Cardiac troponin assays: a review of quantitative point-of-care devices and their efficacy in the diagnosis of myocardial infarction

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Beret E. Amundson ◽  
Fred S. Apple
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Point Of Care ◽  
Hospital Costs ◽  
Sample Type ◽  
Clinical Sensitivity ◽  
Reference Limit ◽  
Negative Results ◽  
Analytical Imprecision ◽  
Upper Reference Limit

AbstractCardiac troponin (cTn) I and T are released from myocardial cells following necrosis, i.e., cell death. An accurate measure of cTn concentrations in a patient’s blood following ischemia/chest pain can enable providers to determine whether or not a myocardial infarction (MI) has occurred. Point-of-care (POC) devices that measure blood cTn concentrations in under 30 min may help to significantly reduce hospital costs by managing and triaging patients out of the emergency department as quickly as possible. The use of POC devices that measure cTnI and cTnT with a coefficient of variation (CV) ≤20% at the 99th percentile upper reference limit (URL) limits both false positive and negative results and provides clinically acceptable findings to assist in appropriate diagnoses. This article reviews nine POC devices that measure cTn in terms of their clinical sensitivity and specificity, analytical imprecision, sample type and preparation, and each assay’s principle of analysis.

scholarly journals Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I

1997 ◽  
Vol 43 (11) ◽  
pp. 2047-2051 ◽  
Author(s):  
Fred S Apple ◽  
Alireza Falahati ◽  
Pamela R Paulsen ◽  
Elizabeth A Miller ◽  
Scott W Sharkey
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Cardiac Troponin I ◽  
Clinical Sensitivity ◽  
Reference Limit ◽  
Normal Limits ◽  
Serial Serum ◽  
Upper Reference Limit ◽  
Serum Cardiac Troponin

Abstract This study compared the diagnostic accuracy of the measurement of serum cardiac troponin I (cTnI) with creatine kinase (CK) MB mass in patients with minor myocardial injury whose measured total CK activity did not exceed twice the upper reference limit (300 U/L for men; 200 U/L for women). Forty-eight consecutive patients presenting with chest pain and with in-hospital documentation of myocardial injury were enrolled. Electrocardiogram, echocardiogram, and serial serum CK-MB mass, cTnI, and total CK were measured over 36 h after admission. Peak total CK activity was within normal limits in 28 patients (58%). The mean (±SD) peak CK-MB mass and cTnI concentrations were: 16.4 (11.8) μg/L and 132 (13.0) μg/L; respectively. The peak biochemical marker index (defined as CK-MB or cTnI divided by its respective upper reference limit) was significantly (P <0.05) higher for cTnI than for CK-MB from 7 to 36 h. The clinical sensitivity for detection of myocardial injury for cTnI was 100% [95% confidence interval (CI): 87.2% to 100%], compared with 81.8% (CI: 67.3% to 91.8%) for CK-MB. Thus, cTnI was more sensitive than CK-MB mass for detection of myocardial injury in patients with small increases of total CK.

Simultaneous Rapid Measurement of Whole Blood Myoglobin, Creatine Kinase MB, and Cardiac Troponin I by the Triage Cardiac Panel for Detection of Myocardial Infarction

1999 ◽  
Vol 45 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Fred S Apple ◽  
Robert H Christenson ◽  
Roland Valdes ◽  
Alexander J Andriak ◽  
Amy Berg ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Creatine Kinase ◽  
Whole Blood ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Point Of Care ◽  
Cardiac Troponin I ◽  
Clinical Sensitivity ◽  
Creatine Kinase Mb ◽  
Acute Mi

Abstract This multicenter study evaluated the Biosite Triage® Cardiac Panel as a quantitative, multimarker, whole blood system for the detection of acute myocardial infarction (MI). Optimum cutoffs for the discrimination of acute MI (n = 192 patients, 59 with MI) as determined by ROC curve analyses were as follows: 0.4 μg/L for cardiac troponin I (cTnI); 4.3 μg/L for the creatine kinase MB isoenzyme (CK-MB); and 107 μg/L for myoglobin. The Triage Panel showed the following concordances for detection or rule-out of MI compared with established devices: cTnI >89%; CK-MB >81%; myoglobin >69%. No significant differences were present between methods for the same marker. Diagnostic efficiencies demonstrated comparable sensitivities and specificities for the diagnosis of MI in patients presenting with symptoms compared with the Dade, Beckman, and Behring CK-MB, cTnI, and myoglobin assays; the ratio of sensitivity to specificity for each marker was as follows: cTnI, 98%:100%; CK-MB, 95%:91%; myoglobin, 81%:92%. The areas under the ROC curves for the Biosite myoglobin, CK-MB, and cTnI were 0.818, 0.905, and 0.970, respectively; the areas were significantly different, P <0.05. In patients with skeletal muscle injury and renal disease, the Triage cTnI showed 94% and 100% specificity, respectively. The Triage panel offers clinicians a whole blood, point-of-care analysis of multiple cardiac markers that provides excellent clinical sensitivity and specificity for the detection of acute MI.

scholarly journals Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e052004
Author(s):  
Alexander Dietl ◽  
Martina E Zimmermann ◽  
Caroline Brandl ◽  
Stefan Wallner ◽  
Ralph Burkhardt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Left Ventricular ◽  
Cardiac Troponin T ◽  
Cross Sectional ◽  
Reference Limit ◽  
Mobile Population ◽  
Upper Reference Limit

ObjectiveEuropean guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age.DesignA cross-sectional analysis was performed in the German AugUR study (Altersbezogene Untersuchungen zur Gesundheit der University of Regensburg).SettingStudy population was the mobile population aged 70+ years living in the city and county of Regensburg, Germany.ParticipantsA random sample was derived from the local population registries of residence. Of the 5644 individuals invited, 1133 participated (response ratio=20.1%). All participants came to the study centre and were mentally and physically mobile to conduct the protocol (face-to-face interview, blood draw and standardised transthoracic echocardiography). None of the participants was in an acute state of myocardial infarction.ResultsAmong the 1129 individuals with hsTnT measurements (overall median=10.0 ng/L(25th, 75th percentile)=(7.0, 15.0 ng/L)), hsTnT was higher among the older individuals and higher among men (men 70–74 years median=9.6 ng/L (7.2, 13.1 ng/L); men 90–95 years median=21.2 ng/L (14.6, 26.0 ng/L); women 70–74 years median=6.3 ng/L (4.7, 8.7 ng/L); and women 90–95 years median=18.0 ng/L (11.0, 21.0 ng/L)). In participants with impaired kidney function (eGFRcrea <60 mL/min/1.73 m2), hsTnT was elevated (median=13.6 ng/L (9.4, 20.6 ng/L)).Specificity of recommended upper reference limit, 14 ng/L, is 68%. Most false positives were among men aged >79 years (specificity=34%). In a healthy subgroup (n=96, none of the following: overt heart disease, impaired renal function, blood pressure >160/100 mm Hg, left ventricular hypertrophy and diastolic/systolic dysfunction), specificity was 90%.ConclusionIn the elderly population without acute myocardial infarction, hsTnT further increases with age showing different levels for men and women. The specificity of the 14 ng/L cut-off is considerably lower than 99%, even in healthy subjects.

Determination of age- and sex-specific 99th percentiles for high-sensitive troponin T from patients: an analytical imprecision- and partitioning-based approach

2018 ◽  
Vol 56 (5) ◽  
pp. 685-696 ◽  
Author(s):  
Denis Monneret ◽  
Martin Gellerstedt ◽  
Dominique Bonnefont-Rousselot
Keyword(s):  
Cardiac Troponin ◽  
Polynomial Regression ◽  
Troponin T ◽  
Age Groups ◽  
Reference Limit ◽  
Proportion Method ◽  
Analytical Imprecision ◽  
Upper Reference Limit ◽  
Age And Sex

AbstractBackground:Detection of acute myocardial infarction (AMI) is mainly based on a rise of cardiac troponin with at least one value above the 99th percentile upper reference limit (99th URL). However, circulating high-sensitive cardiac troponin T (hs-cTnT) concentrations depend on age, sex and renal function. Using an analytical imprecision-based approach, we aimed to determine age- and sex-specific hs-cTnT 99th URLs for patients without chronic kidney disease (CKD).Methods:A 3.8-year retrospective analysis of a hospital laboratory database allowed the selection of adult patients with concomitant plasma hs-cTnT (<300 ng/L) and creatinine concentrations, both assayed twice within 72 h with at least 3 h between measurements. Absence of AMI was assumed when the variation between serial hs-cTnT values was below the adjusted-analytical change limit calculated according to the inverse polynomial regression of analytical imprecision. Specific URLs were determined using Clinical and Laboratory Standards Institute (CLSI) methods, and partitioning was tested using the proportion method, after adjustment for unequal prevalences.Results:After outlier removal (men: 8.7%; women: 6.6%), 1414 men and 1082 women with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2were assumed as non-AMI. Partitioning into age groups of 18–50, 51–70 and 71–98 years, the hs-cTnT 99th URLs adjusted on French prevalence were 18, 33, 66 and 16, 30, 84 ng/L for men and women, respectively. Age-partitioning was clearly required. However, sex-partitioning was not justified for subjects aged 18–50 and 51–70 years for whom a common hs-cTnT 99th URLs of about 17 and 31 ng/L could be used.Conclusions:Based on a laboratory approach, this study supports the need for age-specific hs-cTnT 99th URLs.

scholarly journals 99th Percentile Upper-Reference Limit of Cardiac Troponin and the Diagnosis of Acute Myocardial Infarction

2020 ◽  
Vol 66 (9) ◽  
pp. 1167-1180
Author(s):  
Yader Sandoval ◽  
Fred S Apple ◽  
Amy K Saenger ◽  
Paul O Collinson ◽  
Alan H B Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Specific Treatment ◽  
High Sensitivity ◽  
Prognostic Information ◽  
Reference Limit ◽  
Statistical Heterogeneity ◽  
Acute Mi ◽  
Upper Reference Limit ◽  
Missed Diagnoses

Abstract Background Concerns exist regarding how the 99th percentile upper reference limit (URL) of cardiac troponin (cTn) is determined and whether it should be derived from normal healthy individuals. Content The 99th percentile URL of cTn is an important criterion to standardize the diagnosis of myocardial infarction (MI) for clinical, research, and regulatory purposes. Statistical heterogeneity in its calculation exists but recommendations have been proposed. Some negativity has resulted from the fact that with some high-sensitivity (hs) cTn assays, a greater number of increases above the 99th percentile are observed when transitioning from a contemporary assay. Increases reflect acute or chronic myocardial injury and provide valuable diagnostic and prognostic information. The etiology of increases can sometimes be difficult to determine, making a specific treatment approach challenging. For those reasons, some advocate higher cutoff concentrations. This approach can contribute to missed diagnoses. Contrary to claims, neither clinical or laboratory guidelines have shifted away from the 99th percentile. To support the diagnosis of acute MI, the 99th percentile URL remains the best-established approach given the absence of cTn assay standardization. Importantly, risk stratification algorithms using hs-cTn assays predict the possibility of MI diagnoses established using the 99th percentile. Summary The 99th percentile of cTn remains the best-established criterion for the diagnosis of acute MI. While not perfect, it is analytically and clinically evidence-based. Until there are robust data to suggest some other approach, staying with the 99th percentile, a threshold that has served the field well for the past 20 years, appears prudent.

Neuroblastoma—When are Urinary Catecholamines and Their Metabolites ‘Normal’?

1988 ◽  
Vol 25 (6) ◽  
pp. 620-626 ◽  
Author(s):  
D J Worthington ◽  
E M Hammond ◽  
B B Eldeeb ◽  
A Green ◽  
G M Addison ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
The Other ◽  
Published Data ◽  
Single Test ◽  
Creatinine Concentration ◽  
Urinary Catecholamines ◽  
Clinical Sensitivity ◽  
Reference Limit ◽  
Upper Reference Limit ◽  
The Individual

The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.

scholarly journals High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2386-2394 ◽  
Author(s):  
Jan F. Scheitz ◽  
Guillaume Pare ◽  
Lesly A. Pearce ◽  
Hardi Mundl ◽  
W. Frank Peacock ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Embolic Stroke ◽  
Cardiac Troponin T ◽  
Reference Limit ◽  
End Point ◽  
Upper Reference Limit

Background and Purpose: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. Methods: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. Results: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41–1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25–0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification ( P =0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment ( P =0.3). Conclusions: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.

scholarly journals The 99th percentile upper reference limit for the 5th generation cardiac troponin T assay in the United States

2020 ◽  
Vol 504 ◽  
pp. 172-179
Author(s):  
Robert L. Fitzgerald ◽  
Judd E. Hollander ◽  
W. Frank Peacock ◽  
Alexander T. Limkakeng ◽  
Nancy Breitenbeck ◽  
...  
Keyword(s):  
United States ◽  
Cardiac Troponin ◽  
Troponin T ◽  
The United States ◽  
Cardiac Troponin T ◽  
Reference Limit ◽  
Upper Reference Limit

Emergency department triage of patients with acute chest pain: definition of cardiac troponin I decisional value to manage patients without electrocardiographic evidence of ischemia

2004 ◽  
Vol 42 (5) ◽  
Author(s):  
Pascale Beyne ◽  
Erik Bouvier ◽  
Patrick Werner ◽  
Pierre Bourgoin ◽  
Damien Logeart ◽  
...  
Keyword(s):  
Chest Pain ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Acute Chest Pain ◽  
Final Diagnosis ◽  
Cardiac Troponin I ◽  
Reference Limit ◽  
Coronary Syndrome ◽  
Definition Of ◽  
Upper Reference Limit

AbstractThe aim of this study was to define the use of a new cardiac troponin I (cTnI) assay for emergency patients with chest pain and no specific electrocardiographic changes consistent with the presence of ischemia. Patients (n=106) admitted in Emergency/Cardiology Departments for chest pain and suspicion of acute coronary syndrome (ACS) were randomized into two diagnosis groups (ACS or non-ACS) by two independent cardiologists. cTnI measurements were performed at admission, and 6 hours and 12 hours later with a new generation assay (Access AccuTnI, Beckman Coulter). Using an upper reference limit of 0.04 μg/l, 27 patients had a cTnI elevation not related to the final diagnosis of ischemia; the positive predictive value (PPV) was 67% with specificity 48%. The decisional value was re-defined and set at 0.16 μg/l, a concentration corresponding to the 99th percentile of the non-ACS patient group. Precision (coefficient of variation) was 8% at this level, PPV 97% and specificity 98%. This new decisional value is now used in our institution and could be included in standard care guidelines to improve the management of patients presenting chest pain in emergency departments.

The universal definition of myocardial infarction

2015 ◽  
Author(s):  
Kristian Thygesen ◽  
Joseph S Alpert ◽  
Allan S Jaffe ◽  
Harvey D White
Keyword(s):  
Myocardial Infarction ◽  
Wall Motion ◽  
Regional Wall Motion ◽  
Cardiac Biomarkers ◽  
Regional Wall ◽  
Reference Limit ◽  
Electrocardiographic Changes ◽  
Universal Definition ◽  
Definition Of ◽  
Upper Reference Limit

Myocardial infarction is defined pathologically as myocyte necrosis due to prolonged ischaemia. These conditions are met when there is a detection of a rise and/or fall of cardiac biomarkers, preferably troponins, with at least one value above the 99th percentile of the upper reference limit, together with evidence of myocardial ischaemia, as recognized by at least one of the following: symptoms of ischaemia, electrocardiographic changes of new ischaemia, the development of pathological Q waves, imaging evidence of a new loss of viable myocardium or new regional wall motion abnormality, or the identification of an intracoronary thrombus by angiography or autopsy.

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