Natriuretic Peptide Testing Research Articles

P-26 B-Type Natriuretic Peptide Testing and the Accuracy of Heart Failure Diagnosis in the Emergency Department

P-26 B-Type Natriuretic Peptide Testing and the Accuracy of Heart Failure Diagnosis in the Emergency Department

2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults

2009;53;1343-1382; originally published online Mar 26, 2009; J. Am. Coll. Cardiol. Rahko, Marc A. Silver, Lynne Warner Stevenson, and Clyde W. Yancy Francis, Theodore G. Ganiats, Marvin A. Konstam, Donna M. Mancini, Peter S. Mariell Jessup, William T. Abraham, Donald E. Casey, Arthur M. Feldman, Gary S. Heart and Lung Transplantation Developed in Collaboration With the International Society for Guidelines Cardiology Foundation/American Heart Association Task Force on Practice Management of Heart Failure in Adults: A Report of the American College of 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and This information is current as of August 30, 2010 http://content.onlinejacc.org/cgi/content/full/53/15/1343 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Utility of natriuretic peptide testing in the evaluation and management of acute decompensated heart failure

The B-type natriuretic peptide (BNP) and the amino-terminal fragment of proBNP (NT-proBNP) are increased in heart failure in proportion to severity of symptoms, degree of left ventricular dysfunction, and elevation of cardiac filling pressures. These natriuretic peptides (NPs) are increasingly used for diagnostic and prognostic purposes in acute heart failure. While NP levels on admission provide independent prognostic information, serial determinations during hospitalization and at discharge better reflect adequacy of treatment and prognosis. The addition of BNP and NT-proBNP to usual clinical decision making enhances detection of high-risk patients who need aggressive follow-up and adjustment of treatment.

Clinical burden and health service challenges of chronic heart failure

Heart failure is a common disorder, especially in the elderly, and is assuming major significance for both patients and healthcare systems. We need better identification of patients and more intensive attempts to introduce and maintain therapies for which there is a large evidence base. Given the burden of disease, however, prevention of heart failure is a priority and this requires formalized programs of cardiovascular prevention. © 2009 The Author.

B-Type Natriuretic Peptide Testing, Clinical Outcomes, and Health Services Use in Emergency Department Patients With Dyspnea

B-type natriuretic peptide (BNP) is used to diagnose heart failure, but the effects of using the test on all dyspneic patients is uncertain. To assess whether BNP testing alters clinical outcomes and health services use of acutely dyspneic patients. Randomized, single-blind study. Patients were assigned to a treatment group through randomized numbers in a sealed envelope. Patients were blinded to the intervention, but clinicians and those who assessed trial outcomes were not. 2 Australian teaching hospital emergency departments. 612 consecutive patients who presented with acute severe dyspnea from August 2005 to March 2007. BNP testing (n = 306) or no testing (n = 306). Admission rates, length of stay, and emergency department medications (primary outcomes); mortality and readmission rates (secondary outcomes). There were no between-group differences in hospital admission rates (85.6% [BNP group] vs. 86.6% [control group]; difference, -1.0 percentage point [95% CI, -6.5 to 4.5 percentage points]; P = 0.73), length of admission (median, 4.4 days [interquartile range, 2 to 9 days] vs. 5.0 days [interquartile range, 2 to 9 days]; P = 0.94), or management of patients in the emergency department. Test discrimination was good (area under the receiver-operating characteristic curve, 0.87 [CI, 0.83 to 0.91]). Adverse events were not measured. Most patients were very short of breath and required hospitalization; the findings might not apply for evaluating patients with milder degrees of breathlessness. Measurement of BNP in all emergency department patients with severe shortness of breath had no apparent effects on clinical outcomes or use of health services. The findings do not support routine use of BNP testing in all severely dyspneic patients in the emergency department. Janssen-Cilag.

Evolution of amino-terminal Pro-B type natriuretic peptide testing in heart failure

The use of natriuretic peptide testing has expanded considerably over the recent years. Thanks to clinical trials that have demonstrated significant benefits associated with testing for B-type natriuretic peptide (BNP) and its amino-terminal pro-peptide (NTproBNP), testing for these peptides is now ubiquitous in modern medicine. This review will focus on the use of NTproBNP in clinical medicine, with a discussion of the biologic significance of NT-proBNP, its proven present uses and potential future applications.

The additive value of N-terminal pro-B-type natriuretic peptide testing at the emergency department in patients with acute dyspnoea

Background B-type natriuretic peptide (BNP) and its inactive counterpart NT-proBNP can help to identify or rule out heart failure in patients presenting with acute dyspnoea. It is not well known whether measurement of these peptides can be omitted in certain patient groups. Methods We conducted a prospective observational study of 221 patients presenting with acute dyspnoea at the emergency department. The attending physicians estimated the probability of heart failure by clinical judgement. NT-proBNP was measured, but not reported. An independent panel made a final diagnosis of all available data including NT-proBNP level and judged whether and how NT-proBNP would have altered patient management. Results NT-proBNP levels were highest in patients with heart failure, alone or in combination with pulmonary failure. Additive value of NT-proBNP was present in 40 of 221 (18%) of the patients, and it mostly indicated that a more intensive treatment for heart failure would have been needed. Clinical judgement was an independent predictor of additive value of NT-proBNP with a maximum at a clinical probability of heart failure of 36%. Conclusion NT-proBNP measurement has additive value in a substantial number of patients presenting with acute dyspnoea, but can possibly be omitted in patients with a clinical probability of heart failure of > 70%.

Natriuretic Peptide Testing in Primary Care

The incidence, as well as the morbidity and mortality associated with heart failure (HF) continue to rise despite advances in diagnostics and therapeutics. A recent advance in the diagnostic and therapeutic approach to HF is the use of natriuretic peptide (NP) testing, including both B-type natriuretic peptide (BNP) and its amino terminal cleavage equivalent (NT-proBNP). NPs may be elevated at an early stage among those with symptoms as well among those without. The optimal approach for applying NP testing in general populations is to select the target population and optimal cut off values carefully. Superior diagnostic performance is observed among those with higher baseline risk (such as hypertensives or diabetics). As well, unlike for acute HF, the cut off value for outpatient testing for BNP is 20-40 pg/mL and for NTproBNP it is 100-150 ng/L. In symptomatic primary care patients, both BNP and NT-proBNP serve as excellent tools for excluding HF based on their excellent negative predictive values and their use may be cost effective. Among those with established HF, it is logical to assume that titration of treatment to achieve lower NPs levels may be advantageous. There are several ongoing trials looking at that prospect.

Pulmonary hypertension in COPD

Mild-to-moderate pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD); such a complication is associated with increased risks of exacerbation and decreased survival. Pulmonary hypertension usually worsens during exercise, sleep and exacerbation. Pulmonary vascular remodelling in COPD is the main cause of increase in pulmonary artery pressure and is thought to result from the combined effects of hypoxia, inflammation and loss of capillaries in severe emphysema. A small proportion of COPD patients may present with "out-of-proportion" pulmonary hypertension, defined by a mean pulmonary artery pressure >35-40 mmHg (normal is no more than 20 mmHg) and a relatively preserved lung function (with low to normal arterial carbon dioxide tension) that cannot explain prominent dyspnoea and fatigue. The prevalence of out-of-proportion pulmonary hypertension in COPD is estimated to be very close to the prevalence of idiopathic pulmonary arterial hypertension. Cor pulmonale, defined as right ventricular hypertrophy and dilatation secondary to pulmonary hypertension caused by respiratory disorders, is common. More studies are needed to define the contribution of cor pulmonale to decreased exercise capacity in COPD. These studies should include improved imaging techniques and biomarkers, such as the B-type natriuretic peptide and exercise testing protocols with gas exchange measurements. The effects of drugs used in pulmonary arterial hypertension should be tested in chronic obstructive pulmonary disease patients with severe pulmonary hypertension. In the meantime, the treatment of cor pulmonale in chronic obstructive pulmonary disease continues to rest on supplemental oxygen and a variety of measures aimed at the relief of airway obstruction.

Natriuretic Peptide Testing in Clinical Medicine

Since the discovery of atrial natriuretic factor in 1981 by de Bold et al, there has been tremendous progress in our understanding of natriuretic peptides (NPs). Recently, testing for brain-type NP (BNP) and its amino terminal cleavage equivalent (NT-proBNP) has been rapidly adopted in clinical medicine for numerous indications, including the diagnosis and exclusion of heart failure (HF). In this regard, logical application of BNP or NT-proBNP testing may not only reduce healthcare costs but also potentially reduce adverse clinical outcomes. With respect to this fact, the potential importance of the concentration of the NPs for prognosis and the response of BNP or NT-proBNP to therapeutic intervention in terms of clinical events has been demonstrated. On the basis of these observations it is reasonable to expect that concentrations of these peptides might be useful for the management of patients with HF, acting as a gauge of therapeutic accuracy and/or stability of disease. Besides HF, the prognostic utility of NPs has been explored in other settings, particularly in ischemic heart disease and those conditions that lead to right ventricular dysfunction.

The Role of B-Type and Other Natriuretic Peptides in Health and Disease

Natriuretic peptide (NP) physiology is a complex field. NPs also are known to be highly phylogenetically preserved. NPs can be thought of as counterregulatory hormones antagonizing the effects of the renin-angiotensin-aldosterone and sympathetic systems. These peptides are primarily responsible for maintaining salt and water homeostasis, but they also have vasodilatory properties. It was originally thought that B-type NP (BNP) and N-terminal-pro-BNP are secreted in a 1:1 ratio. However, recent data has shed further light into this area. Commercial assays for NPs will need to keep up with these changes. Currently, BNP levels within Kaiser Permanente are obtained by multiple providers in a variety of clinical scenarios in order to help them manage their patients. Therefore, a basic understanding of the physiology of NPs and the methodology of assays are needed to appropriately interpret an NP test result within the corresponding clinical scenario.

Natriuretic Peptides and Echocardiography in Unselected Acute Dyspnea Patients: Implication of Elevated Levels with Normal Systolic Function

Introduction: Prior evaluations of patients (pts) with acute dyspnea and natriuretic peptide (NP) testing presenting to the emergency department (ED) have selected only a minority of pts for echocardiography. Therefore, the association of NP's with more subtle echocardiographic findings and the potential for NP's provide to additional prognostic information in “all-comers” beyond echocardiography is uncertain. We determined the significance of NP's in acute dyspnea pts with a wide spectrum of echocardiographic findings.

The use of B-type natriuretic peptide in the management of patients with atrial fibrillation and dyspnea

The utility of B-type natriuretic peptide (BNP) testing in patients with atrial fibrillation (AF) is poorly defined. We analyzed patients ( n = 452) included in the BNP for Acute Shortness of Breath Evaluation (BASEL) study. Patients were randomly assigned to a diagnostic strategy with or without the use of BNP. Ninety-nine patients presented with AF ( n = 48 BNP group; n = 51 control group). Although comparable with respect to gender and cardiopulmonary comorbidity, patients with AF were older and more often had heart failure as the cause of dyspnea. In addition, patients with AF had higher in-hospital mortality (13% versus 6%, P = 0.012). The use of BNP significantly reduced time to discharge (BNP group median 8 days [1–16] versus 12 days [IQR 4–21] control group; P = 0.046) in patients with AF. Initial total treatment costs (median) were $4239 [769–7422] in the BNP group and $5940 [4024–10848] in the control group ( P = 0.041). These benefits were maintained after 90 days: patients in the BNP group had spent fewer days in hospital (10 days [2–21] versus 15 days [IQR 9–27]; P = 0.022) and induced lower total treatment costs ($4790 [1260–9387] versus $7179 [4311–13173]; P = 0.016). In conclusion, the use of BNP seems to improve the management of patients with AF presenting with dyspnea.

Cost‐Effectiveness of B‐Type Natriuretic Peptide Testing

As with any other diagnostic method, the cost-effectiveness of B-type natriuretic peptide (BNP) testing depends on the indication of its use and the specific clinical setting. The use of BNP levels, in conjunction with other clinical information, provides information that seems to be particularly helpful in the diagnosis, prognosis, and management of heart failure (HF) as well as screening for left ventricular systolic dysfunction. In the screening for asymptomatic left ventricular systolic dysfunction, BNP testing seems to be cost-effective (<$50,000 per quality-adjusted life-years gained) when used in a population with a prevalence of at least 1%. BNP testing, in fact, results in cost savings in the diagnosis of HF. Although the data are less robust, BNP seems cost-effective in the risk stratification of hospitalized HF patients when compared with echocardiography. Because BNP guidance seems to reduce the number of rehospitalizations in recently hospitalized patients with chronic HF, the use of BNP is also most likely cost-effective in this indication. For the remaining and, in part, evolving indications, further studies are needed to assess cost-effectiveness.

Cost‐Effectiveness of B‐Type Natriuretic Peptide Testing

As with any other diagnostic method, the cost‐effectiveness of B‐type natriuretic peptide (BNP) testing depends on the indication of its use and the specific clinical setting. The use of BNP levels, in conjunction with other clinical information, provides information that seems to be particularly helpful in the diagnosis, prognosis, and management of heart failure (HF) as well as screening for left ventricular systolic dysfunction. In the screening for asymptomatic left ventricular systolic dysfunction, BNP testing seems to be cost‐effective (&lt;$50,000 per quality‐adjusted life‐years gained) when used in a population with a prevalence of at least 1%. BNP testing, in fact, results in cost savings in the diagnosis of HF. Although the data are less robust, BNP seems cost‐effective in the risk stratification of hospitalized HF patients when compared with echocardiography. Because BNP guidance seems to reduce the number of rehospitalizations in recently hospitalized patients with chronic HF, the use of BNP is also most likely cost‐effective in this indication. For the remaining and, in part, evolving indications, further studies are needed to assess cost‐effectiveness.

Effects of functional electrical stimulation on quality of life and emotional stress in patients with chronic heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy: A randomised, placebo‐controlled trial

Functional electrical stimulation (FES) improves exercise capacity and endothelial function in chronic heart failure (CHF) patients. This study evaluates the impact of FES on quality of life and emotional stress in patients with moderate to severe CHF. Thirty patients with stable CHF (24 men; NYHA class II-III; left ventricular ejection fraction <35%) were randomly assigned (2:1) to a 6-week FES training program (n=20) or placebo (n=10). Questionnaires addressing quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall], and emotional stress [Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)], as well as plasma B-type natriuretic peptide (BNP) and 6-min walking distance test (6MWT) were assessed at baseline and after completion of training protocol. A significant improvement in KCCQ functional (F=76.666, p<0.001), KCCQ overall (F =41.508, p<0.001), BDI (F =17.768, p<0.001) and Zung SDS (F =27.098, p<0.001) was observed in the FES group compared to placebo. Patients in the FES group had also a significant increase in 6MWT (F =19.413, p<0.001) and a trend towards reduction in plasma BNP (F =4.252, p=0.053) compared to placebo. FES seems to have a beneficial effect on quality of life, exercise capacity and emotional stress in patients with moderate to severe CHF.

Levosimendan-induced reduction in natriuretic peptide levels during the treatment of decompensated heart failure: Clinical implications — Reply

Although, the potential use of natriuretic peptide testing in treatment monitoring of heart failure remains to be fully clarified, levosimendan-induced reduction in natriuretic peptide levels has consistently been reported to be associated with favorable clinical, hemodynamic, anti-inflammatory and anti-apoptotic effects. Several studies demonstrated that not only is plasma natriuretic peptide level important predictor of long-term outcomes, but changes in natriuretic peptide levels during the treatment of heart failure are also associated with corresponding changes in morbidity and mortality. Re-analysis of the data from our previously published study suggested a greater percentage of NT-proBNP reduction at 48 h in patients who survived compared to those who died in both levosimendan (− 36 ± 8% vs − 24 ± 13%, respectively) and dobutamine (− 32 ± 8% vs + 9 ± 32%, respectively) treatment groups, although not statistically different. The changes in natriuretic peptide levels during therapy reflect short-term hemodynamic improvements and effectiveness of drug regimens, but also may have a role in predicting long-term outcomes.

Biomarkers in heart failure management

Purpose of review Recent literature on the role of biomarkers in heart failure is reviewed, focusing on B-type natriuretic peptide. Recent findings Knowledge of the processes which increase ventricular stress, thus increasing B-type natriuretic peptide, is key to appropriate utilization and interpretation of B-type natriuretic peptide levels. B-type natriuretic peptide is a useful adjunct to confirm or rule out heart failure. B-type natriuretic peptide is a robust prognostic indicator in all stages of heart failure, with prognostic significance in patients undergoing cardiac and noncardiac surgery, and in those with acute coronary syndromes. Serial B-type natriuretic peptide testing predicts outcomes in hospitalized patients with heart failure. The role of B-type natriuretic peptide in screening high-risk populations is promising, but its use in unselected populations is unclear. There is increasing evidence that the use of B-type natriuretic peptide to guide heart failure management is associated with improved clinical outcomes and reduced health costs. Summary Biomarkers play an important role in heart failure, but there remain unanswered questions regarding optimization of their use. They should be used as an adjunct to, not replacement for, clinical assessment. Currently available B-type natriuretic peptide assays have limitations relating to clinical variability and assay specificity. Other neurohormonal, inflammatory and metabolic markers may add complementary information to that provided by currently available B-type natriuretic peptide assays.

N-terminal pro–brain natriuretic peptide testing in the emergency department: Beneficial effects on hospitalization, costs, and outcome

N-terminal pro-brain natriuretic peptide (NT-proBNP) is an established biomarker for heart failure. Assessment of this biomarker in patients with acute dyspnea presenting to the emergency department (ED) may aid diagnostic decision-making, resulting in improved patient care and reduced costs. In a prospective clinical trial, patients presenting with acute dyspnea to the ED of the Erasmus Medical College, Rotterdam, the Netherlands, were randomized for either rapid measurement or no measurement of NT-proBNP. For ruling out heart failure, cutoff values of 93 pg/mL in male and 144 pg/mL in female patients were used, and for ruling in heart failure, a cutoff value of 1,017 pg/mL was used. Time to discharge from the hospital and costs related to hospital admission were primary end points. Bootstrap analysis was used for comparison of costs and 30-day mortality between the NT-proBNP and control group. A total of 477 patients (54% male) was enrolled. The mean age was 59 years, with 44% of patients having a history of cardiac disease. Median time to discharge from the hospital was 1.9 days (interquartile range [IQR], 0.12-8.4 days) in the NT-proBNP group (n = 241) compared with 3.9 days (IQR, 0.16-11.0 days) in the control group (n = 236) (P = .04). Introduction of NT-proBNP testing resulted in a trend toward reduction in costs related to hospital admission and diagnostic investigations of $1,364 per patient (95% CI $-246 to $3,215), whereas 30-day mortality was similar (15 patients in the NT-proBNP and 18 patients in the control group). Introduction of NT-proBNP testing for heart failure in the ED setting reduces the time to discharge and is associated with a trend toward cost reduction.

Amino-terminal Pro-B-type Natriuretic Peptide Testing—Past, Present, and Future Applications

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