title: An approach to rule-out an acute cardiovascular event or death in emergency department patients using outcome-based cutoffs for high-sensitivity cardiac troponin assays and glucose.
abstract: OBJECTIVE
  The application of "undetectable" high-sensitivity cardiac troponin (hs-cTn) concentrations to "rule-out" myocardial infarction is appealing, but there are analytical concerns and a lack of consensus on what concentration should be used to define the lower reportable limit; i.e., limit of detection (LoD) or limit of blank. An alternative approach is to utilize a measurable hs-cTn concentration that identifies patients at low-risk for a future cardiovascular event combined with another prognostic test, such as glucose. We assessed both of these approaches in different emergency department (ED) cohorts to rule-out an event.
  
  
  METHODS
  We used cohort 1 (all-comer ED population, n=4773; derivation cohort) to determine the most appropriate approach at presentation (i.e., Dual Panel test: hs-cTn/glucose vs. LoD vs. LoD/glucose) for an early rule-out of hospital death using the Abbott ARCHITECT hs-cTnI assay. We used cohort 2 (n=144) and cohort 3 (n=127), both early chest pain onset ED populations as the verification datasets (outcome: composite cardiovascular event at 72h) with three hs-cTn assays assessed (Abbott Laboratories, Beckman Coulter, Roche Diagnostics).
  
  
  RESULTS
  In cohort 1, the sensitivity was >99% for all three approaches; however the specificity (11%; 95% CI: 10-12%) was significantly higher for the Dual Panel as compared to the LoD approach (specificity=5%; 95% CI: 4-6%). Verification of the Dual Panel in cohort 2 and cohort 3 revealed 100% sensitivity and negative predictive values for all three hs-cTn assays.
  
  
  CONCLUSIONS
  The combination of a "healthy" hs-cTn concentration with glucose might effectively rule-out patients for an acute cardiovascular event at ED presentation.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: Colleen
authors.initials: C
authors.lastname: Shortt
authors.affiliation: McGill University, Montreal, QC, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Phan
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Hill
authors.affiliation: Division of Emergency Medicine, McMaster University, Hamilton, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worster
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada. Electronic address: kavsakp@mcmaster.ca.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kavsak
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay / Q000379:methods / Q000592:standards*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D002637:Chest Pain / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D015331:Cohort Studies; D004636:Emergency Service, Hospital / Q000592:standards*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I; D005947:Glucose
keywords: Acute coronary syndrome; Emergency department; Glucose; Health outcomes; High-sensitivity cardiac troponin; Rule-out