Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

Multiple Cardiac Biomarker Testing Among Patients With Acute Dyspnea From the ICON-RELOADED Study.

BACKGROUND: Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown. METHODS AND RESULTS: Concentrations of NT-proBNP, high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 were analyzed in 1448 patients presenting with acute dyspnea from the prospective, multicenter International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all 3 biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in 2 biomarkers (18.8%, 44 of 234), 1 biomarker (3.8%, 10 of 260), or no elevated biomarkers (0.4%, 2 of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite end point of mortality and HF rehospitalization. In adjusted models, patients with one, 2, and 3 elevated biomarkers had 3.74 (95% confidence interval [CI], 1.26-11.1, P = .017), 12.3 (95% CI, 4.60-32.9, P < .001), and 12.6 (95% CI, 4.54-35.0, P < .001) fold increased risk of 180-day mortality or HF rehospitalization. CONCLUSIONS: A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic, and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

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.

Outpatient versus observation/inpatient management of emergency department patients rapidly ruled-out for acute myocardial infarction: Findings from the HIGH-US study.

BACKGROUND: The actual Emergency Department (ED) dispositions of patients enrolled in observational studies and meeting criteria for rapid acute myocardial infarction (AMI) rule-out are unknown. Additionally, their presenting clinical profiles, cardiac testing/treatments received, and outcomes have not been reported. METHODS: Patients in the HIGH-US study (29 sites) that ruled-out for AMI using a high-sensitivity cardiac troponin I 0/1-hour algorithm were evaluated. Clinical characteristics of patients having ED discharge were compared to patients placed in observation or hospital admitted (OBS/ADM). Reports of any OBS/ADM cardiac stress test (CST), cardiac catheterization (Cath) and coronary revascularization were reviewed. One year AMI/death and major adverse cardiovascular event rates were determined. RESULTS: Of the 1,020 ruled-out AMI patients 584 (57.3%) had ED discharge. The remaining 436 (42.7%) were placed in OBS/ADM. Patients with risk factors for AMI, including personal or family history of coronary artery disease, hypertension, previous stroke or abnormal ECG were more often placed in OBS/ADM. 175 (40.1%) had a CST. Of these 32 (18.3%) were abnormal and 143 (81.7%) normal. Cath was done in 11 (34.3%) of those with abnormal and 13 (9.1%) with normal CST. Of those without an initial CST 85 (32.6%) had Cath. Overall, revascularizations were performed in 26 (6.0%) patients. One-year AMI/death rates were low/similar (P = .553) for the groups studied. CONCLUSIONS: Rapidly ruled-out for AMI ED patients having a higher clinician perceived risk for new or worsening coronary artery disease and placed in OBS/ADM underwent many diagnostic tests, were infrequently revascularized and had excellent outcomes. Alternate efficient strategies for these patients are needed.

Ideal high sensitivity troponin baseline cutoff for patients with renal dysfunction.

OBJECTIVE: High-sensitivity cardiac troponin assays (hs-cTn) aid in diagnosis of myocardial infarction (MI). These assays have lower specificity for non-ST Elevation MI (NSTEMI) in patients with renal disease. Our objective was to determine an optimized cutoff for patients with renal disease. METHODS: We conducted an a priori secondary analysis of a prospective FDA study in adults with suspected MI presenting to 29 academic urban EDs between 4/2015 and 4/2016. Blood was drawn 0, 1, 2-3, and 6-9 h after ED arrival. We recorded cTn and estimated glomerular filtrate rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration equation. The primary endpoint was NSTEMI (Third Universal Definition of MI), adjudicated by physicians blinded to hs-cTn results. We generated an adjusted hscTn rule-in cutoff to increase specificity. RESULTS: 2505 subjects were enrolled; 234 were excluded. Patients were mostly male (55.7%) and white (57.2%), median age was 56 years 472 patients [20.8%] had an eGFR <60 mL/min/1.73 m2. In patients with eGFR <15 mL/min/1.73 m2, a baseline rule-in cutoff of 120 ng/L led to a specificity of 85.0% and Positive Predictive Value (PPV) of 62.5% with 774 patients requiring further observation. Increasing the cutoff to 600 ng/L increased specificity and PPV overall and in every eGFR subgroup (specificity and PPV 93.3% and 78.9%, respectively for eGFR <15 mL/min/1.73m2), while increasing the number (79) of patients requiring observation. CONCLUSIONS: An eGFR-adjusted baseline rule-in threshold for the Siemens Atellica hs-cTnI improves specificity with identical sensitivity. Further study in a prospective cohort with higher rates of renal disease is warranted.

Performance of Novel High-Sensitivity Cardiac Troponin I Assays for 0/1-Hour and 0/2- to 3-Hour Evaluations for Acute Myocardial Infarction: Results From the HIGH-US Study.

STUDY OBJECTIVE: We determine the accuracy of high-sensitivity cardiac troponin I (hs-cTnI), European-derived, rapid, acute myocardial infarction, rule-out/rule-in algorithms applied to a US emergency department (ED) population. METHODS: Adults presenting to the ED with suspected acute myocardial infarction were included. Plasma samples collected at baseline and between 40 and 90 minutes and 2 and 3 hours later were analyzed in core laboratories using the Siemens Healthineers hs-cTnI assays. Acute myocardial infarction diagnosis was independently adjudicated. The sensitivity, specificity, and negative and positive predictive values for rapid acute myocardial infarction rule-out/rule-in using European algorithms and 30-day outcomes are reported. RESULTS: From 29 US medical centers, 2,113 subjects had complete data for the 0/1-hour algorithm analyses. With the Siemens Atellica Immunoassay hs-cTnI values, 1,065 patients (50.4%) were ruled out, with a negative predictive value of 99.7% and sensitivity of 98.7% (95% confidence interval 99.2% to 99.9% and 96.3% to 99.6%, respectively), whereas 265 patients (12.6%) were ruled in, having a positive predictive value of 69.4% and specificity of 95.7% (95% confidence interval 63.6% to 74.7% and 94.7% to 96.5%, respectively). The remaining 783 patients (37.1%) were classified as having continued evaluations, with an acute myocardial infarction incidence of 5.6% (95% confidence interval 4.2% to 7.5%). The overall 30-day risk of death or postdischarge acute myocardial infarction was very low in the ruled-out patients but was incrementally increased in the other groups (rule-out 0.2%; continued evaluations 2.1%; rule-in 4.8%). Equivalent results were observed in the 0/2- to 3-hour analyses and when both algorithms were applied to the hs-cTnI ADVIA Centaur measurements. CONCLUSION: The European rapid rule-out/rule-in acute myocardial infarction algorithm hs-cTnI cut points can be harmonized with a demographically and risk-factor diverse US ED population.

Ultrarapid Rule-out for Acute Myocardial Infarction Using the Generation 5 Cardiac Troponin T Assay: Results From the REACTION-US Study.

STUDY OBJECTIVE: We determine how well a new Food and Drug Administration-approved single cardiac troponin T (cTnT) Generation 5 baseline measurement below the level of quantification (6 ng/L) and a novel study-derived baseline and 30-minute cTnT Generation 5 algorithm might adequately exclude acute myocardial infarction in patients with suspected acute coronary syndrome in a US emergency department (ED). METHODS: Patients presenting with any symptoms suspicious for acute coronary syndrome were enrolled at a single US ED. Baseline and 30-minute blood samples were obtained and cTnT Generation 5 levels were later batch analyzed in an independent core laboratory. Acute myocardial infarction diagnosis was adjudicated by a cardiologist and an emergency physician. RESULTS: Of the 569 study patients, 44 (7.7%) had an acute myocardial infarction diagnosis. One hundred sixty-four patients (28.8%) had a presentation cTnT Generation 5 level less than 6 ng/L, and none of these individuals had an acute myocardial infarction (negative predictive value of 100% [95% confidence interval 97.8% to 100.0%] and sensitivity of 100% [95% confidence interval 92.0% to 100.0%]). A baseline cTnT Generation 5 value of less than 8 ng/L and a 30-minute Δ of less than 3 ng/L were present in 221 patients (41.0%), and none had acute myocardial infarction (negative predictive value of 100% [95% confidence interval 98.3% to 100.0%] and sensitivity of 100% [95% confidence interval 92.0% to 100.0%]). CONCLUSION: In a single US ED, a single baseline cTnT Generation 5 measurement less than 6 mg/L and values at baseline less than 8 ng/L and a 30-minute Δ of less than 3 ng/L ruled out acute myocardial infarction in 28.8% and 41.0% of patients, respectively. Additional multicenter US studies evaluating these ultrarapid acute myocardial infarction rule-out guidelines are needed, especially to narrow the confidence intervals.

Differentiating type 1 and 2 acute myocardial infarctions using the N-terminal pro B-type natriuretic peptide/cardiac troponin T ratio.

PURPOSE: Differentiation of type 1 (T1MI) from type 2 myocardial infarction (T2MI) is important as recommended treatments for each differ. Patients with T2MI may have more/earlier cardiac wall stress resulting in an increased N-terminal pro B-type natriuretic peptide (NT-proBNP)/cTnT generation 5 ratio (cTnT Gen 5). METHODS: Emergency Department (ED) patients presenting with symptoms suspicious for acute coronary syndrome (ACS) were enrolled from 2013 to 2015. Baseline blood samples were collected within 60 min of a triage ECG, with additional draws at 30, 60 and 180 min. NT-proBNP and cTnT Gen 5 levels were measured later in an independent laboratory. Acute myocardial infarction (AMI) was adjudicated using the Third Universal Definition of Myocardial Infarction. RESULTS: 575 patients were enrolled with 44 (7.7%) having AMI [25 T1MI (59.1%) and 18 T2MI (40.9%)]. Patient characteristics showed very few AMI type differences so accurate clinical differentiation was difficult. The median NT-proBNP/cTnT Gen 5 ratios were significantly higher in T2MI when compared to T2MI at baseline and 30, 60 and 180 min later [7.3 v 53.0 (p = 0.003), 5.8 v 49.5 (p = 0.002), 6.3 v 47.5 (p = 0.003) and 4.3 v 33.7 (p = 0.016) respectively]. CONCLUSIONS: The clinical determination of whether an AMI is type 1 or 2 is difficult as the ED patient characteristics of each are similar. The NT-proBNP/cTnT Gen 5 ratio can aid in making this differentiation. Additional multicenter trials are needed to validate our results.

Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study.

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.

Presenting phenotypes of acute heart failure patients in the ED: Identification and implications.

BACKGROUND: There is little known about the baseline hemodynamic (HD) profiles (beyond pulse/blood pressure) of patients presenting to the Emergency department (ED) with acute heart failure (AHF). Assessing these baseline parameters could help differentiate underlying HD phenotypes which could be used to develop specific phenotypic specific approaches to patient care. METHODS: Patients with suspected AHF were enrolled in the PREMIUM (Prognostic Hemodynamic Profiling in the Acutely Ill Emergency Department Patient) multinational registry and continuous HD monitoring was initiated on ED presentation using noninvasive finger cuff technology (Nexfin, BMEYE, Edwards Lifesciences, Irvine, California). Individuals with clinically suspected and later confirmed AHF were included in this analysis and initial 15minute averages for available HD parameters were calculated. K-means clustering was performed to identify out of 23 HD variables a set that provided the greatest level of inter-cluster discrimination and intra-cluster cohesions. RESULTS: A total of 127 patients had confirmed AHF. The final model, using mean normalized patient baseline HD values was able to differentiate these individuals into 3 distinct phenotypes. Cluster 1: normal cardiac index (CCI) and systemic vascular resistance index (SVRI); cluster 2: very low CI and markedly increased SVRI: and cluster 3: low CI and an elevated SVRI. These clusters were not differentiated using clinically available ED information. CONCLUSIONS: Three distinct clusters were defined using novel noninvasive presenting HD monitoring technology in this cohort of ED AHF patients. Further studies are needed to determine whether phenotypic specific therapies based on these clusters can improve outcomes.

Hemodynamic characteristics of suspected stroke in the emergency department.

BACKGROUND: Systemic hemodynamic characteristics of patients with suspected acute ischemic stroke are poorly described. The objective of this study was to identify baseline hemodynamic characteristics of emergency department (ED) patients with suspected acute stroke. METHODS: This was a planned analysis of the stroke cohort from a multicenter registry of hemodynamic profiling of ED patients. The registry prospectively collected non-invasive hemodynamic measurements of patients with suspicion for acute stroke within 12h of symptom onset. K-means cluster analysis identified hemodynamic phenotypes of all suspected stroke patients, and we performed univariate hemodynamic comparisons based on final diagnoses. RESULTS: There were 72 patients with suspected acute stroke, of whom 38 (53%) had a final diagnosis of ischemic stroke, 10 (14%) had hemorrhagic stroke, and 24 (33%) had transient ischemic attack (TIA). Analysis defined three phenotypic clusters based on low or normal cardiac index (CI) and normal or high systemic vascular resistance index (SVRI). Patients with TIA had lower mean CI (2.3L/min/m2) compared to hemorrhagic or ischemic stroke patients (p<0.01). CONCLUSIONS: The study demonstrates the feasibility of defining hemodynamic phenotypes of ED patients with suspected stroke.

Necessity of hospitalization and stress testing in low risk chest pain patients.

BACKGROUND: Copeptin is a marker of endogenous stress including early myocardial infarction(MI) and has value in early rule out of MI when used with cardiac troponin I(cTnI). OBJECTIVES: The goal of this study was to demonstrate that patients with a normal electrocardiogram and cTnI<0.040µg/l and copeptin<14pmol/l at presentation and after 2 h may be candidates for early discharge with outpatient follow-up potentially including stress testing. METHODS: This study uses data from the CHOPIN trial which enrolled 2071 patients with acute chest pain. Of those, 475 patients with normal electrocardiogram and normal cTnI(<0.040µg/l) and copeptin<14pmol/l at presentation and after 2 h were considered "low risk" and selected for further analysis. RESULTS: None of the 475 "low risk" patients were diagnosed with MI during the 180day follow-up period (including presentation). The negative predictive value of this strategy was 100% (95% confidence interval(CI):99.2%-100.0%). Furthermore no one died during follow up. 287 (60.4%) patients in the low risk group were hospitalized. In the "low risk" group, the only difference in outcomes (MI, death, revascularization, cardiac rehospitalization) was those hospitalized underwent revascularization more often (6.3%[95%CI:3.8%-9.7%] versus 0.5%[95%CI:0.0%-2.9%], p=.002). The hospitalized patients were tested significantly more via stress testing or angiogram (68.6%[95%CI:62.9%-74.0%] vs 22.9%[95%CI:17.1%-29.6%], p<.001). Those tested had less cardiac rehospitalizations during follow-up (1.7% vs 5.1%, p=.040). CONCLUSIONS: In conclusion, patients with a normal electrocardiogram, troponin and copeptin at presentation and after 2 h are at low risk for MI and death over 180days. These low risk patients may be candidates for early outpatient testing and cardiology follow-up thereby reducing hospitalization.

Presenting hemodynamic phenotypes in ED patients with confirmed sepsis.

OBJECTIVES: To derive distinct clusters of septic emergency department (ED) patients based on their presenting noninvasive hemodynamic (HD) measurements and to determine if any clinical parameters could identify these groups. METHODS: Prospective, observational, convenience study of individuals with confirmed systemic infection. Presenting, pretreatment noninvasive HD parameters were compiled using Nexfin (Bmeye/Edwards LifeSciences) from 127 cases. Based on normalized parameters, k-means clustering was performed to identify a set of variables providing the greatest level of intercluster discrimination and intracluster cohesion. RESULTS: Our best HD clustering model used 2 parameters: the cardiac index (CI [L/min per square meter]) and systemic vascular resistance index (SVRI [dynes·s/cm5 per square meter]). Using this model, 3 different patient clusters were identified. Cluster 1 had high CI with normal SVRI (CI, 4.03 ± 0.61; SVRI, 1655.20 ± 348.08); cluster 2 low CI with increased vascular tone (CI, 2.50 ± 0.50; SVRI, 2600.83 ± 576.81); and cluster 3 very low CI with markedly elevated SVRI (CI, 1.37 ± 0.81; SVRI, 5951.49 ± 1480.16). Cluster 1 patients had the lowest 30-day overall mortality. Among clinically relevant variables available during the initial patient evaluation in the ED age, heart rate and temperature were significantly different across the 3 clusters. CONCLUSIONS: Emergency department patients with confirmed sepsis had 3 distinct cluster groupings based on their presenting noninvasively derived CI and SVRI. Further clinical studies evaluating the effect of early cluster-specific therapeutic interventions are needed to determine if there are outcome benefits of ED HD phenotyping in these patients.

Serial sampling of copeptin levels improves diagnosis and risk stratification in patients presenting with chest pain: results from the CHOPIN trial.

BACKGROUND: Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combination with a negative troponin. However, management of patients with chest pain with a positive copeptin in the setting of a negative troponin is unclear. METHODS: The multicentre CHOPIN trial enrolled 2071 patients with acute chest pain. Of these, 476 subjects with an initial negative troponin but an elevated copeptin (>14 pmol/L) were included in this study. Copeptin and troponin levels were rechecked at 2 h and the final diagnosis of AMI was made by two independent, blinded cardiologists. Follow-up at 30 days was obtained for major adverse cardiac events (MACEs), including death, AMI and urgent revascularisation. RESULTS: Of the 476 patients analysed, 365 (76.7%) had a persistently elevated copeptin at 2 h and 111 patients (23.3%) had a copeptin that fell below the cut-off of 14 pmol/L. When the second copeptin was elevated there were 18 AMIs (4.9%) compared with 0 (0%) when the second copeptin was negative (p=0.017), yielding a negative predictive value of 100% (95% CI 96.7% to 100%). On 30-day follow-up there were 36 MACEs (9.9%) in the positive second copeptin group and 2 (1.8%) MACEs in the negative second copeptin group (p=0.006). CONCLUSIONS: Patients with chest pain with an initial negative troponin but positive copeptin are common and carry an intermediate risk of AMI. A second copeptin drawn 2 h after presentation may help risk stratify and potentially rule out AMI in this cohort.

A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma.

BACKGROUND: Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations. METHODS: In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year. Subjects received 1 intravenous infusion of placebo (n = 38) or benralizumab (0.3 mg/kg, n = 36 or 1.0 mg/kg, n = 36) added to outpatient management. The primary outcome was the proportion of subjects with greater than or equal to 1 exacerbation at 12 weeks in placebo vs the combined benralizumab groups. Other outcomes included the time-weighted rate of exacerbations at week 12, adverse events, blood eosinophil counts, asthma symptom changes, and health care resource utilization. RESULTS: The proportion of subjects with greater than or equal to 1 asthma exacerbation at 12 weeks was not different between placebo and the combined benralizumab groups (38.9% vs 33.3%; P = .67). However, compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P = .01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P = .02) in the combined groups. Benralizumab reduced blood eosinophil counts but did not affect other outcomes, while demonstrating an acceptable safety profile. CONCLUSIONS: When added to usual care, 1 dose of benralizumab reduced the rate and severity of exacerbations experienced over 12 weeks by subjects who presented to the ED with acute asthma.

Anticoagulant-induced hemarthrosis presenting as anterior shoulder dislocation.

This is a case of nontraumatic shoulder pain initially diagnosed on x-ray as an anterior dislocation. The patient was on anticoagulants and, in actuality, had severe hemarthrosis that caused the subluxation. Attempts to reduce the dislocation in this situation might have resulted in worsening of the intra-articular bleed. There has been only 1 similar reported case in the European Journal of Emergency Medicine in 2013 of a 53-year-old woman who was thought to have a nontraumatic anterior shoulder dislocation, and attempts were unsuccessful at reduction. Definitive therapy involved hemarthrosis aspiration. Others have reported spontaneous hemarthrosis due to anticoagulants; however, only 1 has reported an initial mistaken joint dislocation diagnosis. Nontraumatic hemarthrosis do occur in patients on anticoagulant therapy, and it is important to recognize that this can be misdiagnosed as a joint dislocation requiring reduction. In a patient who is on anticoagulants presenting with nontraumatic joint pain and anterior shoulder or possibly other dislocations on plain radiographs, it is pertinent to consider hemarthrosis.