B-type natriuretic peptide: issues for the intensivist and pulmonologist

OBJECTIVE: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), although promising as biomarkers for heart failure, are affected by multiple confounders. The purpose of this article is to review the literature on the utility of BNP and NT-proBNP as biomarkers, with a focus on their role in critical illness and pulmonary diseases. DATA SOURCE: Published articles on BNP and NT-proBNP. DATA ANALYSIS: Multiple disorders in the intensive care unit cause elevated BNP and NT-proBNP levels, including cardiac diseases, shock, pulmonary hypertension, acute respiratory distress syndrome, acute pulmonary embolism, chronic obstructive pulmonary disease, renal failure, and other conditions. CONCLUSIONS: Intensivists and pulmonologists should understand that BNP and NT-proBNP levels might be raised to different degrees not only in heart failure but also in critical illness and various pulmonary diseases; in these situations, BNP and NT-proBNP may also serve as markers of severity and prognosis.     

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.     

Natriuretic peptide determinations in critical care medicine: part of routine clinical practice or research test only?

Measurement of N-terminal pro-B-type natriuretic peptide has been shown a good rule-out test for cardiac dysfunction in patients in the intensive care unit. The peptide measurement should not be used as a replacement for other forms of monitoring, and performs best as a diagnostic test when interpreted together with other clinical findings and investigations. At a cutoff value similar to that found in other clinical studies in acute decompensated heart failure, measurement of N-terminal pro-B-type natriuretic peptide offers an additional tool for diagnostic assessment of patients presenting to the intensive care physician.     

Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure

OBJECTIVE: B-type natriuretic peptide (BNP) and N-terminal pro-BNP measurements are used for the diagnosis of congestive heart failure (HF). However, the diagnostic value of these tests is unknown under septic conditions. We compared patients with severe sepsis or septic shock and patients with acute HF to unravel the influence of the underlying diagnosis on BNP and N-terminal pro-BNP levels. DESIGN: Prospective, clinical study. SETTING: Academic medical intensive care unit (ICU). PATIENTS: A total of 249 consecutive patients were screened for the diagnosis of sepsis or HF. Sepsis was defined according to published guidelines. HF was diagnosed in the presence of an underlying heart disease and congestive HF, pulmonary edema, or cardiogenic shock. INTERVENTIONS: BNP and N-terminal pro-BNP were measured from blood samples that were drawn daily for routine analysis. MEASUREMENTS AND MAIN RESULTS: We identified 24 patients with severe sepsis or septic shock and 51 patients with acute HF. At admission, the median (range) BNP and N-terminal pro-BNP levels were 572 (13-1,300) and 6,526 (198-70,000) ng/L in patients with sepsis and 581 (6-1,300) and 4,300 (126-70,000) ng/L in patients with HF. The natriuretic peptide levels increased during the ICU stay, but the differences between the groups were not significant. Nine patients with sepsis and eight patients with HF were monitored with a pulmonary artery catheter. Mean (sd) pulmonary artery occlusion pressure were 16 (4.2) and 22 (5.3) mm Hg (p = .02), and cardiac indexes were 4.6 (2.8) and 2.2 (0.6) L/min/m (p = .03) in patients with sepsis and HF, respectively. Despite these clear hemodynamic differences BNP and N-terminal pro-BNP levels were not statistically different between the two groups. CONCLUSION: In patients with severe sepsis or septic shock, BNP and N-terminal pro-BNP values are highly elevated and, despite significant hemodynamic differences, comparable with those found in acute HF patients. It remains to be determined how elevations of natriuretic peptide levels are linked to inflammation and sepsis-associated myocardial dysfunction.     

The use of B-type natriuretic peptide in the diagnosis of acute dyspnoea

B-type natriuretic peptide (BNP) and NT-proBNP are currently the most prominent members of the natriuretic peptide family. These markers are secreted from both the left and the right cardiac ventricle in response to ventricular volume expansion and pressure overload. Recent studies have suggested that these neurohormones are reliably elevated in the setting of congestive heart failure and may be very helpful in its diagnosis. The use of rapid BNP testing in addition to clinical judgement increased the accuracy of the clinical evaluation. The B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study showed that the increase in accuracy offered by rapid BNP testing resulted in a significant reduction of hospitalisations, use of intensive care, time to discharge and initial treatment cost.     

Cardiac secretion of atrial and brain natriuretic peptides in acuteischaemic heart failure in pigs: effect of angiotensin II receptor antagonism

In amodel of acute ischaemic left ventricular failure in pigs, we compared the plasma levels andcardiac secretion of the three atrial peptides, atrial natriuretic factor (ANF), N-terminalproatrial natriuretic factor (N-terminal proANF) and brain natriuretic peptide (BNP). Acuteischaemic left ventricular failure was induced by embolization of the left coronary artery withplastic microspheres. Thereafter, treatment was given by an intravenous injection of theangiotensin II receptor (AT1) antagonist losartan. Effects of failure induction and treatmentwere documented by measurement of haemodynamic parameters and plasma concentrations ofcatecholamines, plasma renin activity, angiotensin II and aldosterone. Acute left ventricularfailure was accompanied by significant increases in cardiac secretion and plasma levels of allthree atrial peptides, which was considerably more pronounced for ANF and N-terminalproANF than for BNP. Treatment with losartan resulted in significant decreases in plasma ANFand N-terminal proANF, whereas BNP did not change. These findings indicate that ANF andN-terminal proANF may be better suited than BNP as markers of cardiac preload during thedevelopment and treatment of acute heart failure.     

The role of BNP testing in heart failure

Brain natriuretic peptide (BNP) levels are simple and objective measures of cardiac function. These measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money in the emergency department setting. The high negative predictive value of BNP tests is particularly helpful for ruling out heart failure. Treatment with angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, spironolactone, and diuretics reduces BNP levels, suggesting that BNP testing may have a role in monitoring patients with heart failure. However, patients with treated chronic stable heart failure may have levels in the normal range (i.e., BNP less than 100 pg per mL and N-terminal proBNP less than 125 pg per mL in patients younger than 75 years). Increases in BNP levels may be caused by intrinsic cardiac dysfunction or may be secondary to other causes such as pulmonary or renal diseases (e.g., chronic hypoxia). BNP tests are correlated with other measures of cardiac status such as New York Heart Association classification. BNP level is a strong predictor of risk of death and cardiovascular events in patients previously diagnosed with heart failure or cardiac dysfunction.     

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.     

严重脓毒症患者血浆B型脑钠肽水平与PICCO监测指标的相关性分析

目的：探讨严重脓毒症患者脉波指示剂连续心输出量（PICCO）监测指标与外周血脑钠肽（BNP）水平变化的关系以指导临床诊治。方法：收集严重脓毒症患者28例,入重症监护室（ICU）24h按超声心动图检查心功能评估分为心功能正常组和心功能减退组,比较2组血浆BNP水平,并通过PICCO技术记录心功能指数（CFI）、外周血管阻力指数（SVRI）、全心舒张末期容量指数（GEDVI）、血管外肺水指数（EVLWI）和胸腔内血容积指数（ITBVI）,比较其与血浆BNP水平相关性。结果：2组BNP均升高,但心功能减退组BNP升高明显,组间比较有显著差异。心功能减退组BNP与CFI呈负相关,与EVLWI呈正相关,与GEDVI,ITB-VI,SVRI无显著相关。心功能正常组BNP仅与CFI呈负相关,与其他指标均无显著相关。心功能减退组28d病死率显著升高。结论：BNP能够反映严重脓毒症患者心功能状态,在心功能减退组患者还可以间接反映血管外肺水的情况。     

Natriuretic peptide system: physiology and clinical utility

PURPOSE OF REVIEW: This review discusses the physiology of natriuretic peptides as a group and brain natriuretic peptide (BNP) in more detail. It will also highlight implications for the use of the natriuretic peptides in the diagnosis and treatment of patients with cardiovascular disease. RECENT FINDINGS: The heart secretes two major natriuretic peptides: atrial natriuretic peptide (ANP), which is synthesized in the atrial myocardium, and BNP, which is synthesized in the ventricular myocardium. Both ANP and BNP are released in response to atrial and ventricular stretch, respectively, and will cause balanced vasodilation, natriuresis, and inhibition of the sympathetic nervous system and the renin-angiotensin-aldosterone axis. BNP is reported to be the biochemical marker of choice for evaluating the acute risk of patients with cardiovascular disease states ranging from heart failure to myocardial ischemia. Increased blood BNP concentrations are highly predictive of the short- and long-term risk of cardiac death across the entire spectrum of acute coronary syndromes and in patients with decompensated congestive heart failure. Synthetic recombinant human BNP, which mimics the actions of endogenous BNP, has emerged as an important new therapeutic agent in patients with acute heart failure. SUMMARY: Current data suggest that single and serial plasma measurement of BNP concentrations is a useful tool in the diagnosis and risk stratification of patients with heart disease. Nesiritide, the human recombinant form of BNP, is a new promising parenteral treatment in decompensated heart failure.     

BNP对急性脑梗死合并心力衰竭患者的诊断价值

目的评估B型钠尿肽（brain natriuretic peptide,BNP）对急性心肌梗死合并心力衰竭患者的诊断价值。方法利用电化学发光法测定100例急性脑梗死合并心衰患者血浆BNP水平。与对照组比较分析,并绘制出血浆BNP的工作特征（ROC）曲线,找出诊断急性脑梗死合并心力衰竭的最佳临界点。结果急性脑梗死合并心力衰竭组血浆BNP水平显著高于单纯急性脑梗死组（P〈0.01）及正常组（P〈0.01）;BNP作为诊断急性脑梗死合并心力衰竭患者的临界点为299pg/mL,此时灵敏度为81.8%,特异度为83.5%,ROC曲线下的面积是0.888。结论血清BNP是一个判断急性脑梗死是否合并心力衰竭较为可靠的诊断指标。     

The applications of B-type natriuretic peptide measurement in the intensive care unit

PURPOSE OF REVIEW: Plasma B-type natriuretic peptide levels are used to screen for cardiac dysfunction in the emergency department and outpatient population. However, in the critically ill patient elevated plasma B-type natriuretic peptide levels do not necessarily reflect just ventricular dysfunction, as there are important confounding factors to consider. This review summarizes the recent advances in the application of B-type natriuretic peptide measurement in the intensive care unit. RECENT FINDINGS: B-Type natriuretic peptide levels are very useful in identifying cardiac dysfunction but not the specific pathology, whether it is right or left ventricular failure, diastolic or systolic dysfunction. Elevated serum B-type natriuretic peptide levels also occur in severe sepsis or septic shock. It also predicts cardiac dysfunction in sepsis. The lack of correlation of B-type natriuretic peptide concentrations with filling pressures in the intensive care unit precludes its use for monitoring cardiac therapy. Some studies involving patients with sepsis or septic shock demonstrate a positive correlation with mortality, while others failed to establish such a relation. The prognostic value of B-type natriuretic peptide in predicting mortality and morbidity remains controversial, partly due to different study designs. SUMMARY: B-Type natriuretic peptide is potentially a very useful diagnostic tool in the intensive care unit. To date there have been few studies and the results are often contradictory, mainly due to the special setting of the intensive care unit, which is constantly exposed to hemodynamically unstable patients, different case mixes as well as vigorous treatments. All of these are potential confounders to B-type natriuretic peptide levels and make interpretations of B-type natriuretic peptide difficult. We need more research on these confounding factors to accentuate the positive value of B-type natriuretic peptide in the intensive care unit.     

脑钠素对老年心衰患者的诊断价值

目的:评价脑钠素(BNP)在老年心衰患者中的诊断价值。方法:采用ELISA法测定心衰组和非心衰组共38例老年患者的血浆脑钠素水平并进行比较。结果:心衰组患者血浆脑钠素水平显著高于非心衰组(P<0.01),且血浆脑钠素浓度与心衰严重程度呈正相关。结论:血浆脑钠素水平是诊断老年心衰较好的指标,能反映心衰的严重程度,具有广泛的临床应用价值。     

ProBNP-derived peptides in cardiac disease

The natriuretic peptides constitute a family of structurally related peptides that regulate fluid homeostasis, vascular tonus and growth. After the discovery of an endocrine component of the heart almost 25 years ago, the cardiac natriuretic peptides have now been fully accepted as useful markers in diverse aspects of cardiology including as diagnostic, therapeutic and prognostic markers of cardiac disease. In humans, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are mainly synthesized and secreted by the failing heart, whereas the related C-type natriuretic peptide (CNP) appears to be a local regulatory peptide secreted by the vascular endothelium. Accordingly, CNP is not a cardiac peptide. With the recent implementation of sensitive and specific immunoassays, increased plasma concentrations of proBNP-derived peptides have now been associated with several cardiac conditions, where the major application today seems related to ventricular dysfunction. Recently, focus has also turned to ischemic heart disease, since myocardial hypoxia increases the local BNP gene expression. This review recapitulates the established clinical applications of measuring proBNP-derived peptides in plasma. Furthermore, the evidence of increased cardiac BNP expression in ischemic heart disease will be emphasized. In turn, plasma measurement of proBNP-derived peptides may still hold new possibilities in screening for coronary artery disease.     

B型尿钠肽对危重病患者预后的诊断价值研究

目的探讨B型尿钠肽(BNP)水平判断危重病患者预后的诊断价值。方法选择本院重症监护室患者46例,按慢性健康状况评分Ⅱ(APACHEⅡ)随机分为A、B 2组,各23例,每组分别于入院第1天、第4天、第7天检测血浆BNP水平。结果 A组第1天、第4天、第7天血浆BNP水平明显低于B组(P<0.01);2组患者第4天和第7天血浆BNP水平均明显高于第1天,且第7天血浆BNP水平均明显高于第4天(P<0.01)。结论血浆BNP在诊断心力衰竭的同时,也可作为判断危重病患者预后的指标之一。     

An experimental study of cardiac natriuretic peptides as markers of development of congestive heart failure

The use of cardiac peptide measurements as possible diagnostic tools in congestive heart failure has been extensively discussed in the recent literature. Therefore, the aim of this study was to establish a model of experimental chronic heart failure, and thereby perform a comparative study of secretion and circulating levels of the cardiac peptides atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide (N-terminal proANP) and brain natriuretic peptide (BNP) during evolving heart failure. Chronic heart failure was induced in seven pigs by rapid left atrial pacing for three weeks. The effects of failure induction were documented 24 h after pacemaker deactivation. Hemodynamic indices of cardiac preload, like pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP), were all considerably increased compared to sham operated controls. Likewise, plasma endothelin-1, noradrenaline, renin activity, aldosterone and angiotensin II were all markedly increased. Heart failure was accompanied by significant increases in both estimated cardiac secretory rate and plasma concentrations of all three cardiac peptides, significantly correlated to the PCWP. The directional changes during evolving heart failure were similar, although the percentage increase in plasma BNP was much larger than for ANP and N-terminal proANP. In absolute molar terms, however, the BNP concentration changes were minor compared to those of the other two peptides. The larger percentage increase of BNP might indicate its superiority as a marker of heart failure development, provided a functional assay suitable for clinical use can be designed for a peptide circulating in this low concentration range.     

An experimental study of cardiac natriuretic peptides as markers of development of congestive heart failure

The use of cardiac peptide measurements as possible diagnostic tools in congestive heart failure has been extensively discussed in the recent literature. Therefore, the aim of this study was to establish a model of experimental chronic heart failure, and thereby perform a comparative study of secretion and circulating levels of the cardiac peptides atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide (N-terminal proANP) and brain natriuretic peptide (BNP) during evolving heart failure. Chronic heart failure was induced in seven pigs by rapid left atrial pacing for three weeks. The effects of failure induction were documented 24 h after pacemaker deactivation. Hemodynamic indices of cardiac preload, like pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP), were all considerably increased compared to sham operated controls. Likewise, plasma endothelin-L, noradrenaline, renin activity, aldosterone and angiotensin II were all markedly increased. Heart failure was accompanied by significant increases in both estimated cardiac secretory rate and plasma concentrations of all three cardiac peptides, significantly correlated to the PCWP. The directional changes during evolving heart failure were similar, although the percentage increase in plasma BNP was much larger than for ANP and N-terminal proANP. In absolute molar terms, however, the BNP concentration changes were minor compared to those of the other two peptides. The larger percentage increase of BNP might indicate its superiority as a marker of heart failure development, provided a functional assay suitable for clinical use can be designed for a peptide circulating in this low concentration range.     

The emerging roles of BNP and accelerated cardiac protocols in emergency laboratory medicine.

BACKGROUND: The role of the clinical laboratory in emergency cardiac medicine is rapidly evolving; with recent redefinitions of acute myocardial infarction (AMI) and unstable angina (UA) based on troponin levels, recommended acceleration of cardiac testing protocols, and increased clinical measurement of B-type natriuretic peptide (BNP). We briefly review the background pathophysiology of acute coronary syndromes (ACS) and congestive heart failure (CHF), along with an overview of the biochemistry and physiology of the natriuretic peptides. METHODS: The assay principles and performance characteristics of the rapid BNP assays are discussed. The performance characteristics of troponin assays are at the center of controversy regarding the redefinition of AMI and UA, and will be discussed. RESULTS: We review the rapidly expanding evidence regarding the clinical utility of BNP for CHF patients. While BNP has gained wide acceptance as a rapid diagnostic tool, considerable controversy remains concerning its potential for prognosis, screening, and therapeutic monitoring. Although a thorough discussion of the use of cardiac markers is well beyond the scope of this review, overviews of the redefinitions of AMI and UA, and the trend toward accelerated testing protocols to obtain a quicker diagnosis or ruling-out of AMI are included. In addition to accelerating the retesting of existing markers, a recent test for ischemia modified albumin (IMA) promises another quantum leap in cardiac diagnoses. CONCLUSIONS: The positive impact of these developments on the healthcare costs and overall improvement in the quality of healthcare delivery will be discussed. A brief analysis of the downstream costs of BNP testing is also offered.