Elsevier

International Journal of Cardiology

Volume 198, 1 November 2015, Pages 26-30
International Journal of Cardiology

Addition of copeptin improves diagnostic performance of point-of-care testing (POCT) for cardiac troponin T in early rule-out of myocardial infarction — A pilot study

https://doi.org/10.1016/j.ijcard.2015.06.122Get rights and content

Highlights

  • Copeptin was measured in addition to POCT assays for troponin T and hsTnT.

  • Diagnostic performance for rule-out of non-STEMI was improved in all assays.

  • Higher sensitivity and NPV come at a cost of lower specificity.

  • Copeptin and POCT for troponin T may allow initial evaluation at a comparable performance as hsTnT at admission.

Abstract

Background

Point of care testing (POCT) assays for cardiac troponin (cTn) are hampered by lower analytical sensitivity and thus suboptimal rule-out of myocardial infarction (MI). We investigated, whether additional measurement of copeptin using an ultrasensitive assay improves diagnostic performance of POCT for cTn T compared to a high sensitivity troponin T (hsTnT) assay.

Methods

131 patients with suspected acute coronary syndrome were prospectively enrolled in our center 08/2010 to 11/2011. In blood samples obtained at presentation, ultrasensitive copeptin (Kryptor, BRAHMS) and two commercially available POCT assays, AQT90 Flex Radiometer (Radiometer) and Cobas h232 POC-System (Cobas), were tested. HsTnT (Cobas E411, Roche) at baseline and after 3 and 6 h in the central laboratory served as reference.

Results

Copeptin improved rule-out of non-STEMI combined with all tested troponin assays. Addition of copeptin increased sensitivity of Cobas from 67.9% (95% CI: 0.506; 0.852) to 89.3% (95% CI: 0.778; 1.007) and Radiometer from 71.4% (95% CI: 0.547; 0.882) to 85.7% (95% CI: 0.728; 0.987), achieving the sensitivity of hsTnT alone at admission of 85.7% (95% CI: 0.728; 0.987).

The area under the curve (AUC) of Radiometer (0.822) was numerically but insignificantly (p = 0.17) higher than AUC of Cobas (0.725). Addition of copeptin increased AUC of Radiometer to 0.826 (p = 0.96) and AUC of Cobas to 0.814 (p = 0.20).

Conclusions

Additional use of ultrasensitive copeptin improves diagnostic performance of conventional sensitive POCT assays overcoming lower sensitivities at the cost of a drop of clinical specificity. When hsTn is temporarily unavailable, copeptin and POCT for cTn may allow initial evaluation at a comparable performance as hsTnT at admission.

Introduction

For the diagnosis of acute myocardial infarction (AMI), current guidelines recommend the use of ECG and serial measurements of cardiac biomarkers, preferentially cardiac troponins [1]. In addition to clinical indicators of myocardial ischemia, the current universal definition of myocardial infarction (MI) stipulates that a cTn value > 99th percentile of a healthy reference population, together with a relevant change in cTn concentration, are required for diagnosis of acute MI. Total imprecision (as coefficient of variation) at the 99th percentile should be lower than 20% (“clinically usable”) and ideally lower than 10% (“guideline acceptable”) [2]. This precision requirement is fulfilled in most commercially available cTn assays in central laboratory platforms, but only few point of care testing (POCT) assays. A practice guideline published in 2009 by The National Academy for Clinical Biochemistry (NACB) on clinical, analytical and POCT in the context of ACS, demands biomarker measurement with an assay with an imprecision of 10% or less on at least one occasion during the first 24 h after the clinical event [3]. More recently, newer cTn assay generations with higher analytical sensitivity and assay precision have been developed allowing earlier detection of non-ST-elevation-MI (non-STEMI) compared to earlier conventional or contemporary sensitive cTn assay generations.

According to the current guidelines, rule-out of acute myocardial infarction (AMI) is safe after repeated measurement of cTn at admission and after 3 h if hsTn assays are used and after 6–9 h when only conventional troponin assays are available [4].

Recently, increasing evidence suggests that copeptin, the c-terminal part of the vasopressin prohormone; can improve performance of stand-alone troponin testing. In the setting of an acute MI, copeptin is rapidly released from the pituitary gland and starts to return to normal levels within a few hours while cTn concentrations are still normal [5]. The release kinetics of copeptin enables an accurate rule-out of evolving non-STEMI already at presentation [6]. An added benefit for instant rule-out of non-STEMI has been demonstrated when copeptin was combined with several assays, including conventional, contemporary sensitive and high sensitivity troponin assays [7], [8], [9]. This study aimed to investigate the added benefit of ultrasensitive copeptin when added to POCT assays for cTn in early rule-out of MI.

Section snippets

Methods

In a prospective design, 135 patients who presented in the Chest Pain Unit of the University of Heidelberg from August 2010 to November 2011 with suspected acute coronary syndrome and onset of chest pain or chest pain equivalent symptoms within the previous 12 h were enrolled. Patients with STEMI, major surgery or trauma within 4 months before presentation, anemia, endstage renal failure, age under 18 years, or lack of consent were excluded from this study. All measurements were performed on fresh

Baseline characteristics

From 135 enrolled patients, 131 patients qualified for further evaluation. Four patients had to be excluded due to an initial false non-STEMI diagnosis in a patient with subacute STEMI and 3 patients who did not have chest pain or chest pain equivalent.

After re-adjudication of diagnoses, 32.1% (n = 42) of patients were diagnosed with unstable angina (UA), 21.4% (n = 28) with non-STEMI and 24.4% (n = 32) with non-cardiac chest pain. The remaining patients were adjudicated to a final diagnosis of

Discussion

The most important finding of our study is that combination of copeptin measured with a new ultrasensitive assay and cTnT measured on two different commercially available POCT systems (Cobas POCT, Radiometer POCT) improves diagnostic performance of conventional sensitive POCT tests to a level that is similar to the performance of an initial measurement of hsTnT. Copeptin therefore seems to help increase sensitivity and inappropriately low NPV for rule-out of MI associated with POCT for cTnT at

Limitations

The main limitation of this pilot study is its comparatively small case number mainly because of the prospective study design requiring fresh whole blood specimen for POCT testing. Patient recruitment could only be performed during working hours when research study nurses for immediate POCT measurement were available. Due to this fact, a potential selection bias cannot be excluded.

Since a small number of patients were included who presented later than 12 h after symptom onset, this population

Contributors

EG and MV were involved in the conception, design and drafting of this Manuscript. MB, MM, HAS, OH, SH and HAK critically revised the draft manuscript. MV, OH, SH and EG performed statistical analyses. All the authors read and approved the final manuscript.

Funding/support

All reagents, calibrators and controls for AQT90 Flex Radiometer were provided by Radiometer free of charge. A portion of reagents, calibrators and controls for Cobas h232 POC-System were provided free of charge from Roche.

Competing interests

MV has received financial support for clinical trials from Bayer Healthcare Germany and has been reimbursed for travel expenses and fees associated with attending seminars and conferences by Octapharma, Lilly Germany, GlaxoSmithKline, Roche Diagnostics, Brahms, Leo Pharma, and Abbott. MB has received support for clinical trials from AstraZeneca and travel support from Brahms, Germany. HAK has developed the cTnT assay and holds a patent jointly with Roche Diagnostics. He has received grants and

Acknowledgments

We thank study nurses Mrs. Heidi Deigentasch and Mrs. Melanie Magin as well as Mrs. Christa Dewald for their constant support in blood sample preparation and analysis. We also thank Geraldine Rauch for her feedback and support.

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