Cholesteryl ester transfer protein (CETP), HDL capacity of receiving cholesterol and status of inflammatory cytokines in patients with severe heart failure.

BACKGROUND: Heart failure (HF) courses with chronic inflammatory process and alterations in lipid metabolism may aggravate the disease. The aim was to test whether the severity of HF, using brain natriuretic peptide (BNP) as a marker, is associated with alterations in functional aspects of HDL, such as lipid transfer, cholesterol ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) concentration. METHODS: Twenty-five HF patients in NYHA class I/II and 23 in class III/IV were enrolled. Plasma lipids, apolipoproteins, CETP, LCAT, oxidized-LDL (oxLDL) and paraoxonase-1 (PON-1) activity were determined. Lipid transfer from a donor artificial nanoparticle to HDL was measured by in vitro assay. RESULTS: Total cholesterol (p = 0.049), LDL-C (p = 0.023), non-HDL-C (p = 0.029) and CETP, that promotes lipid transfer among lipoproteins (p = 0.013), were lower in III/IV than in I/II group. Triglycerides, HDL-C, apo A-I, apo B, oxLDL, LCAT, enzyme that catalyzes serum cholesterol esterification, PON-1 activity, and in vitro transfers of cholesterol, triglycerides and phospholipids to HDL, important steps in HDL metabolism, were equal. IL-8 was higher in III/IV (p = 0.025), but TNFα, IL-1ß, IL-6 and MCP-1 were equal. BNP was negatively correlated with CETP (r = - 0.294; p = 0.042) and positively correlated with IL-8 (r = 0.299; p = 0.039). CONCLUSIONS: Our results disclosed the relationship between CETP levels and HF severity, by comparing two HF groups and by correlation analysis. Lower CETP levels may be a marker of HF aggravation and possibly of worse prognosis. Practical applications of this initial finding, as the issue whether CETP could be protective against HF aggravation, should be explored in larger experimental and clinical studies.

Heart transplantation: review.

Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.

Heart transplantation: review / Transplante cardíaco: revisão

ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.

RESUMO O transplante cardíaco é atualmente a abordagem cirúrgica definitiva padrão-ouro no tratamento da insuficiência cardíaca refratária. No entanto, a escassez de doadores limita a realização de um número maior de transplantes cardíacos, situação em que vem aumentando a utilização de dispositivos de assistência circulatória mecânica. Com indicações e contraindicações bem estabelecidas, além de diagnóstico e tratamento de rejeição, por meio de protocolos definidos de imunossupressão, os resultados do transplante cardíaco são muito favoráveis. Dentre as complicações precoces que podem impactar a sobrevida, destacamos a disfunção primária do enxerto, a disfunção do ventrículo direito, rejeição e infecções; já as complicações tardias incluem a doença vascular do enxerto e as neoplasias. Apesar das dificuldades para realização do transplante cardíaco, em especial pela escassez de doadores e pela elevada mortalidade em fila de espera, no Brasil, existe um grande potencial, tanto no aumento de doadores efetivos, quanto na utilização de dispositivos de assistência circulatória, o que pode vir a impactar positivamente no número e nos resultados do transplante cardíaco.

How can we know if treatment for heart failure is effective? / Como saber se o tratamento da insuficiência cardíaca é eficaz?

Heart failure is a disease that progresses with high morbidityand mortality, but the correct treatment using neurohormonal inhibitors could alter its natural history. Although more and more patients have been treated, drugs are sometimes prescribed at doses lower than those known to be effective. In heart failure, a marker of treatment efficacy is lacking, since symptomatic improvement does not indicate that the patient will remainstable in the long term. The aim of this study was to evaluate the need for a marker of improvement during treatment. Reverse remodeling, present in clinical trials of drugs that reduced the mortality of patients with heart failure, is a marker of good response to treatment and can be used as a marker of treatment efficacy. Lack of reverse remodeling is indicative of greater severity of the case or of insufficient treatment. The same is true of the analysis of hemodynamic response when there is a reduction in intracardiac pressures, documenting that the treatment is effective. The persistence of heart rate above 70 bpm is another important marker of poor prognosis, and indicative of the need for treatment optimization. Reverse remodeling,improved ejection fraction, hemodynamic improvement, andreduction in heart rate are markers of treatment efficacy and are followed by significant reduction in mortality, and may be used to guide treatment...

A insuficiência cardíaca é uma doença que evolui com alta morbimortalidade, mas o tratamento correto, que emprega bloqueadores neurohormonais, pode modificar sua história natural. Embora cada vez mais os pacientes recebam tratamento, muitas vezes os fármacos são prescritos em doses menores do que as reconhecidas como eficazes. Na insuficiência cardíaca, falta um marcador de eficácia do tratamento, pois a melhora sintomática não indica que o paciente permanecerá estável em longo prazo. O objetivo deste estudo foi avaliar a necessidade de emprego marcador de melhora durante o tratamento. A reversão da dilatação cardíaca, presente nos ensaios clínicos dos fármacos que reduziram a mortalidade dos portadores de insuficiência cardíaca, é um marcador de boa resposta ao tratamento e pode ser empregada como marcador de eficácia do tratamento. A ausência de reversão é indicativa de maior gravidade do casoou de tratamento insuficiente. O mesmo é verdadeiro em relação à análise da resposta hemodinâmica, quando ocorre redução das pressões intracardíacas, documentando que o tratamento está sendo eficaz. A persistência de frequência cardíaca acima de 70 bpmé outro marcador importante de pior prognóstico e indicativo de necessidade de melhora no tratamento. A reversão da dilatação cardíaca, a melhora da fração de ejeção, a melhora hemodinâmica e a redução da frequência cardíaca são marcadores de eficácia do tratamento e são acompanhadas de redução significativa da mortalidade, podendo ser empregadas para orientar o tratamento...

Agreement of BNP and NT-proBNP and the influence of clinical and laboratory variables.

OBJECTIVE: To correlate the serum levels of B type natriuretic peptide and the N-terminal fraction of the pro-B type natriuretic peptide, as well as to analyze the influence of age, obesity, renal failure, left ventricle ejection fraction, diastolic dysfunction, and anemia on serum levels of both markers. METHODS: An observational study in which the agreement was compared between these markers in consecutive samples of 138 patients. For the correlation, Pearson's test was used, and p<0.05 was considered statistically significant. RESULTS: A linear association was observed between the B type natriuretic peptide and N-terminal fraction of the pro-B type natriuretic peptide (r=0.907; p<0.001). When evaluating the categorized measurements as normal and altered, there was good agreement, with 90.6% of agreement classifications (p<0.001) in which altered values of the N-terminal fraction of the pro-B type natriuretic peptide and normal values of the B type natriuretic peptide represented 8.7% of the total; the opposite situation represented 1% of the total. Assessment of the influence of the clinical and laboratorial factors on the levels of natriuretic peptides showed that they rise according to age, but that they fall as the ejection fraction increases. Patients with anemia (p<0.001) or with renal failure (p=0.007) had higher values of both markers. There was no association between obesity and the B type natriuretic peptide. CONCLUSION: There was satisfactory agreement between the B type natriuretic peptide and the N-terminal fraction of the pro-B type natriuretic peptide. Age, creatinine levels, and hemoglobin, as well as ventricular function, influence the serum levels of both natriuretic peptides.

Comparação entre BNP e NT-proBNP quanto à concordância e quanto à influência das variáveis clínicas e laboratoriais / Agreement of BNP and NT-proBNP and the influence of clinical and laboratory variables

OBJETIVO: Correlacionar os níveis séricos do peptídeo natriurético tipo B e da fração N-terminal do pró-peptídeo natriurético tipo B, além de analisar a influência de idade, obesidade, insuficiência renal, fração da ejeção do ventrículo esquerdo, disfunção diastólica e anemia nos níveis séricos de ambos os marcadores. MÉTODOS: Estudo observacional, no qual se comparou a concordância entre esses marcadores em amostras consecutivas de 138 pacientes. Para a correlação, utilizou-se o teste de Pearson e foi considerado estatisticamente significante p<0,05. RESULTADOS: Observou-se associação linear entre peptídeo natriurético tipo B e fração N-terminal do pró-peptídeo natriurético tipo B (r=0,907; p<0,001). Ao se avaliarem as medidas categorizadas como normais e alteradas, encontrou-se boa concordância, com 90,6% de classificações concordantes (p<0,001), sendo que valores alterados da fração N-terminal do pró-peptídeo natriurético tipo B e normais de peptídeo natriurético tipo B representaram 8,7% do total, e o contrário representou 1% do total. A avaliação da influência dos fatores clínicos e laboratoriais nos níveis dos peptídeos natriuréticos mostrou que eles se elevam de acordo com a idade, mas que diminuem conforme aumenta a fração de ejeção. Pacientes com anemia (p<0,001) ou com insuficiência renal (p=0,007) apresentaram valores maiores de ambos os marcadores. Não houve associação entre obesidade e peptídeo natriurético tipo B. CONCLUSÃO: Houve concordância satisfatória entre peptídeo natriurético tipo B e a fração N-terminal do pró-peptídeo natriurético tipo B. Idade, níveis de creatinina e hemoglobina, assim como função ventricular, influenciam os níveis séricos de ambos os peptídeos natriuréticos.

OBJECTIVE: To correlate the serum levels of B type natriuretic peptide and the N-terminal fraction of the pro-B type natriuretic peptide, as well as to analyze the influence of age, obesity, renal failure, left ventricle ejection fraction, diastolic dysfunction, and anemia on serum levels of both markers. METHODS: An observational study in which the agreement was compared between these markers in consecutive samples of 138 patients. For the correlation, Pearson's test was used, and p<0.05 was considered statistically significant. RESULTS: A linear association was observed between the B type natriuretic peptide and N-terminal fraction of the pro-B type natriuretic peptide (r=0.907; p<0.001). When evaluating the categorized measurements as normal and altered, there was good agreement, with 90.6% of agreement classifications (p<0.001) in which altered values of the N-terminal fraction of the pro-B type natriuretic peptide and normal values of the B type natriuretic peptide represented 8.7% of the total; the opposite situation represented 1% of the total. Assessment of the influence of the clinical and laboratorial factors on the levels of natriuretic peptides showed that they rise according to age, but that they fall as the ejection fraction increases. Patients with anemia (p<0.001) or with renal failure (p=0.007) had higher values of both markers. There was no association between obesity and the B type natriuretic peptide. CONCLUSION: There was satisfactory agreement between the B type natriuretic peptide and the N-terminal fraction of the pro-B type natriuretic peptide. Age, creatinine levels, and hemoglobin, as well as ventricular function, influence the serum levels of both natriuretic peptides.

Controle da anticoagulação com Varfarina realizada em ambulatório especializado / Control of anticoagulation with Warfarin in a specialized outpatient clinic

Fundamentos: Em várias cardiopatias a anticoagulação previne eventos tromboembólicos. Varfarina é o anticoagulante oral mais utilizado, entretanto sua eficácia e segurança dependem do monitoramento do tempo de protrombina (TP) e sua padronização pelo INR. Manter INR adequado é um desafio, especialmente em população de baixos níveis educacional e socioeconômico. Ambulatório especializado em anticoagulação representa importante aliado.Objetivo: Avaliar o controle do INR em pacientes acompanhados em ambulatório de anticoagulação.Métodos: Durante dois meses foram selecionados pacientes que utilizavam varfarina e eram acompanhados em ambulatório especializado no controle de TP. Os pacientes são assistidos em intervalo máximo de quatro semanas, recebem orientação sobre riscos e benefícios da anticoagulação e têm carteira específica para o acompanhamento. Foi considerado INR adequado valores entre 2,0 e 3,5. Utilizado o teste t de Student e considerado significativo p<0,05. Resultados: Avaliados 96 pacientes, sendo 50 (56,25 %) homens; média de idade 59±14,9 anos. A indicação para anticoagulação foi fibrilação/flutter atrial em 55,21 %; prótese valvar em 26,04 %; tromboembolismo prévio em 9,38 % e trombo intracardíaco em 9,37 %. O tempo de acompanhamento médio foi 361,26±216,34 dias, e 66 (68,75 %) pacientes apresentaram INR adequado. A dose média diária de varfarina foi 4,93±3,13 mg/dia. A média de idade, o tempo de acompanhamento e a dose média diária foram semelhantes nos dois grupos: com INR adequado e com INR inadequado. Conclusão: A anticoagulação orientada por equipe especializada é efetiva e segura em pacientes com baixa renda e baixo nível educacional, permitindo que seja prescrita para esses pacientes.

Background: In several cardiopathies anticoagulation prevents thromboembolic events. Although warfarin is the most widely used oral anticoagulant, its efficacy and safety depend on monitoring the prothrombin time (PT) and its standardization by INR. Maintaining adequate INR is challenging, especially in populations with low educational, social and economic levels. Clinics specializing in anticoagulation are important allies.Objective: To evaluate INR control among patients monitored at an anticoagulation clinic. Methods: For two months, patients taking warfarin were selected and monitored at a PT control clinic, seen at least every four weeks and receiving guidance on the risks and benefits of anticoagulation, with specific monitoring cards. Appropriate INR values were taken as between 2.0 and 3.5, using the Student t test and a significance of p<0.05.Results: Having evaluated 96 patients, with 50 men (56.25 %) and a mean age of 59±14.9 years, the indication for anticoagulation was atrial fibrillation / atrial flutter for 55.21 %; prosthetic valve for 26.04 %; previous thromboembolism for 9.38 % and intracardiac thrombus for 9.37 %. The median follow-up time at the clinic was 361.26±216.34 days, and 66 (68.75 %) of the patients had an appropriate INR. The mean daily dose of warfarin was 4.93±3.13 mg/day. The average age, monitoring time and mean daily dose were similar for both groups, with adequate and inadequate INR. Conclusion: Anticoagulation guided by specialized staff is effective and safe for patients with lower income and educational levels, allowing it to be prescribed for these patients.

Role of BNP levels on the prognosis of decompensated advanced heart failure.

BACKGROUND: Heart failure (HF) is a condition with poor outcome, especially in advanced cases. Determination of B-type natriuretic peptide (BNP) levels is useful in the diagnosis of cardiac decompensation and has also been proving useful in the prognostic evaluation. OBJECTIVES: To verify whether BNP levels are able to identify patients with a poorer outcome and whether it is an independent prognostic factor considering age, gender, cardiac and renal functions, as well as the cause of heart disease. METHODS: 189 patients in functional class III/IV advanced HF were studied. All had systolic dysfunction and had their BNP levels determined during hospitalization. Variables related to mortality were studied using univariate and multivariate analyses. RESULTS: BNP levels were higher in patients who died in the first year of follow-up (1,861.9 versus 1,408.1 pg/dL; p = 0.044) and in chagasic patients (1,985 versus 1,452 pg/mL; p = 0.001); the latter had a higher mortality rate in the first year of follow-up (56% versus 35%; p = 0.010). The ROC curve analysis showed that the BNP level of 1,400 pg/mL was the best predictor of events; high levels were associated with lower LVEF (0.23 versus 0.28; p = 0.002) and more severe degree of renal dysfunction (mean urea 92 versus 74.5 mg/dL; p = 0.002). CONCLUSION: In advanced HF, high BNP levels identified patients at higher risk of a poorer outcome. Chagasic patients showed higher BNP levels than those with heart diseases of other causes, and have poorer prognosis.

Papel dos níveis de BNP no prognóstico da insuficiência cardíaca avançada descompensada / Role of BNP levels on the prognosis of decompensated advanced heart failure

FUNDAMENTO: A insuficiência cardíaca (IC) é doença que cursa com má evolução, especialmente naqueles com IC avançada. A dosagem de peptídeo natriurético tipo B(BNP), ao lado da utilidade no diagnóstico da descompensação cardíaca, vem se mostrando útil na avaliação prognóstica. OBJETIVOS: Verificar se os níveis de BNP identificam quais pacientes evoluiriam pior e se o BNP seria fator independente de mortalidade considerando-se idade, sexo, funções cardíaca e renal e etiologia da cardiopatia. MÉTODOS: 189 pacientes com IC avançada em classe funcional III/IV foram estudados. Todos tinham disfunção sistólica e dosaram-se os níveis de BNP na hospitalização. Analisaram-se as variáveis relacionadas com a mortalidade através de análises univariada e multivariada. RESULTADOS: Os níveis de BNP foram mais elevados nos pacientes que morreram no primeiro ano de seguimento (1.861,9 versus 1.408,1 pg/dL; p = 0,044) e nos chagásicos (1.985 versus 1.452 pg/mL; p = 0,001), e esses pacientes chagásicos tiveram maior mortalidade no primeiro ano de seguimento (56% versus 35%; p = 0,010). Pela curva ROC, o valor de BNP de 1.400 pg/mL foi o melhor preditor de eventos, estando os valores elevados associados a FEVE mais baixa (0,23 versus 0,28; p = 0,002) e maior grau de disfunção renal (ureia média 92 versus 74,5 mg/dL; p = 0,002). CONCLUSÃO: Na IC avançada, os níveis elevados de BNP identificam pacientes com maior potencial de pior evolução. Os pacientes chagásicos apresentam níveis mais elevados de BNP do que as outras etiologias e têm pior evolução.

BACKGROUND: Heart failure (HF) is a condition with poor outcome, especially in advanced cases. Determination of B-type natriuretic peptide (BNP) levels is useful in the diagnosis of cardiac decompensation and has also been proving useful in the prognostic evaluation. OBJECTIVES: To verify whether BNP levels are able to identify patients with a poorer outcome and whether it is an independent prognostic factor considering age, gender, cardiac and renal functions, as well as the cause of heart disease. METHODS: 189 patients in functional class III/IV advanced HF were studied. All had systolic dysfunction and had their BNP levels determined during hospitalization. Variables related to mortality were studied using univariate and multivariate analyses. RESULTS: BNP levels were higher in patients who died in the first year of follow-up (1,861.9 versus 1,408.1 pg/dL; p = 0.044) and in chagasic patients (1,985 versus 1,452 pg/mL; p = 0.001); the latter had a higher mortality rate in the first year of follow-up (56% versus 35%; p = 0.010). The ROC curve analysis showed that the BNP level of 1,400 pg/mL was the best predictor of events; high levels were associated with lower LVEF (0.23 versus 0.28; p = 0.002) and more severe degree of renal dysfunction (mean urea 92 versus 74.5 mg/dL; p = 0.002). CONCLUSION: In advanced HF, high BNP levels identified patients at higher risk of a poorer outcome. Chagasic patients showed higher BNP levels than those with heart diseases of other causes, and have poorer prognosis.