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Study objective We evaluate associations between pairs of discordant cardiac biomarkers (positive MB band of creatine kinase [CKMB] with negative creatine kinase, positive CKMB with negative cardiac troponin, and positive troponin with negative CKMB) and the presence of acute coronary syndromes in emergency department (ED) chest pain patients. Methods This was a secondary analysis of a prospective registry. Data were obtained from the multicenter Internet Tracking Registry of Acute Coronary Syndromes, which included 17,713 ED visits for possible acute coronary syndrome between June 1999 and August 2001. First visits and first ED cardiac biomarker results from the 9 sites, 8 in the United States and 1 in Singapore, were included. Subjects were excluded for incomplete information or an initial ECG consistent with ST-segment elevation myocardial infarction. Acute coronary syndrome was defined by diagnosis-related group code indicating myocardial infarction, positive invasive or noninvasive diagnostic testing, revascularization, or death during hospitalization or within 30 days. Results Of 8,769 eligible patients, 1,614 (18.4%) had acute coronary syndrome. The CKMB and cardiac troponin results were discordant in 7% of patients (CKMB+/cardiac troponin–, 4.9%, CKMB–/cardiac troponin+ 2.1%), whereas increased CKMB with normal creatine kinase levels occurred in 239 (3.1%) patients. The unadjusted odds ratios with 95% confidence intervals for acute coronary syndrome in patients with and without discordant markers were: CKMB+/CK− 5.7 (4.4-7.4), CKMB+/CK+ 4.4 (3.6-5.2), CKMB−/cTn+ 4.8 (3.4-6.8), CKMB+/cTn− 2.2 (1.7-2.8), CKMB+/cTn+ 26.6 (18.0-39.3). For the group with cardiac troponin, the reference category was negative troponin and negative CKMB; for the group with creatine kinase, the reference category was negative CKMB but either a positive or negative creatine kinase. Conclusion Among the spectrum of ED patients with chest pain, an increased CKMB level with a normal creatine kinase level identifies patients at increased risk for acute coronary syndrome. Similarly, an increased troponin level regardless of CKMB level and an increased CKMB level regardless of troponin level identify patients at higher risk for acute coronary syndrome than those with uniformly normal cardiac biomarker levels. Our data suggest that discordant cardiac biomarkers may identify patients at increased risk for acute coronary syndrome.

Background Emergency department (ED) patients with undifferentiated dyspnea are a diagnostic dilemma. We hypothesized that electronic detection of an S3 would be more accurate in determining decompensated heart failure than physician auscultation, and that combining electronic heart sounds with B-type natriuretic peptide (BNP) would provide additional decision making information to the emergency physician, especially in the BNP indeterminate range (100–500 pg/mL). Methods and Results We collected demographic, clinical, and laboratory data in a convenience sample of ED patients presenting with signs or symptoms of acute decompensated heart failure between September 2003 and June 2004. The electronic presence of an S3 or S4 was determined using the Audicor system, a validated device that algorithmically detects S3 and S4 heart sounds. Two independent reviewers determined the presence or absence of acute decompensated heart failure (primary HF) based on chart review, while blinded to BNP and Audicor results. Test characteristics were determined with 95% confidence intervals. Of 422 enrolled patients, 343 had complete data and were included in the final analysis. Median age was 61 years, 54% were female, and 48% were white. The sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of an electronic S3 for primary HF were 34% (26% to 43%), 93% (89% to 96%), 66% (57% to 74%), 7% (4% to 11%), and 70% (65% to 75%) and for physician auscultation were 16% (11% to 24%), 97% (93% to 99%), 84% (76% to 89%), 3% (2% to 7%), and 66% (61% to 71%). The addition of an Audicor S3 to intermediate BNP levels improved the positive LR from 1.3 to 2.9; the positive predictive value from 53% to 80%. Conclusion An S3 is highly specific for primary HF and it is ideally suited for use in combination with BNP to improve diagnostic accuracy in ED patients with dyspnea of unclear etiology.

Study objective Acute cardiogenic pulmonary edema is a common cause of respiratory distress in emergency department (ED) patients. Noninvasive ventilation by noninvasive positive pressure ventilation or continuous positive airway pressure has been studied as a treatment strategy. We critically evaluate the evidence for the use of noninvasive ventilation on rates of hospital mortality and endotracheal intubation. Methods We searched the databases of MEDLINE, EMBASE, and the Cochrane Library from 1980 to 2005. Additional sources included key journals, bibliographies of selected articles, and expert contact. We included studies that incorporated a randomized design; patients older than 18 years and with acute cardiogenic pulmonary edema; diagnosis and treatment initiated in the ED; noninvasive ventilation in addition to standard medical therapy compared to standard medical therapy alone, or noninvasive positive pressure ventilation compared to continuous positive airway pressure (both in addition to standard medical therapy); and data on hospital mortality or intubation. A random-effects model was used to obtain the summary risk ratios (RRs) and 95% confidence intervals (CIs) for hospital mortality and intubation. Results A pooled analysis of 494 patients suggested that noninvasive ventilation in addition to standard medical therapy significantly reduced hospital mortality compared to standard medical therapy alone (RR 0.61; [95% CI 0.41, 0.91]). Similarly, a meta-analysis of 436 patients suggested that noninvasive ventilation was associated with a significant decrease in intubation rates (RR 0.43; [95% CI 0.21, 0.87]). Conclusion Our results suggest that noninvasive ventilation with standard medical therapy is advantageous over standard medical therapy alone in ED patients with acute cardiogenic pulmonary edema. Future studies, powered appropriately for mortality and intubation rates, are necessary to confirm these findings.

Objective: Appropriate patient selection is critical for maximal observation unit (OU) effectiveness. We hypothesized emergency physicians underuse the OU for admitted patients and overuse the OU for patients who would otherwise be discharged. Methods: Treating emergency physicians were asked about patient suitability for admission to an OU at a busy, urban, academic emergency department (ED) as part of a prospective cohort study of ED patients who were admitted or had an ED length of stay exceeding 4 hours. The OU was closed for renovation during the 2-month study, so physician opinion could be compared with patient course in the absence of observation services. Two blinded emergency physicians reviewed charts using structured forms and explicit definitions to determine actual patient course. Hospitalized patients were considered potential OU candidates according to a priori criteria: (1) hospital length of stay less than 48 hours, (2) no procedure or diagnosis requiring hospitalization, and (3) no death. Results: Of 1747 enrolled patients, 131 were excluded with incomplete data. Median age was 45 years. Patients were 40% white and 48% men. Emergency physicians identified 363 (23%) patients as observation candidates. Of these, 182 (50%) were actually discharged directly. The remaining 181 (50%) were hospitalized; 101 (56%) were observation candidates based on chart review. Of 799 admitted patients not selected for observation, 232 (29%) were suitable for observation by chart review. Conclusions: Selection of patients for observation was suboptimal; emergency physicians routinely identified patients as OU candidates who were not ultimately admitted, and they missed many admitted patients who might have been appropriate OU candidates. Both over- and underuse should be addressed to maximize the effectiveness of OUs.

Study objective B-type natriuretic peptide (BNP) is an established tool for the diagnosis of acute congestive heart failure in patients presenting with dyspnea. Some patients have moderately elevated BNP levels (ie, 100 to 500 pg/mL) in the absence of acute congestive heart failure. The objective of the current study was to identify independent predictors of elevated BNP concentrations in the absence of congestive heart failure. Methods We studied 781 patients without acute congestive heart failure and BNP levels 0 to 500 pg/mL drawn from a cohort of 1,586 patients with acute dyspnea who had BNP levels measured on emergency department arrival. Two cardiologists blinded to BNP results reviewed all clinical data and categorized patients according to whether they had acute congestive heart failure or not. Results Independent predictors of elevated BNP levels (ie, >100 pg/mL) were a medical history of atrial fibrillation, radiographic cardiomegaly, decreased blood hemoglobin concentration, decreased body mass index, and increased age. Conclusion Knowledge of these commonly obtained variables should aid clinicians in the interpretation of moderately elevated BNP results in patients presenting with acute dyspnea in the emergency department.

Emergency-department (ED)-based observation-unit treatment has been shown to reduce inpatient admissions, hospital bed-hours, and costs without adversely affecting outcomes for several conditions. A sequential group design study compared risk-matched, acute decompensated heart failure patients admitted directly to the inpatient setting with those admitted to an ED observation unit for up to 23 hours before ED disposition. Outcomes were 30-day readmissions or repeat ED visits for heart failure or 30-day mortality. Estimates of bed-hours and charges between the groups were compared. Sixty-four patients were enrolled with 36 inpatient admissions and 28 observation unit patients. No patients died within 30 days. Observation unit patients had no significant difference in outcomes, a decrease in time from ED triage to discharge, a saving in mean bed-hours, and less total charges. This pilot trial provides preliminary data that suggest admitted, low-risk heart failure patients may be safely and cost-effectively managed in an ED-based observation unit. These findings need to be further evaluated in a randomized clinical trial.

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 BNPor = 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.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.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.Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNPor = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNPor = 170 pg/mL) could be used to increase specificity.

This study was designed to assess the diagnostic performance of B-type natriuretic peptide (BNP) in the diagnosis of acute congestive heart failure (CHF) in patients with permanent/paroxysmal atrial fibrillation (AF) presenting with acute dyspnea.It is unknown to what extent AF affects the diagnostic performance of BNP in patients presenting with acute dyspnea.We studied 1,431 patients drawn from a cohort of patients (n = 1,586) with acute dyspnea who had BNP levels measured on arrival. Patients were prospectively classified according to the presence or absence of permanent/paroxysmal AF.In total, 292 patients had permanent/paroxysmal AF. In patients without HF, permanent/paroxysmal AF was associated with significantly higher BNP levels (p = 0.001). Conversely, in patients with HF, BNP levels did not differ significantly between patients with and without AF (p = 0.533). A BNP cutoff value of 100 pg/ml had a specificity of 40% and 79% for the diagnosis of acute HF in patients with and without AF, respectively. The areas under the receiver-operating characteristic curves were 0.84 (95% confidence interval 0.78 to 0.89) and 0.91 (95% confidence interval 0.89 to 0.93) for patients with and without AF, respectively.In patients without, but not in those with HF, the presence of AF is associated with higher circulating BNP levels, suggesting that a higher diagnostic threshold should be used in patients with AF.

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.

Diabetes has been implicated in reduced myocardial compliance and changes in the intercellular matrix of the myocardium. We determined the effect of diabetes on B-type natriuretic peptide (BNP) concentrations in patients presenting to the emergency department with dyspnea.The Breathing Not Properly Multinational Study was a prospective evaluation of 1,586 patients. A subset of 922 patients was obtained and subdivided into the following groups: group 1 (n = 324), neither diabetes nor heart failure; group 2 (n = 107), diabetes and no heart failure; group 3 (n = 247), no diabetes and heart failure; group 4 (n = 183), both diabetes and heart failure; group 5 (n = 41), heart failure history with no diabetes; and group 6 (n = 20), heart failure history with diabetes. Patients from groups 1, 3, and 5 were matched to groups 2, 4, and 6, respectively, to have the same mean age, sex distribution, BMI, renal function, and New York Heart Association (NYHA) classification (for heart failure).There was no significant difference in median BNP levels between diabetes and no diabetes among no heart failure patients (32.4 vs.32.9 pg/ml), heart failure patients (587 vs. 494 pg/ml), and those with a heart failure history (180 vs. 120 pg/ml). Receiver-operating characteristic curve analysis of the area under the curve for BNP was not different in diabetic versus nondiabetic patients (0.888 vs. 0.878, respectively). However, in a multivariate model, diabetes was an independent predictor of a final diagnosis of heart failure (odds ratio 1.51, 95% CI 1.03-2.02; P0.05).History of diabetes does not impact BNP levels measured in patients with acute dyspnea in the emergency department. Despite the impact of diabetes on the cardiovascular system, diabetes does not appear to confound BNP levels in the emergency department diagnosis of heart failure.

Heart failure is a disease of epidemic proportions. Almost five million Americans suffer from heart failure and over 400,000 patients are newly diagnosed with heart failure each year. Indeed, heart failure is now the only cardiovascular disease that is increasing in incidence and prevalence. Costs related to heart failure are $18.8 billion per year and are steadily increasing. Although the outpatient management of these patients has seen substantial improvement in the last two decades, emergency department (ED) treatment of acute decompensated heart failure has remained largely unchanged since the late 1970s. Current ED therapy consists of diuretics, intravenous vasodilatators, and inotropes. Recently, the outcomes of several high-profile clinical trials evaluating intravenous nesiritide (human B-type natriuretic peptide) have suggested a benefit in select hospitalized patients. Such a therapy has potential to provide a therapeutic addition or alternative for emergency heart failure management. We discuss these trials' results, suggest their relationship to the ED population, and provide recommendations for appropriate ED use.

African Americans with acute coronary syndromes receive cardiac catheterization less frequently than whites. The objective was to determine if such disparities extend to acute evaluation and non interventional treatment.Data on adults with chest pain (N = 7,935) presenting to eight emergency departments (EDs) were evaluated from the Internet Tracking Registry of Acute Coronary Syndromes. Groups were selected from final ED diagnosis: 1) acute myocardial infarction (AMI), n = 400; 2) unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI), n = 1,153; and 3) nonacute coronary syndrome chest pain (non-ACS CP), n = 6,382. American College of Cardiology/American Heart Association guidelines for AMI and UA/NSTEMI were used to evaluate racial disparities with logistic regression models. Odds ratios (ORs) were adjusted for age, gender, guideline publication, and insurance status. Non-ACS CP patients were assessed by comparing electrocardiographic (ECG)/laboratory evaluation, medical treatment, admission rates, and invasive and noninvasive testing for coronary artery disease (CAD).African Americans with UA/NSTEMI received glycoprotein IIb/IIIa receptor inhibitors less often than whites (OR, 0.41; 95% CI = 0.19 to 0.91). African Americans with non-ACS CP underwent ECG/laboratory evaluation, medical treatment, and invasive and noninvasive testing for CAD less often than whites (p0.05). Other nonwhites with non-ACS CP were admitted and received invasive testing for CAD less often than whites (p0.01). African Americans and other nonwhites with AMI underwent catheterization less frequently than whites (OR, 0.45; 95% CI = 0.29 to 0.71 and OR, 0.40; 95% CI = 0.17 to 0.92, respectively). A similar disparity in catheterization was noted in UA/NSTEMI therapy (OR, 0.53; 95% CI = 0.40 to 0.68 and OR, 0.68; 95% CI = 0.47 to 0.99).Racial disparities in acute chest pain management extend beyond cardiac catheterization. Poor compliance with recommended treatments for ACS may be an explanation.

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, p0.001). 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.

More than 4.5 million Americans have congestive heart failure (CHF), close to 550,000 new cases are diagnosed each year, and one third of known patients with CHF are annually admitted to the hospital. Emergency department diagnosis of CHF is often based on history and physical examination findings along with results of ancillary tests, such as chest radiography and ECG. Although signs and symptoms of fluid overload, such as lower extremity edema and dyspnea, raise the suspicion of CHF, their lack of sensitivity makes them poor screening tools. The natriuretic peptides are promising markers of myocardial dysfunction and heart failure. Because of their relationship to myocardial pressure and stretching, natriuretic peptides have been investigated over the past 5 decades as both diagnostic and prognostic markers in acute coronary syndromes and CHF. This article discusses each of the natriuretic peptides and attempts to delineate their potential diagnostic and prognostic roles in the ED.

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.To determine whether BNP can distinguish new-onset heart failure in patients with COPD or asthma presenting with dyspnea to the ED.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.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 (p0.0001). 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 (highor = 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, p0.0001). 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.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.

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 m 2 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 r ≠ 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 m 2 , 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 m 2 , 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 m 2 . Am J Kidney Dis 41:571-579. © 2003 by the National Kidney Foundation, Inc.

Purpose To compare chest radiographic findings and circulating B-type natriuretic peptide (BNP) levels as an adjunct to clinical findings in the diagnosis of heart failure in patients presenting with acute dyspnea. Methods The diagnostic performance of radiographic evidence of cardiomegaly/redistribution and BNP levels ≥100 pg/mL as indicators of heart failure were assessed in 880 patients presenting with acute dyspnea to the emergency departments of five U.S. and two European teaching hospitals. BNP levels were determined by a rapid, point-of-care device. Two blinded cardiologists reviewed all clinical data and categorized patients as to whether they had acute heart failure (n = 447) or not (n = 433). Results Three-factor analyses showed that BNP levels ≥100 pg/mL contributed significantly to the prediction of heart failure over each of the radiographic indicators. In a multivariate logistic regression analysis, both BNP levels ≥100 pg/mL (odds ratio [OR] = 12.3; 95% confidence interval [CI]: 7.4 to 20.4) and radiographic findings of cardiomegaly (OR = 2.3; 95% CI: 1.4 to 3.7), cephalization (OR = 6.4; 95% CI: 3.3 to 12.5), and interstitial edema (OR = 7.0; 95% CI: 2.9 to 17.0) added significant, predictive information above historical and clinical predictors of heart failure. Conclusion In patients presenting to the emergency department with acute dyspnea, BNP levels and chest radiographs provide complementary diagnostic information that may be useful in the early evaluation of heart failure.

Study objective: To determine whether the excreted metabolites of naloxone hydrochloride cause positive urine toxicologic screens for opiates. Design: Prospective, randomized, double-blinded human protocol. Setting: Urban Level I military emergency department. Participants: Fourteen adult volunteers who took no routinemedications, were not pregnant, had no known sensitivity to naloxone, and who were negative for a pretest urine and serum toxicologic screen. Interventions: We administered either 2 or 4 mg IV naloxoneto 14 subjects. Urine drug screening was obtained before administration and at 60 minutes, 6 hours, and 48 hours after administration. Results: All urine drug screens using the enzyme-multipliedimmunoassay technique were negative for opiates at both dosage levels. The sample size of 14 yielded a power of more than .99 to detect the difference between positive and negative samples. Conclusion: Although the metabolites of naloxone hydrochloride are similar in structure to oxymorphone and are excreted in human urine for several days, naloxone was not associated with a positive enzymatic urine screen for opiates.

Impedance cardiography has been used to detect early hemorrhagic shock, but, to the best of the authors' knowledge, no previous study has looked at the test characteristics of bioimpedance-derived hemodynamic parameters for the detection of a measured loss of blood volume. The authors set out to investigate the effect of controlled hemorrhage on stroke index (SI) using impedance cardiography, and to evaluate the performance of this test for moderate blood loss in comparison with the performance of traditional vital signs.Supine and standing measurements of SI were made using a thoracic electrical bioimpedance monitor in 197 healthy, adult volunteers before and after donation of a standard unit (500 mL) of whole blood. Pre- and post-donation means for supine SI, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP), and for the postural changes in each of these measurements ( triangle up SI, triangle up HR, triangle up SBP, triangle up DBP), were compared using a paired-sample, two-tailed t-test. For each term, receiver operating characteristic (ROC) curves were generated, treating pre- and post-donation populations as independent. Areas under the ROC curves were compared using a method for correlated test result data.Mean +/- SD pre- and post-donation values for SI were 47.0 +/- 6.9 mL/m(2) and 43.9 +/- 7.3 mL/m(2), respectively (p0.0001). Mean pre- and post-donation values for triangle up SI were -7.7 +/- 5.8 mL/m(2) and -9.0 +/- 8.2 mL/m(2), respectively (p = 0.02). For discriminating between pre- and post-donation status, the areas under the ROC curves for SI and triangle up SI were 0.62 and 0.58, respectively. In comparison, the areas under the ROC curves for HR, SBP, DBP, triangle up HR, triangle up SBP, and triangle up DBP were 0.49, 0.61, 0.56, 0.82, 0.53, and 0.50, respectively. The area under the ROC curve for triangle up HR was significantly greater than the area under any of the other curves (p0.0001).Moderate blood loss was associated with a decline in mean SI that was clearly detectable with impedance cardiography. However, as a test for moderate blood loss in this controlled setting, neither SI nor triangle up SI performed better than traditional vital signs.

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 Conclusions — The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.

We appreciate the interest of Dr. De Marco and colleagues in our report [(1)][1] and their interesting observations on the potential use of serum BAG3, possibly in combination with other tests, in monitoring progression of heart failure. We agree that a multiple biomarker approach may add unique

Background —Earlier, rapid evaluation in chest pain units may make patient care more efficient. A multimarker strategy (MMS) testing for several markers of myocardial necrosis with different time-to-positivity profiles also may offer clinical advantages. Methods and Results —We prospectively compared bedside quantitative multimarker testing versus local laboratory results (LL) in 1005 patients in 6 chest pain units. Myoglobin, creatine kinase-MB, and troponin I were measured at 0, 3, 6, 9 to 12, and 16 to 24 hours after admission. Two MMS were defined: MMS-1 (all 3 markers) and MMS-2 (creatine kinase-MB and troponin I only). The primary assessment was to relate marker status with 30-day death or infarction. More patients were positive by 24 hours with MMS than with LL (MMS-1, 23.9%; MMS-2, 18.8%; LL, 8.8%; P =0.001, all comparisons), and they became positive sooner with MMS-1 (2.5 hours, P =0.023 versus LL) versus MMS-2 (2.8 hours, P =0.026 versus LL) or LL (3.4 hours). The relation between baseline MMS status and 30-day death or infarction was stronger (MMS-1: positive, 18.8% event rate versus negative, 3.0%, P =0.001; MMS-2: 21.9% versus 3.2%, P =0.001) than that for LL (13.6% versus 5.5%, P =0.038). MMS-1 discriminated 30-day death better (positive, 2.0% versus negative, 0.0%, P =0.007) than MMS-2 (positive, 1.8% versus negative, 0.2%; P =0.055) or LL (positive, 0.0% versus negative, 0.5%; P =1.000). Conclusions —Rapid multimarker analysis identifies positive patients earlier and provides better risk stratification for mortality than a local laboratory-based, single-marker approach.

Chest pain is the most common cocaine-related complaint. The objective of this study was to describe an emergency department-based chest pain center for patients with cocaine-associated chest pain and to evaluate the safety of this protocol by assessing cardiac complications at 30 days.

The study applied a retrospective follow-up design to determine the prognostic effect of graded exercise testing (GXT) in patients with low- to moderate-risk chest pain evaluated in an emergency department 9-hour protocol chest pain center (CPC) from January 1, 1993 to August 1, 1996. The cohort of 1,209 patients were followed to the date of death or first adverse cardiac event up to 1 year after CPC admission. Cardiac events were defined as coronary artery bypass graft, percutaneous transluminal coronary angioplasty, cardiogenic shock, cardiac-related death, congestive heart failure admission, ventricular tachycardia/ventricular fibrillation arrest, and myocardial infarction. Patients with acute ST-segment elevation or depression of >1 mm, positive enzyme (creatine kinase myocardial band) testing, or unstable angina during their CPC evaluation were admitted without GXT testing. Statistical analysis included chi-square test for complication rates and Cox proportional-hazards modeling. Nine hundred fifty-eight of 1,209 patients underwent GXT testing. Patients with positive, inconclusive, and normal GXTs had complication rates of 36.8% (7 of 19), 3.4% (9 of 267), and 1.1% (5 of 456), respectively. After adjusting for age, sex, and race, the relative risk of complication was 38.9 (95% confidence interval 11.7 to 129.6) with a positive GXT, and 3.6 (95% confidence interval 1.2 to 10.7) with an inconclusive GXT compared with a normal GXT. The GXT is a good prognostic indicator of adverse cardiac events in low- to moderate-risk chest pain in patients evaluated in an emergency department CPC.

Histologic specimens from 41 rabbits were studied for changes resulting from the manual injection of brown recluse spider venom. Major findings included a mixed inflammatory cell infiltrate, coagulative tissue necrosis, and vasculitis. All specimens demonstrated a well-delineated zone of eosinophilic staining recognizable as "mummified" coagulative necrosis of the epidermis and dermis. A dense band of neutrophils bordered the zone of necrosis. Immediately adjacent to the neutrophilic band, small vessel vasculitis was a universal finding. Degranulated eosinophils and neutrophils and macrophages filled with eosinophilic granules were common. Inflammatory foci were often centered on groups of lipocytes within the dermis. Large vessel vasculitis resembling that seen in polyarteritis nodosa was present deep to 7 of the 40 eschars. Large vessel vasculitis may contribute to the large zones of necrosis seen after some brown recluse spider bites. Eosinophils may play a role in tissue damage after envenomation.

Patients with acute cardiogenic pulmonary edema (ACPE) are commonly seen in the emergency department (ED). Although the majority of patients respond to conventional medical therapy, some patients require at least temporary ventilatory support. Traditionally, this has been accomplished via endotracheal intubation and mechanical ventilation, an approach that is associated with a small but significant rate of complications. The past 2 decades have witnessed increasing interest in methods of noninvasive ventilatory support (NVS), notably continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). We review the physiological consequences, clinical efficacy, and practical limitations of CPAP and BiPAP in the management of ACPE.

The emergency department (ED) evaluation of patients with potential acute coronary syndromes (ACS) has traditionally included initial cardiac marker testing for suspected acute myocardial infarction (AMI). While ED management decisions for patients with ACS have largely been based on history, physical examination, and a presenting 12-lead electrocardiogram (ECG), there is ample evidence that markers impact treatment decisions and provide risk stratification. Newer, more sensitive markers of myocardial necrosis have blurred the distinction between patients with and without classically defined AMI, and have focused attention on the continuum of ACS from angina to transmural Q-wave MI. Newer antiplatelet agents, the glycoprotein IIb/IIIa receptor blockers, are likely to receive increased ED utilization. This use will be partially driven by ED cardiac marker determination. Bedside, point-of-care testing is reliable technology that may shorten time to diagnosis and treatment of ACS in the emergency setting. The ED-based chest pain center (CPC) has become a popular tool to evaluate patients at low- to moderate-risk for ACS and a non-diagnostic ECG. Such centers use serial cardiac marker testing as a mainstay for evaluation and risk stratification. Cost issues have driven many diagnostic patient evaluations from the inpatient setting to such ED observation units. As this becomes more common for low- to moderate-risk patients with chest pain, serial assessment of cardiac markers, and their interpretation by emergency physicians, will become essential.

We describe the case of a previously well 2-year-old girl who was found to have primary pulmonary hypertension (PPH) after presenting to the ED with syncope. Although physical examination findings were normal, an ECG and chest radiograph showed signs of PPH. The patient's hospital course was significant for syncopal episodes and sudden death while she awaited a heart transplant. This case illustrates that suspected cardiac syncope in the young warrants a focused ED evaluation with attention to causes of a life-threatening nature.

Objective: To compare lidocaine levels after administration through an IV line, a standard endotracheal (ET) tube, and an ET tube side port (ETSP) designed for medication administration. Methods: A double-blind, prospective, triple crossover canine study was performed. Seventeen anesthetized mongrel dogs were given standard doses of 2% lidocaine via IV (1.5 mg/kg), endotracheally through the main lumen (3 mg/kg diluted in 10 mL normal saline), and endotracheally through the modified side port (3 mg/ kg diluted in 10 mL normal saline). Arterial blood gases (ABGs) and plasma lidocaine levels were measured at time 0, 30 sec, 1 min, 5 min, 10 min, 20 min, 30 min, and 60 min. Mean lidocaine levels across time, comparing the 3 methods of administration, were analyzed with repeated-measures analysis of variance. The main outcome was the comparison of mean ET and ETSP lidocaine levels at each time point using paired t-tests. The attainment and duration of lidocaine levels considered therapeutic in cardiac arrest (1.4 μg/mL) were described. ABGs were measured at each point to describe trends in oxygenation. Results: Mean lidocaine levels, comparing the 3 methods of administration, were significantly different at all time points except time 0. The ETSP levels were significantly lower than the ET main-lumen levels at 30 sec, 1 min, 5 min, and 10 min. IV-administered lidocaine attained quick therapeutic levels and revealed faster elimination. Lidocaine administered through the ET main lumen reached therapeutic levels more slowly, and maintained such levels longer. Lidocaine administered through the ETSP never reached therapeutic levels. Mean Po2s remained >340 torr throughout each method of administration. Conclusion: This nonarrest canine model suggests that lidocaine levels achieved through an ETSP are lower than levels obtained with the same drug dose via an ET main lumen. Therapeutic lidocaine levels are obtainable by IV or ET main-lumen routes, but not via this ETSP.

Study objectives: The presence of abnormal diastolic heart sounds (S3 and S4) is indicative of elevated ventricular filling pressures and suggests decompensated heart failure. We sought to determine the prevalence of abnormal diastolic heart sounds in emergency department (ED) patients presenting with signs or symptoms of decompensated heart failure. We hypothesize that an S3 and S4 will be observed more often in heart failure patients than in patients without heart failure. Methods: The study was a prospective, convenience sample of ED patients who had signs or symptoms of decompensated heart failure. Baseline demographic, clinical, and laboratory data were collected. The presence of an S3/S4 was determined using the Audicor system, a validated device that algorithmically detects S3 and S4 heart sounds. A diagnosis of decompensated heart failure was based on attending physician discharge summary. The prevalence of an S3 or S4 was determined in patients with a primary diagnosis of decompensated heart failure, a secondary diagnosis of heart failure, and a non–heart failure diagnosis. Data are described with 95% confidence intervals (CIs) for proportions. Results: There were 135 patients enrolled; 49.6% were men and 56.3% were black. The prevalence of an S3 was more than threefold higher in decompensated heart failure patients (41.3%) than in non–heart failure patients (13.2%). The prevalence of an S4, although much smaller in magnitude, was also higher in decompensated heart failure patients (17.4%) than in non–heart failure patients (5.9%). Although the differences were not as marked, those patients with a secondary diagnosis of heart failure also had an increased prevalence of S3/S4 compared with the group with a non–heart failure diagnosis. Conclusion: This study suggests that patients with decompensated heart failure are much more likely to have abnormal diastolic heart sounds than patients with dyspnea not related to heart failure. When present, abnormal diastolic heart sounds should alert the physician to an increased likelihood of decompensated heart failure.Table, abstract 318Prevalence of S3 and S4 in all patients.All, No. (%) (N=135)Primary HF, No. (%) (N=46)Secondary HF, No. (%) (N=21)No HF, No. (%) (N=68)Heart sounds: S3 (prevalence)34 (25.2)19 (41.3)6 (28.6)9 (13.2)95% CI18.6–33.128.3–55.713.8–50.07.1–23.3Heart sounds: S4 (prevalence)16 (11.9)8 (17.4)4 (19.0)4 (5.9)95% CI7.4–18.49.1–30.77.7–40.02.3–14.2 Primary HF, Primary diagnosis of decompensated heart failure; Secondary HF, secondary diagnosis of decompensated heart failure; No HF, non–heart failure diagnosis.

Study objective: To determine whether the urine Trinder spot test, performed by emergency physicians, is a sensitive bedside screen for salicylates. Design: Prospective, blinded human protocol with subjects serving as their own controls. Setting: Urban Level I medical center. Participants: Ten male and two female volunteers with negative urine toxicologic screen results before the start of the study. Interventions: Each participant ingested 975 mg of nonenteric coated aspirin. Serum and urine samples were collected before ingestion and 2 and 4 hours after ingestion. Three emergency physicians and a toxicology technician independently performed Trinder spot tests. Results were recorded as positive or negative for salicylate on the basis of color change (a purple reading was considered positive). Results: All postingestion urine specimens were detected by all testers with 100% sensitivity. Two false positives occurred in the preingestion samples. Serum quantitative assays confirmed the presence of salicylates in all postingestion specimens. Conclusion: This pilot study suggests that emergency physicians can use the Trinder spot test as a sensitive bedside salicylate screen, potentially saving time and quantitative assay expense. [King JA, Storrow AB, Finkelstein JA: Urine Trinder spot test: A rapid salicylate screen for the emergency department. Ann Emerg Med September 1995;26:330-333.]

Traumatic dissection of the carotid artery is an infrequent but serious complication of blunt cranial-cervical injury. The typical patient presents with deficits attributable to cerebral ischemia in the distribution of the affected vascular supply. Key considerations in the clinical picture are a delay in symptom presentation, normal initial computed tomography scans, and potential for concomitant cerebral or visceral injury. Because the initial clinical and diagnostic picture may be normal, it is crucial for emergency physicians to aggressively search for this injury in the presence of blunt cranial trauma. We present an unusual case of bilateral high extracranial carotid dissection secondary to blunt trauma. The pathophysiology of carotid artery trauma, treatment options, and key acute care issues are discussed.