B-type natriuretic peptide is released from the ventricles of the heart in response to hemodynamic stress, and blood levels of B-type natriuretic peptide may be useful in the diagnosis of heart ...failure. In this study, a rapid, bedside immunoassay for B-type natriuretic peptide was used to make or exclude the diagnosis of heart failure in patients with acute dyspnea from various causes. The assay was found to have good sensitivity and excellent specificity in the diagnosis of heart failure.
Rapid measurement of this peptide is useful in establishing or excluding the diagnosis of congestive heart failure.
Currently, there are 5 million Americans with congestive heart failure, with nearly 500,000 new cases every year.
1
The prevalence of symptomatic heart failure in the general European population ranges from 0.4 percent to 2.0 percent.
2
Because of the high total direct costs of care for heart failure, estimated at $10 billion to $38 billion per year, the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services) targeted heart failure as the disease most worthy of cost-effective management.
3
To provide cost-effective treatment for patients with congestive heart failure, rapid and accurate differentiation of congestive heart failure from other . . .
OBJECTIVES
The goal of this study was to evaluate the utility of a rapid “bedside” technique for measurement of B-type natriuretic peptide (BNP) in the diagnosis of congestive heart failure (CHF) in ...an urgent-care setting.
BACKGROUND
B-type natriuretic peptide is a protein secreted from the cardiac ventricles in response to pressure overload. One potential application of measurements of BNP in blood is distinguishing dyspnea due to CHF from other causes.
METHODS
B-type natriuretic peptide concentrations were measured in a convenience sample of 250 predominantly male (94%) patients presenting to urgent-care and emergency departments of an academic Veteran’s Affairs hospital with dyspnea. Results were withheld from clinicians. Two cardiologists retrospectively reviewed clinical data (blinded to BNP measurements) and reached a consensus opinion on the cause of the patient’s symptoms. This gold standard was used to evaluate the diagnostic performance of the BNP test.
RESULTS
The mean BNP concentration in the blood of patients with CHF (n = 97) was higher than it was in patients without (1,076 ± 138 pg/ml vs. 38 ± 4 pg/ml, p < 0.001). At a blood concentration of 80 pg/ml, BNP was an accurate predictor of the presence of CHF (95%); measurements less than this had a high negative predictive value (98%). The overall C-statistic was 0.97. In multivariate analysis, BNP measurements added significant, independent explanatory power to other clinical variables in models predicting which patients had CHF. The availability of BNP measurements could have potentially corrected 29 of the 30 diagnoses missed by urgent-care physicians.
CONCLUSIONS
B-type natriuretic peptide blood concentration measurement appears to be a sensitive and specific test to diagnose CHF in urgent-care settings.
B-type natriuretic peptide (BNP) is synthesized in cardiac ventricles in response to volume expansion. This study evaluated BNP levels to determine trends during pregnancy, and to assess BNP as a ...diagnostic tool in preeclampsia.
We studied 163 BNP levels in 118 pregnant women, ranging from first trimester to term. An additional 34 patients with preeclampsia were studied and compared to 25 normal control patients at term. Plasma BNP values were determined using a standard assay.
The median BNP levels during the 1st, 2nd, 3rd trimester, and at term were equivalent (18.4, 17.9, 15.5, and 17.8 pg/mL, respectively,
P
=
.796). The median BNP levels in normal patients, mild preeclamptics, and severe preeclamptics were 17.8, 21.1, and 101 pg/mL, respectively, with the severe group being significantly higher than the mild group (
P
=
.003) and any phase of normal pregnancy (
P < .001 in each case). A BNP cut-off of <40.6 pg/mL had a negative predictive value of 92% in excluding preeclampsia.
In normal pregnancies, median BNP values are <20 pg/mL, and stable throughout gestation. In severe preeclampsia BNP levels are elevated. This may reflect ventricular stress and/or subclinical cardiac dysfunction associated with preeclampsia.
The purpose of the present study was to assess whether preoperative and postoperative B-type natriuretic peptide (BNP) levels could be used as predictors of postoperative complications and outcomes ...in patients after open-heart surgery.
A variety of multifactor indexes have been proposed for preoperative risk assessment of patients undergoing cardiac surgery, but they have shown limited ability and utility in accurately predicting postoperative complications, hospital stay, and mortality.
Subjects consisted of 98 male patients (63 ± 9.1 years) undergoing open-heart surgery at the San Diego Veterans Administration Health System during a 19-month period. B-type natriuretic peptide levels were analyzed, and postoperative data recorded.
There was a higher preoperative BNP level in patients requiring the use of intra-aortic balloon pumps (IABPs) (mean BNP = 387 ± 112 pg/ml vs. 181 ± 25 pg/ml), in patients who died within one year (357 ± 93 pg/ml vs. 184 ± 26 pg/ml), and in patients with postoperative hospital stays of 10 days or more (307 ± 68 pg/ml vs. 179 ± 27 pg/ml). Receiver operating characteristic curves demonstrated preoperative BNP levels as predictors of postoperative IABP use, hospital stay ≤10 days, and mortality <1 year with areas under the curve of 0.70, 0.64, and 0.70, respectively. A BNP cut-off value above 385 pg/ml demonstrated high specificity (=90% in each) and accuracy (=86%, 79%, 85%, respectively) for predicting each of these end points.
Preoperative BNP levels >385 pg/ml predict the postoperative complications and one-year mortality after heart surgery. Postoperatively, elevated peak BNP levels and elevated change to peak BNP levels were associated with prolonged hospital stay and mortality within one year.
Utility of B-Type Natriuretic Peptide (BNP) as a Screen for Left Ventricular Dysfunction in Patients With Diabetes
Victoria Epshteyn , BA 1 ,
Katherine Morrison , BA 1 ,
Padma Krishnaswamy , MD 1 ,
...Radmila Kazanegra , MD 2 ,
Paul Clopton , MS 1 ,
Sunder Mudaliar , MD 1 3 ,
Steven Edelman , MD 1 3 ,
Robert Henry , MD 1 3 and
Alan Maisel , MD, FACC 1 3
1 Department of Medicine, Veteran’s Affairs Medical Center, San Diego, California
2 Biosite Diagnostics, San Diego, California
3 University of California, San Diego, California
Address correspondence and reprint requests to Robert R. Henry, MD, VA San Diego Healthcare System (Mail Code 111G), 3350
La Jolla Village Dr., San Diego, CA 92161. E-mail: rrhenry{at}vapop.ucsd.edu .
Abstract
OBJECTIVE —Routine screening of diabetic patients with echocardiography is not feasible due to its limited availability and high cost.
B-type natriuretic peptide (BNP) is secreted from the left ventricle in response to pressure overload and is elevated in both
systolic and diastolic dysfunction.
RESEARCH DESIGN AND METHODS —BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication
for echocardiography (CIE) ( n = 172) and those without clinical indication for echocardiography (no-CIE) ( n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP.
RESULTS —The 91 patients with no-CIE with echos had similar BNP levels (83 ± 16 pg/ml) to the 215 patients with no-CIE without echos
(63 ± 10, P = 0.10). Patients with CIE and subsequent abnormal left ventricular function ( n = 112) had a mean BNP concentration of 435 ± 41 pg/ml, compared with those with no-CIE, but had abnormal left ventricular
function on echo ( n = 32) (161 ± 40 pg/ml). Twenty-one of 32 patients with no-CIE but with abnormal left ventricular function had diastolic dysfunction
(BNP 190 ± 60pg/ml). A receiver-operating characteristic (ROC) curve revealed that the area under the curve was 0.91 for CIE
patients and 0.81 for no-CIE patients ( P < 0.001). For those with no congestive heart failure (CHF) symptoms, BNP levels showed a high negative predictive value (91%
for BNP values <39 pg/ml), while in those patients who had a CIE, BNP levels showed a high positive predictive value for the
detection of left ventricular dysfunction (96% with BNP levels >90 pg/ml).
CONCLUSIONS —BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction.
AUC, area under the curve
BNP, B-type natriuretic peptide
CHF, congestive heart failure
CIE, clinical indication for echocardiography
IVRT, isovolumetric relaxation time
no-CIE, no clinical indication for echocardiography
NYHA, New York Heart Association
ROC, receiver-operating characteristic
Footnotes
A.M. is a paid consultant for and has received research support and honoraria from Biosite Diagnostics.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
Accepted April 10, 2003.
Received December 31, 2002.
DIABETES CARE
To evaluate positive predictive value (PPV) of visual diagnosis at laparoscopy compared with biopsy findings according to severity of endometriosis.
Retrospective study (Canadian Task Force ...classification II-2).
Academic referral center.
Women who underwent laparoscopic biopsies for suspected endometriosis.
A total of 238 biopsy specimens (73 endometriomas and 165 peritoneal implants) were taken from 104 patients undergoing laparoscopy for evaluation of chronic pelvic pain thought to be caused by endometriosis.
Accuracy of laparoscopic findings compared with histology-proved endometriosis by severity of disease and location of endometriotic lesions. Overall PPV per patient was 86.5%, which was 75.8% for stage I disease compared with 89.7%, 100%, and 90.6%, respectively, for disease stages II to IV (p = .037). The PPV per biopsy specimen of stages I to IV endometriosis was 66.1%, 78.0%, 92.0%, and 81.1%, respectively (.049). When endometriomas and peritoneal biopsy specimens were analyzed separately, no difference in PPV existed (79% vs 77%; p = .67).
High overall PPV existed in our study, especially in patients with advanced disease. The PPV per patient was higher than the PPV per biopsy specimen indicating that ability to diagnose endometriosis may be improved by performing multiple biopsies. This is particularly true in stage I where failure to confirm may be greatest.
Since B-type natriuretic peptide (BNP) is secreted by the left ventricle (LV) in response to volume elevated LV pressure, we sought to assess whether a rapid assay for BNP levels could differentiate ...cardiac from pulmonary causes of dyspnea.
Differentiating congestive heart failure (CHF) from pulmonary causes of dyspnea is very important for patients presenting to the emergency department (ED) with acute dyspnea.
B-natriuretic peptide levels were obtained in 321 patients presenting to the ED with acute dyspnea. Physicians were blinded to BNP levels and asked to give their probability of the patient having CHF and their final diagnosis. Two independent cardiologists were blinded to BNP levels and asked to review the data and evaluate which patients presented with heart failure. Patients with right heart failure from cor pulmonale were classified as having CHF.
Patients with CHF (n = 134) had BNP levels of 758.5 ± 798 pg/ml, significantly higher than the group of patients with a final diagnosis of pulmonary disease (n = 85) whose BNP was 61 ± 10 pg/ml. The area under the receiver operating curve, which plots sensitivity versus specificity for BNP levels in separating cardiac from pulmonary disease, was 0.96 (p < 0.001). A breakdown of patients with pulmonary disease revealed: chronic obstructive pulmonary disease (COPD): 54 ± 71 pg/ml (n = 42); asthma: 27 ± 40 pg/ml (n = 11); acute bronchitis: 44 ± 112 pg/ml (n = 14); pneumonia: 55 ± 76 pg/ml (n = 8); tuberculosis: 93 ± 54 pg/ml (n = 2); lung cancer: 120 ± 120 pg/ml (n = 4); and acute pulmonary embolism: 207 ± 272 pg/ml (n = 3). In patients with a history of lung disease but whose current complaint of dyspnea was seen as due to CHF, BNP levels were 731 ± 764 pg/ml (n = 54). The group with a history of CHF but with a current COPD diagnosis had a BNP of 47 ± 23 pg/ml (n = 11).
Rapid testing of BNP in the ED should help differentiate pulmonary from cardiac etiologies of dyspnea.
Although Doppler echocardiography has been used to identify abnormal left ventricular (LV) diastolic filling dynamics, inherent limitations suggest the need for additional measures of diastolic ...dysfunction. Because data suggest that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we hypothesized that BNP levels could predict diastolic abnormalities in patients with normal systolic function.
We studied 294 patients referred for echocardiography to evaluate ventricular function. Patients with abnormal systolic function were excluded. Cardiologists making the assessment of LV function were blinded to BNP levels. Patients were classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP concentration of 286 +/- 31 pg/mL; those in the normal LV group (n=175) had a mean BNP concentration of 33 +/- 3 pg/mL. Patients with restrictive like filling patterns on echocardiography had the highest BNP levels (408 +/- 66 pg/mL), and patients with symptoms had higher BNP levels in all diastolic filling patterns. The area under the receiver-operating characteristic curve for BNP to detect any diastolic dysfunction was 0.92 (95% CI, 0.87 to 0.95; P<0.001). A BNP value of 62 pg/mL had a sensitivity of 85%, a specificity of 83%, and an accuracy of 84% for detecting diastolic dysfunction.
A rapid assay for BNP can reliably detect the presence of diastolic abnormalities on echocardiography. In patients with normal systolic function, elevated BNP levels and diastolic filling abnormalities might help to reinforce the diagnosis diastolic dysfunction.
We sought to determine the degree to which B-type natriuretic peptide (BNP) adds to clinical judgment in the diagnosis of congestive heart failure (CHF).
The Breathing Not Properly Multinational ...Study was a prospective diagnostic test evaluation study conducted in 7 centers. Of 1586 participants who presented with acute dyspnea, 1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department. Participants underwent routine care and had BNP measured in a blinded fashion. The reference standard for CHF was adjudicated by 2 independent cardiologists, also blinded to BNP results. The final diagnosis was CHF in 722 (47%) participants. At an 80% cutoff level of certainty of CHF, clinical judgment had a sensitivity of 49% and specificity of 96%. At 100 pg/mL, BNP had a sensitivity of 90% and specificity of 73%. In determining the correct diagnosis (CHF versus no CHF), adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. In those participants with an intermediate (21% to 79%) probability of CHF, BNP at a cutoff of 100 pg/mL correctly classified 74% of the cases. The areas under the receiver operating characteristic curve were 0.86 (95% CI 0.84 to 0.88), 0.90 (95% CI 0.88 to 0.91), and 0.93 (95% CI 0.92 to 0.94) for clinical judgment, for BNP at a cutoff of 100 pg/mL, and for the 2 in combination, respectively (P<0.0001 for all pairwise comparisons).
The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.
This study examines B-type natriuretic peptide (BNP) levels in patients with systolic versus non-systolic dysfunction presenting with shortness of breath.
Preserved systolic function is increasingly ...common in patients presenting with symptoms of congestive heart failure (CHF) but is still difficult to diagnose.
The Breathing Not Properly Multinational Study was a seven-center, prospective study of 1,586 patients who presented with acute dyspnea and had BNP measured upon arrival. A subset of 452 patients with a final adjudicated diagnosis of CHF who underwent echocardiography within 30 days of their visit to the emergency department (ED) were evaluated. An ejection fraction of greater than 45% was defined as non-systolic CHF.
Of the 452 patients with a final diagnosis of CHF, 165 (36.5%) had preserved left ventricular function on echocardiography, whereas 287 (63.5%) had systolic dysfunction. Patients with non-systolic heart failure (NS-CHF) had significantly lower BNP levels than those with systolic heart failure (S-CHF) (413 pg/ml vs. 821 pg/ml, p < 0.001). As the severity of heart failure worsened by New York Heart Association class, the percentage of S-CHF increased, whereas the percentage of NS-CHF decreased. When patients with NS-CHF were compared with patients without CHF (n = 770), a BNP value of 100 pg/ml had a sensitivity of 86%, a negative predictive value of 96%, and an accuracy of 75% for detecting abnormal diastolic dysfunction. Using Logistic regression to differentiate S-CHF from NS-CHF, BNP entered first as the strongest predictor followed by oxygen saturation, history of myocardial infarction, and heart rate.
We conclude that NS-CHF is common in the setting of the ED and that differentiating NS-CHF from S-CHF is difficult in this setting using traditional parameters. Whereas BNP add modest discriminatory value in differentiating NS-CHF from S-CHF, its major role is still the separation of patients with CHF from those without CHF.
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