Potential impact of a novel pathway for suspected myocardial infarction utilising a new high-sensitivity cardiac troponin I assay

BackgroundHigh-sensitivity cardiac troponin I (hs-cTnI) assays promise high diagnostic accuracy for myocardial infarction (MI). In an ED where conventional cTnI was in use, we evaluated an assessment pathway using the new Access hsTnI assay.MethodsThis retrospective analysis recruited ED patients with suspected MI between June and September 2019. All patients received routine care with a conventional cTnI assay (AccuTnI +3: limit of detection (LoD) 10 ng/L, 99th centile upper reference limit (URL) 40 ng/L, abnormal elevation cut-point 80 ng/L). Arrival, then 90-minute or 360-minute cTnI levels for low and non-low risk patients, respectively (ED Assessment of Chest pain score) guided diagnosis and disposition which was at treating physician discretion. The same patients had arrival and 90-minute or 180-minute samples drawn for hs-cTnI levels (Access hsTnI: LoD 2 ng/L, 99th centile URL 10 ng/L (females) and 20 ng/L (males); abnormal elevation above the URL and delta >30%). Treating physicians were blinded to the hs-cTnI results. Using the hs-cTnI values, investigators retrospectively assigned likely diagnosis, disposition and likelihood of a 30-day major adverse cardiac event (MACE). Admission was recommended for significantly rising hs-cTnI elevations. The primary objective was to demonstrate an acceptable unexpected 30-day post-discharge MACE rate of <1%. cTnI elevation rates, diagnostic outcomes and ED disposition were also compared between pathways.ResultsFor the 935 patients, unexpected 30-day post-discharge MACE rates were 0/935 (0%, 95% CI 0% to 0.4%) with the conventional or novel pathway. For the high-sensitivity and conventional assays, respectively, abnormal elevation rates were 29% (95% CI 26% to 32%) and 19% (95% CI 17% to 22%), for MI were 9% (95% CI 8% to 11%) and 8% (95% CI 6% to 10%), and for hospital admission were 42% (95% CI 39% to 45%) and 43% (95% CI 40% to 47%).ConclusionThe novel pathway using the Access hsTnI assay has an acceptably low 30-day MACE rate.

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Clinical Use of a New High-Sensitivity Cardiac Troponin I Assay in Patients with Suspected Myocardial Infarction

Clinical Chemistry ◽

10.1373/clinchem.2019.304725 ◽

2019 ◽

Vol 65 (11) ◽

pp. 1426-1436 ◽

Cited By ~ 12

Author(s):

Jasper Boeddinghaus ◽

Raphael Twerenbold ◽

Thomas Nestelberger ◽

Luca Koechlin ◽

Desiree Wussler ◽

...

Keyword(s):

Myocardial Infarction ◽

Diagnostic Accuracy ◽

Cardiac Troponin ◽

Troponin I ◽

Clinical Performance ◽

High Sensitivity ◽

Primary Objective ◽

Cardiac Troponin I ◽

Primary Analysis ◽

Derivation Cohort

Abstract BACKGROUND We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm. RESULTS AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93–0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92–0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90–0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94–0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1–100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4–97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect. CONCLUSIONS The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays. ClinicalTrials.gov Identifier NCT00470587.

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Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac troponin I immunoassay

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0350 ◽

2017 ◽

Vol 56 (1) ◽

Cited By ~ 15

Author(s):

Giuseppe Lippi ◽

Anna Ferrari ◽

Giorgio Gandini ◽

Matteo Gelati ◽

Claudia Lo Cascio ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin I ◽

Limit Of Detection ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Analytical Performance ◽

The Novel ◽

Reference Limit ◽

Automated Immunoassay ◽

Upper Reference Limit

AbstractBackground:This study was aimed to evaluate the analytical performance of the novel chemiluminescent and fully-automated Beckman Coulter Access hsTnI high-sensitivity immunoassay for measurement of cardiac troponin I (cTnI).Methods:The study, using lithium heparin samples, included assessment of limit of blank (LOB), limit of detection (LOD), functional sensitivity, linearity, imprecision (within run, between-run and total), calculation of 99th percentile upper reference limit (URL) in 175 healthy blood donors (mean age, 36±12 years; 47% women) and comparison with two other commercial cTnI immunoassays.Results:The LOB, LOD and functional sensitivity of Access hsTnI were 0.14, 0.34 and 1.35 ng/L, respectively. The within-run, between-run and total imprecision was 2.2%–2.9%, 4.6%–5.4%, and 5.4%–6.1%, respectively. The linearity was excellent in the range of cTnI values between 0.95 and 4195 ng/L (r=1.00). The 99th percentile URL was 15.8 ng/L. Measurable cTnI values were found in 173/175 healthy subjects (98.9%). Good agreement of cTnI values was found with AccuTnI+3 (r=0.97; mean bias, −9.3%), whereas less satisfactory agreement was found with Siemens Dimension Vista cTnI (r=0.95; mean bias, −55%).Conclusions:The results of our evaluation of the Beckman Coulter Access hsTnI indicate that the analytical performance of this fully-automated immunoassay is excellent.

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Clinical Validation of a Novel High-Sensitivity Cardiac Troponin I Assay for Early Diagnosis of Acute Myocardial Infarction

Clinical Chemistry ◽

10.1373/clinchem.2018.286906 ◽

2018 ◽

Vol 64 (9) ◽

pp. 1347-1360 ◽

Cited By ~ 37

Author(s):

Jasper Boeddinghaus ◽

Raphael Twerenbold ◽

Thomas Nestelberger ◽

Patrick Badertscher ◽

Karin Wildi ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Diagnostic Accuracy ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Primary Objective ◽

Cardiac Troponin I ◽

The Novel ◽

Primary Analysis

Abstract BACKGROUND Clinical performance of the novel high-sensitivity cardiac troponin I (Siemens-hs-cTnI-Centaur) assay is unknown. We aimed to clinically validate the Siemens-hs-cTnI-Centaur assay and develop 0/1-h and 0/2-h algorithms. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists including all clinical information twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis); second, using hs-cTnI (Abbott-Architect, secondary analysis) measurements in addition to the clinically applied (hs)-cTn. Siemens-hs-cTnI-Centaur was measured at presentation, 1 h, and 2 h. The primary objective was a direct comparison of diagnostic accuracy, quantified by the area under the ROC curve (AUC), of Siemens-hs-cTnI-Centaur vs the 2 established hs-cTn assays (Roche-hs-cTnT-Elecsys, Abbott-hs-cTnI-Architect). Secondary objectives included the development of Siemens-hs-cTnI-Centaur-specific 0/1-h and 0/2-h algorithms. RESULTS AMI was the final diagnosis in 318 of 1755 (18%) patients (using Roche-hs-cTnT-Elecsys for adjudication). The AUC at presentation for Siemens-hs-cTnI-Centaur was 0.94 (95% CI, 0.92–0.96) and comparable with 0.95 (95% CI, 0.93–0.97) for Roche-hs-cTnT-Elecsys and 0.93 (95% CI, 0.90–0.96) for Abbott-hs-cTnI-Architect. Applying the derived Siemens-hs-cTnI-Centaur 0/1-h algorithm to the validation cohort, 46% of patients were ruled out (sensitivity, 99.1%; 95% CI, 95.3–100), and 18% of patients were ruled in (specificity, 94.1%; 95% CI, 91.8–95.9). The Siemens-hs-cTnI-Centaur 0/2-h algorithm ruled out 55% of patients (sensitivity, 100%; 95% CI, 94.1–100), and ruled in 18% of patients (specificity, 96.0%; 95% CI, 93.1–97.9). Findings were confirmed in the secondary analyses using serial measurements of Abbott-hs-cTnI-Architect for adjudication. CONCLUSIONS Diagnostic accuracy and clinical utility of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587

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High-Sensitivity Cardiac Troponin I Assay for Early Diagnosis of Acute Myocardial Infarction

Clinical Chemistry ◽

10.1373/clinchem.2018.300061 ◽

2019 ◽

Vol 65 (7) ◽

pp. 893-904 ◽

Cited By ~ 20

Author(s):

Jasper Boeddinghaus ◽

Thomas Nestelberger ◽

Raphael Twerenbold ◽

Luca Koechlin ◽

Mario Meier ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Diagnostic Accuracy ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Primary Objective ◽

Cardiac Troponin I ◽

Primary Analysis ◽

Derivation Cohort

Abstract BACKGROUND The aim of this study was to validate the clinical performance of the Beckman Access high-sensitivity cardiac troponin I (hs-cTnI) assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists with all clinical information including cardiac imaging twice: first, using serial hs-cTnT (Elecsys, primary analysis), and second, using hs-cTnI (Architect, secondary analysis) measurements in addition to the clinically used hs-cTn. hs-cTnI Access was measured at presentation and at 1 h. The primary objective was a direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI Access vs the hs-cTnT Elecsys and hs-cTnI Architect assays. Secondary objectives included the derivation and validation of an hs-cTnI Access-specific 0/1-h algorithm. RESULTS AMI was the adjudicated final diagnosis in 243 of 1579 (15.4%) patients. The AUC at presentation for hs-cTnI Access was 0.95 (95% CI, 0.94–0.96), higher than hs-cTnI Architect [0.92 (95% CI, 0.91–0.94; P < 0.001)] and comparable to hs-cTnT Elecsys [0.94 (95% CI, 0.93–0.95; P = 0.12)]. Applying the derived hs-cTnI Access 0/1-h algorithm (derivation cohort n = 686) to the validation cohort (n = 680), 60% of patients were ruled out [sensitivity, 98.9% (95% CI, 94.3–99.8)], and 15% of patients were ruled in [specificity, 95.9% (95% CI, 94.0–97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 100% at 30 days. Findings were confirmed in the secondary analyses by the adjudication including serial measurements of Architect hs-cTnI. CONCLUSIONS Diagnostic accuracy and clinical utility of the Beckman hs-cTnI Access assay are very high and at least comparable to Roche hs-cTnT and Abbott hs-cTnI assays. ClinicalTrials.gov Identifier: NCT00470587.

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

Clinical Chemistry ◽

10.1373/clinchem.2017.283887 ◽

2018 ◽

Vol 64 (5) ◽

pp. 820-829 ◽

Cited By ~ 15

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.

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Faculty Opinions recommendation of One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725420089.793507697 ◽

2015 ◽

Author(s):

Patrick Ray

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Rule Out

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

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-1115 ◽

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.

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