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Objectives We investigated absolute and relative cardiac troponin I (TnI) delta changes, optimal sampling protocols, and decision thresholds for early diagnosis of myocardial infarction (MI). Serial cardiac biomarker values demonstrating a rise and/or fall define MI diagnosis; however the magnitude of change, timing, and diagnostic accuracy of absolute versus relative (percentage) deltas remains unsettled. Methods We prospectively measured TnI (AccuTnI + 3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent symptoms of acute coronary syndrome at 14 medical centers. Diagnosis was adjudicated by an independent central committee. Results Elevated TnI above a threshold of 0.03 ng/mL demonstrated significant diagnostic efficacy (AUC 0.96). For patients with TnI < 0.03 ng/mL and symptom onset ≥ 8 h, 99.1% (NPV) were diagnosed with conditions other than MI. Absolute delta performed significantly better than relative delta at 1–3 h (AUC 0.84 vs 0.69), 3–6 h (0.85 vs 0.73), and 6–9 h (0.91 vs 0.79). Current recommendations propose ≥ 20% delta within 3–6 h; however, results were optimized using an absolute delta of 0.01 or 0.02 ng/mL. Sensitivity results for absolute delta at 1–3 h and 3–6 h (75.8%, 78.3%) were superior to relative delta (48.0%, 61.3%). NPV (rule out) was 99.6% when baseline TnI < 0.03 ng/mL and absolute delta TnI < 0.01 ng/mL. Conclusions Absolute delta performed significantly better than relative delta at all time intervals. Baseline TnI and absolute delta may be used in conjunction to estimate probability of MI. Consensus recommendations are supported for sampling on admission and 3 h later, repeated at 6 h in patients when clinical suspicion remains high. [ABSTRACT FROM AUTHOR]

We examined the relation between B-type natriuretic peptide (BNP) levels and a history of stable angina pectoris and/or healed myocardial infarction in 1,240 patients who were evaluated in the emergency department for possible heart failure. In patients who had heart failure, there was no relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction. However, in patients who did not have heart failure, there was a relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction but no significant independent relation in multiple regression analysis. [Copyright &y& Elsevier]

Context: Acute asthma causes nearly 2 million hospital emergency department (ED) visits in the United States annually, and hospitalization after an ED visit and relapse after ED discharge are common. Objective: To evaluate the adding of therapy with zafirlukast to standardized care for patients with acute asthma in the ED and a 28-day follow-up period. Design and patients: A total of 641 patients presenting to the ED with acute asthma were randomized to receive either single-dose zafirlukast, 160 mg (Z160) [162 patients], zafirlukast, 20 mg (Z20) [158 patients]), or placebo (321 patients) as adjunct treatment to standard care in this double-blind, multicenter trial. Assessments, including spirometry and symptom scores, were obtained before each albuterol treatment and at 4 h. Patients who were discharged from the ED after 4 h continued outpatient therapy over a 28-day period and received either Z20 bid (276 patients) or placebo (270 patients) in addition to prednisone, albuterol, and their previous asthma medications. FEV1 was measured at clinic visits on days 10 and 28. Patients recorded outpatient clinical data twice daily on a home diary card. Main outcome measures: the effect of zafirlukast on relapse after ED discharge. Other assessments were the rate of extended care (ie, ED stay for > 4 h or hospitalization), FEV1, and symptoms. Results: At the end of the outpatient period, 65 of 276 patients (23.6%) treated with zafirlukast and 78 of 270 patients (28.9%) treated with placebo relapsed (p = 0.047; absolute reduction, 5.3%; relative reduction, 18.3%). At the end of the ED period, 16 of 162 patients (9.9%) treated with Z160, 26 of 158 patients (16.5%) treated with Z20, and 48 of 321 patients (15.0%) treated with placebo required extended care (p = 0.052; absolute reduction with Z160 compared to placebo, 5.1%; relative reduction, 34%). These findings were supported by a significant improvement in FEV1 and dyspnea in the ED with the use of Z160 therapy, and by greater improvement in FEV1 and symptoms during the outpatient period for patients treated with Z20. Conclusions: When added to standardized care, therapy with Z20 bid reduced the risk of relapse compared with placebo over a 28-day treatment period. One dose of Z160 in the ED also reduced the rate of extended care. [ABSTRACT FROM AUTHOR]

Background: Increased rates of myocardial infarction, heart failure, arrhythmias, and death occur in patients with chronic kidney disease. We sought to evaluate the processes of care and outcomes in patients with chronic kidney disease presenting to an emergency department with chest discomfort. Methods: We enrolled 817 consecutive patients who underwent evaluation for a possible acute myocardial infarction in a prospective study of cardiac biomarkers. Renal dysfunction did not exclude patients from this study, and baseline renal function and 30-day outcomes were available in 808. Patients were stratified by corrected creatinine clearance rate into quartiles, with those undergoing dialysis (n= 51) as a fifth comparison group. Results: Those patients with advanced renal dysfunction (corrected creatinine clearance rate, <47.0 mL/min [<0.8 mL/s] per 72 kg) or who underwent dialysis had higher rates of diabetes, hypertension, and prior coronary disease. More than 99% of all patients were admitted to a chest pain observation unit or to the hospital. Rates of stress testing were lower as renal dysfunction worsened. Rates of revascularization, however, were similar for all groups. The most frequent in-hospital complication was the development of heart failure, which occurred in 36.5% of those with a corrected creatinine clearance rate of less than 47.0 mL/min per 72 kg. At 30 days, this group had the highest rates of cumulative myocardial infarction, development of heart failure, and death (40.2%). Conclusion: Chronic kidney disease is a marker for inhospital and 30-day outcomes in patients presenting to the emergency department with chest discomfort. [ABSTRACT FROM AUTHOR]

Discusses several issues about the development of emergency medical practice in the U.S. Roles of emergency physicians in managing disease resolution; Clinical assessment of acute diseases; Impact of technology on emergency medicine.

Background: Functional status assessment is common in many cardiovascular diseases but it has undergone limited study in the setting of acute heart failure (AHF). Accordingly, we performed a pilot study of the feasibility of the six-minute walk test (6MWT) at the emergency department (ED) presentation and through the hospitalization in patients with AHF. Methods and Results: From November 2014 to February 2015, we conducted a multicenter, observational study of ED patients, aged 18-85 years, whose primary ED admission diagnosis was AHF. Other criteria for enrollment included a left ventricular ejection fraction ≤40%, systolic blood pressure between 90 and 170 mmHg, and verbal confirmation that the patient was able to walk >30 m at the baseline, prior to ED presentation. Study teams were uniformly trained to administer a 6MWT. Patients underwent a baseline 6MWT within 24 h of ED presentation (Day 1) and follow-up 6MWTs at 24 (Day 2), 48 (Day 3), and 120 h (Day 5). A total of 46 patients (65.2% male, 73.9% African American) had a day one mean walk distance of 137.78 ± 3 m, day 2 of 170.9 ± 100 m, and day 3 of 180.8 ± 98 m. The 6MWT demonstrated good reproducibility, as the distance walked on the first 6MWT on Day 3 was similar to the distance on the repeated 6MWT the same day. Conclusions: Our pilot study demonstrates the feasibility of the 6MWT as a functional status endpoint in AHF patients. A larger study in a more demographically diverse cohort of patients is necessary to confirm its utility and association with 30-day heart failure (HF) events. [ABSTRACT FROM AUTHOR]

Abstract: Although most cases of anaphylaxis are treated in the emergency department (ED), personnel may not immediately recognize anaphylaxis based on presenting symptoms because it has a wide range of clinical manifestations and variable progression. When symptoms happen to be atypical or mild and when no trigger is identified, the diagnosis of anaphylaxis can be challenging. Underdiagnosis of anaphylaxis can lead to delayed use of appropriate first-line epinephrine in favor of treatments that should be used as adjunctive only. Even when anaphylaxis is recognized, the choice between an epinephrine autoinjector or epinephrine ampule can still present a challenge. Treatment of anaphylaxis in the ED should include a combination of intramuscular epinephrine, supplemental oxygen, and intravenous fluids. If there is an incomplete response to the initial dose of epinephrine, additional doses or other measures may be considered. The most important management consideration is avoiding treatment delays, because symptoms can progress rapidly. Upon discharge from the ED, all patients with anaphylaxis should be given a prescription for at least 2 epinephrine autoinjectors, an initial emergency action plan, education about avoidance of triggers, and a referral to an allergist. A significant limitation of current studies is that clinical outcomes in anaphylaxis associated with established poor rates of diagnosis and use of recommended treatments are unclear; such trials must be conducted as supporting evidence for ED management guidelines for anaphylaxis. [Copyright &y& Elsevier]

High-sensitivity cardiac troponin T (hs-cTnT) and the ESC 0/1h-hs-cTnT-algorithm have worse performance in the early diagnosis of myocardial infarction (MI) in patients with prior coronary artery bypass grafting (CABG). It is unknown, whether this concern applies also to hs-cTnI, the most widely used analyte worldwide. In an international multicenter diagnostic study, two cardiologists centrally adjudicated the final diagnosis in patients presenting to the emergency department with symptoms suggestive of MI according to the Third Universal Definition of MI. The objective was to compare the diagnostic accuracy of hs-cTnI assays and their performance within the ESC hs-cTnI 0/1h-algorithms in patients with versus without prior CABG. Findings were externally validated in an U.S. multicenter diagnostic study. A total of 392/5′200 patients (8%) had prior coronary artery bypass grafting (CABG). Diagnostic accuracy of hs-cTnI as quantified by the area under the receiver-operating characteristics-curve (AUC) in these patients was high, but lower versus patients without prior CABG (e.g. hs-cTnI-Architect 0.91 versus 0.95; p = 0.016). Sensitivity/specificity of rule-out/in by the European Society of Cardiology (ESC) 0/1h-hs-cTnI-algorithms remained very high [e.g. hs-cTnI-Architect 100% and 93.5%], but efficacy was lower (52% versus 74%, p < 0.01). External validation (n = 2113) confirmed these findings in 192 patients with prior CABG using hs-cTnI-Atellica, with 52% versus 36% (p < 0.001) remaining in the observe zone. Diagnostic accuracy of hs-cTnI and efficacy of the ESC 0/1h-hs-cTnI-algorithms are lower in patients with prior CABG, but sensitivity/specificity remain very high. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00470587 , number NCT00470587. • Compared to patients without prior CABG, in patients with prior CABG: • Diagnostic accuracy of 4 different hs-cTnI assays was lower. • ESC 0/1 h-hs-cTnI-algorithm still provided high accuracy for rule-in of AMI. • ESC 0/1 h-hs-cTnI-algorithm still provided high safety for rule-out of AMI. • Triage efficacy for rule-out/in of AMI of the ESC 0/1 h-hs-cTnI-algorithm was lower. [ABSTRACT FROM AUTHOR]

Objectives To compare emergency department TnI serial sampling intervals, determine optimal diagnostic thresholds, and report representative diagnostic performance characteristics for early rule-in and rule-out of MI. Methods We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent ischemic symptoms suggestive of acute coronary syndromes at 14 medical centers. Diagnosis was adjudicated by an independent central committee. Results TnI ≥ 0.03 ng/mL provided 96.0% sensitivity and 89.4% specificity at 1–3 h after admission, and 94.9% sensitivity and 86.7% specificity at 3–6 h. NPV (rule-out, non-MI) was 99.5% at 1–3 h, and 99.0% at 3–6 h when TnI is < 0.03 ng/mL. NPV was 99.1% when TnI is < 0.03 ng/mL and time of symptom onset is ≥ 8 h. Approximately 50–58% (PPV) of patients with TnI ≥ 0.03 ng/mL were diagnosed with MI, depending upon time from onset or admission; PPVs emphasize the importance of serial samples and delta TnI (rising or falling pattern) when low cutoffs are used. Nevertheless, even a single elevated TnI value increased the risk of MI. As TnI values rose, the probability of MI increased. Values ≥ 0.20 ng/mL were associated with nearly 90% probability of MI. Conclusions We report a large multicenter prospective adjudicated trial assessing troponin for early rule-in and rule-out using the Universal Definition of MI and conducted in primary care hospital-associated emergency departments. Our study demonstrates high diagnostic accuracy at early observation times, and reinforces consensus recommendations for sampling on admission and 3 h later, repeated at 6 h when clinical suspicion remains high. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the prognostic utility of midregion proadrenomedullin (MR-proADM) in all patients, cardiac and noncardiac, presenting with acute shortness of breath. Background: The recently published BACH (Biomarkers in Acute Heart Failure) study demonstrated that MR-proADM had superior accuracy for predicting 90-day mortality compared with B-type natriuretic peptide (area under the curve: 0.674 vs. 0.606, respectively, p < 0.001) in acute heart failure. Methods: The BACH trial was a prospective, 15-center, international study of 1,641 patients presenting to the emergency department with dyspnea. Using this dataset, the prognostic accuracy of MR-proADM was evaluated in all patients enrolled for predicting 90-day mortality with respect to other biomarkers, the added value in addition to clinical variables, as well as the added value of additional measurements during hospital admission. Results: Compared with B-type natriuretic peptide or troponin, MR-proADM was superior for predicting 90-day all-cause mortality in patients presenting with acute dyspnea (c index = 0.755, p < 0.0001). Furthermore, MR-proADM added significantly to all clinical variables (all adjusted hazard ratios: >3.28), and it was also superior to all other biomarkers. MR-proADM added significantly to the best clinical model (bootstrap-corrected c index increase: 0.775 to 0.807; adjusted standardized hazard ratio: 2.59; 95% confidence interval: 1.91 to 3.50; p < 0.0001). Within the model, MR-proADM was the biggest contributor to the predictive performance, with a net reclassification improvement of 8.9%. Serial evaluation of MR-proADM performed in patients admitted provided a significant added value compared with a model with admission values only (p = 0.0005). More than one-third of patients originally at high risk could be identified by the biomarker evaluation at discharge as low-risk patients. Conclusions: MR-proADM identifies patients with high 90-day mortality and adds prognostic value to natriuretic peptides in patients presenting with acute shortness of breath. Serial measurement of this biomarker may also prove useful for monitoring, although further studies will be required. (Biomarkers in Acute Heart Failure [BACH]; NCT00537628) [Copyright &y& Elsevier]

: ObjectivesThis study examines B-type natriuretic peptide (BNP) levels in patients with systolic versus non-systolic dysfunction presenting with shortness of breath.: BackgroundPreserved systolic function is increasingly common in patients presenting with symptoms of congestive heart failure (CHF) but is still difficult to diagnose.: MethodsThe 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.: ResultsOf 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.: ConclusionsWe 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. [Copyright &y& Elsevier]

Background: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers.Methods: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated.Results: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI.Conclusions: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed.Objectives: This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting.Methods: Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF.Results: Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13).Conclusions: In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF. [ABSTRACT FROM AUTHOR]

To determine the 28 day survival prognostic value of the initial Emergency Department (ED) high sensitivity cardiac troponin I (hs-cTnI) measurement in coronavirus-19 disease 2019 (COVID-19) patients. Recent reports indicate that the presence of cardiac injury [troponin level > the 99th percentile upper reference limit (99th % URL) using mostly contemporary assays] is predictive of death within 30 days during hospitalization of COVID-19 patients. Troponin values ordered in the ED or after hospitalization were used for these analyses. Using an ED centric electronic database of COVID-19 patients (nasopharyngeal swab testing within 1 week prior to or during the ED visit) having at least 1 hs-cTnI (Beckman Coulter, Brea, CA; level of quantitation (LoQ) 4ng/L, non sex specific 99th percentile URL 18 ng/L) value reported during a visit to an urban, academic ED in the United States. All patients were followed for 28 days to determine all-cause mortality. Kaplan Meir survival curves were constructed to compare outcomes amongst predetermined initial hs-cTnI value intervals. From March 16-November 2, 2020 1476 consecutive ED COVID-19 patients were identified with 1044 (70.7%) having at least 1 hs-cTnI value resulted in the ED. Patients' mean age and body mass index were 60.8 ± 16.1 years and 32.4 ± 11.3 kg/m² respectively. 531 (50.9%) were male, 804 (77.0%) self-identified as African American and 615 (58.9%) had 2 or more comorbidities with hypertension (42.5%), diabetes (37.4%) and hyperlipidemia (27.23%) commonest. Hs-cTnI interval values were: 147 (14.1%) < 4 (LoQ), 359 (34.4%) 4-10 and 151 (14.5%) 11-18 ng/L. Hs-cTnI values were > 99th % URL in 387 (37.1%) patients with 230 (22.0%) 19-54, 63 (6.0%) 54-99 and 94 (9.0%) = 100 (laboratory reported critical value) ng/L. 145 (13.9%) patients were discharged directly home and 2 (0.2%) died in the ED. 147 (14.1%) were admitted to an ICU with 104 (70.7%) dying. Each of the interval initial ED hs-cTnI values was associated with a different (p < 0.001) 28 day survival curve (Figure). Most COVID-19 patients had a hs-cTnI value obtained with 85.9% of these > 4 ng/L. No one with an initial hs-cTnI < 4 ng/L died within 28 days while increasing presenting hs-cTnI values > 4 ng/L were associated with decreased 28 day survival. Our findings indicate that in COVID-19 patients detectable initial ED hs-cTnI values, whether reaching thresholds for cardiac injury or not, are highly prognostic of 28 day survival. [ABSTRACT FROM AUTHOR]

Objectives: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States.Design: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol.Setting: Thirteen U.S.-based emergency departments and ICUs.Patients: Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included.Interventions: Procalcitonin was measured daily over the first 5 days.Measurements and Main Results: The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 [95% CI, 1.18-3.30; p < 0.009]) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders.Conclusions: Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care. [ABSTRACT FROM AUTHOR]

The article investigates the changes in emergency asthma care for pregnant women in the U.S. between the 1990s and 2010s. Topics discussed include the improvements in emergency asthma care for pregnant women over the span of time, an increase in corticosteroid treatment during the covered period and the factors that affect the quality of emergency care for asthmatic pregnant women.

Objectives: The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED).Background: Copeptin is secreted from the pituitary early in the course of AMI.Methods: This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99 th percentile 40 ng/l; 10% coefficient of variation 0.03 μg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results.Results: AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001).Conclusions: Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws. [ABSTRACT FROM AUTHOR]

Objectives The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnl) <99th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED). Background Copeptin is secreted from the pituitary early in the course of AMI. Methods This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnl (99th percentile 40 ng/l; 10% coefficient of variation 0.03 µg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results. Results AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnl at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnl alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnl at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnl were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional, predictive value (all p < 0.0001). Conclusions Adding copeptin to cTnl allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in ' 58% of patients without serial blood draws. [ABSTRACT FROM AUTHOR]

Heart failure requiring urgent therapy represents a burgeoning health care burden. Although acute heart failure syndromes are commonly defined as a change in chronic heart failure signs and symptoms requiring urgent therapy, the presentation, development, and response to treatment is highly dependent on individual patient characteristics. This heterogeneity has led to challenges in interpreting widely differing study methods, including eligibility requirements and outcome measures. To improve interpretation of results and translate such information to better patient care, it is essential to present an accurate description of the patient population and study design. Based on existing recommendations and expert consensus, the authors present standardized reporting criteria to improve interpretability of research in this challenging cohort. [Copyright &y& Elsevier]

Aims Biomarkers have proven their ability in the evaluation of cardiopulmonary diseases. We investigated the utility of concentrations of the biomarker procalcitonin (PCT) alone and with clinical variables for the diagnosis of pneumonia in patients presenting to emergency departments (EDs) with a chief complaint of shortness of breath. Methods and results The BACH trial was a prospective, international, study of 1641 patients presenting to EDs with dyspnoea. Blood samples were analysed for PCT and other biomarkers. Relevant clinical data were also captured. Patient outcomes were assessed at 90 days. The diagnosis of pneumonia was made using strictly validated guidelines. A model using PCT was more accurate [area under the curve (AUC) 72.3%] than any other individual clinical variable for the diagnosis of pneumonia in all patients, in those with obstructive lung disease, and in those with acute heart failure (AHF). Combining physician estimates of the probability of pneumonia with PCT values increased the accuracy to >86% for the diagnosis of pneumonia in all patients. Patients with a diagnosis of AHF and an elevated PCT concentration (>0.21 ng/mL) had a worse outcome if not treated with antibiotics (P = 0.046), while patients with low PCT values (<0.05 ng/mL) had a better outcome if they did not receive antibiotic therapy (P = 0.049). Conclusion Procalcitonin may aid in the diagnosis of pneumonia, particularly in cases with high diagnostic uncertainty. Importantly, PCT may aid in the decision to administer antibiotic therapy to patients presenting with AHF in which clinical uncertainty exists regarding a superimposed bacterial infection. [ABSTRACT FROM PUBLISHER]

Hypertension may affect the diagnostic performance of B-type natriuretic peptide (BNP). The objective of the present study was to assess the impact of a history of hypertension or blood pressure elevation on admission on the diagnostic performance of BNP in the diagnosis of heart failure (HF) in patients with acute dyspnea. BNP levels were measured using a rapid point-of-care device in 1,586 patients with acute dyspnea. In patients with HF, BNP levels did not differ between those with and without histories of hypertension. Conversely, in patients without HF, a history of hypertension was associated with higher median BNP levels (38 pg/ml [interquartile range 13 to 119] vs 21 pg/ml [interquartile range 7 to 64], p <0.001). The areas under the receiver-operating characteristic curves were 0.88 and 0.93 for those with and without histories of hypertension, respectively (p <0.001). Blood pressure elevation on admission did not affect the diagnostic accuracy of BNP (areas under the curve 0.90 in the 2 groups). In conclusion, although a history of hypertension is associated with higher BNP levels in patients with acute dyspnea without HF, the impact on the overall diagnostic performance of BNP is modest. Accordingly, BNP performs well as an indicator of HF in patients presenting in emergency departments regardless of a history of hypertension or elevated blood pressure on admission. [Copyright &y& Elsevier]

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. (N Engl J Med 2002;347:161-7.) [ABSTRACT FROM AUTHOR]

Objectives: 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. Background: It is unknown to what extent AF affects the diagnostic performance of BNP in patients presenting with acute dyspnea. Methods: 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. Results: 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. Conclusions: 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. [Copyright &y& Elsevier]

Context: Acute asthma causes nearly 2 million hospital emergency department (ED) visits in the United States annually, and hospitalization after an ED visit and relapse after ED discharge are common.Objective: To evaluate the adding of therapy with zafirlukast to standardized care for patients with acute asthma in the ED and a 28-day follow-up period.Design and Patients: A total of 641 patients presenting to the ED with acute asthma were randomized to receive either single-dose zafirlukast, 160 mg (Z160) [162 patients], zafirlukast, 20 mg (Z20) [158 patients]), or placebo (321 patients) as adjunct treatment to standard care in this double-blind, multicenter trial. Assessments, including spirometry and symptom scores, were obtained before each albuterol treatment and at 4 h. Patients who were discharged from the ED after 4 h continued outpatient therapy over a 28-day period and received either Z20 bid (276 patients) or placebo (270 patients) in addition to prednisone, albuterol, and their previous asthma medications. FEV(1) was measured at clinic visits on days 10 and 28. Patients recorded outpatient clinical data twice daily on a home diary card.Main Outcome Measures: the effect of zafirlukast on relapse after ED discharge. Other assessments were the rate of extended care (ie, ED stay for > 4 h or hospitalization), FEV(1), and symptoms.Results: At the end of the outpatient period, 65 of 276 patients (23.6%) treated with zafirlukast and 78 of 270 patients (28.9%) treated with placebo relapsed (p = 0.047; absolute reduction, 5.3%; relative reduction, 18.3%). At the end of the ED period, 16 of 162 patients (9.9%) treated with Z160, 26 of 158 patients (16.5%) treated with Z20, and 48 of 321 patients (15.0%) treated with placebo required extended care (p = 0.052; absolute reduction with Z160 compared to placebo, 5.1%; relative reduction, 34%). These findings were supported by a significant improvement in FEV(1) and dyspnea in the ED with the use of Z160 therapy, and by greater improvement in FEV(1) and symptoms during the outpatient period for patients treated with Z20.Conclusions: When added to standardized care, therapy with Z20 bid reduced the risk of relapse compared with placebo over a 28-day treatment period. One dose of Z160 in the ED also reduced the rate of extended care. [ABSTRACT FROM AUTHOR]

Objective: 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.Research Design and Methods: 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).Results: 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; P < 0.05).Conclusions: 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. [ABSTRACT FROM AUTHOR]

: PurposeTo 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.: MethodsThe 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).: ResultsThree-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.: ConclusionIn 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. [Copyright &y& Elsevier]

Presents a study that examined the effect of standard and high doses of epinephrine on coronary perfusion pressure (CPP) during cardiopulmonary resuscitation in patients whose cardiac arrest was refractory to advanced cardiac life support. Measurement of aortic and right atrial pressures; Background on epinephrine; Comparison of the effect of standard and high dose epinephrine on CPP in humans during cardiac arrest.

Evaluates the relationship between coronary perfusion pressure (CPP) and return of spontaneous circulation (RSOC) in humans during cardiopulmonary resuscitation and the usefulness of CPP as a predictor of ROSC. Measurement of CPP in patients with cardiac arrest; Comparison of CPP in patients with and without return of ROSC; Differences for the maximal aortic relaxation pressure, the compression-phase aortic-to-right atrial gradient and the arterial PO [sub 2].

Abstract: 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. [Copyright &y& Elsevier]