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Background: Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope., Objective: The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies., Methods: The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE)., Results: Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P <.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P <.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines., Conclusion: ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation., Objective: To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score., Design: Prospective cohort study., Setting: Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents., Participants: Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope., Measurements: Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome)., Results: Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome)., Limitation: Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge., Conclusion: This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain., Primary Funding Source: Swiss National Science Foundation & Swiss Heart Foundation.

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.)

Introduction and Objectives: Release kinetics of high-sensitivity cardiac troponin (hs-cTn) T and I in patients with acute myocardial infarction (AMI) are incompletely understood. We aimed to assess whether hs-cTnT/I release in early AMI is near linear., Methods: In a prospective diagnostic multicenter study the acute release of hs-cTnT and hs-cTnI within 1 and 2hours from presentation to the emergency department was quantified using 3 hs-cTnT/I assays in patients with suspected AMI. The primary endpoint was correlation between hs-cTn changes from presentation to 1 hour vs changes from presentation to 2hours, among all AMI patients and different prespecified subgroups. The final diagnosis was adjudicated by 2 independent cardiologists, based on serial hs-cTnT from the serial study blood samples and additional locally measured hs-cTn values., Results: Among 2437 patients with complete hs-cTnT data, AMI was the adjudicated diagnosis in 376 patients (15%). For hs-cTnT, the correlation coefficient between 0- to 1-hour change and 0- to 2 hour change was 0.931 (95%CI, 0.916-0.944), P <.001. Similar findings were obtained with hs-cTnI (Architect) with correlation coefficients between 0- to 1-hour change and 0- to 2 hour change of 0.969 and hs-cTnI (Centaur) of 0.934 (P <.001 for both). Findings were consistent among type 1 and type 2 AMI and in the subgroup of patients presenting very early after chest pain onset., Conclusions: Patients presenting with early AMI showed a near linear release of hs-cTnT and hs-cTnI. This near linearity provides the pathophysiological basis for rapid diagnostic algorithms using 0- to 1-hour changes as surrogates for 0- to 2 hour or 0- to 3 hour changes. Registered at ClinicalTrials.gov (Identifier: NCT00470587)., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

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.)