title: Comparison of the Efficacy and Safety of Early Rule-Out Pathways for Acute Myocardial Infarction.
abstract: BACKGROUND
  High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the optimal approach is uncertain. We compared the European Society of Cardiology rule-out pathway with a pathway that incorporates lower cardiac troponin concentrations to risk stratify patients.
  
  
  METHODS
  Patients with suspected acute coronary syndrome (n=1218) underwent high-sensitivity cardiac troponin I measurement at presentation and 3 and 6 or 12 hours. We compared the European Society of Cardiology pathway (<99th centile at presentation or at 3 hours if symptoms <6 hours) with a pathway developed in the High-STEACS study (High-Sensitivity Troponin in the Evaluation of Patients With Acute CoronarySyndrome) population (<5 ng/L at presentation or change <3 ng/L and <99th centile at 3 hours). The primary outcome was a comparison of the negative predictive value of both pathways for index type 1 myocardial infarction or type 1 myocardial infarction or cardiac death at 30 days. We evaluated the primary outcome in prespecified subgroups stratified by age, sex, time of symptom onset, and known ischemic heart disease.
  
  
  RESULTS
  The primary outcome occurred in 15.7% (191 of 1218) patients. In those less than the 99th centile at presentation, the European Society of Cardiology pathway ruled out myocardial infarction in 28.1% (342 of 1218) and 78.9% (961 of 1218) at presentation and 3 hours, respectively, missing 18 index and two 30-day events (negative predictive value, 97.9%; 95% confidence interval, 96.9-98.7). The High-STEACS pathway ruled out 40.7% (496 of 1218) and 74.2% (904 of 1218) at presentation and 3 hours, missing 2 index and two 30-day events (negative predictive value, 99.5%; 95% confidence interval, 99.0-99.9;P<0.001 for comparison). The negative predictive value of the High-STEACS pathway was greater than the European Society of Cardiology pathway overall (P<0.001) and in all subgroups, including those presenting early or known to have ischemic heart disease.
  
  
  CONCLUSIONS
  Use of the High-STEACS pathway incorporating low high-sensitivity cardiac troponin concentrations rules out myocardial infarction in more patients at presentation and misses 5-fold fewer index myocardial infarctions than guideline-approved pathways based exclusively on the 99th centile.
  
  
  BACKGROUND
  URL: http://clinicaltrials.gov. Unique identifier: NCT01852123.
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom. a.r.chapman@ed.ac.uk.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Chapman
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Atul
authors.initials: A
authors.lastname: Anand
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Jasper
authors.initials: J
authors.lastname: Boeddinghaus
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Amy V
authors.initials: AV
authors.lastname: Ferry
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Dennis
authors.initials: D
authors.lastname: Sandeman
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Adamson
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Andrews
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tan
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Sheun F
authors.initials: SF
authors.lastname: Cheng
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: D'Souza
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Orme
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Strachan
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nestelberger
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Raphael
authors.initials: R
authors.lastname: Twerenbold
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Patrick
authors.initials: P
authors.lastname: Badertscher
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Tobias
authors.initials: T
authors.lastname: Reichlin
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Gray
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Anoop S V
authors.initials: ASV
authors.lastname: Shah
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: From British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.R.C., A.A., A.V.F., D.S., P.D.A., J.A., S.T., S.F.C., M.D., K.O., F.E.S., A.G., A.S.V.S., D.E.N., N.L.M.); Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Switzerland (J.B., T.N., R.T., P.B.., T.R., C.M.); and Department of Emergency Medicine (A.G.) and EMERGE Research Group (A.G.), Royal Infirmary of Edinburgh, United Kingdom.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003661:Decision Support Techniques; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012606:Scotland; D012737:Sex Factors; D013997:Time Factors; D019210:Troponin I / Q000097:blood*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D019210:Troponin I
keywords: acute coronary syndrome; biomarkers; myocardial infarction; troponin