Early standardized clinical judgement for syncope diagnosis in the emergency department.

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.

B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope.

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.

Comparison of fourteen rule-out strategies for acute myocardial infarction.

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.