Biomarkers and prediction of anthracyclic cardiotoxicity in breast cancer.

BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

Biomarkers and prediction of anthracyclic cardiotoxicity in breast cancer

SUMMARY BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

The Impact of Cardiovascular Risk Factors and Renal Disease on Outcomes in Patients Hospitalized with COVID-19: An Observational Study from Two Public Hospitals in Brazil

Abstract Background Cardiovascular risk factors are prognostic factors in coronavirus disease 2019 (COVID-19) and have been scarcely studied in Brazil. Objective The aim of this study was to assess the impact of cardiovascular risk factors on the outcomes of patients admitted for COVID-19. Methods From July 2020 to February 2021, 200 patients from two public hospitals were enrolled. Patients were included if they had typical symptoms or signs of COVID-19, a positive real-time polymerase chain reaction test (RT-PCR) for COVID-19, and an age above 18 years. This is a prospective, observational, and longitudinal study. Data were collected within 24 h of admission. The primary endpoint was a combination of hospital lethality, mechanical ventilation, hemodialysis, or length of hospital stay >28 days. Continuous variables were compared with the Student's t-test for independent samples or the Mann-Whitney test. For comparisons of proportions, the χ 2 test was applied. ROC curves and survival curves were constructed. Multivariate logistic regression was performed to identify independent predictors of events. The level of significance was 0.05. Results There were 98 (49%) events during the hospital course, and 72 (36%) died in the hospital. Patients with a primary endpoint were older and more likely to have a history of hypertension, diabetes, chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD). Vital signs at admission associated with events were diastolic blood pressure, respiratory rate, and oxygen saturation in ambient air (O 2 Sat). Serum creatinine >1.37 mg/dL at admission had a sensitivity of 51.6 and a specificity of 82% to predict the primary endpoint, with an area under the curve (AUC) of 0.68. In multivariate analysis, age, diabetes, CKD, and COPD were independent predictors of the primary endpoint. Age and CKD were independent predictors of in-hospital lethality. Conclusion Cardiovascular risk factors, such as diabetes and CKD, were related to a worse prognosis in patients hospitalized with COVID-19 in this sample from two public hospitals in the state of Rio de Janeiro.

Tortuosidade das Artérias Coronárias como um Novo Fenótipo para Isquemia sem Doença Arterial Coronariana / Coronary Tortuosity as a New Phenotype for Ischemia without Coronary Artery Disease

Resumo Fundamento As artérias coronárias tendem a ser mais tortuosas que outras artérias e acompanham os movimentos repetidos de flexão e relaxamento que ocorrem durante o ciclo cardíaco. A Tortuosidade das artérias Coronárias (TCor) causa alterações no fluxo coronariano, com uma redução na pressão de perfusão distal, o que pode levar à isquemia miocárdica. Objetivo Avaliar a associação entre TCor e isquemia miocárdica. Métodos Entre janeiro de 2015 e dezembro de 2017, 57 pacientes com angina e doença arterial coronariana não obstrutiva pela angiografia coronária invasiva (ACI) foram incluídos retrospectivamente. Variáveis angiográficas foram analisadas para avaliar a presença e grau de tortuosidade e correlacionadas com seus respectivos territórios vasculares na cintilografia de perfusão miocárdica com estresse. A TCor foi definida como artérias coronárias com três ou mais curvaturas com ângulos ≤ 90o, medidos durante diástole. Um nível de 5% foi estabelecido como estatisticamente significativo. Um nível de 5% foi definido como estatisticamente significativo. Resultados Um total de 17 homens e 40 mulheres foram incluídos (idade média de 58,3 anos). A TCor foi observada em 16 pacientes (28%) e em 24 das 171 artérias. Observou-se uma associação significativa entre TCor e isquemia na análise por artéria (p<0,0001). O fator angiográfico mais associado com isquemia foi o número de curvaturas em uma artéria epicárdica medido na sístole (p=0,021). Conclusão Este estudo mostrou uma associação da TCor com isquemia miocárdica em pacientes com artérias coronárias não obstruídas e angina. Observou-se uma relação entre número aumentado de curvaturas na artéria coronária medido por angiografia durante sístole e isquemia.

Abstract Background Coronary arteries tend to be more tortuous than other arteries and follow the repeated flexion and relaxation movements that occur during the cardiac cycle. Coronary tortuosity (CorT) leads to changes in coronary flow with a reduction in distal perfusion pressure, which could cause myocardial ischemia. Objective To assess the association between CorT and myocardial ischemia. Methods Between January 2015 and December 2017, 57 patients with angina and nonobstructive coronary artery disease detected by invasive coronary angiography (ICA) were retrospectively enrolled. Angiographic variables were analyzed to assess the presence and degree of tortuosity and correlated with their respective vascular territories on stress myocardial perfusion imaging (MPI). CorT was defined as coronary arteries with three or more bend angles ≤90°, measured during diastole. Statistical significance was determined at the 5% level. Results A total of 17 men and 40 women were enrolled (mean age 58.3 years). CorT was observed in 16 patients (28%) and in 24 of 171 arteries. There was a significant association between CorT and ischemia when analyzed per artery (p<0.0001). The angiographic factor most associated with ischemia was the number of bend angles in an epicardial artery measured at systole (p=0.021). Conclusion This study showed an association of CorT and myocardial ischemia in patients with unobstructed coronary arteries and angina. An increased number of coronary bend angles measured by angiography during systole was related to ischemia.

Machine learning with D-dimer in the risk stratification for pulmonary embolism: a derivation and internal validation study.

AIM: To develop a machine learning model to predict the diagnosis of pulmonary embolism (PE). METHODS AND RESULTS: We undertook a derivation and internal validation study to develop a risk prediction model for use in patients being investigated for possible PE. The machine learning technique, generalized logistic regression using elastic net, was chosen following an assessment of seven machine learning techniques and on the basis that it optimized the area under the receiver operator characteristic curve (AUC) and Brier score. Models were developed both with and without the addition of D-dimer. A total of 3347 patients were included in the study of whom, 219 (6.5%) had PE. Four clinical variables (O2 saturation, previous deep venous thrombosis or PE, immobilization or surgery, and alternative diagnosis equal or more likely than PE) plus D-dimer contributed to the machine learning models. The addition of D-dimer improved the AUC by 0.16 (95% confidence interval 0.13-0.19), from 0.73 to 0.89 (0.87-0.91) and decreased the Brier score by 14% (10-18%). More could be ruled out with a higher positive likelihood ratio than by the Wells score combined with D-dimer, revised Geneva score combined with D-dimer, or the Pulmonary Embolism Rule-out Criteria score. Machine learning with D-dimer maintained a low-false-negative rate at a true-negative rate of nearly 53%, which was better performance than any of the other alternatives. CONCLUSION: A machine learning model outperformed traditional risk scores for the risk stratification of PE in the emergency department. However, external validation is needed.

High-output Cardiac Failure: A Forgotten Phenotype in Clinical Practice.

INTRODUCTION: The knowledge on High-Output Cardiac Failure (HOCF) has greatly improved in the last two decades. One of the advances was the identification of a new phenotype of HOCF, characterized by the absence of ventricular dilation, already associated with liver disease, Arteriovenous Fistulas (AVF), lung disease, myelodysplastic syndromes, and obesity. However, it has been noted that any aetiology can present with one of the two phenotypes, depending on the evolution. OBJECTIVE: The study aims to describe, through an integrative review, the physiopathology and aetiologies of HOCF and to discuss phenotypes associated with this condition. METHODS: Revisions, guidelines, case-controls, cohort studies and clinical studies were searched in MEDLINE and LILACS, using the connectives in the "cardiac output, high" database (MeSH Terms) OR "high cardiac output" (All Fields). DISCUSSION: Two distinct phenotypes are currently described in the HOCF, regardless of the aetiology: 1) one with enlarged cardiac chambers; and 2) with normal heart chambers. The mechanisms related to HOCF are vasodilation, arteriovenous shunts that cause increased microvascular density, Reduced Systemic Vascular Resistance (RSVR), and high metabolism. These mechanisms lead to activation of the renin-angiotensin-aldosterone system, sodium and water retention, activation of neprilysin, of the sodium-glucose-2 transporter, which promote interstitial fibrosis, ventricular remodeling and a consequent increase in cardiac output >8L/min. CONCLUSION: Many aetiologies of HOCF have been described, and some of them are potentially curable. Prompt recognition of this condition and proper treatment may lead to better outcomes.

Worsening Renal Function and Congestion in Patients with Acute Heart Failure: A Study with Bioelectrical Impedance Vector Analysis (BIVA) and Neutrophil Gelatinase-Associated Lipocalin (NGAL). / Agravamento da Função Renal e Congestão em Pacientes com Insuficiência Cardíaca Aguda: Estudo com Análise Vetorial de Bioimpedância Elétrica (BIVA) e Lipocalina Associada à Gelatinase Neutrofílica (NGAL).

BACKGROUND: Worsening renal function (WRF) is frequently observed in the setting of aggressive diuresis for the treatment of acute decompensated heart failure (ADHF) and is associated with poor outcomes in some studies. OBJECTIVE: We sought to assess the relationship of WRF and congestion at discharge with events (cardiac death or heart failure hospitalization). METHODS: Eighty patients with ADHF were studied. WRF was defined by an absolute increase in serum creatinine of ≥0.5 mg/dL from the values measured at the time of admission. B-type natriuretic peptide (BNP) and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at admission and at discharge. Congestive state at discharge was assessed using bioelectrical impedance vector analysis (BIVA). Primary endpoint was time to first event defined as a combination of cardiac death or heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis was used to determine the best hydration index cutoff to predict events. Kaplan-Meier event-free survival curves were constructed and compared using the log-rank test. Cox proportional hazards models were used to investigate the association with events. The criterion for determining statistical significance was p<0.05. RESULTS: Mean age was 60.6±15 years, and 48 (60%) were male. Mean ejection fraction was 35.3±7.8%. WRF occurred in 37.5% of the sample. Baseline creatinine was associated with WRF (p<0.001), but neither admission BNP (p=0.35) nor admission NGAL (p=0.18) was predictor of WRF. Using Cox proportional hazard models, hydration index at discharge calculated with BIVA was significantly associated with events (HR 1.39, 95% CI 1.25-1.54, p<0.0001) but not WRF (HR 2.14, 95% CI 0.62-7.35, p=0.22). CONCLUSION: Persistent congestion at discharge was associated with worse outcomes. WRF seems to be related to hemodynamic changes during the decongestion process but not to kidney tubular injuries.

FUNDAMENTO: O agravamento da função renal (AFR) é frequentemente observado na terapia agressiva com diuréticos para o tratamento de insuficiência cardíaca aguda descompensada (ICAD) e está associado com piores desfechos em alguns estudos. OBJETIVO: Avaliar a relação de AFR e congestão na alta hospitalar com ocorrência de eventos (morte cardíaca ou internação por insuficiência cardíaca). MÉTODOS: Oitenta pacientes com ICAD foram estudados. O AFR foi definido por um aumento absoluto (≥0,5 mg/dL) nos níveis séricos de creatinina a partir dos valores obtidos na admissão. Concentrações de peptídeo natriurético do tipo B (BNP) e lipocalina associada à gelatinase neutrofílica (NGAL) foram medidas na admissão e na alta hospitalar. Congestão foi avaliada na alta utilizando a análise vetorial de bioimpedância elétrica (BIVA). O desfecho primário foi o tempo para o primeiro evento, definido como uma combinação de morte cardíaca ou hospitalização por insuficiência cardíaca. Análise de curva Característica de Operação do Receptor (curva ROC) foi realizada para determinar o ponto de corte de IH mais adequado para predição de eventos. Curvas Kaplan-Meier de sobrevida livre de eventos foram construídas e comparadas usando o teste de log-rank. Modelos de riscos proporcionais de Cox foram usados para investigar a associação com eventos. O critério para se estabelecer significância estatística foi um p<0.05. RESULTADOS: A idade média foi 60,6 ± 15,0 anos, e 48 (60%) pacientes eram do sexo masculino. A fração de ejeção média foi 35,3±7,8%. O AFR ocorreu em 37,5% da amostra. A creatinina basal associou-se com AFR (p<0,001), mas nem BNP (p=0,35) nem NGAL (p=0,18) na admissão foram preditores de AFR. Usando modelos de riscos proporcionais de Cox, o índice de hidratação na alta, estimado por BIVA, associou-se significativamente com ocorrência de eventos (HR 1,39; IC95% 1,25-1,54, p<0,0001), mas não com AFR (HR 2,14; IC95% 0,62-7,35, p=0,22). CONCLUSÃO: A congestão persistente na alta associou-se com piores desfechos. O AFR parece estar relacionado com alterações hemodinâmicas durante o processo de descongestionamento, mas não com lesões renais.

Agravamento da Função Renal e Congestão em Pacientes com Insuficiência Cardíaca Aguda: Estudo com Análise Vetorial de Bioimpedância Elétrica (BIVA) e Lipocalina Associada à Gelatinase Neutrofílica (NGAL) / Worsening Renal Function and Congestion in Patients with Acute Heart Failure: A Study with Bioelectrical Impedance Vector Analysis (BIVA) and Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Resumo Fundamento: O agravamento da função renal (AFR) é frequentemente observado na terapia agressiva com diuréticos para o tratamento de insuficiência cardíaca aguda descompensada (ICAD) e está associado com piores desfechos em alguns estudos. Objetivo: Avaliar a relação de AFR e congestão na alta hospitalar com ocorrência de eventos (morte cardíaca ou internação por insuficiência cardíaca). Métodos: Oitenta pacientes com ICAD foram estudados. O AFR foi definido por um aumento absoluto (≥0,5 mg/dL) nos níveis séricos de creatinina a partir dos valores obtidos na admissão. Concentrações de peptídeo natriurético do tipo B (BNP) e lipocalina associada à gelatinase neutrofílica (NGAL) foram medidas na admissão e na alta hospitalar. Congestão foi avaliada na alta utilizando a análise vetorial de bioimpedância elétrica (BIVA). O desfecho primário foi o tempo para o primeiro evento, definido como uma combinação de morte cardíaca ou hospitalização por insuficiência cardíaca. Análise de curva Característica de Operação do Receptor (curva ROC) foi realizada para determinar o ponto de corte de IH mais adequado para predição de eventos. Curvas Kaplan-Meier de sobrevida livre de eventos foram construídas e comparadas usando o teste de log-rank. Modelos de riscos proporcionais de Cox foram usados para investigar a associação com eventos. O critério para se estabelecer significância estatística foi um p<0.05. Resultados: A idade média foi 60,6 ± 15,0 anos, e 48 (60%) pacientes eram do sexo masculino. A fração de ejeção média foi 35,3±7,8%. O AFR ocorreu em 37,5% da amostra. A creatinina basal associou-se com AFR (p<0,001), mas nem BNP (p=0,35) nem NGAL (p=0,18) na admissão foram preditores de AFR. Usando modelos de riscos proporcionais de Cox, o índice de hidratação na alta, estimado por BIVA, associou-se significativamente com ocorrência de eventos (HR 1,39; IC95% 1,25-1,54, p<0,0001), mas não com AFR (HR 2,14; IC95% 0,62-7,35, p=0,22). Conclusão: A congestão persistente na alta associou-se com piores desfechos. O AFR parece estar relacionado com alterações hemodinâmicas durante o processo de descongestionamento, mas não com lesões renais.

Abstract Background: Worsening renal function (WRF) is frequently observed in the setting of aggressive diuresis for the treatment of acute decompensated heart failure (ADHF) and is associated with poor outcomes in some studies. Objective: We sought to assess the relationship of WRF and congestion at discharge with events (cardiac death or heart failure hospitalization). Methods: Eighty patients with ADHF were studied. WRF was defined by an absolute increase in serum creatinine of ≥0.5 mg/dL from the values measured at the time of admission. B-type natriuretic peptide (BNP) and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at admission and at discharge. Congestive state at discharge was assessed using bioelectrical impedance vector analysis (BIVA). Primary endpoint was time to first event defined as a combination of cardiac death or heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis was used to determine the best hydration index cutoff to predict events. Kaplan-Meier event-free survival curves were constructed and compared using the log-rank test. Cox proportional hazards models were used to investigate the association with events. The criterion for determining statistical significance was p<0.05. Results: Mean age was 60.6±15 years, and 48 (60%) were male. Mean ejection fraction was 35.3±7.8%. WRF occurred in 37.5% of the sample. Baseline creatinine was associated with WRF (p<0.001), but neither admission BNP (p=0.35) nor admission NGAL (p=0.18) was predictor of WRF. Using Cox proportional hazard models, hydration index at discharge calculated with BIVA was significantly associated with events (HR 1.39, 95% CI 1.25-1.54, p<0.0001) but not WRF (HR 2.14, 95% CI 0.62-7.35, p=0.22). Conclusion: Persistent congestion at discharge was associated with worse outcomes. WRF seems to be related to hemodynamic changes during the decongestion process but not to kidney tubular injuries.

Growth differentiation factor-15, a novel systemic biomarker of oxidative stress, inflammation, and cellular aging: Potential role in cardiovascular diseases.

Growth differentiation factor-15 (GDF-15) is a cytokine upregulated in multiple pathological conditions where oxidative stress, endothelial dysfunction, tissue aging, and chronic inflammation are the hallmarks. GDF-15 has many sources of production, including cardiac and vascular myocytes, endothelial cells, adipocytes and macrophages in response to metabolic stress, oncogenic transformation and the burden of proinflammatory cytokines or reactive oxygen species. Although the main sources of GDF-15 are extracardiac tissues, it has been shown to be elevated in many cardiac disorders. In experimental models of heart disease, GDF-15 release is induced after an ischemic insult and in pressure overload scenarios. Likewise, in recent years, an increasing body of evidence has emerged linking GDF-15 to the risk of mortality in acute coronary syndromes, atrial fibrillation and heart failure. Additionally, GDF-15 has been shown to add prognostic information beyond other conventional biomarkers such as natriuretic peptides and cardiac troponins. Further studies are needed to assess whether the incorporation of GDF-15 into clinical practice can improve cardiovascular outcomes.

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.

Prognosis of Heart Failure with Preserved Ejection Fraction in Primary Care by the H2FPEF Score

Abstract Background: Primary care physicians have difficulty dealing with patients who have HF with preserved LVEF(HFpEF). The prognosis of HFpEF is poor, and difficult to predict on primary care. Objective: The aim of the study is to apply the H2FPEF score to primary care patients and verify its power to assess the risk of death or hospitalization due to cardiovascular disease. Methods: This longitudinal study included 402 individuals, with signs or symptoms of HF, aged≥45 years and, underwent an evaluation which included clinical examination, BNP and echocardiogram. The diagnosis of HFpEF was confirmed by the criteria of the European Society of Cardiology. After five years, the patients were reassessed as to the occurrence of the composite outcome, death from any cause or hospitalization for cardiovascular disease. H2FPEF used six variables: body mass index, medications for hypertension, age, pulmonary artery systolic pressure, atrial fibrillation and E/e' ratio ranged from 0 to 9 points. The level of statistical significance was p<0.05. Results: HFpEF was diagnosed in 58(14.4%). Among patients with H2FPEF≥4, 30% had HFpEF and in those with a score≤4, HFpEF was present in 12%. Patients with HFpEF and H2FPEF≥4 had 53% of outcomes, whereas patients with HFpEF and a score ≤4 had a 21% of outcomes. BNP values were higher in patients with HFpEF compared to those without HFpEF(p<0.0001). Conclusion: H2FPEF≥4 indicated a worse prognosis in patients with HFpEF assisted in primary care. H2FPEF may be a simple and useful tool for risk stratification in patients with HFpEF at the primary care.

Síndrome Cardiorrenal Aguda: Qual Critério Diagnóstico Utilizar e sua Importância para o Prognóstico? / Acute Cardiorenal Syndrome: Which Diagnostic Criterion to Use And What is its Importance for Prognosis?

Resumo A indefinição de critérios diagnósticos para síndrome cardiorrenal aguda (SCRA) impacta em diferentes resultados prognósticos. Objetivou-se avaliar os critérios diagnósticos da SCRA e o impacto no prognóstico. Procedeu-se à revisão sistemática utilizando-se a metodologia PRISMA e os critérios PICO nas bases MEDLINE, EMBASE e LILACS. A pesquisa incluiu artigos originais do tipo ensaio clínico, coorte, caso-controle e meta-análises publicados no período de janeiro de 1998 até junho de 2018. Não foi encontrada na literatura nem nas diretrizes de insuficiência cardíaca uma definição clara dos critérios diagnósticos da SCRA. O critério diagnóstico mais comumente utilizado é o aumento da creatinina sérica de pelo menos 0,3 mg/dl em relação à basal. Entretanto, existem controvérsias na definição de creatinina basal e de qual deveria ser a creatinina sérica de referência dos pacientes críticos. Esta revisão sistemática sugere que os critérios de SCRA devem ser revistos para que se inclua o diagnóstico de SCRA na admissão hospitalar. A creatinina sérica de referência deve refletir a função renal basal antes do início da injúria renal aguda.

Abstract The absence of a consensus about the diagnostic criteria for acute cardiorenal syndrome (ACRS) affects its prognosis. This study aimed at assessing the diagnostic criteria for ACRS and their impact on prognosis. A systematic review was conducted using PRISMA methodology and PICO criteria in the MEDLINE, EMBASE and LILACS databases. The search included original publications, such as clinical trials, cohort studies, case-control studies, and meta-analyses, issued from January 1998 to June 2018. Neither literature nor heart failure guidelines provided a clear definition of the diagnostic criteria for ACRS. The serum creatinine increase by at least 0.3 mg/dL from baseline creatinine is the most used diagnostic criterion. However, the definition of baseline creatinine, as well as which serum creatinine should be used as reference for critical patients, is still controversial. This systematic review suggests that ACRS criteria should be revised to include the diagnosis of ACRS on hospital admission. Reference serum creatinine should reflect baseline renal function before the beginning of acute kidney injury.

Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study.

BACKGROUND: Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. METHODS: Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS: The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively (P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group (P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group (P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization (V˙O2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION: Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.