Original Contribution
Diagnostic accuracy of heart-type fatty acid–binding protein for the early diagnosis of acute myocardial infarction,☆☆

https://doi.org/10.1016/j.ajem.2010.11.022Get rights and content

Abstract

Objective

The aim of this study was to evaluate the diagnostic efficacy of multiple tests—heart-type fatty acid–binding protein (H-FABP), cardiac troponin I (cTnI), creatine kinase-MB, and myoglobin—for the early detection of acute myocardial infarction among patients who present to the emergency department with chest pain.

Methods

A total of 1128 patients provided a total of 2924 venous blood samples. Patients with chest pain were nonselected and treated according to hospital guidelines. Additional cardiac biomarkers were assayed simultaneously at serial time points using the Cardiac Array (Randox Laboratories Ltd, Crumlin, United Kingdom).

Results

Heart-type fatty acid–binding protein had the greatest sensitivity at 0 to 3 hours (64.3%) and 3 to 6 hours (85.3%) after chest pain onset. The combination of cTnI measurement with H-FABP increased sensitivity to 71.4% at 3 to 6 hours and 88.2% at 3 to 6 hours. Receiver operating characteristic curves demonstrated that H-FABP had the greatest diagnostic ability with area under the curve at 0 to 3 hours of 0.841 and 3 to 6 hours of 0.894. The specificity was also high for the combination of H-FABP with cTnI at these time points. Heart-type fatty acid–binding protein had the highest negative predictive values of all the individual markers: 0 to 3 hours (93%) and 3 to 6 hours (97%). Again, the combined measurement of cTnI with H-FABP increased the negative predictive values to 94% at 0 to 3 hours, 98% at 3 to 6 hours, and 99% at 6 to 12 hours.

Conclusion

Testing both H-FABP and cTnI using the Cardiac Array proved to be both a reliable diagnostic tool for the early diagnosis of myocardial infarction/acute coronary syndrome and also a valuable rule-out test for patients presenting at 3 to 6 hours after chest pain onset.

Introduction

Chest pain is one of the most common complaints in patients presenting to the emergency department (ED). In the United States, this is the second highest reason for admission [1]. Of those admitted, only 10% to 13% have a confirmed acute myocardial infarction (AMI) [1]. In England and Wales, approximately 700 000 present with chest pain to the ED, and two thirds of these are admitted [2]. There are significant challenges with early accurate diagnosis of patients presenting with chest pain of possible cardiac origin because none of the standard diagnostic tests have sufficient diagnostic use to accurately rule out underlying acute coronary syndrome (ACS) in the early stages [3]. Furthermore, there are associated logistic and financial burdens linked to the management of these patients. Inappropriate discharge is associated with a 5-fold increase in mortality and morbidity [4].

The diagnosis of ACS is presently determined by evaluating risk factors, electrocardiographic (ECG) traces, and measurement of cardiac markers. Current biochemical markers used in the diagnosis of ACS include cardiac troponins (cTn), creatine kinase-MB (CK-MB), and myoglobin (MYO). They are limited by either a lack of specificity or a delay of elevation of several hours after symptom onset. Therefore, their clinical use in early diagnosis of AMI is limited. Previous studies have established the success of heart-type fatty acid–binding protein (H-FABP) as an early biochemical marker in the detection of AMI and its use as a prognostic indicator of post-MI recovery [5], [6], [7], [8], [9]. Furthermore, both the European Society of Cardiology (ESC) and National Academy of Clinical Biochemistry [10] have suggested a multimarker approach for the detection of AMI. The Cardiac Array from Randox Laboratories Ltd (Crumlin, United Kingdom) contains the early markers H-FABP and MYO and the late markers cardiac troponin I (cTnI) and CK-MB on a ceramic biochip. The biochip is read using biochip array technology that allows simultaneous measurement of all 4 markers from a small sample volume (50 μL).

The aim of the this study was to determine the diagnostic efficacy of H-FABP with the additional markers present on the Cardiac Array against standard diagnosis using American College of Cardiology (ACC)/ESC guidelines [11], [12] for the early detection of AMI among patients who present to the ED with chest pain.

Section snippets

Study population

This study was undertaken in the ED of an urban university teaching hospital and was approved by St James's/Adelaide and Meath Incorporating the National Children's Hospital Research Ethics Committee. A total of 1128 patients who met the inclusion criteria were enrolled in the study after giving written informed consent. Patients were included in the study if they were 25 years or older and presented to the ED with chest pain of possible cardiac origin. Patients were excluded if they were

Results

All study patients had their samples run on the Cardiac Array as described. Acute MI was confirmed using the predefined criteria [11], [12] in 117 (10.4%) of the 1128 patients enrolled in the study. Patient demographics are displayed in Table 1. Patients diagnosed with AMI tended to be older than non–AMI-diagnosed patients. Of the patients with AMI, only 40.2% presented early enough to receive optimum treatment benefit. Twenty-three patients with AMI (19.7%) presented between 6 and 12 hours,

Discussion

Early accurate diagnosis of ACS in patients presenting to ED with symptoms suggestive of underlying ACS is important in optimizing the care of this large patient cohort. Furthermore, correct identification of patients without AMI is beneficial both for the patient and also financially and logistically for the hospital. Although several diagnostic markers are available, including Tn, CK-MB, and MYO with relatively high specificities, their reduced sensitivities in the first 6 hours after symptom

Conclusion

The current study demonstrated that the combination measurement of H-FABP with cTnI using the Cardiac Array was a reliable method for the diagnosis of AMI within 3 to 6 hours of chest pain onset. The combination marker approach provides earlier AMI diagnostic capability, which should in turn be associated with earlier optimum treatment and better survival. Furthermore, the 98% NPV at this time point may improve the accuracy of discharge decisions in this patient cohort benefiting the patient

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    Ethical approval: this work was approved by the St James's/Adelaide and Meath Incorporating The National Children's Hospital (AMNCH) Research Ethics Committee.

    ☆☆

    This study was supported by funding from Randox Laboratories Ltd, which manufactures the Cardiac Arrays and Evidence instrument. John Lamont, Ivan McConnell, and Drs Crockard, Kurth, and Fitzgerald are employed by Randox Laboratories Ltd. Elizabeth Curtin received grant support from Randox.

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