Evaluation of a new ultrasensitive assay for cardiac troponin I

Abstract

Objectives

We evaluated the analytical and clinical performance of a new ultrasensitive cardiac troponin I assay (cTnI) on the ADVIA Centaur® system (TnI-Ultra™).

Design and methods

The evaluation included the determination of detection limit, within-assay and between-assay variation and comparison with two other non-ultrasensitive methods. Moreover, cTnI was determined in 120 patients with acute chest pain with three methods. To evaluate the ability of the new method to detect MI earlier, it was assayed in 8 MI patients who first tested negative then positive by the other methods.

Results

The detection limit was 0.009 μg/L and imprecision was < 10% at all concentrations evaluated. In comparison with two other methods, 10% of the anginas diagnosed were recategorized to MI.

Conclusions

The ADVIA Centaur® TnI-Ultra™ assay presented high reproducibility and high sensitivity. The use of the recommended lower cutpoint (0.044 μg/L) implied an increased and earlier identification of MI.

Introduction

The role of Laboratory Medicine in the management and diagnosis of myocardial infarction (MI) has become increasingly significant. The first biochemical markers of cardiac necrosis used for the diagnosis of MI were the enzymatic methods AST (Aspartate Aminotransferase) and CK (Creatine Kinase). Afterwards, the electrophoresis methods of CK and LDH (Lactate Dehydrogenase) isoenzymes along with a myoglobin assay improved the diagnostic accuracy. Most recently, highly sensitive and specific immunoassay methods such as CK-MB and cardiac troponins have become available, playing a central role in the evaluation of acute coronary syndrome. In this context, the rise and fall of biochemical markers of myocardial necrosis (cardiac troponins or CK-MB) have become necessary criteria for the diagnosis of acute MI in the American College of Cardiology (ACC) and European Society of Cardiology (ESC) definition of MI [1]. The preferred cardiac marker is troponin because of its high specificity for myocardial damage [1]. In the consensus document, elevation of troponin is defined as a value exceeding the 99th percentile of a reference control group. This implies lower cutoff values for MI than currently used in most laboratories. This recommendation is based on the consideration that any elevation in cardiac troponin is indicative of myocardial injury in the clinical setting of ischemic MI [1], [2], [3], [4]. Accordingly, clinical decisions may be made on the basis of small elevations in cardiac troponin. This recommendation demands highly sensitive, precise and specific troponin assays. A coefficient of variation of < 10% at the 99th percentile of the reference control group is recommended [1]. Two cardiac troponin assays are commercially available for use in clinical laboratories: cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Both cTnT and cTnI are released similarly during MI. The first commercially available cardiac troponin assay was a cTnT immunoassay, but it is currently available from only one manufacturer (Roche Diagnostics). There are several manufacturers of cTnI immunoassays.

In this study, we evaluated the analytical and clinical performance of a new cTnI method on the ADVIA Centaur® system (TnI-Ultra™). The study included a comparison of the ADVIA Centaur TnI-Ultra assay with two other methods: the ADVIA Centaur cTnI and Beckman Coulter Access 2 AccuTnI (AccuTnI) assays. We also evaluated whether or not the ADVIA Centaur TnI-Ultra assay allows for earlier identification of MI relative to the other two assays.