Ischemia Modified Albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T

https://doi.org/10.1016/j.ijcard.2004.05.042Get rights and content

Abstract

Background

The diagnosis of myocardial ischemia in patients with acute chest pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia Modified Albumin (IMA®) is a new biochemical marker of ischemia, which may be useful to characterise acute coronary syndrome (ACS) patients.

Methods

We studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency department with symptoms suggestive of ACS but with normal or non-diagnostic ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest pain episode. Based on hospital diagnostic test results, patients were classified as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists unaware of IMA results.

Results

Mean IMA levels (U/ml) were higher in patients with ACS (98.3±11) compared to patients with NICP (85.5±15); p<0.0001. IMA levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95% CI: 0.70–0.85). If we applied the manufacturer cutoff point of 85 U/ml, the sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative predictive value=84.6%). In combination with cTnT (6–12 h) (>0.05 ng/ml), the sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml (odds ratio=14.6 [95% CI 4.4–48.4]; p<0.0001), age and prior myocardial infarction were independent predictors of ACS.

Conclusion

IMA may be a useful biomarker for the identification of ACS in patients presenting with typical acute chest pain but normal or non-diagnostic ECGs.

Introduction

In the United States alone, approximately 6 million people are admitted with acute chest pain suggestive of acute coronary syndrome (ACS) of whom only 17% are finally diagnosed with ACS [1]. Not infrequently, patients with suspected ACS have normal, equivocal, or non-diagnostic electrocardiograms (ECG) [2], [3] and normal cardiac troponin levels on admission. Currently, sensitive and specific biochemical markers are available for the identification of myocardial necrosis but not, unfortunately, for ischemia which continues to pose a diagnostic challenge.

The Albumin Cobalt Binding test (ACB test) is the first US FDA-cleared assay to detect myocardial ischemia. Myocardial ischemia results in structural changes to the N-terminus of the serum albumin, which reduces its binding capacity for cobalt cations. It has been proposed that these changes are related to the production of reactive oxygen species during ischemia and/or reperfusion, hypoxia and acidosis [4]. Several clinical studies have evaluated the performance of Ischemia Modified Albumin (IMA) in cardiac patients. IMA has been shown to be a rapidly rising, sensitive marker for the diagnosis of myocardial ischemia [5], [6]. IMA at acute chest pain presentation has been also shown to be an early predictor of subsequent elevations of cardiac troponin levels. Of interest, normal IMA levels at presentation to the emergency department with acute chest pain have been shown to predict subsequent negative troponin results indicating that IMA has a role in the early rule out of ACS [7]. A recent study by Sinha et al. [8] has substantiated previous findings [7] and shown that IMA is highly sensitive for the identification of ACS and, in combination with the ECG and troponin, has both high sensitivity and negative predictive value.

The present study is the first to specifically evaluate the clinical utility of IMA in patients presenting to the emergency department with chest pain suggestive of ACS but with normal or non-diagnostic ECGs and a negative cardiac troponin T result at presentation.

Section snippets

Patients and study design

We assessed 131 patients with suspected ACS attending the emergency department (ED) at St. George's Hospital, London, UK, recruited prospectively and consecutively between December 2000 and June 2001. Patients who met all of the following criteria were selected for study: (a) arrival to the ED within 3 h of last chest pain episode, (b) a normal or non-diagnostic ECG on arrival and (c) negative cardiac troponin results on ED admission. ECGs were considered to be non-diagnostic or uninterpretable

Results

After full ED work up, 67 (51.1%) patients were discharged home with a final diagnosis of NICP and 64 (48.9%) were admitted with ACS (48 had unstable angina and 16 non-ST segment elevation myocardial infarction). Table 1 shows demographic and baseline clinical characteristics of the study patients. In the non-ST segment elevation myocardial infarction group, 14 patients had >70% stenosis on angiography and 2 had 50% stenoses. In the unstable angina group, a clinical diagnosis was made in 10

Discussion

The present study has shown for the first time that IMA is a sensitive biomarker for the identification of ACS in patients presenting to the ED with acute chest pain, normal or non-diagnostic ECGs and negative cTnT. Furthermore, we have demonstrated that a raised IMA level on admission is an independent predictor of ACS. This early prediction by a biochemical marker of ischemia is important as it may improve our ability to risk stratify acute chest pain patients and guide therapeutic decisions.

Conclusion

In our patients, IMA was useful to distinguish those with ACS from NICP subjects and this biomarker may therefore constitute a useful adjunct to our current diagnostic armamentarium in the ED setting. Whether raised IMA levels are a predictor of short-term clinical outcome warrants further investigation in studies designed to specifically answer this question.

References (18)

There are more references available in the full text version of this article.

Cited by (101)

  • 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/Non-ST-Elevation myocardial infarction: A report of the american college of cardiology Foundation/American Heart Association task force on practice guidelines

    2013, Journal of the American College of Cardiology
    Citation Excerpt :

    An example is ischemia-modified albumin found soon after transient coronary occlusion and preceding any significant elevations in myoglobin, CK-MB, or cTnI. This modified albumin depends on a reduced capacity of human albumin to bind exogenous cobalt during ischemia (270,271). Choline is released upon the cleavage of phospholipids and could also serve as a marker of ischemia.

View all citing articles on Scopus
1

The first two authors contributed equally to the manuscript.

View full text