Standards of Laboratory Practices
"Use of Cardiac Markers in Coronary Artery Diseases"
[ Click here for the schedule for the 1998 NACB SOLP on Recommendations for use of Cardiac Markers ]
NACB Committee: Alan Wu, Ph.D., Chair, Fred S. Apple, Ph.D., Brian
Gibler, M.D., Robert Jesse, M.D., Myron Warshaw, Ph.D., and Roland Valdes, Jr., Ph.D.
American Association for Clinical Chemistry 1998 National Meeting,
Session I: Recommendations for markers in the triage of patients with
1. The triage of patients with chest pain from the emergency department
is one of the most difficult challenges that face emergency physicians today. Admission of
patients with a low probability of acute coronary disease often lead to excessive hospital
costs (2). A strategy that is too liberal with regard to ED discharges will lead to
higher numbers of patients released with AMIs. The ED release rate for AMI have been
estimated to be between 2 to 5% (3,4).
Recommendation: Emergency departments,
departments of medicine, divisions of cardiology, and clinical laboratories should work
collectively to develop an accelerated protocol for use of biochemical markers for the
evaluation of patients with possible acute coronary syndromes (ACS).
Patients with chest pain and negative results for biochemical markers
do not have myocardial necrosis as the cause for their pain represent a low risk group for
myocardial infarction. However, such patients may have coronary artery disease, which may
require additional testing such as echocardiology, exercise or pharmacologic stress tests,
nuclear imaging, etc. Establishment of a clinical practice guideline for the evaluation of
patients with chest pain will reduce the variability of practice among physicians and
2. Although the onset of chest pain in AMI is sometimes known, for the
majority of patients with unstable angina and other cardiac diseases, this information is
either unknown or unreliable. It is not uncommon for these patients to report multiple
episodes of chest pain over the hours and days prior to admission. Intermittent closure
and spontaneous reperfusion of coronary arteries with ruptured plaques reflect the dynamic
nature of these diseases. In the elderly, or in patients with insulin-dependent diabetes,
there may be altered thresholds or a blunted response to pain. Indeed, there are many
patients with ACS who experience no pain during occlusive episodes (silent ischemia) (6).
Recommendation: For routine clinical practice,
all blood collections should be referenced relative to the time of presentation to the ED
and not from the reported time of chest pain onset.
3. The ideal biochemical marker is one that has high clinical
sensitivity and specificity, appears early after AMI to facilitate early diagnosis,
remains abnormal for several days after AMI, and can be assayed with a rapid turnaround
time (7,8). As currently there is no single marker that meets all of these
criteria, a multi-analyte approach has the most merit.
Recommendation: Two biochemical markers should
be used for routine AMI diagnosis: an early marker (reliably increased in blood within 6 h
after onset of symptoms), and a definitive marker (increased in blood after 6-9 hours but
has high sensitivity and specificity for myocardial injury, and remains abnormal for
several days after onset).
Because the interval between the onset of pain and ED presentation is
variable from patient to patient, two markers are needed to enable detection of patients
who present early and late. Currently, myoglobin is the marker that most effectively fits
the role as an early marker. Myoglobin is detectable in blood as early as 1-2 h after
onset and can be highly effective for AMI ruleout (9). Automated immunoassays for
myoglobin are commercially available. Myoglobin is not cardiac specific, and patients with
renal failure, skeletal muscle injury, trauma, or disease can have abnormal concentrations
in the absence of AMI. CK-MB isoforms have also been shown to be an early marker for AMI (10).
However, several investigators have questioned the early diagnostic utility and
convenience of isoforms measurement (11,12). Nevertheless, automated stat isoform
measurements are being used in many hospitals as an early measure of myocardial injury.
Other early markers are also being investigated (see above recommendation) (13,14).
Cardiac troponin T or I are currently the best markers for definitive
AMI diagnosis. Troponin appears in the searm relatively early after symptoms onset (6-9 h)
and remains abnormal for 4-10 days. Results are not increased in the presence of skeletal
muscle troponin (15,16). Early studies questioned the clinical specificity of
cardiac troponin T assays in patients with chronic renal failure (17). With the
development of a second generation ELISA assay for cTnT, the frequency of positive results
in these patients is lower than the first generation assay, although still higher than for
troponin I (18).
4. About 50-70% of AMI patients will present to the ED with evidence of
acute myocardial injury on the electrocardiogram (ECG). Acute intervention with
thrombolytic therapy or angioplasty should be considered in these patients who present
within 6-12 hours after the onset of symptoms (19,20).
Recommendation: Cardiac marker testing is
unnecessary for diagnostic purposes in patients who have an ECG with ST-segment elevations
diagnostic for AMI on presentation.
The basis for this recommendation is the fact that specific ECG
changes, when interpreted by competent physicians, is highly specific (21).
Retrospective testing at a reduced frequency of blood collection (e.g., once per day) may
be useful to qualitatively estimate the size of the infarct in the absence of reperfusion,
or to detect the presence of complications such as an reinfarction. In the latter case, a
marker that returns to normal quickly, such as myoglobin, may be the most effective. As in
the case of the initial AMI, serial measurements of myoglobin will be necessary to rule in
reinfarction as well.
5. Cardiac markers play an essential diagnostic role in non-Q wave or
subendocardial AMIs. There is great variability from hospital to hospital in the frequency
of blood collections. The American College of Physicians (ACP) recommend a conservative
testing guideline based on total CK and CK-MB for blood collected on admission, 12, and 24
h, and using lactate dehydrogenase isoenzymes when admission is more than 24 hours after
onset (22). This committee feels that this strategy is not adequate.
Recommendation: For detection of AMI by enzyme
or protein markers, in the absence of definitive ECGs, the following sampling frequency is
|early (<6 h)
|late (>6 h)
(x) indicates optional sampling
A single positive results for the definitive marker would trigger a
diagnosis of AMI and triage of the patient to the appropriate level of care (23,24),
the without the need for necessarily completing this algorithm (25). Myocardial
necrosis for most patients will be effectively ruled in or ruled out within 6-9 h after
The need to perform the 2-4 hour blood collection for the late marker
can be questioned. In particular, negative results at admission and 2-4 hours for the
early marker and negative results at admission for the late marker would largely obviate
the need for measuring the 3 hour sample. The Committee felt that the laboratory does not
currently have a mechanism for "reflexing testing." Reflex testing involves the
ordering or cancellation of followup tests on a given sample based on the results of
preliminary testing. Use of reflex testing involves pre-approval of physicians to
computerized algorithm that makes reflex decisions. These algorithms would ideally be
preloaded onto immunochemistry analyzers so that sequential testing can automatically be
performed with a minimum amount of turnaround time delay. Until reflex testing becomes
common practice, if ever, it may be more convenient for a laboratory to perform myoglobin
and troponin on all samples.
Among chest pain centers, there are many variations to the protocol for
blood sampling. Some centers use intervals of every 3 hours, while others use every 4
hours. In one study, chest pain patients were triaged with only two samples were
collected: one at admission and one at 4 hours (26), (with a third sample collected
only on patients presenting with <2 h history of chest pain). Because of the
unreliability of the chest pain history, the committee has taken a more conservative
approach of recommending the collection of at least three blood samples during the early
triage period. A blood collection at 12-24 h may be useful for detection of reinfarction
or myocardial extension, or for risk stratification of patients with unstable angina.
6. Some emergency departments are slow to develop a rapid rule out
chest pain center because of financial expenses, space, and/or knowledge of the potential
benefits. In these centers, the extra laboratory tests bring additional costs without a
reduction in lengths of stay or frequence of missed AMIs.
Recommendation: For those emergency departments
who do not have an area for rapid rule out of chest pain patients, and therefore patient
triage decisions are not made within the first few hours after onset, the use of an early
marker such as myoglobin is unnecessary. In this case, only a single definitive cardiac
marker is needed. The frequency of blood collection should also be reduced.
Session II: Recommendations for markers in acute coronary
1. The acute coronary syndrome is a pathophysiologic continuum that
results from rupture of an atherosclerotic plaque and an associated thrombus (27).
It can ultimately result in clinical presentations ranging from entirely asymptomatic to
unstable angina to massive acute myocardial infarction. Advances in the diagnostic assays
for myocardial necrosis have led to some confusion as to the performance of newer assays
have exceeded existing "gold standards." Regardless of the standards set for
diagnostic thresholds, even small elevations of markers of myocardial necrosis define
patients at high short and long term risk for adverse cardiac events including AMI and
death. Patients with minor myocardial injury, those with elevations of markers between the
lower limit of detectability and upper limit of normal, should be acknowledged as being at
high risk even in the absence of AMI. The degree of risk is directly related to the extent
of marker elevations for both cTnT (28) and cTnI (29).
Recommendation: Two cutoff limits are needed for
the optimum use of sensitive and specific cardiac markers such as cardiac troponin T or I.
A low abnormal value establishes the presence of minor myocardial injury and a higher
value establishes the diagnosis of AMI. Properly designed studies should be performed to
establish these cutoffs.
The first cutoff is determined as the upper 2.5 percentile (one-tail
test) of results from a normal healthy population (30). The second cutoff is
determined as the lower 2.5 percentile (one-tail test) of results from marker
concentrations collected within the established diagnostic window for that marker, on
patients with confirmed AMI (WHO criterion).
2. The short term risk for death or AMI for patients with minor
myocardial injury may be similar to death and reinfarction rate of patients who suffer
their first AMI. However it is important to not classify these patients as such, because
they may be disadvantaged from a social, psychological, and socio-economic standpoint.
With reference to CK-MB, results between the upper limit of normal and the AMI cutoff has
been termed a "gray zone." This practice was appropriate because CK-MB is not
specific to the heart, and there are normal subjects who have measurable CK-MB
concentrations from skeletal muscle release within this range, and would have been
incorrectly classified as having high cardiac risk. For cTnT and cTnI, the term gray zone
should not be used, as it connotes uncertainty in the measurement and/or clinical
Recommendation: Chest pain patients with
laboratory results for cTnT and cTnI between the upper limit of the reference limit and
the cutoff for AMI should be labeled as having "minor myocardial injury" or
other appropriate terms to indicate that ischemic injury is present. These patients should
be appropriately managed on a prospective basis (31,32).
3. The World Health Organization (WHO) has defined the diagnosis of
acute myocardial infarction (AMI) as a triad (1). Two of which must be present for
a) The history is typical if severe and prolonged chest pain is
b) Unequivocal electrocardiographic (ECG) changes are the development
of abnormal, persistent Q or QS waves, and evolving injury lasting longer than 1 day; and
c) Unequivocal change consisting of serial enzyme change, or initial
rise and subsequent fall of levels. The change must be properly related to the particular
enzyme and to the delay time between onset of symptoms and blood sampling.
With the development of biochemical markers that are not themselves
enzymes, such as cardiac troponin T and I, and myoglobin, etc., the third criterion of the
WHO triad should be revised.
Recommendation: The WHO definition of AMI should
be expanded to include the use of serial biochemical markers, and not be limited to enzyme
changes. It should be emphasized that rule out of AMI is not be made on the basis of data
from a single blood collection. However, when very specific cardiac markers are used, the
presence of an abnormal concentration from a single specimen can be highly diagnostic of
4. The analysis of blood for lipids such as cholesterol, and
lipoproteins such as low and high density lipoproteins is well established in the
assessment of coronary artery disease risk (33). As such, these markers are being
used to screen asymptomatic individuals. Because sensitive cardiac markers have also been
shown to provide risk stratification, there may be an impetus to use these markers as part
of a biochemical panel for routine health screening to detect the presence of silent
ischemia, or after exercise stress testing to detect presence of ischemic injury.
Recommendation: At this time, there is no data
available to recommend use of cardiac markers such as cTnT or cTnI for screening
asymptomatic patients for the presence of acute coronary syndromes. The likelihood of
detecting silent ischemia is extremely low, and cannot justify the costs of screening
programs. Additionally, there is also no evidence that cardiac marker analysis of blood
following stress testing can indicate the presence of coronary artery disease.
Studies of biochemical markers before and after nuclear
ventriculography of chest pain patients have shown that neither cTnT or cTnI are increased
after stress testing, even in patients with documented evidence of flow defects (34).
These markers are not sufficiently sensitive enough to detect myocardial ischemia that is
not associated with irreversible injury or myocardial necrosis.
Session III: Recommendations for markers in clinical applications other
than AMI and research.
1. Acute revascularization is now standard practice for patients with
ST-segment elevation AMI. The objectives for thrombolytic therapy and/or emergent
percutaneous transluminal coronary angioplasty (PTCA) are to recanalize occluded arteries
and to reduce mortality. Cardiac markers can be used to assess the success or failure of
such therapy. AMI patients who develop patent coronary circulation will release a bolus
amount of enzymes and proteins into the circulation ("washout phenomenon") when
compared to AMI patients with permanent occlusions (35). The gold standard
measurement of reperfusion status is coronary angiography. Blood flow is assessed
according to a scale determined by the Thrombolysis in Myocardial Infarction Investigators
a) Grade 0: no antegrade flow beyond the point of occlusion,
b) Grade 1 (penetration without perfusion): contrast media passes
beyond the area of obstruction but fails to opacify the entire coronary bed distal to the
obstruction for the duration of the filming,
c) Grade 2 (partial perfusion): contrast media passes across the
obstruction and opacifies the coronary bed distal to the obstruction, however, the rate of
entry into the vessel distal to the obstruction or its rate of clearance from the distal
bed (or both) are perceptibly slower than its entry into or clearance from comparable
areas not perfused by the previously occluded vessel (i.e., the opposite coronary artery
or coronary bed proximal to the obstruction), and
d) Grade 3 (complete perfusion): antegrade flow into the bed distal to
the obstruction occurs as promptly as antegrade flow into the bed proximal to the
obstruction, and clearance of contrast material from the involved bed is as rapid as
clearance from an uninvolved bed in the same vessel or the opposite artery.
Grades 0-2 indicate various stages of occluded blood flow while grade 3
indicate reperfusion. The time interval of collection of samples is important for the
proper interpretation of results.
Recommendation: For assessment of reperfusion
status following thrombolytic therapy, at least two blood samples are collected and marker
concentration compared: time 0 defined as just before initiation of therapy and time 1 as
90 minutes after the start. From these values, the determination of the a) slope value
(markert=90-markert=0/90 minutes), b) absolute value of markert=90
minutes or c) the ratio of markert=90/markert=0 be used as the
discriminating factors between successful and unsuccessful reperfusion.
When reperfusion is successful, it is produced in the majority of cases
within 90 minutes after the initiation of therapy (36,37). Sampling blood prior to
90 minutes may be helpful in the early determination of successful reperfusion, but cannot
be used in place of the 90 minute blood sample. Some investigators have suggested a
120-minute sample (38). This time interval is also acceptable, however, this will
delay any subsequent prospective management decision. Other investigators have used the
time to peak as the discriminating factor. This requires more blood sampling, and a delay
particularly in the non-reperfused group, before an final assessment can be made.
2. Cardiac markers have also been used to detect presence of
perioperative AMI, in patients undergoing surgical procedures (39). Use of
nonspecific cardiac markers such as CK, CK-MB, and LD have limited usefulness as they are
released from non-cardiac tissues as a result of the procedure itself (40).
Recommendation: Cardiac troponin T or I should
be used for detection of perioperative AMI in patients undergoing non-cardiac surgical
procedures. The same AMI cutoff concentrations should be used. For cardiac surgery
procedures, a higher threshold concentration may be necessary for the assessment of
perioperative myocardial damage.
The performance of cardiac troponin for detection of perioperative AMI
has been shown to be superior to other cardiac markers such as CK-MB (41,42).
However, a protocol for frequency of blood collection and interpretation of results will
require more clincial studies before further recommendations can be made. Studies will
also be required to determine the proper cutoff concentration for perioperative AMI. If
cardiac troponin is highly specific, then can the existing AMI cutoff concentrations be
used? If the surgical procedure involves the heart, e.g., coronary artery bypass graft,
some injury to the myocardium itself is expected. Should a higher AMI cutoff concentration
be used in open heart surgeries? In a study by Metzler et al., a cTnT concentration of 0.6
µ/L had a positive predictive value for an adverse outcome of 87.5% with a negative value
of 98% (43).
3. Cardiac markers have been used in other monitoring roles such as
myocardial infarct sizing (44). Infarct sizing involves serial collection of
cardiac markers and integrating the area under the curve of a plot of enzyme activity or
protein concentration vs. time. For cardiac markers that exhibit the washout phenomenon,
infarct sizing estimates are innaccurate when reperfusion is successful (45). Other
markers that are not sensitive to reperfusion status, such as myosin heavy chains (46),
may provide more accurate estimates but not at an early time period.
Recommendation: Cardiac markers should not be
routinely used for infarct sizing because the existing markers are inaccurate in the
presence of spontaneous, pharmacologic, or surgical reperfusion.
Assessment of infarct sizing may be useful in clinical trials on new
drugs designed to limit the extent of myocardial injury, such as those following IV
thrombolytic therapy or angioplasty (e.g., glycogen IIb/IIIa inhibitors).
4. The establishment of the normal ranges and cutoff concentrations for
new biochemical markers is essential for the interpretation of results. Often, studies
from the literature are quoted for normal ranges, and such studies are only carried out
for the investigational marker in question.
Recommendation: Reference ranges are established
for each marker using a population of normal healthy individuals. Standardized receiver
operating characteristic (ROC) curves should be used to establish AMI cutoff
Henderson and Bhayana have established
recommendations for standardization of ROC curves (47). These include inclusion of
the decision thresholds used on the curve for diagnostic rule in and rule out,
determination of the area under the ROC curve (including standard error and the confidence
interval), and the P (or z) value when two or more ROC plots are compared. The
manufacturer cutoffs are designed as guidelines and should not supercede the need for ROC
5. New markers will continue to be developed and examined for patients
with acute coronary syndromes, as new information is acquired regarding the
pathophysiology of the disease, and with the development of new therapeutic strategies.
When a marker such as cardiac troponin demonstrates significant advantages over existing
markers, there is a rush by commercial manufacturers to develop and market assays. In the
specific cases of CK-MB mass assay and cardiac troponin I, there was no agreement in the
standardization of reference materials. As a result, commercial assays produced results on
patient samples that differs from one another, sometimes by a factor of 10 or more.
Recommendation: Early in the process,
manufacturers should seek assistance and provide support to organizations such as the
American Association (AACC) or International Federation of Clinical Chemistry (IFCC) to
develop committees for the standardization of new analytes. These organizations will
determine the need for analyte standardization based on the potential clinical importance
of the marker, and gather the necessary scientific expertise for the formation of a
The committee recognizes that the exclusive release of new markers may
be in their best interests in terms of profitability, and therefore they may be reluctant
to share ideas and needs with their colleagues. Nevertheless, implementation of new tests
is more easily integrated into the laboratory when these markers are available on a wide
spectrum of analyzers, and it is in the best interests of the medical community and the in
vitro diagnostic industry that assays correlate to one another.
6. New biochemical markers have and will continue to be developed over
the next few years. Much of the focus has been on the development of tests that can detect
earlier steps within the pathophysiology of acute coronary syndromes, such as
inflammation, thrombus formation, platelet aggregation, and reversible ischemia. Some of
the markers examined for these processes include C-reactive protein, amyloid protein A,
thrombus precursor protein, p-selectin, and glycogen phosphorylase isoenzyme BB. Other
markers are designed to be used to improve the specificity of myoglobin including heart
fatty acid binding protein and carbonic anhydrase III isoenzyme. For research studies
involving these new markers, time of admission is not useful when comparing results
against conventional markers of myoglobin, CK-MB, and cardiac troponin, because the
admission time is variable from institution to institution (48,49).
Recommendation: For research studies involving
the kinetics of release and appearance of new biochemical markers, the time course of
release and appearance in blood must be defined relative to the onset of clinical
symptoms. However for clinical studies, the time of presentation is acceptable.
Session IV: Recommendations for assay platforms and markers of acute
1. Creatine kinase-MB is currently considered the "gold
standard" for the laboratory diagnosis of AMI (50). The development,
characterization, and clinical interpretation of cardiac troponin T and I seriously
challenges the role of CK-MB. Cardiac troponin T and I appears in the blood at or near the
same time as CK-MB, but remains abnormal for 7-10 days.
Recommendation: Cardiac troponin (T or I) is the
new standard for myocardial cell damage, replacing CK-MB. In addition, there is no longer
a role for lactate dehydrogenase and its isoenzymes for diagnosis of caridac diseases.
Use of CK-MB should be phased out over the ensuing years as more cTnT
and cTnI assays become available, and the cost for such assays becomes competitive to
CK-MB mass assays (51). Measurement of lactate dehydrogenase isoenzymes and
ß-hydroxybutyric dehydrogenase should be immediately discontinued (16,52).
2. New biochemical markers will continue to be developed especially in
the area of early AMI diagnosis. Tests that detect the presence of early pathophysiologic
events of acute coronary syndrome such as inflammation, platelet activation and
aggregation, thrombus formation, and early ischemia, are being studied. Standardization of
clinical protocols which incorporate these tests will be important. The accuracy of these
new biochemical markers may be unnecessarily compromised if the diagnosis of AMI is based
on laboratory procedures that are themselves have limitations (e.g., total CK and CK-MB).
Recommendation: In clinical studies for new
markers, AMI diagnosis is established by the WHO criteria, with the replacement of cTnT or
cTnI as the principal biochemical marker. Reference to CK-MB alone may reduce the accuracy
of the study conclusions.
3. It is recognized that testing cardiac markers on a continuous
random-access basis will likely increase costs for providing this service (53,54).
However, when considering the potential costs for delaying critical management decisions
that might occur if testing were performed on an infrequent (batched) basis, the overall
hospital costs for management chest pain patients is likely to be higher.
Recommendation: The laboratory should perform
stat cardiac marker testing on a continuous random-access basis, with a target turnaound
time (TAT) of 1 hour or less. The TAT is defined as the time by which blood is collected
to the reporting of results.
The factors that affect turnaround times include the delay in the
delivery of the sample to the laboratory, the pre-analytical steps necessary to prepare
the sample, the analysis time itself, and the effort it takes to deliver results to the
ordering physician. The committee recognizes that the time taken for the delivery of
samples to the laboratory is not under the control of the laboratory. Nevertheless,
laboratory personnel should work closely with hospital administration and nursing units to
minimize the delays. This could be accomplished with the implementation of pneumatic tubes
that delivery samples directlyl to the central laboratory. Use of satellite laboratories
is another mechanism to reduce delivery times. The pre-analytical time include the time
required for blood clotting and centrifugation.
Recommendation: Heparinized plasma or whole
blood are the specimen of choice for the stat analysis of cardiac markers.
Most patients with cardiac diseases are usually
heparinized. When serum is collected from these patients, full clot retraction from
unpreserved tubes can take 10-15 minutes or more. Clots can continue to form after the
sample has been centrifuged and the serum placed onto immunoassay analyzers. When this
occurs, instrument probes can be blocked by these clots. For automated immunoassay
analysis, the use of plasma will eliminate the extra time needed for clotting, thereby
reducing the overall pre-analytical turnaround times. Manufacturers should target their
assays for use in plasma. Whole blood is not curently an option for automated immunoassay
analysis. Whole blood testing is reserved for point-of-care testing.
Assay turnaround times will also play a factor. Current times for
immunoassays for myoglobin, CK-MB, and troponin range from 10-20 minutes. For some
samples, dilutions will be necessary to report quantitative results that are within the
limits of reportable range. Electronic transmission of results is essential for efficient
delivery of results. Some emergency physicians may argue that 30 minutes is the target
turnaround time. However, at this time, it is unlikely that a laboratory will be able to
consistently (>90%) deliver stat cardiac marker results in under 30 minutes using
laboratory-based serum or plasma assays.
5. Some laboratory do not have automated equipment or staffing to
deliver results to within 1 hour.
Recommendations: Institutions that cannot
consistently deliver cardiac marker turnaround times of £ 1 h
should consider the implementation of point-of-care (POC) testing devices.
Qualitative POC testing devices are now available
for myoglobin, CK-MB, cardiac troponin T and I (55,56). These make use of
anticoagulated whole blood, and have turnaround times of under 20 minutes. Elimination of
the need to deliver samples to the central laboratory, and the need for centrifugation
enables turnaround times of under 30 minutes. Recently multipanel quantitative POC
testing devices have been developed and are currently being evaluated. There are a few POC
devices that have received approval for use by the Food and Drug Administration. These
devices may ultimately be more useful than qualitative POC devices.
6. Point-of-care devices are designed for testing to be performed at or
near bedside by the primary care givers. However, the responsibility for this testing must
reside with the laboratory. Success of POC program will be dependent on cooperation and
acknowledge of the laboratory's responsibility by hospital administration, nursing, and
the appropriate units within the hospital (e.g., the ED).
Recommendation: Among other tasks, laboratory
personnel must be involved in the selection of devices, training of individuals that
perform the analysis, maintaining POC equipment, ensure proficiency of operators on a
regular basis, and document compliances to regulatory agencies such as HCFA and CLIA 88.
When the laboratory staff recognizes a situation of non-compliance they
should have the authority and exercise their right to remove the POC testing devices from
the affected units until the deficiencies have been satisfactorily corrected.
7. Assays for cardiac markers for early diagnosis, rule out, triaging
of patients from the emergency department, or determination of successful reperfusion
requires markers that have a short assay time.
Recommendation: To meet reporting TATs, assays
for cardiac markers must have a TAT of <30 minutes, and a precision of <10% CV at
the AMI decision limits. Prior to launch, assays must be characterized with respect to
potentially interferring substances (e.g., other related proteins, human anti-mouse
antibodies (57), etc).
The Committee recognizes the importance of establishing objective goals
for imprecision of assays for new cardiac markers. This will assist manufacturers in the
construction of new assays. The total precision required for a particular assay is
dependent on the biological variation of the analyte. The biologic variation for cardiac
troponin has not been established. As such this recommendation for total precision was
arbitrarily set at 10% without a scientific basis. Prior to the publication of the final
recommendations, the committee will seek guidance from the NACB membership and attendance
of the SOLP, in an attempt to reach some consensus.
While outcome studies have shown that stat reporting of results for
cardiac markers reduces hospital length of stay and laboratory costs for cardiac patients,
there are no outcome studies to validate the specific need for a 1 hour turnaround time.
It is clear, however, that early treatment of Q-wave AMI patients with thrombolytic
therapy is important for the success in terms of reducing mortality and increasing the
rate of coronary artery patency. With the development of new therapeutic strategies for
unstable angina and the non-Q-wave AMI, the committee anticipates that early detection of
minor myocardial injury will also be beneficial in the management of these patients. For
those patients who do rule out for acute coronary syndromes, it is expected that early
reporting of laboratory data will also reduce overall hospital costs. The committee
encourages prospective outcome studies to examine the putative advantage of reporting
turnaround times within 1 hour.
Schedule for the 1998 NACB SOLP on Recommendations for use of Cardiac Markers
[ Top ]
The NACB Standards of Laboratory Practice will be presented as a 2-day Edutrak at the AACC 50th Annual Meeting and
Clinical Laboratory Exposition to be held August 2-6, 1998 in Chicago, IL.
Tuesday, August 4, 1998
10:30-noon Session I: Recommendations for markers in triage of
patients with chest pain.
Brian Gibler, M.D., Department of Emergency Medicine, University
of Cincinnati,, Cincinnati, OH
Rebuttle: James W. Hoekstra M.D., Department of Emergency
Medicine, Ohio State University, Columbus, OH (to be confirmed)
2:45-5:00 Session II: Recommendations for markers in acute coronary
Robert Jesse, M.D., Ph.D., Division of Cardiology, Medical
College of Virginia, Richmond, VA
Rebuttle: Allan Jaffe, M.D., Department of Medicine, State
Universityi of New York, Syracuse, NY
Wednesday, August 5, 1998
8:45-10:00 Keynote address: Pathophysiology of unstable angina
Eugene Braunwald, M.D., Harvard Medical School, Boston, MA
10:30-noon Session III: Recommendations for markers in clinical
applications other than AMI and research.
Fred S, Apple, Ph.D., Department of Pathology and Laboratory
Medicine, Hennepin County Medical Center, Minneapolis, MN
Rebuttle: Michael Salinger, M.D., Department of Medicine,
Evanston Northwestern Healthcare, Evanston, IL.
2:45-5:00 Session IV: Recommendations for assay platforms and
markers of acute myocardial infarction.
Alan Wu, Ph.D., Department of Pathology and Laboratory Medicine,
Hartford Hospital, Hartford, CT
Rebuttle: Paul O. Collinson, Department of Chemical Pathology,
Mayday University Hospital, Croydon, Surrey, Surrey, UK
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