TITLE: Cardiac Troponin for the Diagnosis of Acute Coronary Syndrome in the Emergency Department: A Review of Guidelines

Transcription

1 TITLE: Cardiac Troponin for the Diagnosis of Acute Coronary Syndrome in the Emergency Department: A Review of Guidelines DATE: 11 January 2013 CONTEXT AND POLICY ISSUES Cardiac troponin (ctn) is a cardiomyocyte-specific protein detectable in the blood stream upon cardiac injury and is the recommended biochemical marker to diagnose myocardial infarction (MI). 1-7 In the emergency department (ED), troponin levels in patient blood samples are quantified using commercially available assays. Troponin testing plays a vital role in the differentiation of MI from alternate causes of acute coronary syndrome (ACS) 1-7. Patients presenting in the ED with chest pain, referred pain, nausea, vomiting, dyspnea or other symptoms of ACS require a troponin measurement. This measurement allows differentiation between unstable angina (UA) and non-st segment elevation MI (NSTEMI) if electrocardiogram (ECG) has ruled out ST segment elevation MI (STEMI). 1-7 Commercially available troponin tests are specific to either troponin T or troponin I and are high sensitivity or conventionally sensitive. Guidelines suggest that optimal use of these different troponin assays is critical for timely diagnosis of life threatening cardiac conditions in patients presenting with symptoms of ACS. 1-7 The purpose of this report is to retrieve and review the existing guidelines on optimal use of the available cardiac troponin assays for evaluation of patients presenting ACS symptoms in the emergency department. RESEARCH QUEST IONS 1. What are the clinical practice guidelines and evidence-based treatment algorithms for the use of high sensitivity troponin T (hs-ctnt) in patients with suspected ACS symptoms presenting in the emergency department? 2. What are the clinical practice guidelines and evidence-based treatment algorithms for the use of high sensitivity troponin I (hs-ctni) in patients with suspected ACS symptoms presenting in the emergency department? 3. What are the clinical practice guidelines and evidence-based treatment algorithms for the use of sensitive troponin I (ctni) in patients with suspected ACS symptoms presenting in the emergency department? KEY MESSAGE Seven guidelines were retrieved which indicate that cardiac troponin is the preferred biomarker to inform diagnosis of ACS, and recommend that patients presenting to the emergency department have a cardiac troponin test as part of their initial assessment. There is lack of consensus across guidelines regarding the requirements for repeat troponin testing, interval for repeat testing, and the quantification of troponin elevation. Information on the interpretation of

2 borderline elevated cardiac troponin levels was lacking. No Canadian guidelines or recommendations were identified. METHODS Literature Search Strategy A limited literature search was conducted on key resources including PubMed, Medline, Embase, The Cochrane Library (2012, Issue 12), University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses and guidelines. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2007 and December 20, Selection Criteria and Methods One reviewer screened the titles and abstracts of the retrieved citations and examined the fulltext publications for the final article selection. Selection criteria are outlined in Table 1. Table 1: Selection Criteria Population Patients presenting symptoms suggestive of acute coronary syndrome in the emergency department Intervention Q1. high sensitivity cardiac troponin T test Q2. high sensitivity cardiac troponin I test Q3. conventional sensitivity cardiac troponin I test Comparator Time of test administration and levels of troponin used for differential diagnosis Outcomes Guidelines and evidence-based therapeutic algorithms for troponin testing Study Designs Evidence based guidelines Exclusion Criteria Guidelines and recommendations were excluded if they did not meet the selection criteria in Table 1 or were published in a language other than English. Guidelines were also excluded if they were superseded by more recent guidelines. Critical Appraisal of Individual Studies Guidelines were assessed for quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. 8 The domains of the AGREE instrument evaluated were scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence. Strengths and limitations of each guideline were described narratively instead of assigning a numerical score. Troponin for ACS: Guidelines 2

3 SUMMARY OF EVIDENCE Quantity of Research Available The literature search strategy identified 72 articles and an additional 23 publications were identified through grey literature searching. Screening of titles and available abstracts yielded 45 reports for full-text retrieval. Upon review, seven of these reports met the selection criteria (Table 1). Of the excluded 38 retrieved citations 25 were primary research articles, reviews, recommendations or guidelines that did not meet the selection criteria, five were superseded by more recent guidelines, and eight were irrelevant and did not meet the selection criteria (Appendix 1). Summary of Study Characteristics Origin of Reports Guidelines and recommendations meeting the selection criteria were no older than 2007 and as recent as The selected guidelines and recommendations represent the work of eleven different societies, groups, collaborations or countries: the Joint European Society of Cardiology (ESC)/American College of Cardiology Foundation (ACCF)/American Heart Association, Inc. (AHA)/World Heart Federation (WHF) Task Force, 1 the European Society of Cardiology (ESC), 2 the South African Heart Association, 3 a collaboration of the National Heart Foundation of Australia (NHF), the Cardiac Society of Australia (CSA) and New Zealand (NZ), 4 the Institute for Clinical Systems Improvement (ICSI), 5 the National Academy of Clinical Biochemistry (NACB), 6 and the Scottish Intercollegiate Guidelines Network (SIGN). 7 There were no Canadian guidelines identified meeting the selection criteria (Table 1). Interventions All seven selected guidelines provide recommendations for the use of the conventionally sensitive troponin tests, both ctnt and ctni, while the five most recently published reports also refer specifically to the high-sensitivity troponin tests, hs-ctnt and hs-ctni. 1-5 Guidelines and recommendations specific to high-sensitivity troponin tests are limited to three reports. 2-4 The consensus statement from the South African Heart Association has recommendations specific to hs-ctnt and to hs-ctni. 3 Grading of recommendations and levels of evidence Guidelines and recommendations reviewed are evidence based. The methodology of literature selection was described in three guidelines. 5-7 Five of the guidelines reported a level of evidence used for relevant recommendations, 2,4-7 and four of these guidelines also assigned grades to the recommendations based on the evidence used. 2,4,6,7 The grading systems used to assign levels of evidence and strength of recommendations for the included guidelines are summarized in Appendix 2. Summary of Critical Appraisal All guidelines had clearly stated objectives related to defined clinical questions, and the guideline development groups are representative of, or consult with, relevant professional groups, including nurses, ED physicians and cardiologists. 1-7 Evidence development strategy Troponin for ACS: Guidelines 3

4 including a systematic search was referred to in three of the guidelines, 5-7 while clear evidence selection criteria was absent in all the reviewed guidelines. Methods used for formulation of recommendations from selected evidence were presented in two guidelines 5,6 and cited in two guidelines. 2,7 Six of the seven included guidelines also contained clearly stated and easily identifiable recommendations. 2-7 Five of the reviewed guidelines assigned a level of evidence used to formulate relevant recommendations, 2,4-7 while four of these guidelines additionally assigned grades to the recommendations explicitly linked to the evidence used. 2,4,6,7 Three of the guidelines include references to special patient populations, including the elderly, and patients with ongoing chronic conditions, however specially tailored guidelines were not presented. 1,2,6 Three guidelines mentioned the importance of patient views 2,4,5 although there was no mention of specific patient input into the guidelines. Five of the guidelines have methods for implementation of the recommendations, 1,2,5-7 while four guidelines have methods for future development of the reported guidelines. 1,4,5,7 As the guideline from NHF, CSA and NZ was specifically written as an update of previous guidelines, updated information was conveniently highlighted. 4 A summary of individual guideline strengths and limitations is provided in Appendix 3. Summary of Findings The seven identified reports present guidelines and recommendations for the use of troponin testing for the emergency assessment of patients with suspected ACS. 1-7 An overview of the recommendations is presented in Table 2. Table 2: Summary of Recommendations by Troponin Test Troponin Recommendations [recommendation grade, level of evidence] Test ctni Samples for ctn measurement to be taken upon initial presentation 1 [IA] 2 [1++C] 7 Repeat samples taken 6-9 hours 3 [IA] 2 [IIIC] 4 [IC] 6 after initial presentation or 12 hours [1++B] 7 after symptom onset Within 24 hours of symptom onset, a measurement > URL is indicative of MI [IC] 6 Two measurements of ctni > URL is diagnostic of MI [Low Quality Evidence] 5 hs-ctnt and hs-ctni hs-ctnt Rule Out MI: if hs-ctn < URL 6 or more hours post symptom onset 3 [IB] 2 [IIIC] 4 Rule In MI: if initial hs-ctn > WHO cut-off (assay manufacturer specific) 3 Second sample taken 3 hours after first sample and 6 hours after symptom onset: if either initial hs-ctn or second hs-ctn > URL with CV 10% [IIIC] 4 and 50% change between initial hs-ctn value and second hs-ctn[ib] 2 if 50% change between initial hs-ctn value and second hs-ctn [IIIC] 4 if initial hs-ctnt measurement is below WHO cut-off, then a second hs-ctnt measurement taken 3 hours. If second hs-ctnt value changes 50% when initial value < 53ng/L or if second hs-ctnt value changes 20% when initial value ng/L, MI is confirmed 3 Troponin for ACS: Guidelines 4

5 Troponin Test Recommendations [recommendation grade, level of evidence] hs-ctni if initial hs-ctni is below WHO cut-off then a second hs-ctni measurement taken 3 hours. If second hs-ctni changes 50% from initial value, MI is confirmed 3 ctn=cardiac troponin; ctni=cardiac troponin I; ctnt=cardiac troponin T; hs-ctn=high sensitivity cardiac troponin; MI=myocardial infarction; URL=upper reference limit; WHO=World Health Organization For interpretation of grading of recommendation, please see Appendix 2. All guidelines report that troponin is the preferred biomarker for diagnosis of MI in patients presenting to the ED with symptoms of ACS. 1-7 Guidelines support taking blood samples for an available troponin test upon first assessment of these patients. 1,2,7 Four guidelines recommend a second sample be taken 6 to 9 hours after initial presentation, 2-4,6 while the SIGN guidance recommends a subsequent sample at 12 hours after symptom onset. 7 The ESC recommends that either initial measurement or a second ctn measurement taken at 6 to 9 hours after symptom onset be over the upper reference limit (URL) with a coefficient of variation less than 10% (CV<10%) for diagnosis of MI. 2 The NACB recommends that a ctn measurement over the URL within 24 hours of symptom onset is indicative of MI. 4 The ICSI recommends two ctn measurements over the URL also demonstrating significant change when taken three hours apart, be required for MI diagnosis. 5 The Joint ESC/ACCF/AHA/WHF Task Force recommends that a ctn over the URL be accompanied by a significant change in a second sample taken 3 to 6 hours later. 1 Three guidelines have recommendations for rapid rule-in and rule-out for the diagnosis of MI using the high sensitivity troponin tests, hs-ctnt and hs-ctni. 2-4 A single measurement of hsctnt or hs-ctni, taken at least 6 hours after the onset of ACS symptoms, and falling below the URL (CV<10%) rules out MI. 2-4 For rule-in of MI, the ESC, NSF, CSA and NZ recommend a hsctn measurement above the URL (CV<10%) or a change in hs-ctn of greater than 50% in a second sample taken more than 3 hours of the first sample and 6 hours from symptom onset. 4 The rapid protocol recommended by ESC requires a significant change in serial samples taken 3 hours apart at least 6 hours after symptom onset and one hs-ctn over the URL with CV<10%. 2 The South African Heart Association recommends a diagnosis of MI in the case of hs-ctn above the WHO cut-off value. 3 These values are specific for each manufacturers assay. 3 When hs-ctn is below the WHO cut-off value the SA Heart Association recommends that another sample be taken 3 to 6 hours after the initial. In the case where the initial sample is less than 53ng/L a diagnosis of MI is recommended when a 50% or greater change in hs-ctnt is observed. If the initial value is between 53 and 100ng/L a 20% or greater change in hs-ctnt is diagnostic of MI. 3 If, in the second sample, a 50% or greater change in hs-ctni is observed, a diagnosis of MI is recommended regardless of the initial absolute value of hs-ctni. 3 Guidelines and recommendations are also summarized by source in Appendix 4. Limitations Guidelines suggest that elevation of cardiac troponin levels in isolation are not sufficient for diagnosis of MI. 1-7 The reviewed guidelines have specific recommendations for the use of ctn levels in patients presenting in the ED with symptoms consistent with ACS, and most reports address the concern of high ctn levels in patients with ongoing chronic cardiac and other conditions resulting in potentially false-positive test results. 1-5,7 Four reviewed guidelines describe other necessary clinical observations, possible chronic conditions and risk factors Troponin for ACS: Guidelines 5

6 required for considering a diagnosis of MI. 1,2,4,5,7 Elevations in ctni and ctnt, even without definitive ACS, are associated with adverse prognosis. 2,6 Outside of an ACS diagnosis the reported guidelines do not have recommendations about ctn prognostic values or borderline ctn values. Of the guidelines included in this review only the South African Heart Association has recommendations that differentiated between hs-ctnt and hs-ctni, based upon one prospective multicenter study. 3 None of the reviewed guidelines were published by a Canadian stakeholder and therefore the recommendations may have limited applicability in a Canadian setting. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING Seven guidelines were retrieved which indicate that cardiac troponin is the preferred biomarker to inform diagnosis of ACS, and recommend that patients presenting to the emergency department have a cardiac troponin test as part of their initial assessment. There is lack of consensus across guidelines regarding a requirement for repeat troponin testing, interval for repeat testing, and the quantification of troponin elevation. There are no strong evidence-based recommendations for the preferential use of hs-ctn assays over conventionally sensitive tests. 2,4 Most guidelines specifically recommend a troponin sample be taken upon initial assessment, 1,2,5-7 while other imply that a sample is taken as soon as ACS is suspected. 3,4 Three guidelines agree that one normal ctn measurement taken at more than six hours post symptom onset rules out MI. 2-4 The ESC guidelines strongly recommend, based on two multicenter studies, 9,10 the use of a rapid rule out protocol (0 and 3 hours) when hs-ctn assays are available. 2 A rapid protocol, also recommended by NHF/CSA/NZ and SA Heart Association, is the major difference between the reviewed guidelines for use of conventional sensitive troponin assays and high sensitivity assays. 3,4 Information on the interpretation of borderline elevated cardiac troponin levels was lacking. No Canadian guidelines or recommendations were identified. PREPARED BY: Canadian Agency for Drugs and Technologies in Health Tel: Troponin for ACS: Guidelines 6

7 REFERENCES 1. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Nat Rev Cardiol Nov;9(11): Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J Dec;32(23): Jardine RM, Dalby AJ, Klug EQ, Vermaak WH, White HD, Badenhorst JCW, et al. Consensus statement on the use of high sensitivity cardiac troponins. SAHJ [Internet] [cited 2013 Jan 3];9(3): Available from: %5D=237&path%5B%5D= Chew DP, Aroney CN, Aylward PE, Kelly AM, White HD, Tideman PA, et al Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the management of acute coronary syndromes (ACS) Heart Lung Circ Aug;20(8): Davis T, Bluhm J, Burke R, Iqbal Q, Kim K, Kokoszka M, et al. Diagnosis and treatment of chest pain and acute coronary syndrome (ACS) [Internet]. Bloomington (MN): Institute for Clinical Systems Improvement; 2012 Nov. [cited 2013 Jan 3]. (Health care guideline). Available from: 6. Morrow DA, Cannon CP, Jesse RL, Newby LK, Ravkilde J, Storrow AB, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem Apr;53(4): Acute coronary syndromes [Internet]. Edinburgh: Scottish Intercollegiate Guidelines Network (SIGN); 2007 Feb. [cited 2013 Jan 3]. (A national clinical guideline 93). Available from: 8. Brouwers M, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting and evaluation in healthcare. CMAJ Dec;182:E839-E Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med Aug 27;361(9): Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med Aug 27;361(9): Troponin for ACS: Guidelines 7

8 List of Abbreviations ACCF ACS AGREE AHA COI CSA CV ctn ctni ctnt ED ESC hs-ctn ICSI MA MI N/A NACB NHF NR NZ RCT SIGN UA URL WHF WHO American College of Cardiology Foundation Acute Coronary Syndrome Appraisal of Guidelines for Research and Evaluation American Heart Association conflicts of interest Cardiac Society of Australia coefficient of variance cardiac troponin cardiac troponin I cardiac troponin T Emergency Department European Society of Cardiology high sensitivity cardiac troponin Institute for Clinical Systems Improvement meta-analyses myocardial infarction not applicable National Academy of Clinical Biochemistry National Heart Foundation of Australia not reported New Zealand randomized controlled trial Scottish Intercollegiate Guidelines Network unstable angina upper reference limit World Heart Federation World Health Organization Troponin for ACS: Guidelines 8

9 APPENDIX 1: Selection of Included Studies 72 citations identified from electronic literature search and screened 50 citations excluded 22 potentially relevant articles retrieved for scrutiny (full text, if available) 23 potentially relevant reports retrieved from other sources (grey literature, hand search) 45 potentially relevant reports 38 reports excluded: -irrelevant population (3) -irrelevant intervention (3) -irrelevant comparator (2) -replaced by more recent guidelines (5) -other (review articles, editorials)(25) 7 reports included in review Troponin for ACS: Guidelines 9

10 APPENDIX 2: Grading of Recommendations and Levels of Evidence Guideline Society or Institute Joint ESC/ACCF/AHA/WHF Task Force 1 Recommendation Level of Evidence Grading of recommendations and levels of evidence were not provided in these guidelines. ICSI 5 N/A High Quality Evidence: Future evidence very unlikely to alter confidence Moderate Quality Evidence: Future evidence likely to have important impact on confidence Low Quality Evidence: Future evidence very likely to have important impact on confidence and estimates are uncertain South African Heart Association 3 ESC 2, NACB 6 NHF, CSA and NZ 4 SIGN 7 Grading of recommendations and levels of evidence were not provided in these guidelines. Class I: Consistent evidence and general agreement Class II: Conflicting evidence and/or divergence of opinion Class IIa: Weight of evidence in favour Class IIb: Evidence/opinion less in favour Class III: Evidence and/or general agreement not in favour A: Evidence trusted to guide practice B: Evidence trusted to guide practice in most situations C: Evidence provides some support for recommendations D: Evidence is weak, recommendation applied with caution N/A: Recommendation cannot be graded A: At least one MA, systematic review of RCTs or RCT rated as 1++, consistent evidence rated as 1+ B: Evidence overall consistent studies of 2++, or extrapolated evidence from 1++ or 1+ C:Evidence overall consistent studies of 2+, or extrapolated evidence from 2++ D: Evidence 3 or 4, or extrapolated evidence from 2+ A: Multiple RCTs or MAs B: A single RCT or large nonrandomized studies. C: Consensus of opinion of experts and/or small or retrospective studies I: A systematic review of RCTs II: A single RCT III-1: A pseudo-randomized controlled trial III-2: A comparative study with concurrent controls III-3: A comparative study without concurrent controls IV: Case studies 1++: High quality MAs, systematic reviews of RCTs or RCTs with very low bias risk 1+: Well conducted MAs, systematic reviews of RCTs or RCTs with low bias risk 1-: MAs, systematic review of RCTs or RCTs with high bias risk 2++: High quality systematic reviews of case control or cohort studies with very low bias risk 2+: Well conducted case control Troponin for ACS: Guidelines 10

11 Guideline Society or Institute Recommendation Level of Evidence Good practice point: Expert opinion or cohort studies with low bias risk 2-: Case control or cohort studies with high bias risk and/or significant risk that relationship is not causal 3: non-analytic studies 4: expert opinion ACCF American College of Cardiology Foundation; ACS Acute Coronary Syndrome; AHA American Heart Association; ESC European Society of Cardiology; hs-ctn high sensitivity cardiac troponin; ICSI Institute for Clinical Systems Improvement; MA meta-analyses; NACB National Academy of Clinical Biochemistry; NHF National Heart Foundation of Australia; NZ New Zealand; RCT randomized control trial; SIGN Scottish Intercollegiate Guidelines Network; WHF World Heart Federation; Troponin for ACS: Guidelines 11

12 APPENDIX 3: Summary of Critical Appraisal Using AGREE Guideline Society, Country, Author and Year Joint ESC/ACCF/AHA/WHF Task Force, Thygesen et al., Strengths Recommendations for use of hs-ctn tests Full disclosure of COIs Limitations Evidence development NR Recommendations not clearly identifiable ICSI, US, Davis T et al., SA Heart Association, South Africa, Jardine et al., ESC, Hamm CW et al., NHF, CSA and NZ, Australia and New Zealand, Chew DP et al., NACB, US, Christensen RH et al., SIGN, Scotland, Explicitly stated scope and target population Evidence development methodology outlined Recommendations linked to graded evidence Recommendations for use of hs-ctn Clear consensus-based recommendations Recommendations for use of hs-ctn Recommendations graded and linked to level of evidence Recommendations graded and linked to level of evidence Recommendations for use of hs-ctn and ctn assays Discussions of limitations, complications and local applicability Full disclosure of COIs Explicitly stated scope, target population and stakeholder involvement Basic search methodology outlined Recommendations graded and linked to level of evidence Basic search methodology outlined Recommendations graded based on weight of hierarchy of evidence Recommendations for use of ctn made upon one citation of low quality evidence Evidence development NR Evidence for recommendations unclear or based on consensus Potential COI NR Acknowledgement of limited evidence for recommendations for hs-ctn Evidence development NR Evidence development NR Does not evaluate use of hs-ctn Does not evaluate use of hs-ctn ACCF American College of Cardiology Foundation; ACS Acute Coronary Syndrome; AHA American Heart Association; COI conflicts of interest; CSA Cardiac Society of Australia; ctn cardiac troponin; ctni cardiac troponin I; ctnt cardiac troponin T; ESC European Society of Cardiology; hs-ctn high sensitivity cardiac troponin; ICSI Institute for Clinical Systems Improvement; NACB National Academy of Clinical Biochemistry; NHF National Heart Foundation of Australia; NR not reported; NZ New Zealand; SIGN Scottish Intercollegiate Guidelines Network; WHF World Heart Federation; Troponin for ACS: Guidelines 12

13 APPENDIX 4: Summary of Recommendations by Source Guideline Society or Institute, Year Recommendations [recommendation grade, level of evidence] ESC/ACCF/AHA /WHF ICSI SA Heart Association ESC NHF, CSA and NZ NACB SIGN ctn upon initial presentation and 6-9 hours afterwards Any change in ctn with at least one ctn>url with CV 10% is diagnostic of MI hs-ctni has the best performance characteristics [Low Quality Evidence] ctn measurements taken upon initial presentation and 3 hours of observation [Low Quality Evidence] Diagnosis of ACS established with two ctn measurements. A second ctn > URL with significant change[low Quality Evidence] hs-ctn abolishes the need for other biomarkers results should be available within 1 hour normal hs-ctn > 6 hours after symptom onset rules out MI hs-ctn above WHO cut-off (assay manufacturer specific) rules in MI if below WHO cut-off, a hs-ctn second sample 3hours after the first sample if second sample hs-ctni changes 50% from initial value this is diagnostic of MI if second sample hs-ctnt changes 50% when initial value < 53ng/L or 20% change when initial value is ng/L, this is diagnostic of MI ctn measurement taken upon initial presentation and 6-9 hours afterwards [IA] normal hs-ctn > 6 hours after symptom onset rules out MI [IB] hs-ctn second sample taken 3hours after the first sample and 6 hours after symptom onset. If hs-ctn change 50% from first measurement and either hs-ctn measurement > URL with CV 10% this is diagnostic of MI [IB] hs-ctn assays should be used in preference to conventional assays [N/A N/A] ctn results should be available within 1 hour [N/A N/A] normal hs-ctn > 6 hours after symptom onset rules out MI [IIIC] ctn > URL accompanied by a > 20% change with serial sampling rules in MI [NR] hs-ctn second sample taken 3hours after the first sample and 6 hours after symptom onset if hs-ctn 50% change is diagnostic of MI [N/A Consensus] if hs-ctn 50% change assay is negative for MI [IIIC] ctn is the preferred biomarker for assessing ACS [IA] ctn sample upon initial presentation and 6-9 hours afterwards [IC] One ctn > URL with CV 10% within 24 hours is indicative of MI [IC] ctnt and ctni are of equal clinical value[1++] ctn measurement upon initial presentation[1++c] ctn measurements taken 12 hours from symptom onset[1++b] if symptom onset time is uncertain ctn measurement 12 hours from initial presentation [1++Expert Opinion] 12 hour ctnt < 0.01μg/L is defined as ACS with UA [NR] 12 hour ctnt 0.01μg/L and <1.0μg/L is defined as ACS w/ myocyte necrosis [NR] 12 hour ctnt 1.0μg/L is defined as ACS with clinical MI [NR] ACCF American College of Cardiology Foundation; ACS Acute Coronary Syndrome; AHA American Heart Association; COI conflicts of interest; CSA Cardiac Society of Australia; CV coefficient of variance; ctn cardiac troponin; ctni cardiac troponin I; ctnt cardiac troponin T; ESC European Society of Cardiology; hs-ctn high sensitivity cardiac troponin; ICSI Institute for Clinical Systems Improvement; MA meta-analyses; N/A not applicable; NACB National Academy of Clinical Biochemistry; NHF National Heart Foundation of Australia; NR not reported; NZ New Zealand; RCT randomized control trial; SIGN Scottish Intercollegiate Guidelines Network; URL upper reference limit; WHF World Heart Federation; Troponin for ACS: Guidelines 13