Analytical Validation of a High-Sensitivity Cardiac Troponin T Assay

Medizinische Klinik, Abteilung für Innere Medizin III, Universitätsklinikum Heidelberg, Germany.
Clinical Chemistry (Impact Factor: 7.91). 12/2009; 56(2):254-61. DOI: 10.1373/clinchem.2009.132654
Source: PubMed


We report the development of a novel high-sensitivity cardiac troponin T (hs-cTnT) assay, a modification of the Roche fourth-generation cTnT assay, and validation of the analytical performance of this assay.
Validation included testing of analytical sensitivity, specificity, interferences, and precision. We established the 99th percentile cutoff from healthy reference populations (n = 616). In addition, we studied differences in time to a positive result when using serial measurements of hs-cTnT vs cTnT in patients with a confirmed diagnosis of non-ST elevation myocardial infarction (non-STEMI).
The hs-cTnT assay had an analytical range from 3 to 10 000 ng/L. At the 99th percentile value of 13.5 ng/L, the CV was 9% using the Elecsys 2010 analyzer. The assay was specific for cTnT without interferences from human cTnI or cTnC, skeletal muscle TnT, or hemoglobin concentrations up to 1000 mg/L, above which falsely lower values would be expected. When the assay was evaluated clinically, a hs-cTnT higher than the 99th percentile concentration identified a significantly higher number of patients with non-STEMI on presentation (45 vs 20 patients, P = 0.0004) compared with cTnT, and a final diagnosis of non-STEMI was made in 9 additional patients (55 vs 46 patients, P = 0.23) after serial sampling. Time to diagnosis was significantly shorter using hs-cTnT compared with cTnT [mean 71.5 (SD 108.7) min vs 246.9 (82.0) min, respectively; P < 0.01].
The analytical performance of hs-cTnT complies with the ESC-ACCF-AHA-WHF Global Task Force recommendations for use in the diagnosis of MI.

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    • "The limit of blank (LoB) and LoD of the Roche hs-cTnT (Elecsys 2010, Roche Diagnostics) assay were determined to be 3 ng/l and 5 ng/l respectively . The 99th-percentile of a healthy reference population was reported at 14 ng/l with an imprecision corresponding to 10% CV at 13 ng/l[31]. Calculation of the estimated glomerular filtration rate (eGFR) was performed using the abbreviated Modification of Diet in Renal disease formula.[32].2.5. "
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    ABSTRACT: Objective: The novel high-sensitivity cardiac troponin (hs-cTn) 0h/1h-algorithm substantially improves the early triage of patient's assigned "rule-out" or "rule-in" of acute myocardial infarction (AMI), while diagnostic uncertainty remains in that 25-30% of patients assigned to "observe". We aimed to better characterize these patients. Methods: In a prospective multicenter diagnostic study, we applied the hs-cTnT 0h/1h-algorithm in 2213 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists using all available information. Survival at 720-days was the prognostic endpoint. Findings were validated using a hs-cTnI 0h/1h-algorithm. Results: Twenty-four percent (n=523) of patients were assigned to "observe" by the hs-cTnT 0h/1h-algorithm. These patients differed significantly in multiple characteristics from "rule-out" and "rule-in" patients: they were older, in 75% male, and very often (57%) had pre-existing coronary artery disease (CAD). Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% of patients were suitable for coronary computed tomography angiography (CCTA). The most common final adjudicated diagnoses were non-cardiac disease (38%), non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%). Absolute hs-cTnT-changes within 3h had the highest diagnostic accuracy for AMI (AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantly lower as compared to "rule-out" (p<0.001) and comparable to "rule-in" (p=ns). Findings were similar for the hs-cTnI "observe" zone. Conclusion: "Observe" patients are typically elderly men with pre-existing CAD and high long-term mortality. Absolute hs-cTn-changes within 3h, functional stress imaging and coronary angiography are the key diagnostic modalities.
    Full-text · Article · Jan 2016 · International journal of cardiology
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    • "Gender specific reference intervals for cTnI were determined at the Changi General Hospital [4]. Corresponding ranges for cTnT were previously validated [5], and verified at Changi General. "
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    ABSTRACT: Cardiac troponin is used as a marker for all types of myocardial infarction. Assays for high-sensitivity troponin T and I were performed before, immediately and 24hours after a 40km bicycle ride in two middle aged individuals. There was a significant increase in cardiac troponin immediately after exercise in both individuals. This was accompanied by a return to baseline levels within 24hours. A CT angiogram was normal in one while the other had a significant occlusion in the mid right coronary artery. After a stent placement, in this latter individual, there was no major increase in troponin after a second bicycle ride. Using high sensitivity assays, at least one of these two subjects may have suffered a type 2 myocardial infarction had the increases in hs-cTnI were accompanied by other acceptable evidence of myocardial ischemia (symptoms, ECG, etc.).. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Apr 2015 · Clinica chimica acta; international journal of clinical chemistry
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    • "such a change within a North American city. There are, however, national and international materials published on the analytical aspects [4] [5] [6], and there has been excellent evaluation studies, both single center [7] [8] and multicenter studies [9] [10] on the two clinically approved hs-cTn assays in Canada (Roche Diagnostics hs-cTnT and Abbott Diagnostics hs-cTnI). So why has there been problems, considering the reported analytical and clinical performance of the hs-cTn assays has always been demonstrated to be superior to the contemporary assays [11] [12] [13] [14]? "
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    ABSTRACT: Despite several publications on the analytical performance of high-sensitivity cardiac troponin (hs-cTn) assays, there has been little information on how laboratories should validate and implement these assays into clinical service. Our study provides a practical approach for the validation and implementation of a hs-cTn assay across a large North American City.
    Full-text · Article · Apr 2015
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