- Email: [email protected]
Reality check for cardiac troponin testing – Sometimes the result is wrong
Reality check for cardiac troponin testing – sometimes the result is wrong Peter A. Kavsak, Amy K. Saenger, Peter E. Hickman PII: DOI: Reference:
S0009-9120(16)30210-7 doi: 10.1016/j.clinbiochem.2016.09.007 CLB 9372
To appear in:
Clinical Biochemistry
Received date: Accepted date:
6 September 2016 7 September 2016
Please cite this article as: Kavsak Peter A., Saenger Amy K., Hickman Peter E., Reality check for cardiac troponin testing – sometimes the result is wrong, Clinical Biochemistry (2016), doi: 10.1016/j.clinbiochem.2016.09.007
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Type: Editorial Short Title: Analytical concerns for cardiac troponin testing
RI P
T
Title: Reality check for cardiac troponin testing – sometimes the result is wrong
a
SC
Peter A. Kavsaka, Amy K. Saengerb, Peter E Hickmanc
McMaster University, Hamilton, ON, Canada; bUniversity of Minnesota, Minneapolis, MN, United
ED
MA
NU
States; cAustralian National University, Canberra, ACT, Australia
Conflict of Interest: Dr. Kavsak has received grants/reagents/consultant/advisor/honoria from Abbott
PT
Laboratories, Abbott Point of Care, Abbott Diagnostics Division Canada, Beckman Coulter, Ortho
CE
Clinical Diagnostics, Randox Laboratories, Roche Diagnostics and Siemens Healthcare Diagnostics.
biomarker field.
AC
McMaster University has filed patents with Dr. Kavsak listed as an inventor in the acute cardiovascular
Funding: None to declare
Correspondence: Juravinski Hospital and Cancer Centre (Core Lab Section) 711 Concession Street Hamilton, ON Canada L8V 1C3 Fax: 905-575-2581; Email: [email protected]
Key words: cardiac troponin; analytical errors; interferences; variation; laboratory testing, guidelines
1/7
ACCEPTED MANUSCRIPT Errors occur in the provision of medical care; in laboratory medicine where measurements are performed this is unavoidable. The clinical laboratory allocates a significant amount of time and energy in the pursuit of providing accurate and high quality test results, and provides an essential service for a
RI P
T
majority of clinicians. The literature is abundant on improving quality for laboratory testing with a special place in the heart for cardiac troponin as evident by a special issue last year focusing on cardiac
SC
biomarkers in Clinical Biochemistry [1,2].
NU
For cardiac troponin T (cTnT) or cardiac troponin I (cTnI) testing, the introduction of the high-
MA
sensitivity assays has been a guideline changer [3], notwithstanding the existing gaps in understanding and applying these assays for clinical care [4,5]. Among the areas that laboratory professionals are
ED
intimately aware of that impact on quality testing are processes that lead to inaccurate or even erroneous cardiac troponin results. Simply put, sometimes the cardiac troponin result is just wrong.
PT
Laboratories have standard operating procedures and skilled staff overseeing and performing this
CE
testing but errors do occur and clinical users and other stakeholders need to be aware of this. In this issue of Clinical Biochemistry two articles highlight important practical examples which demonstrate
AC
that regardless if a high-sensitivity or conventional cardiac troponin assay is employed the expected performance and the results generated may be different than the clinical users expectations [6,7].
One area that has garnered much attention is using a very low concentration of cardiac troponin to ruleout myocardial infarction (MI), which is only achievable when utilizing a high-sensitivity assay [3]. Chenevier-Gobeaux and colleagues evaluate the utility of a single high-sensitivity cardiac troponin T (hs-cTnT) measurement at presentation to rule-out MI in the emergency department (ED) [6]. Despite the excellent precision of 11.7% at the limit of detection (LoD) of 5 ng/L used to rule-out MI, from a population of 413 patients there were 71 MIs, 2 of which had hs-cTnT concentrations < 5 ng/L [6]. The authors conclude that a single measurement of hs-cTnT < 5 ng/L is “not enough to rule out safely 2/7
ACCEPTED MANUSCRIPT NSTEMI for very early presenters” [6]. The European Society of Cardiology (ESC) guidelines place an asterisk beside the 0 hour rule-out cutoffs stating “*Only applicable if chest pain onset > 3h” [3], but
RI P
T
could there be other analytical factors at play that affected the performance of hs-cTnT in this study?
We are cognizant to the fact that different reagent lots of cardiac troponin can yield divergent results
SC
[8]; with previous lots of hs-cTnT demonstrating a negative bias at concentrations below, but not above, the 99th percentile [9]. We also recognize that there is considerable variation of the assay at the
NU
low analytical range end (i.e., near the LoD) that exists within and across different platforms [10], a
MA
finding that is not unique to hs-cTnT since this variation exists for high-sensitivity cardiac troponin I (hs-cTnI) as well [11,12]. Finally, there are several pre-analytical factors that could affect results. For
ED
example, even mild hemolysis falsely lowers the cTnT concentration [13,14], and the tube and specimen type may also affect cTnT concentrations [15], which collectively can alter the utility of
PT
using the LoD to rule-out MI [16]. These pre-analytical variables are also a concern for cTnI [17-19],
CE
emphasizing the fact that no assay is impermeable to factors affecting the accuracy of the result.
AC
On the opposite end, a high concentration of cardiac troponin can be used to rule-in or identify highrisk patients [3]. Just as factors can affect the accuracy of cardiac troponin results at the low end, these same variables and different ones can result in erroneous high concentrations. In this issue, Herman and colleagues report on endogenous alkaline phosphatase (ALP) causing a higher result for cTnI in assays that use ALP as the label to generate light in the chemiluminescent immunoassay method [7]. Interestingly, their findings suggest that the liver isoform of ALP is likely the culprit here; suggesting certain hepatobiliary patients may yield erroneous results with ALP labelled chemiluminescent immunoassays [7]. This appears different to other disease states that may also cause an increase in cardiac troponin results from noncardiac causes [20]. Falsely elevated cardiac troponin results are not a new phenomenon, but eliminating these “flyers” is an 3/7
ACCEPTED MANUSCRIPT area that has dedicated significant resources and effort from industry, scientists and clinical researchers. In fact, the newer hs-cTnI assay evaluated by Herman and colleagues did not appear to be as affected by ALP as the contemporary assay [7]. Moreover, it is unknown if this positive effect from ALP would
RI P
T
be evident in EDTA plasma samples, as this matrix that has been demonstrated for some cardiac
SC
troponin assays to provide superior performance compared to lithium heparin plasma [17,18].
How can one reconcile the fact that erroneous cardiac troponin results will occur and the laboratory
NU
cannot prevent them all? Primarily by understanding that the cardiac troponin results should never be
MA
used in isolation and a clinician should make a diagnosis based on more than just the cardiac troponin result. This by no means absolves the laboratory, as laboratory professionals still need to strive for
ED
excellence in quality testing, with the awareness there is always the potential for error. Laboratory professionals need to have a continuous, ongoing dialogue with all stakeholders, as timely
AC
CE
PT
communication is vital for proper interpretation of all laboratory results (even the inaccurate ones).
Word Count: 889
4/7
ACCEPTED MANUSCRIPT References (Max 20) 1. Kavsak PA, Lai L, Langman L, Jones PM, Hammett-Stabler CA. Clinical Biochemistry 2015 year in review: Material not for the faint of heart. Clin Biochem 2015;48:1211-2.
RI P
T
2. Apple FS, Jaffe AS, Collinson P, Mockel M, Ordonez-Llanos J, Lindahl B, et al. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac
SC
troponin assays. Clin Biochem 2015;48:201-3.
3. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC
NU
Guidelines for the management of acute coronary syndromes in patients presenting without
MA
persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of
ED
Cardiology (ESC). Eur Heart J 2016;37:267-315. 4. Kavsak PA, Jaffe AS, Hickman PE, Mills NL, Humphries KH, McRae A, et al. Canadian
PT
Institutes of Health Research dissemination grant on high-sensitivity cardiac troponin. Clin
CE
Biochem 2014;47:155-7.
5. Pickering JW, Greenslade JH, Cullen L, Flaws D, Parsonage W, George P, et al. Validation of
AC
presentation and 3 h high-sensitivity troponin to rule-in and rule-out acute myocardial infarction. Heart 2016;102:1270-8. 6. Chenevier-Gobeaux C, Meune C, Lefevre G, Doumenc B, Sorbets E, Peschanski N, Ray P. A single value of high-sensitive troponin T below the limit of detection is not enough for ruling out non ST elevation myocardial infarction in the emergency department. Clin Biochem. 2016 May 24. pii: S0009-9120(16)30092-3. doi: 10.1016/j.clinbiochem.2016.05.021. [Epub ahead of print]. 7. Herman DS, Ranjitkar P, Yamaguchi D, Grenache DG, Greene DN. Endogenous alkaline phosphatase interference in cardiac troponin I and other sensitive chemiluminescence immunoassays that use alkaline phosphatase activity for signal amplification. Clin Biochem. 5/7
ACCEPTED MANUSCRIPT 2016 Jun 16. pii: S0009-9120(16)30123-0. doi: 10.1016/j.clinbiochem.2016.06.006. [Epub ahead of print]. 8. Hickman PE, Miller E, Koerbin G, Potter JM. Changes in troponin kits preclude meaningful
RI P
T
collection of data on population 99th percentiles. Ann Clin Biochem 2004;41:503-504. 9. Kavsak PA, Hill SA, McQueen MJ, Devereaux PJ. Implications of adjustment of high-
SC
sensitivity cardiac troponin T assay. Clin Chem 2013;59:574-6.
10. Saenger AK, Beyrau R, Braun S, Cooray R, Dolci A, Freidank H, et al. Multicenter analytical
NU
evaluation of a high-sensitivity troponin T assay. Clin Chim Acta 2011;412:748-54.
MA
11. Kavsak PA, Don-Wauchope AC, Hill SA, Worster A. Acceptable Analytical Variation May Exceed High-Sensitivity Cardiac Troponin I Cutoffs in Early Rule-Out and Rule-In Acute
ED
Myocardial Infarction Algorithms. Clin Chem 2016;62:887-9. 12. Kavsak PA, Beattie J, Pickersgill R, Ford L, Caruso N, Clark L. A practical approach for the
PT
validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a
CE
North American city. Pract Lab Med 2015;1:28-34. 13. Lyon ME, Ball CL, Krause RD, Slotsve GA, Lyon AW. Effect of hemolysis on cardiac troponin
AC
T determination by the Elecsys 2010 immunoanalyzer. Clin Biochem. 2004 Aug;37(8):698-701. 14. Bais R. The effect of sample hemolysis on cardiac troponin I and T assays. Clin Chem. 2010 Aug;56(8):1357-9. 15. Kock CD, Wockenfus AM, Saenger AK, Jaffe AS, Karon B. BD rapid serum tubes reduce false positives plasma troponin T results on the Roche Cobas e411 analyzer. Clin Biochem 2012;842844. 16. Kavsak PA, Worster A. Dichotomizing high-sensitivity cardiac troponin T results and important analytical considerations. J Am Coll Cardiol 2012;59:157. 17. Simons J, Beach L, Clark L, Kavsak PA. Matrix and bilirubin interference for high-sensitivity cardiac troponin I. Clin Chim Acta 2015;442:49-51. 6/7
ACCEPTED MANUSCRIPT 18. Kavsak PA, Caruso N, Beattie J, Clark L. Centrifugation--an important pre-analytical factor for the Abbott Architect high-sensitivity cardiac troponin I assay. Clin Chim Acta 2014;436:273-5. 19. Puelacher C, Twerenbold R, Mosimann T, Boeddinghaus J, Rubini Gimenez M, Wildi K, et al.
myocardial infarction. Int J Cardiol 2015;187:313-5
RI P
T
Effects of hemolysis on the diagnostic accuracy of cardiac troponin I for the diagnosis of
SC
20. Jaffe AS, Vasile VC, Milone M, Saenger AK, Olson KN, Apple FS. Disease skeletal muscle a noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll
AC
CE
PT
ED
MA
NU
Cardiol 2011;58:1819-24.
7/7
S0009-9120(16)30210-7 doi: 10.1016/j.clinbiochem.2016.09.007 CLB 9372
To appear in:
Clinical Biochemistry
Received date: Accepted date:
6 September 2016 7 September 2016
Please cite this article as: Kavsak Peter A., Saenger Amy K., Hickman Peter E., Reality check for cardiac troponin testing – sometimes the result is wrong, Clinical Biochemistry (2016), doi: 10.1016/j.clinbiochem.2016.09.007
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Type: Editorial Short Title: Analytical concerns for cardiac troponin testing
RI P
T
Title: Reality check for cardiac troponin testing – sometimes the result is wrong
a
SC
Peter A. Kavsaka, Amy K. Saengerb, Peter E Hickmanc
McMaster University, Hamilton, ON, Canada; bUniversity of Minnesota, Minneapolis, MN, United
ED
MA
NU
States; cAustralian National University, Canberra, ACT, Australia
Conflict of Interest: Dr. Kavsak has received grants/reagents/consultant/advisor/honoria from Abbott
PT
Laboratories, Abbott Point of Care, Abbott Diagnostics Division Canada, Beckman Coulter, Ortho
CE
Clinical Diagnostics, Randox Laboratories, Roche Diagnostics and Siemens Healthcare Diagnostics.
biomarker field.
AC
McMaster University has filed patents with Dr. Kavsak listed as an inventor in the acute cardiovascular
Funding: None to declare
Correspondence: Juravinski Hospital and Cancer Centre (Core Lab Section) 711 Concession Street Hamilton, ON Canada L8V 1C3 Fax: 905-575-2581; Email: [email protected]
Key words: cardiac troponin; analytical errors; interferences; variation; laboratory testing, guidelines
1/7
ACCEPTED MANUSCRIPT Errors occur in the provision of medical care; in laboratory medicine where measurements are performed this is unavoidable. The clinical laboratory allocates a significant amount of time and energy in the pursuit of providing accurate and high quality test results, and provides an essential service for a
RI P
T
majority of clinicians. The literature is abundant on improving quality for laboratory testing with a special place in the heart for cardiac troponin as evident by a special issue last year focusing on cardiac
SC
biomarkers in Clinical Biochemistry [1,2].
NU
For cardiac troponin T (cTnT) or cardiac troponin I (cTnI) testing, the introduction of the high-
MA
sensitivity assays has been a guideline changer [3], notwithstanding the existing gaps in understanding and applying these assays for clinical care [4,5]. Among the areas that laboratory professionals are
ED
intimately aware of that impact on quality testing are processes that lead to inaccurate or even erroneous cardiac troponin results. Simply put, sometimes the cardiac troponin result is just wrong.
PT
Laboratories have standard operating procedures and skilled staff overseeing and performing this
CE
testing but errors do occur and clinical users and other stakeholders need to be aware of this. In this issue of Clinical Biochemistry two articles highlight important practical examples which demonstrate
AC
that regardless if a high-sensitivity or conventional cardiac troponin assay is employed the expected performance and the results generated may be different than the clinical users expectations [6,7].
One area that has garnered much attention is using a very low concentration of cardiac troponin to ruleout myocardial infarction (MI), which is only achievable when utilizing a high-sensitivity assay [3]. Chenevier-Gobeaux and colleagues evaluate the utility of a single high-sensitivity cardiac troponin T (hs-cTnT) measurement at presentation to rule-out MI in the emergency department (ED) [6]. Despite the excellent precision of 11.7% at the limit of detection (LoD) of 5 ng/L used to rule-out MI, from a population of 413 patients there were 71 MIs, 2 of which had hs-cTnT concentrations < 5 ng/L [6]. The authors conclude that a single measurement of hs-cTnT < 5 ng/L is “not enough to rule out safely 2/7
ACCEPTED MANUSCRIPT NSTEMI for very early presenters” [6]. The European Society of Cardiology (ESC) guidelines place an asterisk beside the 0 hour rule-out cutoffs stating “*Only applicable if chest pain onset > 3h” [3], but
RI P
T
could there be other analytical factors at play that affected the performance of hs-cTnT in this study?
We are cognizant to the fact that different reagent lots of cardiac troponin can yield divergent results
SC
[8]; with previous lots of hs-cTnT demonstrating a negative bias at concentrations below, but not above, the 99th percentile [9]. We also recognize that there is considerable variation of the assay at the
NU
low analytical range end (i.e., near the LoD) that exists within and across different platforms [10], a
MA
finding that is not unique to hs-cTnT since this variation exists for high-sensitivity cardiac troponin I (hs-cTnI) as well [11,12]. Finally, there are several pre-analytical factors that could affect results. For
ED
example, even mild hemolysis falsely lowers the cTnT concentration [13,14], and the tube and specimen type may also affect cTnT concentrations [15], which collectively can alter the utility of
PT
using the LoD to rule-out MI [16]. These pre-analytical variables are also a concern for cTnI [17-19],
CE
emphasizing the fact that no assay is impermeable to factors affecting the accuracy of the result.
AC
On the opposite end, a high concentration of cardiac troponin can be used to rule-in or identify highrisk patients [3]. Just as factors can affect the accuracy of cardiac troponin results at the low end, these same variables and different ones can result in erroneous high concentrations. In this issue, Herman and colleagues report on endogenous alkaline phosphatase (ALP) causing a higher result for cTnI in assays that use ALP as the label to generate light in the chemiluminescent immunoassay method [7]. Interestingly, their findings suggest that the liver isoform of ALP is likely the culprit here; suggesting certain hepatobiliary patients may yield erroneous results with ALP labelled chemiluminescent immunoassays [7]. This appears different to other disease states that may also cause an increase in cardiac troponin results from noncardiac causes [20]. Falsely elevated cardiac troponin results are not a new phenomenon, but eliminating these “flyers” is an 3/7
ACCEPTED MANUSCRIPT area that has dedicated significant resources and effort from industry, scientists and clinical researchers. In fact, the newer hs-cTnI assay evaluated by Herman and colleagues did not appear to be as affected by ALP as the contemporary assay [7]. Moreover, it is unknown if this positive effect from ALP would
RI P
T
be evident in EDTA plasma samples, as this matrix that has been demonstrated for some cardiac
SC
troponin assays to provide superior performance compared to lithium heparin plasma [17,18].
How can one reconcile the fact that erroneous cardiac troponin results will occur and the laboratory
NU
cannot prevent them all? Primarily by understanding that the cardiac troponin results should never be
MA
used in isolation and a clinician should make a diagnosis based on more than just the cardiac troponin result. This by no means absolves the laboratory, as laboratory professionals still need to strive for
ED
excellence in quality testing, with the awareness there is always the potential for error. Laboratory professionals need to have a continuous, ongoing dialogue with all stakeholders, as timely
AC
CE
PT
communication is vital for proper interpretation of all laboratory results (even the inaccurate ones).
Word Count: 889
4/7
ACCEPTED MANUSCRIPT References (Max 20) 1. Kavsak PA, Lai L, Langman L, Jones PM, Hammett-Stabler CA. Clinical Biochemistry 2015 year in review: Material not for the faint of heart. Clin Biochem 2015;48:1211-2.
RI P
T
2. Apple FS, Jaffe AS, Collinson P, Mockel M, Ordonez-Llanos J, Lindahl B, et al. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac
SC
troponin assays. Clin Biochem 2015;48:201-3.
3. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC
NU
Guidelines for the management of acute coronary syndromes in patients presenting without
MA
persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of
ED
Cardiology (ESC). Eur Heart J 2016;37:267-315. 4. Kavsak PA, Jaffe AS, Hickman PE, Mills NL, Humphries KH, McRae A, et al. Canadian
PT
Institutes of Health Research dissemination grant on high-sensitivity cardiac troponin. Clin
CE
Biochem 2014;47:155-7.
5. Pickering JW, Greenslade JH, Cullen L, Flaws D, Parsonage W, George P, et al. Validation of
AC
presentation and 3 h high-sensitivity troponin to rule-in and rule-out acute myocardial infarction. Heart 2016;102:1270-8. 6. Chenevier-Gobeaux C, Meune C, Lefevre G, Doumenc B, Sorbets E, Peschanski N, Ray P. A single value of high-sensitive troponin T below the limit of detection is not enough for ruling out non ST elevation myocardial infarction in the emergency department. Clin Biochem. 2016 May 24. pii: S0009-9120(16)30092-3. doi: 10.1016/j.clinbiochem.2016.05.021. [Epub ahead of print]. 7. Herman DS, Ranjitkar P, Yamaguchi D, Grenache DG, Greene DN. Endogenous alkaline phosphatase interference in cardiac troponin I and other sensitive chemiluminescence immunoassays that use alkaline phosphatase activity for signal amplification. Clin Biochem. 5/7
ACCEPTED MANUSCRIPT 2016 Jun 16. pii: S0009-9120(16)30123-0. doi: 10.1016/j.clinbiochem.2016.06.006. [Epub ahead of print]. 8. Hickman PE, Miller E, Koerbin G, Potter JM. Changes in troponin kits preclude meaningful
RI P
T
collection of data on population 99th percentiles. Ann Clin Biochem 2004;41:503-504. 9. Kavsak PA, Hill SA, McQueen MJ, Devereaux PJ. Implications of adjustment of high-
SC
sensitivity cardiac troponin T assay. Clin Chem 2013;59:574-6.
10. Saenger AK, Beyrau R, Braun S, Cooray R, Dolci A, Freidank H, et al. Multicenter analytical
NU
evaluation of a high-sensitivity troponin T assay. Clin Chim Acta 2011;412:748-54.
MA
11. Kavsak PA, Don-Wauchope AC, Hill SA, Worster A. Acceptable Analytical Variation May Exceed High-Sensitivity Cardiac Troponin I Cutoffs in Early Rule-Out and Rule-In Acute
ED
Myocardial Infarction Algorithms. Clin Chem 2016;62:887-9. 12. Kavsak PA, Beattie J, Pickersgill R, Ford L, Caruso N, Clark L. A practical approach for the
PT
validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a
CE
North American city. Pract Lab Med 2015;1:28-34. 13. Lyon ME, Ball CL, Krause RD, Slotsve GA, Lyon AW. Effect of hemolysis on cardiac troponin
AC
T determination by the Elecsys 2010 immunoanalyzer. Clin Biochem. 2004 Aug;37(8):698-701. 14. Bais R. The effect of sample hemolysis on cardiac troponin I and T assays. Clin Chem. 2010 Aug;56(8):1357-9. 15. Kock CD, Wockenfus AM, Saenger AK, Jaffe AS, Karon B. BD rapid serum tubes reduce false positives plasma troponin T results on the Roche Cobas e411 analyzer. Clin Biochem 2012;842844. 16. Kavsak PA, Worster A. Dichotomizing high-sensitivity cardiac troponin T results and important analytical considerations. J Am Coll Cardiol 2012;59:157. 17. Simons J, Beach L, Clark L, Kavsak PA. Matrix and bilirubin interference for high-sensitivity cardiac troponin I. Clin Chim Acta 2015;442:49-51. 6/7
ACCEPTED MANUSCRIPT 18. Kavsak PA, Caruso N, Beattie J, Clark L. Centrifugation--an important pre-analytical factor for the Abbott Architect high-sensitivity cardiac troponin I assay. Clin Chim Acta 2014;436:273-5. 19. Puelacher C, Twerenbold R, Mosimann T, Boeddinghaus J, Rubini Gimenez M, Wildi K, et al.
myocardial infarction. Int J Cardiol 2015;187:313-5
RI P
T
Effects of hemolysis on the diagnostic accuracy of cardiac troponin I for the diagnosis of
SC
20. Jaffe AS, Vasile VC, Milone M, Saenger AK, Olson KN, Apple FS. Disease skeletal muscle a noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll
AC
CE
PT
ED
MA
NU
Cardiol 2011;58:1819-24.
7/7