Clinical Biochemistry 47 (2014) 155–157
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Opinion Piece
Canadian Institutes of Health Research dissemination grant on high-sensitivity cardiac troponin Peter A. Kavsak a,⁎, Allan S. Jaffe b, Peter E. Hickman c, Nicholas L. Mills d, Karin H. Humphries e, Andrew McRae f, P.J. Devereaux a, Andre Lamy a, Richard Whitlock a, Sukhbinder K. Dhesy-Thind a, Julia M. Potter c, Andrew Worster a a
McMaster University, Hamilton, Ontario, Canada Mayo Clinic, Rochester, MN, USA c Australian National University Medical School, Canberra, Australian Capital Territory, Australia d BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK e University of British Columbia, Vancouver, British Columbia, Canada f Department of Emergency Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada b
a r t i c l e
i n f o
Available online 7 October 2014 Keywords: High-sensitivity cardiac troponin Emergency medicine Noncardiac surgery Cardiac surgery Cancer Research
Need for a workshop on high-sensitivity cardiac troponin Presently in clinical practice there are two putative high-sensitivity cardiac troponin (hs-cTn) assays available outside the United States (Abbott Diagnostics hs-cTnI and Roche Diagnostics hs-cTnT) with many more research hs-cTn assays available in the market place. Despite the hs-cTn assays achieving regulatory approval, there is still much uncertainty on their proper use in the acute care setting [1]. Moreover, there appear to be regional differences in the uptake and in the application of hs-cTn assays for clinical care. Specifically, within Canada there is a paucity of published data on hs-cTn performance on patients with suspected acute coronary syndrome (ACS) in the emergency department, with a published report from the Canadian Agency for Drugs and Technologies in Health (CADTH) [2], only referencing small Canadian studies in this area [3–5]. In fact, the CADTH's Health Technology Expert Review Panel statement “…encourages further research exploring different clinical algorithms to optimize patient and health system outcomes associated with high-sensitivity cardiac troponin testing.” [6]. Their statement was based on the fact that there
⁎ Corresponding author at: Juravinski Hospital and Cancer Centre (Core Lab Section) 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada. Fax: +1 905 575 2581. E-mail address:
[email protected] (P.A. Kavsak).
is a gap in research regarding optimal clinical algorithms for the hscTn assays; and that there is a lack of consensus and no Canadian guidelines on hs-cTn result interpretation [6]. This gap could lead to groups and/or individuals developing specific approaches that may or may not be data driven. In the interim, laboratory guidelines on hs-cTnassay cutoffs have been published [7] and knowledge translation and dissemination events have recently been held in Canada and the United Kingdom to discuss, share and exchange data, ideas and thoughts on the use of hs-cTn assays in the acute care setting. Through a dissemination grant from the Canadian Institutes of Health Research (CIHR), a two-day workshop on the hs-cTn assays was held on May 30 and 31, 2014 where CIHR-funded researchers and international experts assembled to discuss and interpret the findings of recent and ongoing studies involving the hs-cTn assays. Objectives for hs-cTn workshop The purpose of the workshop was to disseminate knowledge regarding the hs-cTn assays that will further the discussion in this area via the following three specific objectives: 1. Knowledge dissemination on what constitutes a ‘high-sensitivity’ cardiac troponin assay; 2. Dissemination of Canadian research findings and discussion with respect to the rest of the world research findings; 3. A document to be published on gaps in hs-cTn testing in a clinical journal. Participants attending the workshop (in person or via internet) were from across Canada, the United States, Europe and Australia and included physicians, clinical biochemists, medical laboratory technologists, laboratory directors, administration, clinical and veterinary researchers, university researchers, regulatory agencies, and industry representatives. One area, however, where there appears to be growing consensus is what constitutes a hs-cTn assay. Specifically for the hs-cTn assays ≥ 50% of healthy subjects will have measurable cardiac troponin concentrations (reported in ng/L units) [1,7]; thus physicians and laboratory professionals will need to become accustomed to managing
http://dx.doi.org/10.1016/j.clinbiochem.2014.10.002 0009-9120/© 2014 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
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patients and monitoring assays with “normal” cardiac troponin concentrations, respectively. Gaps in hs-cTn testing Despite the central role of cardiac troponin to aid in the diagnosis of myocardial infarction [8], there is still much data needed to fully optimize the sensitivity/utility of the hs-cTn assays in the diagnosis or exclusion of ACS. Moreover, there are many other hospitalized populations where hs-cTn may play an important role in risk stratification and identification of myocardial injury. To that end, we have identified areas where there are knowledge gaps and where further research is necessary for clinicians to fully utilize the results yielded by the hs-cTn assays: 1. The calculation and clinical utility of the 99th percentile for the “healthy population” as measured by the hs-cTn assays. This is an on-going and evolving area where the use of additional laboratory markers and cardiovascular imaging will drastically change the 99th percentile cutoff [9]. Additional data and consensus on what criteria should be applied to derive a representative healthy population are required. 2. Additional studies assessing outcome-based cutoffs for the hs-cTn assays for both diagnosis and prognosis. Research in patients with stable coronary artery disease has suggested utility in risk stratification [10–13]; however, data is needed in the acute care setting in various hospitalized patient groups at risk for myocardial injury [1, 14–18]. Specifically, outcome-based cutoffs (either alone or in combination with clinical variables) that accurately identify emergency department patients with symptoms of possible ACS who are at short-term risk of adverse cardiac events are essential for the appropriate identification of emergency department patients in need of admission for invasive coronary investigations. 3. Sex-specific cutoffs for diagnosis and prognosis. A large randomized controlled trial is currently assessing the utility of sex-specific cutoffs [19]. There are abundant data demonstrating differences in hs-cTn between men and women [9,20,21], however, outcome data assessing sex versus age-specific cutoffs are needed to understand these two important variables [22,23]. 4. Change in cardiac troponin concentrations (i.e., delta) has an important role in understanding the (patho)physiological consequence of a measurable concentration determined by the hs-cTn assays [24,25]. Criteria need to be established for each hs-cTn assay with an important variable being the time between sampling and if measurements are obtained early after pain onset as opposed to late presenters [26–30]. 5. The clinical utility and validity of single hs-cTn results in clinical decision making [31–33]. It may be appropriate to use different thresholds to rule out myocardial infarction than are currently recommended for diagnosing myocardial infarction that would permit earlier clinical decisions based on a single hs-cTn measurement at presentation. However, the optimal threshold for ruling out myocardial infarction and the reproducibility of hs-Tn assays at thresholds below the 99th percentile are uncertain [34,35] and such approaches have not been prospectively tested. 6. The pattern of release of hs-cTn after cardiac surgery including rate and duration of rise, thresholds reached, and rate of fall that determine a pathological pattern versus normal post-operative process for cardiac surgery is unknown. Specific type of cardiac surgery will likely need to be accounted for as well; i.e. coronary bypass versus intra-cardiac procedures [36]. There are many more areas that require additional research assessing important analytical and clinical questions. However, the above items represent areas where already much research performed has led to a better understanding of hs-cTn assays. Further research aimed at closing the gaps in hs-cTn testing will be needed before
excellent analytical sensitivity will equate to excellent clinical care for patients being monitored with the hs-cTn assays. Funding Canadian Institutes of Health Research (Funding Reference number: KDE-133844). Disclosures Dr. Kavsak has obtained grants/honorarium/advisory or consultant fees from Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, and the Canadian Agency for Drugs and Technologies in Health. Dr. Jaffe has or does consult for most of the major diagnostic companies. Dr. Mills has obtained research grant support and honorarium from Abbott Laboratories, and acted as a consultant for Abbott Laboratories and Beckman-Coulter. Dr. McRae has grant support from CIHR and Roche Diagnostics, Canada. Dr. Worster has received ‘in kind’ support in the form of reagents from Roche Diagnostics and Abbott Laboratories and has received consulting fees from the Canadian Agency for Drugs and Technologies in Health. Dr. Whitlock has received ‘in kind’ support in the form of reagents from Roche Diagnostics and Abbott Laboratories. Dr. Devereaux has received funding from Abbott and Roche Diagnostics to help support investigator initiated studies. References [1] Kavsak PA, Allen LC, Apple FS, Booth RA, Chan PC, Delvin E, et al. Cardiac troponin testing in the acute care setting: ordering, reporting, and high sensitivity assays — an update from the Canadian society of clinical chemists (CSCC). Clin Biochem 2011;44:1273–7. [2] High-Sensitivity Cardiac Troponin for the Rapid Diagnosis of Acute Coronary Syndrome in the Emergency Department: A Clinical and Cost-Effectiveness Evaluation [Internet]. . Source Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; Mar. 2013 [http://www.cadth.ca/en/products/optimal-use/ high-sensitivity-troponin]. [3] Kavsak PA, Hill SA, Supapol WB, Devereaux PJ, Worster A. Biomarkers for predicting serious cardiac outcomes at 72 hours in patients presenting early after chest pain onset with symptoms of acute coronary syndromes. Clin Chem 2012;58:298–302. [4] Kavsak PA, Wang X, Ko DT, MacRae AR, Jaffe AS. Short- and long-term risk stratification using a next-generation, high-sensitivity research cardiac troponin I (hs-cTnI) assay in an emergency department chest pain population. Clin Chem 2009;55: 1809–15. [5] Kavsak PA, MacRae AR, Yerna MJ, Jaffe AS. Analytic and clinical utility of a next-generation, highly sensitive cardiac troponin I assay for early detection of myocardial injury. Clin Chem 2009;55:573–7. [6] Recommendations for the Use of Troponin Assays for Rapid Diagnosis of Acute Coronary Syndrome in the Emergency Department. CADTH Optimal Use Report, vol. 2 (1B); March 2013. p. 6. [7] Apple FS, Jaffe AS, Collinson P, Mockel M, Ordonez-Llanos J, Lindahl B, et al. On behalf of the International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem Sep. 7 2014. http://dx.doi.org/10.1016/j.clinbiochem.2014.08.021 [pii: S00099120(14)00656-0]. [8] Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Joint ESC/ACCF/ AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. Circulation 2012;126:2020–35. [9] Koerbin G, Abhayaratna WP, Potter JM, Apple FS, Jaffe AS, Ravalico TH, et al. Effect of population selection on 99th percentile values for a high sensitivity cardiac troponin I and T assays. Clin Biochem 2013;46(16–17):1636–43. [10] Omland T, de Lemos JA, Sabatine MS, Christophi CA, Rice MM, Jablonski KA, et al. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 2009;361:2538–47. [11] Kavsak PA, Xu L, Yusuf S, McQueen MJ. High-sensitivity cardiac troponin I measurement for risk stratification in a stable high-risk population. Clin Chem 2011;57:1146–53. [12] McQueen MJ, Kavsak PA, Xu L, Shestakovska O, Yusuf S. Predicting myocardial infarction and other serious cardiac outcomes using high-sensitivity cardiac troponin T in a high-risk stable population. Clin Biochem 2013;46:5–9.
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