Functional training improves peak oxygen consumption and quality of life of individuals with heart failure: a randomized clinical trial.

BACKGROUND: Functional training may be an effective non-pharmacological therapy for heart failure (HF). This study aimed to compare the effects of functional training with strength training on peak VO2 and quality of life in individuals with HF. METHODS: A randomized, parallel-design and examiner-blinded controlled clinical trial with concealed allocation, intention-to-treat and per-protocol analyses. Twenty-seven participants with chronic HF were randomly allocated to functional or strength training group, to perform a 12-week physical training, three times per week, totalizing 36 sessions. Primary outcomes were the difference on peak VO2 and quality of life assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire, respectively. Secondary outcomes included functionality assessed by the Duke Activity Status Index and gait speed test, peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively, endothelial function by brachial artery flow-mediated dilation, and lean body mass by arm muscle circumference. RESULTS: Participants were aged 60 ± 7 years, with left ventricular ejection fraction 29 ± 8.5%. The functional and strength training groups showed the following results, respectively: peak VO2 increased by 1.4 ± 3.2 (16.9 ± 2.9 to 18.6 ± 4.8 mL.kg-1.min-1; p time = 0.011) and 1.5 ± 2.5 mL.kg-1.min-1 (16.8 ± 4.0 to 18.6 ± 5.5 mL.kg-1.min-1; p time = 0.011), and quality of life score decreased by 14 ± 15 (25.8 ± 14.8 to 10.3 ± 7.8 points; p time = 0.001) and 12 ± 28 points (33.8 ± 23.8 to 19.0 ± 15.1 points; p time = 0.001), but no difference was observed between groups (peak VO2: p interaction = 0.921 and quality of life: p interaction = 0.921). The functional and strength training increased the activity status index by 6.5 ± 12 and 5.2 ± 13 points (p time = 0.001), respectively, and gait speed by 0.2 ± 0.3 m/s (p time = 0.002) in both groups. CONCLUSIONS: Functional and strength training are equally effective in improving peak VO2, quality of life, and functionality in individuals with HF. These findings suggest that functional training may be a promising and innovative exercise-based strategy to treat HF. TRIAL REGISTRATION: NCT03321682. Registered date: 26/10/2017.

Comparison of COVID-19 hospitalization costs across care pathways: a patient-level time-driven activity-based costing analysis in a Brazilian hospital.

BACKGROUND: The COVID-19 pandemic raised awareness of the need to better understand where and how patient-level costs are incurred in health care organizations, as health managers and other decision-makers need to plan and quickly adapt to the increasing demand for health care services to meet patients' care needs. Time-driven activity-based costing offers a better understanding of the drivers of cost throughout the care pathway, providing information that can guide decisions on process improvement and resource optimization. This study aims to estimate COVID-19 patient-level hospital costs and to evaluate cost variability considering the in-hospital care pathways of COVID-19 management and the patient clinical classification. METHODS: This is a prospective cohort study that applied time-driven activity-based costing (TDABC) in a Brazilian reference center for COVID-19. Patients hospitalized during the first wave of the disease were selected for their data to be analyzed to estimate in-hospital costs. The cost information was calculated at the patient level and stratified by hospital care pathway and Ordinal Scale for Clinical Improvement (OSCI) category. Multivariable analyses were applied to identify predictors of cost variability in the care pathways that were evaluated. RESULTS: A total of 208 patients were included in the study. Patients followed five different care pathways, of which Emergency + Ward was the most followed (n = 118, 57%). Pathways which included the intensive care unit presented a statistically significant influence on costs per patient (p <  0.001) when compared to Emergency + Ward. The median cost per patient was I$2879 (IQR 1215; 8140) and mean cost per patient was I$6818 (SD 9043). The most expensive care pathway was the ICU only, registering a median cost per patient of I$13,519 (IQR 5637; 23,373) and mean cost per patient of I$17,709 (SD 16,020). All care pathways that included the ICU unit registered a higher cost per patient. CONCLUSIONS: This is one of the first microcosting study for COVID-19 that applied the TDABC methodology and demonstrated how patient-level costs vary as a function of the care pathways followed by patients. These findings can be used to develop value reimbursement strategies that will inform sustainable health policies in middle-income countries such as Brazil.

Prognostic Impact of Cardiovascular Versus Noncardiovascular Hospitalizations in Heart Failure With Preserved Ejection Fraction: Insights From TOPCAT.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction are commonly admitted to the hospital for both cardiovascular (CV) and noncardiovascular (non-CV) reasons. The prognostic implications of non-CV hospitalizations in this population are not well understood. In this study, we aimed to examine the prognostic implications of hospitalizations owing to CV and non-CV reasons in a HF with preserved ejection fraction population. METHODS AND RESULTS: The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) randomized 3445 stable outpatients with chronic HF with a left ventricular ejection fraction of 45% or greater and either prior hospitalization for HF or elevated natriuretic peptides to treatment with spironolactone or placebo. Hospitalizations for any cause were reported by investigators during study follow-up and characterized according to prespecified category causes. This analysis focused on the subset of TOPCAT participants enrolled in the Americas (n = 1767), in which 2973 hospitalizations were observed in 1062 subjects (60%) over a mean follow-up of 3.3 years of study follow-up, of which 1474 (49%) were ascribed to CV causes. Among 1056 first hospitalizations, 478 (45%) were for CV reasons and 578 (55%) for non-CV reasons. Mortality rates were lowest for participants not hospitalized during the trial (3.2 per 100 patient-years [PY]), but similarly elevated after first hospitalization for CV and non-CV reasons (11.0 per 100 PY vs 12.6 per 100 PY, respectively; P = .24). Among those hospitalized for CV reasons, mortality rates were similar after hospitalization for HF and non-CV related reasons (15.2 per 100 PY vs 12.6 per 100 PY; P = .23). Recurrent hospitalization, whether owing to CV or non-CV causes, was associated with a heightened risk for subsequent mortality, with similar death rates after hospitalization twice for CV reasons (18.5 per 100 PY), twice for non-CV reasons (21.6 per 100 PY), or once each for CV and non-CV reasons (18.4 per 100 PY). CONCLUSIONS: Among patients with HF with preserved ejection fraction, hospitalization for any cause is associated with a heightened risk for postdischarge mortality, with an even higher risk associated with recurrent hospitalization. Given the high burden of non-CV hospitalizations in this population, the targeted management of comorbid medical illness may be critical to decreasing morbidity and mortality.

Challenges for expansion of thoracic transplant clinical pharmacy in a developing country: comparison with U.S. accredited centres and call for action.

WHAT IS KNOWN AND OBJECTIVE: Clinical pharmacists' involvement in the care of solid organ transplant recipients has been discussed worldwide given its potential to improve clinical outcomes. As thoracic transplant activity grows in Brazil, it is important to understand how pharmacists are inserted in transplant programmes nationwide. We conducted a survey to explore clinical pharmacy activities in thoracic transplant centres in Brazil and compared them with accredited programmes in the United States. METHODS: An electronic questionnaire was distributed to all 40 heart and lung transplant centres registered in the Brazilian Organ Transplantation Agency (ABTO) in May 2019. Survey findings were compared to previously published data from accredited U.S. centres. RESULTS AND DISCUSSION: From 22 centre respondents, ten (45.5%) declared not to have a pharmacist at any part of the transplantation process, which translated into 158 (37.6%) transplant recipients without any direct pharmaceutical care. In centres with pharmacists (n = 12), none had a full-time professional dedicated to their heart and/or lung programmes. When compared to U.S. centres, there was a significantly lower insertion of clinical pharmacist activities among Brazilian centres. WHAT IS NEW AND CONCLUSION: Our findings point to an unmet need related to clinical pharmacy activity within thoracic transplant programmes, especially in a developing country, and highlight a call for action in order to reach higher accredited regulatory standards regarding pharmacist-driven workforce in transplant care worldwide.

Cardiopulmonary exercise capacity and quality of life of patients with heart failure undergoing a functional training program: study protocol for a randomized clinical trial.

BACKGROUND: Exercise intolerance is a common finding in heart failure that generates a vicious cycle in which the individual starts to limit his activities even more due to progressive fatigue. Regular physical exercise can increase the cardiopulmonary exercise capacity of these individuals. A new approach to physical exercise, known as functional training, could improve the oxygen consumption and quality of life of patients with heart failure; however, there is no information about the effect of this modality of exercise in this patient population. This randomized trial will compare the effects of 36 sessions of functional training versus strength training in heart failure patients. METHODS: This randomized parallel-design examiner-blinded clinical trial includes individuals of both sexes aged ≥40 years receiving regular follow-up at a single academic hospital. Subjects will be randomly allocated to an intervention group (for 12-week functional training) or an active comparator group (for 12-week strength training). The primary outcomes will be the difference from baseline to the 3-month time point in peak oxygen consumption on cardiopulmonary exercise testing and quality of life assessed by the Minnesota Living with Heart Failure Questionnaire. Secondary outcome measures will include functionality assessed by the Duke Activity Status Index and gait speed test; peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively; endothelial function by brachial artery flow-mediated dilation; lean body mass by arm muscle circumference; and participant adherence to the exercise programs classified as a percentage of the prescribed exercise dose. DISCUSSION: The functional training program aims to improve the functional capacity of the individual using exercises that relate to his specific physical activity transferring gains effectively to one's daily life. In this context, we believe that that functional training can increase the cardiopulmonary exercise capacity and quality of life of patients with heart failure. The trial has been recruiting patients since October 2017. TRIAL REGISTRATION: NCT03321682. Registered on October 26, 2017.

Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system.

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain ß-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.

Heart Transplantation Cost Composition in Brazil: A Patient-Level Microcosting Analysis and Comparison With International Data.

BACKGROUND: Advanced heart failure (HF) therapies, such as heart transplantation, are resource intensive and costly. In Brazil, only one-fifth of the estimated population need is fulfilled. We examined cost expenditures of heart transplants in a public institution in Brazil. METHODS AND RESULTS: We used microcosting analysis (time-driven activity-based costing) to examine total costs and individual cost components related to the index transplant hospital admission of all consecutive heart transplant recipients at a single center from July 2015 to June 2017. Average total cost for the 27 patients included was US$ 74,341 which exceeds the reimbursement value per patient by 60%. Major cost drivers were hospital structure and personnel, similarly to what is observed in the United States (US) and other developed countries. Total costs for index transplant admission were ∼50% lower than in the US, but approximate to values reported in some European countries. Costs of heart transplantation in Brazil were lower than those reported for developed countries, and higher than national reimbursement values. CONCLUSIONS: Advanced microcosting methodologies represent an important quality contribution to economic studies in health care and may provide insights for transplant-related health care policies in developing countries.

Spironolactone for heart failure with preserved ejection fraction.

BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 µmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial.

BACKGROUND: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). METHODS AND RESULTS: To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. CONCLUSIONS: This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study).

AIMS: Pre-clinical and few clinical studies suggest that transplantation of autologous bone marrow mononuclear cells (BMNC) improves heart function in dilated cardiomyopathies. Our objective was to determine if intracoronary injection of autologous BMNC improves the left ventricular ejection fraction (LVEF) of patients with non-ischaemic dilated cardiomyopathy (NIDCM). METHODS AND RESULTS: This study was a multicentre, randomized, double-blind, placebo controlled trial with a follow-up of 12 months. Patients with NIDCM and LVEF <35% were recruited at heart failure ambulatories in specialized hospitals around Brazil. One hundred and sixty subjects were randomized to intracoronary injection of BMNC or placebo (1:1). The primary endpoint was the difference in change of LVEF between BMNC and placebo groups as determined by echocardiography. One hundred and fifteen patients completed the study. Left ventricular ejection fraction decreased from 24.0% (21.6-26.3) to 19.9% (15.4-24.4) in the BMNC group and from 24.3% (22.1-26.5) to 22.1% (17.4-26.8) in the placebo group. There were no significant differences in changes between cell and placebo groups for left ventricular systolic and diastolic volumes and ejection fraction. Mortality rate was 20.37% in placebo and 21.31% in BMNC. CONCLUSION: Intracoronary injection of autologous BMNC does not improve left ventricular function in patients with NIDCM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00333827.

Transcoronary gradient of plasma microRNA 423-5p in heart failure: evidence of altered myocardial expression.

CONTEXT: Elevated plasmatic microRNAs (miRs) are observed in heart failure (HF). However, the cardiac origin of these miRs remains unclear. OBJECTIVE: We calculated transcoronary gradients of miR-29b, miR-133a and miR-423-5p in 17 outpatients with stable systolic HF and in controls without structural cardiac disease. MATERIALS AND METHODS: MicroRNAs were measured by quantitative real-time polymerase chain reaction. RESULTS: Positive transcoronary miR gradients were observed in patients with HF but not in controls (p = 0.03). B-type natriuretic peptide (BNP) moderately correlated with the transcoronary gradients of miR-133a and miR-423-5p. DISCUSSION AND CONCLUSIONS: The difference in transcoronary gradients between HF outpatients and controls suggests that miR-423-5p has a cardiac origin. The positive correlation between miR-423-5p and BNP transcoronary gradients supports this hypothesis.

Serum levels and polymorphisms of matrix metalloproteinases (MMPs) in carotid artery atherosclerosis: higher MMP-9 levels are associated with plaque vulnerability.

CONTEXT: Matrix metalloproteinases are involved in atherosclerosis and plaque vulnerability. OBJECTIVE: To investigate serum levels and genetic polymorphisms of matrix metalloproteinases (MMPs) -1, -3 and -9 in patients submitted to carotid endarterectomy. METHODS: Genetic polymorphisms were evaluated using polymerase chain reaction (PCR-RFLP); serum levels were measured using ELISA; histological sections were stained with Picrosirius Red to analyze the fibrous cap thickness, lipid core and collagen content and with hematoxylin--eosin to detect the presence of intraplaque hemorrhage. RESULTS: MMP-9 serum levels were significantly higher in patients with a thinner fibrous cap (p = 0.033) or acute or recent intraplaque hemorrhage (p = 0.008) on histology, as well as in patients with previous stroke (p = 0.009) or peripheral vascular disease (p = 0.049). No consistent associations were observed between different MMP genotypes and fibrous cap thickness, lipid core, collagen content or intraplaque hemorrhage. CONCLUSIONS: MMP-9 serum levels were consistently associated with markers of carotid atherosclerosis and lesion vulnerability, whereas specific MMP genotypes were not.

Anemia in heart failure: association of hepcidin levels to iron deficiency in stable outpatients.

BACKGROUND: Anemia is a prevalent condition in heart failure with multiple potential causes. The complex interaction between iron stores, hepcidin, inflammation and anemia is poorly comprehended. We tested the hypothesis that, in stable heart failure patients with anemia, hepcidin is associated with iron deficiency status irrespective of inflammation. METHODS AND RESULTS: Stable systolic heart failure outpatients with and without anemia underwent a complete iron panel, erythropoietin, hepcidin and tumor necrosis factor (TNF)-α assessment. Sixty outpatients were studied. Anemic patients (n = 38, mean hemoglobin 11.4 ± 1 g/dl) were older (69.6 ± 9.6 vs. 58 ± 10.8 years old, p < 0.01) compared with nonanemic patients (n = 22, mean hemoglobin 13.8 ± 1.1 g/dl). Iron deficiency was present in 42% of patients with anemia. TNF-α and hepcidin were 29 and 21% higher in patients with anemia, respectively, compared to nonanemic patients; however, no correlations were found between hepcidin and TNF-α levels. Hepcidin levels in the lower tertile (<31.7 ng/ml) were strongly associated with iron deficiency (OR 16.5, 95% CI 2.2-121.2; p < 0.01). CONCLUSION: In stable heart failure patients with anemia, hepcidin levels may be more importantly regulated by patients' iron stores than by inflammation.

Critical appraisal of costly therapy modalities for heart failure in a developing country.

Contemporaneous challenges in heart failure management include strategies to rationally use health economic resources and relative donor shortage to adequately offer electric devices (cardiac resynchronization therapy [CRT] and implantable cardioverter defibrillators [ICD]), ventricular assist devices (VADs) and heart transplant, respectively. These issues are particularly important in countries with middle-income rates and limited structured heart transplant centers, such as Brazil. Use of CRT and ICDs need to follow strict guidelines, further customized to public financial health conditions. Experience with VADs in is the early days in Brazil and will require extreme caution to allocate health public resources to develop VAD programs in highly selected centers. Chagas' disease is epidemiologically important in Brazil; outcomes of patients with Chagas' on electric devices are unclear while these patients fare better post-transplant than non-Chagas' patients. Thus, heart transplant remains an attractive option regarding both favorable outcomes and resource allocation for advanced heart failure patients in Brazil.

Use of the ADHERE Risk Model as a Predictor of Risk of in-Hospital Worsening Heart Failure in a Cohort. / Uso do Modelo de Risco ADHERE como Preditor de Piora Intra-Hospitalar de Insuficiência Cardíaca em uma Coorte.

BACKGROUND: Patients admitted with acute decompensated heart failure (HF) are subject to developing worsening episodes that require more complex interventions. The Acute Decompensated Heart Failure National Registry (ADHERE) risk model was developed in the United States to predict the risk of in-hospital worsening HF. OBJECTIVE: To use the ADHERE risk model in the assessment of risk of in-hospital worsening HF and to determine its sensitivity and specificity in hospitalized patients. METHODS: This cohort study was conducted at a Brazilian public university hospital, and data from 2013 to 2020 were retrospectively collected. P values < 0.05 were considered statistically significant. RESULTS: A total of 890 patients with a mean age of 74 ± 8 years were included. The model showed that, in the group of 490 patients at risk, 254 (51.8%) developed in-hospital worsening HF. In the group of 400 patients not at risk, only 109 (27.2%) experienced worsening HF. The results demonstrated a statistically significant curve (area under the curve = 0.665; standard error = 0.018; P < 0.01; confidence interval = 0.609 to 0.701), indicating good accuracy. The model had a sensitivity of 69.9% and a specificity of 55.2%, with a positive predictive value of 52% and a negative predictive value of 72.7%. CONCLUSIONS: In this cohort, we showed that the ADHERE risk model was able to discriminate patients who in fact developed worsening HF during the admission period, from those who did not.

FUNDAMENTO: Pacientes hospitalizados com insuficiência cardíaca (IC) aguda descompensada estão sujeitos a desenvolver episódios de piora que requerem intervenções mais complexas. O modelo de predição de risco "Acute Decompensated Heart Failure National Registry" (ADHERE) foi desenvolvido nos Estados Unidos para prever o risco de piora intra-hospitalar da IC. OBJETIVO: Utilizar o modelo de predição de risco ADHERE para avaliar o risco de piora intra-hospitalar da IC e determinar a sua sensibilidade e especificidade em pacientes hospitalizados. MÉTODOS: O presente estudo de coorte foi realizado em um hospital universitário público brasileiro e os dados de 2013 a 2020 foram coletados retrospectivamente. Foram considerados estatisticamente significativos valores de p < 0,05. RESULTADOS: Foram incluídos 890 pacientes com idade média de 74 ± 8 anos. O modelo mostrou que no grupo de 490 pacientes de risco, 254 (51,8%) desenvolveram piora intra-hospitalar da IC. No grupo de 400 pacientes sem risco, apenas 109 (27,2%) apresentaram piora da IC. Os resultados demonstraram uma curva estatisticamente significativa (área sob a curva = 0,665; erro padrão = 0,018; p < 0,01; intervalo de confiança = 0,609 a 0,701), indicando boa precisão. O modelo apresentou sensibilidade de 69,9% e especificidade de 55,2%, com valor preditivo positivo de 52% e valor preditivo negativo de 72,7%. CONCLUSÕES: Na presente coorte, demonstramos que o modelo de predição de risco ADHERE foi capaz de discriminar pacientes que, de fato, desenvolveram piora da IC durante o período de internação daqueles que não desenvolveram.

Prognostic value of nutritional screening tools in hospitalized patients with decompensated heart failure: A systematic review and meta-analysis.

Nutritional risk screening is fundamental to prevent undesirable outcomes in heart failure (HF). Current reviews of nutritional screening tools encompass both hospitalized and outpatient settings, which may not be suitable because of different clinical manifestations. We hypothesize that multidimensional tools would better identify prognosis of decompensated patients because the tools assess more than isolated aspects. This systematic review aims to explore the association of multidimensional nutritional risk screening tools and prognosis in patients hospitalized with decompensated HF. Five databases were searched for studies that assessed nutritional risk through multidimensional screening tools and its association with prognosis in adults hospitalized with decompensated HF. The 95% confidence interval and relative risk were computed using a random-effects model. Inverse variance method was used. Thirty-eight studies were included. Most studies demonstrated higher nutritional risk was significantly associated with worse prognosis. Quantitative analysis identified higher nutritional risk by using the Mini Nutritional Assessment Short Form (MNA-SF), Controlling Nutritional Status, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index to be associated with all-cause mortality. The MNA-SF demonstrated greater magnitude of association with all-cause mortality in older subjects (relative risk, 4.85; 95% confidence interval, 2.0-11.75). Higher nutritional risk was associated with poor prognosis and higher mortality in patients hospitalized with decompensated HF, especially when screened by MNA-SF. Tools were not directly compared. That might reinforce the importance of evaluating multiple aspects when screening hospitalized HF patients once symptoms associated with decompensation frequently mask the underlying nutritional status and risk. PROSPERO registration number (CRD42021256271).

Polymorphisms of endothelial nitric oxide synthase gene in systolic heart failure: an haplotype analysis.

BACKGROUND: Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been associated with the pathogenesis of cardiovascular diseases, but few studies have evaluated the role of eNOS haplotypes on the risk and prognosis of heart failure (HF). This prospective study was designed to analyze the impact of three eNOS polymorphisms (T-786C, VNTR4a/b and Glu298Asp) and their haplotypes on the susceptibility and clinical outcomes in HF outpatients with systolic dysfunction. METHODS AND RESULTS: We conducted a case-control and a cohort study in which 316 HF patients and 360 healthy controls were recruited from a tertiary care university hospital. DNA was extracted from peripheral blood and eNOS polymorphisms were detected by PCR or PCR-RFLP. Patients were predominantly men, had a mean left ventricular ejection fraction of 31% and were followed-up for a median of 41months; there were 96 deaths, including 58 HF-related deaths. Genotype distribution of the eNOS T-786C, VNTR 4a/b and Glu298Asp was similar between HF patients and controls. Haplotype frequencies differed between HF patients and controls only in African-Brazilians (p=0.043). African-Brazilian patients that carried the haplotype -786C/4b/Asp298 had a better prognosis than patients that carried other haplotypes (log rank p value=0.016 for all-cause mortality). In a Cox proportional hazard model adjusted for clinical variables of risk, the -786C/4b/Asp298 haplotype remained as an independent genetic predictor of survival (adjusted HR=0.11; 95% CI=0.01-0.83; p=0.03). CONCLUSIONS: The -786C/4b/Asp298 eNOS haplotype had a significant impact on HF susceptibility and prognosis, particularly in African-Brazilian patients.

Trepopnea may explain right-sided pleural effusion in patients with decompensated heart failure.

BACKGROUND: Physicians often overlook trepopnea as a symptom, and its prevalence and clinical repercussions are not usually described. We propose that trepopnea is a common symptom in heart failure (HF) and, because of patient avoidance of left lateral decubitus position, contributes to the greater prevalence of right-sided pleural effusion in patients with HF. Accordingly, this study aimed to determine trepopnea prevalence and to evaluate the association of trepopnea and the laterality of pleural effusion in decompensated HF. METHODS: Consecutive patients (n = 37) with decompensated HF and evidence of pleural effusion by chest x-ray were included. Data were collected at the emergency department by a standard clinical examination in which patients were specifically asked about the presence of trepopnea and preferred decubitus position while recumbent. Chest x-ray and echocardiographic parameters were recorded. RESULTS: Of the 37 patients, 19 (51%) reported trepopnea. Most patients presented with right-sided pleural effusion; only 2 patients (5.4%) presented with left-sided pleural effusion. Patients who reported trepopnea had predominant right-sided pleural effusion more frequently than patients without this symptom (73.7% vs 26.3%; P = .049). The participants that reported trepopnea or avoidance of left lateral decubitus position while recumbent or both had a greater probability of having predominant right-sided pleural effusion (likelihood ratio, 1.85; 95% confidence interval, 1.02-3.35). CONCLUSIONS: Trepopnea is a common symptom in patients with decompensated HF and is associated with predominant right-sided pleural effusion in this population. Our results indicate that trepopnea may be a contributory factor for pleural effusion laterality in patients with decompensated HF.

Early loss of cardiac function in acute myocardial infarction is associated with redox imbalance.

BACKGROUND: The loss of viable myocardium subsequent to myocardial infarction (MI) impairs cardiac function, and oxidative stress is considered to be critical in this process. OBJECTIVES: To assess cardiac function and correlate it with oxidative stress and antioxidant levels in cardiac tissue at 48 h post-MI. METHODS: Adult male Wistar rats (n=6 per group) with a mean (± SD) weight of 229±24 g were randomly assigned to either an infarcted group or a control group. MI was induced by occlusion of the left coronary artery. Cardiac function was evaluated by measuring left ventricular (LV) ejection fraction, LV fractional shortening, cardiac output, myocardial performance index and the peak early diastolic velocity/peak atrial velocity ratio using echocardiography. The myocardial oxidative stress profile was assessed by measuring the reduced glutathione/oxidized glutathione ratio, H2O2 levels, peroxiredoxin-6 protein levels and activity levels of superoxide dismutase, catalase and glutathione peroxidase. Lipid peroxidation was quantified using chemiluminescence, and protein oxidation was determined by measuring protein carbonyl levels. RESULTS: LV ejection fraction and LV fractional shortening were lower in the infarcted group compared with the sham group, whereas the peak early diastolic velocity/peak atrial velocity ratio and myocardial performance index were significantly increased, indicating systolic dysfunction. Lipid peroxidation, protein carbonyls and superoxide dismutase and catalase activity levels did not differ between the groups. Peroxyredoxin-6 levels were increased in the infarcted group, while H2O2 levels were reduced. The reduced glutathione/oxidized glutathione ratio and the glutathione peroxidase activity were reduced in the infarcted group compared with control. DISCUSSION AND CONCLUSION: These data suggest that MI-induced cardiac dysfunction and impaired redox balance may be associated with the activation of counter-regulatory responses to maintain reduced H2O2 concentrations and, thereby, prevent further oxidative damage at this early time point.