Evaluation of a new ultrasensitive assay for cardiac troponin I
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.
Section snippets
Assay principle
The ADVIA Centaur TnI-Ultra assay is a three-site sandwich immunoassay using direct chemiluminometric technology. An ancillary reagent is included to reduce nonspecific binding. The assay includes a polyclonal goat anti-troponin I antibody labeled with acridinium ester and 2 biotinylated mouse monoclonal anti-troponin I antibodies. The capture monoclonal antibodies recognize amino acid sequences 87–91 and 41–49 located in the stable region of the TnI molecule; the signal antibody recognizes
Detection limit
The analytical detection limit value obtained with the ADVIA Centaur TnI-Ultra assay was calculated as the lowest TnI concentration corresponding to a signal 2 SD above the mean of 20 replicates of the zero calibrator in a single run. The value obtained was 0.009 μg/L.
Imprecision
TnI-Ultra within-assay, between-assay and total imprecision for the six TnI controls with concentrations between 0.033 and 14.626 μg/L are presented in Table 1a. All coefficient of variation estimates were below 10%. Between-assay
Discussion
The results from our study demonstrate that the TnI-Ultra assay is highly reproducible and sensitive based on the examination of the imprecision and detection limit results. Within-assay, between-assay and total imprecision were below 10% at all concentrations evaluated ranging between 0.033 μg/L and 14.626 μg/L. The observed detection limit was 0.009 μg/L. One concentration evaluated in our study (control A, 0.033 μg/L) was well below the TnI-Ultra cutoff value provided by the manufacturer
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2015, Clinical BiochemistryCitation Excerpt :The reference assay employs two monoclonal solid phase antibodies, which recognize epitopes in the stable midfragment (amino acids 41–49 & 87–91). The third monoclonal detection antibody recognizes amino acids at amino acid residues 27–40 [23]. The novel assay was designed to employ cTnI-specific antibodies recognizing epitopes outside the stable midfragment, thus circumventing inhibiting effects of circulating autoantibodies [30,31].
Analytical validation and clinical evaluation of a commercially available high-sensitivity immunoassay for the measurement of troponin i in humans for use in dogs
2014, Journal of Veterinary CardiologyCitation Excerpt :The main distinguishing characteristic of hs-cTnI assays is a lower level of cTnI detection compared to standard sensitivity cTnI assays which make them capable of detecting lower concentrations of circulating cTnI, potentially providing better sensitivity for detecting myocardial damage.10,11 In human medicine, cTnI assays can identify increases in serum cTnI in patients with acute diseases such as myocardial infarction,10,11 but also in chronic heart disease,12,13 congenital heart disease,14,15 and patients with clinically significant arrhythmias.16–18 In veterinary medicine, serum cTnI concentrations have been reported using standard sensitivity cTnI assays in dogs with myxomatous mitral valve disease (MMVD), dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and congenital heart disease.6,7,19–22
New insights in the pathophysiology of acute myocardial infarction detectable by a contemporary troponin assay
2013, Clinical BiochemistryCitation Excerpt :In fact, the general improvement of analytical sensitivity has sparked marked debate and discussion regarding the definition of MI and even replacing the concept of traditional decision threshold with “decision marker increase” for diagnosis [20]. In the present study, we have exploited the increased sensitivity of a contemporary assay [8] to compare the patterns of cTnI release between STEMI and NSTEMI patients that have undergone early reperfusion after admission in the evolution of the acute event to catch differences in the biochemical substrates. In addition, the possible modulatory effects of patient features on cTnI releases have been investigated.
Cardiac biomarkers in acute myocardial infarction
2013, International Journal of CardiologyCitation Excerpt :The lack of standardization has lead to discrepancies in cut-point values [74,75,79,80] with over a 30–40 fold differences documented [81,82] and in the past have been notorious for poor performance at the lower end of the reference range. However, later generation assays are much improved and now many meet or are near to meeting, precision guidelines [81,83–85]. The early cTnT assay had slightly limited specificity in patients with skeletal muscle disease because of cross reactivity of the signal antibody with skeletal muscle and re-expression of foetal forms of cTnT (cTnI isoforms are not present in foetal skeletal muscle) in conditions such as rhabdomyolysis and chronic skeletal muscle diseases such as muscular dystrophy and myositis.