TNF blockers alone and associated with Benznidazole impact in vitro cytokine dynamics in chronic Chagas disease.

Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]-4 and IL-10) and inflammatory (TNF, interferon-gamma [IFN-γ], IL-2 and IL-6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms-IND (n = 13) mild heart form-CARD1 (n = 13) and severe cardiac form-CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN-γ increased in the CARD2 group after treatment with ETA relative to ADA. IL-4 had its levels decreased when treated by both drugs. IL-2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL-2/TNF and increased IL-4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients.

In-Hospital Management and Long-term Clinical Outcomes and Adherence in Patients With Acute Decompensated Heart Failure: Primary Results of the First Brazilian Registry of Heart Failure (BREATHE).

BACKGROUND: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America. METHODS: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 SUGGESTION FOR REPHRASING: In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated. RESULTS: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. CONCLUSIONS: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up.

In-Hospital Management and Long-term clinical outcomes and adherence in patients with acute decompensated heart failure: primary results of the first brazilian registry of heart failure (BREATHE)

BACKGROUND: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognosis of patients with HF in Latin America. METHODS: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute HF. Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018. In-hospital management and 12-month clinical outcomes were assessed, and adherence to evidence-based therapies was evaluated. RESULTS: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors, and spironolactone numerical decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. CONCLUSIONS: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and 12 months of follow-up.

How people affected by Chagas disease have struggled with their negligence: history, associative movement and World Chagas Disease Day.

It is well documented that Chagas disease (CD) can pose a public health problem to countries. As one of the World Health Organization Neglected Tropical Diseases undoubtedly calls for comprehensive healthcare, transcending a restricted biomedical approach. After more than a century since their discovery, in 1909, people affected by CD are still frequently marginalised and/or neglected. The aim of this article is to tell the story of their activism, highlighting key historical experiences and successful initiatives, from 1909 to 2019. The first association was created in 1987, in the city of Recife, Brazil. So far, thirty associations have been reported on five continents. They were created as independent non-profit civil society organisations and run democratically by affected people. Among the common associations' objectives, we notably find: increase the visibility of the affected; make their voice heard; build bridges between patients, health system professionals, public health officials, policy makers and the academic and scientific communities. The International Federation of Associations of People Affected by CD - FINDECHAGAS, created in 2010 with the input of the Americas, Europe and the Western Pacific, counts as one of the main responses to the globalisation of CD. Despite all the obstacles and difficulties encountered, the Federation has thrived, grown, and matured. As a result of this mobilisation along with the support of many national and international partners, in May 2019 the 72nd World Health Assembly decided to establish World Chagas Disease Day, on 14 April. The associative movement has increased the understanding of the challenges related to the disease and breaks the silence around Chagas disease, improving surveillance, and sustaining engagement towards the United Nations 2030 agenda.

Prognosis of chronic Chagas heart disease and other pending clinical challenges.

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Is a negative correlation between sTNFR1 and TNF in patients with chronic Chagas disease the key to clinical progression?

Soluble TNF receptors (sTNFR1 and sTNFR2) are natural endogenous inhibitors of TNF and are elevated in inflammatory, autoimmune, and chronic degenerative diseases. In Chagas disease, pleiotropic cytokine TNF is considered key in immunopathology. Thus, we aimed to evaluate the levels of TNF, sTNFR1, and sTNFR2 in the serum of patients with chronic Chagas disease. TNF and its soluble receptors were quantified using Cytometric Bead Array in the serum of 132 patients, of which 51 had the indeterminate form (IND), 39 the mild cardiac form (CARD 1), 42 the severe cardiac form (CARD 2), and 20 non-infected individuals (NI). The results indicate that the soluble receptors may regulate TNF in Chagas disease, as their leves were higher in T. cruzi-infected individuals when compared to non-infected individuals. We found a moderate negative correlation between sTNFR1 and TNF in individuals with the IND form, suggesting a relationship with non-progression to more severe forms, such as heart disease. sTNFR1 and sTNFR2 were increased in all clinical forms, but with a moderate positive correlation in more severe patients (r = 0.50 and p = 0.0005). TNF levels showed no statistical differences in the groups of patients. These findings suggest the importance of the endogenous balance of the levels of soluble TNF receptors in the protection and balance in patients with chronic Chagas disease, besides revealing the immunological complexity in chronic T. cruzi-infected individuals.

Association between performance on the Glittre ADL-test and the functional capacity of patients with HF: A cross-sectional study.

Background: The Weber classification based on peak VO2 is a well-established method for categorizing patients with heart failure (HF) regarding severity. However, other submaximal tests such as the Glittre ADL-Test have been gaining prominence in practice due to a coherent and more comprehensive correlation with limitations for performing activities of daily living in patients with heart failure.Objective: To investigate the correlation between the time required to perform the Glittre ADL-Test and the peak VO2 in patients with HF.Methods: A cross-sectional study conducted with 40 adult individuals (21 to 65 years) diagnosed with HF of all etiologies, with LVEF<50% and NYHA II and III.Results: The average time for performing the Glittre ADL-Test was 284.9 seconds, and a significant difference was found between Weber classification classes A and C (p = .01). Significant correlations with peak VO2 were also found (r = -0.424 - p < .01). Thirty (30) patients performed a second test, and the ICC found in the reproducibility analysis was 0.75 (95% CI 0.14-0.91) and p < .01.Conclusion: The Glittre ADL-Test was able to reflect the functional performance of individuals with HF, suggesting that it represents an evaluation tool which can be safely used in clinical practice.

How people affected by Chagas disease have struggled with their negligence: history, associative movement and World Chagas Disease Day

It is well documented that Chagas disease (CD) can pose a public health problem to countries. As one of the World Health Organization Neglected Tropical Diseases undoubtedly calls for comprehensive healthcare, transcending a restricted biomedical approach. After more than a century since their discovery, in 1909, people affected by CD are still frequently marginalised and/or neglected. The aim of this article is to tell the story of their activism, highlighting key historical experiences and successful initiatives, from 1909 to 2019. The first association was created in 1987, in the city of Recife, Brazil. So far, thirty associations have been reported on five continents. They were created as independent non-profit civil society organisations and run democratically by affected people. Among the common associations' objectives, we notably find: increase the visibility of the affected; make their voice heard; build bridges between patients, health system professionals, public health officials, policy makers and the academic and scientific communities. The International Federation of Associations of People Affected by CD - FINDECHAGAS, created in 2010 with the input of the Americas, Europe and the Western Pacific, counts as one of the main responses to the globalisation of CD. Despite all the obstacles and difficulties encountered, the Federation has thrived, grown, and matured. As a result of this mobilisation along with the support of many national and international partners, in May 2019 the 72nd World Health Assembly decided to establish World Chagas Disease Day, on 14 April. The associative movement has increased the understanding of the challenges related to the disease and breaks the silence around Chagas disease, improving surveillance, and sustaining engagement towards the United Nations 2030 agenda.

Prognosis of chronic Chagas heart disease and other pending clinical challenges

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Implications for clinical practice from a multicenter survey of heart failure management centers

OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

Predictors of Post-Discharge 30-Day Hospital Readmission in Decompensated Heart Failure Patients

Abstract Background Heart failure (HF) is worldwide known as a public health issue with high morbimortality. One of the issues related to the evolution of HF is the high rate of hospital readmission caused by decompensation of the clinical condition, with high costs and worsening of ventricular function. Objective To quantify the readmission rate and identify the predictors of rehospitalization in patients with acute decompensated heart failure. Methods Hospital-based historic cohort of patients admitted with acute decompensated HF in a private hospital from Recife/PE, from January 2008 to February 2016, followed-up for at least 30 days after discharge. Demographic and clinical data of admission, hospitalization, and clinical and late outcomes were analyzed. Logistic regression was used as a strategy to identify the predictors of independent risks. Results 312 followed-up patients, average age 73 (± 14), 61% males, 51% NYHA Class III, and 58% ischemic etiology. Thirty-day readmission rate was 23%. Multivariate analysis identified the independent predictors ejection fraction < 40% (OR = 2.1; p = 0.009), hyponatremia (OR = 2.9; p = 0.022) and acute coronary syndrome (ACS) as the cause of decompensation (OR = 1.1; p = 0,026). The final model using those three variables presented reasonable discriminatory power (C-Statistics = 0.655 - HF 95%: 0.582 - 0.728) and good calibration (Hosmer-Lemeshow p = 0.925). Conclusions Among hospitalized patients with acute decompensated heart failure, the rate of readmission was high. Hyponatremia, reduced ejection fraction and ACS as causes of decompensation were robust markers for the prediction of hospital readmission within 30 days of discharge. (Int J Cardiovasc Sci. 2020; 33(2):175-184)

Decompensated Heart Failure with Mid-Range Ejection Fraction: Epidemiology and In-Hospital Mortality Risk Factors

Abstract Background: Recently, a new HF entity, with LVEF between 40-49%, was presented to comprehend and seek better therapy for HF with preserved LVEF (HFpEF) and borderline, in the means that HF with reduced LVEF (HFrEF) already has well-defined therapy in the literature. Objective: To compare the clinical-therapeutic profile of patients with HF with mid-range LVEF (HFmrEF) with HFpEF and HFrEF and to verify predictors of hospital mortality. Method: Historical cohort of patients admitted with decompensated HF at a supplementary hospital in Recife/PE between April/2007 - August/2017, stratified by LVEF (< 40%/40 - 49/≥ 50%), based on the guideline of the European Society of Cardiology (ESC) 2016. The groups were compared and Logistic Regression was used to identify predictors of independent risk for in-hospital death. Results: A sample of 493 patients, most with HFrEF (43%), HFpEF (30%) and HFmrEF (26%). Average age of 73 (± 14) years, 59% men. Hospital mortality 14%, readmission within 30 days 19%. In therapeutics, it presented statistical significance among the 3 groups, spironolactone, in HFrEF patients. Hospital death and readmission within 30 days did not make difference. In the HFmrEF group, factors independently associated with death were: valve disease (OR: 4.17, CI: 1.01-9.13), altered urea at admission (OR: 6.18, CI: 1.78-11.45) and beta-blocker hospitalization (OR: 0.29, CI: 0.08-0.97). In HFrEF, predictors were: prior renal disease (OR: 2.84, CI: 1.19-6.79), beta-blocker at admission (OR: 0.29, CI: 0.12-0.72) and ACEI/ ARB (OR: 0.21, CI: 0.09-0.49). In HFpEF, only valve disease (OR: 4.61, CI: 1.33-15.96) and kidney disease (OR: 5.18, CI: 1.68-11.98) were relevant. Conclusion: In general, HFmrEF presented intermediate characteristics between HFrEF and HFpEF. Independent predictors of mortality may support risk stratification and management of this group.

Quality of life related to health for heart failure patients.

OBJECTIVE: To assess the quality of life related to health for heart failure patients and to relate sociodemographic and clinical data. METHOD: It is an observational and transversal study, with quantitative approach, carried out in a heart failure ambulatory in the state of Pernambuco. RESULTS: In the sample (n=101), there was prevalence of men older than 60 years old, married and professionally inactive. The quality of life related to health, based on the Minnesota Living With Heart Failure Questionnaire, was considered moderate (34.3±21.6), being significantly related to age (p=0.004), functional class (p<0.001), and patients with chagasic cardiopathy (p=0.02). CONCLUSION: The quality of life in the HF group of chagasic etiology was more compromised, specially in the emotional dimension. It is suggested that studies on the hypothesis that longer ambulatory follow-up improves quality of life and that having Chagas disease interferes negatively with the quality of life of heart failure patients.

Global Longitudinal Strain Predicts Poor Functional Capacity in Patients with Systolic Heart Failure / Strain Longitudinal Global é Preditor de Baixa Capacidade Funcional em Pacientes com Insuficiência Cardíaca Sistólica

Abstract Background: Left ventricular global longitudinal strain value (GLS) can predict functional capacity in patients with preserved left ventricular ejection fraction (LVEF) heart failure (HF) and to assess prognosis in reduced LVEF HF. Objetive: Correlate GLS with parameters of Cardiopulmonary Exercise Test (CPET) and to assess if they could predict systolic HF patients that are more appropriated to be referred to heart transplantation according to CPET criteria. Methods: Systolic HF patients with LVEF < 45%, NYHA functional class II and III, underwent prospectively CPET and echocardiography with strain analysis. LVEF and GLS were correlated with the following CPET variables: maxVO2, VE/VCO2 slope, heart rate reduction during the first minute of recovery (HRR) and time needed to reduce maxVO2 in 50% after physical exercise (T1/2VO2). ROC curve analysis of GLS to predict VO2 < 14 mL/kg/min and VE/VCO2 slope > 35 (heart transplantation's criteria) was performed. Results: Twenty six patients were selected (age, 47 ± 12 years, 58% men, mean LVEF = 28 ± 8%). LVEF correlated only with maxVO2 and T1/2VO2. GLS correlated to all CPET variables (maxVO2: r = 0.671, p = 0.001; VE/VCO2 slope: r = -0.513, p = 0.007; HRR: r = 0.466, p = 0.016, and T1/2VO2: r = -0.696, p = 0.001). GLS area under the ROC curve to predict heart transplantation's criteria was 0.88 (sensitivity 75%, specificity 83%) for a cut-off value of -5.7%, p = 0.03. Conclusion: GLS was significantly associated with all functional CPET parameters. It could classify HF patients according to the functional capacity and may stratify which patients have a poor prognosis and therefore to deserve more differentiated treatment, such as heart transplantation.

Resumo Fundamento: O strain longitudinal global (SLG) é capaz de predizer a capacidade funcional dos pacientes com insuficiência cardíaca (IC) e fração de ejeção do ventrículo esquerdo (FEVE) preservada, e avaliar o prognóstico na IC com FEVE reduzida. Objetivo: Correlacionar o SLG com parâmetros do teste de exercício cardiopulmonar (TECP), e avaliar se o SLG seria capaz de predizer quais pacientes com IC sistólica deveriam ser encaminhados ao transplante cardíaco de acordo com os critérios do TECP. Métodos: Os pacientes com IC sistólica com FEVE <45%, classe funcional NYHA II e III, submeteram-se prospectivamente ao TECP e à ecocardiografia com análise do strain. A FEVE e o SLG foram correlacionados com as seguintes variáveis do TECP: maxVO2, inclinação de VE/VCO2, redução da frequência cardíaca durante o primeiro minuto de recuperação (RFC), e tempo necessário para a redução do maxVO2 em 50% após o exercício físico (T1/2VO2). Foi realizada análise da curva ROC do SLG em predizer um VO2 < 14 mL/kg/min e uma inclinação de VE/VCO2 > 35 (critérios para transplante cardíaco). O nível de significância adotado na análise estatística foi de p < 0,05. Resultados: Vinte e seis pacientes foram selecionados para o estudo (idade, 47±12 anos, 58% homens, FEVE média LVEF = 28 ± 8%). A FEVE correlacionou-se somente com o maxVO2 e o T1/2VO2. O SLG correlacionou-se com todas as variáveis do TECP (maxVO2: r = 0,671; p = 0,001; inclinação de VE/VCO2: r = -0,513; p = 0,007; RFC: r = 0,466; p = 0,016; e T1/2VO2: r = -0,696, p = 0,001). A área sob a curva ROC para o SLG para predizer os critérios para transplante cardíaco foi de 0,88 (sensibilidade 75%, especificidade 83%) para um ponto de corte de -5,7%, p = 0,03. Conclusão: O SLG apresentou associação significativa com todos os parâmetros funcionais do TECP. O SLG foi capaz de classificar os pacientes com IC segundo capacidade funcional e possivelmente pode identificar quais pacientes têm um prognóstico ruim e, portanto, se beneficiariam de um tratamento diferenciado, tal como o transplante cardíaco.

Global Longitudinal Strain Predicts Poor Functional Capacity in Patients with Systolic Heart Failure.

BACKGROUND: Left ventricular global longitudinal strain value (GLS) can predict functional capacity in patients with preserved left ventricular ejection fraction (LVEF) heart failure (HF) and to assess prognosis in reduced LVEF HF. OBJETIVE: Correlate GLS with parameters of Cardiopulmonary Exercise Test (CPET) and to assess if they could predict systolic HF patients that are more appropriated to be referred to heart transplantation according to CPET criteria. METHODS: Systolic HF patients with LVEF < 45%, NYHA functional class II and III, underwent prospectively CPET and echocardiography with strain analysis. LVEF and GLS were correlated with the following CPET variables: maxVO2, VE/VCO2 slope, heart rate reduction during the first minute of recovery (HRR) and time needed to reduce maxVO2 in 50% after physical exercise (T1/2VO2). ROC curve analysis of GLS to predict VO2 < 14 mL/kg/min and VE/VCO2 slope > 35 (heart transplantation's criteria) was performed. RESULTS: Twenty six patients were selected (age, 47 ± 12 years, 58% men, mean LVEF = 28 ± 8%). LVEF correlated only with maxVO2 and T1/2VO2. GLS correlated to all CPET variables (maxVO2: r = 0.671, p = 0.001; VE/VCO2 slope: r = -0.513, p = 0.007; HRR: r = 0.466, p = 0.016, and T1/2VO2: r = -0.696, p = 0.001). GLS area under the ROC curve to predict heart transplantation's criteria was 0.88 (sensitivity 75%, specificity 83%) for a cut-off value of -5.7%, p = 0.03. CONCLUSION: GLS was significantly associated with all functional CPET parameters. It could classify HF patients according to the functional capacity and may stratify which patients have a poor prognosis and therefore to deserve more differentiated treatment, such as heart transplantation.