EXPRESS: Repeat measurements on patient samples identifies unpredictable and poorly reproducible cardiac troponin results with a high-sensitivity cardiac troponin assay

2021 ◽  
pp. 000456322110358
Author(s):  
Simone Drummond ◽  
Ching-Tong Mark ◽  
Nadia Caruso ◽  
Lorna Clark ◽  
Pete Kavsak
Keyword(s):  
Cardiac Troponin ◽  
High Sensitivity ◽  
Stability Study ◽  
Clinical Diagnostics ◽  
Heparin Plasma ◽  
Edta Plasma ◽  
Analytical Imprecision ◽  
Ortho Clinical Diagnostics ◽  
European Society Of Cardiology ◽  
Rule Out

There is much current interest in the use of low-normal high-sensitivity cardiac troponin (hsTn) concentrations, with or without minimal change, to rule out myocardial infarction (MI). Clifford-Mobley’s observations demonstrate that this a challenge even for platforms measuring hsTnT.1 Analytical imprecision may also affect algorithms that use hsTn change alone to rule in MI. For example, the imprecision observed with the Ortho hsTnI assay (Ortho Clinical Diagnostics, New Jersey, United States), using quality control or patient pools, has been found to exceed the European Society of Cardiology 0/1h algorithm criterion.2 The Ortho hsTnI assay has also been shown to yield high and non-reproducible results (i.e., outliers), in addition to the problems with imprecision.3 Outliers are often identified by repeat centrifugation and repeat testing. However, Ortho hsTnI results above the 99th percentile cutoffs may be discordant with respect to other cardiac troponin assays and the clinical diagnosis, even when imprecision from duplicate analysis is acceptable.4 As part of a stability study assessing Ortho hsTnI concentrations in both EDTA plasma and lithium heparin plasma over 24h, we have observed that this interference is random and not related to time on cells.

scholarly journals Disagreement between Cardiac Troponin Tests Yielding a Higher Incidence of Myocardial Injury in the Emergency Setting

2021 ◽  
Vol 8 (3) ◽  
pp. 31
Author(s):  
Peter A. Kavsak ◽  
Shawn E. Mondoux ◽  
Janet Martin ◽  
Mark K. Hewitt ◽  
Lorna Clark ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Ethylenediaminetetraacetic Acid ◽  
High Sensitivity ◽  
Clinical Diagnostics ◽  
Emergency Setting ◽  
Analytical Sensitivity ◽  
Edta Plasma ◽  
Ortho Clinical Diagnostics

Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, n = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, n = 1147 samples), from five different EDs. The incidence of injury in study 1 was higher with the OCD hs-cTnI assay (30.9%; 95% CI: 26.9 to 35.2) compared to that of the Abbott hs-cTnI (17.3%; 95% CI: 14.1 to 21.0) and the OCD cTnI ES (15.4%; 95% CI: 12.4 to 18.9) assays, with repeat testing identifying 4.8% (95% CI: 3.0 to 7.5) of the OCD hs-cTnI results with poor reproducibility. In study 2, 4.6% (95% CI: 3.5 to 6.0) of the results were not reported for the OCD hs-cTnI assay (i.e., poor reproducibility) with 12.7% (95%CI: 8.7 to 17.8) of the OCD hs-cTnI results positive for injury being negative for injury with the Abbott hs-cTnI assay. In summary, the OCD hs-cTnI assay yields higher rates of biochemical injury with a higher rate of poor reproducible results in different ED populations.

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 <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.

Analytical assessment of ortho clinical diagnostics high-sensitivity cardiac troponin I assay

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Peter A. Kavsak ◽  
Tara Edge ◽  
Chantele Roy ◽  
Paul Malinowski ◽  
Karen Bamford ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
Clinical Performance ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Clinical Diagnostics ◽  
Ortho Clinical Diagnostics

AbstractObjectivesTo analytically evaluate Ortho Clinical Diagnostics VITROS high-sensitivity cardiac troponin I (hs-cTnI) assay in specific matrices with comparison to other hs-cTn assays.MethodsThe limit of detection (LoD), imprecision, interference and stability testing for both serum and lithium heparin (Li-Hep) plasma for the VITROS hs-cTnI assay was determined. We performed Passing-Bablok regression analyses between sample types for the VITROS hs-cTnI assay and compared them to the Abbott ARCHITECT, Beckman Access and the Siemens ADVIA Centaur hs-cTnI assays. We also performed Receiver-operating characteristic curve analyses with the area under the curve (AUC) determined in an emergency department (ED)-study population (n=131) for myocardial infarction (MI).ResultsThe VITROS hs-cTnI LoD was 0.73 ng/L (serum) and 1.4 ng/L (Li-Hep). Stability up to five freeze-thaws was observed for the Ortho hs-cTnI assay, with the analyte stability at room temperature in serum superior to Li-Hep with gross hemolysis also affecting Li-Hep plasma hs-cTnI results. Comparison of Li-Hep to serum concentrations (n=202), yielded proportionally lower concentrations in plasma with the VITROS hs-cTnI assay (slope=0.85; 95% confidence interval [CI]:0.83–0.88). In serum, the VITROS hs-cTnI concentrations were proportionally lower compared to other hs-cTnI assays, with similar slopes observed between assays in samples frozen <−70 °C for 17 years (ED-study) or in 2020. In the ED-study, the VITROS hs-cTnI assay had an AUC of 0.974 (95%CI:0.929–0.994) for MI, similar to the AUCs of other hs-cTn assays.ConclusionsLack of standardization of hs-cTnI assays across manufacturers is evident. The VITROS hs-cTnI assay yields lower concentrations compared to other hs-cTnI assays. Important differences exist between Li-Hep plasma and serum, with evidence of stability and excellent clinical performance comparable to other hs-cTn assays.

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.

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.

scholarly journals Early Rule-Out Strategies in the Emergency Department Utilizing High-Sensitivity Cardiac Troponin Assays

2020 ◽  
Author(s):  
Pedro Lopez-Ayala ◽  
Jasper Boeddinghaus ◽  
Luca Koechlin ◽  
Thomas Nestelberger ◽  
Christian Mueller
Keyword(s):  
Cardiac Troponin ◽  
Acute Chest Pain ◽  
High Sensitivity ◽  
Clinical Risk Score ◽  
Clinical Implementation ◽  
The Past ◽  
Attractive Option ◽  
European Society Of Cardiology ◽  
Patient Subgroups ◽  
Rule Out

Abstract Background Over the past decade, intense collaboration between academic investigators and the diagnostic industry have allowed the integration of high-sensitivity cardiac troponin (hs-cTn) assays into clinical practice worldwide. The hs-cTn assays, with their increased diagnostic accuracy for acute myocardial infarction (AMI), have facilitated the maturation of early rule-out strategies. The first iteration was complex and required the combination of a biomarker panel, the electrocardiogram, and a clinical risk score and allowed the safe rule-out of AMI in only 10% of patients with acute chest pain. In contrast, the latest iterations, including the European Society of Cardiology (ESC) 0/1-h algorithm, are simple. They are based on hs-cTn concentrations only and allow the safe rule-out or rule-in of AMI in up to 75% of patients. Content The purposes of this minireview are (a) to describe the best validated hs-cTn–based strategies for early rule-out of AMI, (b) to discuss the advantages and limitations of the different strategies, (c) to identify patient subgroups requiring particular attention, (d) to recognize challenges for widespread clinical implementation, and (e) to provide guidance on strategies for their safe and effective clinical implementation. Summary Physicians and institutions may choose among several well-validated rule-out algorithms. The ESC 0/1-h algorithm for hs-cTnT or hs-cTnI seems to be the most attractive option today. It best balances safety and efficacy, and it has been derived and validated for all currently available hs-cTnT/I assays, facilitating widespread clinical implementation.

scholarly journals Use of historical high-sensitivity cardiac troponin T levels to rule out myocardial infarction

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001682
Author(s):  
Andreas Roos ◽  
Martin J Holzmann
Keyword(s):  
Myocardial Infarction ◽  
Emergency Department ◽  
Chest Pain ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Cardiac Troponin T ◽  
All Cause Mortality ◽  
European Society Of Cardiology ◽  
Rule Out

ObjectiveSeveral high-sensitivity cardiac troponin (hs-cTn)-based strategies exist for rule-out of myocardial infarction (MI). It is unknown whether historical hs-cTnT concentrations can be used. This study aim to evaluate the performance of a rule-out strategy based on the European Society of Cardiology (ESC) 0/1-hour algorithm, using historical hs-cTnT concentrations.MethodsAll visits among patients with chest pain in the emergency department at nine different hospitals in Sweden from 2012 to 2016 were eligible (221 490 visits). We enrolled patients with a 0-hour hs-cTnT of <12 ng/L, a second hs-cTnT measured within 3.5 hours, and ≥1 historical hs-cTnT available. We calculated the risks of MI and all-cause mortality using two rule-out strategies: (1) a delta hs-cTnT of <3 ng/L between the 0-hour hs-cTnT and the second hs-cTnT (modified ESC algorithm) and (2) a historical hs-cTnT <12 ng/L and a delta hs-cTnT of <3 ng/L in relation to the 0-hour hs-cTnT (historical-hs-cTnT algorithm).ResultsA total of 8432 patients were included, of whom 84 (1.0%) had an MI. The modified ESC algorithm triaged 8100 (96%) patients toward ruled-out, for whom 30-day MI risk and negative predictive value (NPV) for MI (95% CI) were 0.4% (0.3% to 0.6%) and 99.6% (99.4% to 99.7%), respectively. The historical-hs-cTnT algorithm ruled out 6700 (80%) patients, with a 30-day MI risk of 0.5% (0.4% to 0.8%) and NPV of 99.5% (99.2% to 99.6%).ConclusionsThe application of algorithm resulted in similar MI risk and NPV to an established algorithm. The usefulness of historical hs-cTnT concentrations should merit further attention.

scholarly journals Acute Phase Response and Non-Reproducible Elevated Concentrations with a High-Sensitivity Cardiac Troponin I Assay

2021 ◽  
Vol 10 (5) ◽  
pp. 1014
Author(s):  
Peter A. Kavsak ◽  
Lorna Clark ◽  
Janet Martin ◽  
Ching-Tong Mark ◽  
Guillaume Paré ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
High Sensitivity ◽  
Clinical Diagnostics ◽  
Phase Response ◽  
Coronary Syndrome ◽  
Ortho Clinical Diagnostics

High-sensitivity cardiac troponin (hs-cTn) testing has enabled physicians to make earlier diagnostic and prognostic decisions in the hospital setting than previous cardiac troponin assays. Analytical improvements have permitted one to measure cardiac troponin precisely in the nanogram per litre (ng/L) range with hs-cTn assays which has resulted in fast 0/1-h and 0/2-h algorithms for ruling-in and ruling-out myocardial infarction. Although analytical interferences that affect the reporting of hs-cTn are uncommon, not all hs-cTn assays are designed the same nor have undergone the same clinical and analytical validations. Here, after investigating an initial case of discrepant hs-cTnI results, we report that patients with an acute phase response (e.g., patients with inflammatory or infectious illnesses) can yield high and non-reproducible results with the Ortho Clinical Diagnostics hs-cTnI assay. Compared to Abbott Diagnostics hs-cTnI, Ortho Clinical Diagnostics hs-cTnI assay misclassifies biochemical injury in approximately 10% of the population being assessed for myocardial injury with imprecise results in approximately half of this population (i.e., 5%). In conclusion, caution is warranted in interpreting Ortho Clinical Diagnostics hs-cTnI alone in patients being evaluated for myocardial injury, especially in patients whose primary presentation is related to an acute phase response and not an acute coronary syndrome symptom.

Performance of the European Society of Cardiology 0/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin: Systematic review and meta-analysis

2020 ◽  
pp. 204887262093539 ◽  
Author(s):  
Lucrecia M Burgos ◽  
Marcelo Trivi ◽  
Juan P Costabel
Keyword(s):  
Myocardial Infarction ◽  
Acute Coronary Syndrome ◽  
Diagnostic Accuracy ◽  
Likelihood Ratio ◽  
European Society ◽  
Cardiac Troponin ◽  
High Sensitivity ◽  
Coronary Syndrome ◽  
European Society Of Cardiology ◽  
Rule Out

Introduction: A rapid rule-out or rule-in protocol based on the 0-hour/1-hour algorithm using high-sensitivity cardiac troponin (hs-cTn) is recommended by the European Society of Cardiology (ESC); recently multiple studies have validated it in their settings. We aimed to assess the diagnostic accuracy of the 2015 ESC guidelines for management of acute coronary syndrome in patients without ST-segment elevation 0-hour/1-hour algorithm using hs-cTn for the early rule-out and rule-in of acute myocardial infarction (AMI) on presentation. Methods: Systematic searches were conducted using PubMed, the Cochrane Library and the International Clinical Trials Registry Platform to identify prospective studies from 2015 to October 2019 involving adults presenting to the emergency department with possible acute coronary syndrome in which hs-cTn measurements were obtained according to the ESC algorithm and AMI outcomes were adjudicated during the initial hospitalization. Results: Eleven studies, involving 19,213 patients, were identified. Pooled prevalence of AMI during the index hospitalization was 11.3% (95% confidence interval (CI) 3.9–18.8%). Summary sensitivity and specificity in diagnosing AMI were 99% (95% CI 98–99%; I2 63%) and 91% (95% CI 91–92%; I2 96%) respectively. The summary positive likelihood ratio was 11.6 (95% CI 8.5–15.8; I2 97%) and the pooled likelihood ratio negative 0.02 (0.01–0.03; I2 52%). Cumulative all-cause mortality at 30 days in the rule-out group was 0.11%, and 2.8% in the rule-in group, and 30 days AMI in the rule-out group was 0.08%. Conclusion: The ESC 0-hour/1-hour algorithm using high-sensitivity cardiac troponin has high diagnostic accuracy; it allows safe rule-out as well as accurate rule-in of AMI, with low cumulative 30-day mortality and AMI in patients assigned the rule-out zone.

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