What is the value of B-type natriuretic peptide testing for diagnosis, prognosis or monitoring of critically ill adult patients in intensive care?

BACKGROUND: B-natriuretic peptide (BNP) and aminoterminal proBNP (NT-proBNP) are clinically useful for the diagnosis of decompensated heart failure and for prognosis in heart failure and acute coronary syndromes. Clinical use of these biomarkers in critically ill patients being treated in intensive care is not well established. METHODS: This is a narrative review of evidence identified searching MEDLINE with the strategy [(BNP OR NT-proBNP) AND (critical illness AND intensive care)]. Seven primary reports and two narrative reviews were retrieved. For completeness, literature from each of the following searches was reviewed: [(BNP OR NT-proBNP) AND (critical illness)] and [(BNP OR NT-proBNP) AND (intensive care)]. RESULTS: Primary literature used BNP and NT-proBNP for diagnosis, prognosis and monitoring. For diagnosis of acute lung injury in unselected intensive care patients and for diagnosis of heart failure in trauma patients, the biomarkers had low sensitivity and are of modest use. BNP and NT-proBNP were found to have a significant ability to prognosticate adverse outcomes in critically ill patients. A single paper examined the use of BNP as a non-invasive replacement for pulmonary capillary wedge pressure, finding little value. The impact of renal insufficiency on the markers was noted as a confounder in most studies. In the secondary searches, some preliminary data suggested a possible role for the natriuretic peptides in exclusion of a cardiac cause for certain conditions among intensive care unit (ICU) patients. However, the general findings were that the performance of BNP and NT-proBNP is unimpressive among ICU patients. CONCLUSIONS: Currently, utilization of BNP and NT-proBNP does not appear to provide much useful information or have a substantial role in the care of critically ill patients in intensive care.     

New horizons: NT-proBNP for risk stratification of patients with shock in the intensive care unit

B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) are promising cardiac biomarkers that have recently been shown to be of diagnostic value in decompensated heart failure, acute coronary syndromes and other conditions resulting in myocardial stretch and volume overload. In view of the high prevalence of cardiac disorders in the intensive care unit, the experience of elevated natriuretic peptide levels in the critically ill might be of enormous diagnostic and therapeutic value. BNP and NT-proBNP levels rise to different degrees in critical illness and may also serve as markers of severity and prognosis in diseases beyond acute or chronic heart failure. The diagnostic and prognostic use of natriuretic peptides in the intensive care setting for patients with various forms of shock could be an attractive alternative as noninvasive markers of cardiac dysfunction that could obviate the need for pulmonary artery catheterization in some patients.     

Natriuretic peptide testing: a window into the diagnosis and prognosis of heart failure

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels can indicate a variety of heart problems, as well as general critical illness. BNP and NT-proBNP assays are useful for evaluating patients with acute dyspnea, as a low level of natriuretic peptide can help rule out congestive heart failure (CHF) and reduce reliance on echocardiography. Conversely, these assays can be particularly useful in recognizing CHF in a patient with acute dyspnea and a history of chronic obstructive pulmonary disease. However, clinical judgment must always be part of the evaluation of BNP or NT-proBNP assay results.     

B-type natriuretic peptide (BNP) is more sensitive to rapid hemodynamic changes in acute heart failure than N-terminal proBNP

BACKGROUND: We examined whether B-type natriuretic peptide (BNP) and its precursor fragment, N-terminal proBNP (NT-proBNP), can serve as non-invasive markers of hemodynamic response to treatment in acute heart failure in a prospective observational study. METHODS: 29 unselected, consecutive patients (mean age: 61.6, 39-83 years; 25 males, 4 females) in urgent need for positive inotropic support and invasive hemodynamic monitoring by a Swan-Ganz catheter. Positive hemodynamic response to treatment was defined as > or =25% decrease in pulmonary artery occlusion pressure after 24 h. Hemodynamics were recorded simultaneously with blood sampling for BNP and NT-proBNP testing before and 24 h after initiation of inotropic support. BNP (Bayer Diagnostics) and NT-proBNP (Roche Diagnostics) were measured by commercial immunoassays. RESULTS: Both markers were markedly elevated. However, there were no close correlations (r<0.43, p<0.05) of BNP or NT-proBNP with hemodynamic parameters at baseline or 24 h thereafter. Only BNP showed a significant (p=0.023) decrease compared to baseline values in hemodynamic responders. The area under receiver operating characteristics curve for relative changes of BNP for the prediction of hemodynamic response was 0.76. CONCLUSIONS: Our preliminary results indicate that BNP is more sensitive to acute hemodynamic changes than NT-proBNP. This study also highlights limitations of both markers as surrogates of hemodynamics in critically ill acute heart failure patients.     

Comparison of the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP immunoassays in chronic and acute heart failure: a systematic review

BACKGROUND: We used evidence-based laboratory medicine principles to compare the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) assays for the diagnosis of heart failure. METHODS: In May 2006, we performed a computerized literature search of the online National Library of Medicine to select studies specifically designed to compare the diagnostic accuracy of BNP and NT-proBNP assays. The comparison took into account the area under the curve and diagnostic odds ratio (DOR) derived from ROC analysis of original studies. RESULTS: Both BNP and NT-proBNP assays were found to be clinically useful for the diagnosis of heart failure. Metaanalysis of these data was difficult because of the heterogeneity of data regarding patient population, diagnostic criteria, end-points, and immunoassay methods for both BNP and NT-proBNP. Separate metaanalyses were performed for acute and chronic heart failure. In chronic heart failure, the diagnostic DOR for BNP (8.44, 95% CI 4.66-15.30) was not significantly different from that of NT-proBNP (23.36, 95% CI 9.38-58.19). In patients with acute heart failure, the mean DOR for BNP (16.46, 95% CI 10.65-25.43) was not significantly different from that of NT-proBNP (18.61, 95% CI 12.99-26.65). CONCLUSION: Our results indicate that both BNP and NT-proBNP assays have a high degree of diagnostic accuracy and clinical relevance for both acute and chronic heart failure.     

Plasma N-terminal pro-brain natriuretic peptide and brain natriuretic peptide in assessment of acute dyspnea.

We examined the analytical correlation between non-radioimmunometric plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) and evaluated whether NT-proBNP or BNP was superior in the emergency diagnosis of heart failure and whether this was influenced by age, gender, body mass index (BMI) and renal function. Data were collected prospectively from patients admitted to the emergency department for acute dyspnea. Plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche diagnostic(R)) were measured at admission in addition to other standard biological parameters and clinical variables. Reference diagnosis was adjudicated by two independent cardiologists using the European society of cardiology guidelines. We evaluated the influence of creatinine clearance, age, gender and BMI on plasma BNP and NT-proBNP levels. One hundred and sixty consecutive patients were included: 84 females and 76 males, mean age 80.1 + 13.5 (16-98). The analytical correlation between the automated electro-chemiluminescence immunoassay for NT-proBNP and the single use fluorescence immunoassay for BNP was satisfactory using the equation: NT-proBNP = 1.1 BNP + 0.57 and a correlation r = 0.93. This was established over a wide range of concentration (5-6400 pg/ml for BNP). Areas under receiver operating characteristic (ROC) curve for BNP and NT-proBNP as a diagnostic marker for heart failure were 0.82 and 0.84, respectively and a BNP level of 150 pg/ml has similar sensitivity and specificity that NT-proBNP level of 1000 pg/ml. The correlation was not influenced by age, gender and BMI of patients. Renal dysfunction did not affect significantly this correlation (r = 0.93). We conclude that NT-proBNP, as assayed in the present study, correlates closely with BNP. This correlation is only slightly modulated by creatinine clearance values. The NT-proBNP appears as accurate as BNP according to area under ROC curve. Used in conjunction with other clinical information, rapid measurement of BNP or NT-proBNP is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.     

急性冠脉综合征患者血浆脑钠素变化及其临床意义的研究进展

心肌缺血损伤是血浆脑钠素 (BNP)释放的重要触发因素之一。急性冠脉综合征 (ACS)患者血浆BNP和氮端前体BNP(NT -proBNP)水平升高是患者危险分层的重要生物标志物 ,独立于传统的临床症状及其他生化指标如肌钙蛋白和C反应蛋白 (CRP)。血浆BNP和NT -proBNP水平越高 ,患者的心力衰竭的程度越重 ,病死率越高。     

Monitoring the response to pharmacologic therapy in patients with stable chronic heart failure: Is BNP or NT-proBNP a useful assessment tool?

OBJECTIVES: B-type natriuretic peptides are biomarkers of heart failure (HF) that can decrease following treatment. We sought to determine whether B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) concentration changes occurred in parallel to changes in other measures of heart failure following treatment. METHODS: We conducted a systematic review of the literature for studies that assessed B-type natriuretic peptide measurements in treatment monitoring of patients with stable chronic heart failure. Selected studies had to include at least three consecutive measurements of BNP or NT-proBNP. RESULTS: Of 4338 citations screened, only 12 met all of the selection criteria. The selected studies included populations with a wide range of heart failure severity and therapy. BNP and NT-proBNP decreased following treatment in nine studies and was associated with improvement in clinical measures of HF. CONCLUSIONS: There was limited data to support using BNP or NT-proBNP to monitor therapy in patients with HF.     

B-type natriuretic peptide in pediatrics

OBJECTIVES: There has been growing interest in the use of serum B-type natriuretic peptide (BNP) and the N-terminal segment of its pro-hormone (NT-proBNP) as biomarkers for cardiac disease. The aim of this review is to summarize the current state of knowledge regarding BNP and NT-proBNP measurement in the pediatric population. DESIGN AND METHODS: A computerized literature search on the National Library of Medicine was done and all articles including BNP and pediatrics were selected and discussed. RESULTS: The data from several studies suggest that the measurement of BNP may be useful in diagnosing and managing pediatric heart failure, congenital heart disease, cardiac transplantation and patients on chemotherapy. There are difficulties in establishing appropriate reference ranges in children. CONCLUSION: There is insufficient evidence for the routine use of BNP or NT-proBNP. Further research to clearly define the clinical utility in the pediatric age group is eagerly anticipated.     

BNP和NT-proBNP在鉴别舒张性心力衰竭中的应用研究

目的 研究慢性心力衰竭患者血浆BNP及NT-proBNP浓度的变化,评价BNP及NT-proBNP对鉴别舒张性心力衰竭的作用.方法 对2004-2006年在解放军总医院临床诊断为舒张性心力衰竭129例患者和收缩性心力衰竭109例患者进行血浆BNP和NT-proBNP浓度测定,通过与对照组(77名)的比较,分析血浆BNP和NT-proBNP升高的相关因素,并用ROC曲线评价BNP和NT-proBNP对鉴别舒张性心力衰竭的作用.结果 和对照组(血浆BNP和NT-proBNP浓度中位数分别为58.51 ng/L和69.80 ng/L)比较,慢性心力衰竭患者血浆BNP和NT-proBNP浓度明显升高,其中舒张性心力衰竭和收缩性心力衰竭组患者血浆BNP浓度中位数分别为254.16 ng/L和923.08 ng/L,NT-proBNP浓度中位数分别为899 ng/L和3 695 ng/L,血浆BNP和NT-proBNP升高的程度与NYHA心功能分级显著相关(β值分别为0.201和0.323,P值均<0.001).BNP和NT-proBNP诊断慢性心力衰竭的曲线下面积分别为0.906(95%可信区间:0.865～0.946)和0.956(95%可信区间:0.932～0.980),BNP鉴别舒张性心力衰竭和收缩性心力衰竭的曲线下面积为0.781(95%可信区间:0.710～0.852),NT-proBNP鉴别舒张性心力衰竭和收缩性心力衰竭的曲线下面积为0.757(95%可信区间:0.686～0.828).结论 慢性心力衰竭患者的血浆BNP和NT-proBNP水平均明显升高,升高的程度和NYHA心功能分级相关,两者是诊断慢性心力衰竭的良好指标,但对鉴别舒张性心力衰竭的作用不大.     

Integrating Optimal Use of Echocardiography and Biomarkers in Heart Disease

Echocardiography remains the primary modality to identify cardiac structural and functional abnormalities in patients with signs and symptoms of heart failure. Echocardiography may also have a role in identifying patients at risk of heart failure, in other words, differentiating patients from ACC/AHA stage A (risk factors for heart failure) to stage B (structural abnormalities in the absence of symptoms). In recent years soluble (blood based) cardiac specific biomarkers have been broadly introduced into clinical practice for the diagnosis of acute myocardial infarction (cardiac troponins) and diagnosing and prognosticating patients with heart failure (the natriuretic peptide tests, B-type natriuretic peptide [BNP] and the amino-terminal of proBNP [NT-proBNP]). Specifically, a large number of studies have evaluated the use of natriuretic peptides to complement the results of echocardiography in a spectrum of cardiovascular diseases ranging from asymptomatic community based populations to prognosticating patients with cardiomyopathies, valve disease and pulmonary embolism. The focus of this review will be to assess the state of the evidence from a variety of scenarios where natriuretic peptide testing and echocardiography can provide complementary information for diagnosis, prognosis and potentially guiding therapy.     

Utility of natriuretic peptides to assess and manage patients with heart failure receiving angiotensin receptor blocker/neprilysin inhibitor therapy

Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal fragment of its prohormone (NT-proBNP), are well-established biomarkers for patients with heart failure (HF). Although these biomarkers have consistently demonstrated their value in the diagnosis and prognostication of HF, their ability to help clinicians in making treatment decisions remains debated. Moreover, some new HF drugs can affect concentrations of NPs, such as the prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors (ARNIs), and may present a challenge in the interpretation of levels of BNP. Use of NT-proBNP measurement has been suggested in the context of ARNI therapy because its concentrations are not affected by neprilysin inhibition. As biomarkers are reconsidered in the context of ARNI therapy, cutoff levels and the effects of individual patient characteristics, such as renal function and age, on biomarker concentrations should be reassessed.     

B-type natriuretic peptide concentrations predict the progression of nondiabetic chronic kidney disease: the Mild-to-Moderate Kidney Disease Study

BACKGROUND: Plasma concentrations of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are diagnostic and prognostic biomarkers of heart failure and are also increased in patients with chronic kidney disease (CKD). We examined the relevance of BNP and NT-proBNP as predictors of CKD progression. METHODS: Of 227 nondiabetic patients with mild-to-moderate renal insufficiency, 177 patients ages 18-65 years were followed in a prospective multicenter cohort study for a period of < or = 7 years. CKD progression was assessed by recording renal endpoints, defined as doubling of baseline serum creatinine or end-stage renal disease (ESRD) requiring renal replacement therapy. RESULTS: BNP and NT-proBNP were significantly higher among 65 patients who reached the combined renal endpoint than among the 112 who did not [median (interquartile range) 61 (27-98) ng/L vs 39 (20-70) ng/L, P = 0.023, for BNP; 320 (117-745) ng/L vs 84 (44-176) ng/L, P <0.001, for NT-proBNP)]. Each increment of 1 SD in log-transformed BNP and NT-proBNP increased the risk of CKD progression by hazard ratios of 1.38 (95% CI 1.09-1.76, P = 0.009) and 2.28 (1.76-2.95, P <0.001), respectively. After adjustment for other established prognostic factors of CKD progression, NT-proBNP but not BNP remained a significant independent predictor of the combined renal endpoint. CONCLUSIONS: Increased BNP and NT-proBNP concentrations indicate an increased risk for accelerated progression of CKD to ESRD and may prove to be valuable biomarkers for the assessment of prognosis in patients with CKD.     

The brain natriuretic peptide (BNP) precursor is the major immunoreactive form of BNP in patients with heart failure

BACKGROUND: Peptides derived from brain natriuretic peptide (BNP) precursor (proBNP), BNP, and the N-terminal fragment of proBNP (NT-proBNP) are used as biomarkers of heart failure. It remains unclear which forms of these peptides circulate in blood and which forms are measured by assays for these natriuretic peptides. METHODS: To design assays for immunodetection of proBNP, NT-proBNP, and BNP, we used a panel of BNP- and NT-proBNP-specific monoclonal antibodies (MAbs). All MAbs were tested in 2-site combinations in time-resolved fluoroimmunoassays with recombinant or synthetic antigens and plasma from heart failure (HF) patients. ProBNP and related molecules were assayed in HF plasma samples and plasma extracts by means of gel filtration fast protein liquid chromatography (FPLC) before and after protein fractionation on Sep-Pak C18 cartridges. RESULTS: The limits of detection for BNP, proBNP, and NT-proBNP assays were 0.4, 3, and 10 ng/L, respectively. Gel filtration-FPLC studies revealed 1 peak of NT-proBNP (approximately 25 kDa), 1 peak of proBNP (approximately 37 kDa), and 2 peaks of BNP immunoreactivity, a major peak (approximately 37 kDa) for proBNP, and a minor peak (approximately 4 kDa) for BNP. In patient plasma, the molar concentration of NT-proBNP was almost 10 times that of proBNP. The mean proBNP:BNP ratio in patient plasma was 6.3, ranging from 1.8 to 10.8. CONCLUSIONS: ProBNP is the major BNP-immunoreactive form in human blood. The proBNP:BNP ratio in plasma samples is dependent on the methods used for sample handling and for the measurement of the peptides.     

B-type natriuretic peptides: prognostic markers in stable coronary artery disease

Circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment (NT) of its prohormone (proBNP) are related to cardiac function and have emerged as clinically useful tools for the diagnosis of heart failure and for the estimation of prognosis in patients with heart failure and acute coronary syndromes. Recent studies have also convincingly documented that both BNP and NT-proBNP are powerful, independent prognostic indicators in patients with stable coronary artery disease. The associations are strongest for the end-points of death and heart failure, whereas the association with cardiac ischemic events is weaker or nonexistent, after adjustment for confounding factors. Importantly, BNP and NT-proBNP appear to provide incremental prognostic information to conventional risk factors, including markers of ventricular function and ischemia. Data documenting that BNP or NT-proBNP measurements can be used to guide treatment decisions in patients with stable coronary artery disease are still lacking.     

Clinical relevance of measurement of brain natriuretic peptide and N-terminal pro-brain natriuretic peptide in pediatric cardiology

BACKGROUND: The aim of this review is to understand the clinical usefulness of Brain Natriuretic Peptide (BNP) and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in pediatric cardiology. METHODS: A computerized literature search on National Library of Medicine using the keywords "BNP assay" and "NT-proBNP assay" was performed. Then, we refined the analysis to include only the studies specifically designed to evaluate the clinical usefulness of BNP and NT-proBNP assays in patients with congenital heart disease. RESULTS: BNP and NT-proBNP are useful marker for diagnosis of heart failure, for the assessment of clinical severity and for the follow-up of congenital and pediatric heart diseases. However, results from different studies are often partial and not always univocal. Moreover, reference intervals in pediatric population have not yet been extensively evaluated. CONCLUSIONS: BNP and NT-proBNP may be considered helpful markers for the integrated diagnosis and management of pediatric patients, though further studies are needed to support their routine use.     

Pathophysiology and significance of natriuretic peptides in patients with end-stage kidney disease

Natriuretic peptides (NP), especially B type (BNP) and its N-terminal pro-B type natriuretic peptide (NT-proBNP), have long been regarded as biomarkers of volume overload and tools to exclude heart failure in the general population. However, their role in end-stage kidney disease (ESKD) is less certain given that BNP and NT-proBNP are excreted by the kidney and so serum concentrations of NPs are nearly universally elevated compared to controls. Nevertheless, the accumulated evidence suggests that serum concentrations of NPs in patients with ESKD show moderate or strong positive relationships with underlying heart disease, abnormal cardiac structure or function and mortality. Limited evidence also supports the role of BNP including NT-proBNP, ANP in some studies, rather than CNP or DNP in risk stratification among ESKD patients as well as the utility of BNP samplings pre- and post- hemodialysis. However, studies of the cut-off values of NPs have yielded inconsistent results, such that further large-scale studies are needed to clarify these issues. This review summarizes the pathophysiology and significance of NPs in ESKD patients, especially their potential role as risk stratification biomarkers in clinical management.     

The potential role of natriuretic peptides and other biomarkers in heart failure diagnosis,prognosis and management

Heart failure (HF) is a complex disease process that is challenging to diagnose and manage. For more than 15 years, biomarkers have been used to diagnose and the guide the management of patients with this disease. The gold standard biomarkers for HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP); both are used for diagnosis and prognosis. More recently, there has been an interest in use of BNP and NT-proBNP for HF management as well. Important aspects regarding production and clearance of BNP and NT-proBNP exist, which are vital for the clinician to understand. Beyond BNP or NT-proBNP, other newer biomarkers such as mid-regional pro-atrial natriuretic peptide, soluble ST2, highly sensitive troponin and renal biomarkers may add value for prognostication and possibly, patient management. In this article, the authors will discuss the established and evolving role of BNP and NT-proBNP in HF, along with consideration of select newer biomarkers in this setting.     

B-type natriuretic peptide in acute pulmonary embolism

Myocardial stretch leads to the natriuretic peptides release in acute or chronic left ventricular dysfunction. However, there is an accumulating evidence that B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) may originate from right ventricle and their concentrations are elevated in patients with acute pulmonary embolism (APE) especially when resulting in right ventricular dysfunction (RVD). Recently it is underlined that severity assessment of APE as well as the risk stratification and therapy selection is based both on patients' hemodynamic status and markers of myocardial injury and RVD. BNP and NT-proBNP are helpful in identifying patients with RVD in APE, emerging as an adjunctive tool to echocardiography. Elevated BNP or NT-proBNP levels are also significant predictors of death and/or complicated clinical course in APE.     

Natriuretic peptides in acute pulmonary embolism: a systematic review

Background  Patients with pulmonary embolism (PE) have a high risk of death, and it is important to recognize factors associated with higher mortality. Recently, several biomarkers have been studied for risk stratification in patients with PE. Objectives  Evaluate the available evidence on (a) the accuracy of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) for the diagnosis of right ventricular dysfunction and (b) their value as a prognostic factor of all-cause in-hospital or short-term mortality in patients with PE. Data sources  MEDLINE, Embase, and citation review of relevant primary and review articles. Selection criteria  We selected studies evaluating the accuracy of BNP or NT-proBNP for the diagnosis of right ventricular dysfunction. We also selected studies that reported data on BNP or NT-proBNP as a predictor of short-term mortality in patients with PE. Results  Sixteen studies met our inclusion criteria. The pooled diagnostic odds ratio for the diagnosis of right ventricular dysfunction in pulmonary embolism was 39.45 (95% CI; 15.54–100.12) and 24.73 (95% CI 2.02–302.37) for BNP and NT-proBNP, respectively. The pooled odds ratio for all-cause in-hospital or short-term mortality was 6 (95% CI 1.31–27.43; p: 0.021) and 16.12 (95% CI 3.1–83.68; p: 0.001) for BNP (cutoff: 100 pg/ml) and NT-proBNP (cutoff: 600 ng/L), respectively. Conclusion  The results of this meta-analysis indicate that BNP and NT-proBNP are associated with the diagnosis of right ventricular dysfunction (RVD) in patients with an acute PE and are significant predictors of all-cause in-hospital or short-term mortality in these patients.