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cute coronary syndrome (ACS) is one of the leading causes annually. Not included in these estimates are additional unneces-
of mortality in the United States. Since the 2000 Ameri- sary expenditure and potential harm associated with subsequent
can College of Cardiology (ACC)/European Society of noninvasive and invasive testing that may result from false-
Cardiology (ESC) redefinition of acute myocardial infarction positive results.
(AMI), which was revised into the 2007 and 2012 Universal Defi- Once the cornerstone of AMI diagnosis, CK-MB has not yet been
nition of AMI, cardiac troponin (cTn) has been the biomarker of eliminated from practice despite considerable evidence support-
choice owing to its nearly absolute myocardial tissue specificity ing cTn as the preferred biomarker.8,11 Data published after distri-
and high clinical sensitivity for myocardial injury.1,2 Cardiac tro- bution of the ACC/ESC/AHA3-5 recommendations show the these
ponin is preferred by both clinical (ACC/ESC/American Heart clinical practice guidelines have not succeeded in refining practice.
Association [AHA]) 3-5 and biochemical (National Academy of Specifically, CK-MB is still used in many US clinical pathology
Clinical Biochemistry)6,7 guideline groups, for similar reasons. In laboratories and US EDs.12,13 Based on the College of American Pa-
the most recent universal definition of AMI, creatine kinase- thologists proficiency survey in 2013, 1558 of 1995 national US
myocardial band (CK-MB) is described as an alternative to be used laboratories (77%) still use CK-MB.12 In 2009, Parker and Suter13 sur-
only if cTn is not available.2 The 2014 AHA/ACC guidelines con- veyed 98 ED physician leaders in 21 academic and 77 community
clude that CK-MB provides no additional value for diagnosing AMI EDs regarding the use of cardiac biomarkers and found that 77%
(class III, level of evidence A).5 (76 of 98) still use CK-MB. Collinson et al14 found that of the nearly
The ideal biomarker test for the diagnosis of AMI should be 40% of North American and European laboratories (n = 533) offer-
highly sensitive and specific, rapidly obtained and analyzed, and ing CK-MB testing in 2006, 25% continued to offer the test even af-
lead to treatment decisions that provide high value, in terms of ter the national guidelines discussed above recommended against
clinical benefit relative to cost.8 The importance of this goal stems its use. Cappelletti et al15 added to the findings by Collinson et al14
from the sheer number of patients receiving cardiac biomarker by adding data from Italy (n = 126 laboratories) that showed 20.2%
testing and the resulting contribution to health care expenditure of laboratories continue to use CK-MB.
in the United States each year. In 2010, Makam and Nguyen9 This retention of CK-MB has been attributed to clinicians re-
showed via the National Hospital Ambulatory Medical Care Sur- luctance to rely on cTn in certain clinical situations, as well as clini-
vey (n = 44 448 emergency department [ED] visits) that cardiac cian familiarity.8,11 In 2010, a study coauthored by 7 large academic
biomarker testing (both cTn and CK-MB) occurred in 16.9% of all medical centers labeled CK-MB as 1 of 10 tests that no longer pro-
visits to the ED. The authors extrapolated this to represent 28.6 vide value,16 and a growing number of medical centers have aban-
million ED visits nationwide. Considering Medicares 2016 Clinical doned use of CK-MB.8 With the goal of advancing high value prac-
Diagnostic Laboratory Fee Schedule 1 0 (national payment tice, as defined by the ACC, ESC, AHA3-5 and National Academy of
amounts for cTn and CK-MB of $13.40 and $15.73, respectively), Clinical Biochemistry, this implementation guideline is designed to
approximately $416 million is spent on cardiac biomarker testing assist institutions in eliminating unnecessary CK-MB testing.
jamainternalmedicine.com (Reprinted) JAMA Internal Medicine Published online August 14, 2017 E1
E2 JAMA Internal Medicine Published online August 14, 2017 (Reprinted) jamainternalmedicine.com
tient (95% CI, 1.00 to 0.92). The authors estimated a 95% reduc-
Figure 1. Best Practice Alert Example
tion in CK-MB tests, translating to $720 000 in annual savings.
Best Practice Alert CK-MB Lab Test Similarly, Baron et al43 removed CK-MB from routine order sets
and implemented a BPA into their CPOE system without additional
Based on national evidence-based guidelines1,2,3:
- Troponin is the preferred marker in diagnosing AMI/ACS educational sessions. After only 2 months postimplementation, they
- CK-MB in addition to troponin adds no incremental diagnostic value
noted an 87% decrease in CK-MB orders. In addition, they noted
1. Anderson JL, Adams CD, Antman EM, et al. 2012 ACCF/AHA focused update
incorporated into the ACCF/AHA 2007 guidelines for the management of patients with
fewer orders after searches and fewer searches for CK-MB over this
unstable angina/non-ST-elevation MI. J Am Coll Cardiol. 2013; 61:e179-e347.
2. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the
time, arguing for a long-term educational benefit for the BPA. Mul-
Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of tiple other groups, including Mayo Clinic, simply removed CK-MB
the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines. J Am Coll Cardiol. 2014; 64:e139-228. from routine order sets and found 80.0% to 99.8% reductions in
3. OGara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the
management of ST elevation MI. J. Am Coll Cardiol. 2013; 61:e78-e140. CK-MB orders with significant cost savings and without negative im-
pact on patient care or missed AMI diagnoses.8,12,43-46
An example of a Best Practice Alert to appear in the physician ordering system
when attempting to order a creatine kinasemyocardial band.
Implementation Blueprint:
advised practitioners to order cTn alone, without CK-MB. The au-
Eliminating CK-MB Testing
thors then implemented multiple interventions, including educa-
tional sessions for internal medicine and ED physicians, dissemina- With clear evidence to support elimination of CK-MB from clinical
tion of pocket-sized quick reference cards with the recommended care for the diagnosis of ACS and based on experience eliminating
ordering algorithm, and removal of CK-MB from ACS routine order sets CK-MB at our respective institutions, we devised a blueprint for other
within the computerized provider order entry (CPOE) system. A Best institutions to use in enacting quality improvement initiatives. The
Practice Advisory (BPA) was created in the CPOE system using the in- methodology and theory of the blueprint and quality improve-
stitutional guideline to alert physicians who attempted to order CK- ment initiative are based on the US Health Resources and Services
MB. Physicians could, if desired, order CK-MB manually. By 12 months Administration strategies for developing and implementing a qual-
postintervention, the estimated number of CK-MB tests per patient ity improvement initiative, with a focus on education, action, and
was 0, representing an absolute change of 0.96 CK-MB tests per pa- measurement of results.47 The leader of each institution should
jamainternalmedicine.com (Reprinted) JAMA Internal Medicine Published online August 14, 2017 E3
ARTICLE INFORMATION Department of Medicine, Johns Hopkins Bayview collaborating on quality improvement, research,
Accepted for Publication: June 12, 2017. Medical Center, Baltimore, Maryland (Ziegelstein, and education related to high-value healthcare.
Trost).
Published Online: August 14, 2017. REFERENCES
doi:10.1001/jamainternmed.2017.3597 Conflict of Interest Disclosures: None reported.
Acknowledgements: This article is the first 1. Thygesen K, Alpert JS, White HD, et al; Joint
Author Affiliations: Department of Radiology and ESC/ACCF/AHA/WHF Task Force for the
Radiological Sciences, Johns Hopkins Hospital, collaborative scholarly activity produced by faculty
in the High Value Practice Academic Alliance Redefinition of Myocardial Infarction. Universal
Baltimore, Maryland (Alvin); Division of Cardiology, definition of myocardial infarction. Circulation.
Department of Medicine, Mayo Clinic, Rochester, (HVPAA). The HVPAA organization includes faculty
from more than 80 academic medical centers 2007;116(22):2634-2653.
Minnesota (Jaffe); Division of Cardiology,
E4 JAMA Internal Medicine Published online August 14, 2017 (Reprinted) jamainternalmedicine.com
2. Thygesen K, Alpert JS, Jaffe AS, et al; Joint 14. Collinson P, Hammerer-Lercher A, Suvisaari J, 28. Kavsak PA, MacRae AR, Newman AM, et al.
ESC/ACCF/AHA/WHF Task Force for the Universal et al; Working Group for Cardiac Markers, European Effects of contemporary troponin assay sensitivity
Definition of Myocardial Infarction. Third universal Federation of Clinical Chemistry and Laboratory on the utility of the early markers myoglobin and
definition of myocardial infarction. Circulation. Medicine. How well do laboratories adhere to CKMB isoforms in evaluating patients with possible
2012;126(16):2020-2035. recommended clinical guidelines for the acute myocardial infarction. Clin Chim Acta. 2007;
3. Anderson JL, Adams CD, Antman EM, et al. 2012 management of myocardial infarction: the CARdiac 380(1-2):213-216.
ACCF/AHA focused update incorporated into the MArker Guidelines Uptake in Europe Study 29. Newby LK, Roe MT, Chen AY, et al; CRUSADE
ACCF/AHA 2007 guidelines for the management of (CARMAGUE). Clin Chem. 2016;62(9):1264-1271. Investigators. Frequency and clinical implications of
patients with unstable angina/non-ST-elevation 15. Cappelletti P, Morandini M, Moretti M, Malloggi discordant creatine kinase-MB and troponin
myocardial infarction: a report of the American L, Stenner E; Working Group on Myocardial Markers measurements in acute coronary syndromes. J Am
College of Cardiology Foundation/American Heart of Italian Society for Clinical Pathology and Coll Cardiol. 2006;47(2):312-318.
Association Task Force on Practice Guidelines. J Am Laboratory Medicine (GdS MM SIPMeL). How well 30. Goodman SG, Steg PG, Eagle KA, et al; GRACE
Coll Cardiol. 2013;61(23):e179-e347. do laboratories adhere to recommended clinical Investigators. The diagnostic and prognostic impact
4. OGara PT, Kushner FG, Ascheim DD, et al; guidelines for the management of myocardial of the redefinition of acute myocardial infarction:
American College of Emergency Physicians; Society infarction? the Italian experience. Clin Chem. 2017; lessons from the Global Registry of Acute Coronary
for Cardiovascular Angiography and Interventions. 63(2):610-612. Events (GRACE). Am Heart J. 2006;151(3):654-660.
2013 ACCF/AHA guideline for the management of 16. Wu AH, Lewandrowski K, Gronowski AM, 31. Storrow AB, Lindsell CJ, Han JH, et al;
ST elevation myocardial infarction. J Am Coll Cardiol. Grenache DG, Sokoll LJ, Magnani B. Antiquated EMCREG-i*trACS Investigators. Discordant cardiac
2013;61(4):e78-e140. tests within the clinical pathology laboratory. Am J biomarkers: frequency and outcomes in emergency
5. Amsterdam EA, Wenger NK, Brindis RG, et al; Manag Care. 2010;16(9):e220-e227. department patients with chest pain. Ann Emerg Med.
American College of Cardiology; American Heart 17. Aldous SJ, Richards MA, Cullen L, Troughton R, 2006;48(6):660-665.
Association Task Force on Practice Guidelines; Than M. A new improved accelerated diagnostic 32. Panteghini M, Cuccia C, Bonetti G, Giubbini R,
Society for Cardiovascular Angiography and protocol safely identifies low-risk patients with Pagani F, Bonini E. Single-point cardiac troponin T
Interventions; Society of Thoracic Surgeons; chest pain in the emergency department. Acad at coronary care unit discharge after myocardial
American Association for Clinical Chemistry. 2014 Emerg Med. 2012;19(5):510-516. infarction correlates with infarct size and ejection
AHA/ACC Guideline for the Management of Patients 18. Katus HA, Remppis A, Neumann FJ, et al. fraction. Clin Chem. 2002;48(9):1432-1436.
with Non-ST-Elevation Acute Coronary Syndromes: Diagnostic efficiency of troponin T measurements
a report of the American College of 33. Licka M, Zimmermann R, Zehelein J, Dengler TJ,
in acute myocardial infarction. Circulation. 1991;83 Katus HA, Kbler W. Troponin T concentrations 72
Cardiology/American Heart Association Task Force (3):902-912.
on Practice Guidelines. J Am Coll Cardiol. 2014;64 hours after myocardial infarction as a serological
(24):e139-e228. 19. Adams JE III, Bodor GS, Dvila-Romn VG, et al. estimate of infarct size. Heart. 2002;87(6):520-524.
Cardiac troponin I. A marker with high specificity for 34. Gibbons RJ, Valeti US, Araoz PA, Jaffe AS. The
6. Apple FS, Jesse RL, Newby LK, et al; IFCC cardiac injury. Circulation. 1993;88(1):101-106.
Comittee on Standardization of Markers of Cardiac quantification of infarct size. J Am Coll Cardiol.
Damege; National Academy of Clinical 20. Hawkins RC, Tan HL. Comparison of the 2004;44(8):1533-1542.
Biochemistry. National Academy of Clinical diagnostic utility of CK, CK-MB (activity and mass), 35. Giannitsis E, Steen H, Kurz K, et al. Cardiac
Biochemistry and IFCC Committee for troponin T and troponin I in patients with magnetic resonance imaging study for
Standardization of Markers of Cardiac Damage suspected acute myocardial infarction. Singapore quantification of infarct size comparing directly
Laboratory Medicine Practice Guidelines: analytical Med J. 1999;40(11):680-684. serial versus single time-point measurements of
issues for biochemical markers of acute coronary 21. Lin JC, Apple FS, Murakami MM, Luepker RV. cardiac troponin T. J Am Coll Cardiol. 2008;51(3):
syndromes. Clin Chem. 2007;53(4):547-551. Rates of positive cardiac troponin I and creatine 307-314.
7. Morrow DA, Cannon CP, Jesse RL, et al; National kinase MB mass among patients hospitalized for 36. Apple FS, Murakami MM. Cardiac troponin and
Academy of Clinical Biochemistry. National suspected acute coronary syndromes. Clin Chem. creatine kinase MB monitoring during in-hospital
Academy of Clinical Biochemistry Laboratory 2004;50(2):333-338. myocardial reinfarction. Clin Chem. 2005;51(2):
Medicine Practice Guidelines: clinical characteristics 22. Adams JE III, Abendschein DR, Jaffe AS. 460-463.
and utilization of biochemical markers in acute Biochemical markers of myocardial injury. Is MB 37. Cannon CP, Weintraub WS, Demopoulos LA,
coronary syndromes. Clin Chem. 2007;53(4):552- creatine kinase the choice for the 1990s? Circulation. et al; TACTICS (Treat Angina with Aggrastat and
574. 1993;88(2):750-763. Determine Cost of Therapy with an Invasive or
8. Saenger AK, Jaffe AS. Requiem for a 23. Antman EM, Tanasijevic MJ, Thompson B, et al. Conservative Strategy)Thrombolysis in Myocardial
heavyweight: the demise of creatine kinase-MB. Cardiac-specific troponin I levels to predict the risk Infarction 18 Investigators. Comparison of early
Circulation. 2008;118(21):2200-2206. of mortality in patients with acute coronary invasive and conservative strategies in patients
9. Makam AN, Nguyen OK. Use of cardiac syndromes. N Engl J Med. 1996;335(18):1342-1349. with unstable coronary syndromes treated with the
biomarker testing in the emergency department. 24. Flores-Sols LM, Hernndez-Domnguez JL. glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med.
JAMA Intern Med. 2015;175(1):67-75. Cardiac troponin I in patients with chronic kidney 2001;344(25):1879-1887.
10. Centers for Medicare and Medicaid Services. disease stage 3 to 5 in conditions other than acute 38. Grines CL, Dixon S. A nail in the coffin of
Medicare Clinical Laboratory Fee Schedule. 2016. coronary syndrome. Clin Lab. 2014;60(2):281-290. troponin measurements after percutaneous
https://www.cms.gov/apps/ama/license.asp?file 25. Jaffe AS, Ritter C, Meltzer V, Harter H, Roberts coronary intervention. J Am Coll Cardiol. 2011;57(6):
=/Medicare/Medicare-Fee-for-Service-Payment R. Unmasking artifactual increases in creatine 662-663.
/ClinicalLabFeeSched. Accessed December 19, kinase isoenzymes in patients with renal failure. 39. Jaffe AS, Apple FS, Lindahl B, Mueller C, Katus
2016. J Lab Clin Med. 1984;104(2):193-202. HA. Why all the struggle about CK-MB and PCI? Eur
11. Trost J, Feldman L. Creatine kinase-myocardial 26. Eggers KM, Oldgren J, Nordenskjld A, Lindahl Heart J. 2012;33(9):1046-1048.
band for chest pain and suspected acute coronary B. Diagnostic value of serial measurement of 40. Wilson G, Barkley K, Slicker K, Kowal R, Pope B,
syndrome. J Hosp Med. 2015;10(12):827-829. cardiac markers in patients with chest pain: limited Michel J. Overuse of troponin? a comprehensive
12. Singh G, Baweja PS. Creatine kinase-MB: the value of adding myoglobin to troponin I for evaluation of testing in a large hospital system.
journey to obsolescence. Am J Clin Pathol. 2014;141 exclusion of myocardial infarction. Am Heart J. J Hosp Med. 2017;12(5):329-331.
(3):415-419. 2004;148(4):574-581. 41. Fraga OR, Sandoval Y, Love SA, et al. Cardiac
13. Parker R, Suter R. Survey examines EDs use of 27. Ilva T, Eriksson S, Lund J, et al. Improved early troponin testing is overused after the rule-in or
cardiac markers. ACEP News. September 2009. risk stratification and diagnosis of myocardial rule-out of myocardial infarction. Clin Chem. 2015;
https://www.acep.org/ClinicalPractice infarction, using a novel troponin I assay concept. 61(2):436-438.
-Management/Survey-Examines-EDsUse-of Eur J Clin Invest. 2005;35(2):112-116.
-Cardiac-Markers/. Accessed December 1, 2016.
jamainternalmedicine.com (Reprinted) JAMA Internal Medicine Published online August 14, 2017 E5
42. Pierce GF, Jaffe AS. Increased creatine kinase 45. Le RD, Kosowsky JM, Landman AB, Bixho I, 48. Shea CM, Jacobs SR, Esserman DA, Bruce K,
MB in the absence of acute myocardial infarction. Melanson SE, Tanasijevic MJ. Clinical and financial Weiner BJ. Organizational readiness for
Clin Chem. 1986;32(11):2044-2051. impact of removing creatine kinase-MB from the implementing change: a psychometric assessment
43. Baron JM, Lewandrowski KB, Kamis IK, Singh routine testing menu in the emergency setting. Am of a new measure. Implement Sci. 2014;9:7.
B, Belkziz SM, Dighe AS. A novel strategy for J Emerg Med. 2015;33(1):72-75. 49. Helfrich CD, Li YF, Sharp ND, Sales AE.
evaluating the effects of an electronic test ordering 46. Sullivan P, Waymack J, Griffen D, Jaeger C. Organizational readiness to change assessment
alert message: optimizing cardiac marker use. Effectively reducing CK-MB utilization using (ORCA): development of an instrument based on
J Pathol Inform. 2012;3:3. computer order entry in the emergency the Promoting Action on Research in Health
44. Larochelle MR, Knight AM, Pantle H, Riedel S, department. Am J Med Qual. 2017;32(1):107. Services (PARIHS) framework. Implement Sci.
Trost JC. Reducing excess cardiac biomarker testing 47. Health Resources and Services Administration. 2009;4:38.
at an academic medical center. J Gen Intern Med. Quality Improvement. https://www.hrsa.gov
2014;29(11):1468-1474. /quality/toolbox/methodology
/qualityimprovement/. Accessed May 12, 2017.
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