Original ContributionEarly rule out of acute myocardial infarction in ED patients: value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission☆,☆☆
Introduction
Chest pain is one of the most common reason patients present to emergency departments (EDs) worldwide. Rapid and accurate identification of patient with acute coronary syndrome, while appropriately discharging patients not requiring urgent therapy and hospitalization, is a critical issue to the emergency physician [1]. International clinical practice guidelines for the diagnosis and management of acute myocardial ischemia currently define clinical history, serial electrocardiogram (ECG), and serial cardiac marker measurement as the main evaluation tools [2], [3]. However, diagnosis and management of patient presenting without persistent elevation of the ST segment, including non–ST-elevation myocardial infarction (NSTEMI), are a continuous challenge. For ED patients with NSTEMI, the incidence of death and recurrent myocardial infarction within the hospital stay has been reported to be close to 10%; and 1-year mortality rate, as high as 25% [4].
High-sensitivity cardiac troponin (hs-cTn) assays have widely replaced conventional troponin assays [5]. Recent studies have shown that hs-cTn assays improve the early diagnosis of patients with suspected acute myocardial infarction (AMI) [6], [7], [8], [9]. However, sensitivity of hs-cTn has been increased at the expense of specificity. Furthermore, studies comparing conventional to high-sensitivity cardiac troponin assays have failed to show better negative predictive value (NPV) even for patients with low pretest probability who could benefit from earlier ED discharge [10], [11].
Copeptin, the C-terminal portion of the arginine vasopressin precursor, is released in clinical situation of acute physiologic stress, including myocardial ischemia, septic shock, and cardiac arrest. It has been proposed as a new tool to aid in the early screening of acute coronary syndrome because of its immediate rise after onset of chest pain before cardiac troponin is detectable [12]. Copeptin assessment in the initial evaluation of ED patients with chest pain could allow early rule out of patients with myocardial ischemia [13], [14], [15], [16], [17].
Recent advances in copeptin assays have led to a newly developed sensitive assay differing from the conventional assay by a lower detection level in a majority of healthy people. The potential incremental value of copeptin when combined with more sensitive troponins for the early rule out of myocardial infarction on admission is still under debate [18], [19], [20]. Some studies have focused on specific patient populations, including either low- or high-risk patients. Others did not meet timely consideration regarding the temporal release of the stress-induced copeptin marker. This could have contributed to the reported discrepancies in the ED. Further investigation is warranted, including retrospective validation in multiple patient populations followed by prospective and interventional studies designed to assess the impact of the combination of sensitive cardiac troponin and copeptin in the real clinical setting.
In the present study, we sought to assess the added value of ultrasensitive copeptin (us-copeptin) combined with high-sensitivity cardiac troponin T (hs-cTnT) for early rule out of AMI, especially NSTEMI, at ED admission in consecutive patients with chest pain presenting within 12 hours of onset of symptoms.
Section snippets
Study design and setting
This was a prospective, diagnostic accuracy study according to the Standards for the Reporting of Diagnostic accuracy studies criteria.
Patients were enrolled from December 2009 to November 2011 at the ED of an urban-based university hospital with a yearly census of 50,000 patients. Sample collection was registered at the French Health Ministry (no. DC-2009-1052). All patients provided written informed consent. The study was performed according to the principles of the Declaration of Helsinki
Analytical performances of the B·R·A·H·M·S Copeptin Kryptor Compact Plus assay
The linearity was tested in the 19- to 0.9-pmol/L range according to the LoD claimed by the manufacturer (0.9 pmol/L). Recoveries for different dilutions ranged from 50% to 89%. Within- and between-assay imprecision ranged from 2.4% to 11.3% and from 3.9% to 10.2%, respectively.
The functional sensitivity at a total imprecision of 20% (which corresponds to the limit of quantification) was 1.1 pmol/L. The lowest concentration giving CV of 10% was 3 pmol/L.
The LoD was 1.90 pmol/L in our
Discussion
To our knowledge, our study is one of the first to assess the newly developed us-copeptin assay as a diagnostic tool for AMI in ED patients with chest pain.
Our results highlight the added value of us-copeptin in conjunction with hs-cTnT for early rule out of AMI, particularly NSTEMI, at ED admission in a prospective cohort of patients presenting to the ED with chest pain and onset within the previous 12 hours.
The newly developed us-copeptin assay clearly shows improved analytical performances
Acknowledgments
The authors would like to thank the nursing, technical, and medical staff at the ED and biochemistry laboratory for their assistance throughout the study. We are grateful to Dr Jonathan Clarke for English revisions of the manuscript. Reagents for the Kryptor Compact Plus and hs-cTnT assays used in this study were kindly provided by ThermoFisher Scientific and Roche Diagnostics, France, respectively.
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Cited by (0)
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Presentation information: This study has never been presented. Sample collection is registered at the French Health Ministry as DC-2009-1052.
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Funding and source of support: This study received no financial support from the manufacturer or another agency. The study was supported by Montpellier University Hospital. Reagents for the Kryptor Compact Plus and high-sensitivity cardiac troponin T assays were kindly provided by ThermoFisher Scientific and Roche Diagnostic, France, respectively.