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.

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 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 &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 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

Abstract 19710: Causes for Increased Cardiac Troponin I Using Gender-Specific 99th Percentiles From a High Sensitivity Assay in a US Population

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yader Sandoval ◽  
Stephen W Smith ◽  
Karen M Schulz ◽  
MaryAnn M Murakami ◽  
Fred S Apple
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Plaque Rupture ◽  
High Sensitivity ◽  
The United States ◽  
Universal Definition ◽  
Definition Of ◽  
Gender Specific

Introduction: High-sensitivity cardiac troponin (hs-cTn) assays have not yet been FDA cleared for clinical use in the United States (US). Pending expected approval of hs-cTn assays, which will use gender-specific cutoffs (GSC), it is relevant to recognize the causes of cTn increases using hs-cTnI assays in a US population. Our purpose was to describe the frequency of distinct etiologies of hs-cTnI assay increases using GSC. Methods: Retrospective study of 310 patients with serial hs-cTnI (Abbott ARCHITECT, 99th percentiles: F:16 ng/L; M:34 ng/L) measurements. Patients with an increased hs-cTnI were adjudicated into categories according to the 3rd Universal Definition of MI. Categories included, A: primary myocardial ischemia (i.e. plaque rupture); B: injury secondary to supply/demand imbalance; C: injury not related to myocardial ischemia (i.e. cardiac contusion, ablation, shock, surgery); D: multifactorial or indeterminate myocardial injury (i.e. heart failure, critically ill, pulmonary HTN, sepsis, stroke, renal failure, pulmonary embolism); E: Unknown. Results: 127 (41%) had an increased hs-cTnI above the GSC 99th percentile, whereas 183 (59%) had a normal hs-cTnI. The most common causes of hs-cTnI increases were: a) multifactorial or indeterminate injury - 43% among all patients and 52% in males, and b) supply/demand imbalance - 39% in women (Table). Injury related to primary myocardial ischemia was present in 10% (n=13). Females had more injury related to supply/demand ischemia than males (39% vs. 18%, p=0.01), whereas males had more multifactorial or indeterminate injury (52% vs. 33%, p=0.05). Conclusions: Most increased hs-cTnI values were explained by non-plaque rupture conditions. Males tended to have hs-cTnI increases due to multifactorial/indeterminate causes, whereas in women supply/demand imbalance was the most common etiology. Investigations are needed to better understand if etiologies of myocardial injury have gender differences.

scholarly journals Markers of Myocardial Stress, Myocardial Injury, and Subclinical Inflammation and the Risk of Sudden Death

Circulation ◽  
2020 ◽  
Vol 142 (12) ◽  
pp. 1148-1158
Author(s):  
Brendan M. Everett ◽  
M.V. Moorthy ◽  
Jani T. Tikkanen ◽  
Nancy R. Cook ◽  
Christine M. Albert
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
C Reactive Protein ◽  
Cholesterol Ratio ◽  
Reactive Protein

Background: The majority of sudden cardiac deaths (SCDs) occur in low-risk populations often as the first manifestation of cardiovascular disease (CVD). Biomarkers are screening tools that may identify subclinical cardiovascular disease and those at elevated risk for SCD. We aimed to determine whether the total to high-density lipoprotein cholesterol ratio, high-sensitivity cardiac troponin I, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity C-reactive protein individually or in combination could identify individuals at higher SCD risk in large, free-living populations with and without cardiovascular disease. Methods: We performed a nested case-control study within 6 prospective cohort studies using 565 SCD cases matched to 1090 controls (1:2) by age, sex, ethnicity, smoking status, and presence of cardiovascular disease. Results: The median study follow-up time until SCD was 11.3 years. When examined as quartiles or continuous variables in conditional logistic regression models, each of the biomarkers was significantly and independently associated with SCD risk after mutually controlling for cardiac risk factors and other biomarkers. The mutually adjusted odds ratios for the top compared with the bottom quartile were 1.90 (95% CI, 1.30–2.76) for total to high-density lipoprotein cholesterol ratio, 2.59 (95% CI, 1.76–3.83) for high-sensitivity cardiac troponin I, 1.65 (95% CI, 1.12–2.44) for NT-proBNP, and 1.65 (95% CI, 1.13–2.41) for high-sensitivity C-reactive protein. A biomarker score that awarded 1 point when the concentration of any of those 4 biomarkers was in the top quartile (score range, 0–4) was strongly associated with SCD, with an adjusted odds ratio of 1.56 (95% CI, 1.37–1.77) per 1-unit increase in the score. Conclusions: Widely available measures of lipids, subclinical myocardial injury, myocardial strain, and vascular inflammation show significant independent associations with SCD risk in apparently low-risk populations. In combination, these measures may have utility to identify individuals at risk for SCD.

scholarly journals Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome

2014 ◽  
Vol 60 (1) ◽  
pp. 158-164 ◽  
Author(s):  
Erin A Bohula May ◽  
Marc P Bonaca ◽  
Petr Jarolim ◽  
Elliott M Antman ◽  
Eugene Braunwald ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
High Sensitivity ◽  
Cardiovascular Death ◽  
Cardiac Troponin I ◽  
Fourth Generation ◽  
Prognostic Performance ◽  
Coronary Syndrome ◽  
Low Concentrations ◽  
Increased Risk

Abstract BACKGROUND High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. METHODS We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. RESULTS All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI &lt;99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3–5.7; P &lt; 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend &lt; 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (&lt;10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI &lt;26 ng/L (9.2% vs 2.9%, P = 0.002). CONCLUSIONS Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.

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