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Background: The non-ST elevation myocardial infarction (NSTEMI) guidelines of the European Society of Cardiology (ESC) recommend a 3h cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-algorithm; however, no specific cut-off for further triage is endorsed. Recently, a specific cut-off for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7ng/L) was proposed warranting external validation. Methods: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI, based on complete cardiac work-up, cardiac imaging and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1h and 3h. The objective was to externally validate the proposed cut-off, and if necessary, derive and internally as well as externally validate novel 0/3h-criteria for the observe-zone of the ESC 0/1h-hs-cTnT-algorithm in an independent multicenter cohort. Results: Among 2076 eligible patients, application of the ESC 0/1h-hs-cTnT-algorithm triaged 1512 patients (72.8%) to either rule-out or rule-in of NSTEMI, remaining 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of <7ng/L triaged 517 patients (91.7%) towards rule-out, resulting in a sensitivity of 33.3% (95%CI 25.5-42.2), missing 80 patients with NSTEMI, and ≥7ng/L triaged 47 patients towards rule-in (8.3%), resulting in a specificity of 98.4% (95%CI 96.8-99.2). Novel derived 0/3h-criteria for the observe-zone patients ruled-out NSTEMI with a 3h hs-cTnT concentration <15 ng/L and a 0/3h-hs-cTnT absolute change <4 ng/L, triaging 138 patients (25%) towards rule-out, resulting in a sensitivity of 99.2% (95%CI 96.0-99.9), missing 1 patient with NSTEMI. A 0/3h-hs-cTnT absolute change ≥6 ng/L triaged 63 patients (11.2%) towards rule-in, resulting in a specificity of 98% (95%CI 96.2-98.9) Thereby, the novel 0/3h-criteria reduced the number of patients in the observe zone by 36%, and the number of T1MI by 50%. Findings were confirmed in both internal and external validation. Conclusions: A combination of a 3h hs-cTnT concentration (<15 ng/L) and a 0/3h absolute change (<4 ng/L) is necessary to safely rule-out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnT-algorithm. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT00470587

Aims Diagnosis of acute myocardial infarction (AMI) can be challenging in patients with prior coronary artery bypass grafting (CABG). Methods and results Final diagnoses were adjudicated by two independent cardiologists using the universal definition of AMI among patients presenting to the emergency department (ED) with suspected AMI. Diagnostic accuracy of 34 chest pain characteristics (CPCs) and four electrocardiogram (ECG) signatures stratified according to the presence or absence of prior CABG were prospectively quantified. Among 4015 patients (no prior CABG: n = 3686; prior CABG: n = 329), prevalence of AMI and unstable angina were higher in patients with prior CABG (35% vs. 18%; 26% vs. 8%; both P &lt; 0.001). Three CPCs (9%) and two electrocardiographic findings (50%) showed a different diagnostic performance (interaction P &lt; 0.05) with loss of diagnostic value in patients with prior CABG. The diagnostic accuracy as quantified by the area under the curve (AUC) of the integrated clinical judgement was moderate to good in patients with prior CABG, and significantly lower compared to patients without prior CABG [AUC 0.80 (95% confidence interval (CI) 0.75–0.84) vs. AUC 0.87 (95% CI 0.86–0.89); P = 0.004]. Time to discharge from the ED was significantly longer in patients with prior CABG [359 (215–525) min vs. 300 (192–435) min; P &lt; 0.001]. Key findings were confirmed in a large independent external validation cohort (n = 13 653). Conclusions Patients with prior CABG presenting with suspected AMI have a high prevalence of AMI and unstable angina and lower diagnostic accuracy of CPCs and the ECG, possibly justifying liberal use of early coronary angiography in these vulnerable patients. ClinicalTrials.gov registry Number NCT00470587.