Pedro Lopez-Ayala1,2, Thomas Nestelberger1,2,3, Jasper Boeddinghaus1,2, Luca Koechlin1,4,2, Paul David Ratmann1,2, Ivo Strebel1,2, Juliane Gehrke1,2, Severin Meier1, Joan Walter1,2,5, Maria Rubini Gimenez2,6, Eugenio Mutschler1, Òscar Miró2,7, Beatriz López-Barbeito2,7, Francisco Javier Martín-Sánchez2,8, Esther Rodríguez-Adrada8, Dagmar I Keller9, L Kristin Newby10, Raphael Twerenbold1,2,11, Evangelos Giannitsis12, Bertil Lindahl13,14, Christian Mueller1,2. 1. Cardiovascular Research Institute Basel and Department of Cardiology (P.L.-A., T.N., J.B., L.K., P.D.R., I.S., J.G., S.M., J.W., E.M., R.T., C.M.), University Hospital Basel, University of Basel, Switzerland. 2. Global Research on Acute Conditions Team Network, Rome, Italy (P.L.-A., T.N., J.B., L.K., P.D.R., I.S., J.G., J.W., M.R.G., O.M., B.L.-B., F.J.M.-S., R.T., C.M.). 3. Division of Cardiology, Vancouver General Hospital, University of British Columbia, Canada (T.N.). 4. Department of Cardiac Surgery (L.K.), University Hospital Basel, University of Basel, Switzerland. 5. Institute of Diagnostic and Interventional Radiology (J.W.), University Hospital Zurich, Switzerland. 6. Cardiology Department, Herzzentrum Leipzig, Germany (M.R.G.). 7. Emergency Department, Hospital Clinic, University of Barcelona, Spain (O.M., B.L.-B.). 8. Emergency Department, Hospital Clínico San Carlos, Madrid, Spain (F.J.M.-S., E.R.-A.). 9. Emergency Department (D.I.K.), University Hospital Zurich, Switzerland. 10. Division of Cardiology, Department of Medicine and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (L.K.N.). 11. University Center of Cardiovascular Science and Department of Cardiology, University Heart and Vascular Center Hamburg, Germany (R.T.). 12. Department of Medicine III, University Hospital Heidelberg, Germany (E.G.). 13. Department of Medical Sciences, Uppsala University, Sweden (B.L.). 14. Uppsala Clinical Research Center, Sweden (B.L.).
Abstract
BACKGROUND: The non-ST-segment-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 cutoff for further triage is endorsed. Recently, a specific cutoff for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7 ng/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 2 independent cardiologists applying the fourth universal definition of myocardial infarction, on the basis of complete cardiac workup, cardiac imaging, and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1 hour, and after 3 hours. The objective was to externally validate the proposed cutoff, 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 NSTEMI, leaving 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence, 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of <7 ng/L triaged 517 patients (91.7%) toward rule-out, resulting in a sensitivity of 33.3% (95% CI, 25.5-42.2), missing 80 patients with NSTEMI, and ≥7 ng/L triaged 47 patients toward 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%) toward 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%) toward 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%s and the number of type 1 myocardial infarction 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. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT00470587.
BACKGROUND: The non-ST-segment-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 cutoff for further triage is endorsed. Recently, a specific cutoff for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7 ng/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 2 independent cardiologists applying the fourth universal definition of myocardial infarction, on the basis of complete cardiac workup, cardiac imaging, and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1 hour, and after 3 hours. The objective was to externally validate the proposed cutoff, 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 NSTEMI, leaving 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence, 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of <7 ng/L triaged 517 patients (91.7%) toward rule-out, resulting in a sensitivity of 33.3% (95% CI, 25.5-42.2), missing 80 patients with NSTEMI, and ≥7 ng/L triaged 47 patients toward 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%) toward 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%) toward 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%s and the number of type 1 myocardial infarction 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. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT00470587.
Entities:
Keywords:
NSTEMI; algorithms; biomarkers; myocardial infarction; triage; troponin; troponin T