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Circulation. 2021;144:e368–e454. DOI: 10.1161/CIR.0000000000001029 November 30, 2021 e425 CLINICAL STATEMENTS AND GUIDELINES

ciety of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the Definition of Myocardial Infarction. Clin Chem. 2010;56:941–943. 9.	 Morrow DA, Cannon CP, Jesse RL, et al. National academy of clinical biochemistry laboratory medicine practice guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Circulation. 2007;115:e356–e375. 10.	 Mueller C, Giannitsis E, Christ M, et al. Multicenter evaluation of a 0-hour/1hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T. Ann Emerg Med. 2016;68:76–87, e4. 11.	 Odqvist M, Andersson PO, Tygesen H, et al. High-sensitivity troponins and outcomes after myocardial infarction. J Am Coll Cardiol. 2018;71:2616– 2624. 12.	 Peacock WF, Baumann BM, Bruton D, et al. Efficacy of high-sensitivity troponin T in identifying very-low-risk patients with possible acute coronary syndrome. JAMA Cardiol. 2018;3:104–111. 13.	 Reichlin T, Schindler C, Drexler B, et al. One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med. 2012;172:1211–1218. 14.	 Reichlin T, Twerenbold R, Maushart C, et al. Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays. Am Heart J. 2013;165:371–378.e3. 15.	 Rubini Gimenez M, Hoeller R, Reichlin T, et al. Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin. Int J Cardiol. 2013;168:3896–3901. 16.	 Rubini Gimenez M, Twerenbold R, Jaeger C, et al. One-hour rule-in and ruleout of acute myocardial infarction using high-sensitivity cardiac troponin I. Am J Med. 2015;128:861–870, e4. 17.	 Twerenbold R, Boeddinghaus J, Nestelberger T, et al. Clinical use of highsensitivity cardiac troponin in patients with suspected myocardial infarction. J Am Coll Cardiol. 2017;70:996–1012. 18.	 Twerenbold R, Neumann JT, Sorensen NA, et al. Prospective validation of the 0/1-h algorithm for early diagnosis of myocardial infarction. J Am Coll Cardiol. 2018;72:620–632. 19.	 Wildi K, Nelles B, Twerenbold R, et al. Safety and efficacy of the 0 h/3 h protocol for rapid rule out of myocardial infarction. Am Heart J. 2016;181:16–25. 20.	 Zhelev Z, Hyde C, Youngman E, et al. Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis. BMJ. 2015;350:h15. 21.	 Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Circulation. 2018;138:e618–e651. 22.	 Cullen L, Mueller C, Parsonage WA, et al. Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome. J Am Coll Cardiol. 2013;62:1242–1249. 23.	 Lipinski MJ, Baker NC, Escarcega RO, et al. Comparison of conventional and high-sensitivity troponin in patients with chest pain: a collaborative meta-analysis. Am Heart J. 2015;169:6–16, e6. 24.	 Twerenbold R, Wildi K, Jaeger C, et al. Optimal cutoff levels of more sensitive cardiac troponin assays for the early diagnosis of myocardial infarction in patients with renal dysfunction. Circulation. 2015;131: 2041–2050. 25.	 van Wijk S, Jacobs L, Eurlings LW, et al. Troponin T measurements by highsensitivity vs conventional assays for risk stratification in acute dyspnea. Clin Chem. 2012;58:284–292. 26.	 Neumann JT, Twerenbold R, Ojeda F, et al. Application of high-sensitivity troponin in suspected myocardial infarction. N Engl J Med. 2019;380:2529– 2540. 27.	 Aviles RJ, Wright RS, Aviles JM, et al. Long-term prognosis of patients with clinical unstable angina pectoris without elevation of creatine kinase but with elevation of cardiac troponin I levels. Am J Cardiol. 2002;90:875–878. 28.	 Eggers KM, Oldgren J, Nordenskjold A, et al. Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction. Am Heart J. 2004;148:574–581. 29.	 Kavsak PA, MacRae AR, Newman AM, et al. Effects of contemporary troponin assay sensitivity on the utility of the early markers myoglobin and CKMB isoforms in evaluating patients with possible acute myocardial infarction. Clin Chim Acta. 2007;380:213–216. 30.	 Kontos MC, de Lemos JA, Ou FS, et al. Troponin-positive, MB-negative

patients with non-ST-elevation myocardial infarction: an undertreated but high-risk patient group: results from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network- Get With The Guidelines (NCDR ACTION-GWTG) Registry. Am Heart J. 2010;160:819–825. 31.	 Newby LK, Roe MT, Chen AY, et al. Frequency and clinical implications of

discordant creatine kinase-MB and troponin measurements in acute coronary syndromes. J Am Coll Cardiol. 2006;47:312–318. 32.	 Volz KA, McGillicuddy DC, Horowitz GL, et al. Creatine kinase-MB does not add additional benefit to a negative troponin in the evaluation of chest pain. Am J Emerg Med. 2012;30:188–190. 33.	 Reichlin T, Twerenbold R, Wildi K, et al. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a highsensitivity cardiac troponin T assay. CMAJ. 2015;187:E243–E252. 34.	 Shah AS, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. 2015;350:g7873. 35.	 Morrow DA. The Fourth Universal Definition of Myocardial Infarc-

tion and the Emerging Importance of Myocardial Injury. Circulation. 2020;141:172–175.

3 CARDIAC TESTING GENERAL

CONSIDERATIONS

1 Wolk MJ, Bailey SR, Doherty JU, et al. ACCF/AHA/ASE/ASNC/HFSA/

HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2014;63:380–406. 2.	 Medicare Program: Changes to Hospital Outpatient Prospective Payment

and Ambulatory Surgical Center Payment Systems and Quality Reporting Programs; Revisions of Organ Procurement Organizations Conditions of Coverage; Prior Authorization Process and Requirements for Certain Covered Outpatient Department Services; Potential Changes to the Laboratory Date of Service Policy; Changes to Grandfathered Children's Hospitals- Within-Hospitals; Notice of Closure of Two Teaching Hospitals and Opportunity To Apply for Available Slots. Available at: https://www.cms.gov/ Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/ Hospital-Outpatient-Regulations-and-Notices-Items/CMS-1717-FC. Accessed September 14, 2020.

3.1 Anatomic Testing

3.1.1 Coronary Computed Tomography Angiography

1 Gaur S, Ovrehus KA, Dey D, et al. Coronary plaque quantification and frac-

tional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions. Eur Heart J. 2016;37:1220–1227. 2.	 Ferencik M, Mayrhofer T, Bittner DO, et al. Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain: a secondary analysis of the PROMISE randomized clinical trial. JAMA Cardiol. 2018;3:144–152. 3.	 Budoff MJ, Mayrhofer T, Ferencik M, et al. Prognostic value of coronary artery calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) Circulation. 2017;136:1993–2005. 4.	 Ferencik M, Mayrhofer T, Puchner SB, et al. Computed tomography-based high-risk coronary plaque score to predict acute coronary syndrome among patients with acute chest pain–Results from the ROMICAT II trial. J Cardiovasc Comput Tomogr. 2015;9:538–545. 5.	 Puchner SB, Liu T, Mayrhofer T, et al. High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol. 2014;64:684–692. 6.	 Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary com-

puted tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J Am Coll Cardiol. 2015;66:337–346.

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