Resuscitation 82 (2011) 1041–1046 Contents lists available at ScienceDirect Resuscitation jo u rn al hom epage : www.elsevier.com/locate/resuscitation Clinical paper A FABP-ulous ‘rule out’ strategy? Heart fatty acid binding protein and troponin for rapid exclusion of acute myocardial infarction  Richard Body a,∗ , Garry McDowell a , Simon Carley b , Christopher Wibberley c , Jamie Ferguson b , Kevin Mackway-Jones b a University of Manchester, Oxford Road, Manchester, M13 9WL, United Kingdom b Emergency Department, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, United Kingdom c Manchester Metropolitan University, Faculty of Health, Psychology and Social Care, Hathersage Road, Manchester, M13 0JA, United Kingdom a r t i c l e i n f o Article history: Received 18 January 2011 Received in revised form 10 March 2011 Accepted 15 March 2011 Keywords: Acute myocardial infarction Acute coronary syndromes Troponins Heart fatty acid binding protein Myoglobin CK-MB Myeloperoxidase Brain natriuretic peptide d-Dimer Diagnosis Sensitivity and specificity a b s t r a c t 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. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Background The use of biochemical markers is already an essential part of the risk stratification of patients with suspected acute coronary syndromes (ACS) in the Emergency Department (ED). Measure- ment of cardiac troponins is an established standard of practice for these patients and forms an important part of the gold stan- dard for the diagnosis of acute myocardial infarction (AMI). 1–3 However the insufficient sensitivity of troponins at the time of pre- sentation mandates that the majority of patients are admitted to hospital pending their evaluation. 1,2,4 Following investigation, only  A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2011.03.015. ∗ Corresponding author at: Cardiovascular Sciences Research Group, 3rd Floor, Core Technology Facility, The University of Manchester, 46, Grafton Street, Manch- ester, M13 9WL, United Kingdom. Tel.: +44 0 7880 712 929; fax: +44 161 276 6925. E-mail address: rbody@doctors.org.uk (R. Body). a minority of the patients admitted are actually diagnosed with ACS, suggesting that there is tremendous potential to reduce unneces- sary hospital admissions (and unnecessary empirical treatment) in this patient group by improving diagnostic technology. 5 In recent years there has therefore been a growing interest in identifying combinations of biomarkers that may facilitate early exclusion of ACS at the time of presentation. To date, however, none of the mul- timarker panels investigated have been recommended for this use in practice. 6–9 Creatine kinase-MB (CK-MB) and myoglobin are biomarkers of myocardial necrosis, levels of which are known to rise early after the onset of myocardial necrosis. Used in isolation these biomark- ers lack sufficient sensitivity to enable safe exclusion of AMI in the ED. 10 However, ‘triple marker testing’ using the combination of CK-MB, myoglobin (‘early markers’) and troponin (a ‘late marker’), improves sensitivity. 11,12 Indeed, studies have suggested that this strategy is safe and effective and clinical protocols incorporating triple marker testing continue to be used in clinical practice at many institutions. 13,14 Serial sampling remains necessary, how- 0300-9572/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2011.03.015