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Background: Emergency department (ED) presentations after a ground-level fall (GLF) are common. Falls were suggested to be another possible presenting feature of a myocardial infarction (MI), as unrecognized MIs are common in older adults. Elevated high-sensitivity cardiac troponin (hs-cTn) concentrations could help determine the etiology of a GLF in ED. We investigated the prevalence of both MI and elevated high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), as well as the diagnostic accuracy of hs-cTnT and hs-cTnI regarding MI, and their prognostic value in older ED patients presenting after a GLF., Methods: This was a prospective, international, multicenter, cohort study with a follow-up of up to 1 year. Patients aged 65 years or older presenting to the ED after a GLF were prospectively enrolled. Two outcome assessors independently reviewed all discharge records to ascertain final gold standard diagnoses. Hs-cTnT and hs-cTnI levels were determined from thawed samples for every patient., Results: In total, 558 patients were included. Median (IQR) age was 83 (77-89) years, and 67.7% were female. Elevated hs-cTnT levels were found in 384 (68.8%) patients, and elevated hs-cTnI levels in 86 (15.4%) patients. Three patients (0.5%) were ascertained the gold standard diagnosis MI. Within 30 days, 18 (3.2%) patients had died. Nonsurvivors had higher hs-cTnT and hs-cTnI levels compared with survivors (hs-cTnT 40 [23-85] ng/L in nonsurvivors and 20 [13-33] ng/L in survivors; hs-cTnI 25 [14-54] ng/L in nonsurvivors and 8 [4-16] ng/L in survivors; p < 0.001 for both)., Conclusions: A majority of patients (n = 364, 68.8%) presenting to the ED after a fall had elevated hs-cTnT levels and 86 (15.4%) elevated hs-cTnI levels. However, the incidence of MI in these patients was low (n = 3, 0.5%). Our data do not support the opinion that falls may be a common presenting feature of MI. We discourage routine troponin testing in this population. However, hs-cTnT and hs-cTnI were both found to have prognostic properties for mortality prediction up to 1 year., (© 2024 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Background: Cognitive impairment (CI) is common among older patients presenting to the emergency department (ED). The failure to recognize CI at ED presentation constitutes a high risk of additional morbidity, mortality, and functional decline. The Clock Drawing Test (CDT) is a well-established cognitive screening test., Aim: In patients presenting to the ED with non-specific complaints (NSCs), we aimed to investigate the usability of the CDT and its prognostic value regarding length of hospital stay (LOS) and mortality., Method: Secondary analysis of the Basel Non-specific Complaints (BANC) trial, a prospective delayed type cross-sectional study with a 30-day follow-up. In three EDs, patients presenting with NSCs were enrolled. The CDT was administered at enrollment., Results: In the 1,278 patients enrolled, median age was 81 [74, 87] years and 782 were female (61.19%). A valid CDT was obtained in 737 (57.7%) patients. In patients without a valid CDT median LOS was higher (29 [9, 49] days vs. 22 [9, 45] days), and 30-day mortality was significantly higher than in patients with a valid CDT (n = 45 (8.32%) vs. n = 39 (5.29%)). Of all valid CDTs, 154 clocks (20.9%) were classified as normal, 55 (7.5%) as mildly deficient, 297 (40.3%) as moderately deficient, and 231 (31.3%) as severely deficient. Mortality and LOS increased along with the CDT deficits (p = 0.012 for 30-day mortality; p < 0.001 for LOS)., Conclusion: The early identification of patients with CI may lead to improved patient management and resource allocation. The CDT could be used as a risk stratification tool for older ED patients presenting with NSCs, as it is a predictor for 30-day mortality and LOS., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED)., Methods: The PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning., Discussion: The PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful. The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance., Trial Registration: This study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406., Trial Status: Recruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023., (© 2024. The Author(s).)

Background: Adequate management is crucial to reduce symptoms, hospitalization, and relapses in patients with asthma. Hospitals often struggle to meet treatment guidelines, and no recent data for Switzerland are available., Objectives: The aim of the study was to audit the asthma exacerbation management in the Cantonal Hospital of Baselland in order to evaluate the level of compliance with guidelines in a narrative discussion., Method: The study design is a retrospective observational cohort study. We evaluated all adult patients presenting to the hospital with a physician-diagnosed asthma exacerbation in 2018 and 2019. The asthma management patients received was compared to the Swiss guidelines and the international GINA guidelines., Results: 160 patients were included (mean age: 50 years old, 57.5% female). SpO2 and heart rate were assessed at presentation in nearly all patients. Peak expiratory flow (PEF) was measured in only 14%. Adequate management of asthma exacerbation with inhaled bronchodilator medication in a combination of short-acting beta-agonists and short-acting anticholinergics was administered to 96% of the patients. Patients with severe symptoms received systemic glucocorticosteroids within 6 h in 55%. At discharge, a reliever medication was prescribed for 64% of the patients and 55% received a new or increased controller therapy with inhaled glucocorticosteroid (ICS). 49% of the patients had no follow-up organized., Conclusion: To increase the guideline conformity and quality of asthma exacerbation management, the severity should be better assessed, especially by routinely performing PEF measurements. Treatment needs to be intensified; in particular, the ICS dose should be increased significantly and systemic glucocorticosteroids should be given with a lower threshold., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Aims: To directly compare the diagnostic accuracy of high-sensitivity cardiac troponin (hs-cTn) T vs. hs-cTnI in the early non-invasive differentiation of Type 1 myocardial infarction (T1MI) due to plaque rupture and atherothrombosis from Type 2 myocardial infarction (T2MI) due to supply-demand mismatch., Methods and Results: In a prospective multicentre diagnostic study, two independent cardiologists centrally adjudicated the final diagnosis of T1MI vs. T2MI according to the fourth universal definition of myocardial infarction (MI), using all available clinical information including cardiac imaging in patients presenting with acute chest pain. Diagnostic accuracy was quantified by the area under the receiver operating characteristics curve (AUC). The most extensively validated hs-cTnT-Elecsys and hs-cTnI-Architect assays were measured at presentation, 1 h, and 2 h. Among 5887 patients, 1106 (19%) had a final diagnosis of MI, including 860 (78%) T1MI and 246 (22%) T2MI. The AUC of hs-cTnT-Elecsys to differentiate T1MI from T2MI was moderate and comparable to that provided by hs-cTnI-Architect: hs-cTnT-Elecsys AUC-presentation 0.67 [95% confidence interval (CI) 0.64-0.71], AUC-1 h 0.70 (95% CI 0.66-0.74), and AUC-2 h 0.71 (95% CI 0.66-0.75) vs. hs-cTnI-Architect AUC-presentation 0.71 (95% CI 0.67-0.74), AUC-1 h 0.72 (95% CI 0.68-0.76), and AUC-2 h 0.74 (95% CI 0.69-0.78), all P = not significant (NS). Similarly, the AUC of absolute changes was moderate and comparable for hs-cTnT-Elecsys and hs-cTnI-Architect (all P = NS). Cut-off concentrations achieving at least 90% specificity for the differentiation of T1MI vs. T2MI were >114 ng/L for hs-cTnT-Elecsys [odds ratio (OR) 4.2, 95% CI 2.7-6.6] and >371 ng/L for hs-cTnI-Architect (OR 4.0, 95% CI 2.6-6.2)., Conclusion: hs-cTnT-Elecsys and hs-cTnI-Architect provided comparable, albeit only moderate, diagnostic accuracy for the early differentiation of T1MI vs. T2MI., Clinical Trial Registration: ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objective: To develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years., Methods: In a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients., Results: In the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance., Conclusion: In patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause., Trial Registration Number: NCT01548352 (BASEL IX), NCT01802398 (SRS study)., Competing Interests: Competing interests: The authors designed the study, gathered and analysed the data, vouch for the data and analysis, wrote the paper and decided to publish. TZ, JD and CM had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors have read and approved the manuscript. The sponsors had no role in designing or conducting the study and no role in gathering or analysing the data or writing the manuscript. The manuscript and its contents have not been published previously and are not being considered for publications elsewhere in whole or in part in any language, including publicly accessible websites or e-print servers. TZ has received research support from the Freiwillige Akademische Gesellschaft Basel (Switzerland). JEW reports a research grant from the Swiss Heart Foundation, the Swiss Academy of Medical Sciences and the Bangerter Foundation (YTCR 23/17). PB has received research funding from the University of Basel, the "Stiftung für Herzschrittmacher und Elektrophysiologie" and the Freiwillige Akademische Gesellschaft Basel. LC reports grants and personal fees from Abbott Diagnostics, grants and personal fees from Beckman Coulter, grants and personal fees from Siemens, outside the submitted work. MT reports grants and personal fees from Abbott, grants and personal fees from Alere, grants from Beckman, grants and personal fees from Roche, outside the submitted work. FJM-S received speaker, advisory or consulting fees from Novartis, MSD, Bristol-Myers Squibb, Pfizer, The Medicine Company, Otsuka, Thermo Fisher, Cardiorentis, Sanofi, and research grants from the Spanish Ministry of Health and FEDER, Mapfre, Novartis, Bayer, MSD, Abbot and Orion-Pharma, outside the submitted work. WFP reports research grants from Abbott, Braincheck, Immunarray, Janssen, Roche and ZS Pharma, having served as a consultant for Abbott, AstraZeneca, Bayer, Beckman, Boehrhinger-Ingelheim, Ischemia Care, Dx, Immunarray, Instrument Labs, Janssen, Ortho Clinical Diagnostics, Relypsa, Roche and Siemens, having provided expert testimony for Johnson and Johnson, and having ownership interests in Comprehensive Research Associates, and Emergencies in Medicine, Ischemia DX. MK reports personal fees from Bayer, personal fees from Daiichi-Sankyo, personal fees from Pfizer-BMS, personal fees from Böhringer-Ingelheim, outside the submitted work. TR has received research grants from the Goldschmidt-Jacobson Foundation, the Swiss National Science Foundation (PASMP3-136995), the Swiss Heart Foundation, the Professor Max Cloëtta Foundation, the University of Basel and the University Hospital Basel as well as speaker honoraria from Abbott, Bayer, Biosense, Brahms, Medtronic, Pfizer-BMS and Roche. BS has received consulting honoraria from Medtronic, outside the submitted work. CM has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the KTI, the Cardiovascular Research Foundation Basel, the University Basel, the University Hospital Basel, Abbott, AstraZeneca, Beckman Coulter, BRAHMS, Critical Diagnostics, Idorsia, Novartis, Ortho Clinical Diagnostics, Roche, Sanofi, Siemens and Singulex, as well as speaker/consulting honoraria or travel support from Acon, Amgen, Bayer, BMS, Boehringer Ingelheim, Idorsia, Medtronic, Novartis, Osler, Roche, Sanofi, Siemens and Singulex., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The diagnosis of cardiac syncope remains a challenge in the emergency department (ED)., Objective: Assessing the diagnostic accuracy of the early standardized clinical judgement (ESCJ) including a standardized syncope-specific case report form (CRF) in comparison with a recommended multivariable diagnostic score., Methods: In a prospective international observational multicentre study, diagnostic accuracy for cardiac syncope of ESCJ by the ED physician amongst patients ≥ 40 years presenting with syncope to the ED was directly compared with that of the Evaluation of Guidelines in Syncope Study (EGSYS) diagnostic score. Cardiac syncope was centrally adjudicated independently of the ESCJ or conducted workup by two ED specialists based on all information available up to 1-year follow-up. Secondary aims included direct comparison with high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) concentrations and a Lasso regression to identify variables contributing most to ESCJ., Results: Cardiac syncope was adjudicated in 252/1494 patients (15.2%). The diagnostic accuracy of ESCJ for cardiac syncope as quantified by the area under the curve (AUC) was 0.87 (95% CI: 0.84-0.89), and higher compared with the EGSYS diagnostic score (0.73 (95% CI: 0.70-0.76)), hs-cTnI (0.77 (95% CI: 0.73-0.80)) and BNP (0.77 (95% CI: 0.74-0.80)), all P < 0.001. Both biomarkers (alone or in combination) on top of the ESCJ significantly improved diagnostic accuracy., Conclusion: ESCJ including a standardized syncope-specific CRF has very high diagnostic accuracy and outperforms the EGSYS score, hs-cTnI and BNP., (© 2021 Association for Publication of The Journal of Internal Medicine.)

Aims: The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE)., Methods and Results: We characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18-22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11-2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54-2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified >3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64-2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26-2.77) and MACE (HR 2.69, 95% CI 2.02-3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation., Conclusion: Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE., Trial Registration: BAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Recent advances in digital electrocardiography technology allow evaluating ST-segment deviations in all 12 leads as quantitative variables and calculating summed ST-segment deviation scores. The diagnostic and prognostic utility of summed ST-segment deviation scores is largely unknown., Methods: We aimed to explore the diagnostic and prognostic utility of the conventional and the modified ST-segment deviation score (Better Analysis of ST-segment Elevations and Depressions in a 12- Lead-ECG-Score (BASEL-Score): sum of elevations in the augmented voltage right - lead (aVR) plus absolute, unsigned ST-segment depressions in the remaining leads) in patients presenting with suspected non-ST-segment elevation myocardial infarction. The diagnostic endpoint was non-ST-segment elevation myocardial infarction, adjudicated by two independent cardiologists. Prognostic endpoint was mortality during two-year follow up., Results: Among 1330 patients, non-ST-segment elevation myocardial infarction was present in 200 (15%) patients. Diagnostic accuracy for non-ST-segment elevation myocardial infarction as quantified by the area under the receiver-operating-characteristics curve was significantly higher for the BASEL-Score (0.73; 95% confidence interval 0.69-0.77) as compared to the conventional ST-segment deviation score (0.53; 95% confidence interval 0.49-0.57, p <0.001). The BASEL-Score provided additional independent diagnostic value to dichotomous electrocardiogram variables (ST-segment depression, T-inversion, both p <0.001) and to high-sensitivity cardiac troponin ( p <0.001) as well as clinical judgment at 90 min ( p <0.001). Similarly, only the BASEL-Score proved to be an independent predictor of two year mortality., Conclusions: The modified ST-segment deviation score BASEL-Score focusing on ST-segment elevation in aVR and ST-segment depressions in the remaining leads provides incremental diagnostic and prognostic information.

Background: We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS ® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay., Methods: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm., Results: AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93-0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92-0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90-0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94-0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1-100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect., Conclusions: The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays., Clinicaltrialsgov Identifier: NCT00470587., (© 2019 American Association for Clinical Chemistry.)

Background: Rapid and reliable diagnosis of ST-elevation myocardial infarction (STEMI) as a surrogate for acute coronary occlusion is critical for early reperfusion therapy., Objectives: We aimed to examine the diagnostic performance of current guideline-recommended Electrocardiogram (ECG) STEMI criteria., Methods: In a prospective diagnostic multicenter study, we objectively quantified the extent of ST-segment elevation in all ECG leads using an automated software-based analysis of the digital 12-lead-ECG in adult patients presenting to the emergency department (ED) with suspected myocardial infarction (MI). Classification according to current guideline-recommended ECG criteria for STEMI at ED presentation was compared against a final diagnosis adjudicated by two independent cardiologists after reviewing all available medical records including serial ECGs, cardiac imaging and coronary angiograms., Results: Among 2486 patients, 52 (2%) were found to have significant ST-segment elevation on ECG at ED presentation according to current guideline-recommended ECG criteria for STEMI. Eighty-one (3%) patients received a final adjudicated diagnosis of STEMI. Only 35% (28 of 81) of all patients with a final diagnosis of STEMI were correctly identified (PPV 54% (95% CI 41-66%), sensitivity 35% (95% Cl 24-46%), NPV 97.8% (95% CI 97.5-98.1%). Four reasons for missing STEMIs emerged: timing (significant STE at an earlier/later time point) in 25%, incorrect measurement points in 30%, non or borderline-significant STE in 36% and inferoposterior MI localisation in 9%., Conclusions: A computerized analysis of current guideline-recommended ECG criteria for STEMI showed suboptimal diagnostic performance when applied to a single 12‑lead ECG performed at ED presentation., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Early and accurate detection of short-term major adverse cardiac events (MACE) in patients with suspected acute myocardial infarction (AMI) is an unmet clinical need., Objectives: The goal of this study was to test the hypothesis that adding clinical judgment and electrocardiogram findings to the European Society of Cardiology (ESC) high-sensitivity cardiac troponin (hs-cTn) measurement at presentation and after 1 h (ESC hs-cTn 0/1 h algorithm) would further improve its performance to predict MACE., Methods: Patients presenting to an emergency department with suspected AMI were enrolled in a prospective, multicenter diagnostic study. The primary endpoint was MACE, including all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days including index events. The secondary endpoint was MACE + unstable angina (UA) receiving early (≤24 h) revascularization., Results: Among 3,123 patients, the ESC hs-cTnT 0/1 h algorithm triaged significantly more patients toward rule-out compared with the extended algorithm (60%; 95% CI: 59% to 62% vs. 45%; 95% CI: 43% to 46%; p < 0.001), while maintaining similar 30-day MACE rates (0.6%; 95% CI: 0.3% to 1.1% vs. 0.4%; 95% CI: 0.1% to 0.9%; p = 0.429), resulting in a similar negative predictive value (99.4%; 95% CI: 98.9% to 99.6% vs. 99.6%; 95% CI: 99.2% to 99.8%; p = 0.097). The ESC hs-cTnT 0/1 h algorithm ruled-in fewer patients (16%; 95% CI: 14.9% to 17.5% vs. 26%; 95% CI: 24.2% to 27.2%; p < 0.001) compared with the extended algorithm, albeit with a higher positive predictive value (76.6%; 95% CI: 72.8% to 80.1% vs. 59%; 95% CI: 55.5% to 62.3%; p < 0.001). For 30-day MACE + UA, the ESC hs-cTnT 0/1 h algorithm had a higher positive predictive value for rule-in, whereas the extended algorithm had a higher negative predictive value for the rule-out. Similar findings emerged when using hs-cTnI., Conclusions: The ESC hs-cTn 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, whereas the extended algorithm is the preferred option for the rule-out of 30-day MACE + UA. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587)., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Background: The prevalence of pulmonary embolism (PE) in patients presenting with syncope to the emergency department (ED) is largely unknown. This information, however, is necessary to balance the potential medical benefit or harm of systematic PE screening in patients presenting with syncope to the ED., Objectives: This study sought to determine the prevalence of PE in patients with syncope., Methods: Unselected patients presenting with syncope to the ED were prospectively enrolled in a diagnostic multicenter study. Pre-test clinical probability for PE was assessed using the 2-level Wells score and the results of D-dimer testing using age-adapted cutoffs. Presence of PE was evaluated by imaging modalities, when ordered as part of the clinical assessment by the treating ED physician or by long-term follow-up data., Results: Long-term follow-up was complete in 1,380 patients (99%) at 360 days and 1,156 patients (83%) at 720 days. Among 1,397 patients presenting with syncope to the ED, PE was detected at presentation in 19 patients (1.4%; 95% confidence interval [CI]: 0.87% to 2.11%). The incidence of new PEs or cardiovascular death during 2-year follow-up was 0.9% (95% CI: 0.5% to 1.5%). In the subgroup of patients hospitalized (47%), PE was detected at presentation in 15 patients (2.3%; 95% CI: 1.4% to 3.7%). The incidence of new PEs or cardiovascular death during 2-year follow-up was 0.9% (95% CI: 0.4% to 2.0%)., Conclusions: PE seems to be a rather uncommon cause of syncope among patients presenting to the ED. Therefore, systematic PE-screening in all patients with syncope does not seem warranted. (BAsel Syncope EvaLuation Study [BASEL IX]; NCT01548352)., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Older patients frequently present to the emergency department (ED) with nonspecific complaints (NSC), such as generalized weakness. They are at risk of adverse outcomes, and early risk stratification is crucial. Triage using Emergency Severity Index (ESI) is reliable and valid, but older patients are prone to undertriage, most often at decision point D. The aim of this study was to assess the predictive power of additional clinical parameters in NSC patients., Methods: Baseline demographics, vital signs, and deterioration of activity of daily living (ADL) in patients with NSC were prospectively assessed at four EDs. Physicians scored the coherence of history and their first impression. For prediction of 30-day mortality, we combined vital signs at decision point D (heart rate, respiratory rate, oxygen saturation) as "ESI vital," and added "ADL deterioration," "incoherence of history," or "first impression," using logistic regression models., Results: We included 948 patients with a median age of 81 years, 62% of whom were female. The baseline parameters at decision point D (ESI vital) showed an area under the curve (AUC) of 0.64 for predicting 30-day mortality in NSC patients. AUCs increased to 0.67 by adding ADL deterioration to 0.66 by adding incoherence of history, and to 0.71 by adding first impression. Maximal AUC was 0.73, combining all parameters., Conclusion: Adding the physicians' first impressions to vital signs at decision point D increases predictive power of 30-day mortality significantly. Therefore, a modified ESI could improve predictive power of triage in older patients presenting with NSCs., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Background: The utility of BNP (B-type natriuretic peptide), NT-proBNP (N-terminal proBNP), and hs-cTn (high-sensitivity cardiac troponin) concentrations for diagnosis and risk-stratification of syncope is incompletely understood., Methods: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against those of clinical assessments, in patients >45-years old presenting with syncope to the emergency department in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by 2 physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic end point. EGSYS (Evaluation of Guidelines in Syncope Study), a syncope-specific diagnostic score, served as the diagnostic comparator. Death and major adverse cardiac events at 30 and 720 days were the prognostic end points. Major adverse cardiac events were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding, or valvular surgery. ROSE (Risk Stratification of Syncope in the Emergency Department), OESIL (Osservatorio Epidemiologico della Sincope nel Lazio), SFSR (San Fransisco Syncope Rule), and CSRS (Canadian Syncope Risk Score) served as the prognostic comparators., Results: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope versus other causes ( P <0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve, was 0.77 to 0.78 (95% CI, 0.74-0.81) for all 4 biomarkers, and superior to EGSYS (area under the curve, 0.68 [95%-CI 0.65-0.71], P <0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an area under the curve of 0.81 ( P <0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving predefined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ≈30% of all patients. A total of 450 major adverse cardiac events occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for major adverse cardiac events was moderate-to-good (area under the curve, 0.75-0.79), superior to ROSE, OESIL, and SFSR, and inferior to CSRS., Conclusions: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in emergency department patients with syncope., Clinical Trial Registration: URL: https://www., Clinicaltrials: gov. Unique identifier: NCT01548352.

Background: The clinical availability of high-sensitivity cardiac troponin (hs-cTn) has enabled the development of several innovative strategies for the rapid rule-out of acute myocardial infarction (AMI). Due to the lack of direct comparisons, selection of the best strategy for clinical practice is challenging., Methods: In a prospective international multicenter diagnostic study enrolling 3696 patients presenting with suspected AMI to the emergency department, we compared the safety and efficacy of 14 different hs-cTn-based strategies: hs-cTn concentrations below the limit of detection (LoD), dual-marker combining hs-cTn with copeptin, ESC 0 h/1 h-algorithm, 0 h/2 h-algorithm, 2 h-ADP-algorithm, NICE-algorithm, and ESC 0 h/3 h-algorithm, each using either hs-cTnT or hs-cTnI. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations., Results: AMI was the final diagnosis in 16% of patients. Using hs-cTnT, safety quantified by the negative predictive value (NPV) and sensitivity was very high (99.8-100% and 99.5-100%) and comparable for all strategies, except the dual-marker approach (NPV 98.7%, sensitivity 96.7%). Similarly, using hs-cTnI, safety quantified by the NPV and sensitivity was very high (99.7-100% and 98.9-100%) and comparable for all strategies, except the dual-marker approach (NPV 96.9%, sensitivity 90.4%) and the NICE-algorithm (NPV 99.1%, sensitivity 94.7%). Efficacy, quantified by the percentage of patients eligible for rule-out, differed markedly, and was lowest for LoD-algorithm (15.7-26.8%)., Conclusion: All rapid rule-out algorithms, except the dual-marker strategy and the NICE-algorithm using hs-cTnI, favorably combine safety and efficacy, and can be considered for routine clinical practice., Clinical Trial Registration: NCT00470587, http://clinicaltrials.gov/show/NCT00470587., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: It is unknown whether cardiac syncope, and possibly also other syncope aetiologies exhibit circadian, weekly, seasonal, and temperature-dependent patterns., Methods and Results: We prospectively recorded the exact time, date, and outside temperature of syncope of patients >40 years old presenting with syncope to the emergency department in a diagnostic multicentre study. Two independent cardiologists/emergency physicians adjudicated the final diagnosis based on all information becoming available during clinical work-up including 1-year follow-up. Among 1230 patients, the adjudicated aetiology was cardiac in 14.6%, reflex in 39.2%, orthostatic in 25.7%, other non-cardiac in 9.7%, and unknown in 10.8% of patients. All syncope aetiologies occurred much more frequently during the day when compared with the night (P < 0.01). While reflex and orthostatic syncope showed a broad peak of prevalence with 80.9% of these events occurring between 4 am and 4 pm, cardiac syncope showed a narrow peak of prevalence with 70.1% of all events occurring between 8 am and 2 pm. A weekly pattern was present for most syncope aetiologies, with events occurring mainly from Monday to Friday (P < 0.01). Reflex syncope displayed a seasonal rhythm and was more common in winter (P < 0.01), while cardiac syncope stayed constant over the year. Syncope occurred most often when the outside temperature was coldest. Overall the patterns observed for cardiac syncope were similar to the patterns observed for its differential diagnosis., Conclusion: Syncope aetiologies in patients >40 years old display circadian, weekly, seasonal, and temperature-dependent patterns. Unfortunately, these patterns do not allow to reliably differentiate cardiac syncope from other aetiologies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: The early diagnosis of urgent abdominal pain (UAP) is challenging. Most causes of UAP are associated with extensive inflammation. Therefore, we hypothesized that quantifying inflammation using interleukin-6 and/or procalcitonin would provide incremental value in the emergency diagnosis of UAP., Methods: This was an investigator-initiated prospective, multicenter diagnostic study enrolling patients presenting to the emergency department (ED) with acute abdominal pain. Clinical judgment of the treating physician regarding the presence of UAP was quantified using a visual analog scale after initial clinical and physician-directed laboratory assessment, and again after imaging. Two independent specialists adjudicated the final diagnosis and the classification as UAP (life-threatening, needing urgent surgery and/or hospitalization for acute medical reasons) using all information including histology and follow-up. Interleukin-6 and procalcitonin were measured blinded in a central laboratory., Results: UAP was adjudicated in 376 of 1038 (36%) patients. Diagnostic accuracy for UAP was higher for interleukin-6 [area under the ROC curve (AUC), 0.80; 95% CI, 0.77-0.82] vs procalcitonin (AUC, 0.65; 95% CI, 0.62-0.68) and clinical judgment (AUC, 0.69; 95% CI, 0.65-0.72; both P < 0.001). Combined assessment of interleukin-6 and clinical judgment increased the AUC at presentation to 0.83 (95% CI, 0.80-0.85) and after imaging to 0.87 (95% CI, 0.84-0.89) and improved the correct identification of patients with and without UAP (net improvement in mean predicted probability: presentation, +19%; after imaging, +15%; P < 0.001). Decision curve analysis documented incremental value across the full range of pretest probabilities. A clinical judgment/interleukin-6 algorithm ruled out UAP with a sensitivity of 97% and ruled in UAP with a specificity of 93%., Conclusions: Interleukin-6 significantly improves the early diagnosis of UAP in the ED., (© 2018 American Association for Clinical Chemistry.)

Aims: We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients., Methods and Results: We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5-99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767)., Conclusion: While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587 and NCT02355457 (BACC).

Background: Various scores have been derived for the assessment of syncope patients in the emergency department (ED) but stay inconsistently validated. We aim to compare their performance to the one of a common, easy-to-use CHADS 2 score., Methods: We prospectively enrolled patients ≥ 40 years old presenting with syncope to the ED in a multicenter study. Early clinical judgment (ECJ) of the treating ED-physician regarding the probability of cardiac syncope was quantified. Two independent physicians adjudicated the final diagnosis after 1-year follow-up. Major cardiovascular events (MACE) and death were recorded during 2 years of follow-up. Nine scores were compared by their area under the receiver-operator characteristics curve (AUC) for death, MACE or the diagnosis of cardiac syncope., Results: 1490 patients were available for score validation. The CHADS 2 -score presented a higher or equally high accuracy for death in the long- and short-term follow-up than other syncope-specific risk scores. This score also performed well for the prediction of MACE in the long- and short-term evaluation and stratified patients with accuracy comparative to OESIL, one of the best performing syncope-specific risk score. All scores performed poorly for diagnosing cardiac syncope when compared to the ECJ., Conclusions: The CHADS 2 -score performed comparably to more complicated syncope-specific risk scores in the prediction of death and MACE in ED syncope patients. While better tools incorporating biochemical and electrocardiographic markers are needed, this study suggests that the CHADS 2 -score is currently a good option to stratify risk in syncope patients in the ED., Trial Registration: NCT01548352., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Clinical performance of the novel high-sensitivity cardiac troponin I (Siemens-hs-cTnI-Centaur) assay is unknown. We aimed to clinically validate the Siemens-hs-cTnI-Centaur assay and develop 0/1-h and 0/2-h algorithms., Methods: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists including all clinical information twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis); second, using hs-cTnI (Abbott-Architect, secondary analysis) measurements in addition to the clinically applied (hs)-cTn. Siemens-hs-cTnI-Centaur was measured at presentation, 1 h, and 2 h. The primary objective was a direct comparison of diagnostic accuracy, quantified by the area under the ROC curve (AUC), of Siemens-hs-cTnI-Centaur vs the 2 established hs-cTn assays (Roche-hs-cTnT-Elecsys, Abbott-hs-cTnI-Architect). Secondary objectives included the development of Siemens-hs-cTnI-Centaur-specific 0/1-h and 0/2-h algorithms., Results: AMI was the final diagnosis in 318 of 1755 (18%) patients (using Roche-hs-cTnT-Elecsys for adjudication). The AUC at presentation for Siemens-hs-cTnI-Centaur was 0.94 (95% CI, 0.92-0.96) and comparable with 0.95 (95% CI, 0.93-0.97) for Roche-hs-cTnT-Elecsys and 0.93 (95% CI, 0.90-0.96) for Abbott-hs-cTnI-Architect. Applying the derived Siemens-hs-cTnI-Centaur 0/1-h algorithm to the validation cohort, 46% of patients were ruled out (sensitivity, 99.1%; 95% CI, 95.3-100), and 18% of patients were ruled in (specificity, 94.1%; 95% CI, 91.8-95.9). The Siemens-hs-cTnI-Centaur 0/2-h algorithm ruled out 55% of patients (sensitivity, 100%; 95% CI, 94.1-100), and ruled in 18% of patients (specificity, 96.0%; 95% CI, 93.1-97.9). Findings were confirmed in the secondary analyses using serial measurements of Abbott-hs-cTnI-Architect for adjudication., Conclusions: Diagnostic accuracy and clinical utility of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587., (© 2018 American Association for Clinical Chemistry.)

Background: The safety of the European Society of Cardiology (ESC) 0/1-h algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn) has been questioned., Objectives: This study aimed to validate the diagnostic performance of the 0/1-h algorithm in a large multicenter study., Methods: The authors prospectively enrolled unselected patients in 6 countries presenting to the emergency department with symptoms suggestive of NSTEMI. Final diagnosis was centrally adjudicated by 2 independent cardiologists. Hs-cTnT and hs-cTnI blood concentrations were measured at presentation and after 1 h. Safety of rule-out was quantified by the negative predictive value (NPV) for NSTEMI, accuracy of rule-in by the positive predictive value (PPV), and overall efficacy by the proportion of patients triaged towards rule-out or rule-in within 1 h., Results: Prevalence of NSTEMI was 17%. Among 4,368 patients with serial hs-cTnT measurements available, safety of rule-out (NPV 99.8%, 2,488 of 2,493), accuracy of rule-in (PPV 74.5%, 572 of 768), and overall efficacy were high by assigning three-fourths of patients either to rule-out (57%, 2,493 to 4,368) or rule-in (18%, 768 to 4,368). Similarly, among 3,500 patients with serial hs-cTnI measurements, safety of rule-out (NPV 99.7%, 1,528 of 1,533), accuracy of rule-in (PPV 62.3%, 498 of 800), and overall efficacy were high by assigning more than two-thirds of patients either to rule-out (44%, 1,533 of 3,500) or rule-in (23%, 800 of 3,500). Excellent safety was confirmed in multiple subgroup analyses including patients presenting early (≤3 h) after chest pain onset., Conclusions: The ESC 0/1-h algorithm using hs-cTnT and hs-cTnI is very safe and effective in triaging patients with suspected NSTEMI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587; and Biomarkers in Acute Cardiac Care [BACC]; NCT02355457)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is concern that high-sensitivity cardiac troponin (hs-cTn) may have low diagnostic accuracy in patients with low acute coronary syndrome (ACS) probability., Methods: We prospectively stratified patients presenting with acute chest discomfort to the emergency department (ED) into 3 groups according to their probability for ACS as assessed by the treating ED physician using a visual analog scale: ≤10%, 11% to 79%, and ≥80%, reviewing all information available at 90 min. hs-cTnT and hs-cTnI concentrations were determined in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis., Results: Among 3828 patients eligible for analysis, 1189 patients had low (≤10%) probability for ACS. The incidence of non-ST-segment elevation myocardial infarction (NSTEMI) increased from 1.3% to 12.2% and 54.8% in patients with low, intermediate, and high ACS probability, respectively. The positive predictive value of hs-cTnT and hs-cTnI was low in patients with low ACS probability and increased with the incidence of NSTEMI, whereas the diagnostic accuracy of hs-cTnT and hs-cTnI for NSTEMI as quantified by the area under the curve (AUC) was very high and comparable among all 3 strata, e.g., AUC hs-cTnI, 0.96 (95% CI, 0.94-0.97); 0.87 (95% CI, 0.85-0.89); and 0.89 (95% CI, 0.87-0.92), respectively. Findings were validated using bootstrap analysis as an alternative methodology to define ACS probability. Similarly, higher hs-cTnT/I concentrations independently predicted all-cause mortality within 2 years (e.g., hs-cTnT hazard ratio, 1.39; 95% CI, 1.27-1.52), irrespective of ACS probability., Conclusions: Diagnostic and prognostic accuracy and utility of hs-cTnT and hs-cTnI remain high in patients with acute chest discomfort and low ACS probability.ClinicalTrials.gov Identifier: NCT00470587., (© 2017 American Association for Clinical Chemistry.)

Background: The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non-ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD., Methods: In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non-ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m 2 , and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample., Results: Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non-ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P <0.001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6-100.0] versus 99.2% [95% CI, 97.6-99.8]; P =0.559), lower specificity of rule-in (88.7% [95% CI, 84.8-91.9] versus 96.5% [95% CI, 95.7-97.2]; P <0.001), and lower overall efficacy (51% versus 81%, P <0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P <0.001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0-99.8] versus 98.5% [95% CI, 96.5-99.5]; P =1.0), lower specificity of rule-in (84.4% [95% CI, 79.9-88.3] versus 91.7% [95% CI, 90.5-92.9]; P <0.001), and lower overall efficacy (54% versus 76%, P <0.001; proportion ruled out, 18% versus 58%, P <0.001) compared with patients with normal renal function., Conclusions: In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587., (© 2017 The Authors.)

Background: While prolongation of QRS duration and QTc interval during acute myocardial infarction (AMI) has been reported in animals, limited data is available for these readily available electrocardiography (ECG) markers in humans., Methods: Diagnostic and prognostic value of QRS duration and QTc interval in patients with suspected AMI in a prospective diagnostic multicentre study were prospectively assessed. Digital 12-lead ECGs were recorded at presentation. QRS duration and QTc interval were automatically calculated in a blinded fashion. Final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all-cause mortality during 24 months of follow-up., Results: Among 4042 patients, AMI was the final diagnosis in 19% of patients. Median QRS duration and median QTc interval were significantly greater in patients with AMI compared to those with other final diagnoses (98 ms [IQR 88-108] vs. 94 ms [IQR 86-102] and 436 ms [IQR 414-462] vs. 425 ms [IQR 407-445], p < 0.001 for both comparisons). The diagnostic value of both ECG signatures however was only modest (AUC 0.56 and 0.60). Cumulative mortality rates after 2 years were 15.9% vs. 5.6% in patients with a QRS > 120 ms compared to a QRS duration ≤ 120 ms (p < 0.001), and 11.4% vs. 4.3% in patients with a QTc > 440 ms compared to a QRS duration ≤ 440 ms (p < 0.001). After adjustment for age and important ECG and clinical parameters, the QTc interval but not QRS duration remained an independent predictor of mortality., Conclusions: Prolongation of QRS duration > 120 ms and QTc interval > 440 ms predict mortality in patients with suspected AMI, but do not add diagnostic value.

Background: The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin., Methods and Results: We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1-year follow-up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes ( P <0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76-0.84), 0.69 (95% CI, 0.64-0.74), 0.58 (95% CI, 0.52-0.63), and 0.68 (95% CI, 0.63-0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82-0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87-0.93), which was significantly higher than for the ED probability alone ( P =0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of <77 pmol/L and an ED probability of <20% had a sensitivity and a negative predictive value of 99%., Conclusions: The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01548352., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Uncertainties regarding the most appropriate definition and treatment of type 2 myocardial infarction (T2MI) due to supply-demand mismatch have contributed to inconsistent adoption in clinical practice., Objectives: This study sought a better understanding of the effect of the definition of T2MI on its incidence, treatment, and event-related mortality, thereby addressing an important unmet clinical need., Methods: The final diagnosis was adjudicated in patients presenting with symptoms suggestive of myocardial infarction by 2 independent cardiologists by 2 methods: 1 method required the presence of coronary artery disease, a common interpretation of the 2007 universal definition (T2MI 2007 ); and 1 method did not require coronary artery disease, the 2012 universal definition (T2MI 2012 )., Results: Overall, 4,015 consecutive patients were adjudicated. The incidence of T2MI based on the T2MI 2007 definition was 2.8% (n = 112). The application of the more liberal T2MI 2012 definition resulted in an increase of T2MI incidence of 6% (n = 240), a relative increase of 114% (128 reclassified patients, defined as T2MI 2012reclassified ). Among T2MI 2007 , 6.3% of patients received coronary revascularization, 22% dual-antiplatelet therapy, and 71% high-dose statin therapy versus 0.8%, 1.6%, and 31% among T2MI 2012reclassified patients, respectively (all p < 0.01). Cardiovascular mortality at 90 days was 0% among T2MI 2012reclassified , which was similar to patients with noncardiac causes of chest discomfort (0.2%), and lower than T2MI 2007 (3.6%) and type 1 myocardial infarction (T1MI) (4.8%) (T2MI 2012reclassified vs. T2MI 2007 and T1MI: p = 0.03 and 0.01, respectively)., Conclusions: T2MI 2012reclassified has a substantially lower event-related mortality rate compared with T2MI 2007 and T1MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application., Methods: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm., Results: Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%-100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%-98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P =0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies ( P <0.01 for LOD versus each of the other strategies)., Conclusions: All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587., (© 2017 American Heart Association, Inc.)

Patients with nonspecific complaints (NSC) presenting to the emergency department (ED) are at risk of life-threatening conditions. New stress biomarkers such as the midregional portion of adrenomedullin (MR-proADM) promise to support decision-making. This study tested the following hypotheses: biomarker-assisted disposition of patients with NSC will not increase mortality. Second, discharge from the ED will increase if clinical risk assessment is combined with low MR-proADM levels. Third, inappropriate disposition to a lower level of care will decrease, if clinical assessment is combined with high MR-proADM levels, and fourth that this algorithm is feasible in the ED setting. Prospective, multicenter, randomized, controlled interventional feasibility study with a 30-day follow-up, including patients with NSC. Patients were randomly assigned to either the standard group (decision-making solely based on clinical assessment) or the Novum group (biomarker-assisted). Regarding disposition, patients were assigned to 1 of 3 risk classes: high-risk (admission to hospital), intermediate risk (community geriatric hospital), and low-risk patients (discharge). In the Novum group, in addition to clinical risk assessment, the information of the MR-proADM level was used. Unless there were overruling criteria, patients were transferred or discharged according to the risk assessment. Primary endpoint was 30-day mortality. Secondary endpoints were comparisons of patient disposition and related mortality rates, ED, and hospital length of stay and readmission. The final study cohort consisted of 398 patients (210 in the Standard group and 188 in the Novum group). Overruling, that is, disposition not according to the result of the proposed algorithm occurred in 51 cases. Baseline characteristics between Standard and Novum groups were similar. The mortality rate in the Novum group was 4.3%, as compared to the Standard group mortality of 6.2%, which was not significantly different (intention-to treat analysis). This was confirmed by the perprotocol analysis as well as by sensitivity analysis. For the secondary endpoints, no significant differences were detected. Biomarker-assisted disposition is safe in patients with NSC. Discharge rates did not increase. Feasibility could only partly be shown due to an unexpectedly high overruling rate. Inappropriate disposition to lower levels of care did not change. ClinicalTrials. gov Identifier: NCT00920491.

The prevalence of diagnoses, morbidity, and mortality of patients with nonspecific complaints (NSC) presenting to the emergency department (ED) is unknown.To determine the prevalence of diagnoses, acute morbidity, and mortality of patients with NSC.Prospective observational study with a 30-day follow-up. Patients presenting to 2 EDs were enrolled by a study team and diagnosed according to the World Health Organization ICD-10 System.Of 217,699 presentations to the ED from May 2007 through to February 2011, a total of 1300 patients were enrolled. After exclusion of 90 patients who fulfilled exclusion criteria, 1210 patients were analyzed. No patient was lost to follow-up. In patients with NSC, the underlying diseases were spread throughout 18 chapters of the ICD-10. A total of 58.7% of the patients were diagnosed with acute morbidity. Thirty-day mortality was 6.4% overall. Patients with acute morbidity and suffering from heart failure and pneumonia had mortalities >15%; patients lacking acute morbidity, but suffering from functional impairment or depression/anxiety had mortalities of 0%. Although the history did not allow any prediction, age and sex were predictive of morbidity and mortality.The differential diagnoses in patients presenting with NSC is broad. Acute morbidity and mortality were high in the presented cohort, the predictors of morbidity and mortality being age and sex rather than the nature of the complaints. Urgently needed management strategies could be based on these results.ClinicalTrials.gov (#NCT00920491).

The association between the physician's first clinical impression of a patient with nonspecific complaints and morbidity and mortality is unknown. The aim was to evaluate the association of the physician's first clinical impression with acute morbidity and mortality. We conducted a prospective observational study with a 30-day follow-up. This study was performed at the emergency departments (EDs) of 1 secondary and 1 tertiary care hospital, from May 2007 to February 2011. The first clinical impression ("looking ill"), expressed on a numerical rating scale from 0 to 100, age, sex, and the Charlson Comorbidity Index (CCI) were evaluated. The association was determined between these variables and acute morbidity and mortality, together with receiver operating characteristics, and validity. Of 217,699 presentations to the ED, a total of 1278 adult nontrauma patients with nonspecific complaints were enrolled by a study team. No patient was lost to follow-up. A total of 84 (6.6%) patients died during follow-up, and 742 (58.0%) patients were classified as suffering from acute morbidity. The variable "looking ill" was significantly associated with mortality and morbidity (per 10 point increase, odds ratio 1.23, 95% confidence interval [CI] 1.12-1.34, P < 0.001, and odds ratio 1.19, 95% CI 1.14-1.24, P < 0.001, respectively). The combination of the variables "looking ill," "age," "male sex," and "CCI" resulted in the best prediction of these outcomes (mortality: area under the curve [AUC] 0.77, 95% CI 0.72-0.82; morbidity: AUC 0.68, 95% CI 0.65-0.71). The physician's first impression, with or without additional variables such as age, male sex, and CCI, was associated with morbidity and mortality. This might help in the decision to perform further diagnostic tests and to hospitalize ED patients.

Importance: Whether sex-specific chest pain characteristics (CPCs) would allow physicians in the emergency department to differentiate women with acute myocardial infarction (AMI) from women with other causes of acute chest pain more accurately remains unknown. OBJECTIVE To improve the management of suspected AMI in women by exploring sex-specific CPCs., Design, Setting, and Participants: From April 21, 2006, through August 12, 2012, we enrolled 2475 consecutive patients (796 women and 1679 men) presenting with acute chest pain to 9 emergency departments in a prospective multicenter study. The final diagnosis of AMI was adjudicated by 2 independent cardiologists., Interventions: Treatment of AMI in the emergency department., Main Outcomes and Measures: Sex-specific diagnostic performance of 34 predefined and uniformly recorded CPCs in the early diagnosis of AMI., Results: Acute myocardial infarction was the adjudicated final diagnosis in 143 women (18.0%) and 369 men (22.0%). Although most CPCs were reported with similar frequency in women and men, several CPCs were reported more frequently in women (P < .05). The accuracy of most CPCs in the diagnosis of AMI was low in women and men, with likelihood ratios close to 1. Thirty-one of 34 CPCs (91.2%) showed similar likelihood ratios for the diagnosis of AMI in women and men, and only 3 CPCs (8.8%) seemed to have a sex-specific diagnostic performance with P < .05 for interaction. These CPCs were related to pain duration (2-30 and >30 minutes) and dynamics (decreasing pain intensity). However, because their likelihood ratios were close to 1, the 3 CPCs did not seem clinically helpful. Similar results were obtained when examining combinations of CPCs (all interactions, P ≥ .05)., Conclusions and Relevance: Differences in the sex-specific diagnostic performance of CPCs are small and do not seem to support the use of women-specific CPCs in the early diagnosis of AMI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00470587.

Objectives: To the authors' knowledge, no prospectively validated, biomarker-based risk stratification tools exist for elderly patients presenting to the emergency department (ED) with nonspecific complaints (NSCs), such as generalized weakness, despite the fact that an acute serious disease often underlies nonspecific disease presentation. The primary purpose for this study was to validate the retrospectively derived model for outcome prediction using copeptin and peroxiredoxin 4 (Prx4), in a different group of patients, in a prospective fashion, in a multicenter setting. The secondary goals were to evaluate the potential contribution of the midregional portion of the precursor of adrenomedullin (MR-proADM) for outcome prediction and to investigate whether disposition decisions show promise for potential improvement by using biomarker levels in addition to a clinical assessment., Methods: The Basel Nonspecific Complaints (BANC) study is a delayed-type cross-sectional diagnostic study, carried out in three EDs in Switzerland, with a prospective 30-day follow-up. Patients presenting to the ED with NSCs, as defined previously, were included if their vital signs were within predefined limits. Measurement of biomarkers was performed in serum samples with sandwich immunoluminometric assays. To examine the disposition process, the final disposition was compared with a combination of the first clinical disposition decision and the risk assessment, which included the biomarker MR-proADM in a retrospective simulation. Patients were divided into three groups according to MR-proADM concentration, defining three risk classes with three disposition possibilities (admission to tertiary care, transfer to geriatric hospital, discharge)., Results: Thirty-three 30-day nonsurvivors were observed from among 504 study patients with NSCs. Biomarker levels were significantly greater in nonsurvivors than survivors (p < 0.0001 for all three biomarkers). Univariate Cox models reveal a C-index of 0.732 for MR-proADM, 0.719 for Prx4, and 0.723 for copeptin. The incremental added value for chi-square obtained via multivariate modeling showed that models inclusive of MR-proADM, copeptin, or Prx4 are superior to and independent of models limited to sex and age. The incrementally added chi-square for MR-proADM, beyond the chi-square of a base model consisting of age and sex, was 29.79 (p < 0.00001). In a multimarker approach, only Prx4 provided additional information to MR-proADM alone (C-index = 0.77). Applying an algorithm combining physicians' first clinical assessment plus biomarker information to derive a modified risk assessment, reassignment would lead to a potential decrease of 48 admissions to acute care, seven additional transfers to geriatric care, and 41 additional discharges (negative likelihood ratio [-LR] = 0.13). Analysis of 30-day mortality reveals that our algorithm is not inferior in terms of safety., Conclusions: In this study the authors confirm that these new stress biomarkers permit reliable prognostication of adverse outcomes in a heterogeneous group of patients with NSCs. A simulation showed that this prognostic information could be useful to enhance the appropriateness of disposition decisions of ED patients with NSC. The use of biomarkers for risk stratification in this patient group should be evaluated with prospective intervention studies., (© 2013 by the Society for Academic Emergency Medicine.)