Summary
Background
Heart-fatty acid binding protein (h-FABP) has been proposed as a cardiac marker for the early detection of acute coronary syndrome (ACS). In a study of 677 patients admitted to the emergency department (ED) for chest pain, we found that a semiquantitative point-of-care test that detects h-FABP (Cardiodetect ® ) had low sensitivity for the prediction of ACS.
Objective
The aim of this ancillary study was to analyze and compare the performance of h-FABP for early ACS diagnosis in this large cohort of unselected patients, using a quantitative immunoassay and Cardiodetect ® .
Methods
h-FABP was measured with a ready-to-use, solid-phase, enzyme-linked immunosorbent assay (ELISA) in 677 patients admitted to the ED with chest pain and suspected non-ST-segment elevation ACS. Two physicians, blinded to the results of the marker, categorized patients as having or not having non-ST-segment elevation ACS.
Results
Non-ST-segment elevation ACS was diagnosed in 185 patients (27.3%). The median h-FABP level was higher in patients with ACS (1.36 μg/L, interquartile range [IQR] 0.59–3.55) than in those without ACS (0.58 μg/L, IQR 0.24–1.34; P < 0.01). The area under the curve was 0.68 (95% confidence interval [CI] 0.63–0.73). h-FABP did not improve the performance of a model that included the usual diagnostic tools for ACS management (odds ratio 0.92, 95% CI 0.32–2.70). The classification agreement between the ELISA and Cardiodetect ® was 92.1% (kappa 0.39).
Conclusion
In this study, we confirmed that measurement of h-FABP was insufficient to be used as a marker of ACS and NSTEMI in ED, whatever the analytical technique used.
Résumé
Contexte
L’ heart-fatty acid binding protein (h-FABP) a été proposée comme marqueur cardiaque pour la détection précoce d’un syndrome coronaire aigu (SCA). Dans une étude de 677 patients admis pour douleur thoracique dans un service d’urgence, nous avons trouvé que le test semi-quantitatif Cardiodetect ® qui mesure l’h-FABP avait une faible sensibilité pour prédire le diagnostic de SCA.
Objectifs
L’objectif de cette étude ancillaire est d’analyser et de comparer les performances de l’h-FABP mesurées par une méthode immunologique quantitative à celles mesurées avec le Cardiodetect ® mesurée par une méthode semi-quantitative pour le diagnostic de SCA sans élévation du segment ST dans une large cohorte de patients non sélectionnés.
Méthodes
L’h-FABP a été mesurée par un dosage immuno-enzymatique sur support solide (Elisa) chez 677 patients admis aux urgences pour une douleur thoracique évocatrice de SCA sans élévation du segment ST. Deux médecins en aveugle des résultats des dosages ont catégorisé les patients en deux groupes avec ou sans SCA.
Résultats
Le diagnostic de SCA était fait chez 185 patients (27,3 %). La valeur médiane de l’h-FABP des patients avec SCA (1,36 μg/L, interquartile range [IQR] 0,59–3,55) était supérieure à celle des patients sans SCA (0,58 μg/L, IQR 0,24–1,34 ; p < 0,01). L’aire sous la courbe était 0,68 (intervalle de confiance [IC] 95 % 0,63–0,73). L’h-FABP n’améliorait pas les performances du modèle incluant les outils habituellement utilisés pour le diagnostic de SCA (odds ratio 0,92, IC 95 % 0,32–2,70). La concordance entre le test Elisa et le Cardiodetect ® était de 92,1 % (kappa 0,39).
Conclusion
Cette étude confirme que les performances de l’h-FABP sont insuffisantes pour utiliser ce test comme marqueur de SCA aux urgences, quelle que soit la méthode de dosage utilisée.
Background
The diagnosis of acute coronary syndrome (ACS) in unselected chest pain patients presenting to the emergency department (ED) remains challenging for physicians . Besides the new highly sensitive troponin assays, very early biomarkers of cardiac damage, such heart-fatty acid binding protein (h-FABP), may prove to be diagnostically superior . Point-of-care tests have been developed to make an early ACS diagnosis . We recently reported that the semiquantitative assay of h-FABP (Cardiodetect ® ) predicted ACS diagnosis with high specificity (96.8%) but low sensitivity (13.5%) in a prospective study of 677 consecutive patients admitted to our ED for chest pain . This test did not provide significant incremental information to a predictive model that included the usual tools for non-ST-segment elevation ACS management. A better h-FABP performance for ACS diagnosis was found with a quantitative assay in a selected population for ACS risk . We hypothesize that the low performance of h-FABP found in our population was related to the semiquantitative assay used.
The aim of this study was, therefore, to analyze and compare the performance of h-FABP for early ACS diagnosis in this large cohort of unselected patients, using a quantitative immunoassay and the semiquantitative Cardiodetect ® assay.
Methods
Study design
This was an ancillary study of a large, prospective, single-centre study of diagnostic accuracy, published recently . This second analysis was done retrospectively. The institutional review board approved the study protocol.
Study setting and population
The study was carried out at a large urban university hospital as previously described . Briefly, 677 patients admitted to the ED with chest pain evolving within 12 hours and suspected of having ACS were included by the emergency treating physician. Patients with ST-segment elevation on a 12-lead electrocardiogram were excluded. Patients signed informed written consent before inclusion in the main study, for the main study, for the serum bank and for analysis of the sample from the serum bank to study new biomarkers in the context of ACS.
Study protocol
After obtaining written consent, the clinical history, physical evaluation, serial 12-lead electrocardiogram, standard blood tests, cardiac troponin I (cTnI) measurements and chest X-rays were performed for all patients according to the usual procedures and reported on a case report form by the treating physician. After 1 month, major cardiac events, including death, admission to hospital for ACS and the results of the cardiovascular diagnostic tests carried out during the 30 days after ED discharge, were collected by the research assistant. The diagnosis of ACS, based on current international guidelines, was made by two independent experts as previously described . Patients with ACS were classified as having non-ST-segment elevation myocardial infarction (NSTEMI) when the cTnI was above 0.1 μg/L on serial testing.
Study measurements
Serial plasma samples were collected shortly after ED admission, and were immediately centrifuged. cTnI concentrations were measured immediately on an Advia Centaur TnIc system (Bayer Diagnostics, Leverkusen, Germany) (99th percentile at 0.1 μg/L) at admission and after 6 hours.
Plasma samples at admission were frozen at –80 °C and the h-FABP assays were performed a few months later. The h-FABP enzyme-linked immunosorbent assay (ELISA) test was based on the principle of a ready-to-use, solid-phase ELISA (HyCult Biotech, Uden, The Netherlands). The acute myocardial infarction (AMI) cut-off concentrations reported in other studies were between 5 and 7.3 ng/mL . Measurement of the h-FABP ELISA test was performed by the biologist, who was blinded to the Cardiodetect ® results and to the final diagnosis. Data analysis of the performance of the quantitative h-FABP was performed blinded to the performance of Cardiodetect ® .
Data analysis
Baseline characteristics were assessed using Student’s t test or the Mann-Whitney U test for continuous variables and the Khi 2 test for categorical variables. P values less than 0.05 were taken as significant. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the ELISA h-FABP assay for the final diagnosis of ACS and NSTEMI. The cut-off level of 7 ng/mL was used to assess clinical sensitivity and specificity. Classification agreement of the two tests (ELISA h-FABP and Cardiodetect ® ) for the cut-off value of 7 ng/mL was examined using the kappa test.
To assess if plasma h-FABP levels provided additional information beyond the criteria usually used for ACS diagnosis, we compared the model with the usual immediately available data for the diagnosis of ACS as described previously and a model with the h-FABP values in addition to the previous variables. The usual available data were: age, sex, cardiovascular risk factors (smoking status, hyperlipidaemia, diabetes, family history of ischaemic heart disease, hypertension), previous coronary artery syndrome, clinical presentation with persistent chest pain, ischaemic electrocardiogram abnormalities and cTnI measurement on admission. A likelihood ratio test was carried out between both models and the accuracy of each was calculated for a cut-off at 0.5.
Results
Among 677 consecutive patients (454 men, 223 women, mean age 57 ± 17 years) included in the study, non-ST-segment elevation ACS was diagnosed in 185 patients (27.3%) including 99 NSTEMIs (53.5%). The classification agreement between the experts for ACS status measured by the kappa test was 0.71. Baseline characteristics of the patients are reported Table 1 .
