Diagnosis of stage I endometriosis: comparing visual inspection to histologic biopsy specimen.

STUDY OBJECTIVE: To evaluate positive predictive value (PPV) of visual diagnosis at laparoscopy compared with biopsy findings according to severity of endometriosis. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Academic referral center. PATIENTS: Women who underwent laparoscopic biopsies for suspected endometriosis. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSION: 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.

How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study.

BACKGROUND: B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis. METHODS: The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results. RESULTS: Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively (P < .05 for all comparisons except 35 vs 25). B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients. CONCLUSIONS: Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP > or = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP > or = 170 pg/mL) could be used to increase specificity.

Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the Breathing Not Properly Multinational Study.

PURPOSE: B-type natriuretic peptide is known to correlate with hemodynamic state, presence and severity of congestive heart failure, and prognosis. Although low-range B-type natriuretic peptide less than 100 pg/mL has a high negative predictive value (90%), and high-range B-type natriuretic peptide greater than 500 pg/mL has a high positive predictive value (87%), there remains some ambiguity in the interpretation of results in the medium range (100-500 pg/mL). We hypothesized that taking into account the history of congestive heart failure along with other clinical variables would be helpful in this range of B-type natriuretic peptide levels. METHOD: The Breathing Not Properly Multicenter Study was an international, 7-center, prospective study including 1475 patients with a mean age of 63 years (57% were male, and 54% were female); 35% of patients with a history of congestive heart failure were enrolled, and a final diagnosis of congestive heart failure was made in 46%. The index criteria was defined as positive if any 2 index findings (ie, history of coronary artery disease, lower extremity edema, pulmonary edema, cephalization of the pulmonary arteries, and cardiomegaly) were present. RESULTS: The interval likelihood ratios (LR) for low, medium, and high B-type natriuretic peptide ranges are 0.13, 1.85, and 8.1, respectively. For medium B-type natriuretic peptide levels a positive history of congestive heart failure makes the diagnosis of congestive heart failure more probable with a cumulative LR of 4.3. Also in this range a positive index criterion was strongly indicative of congestive heart failure even in the absence of a history of congestive heart failure (LR 3.3). Where there are both a positive history of congestive heart failure and a positive index criteria for the medium B-type natriuretic peptide group, the cumulative LR (10.2) is similar to that of a high B-type natriuretic peptide level (8.1). CONCLUSION: Even in the medium range (100-500 pg/mL), when using the history of congestive heart failure and index criteria, B-type natriuretic peptide can be a powerful diagnostic tool in the hands of clinicians in the emergency department.

Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus.

OBJECTIVES: We hypothesized that B-type natriuretic peptide (BNP) levels can predict cardiac mortality in diabetic patients. BACKGROUND: Detection of cardiovascular disease in diabetics can be difficult until overt events occur. METHODS: A total of 482 diabetics (majority male with type 2 diabetes) at the Veterans Affairs Medical Center San Diego were divided into two groups: 1) referred patients for echocardiogram on the basis of clinical suspicion of cardiac dysfunction (referred [R], n = 180); 2) patients randomly selected from the diabetic clinic without any suspicion of cardiac dysfunction (not referred [N-R], n = 302). We examined cardiac events and all-cause mortality in relation to initial BNP levels during the follow-up. RESULTS: A total of 71 (14.7%) patients died during this period: 52 of 180 (29%) in the R group (30 of 52 [58%] cardiac, 10 of 52 [19%] non-cardiac, 2 of 52 [4%] renal, 10 of 52 [19%] unknown cause) and 19 of 302 (6%) in N-R group (6 of 19 [32%] cardiac). The median BNP level in the R and N-R groups who died of cardiac, non-cardiac, and unknown cause was 537 and 87, 80 and 53, and 343 and 38 pg/ml, respectively. The receiver-operating characteristic (ROC) values for mortality in two groups in relation to BNP revealed the area under the curve to be 0.720 and 0.691, respectively (p < 0.01 in both). Among commonly used prognostic indicators in diabetics, only the ROC for triglycerides was significant. The most accurate cut-point in both the N-R group (87%) and R group (61%) was 120 pg/ml of BNP. Cox regression analysis showed BNP to be the most significant predictor of all-cause mortality in the R group. There was a marked decrease in survival in the patient group with BNP >120 pg/ml. CONCLUSIONS: B-type natriuretic peptide appears to be a reliable predictor of future cardiac and all-cause mortality in diabetic patients.

A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction.

BACKGROUND: Although echocardiography is the gold standard test for suspected left ventricular dysfunction, its cost and availability limits its use as a routine screening tool. The high negative predictive value of B-natriuretic peptide (BNP) in dyspneic patients suggests its possible utility in screening patients prior to echocardiography. Determining an appropriate BNP level below which the need for echocardiography is precluded would be valuable. We hypothesized that a fixed plasma BNP level of 20 pg/mL and simple clinical parameters are an effective pre-echocardiographic screening tool for left ventricular dysfunction. METHODS: Two hundred and two patients at a Veterans Administration facility with symptoms suggestive of heart disease (male to female ratio 193:9, mean age 65 years) were screened prior to echocardiography. Patients with known cardiac dysfunction were excluded. RESULTS: BNP levels of > or =20 pg/mL were 79% sensitive and 44% specific in screening for any abnormality of ventricular function. The negative predictive value was 69%. When broken down into categories of dysfunction, the cutoff point of 20 pg/mL had a better negative predictive value for those with systolic dysfunction (96%) or systolic plus diastolic dysfunction (100%) if patients with diastolic dysfunction were excluded. The majority of patients with falsely low BNP levels (<20 pg/mL with positive echocardiographic findings) had mild diastolic dysfunction, with 3 patients exhibiting mild systolic dysfunction. CONCLUSIONS: BNP may be a useful screening tool for left ventricular dysfunction in patients with history suggestive of heart disease and be used to assist in forming a pretest probability, which in turn could greatly assist in appropriateness of patient referral and in optimization of drug therapy.

Combination of B-type natriuretic peptide levels and non-invasive hemodynamic parameters in diagnosing congestive heart failure in the emergency department.

This study aimed to assess whether the combination of a B-type natriuretic peptide (BNP) level with various noninvasive hemodynamic parameters can help physicians more quickly and accurately diagnose congestive heart failure and determine the type of left ventricular dysfunction present in patients presenting to the emergency department with dyspnea. Subjects were 98 men (aged 64.57+/-1.23 years) that presented to the VA San Diego Healthcare System. Hemodynamic parameters were measured using impedance cardiography, and BNP levels were quantified using a rapid immunoassay. All patients with a BNP <100 pg/mL (n=37) had no evidence of congestive heart failure 97% of the time. In those with a BNP >100 pg/mL (601+/-55 pg/mL; n=61), a cardiac index of 2.6 L/min/m2 is 65% sensitive and 88% specific in determining systolic dysfunction. In patients with a BNP >100 pg/mL, a multivariate model consisting of noninvasive hemodynamic measurements was able to predict cardiac deaths, readmissions, and emergency department visits within 90 days with 83% accuracy. The authors conclude that, in patients presenting to an emergency department with dyspnea, the addition of impedance cardiography measurements to BNP level measurements will more effectively diagnose congestive heart failure and determine both the type of heart dysfunction and the severity of illness.

Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study.

BACKGROUND: B-type natriuretic peptide (BNP) is secreted from the cardiac ventricles in response to increased wall tension. METHODS: The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. The gold standard for congestive heart failure (CHF) was adjudicated by two independent cardiologists, blinded to BNP results, who reviewed all clinical data and standardized scores. The current study explores the effect of these variables on BNP decision statistics as well as the impact that changing cutoffs might have on the cost-effectiveness of diagnostic decisions that use BNP information. RESULTS: Significant differences in CHF rates were found on the basis of age (P <.001) and racial group (P =.020) but not sex (P =.424). BNP levels increased with increasing age (P <.001). To evaluate potential differences in the diagnostic utility of BNP levels as a function of demographic variables, separate receiver operating characteristic curves were performed. BNP was a stronger predictor in younger subjects than in older subjects and slightly weaker for female patients than for male patients (area under the curve = 0.918 and 0.870, respectively). An even smaller difference was noted between the white and black racial groups (area under the curve = 0.888 and 0.903, respectively). The differences in specificity as a function of age are larger than other differences in specificity or sensitivity. When logistic regression was used in a multivariate approach to combine the demographic variables with BNP information in the prediction of CHF, only BNP contributed significantly to the prediction of acute CHF. When the model was expanded to include terms for the interaction of each of the demographic variables with log(10) BNP, a significant interaction was found for sex. Since the relative consequences of false-positives and false-negatives are unlikely to be equivalent, the BNP cut-points that would be selected based on the current data as a function of relative costs are presented. Sharply rising consequences are seen for BNP cut-points >100 pg/mL. CONCLUSIONS: If one assumes that failing to treat cases of CHF is worse than treating negative cases, then relatively low BNP cut-points (eg, not >100 pg/mL) should be used in patients presenting to the Emergency Department with a chief complaint of dyspnea, regardless of age, sex, or ethnicity.

Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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 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.

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 echoes had similar BNP levels (83 +/- 16 pg/ml) to the 215 patients with no-CIE without echoes (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 +/- 60 pg/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.

Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study.

OBJECTIVES: This study examines B-type natriuretic peptide (BNP) levels in patients with systolic versus non-systolic dysfunction presenting with shortness of breath. BACKGROUND: Preserved systolic function is increasingly common in patients presenting with symptoms of congestive heart failure (CHF) but is still difficult to diagnose. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study.

BACKGROUND: Both B-type natriuretic peptide (BNP) and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, relationships between BNP, renal function, and heart failure as an emergency diagnosis are unknown. METHODS: The Breathing Not Properly Multinational Study was a prospectively designed diagnostic test evaluation study conducted in seven centers. Of 1,586 participants who presented with acute dyspnea, 1,452 patients (91.6%) had both BNP level and baseline estimated glomerular filtration rate (eGFR) available. Patients with an eGFR less than 15 mL/min/1.73 m2 and those on dialysis therapy were excluded. The final diagnosis was adjudicated by two independent cardiologists who were blinded to BNP results. RESULTS: The final diagnosis was CHF in 715 patients (49.2%). Raw and log-log transformed correlations between BNP and eGFR values were r = -0.19 and r = -0.17 for those with CHF and r = -0.20 and r = -0.31 for those without CHF (both P < 0.0001 for r not equal 0). Mean BNP levels were 561.6 pg/mL (162.3 fmol/mL), 647.5 pg/mL (187.1 fmol/mL), 745.6 pg/mL (215.5 fmol/mL), and 850.7 pg/mL (245.8 fmol/mL) for those with CHF and 85.4 pg/mL (24.7 fmol/mL), 131.7 pg/mL (38.1 fmol/mL), 297.2 pg/mL (85.9 fmol/mL), and 285.0 pg/mL (82.3 fmol/mL) for those without CHF in eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. The area under the receiver operating characteristic curve and optimum cut points for BNP were 0.91 and 70.7 pg/mL (20.4 fmol/mL), 0.90 and 104.3 pg/mL (30.1 fmol/mL), 0.81 and 201.2 pg/mL (58.1 fmol/mL), and 0.86 and 225.0 pg/mL (65.0 fmol/mL) for the eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. CONCLUSION: Renal function correlates weakly with BNP and influences the optimal cut point for BNP, particularly in those with an eGFR less than 60 mL/min/1.73 m2.

Uncovering heart failure in patients with a history of pulmonary disease: rationale for the early use of B-type natriuretic peptide in the emergency department.

UNLABELLED: Plasma B-type natriuretic peptide (BNP) can reliably identify acute congestive heart failure (CHF) in patients presenting to the emergency department (ED) with acute dyspnea. Heart failure, asthma, and chronic obstructive pulmonary disease (COPD) are syndromes where dyspnea and wheezing are overlapping signs, and hence, these syndromes are often difficult to differentiate. OBJECTIVE: To determine whether BNP can distinguish new-onset heart failure in patients with COPD or asthma presenting with dyspnea to the ED. METHODS: The BNP Multinational Study was a seven-center prospective study of 1,586 adult patients presenting to the ED with acute dyspnea who had blinded BNP levels measured on arrival with a rapid, point-of-care device. This study evaluated the 417 patients with no previous history of heart failure and a history of asthma or COPD as a subgroup from the 1,586 adult patients in the BNP Multinational Study. The reference standard for CHF was adjudicated by two independent cardiologists, also blinded to BNP results, who reviewed all clinical data and standardized CHF scores. RESULTS: A total of 417 subjects (mean age 62.2 years, 64.4% male) had a history of asthma or COPD without a history of CHF. Of these, 87/417 (20.9%, 95% CI = 17.1% to 25.1%) were found to have CHF as the final adjudicated diagnosis. The emergency physicians identified a minority, 32/87 (36.8%), of these patients with CHF. The mean BNP values (+/- SD) were 587.0 +/- 426.4 and 108.8 +/- 221.3 pg/mL for those with and without CHF (p < 0.0001). At a cutpoint of 100 pg/mL, BNP had the following decision statistics: sensitivity 93.1%, specificity 77.3%, positive predictive value 51.9%, negative predictive value 97.7%, accuracy 80.6%, positive likelihood ratio 4.10, and negative likelihood ratio 0.09. If BNP would have been added to clinical judgment (high > or = 80% probability of CHF), at a cutpoint of 100 pg/mL, 83/87 (95.4%) of the CHF subjects would have been correctly diagnosed. Multivariate analysis found BNP to be the most important predictor of CHF (OR = 12.1, 95% CI = 5.4 to 27.0, p < 0.0001). In the 87 subjects found to have CHF, 39.0%, 22.2%, and 54.8% were taking angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), and diuretics on a chronic basis, respectively. CONCLUSIONS: The yield of adding routine BNP testing in patients with a history of asthma or COPD in picking up newly diagnosed CHF is approximately 20%. This group of patients presents a substantial therapeutic opportunity for the initiation and chronic administration of ACEI and BB therapy, as well as other CHF management strategies.

B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study.

BACKGROUND: 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). METHODS AND RESULTS: 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). CONCLUSIONS: The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.

Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension. METHODS: We conducted a prospective study of 1586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay. The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists, who were blinded to the results of the B-type natriuretic peptide assay. RESULTS: The final diagnosis was dyspnea due to congestive heart failure in 744 patients (47 percent), dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction (5 percent), and no finding of congestive heart failure in 770 patients (49 percent). B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea. The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4 percent. The negative predictive value of B-type natriuretic peptide at levels of less than 50 pg per milliliter was 96 percent. In multiple logistic-regression analysis, measurements of B-type natriuretic peptide added significant independent predictive power to other clinical variables in models predicting which patients had congestive heart failure. CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.

Stability of B-type natriuretic peptide levels during exercise in patients with congestive heart failure: implications for outpatient monitoring with B-type natriuretic peptide.

BACKGROUND: B-natriuretic peptide (BNP), a neurohormone secreted from the cardiac ventricles, reflects left ventricular pressure and correlates to disease severity and prognosis. The fact that BNP levels can now be measured by a rapid assay suggests its potential usefulness in the outpatient clinic. However, if patient activity were to markedly alter BNP levels, its use would be less attractive for monitoring patients in the outpatient clinical setting. METHODS: A total of 30 patients (10 normal, 10 New York Heart Association [NYHA] class I-II, 10 NYHA class III-IV) exercised with an upright bicycle protocol. Exercise was carried out to 75% of maximum heart rate, and venous blood was sampled before, immediately after, and 1 hour after completion of exercise. Plasma levels of BNP, epinephrine, and norepinephrine were measured. RESULTS: BNP levels at baseline were 29 +/- 11 pg/mL for normal subjects, 126 +/- 26 pg/mL for NYHA I-II subjects, and 1712 +/- 356 pg/mL for NYHA III-IV subjects. The change in BNP levels with exercise was significantly lower than the change in epinephrine and norepinephrine (P <.001). In normal subjects, BNP increased from 29 pg/mL to 44 pg/mL with peak exercise, still within the range of normal (<100 pg/mL). This is compared with larger increases of norepinephrine (716 pg/mL to 1278 pg/mL) and epinephrine (52 pg/mL to 86 pg/mL) with exercise in normal subjects. There were also only small increases in BNP with exercise in patients with congestive heart failure (NYHA I-II, 30%; NYHA III-IV, 18%). For the same groups, epinephrine levels increased by 218% and 312%, respectively, and norepinephrine levels increased by 232% and 163%, respectively. One hour after completion of exercise, there were only minimal changes in BNP levels from baseline state in normal subjects (+0.9%) and patients with NYHA I-II (3.8%). In patients with NYHA III-IV, there was a 15% increase from baseline 1 hour after exercise. CONCLUSIONS: BNP levels show only minor changes with vigorous exercise, making it unlikely that a normal patient would be classified as having congestive heart failure based on a BNP level obtained after activity. Prior activity should not influence BNP levels in patients with congestive heart failure. Therefore, when a patient presents to clinic with a marked change in their BNP level, it may reflect a real change in their condition.

Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

B-type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea.

STUDY OBJECTIVE: B-Type natriuretic peptide (BNP) is a neurohormone secreted from the cardiac ventricles in response to volume expansion and pressure overload. We have recently demonstrated that BNP can differentiate congestive heart failure (CHF) from other causes of dyspnea in patients presenting to the emergency department. In this study, we assess whether BNP levels drawn in patients presenting with dyspnea to the ED were a predictor of future cardiac events. METHODS: In 325 patients presenting with dyspnea to the ED, BNP levels were determined. Patients were then followed up for 6 months to determine the following end points: death (cardiac and noncardiac), hospital admissions (cardiac), and repeat ED visits for CHF. Receiver operating characteristic (ROC) curves, relative risks (RRs), and Kaplan-Meier plots were used to assess the ability of BNP levels to predict future cardiac events. RESULTS: The area under the ROC curve using BNP to detect a CHF end point-a CHF death, hospital admission, or repeat ED visit-was 0.870 (95% confidence interval [CI] 0.826 to 0.915). A BNP value of 480 pg/mL had a sensitivity of 68%, specificity of 88%, and an accuracy of 85% for predicting a subsequent CHF end point. The area under the ROC curve using BNP to detect death from CHF was 0.881 (95% CI 0.807 to 0.954) and for any cardiac death was 0.877 (95% CI 0.822 to 0.933). BNP was not associated with death from noncardiac causes. Using Kaplan-Meier plots for all CHF events, rising BNP levels were associated with a progressively worse prognosis. Patients with BNP levels more than 480 pg/mL had a 51% 6-month cumulative probability of a CHF event. Alternatively, patients with BNP levels less than 230 pg/mL had an excellent prognosis with only 2.5% incidence of CHF end points. The RR of 6-month CHF death in patients with BNP levels more than 230 pg/mL was 24.1. The RR of 6-month noncardiac death with BNP levels more than 230 pg/mL was 1.1. BNP levels were also predictive of CHF events in subsets of patients with positive CHF histories and ED diagnoses. CONCLUSION: In this study population, BNP levels measured in patients presenting with dyspnea to the ED are highly predictive of cardiac events over the next 6 months.

Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea.

OBJECTIVES: 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. BACKGROUND: Differentiating congestive heart failure (CHF) from pulmonary causes of dyspnea is very important for patients presenting to the emergency department (ED) with acute dyspnea. METHODS: 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. RESULTS: 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). CONCLUSIONS: Rapid testing of BNP in the ED should help differentiate pulmonary from cardiac etiologies of dyspnea.