title: Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a sensitive troponin I assay.
abstract: OBJECTIVE
  With a high-sensitivity troponin assay, it may be possible to exclude acute myocardial infarction with a single blood test on arrival in the emergency department by using a novel 'rule out' cut-off set at the limit of detection of the assay. We aimed to determine whether this can also be achieved using a contemporary sensitive troponin assay that does not meet 'high-sensitivity' criteria.
  
  
  METHODS
  In a prospective diagnostic cohort study, we included patients presenting to the emergency department with suspected cardiac chest pain. For this secondary analysis, serum samples drawn on arrival were tested using a contemporary sensitive troponin I assay (s-cTnI; Siemens Ultra ADVIA Centaur, 99th percentile 40 ng/L, limit of detection 6 ng/L). Acute myocardial infarction was adjudicated by two independent investigators based on reference standard troponin testing ≥12 h after symptom onset.
  
  
  RESULTS
  Of 414 participants, 70 (16.9%) had acute myocardial infarction and 205 (49.5%) had initial s-cTnI concentrations below the limit of detection. Using the limit of detection as a 'rule out' cut-off gave a sensitivity of 94.3% (95% CI 86.0-98.4%) for acute myocardial infarction. If only patients with s-cTnI below the limit of detection and no electrocardiogram ischaemia were considered to have acute myocardial infarction 'ruled out' (41.8% of the cohort, n = 174), sensitivity would rise to 97.1% (90.1-99.7%) and negative predictive value to 98.8% (95.9-99.9%).
  
  
  CONCLUSIONS
  Acute myocardial infarction cannot be excluded in patients with s-cTnI concentrations below the limit of detection using the contemporary sensitive assay evaluated. Future work with this assay should focus on serial sampling over 1-3 h and combination with clinical information and/or additional biomarkers.
authors.affiliation: Cardiovascular Sciences Research Group, The University of Manchester, Manchester, UK Emergency Department, Central Manchester NHS Foundation Trust, Manchester, UK richard.body@manchester.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Body
authors.affiliation: Biochemistry Department, Stockport NHS Foundation Trust, Stockport, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Burrows
authors.affiliation: Emergency Department, Central Manchester NHS Foundation Trust, Manchester, UK Centre for Effective Emergency Care, Manchester Metropolitan University, Manchester, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Carley
authors.affiliation: Cardiology Department, Stockport NHS Foundation Trust, Stockport, UK.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Lewis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002637:Chest Pain / Q000097:blood / Q000175:diagnosis; D015331:Cohort Studies; D004636:Emergency Service, Hospital / Q000592:standards*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis*; D011446:Prospective Studies; D013997:Time Factors; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I
keywords: Acute myocardial infarction; acute coronary syndromes; diagnosis; high sensitivity; sensitivity and specificity; troponins