Sample matrix and high-sensitivity cardiac troponin I assays

2019 ◽  
Vol 57 (5) ◽  
pp. 745-751 ◽  
Author(s):  
Peter A. Kavsak ◽  
Chantele Roy ◽  
Paul Malinowski ◽  
Lorna Clark ◽  
Shana Lamers ◽  
...  
Keyword(s):  
Excellent Agreement ◽  
Cardiac Troponin ◽  
Troponin I ◽  
High Sensitivity ◽  
Reference Interval ◽  
Storage Conditions ◽  
Reference Intervals ◽  
Limit Of Quantification ◽  
Heparin Plasma ◽  
Edta Plasma

Abstract Background Manufacturers of high-sensitivity cardiac troponin (hs-cTn) assays have restricted use of what sample types or matrices are acceptable to use for measurement. Our goal was to evaluate the comparability of the Siemens ADVIA Centaur hs-cTnI assay across different matrices and under different storage conditions. Methods Three different QC-plasma matrices were evaluated for imprecision <10 ng/L. Passing-Bablok regression and difference plots were determined for cTnI concentrations spanning the reference interval (limit of quantification to male 99th-percentile: 2.5 ng/L to <60 ng/L) between serum and lithium heparin plasma, lithium heparin and EDTA plasma and between the Siemens and Abbott hs-cTnI assays. Stability at room temperature (RT) and 2–8 °C was also assessed across the three matrices. Results Over 16-weeks the SDs were ≤1.0 ng/L for QCs ranging from 5.0 to 8.3 ng/L. Across the reference interval there was excellent agreement between lithium heparin plasma and serum for the Siemens hs-cTnI assay (slope=0.98/intercept=–0.1), however, cTnI concentrations were proportionally lower in EDTA as compared to lithium heparin plasma (slope=0.90, 95% CI: 0.88–0.92). In lithium heparin plasma the Siemens hs-cTnI concentrations were higher than the Abbott hs-cTnI concentrations (slope=1.26/intercept=–0.2). Stability of cTnI in lithium heparin plasma as compared in serum and EDTA plasma appeared more labile, with decreases ≥20% in concentrations evident as early as 1-day in storage at RT. Conclusions There is excellent agreement in concentrations between lithium heparin plasma and serum with the Siemens ADVIA Centaur hs-cTnI assay; however, cTnI concentrations in EDTA plasma are lower. Reference intervals and clinical studies in EDTA plasma for the Centaur hs-cTnI assay are required before clinical use.

Assessing matrix, interferences and comparability between the Abbott Diagnostics and the Beckman Coulter high-sensitivity cardiac troponin I assays

2018 ◽  
Vol 56 (7) ◽  
pp. 1176-1181 ◽  
Author(s):  
Peter A. Kavsak ◽  
Paul Malinowski ◽  
Chantele Roy ◽  
Lorna Clark ◽  
Shana Lamers
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Matrix Effects ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Mean Difference ◽  
Plasma Samples ◽  
Matrix Interferences ◽  
Heparin Plasma ◽  
Edta Plasma

Abstract Background: Analytical evaluation of high-sensitivity cardiac troponin (hs-cTn) assays, with particular attention to imprecision, interferences and matrix effects, at normal cTn concentrations, is of utmost importance as many different clinical algorithms use concentration cutoffs <10 ng/L for decision-making. The objective for the present analytical study was to compare the new Beckman Coulter hs-cTnI assay (Access hsTnI) to Abbott’s hs-cTnI assay in different matrices and for different interferences, with a focus on concentrations <10 ng/L. Methods: The limit of blank (LoB) and the limit of detection (LoD) were determined in different matrices for the Beckman hs-cTnI assay. Passing-Bablok regression and difference plots were determined for 200 matched lithium heparin and EDTA plasma samples for the Beckman assay and 200 lithium heparin samples for the Abbott assay. Both EDTA and heparin plasma samples were also evaluated for stability under refrigerated conditions, for endogenous alkaline phosphatase interference and for hemolysis and icterus. Results: The Beckman hs-cTnI assay LoB was 0.5 ng/L with the following range of LoDs=0.8–1.2 ng/L, with EDTA plasma yielding lower concentrations as compared to lithium heparin plasma (mean difference=−14.9%; 95% CI=−16.9 to 12.9). Below 10 ng/L, lithium heparin cTnI results from the Beckman assay were on average 1.1 ng/L (95% CI=0.7 to 1.5) higher than the Abbott results, with no difference between the methods when using EDTA plasma (mean difference =−0.1 ng/L; 95% CI=−0.3 to 0.2). Low cTnI concentrations were less effected by interferences in EDTA plasma. Conclusions: The Access hsTnI method can reliably detect normal cTnI concentrations with both lithium heparin and EDTA plasma being suitable matrices.

scholarly journals Analytical validation of cardiac troponin I assays in horses

2017 ◽  
Vol 30 (2) ◽  
pp. 226-232 ◽  
Author(s):  
Tanya M. Rossi ◽  
Peter A. Kavsak ◽  
M. Grant Maxie ◽  
David L. Pearl ◽  
W. Glen Pyle ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Clinical Pathology ◽  
Reference Intervals ◽  
Cardiac Troponin I ◽  
Analytical Validation ◽  
Limit Of Quantification ◽  
Equine Medicine ◽  
American Society ◽  
Diagnostic Decision Making

Human cardiac troponin I (cTnI) assays have been used in equine medicine, often without prior analytical validation for equine use. In the absence of appropriate validation, the clinical significance of assay results is uncertain and can lead to misdiagnosis. We followed the American Society for Veterinary Clinical Pathology guidelines and investigated linearity, precision, limit of quantification (LoQ), and comparative recovery for 6 commercial cTnI assays developed for use in human medicine. Clinically acceptable linearity was observed in assays A–D, whereas assay E did not detect equine cTnI in any sample. Comparative recovery revealed 1–3-fold differences between assay results, and low analyte recoveries (2.2–3.4%) were observed in assay F. Precision was investigated in assays A and B, and found to be within acceptable limits. The LoQ was 1.53 ng/L for assay A, and 0.031 µg/L for assay B. Assays A and B performed within clinically acceptable limits and were deemed suitable for use in equine medicine. Assays C and D did not undergo full validation but had acceptable linearity, which demonstrates their potential for use in equine medicine. Assays E and F are unsuitable for use in horses given issues with detection of equine cTnI. The variability in results between assays indicates that reference intervals and cutoffs for diagnostic decision-making are assay specific and should be established prior to adoption by diagnostic laboratories.

Evaluation of analytical performance of a new high-sensitivity immunoassay for cardiac troponin I

2018 ◽  
Vol 56 (3) ◽  
pp. 492-501 ◽  
Author(s):  
Silvia Masotti ◽  
Concetta Prontera ◽  
Veronica Musetti ◽  
Simona Storti ◽  
Rudina Ndreu ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Analytical Performance ◽  
Analytical Sensitivity ◽  
Plasma Samples ◽  
Serum Samples ◽  
Significant Difference ◽  
Heparin Plasma

AbstractBackground:The study aim was to evaluate and compare the analytical performance of the new chemiluminescent immunoassay for cardiac troponin I (cTnI), called Access hs-TnI using DxI platform, with those of Access AccuTnI+3 method, and high-sensitivity (hs) cTnI method for ARCHITECT platform.Methods:The limits of blank (LoB), detection (LoD) and quantitation (LoQ) at 10% and 20% CV were evaluated according to international standardized protocols. For the evaluation of analytical performance and comparison of cTnI results, both heparinized plasma samples, collected from healthy subjects and patients with cardiac diseases, and quality control samples distributed in external quality assessment programs were used.Results:LoB, LoD and LoQ at 20% and 10% CV values of the Access hs-cTnI method were 0.6, 1.3, 2.1 and 5.3 ng/L, respectively. Access hs-cTnI method showed analytical performance significantly better than that of Access AccuTnI+3 method and similar results to those of hs ARCHITECT cTnI method. Moreover, the cTnI concentrations measured with Access hs-cTnI method showed close linear regressions with both Access AccuTnI+3 and ARCHITECT hs-cTnI methods, although there were systematic differences between these methods. There was no difference between cTnI values measured by Access hs-cTnI in heparinized plasma and serum samples, whereas there was a significant difference between cTnI values, respectively measured in EDTA and heparin plasma samples.Conclusions:Access hs-cTnI has analytical sensitivity parameters significantly improved compared to Access AccuTnI+3 method and is similar to those of the high-sensitivity method using ARCHITECT platform.

scholarly journals Evidence on clinical relevance of cardiovascular risk evaluation in the general population using cardio-specific biomarkers

2021 ◽  
Vol 59 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Aldo Clerico ◽  
Martina Zaninotto ◽  
Claudio Passino ◽  
Nadia Aspromonte ◽  
Massimo Francesco Piepoli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Risk ◽  
General Population ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Cost Benefit Analysis ◽  
Cost Benefit ◽  
High Sensitivity ◽  
Reference Intervals ◽  
Major Cardiovascular Events

AbstractIn recent years, the formulation of some immunoassays with high-sensitivity analytical performance allowed the accurate measurement of cardiac troponin I (cTnI) and T (cTnT) levels in reference subjects. Several studies have demonstrated the association between the risk of major cardiovascular events and cardiac troponin concentrations even for biomarker values within the reference intervals. High-sensitivity cTnI and cTnT methods (hs-cTn) enable to monitor myocardial renewal and remodelling, and to promptly identify patients at highest risk ofheart failure. An early and effective treatment of individuals at higher cardiovascular risk may revert the initial myocardial remodelling and slow down heart failure progression. Specific clinical trials should be carried out to demonstrate the efficacy and efficiency of the general population screening by means of cost-benefit analysis, in order to better identify individuals at higher risk for heart failure (HF) progression with hs-cTn methods.

scholarly journals Determination of 19 Cardiac Troponin I and T Assay 99th Percentile Values from a Common Presumably Healthy Population

2012 ◽  
Vol 58 (11) ◽  
pp. 1574-1581 ◽  
Author(s):  
Fred S Apple ◽  
Ranka Ler ◽  
MaryAnn M Murakami
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Point Of Care ◽  
High Sensitivity ◽  
Clinical Diagnostics ◽  
Healthy Population ◽  
Heparin Plasma ◽  
Ortho Clinical Diagnostics ◽  
Study Participants

BACKGROUND Between-assay comparability of 99th percentiles for cardiac troponin concentrations has not been assessed systematically in a single population for a large number of assays. METHODS We determined 99th percentiles for 19 cardiac troponin assays in heparin plasma samples from a population of 272 and 252 presumably healthy males and females, respectively. The assays evaluated included 1 cardiac troponin T (cTnT) assay from Roche and 18 cTnI assays from Abbott, Alere, Beckman, bioMerieux, Instrumentation Laboratory, Ortho-Clinical Diagnostics, Singulex, Siemens, and Roche. Five of these assays were categorized as high-sensitivity, 9 as sensitive-contemporary, and 5 as point-of-care (POC) assays. RESULTS For high-sensitivity cTnI (hs-cTnI) assays 99th percentiles varied from 23 to 58 ng/L. At least 80% of individuals had measurable hs-cTnI, whereas only 25% had measurable high-sensitivity cTnT. All high-sensitivity cardic troponin assays had 99th percentiles that were 1.2–2.4-fold higher in males than females. For the 9 sensitive-contemporary cTnI assays, 99th percentiles varied from 12 to 392 ng/L, and only the Beckman assay gave measurable concentrations in a substantial portion of the population (35% vs ≤6% for the others). Seven of these 9 assays had 1.3–5.0-fold higher 99th percentiles for males than females. For 5 cTnI POC assays, 99th percentiles varied from &lt;10 to 40 ng/L. The Instrumentation Laboratory assay gave measurable results in 27.8% of study participants vs ≤6% for the others. Correlations were generally poor among assays. CONCLUSIONS Among cardiac troponin assays 99th percentile concentrations appear to differ. High-sensitivity assays provide measurable cardiac troponin results in a substantially greater fraction of presumably healthy individuals.

scholarly journals Cardiac Troponin Assays: Guide to Understanding Analytical Characteristics and Their Impact on Clinical Care

2017 ◽  
Vol 63 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Fred S Apple ◽  
Yader Sandoval ◽  
Allan S Jaffe ◽  
Jordi Ordonez-Llanos
Keyword(s):  
Clinical Practice ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
Troponin T ◽  
Clinical Care ◽  
High Sensitivity ◽  
Reference Population ◽  
Limit Of Quantification ◽  
Coronary Syndrome

Abstract 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 calculation, (d) clarify how an assay becomes designated as “high sensitivity,” and (e) provide guidance on determining delta (Δ) change values. SUMMARY This review raises important educational information regarding cTnI and cTnT assays, their 99th percentile upper reference limits (URL) differentiated by sex, and specifically addresses high-sensitivity (hs)-assays used to measure low concentrations. Recommendations are made to help clarify the nomenclature and analytical and clinical characteristics to define hs-assays. The review also identifies challenges for the evolving implementation of hs-assays into clinical practice. It is hoped that with the introduction of these concepts, laboratorians, clinicians and researchers can develop a more unified view of how these assays should be used worldwide.

scholarly journals Incidence of Undetectable, Measurable, and Increased Cardiac Troponin I Concentrations Above the 99th Percentile Using a High-Sensitivity vs a Contemporary Assay in Patients Presenting to the Emergency Department

2016 ◽  
Vol 62 (8) ◽  
pp. 1115-1119 ◽  
Author(s):  
Sara A Love ◽  
Yader Sandoval ◽  
Stephen W Smith ◽  
Jennifer Nicholson ◽  
Jing Cao ◽  
...  
Keyword(s):  
Emergency Department ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Clinical Indication ◽  
Edta Plasma ◽  
Abbott Architect ◽  
F 31

Abstract INTRODUCTION We compared the incidence of undetectable [below the limit of detection (LoD)], measurable (LoD to 99th percentile), and increased cardiac troponin I (cTnI) concentrations above the 99th percentile between Abbott high-sensitivity cTnI (hs-cTnI) and contemporary cTnI assays in a US emergency department population. METHODS Patients (n = 2100) presenting to the emergency department who had serial cTnI (0, 3, 6, 9 h) measurements ordered on clinical indication were enrolled. Contemporary cTnI [Abbott Architect used clinically; 99th percentile: 0.030 μg/L (30 ng/L)] and hs-cTnI [Abbott investigational; sex-specific 99th percentiles: female (F) 16 ng/L, male (M) 34 ng/L] assays simultaneously measured fresh EDTA plasma. RESULTS The hs-cTnI assay measured fewer undetectable cTnI concentrations compared to the contemporary cTnI assay across baseline (F: 31% vs 47%, M: 22% vs 40%) and serial (F: 21% vs 46%; M: 19% vs 54%) measurements. Conversely, the proportion of measurable cTnI concentrations was higher using hs-cTnI compared to contemporary cTnI assay across both baseline (F: 46% vs 31%; M: 60% vs 33%) and serial (F: 48% vs 28%; M: 83% vs 40%) measurements. The overall proportion of patients with increased cTnI concentrations above the 99th percentile was not significantly different between the contemporary (31%) and hs-cTnI (26%) assays (P = 0.09). CONCLUSIONS In patients presenting to the emergency department, the use of the Abbott hs-cTnI assay provides clinicians with more numeric cTnI concentrations. This occurs via a shift from results below the LoD to those between the LoD and the 99th percentile and does not increase in the number of cTnI concentrations above the 99th percentile.

Cardiac Troponin I Associated with the Development of Unrecognized Myocardial Infarctions Detected with MRI

2014 ◽  
Vol 60 (10) ◽  
pp. 1327-1335 ◽  
Author(s):  
Charlotte Ebeling Barbier ◽  
Raquel Themudo ◽  
Tomas Bjerner ◽  
Lars Johansson ◽  
Bertil Lindahl ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Plasma Concentrations ◽  
High Sensitivity ◽  
Reference Interval ◽  
Late Enhancement ◽  
Cardiac Troponin I ◽  
Myocardial Infarctions ◽  
Community Living ◽  
Unit Increase

Abstract BACKGROUND Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI. METHODS After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments. RESULTS New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17–3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028). CONCLUSIONS hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.

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