Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile

Peter A Kavsak; Lorna Clark; Saranya Arnoldo; Amy Lou; Jennifer L. Shea; Shaun Eintracht; Andrew W. Lyon; Vipin Bhayana; Laurel Thorlacius; Joshua E. Raizman; Albert Tsui; Rose Djiana; Michael Chen; Yun Huang; Ali Haider; Ronald A. Booth; Chris Mccudden; Paul M. Yip; Daniel R. Beriault; David Blank; Angela W.s. Fung; Jennifer Taher; Julie St-Cyr; Sameer Sharif; Emilie Belley-cote; Beth L Abramson; Steven M. Friedman; Jafna L. Cox; Marco L.a. Sivilotti; Annabel Chen-Tournoux; Jesse Mclaren; Susanna Mak; Venkatesh Thiruganasambandamoorthy; Frank Scheuermeyer; Karin H Humphries; Andrew Worster; Dennis Ko; Kristin M Aakre; Nicholas L Mills; Allan S Jaffe

doi:10.1016/j.clinbiochem.2024.110731

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile

Peter A Kavsak^*, Lorna Clark, Saranya Arnoldo, Amy Lou, Jennifer L. Shea, Shaun Eintracht, Andrew W. Lyon, Vipin Bhayana, Laurel Thorlacius, Joshua E. Raizman, Albert Tsui, Rose Djiana, Michael Chen, Yun Huang, Ali Haider, Ronald A. Booth, Chris Mccudden, Paul M. Yip, Daniel R. Beriault, David BlankAngela W.s. Fung, Jennifer Taher, Julie St-Cyr, Sameer Sharif, Emilie Belley-cote, Beth L Abramson, Steven M. Friedman, Jafna L. Cox, Marco L.a. Sivilotti, Annabel Chen-Tournoux, Jesse Mclaren, Susanna Mak, Venkatesh Thiruganasambandamoorthy, Frank Scheuermeyer, Karin H Humphries, Andrew Worster, Dennis Ko, Kristin M Aakre, Nicholas L Mills, Allan S Jaffe

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤10.0% at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays.

Methods: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n=64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated.

Results: The CVs for all individual instruments and overall were ≤10.0% for two manufacturers (Abbott CVpooled=6.3% and Beckman CVpooled =7.0%). One of four Siemens Atellica instruments yielded a CV >10.0% (CVpooled =7.7%), whereas 15 of 41 Roche instruments yielded CVs >10.0% at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) CVpooled=11.7%). Four Roche instruments also yielded CVs >10.0% near the female URL of 14 ng/L used in the United States (CVpooled=8.5%).

Conclusions: The number of instruments achieving a CV ≤10.0% at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

Original language	English
Article number	110731
Number of pages	6
Journal	Clinical Biochemistry
Volume	125
Early online date	14 Feb 2024
DOIs	https://doi.org/10.1016/j.clinbiochem.2024.110731
Publication status	Published - 1 Mar 2024

Keywords / Materials (for Non-textual outputs)

Imprecision
female 99th percentile
upper reference limit
high-sensitivity cardiac troponin

Access to Document

10.1016/j.clinbiochem.2024.110731Licence: Creative Commons: Attribution (CC-BY)

Imprecision of high-sensitivity_KAVSAK_DOA08022024_VOR_CC-BYFinal published version, 548 KBLicence: Creative Commons: Attribution (CC-BY)

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British Heart Foundation Chair of Data Driven Innovation in Cardiology
Mills, N.
UK-based charities
1/08/21 → 31/07/26
Project: Research
High-Sensitivity Cardiac Troponin Beyond the Acute Coronary Syndrome
Mills, N., Anand, A., Chapman, A., Ferry, A., Newby, D., Strachan, F. & Tsanas, T.
UK-based charities
1/06/20 → 31/05/25
Project: Research

Cite this

Kavsak, P. A., Clark, L., Arnoldo, S., Lou, A., Shea, J. L., Eintracht, S., Lyon, A. W., Bhayana, V., Thorlacius, L., Raizman, J. E., Tsui, A., Djiana, R., Chen, M., Huang, Y., Haider, A., Booth, R. A., Mccudden, C., Yip, P. M., Beriault, D. R., ... Jaffe, A. S. (2024). Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile. Clinical Biochemistry, 125, Article 110731. https://doi.org/10.1016/j.clinbiochem.2024.110731

@article{378e6b6384c94f308c035ebdb8b4af34,

title = "Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile",

abstract = "Background: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤10.0% at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays.Methods: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n=64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. Results: The CVs for all individual instruments and overall were ≤10.0% for two manufacturers (Abbott CVpooled=6.3% and Beckman CVpooled =7.0%). One of four Siemens Atellica instruments yielded a CV >10.0% (CVpooled =7.7%), whereas 15 of 41 Roche instruments yielded CVs >10.0% at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) CVpooled=11.7%). Four Roche instruments also yielded CVs >10.0% near the female URL of 14 ng/L used in the United States (CVpooled=8.5%). Conclusions: The number of instruments achieving a CV ≤10.0% at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.",

keywords = "Imprecision, female 99th percentile, upper reference limit, high-sensitivity cardiac troponin",

author = "Kavsak, {Peter A} and Lorna Clark and Saranya Arnoldo and Amy Lou and Shea, {Jennifer L.} and Shaun Eintracht and Lyon, {Andrew W.} and Vipin Bhayana and Laurel Thorlacius and Raizman, {Joshua E.} and Albert Tsui and Rose Djiana and Michael Chen and Yun Huang and Ali Haider and Booth, {Ronald A.} and Chris Mccudden and Yip, {Paul M.} and Beriault, {Daniel R.} and David Blank and Fung, {Angela W.s.} and Jennifer Taher and Julie St-Cyr and Sameer Sharif and Emilie Belley-cote and Abramson, {Beth L} and Friedman, {Steven M.} and Cox, {Jafna L.} and Sivilotti, {Marco L.a.} and Annabel Chen-Tournoux and Jesse Mclaren and Susanna Mak and Venkatesh Thiruganasambandamoorthy and Frank Scheuermeyer and Humphries, {Karin H} and Andrew Worster and Dennis Ko and Aakre, {Kristin M} and Mills, {Nicholas L} and Jaffe, {Allan S}",

note = " Grant from the Canadian Institutes of Health Research (Kavsak). Chair Award, Programme Grant, and Research Excellence Award (CH/F/21/90010, RG/20/10/34966, RE/18/5/34216) from the British Heart Foundation (Mills).",

year = "2024",

month = mar,

day = "1",

doi = "10.1016/j.clinbiochem.2024.110731",

language = "English",

volume = "125",

journal = "Clinical Biochemistry",

issn = "0009-9120",

publisher = "Elsevier",

}

Kavsak, PA, Clark, L, Arnoldo, S, Lou, A, Shea, JL, Eintracht, S, Lyon, AW, Bhayana, V, Thorlacius, L, Raizman, JE, Tsui, A, Djiana, R, Chen, M, Huang, Y, Haider, A, Booth, RA, Mccudden, C, Yip, PM, Beriault, DR, Blank, D, Fung, AWS, Taher, J, St-Cyr, J, Sharif, S, Belley-cote, E, Abramson, BL, Friedman, SM, Cox, JL, Sivilotti, MLA, Chen-Tournoux, A, Mclaren, J, Mak, S, Thiruganasambandamoorthy, V, Scheuermeyer, F, Humphries, KH, Worster, A, Ko, D, Aakre, KM, Mills, NL & Jaffe, AS 2024, 'Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile', Clinical Biochemistry, vol. 125, 110731. https://doi.org/10.1016/j.clinbiochem.2024.110731

TY - JOUR

T1 - Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile

AU - Kavsak, Peter A

AU - Clark, Lorna

AU - Arnoldo, Saranya

AU - Lou, Amy

AU - Shea, Jennifer L.

AU - Eintracht, Shaun

AU - Lyon, Andrew W.

AU - Bhayana, Vipin

AU - Thorlacius, Laurel

AU - Raizman, Joshua E.

AU - Tsui, Albert

AU - Djiana, Rose

AU - Chen, Michael

AU - Huang, Yun

AU - Haider, Ali

AU - Booth, Ronald A.

AU - Mccudden, Chris

AU - Yip, Paul M.

AU - Beriault, Daniel R.

AU - Blank, David

AU - Fung, Angela W.s.

AU - Taher, Jennifer

AU - St-Cyr, Julie

AU - Sharif, Sameer

AU - Belley-cote, Emilie

AU - Abramson, Beth L

AU - Friedman, Steven M.

AU - Cox, Jafna L.

AU - Sivilotti, Marco L.a.

AU - Chen-Tournoux, Annabel

AU - Mclaren, Jesse

AU - Mak, Susanna

AU - Thiruganasambandamoorthy, Venkatesh

AU - Scheuermeyer, Frank

AU - Humphries, Karin H

AU - Worster, Andrew

AU - Ko, Dennis

AU - Aakre, Kristin M

AU - Mills, Nicholas L

AU - Jaffe, Allan S

N1 - Grant from the Canadian Institutes of Health Research (Kavsak). Chair Award, Programme Grant, and Research Excellence Award (CH/F/21/90010, RG/20/10/34966, RE/18/5/34216) from the British Heart Foundation (Mills).

PY - 2024/3/1

Y1 - 2024/3/1

N2 - Background: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤10.0% at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays.Methods: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n=64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. Results: The CVs for all individual instruments and overall were ≤10.0% for two manufacturers (Abbott CVpooled=6.3% and Beckman CVpooled =7.0%). One of four Siemens Atellica instruments yielded a CV >10.0% (CVpooled =7.7%), whereas 15 of 41 Roche instruments yielded CVs >10.0% at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) CVpooled=11.7%). Four Roche instruments also yielded CVs >10.0% near the female URL of 14 ng/L used in the United States (CVpooled=8.5%). Conclusions: The number of instruments achieving a CV ≤10.0% at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

AB - Background: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤10.0% at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays.Methods: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n=64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. Results: The CVs for all individual instruments and overall were ≤10.0% for two manufacturers (Abbott CVpooled=6.3% and Beckman CVpooled =7.0%). One of four Siemens Atellica instruments yielded a CV >10.0% (CVpooled =7.7%), whereas 15 of 41 Roche instruments yielded CVs >10.0% at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) CVpooled=11.7%). Four Roche instruments also yielded CVs >10.0% near the female URL of 14 ng/L used in the United States (CVpooled=8.5%). Conclusions: The number of instruments achieving a CV ≤10.0% at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

KW - Imprecision

KW - female 99th percentile

KW - upper reference limit

KW - high-sensitivity cardiac troponin

U2 - 10.1016/j.clinbiochem.2024.110731

DO - 10.1016/j.clinbiochem.2024.110731

M3 - Article

SN - 0009-9120

VL - 125

JO - Clinical Biochemistry

JF - Clinical Biochemistry

M1 - 110731

ER -

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

British Heart Foundation Chair of Data Driven Innovation in Cardiology

High-Sensitivity Cardiac Troponin Beyond the Acute Coronary Syndrome

Cite this