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 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.

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.

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.

High-sensitivity cardiac troponin: do think twice, it’s not all right

2017 ◽  
Vol 55 (11) ◽  
Author(s):  
Jacobus P.J. Ungerer ◽  
Carel J. Pretorius
Keyword(s):  
Cardiac Troponin ◽  
High Sensitivity ◽  
Objective Evaluation ◽  
Analytical Sensitivity ◽  
International Union ◽  
Low Concentrations ◽  
Scientific Approach ◽  
Definition Of ◽  
Dichotomous Classification

AbstractA questionable scientific approach to measuring at low concentrations and inappropriate censoring of results below certain cut-offs have resulted in the dichotomous classification of troponin assays based on their so-called analytical sensitivity. The definition of “high-sensitivity” cardiac troponin is flawed. Evidence suggests that its apparent diagnostic superiority may be explained by the censoring of data. In the evaluation of the detection and quantification capabilities of analytical methods we recommend alignment with International Union of Pure and Applied Chemistry (IUPAC) guidelines, including reporting of all results. This will allow the objective evaluation of the diagnostic performance of troponin assays and will render the current troponin assay classification and nomenclature obsolete.

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 Analytic and Clinical Utility of a Next-Generation, Highly Sensitive Cardiac Troponin I Assay for Early Detection of Myocardial Injury

2009 ◽  
Vol 55 (3) ◽  
pp. 573-577 ◽  
Author(s):  
Peter A Kavsak ◽  
Andrew R MacRae ◽  
Marie-Jeanne Yerna ◽  
Allan S Jaffe
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Low Concentrations ◽  
Acute Myocardial Injury ◽  
Edta Plasma ◽  
Increased Sensitivity ◽  
Concentration Changes

Abstract Background: Improvements in cardiac troponin (cTn) assays have increased the rapidity with which clinicians can identify patients with changing cTn concentrations (rise or fall) indicative of acute myocardial injury. The aim of the present study was to characterize a new, high-sensitivity cTnI (hs-cTnI) assay and examine whether increased sensitivity can result in still earlier detection of evolving injury. Methods: We determined the limit of detection, precision profiles, and preliminary estimates of the 99th percentile for the Beckman Coulter hs-cTnI assay in 125 healthy individuals (age &lt;55 years, 54% male). We compared AccuTnI® and hs-cTnI to assess whether change criteria for early concentration changes (i.e., ≥3SD for low concentrations and 20% difference for concentrations &gt;0.10 μg/L) were exceeded in the first 2 specimens (median time between specimens, 1 h; 25th–75th percentile, 1–3 h) from subjects with symptoms suggestive of cardiac ischemia (n = 290). Results: The limit of detection for the hs-cTnI assay was 2.06 ng/L, and the 20% CV and 10% CV concentrations were 2.95 and 8.66 ng/L, respectively. The preliminary 99th percentile estimates in lithium heparin, serum, and EDTA plasma were 9.20, 8.00, and 8.60 ng/L, respectively. In 108 patients with myocardial injury based on the peak AccuTnI concentration, applying the change criteria on the 2 earliest specimens identified 81% (95% CI 73%–88%) of patients using the hs-cTnI assay compared to 62% (53%–71%) using the AccuTnI assay (P &lt; 0.001). Conclusions: Although more extensive validation studies are required, this Beckman Coulter hs-cTnI assay appears to detect patients with evolving myocardial injury earlier.

A single high-sensitivity cardiac troponin T compared to the HEART score for a rapid rule-out of acute myocardial infarction at a prehospital emergency clinic

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T.R Johannessen ◽  
D Atar ◽  
O.M Vallersnes ◽  
A.C.K Larstorp ◽  
I Mdala ◽  
...  
Keyword(s):  
Primary Care ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Low Risk ◽  
Symptom Duration ◽  
Funding Source ◽  
Emergency Setting ◽  
Heart Score ◽  
Rule Out

Abstract Background Patients presenting with acute chest pain outside of hospitals represent a diagnostic challenge. Purpose We aimed to validate whether a single high-sensitivity cardiac troponin T (hs-cTnT) safely can rule out acute myocardial infarction (AMI) in a primary care emergency setting. In addition, we aimed to investigate if the hs-HEART (History, Electrocardiogram (ECG), Age, Risk factors, and hs-Troponin) score would add valuable diagnostic information. Methods This is a secondary analysis from a prospective diagnostic study, including 1711 patients with acute non-specific chest pain presenting to a primary care emergency clinic from November 2016 to October 2018. The European Society of Cardiology (ESC) 0/1-hour algorithm triages patients towards direct rule-out if the 0-hour hs-cTnT is below 5 ng/L, combined with a normal ECG and a 3-hour symptom duration. The hs-HEART score (0–10 points) was calculated retrospectively, and a score ≤3 points was considered low-risk. In addition, a modified hs-HEART score, with more comparable hs-cTnT cut-off values, was applied. The primary endpoint was AMI during the index episode; the secondary the 90-day incidence of AMI (including index) and all-cause death. Results Among 1711 patients, 61 (3.6%) had an AMI, and 525 (30.7%) were assigned towards direct rule-out. With no AMIs in this group, the rule-out safety was high (negative predictive value (NPV) and sensitivity 100%). The hs-HEART score triaged more patients (n=966) as low-risk, but missed six AMIs (NPV 99.4% and sensitivity 90.2%). The modified hs-HEART score (n=707, AMI=3) increased the low-risk sensitivity to 95.1%. The 90-day incidence of AMI and all-cause death in the direct rule-out, low-risk hs-HEART, and modified hs-HEART group, were 0.0%, 0.7%, and 0.4%, respectively. Conclusions The ESC direct rule-out approach, with a single hs-cTnT below 5 ng/L, combined with a normal ECG, and a 3-hour symptom duration, is superior to the two hs-HEART scores in ruling out AMI in a primary care emergency setting. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Norwegian Research Fund for General Practice

scholarly journals Misclassification of Myocardial Injury by a High-Sensitivity Cardiac Troponin I Assay

2021 ◽  
Author(s):  
Peter A. Kavsak ◽  
Shawn Mondoux ◽  
Andrew Worster ◽  
Janet Martin ◽  
Vikas Tandon ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
High Sensitivity ◽  
Cardiac Troponin I

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.

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