Evaluation of Chest Pain

and A cute Coronary

Sy ndromes
Anna Marie Chang, MD, MSCEa,*, David L. Fischman, MDb,
Judd E. Hollander, MDc

KEYWORDS

Chest pain
Acute coronary syndrome
Troponin
Coronary CT angiography

KEY POINTS

Chest pain is a common complaint in the emergency department, but less than 15% of patients are
diagnosed with acute coronary syndrome.

Risk stratification tools incorporating cardiac troponins have created new accelerated diagnostic
pathways that are highly accurate and sensitive.

Coronary computed tomography angiography can be used in low-risk to intermediate-risk patients
for diagnostic testing with high accuracy.

INTRODUCTION care providers can be a complicated and often

Chest pain currently represents the second most
common chief complaint of patients presenting
to emergency departments (EDs) in the United
States, representing approximately 8 million
visits.1 Only 10% to 20% of patients are ultimately
diagnosed with acute coronary syndrome (ACS),
with only one-third with acute myocardial infarc-
tion (AMI).1,2 Despite decades of research, 2% to
10% of ACS cases are still missed.3,4 Although
the tools for evaluating chest pain continue to
evolve and improve, translating these new tests
and imaging studies into an updated but meaning-
ful and efficient clinical evaluation within the time
and resource constraints faced by emergency
confusing task.
Myocardial Ischemia is a Spectrum
ACS encompasses both unstable angina and AMI.5
In ACS, atherosclerotic plaque rupture and platelet-
rich thrombus develop. Coronary blood flow is
reduced, and myocardial ischemia occurs. The de-
gree and duration of the oxygen supply-demand
mismatch determines whether the patient develops
reversible myocardial ischemia without necrosis
(unstable angina) or myocardial ischemia with ne-
crosis (myocardial infarction [MI]). More severe
and prolonged obstruction increases the likelihood
of infarction. The most recent definition of MI was

Disclosure: Dr A.M. Chang has research grants from Janssen. She has done consulting work for Siemens. Dr D.L.
Fischman has stock ownership in Medtronic Corporation and Boston Scientific Corporation (which has no
bearing on the material covered in this article). Dr J.E. Hollander has research grants from Alere, Siemens,
Trinity Biotech, and Roche. He has also done consulting work for Janssen.
cardiology.theclinics.com

a
Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Thomas
Jefferson University Hospital, 1020 Sansom Street, Suite 241, Thompson Building, Philadelphia, PA 19107, USA;
b
Cardiac Catheterization Laboratory, Sidney Kimmel Medical College, Thomas Jefferson University, Thomas
Jefferson University Hospital, 925 Chestnut Street, Philadelphia, PA 19107, USA; c Finance and Healthcare En-
terprises, Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University,
Thomas Jefferson University Hospital, 1025 Walnut Street, Suite 300, Philadelphia, PA 19107, USA
* Corresponding author.
E-mail address: Anna.m.chang@jefferson.edu

Cardiol Clin - (2017) -–-

http://dx.doi.org/10.1016/j.ccl.2017.08.001
0733-8651/17/Ó 2017 Elsevier Inc. All rights reserved.
2 Chang et al
published in 2012,5 which defined this as myocar-
dial cell death caused by prolonged ischemia. MI
is determined by clinical features including electro-
cardiogram (ECG) and biomarker findings. There
are 5 classifications of acute MI (Table 1), and clini-
cians should be aware of these. Usually, clinicians
are focused on type I MI, but supply-demand
mismatch or infarction in the absence of thrombotic
occlusion (type 2) is also common.
RISK STRATIFICATION IN THE EMERGENCY
DEPARTMENT
History
Recent systematic reviews of investigations indi-
cate that history and physical examination are
not helpful in symptomatic patients with acute
chest symptoms. Swap and Nagurney6 conducted
a systematic review of chest pain characteristics
from observational studies and found that certain
characteristics increased or decreased the likeli-
hood of ACS or AMI, but none are useful to dispo-
sition the patient. Fanaroff and colleagues7
Table 1
Classification of acute myocardial infarction
types
Type 1 Spontaneous MI related to ischemia
caused by a primary coronary
event such as plaque erosion and/
or rupture, fissuring, or dissection
Type 2 MI secondary to ischemia caused by
either increased oxygen demand
or decreased supply such as caused
by coronary artery spasm,
coronary embolism, anemia,
arrhythmias, hypertension, or
hypotension
Type 3 Sudden unexpected cardiac death,
including cardiac arrest, often
with symptoms suggestive of
myocardial ischemia,
accompanied by new ST elevation,
or new left bundle branch block,
or evidence of fresh thrombus in a
coronary artery by angiography
and/or at autopsy, but death
occurring before blood samples
could be obtained, or at a time
before the appearance of cardiac
biomarkers in the blood
Type 4a MI associated with percutaneous
coronary intervention
Type 4b MI associated with stent thrombosis
by angiography or autopsy
Type 5 MI associated with coronary artery
bypass grafting
conducted a systematic review of the accuracy
of the history, physical examination, ECG, and
risk factors. Similarly, symptoms were not useful
in isolation for risk stratification. In both studies, ra-
diation to right arm or both arms was more specific
than radiation to left arm (specificity, 96%; likeli-
hood ratio (LR), 2.6 [95% confidence interval (CI),
1.8–3.7] vs specificity 69%; LR, 1.3 [95% CI, 1.2–
1.4]). Other helpful historical factors included
similar to prior ischemia or MI (specificity, 79%;
LR, 2.2 [95% CI, 2.0–2.6]) and associated diapho-
resis. There were mixed responses associated
with nausea and vomiting. Response to nitroglyc-
erin was also unhelpful, whereas descriptions of
the pain, such as pleuritic, positional, or sharp,
were only minimally helpful in decreasing the likeli-
hood of ACS. In addition, these features, which are
usually associated with lower probability of ACS,
have only poor to fair interrater reliability.8
In recent years, pain scores have received a lot
of attention; however, Edwards and colleagues9
found that there was no difference in AMI or 30-
day outcomes in patients with pain rated as severe
(9 or 10 on 10-point scale) or not.
Cardiac Risk Factors
Traditional cardiac risk factors such as hyperten-
sion, diabetes, hyperlipidemia, and tobacco use
are often used to predict the long-term risk of cor-
onary artery disease (CAD) and are included in
models such as the Framingham Risk Score.10
However, these are not useful for predicting ACS
in symptomatic patients in the ED. Recent studies
have found that up to 12% of patients with AMI
had no cardiac risk factors.11,12
Prior Cardiac History
Patients with a prior normal stress test are at the
same risk of 30-day adverse cardiovascular events
as patients who have not previously undergone
stress testing.13,14 Stress testing does not assess
whether nonobstructive plaque existing at the
time of the test will subsequently rupture leading
to ischemia. Thus, knowledge of a recent normal
stress test may not help inform current ACS risk;
patients with a prior normal stress test still had a
5% event rate at 30 days. In contrast, prior invasive
coronary angiography results are useful for risk
stratification of patients. Patients with no or minimal
(<25%) stenosis have an excellent long-term prog-
nosis, with 90% free from 1-vessel disease and
greater than 98% free from MI nearly a decade
later.15,16 Thus, recent coronary angiography with
normal or minimally diseased vessels makes the
development of an ACS extremely unlikely and
may be helpful during the current visit.

Physical Examination
There are few studies evaluating the performance
of physical examination findings in diagnosing
ACS. In a systematic review, hypotension was
the strongest clinical indicator,7 so signs of acute
heart failure may indicate that expeditious treat-
ment is necessary.17 Some studies suggest that
reproducible pain with palpation decreased the
likelihood, but not to low enough levels to facilitate
discharge from the ED.18
Electrocardiogram
Current guidelines recommend ECG interpretation
within 10 minutes of the patient’s arrival. The ECG
is the most important initial diagnostic test. If sus-
picion is high, the ECG should be repeated (eg, at
intervals of 15 to 30 minutes during the first hour).
A normal ECG does not exclude ACS and occurs
in 1% to 6% of such patients.18 A normal ECG is
more common with left circumflex or right coro-
nary artery occlusions, which can be electrically si-
lent (in which case posterior electrocardiographic
leads [V7–V9] may be helpful). Right-sided leads
(V3R–V4R) can be used in the case of inferior ST-
elevation myocardial infarction (STEMI) to detect
evidence of right ventricular infarction.
The guidelines recommend primary percuta-
neous coronary intervention (PCI) for STEMI, with
first medical provider to balloon inflation time of
90 minutes or less, or transfer for primary PCI
with a goal time to balloon inflation of 120 minutes
or less. Thrombolytic therapy is recommended in
eligible patients if these goals cannot be achieved.
The most recent guidelines have removed the
recommendation for primary PCI in isolated left
bundle branch block.19 Misclassifications rates
range from 5.9% to 29%.20,21 False-positive inter-
pretations of the ECG occur in at least 11% to 14%
of presumed STEMI cases.22 Thus, an important
skill for emergency physicians is understanding
the criteria for activation and/or transfer. In addi-
tion to determining the presence of an STEMI, un-
derstanding high-risk ECG patterns may help
improve patient morbidity and mortality. Although
these patterns may not indicate immediate cardiac
catheterization activation, cardiology consultation
and admission are warranted.
Imaging
A chest radiograph is commonly used in patients
with acute chest pain the ED and may be useful
for detecting abnormalities such as pneumonia
or pneumothorax. However, the yield of this test
is low in patients with suspected ACS. In prospec-
tive studies, only between 6% and 12% of chest
Chest Pain and Acute Coronary Syndromes 3
radiographs revealed abnormalities that required
interventions,23,24 but no clinical decision rule
was sufficiently sensitive or specific to identify
the patients who would benefit the most from
chest radiographs.
Biomarkers
Given that the clinical assessment of ACS is insuf-
ficient, the addition of blood tests to measure the
concentration of cardiac troponin (cTn) T or I is
necessary to aid in the early diagnosis of AMI.
The “Third Universal Definition of Myocardial
Infarction” recommends that cTn is useful in the
detection of myocardial necrosis, and that detec-
tion of an increase/and or decrease is “essential
to the diagnosis of AMI.”5 These assays quantify
the amount of cardiomyocyte necrosis, and thus
the higher the level the more cell death has
occurred. An increased cTn concentration is
defined as a value exceeding the 99th percentile
of a normal reference population (upper reference
limit [URL]). This discriminatory 99th percentile is
designated as the decision level for the diagnosis
of MI and must be determined for each specific
assay with appropriate quality control in each lab-
oratory, and can be found in the package inserts.
The United States Food and Drug Administration
(FDA) cleared the first fifth-generation troponin T,
which has been use in Europe and other regions
for more than 5 years.25 By expert consensus, a
high-sensitivity assay is defined so that they
detect a level in greater than 50% of apparently
healthy persons, and they have a coefficient of
variation of less than 10% at the 99th percentile
URL of the assay. These assays allow the earlier
detection of AMI as well as the detection of smaller
AMIs. However, physicians need to be cognizant
that not all increases in troponin level represent
AMI, and that myocardial injury may occur from
other disease processes.5 Any increase in troponin
indicates increased morbidity and mortality risk,
no matter the condition or chronicity, and thus
emergency physicians should never disregard an
increase and call it a troponin leak. Any detectable
troponin is always worse than no troponin and
higher levels of troponin always portend a worse
prognosis than lower levels of troponin.
When Should Troponin Testing Be Done?
Current guidelines recommend troponin testing
should be measured at presentation and 3 to 6 hours
after symptoms onset and additional levels ob-
tained beyond 6 hours after symptom onset for an
intermediate or high index of suspicion. In addition,
if symptom onset is ambiguous, the time of presen-
tation should be considered to be the onset time.18
4 Chang et al
Given the ability of new highly sensitive troponin
assays to detect smaller amounts of cardiomyo-
cyte damage within a shorter time of onset,
many new biomarker strategies have been evalu-
ated for the rapid rule-out of AMI. In 2015 the Eu-
ropean Society of Cardiology recommended
troponin testing at 0 and 3 hours, or at 0 and 1
hour with the use of validated algorithms for the
select group of patients.26 As with any algorithms
for patient care, there are some caveats: these
should only be used in conjunction with all avail-
able clinical information; if a patient presents early
in chest pain, the second cTn level should be ob-
tained at 3 hours, because of the time dependency
of troponin release; and because late increases in
cTn level have been described, serial cTn testing
should be pursued if the clinical suspicion remains
high or whenever the patient develops recurrent
chest pain. Table 2 provides a summary of these
pathways for troponin testing times.
In the 3-hour protocol, AMI is ruled out if concen-
trations of high-sensitivity cTn (hs-cTn) remain in the
normal range at presentation and at 3 hours later,
and if the patients remained pain free and continue
to be at low risk of in-hospital mortality as quantified
by a Global Registry of Acute Coronary Events
(GRACE) score less than 140.26 In patients present-
ing more than 6 hours after chest pain onset (which
can be reliably quantified), a single blood draw at
presentation is considered sufficient. Patients are
considered ruled in if they have a clearly increased
hs-cTn blood concentration at presentation or if
the 3-hour sample shows an assay-specific relevant
change. A similar approach using hs-cTn achieves a
high negative predictive value and sensitivity by also
taking into account absolute concentration changes
within 2 hours, and allows clinicians to safely rule
out AMI even in patients with mild nonspecific
ECG abnormalities. This strategy allows the rapid
rule-out of AMI in up to 60% of patients.27–29 More-
over, this strategy also includes a rule-in algorithm
that provides a positive predictive value of 70% to
80% for AMI.
The 1-hour algorithm is identical to that of the
0-hour and 2-hour algorithm and is based on infor-
mation provided by hs-cTn blood concentrations.
This approach may allow for safe rule-out of AMI
even in patients with mild nonspecific ECG abnor-
malities. This strategy is very effective and allows
an accurate disposition for about 75% of patients:
60% rule-out and 15% rule-in of AMI. Another
quarter of the patients are ultimately ruled in.30
Importantly, these rapid pathways have not been
used in the United States in a clinical setting, but will
soon be available in clinical practice. It is also crit-
ical to note that, once these patients have been
ruled out, the guidelines still recommend
provocative testing, specifically stress imaging
during admission or shortly after discharge. In addi-
tion, although these strategies may effectively help
rule out or rule in AMI in a significant proportion of
patients, the European Society of Cardiology
(ESC) also incorporates an observe middle ground,
in which troponin level increases do not meet
criteria to rule in and no alternative explanation for
the increase is identified.26 Clinicians need to use
judgment in determining the best further test.
Risk Stratification Scores
Clinical prediction rules and decision aids have
helped clinicians incorporate clinical and
biomarker findings to risk stratify patients. These
rules and aids are helpful in estimating pretest
probability, and may help facilitate patient safety.
Common risk assessment rules used in the ED
include the Thrombolysis in Myocardial Infarction
(TIMI) risk score,31,32 and more recently, the
HEART (History, ECG, Age, Risk factors and
Troponin) score.33 Other scores include the
Platelet Glycoprotein IIb/IIIa in Unstable Angina:
Receptor Suppression Using Integrilin Therapy
(PURSUIT) risk score,34 the GRACE risk score,35
Vancouver rule,36,37 and North American Chest
Pain Rule.38 Table 3 shows the risk scores and
early discharge criteria based on these scores.
The TIMI score was derived from a group of pa-
tients with non–ST-elevation myocardial infarction
but has been validated for use in the ED setting.
The TIMI risk score is a 7-item score that, when com-
bined into a score of 0 to 7, allows emergency phy-
sicians to risk stratify patients whether or not they
have ACS. When applied to a broad-based popula-
tion of patients with chest pain, it performed similarly
and was able to risk stratify the patients with respect
to 30-day death, AMI, and revascularization.32 The
ASPECT (ASIA PACIFIC EVALUATION OF CHEST
PAIN TRIAL) and ADAPT (A 2hr Accelerated Diag-
nostic Protocol to Assess patients with chest Pain
symptoms using contemporary Troponins as the
only biomarker) studies combined the use of a modi-
fied TIMI risk score with 0-hour and 2-hour troponin
measurements.27,39 Between 10% and 20% of pa-
tients were considered low risk if a TIMI score of
0 was used, and up to 40% for TIMI less than or
equal to 1. The negative predictive value was
99.7%. This study is widely implemented in Queens-
land, Australia, but has not been replicated in the
United States.
The HEART score relies on a 10-point scale
based on the patient’s history (H), ECG results
(E), age (A), risk factors (R), and troponin test result
(T), and a score less than or equal to 3 is consid-
ered a low-risk cohort.40 Backus and colleagues33
 Table 2
Accelerated diagnostic pathways

0-h/1-h Algorithm 0-h/2-h Algorithm 2-h ADP 0-h/3-h ESC

Clinical Scoring System None None TIMI score 1 GRACE <140 and pain free
ECG normal at 0 h/2 h
Blood Drawsa 2a 2a 2a 2a
Indication Rule out and rule in Rule out and rule in Rule out Rule out and rule in
Negative Predictive Value for AMI (%) 99.1–100 99.5–99.9 99.1–100b 99.6–100
Eligible Population Size 111 111 11 11(1)
Biomarker Rule-out Criteriac
Using hs-cTnT (ng/L) hs-cTnT <12 hs-cTnT <14 at 0 and 2 h hs-cTnT <14 at 0 and 2 h hs-cTnT <14 at 0 and 3 h
And And
1-h delta <3 2-h delta <4
Using hs-cTnI (ng/L) hs-cTnI <5 hs-cTnI <6 at 0 and 2 h hs-cTnI <26 at 0 and 2 h hs-cTnI <26 at 0 and 3 h
And And

Chest Pain and Acute Coronary Syndromes

1-h delta <2 2-h delta <2
Biomarker Rule-in Criteria
Using hs-cTnT (ng/L) hs-cTnT 52 hs-cTnT 53 — —
Or Or
1-h delta 5 2-h delta 10
Using hs-cTnI (ng/L) hs-cTnI 52 hs-cTnI 64 — —
Or Or
1-h delta 5 2-h delta 15
Feasibility 111 111 11 11
Requires use of TIMI score Requires GRACE score

Eligible population size is quantified by the percentage of consecutive patients with chest pain eligible for this early triage strategy: 1, z20%; 11, z40%; 111, z50% to 75%.
Abbreviations: ADP, accelerated diagnostic protocol; ESC, European Society of Cardiology; GRACE, Global Registry of Acute Coronary Events; hs-cTnI, high-sensitivity cardiac
troponin I; hs-cTnT, high-sensitivity cardiac troponin T; TIMI, Thrombolysis in Myocardial Infarction.
a
For some patients, only 1 blood draw is necessary.
b
For major adverse cardiac events (death, AMI, major arrhythmias).
c
Characteristics are provided for the hs-cTnT (Elecsys) and hs-cTnI (Architect). Cutoff levels differ for other hs-cTn assays becoming available for clinical use in the future.

5
6 Chang et al

Table 3
Risk stratification scores and established criteria for discharge from the emergency department

Rule Characteristics of Risk Score Early Discharge Criteria

HEART score 5 criteria each graded 0, 1, or 2 Total score 3
for no, moderate, or highly
suspicious:
History
ECG
Age
Risk factors
Troponin
North American Chest Pain — Absence of new ischemia on
Rule ECG; no history of coronary
disease, not typical pain,
age <40 y, and initial cTn
negative; if age 41–50 y, add
repeat troponin at 6 h
Vancouver Chest Pain — Absence of ongoing pain,
Algorithm angina; physical findings
consistent with heart
failure, murmur, or
hemodynamic instability;
ischemic ECG, and increased
cTn level
EDACS 4 different categories with Total score 16, no new
variable-point assignments. ischemia on ECG, both 0-h
Age groups, history of and 2-h cTn negative (see
premature CAD or 4 risk https://www.mdcalc.com/
factors, 4 symptoms emergency-department-
associated with pain, assessment-chest-pain-
gender. Range of scores score-edacs)
usually requiring computer
or a smartphone application
Modified TIMI score 5 criteria each worth 1 point: —
age, 3 or more CAD risk
factors, known CAD, ASA in
past 7 d, recent severe
angina

Abbreviations: ASA, acetylsalicylic acid; EDACS, Emergency Department Assessment of Chest Pain Score.

initially tested the score on 880 patients, yielding a
98.1% sensitivity, 41.6% specificity, and 99%
negative predictive value for major adverse cardio-
vascular events (MACE) at 6 weeks. Validation
studies conducted in Europe and Asian have
shown sensitivities of 95% to 96%, and negative
predictive values of 98%.33,41 In the United States,
Mahler and colleagues42 tested the HEART score
on a registry cohort of 1070 patients. The score
achieved a 58.3% sensitivity and an 85.0% spec-
ificity, with 5 MACE in the low-risk cohort. A small
randomized controlled trial (RCT) used a modified
version of the HEART score that uses structured
criteria to categorize history and excludes patients
from being classified as low risk if there is a posi-
tive troponin result from blood sampling at 0 and
3 hours from arrival at the ED. This group was
much lower risk than those in the European
studies, with an overall MACE of 6%. The sensi-
tivity for MACE for 141 patients randomized to
the modified HEART pathway was 100%.43 The
TRAPID-AMI (The High Sensitivity Cardiac
Troponin T Assay for Rapid Rule-out of Acute
Myocardial Infarction) study retrospectively incor-
porated a modified HEART score with hs-cTnT
and, using the protocol, 515 or 1282 (40%) pa-
tients had a HEART score less than or equal to 3
and negative delta troponin evaluations at
1 hour, with only one 30-day MACE (0.2%) in this
low-risk cohort. In patients with negative delta tro-
ponins but a HEART score greater than or equal to
4, the risk of MACE was more than 2%.44
Other clinical decision rules have not been used
as frequently in the ED setting. The North

American Chest Pain Rule was 100% sensitive for
a cardiac event within 30 days and categorized
18% of patients as safe for early discharge.38
The model was internally validated using statistical
bootstrapping techniques, but has not yet been
validated in an external data set.
The Emergency Department Assessment of
Chest Pain Score (EDACS) Accelerated Diagnostic
Pathway (ADP) was created with 2 goals: to develop
a risk stratification score, and then to pair this with 2-
hour serial troponin testing to create a diagnostic
pathway. This protocol was validated and tested
for reproducibility using prospectively collected
data from separate cohorts of patients from the
same sites in Australia and New Zealand. An EDACS
less than 16 was considered low risk. In the ADP, the
ECG had to have no new ischemic changes and
both 0-hour and 2-hour troponins were negative. In
the derivation and validation cohorts, the EDACS-
ADP classified more than 40% of patients as low
risk.45 A subsequent validation of the EDACS-ADP
using a Canadian cohort of patients classified a
similar proportion of patients as low risk.46 The
EDACS-ADP has now been validated in a RCT and
is being used in multiple hospitals in New Zealand
and Australia.47 However, a recent secondary anal-
ysis of data collected in the United States attempted
to validate these results, and found that the sensi-
tivity for MACE was only 88.2%.48
Clinical decision aids with or without clinical
gestalt have the potential to be important tools in
the assessment of patients presenting to the ED
with possible AMI, and accelerated decision-
making processes incorporating such aids can be
used to facilitate safe early discharge. Clinicians
or departments thinking of adopting an ADP for
local implementation should carefully decide on
the outcome of importance (ie, early rule-out of
AMI vs rule-out of ACS). Consideration should
also be given to the prevalence of the disease in
the hospitals where ADPs were studied. An ADP
that was developed and tested in a low-
prevalence population must be transferred with
caution to a setting in which the disease preva-
lence is high and for this reason it is important to
consider both the sensitivity and the negative pre-
dictive value of the rule-out strategy. The pathways
based on ADAPT, EDACS, and HEART have the
most extensive evidence base behind them.
DIAGNOSTIC TESTING
Coronary Computed Tomography
Angiography
Large studies and meta-analyses have estab-
lished the diagnostic accuracy of coronary
computed tomography angiography (CTA), and it
Chest Pain and Acute Coronary Syndromes 7
has been found comparable with invasive angiog-
raphy. Technological improvement has increased
sensitivity of detection of coronary artery stenosis
from 84% for 4-slice computed tomography (CT)
to 83% for 16-slice CT to 93% for 64-slice CT,
with concurrent specificities from 93%, 96%, to
96%, respectively.49 A systematic review of 41
studies totaling 2515 patients indicated a sensi-
tivity of 95% and specificity of 85% for detection
of CAD in all types of scanners combined.50 A
report by the ESC and the European Council of
Nuclear Cardiology reporting a pooled analysis of
800 patients found a sensitivity of 89% (95% CI,
87–90) with a specificity of 96% (95% CI, 96–97)
in 64-slice CT.51
Budoff and colleagues52 compared the diag-
nostic accuracy of coronary CTA with that of inva-
sive coronary angiography (ICA) in 230 patients.
On a per-patient basis, the sensitivity, specificity,
and positive and negative predictive values to
detect greater than or equal to 50% stenosis
were 95%, 83%, 64%, and 99%, respectively.
Miller and colleagues53 also compared the accu-
racy of coronary CTA with ICA in 291 patients
and found similar results. Further examples of
large studies comparing 64-slice coronary CTA
with ICA are shown in Table 1. These sensitivities
and specificities translate to a high negative pre-
dictive value for low-risk to intermediate-risk pa-
tients in the ED.
Meijboom and colleagues54 evaluated the diag-
nostic utility of patients at high, intermediate, and
low pretest risk of CAD. In the low pretest proba-
bility group, a negative coronary CTA was present
in 75% of the patients. The negative predictive
value of coronary CTA to exclude significant CAD
was excellent in these patients, reducing the esti-
mated posttest probability to zero, and the investi-
gators concluded that these patients would not
need further downstream diagnostic tests. Coro-
nary CTA was of limited clinical value in the evalu-
ation of the group with high estimated pretest
probability.
THIRTY-DAY EVENTS
The literature shows that negative coronary CTA
(defined as maximal stenosis <50% in all vessels)
is useful in the prediction of freedom from 30-day
cardiovascular events of MI, coronary revasculari-
zation, or death. In a recent meta-analysis of
studies of 1559 patients with symptoms sugges-
tive of ACS who presented to EDs, the sensitivity
was 93.3%, specificity was 89.9%, positive pre-
dictive value was 48.1%, and negative predictive
value was 99.3% for 30-day cardiovascular
events.55
8 Chang et al
The American College of Radiology Imaging
Network (ACRIN) 4005 trial randomized 1370 pa-
tients to either coronary CTA or traditional care.
Patients with a negative CTA (<50% maximal ste-
nosis) were free from cardiac death or MI at
30 days (upper limit of 95% CI was 0.57%). In
addition, a coronary CTA–based strategy resulted
in double the discharge rate (50% vs 23%) and
considerably shorter lengths of stay (18 vs
25 hours), whereas it identified more patients
with coronary disease (9% vs 3%). Although
some clinicians worry that testing with CTA might
lead to more testing, this trial found that the likeli-
hood of receiving a negative invasive angiogram
was decreased in the CTA group relative to pa-
tients managed traditionally.56 Similarly, the Rule
Out Myocardial Infarction/Ischemia Using Com-
puter Assisted Tomography (ROMICAT)-II study
was a multicenter RCT comparing the effective-
ness of coronary CTA evaluation versus standard
evaluation. The patients who received CT evalua-
tion had shorter lengths of stay and were more
likely to be discharged from the ED (47% vs
12%). Overall, there was no difference in clinical
adverse events between the two groups, and no
undetected ACS at 28 days. These data suggest
that patients with a maximal stenosis of less than
50% can be safely discharged home from the
ED. The Prospective Multicenter Imaging Study
for Evaluation of Chest Pain (PROMISE) compared
health outcomes in patients who presented with
new symptoms suggestive of CAD that required
further evaluation and who were randomly
assigned to an initial strategy of anatomic testing
with the use of CTA or functional testing, and
found no difference in patient outcomes at 1 year.
In our experience, patients without any stenosis
of 50% or more in any vessel can be safely dis-
charged home from the ED. Box 1 shows how
the authors use coronary CTA in our ED.
LONGER TERM OUTCOMES
Hollander and colleagues57 evaluated 588 low-risk
patients who received coronary CTA in the ED. Of
the 481 patients with a less than 50% stenosis in
any vessel, who also did not have depressed left
ventricular function, 53 patients (11%) were reho-
spitalized and 51 patients (11%) received further
diagnostic testing (stress or catheterization) over
the subsequent year. There was only 1 death
(0.2%) and no AMI during this time period. Hada-
mitzky and colleagues58 enrolled 1256 consecutive
patients with suspected CAD undergoing 64-slice
coronary CTA and observed them prospectively
for the occurrence of cardiac death, MI, or unstable
angina requiring hospitalization. In the 802 patients
Box 1
Appropriate indications for coronary computed
tomography angiography in patients with
acute chest pain syndromes
Indications
ECG negative or indeterminate for myocardial
ischemia
Low to intermediate pretest likelihood by risk
stratification tools
TIMI score 0 to 2 (low risk) ideal or TIMI 3 to 4
(intermediate) in some cases
HEART score less than 3
One or more negative troponin values,
including point-of-care assays
Equivocal or inadequate previous functional
testing during index ED or within previous
6 months
Equivocal indications
High clinical likelihood of ACS by clinical assess-
ment and standard risk criteria (eg, TIMI
score >4)
Previously known CAD
Known calcium score greater than 400
Relative contraindications
History of allergic reaction to iodinated
contrast
GFR less than 60 mL/min/1.73 m2
Factors likely to lead to nondiagnostic scans;
specifics vary with scanner technology and site
capabilities
Heart rate greater than site maximum for reli-
ably diagnostic scans after b-blockers (usually
70–80 beats/min)
Contraindications to b-blockers and heart
rate not controlled
Atrial fibrillation or other markedly irregular
rhythm
BMI greater than 39 kg/m2
Absolute contraindications
Known ACS
GFR less than 30 mL/min/1.73 m2 unless on
chronic dialysis
Previous anaphylaxis after iodinated contrast
administration
Previous episode of contrast allergy after
adequate steroid/antihistamine preparation
Pregnancy
Abbreviations: ATN, acute tubular necrosis; BMI, body
mass index; GFR, glomerular filtration rate.

without any stenosis greater than 50%, only 1 case
of unstable angina occurred during the initial
90 days. Within a median of 18 months there
were only 4 events in these 802 patients (<0.5%),
whereas there were 17 events in the 348 patients
(5%) with obstructive CAD. The ACRIN 4005 trial
showed there was no difference in 1-year MACE
(1.4% vs 1.1%), ED revisits, hospital admissions,
or subsequent cardiac testing. There was only 1
patient with a negative coronary CTA who had a
MACE within the year.59
Two smaller studies focused on low-risk to
intermediate-risk patients with chest pain. The
ROMICAT trial reported 2-year outcomes for their
cohort in 368 ED patients with acute chest pain,
negative initial troponin, and a nonischemic
ECG. Cumulative probability of 2-year events
increased across strata for CAD but none
occurred in patients without disease (no CAD,
0%; nonobstructive CAD, 4.6%; obstructive
CAD, 30.3%).60
In a European cohort of 227 patients with 2.3-
year follow-up, there were no cardiovascular
events in the 96 patients without CAD (0%), 2
events in the 76 patients with nonobstructive
CAD (2.6%), and 11 in the 55 patients (20%) with
obstructive CAD. Abdulla and colleagues con-
ducted a meta-analysis that included 5675 pa-
tients who were mostly intermediate to high risk
in 10 studies with mean follow-up of 21 months.
The event rate was 0.5% in 2045 patients with
normal CTA, 3.5% in 2068 patients with nonob-
structive CAD, and 16% in the 1562 patients with
obstructive CAD. The CONFIRM (COroNary CT
Angiography Evaluation For Clinical Outcomes:
An InteRnational Multicenter Registry) multina-
tional registry includes more than 12,000 patients
from 12 sites in 6 countries.61 In patients without
CAD, the annualized MACE rate was only 0.31%
versus 2.06% in those with obstructive disease.62
Thus it seems clear that a negative coronary
CTA is associated with a very low event rate and
discharge directly from the ED is safe in the short
and longer term.
Triple Rule-out
Coronary CTA has a limited capacity to diagnose
noncardiac causes of chest pain arising from sour-
ces outside the anatomic window it interrogates.
Technical advances in cardiac CT and intravenous
contrast injection protocols have made a triple
rule-out protocol feasible, which can effectively
image the coronary, aortic, and pulmonary arterial
beds, to exclude CAD, aortic dissection, and pul-
monary embolism as causes of acute chest pain.
Takakuwa and colleagues63 evaluated 197
Chest Pain and Acute Coronary Syndromes 9
patients who had a triple rule-out protocol per-
formed. No further diagnostic testing was per-
formed in 133 (76%) of 175 of patients with no to
mild coronary disease within 30 days. Three cases
of pulmonary embolism were found, and 1 case of
aortic dissection. Rogers and colleagues64 ran-
domized patients to receive comprehensive
cardiothoracic CT or a coronary CTA in 59 pa-
tients. No significant difference was found in the
median length of stay, rate of hospital discharge
without additional imaging, costs of care, or the
number of revisits between the dedicated and
comprehensive arms, respectively. Furthermore,
radiation dosages were similar between the two
arms. Madder and colleagues65 identified patients
who underwent triple rule-out or coronary CTA at 2
hospitals in Michigan; 272 patients had triple rule-
out and 1796 patients had coronary CTA per-
formed. Pulmonary embolism was identified in
only 1.1% of triple rule-out and 0.2% of cardiac
CT examinations, and there were no aortic dissec-
tions. At 90 days, there were no differences in
death, ACS, pulmonary embolism, or aortic
dissection diagnosis, or major differences in
downstream resource use. Given that the radiation
dose and intravenous contrast dose are higher in
triple rule-out scans, it does not seem to provide
enough additional information to warrant the ex-
amination in most patients.
SUMMARY
It is imperative for providers to understand the
evidence-based decision making for chest pain
evaluation. Although the history and physical ex-
amination may be useful to identify other causes
of chest pain, they are not useful for ruling in
ACS. New improved cTn assays, used in conjunc-
tion with clinical decision rules, will help clinicians
rapidly rule out a larger proportion of patients with
potential ACS. Coronary CTA is now a proven
technology and should be incorporated into more
chest pain rule-out pathways.
REFERENCES
1. Bhuiya FA, Pitts SR, McCaig LF. Emergency depart-
ment visits for chest pain and abdominal pain:
United States, 1999-2008. NCHS Data Brief
2010;(43):1–8.
2. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease
and stroke statistics—2015 update. Circulation 2014.
http://dx.doi.org/10.1161/CIR.0000000000000152.
3. Pope JH, Aufderheide TP, Ruthazer R, et al. Missed
diagnoses of acute cardiac ischemia in the emer-
gency department. N Engl J Med 2000;342(16):
1163–70.
10 Chang et al
4. Moy E, Barrett M, Coffey R, et al. Missed diagnoses of
acute myocardial infarction in the emergency depart-
ment: variation by patient and facility characteristics. j
AHRQ Patient Safety Network. Available at: https://
psnet.ahrq.gov/resources/resource/28747/missed-
diagnoses-of-acute-myocardial-infarction-in-the-
emergency-department-variation-by-patient-and-
facility-characteristics. Accessed June 19, 2016.
5. Thygesen K, Alpert JS, Jaffe AS, et al. Third univer-
sal definition of myocardial infarction. J Am Coll Car-
diol 2012;60(16):1581–98.
6. Swap CJ, Nagurney JT. Value and limitations of
chest pain history in the evaluation of patients with
suspected acute coronary syndromes. JAMA 2005;
294(20):2623–9.
7. Fanaroff AC, Rymer JA, Goldstein SA, et al. Does
this patient with chest pain have acute coronary syn-
drome?: the rational clinical examination systematic
review. JAMA 2015;314(18):1955–65.
8. Hickam DH, Sox HC, Sox CH. Systematic bias in
recording the history in patients with chest pain.
J Chronic Dis 1985;38(1):91–100.
9. Edwards M, Chang AM, Matsuura AC, et al. Rela-
tionship between pain severity and outcomes in pa-
tients presenting with potential acute coronary
syndromes. Ann Emerg Med 2011;58(6):501–7.
10. Wilson PWF, D’Agostino RB, Levy D, et al. Prediction
of coronary heart disease using risk factor cate-
gories. Circulation 1998;97(18):1837–47.
11. Han JH, Lindsell CJ, Storrow AB, et al. The role of
cardiac risk factor burden in diagnosing acute coro-
nary syndromes in the emergency department
setting. Ann Emerg Med 2007;49(2):145–52, 152.e1.
12. Body R, Carley S, Wibberley C, et al. The value of
symptoms and signs in the emergent diagnosis of
acute coronary syndromes. Resuscitation 2010;
81(3):281–6.
13. Nerenberg RH, Shofer FS, Robey JL, et al. Impact of
a negative prior stress test on emergency physician
disposition decision in ED patients with chest pain
syndromes. Am J Emerg Med 2007;25(1):39–44.
14. Shaver KJ, Marsan RJ, Sease KL, et al. Impact of a
negative evaluation for underlying coronary artery
disease on one-year resource utilization for patients
admitted with potential acute coronary syndromes.
Acad Emerg Med 2004;11(12):1272–7.
15. Pitts WR, Lange RA, Cigarroa JE, et al. Repeat cor-
onary angiography in patients with chest pain and
previously normal coronary angiogram. Am J Car-
diol 1997;80(8):1086–7.
16. Papanicolaou MN, Califf RM, Hlatky MA, et al. Prog-
nostic implications of angiographically normal and
insignificantly narrowed coronary arteries. Am J Car-
diol 1986;58(13):1181–7.
17. Disla E, Rhim HR, Reddy A, et al. Costochondritis. A
prospective analysis in an emergency department
setting. Arch Intern Med 1994;154(21):2466–9.
18. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014
AHA/ACC guideline for the management of patients
with non–ST-elevation acute coronary syndromes.
J Am Coll Cardiol 2014;64(24):e139–228.
19. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013
ACCF/AHA guideline for the management of ST-
elevation myocardial infarction a report of the Amer-
ican College of Cardiology Foundation/American
Heart Association Task Force on Practice Guide-
lines. Circulation 2013;127(4):e362–425.
20. Brady WJ, Perron A, Ullman E. Errors in emergency
physician interpretation of ST-segment elevation in
emergency department chest pain patients. Acad
Emerg Med 2000;7(11):1256–60.
21. Vijayaraghavan R, Yan AT, Tan M, et al. Local hospi-
tal vs. core-laboratory interpretation of the admission
electrocardiogram in acute coronary syndromes:
increased mortality in patients with unrecognized
ST-elevation myocardial infarction. Eur Heart J
2008;29(1):31–7.
22. Larson DM, Menssen KM, Sharkey SW, et al. “False-
positive” cardiac catheterization laboratory activa-
tion among patients with suspected ST-segment
elevation myocardial infarction. JAMA 2007;
298(23):2754–60.
23. Poku JK, Bellamkonda-Athmaram VR, Bellolio MF,
et al. Failure of prospective validation and derivation
of a refined clinical decision rule for chest radiog-
raphy in emergency department patients with chest
pain and possible acute coronary syndrome. Acad
Emerg Med 2012;19(9):E1004–10.
24. Goldschlager R, Roth H, Solomon J, et al. Validation
of a clinical decision rule: chest X-ray in patients with
chest pain and possible acute coronary syndrome.
Emerg Radiol 2014;21(4):367–72.
25. Phend C. Next-generation troponin test cleared
by FDA. Published January 19, 2017. Available
at: https://www.medpagetoday.com/Cardiology/
MyocardialInfarction/62620. Accessed April 20,
2017.
26. Roffi M, Patrono C, Collet J-P, et al. 2015 ESC guide-
lines for the management of acute coronary syn-
dromes in patients presenting without persistent
ST-segment elevation. Task Force for the Manage-
ment of Acute Coronary Syndromes in Patients Pre-
senting Without Persistent ST-segment Elevation of
the European Society of Cardiology (ESC). G Ital
Cardiol (Rome) 2016;17(10):831–72 [in Italian].
27. Than M, Cullen L, Reid CM, et al. A 2-h diagnostic
protocol to assess patients with chest pain symp-
toms in the Asia-Pacific region (ASPECT): a pro-
spective observational validation study. Lancet
2011;377(9771):1077–84.
28. Than M, Aldous S, Lord S, et al. A 2-hour diagnostic
protocol for possible cardiac chest pain in the emer-
gency department: a randomized clinical trial. JAMA
Intern Med 2014;174(1):51–8.

29. Boeddinghaus J, Reichlin T, Cullen L, et al. Two-hour
algorithm for triage toward rule-out and rule-in of
acute myocardial infarction by use of high-
sensitivity cardiac troponin I. Clin Chem 2016;
62(3):494–504.
30. Mueller C, Giannitsis E, Christ M, et al. Multicenter
evaluation of a 0-hour/1-hour algorithm in the diag-
nosis of myocardial infarction with high-sensitivity
cardiac troponin T. Ann Emerg Med 2016;68(1):76–
87.e4.
31. Antman EM, Cohen M, Bernink PJLM, et al. The TIMI
risk score for unstable angina/non–ST elevation MI.
JAMA 2000;284(7):835–42.
32. Chase M, Robey JL, Zogby KE, et al. Prospective
validation of the thrombolysis in myocardial infarc-
tion risk score in the emergency department chest
pain population. Ann Emerg Med 2006;48(3):252–9.
33. Backus BE, Six AJ, Kelder JC, et al. A prospective
validation of the HEART score for chest pain patients
at the emergency department. Int J Cardiol 2013;
168(3):2153–8.
34. Peterson JG, Topol EJ, Roe MT, et al. Prognostic
importance of concomitant heparin with eptifibatide
in acute coronary syndromes. PURSUIT Investiga-
tors. Platelet glycoprotein IIb/IIIa in unstable angina:
receptor suppression using integrilin therapy. Am J
Cardiol 2001;87(5):532–6.
35. Eagle KA, Lim MJ, Dabbous OH, et al. A validated
prediction model for all forms of acute coronary syn-
drome: estimating the risk of 6-month postdischarge
death in an international registry. JAMA 2004;
291(22):2727–33.
36. Scheuermeyer FX, Wong H, Yu E, et al. Develop-
ment and validation of a prediction rule for early
discharge of low-risk emergency department pa-
tients with potential ischemic chest pain. Can J
Emerg Med 2014;16(2):106–19.
37. Cullen L, Greenslade JH, Than M, et al. The new
Vancouver Chest Pain Rule using troponin as the
only biomarker: an external validation study. Am J
Emerg Med 2014;32(2):129–34.
38. Hess EP, Brison RJ, Perry JJ, et al. Development of a
clinical prediction rule for 30-day cardiac events in
emergency department patients with chest pain
and possible acute coronary syndrome. Ann Emerg
Med 2012;59(2):115–25.e1.
39. Than M, Cullen L, Aldous S, et al. 2-Hour acceler-
ated diagnostic protocol to assess patients with
chest pain symptoms using contemporary troponins
as the only biomarker: the ADAPT trial. J Am Coll
Cardiol 2012;59(23):2091–8.
40. Six AJ, Backus BE, Kelder JC. Chest pain in the
emergency room: value of the HEART score. Neth
Heart J 2008;16(6):191–6.
41. de Hoog VC, Lim SH, Bank IE, et al. HEART score
performance in Asian and Caucasian patients pre-
senting to the emergency department with
Chest Pain and Acute Coronary Syndromes 11
suspected acute coronary syndrome. Eur Heart J
Acute Cardiovasc Care 2017. http://dx.doi.org/10.
1177/2048872617700870. 2048872617700870.
42. Mahler SA, Hiestand BC, Goff DC, et al. Can the
HEART score safely reduce stress testing and car-
diac imaging in patients at low risk for major
adverse cardiac events? Crit Pathw Cardiol 2011;
10(3):128–33.
43. Mahler SA, Riley RF, Hiestand BC, et al. The HEART
pathway randomized trial identifying emergency
department patients with acute chest pain for early
discharge. Circ Cardiovasc Qual Outcomes 2015.
http://dx.doi.org/10.1161/CIRCOUTCOMES.114.
001384.
44. McCord J, Cabrera R, Lindahl B, et al. Prognostic
utility of a modified HEART score in chest pain pa-
tients in the emergency department. Circ Cardio-
vasc Qual Outcomes 2017;10(2). http://dx.doi.org/
10.1161/CIRCOUTCOMES.116.003101.
45. Than M, Flaws D, Sanders S, et al. Development and
validation of the emergency department assess-
ment of chest pain score and 2 h accelerated diag-
nostic protocol. Emerg Med Australas 2014;26(1):
34–44.
46. Flaws D, Than M, Scheuermeyer FX, et al. External
validation of the emergency department assess-
ment of chest pain score accelerated diagnostic
pathway (EDACS-ADP). Emerg Med J 2016. http://
dx.doi.org/10.1136/emermed-2015-205028.
47. Than MP, Pickering JW, Aldous SJ, et al. Effective-
ness of EDACS versus ADAPT accelerated diag-
nostic pathways for chest pain: a pragmatic
randomized controlled trial embedded within prac-
tice. Ann Emerg Med 2016;68(1):93–102.e1.
48. Stopyra JP, Miller CD, Hiestand BC, et al. Perfor-
mance of the EDACS-accelerated diagnostic
pathway in a cohort of US patients with acute chest
pain. Crit Pathw Cardiol 2015;14(4):134–8.
49. Vanhoenacker PK, Heijenbrok-Kal MH, Van
Heste R, et al. Diagnostic performance of multide-
tector CT angiography for assessment of coronary
artery disease: meta-analysis. Radiology 2007;
244(2):419–28.
50. Janne d’Othée B, Siebert U, Cury R, et al.
A systematic review on diagnostic accuracy of CT-
based detection of significant coronary artery dis-
ease. Eur J Radiol 2008;65(3):449–61.
51. Schroeder S, Achenbach S, Bengel F, et al. Cardiac
computed tomography: indications, applications,
limitations, and training requirements. Eur Heart J
2008;29(4):531–56.
52. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic per-
formance of 64-multidetector row coronary
computed tomographic angiography for evaluation
of coronary artery stenosis in individuals without
known coronary artery disease: results from the Pro-
spective Multicenter ACCURACY (Assessment by
12 Chang et al
Coronary Computed Tomographic Angiography of
Individuals Undergoing Invasive Coronary Angiog-
raphy) trial. J Am Coll Cardiol 2008;52(21):1724–32.
53. Miller JM, Rochitte CE, Dewey M, et al. Diagnostic
performance of coronary angiography by 64-row
CT. N Engl J Med 2008;359(22):2324–36.
54. Meijboom WB, van Mieghem CAG, Mollet NR, et al.
64-Slice computed tomography coronary angiog-
raphy in patients with high, intermediate, or low pre-
test probability of significant coronary artery
disease. J Am Coll Cardiol 2007;50(15):1469–75.
55. Takakuwa KM, Keith SW, Estepa AT, et al. A meta-
analysis of 64-section coronary CT angiography
findings for predicting 30-day major adverse car-
diac events in patients presenting with symptoms
suggestive of acute coronary syndrome. Acad Ra-
diol 2011;18(12):1522–8.
56. Litt HI, Gatsonis C, Snyder B, et al. CT angiography
for safe discharge of patients with possible acute cor-
onary syndromes. N Engl J Med 2012. http://dx.doi.
org/10.1056/NEJMoa1201163. 120326111245004.
57. Hollander JE, Chang AM, Shofer FS, et al. One-year
outcomes following coronary computerized tomo-
graphic angiography for evaluation of emergency
department patients with potential acute coronary
syndrome. Acad Emerg Med 2009;16(8):693–8.
58. Hadamitzky M, Distler R, Meyer T, et al. Prognostic
value of coronary computed tomographic angiog-
raphy in comparison with calcium scoring and
clinical risk scores/clinical perspective. Circ Cardio-
vasc Imaging 2011;4(1):16–23.
59. Hollander JE, Gatsonis C, Greco EM, et al. Coronary
computed tomography angiography versus tradi-
tional care: comparison of one-year outcomes and
resource use. Ann Emerg Med 2016;67(4):460–8.e1.
60. Schlett CL, Banerji D, Siegel E, et al. Prognostic
value of CT angiography for major adverse cardiac
events in patients with acute chest pain from the
emergency department: 2-year outcomes of the RO-
MICAT trial. JACC Cardiovasc Imaging 2011;4(5):
481–91.
61. Min JK, Dunning A, Lin FY, et al. Rationale and
design of the CONFIRM (COronary CT angiography
EvaluatioN for clinical outcomes: an InteRnational
Multicenter) Registry. J Cardiovasc Comput Tomogr
2011;5(2):84–92.
62. Leipsic J, Taylor CM, Grunau G, et al. Cardiovascu-
lar risk among stable individuals suspected of hav-
ing coronary artery disease with no modifiable risk
factors: results from an international multicenter
study of 5262 patients. Radiology 2013;267(3):
718–26.
63. Takakuwa KM, Halpern EJ. Evaluation of a “triple
rule-out” coronary CT angiography protocol: use
of 64-section CT in low-to-moderate risk emer-
gency department patients suspected of having
acute coronary syndrome. Radiology 2008;248(2):
438–46.
64. Rogers IS, Banerji D, Siegel EL, et al. Usefulness
of comprehensive cardiothoracic computed to-
mography in the evaluation of acute undifferenti-
ated chest discomfort in the emergency
department (CAPTURE). Am J Cardiol 2011;
107(5):643–50.
65. Madder RD, Raff GL, Hickman L, et al. Comparative
diagnostic yield and 3-month outcomes of “triple
rule-out” and standard protocol coronary CT angiog-
raphy in the evaluation of acute chest pain.
J Cardiovasc Comput Tomogr 2011;5(3):165–71.