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Abstract
Hospitals are constantly besieged with congestive heart failure admissions. Current studies show that the advent of the B-type natriuretic peptide (BNP) rapid assay as a quick and easy blood test is beneficial to nurses in confirming the diagnosis of heart failure. B-type natriuretic peptide is a neurohormone produced by the failing heart in response to increased volume and cardiac overload. The BNP rapid assay measures the presence of BNP levels present in the circulating bloodstream to confirm the diagnosis of congestive heart failure. It is a simple blood test that can be done at the bedside or at the clinic so it is a valid point-of-care modality. Elevated levels suggest severity of heart failure and possibility of sudden death. This article focuses on the description of the diagnostic performance of the BNP rapid assay, its clinical dimensions, and its implications to nursing practice and collaborative practice models.
An epidemic disease and a major cause of chronic disability-congestive heart failure (CHF) adversely affects the health of millions. Congestive heart failure is the second most frequent cause of office or hospital visits for cardiovascular disease, with both men and women having a 21% risk of developing the syndrome.1 Incidence includes 550,000 CHF cases annually or 10 per 1,000 after age 65.2 For 1999, prevalence was 3.0 million cases; by 2030, this figure is projected nearly to double-to 5.7 million.1 Worst of all, CHF patients suffer sudden cardiac death 6 to 9 times more frequently than the general population.2 In addition to these disturbing statistics, CHF is the most frequent cause for hospital readmissions, being higher within the first 30 days after discharge than those within 60 to 90 days.2 Thus, CHF has an enormous, constantly escalating financial impact on healthcare expenditures. In 1999, CHF cost Medicare $5,471 per discharge. Costs are estimated to be $27.8 billion for 2005.2 Decreasing readmission rates and hospital length of stay could significantly reduce healthcare costs. This is critical because there is a national imperative to control healthcare spending and to redesign the healthcare system.
Elevated B-type natriuretic peptide (BNP) level is a biomarker of heart failure, and that early detection of increased BNP levels may lead to early diagnosis and treatment of CHF, thereby decreasing readmissions, reducing healthcare expenditure, and improving patients' quality of life.3-5 Current treatment strategies may ignore plasma neurohormone concentrations (BNP), although they are independent markers of cardiac status and prognosis of heart disease, including heart failure.6 Current CHF guidelines do not target any diagnostic criteria such as BNP levels prior to hospital discharge because most efforts have been focused on the use of pharmacologic therapy and CHF management clinics.6 However, BNP is more widely targeted and accepted today. In light of these facts, there is an increasing need to know about the BNP rapid assay and its importance in nursing practice and healthcare. Therefore, this article will present an overview of the BNP rapid assay and stress its importance as a point-of-care modality.
WHAT IS BNP?
B-type natriuretic peptide is a group of natriuretic peptides that are involved in the regulation of diuresis. B-type natriuretic peptide antagonizes or counteracts the vasoconstricting effects of the renin-angiotensin-aldosterone system, thereby regulating blood pressure and fluid balance. B-type natriuretic peptide is a cardiac neurohormone secreted from the cardiac ventricles as a response to ventricular volume expansion and fluid overload evident in the early phases of CHF.
B-type natriuretic peptide levels are elevated in cardiac disease and are sensitive to increased ventricular stretch.7 B-type natriuretic peptide levels are reflective of left ventricular diastolic filling pressure and therefore correlate with pulmonary capillary wedge pressure.8-13 Therefore, it becomes a marker for heart failure. Volume overload from the cardiac ventricles stimulates BNP production and electrophysiologic arrhythmias, suggesting the relationship between BNP and sudden death. Increased BNP levels are therefore suggestive of fluid overload and a strong predictor of sudden death.14,15 An elevated BNP of over 100 pg/mL is predictive of heart failure and increased risk.
ROLE OF BNP RAPID ASSAY IN CHF
The role of BNP rapid assay testing in outpatient or primary care clinics is relevant in the titration of therapies and interventions, as well as in evaluating the state of BNP compensation of the patient.9,16 Highly elevated BNP levels in patients with symptoms of leg swelling can be treated aggressively by increasing the use of diuretics, placing on fluid restriction or initiating a positive inotrophic intravenous drip to increase renal perfusion, augment urine output and ultimately ease difficulty of breathing. In asymptomatic patients with moderate BNP levels, the result may be an effective way to detect and monitor the disease process (CHF). Detecting increased BNP levels during the detectable preclinical phase will result in a better prognosis rather than waiting for treatment to be given after the development of severe symptoms. This would prevent hospital readmissions and decrease overall healthcare cost. Also, these patients are difficult to diagnose. Many have other conditions, so BNP is useful in the early diagnosis, interventions, and patient teaching.
THE ADVENT OF THE BNP RAPID ASSAY
The BNP rapid assay is a blood test that measures the presence of BNP levels present in the circulating bloodstream to confirm the diagnosis of CHF and differentiate cardiac from pulmonary causes of dyspnea.8,9 It is called a rapid assay because it takes 15 minutes to complete and can be done at the bedside or in the clinic. Unlike cardiac enzymes that are ordered in series, BNP assays are performed on an as-needed basis. B-type natriuretic peptide testing in the hospital and outpatient clinic is feasible because BNP testing is not affected by food or exercise. It is used when there is a need to have immediate results. B-type natriuretic peptide levels may help diuretic adjustment after discharge, reflect CHF exacerbation, or may reflect successful treatment or titration.9
One study found that BNP levels = 100 pg/mL contributed significantly (odds ration [OR] = 12.3; 95% confidence interval [CI]: 7.4-20.4) compared with the use of chest x-rays for cardiomegaly (OR = 7.0; 95% CI:1.4-3.7), cephalization (OR = 6.4; 95% CI: 3.3-12.5), and interstitial edema (OR = 7.0; 95% CI: 2.9-17.0), and provided complementary diagnostic information in the diagnosis of heart failure (n = 880).17 Elnoamany and Abdelhameed18 conducted a study assessing the accuracy of mitral annular motion as evaluated by Doppler tissue imaging and M-mode echocardiography for determination of left ventricular dysfunction in comparison with BNP levels. Results revealed that BNP levels had significant correlations (P <. 0001, n = 133) between all echocardiographic variables that determined left ventricular dysfunction and was more strongly correlated with pulsed-wave Doppler tissue imaging (r = 0.815, P < .001).18
According to the American College of Cardiology and the American Heart Association Task Force on Heart Failure Guidelines, BNP levels greater than 100 pg/mL predict the diagnosis of symptomatic heart failure.19 The 2 most commonly used criteria for diagnosing heart failure are those of the National Health and Nutrition Examination Survey (NHANES) and the Framingham criteria. When compared with the NHANES and the Framingham criteria for diagnosing heart failure, the BNP screening test is more accurate at 83%, whereas the NHANES showed an accuracy of 67%, and the Framingham criteria at 73% in confirming the diagnosis of heart failure.9
BNP RAPID ASSAY: CLINICAL DIMENSION
The Triage BNP rapid assay (the only currently approved BNP rapid assay for beside testing) has been utilized in several large-scale multisite, multinational clinical trials for heart failure. For this reason, and as a diagnostic method and screening device, it is imperative to know and understand the sensitivity, specificity, predictive negative value, relative risk, and performance characteristics of the Triage BNP rapid assay as it relates to clinical studies. Also, the BNP rapid assay is a reliable, diagnostic 15-minute bedside test and can be used as a point-of-care modality in critical care units, clinics, physician offices, and emergency departments. The test can also be readily used by rapid response teams.
Sensitivity or clinical sensitivity refers to the proportion of subjects with the disease who have a positive test and indicates how good a test is at identifying the disease.20 One study using the BNP Triage Immunoassay kit, the BNP cutoff value of 100 pg/mL had a sensitivity of 90%, meaning that approximately 90 heart failure patients will test positive for heart failure and 10 patients will test false negative.9
Specificity or clinical specificity refers to the proportion of subjects without the disease who have a negative test and indicates how good a test is at identifying the nondiseased subjects.21 In the Breathing Not Properly study9 using the BNP Triage Immunoassay kit, the specificity was 76% with a predictive negative value of 90% (cutoff value of 100 pg per mL).
Predictive negative value (PV-) is defined as the probability that a person who does not have the disease will produce a negative result.21 The PV- of the BNP level at a cutoff value of 50 pg/mL was 96%, which means that 96 patients out of 100 will test negative for heart failure that actually do not have the disease (CHF).
Relative risk compares the incidence of disease among exposed with the incidence of disease among nonexposed by means of a ratio.20 A BNP level of 230 pg/mL is correlated with a relative risk of 7.0.9 A relative risk of 7.0 means that the incidence of heart failure is 7 times as high in patients with heart failure as opposed to those without heart failure.
Table 1 illustrates comparison decision statistics using the BNP Triage Immunoassay kit as reported from several studies. Because decision statistics on the research studies were based on using the Triage BNP rapid assay, a description of the performance characteristic on this specific instrument is provided.
 | TABLE 1 Summary of Studies Utilizing the BNP Triage Immunoassay Kit |
PERFORMANCE CHARACTERISTICS OF THE TRIAGE BNP TEST
The Triage BNP test uses a fluorescence immunoassay that measures BNP in whole blood and plasma specimens using trisodium ethylenediaminetetraacetate trihydrate(EDTA) as the anticoagulant.22 There is no time to first result because the BNP immunoassay is not an analyzer and does not run tests in batch modes. Calibration of the test is done by using the provided assayed controls supplied by Biosite. Controls used should result in numbers not less than 5 pg/mL or higher than 5,000 pg/mL.
The Triage BNP Immunoassay kit has a reportable range of 5 to 5,000 pg/mL.22 B-type natriuretic peptide results of less than 100 pg/mL are representative of normal values in patients without CHF. B-type natriuretic peptide results higher than 100 pg/mL is considered abnormal and suggestive of CHF. According to Maisel,4 the mean BNP values among New York Heart Association (NYHA) Class I is 244 pg/mL, NYHA Class II is 389 pg/mL, NYHA Class III is 640 pg/mL and 817 pg/mL among NYHA Class IV. B-type natriuretic peptide results higher than 5,000 pg/mL are considered very high values and exceed the upper limits of the BNP test. Higher BNP concentrations measured in the first 72 hours after an acute coronary syndrome are associated with an increased risk of death, myocardial infarction, and CHF.22 The Triage BNP Immunoassay kit uses a sample type of either whole blood or plasma drawn in plastic tubes. Sample collection and storage for whole blood and plasma is up to 24 hours at room temperature or 2°C to 8°C in a refrigerator. Reagent stability is good until expiration date on the box or up to 14 days at room temperature. The BNP analysis is based on the amount of fluorescence the meter detects within a measurement zone on the device. A greater amount of fluorescence detected by the meter indicates a higher BNP value.22
Plasma specimens anticoagulated with EDTA were spiked with purified BNP to final concentration of 5,000 pg/mL. Each spiked plasma specimen was diluted gravimetrically with unspiked plasma to obtain BNP values throughout the range of the Triage BNP test. Linear regression analysis of the data indicates that the assay is linear throughout the measurable range of the test.22
Hemoglobin up to 10,000 mg/dL, cholesterol up to 1,000 mg/dL, triglycerides up to 1,000 mg/dL, and bilirubin up to 20 mg/dL added to plasma concentrations containing BNP did not interfere with the recovery of BNP. Hematocrit varied between 27% and 51% with no significant effect on the recovery of BNP.22
Analytical sensitivity differs from clinical sensitivity because this refers to the test and not the patient population. Analytical sensitivity refers to the lowest value that the test can read that distinguishes from zero (0).22 The average 95% confidence limit of the analytical sensitivity of the Triage BNP test was less than 5 pg/mL (95% CI: 0.2 to 4.8 pg/L). Thus, the test cannot be exactly zero. Analytical sensitivity or the lowest detectable concentration that is distinguishable from zero for the BNP test was determined by testing a zero calibrator 20 times each using 3 lots of reagents and 5 meters on 5 days.22
Analytical specificity refers to the accurateness on how the test is able to detect the correct molecule, BNP. Precision of the BNP machine, the use of various pharmaceuticals, and the use of blood and plasma for drawing BNP levels are discussed below as it relates to the analytical specificity of the BNP assay.22
The average within-day and total precision of the BNP assay was determined using the analysis of variance model by testing control materials that had BNP added at concentrations near the decision points of the assay and throughout the range of the standard curve. This study was done over 12 days, testing each control 10 times a day. Each device was read on 5 triage meters.22 It is noted that the use of different triage meters does not significantly affect the test precision. Coefficient of variation (CV) is equal to the standard deviation multiplied by 100 divided by the mean.19 This means that the higher the CV the less precise the test. Biosite22 reports that the average total imprecision of a mean BNP level of 71.3 pg/mL with a standard deviation (SD) of 7.0 has a CV of 9.9%; a mean BNP level of 629.9 pg/mL with an SD of 75.5 has a CV of 12.0%; a mean BNP level of 4,087.9 pg/mL with an SD of 500.1 has a CV of 12.2%. It is of note that the Triage BNP is an immunoassay and a point-of-care test.
Fifty-four drugs ranging from the common acetaminophen to angiotensin-converting enzymes inhibitors, diuretics, beta-blockers, statin drugs, antibiotics were evaluated for potential cross-reactivity and interference of the Triage BNP test. Results showed none of the drugs interfered with the recovery of BNP and these drugs did not produce a significant response when tested in a specimen not containing BNP. There was no significant interference with the BNP measurement and no assay cross-reactivity.22 Serial BNP measurement can predict outcomes in patients hospitalized for decompensated heart failure.
A study comparison performed on EDTA whole blood versus plasma showed the correlation data as r2 = 0.9878, y = 0.925x + 13.439. Plasma is indicated by y and whole blood by x.22 This means that there is a slight difference in using plasma and whole blood but the correlation is high enough that it does not make any difference when the test is run by either whole blood or plasma.
IMPLICATIONS OF THE BNP RAPID ASSAY IN NURSING PRACTICE AND EDUCATION
Nurses' knowledge of BNP levels as an additive diagnostic tool, along with other clinical information, is useful in determining and confirming the diagnosis of heart failure. Based on the BNP rapid assay results, patients' physical condition could benefit from providing aggressive treatment or titration of medications. Clinical assessment and the use of BNP as a screening tool can aid in earlier diagnosis and treatment. It can also be used to exclude other disorders that mimic the symptoms of heart failure.
Nurses are the forefront in patient education. When a heart failure patient presents to the admitting department, the nurse takes on an educator role. To improve health compliance, patient education regarding BNP level awareness, pathophysiology of the disease process, signs and symptoms of heart failure, importance of a low-salt diet, monitoring of daily weights, fluid restriction, and action of medications is a must.
Unlike patients diagnosed with diabetes, blood glucose levels are objectively monitored, whereas when a patient with heart failure gains 3 to 5 pounds, they are already ill. Therefore, physical indicators of heart failure are not obvious as compared to patients with diabetes.23 This is more reason that knowledge of BNP rapid assay as an indicator of the severity of CHF needs to be disseminated.
Nurses' knowledge of BNP can indirectly impact the economic burden of heart failure. Utilizing the BNP rapid assay as a predictor of heart failure could possibly mean a decrease in hospital readmission rates, a reduction of economic cost or expenditure, billions of dollars saved, and better health risk ratio rating for the healthy population. The advent of the BNP rapid assay in the diagnosis of heart failure has become an important part in the armamentarium of diagnostic strategies that nurses can employ in assisting heart failure patients in the management of their symptoms, avoiding CHF exacerbations and delay or potentially preventing hospital readmissions.
CONCLUSION
Congestive heart failure is becoming one of the most chronic, debilitating, and progressive disease in the United States. Despite a high level of public awareness of this disease, the majority of the population are unaware of their risks of having heart failure. Nurses can help empower heart failure patients by providing the knowledge regarding the use of BNP rapid assay for an early and timely detection and identification of heart failure symptoms. This could further lead to better assessment of their medical condition and circumvent the development of this clinical syndrome.
References
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