title: A FABP-ulous 'rule out' strategy? Heart fatty acid binding protein and troponin for rapid exclusion of acute myocardial infarction.
abstract: OBJECTIVE
  Many Emergency Departments (EDs) utilise 'triple marker' testing with CK-MB, myoglobin and troponin I (cTnI) to exclude acute myocardial infarction (AMI) within hours of presentation. We evaluated the ability of 8 biomarkers to rapidly exclude AMI at the point of presentation and investigated whether 'triple marker' testing represents the optimal multimarker strategy.
  
  
  METHODS
  We recruited patients who presented to the ED with suspected cardiac chest pain occurring within 24 h. Blood was drawn at the time of presentation. Diagnostic value was assessed by calculating the area under the ROC curve (AUC) and a multivariate model was constructed by logistic regression. The primary outcome was a diagnosis of AMI, established by ≥12-h troponin testing in all patients.
  
  
  RESULTS
  705 included patients underwent venepuncture a median of 3.5 h after symptom onset. Heart fatty acid binding protein (H-FABP) had an AUC of 0.86 (95% CI 0.82-0.90), which was significantly higher than any other biomarker including cTnI. While no single biomarker could enable exclusion of AMI, multivariate analysis identified cTnI and H-FABP as the optimal biomarker combination. Combined with clinical risk stratification, this strategy had a sensitivity of 96.9%, specificity of 54.7%, PPV 32.4% and NPV 98.8%.
  
  
  CONCLUSIONS
  We have derived an algorithm that would enable AMI to be immediately excluded in 315 (44.7%) patients at the cost of missing 6 AMIs per 1000 patients treated. While the risk is likely to be unacceptable for clinical implementation, we have highlighted an area for future development using serial testing and increasingly sensitive assays.
authors.affiliation: Cardiovascular Sciences Research Group, University of Manchester, Oxford Road, Manchester, M13 9WL, United Kingdom. rbody@doctors.org.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Body
authors.forename: Garry
authors.initials: G
authors.lastname: McDowell
authors.forename: Simon
authors.initials: S
authors.lastname: Carley
authors.forename: Christopher
authors.initials: C
authors.lastname: Wibberley
authors.forename: Jamie
authors.initials: J
authors.lastname: Ferguson
authors.forename: Kevin
authors.initials: K
authors.lastname: Mackway-Jones
mesh_terms: D000209:Acute-Phase Proteins; D000465:Algorithms; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D003937:Diagnosis, Differential; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D009211:Myoglobin / Q000097:blood; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009195:Peroxidase / Q000097:blood; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood; D012372:ROC Curve; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D005338:Fibrin Fibrinogen Degradation Products; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D009211:Myoglobin; D011518:Proto-Oncogene Proteins; D019210:Troponin I; C036309:fibrin fragment D; D020097:Natriuretic Peptide, Brain; D009195:Peroxidase; D052279:Creatine Kinase, MB Form