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 <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 >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 < 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.

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.

scholarly journals Rapid Rule-Out of Acute Myocardial Injury Using a Single High-Sensitivity Cardiac Troponin I Measurement

2017 ◽  
Vol 63 (1) ◽  
pp. 369-376 ◽  
Author(s):  
Yader Sandoval ◽  
Stephen W Smith ◽  
Anoop S V Shah ◽  
Atul Anand ◽  
Andrew R Chapman ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Cardiac Death ◽  
Myocardial Injury ◽  
Troponin I ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Diagnostic Sensitivity ◽  
Clinical Indication ◽  
Acute Myocardial Injury ◽  
Rule Out

Abstract BACKGROUND Rapid rule-out strategies using high-sensitivity cardiac troponin assays are largely supported by studies performed outside the US in selected cohorts of patients with chest pain that are atypical of US practice, and focused exclusively on ruling out acute myocardial infarction (AMI), rather than acute myocardial injury, which is more common and associated with a poor prognosis. METHODS Prospective, observational study of consecutive patients presenting to emergency departments [derivation (n = 1647) and validation (n = 2198) cohorts], where high-sensitivity cardiac troponin I (hs-cTnI) was measured on clinical indication. The negative predictive value (NPV) and diagnostic sensitivity of an hs-cTnI concentration &lt;limit of detection (LoD) at presentation was determined for acute myocardial injury and for AMI or cardiac death at 30 days. RESULTS In patients with hs-cTnI concentrations &lt;99th percentile at presentation, acute myocardial injury occurred in 8.3% and 11.0% in the derivation and validation cohorts, respectively. In the derivation cohort, 27% had hs-cTnI &lt; LoD, with NPV and diagnostic sensitivity for acute myocardial injury of 99.1% (95% CI, 97.7–99.8) and 99.0% (97.5–99.7) and an NPV for AMI or cardiac death at 30 days of 99.6% (98.4–100). In the validation cohort, 22% had hs-cTnI &lt;LoD, with an NPV and diagnostic sensitivity for acute myocardial injury of 98.8% (97.9–99.7) and 99.3% (98.7–99.8) and an NPV for AMI or cardiac death at 30 days of 99.1% (98.2–99.8). CONCLUSIONS A single hs-cTnI concentration &lt;LoD rules out acute myocardial injury, regardless of etiology, with an excellent NPV and diagnostic sensitivity, and identifies patients at minimal risk of AMI or cardiac death at 30 days. ClinicalTrials.gov Identifier: NCT02060760

scholarly journals Incidence of Undetectable, Measurable, and Increased Cardiac Troponin I Concentrations Above the 99th Percentile Using a High-Sensitivity vs a Contemporary Assay in Patients Presenting to the Emergency Department

2016 ◽  
Vol 62 (8) ◽  
pp. 1115-1119 ◽  
Author(s):  
Sara A Love ◽  
Yader Sandoval ◽  
Stephen W Smith ◽  
Jennifer Nicholson ◽  
Jing Cao ◽  
...  
Keyword(s):  
Emergency Department ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Clinical Indication ◽  
Edta Plasma ◽  
Abbott Architect ◽  
F 31

Abstract INTRODUCTION We compared the incidence of undetectable [below the limit of detection (LoD)], measurable (LoD to 99th percentile), and increased cardiac troponin I (cTnI) concentrations above the 99th percentile between Abbott high-sensitivity cTnI (hs-cTnI) and contemporary cTnI assays in a US emergency department population. METHODS Patients (n = 2100) presenting to the emergency department who had serial cTnI (0, 3, 6, 9 h) measurements ordered on clinical indication were enrolled. Contemporary cTnI [Abbott Architect used clinically; 99th percentile: 0.030 μg/L (30 ng/L)] and hs-cTnI [Abbott investigational; sex-specific 99th percentiles: female (F) 16 ng/L, male (M) 34 ng/L] assays simultaneously measured fresh EDTA plasma. RESULTS The hs-cTnI assay measured fewer undetectable cTnI concentrations compared to the contemporary cTnI assay across baseline (F: 31% vs 47%, M: 22% vs 40%) and serial (F: 21% vs 46%; M: 19% vs 54%) measurements. Conversely, the proportion of measurable cTnI concentrations was higher using hs-cTnI compared to contemporary cTnI assay across both baseline (F: 46% vs 31%; M: 60% vs 33%) and serial (F: 48% vs 28%; M: 83% vs 40%) measurements. The overall proportion of patients with increased cTnI concentrations above the 99th percentile was not significantly different between the contemporary (31%) and hs-cTnI (26%) assays (P = 0.09). CONCLUSIONS In patients presenting to the emergency department, the use of the Abbott hs-cTnI assay provides clinicians with more numeric cTnI concentrations. This occurs via a shift from results below the LoD to those between the LoD and the 99th percentile and does not increase in the number of cTnI concentrations above the 99th percentile.

scholarly journals Diagnostic Accuracy of a High-Sensitivity Cardiac Troponin Assay with a Single Serum Test in the Emergency Department

2019 ◽  
Vol 65 (8) ◽  
pp. 1006-1014 ◽  
Author(s):  
Richard Body ◽  
Raphael Twerenbold ◽  
Catrin Austin ◽  
Jasper Boeddinghaus ◽  
Malak Almashali ◽  
...  
Keyword(s):  
Emergency Department ◽  
Diagnostic Accuracy ◽  
High Precision ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Multicenter Studies ◽  
Low Concentrations ◽  
Similar Accuracy

Abstract OBJECTIVES We sought to evaluate diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay for acute coronary syndromes (ACS) in the emergency department (ED). The assay has high precision at low concentrations and can detect cTnI in 96.8% of healthy individuals. METHODS In successive prospective multicenter studies (“testing” and “validation”), we included ED patients with suspected ACS. We drew blood for hs-cTnI [Singulex Clarity® cTnI; 99th percentile, 8.67 ng/L; limit of detection (LoD), 0.08 ng/L] on arrival. Patients also underwent hs-cTnT (Roche Elecsys) testing over ≥3 h. The primary outcome was an adjudicated diagnosis of ACS, defined as acute myocardial infarction (AMI; prevalent or incident), death, or revascularization within 30 days. RESULTS The testing and validation studies included 665 and 2470 patients, respectively, of which 94 (14.1%) and 565 (22.9%) had ACS. At a 1.5-ng/L cutoff, hs-cTnI had good sensitivity for AMI in both studies (98.7% and 98.1%, respectively) and would have “ruled out” 40.1% and 48.9% patients. However, sensitivity was lower for ACS (95.7% and 90.6%, respectively). At a 0.8-ng/L cutoff, sensitivity for ACS was higher (97.5% and 97.9%, ruling out 28.6% patients in each cohort). The hs-cTnT assay had similar performance at the LoD (24.6% ruled out; 97.2% sensitivity for ACS). CONCLUSIONS The hs-cTnI assay could immediately rule out AMI in 40% of patients and ACS in &gt;25%, with similar accuracy to hs-cTnT at the LoD. Because of its high precision at low concentrations, this hs-cTnI assay has favorable characteristics for this clinical application.

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 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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