Download Is Computed Tomography Coronary Angiography the Most Accurate

CONTROVERSIES IN
IMAGING
Is Computed Tomography Coronary
Angiography the Most Accurate and
Effective Noninvasive Imaging Tool to
Evaluate Patients With Acute Chest Pain in
the Emergency Department?
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CT Coronary Angiography Is the Most Accurate and Effective
Noninvasive Imaging Tool for Evaluating Patients Presenting
With Chest Pain to the Emergency Department
Udo Hoffmann, MD, MPH; Fabian Bamberg, MD, MPH
P
atients with acute chest pain (ACP) represent a global
health and economical challenge for the US healthcare
system. The more than 8 million annual emergency department (ED) visits impart a significant economic burden in
excess of $8 billion annually,1–3 particularly as 80% of these
patients are admitted to the hospital and subsequently undergo extensive testing for what often turns out to be
noncardiac chest pain. However, 2% to 8% of discharged
patients inadvertently have acute coronary syndrome
(ACS),4 –7 which accounted for 26% of all money paid in
closed malpractice claims in emergency medicine from 1985
to 2003.8,9
direct and noninvasive assessment of coronary artery disease
(CAD). To provide a rationale for the use of cardiac CT, we
provide a summary of available data on the accuracy of
cardiac CT for the detection of coronary atherosclerotic
plaque and stenosis, as well as the assessment of left
ventricular function. Based on a discussion of the health and
economic risk benefit aspects of this new technology, we
suggest how cardiac CT could be implemented into the
current guidelines to improve accuracy and efficacy of
current treatment of patients with acute chest pain.
Classification of Acute Coronary Syndrome
Acute coronary syndrome is an operational term and describes a clinical syndrome that comprises both the diagnosis
of acute myocardial infarction (AMI) and unstable angina
pectoris.10 Although myocardial necrosis caused by ischemia
is the histological substrate of AMI, unstable angina pectoris
(UAP) is characterized by ischemia without sufficient myo-
Response by Hendel on p 263
Based on the current classification, diagnosis, and management of patients with ACP, this article reviews the role of
currently available functional diagnostic tests and potential of
cardiac CT to improve management of these patients by
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
From the Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
This article is Part I of a 2-part article. Part II appears on page 264.
Correspondence to Udo Hoffmann, MD, MPH, Cardiac MR PET CT Program, 165 Cambridge St, Suite 400, Boston, MA 02114. E-mail
[email protected]
(Circ Cardiovasc Imaging. 2009;2:251-263.)
© 2009 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
251
DOI: 10.1161/CIRCIMAGING.109.850347
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May 2009
Figure 1. Algorithm for evaluation and management of patients suspected of having ACS according to the current ACC/AHA UA/NSTEMI guideline
revision. Patients with “possible ACS” present with
atypical ischemia but are pain free on ED presentation, whereas patients with typical episode of
chest pain, consistent with unstable angina (new
onset, severe, or occurs in accelerating pattern)
are initially classified as definite ACS. SAP indicates stable angina pectoris; Dx, diagnosis. Modified with permission from Anderson et al.11
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cardial damage to release detectable quantities of markers of
myocardial injury.10 The presence of characteristic ECG
changes, for example, ST-segment elevation, and/or the
detection of biomarkers of myocardial necrosis enable further
differentiation of AMI into ST-segment elevation myocardial
infarction (STEMI) or non–ST-segment elevation myocardial
infarction (NSTEMI), respectively.11
Pathophysiology of Acute
Coronary Syndromes
The most common mechanism for ACS is an imbalance
between the myocardial oxygen supply and demand.12 As
identified through histological studies of patients who died of
ACS, sudden rupture of the thin fibrous cap of a lipid-rich
atheroma (thin cap fibrous atheroma) is the most common
cause (55% to 60%), followed by erosion of the cap (30%),
and, less often, calcified nodules within a noncalcified plaque
(⬍10%).13 Consistently, several studies have suggested that
thrombosis of a previously nonstenotic plaque has the most
dramatic consequences. Overall, significant luminal narrowing
on the basis of CAD is the most common cause of ACS
(⬎90%), and such stenosis is found in nearly all STEMI and in
approximately 90% of NSTEMI during subsequent coronary
angiography.14,15 Additional factors are location of the stenosis,
size of the dependent myocardial territory, preexisting CAD
leading to formation of collateral circulation (a phenomenon
known as preconditioning), and blood coagulatory state, with
proximal stenosis location, lack of preconditioning, and hypercoagulability as predictors for sudden death or STEMI.16 –19
Less common causes of ACS include coronary vasospasm,20–23
coronary thrombosis from hypercoagulable states,24,25 coronary embolization,26,27 and potentially endothelial dysfunction.19,28 In addition, myocarditis may mimic ACS and has
been suggested as a common finding in patients with
normal coronary angiogram.29 Women are especially more
likely to have normal angiography during investigation for
acute chest pain.30,31
Current Management of Patients With Acute
Chest Pain
Current guidelines recommend classification of patients with
acute chest into (1) noncardiac diagnosis, (2) chronic stable
angina, (3) possible ACS, and (4) definite ACS (Figure 1),
based on the patient’s history, physical examination, 12-lead
ECG, and initial biomarker tests.11 However, neither a single
set of biochemical markers for myocardial necrosis (troponin
I, troponin T, creatine kinase MB-type [CK-MB]),32,33 nor
initial 12-lead ECG alone or in combination (acute cardiac
ischemia time-insensitive predictive instrument) identifies a
group of patients who can be safely discharged home without
further diagnostic testing.34 –36 Thus, accurate early triage of
patients presenting with acute chest pain to the ED remains
difficult.4,37
As a result, special chest pain observation units (CPU),
originally pioneered by Raymond Bahr in 1982, have gained
popularity rapidly and have been adopted by ED departments
worldwide to master the challenge of the sheer number of
patients with acute chest pain and the intensive testing they
require.38,39 The purpose of a CPU is to facilitate the standard
“rule out” myocardial infarction (MI) protocol, which consists of serial ECG and cardiac biomarker measurements, and
usually a diagnostic test to evaluate for obstructive CAD as the
underlying etiology of the chest pain.40 Currently, the standard
diagnostic test is a functional test, such as exercise treadmill
testing. Although this strategy reduces the number of cases of
missed ACS as compared with traditional in-hospital evaluation,41 this practice has also increased the overall number of
hospitalized patients due to a lower threshold of admitting
patients with acute chest pain to such units.2,42– 45
Hoffmann and Bamberg
Current Standard Diagnostic Testing
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Current American Heart Association/American College of
Cardiology (AHA/ACC) guidelines recommend various testing strategies. Symptom-limited exercise treadmill testing is
recommended in patients who are capable of exercise and
who are free of confounding features on the baseline ECG
(eg, left bundle-branch block, left ventricular hypertrophy,
and paced rhythms; class I recommendation, level of evidence C). In the remaining patients, pharmacological stress
testing with nuclear perfusion imaging, 2D echocardiography, or magnetic resonance should be considered (class I
recommendation, level of evidence C).46
Data on the diagnostic performance of immediate stress
ECG for the detection of ACS are limited.47– 49 However, in a
study of 100 patients with acute chest pain who underwent
exercise ECGs ⬍1 hour after admission, 23% had positive
tests; 38% had negative tests, and 39% had nondiagnostic
tests, whereas an uncomplicated non–Q-wave AMI was
diagnosed in 2%, indicating limited feasibility of this test for
early triage.48,49
Single-photon emission computed tomography (SPECT),
the most commonly performed diagnostic test, is complex,
costly, and time-consuming (ie, ⬇150 minutes for stress
SPECT). In addition, this test is generally not available 24/7
due to the need to have a specifically trained personnel
on-site.48 A number of observational studies demonstrated
that rest SPECT detects significant stenosis with excellent
sensitivity ⬎90% and good specificity (67% to 78%) when
compared with coronary angiography.50 –53 A large randomized multicenter clinical trial in 2475 patients by Udelson et
al demonstrated that incorporating rest SPECT in the initial
evaluation of patients with chest pain results in fewer hospitalizations among patients without acute cardiac ischemia
(n⫽2146, 52% with usual care versus 42% with SPECT
imaging; rate risk ratio, 0.84; 95% CI, 0.77 to 0.92) without
missing more ACS.54 However, according to current guidelines, most CPU order stress SPECT if serial 12-lead ECG
and cardiac biomarker measurements are normal, which has
been shown to improve diagnostic accuracy.34,55 Conversion
of nondiagnostic exercise studies (achieve ⬍85% of maximal
heart rate) to pharmacological stress (eg, adenosine) is recommended. A drawback to rest-stress SPECT studies is
radiation exposure, which is estimated to average 11.3 mSv
with sestamibi and 9.3 mSv with tetrofosmin and is greater
than the exposure from most diagnostic invasive angiograms
(average, 5 to 7 mSv).56 Studies performed with thallium and
a combination of thallium and sestamibi can produce significantly greater exposure (eg, 21 to 29 mSv).
Although rest echocardiography is relatively inexpensive,
easy to perform, and widely available, available data suggest
a similar or slightly lower sensitivity of rest echocardiography when compared with rest SPECT for the detection of
myocardial ischemia.57–59 Stress echocardiography adds significant value to functional assessment at rest and increases
both negative predictive value (NPV) (98.8%) and positive
Cardiac CT for Acute Chest Pain
253
predictive value (PPV) (78%), as demonstrated by Bedetti et
al in 522 patients with acute chest pain, inconclusive ED
evaluation, and normal resting left ventricular (LV) function.
However, stress echocardiography requires highly experienced sonographers and interpreting physicians and is often
not available 24/7.
Overall, available functional tests are limited in their
utilization for early triage because of the complexities connected by their restricted use before the report of serial
negative cardiac biomarkers, the specific training requirements on personnel, and the frequency of nondiagnostic tests.
Although they provide valuable information for risk stratification, their diagnostic accuracy for the detection of significant CAD is limited, leading to unnecessary invasive coronary angiograms in 33% to 44% of patients with suspected
ACS.48,60 Thus, treatment of patients with acute chest pain,
especially early and safe triage of patients at low to intermediate risk for ACS, remains challenging.
Features of Cardiac CT That Make the
Technology Suitable for ED Indications
There are a number of features that are unique to cardiac CT
imaging, which predispose this technique to improve the
diagnostic workup of patients with acute chest pain in a cost
effective manner.
1. Cardiac CT is unique in its ability to noninvasively
visualize CAD and to accurately detect significant stenosis. Moreover, this test extends the spectrum of disease by
visualizing nonobstructive coronary atherosclerotic plaque.
Recent AHA/ACC guidelines for the first time recommend
coronary CT as an alternative to conventional stress testing
(class IIa recommendation, level of evidence B).
2. Cardiac CT is a quick and relatively simple procedure that
can be performed within 10 to 20 minutes. Administration
of ␤-blockers before the scan, for example, with either
intravenous metoprolol (often given in 5-mg increments
every 5 minutes up to a total dose of 25 mg under cardiac
monitoring) or oral atenolol or metoprolol, is recommended for heart rates ⬎65 beats per minute, except when
a scanner with a temporal resolution ⬍100 ms are used.61
3. Advanced cardiac CT technology using at least 64-slice
CT technology, spatial resolution of 0.5 mm in z axis, and
temporal resolution of ⬍250 ms to enable coverage of the
entire coronary artery tree during a short breath hold with
robust image quality62– 64 is becoming widely available in
EDs. Today, ⬇3000 cardiac CT systems based on at least
64-slice are installed around the country.
4. Information on noncoronary cardiac pathologies such
resting global and regional LV function as well as
extracardiac pathologies or “incidental noncardiac findings” can be obtained at no additional cost.
Proper Validation of Diagnostic Imaging for
Clinical Indications
More rigorous validation of diagnostic imaging test for
certain clinical indications is a relatively new requirement
triggered by fast technical developments providing new
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May 2009
options for diagnosis and management as well as the fact that
imaging costs account for a disproportionate share of the
recent increases in national healthcare costs.65 There is not yet
a clear understanding how to validate diagnostic tests. Thus,
we suggest the following steps for validation of diagnostic
tests in reference to the design pharmaceutical trials with a
special emphasis on cardiac CT in patients with ACP.
Phase I
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Feasibility studies determine the diagnostic accuracy of the
technology compared with the gold standard for findings
relevant to the clinical outcome (ie, cardiac CT for the
assessment of coronary atherosclerotic plaque, stenosis, and
LV function as compared with intravascular ultrasound,
invasive coronary angiography, and MRI, respectively).
Phase II
Observational studies determine the population in which the
test has the highest clinical utility by assessing the prevalence
of findings in these populations, the diagnostic accuracy for
clinical outcomes, and the prevalence of these outcomes. The
diagnostic accuracy provides information on the safety of the
test (ie, safe and early ED discharge) and the prevalence of
these findings (ie, plaque and stenosis) and the outcomes
(ACS) provides information on the efficacy. In addition,
diagnostic test characteristics can be explored for several
diagnostic thresholds. However, an unbiased assessment of
these measures is valid only if a blinded design (subjects and
caregivers remain blinded to the results of the diagnostic test)
is used. Thus, such studies can usually be performed only at
a stage when the new technology is not yet clinically
adopted and equipoise exists for blinding the results.
Overall, results from observational trials provide rationale
for guidelines, management decisions, and costeffectiveness analysis although they neglect variations in
“physician-based decision-making.”
Phase III
Randomized diagnostic trials (RDT) determine the efficiency
of a new diagnostic imaging test compared with the standard
of care in the clinical world. They determine how information
from the test will be used by physicians. These trials are
performed unblinded, and information of the new test is used
for decision-making and patient care. Effect measures for
these trials are health outcomes (ie, myocardial infarction,
cardiac death, revascularization) and management and cost
end points (ie, discharge rates, length of hospital stay, time to
diagnosis, diagnosis made, subsequent tests and treatment,
costs). Most likely to change practice are trials that demonstrate superiority of health outcomes. Major characteristics
of trial design are related to balance generalizability versus
precision with respect to study of population, control of
clinical decision-making, hospital setting, and knowledge
and skills of participating physicians. Although less controlled designs permit more generalizable conclusions, it is
sometimes more difficult to establish causality between
results and conditions within the trial (ie, whether physician knowledge, hospital administration, technical challenges with tests).
Phase IV
Clinical algorithms and registries are performed to determine
the clinical usefulness in a broader clinical setting and to
confirm results of RDT. These studies are usually performed
once major societies and regulatory bodies have established
the test at least as a class 2A indication. Their problem is
often an uncontrolled environment, which may make it even
harder to explain the decision-making patterns encountered.
The following paragraphs summarize the status of cardiac
CT research and its role for the triage of patients with acute
chest pain according to these phases.
Phase I: Feasibility Studies on Cardiac CT
Feasibility for the Detection of Obstructive
Coronary Artery Stenosis
To date, ⬎60 studies with ⬎5000 patients have been published investigating the accuracy of cardiac CT to detect
significant coronary artery stenosis. The majority of these
studies are single-center studies typically including middleaged white men at high risk for CAD (⬇60% prevalence of
significant CAD). The results indicate an excellent sensitivity
and NPV and moderate to good specificity and PPV on a
per-patient basis, consistent with the capability to efficiently
rule out the presence of significant stenosis.66 In a recent
systematic review, Stein et al67 summarized single-center
results by pooling available data of 2045 patients on the
diagnostic accuracy of 64-slice CT for the detection of
significant coronary stenosis (⬎50% luminal narrowing). In
this analysis, the investigators derive a summary estimate
of a sensitivity of 98% (96% to 98%), a specificity of 88%
(85% to 89%), an NPV of 96% (94% to 97%), and a PPV
of 93%. Recently published multicenter studies, with the
exception of “Core 64,”68 have now confirmed the excellent sensitivity and NPV coupled with a moderate to good
specificity and PPV across a wide range of disease
prevalence (25% to 68%, Table 1).
For the population of patients with chest pain with a low to
intermediate pretest probability of obstructive CAD, studies
with a low prevalence of disease, such as the ACCURACY
trial, are most relevant. They suggest that cardiac CT can
safely rule out the presence of significant stenosis. However,
they also indicate that the clinical impact of positive findings
may be limited due to the low PPV (47%), which is most
often due to severe calcification. In addition, a number of
considerations that are relevant in the setting of acute chest
pain have not been addressed yet.
1. Although it is known that severe coronary calcification
impairs specificity for stenosis detection, there is no
established calcification threshold based on a non–
contrast-enhanced scan to suggest when not to perform
the standard contrast-enhanced scan.
Hoffmann and Bamberg
Cardiac CT for Acute Chest Pain
255
Table 1. Summary of Published Multicenter Trials on the Diagnostic Accuracy of Cardiac CT for the Detection of Significant
Coronary Artery Stenosis (>50% Luminal Narrowing)
Prevalence,
%
Sensitivity,
%
PPV, %
NPV, %
59.8⫾9,
68% male
32
94 (89 –100)
51 (43–59)
28 (19 –36)
98 (94 –100)
54 (19–83) y,
76% male
58
94 (89–97)
88 (81–93)
91 (86–95)
91 (85–95)
58⫾10 y,
59% male
25
95 (85–99)
83 (76 to 88)
64 (53 to 75)
99 (96 to 100)
⬎40 y body mass index,
⬎40 calcium score ⬎600,
vessels ⬍1.5-mm
diameter
59 median;
IQR, 52–66;
74% male
56
85 (79–90)
90 (83–94)
91 (86–95)
83 (75–89)
⬍50 y and ⬎70 y
60⫾6 68% male
68
99 (98–100)
64 (55–73)
86 (82–90)
97 (94–100)
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Author
Year
Scanner
Patients
Exclusion Criteria
Population
Garcia et al69*
CATSCAN
2006
16
187 patients at 11
centers in 7 countries
⬍2-mm diameter
Marano et al70
NIMISCAD†
2008
16/64
327 patients at 20 sites
in Italy (63 with 64S)
Sustained heart rate ⬎70
bpm
Budoff et al71
ACCURACY
2008
64
230 patients at 16 US
sites
Miller et al68
CORE64
2008
64
291 patients at 9 sites
in 7 countries
Meijboom
et al72
2008
64
360 patients at 3 sites
in Holland
Specificity, %
*Per-patient base analysis with nonevaluable segments graded as positive.
†Per-patient on-site evaluation.
2. Studies have typically excluded smaller (⬍1.5 mm in
diameter) side branches from their accuracy analysis,
which may harbor culprit lesions of small infarcts.68,69
3. Most studies have used ⬎50% stenosis as a criteria for
significance; however, from an interventional point of
view, ⬎70% is typically considered significant. Moreover, although initial data suggest that quantitative
measurement of the degree of stenosis is feasible and
correlates well to invasive coronary angiography in
selected high-image quality examinations,73 it remains
unclear whether accurate separation between 50% and
70% can be achieved. Thus, the feasibility of CT to
support indications for revascularization is unclear.
4. Finally, the feasibility of stenosis detection in a broader
clinical setting that includes community hospitals and
private practices has not been tested in a multicenter,
multivendor feasibility trial.
Feasibility for the Detection and Characterization
of Coronary Atherosclerotic Plaque
Several small studies using 16-slice74,75 and 64-slice CT
technology76 –78 demonstrated the feasibility of cardiac CT to
detect and quantify nonobstructive coronary plaque in the
proximal coronary segments of selected high-quality examinations (sensitivity, 83%; specificity, 94% for the detection of
any atherosclerotic plaque76) as compared with intravascular
ultrasound. Notably, the diagnostic accuracy for the detection
of calcified plaque is significantly higher than for noncalcified plaque.76 –78 Moreover, further characterization of noncalcified plaque into fibrous or lipid-rich plaque may not yet
be possible.79 However, 2 studies have demonstrated that
positive remodeling, higher prevalence of either spotty calcification or exclusively noncalcified plaque, and higher plaque
volume but not the degree of stenosis differentiate culprit
lesions in ACS patients from nonculprit lesions and lesions in
patients with stable angina.80,81
Feasibility of Cardiac CT to Assess Global and
Regional LV Function and Perfusion
The ability of cardiac CT to perform a combined assessment
of coronary morphology and global and regional LV function
without additional radiation exposure or contrast administration constitutes an attractive feature of the modality specifically in the setting of acute chest pain. Cardiac CT is highly
reproducible (␬⫽0.86) and accurate for the detection of
global and regional LV dysfunction when compared with cine
MRI (r⫽0.91).82– 87 Initial studies also suggest that CT may
be feasible to detect myocardial perfusion abnormalities
using first-pass and late enhancement techniques.88 –90
Phase II: Observational Studies on
Cardiac CT
In the 1990s, 3 major studies comprising ⬎400 patients determined the clinical utility of non– contrast-enhanced electronbeam computed tomography imaging of coronary artery calcification (CAC) to rule out ACS in patients with acute chest pain
but inconclusive initial ED evaluation and no known CAD. The
results suggested that the occurrence of ACS among patients
with no or minimal coronary calcification is extremely rare
(NPV, 99% to 100%) but that the detection of CAC renders very
limited PPV.91 Moreover, in a 5-year follow-up, none of the
patients without CAC at baseline had a major adverse cardiovascular event (MACE), demonstrating the excellent midterm
prognostic value of CAC.92
Only 1 observational cohort study using contrast-enhanced
64-slice CT (Rule Out Myocardial Infarction Using Computer Assisted Tomography, ROMICAT) has been published.93 Among 103 patients who presented with ACP but
had an inconclusive initial ED evaluation (nondiagnostic
ECG and negative cardiac enzymes) 14 had ACS (13% event
rate). Both caregivers and patients were blinded to the results
of CT. In this study, none of the patients without CAD
(Figure 2) or stenosis ⬍50% (Figure 3) had ACS (sensitivity,
100%; NPV, 100%). The data suggested that a significant
fraction of patients (⬎40%) may be eligible for early and safe
discharge by using CT, whereas the presence of stenosis
(Figure 4) had limited PPV (47%). The study also suggested
that CT is not feasible in patients with a history of CAD and
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Figure 2. Cardiac CT of a 48 year-old woman who presented to the emergency room with atypical ACP. Initial cardiac biomarkers were
negative and the ECG demonstrated nonspecific t-wave changes. On hospital admission, the patient underwent serial blood sampling
and a stress nuclear perfusion imaging the next day. All tests were normal. Cardiac CT demonstrated the absence of significant coronary stenosis and plaque in all coronary vessels. A, Maximum-intensity projection of the right coronary artery (white arrows). B, Curved
multiplanar reformation of the left anterior descending coronary artery (white arrows). C, 3D volume–rendered reconstruction of the left
main coronary artery (black arrow), the left anterior descending coronary artery (white arrow), and the left circumflex coronary artery
(arrowhead) in an anterior view of the heart. RV indicates right ventricle; LV, left ventricle; AA, ascending aorta.
that the spectrum of CAD is extended compared to stress
functional testing.
evaluations for recurrent chest pain (2% versus 7%, P⫽0.1)
as compared with the stress nuclear perfusion imaging
strategy.
Phase III: Randomized Diagnostic Trials
To date, only 1 single-center, randomized controlled clinical
trial in 197 subjects at very low risk for ACS has been
published.94 Subjects with negative serial troponin and no
history of CAD were randomly assigned to a cardiac CTbased triage system or a stress SPECT-based triage system. In
the CT arm, those with no or minimal CAD were discharged
from the ED, those with intermediate stenosis (25% to 75%)
crossed over to the stress SPECT arm, and those with severe
stenosis were referred to invasive coronary angiography.
There were no events (MI, unstable angina) in the entire study
population during index hospitalization or after 6 months’
follow-up (sensitivity and NPV: 100%). However, consistent
with the superior sensitivity of cardiac CT for the detection of
stenosis, the number of subsequent invasive coronary angiograms was increased (11.1% versus 3.1%, P⫽0.03). The
results supported previous findings that subjects with no or
minimal CAD on CT can be safely discharged. Furthermore,
the CT-based strategy significantly shortened time to diagnosis (3.4 versus 15.0 hours, P⬍0.001) and reduced costs
($1586 versus $1872, P⬍0.001) and resulted in fewer repeat
Phase IV: Clinical Practice Algorithm Studies
on Cardiac CT
Given these encouraging results, there are a growing number
of clinical centers that have incorporated cardiac CT in their
clinical practice. An interesting design was applied in a small
study of 58 patients, including those with a history of CAD,
by Rubinshtein et al.95 Patients received standard ED triage
along with cardiology consultation, after which a presumptive
diagnosis of ACS was made where warranted with recommendations for hospitalization and early invasive treatment.
Cardiac CT was then performed in all patients and recommendations adjusted based on CT findings (discharge with
⬍50% stenosis). Patients were followed for MACE over a
mean of 12 months of follow-up. Cardiac CT results led to a
revised ACS diagnosis in 18 of 41 patients, canceled hospitalizations in 21 of 47, and altered early invasive treatment in
25 of 58. Sensitivity of significant stenosis by cardiac CT for
the detection of MACE during follow-up was 95% (NPV:
97%). The results confirmed that a negative CT has excellent
NPV for ACS and MACE. There is also initial evidence
Figure 3. A 56-year-old man with multiple risk factors who presented to the ED with 2 hours of substernal chest pain and in whom the
initial ED evaluation was inconclusive. Cardiac CT performed before hospital admission demonstrated nonobstructive atherosclerotic
plaque but no significant stenosis. A, Maximum-intensity projection of the right coronary artery demonstrating nonobstructive calcified
plaque in the proximal and distal segment of the vessel (white arrows). B, Curved multiplanar reformation of the left anterior descending
coronary artery demonstrating nonobstructive calcified (white arrow) and noncalcified plaque (dashed arrow). C, Curved multiplanar reformation of the left circumflex coronary artery (white arrow) demonstrating the absence of plaque and stenosis. RV indicates right ventricle; LV, left ventricle; AA, ascending aorta.
Hoffmann and Bamberg
Cardiac CT for Acute Chest Pain
257
in large cohort, Hollander et al97 followed 568 patients who
underwent cardiac CT either immediately in the ED (n⫽285)
or after a brief observation period (n⫽283). Their results
indicate that none of the discharged patients (n⫽476, 84%)
who all had absence of significant stenosis (⬎50%) had a
cardiovascular event (cardiovascular death, nonfatal myocardial infarction) during a 30-day follow-up period. Table 2
summarizes the major phase II and III studies.
Based on the existing evidence, Figure 5 lays out a
proposal on how to use cardiac CT to manage patients with
ACP and no history of CAD considering the latest ACC/AHA
guidelines.
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The “Triple Rule Out” Protocol
Figure 4. A 67-year-old man who presented to the ED with
repeated episodes of increasing stabbing chest pain but inconclusive initial ED evaluation. Cardiac CT performed 3 hours after
presentation to the ED demonstrated a subtotal occlusion of the
proximal right coronary artery (RCA). The patient underwent
stress nuclear perfusion imaging, which demonstrated a reversible inferolateral and inferoseptal perfusion defect. This patient
was diagnosed with unstable angina pectoris (biomarkers
remained negative) and received a percutaneous coronary intervention with stent placement. A, Maximum-intensity projection
of the RCA showing a significant stenosis in the proximal segment of the vessel (white arrow), whereas the distal segment
does not contain any plaque (dashed arrow). B, Curved multiplanar reformation of the left anterior descending coronary
artery demonstrating nonobstructive calcified plaque (white
arrow). C, Curved multiplanar reformation of the normal left
main (white arrow) and left circumflex coronary artery (dashed
arrow). RV indicates right ventricle; LV, left ventricle; AA,
ascending aorta.
suggesting that cardiac CT is at least comparable to stress
nuclear imaging for the detection and exclusion of an ACS in
low-risk patients with chest pain. Gallagher et al96 in 92
patients reported a sensitivity of 71% and a NPV of 97% for
stress nuclear imaging compared with 86% and 99% for
cardiac CT for the detection of ACS, respectively. Notably,
the end point of this study was the presence of significant
stenosis ⬎50%. In a report of a clinical practice CT algorithm
Recent technical developments now permit acquisition of
high-quality images of the coronary arteries, thoracic aorta,
and pulmonary arteries in a single comprehensive cardiothoracic CT scan. The so-called “triple rule out protocol,”
referring to the ability to exclude obstructive CAD, pulmonary embolism, and aortic dissection at once may be an
attractive option to evaluate patients with undifferentiated
chest pain in whom any of the 3 dedicated CT scans may be
performed as standard of care. Initial data suggest that the
protocol is feasible and that extracardiac findings (such as
pneumonia) will be detected in some patients, which will
change management.99 –101 However, research that clearly
demonstrates a benefit of comprehensive CT in these
populations is warranted before clinical implementation,
especially given the overall extremely low event rate in
such studies and the increased exposure to radiation due to
the greater scan length needed to completely image the
thoracic aorta.
Cost-Effectiveness Analysis
As very few questions and scenarios can be addressed within
the confines of a clinical trial, decision-analytic Markov
model– based approaches with the flexibility to model characteristics of populations, diagnostic tests, and patient care
have been used to project possible economic and health
consequences of diagnostic tests. These models enable us to
assess the utility of diagnostic tests from a broader perspective that includes potential risks and benefits associated with
the tests and a lifelong horizon. They are especially helpful
considering that a broad adoption of cardiac CT as a noninvasive imaging option for CAD detection would have an
enormous clinical and financial impact on systems of care.
The results of various modeling approaches agree in their
assessment that an appropriate use of cardiac CT in low- to
intermediate-risk patients with ACP is associated with cost
savings compared with stress testing, especially in younger
men and women.102–104
Incidental Findings
Reporting of incidental findings is a hotly debated topic
because subsequent testing and diagnoses of incidental find-
258
Table 2.
Circ Cardiovasc Imaging
May 2009
Studies Examining the Diagnostic Value of Cardiac CT in Patients Presenting With Acute Chest Pain to the ED
Downloaded from http://circimaging.ahajournals.org/ by guest on June 14, 2017
Year
Study Type
n
Subjects
Outcome of
Interest
Prevalence,
%
Hoffmann
et al93
ROMICAT
2006
Validation cohort
103
54⫾12 y,
60% male
ACS or MACE
at 6 mo
13.6
Gallagher
et al98
2007
Clinical practice
algorithm
85
49⫾11 y,
53% male
Sig stenosis in
ICA or MACE at
30 d
8
Goldstein
et al94*
2007
Randomized
diagnostic trial
99 in CT arm
(197 total)
48⫾11 y,
43% male
Sig stenosis or
MACE 6 mo,
costs, time to
diagnose, no.
of tests
8
Rubinshtein
et al95
2007
Clinical practice
algorithm
58
56⫾10 y,
64% male
1. ACS during
index hosp;
2. MACE 15-mo
follow-up
34; 22
Sensitivity,
%
Specificity,
%
NPV, %
PPV, %
100
100
82
46
100
100
47
23
Sig stenosis
86
92
99
50
Sig stenosis
100
97
100
73
1. Sig stenosis;
2. Sig stenosis
100;
92
92;
76
100;
97
87;
52
CT Criterion
1. Sig stenosis
2. Plaque
Sig indicates significant.
*Testing costs were higher in the CT arm, but shorter average ED time resulted in lower total costs per patient (approximately $300) in the CT arm.
ings may impair cost savings by cardiac CT. In the ROMICAT study, clinically important findings were detected in up
to 5% of patients, but only very few led to a direct change
patient treatment. Further imaging tests were recommended
in ⬇20% of patients, most often to follow up pulmonary
nodules, resulting in invasive procedures and detection of
cancer in few patients.105 Overall, it appears that reporting of
incidental findings is mandatory in symptomatic patients for
medical, ethical, and legal reasons.66
Radiation Exposure
Cardiac CT, SPECT, and invasive angiography all expose
patients to radiation. Radiation doses of retrospectively gated
64-slice CT typically range from 7 to 14 mSv when dose
modulation strategies are used.106 This exposure is comparable to stress SPECT (9 to 12 mSv) and lower than a thallium
myocardial perfusion scan (18 to 21 mSv)107,108 but higher
than the effective radiation dose from an invasive coronary
angiography (5 to 7 mSv). Model-based calculations suggest
that lifetime cancer risk from standard cardiac CT scans
varies from 1 in 143 (0.007%) for a 20-year-old woman to 1
in 3261 for an 80-year-old man (⬍0.0001), with significantly
lower risks using dose modulation (1 in 715 and 1 in 1911,
respectively, for a 60-year-old woman and men.106 In comparison, US women have a 1 in 8 (12.5%) lifetime chance of
developing invasive breast cancer, and the overall cancer risk
for 75-year-old men/women is 6%. Thus, even if the modelbased assumptions of the cardiac CT– based cancer risk
estimates are valid, the incremental risk seems low but
nonneglectable. Moreover, advances using prospective ECG
gating indicate that a low radiation scan option (⬍5 mSv)
may be increasingly feasible to image-selected populations of
ED patients.109,110
Figure 5. Proposed algorithm incorporating cardiac CT in the evaluation of patients with a low to
intermediate pretest probability of CAD (and without history of CAD) who present with suspected
ACS. CT results are used to classify subjects
according to coronary findings (no plaque, plaque
but no stenosis, nondiagnostic [unable to exclude
significant stenosis], and significant stenosis) and
the presence and absence of regional LV wall
motion abnormalities (RWMA⫹ and RWMA⫺,
respectively). SAP indicates stable angina pectoris.
*If 2nd troponin is positive, admit to the hospital
for further evaluation and management according
to current guidelines.
Hoffmann and Bamberg
Future Research and Open Questions
There are a number of major research efforts underway to
complement available data, specifically randomized multicenter trials such as ROMICAT II and CT-STAT; and
registries such as SPARC and the Michigan Blue Cross Blue
Shield registry. We hope that these efforts will be able to
answer some of the important remaining questions about
cardiac CT in the ED, including:
Downloaded from http://circimaging.ahajournals.org/ by guest on June 14, 2017
1. How adequate and how safe is the criterion-significant
CAD defined as 50% stenosis as a discharge criterion,
given that between 10% and 15% of patients with
non-STEMI ACS have no significant stenosis?
2. Cardiac CT improves the sensitivity for the detection of
CAD in the population of low- to intermediate-risk
patients. Will cardiac CT lead to an increase in percutaneous coronary interventions on lesions that would
not have been detected as physiologically significant on
functional imaging studies, or will cardiac CT lead to an
increase in dual diagnostic testing?
3. Cardiac CT extends the detectable spectrum of CAD.
Will the detection of nonobstructive plaque trigger
medical therapy and result in decrease of future cardiovascular events in patients with CAD but no ACS?
4. Can patients be sent home on the basis of CT before a
second troponin is available, which would constitute a
major paradigm shift?
5. Would a negative CAC screening constitute sufficient
evidence for discharge in very low-risk and low-risk
patients?
6. Is there a minimal event rate that justifies the use of
coronary CT and stress nuclear imaging?
7. What is the effect on care for other ED patients who
could be treated more quickly?
Clinical Implementation of Cardiac CT in the ED
CT scanning for pulmonary embolism in the ED could
potentially provide a paradigm for cardiac CT scanning in
patients with ACP, which has been shown to improve patient
outcomes and care.111,112 However, to achieve widespread use
and acceptance by ED physicians, availability of such services
24/7 may be required. Readers will be required to have at least
COCATS II criteria (2 months of training with at least 200
cases). Recent AHA/ACC consensus documents outline the
standard requirements for reporting of cardiac CT scanning.113
Conclusions
In summary, available data suggest that cardiac CT may be
superior to competing tests in the management and especially
the early triage of acute chest pain patients because (1) it is a
fast, relatively simple, and robust test with the potential to be
available 24/7 in both tertiary and community hospital settings, (2) it uniquely provides a direct and noninvasive
visualization for CAD, (3) rapid early discharge of nearly half
of all patients with cardiac pain may be possible by excluding
CAD, (4) extending the spectrum of CAD through the
detection of nonobstructive CAD may result in a more
accurate short- and long-term prediction of cardiovascular
Cardiac CT for Acute Chest Pain
259
event risk and in improved preventive strategies. However,
the growing availability of cardiac CT in EDs across the
United States not only expands the opportunities for its
clinical application but also heightens the need to ensure that
clinical practice is dictated by evidence-based medicine.
Recent attention to radiation exposure, which is inherent with
both SPECT and CT imaging, should also cause us to
carefully consider the appropriate use of these modalities.
Thus, a number of important questions need to be addressed
to justify widespread routine clinical application.
Sources of Funding
Dr Hoffmann was supported by research grants from General
Electric, Siemens Medical Solutions, Bracco Diagnostics, and Bayer
Healthcare.
Disclosures
None.
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Response to Hoffman and Bamberg
Robert C. Hendel, MD
Drs Hoffmann and Bamberg provide an excellent review of the contemporary literature for computed tomography coronary
angiography (CCTA), with a focus on acute chest pain syndromes. This scholarly work also provides an outstanding
paradigm for the validation of CCTA. The data presented are factual but provide only limited support for the routine use
of CCTA for acute chest pain and highlight using this technique in patients without known ischemic heart disease or only
those at very low risk. The discussion regarding the threshold of a significant stenosis is intriguing, including that “the
feasibility of CT to support indications for revascularization is unclear.” This certainly would be a limitation and provides
support for physiological testing, such as with stress testing. Recent advances supporting the use of CT for “triple rule out”
are exciting and may alter practice habits, but the additional radiation and contrast exposure must be considered. The
authors correctly point out the frequent nondiagnostic nature of exercise ECGs, and I also share concern about providing
single-photon emission computed tomography imaging on a 24/7 basis. However, CT coronary angiography also has
significant logistic problems. Their proposed algorithm lacks advice regarding a postadmission strategy and excludes stress
testing completely. In their conclusion, the authors state that “a number of important questions need to be addressed to
justify widespread routine clinical application,” a point with which I completely concur. Although the technology provides
great images and has outstanding clinical potential, it is still premature to state that CCTA is the most accurate and effective
tool for acute chest pain evaluation.
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Is Computed Tomography Coronary Angiography the Most Accurate and Effective
Noninvasive Imaging Tool to Evaluate Patients With Acute Chest Pain in the Emergency
Department?: CT Coronary Angiography Is the Most Accurate and Effective Noninvasive
Imaging Tool for Evaluating Patients Presenting With Chest Pain to the Emergency
Department
Udo Hoffmann and Fabian Bamberg
Circ Cardiovasc Imaging. 2009;2:251-263
doi: 10.1161/CIRCIMAGING.109.850347
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