Clinical Review & Education

JAMA Internal Medicine | Special Communication | LESS IS MORE

Eliminating Creatine KinaseMyocardial Band Testing

in Suspected Acute Coronary Syndrome
A Value-Based Quality Improvement
Matthew D. Alvin, MD, MBA, MS, MA; Allan S. Jaffe, MD; Roy C. Ziegelstein, MD, MACP; Jeffrey C. Trost, MD

Author Audio Interview

Cardiac biomarker testing is estimated to occur in nearly 30 million emergency department
visits nationwide each year in the United States. The American College of Cardiology/
European Society of Cardiology indicate that cardiac troponin is the biomarker of choice
owing to its nearly absolute myocardial tissue specificity and high clinical sensitivity for
myocardial injury. Multiple academic medical centers have implemented interventions to
eliminate the routine ordering of creatine kinasemyocardial band tests, with published
patient safety outcomes data; however, creatine kinasemyocardial band testing is still
Author Affiliations: Author
ordered in many hospitals and emergency departments. Eliminating a simple laboratory test affiliations are listed at the end of this
that provides no incremental value to patient care can lead to millions of health care dollars article.
saved without adversely affecting patient care quality, and in this case potentially improving Corresponding Author: Jeffrey C.
patient care. Trost, MD, Division of Cardiology,
Department of Medicine, Johns
Hopkins University School of
JAMA Intern Med. doi:10.1001/jamainternmed.2017.3597 Medicine, 301 Mason F. Lord Bldg,
Published online August 14, 2017. Baltimore, MD 21224
(jtrost2@jhmi.edu).

A
cute coronary syndrome (ACS) is one of the leading causes
of mortality in the United States. Since the 2000 Ameri-
can College of Cardiology (ACC)/European Society of
Cardiology (ESC) redefinition of acute myocardial infarction
(AMI), which was revised into the 2007 and 2012 Universal Defi-
nition of AMI, cardiac troponin (cTn) has been the biomarker of
choice owing to its nearly absolute myocardial tissue specificity
and high clinical sensitivity for myocardial injury.1,2 Cardiac tro-
ponin is preferred by both clinical (ACC/ESC/American Heart
Association [AHA]) 3-5 and biochemical (National Academy of
Clinical Biochemistry)6,7 guideline groups, for similar reasons. In
the most recent universal definition of AMI, creatine kinase-
myocardial band (CK-MB) is described as an alternative to be used
only if cTn is not available.2 The 2014 AHA/ACC guidelines con-
clude that CK-MB provides no additional value for diagnosing AMI
(class III, level of evidence A).5
The ideal biomarker test for the diagnosis of AMI should be
highly sensitive and specific, rapidly obtained and analyzed, and
lead to treatment decisions that provide high value, in terms of
clinical benefit relative to cost.8 The importance of this goal stems
from the sheer number of patients receiving cardiac biomarker
testing and the resulting contribution to health care expenditure
in the United States each year. In 2010, Makam and Nguyen9
showed via the National Hospital Ambulatory Medical Care Sur-
vey (n = 44 448 emergency department [ED] visits) that cardiac
biomarker testing (both cTn and CK-MB) occurred in 16.9% of all
visits to the ED. The authors extrapolated this to represent 28.6
million ED visits nationwide. Considering Medicares 2016 Clinical
Diagnostic Laboratory Fee Schedule 1 0 (national payment
amounts for cTn and CK-MB of $13.40 and $15.73, respectively),
approximately $416 million is spent on cardiac biomarker testing
annually. Not included in these estimates are additional unneces-
sary expenditure and potential harm associated with subsequent
noninvasive and invasive testing that may result from false-
positive results.
Once the cornerstone of AMI diagnosis, CK-MB has not yet been
eliminated from practice despite considerable evidence support-
ing cTn as the preferred biomarker.8,11 Data published after distri-
bution of the ACC/ESC/AHA3-5 recommendations show the these
clinical practice guidelines have not succeeded in refining practice.
Specifically, CK-MB is still used in many US clinical pathology
laboratories and US EDs.12,13 Based on the College of American Pa-
thologists proficiency survey in 2013, 1558 of 1995 national US
laboratories (77%) still use CK-MB.12 In 2009, Parker and Suter13 sur-
veyed 98 ED physician leaders in 21 academic and 77 community
EDs regarding the use of cardiac biomarkers and found that 77%
(76 of 98) still use CK-MB. Collinson et al14 found that of the nearly
40% of North American and European laboratories (n = 533) offer-
ing CK-MB testing in 2006, 25% continued to offer the test even af-
ter the national guidelines discussed above recommended against
its use. Cappelletti et al15 added to the findings by Collinson et al14
by adding data from Italy (n = 126 laboratories) that showed 20.2%
of laboratories continue to use CK-MB.
This retention of CK-MB has been attributed to clinicians re-
luctance to rely on cTn in certain clinical situations, as well as clini-
cian familiarity.8,11 In 2010, a study coauthored by 7 large academic
medical centers labeled CK-MB as 1 of 10 tests that no longer pro-
vide value,16 and a growing number of medical centers have aban-
doned use of CK-MB.8 With the goal of advancing high value prac-
tice, as defined by the ACC, ESC, AHA3-5 and National Academy of
Clinical Biochemistry, this implementation guideline is designed to
assist institutions in eliminating unnecessary CK-MB testing.

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 Clinical Review & Education Special Communication
Evidence-Based Guidelines:
Troponin and CK-MB Tests
NumerousstudieshavecomparedCK-MBandcTnwithrespecttotheir
diagnostic precision related to the initial diagnosis of AMI, the assess-
ment of reinfarction, and prognosis after major cardiovascular events.
Cardiac troponin has been shown to be highly sensitive for AMI
(99.2%)17 and to be more specific than CK-MB (lower false-positive
rate) owing to its exclusivity in cardiac myocytes (vs CK-MB, which may
be elevated with skeletal muscle damage).16-19 Hawkins et al20 cal-
culated a specificity of cTn testing as high as 92% compared with 40%
for CK-MB. Lin et al21 observed that among patients with suspected
AMI who also had negative cTn results, approximately 10% of pa-
tients had abnormally high CK-MB.22 Similarly, Antman et al23 evalu-
ated cardiac biomarker levels in patients with ACS symptoms and
found that 238 of 948 patients (25%) initially classified as having un-
stable angina owing to normal CK-MB tests actually had elevated cTn
levels. Thus, the use of CK-MB may potentially misclassify individu-
als with ACS by mistakenly diagnosing unstable angina in some pa-
tients with true myocardial infarction.
In patients with chronic renal disease, the diagnosis of ACS can
be challenging, as cTn levels may be chronically elevated. However,
CK-MB has been shown to provide no incremental value over cTn in
the diagnosis of ACS in patients with chronic renal disease.24,25 In
fact, CK-MB levels are often elevated in patients on dialysis in the
absence of ACS signs and/or symptoms.25
In terms of time to diagnosis, both CK-MB and troponin are
equally rapid in ACS diagnosis,8 but with more sensitive assays, cTn
rises much more rapidly.26-28 In addition to its superior sensitivity
and specificity, cTn yields stronger prognostic information. In pa-
tients with ACS, the CRUSADE investigators (n = 29 357)29 showed
that elevated cTn is associated with in-hospital mortality, regard-
less of CK-MB levels. However, when CK-MB levels are elevated in
the presence of a normal cTn, in-hospital mortality is comparable to
CK-MB levels and cTn both being negative.29-31 Most important, those
with elevated CK-MB values but normal cTn levels do not manifest
an adverse prognosis.29-31
Despite a longstanding, commonly held physician belief that
CK-MB is more useful than cTn for detecting reinfarction, no study
has shown that CK-MB levels are superior to cTn in this regard.32,33
Indeed, most data confirm that cTn provides far better estimates be-
cause it is less impacted by changes in the amount of marker re-
leased with reperfusion.34 Single values correlate closely with in-
farct size as determined by cardiac magnetic resonance imaging.35
Apple et al36 showed that both biomarker levels rise similarly with
reinfarction. The most recent ACC/AHA/ESC guidelines support the
use of cTn over CK-MB for diagnosing reinfarction.3-5
Most patients with ACS are treated with either surgical or per-
cutaneous revascularization.37,38 The use of CK-MB or cTn follow-
ing percutaneous coronary intervention (PCI) is controversial, as
there is no current consensus regarding the definition, prognosis,
and subsequent treatment of periprocedural myocardial infarction
diagnosed by cardiac biomarker elevation alone. Some groups have
suggested that CK-MB is superior to cTn in terms of detecting peri-
procedural myocardial infarction,38 while others have argued that
post-PCI cardiac biomarkers are not useful because prognosis is re-
lated to the pre-PCI cTn value, and when that is taken into account,
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Eliminating Creatine KinaseMyocardial Band Testing in Suspected ACS
post-PCI myocardial injury is not an important clinical end point.39
Even if clinicians decide to assess cardiac biomarkers in this setting,
post-PCI cTn and CK-MB values provide equally accurate prognos-
tic information.39 Because this guideline is focused on cardiac bio-
marker use in routine ACS diagnosis, rather than cardiac biomarker
use following PCI, we defer further discussion and/or recommen-
dation with respect to this ongoing clinical controversy.
Another potential area of controversy concerns the appropri-
ate use of cTn in clinical practice.40 The major strength of using
cTnits specificity for cardiac injuryis also a potential shortcom-
ing, because cTn detects myocardial injury irrespective of the spe-
cific cause. Consequently, many noncardiac conditions associated
with secondary myocardial injury, such as pulmonary embolus, se-
vere anemia, and severe hypotension from any cause, are associ-
ated with abnormal cTn. Wilson et al40 reported a high prevalence
of elevated cTn in a large group of hospitalized patients due to non-
cardiac conditions and has suggested that this may represent an ex-
ample of overuse of cTn. Another group has reported a small series
of patients in which the quantity of troponins ordered per patient
exceeded guideline recommendations.41 We acknowledge that the
real-world use of cTn, with respect to appropriate clinical indica-
tion and quantity over time, deserves further study and quality im-
provement initiatives designed to refine usage.
Finally, Saenger et al8 have observed that concomitant use of
CK-MB and cTn is often confusing for physicians, and they are aware
of situations in which such confusion has negatively affected pa-
tient care. An example of a potentially confusing clinical situation is
when a patient is admitted with possible symptoms of ACS and is
found to have an abnormally elevated CK-MB levels in the setting
of sequentially normal troponin levels. Although normal sequen-
tial troponin values exclude the diagnosis of acute myocardial
injuryand are associated with a favorable short-term prognosis
regardless of the CK-MB levelssome physicians might errone-
ously conclude that the patient has suffered acute myocardial
injury due to CK-MB elevation. Others might wonder if there is
another condition (ie, skeletal muscle breakdown) responsible for
the CK-MB elevation and might erroneously devalue the impor-
tance of the patients symptoms and electrocardiogram in making
the diagnosis of ACS.42 We would argue that elimination of rou-
tine CK-MB ordering is not only high value because it offers no
benefit and results in considerable cost but also because elimina-
tion of CK-MB may reduce physician confusion, improve under-
standing of the proper use of cTn, and consequently reduce
potential patient harm.
Safety and Quality Outcomes Data:
Eliminating CK-MB Testing
Multiple academic medical centers have implemented interventions
to eliminate the routine ordering of CK-MB and measured associ-
ated cost savings and impact on patient safety (Table).12,43-46
Larochelle et al44 recorded data on patients with suspected ACS
(n = 60 494 patients preintervention; n = 24 341 patients postinter-
vention) over a period of 43 months (31 months preintervention; 12
months postintervention). They initially developed an institutional
guideline in collaboration with cardiologists to specify appropriate or-
dering of cardiac biomarkers for the diagnosis of AMI. The guideline
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 Eliminating Creatine KinaseMyocardial Band Testing in Suspected ACS Special Communication Clinical Review & Education

Table. Trials Eliminating CK-MB Testing

Source No. Duration Intervention Results

Baron et al,43 2012 Not specified 4 mo Implemented BPA in the CPOE 87% reduction in CK-MB tests
system when physicians (n = 1106 to 139/mo)
searched for CK-MB, tracked Fewer orders after searches for
searches/Orders by provider CK-MB testing
Restricted CK-MB testing to Fewer searches for CK-MB testing
patients who were post-PCI Physicians who had not seen the
and postcardiac surgery BPA (0 prior searches) were more
likely (P < .01) to place a search
Larochelle et al,44 2014 84 835 12 mo Developed institutional 95% reduction in CK-MB tests
guideline in consultation with with $720 000 in annual savings
cardiologists to order No decrease in ACS incidence
troponin alone in patients
with suspected ACS
Conducted educational
sessions with IM and ED
physcians
Disseminated a pocket-size
guideline reference card
Removed CK-MB from CPOE
ACS routine order sets and
created BPA when physicians
attempted to order CK-MB
tests
Singh and Baweja,12 2014 37 418 6y Removed CK-MB testing from 99.8% reduction in CK-MB tests
CPOE ACS routine order sets (12 057 in 2007, 36 in 2013)
Reviewed cases (n = 171) No CK-MB test for the 171
where CK-MB tests were still patients provided diagnostic or
ordered prognostic value
Le et al,45 2015 14 571 12 mo Removed CK-MB testing from 80% reduction in CK-MB tests
CPOE ACS routine order sets with $47 286 in annual savings
No missed diagnosis of ACS
Sullivan et al,46 2016 Not specified 12 mo Removed CK-MB testing from
84% reduction in CK-MB tests
CPOE ACS routine order sets
(43.7 to 6.8 tests per day)
Costs decreased from $546 per
day to $85 per day, $168 000
annual savings
No adverse effects on mortality
Abbreviations: ACS, acute coronary syndrome BPA, best practice alert; CK-MB, creatine kinasemyocardial band; CPOE, computerized provider order entry;
ED, emergency department; IM, internal medicine; PCI, percutaneous intervention.

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.

advised practitioners to order cTn alone, without CK-MB. The au-
thors then implemented multiple interventions, including educa-
tional sessions for internal medicine and ED physicians, dissemina-
tion of pocket-sized quick reference cards with the recommended
ordering algorithm, and removal of CK-MB from ACS routine order sets
within the computerized provider order entry (CPOE) system. A Best
Practice Advisory (BPA) was created in the CPOE system using the in-
stitutional guideline to alert physicians who attempted to order CK-
MB. Physicians could, if desired, order CK-MB manually. By 12 months
postintervention, the estimated number of CK-MB tests per patient
was 0, representing an absolute change of 0.96 CK-MB tests per pa-
Implementation Blueprint:
Eliminating CK-MB Testing
With clear evidence to support elimination of CK-MB from clinical
care for the diagnosis of ACS and based on experience eliminating
CK-MB at our respective institutions, we devised a blueprint for other
institutions to use in enacting quality improvement initiatives. The
methodology and theory of the blueprint and quality improve-
ment initiative are based on the US Health Resources and Services
Administration strategies for developing and implementing a qual-
ity improvement initiative, with a focus on education, action, and
measurement of results.47 The leader of each institution should

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 Clinical Review & Education Special Communication
Figure 2. Pocket Card
High Value Practice Academic Alliance Pocket Card
Cardiac Biomarker Ordering for ACS/AMI
Obtain troponin you suspect Acute Coronary Syndrome (ACS)/Acute Myocardial Infarction (AMI)
Initial presentation
6-9 hours later
12-24 hours later intermediate to high clinical suspicion and/or recurrence of
symptoms
STOP CHECKING. If troponin is abnormal:
correlate with clinical presentation to determine likihood of ACS
there is no utility to trending abnormal troponin to peak or resolution
patient has ACS, there is clinical concern for reinfarction, additional
troponin measurements may be useful
CK-MB in addition to troponin offers no incremental diagnostic value.
An example of a pocket card for mass distribution to faculty and house staff
regarding creatine kinasemyocardial band and troponin testing.
assess applicability of this blueprint based on the CK-MB ordering
frequency at their respective institution.
1. Design and implement a hospital-wide educational campaign.
Prior to implementation, it is important for health care leaders
to establish sufficient organizational readiness for change, spe-
cifically in conjunction with these stakeholders, whose order-
ing practices will be affected by such changes. Tools to mea-
sure readiness for change have been previously studied and may
be used.48,49
Collaborate with physician representatives from the departments
of cardiology, internal medicine, and emergency medicine. Front-
line physicians in these departments order the majority of car-
diac biomarkers within most health care institutions and are the
primary stakeholders in the current system of care for ACS
patients.
Academic institutions must engage the house staff as members
of the quality improvement team for an effective initiative.
Collaborate with secondary stakeholders, such as pathology
and/or laboratory staff, to acquire insight and advice on these
changes.
Inform physicians that CK-MB adds to the health care system
financial burden without adding value to patient care.
Present the evidence supporting elimination of CK-MB and ex-
clusive use of cTn to diagnose AMI, identify reinfarction, and es-
timate infarct size. Education may be provided through vari-
ous venues, including lectures, pocket cards (Figure 2), online
modules, social media demonstrations, and simulations.44
ARTICLE INFORMATION
Accepted for Publication: June 12, 2017.
Published Online: August 14, 2017.
doi:10.1001/jamainternmed.2017.3597
Author Affiliations: Department of Radiology and
Radiological Sciences, Johns Hopkins Hospital,
Baltimore, Maryland (Alvin); Division of Cardiology,
Department of Medicine, Mayo Clinic, Rochester,
Minnesota (Jaffe); Division of Cardiology,
E4 JAMA Internal Medicine Published online August 14, 2017 (Reprinted)
2017 American Medical Association. All rights reserved.
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Eliminating Creatine KinaseMyocardial Band Testing in Suspected ACS
2. Partner with information technology and/or laboratory medi-
cine staff to remove CK-MB from standardized ACS routine
order sets. Doing this simple step alone has been shown to sig-
nificantly reduce CK-MB ordering (Table).8,12,45,46
3. Partner with information technology and/or laboratory medi-
cine staff to create and integrate a best practice alert into the
CPOE to appear when clinicians order CK-MB, such as:
According to national guidelines, troponin is the preferred bio-
marker for detecting myocardial injury; CK-MB is only appro-
priate if troponin testing is unavailable. Figure 1 provides an
example.43,44
4. Measure data preintervention and postintervention (efficacy
points).
Number of cTn and CK-MB tests ordered, including stratifica-
tion by department and patient setting (ED, inpatient, medi-
cine vs nonmedicine units, ICU vs non-ICU).
Incidence, missed diagnoses, and mortality of AMI to ensure pa-
tient safety.
Review cases where CK-MB is still ordered to determine if it
provides value.
If necessary, track usage by physician to develop performance
feedback profiles.
Calculate reduction in charges to patients and health plans, as
well as any decrease in hospital costs.
Though seemingly straightforward to articulate, we acknowl-
edge that significant barriers to implementation exist, and in this case
the biggest hurdle has been convincing physicians who have or-
dered CK-MB for years to change their practice. Successful deimple-
mentation of CK-MB requires leadership support, education, and re-
assurance that diagnostic efficacy will not be compromised. Other
challenges relate to manpower as well as modifications and data col-
lection from the electronic medical record. To optimize manpower,
academic centers can engage house staff because this will also
ensure longstanding change. Again, leadership commitment to al-
locating information technology resources for data collection and
clinical decision support tools is critical.
Conclusions
Creatine kinasemyocardial band testing provides no incremental
value to patient care, and its elimination can lead to millions of health
care dollars saved without adversely affecting patient care. This is
backed by both strong evidence-based guidelines and experiences
from multiple institutions. The blueprint presented here should be
carefully considered by health care leaders and clinicians as the first
step to finally putting the CK-MB laboratory test to rest.
Department of Medicine, Johns Hopkins Bayview collaborating on quality improvement, research,
Medical Center, Baltimore, Maryland (Ziegelstein, and education related to high-value healthcare.
Trost).
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Conflict of Interest Disclosures: None reported.
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