Characteristics of cardiac troponin measurements (original) (raw)
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Clinical Chemistry, 2016
BACKGROUND Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) determinations are fixtures in clinical practice and research. Cardiac troponin testing has been the standard of practice for the diagnosis of acute myocardial infarction (AMI), early rule-out, risk stratification, and outcomes assessment in patients presenting with acute coronary syndrome (ACS) and non-ACS myocardial injury. We recognize from reading the literature over the past several years how poorly understood the analytical characteristics are for cTnI and cTnT assays by laboratorians, clinicians, and scientists who use these assays. CONTENT The purposes of this mini-review are (a) to define limit of blank, limit of detection, limit of quantification, and imprecision, (b) overview the analytical characteristics of the existing cardiac troponin assays, (c) recommend approaches to define a healthy (normal) reference population for determining the 99th percentile and the appropriate statistic to use for this calcu...
Standardization of troponin I measurements: an update
Clinical Chemistry and Laboratory Medicine, 2008
Standardization of cardiac troponin I (cTnI) measurement is important because of the central role for diagnosis of myocardial infarction. In blood, cTnI is present as a heterogeneous mixture of different molecular species. The analytical problem caused by this heterogeneity may be circumvented by recognition of a unique, invariant part of the molecule that is common to all components of the mixture. Antibodies used for the development of cTnI assays should selectively recognize epitopes within this invariant part, leading to a consequential increase in the homogeneity of immunoassay reactivity. This should be associated with the use of a reference material that represents the natural and major antigen in blood after tissue release, i.e., the troponin complex. Although a primary reference material for cTnI is available, studies indicate that cTnI assays remain 1) This article is related to a presentation at the 1st IFCC-Ortho Clinical Diagnostics Conference on ''Biochemical markers in clinical cardiology: perspectives from present to future'',
Clinical chemistry and laboratory medicine : CCLM / FESCC, 2015
As a part of an International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) project to prepare a commutable reference material for cardiac troponin I (cTnI), a pilot study evaluated current cTnI assays for measurement equivalence and their standardization capability. cTnI-positive samples collected from 90 patients with suspected acute myocardial infarction were assessed for method comparison by 16 cTnI commercial assays according to predefined testing protocols. Seven serum pools prepared from these samples were also assessed. Each assay was assessed against median cTnI concentrations measured by 16 cTnI assays using Passing-Bablok regression analysis of 79 patient samples with values above each assay's declared detection limit. We observed a 10-fold difference in cTnI concentrations for lowest to highest measurement results. After mathematical recalibration of assays, the between-assay variation for patient samples reduced on average from 40% to 22% at low cT...
The Journal of Applied Laboratory Medicine: An AACC Publication
Background: We examined the concordance of 13 commercial cardiac troponin (cTn) assays [point-of-care, high-sensitivity (hs), and conventional] using samples distributed across a continuum of results. Methods: cTnI (11 assays) and cTnT (2 assays) were measured in 191 samples from 128 volunteers. cTn assays included Abbott (iSTAT, STAT, and hs), Alere (Cardio 3), Beckman (AccuTnI+3), Pathfast (cTnI-II), Ortho (Vitros), Siemens (LOCI, cTnI-Ultra, Xpand, Stratus CS), and Roche [4th Generation (Gen), hs]. Manufacturer-derived 99th percentile cutoffs were used to classify results as positive or negative. Alternative 99th percentile cutoffs were tested for some assays. Correlation was assessed using Passing-Bablok linear regression, bias was examined using Bland-Altman difference plots, and concordance/discordance of each method comparison was determined using the McNemar method. Results: Regression slopes ranged from 0.63 to 1.87, y-intercepts from 0.00 to 0.03 ng/mL, and r values from 0.93 to 0.99. The cTnT methods had a slope of 0.93, y-intercept of 0.02 ng/mL, and r value of 0.99. For the cTnI assays, positive, negative, and overall concordance was 76.2%-100%, 66.0%-100%, and 82.9%-98.4%, respectively. Overall concordance between the 4th Gen cTnT and hsTnT assays was 88.9%. A total of 30 of the 78 method comparisons showed significant differences in classification of samples (P <0.001); the iSTAT showed 10, hsTnT showed 9, AccuTnI+3 showed 5, Xpand showed 5, and Stratus CS showed 1. Using alternative 99th percentile cutoffs to those listed by manufacturers lowered the method discordance by 6-fold, from 30 to 5 (all involved iSTAT). Conclusions: These data provide insight into characteristics of cTn methods and will assist the healthcare community in setting expectations for relationships among commercial cTn assays. IMPACT STATEMENT This study demonstrates the analytical relationships among 13 commercial cTn assay systems that included 4 point-ofcare assays, 2 high-sensitivity (hs) assays, and 7 central laboratory systems in a multicenter setting. The data can be used to set expectations for the relative differences between cTn assays in terms of classifying negative and positive results. Alternative 99th percentile cutoffs improved agreement between most discordant assays. These data provide insight into relationships between available commercial assays and will assist the laboratory and healthcare community in setting expectations for comparisons among cTn assays.
High-sensitivity cardiac troponin assays: Answers to frequently asked questions
Archives of Cardiovascular Diseases, 2015
Cardiac troponin (cTn) assays have quickly gained in analytical sensitivity to become what are termed 'high-sensitivity cardiac troponin' (hs-cTn) assays, bringing a flurry of dense yet incomplete literature data. The net result is that cTn assays are not yet standardized and there are still no consensus-built data on how to use and interpret cTn assay results. To address these issues, the authors take cues and clues from multiple disciplines to bring responses to frequently asked questions. In brief, the effective use of hs-cTn hinges on knowing: specific assay characteristics, particularly precision at the 99th percentile of a reference population; factors of variation at the 99th percentile value; and the high-individuality of hs-cTn assays, for which the notion of individual kinetics is more informative than straight reference to 'normal' values. The significance of patterns of change between two assay measurements has not yet been documented for every hs-cTn assay. Clinicians need to work hand-in-hand with medical biologists to better understand how to use hs-cTn assays in routine practice. Troponine ; Haute sensibilité ; Infarctus du myocarde ; Syndrome coronarien aigu ; Douleur thoracique Résumé L'évolution rapide des méthodes de dosage des troponines cardiaques (cTn) vers une meilleure sensibilité analytique (cTn de haute sensibilité, ou cTn HS) s'accompagne de nombreuses données de la littérature mais encore incomplètes. En l'absence de standardisation des cTn et de données consensuelles sur l'utilisation et l'interprétation des résultats, les auteurs de cette revue proposent, à partir d'une revue de la littérature, et de façon multidisciplinaire, des éléments de réponses aux questions fréquemment posées. En conclusion, le bon usage des cTn HS repose sur la connaissance : des caractéristiques propres de la méthode utilisée, en particulier de la précision obtenue au 99 e percentile d'une population de référence ; des facteurs de variation de la valeur du 99 e percentile ; de la forte individualité des dosages de cTn HS, pour lesquels la notion de cinétique individuelle est plus informative que la simple référence à des valeurs usuelles. La significativité des variations entre deux dosages, n'est pas encore documentée pour toutes les méthodes HS. La collaboration entre cliniciens et biologistes est nécessaire à une meilleure utilisation des troponines au quotidien.
High-sensitive troponin T measurements: what do we gain and what are the challenges?
European Heart Journal, 2012
Cardiac troponin (cTn) I and T are structural proteins unique to the heart. Detection of cTn in peripheral blood indicates cardiomyocyte damage. As acute myocardial infarction (AMI) is the most important cause of cardiomyocyte damage, cTns have become an integral part in the diagnosis of AMI. For this indication, cTns are superior to all other biomarkers and therefore are the preferred marker for the diagnosis of AMI. However, cTn indicates and provides an estimate of cardiomyocyte damage irrespective of its cause. The major limitation of contemporary cTn assays is that they are often not elevated during the initial hours of AMI. Recent advances in assay technology have led to more sensitive and precise cTn assays that will have a profound impact on clinical practice. High-sensitive cTn (hs-cTn) assays have two differentiating features from contemporary cTn assays: (i) detection of cTn in a majority of healthy persons and (ii) precise definition of what is 'normal' (¼the 99th percentile). Recent multicentre studies have shown that hs-cTn assays improve the early diagnosis of patients with suspected AMI, particularly the early rule-out. To achieve best clinical use, cTn has to be interpreted as a quantitative variable. Rising and/or falling levels differentiate acute from chronic cardiomyocyte damage. The terms 'troponin-positive' and 'troponin negative' should therefore be avoided. 'Detectable' levels will become the norm and will have to be differentiated from 'elevated' levels. The differential diagnosis of a small amount of cardiomyocyte damage and therefore minor elevations of cTn is broad and includes acute and chronic cardiac disorders. The differential diagnosis of larger amount of injury and therefore more substantial elevations of cTn is largely restricted to AMI, myocarditis, and a rare patient with
Multicenter evaluation of an automated assay for troponin I
Clinical chemistry, 2002
Cardiac troponin I (cTnI) is a powerful tool to aid in the diagnosis of myocardial infarction and cardiac muscle damage. We describe an assay that overcomes problems of early assays that were often affected by cTnI degradation, assay interference, poor sensitivity, and imprecision. The analytical performance of the Access AccuTnI assay (Beckman Coulter) was evaluated at five institutions. Controls, zero calibrator, and diluted patient samples were used to determine precision, detection limit, functional sensitivity, and linearity. The 97.5 and 99 percentiles of a reference population were determined. Common interferents and heterophilic patient samples were tested. Equimolarity was determined by assaying samples with various ratios of free and complexed cTnI. Matched samples drawn into serum, EDTA, lithium heparin, and sodium heparin sample tubes were compared. Total imprecision (CVs) was 4.0-8.8% between 0.40 and 31 microg/L cTnI. The detection limit was <0.01 microg/L. The 97.5...