of an increasingly studied population of T lymphocytes: the T-regulatory lymphocytes. These cells can suppress inflammation and may exert beneficial vascular effects in animal models of hypertension.

Vascular dysfunction as target organ damage in animal models of hypertension.

Endothelial dysfunction is one of the main characteristics of chronic hypertension and it is characterized by impaired nitric oxide (NO) bioactivity determined by increased levels of reactive oxygen species. Endothelial function is usually evaluated by measuring the vasodilation induced by the local NO production stimulated by external mechanical or pharmacological agent. These vascular reactivity tests may be carried out in different models of experimental hypertension such as NO-deficient rats, spontaneously hypertensive rats, salt-sensitive rats, and many others. Wire myograph and pressurized myograph are the principal methods used for vascular studies. Usually, increasing concentrations of the vasodilator acetylcholine are added in cumulative manner to perform endothelium-dependent concentration-response curves. Analysis of vascular mechanics is relevant to identify arterial stiffness. Both endothelial dysfunction and vascular stiffness have been shown to be associated with increased cardiovascular risk.

Efeitos cardiovasculares da transferência adotiva de linfócitos T reguladores em camundongos submetidos à infusão crônica de angiotensina II e de aldosterona / Cardiovascular effects of adoptive transfer of regulatory T lymphocytes in mice submitted to chronic infusion of angiotensin II and aldosterone

A angiotensina (Ang) II e aldosterona induzem hipertensão arterial por mecanismos em parte mediados pela imunidade adaptativa, envolvendo linfócitos T auxiliares respondedores (Tresp). Os linfócitos T reguladores (Treg) são capazes de suprimir os efeitos pró-inflamatórios do sistema imune. O presente estudo avaliou se a transferência adotiva de Treg é capaz de prevenir a hipertensão e a lesão vascular induzidas pela AngII ou pela aldosterona, em dois protocolos distintos. No protocolo com Ang II, camundongos machos C57BL/6 sofreram a injeção endovenosa de Treg ou Tresp, sendo depois infundidos com Ang II (1ug/kg/min), ou salina (grupo controle) por 14 dias. No protocolo com aldosterona, um outro conjunto de animais sofreu injeções de Treg ou Tresp, sendo depois infundido com aldosterona (600ug/kg/d) ou salina (grupo controle), pelo mesmo intervalo de tempo. O grupo tratado com aldosterona recebeu salina 1% na água. Tanto o grupo Ang II como aldosterona apresentaram elevação da pressão arterial sistólica (43% e 31% respectivamente), da atividade da NADPH oxidase na aorta (1,5 e 1,9 vezes, respectivamente) e no coração (1,8 e 2,4 vezes, respectivamente) e uma redução da resposta vasodilatadora à acetilcolina (de 70% e 56%, respectivamente), quando comparados com os respectivos controles (P<0,05). Adicionalmente, a administração de Ang II proporcionou um aumento rigidez vascular (P<0,001), na expressão de VCAM-1 nas artérias mesentéricas (P<0,05), na infiltração aórtica de macrófagos e linfócitos T (P<0,001) e nos níveis plasmáticos das citocinas inflamatórias interferon (INF)-y, interleucina (IL)-6, Tumor necrosis factor (TNF)-a e IL-10 (P<0,05). Ang II causou uma queda de 43% no número de células Foxp3+ no córtex renal, enquanto que a transferência adotiva de Treg aumentou as células Foxp3+ em duas vezes em comparação com o controle. A administração de Treg preveniu o remodelamento vascular induzido pela aldosterona, observado na relação média/lúmen...

Angiotensin (Ang) II and aldosterone (aldo) induce hypertension through mechanisms in part mediated by adaptive immunity and T responder lymphocytes. T regulatory (Treg) lymphocytes suppress pro-inflammatory mediators of the immune system. We questioned whether Treg adoptive transfer will blunt Ang II or aldo-induced hypertension and vascular injury, by evaluating two distinct protocols. In the Ang II protocol, male C57BL/6 mice were injected i.v. with Treg or T responder cells, and then infused with Ang II (1ug/kg/min) or saline, for 14 days. In the aldosterone protocol, another set of animals was injected with Treg or T responder cells, and then infused with aldosterone (600ug/kg/d) or saline, for the same period. The aldosterone group received saline 1% in drinking water. Both Ang II and aldosterone treated mice presented an increase in systolic blood pressure (43% and 31% respectively), of NADPH oxidase activity in aorta (1.5 and 1.9 fold, respectively) and heart (1.8 and 2.4 fold respectively) and an impaired vasodilatory response do acetylcholine (by 70% and 56% respectively), when compared to their controls (P<0.05). In addition, Ang II administration resulted in increased vascular stiffness (P<0.001), mesenteric artery vascular cell adhesion molecule (VCAM-1) expression (P<0.05), aortic macrophage and T cell infiltration (P<0.001), and the plasma levels of the inflammatory cytokines INF-y, IL-6, TNF-a, and IL-10 (P<0,05). And II caused a 43% decrease in the number of Foxp3+ cells in the renal cortex, while Treg adoptive transfer increased Foxp3+ cells 2-fold compared to control. Treg administration prevented aldosterone-induced vascular remodelling, as observed by media to lumen ratio and media cross sectional area analysis of mesenteric arteries (P<0,05). All the above were prevented by Treg but not by T responder cell adoptive transfer. These results demonstrate that Treg suppress Ang II of aldo-mediated vascular injury and BP elevation...

O que dizem as diretrizes brasileira, americana, europeia e canadense em relação às metas?: [revisão] / What do Brazilian, American, European and Canadian guidelines say with regardto blood pressure targets?: [review]

O objetivo do tratamento anti-hipertensivo é reduzir a morbidade e a mortalidade cardiovascular. Para isso, o principal é reduzir os níveis de pressão arterial. Entretanto, a abordagem dos fatores de risco e o controle das condições clínicas associadas também são necessários para definir a meta de pressão arterial a ser atingida. De maneira geral,as duas metas de pressão arterial reconhecidas por todas as diretrizes são abaixo de 140/90 mmHg para a população de hipertensos de baixo risco e abaixo de 130/80 mmHg para pacientes diabéticos ou com doença renal. Por outro lado, outros subgrupos de hipertensos são abordados de maneira diferente entre as diferentes diretrizes. Em contraste com algumas diretrizes, recentes estudos controlados randomizados e revisão sistemática indicam que uma redução mais intensa da pressão arterial não resulta na diminuição do aparecimento de eventos cardiovasculares ou da mortalidade nos indivíduos hipertensos.

The goal of antihypertensive treatment is to reduce cardiovascular morbidity and mortality. To reach this objective,the main recommendation is to reduce levels of blood pressure. However, risk factor assessment and control of associated clinical conditions are also necessary to define the blood pressure target to be reached. In general, the two blood pressure targets recognized by all the guidelines are below 140/90 mmHg for hypertensive population at low risk and below 130/80 mmHg for patients with diabetes or kidney disease. On the other hand, other subgroups of hypertensive patients are treated differently among the different guidelines. In contrast to some guidelines, recent randomized controlled trials and systematic reviews indicate that a greater reduction in blood pressure does not result in reducing the occurrence of cardiovascular events or mortality in hypertensive patients.