Elsevier

American Heart Journal

Volume 162, Issue 2, August 2011, Pages 276-282.e1
American Heart Journal

Clinical Investigation
Acute Ischemic Heart Disease
A multicenter comparison of established and emerging cardiac biomarkers for the diagnostic evaluation of chest pain in the emergency department

https://doi.org/10.1016/j.ahj.2011.05.022Get rights and content

Background

The aim of this study is to assess the role of novel biomarkers for the diagnostic evaluation of acute coronary syndrome (ACS).

Methods

Among 318 patients presenting to an emergency department with acute chest discomfort, we evaluated the diagnostic value of 5 candidate biomarkers (amino terminal pro–B-type natriuretic peptide [NT-proBNP], ischemia modified albumin, heart fatty acid binding protein, high-sensitivity troponin I [hsTnI], and unbound free fatty acids [FFAu]) for detecting ACS, comparing their results with that of conventional troponin T (cTnT).

Results

Sixty-two subjects (19.5%) had ACS. The sensitivity and negative predictive values of NT-proBNP (73%, 90%) and hsTnI (57%, 89%) were higher than that of cTnT (22%, 84%). Unbound free fatty acids had the highest overall combination of sensitivity (75%), specificity (72%), and negative predictive values (92%) of all the markers examined. A significant increase in the C-statistic for cTnT resulted from the addition of results for NT-proBNP (change 0.09, P = .001), hsTnI (change 0.13, P < .001), and FFAu (change 0.15, P < .001). In integrated discrimination improvement and net reclassification improvement analyses, NT-proBNP, hsTnI, and FFAu added significant diagnostic information to cTnT; when changing the diagnostic criterion standard for ACS to hsTnI, FFAu still added significant reclassification for both events and nonevents. In serial sampling (n = 180), FFAu added important reclassification information to hsTnI.

Conclusion

Among emergency department patients with symptoms suggestive of ACS, neither ischemia modified albumin nor heart fatty acid binding protein detected or excluded ACS, whereas NT-proBNP, hsTnI, or FFAu added diagnostic information to cTnT. In the context of hsTnI results, FFAu measurement significantly reclassified both false negatives and false positives at baseline and in serial samples.

Section snippets

The IMAGINE Study

The IMAGINE study (Clinicaltrials.gov no. NCT00355992) was a multicenter, blinded prospective cohort study designed to evaluate subjects presenting to ED with symptoms suggestive of ACS, with primary goals of evaluating the diagnostic and prognostic use of IMA. With respect to the goal of evaluating the diagnostic value of IMA, the purpose was to validate the previously published negative predictive value (NPV) of the biomarker; for prognostic value, the goal was to explore the potential value

Study setting and population

Those consenting patients presenting with symptoms suggestive of a possible ACS meeting inclusion and exclusion criteria (Table I) were enrolled. Results of history, physical examination, chest x-ray, electrocardiogram (ECG), and laboratory assessments were recorded. Patients were followed up for 30 days from presentation; and all clinical information, including discharge diagnosis, was documented for the purpose of this study. The diagnosis of ACS was judged using standard criteria8; in brief,

Patient demographics and clinical factors:

Of the 318 patients enrolled in the study, 62 (19.5%) had a final diagnosis of ACS, of which 40 had UAP, according to standard criteria.8 Of the 62 patients with ACS, 43 had an abnormal angiography; 19, an abnormal stress test; and remaining few were adjucated the diagnosis on basis of clinical presentation. There were no cases of ST-segment elevation MI. Table II details clinical characteristics of study subjects as a function of diagnosis. Of note, very few patients demonstrated diagnostic

Discussion

The importance of biomarker testing for the diagnostic evaluation of the patient with suspected ACS is clearly established. Unfortunately, currently used biomarkers—such as cTnT—are time dependent for their detection; and at present, a reliable biomarker of coronary ischemia—that would detect all ACS, not just with myocardial necrosis—remains elusive. With this in mind, we compared, in rigorous statistical fashion, several biomarkers that are extensively discussed—but poorly validated—for

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