Original Contribution
Early rule out of acute myocardial infarction in ED patients: value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission,☆☆

https://doi.org/10.1016/j.ajem.2013.04.033Get rights and content

Abstract

Objective

We sought to evaluate the added value of ultrasensitive copeptin (us-copeptin) for early rule out of acute myocardial infarction in a prospective cohort of emergency department (ED) patients with acute chest pain.

Methods

This was a prospective study including consecutive patients with acute chest pain presenting to the ED within 12 hours of symptom onset. High-sensitivity cardiac troponin T (hs-cTnT, Roche Diagnostics, Meylan, France) and us-copeptin (ThermoFisher Scientific, Clichy, France) were blindly assayed from venous blood samples obtained at admission. Diagnosis was made by 2 ED physicians using all available data and serial cardiac troponin I as the biochemical standard. Diagnostic performances of us-copeptin combined with hs-cTnT were assessed using logistic regression. Analysis was conducted in all patients and in patients without ST-elevation myocardial infarction.

Results

A total of 194 patients were included (age, 61 [48-75] years; male sex, 63%). Acute myocardial infarction occurred in 52 (27%) patients, including non–ST-elevation myocardial infarction (NSTEMI) in 25 (13%). Patients with acute myocardial infarction had higher levels of hs-cTnT (50 [95% confidence interval, 19-173] ng/L) and us-copeptin (30 [13-113] pmol/L) at admission compared with those without (P < .05). Combination of markers significantly improved receiver operating characteristic area under the curve (from 0.89 [0.85-0.92] for hs-cTnT alone to 0.93 [0.89-0.97], P = .018). Sensitivity and negative predictive value were increased, particularly for NSTEMI diagnosis (sensitivity, 76% [54.9-90.6] to 96% [79.6-99.9]; negative predictive value, 95% [90.4-98.3] to 98.9% [94.2 to 100]).

Conclusion

Assessment of us-copeptin combined with hs-cTnT on ED admission could allow safe and early rule out of NSTEMI for patients with negative results on both markers and help identify patients who may be suitable for discharge.

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.

References (36)

  • R. Twerenbold et al.

    High-sensitive troponin T measurements: what do we gain and what are the challenges?

    Eur Heart J

    (2012)
  • T. Reichlin et al.

    Early diagnosis of myocardial infarction with sensitive cardiac troponin assays

    N Engl J Med

    (2009)
  • J.L. Januzzi et al.

    High-sensitivity troponin T concentrations in acute chest pain patients evaluated with cardiac computed tomography

    Circulation

    (2010)
  • P. Haaf et al.

    High-sensitivity cardiac troponin in the distinction of acute myocardial infarction from acute cardiac noncoronary artery disease

    Circulation

    (2012)
  • K. Thygesen et al.

    How to use high-sensitivity cardiac troponins in acute cardiac care

    Eur Heart J

    (2012)
  • T. Keller et al.

    Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction

    JAMA

    (2011)
  • Y. Freund et al.

    High-sensitivity versus conventional troponin in the emergency department for the diagnosis of acute myocardial infarction

    Crit Care

    (2011)
  • C.H. Nickel et al.

    The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department

    BMC Med

    (2012)
  • Cited by (0)

    Presentation information: This study has never been presented. Sample collection is registered at the French Health Ministry as DC-2009-1052.

    ☆☆

    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.

    View full text