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 Detectable High-Sensitivity Cardiac Troponin within the Population Reference Interval Conveys High 5-Year Cardiovascular Risk: An Observational Study

2018 ◽  
Vol 64 (7) ◽  
pp. 1044-1053 ◽  
Author(s):  
Martin P Than ◽  
Sally J Aldous ◽  
Richard W Troughton ◽  
Christopher J Pemberton ◽  
A Mark Richards ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Cox Regression ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Major Adverse Cardiovascular Events ◽  
Reference Limit ◽  
Coronary Syndrome ◽  
Increased Risk

Abstract BACKGROUND Increased cardiac troponin I or T detected by high-sensitivity assays (hs-cTnI or hs-cTnT) confers an increased risk of adverse prognosis. We determined whether patients presenting with putatively normal, detectable cTn concentrations [> limit of detection and < upper reference limit (URL)] have increased risk of major adverse cardiovascular events (MACE) or all-cause mortality. METHODS A prospective 5-year follow-up of patients recruited in the emergency department with possible acute coronary syndrome (ACS) and cTn concentrations measured with hs-cTnI (Abbott) and hs-cTnT (Roche) assays. Cox regression models were generated with adjustment for covariates in those without MACE on presentation. Hazard ratios (HRs) for hs-cTn were calculated relative to the HRs at the median concentration. RESULTS Of 1113 patients, 836 were without presentation MACE. Of these, 138 incurred a MACE and 169 died during a median 5.8-year follow-up. HRs for MACE at the URLs were 2.3 (95% CI, 1.7–3.2) for hs-cTnI and 1.8 (95% CI, 1.3–2.4) for hs-cTnT. Corresponding HRs for mortality were 1.7 (95% CI, 1.2–2.2) for hs-cTnI and 2.3 (95 % CI, 1.7–3.1) for hs-cTnT. The HR for MACE increased with increasing hs-cTn concentration similarly for both assays, but the HR for mortality increased at approximately twice the rate for hs-cTnT than hs-cTnI. Patients with hs-cTnI ≥10 ng/L or hs-cTnT ≥16 ng/L had the same percentage of MACE at 5-year follow-up (33%) as patients with presentation MACE. CONCLUSIONS Many patients with ACS ruled out and putatively normal but detectable hs-cTnI concentrations are at similar long-term risk as those with MACE. hs-cTnT concentrations are more strongly associated with 5-year mortality than hs-cTnI.

High-sensitivity cardiac troponin T is superior to troponin I in the prediction of mortality in patients without acute coronary syndrome

2018 ◽  
Vol 259 ◽  
pp. 186-191 ◽  
Author(s):  
Ásthildur Árnadóttir ◽  
Kirstine Roll Vestergaard ◽  
Jannik Pallisgaard ◽  
György Sölétormos ◽  
Rolf Steffensen ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
High Sensitivity ◽  
Cardiac Troponin T ◽  
Coronary Syndrome ◽  
Prediction Of Mortality

scholarly journals Evaluating Rapid Rule-out of Acute Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay at Presentation

2018 ◽  
Vol 64 (5) ◽  
pp. 820-829 ◽  
Author(s):  
Jaimi Greenslade ◽  
Elizabeth Cho ◽  
Christopher Van Hise ◽  
Tracey Hawkins ◽  
William Parsonage ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Coronary Syndrome ◽  
Number Of Patients ◽  
Rule Out

Abstract BACKGROUND Low concentrations of cardiac troponin (cTn) have been recommended for rapid rule-out of acute myocardial infarction (AMI). We examined the Beckman Coulter Access high-sensitivity cardiac troponin I (hs-cTnI) assay to identify a single test threshold that can safely rule out AMI. METHODS This analysis used stored samples collected in 2 prospective observational studies. In all, 1871 patients presenting to a tertiary emergency department with symptoms of acute coronary syndrome had blood taken for measurement of cTnI on presentation. The endpoint was type 1 myocardial infarction (T1MI). Sensitivity and negative predictive value (NPV) were calculated for hs-cTnI values below the 99th percentile. RESULTS Ninety-eight patients had T1MI (5.2%), and 638 (34.1%) patients had an hs-cTnI <2 ng/L (limit of detection), with sensitivity of 99.0% (95% CI, 94.4%–100%) and NPV of 99.8% (95% CI, 99.1%–100%). No hs-cTnI value above a concentration of 2 ng/L achieved sensitivity of 99%. However, an NPV of 99.5% was achieved at values <6 ng/L. A cutoff <6 ng/L enabled 1475 (78.8%) patients to be ruled out on presentation with sensitivity of 93.9% (95% CI, 87.1%–97.7%). CONCLUSIONS A single baseline cTn <2 ng/L measured with the Access hs-cTnI assay performed well for rule-out of AMI. This cutoff concentration identified 99% of patients with AMI and could reduce the number of patients requiring lengthy assessment. A cutoff of <6 ng/L yielded a high NPV but missed more cases of AMI than would be acceptable to clinicians.

scholarly journals Reference Population and Marathon Runner Sera Assessed by Highly Sensitive Cardiac Troponin T and Commercial Cardiac Troponin T and I Assays

2009 ◽  
Vol 55 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Alma Mingels ◽  
Leo Jacobs ◽  
Etienne Michielsen ◽  
Joost Swaanenburg ◽  
Will Wodzig ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
Troponin T ◽  
Reference Population ◽  
Clinical Implications ◽  
Cardiac Troponin T ◽  
Low Concentrations ◽  
Highly Sensitive ◽  
Almost All

Abstract Background: Endurance exercise can increase cardiac troponin (cTn) concentrations as high as those seen in cases of minor myocardial infarction. The inability of most cTn assays to reliably quantify cTn at very low concentrations complicates a thorough data analysis, and the clinical implications of such increases remain unclear. The application of recently developed highly sensitive cTn immunoassays may help resolve these problems. Methods: We evaluated the precommercial highly sensitive cardiac troponin T (hs-cTnT) assay from Roche Diagnostics and the Architect cardiac troponin I (cTnI-Architect) assay from Abbott Diagnostics by testing samples from a reference population of 546 individuals and a cohort of 85 marathon runners. We also measured the samples with the current commercial cTnT assay for comparison. Results: Although the hs-cTnT and cTnI-Architect assays were capable of measuring cTn concentrations at low concentrations (<0.01 μg/L), only the hs-cTnT assay demonstrated a CV of <10% at the 99th percentile of the reference population and a near-gaussian distribution of the measurements. After a marathon, 86% of the runners had cTnT concentrations greater than the 99th percentile with the hs-cTnT assay, whereas only 45% of the runners showed increased concentrations with the current cTnT assay. cTn concentrations remained significantly increased the day after the marathon. A multiple regression analysis demonstrated marathon experience and age to be significant predictors of postmarathon cTn concentrations (P < 0.05). Conclusions: The hs-cTnT assay was the only assay tested with a performance capability sufficient to detect cTn concentrations in healthy individuals. The number of runners with increased cTn concentrations after a marathon depends highly on an assay’s limit of detection (LOD). The assay with the lowest LOD, the hs-cTnT assay, showed that almost all runners had increased cTn concentrations. The clinical implications of these findings require further investigation.

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.

scholarly journals Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making

2009 ◽  
Vol 55 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Kai M Eggers ◽  
Allan S Jaffe ◽  
Lars Lind ◽  
Per Venge ◽  
Bertil Lindahl
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Reference Population ◽  
Cardiac Troponin I ◽  
Coronary Syndrome ◽  
Artery Disease

Abstract Background: The aim of this study was to evaluate factors influencing the 99th percentile for cardiac troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease. Methods: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined cTnI cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome. Results: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 μg/L to 0.028 μg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9–5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7–4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction. Conclusions: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.

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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