Advances in Computed Tomography, 2013, 2, 13-19
http://dx.doi.org/10.4236/act.2013.21003 Published Online March 2013 (http://www.scirp.org/journal/act)
How to Reduce Unnecessary Invasive Angiograms When
Patients Are Initially Evaluated by Coronary Computed
Tomography?
Edouard Cheneau1, Bruno Vahdat1, Noémie Resseguier2, Laurent Bernard1, Annamaria Molon1,
Roch Giorgi2, Dimitri Panagides1
1Service de Cardiologie, Clinique Bouchard, Marseille, France
2Service de Santé Publique et d’Information Médicale, Hôpital de la Timone, Marseille, France
Received November 5, 2012; revised December 16, 2012; accepted December 26, 2012
ABSTRACT
Purpose: When Coronary Computed Tomography (CCT) detects coronary obstruction, patients are regularly referred to
invasive angiogram. With higher sensitivity than specificity, CCT might induce unnecessary angiograms (“false posi-
tive CCT”). We sought to determine the patients and CCT findings associated with false positive CCT. Methods: Pa-
tients were prospectively referred to CCT with a 64-slice CT scan for suspected CAD. Inclusion criteria were: 1) clini-
cally suspected angina pectoris; or 2) suspected silent ischemia on resting EKG. Exclusion criteria were acute coronary
syndrome and non sinus rhythm. Invasive coronary angiogram (ICA) was performed on the basis of CCT findings
(stenosis >50%). Analysis was performed on a per patient basis. Results: Out of 702 patients, 228 had suspected sig-
nificant stenosis by CCT and ICA was performed in 176 patients. Coronary stenosis >50% was not confirmed by ICA
in 44 (25%). In multivariate analysis, we observed that atypical angina (OR 3.63, CI 1.43 - 9.66), silent ischemia (OR
5.11, CI 1.89 - 14.6) and number of suspected stenosed arteries by CCT (OR 1.81, CI 1.15 - 2.94) were independently
predictive of false positive CCT (p < 0.05). Lesion location and coronary plaque characteristics did not impact on CCT
accuracy. Conclusions: Performing CCT for atypical angina or silent ischemia is associated with higher rate of unnec-
essary invasive coronary angiograms. We failed to identify lesions characteristics prone to be “false positive” of CCT.
Keywords: Angina; Coronary Disease; Diagnosis; CCT
1. Introduction
Coronary computed tomography (CCT) is a rapidly de-
veloping technique and plays a rising role in angina di-
agnosis [1,2]. CCT has shown high sensibility for de-
tecting obstructive coronary disease in a non-invasive
manner [3,4]. Despite CCT can adequately rule out ob-
structive coronary artery disease (CAD), its high sensi-
tivity is associated with a lower positive predictive value
and a number of coronary stenosis on CCT are not con-
firmed on invasive coronary angiograms. Since CCT has
a growing role as first line work-up for angina pectoris
diagnosis, referring patients with a positive CCT to inva-
sive coronary angiography might induce numerous un-
necessary invasive angiograms [5]. From retrospective
analysis, CCT usefulness appears to be dependent on
pre-test probability for having CAD and might be most
advantageous in subsets of patients, especially those with
an intermediate risk [6]. Consequently, patient selection
prior to CCT enables to increase CCT accuracy.
A complementary approach would be to individualize
subset of patients or CCT findings that are more likely to
be false positive of CCT after they were screened by this
technique. In these patients, a positive CCT would not
justify to directly undergo cardiac catheterization and al-
ternative work-up might be developed. In this study, we
sought to determine the patient characteristics and CCT
findings associated with false positive CCT.
2. Material and Method
2.1. Patients
We included all patients referred to our center for CT
scan as initial work up test to evaluate possible obstruc-
tive coronary heart disease. Patients presenting with ty-
pical or atypical angina pectoris or suspected silent
ischemia on resting EKG were referred for CCT and
prospectively included into the study. CCT is the front-
line test routinely used in our institution for CAD diag-
nosis. Inclusion criteria were patients referred for CCT
without previous myocardial stress imaging or treadmill
C
opyright © 2013 SciRes. ACT

E. CHENEAU ET AL. 14
test and patients with preceding equivocal stress test dur-
ing a six month period.
A dedicated information sheet and database was used
for data collection. Inclusions were opened from January
2009 to December 2010. Typical angina was defined as
having three characteristics: 1) substernal discomfort; 2)
that is precipitated by physical exertion or emotion; and 3)
relieved with rest or sublingual nitroglycerin. Atypical
angina pectoris was defined as having 2 of 3 of the defi-
nition characteristics. Suspected silent ischemia was de-
fined as Q wave or negative T wave on resting EKG in at
least in two derivations in patients with at least one risk
factor. Inclusion criteria were patients referred for CCT
as initial work up test and patients with preceding equi-
vocal stress test. Exclusion criteria were non sinus rhy-
thm, acute coronary syndromes, impaired renal function
(serum creatinine >120 µmol/l) and known allergy to io-
dinated contrast material. The estimated pretest prob-
ability for obstructive CAD was estimated using the
Duke Clinical Score, which includes type of chest dis-
comfort, age, gender, and traditional risk factors [7]. The
protocol was reviewed and accepted by the ethic com-
mittee of our Board of Cardiology.
2.2. Scan Protocol
Patients with a heart rate exceeding 70 beats/min re-
ceived IV beta-blockers (Atenolol 5 to 15 mg) before CT
examination. All scans were performed with a 64-slice
CT scanner (Lightspeed VCT, General Electric Health-
care) that features a gantry rotation time of 350 ms, a
temporal resolution of 175 ms, and a spatial resolution of
0.54 mm3. Tube voltage was 120 kV( 100 kV for patients
weight <70 kg), X-ray tube current was prospectively
modulated on EKG (250 to 650 mA). CT was acquired in
a breath-hold and ECG-gated. Rotation speed and pitch
were adjusted to the acquisition protocols and the heart
rate. Calcium scoring was not performed. A bolus of con-
trast media (Ioxaglate 320 mG I/mL, Guerbet) was in-
fused in an antebrachial vein with use of a dual-barrel
injector (70 cc of contrast media at 5 cc/s washed out by
30 cc of isotonic solution at 3.5 cc/s). CT data were ana-
lyzed by the use of an offline Advantage Workstation
(General Electric) using (curved) multiplanar reconstruc-
tion. Phases from 0 to 90% every 10% were systemati-
cally reconstructed to allow for imaging coronary arteries.
Segments were scored positive for significant CAD if
there was ≥50% diameter reduction of the lumen (at least
2 mm) by visual assessment. Three experienced (more
than 500 CT coronary angiograms) observers blinded
about previous medical history and symptoms partici-
pated in the study. Optimal quality CT scan was defined
as lumen visual assessment available in all >2 mm di-
ameter coronary arteries. Patients with non-optimal qual-
ity CT (including heavy calcification without lumen as-
sessment) were scored positive for significant CAD. All
patients with significant stenosis by CCT were suggested
to undergo to ICA.
2.3. Angiographic Analysis
Baseline quantitative angiography was performed using
the contrast-filled injection catheter for image calibration.
Cine Angiographic stenosis was defined as stenosis grea-
ter than 50%. Quantitative coronary angiographic (QCA)
analysis was performed using the Integris H5000C soft-
ware (Philips, The Netherlands). Patients were classified
as positive for significant CAD if at least one (>2 mm
diameter) coronary artery showed a significant stenosis
(>50%). Patients were classified as true positive CCT if
they were classified as positive for CAD by both CCT
and ICA and false positive CCT if significant stenosis by
CCT was not confirmed by ICA.
2.4. Statistics
All statistical analyses were realized using the R software,
version 2.12.0 (R Foundation for Statistical Computing,
Vienna, Austria). First, a descriptive analysis of all re-
corded data was performed among the overall study po-
pulation. Bivariate analysis was then performed by com-
paring the patients and lesions characteristics of the two
groups, i.e. true positive CCT and false positive CCT.
Continuous variables were expressed as mean ± standard
deviation, and were compared using t-test after graphi-
cally checking of the conditions of the test. Categorical
variables were expressed as number of patients and per-
centages, and were compared using chi-square test or
Fisher test, when appropriate. Variables were retained for
the multivariate analysis when their effect had a p-value
less than 0.25 for the bivariate analysis.
A multivariate logistic regression model was built. A
backward stepwise selection procedure was applied to
retain the significant (p < 0.05) independent variables
and their interactions in the final model. Significance was
determined using likelihood ratio test. The accuracy of
the final model was assessed by Hosmer-Lemeshow test
(HLgof.test R package).
3. Results
We evaluated 702 patients (male 66%) by CCT. Age was
61 ± 11 years. CCT image quality was inadequate in 74
patients (10.5%). Significant obstruction was suspected
in 228 patients (32%) by CCT and invasive coronary
angiogram was performed in 176 patients. Coronary
stenosis was >50% in 132 patients (75%) by ICA. False
positive CCT were observed in 44 patients (25%).
Patients’ characteristics were compared between true

E. CHENEAU ET AL. 15
positive CCT and false positive CCT and Table 1 shows
a higher rate of false positive CCT in women as com-
pared to men, in atypical angina and silent ischemia as
compared to typical angina symptoms. Lesion location
and characteristics detected by CCT were also compared
between the two groups (Table 2). We observed that
false positive CCT was less likely when more coronary
plaques and segment with obstruction were detected by
CCT.
In multivariate analysis, atypical angina (OR 3.63, CI
1.43 - 9.66, p = 0.008), silent ischemia (OR 5.11, CI 1.89 -
14.6, p = 0.002) and number of suspected stenosed ar-
teries by CCT (OR 1.81, CI 1.15 - 2.94, p = 0.010) were
predictive of false positive CCT (Table 3).
Table 1. Indicating patients characteristics.
Stenosis by ICA
(True positive CCT)
N = 132
No stenosis by ICA
(False positive CCT)
N = 44
p
Age (years) 64 ± 12 64 ± 12 0.96
Male 105 (80%) 28 (20%) 0.03
Female 27 (64%) 16 (36%)
Previous CAD 39 (30%) 7 (16%) 0.07
Pretest likelihood for CAD (%) 59 ± 29 53 ± 32 0.20
Angina typical 69 (52%) 13 (30%) 0.03
Atypical 37 (28%) 17 (39%)
Silent ischemia 26 (20%) 14 (32%)
Hypercholesterolemia 62 (47%) 26 (59%) 0.16
Diabetics 35 (26%) 9 (20%) 0.42
Hypertension 63 (48%) 19 (43%) 0.60
Smokers 43 (33%) 10 (23%) 0.22
ST changes by rest EKG 10 (7.6%) 3 (6.8%) >0.99
Q waves 8 (6.1%) 0 (0%) 0.20
Table 2. Indicating lesion characteristics observed by coronary computed tomography.
Stenosis by ICA
(True positive CCT)
N = 132
No stenosis by ICA
(False positive CCT)
N = 44
p
Number of atherosclerotic plaques 1.9 ± 0.8 1.6 ± 0.9 0.047
Number of plaques with stenosis >50% 1.5 ± 1.0 1.1 ± 0.9 0.036
Ostial lesions 12 (10%) 8 (22%) 0.08
Calcified lesions 93 (73%) 31 (79%) 0.43
Left Main 6 (5%) 3 (7%) 0.69
LAD 76 (62%) 19 (53%) 0.31
Diagonal 14 (11%) 6 (17%) 0.40
LCX 31 (25%) 4 (11%) 0.07
Obtuse marginal 12 (10%) 2 (6%) 0.73
RCA 50 (41%) 14 (39%) 0.82
Graft 4 (3%) 0 (0%) 0.57

E. CHENEAU ET AL. 16
Table 3. Indicating predictive factors for true positive corornary computed tomography by multivariate analysis.
OR Lower CI OR Upper CI OR P
Angina
Typical 1
Atypical 3.63 1.43 9.66 0.0076
Silent 5.11 1.89 14.63 0.0016
Number of plaques with stenosis >50% 1.81 1.15 2.94 0.0130
Explanations for false positive CCT were retrospec-
tively analyzed in view of ICA (some patients with more
than one explanation). They were related to stenosis
overestimation (N = 28), inadequate lumen measurement
flanking calcified plaque (N = 17) or ulcerated plaque (N
= 3), myocardial bridge (N = 2), abnormal origin of the
artery (N = 1), and instent lumen assessment (N = 4).
Poor CCT imaging acquisition contributed to eleven
cases of false positive CCT: supraventricular arrhythmia
during acquisition (N = 3), heart rate > 75/min (N = 2),
breathing artifact (N = 2).
Off note, 31 patients out of 144 patients correctly clas-
sified as significant CAD in the true positive CCT group
had one lesion false positive by CCT.
4. Discussion
In this unselected group of patients with suspected CAD,
a positive CCT followed by invasive coronary angiogram
resulted in 25% of unnecessary invasive procedures. The
lowest diagnostic yield of CCT was observed in patients
with atypical angina and suspected silent ischemia. Sec-
ondary, we searched to establish whether some CCT
findings were more likely to be false positive but we
failed to individualize lesion patterns or localization in
which CCT was more imprecise.
Risk stratification and diagnostic strategies are re-
quired for efficient utilization of ICA. However, the di-
agnostic yield of ICA remains low and recent studies
suggest that one fourth to one half of patients who un-
dergo ICA are found to have no obstructive CAD [8,9].
CCT has been compared with invasive coronary an-
giography for the detection of significant coronary artery
lesions in several studies [10]. These studies demon-
strated that significant coronary artery lesions can be
identified with high sensitivity, especially since introduc-
tion of newer imaging modalities of 64 or more detectors
tomography. Appropriate use criteria of CCT are grow-
ing and CCT is increasingly performed for CAD diagno-
sis [5]. When CCT detects coronary obstruction, patients
are usually referred to invasive angiography to confirm
coronary findings and establish treatment. Since CCT
positive predictive value ranges from 80% to 95%, a step
by step approach with upstream CCT will likely be asso-
ciated to unnecessary invasive angiograms [11,12]. In
our study, we included unselected patients with sus-
pected CAD and also observed that 25% of patients did
not have obstructive CAD despite initial positive CCT
finding. This result is encouraging and support findings
that estimate a decrease in normal rate of ICA when car-
diac CT programs are implemented [13]. CCT prevents
to perform invasive angiography more frequently than it
indicates the need for an ‘unnecessary’ invasive testing
[14].
Since CCT is not a perfect “gatekeeper” to ICA, we
investigated the patients characteristics associated to
false positive CCT. We observed that patients with aty-
pical angina and silent ischemia were not good candi-
date for CCT in this regard. These findings are also ob-
served when functional testing is performed before ICA:
a positive stress test has minimal effect on the predictive
ability of diagnosis model of obstructive coronary artery
disease [8]. Therefore, the diagnostic yield of CCT likely
won’t outperform functional tests in suspected silent
ischemia.
Female gender is a consistent predictor of failed strat-
egy for CAD diagnosis with functional tests and women
have more frequently non obstructive invasive angio-
grams [9]. In our study, we did not show a lack of per-
formance of CCT in women. Meijboom et al. found that
positive predictive value of CCT was lower in women
[15]. They attributed the difference to women having
smaller arteries. Since CCT accuracy decreases with
vessel size, higher rate of false positive findings are ob-
served in women on a per-vessel analysis. In our study
that included 240 women, we did not observe that wo-
men had a higher rate of normal angiogram in the multi-
variate analysis. Theoretical limitations of CCT in wo-
man are not translated in large scale analysis on a per-
patient basis. This encouraging finding suggests that a
strategy with CCT as first line test might be useful to take
over difficulties in evaluating chest pain in women [16].
Among patients characteristics, we also confirmed that
age does not impact on CCT accuracy despite older age
is associated with more calcified arteries [17]. This sug-
gests that patients can undergo CCT imaging, independently

E. CHENEAU ET AL. 17
from their age.
Once CCT detects coronary obstruction in epicardial
coronary vessel, patients are commonly referred for ca-
theterization. The goal is to confirm CCT findings and
decision-making for potential revascularization. However,
a greater focus should be placed on CCT findings and
evaluate the likelihood of false positive CCT. That strat-
egy might avoid unnecessary catheterization. In studies
evaluating 64-slice CT to invasive coronary angiogra-
phy, positive predictive value differed between vessels: it
was lower in left circumflex and right coronary arteries
as compared to left descending and left main arteries as
well as in stent and distal segments as compared to native
and proximal segments [18]. However, positive predic-
tive value of CCT remained constantly high in a narrow
range (85% to 93%). As a result, lesion location im-
pacted so slightly on CCT accuracy that anatomical fea-
tures could not be predictive of false positive CCT.
When we compared patients with or without confirmed
coronary obstruction by ICA, we did not see difference
in lesion characteristics or location. No anatomical sub-
group can be identified as “prone to be false positive
CCT”. Though, we logically found that risk for false
positive decreased when more plaques and more signifi-
cant lesions were detected by CCT. Our per-patient ana-
lysis emphasizes the impact of the number of diseased
vessels. Thus, patients with one vessel disease justify con-
sideration before referring to catheterization although
patients with more than one stenosed vessel by CCT can
be more evidently directed to ICA. Performance of CCT
was equivalent in calcified versus non-calcified plaques
and lesion location did not impact on CCT accuracy. At a
patient level, the CORE—64 trials did not find calcium
score as a predictor of diagnostic accuracy of CCT [12].
Even if calcified lesions remain challenging in a per le-
sion analysis, this suggests that calcium does not de-
crease diagnosis accuracy on a per patient basis since the
introduction of 64 detectors scans [18,19].
Overall, we observed that image quality had the great-
est impact on false positive CCT. Our data sustain the
previously described influence of heart rate and rhythm
on image reconstruction [19-21]. In addition, we have
faced overestimation in stenosis measurement. This oc-
currence of stenosis overestimation is likely the most
common mechanism leading to perform non obstructive
invasive angiograms, especially in intermediate stenosis
and complex lesions [22,23]. The definition of positive
CCT we utilized was “50% diameter reduction of the
lumen by visual assessment” to determine significant
stenosis by CCT. Even if this definition is commonly
accepted, it might be insufficient to quantify CAD ob-
struction. New tools are developed to better evaluate lu-
men stenosis with automated quantification [24]. Thus,
predictive value of CCT might increase with computed
quantification, especially in high-quality image recon-
struction [25]. Overall, we utilized best acquisition and
reconstruction methods available at the time of the study
inclusion. However, we didn’t anticipate false positive
CCT and did not implement our strategy in order to de-
crease those occurrences throughout the study. We can-
not state that a higher lumen percent stenosis threshold
might have impacted on “false positive” CCT rate.
This study had limited exclusion criteria. Therefore, it
reflects a “real life” study evaluating coronary artery
disease in a wide spectrum of patients. No functional
testing was requested in the inclusion criteria and the
impact of such test on CCT accuracy has not been evalu-
ated. Secondly, the negative predictive value of CCT has
not been established in this study. Definition for positive
CCT might have been too restrictive and increase posi-
tive predictive value and lower negative predictive value
of CCT. Nevertheless, we observed a negative predictive
value of 99% in a previous study with same inclusion
criteria, CCT methods and analysis criteria [26]. This
suggests that definitions we utilized in the current study
were adequately set in order to preserve high negative
predictive value of CCT.
5. Conclusion
Performing CCT for atypical angina or silent ischemia is
associated with higher rate of unnecessary invasive
coronary angiograms. We failed to identify lesions char-
acteristics prone to be “false positive” of CCT. Improv-
ing CCT imaging and lumen stenosis measurement ap-
pear the best means to reduce the rate of unnecessary an-
giogram following CCT.
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