Diagnosing Acute Cardiac Ischemia in the Emergency
A Cost-Effectiveness Analysis
Catherine Milch, MD
Ethan Balk, MD, MPH
Deeb Salem, MD
Joseph Lau, MD
Evidence-based Practice Center
Division of Clinical Care Research, and Division of
Department of Medicine
New England Medical Center
This study was conducted by the New England Medical
Center Evidence-based Practice Center under contract to the Agency
for Healthcare Research and Quality, contract No. 290-97-0019, Rockville,
KEY WORDS: cost-effectiveness analysis, acute cardiac
ischemia, myocardial infraction, emergency department, triage
Objective: To assess the effectiveness of and costs
associated with diagnostic tests for detecting acute cardiac ischemia
(ACI) among patients presenting to the emergency department (ED).
Design: We developed a decision model with an institutional
perspective which evaluates diagnostic test performance, patient outcomes,
and associated costs of ED triage.
Data Sources: All studies of diagnostic test performance
in the ED and national cost data for patient care.
Target Population: We applied the decision model to
two different patient populations: all ED patients presenting with
possible ischemia and a low-risk subgroup.
Time Horizon: 30 days
from ED presentation.
Interventions: Biomarkers, imaging studies, stress tests,
algorithms and computer-based models, and combinations of tests.
Measures: Appropriate triage (hospitalization) for patients with ACI.
Biomarkers were least costly and least effective for diagnosing ACI;
imaging and stress testing were more costly but more effective. Among
all ED patients, the Acute Cardiac Ischemia Time-Insensitive Predictive
Instrument (ACI-TIPI) was the most effective with an incremental cost-effectiveness
ratio of $7,860 per appropriate triage for ACI compared with serial
troponin T. The combination troponin T-echocardiography was the next
most effective test, but it was associated with an incremental cost-effectiveness
ratio of $27,000 compared with serial troponin T. It was substantially
less cost-efficient than ACI-TIPI. Among low-risk patients, exercise
electrocardiogram testing (ETT) and sestamibi imaging were the most
effective diagnostic tests. ETT was nearly $700 per patient less costly
than sestamibi imaging and had a low incremental cost-effectiveness
ratio of $2,705 per appropriate triage for ACI compared with single
troponin T. Increasing the prevalence (likelihood) of ACI reduced
Conclusions: ACI-TIPI and combination troponin T-echocardiography
among all ED patients, and ETT and sestamibi imaging among low-risk
ED patients, are effective diagnostic tests for detecting ACI in the
ED. ACI-TIPI and ETT are effective and cost-efficient options at low
to high rates of ACI prevalence.
Over six million patients present to emergency departments
(EDs) in this country with symptoms of possible acute cardiac ischemia
(ACI), yet over half do not have ACI.1 An ED physician must decide
which patients require admission and treatment for ACI, which includes
both acute myocardial infarction (AMI) and unstable angina pectoris
(UAP). Over the past decade, a variety of tests have gained popularity
for the diagnosis of ACI, including the biochemical markers troponin
and myoglobin, and cardiac perfusion imaging studies such as sestamibi
Few studies have compared the costs and implications
of diagnostic tests for ACI in the ED. The more accurate diagnostic
tests may also be more costly. An explicit analysis of the trade-offs
between cost and effectiveness of alternative tests may assist ED
physicians in their choice of diagnostic tests.
To address these issues, we developed a decision analytic
model that assesses triage outcomes and costs for 12 individual tests
and four combinations of tests for the diagnosis of ACI in ED patients.
Because some of these diagnostic strategies are not applicable for
certain patients, we applied the decision model to two different patient
populations: all ED patients presenting with possible ischemia, and
a low-risk subgroup in whom the presenting ECG was normal or nondiagnostic.
We focused our analyses on the diagnosis of and triage for ACI rather
than long-term management and life expectancy. Thus, our effectiveness
measure was appropriate triage for ACI. We used actual test diagnostic
performance data obtained from high-quality studies performed in the
We focused our evaluation on ACI, which includes both
myocardial infarction and unstable angina, because unstable angina
is a common condition, is often hard to differentiate from AMI in
the ED, and necessitates appropriate evaluation and management. The
decision model shows how the diagnostic performance of a test affects
total costs and appropriate triage for patients with ACI when the
test is applied to patients presenting to the ED with signs and symptoms
decision analysis model compared the costs and patient outcomes associated
with using different diagnostic tests for patients presenting to the
ED with symptoms suggestive of ACI. The model represents the triage
decisions and 30-day patient outcomes as a consequence of a negative
or positive test result. All patient dispositions and outcomes occurring
within 30 days of ED presentation, including initial and subsequent
admission to the hospital, sequelae from missed AMI or
UAP, outpatient follow-up, and death, were included in the model (Figure
1). Patients with either UAP or AMI were considered to have ACI; patients
with stable angina were considered to have nonacute cardiac ischemia.
Patients in cardiac arrest were not considered in the analyses.
The tests and combinations of tests evaluated in the
decision analysis included those that are commonly available and have
been evaluated in ED patients. Tests were chosen based on the National
Heart Attack Alert Program recent update1 and an extensive systematic
review of diagnostic tests for ACI.24 Tests and combinations
of tests that had not been evaluated in a population of ED patients
were excluded (such as stress tests with imaging). We evaluated 16
Serum biochemical markers: single and serial CK-MB,
troponin T, and myoglobin;
Electrocardiogram-based tests, algorithms, and instruments:
continuous and/or serial electrocardiograms (ECG), Acute Cardiac Ischemia
Time-Insensitive Predictive Instrument (ACI-TIPI), Goldman chest pain
protocol, exercise stress ECG testing;
Imaging studies: rest echocardiography and rest sestamibi
Combinations of two tests: single and serial CK-MB and
myoglobin; single CK-MB and serial ECG; single troponin T and echocardiography.
A single biochemical test was defined as one that occurred
within the initial 4-hour period after presentation to the ED; serial
testing was defined as repeated testing occurring within a period
of up to 6 hours after presentation to the ED.
certain diagnostic tests (such as stress testing) can not or should
not be used in some patients with possible ACI, we applied the decision
model to two different patient populations with possible ACI: all
ED patients and a low-risk subgroup with normal or non-diagnostic
ECG on presentation to the ED. Thus, tests that may be applicable
to or have been evaluated in only low-risk patients, such as stress
testing, serial ECGs, and sestamibi imaging, were evaluated in the
low-risk subgroup only. Because some ED patients may be at high risk
for AMI, we did not evaluate these diagnostic tests in the analyses
of all ED patients. Additionally, we did not include two tests, ACI-TIPI
and the Goldman chest pain protocol, in the low-risk subgroup analyses
because their diagnostic performance has not been evaluated in ED
To reflect the differences in pretest likelihood of
ACI among patients in the two populations, we used different prevalence
rates for both AMI and ACI. Prevalence rates for ACI and AMI in the
general ED patient population were obtained from a large clinical
trial of patients presenting to EDs with any sign or symptom suggestive
of ACI.5 The prevalence rate for AMI among low-risk patients
was estimated to be approximately half that among all ED patients.6
The prevalence of UAP was the same in both models. Additionally, because
ACI prevalence rates vary among EDs, we performed sensitivity analyses
altering the prevalence rates of ACI in both models.
Test Performance Data
diagnostic performance data were obtained from published results of
all studies performed in ED patients between 1966 and 1999 and that
were included in a recent extensive systematic review.1,2 Because
patient inclusion criteria, ACI prevalence rates, and reported diagnostic
test performance varied among individual studies, we relied on meta-analyses
or pooled results. For biochemical tests, values for AMI sensitivity
and ACI specificity were based on results obtained from meta-analyses
of all studies of ED patients.3 For the low-risk subgroup, we used
test sesitivity based on the lower 95% confidence interval from the
meta-analyses to reflect the lower test sensitivity in low prevalence
populations. Because data on UAP sensitivity were sparse, we used
test sensitivity for detection of coronary artery disease requiring
revascularization in those studies that reported results.
diagnostic data for nonbiochemical tests were obtained from individual
studies, or pooled results, in the appropriate ED population.2,4 Because
ACI-TIPI reports a predicted probability of ACI for a patient instead
of a dichotomous test result, its diagnostic performance values were
based on a probability cut-point that approximates its clinical effectiveness
as observed in a large clinical trial.5 Table 1 shows the sensitivity
and specificity of each test and data sources.
The triage of an ED patient was determined by the test
result. A positive test result would lead to hospitalization and a
negative test result would lead to discharge from the ED. Appropriate
triage was defined as hospitalization for any patient with ACI; inappropriate
triage was defined as discharge from the ED of a patient with ACI.
Thirty-day outcomes were determined by patients true diagnosis
(ACI or non-ACI), patient triage (hospitalization or discharge from
the ED based on diagnostic test result), follow-up evaluation, and
the risk of survival or death from appropriate or inappropriate triage.
Inpatient and outpatient mortality rates for patients with ACI appropriately
hospitalized or inappropriately discharged from the ED and subsequent
hospitalization rates for patients with ACI inappropriately discharged
were based on national data from large clinical trials of ED patients.4547
The transition probabilities affecting patient disposition are shown
in Table 2.
Patient disposition assumptions included: 1) all patients
with ACI survive or die, and a certain percentage of patients will
die from ACI, regardless of appropriate or inappropriate triage; 2)
all patients with ACI who survive are either hospitalized or undergo
outpatient evaluation; 3) all patients with ACI who are hospitalized
receive definitive treatment for ACI during the hospitalization; 4)
a small percentage of patients with UAP who are inappropriately discharged
from the ED will subsequently develop AMI; 5) all patients without
ACI survive; and 6) all patients with serious non-ACI disease (but
in whom the diagnosis of ACI was entertained, such as those with valvular
heart disease, pulmonary embolus, biliary tract disease, etc) receive
definitive treatment for their condition but their outcomes and associated
costs of care are not included in the decision analysis. Table 3 lists
the 14 possible patient dispositions.
We did not include complications that may arise from
some of the tests, such as stress testing, because of the extremely
low rate of death or clinically significant complications reported
in studies. (None of the studies evaluating the use of sestamibi imaging
or exercise ECG testing in ED patients with possible ACI reported
deaths or significant morbidity such as complications altering the
care given to a patient). Also, these tests were only evaluated in
low-risk patients.2830,48 We also excluded complications from
in-hospital treatment for ACI (such as restenosis after angioplasty)
because the focus of the analysis was on triage for, rather than management
The total costs used in the analysis represent the total
reimbursement to the hospital and outpatient clinic for patient services
for 30 days from the initial ED visit. The total cost of using a test
included not only the cost of the test itself, but also the cost of
subsequent patient management (such as, hospitalization and outpatient
follow-up) and outcome (Table 4). Costs associated with treatment
for conditions other than suspected ACI were not considered. The diagnostic
test used in the ED and the level of suspicion for ACI determined
the extensiveness and costs of further diagnostic testing after discharge
from the ED. Four different outpatient follow-up scenarios, based
on likelihood of ACI, were evaluated in the low-risk subgroup model
because more intensive and costly studies, such as echocardiography
and sestamibi imaging, may lead to less costly outpatient evaluations
after ED discharge. For example, an outpatient evaluation of a patient
in whom the likelihood of ACI is considered very low may not have
a follow-up stress test after a negative sestamibi scan in the ED.
Test costs and reimbursements for hospital admission
were based on 1999 national median fees49 and average national payments
for specific DRG codes.50 These are shown in Table 5. Because the
standard of care is to obtain an ECG on all ED patients evaluated
for ACI, we did not use an additional cost for an initial ECG. Outpatient
visit reimbursements were calculated from median fees for tests performed
as part of the outpatient work-up and for the professional component
of the outpatient visit.50 Discounting was unnecessary because of
the short time horizon of the analysis.
The cost-effectiveness (CE) of a specific diagnostic
test was the sum of all the costs incurred during the 30-day period
from ED presentation, divided by its effectiveness. The effectiveness
of a test, determined by its ability to detect UAP or AMI in the ED,
was defined as the proportion of appropriately triaged (hospitalized)
patients with ACI. The decision model projects the costs and number
of patients with ACI appropriately triaged from a cohort of 1000 ED
patients for each test.
The cost-effectiveness analyses involved comparing incremental
cost-effectiveness ratios of tests. First, diagnostic tests were ranked
by increasing cost. More expensive tests that were less effective
were eliminated by simple dominance. For remaining strategies,
the incremental cost-effectiveness ratio was calculated as the additional
cost to diagnose and appropriately triage one additional patient with
ACI compared with the next less costly and less effective alternative.
Tests that had a higher incremental CE ratio than more effective alternatives
were eliminated by weak dominance because they were not
as cost-efficient as the other tests. Sensitivity analyses
on relevant variables were performed to assess the stability of the
results. Decision models and cost-effectiveness analyses were created
in and performed with Data TreeAge 3.5 software (Williamstown, MA).
Analysis for All Emergency
The prevalence of ACI and AMI used for the decision
model to represent all ED patients was 18% and 8%, respectively. Thus,
a test with perfect sensitivity would lead to appropriate triage of
all 180 patients with ACI per 1000 ED patients evaluated for ACI.
Triage Accuracy: The proportion of ED patients with
ACI who would be correctly detected and hospitalized by each test
is shown in Figure 2. As expected, tests with higher diagnostic accuracy
for both AMI and UAP had higher values for appropriate triage for
patients with ACI. The biochemical tests and the Goldman protocol
did not perform as well as echocardiography because they are generally
not designed or used to detect UAP. Serial testing or combinations
of biochemical tests improved ACI detection, with serial troponin
T having the best triage accuracy for ACI among the biomarkers. ACI-TIPI
and the combination of troponin T-echocardiography had the best detection
rates for ACI because they detect both AMI and UAP.
Base Case Cost-effectiveness Analysis: Figure 3 shows
the proportion of patients with ACI appropriately triaged (effectiveness,
on the y-axis) by and the associated costs (on the x-axis) of each
diagnostic test. Test costs generally increase with increasing accuracy
because the cost of appropriate hospitalization is more costly than
that of inappropriate discharge in the base case. The single biochemical
tests, clustered near the lower left corner of the graph, are the
least costly and have the lowest values for appropriate triage. Serial
testing improves effectiveness and raises costs. Echocardiography,
troponin T-echocardiography, and ACI-TIPI are more effective and more
The tests connected by the line or that lie very close
to the line are the nondominated tests and are thus considered the
most cost-efficient. That is, for a given cost they are more effective
than tests that lie far from the line. Thus, single myoglobin and
troponin T, serial myoglobin and troponin T, and ACI-TIPI are cost-efficient
tests compared with tests that lie far below the line such as the
combination CK-MB and myoglobin or echocardiography. The slope of
the line reflects the inverse of the cost-effectiveness ratio. Thus,
the flatter the slope, the higher the incremental cost-effectiveness,
indicating less additional effectiveness for a given additional cost.
The slope of the line connecting single myoglobin and serial troponin
T is fairly steep, indicating that the additional cost associated
with serial testing leads to substantially more appropriate triage,
making serial testing cost-efficient. The slope of the line connecting
serial troponin T and ACI-TIPI is less steep, indicating a higher
incremental cost-effectiveness ratio between these two tests than
between single myoglobin and serial troponin T.
costs, effectiveness values, and, for nondominated tests, the incremental
CE ratios, are shown in Table 6. Eight tests are more effective and
less costly than the alternatives: single myoglobin and troponin T,
serial CK-MB, myoglobin, troponin T, rest echocardiography, troponin
T-echocardiography, and ACI-TIPI. Five of these tests are dominated
by weak dominance because their incremental CE ratios
are higher than that for the next more effective and more costly test.
For example, troponin T-echocardiography costs approximately $27 more
per patient than echocardiography alone but leads to appropriate triage
for 10 additional patients. Thus, its incremental CE ratio is $2,700
(as calculated among 1000 ED patients), which is higher than the incremental
CE ratio of the next more effective test, ACI-TIPI ($1,477, calculated
by comparing costs and number of patients with ACI appropriately triaged
between troponin T-echocardiography and ACI-TIPI). Thus, troponin
T-echocardiography is not as cost-efficient as other tests and is
eliminated by weak dominance.
Three tests are not dominated by other tests: single
myoglobin, serial troponin T, and ACI-TIPI. Although the CE of ACI-TIPI
is relatively high compared with serial troponin T, it leads to appropriate
triage for 60 additional patients with ACI at an additional cost of
$473 per patient.
Sensitivity Analyses for All ED Patients
of ACI Prevalence Rates: The ED physicians a priori impression
of the likelihood of ACI in a patient presenting to the ED with signs
and symptoms suggestive of ACI often influences the interpretation
of test results as well as the final triage decision. We attempted
to model pretest likelihood of coronary artery disease by varying
the prevalence of ACI in the model. For example, a 5% prevalence of
ACI may represent a low pretest likelihood, such as for a 40-year-old
woman with nonspecific chest pain. Moderate pretest likelihood may
be modeled by an ACI prevalence rate of 30% (represented by a 45-year-old
man with chest pain atypical for angina). A high pretest likelihood
may be represented by an ACI prevalence rate of 80%, represented by
a 65-year-old man with typical angina.51,52
Varying the ACI prevalence affects the costs and
incremental cost-effectiveness ratios of tests. As ACI prevalence
increases, the costs and effectiveness values of a test increase linearly.
Costs increase because there are more patients with ACI and more hospitalizations.
However, the number of appropriate triages for ACI increases more
steeply (because test effectiveness is affected by both prevalence
of ACI and test sensitivity for ACI), leading to an exponential decrease
in incremental CE ratios. Thus, tests become more cost-efficient,
because application of diagnostic tests to a cohort of patients with
a high ACI prevalence makes each appropriate triage less costly than
at low ACI prevalence. The relative effectiveness rankings of tests
however are not altered.
Comparing the incremental
CE ratios as prevalence changes provides information regarding the
most cost-effective option for patients with different likelihood
rates of ACI. At very low pretest likelihood rates of ACI (representing
a population of ED patients at very low risk for ACI), the incremental
CE ratios of all tests are substantially higher than in the base case.
ACI-TIPI has a very high incremental CE ratio compared with serial
troponin T, nearly $150,000, which is over 15 times its base case
ratio, and greater than typical thresholds used in cost-effectiveness
analyses. As ACI prevalence increases, the differences among incremental
CE ratios decrease. At ACI prevalence rates of 30% and 50%, ACI-TIPI
has CE ratios of only $4000 and $2600, respectively, compared with
serial troponin T. At higher ACI prevalence rates, the Goldman protocol
becomes a cost-efficient test along with serial troponin T and ACI-TIPI.
Variation of Test
Performance Characteristics: Because ACI-TIPI does not have
a cut-point or threshold probability for a positive result
for detection of ACI, we used various thresholds to evaluate how the
effectiveness and cost-effectiveness of ACI-TIPI changes relative
to the other tests. As the cut-point for a positive test result increases
from 10% to 25% (thereby decreasing the sensitivity but increasing
the specificity of the predictive instrument), the costs associated
with using ACI-TIPI decrease relative to other tests, so that it is
no longer the most costly test to use. At a cut-point as high as 25%
(ie, patient has a positive test result only if the predictive
instrument gives a likelihood of ACI of 25% or more), ACI-TIPI remains
the most effective test, with an incremental CE ratio of $6300 per
additional patient with ACI appropriately triaged compared with serial
troponin T, making it as cost-efficient as the base case. The sensitivity
of ACI-TIPI for both AMI and UAP would have to fall to below 70% (a
cut-point near 35%) for it to be no longer a cost-efficient alternative.
We also performed sensitivity analyses for the Goldman
chest pain protocol because of the difficulty in estimating its diagnostic
performance for patients with UAP. Because the protocol is not designed
to aid in the detection of patients with UAP, we theoretically altered
its sensitivity for UAP. The protocol is dominated by other tests
until its theoretical sensitivity for UAP increases to over 40%. At
a sensitivity near 50% for UAP, it is the second most effective test
along with combination troponin T and echocardiography, with a cost-efficient
incremental CE of $6400 compared with troponin T serial.
Variation of Cost of ACI-TIPI: Because ACI-TIPI can
be incorporated into ECG machines, the base case analysis assumes
no additional cost, over that for an ECG in the ED, for the actual
test. However, not every ED has an ECG machine in which the predictive
instrument has been incorporated. Thus, hospitals may have to purchase
new ECG machines that have the predictive instrument. We performed
sensitivity analyses to determine how much ACI-TIPI would have to
cost per test to lose its dominant cost-effectiveness status. ACI-TIPI
is no longer cost-efficient at a cost of approximately $4000 per patient
use. However, the addition of the predictive instrument adds only
$800 to $1000 to the total retail cost of each ECG machine.53
Variation of Costs of Patient Dispositions: One assumption
of the decision analysis model is that the reimbursement for hospital
admission for patients without ACI is less than that for patients
with ACI, reflecting the 23-hour observation status of
most non-ACI patients, as well as the exclusion of non-ACI related
treatment costs in the analysis. This assumption favors tests that
may be very sensitive but not very specific for ACI. However, the
cost of hospital admission for some patients without ACI may exceed
the reimbursement for a rule-out AMI admission assumed
in the model. We therefore performed sensitivity analyses on the cost
of hospital admission for patients without ACI to assess the effect
on cost-effectiveness of tests. As the cost of inappropriate hospital
admission for a patient without ACI increases, the incremental CE
ratio of tests with poor specificity increase, making them less cost-efficient.
example, at a cost of inappropriate admission double that of the base
case, the incremental CE ratio of ACI-TIPI compared with serial troponin
T increases to approximately $33,000, almost 6 times higher than in
the base case. When the cost of inappropriate admission for ACI increases
fivefold, the CE ratio of ACI-TIPI increases 10-fold over the base
case. Although it remains a very effective test for detecting patients
with ACI, its cost-efficiency relative to other, less effective tests
analysis was also performed on the cost of inappropriate ED discharge
of a patient with ACI, which may result in death. We varied the cost
of death associated with missed ACI from a low of $600 for a
return ED visit and resuscitation attempt, to the cost of a malpractice
settlement ($2 million). ACI-TIPI retains its cost-effectiveness as
the cost of inappropriate ED discharge increases, dominating all other
strategies at costs over $400,000.
Low-risk Subgroup Analysis
This model estimates the total costs and effectiveness
of applying tests to a low-risk population of ED patients with signs
and symptoms of ACI in whom the initial ECG is normal or nondiagnostic.
The prevalence rates of ACI and AMI in this population are 13% and
Figure 4 shows the percentage of patients with ACI appropriately diagnosed
by each of the tests. The results are similar to those for all ED
patients. The biomarkers do not perform as well as other tests because
they are not used to detect UAP. The imaging studies, ECG exercise
testing, and the combination of troponin T-echocardiography have the
best triage accuracy. Sestamibi imaging and exercise ECG testing perform
nearly equally well, identifying slightly more than 85% of all patients
Case Cost-effectiveness Analysis: Four different outpatient evaluation
scenarios were used for the cost-effectiveness analysis for the low-risk
subgroup to illustrate different outpatient evaluation strategies
for those patients who undergo more costly and effective tests in
the ED such as exercise testing and sestamibi imaging. The base case
model assumes that all patients who return for outpatient evaluation
have exercise ECG testing, except patients who have had negative exercise
testing or sestamibi imaging in the ED. These patients do not have
further diagnostic testing during the 30-day follow-up period.
total costs and proportion of patients with ACI appropriately triaged
for each test are shown in Figure 5. The most cost-efficient tests,
compared with alternatives, are near or on the line: single myoglobin,
CK-MB, and troponin T, serial myoglobin and troponin T, and ECG exercise
testing. The slope of the line between single troponin T and exercise
ECG testing is fairly steep, indicating a relatively low incremental
cost-effectiveness ratio and high cost-efficiency for exercise ECG
testing compared with other tests.
Table 7 shows the costs, effectiveness, and incremental
cost-effectiveness ratios for each test. Six tests are more effective
and less costly than the alternatives: single myoglobin and troponin
T, serial CK-MB, myoglobin and troponin T, and exercise ECG testing.
The serial biomarkers are eliminated by weak dominance. Exercise testing
dominates all the imaging and ECG-based tests because it is less costly
and more effective. Although exercise testing and sestamibi imaging
are nearly equal in effectiveness, exercise testing costs $700 less
per ED patient than sestamibi imaging. Its incremental CE ratio is
$2,705 per additional appropriate triage for a patient with ACI compared
with single troponin T.
Sensitivity analyses for
Variations in Cost
of Follow-up: Changing the outpatient follow-up evaluation changes
the cost of follow-up and therefore changes the incremental cost-effectiveness
of tests (effectiveness of tests does not change). In the base case,
all patients except those who had undergone exercise testing or sestamibi
imaging in the ED undergo exercise ECG testing as part of their outpatient
follow-up. If all patients who return for outpatient evaluation have
no further diagnostic testing, exercise ECG testing is still the most
cost-efficient test, but its incremental cost-effectiveness increases
to nearly $7000 (from $2700 in the base case) compared with single
patients with a negative exercise test in the ED have stress sestamibi
imaging, instead of follow-up exercise ECG, as part of their outpatient
evaluation, the costs associated with a false negative exercise test
increase. ECG exercise testing becomes more expensive than sestamibi
imaging (about $2500 per ED patient), and its incremental CE ratio
compared with single troponin T increases fourfold. Because exercise
testing and sestamibi imaging have nearly the same effectiveness,
both tests would have nearly identical CE ratios. If stress sestamibi
is part of the outpatient evaluation for patients who have had sestamibi
imaging in the ED, then sestamibi imaging once again becomes more
costly than exercise testing, and exercise testing dominates. Thus,
as the cost of a false-negative ECG exercise test increases, it becomes
less cost-efficient than in the base case. However, it remains a cost-effective
alternative due to its sensitivity in detecting AMI and relatively
low cost compared with other tests.
in ACI Prevalence Rates: As in the analyses of all ED patients, as
prevalence of ACI increases, the costs, and the effectiveness of all
strategies increase linearly, and the cost-effectiveness of the tests
decrease exponentially. The relative CE among the tests changes little
as prevalence of ACI increases. Exercise testing and sestamibi imaging
are the most effective strategies at all prevalence rates. Because
exercise testing is less costly than sestamibi imaging, it also dominates
sestamibi imaging at all prevalence rates. Its incremental CE ratio
does not change substantially at ACI prevalence rates above that in
the base case, remaining around $1800.
This cost-effectiveness analysis attempts to incorporate
all costs associated with use of diagnostic tests in the ED. Considering
only the cost of a diagnostic test neglects the effect of the test
on patient triage. Generally, more effective tests, such as imaging
studies, lead to higher total costs than less effective tests because:
1) the tests themselves cost more (eg, sestamibi imaging vs biomarkers),
and 2) for patients with ACI, the costs of hospitalization exceed
those for discharge home and outpatient follow-up. However, more-effective
tests also lead to fewer inappropriate hospitalizations for patients
without ACI, so the ratio of total costs to the cost of a test decreases
exponentially as test effectiveness increases. Thus, the more effective
(and more costly) tests lead to proportionately lower total costs
than less effective (and less costly) tests.
The results of the
decision analysis indicate that the biomarkers have the lowest triage
accuracy for patients with ACI, primarily because their diagnostic
performance in patients with UAP is poor. The ECG-based tests, algorithms,
and combinations of tests perform better. Among all ED patients, ACI-TIPI
has the best triage accuracy for ACI and is a cost-efficient test
with a relatively low incremental CE. Among low-risk patients, sestamibi
imaging and ECG exercise testing are very effective for triage of
patients with ACI, but exercise testing is substantially less costly,
and thus more cost-efficient. As ACI prevalence or pretest likelihood
for ACI increases, incremental CE ratios decrease, making both ACI-TIPI
and exercise ECG testing more cost-efficient than in the base case.
Sestamibi imaging has excellent diagnostic accuracy
for ACI but has not been tested in ED patients at moderate or high
risk for ACI. Exercise testing may not be applicable to the majority
of ED patients presenting with possible ACI, specifically patients
at moderate to high risk for ACI. Sestamibi imaging may be a safer
choice for these patients. Although we evaluated sestamibi imaging
only in the low-risk subgroup, it may be applicable to a more general
population of ED patients because of its low-risk of complications.
The cost-effectiveness of exercise ECG testing and sestamibi imaging
in a more general ED population requires further evaluation.
There are several
limitations to the decision analysis. Little data exist on the diagnostic
performance of most tests for UAP, thus the values for UAP sensitivity
used in the decision model are estimates, which add uncertainty to
the cost-effectiveness analyses. Also, we did not model the possible
complications arising from waiting for test results in the ED (such
as serial biomarkers) because of lack of data.
All tests were compared
equally in the decision analysis despite differences in their application.
Exercise tests and imaging studies require specialized equipment and
trained personnel to administer and interpret results. These tests
may not be available in all EDs or on a 24-hour basis as is possible
with serum tests. Additionally, some tests, such as exercise ECG testing
and sestamibi imaging, may be used to predict prognosis,52 and thus
may provide information to clinicians beyond detection of ACI. For
example, sestamibi imaging may be able to detect the sickest
patients with ACI. This may be reflected in decreased mortality rates
compared with other tests (ie, biomarkers) in patients with ACI but
negative test results (ie, patients inappropriately discharged from
Finally, test diagnostic performance values used in
the analyses were obtained from published reports and may not reflect
ED physicians decisions on patient triage. Data on how results
from diagnostic tests influence physicians triage decisions
are lacking for most of the tests other than ACI-TIPI, and reliance
on published data of test performance may not accurately reflect actual
triage decisions in the ED. Test diagnostic performance varies among
different patient populations, as shown in Table 1. Furthermore, triage
decisions are often determined in the context of a patients
pretest likelihood of ACI, and not based solely on diagnostic test
Despite these caveats, our study has several strengths.
The analyses focused on how test diagnostic performance affects patient
triage in the ED. We did not include long-term management and outcomes
to prevent obscuring the effects of these tests in the ED. Our outcome
measure was appropriate triage for ACI and not quality of life outcomes
because the focus of the analysis was detection of ACI in the ED.
The short (30-day) time horizon reflects this as well.
We attempted to make the decision model generalizable
and reflect reality. Thus, data on diagnostic test performance were
obtained from a recent extensive systematic review and meta-analysis
of all diagnostic tests for ACI in the ED. We also varied test diagnostic
performance to reflect how tests would perform among specific patient
populations, such as those with non-diagnostic ECG changes. We used
national data for costs and for most transition probabilities for
patient disposition and outcomes.
Our definition of test effectiveness was
its sensitivity for ACI, and did not include its actual use in clinical
practice (except for ACI-TIPI) because data on clinical effectiveness
for most of the evaluated tests was exceedingly sparse. Furthermore,
a tests sensitivity and specificity, may represent its true
triage accuracy. The contribution of clinical decision-making is uncertain
as it may sometime lead to incorrect diagnosis and triage. However,
in an attempt to capture aspects of triage decision-making, we varied
ACI prevalence to model pretest likelihood.
The results of the cost-effectiveness analyses are not
intended to direct clinical recommendations for individual patients
because the decision models apply to populations of ED patients. The
most effective or cost-effective tests may
not be appropriate for a particular patient. Furthermore, age-related
mortality rates were not explicitly modeled. Additionally, the tests
evaluated in the decision analysis may not be applicable even in the
patient population in which they were evaluated. For example, stress
tests may be highly restricted even in the low-risk patient population,
The results of the decision analysis should be used for understanding
the factors that are involved in and as an aid in decision-making
for triage of patients with ACI in the ED. Prospective trials on the
effect of individual diagnostic tests on ED patient triage and outcomes
are required before definitive conclusions can be made.
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Table 1. Values for Test Diagnostic Performance*
Myocardial Infarction Unstable
Angina Non-Acute Cardiac Ischemia
Test Sensitivity Source Sensitivity Source Specificity
CK-MB single All:
0.41 Meta-analysis3 0.05
CK-MB serial All:
0.55 Meta-analysis3 0.07
Estimated from Hedges8
Myoglobin single All:
0.5 Meta-analysis3 0.05
Kennedy14 0.95 Estimated from Levitt,15
Myoglobin serial All:
0.82 Meta-analysis3 0.20
Estimated from Brogan7
0.95 Estimated from Levitt,15
Troponin T single All:
0.4 Meta-analysis3 0.20
Mohler,16 Hamm10 0.98 Mohler,16 Green17
Troponin T serial All:
0.9 Meta-analysis3 0.30
Mohler,16 Hamm10 0.98 Estimated from Green17
0.93 Sabia19; Peels20 0.35
Sasaki,22 Mohler16 0.85 Estimated from
0.95 and Kontos21
meta-analysis4 and Kontos21
0.96 Estimated from 0.8
Estimated from Hilton,27
0.77 Kontos,26 Stewart,25
Stewart25 and Kontos21,26
Kontos,21,26 and Stewart25
Table 2. Transition
All ED patients: 18%;
low-risk patients: 13%;
(range for sensitivity
All: 8.4%; low-risk: 4%
Both models: 9%
Pope45 and analysis of
ACI-TIPI data from Selker5
within 30 days for
survival rate for
hospitalized patients with
survival rate for
discharged from the ED
of patients with
All ED patients: 9%;
Estimate based on
UAP who develop
low-risk subgroup: 5%
expert opinion and
within 30 days
National Cooperative Study
Group46 and Mulcahy47
of ACI-TIPI data
patient without ACI discharged
of appropriate triage
for patients with ACI
of inappropriate triage
for patients with ACI
of triage for patients with
Table 3. Possible
Patient Dispositions Within 30 Days of Presentation to the ED
Condition of Patient Possible Disposition
Patients with AMI
Hospitalized Survives; dies
Discharged Survives, returns for hospitalization;
Patients with UAP
Hospitalized Survives; dies
Discharged Survives, develops AMI, returns
for hospitalization; survives, UAP continues,
returns for hospitalization; survives, UAP continues, outpatient evaluation;
Patients with non-ACI
Discharged Survives, returns for hospitalization;
survives, outpatient evaluation
AMI = acute myocardial infarction; Non-ACI = non acute
cardiac ischemia; UAP = unstable angina.
Table 4. Factors
Involved in Calculating Total Costs (Reimbursements)
Factors Involved in Total Cost Calculation
with ACI appropriately triaged (admitted)
Costs of test + hospitalization*
with ACI inappropriately discharged, dies
Costs of: test + ED
visit + missed
with ACI inappropriately discharged, survives
Cost of: test + ED visit + subsequent
hospitalization or outpatient evaluation
with UAP inappropriately discharged,
Costs of: test + ED
visit + subsequent
develops AMI, survives
hospitalization for AMI*
patient admitted for ACI treatment
Costs of: test + 23-hr
patient discharged from ED
Costs of: test + ED visit + subsequent
hospitalization or outpatient evaluation
Table 5. Reimbursement
Tests & Combinations Factors Involved in
single CK-MB and myoglobin
serial CK-MB and myoglobin
single CK-MB and serial ECG
single troponin T and rest ECHO
Rule-out MI protocol
(23 hour observation)
Admission for ACI¶ Average
of an average admission 4,400
for an uncomplicated AMI ($4,627)
and admission for UAP with
Initial and return ED
visits** Includes all services
provided by 600
the ED, including resuscitation
with diagnostic Includes professional
fee + cost of 430
ECG exercise testing (usual follow-up)
with diagnostic stress
Includes professional fee + cost of
sestamibi imaging (high ACI likelihood
stress sestamibi scan
Outpatient visit, no
diagnostic testing Professional
(low ACI likelihood follow-up)
Table 5. Reimbursement
Tests & Combinations Factors Involved in
Cost of death from missed diagnosis
of ACI In sensitivity analysis ranges Base case: 0;
from an ED visit for attempt at
resuscitation to settlement of
Table 6. All
ED patients: Cost per Patient, Number of Patients With ACI Appropriately
Triaged, and Incremental Cost-effectiveness Ratios of Diagnostic Tests
Number of additional
ACI with ACI Incremental
Cost per Incremental appropriately appropriately Cost-
ED patient Cost triaged§ triaged¶ effectiveness**
single $1,677 46
single $1,684 $7 39
T, single $1,691 $14 53
7 Weakly dominated
serial $1,760 $70 74
21 Weakly dominated
serial $1,780 $20 94
21 Weakly dominated
T, serial $1,796 $16 107
& $1,817 $21 80
Goldman $1,829 $33 76
rest $2,175 $379 112
5 Weakly dominated
T & ECHO $2,202 $27 122
10 Weakly dominated
ACI-TIPI $2,269 $67 168
Table 7. Low-Risk
Patients: Cost per Patient, Number of Patients With ACI Appropriately
Triaged, and Incremental Cost-effectiveness Ratios of Diagnostic Tests
Number of additional
ACI with ACI Incremental
Cost per Incremental appropriately appropriately Cost-
ED patient Cost triaged§ triaged¶ effectiveness**
single $1,535 22
single $1,548 $13
T, single $1,554 $19 34
serial $1,608 $54
35 1 Weakly dominated
serial $1,622 $14 50
15 Weakly dominated
T, serial $1,637 $15 61
11 Weakly dominated
& $1,657 $20 30
protocol $1,685 $48 36
ECG $1,764 $127 112 50 $2,705
Continuous/ $1,820 $57
CK-MB $1,964 $200 50
& serial ECG
T & ECHO $2,047 $283 76
imaging $2,420 $656 110
by increasing cost.
Costs are total costs (in 1999
$) of applying test to an ED patient with symptoms suggestive of ACI.
Difference in cost between test
and previous test. Calculations directly from table may be off due
§Among 1,000 low-risk ED patients
in whom prevalence of ACI is 13%, a test with 100% sensitivity for
ACI would lead to appropriate triage for 130 patients with ACI.
¶Compared with previous non-dominated
*Incremental CE ratios were calculated
by dividing the difference in costs by the difference in effectiveness
between a test and the previous most effective and less costly non-dominated
test. Tests that were less effective and more costly than another
test were eliminated by simple dominance. Tests that were
less effective and had a higher incremental CE ratio were eliminated
by weak dominance. Calculations directly from table may
be off due to rounding.
ACI = acute cardiac ischemia;
CK-MB = creatine kinase MB; ECG = electrocardiogram; ECHO = echocardiogram;
ED = Emergency department.
Figure 1. Decision
Tree. The decision model represents the possible dispositions and
outcomes that occur for each patient presenting to the emergency department
(ED) with signs and symptoms suggestive of acute cardiac ischemia
(ACI). Shown is a decision node branch of the tree for one diagnostic
test. The branches emanating from a chance node, depicted by a circle,
represent the possible outcomes that could occur. The probabilities
of AMI, UAP, and non-ACI are determined by the prevalence rates of
these conditions in the population of patients presenting to the ED.
The probabilities of the possible outcomes are determined by the probabilities
of all choices that have occurred along the path to the outcome. The
proportion of patients at each of the terminal nodes is determined
by the probabilities of all choices that have occurred along the way
to each node. OPFU = Outpatient follow-up evaluation; ACI = acute
cardiac ischemia; ED = Emergency department.
Figure 2. Triage
accuracy of tests for patients with acute cardiac ischemia (ACI) among
all emergency department (ED) patients with symptoms suggestive for
ACI. ECHO = echocardiograph; Goldman = Goldman chest pain protocol.
Figure 3. Diagnostic test costs
per ED patient and percentage of patients appropriately triaged for
acute cardiac ischemia (ACI) among all emergency department (ED) patients
with symptoms suggestive of ACI. ACI-TIPI = Acute Cardiac Ischemia
Time Insensitive Predictive Instrument; ECG = electrocardiograph;
ECHO = echocardiograph; Goldman = Goldman chest pain protocol.
Figure 4. Triage accuracy of tests
for patients with acute cardiac ischemia (ACI) among low-risk emergency
department (ED) patients with symptom suggestive for ACI. ACI-TIPI
= Acute Cardiac Ischemia Time Insensitive Predictive Instrument; ECG
= electrocardiograph; ECHO = echocardiograph; ETT = exercise ECG test;
Goldman = Goldman chest pain protocol.
Figure 5. Diagnostic
test costs per emergency department (ED) patient and percentage of
patients appropriately triaged for acute cardiac ischemia (ACI) among
low-risk ED patients with symptoms suggestive for ACI. ECG = electrocardiograph;
ECHO = echocardiograph; ETT = exercise ECG test; Goldman = Goldman
chest pain protocol.