Aplicações clínicas do peptídeo natriurético do tipo B
Hospital Pró-Cardíaco - Rio de Janeiro, RJ
O sistema peptídeo natriurético é ativado sempre que o coração sofre uma agressão, seja ela crônica seja aguda, na tentativa de compensar os sistemas vasoconstritores que são ativados nessas situações. As principais ações desse sistema são a promoção de diurese e vasodilatação. Sabe-se, no entanto, que uma série de efeitos adicionais é deflagrada com a liberação desses peptídeos, como inibição do sistema renina-angiotensina-aldosterona, inibição simpática, inibição de crescimento de células musculares lisas e possivelmente redução de apoptose1.
Três peptídeos são conhecidos – o peptídeo do tipo A (liberado pelos átrios), o do tipo B (liberado pelos ventrículos) e o do tipo C, liberado por células vasculares. O peptídeo do tipo B (BNP), por ser liberado diretamente pelos ventrículos, é o que melhor reflete a situação cardíaca, tendo alcançado maior aplicabilidade clínica. O estimulo para sua liberação é o estiramento das fibras ventriculares causado por uma sobrecarga de pressão ou de volume1,2. Mais recentemente demonstrou-se que isquemia miocárdica, levando a aumento de tensão parietal por disfunção sistólica e/ou diastólica, também pode promover liberação de BNP3.
Antes de sua liberação na circulação, o BNP apresenta precursores. No interior do miócito, o pro-BNP é clivado e libera na circulação duas moléculas – o BNP, que é a fração ativa, e a fração N-Terminal-pro-BNP (NT-pro-BNP), que é inativa, mas que também pode ser dosada no sangue.
Esses peptídeos agem através da ligação com receptores específicos, do tipo A e B. A degradação e eliminação são feitas através da ligação com receptores do tipo C, e por ação de uma enzima chamada endopeptidase neutra.
Em indivíduos normais, o BNP é influenciado por idade e sexo, sendo mais elevado nos idosos e nas mulheres quando comparados a homens da mesma faixa etária4.
As primeiras técnicas desenvolvidas para dosagem do BNP eram complicadas e demoradas, o que dificultava sua utilização, principalmente em situações de emergência. O desenvolvimento de testes de dosagem rápida (sistema
O BNP é dosado por imunofluorescência. Devem-se coletar 5 ml de sangue em tubo contendo EDTA. Uma gota é colocada na tira e introduzida no aparelho, obtendo-se resultado em quinze minutos. O BNP é estável por pelo menos quatro horas à temperatura ambiente, por até dois dias refrigerado (4-8ºC) e por pelo menos doze meses quando estocado a -20ºC.
A maior aplicação do BNP, até o momento, é no diagnóstico e manuseio de pacientes com insuficiência cardíaca (IC). Comentamos a seguir algumas situações em que o BNP pode ser útil nessa síndrome.
Estudos populacionais mostram utilidade do BNP como exame de triagem para o diagnóstico de disfunção sistólica de VE. Em um estudo escocês, BNP maior que 17,9 pg/ml apresentou sensibilidade de 76% e especificidade de 87% em detectar disfunção ventricular grave (fração de ejeção menor que 30%). Em indivíduos acima de 65 anos a acurácia foi ainda maior5.
Em nosso meio, Ribeiro e cols.6 estudaram a capacidade do BNP em detectar disfunção sistólica de VE em pacientes portadores de doença de Chagas. Naqueles com eletrocardiograma ou radiografia de tórax alterados, um valor de BNP acima de 60,7 pg/ml apresentou sensibilidade e valor preditivo positivo (VPP) de 80% e especificidade e valor preditivo negativo (VPN) de 97% em detectar disfunção sistólica6.
O diagnóstico ambulatorial da IC por vezes pode oferecer dificuldades, principalmente em ambientes de atendimento primário. De fato, em vários estudos populacionais, menos de 40% dos pacientes com suspeita de IC feita pelo médico generalista tiveram esse diagnóstico confirmado, quando avaliados por cardiologistas7. No Hillindon Heart Failure Study8 realizado em Londres, de 122 pacientes encaminhados pelo médico do atendimento primário para uma clínica especializada, 35 (29%) tiveram o diagnóstico de IC confirmado. O desempenho do BNP no diagnóstico de IC nessa população foi muito bom (usando a curva ROC, a área sob a curva foi de 0,96). Com um valor de corte de 76,4 pg/ml, obteve-se um elevado VPN (98%), com aceitável VPP (70%). A sensibilidade e a especificidade foram, respectivamente, 97% e 84%. Os resultados desse estudo serão validados em um estudo multicêntrico (The UK Natriuretic Peptide Diagnosis Study).
Em relação ao prognóstico, um estudo avaliou 290 pacientes consecutivos que foram submetidos a cateterismo cardíaco por disfunção sistólica de VE assintomática ou levemente sintomática9. Em um seguimento de 27 meses, 24 pacientes faleceram de causa cardíaca e 25 foram hospitalizados por IC ou infarto agudo do miocárdio (IAM). Os níveis de BNP medidos na ocasião do cateterismo correlacionaram-se de modo independente tanto com mortalidade cardíaca quanto com eventos cardíacos (morte somada a hospitalizações). Houve aumento de 4% no risco, para cada aumento de 10 pg/ml nos níveis de BNP.
Outro estudo avaliou pacientes com IC de recente começo, sendo estudados um subgrupo de 108 pacientes que faziam parte de um estudo populacional de pacientes diagnosticados pela primeira vez com IC, em Bromley, Londres10. BNP, NT-pro-BNP e NT-pro-ANP foram medidos no momento em que o paciente foi visto pela primeira vez, antes, portanto, da estabilização clínica. No seguimento de 38 meses, quarenta pacientes morreram, sendo 34 de causas cardiovasculares. Os três peptídeos foram fortes preditores de mortalidade (área sob a curva 0,70, 0,73 e 0,68, respectivamente).
Vem-se estudando também sua utilidade para guiar a terapêutica, fazendo-se a progressão das doses de medicamentos guiada pelo BNP. Um estudo piloto mostrou que a taxa de eventos cardiovasculares foi menor no grupo guiado por BNP, comparado ao grupo tratado convencionalmente11. Um estudo multicêntrico está em andamento para avaliar essa questão.
A situação em que o valor do BNP está mais sedimentado é no manuseio de pacientes com IC hospitalizados. Esses pacientes apresentam níveis elevados de BNP, o que facilita sua discriminação em relação a pacientes sem IC. Em relação a diagnóstico, o maior estudo foi o realizado por Maisel e cols., em que foram avaliados 1.538 pacientes com dispnéia aguda atendidos em unidades de emergência12,13. Nesse estudo multicêntrico, os pacientes com IC puderam ser facilmente diferenciados daqueles com outros diagnóstico. Os valores medianos de BNP no grupo com IC e sem IC foram, respectivamente, 675 ± 65
Em nossa instituição, a dosagem de BNP foi introduzida na prática clínica em abril de 2001. No mesmo período, foi iniciado um protocolo para estudar a utilidade do BNP no diagnóstico e prognóstico de pacientes com IC. Os dados sobre os primeiros setenta pacientes que chegaram à unidade de emergência com dispnéia aguda já foram publicados em 200214. Os níveis de BNP em pacientes com IC e sem IC foram, respectivamente, 990 ± 550 e 80 ± 67 pg/ml. Um corte de 200 pg/ml apresentou sensibilidade, especificidade, VPP e VPN, respectivamente, de 100%, 97,1%, 97,3% e 100%.
No estudo Redhot15, em que foram avaliados pacientes com IC descompensada na unidade de emergência, observou-se uma falta de correlação entre o que o plantonista da unidade de emergência classificava como paciente grave e a evolução desse paciente. A utilização do BNP mostrou melhor correlação com a evolução do que a impressão do plantonista isoladamente. No estudo Basel, demonstrou-se que a utilização do BNP em pacientes com dispnéia aguda agiliza o diagnóstico ou exclusão da IC, resultando em menor tempo de internação e menor custo16.
Maisel e cols. avaliaram 294 indivíduos encaminhados para realização de ecocardiograma17. Os pacientes com disfunção diastólica no ecocardiograma apresentaram valores médios de BNP de 286 ± 31 pg/ml contra 33 ± 3 pg/ml naqueles com função normal. Pacientes com o padrão restritivo apresentaram os maiores valores de BNP (408 ± 66 pg/ml) e aqueles sintomáticos tinham valores altos de BNP independentemente do tipo de padrão de enchimento diastólico. A área sob a curva para detectar qualquer tipo de disfunção diastólica foi 0,92 e um corte de 62 pg/ml mostrou sensibilidade de 85%, especificidade de 83% e acurácia de 84%.
No estudo multicêntrico BNP Trial18, um corte de BNP de 100 pg/ml apresentou sensibilidade de 86%, VPN de 96% e acurácia de 75% para detectar disfunção diastólica. Em casuística em nossa instituição, os pacientes com IC e disfunção sistólica de VE apresentaram maiores níveis de BNP que aqueles com função sistólica preservada (1.180 ± 330
Em um estudo populacional, no entanto, o BNP não foi um bom preditor de disfunção diastólica pré-clínica, sugerindo que nos pacientes com disfunção diastólica, apenas aqueles com disfunção mais acentuada ou com IC clínica manifesta podem ser detectados com o uso do BNP20.
Em um estudo do Hospital dos veteranos, em San Diego, tanto o BNP de internação quanto sua variação durante a hospitalização foram preditores de evolução21. Pacientes cujos valores de BNP reduziram durante a internação tiveram o melhor prognóstico. Aqueles em que não houve variação do BNP apresentaram maior taxa de reinternação hospitalar em trinta dias, e aqueles com elevação do BNP tiveram maior mortalidade hospitalar e em até trinta dias de seguimento. Em nossa instituição, pacientes com BNP na internação maior que 760 pg/ml apresentaram maior taxa de mortalidade ou reinternação em trinta dias. A sensibilidade e a especificidade para predizer eventos em pacientes com BNP acima desse corte foram de 72% e 69%, respectivamente22.
O BNP vem se mostrando importante marcador prognóstico em pacientes com síndromes coronariana aguda, tanto naqueles com IAM com supradesnivelamento de ST quanto em pacientes com IAM sem supradesnivelamento ou angina instável23-25. No maior estudo realizado nessa área, o BNP basal dosado em pacientes IAM com ou sem supradesnivelamento de ST e em angina instável correlacionou-se com a mortalidade e com o risco de desenvolver IC ou IAM em trinta dias e aos dez meses. A razão de chances para mortalidade aos dez meses, para o segundo, terceiro e quarto quartis de BNP, foi, respectivamente, de 3,8, 4,0 e 5,8.
Nosso grupo estudou o valor do BNP na internação em 631 pacientes atendidos com dor torácica em nossa unidade de emergência, no diagnóstico de IAM sem supradesnivelamento de ST26. Os pacientes com supradesnivelamento de ST foram excluídos. No momento da chegada à unidade de emergência eram dosados BNP, troponina I e CKMB-massa. Após três e nove horas eram repetidas as dosagens de troponina e CKMB-massa. O diagnóstico final de IAM baseou-se na positividade em qualquer momento, da troponina ou da CKMB-massa. Procuramos avaliar se a dosagem do BNP na internação do paciente com dor torácica aumentava a acurácia do diagnóstico de IAM ao longo da internação na unidade de emergência. A média dos valores de BNP nos pacientes com IAM, angina instável e com outros diagnósticos que não insuficiência coronariana aguda foi, respectivamente, 200 pg/ml, 78 pg/ml e 28 pg/ml. A sensibilidade da CKMB-massa, troponina, BNP e com os três marcadores juntos foi de 46%, 51%, 71% e 87%, respectivamente (p < 0,001 para comparação de BNP isoladamente e todos os marcadores juntos em relação a CKMB-massa e troponina). O valor preditivo negativo para os respectivos marcadores foram 93%, 93%, 95% e 98% (p = 0,0016 para comparação entre todos os marcadores juntos em relação a CKMB-massa e troponina). Por meio de análise multivariada, os preditores independentes de IAM foram infradesnivelamento de ST (razão de chances de 6,0), BNP >100 pg/ml (RC = 2,3), diabetes (RC = 2,5), CKMB-massa > 5 (RC = 11,9) e troponina > 1,0 (RC = 36,6). Esses dados sugerem que a adição do BNP aos marcadores convencionais melhora a sensibilidade e o VPN do diagnóstico do IAM em pacientes sem supradesnivelamento de ST.
Um grande estudo populacional, com 3.346 pacientes, publicado recentemente, procurou estabelecer a relação entre o BNP e o NT-pro-ANP com o risco para morte por qualquer causa, assim como a relação com o risco de desenvolver um evento cardiovascular, IC, fibrilação atrial, acidente vascular encefálico ou ataque isquêmico transitório e doença arterial coronariana27. Após um seguimento de 5,2 anos, 119 indivíduos faleceram e 79 tiveram um primeiro evento cardiovascular. Após ajuste para os fatores de risco cardiovascular, cada aumento de um desvio padrão nos valores logarítmicos de BNP esteve associado a aumento de 27% no risco de morte por qualquer causa, 28% no risco de um primeiro evento cardiovascular, 77% no risco de desenvolver IC, 66% no risco de desenvolver FA, e um aumento de 53% no risco de apresentar um acidente vascular encefálico ou ataque isquêmico transitório. Não houve relação com o desenvolvimento de eventos relacionados a doença arterial coronariana. Resultados semelhantes foram observados com o NT-pro-ANP.
Em pacientes com IC, a dosagem do BNP pode identificar os pacientes de maior risco para desenvolver morte súbita, podendo vir a fazer parte da avaliação desses pacientes quanto à indicação de desfibrilador. Em um estudo austríaco28, somente 1% dos pacientes com valores logarítmicos de BNP abaixo de 2,11 apresentou morte súbita, comparado com 19% naqueles com valores acima desse limite. Nesse estudo foram avaliados 452 indivíduos. Em três anos, 89 pacientes faleceram, sendo 44 por morte súbita. A dosagem de BNP foi o único preditor independente de morte súbita. O mesmo grupo está organizando um estudo multicêntrico para comprovar esses achados.
Em portadores de estenose aórtica, os valores de BNP estão elevados naqueles com sintomas29. Uma vez que a presença de sintomas é um dos fatores para avaliação da indicação de cirurgia nesses pacientes, o BNP poderia ser incorporado a essa avaliação auxiliando na indicação cirúrgica.
O ventrículo direito, quando sob estresse, pode produzir BNP, embora em quantidade menor que o ventrículo esquerdo1. Pacientes com embolia pulmonar, principalmente aqueles com disfunção de ventrículo direito (VD), apresentam alguma elevação de BNP. Em pacientes atendidos em unidade de emergência com dispnéia e diagnóstico final de embolia pulmonar, esses valores usualmente variam de 100 a 400 pg/ml12,14. Nos pacientes com embolia pulmonar, os valores de BNP correlacionam-se com a presença de disfunção de VD e são preditores de pior evolução30,31.
Em um estudo com sessenta pacientes portadores de hipertensão pulmonar primária, o BNP foi um preditor independente de mortalidade32. Os pacientes foram tratados com prostaciclina. Três meses após o diagnóstico, dosou-se novamente o BNP. Nos sobreviventes, em um seguimento de 24 meses, observou-se queda do BNP entre as duas medidas (217 ± 38
Tanimoto e cols.33 estudaram 148 pacientes consecutivos com síncope: 61 desses pacientes tiveram síncope de etiologia cardíaca. Usando um corte de 40 pg/ml, a dosagem de BNP apresentou sensibilidade de 82% e especificidade de 92% em identificar pacientes com etiologia cardíaca para a síncope.
A dosagem do BNP vem ganhando grande número de possíveis utilidades na prática clínica. Desde sua aplicação inicial, de identificar disfunção sistólica de VE, inúmeras outras situações cardiovasculares foram acrescentadas à lista de doenças possíveis de ser manuseadas com o uso de BNP. Sua utilidade em pacientes com IC está bem estabelecida. Nas outras enfermidades cardiovasculares, cada dia mais evidências se acumulam, sugerindo que, num futuro próximo, o BNP possa ser acrescentado ao manuseio desses pacientes.
1. Cowie MR and Mendez GF. BNP and Congestive Heart Failure. Curr Probl Cardiol 2003; 44: 264-311.
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15. Maisel A, Hollander JE, Guss D et al. Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT): a multicenter study of b-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol 2004; 44: 1328-33.
16. Mueller C, Scholer A, Laule-Kilian K et al. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. New Engl J Med 2004; 350: 647-54.
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Humberto Villacorta Jr. Rua Raimundo Correa, 23/601 22040-040 – Rio de Janeiro, RJ E-mail:
Recebido em 20/05/04
Aceito em 22/08/05
Clinical applications of B-type natriuretic peptide assays
Hospital Pró-Cardíaco - Rio de Janeiro, RJ - Brazil
The natriuretic peptide system is activated every time the heart is subjected to injury, whether acute or chronic, as a compensatory mechanism for the effects of vasoconstriction changes that take place in these situations. The primary role of the system is to promote urine output and vasodilation. It is known, however, that a series of additional effects are triggered when these peptides are released, such as the inhibition of the renin-angiotensin-aldosterone system, sympathetic nervous system and smooth muscle cells growth, and possibly the reduction of apoptosis1.
Three types of peptides are known: type-A peptide (ANP) - released from the atria; type-B (BNP) - released from the ventricles and type-C - released from vascular cells. Because it is released directly from the ventricles, type-B peptide (BNP) is the one that best reflects the condition of the cardiac muscle and, therefore, the one that has obtained greater clinical applicability. The stimulus for its release is the stretching of ventricular muscle cells caused by a pressure or volume overload1,2. More recently, it was shown that myocardial ischemia, which leads to an increase in parietal tension due to systolic and/or diastolic dysfunction, can also promote the release of BNP3.
Before it is released into the blood stream, BNP is present in the form of its precursors. Inside the myocyte, Pro-BNP is split to produce two molecules: BNP, the active portion, and the NT-proBNP portion which is inactive, but can also be measured in the blood.
These peptides bind to specific type-A and type-B receptors. Breakdown and clearance take place by means of binding to type-C receptors, as well as by an enzyme called neutral endopeptidase.
In healthy individuals, BNP levels vary according to sex and age, and are higher in elderly people and in women when compared to men in the same age group4.
The first BNP measurement techniques developed were time-consuming and difficult to perform, making them inappropriate mainly for emergency situations. With the development of rapid blood tests for BNP (point-of-care), this biochemical marker started to be used in a large variety of clinical setting situations. The first rapid point-of-care blood test performed, and the only utilized up until now, was developed in San Diego, USA, and it has been commercially available in Brazil since 2001. A test for the measurement of NT-Pro-BNP, although not the "point-of-care" type, is also available in Brazil.
BNP is measured by immunofluorescence. Five mL of blood are collected into a tube containing EDTA. One drop is placed on the strip which is then introduced into the device, and the result is ready within 15 minutes. BNP remains stable for at least 4 hours at room temperature, for 2 days when refrigerated at 4-8ºC, and for at least 12 months when stored at –20ºC.
So far, the main application of BNP testing is in the diagnosis and treatment of patients with heart failure (HF). We comment, below, on a few heart failure situations in which BNP testing can be helpful.
Population studies have shown the usefulness of BNP as a triage test for the diagnosis of left ventricular (LV) systolic dysfunction. In a Scottish study, a blood concentration of BNP over 17.9 pg/mL, showed 76% sensitivity and 87% specificity as a detector of severe ventricular dysfunction (ejection fraction less than 30%). In individuals over 65 years of age, accuracy was even higher5.
In Brazil, Ribeiro
The ambulatory diagnosis of HF may sometimes be difficult to make, especially in primary care settings. Actually, several population studies have shown that less than 40% of patients with suspected HF diagnosed by the general practitioner [GP] had this diagnosis confirmed when evaluated by cardiologists7. The Hillindon Heart Failure Study conducted in London indicated that out of 122 patients referred by primary physicians to a specialized clinic, 35 (29%) were confirmed as having HF. BNP testing proved to be very useful in such a population (are under ROC curve was 0.96). With a cut-off value set at 76.4 pg/mL, a high NPV value (98%) and an acceptable PPV value (70%) were obtained. Sensitivity and specificity were 97% and 84%, respectively. The results of this study will be validated by a multicentric study (The UK Natriuretic Peptide Diagnosis Study).
With regards to prognosis, another study evaluated 290 consecutive patients who underwent cardiac catheterism due to asymptomatic or mildly symptomatic LV systolic dysfunction9. During a 27-month follow-up period, 24 patients died due to cardiac causes and 25 were hospitalized because of HF or acute myocardial infarction (AMI). BNP levels measured at the time of catheterism correlated independently with cardiac deaths, as well as with cardiac events (death and hospital admissions). There was also a 4% increase in risk for each 10 pg/mL increment in BNP levels.
Another study evaluated patients with recent onset HF. A subgroup of 108 patients, who were part of a population study of individuals diagnosed with HF for the first time, was evaluated in Bromley, London10. BNP, NT-proBNP and NT-proANP levels were measured at the first timepoint the patient was seen, that is, before clinical stabilization. During the 38-month follow-up period, 40 patients died, 34 of them due to cardiovascular causes. The three peptide levels were strong predictors of mortality (area under the ROC curve was 0.70, 0.73 and 0.68, respectively).
The usefulness of BNP testing in guiding therapy has also been studied, with doses being adjusted according to patient BNP levels. A pilot study showed that the rate of cardiovascular events was smaller in the group with treatment administered according to BNP levels in comparison to the group submitted to conventional treatment11. A multicentric study is currently underway to evaluate this issue.
The primary use of BNP level measurements is in managing hospitalized HF patients. These patients have high BNP levels, which makes it easier to differentiate them from patients without HF. In terms of diagnosis, the largest study was conducted by Maisel
At our institution, the use of BNP level measurements was introduced into daily clinical practice in April 2001. At the same time, a protocol was initiated to assess the usefulness of BNP in the diagnosis and prognosis of heart failure patients. Data on the first 70 patients admitted to the emergency department with acute dyspnea were published in 200214. BNP levels in patients with and without HF were 990±550 and 80±67 pg/mL, respectively. At a cut-off level of 200 pg/mL, BNP showed sensitivity, specificity, PPV, and NPV values of 100%, 97.1%, 97.3% and 100%, respectively.
In the REDHOT15 study, which evaluated patients with decompensated HF in the emergency department, a lack of correlation was observed between what the physician at the emergency room classified as a critically ill patient and the clinical progress of that patient. The use of BNP showed a better correlation with the clinical progress than the assessment made by the physician alone. In the BASEL study, it was shown that the use of BNP testing in patients with acute dyspnea helps to speed-up the confirmation or exclusion of heart failure diagnosis, resulting in a shorter hospital stay and lower costs16.
Maisel
In the multicentric BNP Trial18, with a BNP cut-off value set at 100 pg/mL, sensitivity was 86%, NPV 96%, and accuracy 75% in detecting diastolic dysfunction. At our institution, patients with HF and LV systolic dysfunction showed higher BNP levels than those with preserved systolic function (1,180±330 vs 753±228 pg/mL, p=0.029). However, it was possible to differentiate HF patients with normal systolic function from patients without HF, whose average BNP levels were 753±228 and 89±28 pg/mL, respectively (p<0.001)19.
In a population study, however, BNP levels were not good predictors of pre-clinical diastolic dysfunction, suggesting that among patients with diastolic dysfunction, only those with the most marked dysfunction or clinically manifested HF can be identified with the use of BNP20.
In a Veterans' hospital in San Diego, both the BNP levels measured at admission, as well as their variation during hospitalization were predictors of clinical progress21. Patients whose BNP levels decreased during their hospital stay had the best prognosis. Those whose BNP levels did not vary had a higher rate of hospital readmission within 30 days, and those with an increase in BNP levels had higher mortality rates while in the hospital and within up to 30 days of follow-up. At our institution, patients with BNP levels over 760 pg/mL at admission had greater rates of mortality or readmission to the hospital within 30 days. Sensitivity and specificity to predict events in patients with BNP above this cut-off value were 72% and 69%, respectively22.
BNP testing has proved to be an important prognostic marker in patients with acute coronary syndrome, both those with ST-segment elevation AMI, as well as those with non-ST-segment elevation AMI or unstable angina23-25. In the largest study conducted in this area, the baseline BNP determined for AMI patients, with or without ST-segment elevation and with unstable angina, correlated with mortality and with the risk of developing HF or AMI within 30 days and at 10 months. The odds ratio for mortality at 10 months for the second, third and fourth BNP quartiles were 3.8, 4.0 and 5.8, respectively.
Our group assessed the BNP level at admission in 631 patients presenting with chest pain at our emergency department, for the diagnosis of non-ST-segment elevation AMI26. Patients with ST-segment elevation were excluded. Upon arrival at the emergency room, patients' levels of BNP, troponin I and CKMB-mass were measured. After 3 hours and 9 hours of admission, the troponin and CKMB-mass measurements were repeated. The final AMI diagnosis was based on a positive result for troponin or CKMB-mass at any timepoint. We tried to evaluate if the BNP measurement upon admission of the patient with chest pain increased the accuracy of an AMI diagnosis during his/her stay in the emergency department. The average BNP values in patients with AMI, unstable angina and diagnoses other than acute coronary heart failure were 200 pg/mL, 78 pg/mL, and 28 pg/mL, respectively. The sensitivity values for CKMB-mass, troponin I, BNP, and the three markers combined were 46%, 51%, 71% and 87%, respectively (p<0.001 to compare BNP alone and all the markers combined relative to CKMB-mass and troponin). The negative predictive values for the respective markers were 93%, 93%, 95% and 98% (p=0.0016 to compare combined markers relative to CKMB-mass and troponin). The multivariate analysis showed that ST-segment depression (odds ratio of 6.0), BNP>100 pg/mL (OR=2.3), diabetes (OR=2.5), CKMB-mass>5 (RC=11.9), and troponin>1.0 (OR=36.6) were independent predictors of AMI. These data suggest that adding BNP levels to the conventional markers improves the sensitivity and the NPV value of HF diagnosis in patients with non-ST segment elevation acute myocardial infarction.
A recently published large population study comprising 3,346 patients sought to establish the relationship between BNP and NP-pro-ANP, and the risk of all-cause death. The study aimed also to establish the relationship between the risk to develop a cardiovascular event, HF, atrial fibrillation, cerebrovascular accident or transient ischemic attack, and coronary artery disease27. After a 5.2-year follow-up, 119 patients died and 79 suffered a first cardiovascular event. After adjusting for cardiovascular risk factors, each standard deviation increment in BNP logarithmic values was associated with a 27% increase in the risk of all-cause death, 28% in the risk of a first cardiovascular event, 77% in the risk of developing HF, 66% in the risk of developing AF, and a 53% increase in the risk of suffering a cerebrovascular accident or transient ischemic attack. No relationship was observed with the development of events related to coronary artery disease. Similar results were observed with NT-pro-ANP levels.
Among HF patients, BNP measurements can identify those with greatest risk of sudden death, and be a good guiding referral for the use of defibrillator. In an Austrian study28, only 1% of patients with BNP logarithmic values under 2.11 experienced sudden death compared to 19% of those who had higher values. In this study, 452 individuals were assessed. Within 3 years, 89 patients died, 44 of whom from sudden death. BNP measurement was the only independent predictor of sudden death. The same group is organizing a multicentric study to further confirm these findings.
In patients with aortic stenosis, BNP values are higher in those who are symptomatic29. Since the presence of symptoms is one of the factors taken into consideration in assessing the indication of surgery for such patients, BNP testing could be included in the evaluation and be of help in indicating surgery.
When submitted to stress, the right ventricle can produce BNP although in smaller quantities than the left ventricle1. Patients with pulmonary embolism, mainly those with right ventricular dysfunction (RV), have slightly increased BNP levels. In patients admitted to the emergency department with dyspnea and a final diagnosis of pulmonary embolism, BNP levels may vary from 100 to 400 pg/mL12,14. In patients with pulmonary embolism, BNP values correlate with the presence of RV dysfunction and are predictors of a worse clinical progression30,31.
In a study involving 60 patients with primary pulmonary hypertension, BNP was an independent predictor of mortality32. Patients were treated with prostacyclin and three months after the diagnosis, the BNP level was measured again. During a follow-up of 24 months, the survivors presented a decrease in BNP to levels between the two measurements (217±38 vs 149±30), whereas in those patients who died, there was an increase in BNP levels (365±77 vs 544±68). Survival was extremely low for patients with BNP>180 pg/mL.
Tanimoto
BNP measurement has been gaining an increasingly greater role in clinical practice. Since its initial application, that of identification of LV systolic dysfunction, many other cardiovascular situations have been added to the list of diseases that can be managed with BNP measurement. Its usefulness in treating patients with HF is well established. In other cardiovascular diseases, increasing evidence has been obtained, suggesting that in the near future BNP testing can be added to the management of these patients.
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Humberto Villacorta Jr. Rua Raimundo Correa, 23/601 22040-040 – Rio de Janeiro, RJ - Brazil E-mail:
Received on 05/20/04
Accepted on 08/22/05
Tanimoto e cols.33 estudaram 148 pacientes consecutivos com síncope: 61 desses pacientes tiveram síncope de etiologia cardíaca. Usando um corte de 40 pg/ml, a dosagem de BNP apresentou sensibilidade de 82% e especificidade de 92% em identificar pacientes com etiologia cardíaca para a síncope.