ORIGINAL ARTICLE

Complementary pre-operative risk assessment

using coronary computed tomography
angiography and nuclear myocardial perfusion
imaging in non-cardiac surgery: A VISION-CTA
sub-study
Taylor F. Dowsley, MD, PhD,a,b Tej Sheth, MD,c and Benjamin J. W. Chow, MD,
FRCPC, FACC, FASNC, FSCCTa,d
a
Department of Medicine (Cardiology and Nuclear Medicine), University of Ottawa Heart
Institute, Ottawa, ON, Canada
b
Department of Cardiology, Sanford Health, Fargo, ND
c
Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research
Institute, Hamilton, ON, Canada
d
Department of Radiology, University of Ottawa, Ottawa, Canada

Received Aug 16, 2018; accepted Apr 22, 2019

doi:10.1007/s12350-019-01779-9

Background. The incremental value and optimal utilization of non-invasive testing for
prediction of peri-operative cardiac events during non-cardiac surgery are not clear.
Methods. A sub-study of VISION-CTA was performed using patients who underwent both
coronary computed tomography angiography (CCTA) and nuclear myocardial perfusion
imaging (MPI) as part of their pre-operative assessment. CCTA images were compared with
MPI to determine the correlation between ischemia and obstructive coronary artery disease
(CAD). Patients were followed post-operatively for 30 days and primary outcomes were all-
cause death and non-fatal myocardial infarction. The predictive capacity of CCTA and nuclear
MPI in predicting peri-operative major adverse cardiac event (MACE) was analyzed.
Results. A total of 55 patients (mean age 68.5 ± 8.4 years, 80.0% male) were analyzed.
There was a strong correlation between the degree of obstructive CAD and the severity of
perfusion abnormalities. Patients with severe CAD (‡ 70% stenosis) had a higher summed
stress score than those without severe CAD [4.88 ± 1.22 and 1.30 ± 0.62, respectively (P < .05)].
Similarly summed difference score was significantly higher in patients with severe CAD
[1.33 ± 0.46 and 0.17 ± 0.17 (P < .05)]. At 30 days there was a total of 8 (14.5%) MACE. The
rate of MACE was higher in patients with severe CAD than those without (20.7% and 7.7%,
respectively). Myocardial ischemia appeared to be predictive of MACE with an unadjusted
odds ratio of 14.63 (P = .003). The predictive capacity of MPI further improved when only
those patients with severe CAD were included (33.00) with a sensitivity, specificity, positive

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Copyright Ó 2019 American Society of Nuclear Cardiology.

1331
1332 Dowsley et al Journal of Nuclear CardiologyÒ
Complementary pre-operative risk assessment using coronary computed tomography angiography July/August 2020

predictive value, and negative predictive value of 100% (79.4-100.0), 72.7% (49.8-89.3), 50.0%
(21.1-78.9), and 100% (79.4-100.0), respectively.
Conclusion. Although patients with significant obstructive disease are at risk of peri-
operative MACE, the absolute event rate is low. Our data, albeit hypothesis generating, suggest
that the peri-operative risk may be refined further by employing nuclear MPI in those with
obstructive disease on CCTA. (J Nucl Cardiol 2020;27:1331–7.)
Key Words: CAD Æ myocardial ischemia and infarction Æ CT Æ MPI

Abbreviations tomography angiography (CCTA) prior to non-cardiac

MACE Major adverse cardiac event
CCTA Coronary computed tomography
angiography
MPI Myocardial perfusion imaging
PCI Percutaneous coronary intervention
INTRODUCTION
Patients undergoing non-cardiac surgery are at risk
of major adverse cardiac event (MACE) (cardiac death,
non-fatal myocardial infarction (MI), non-fatal cardiac
arrest) during the first 30 days after surgery.1 As such,
there is an interest in identifying patients at greatest risk
of peri-operative cardiac events thereby enabling deci-
sions regarding the best pre-operative and peri-operative
strategies as well as in weighing the risk/benefits of
proceeding with surgery. Traditionally, clinical risk
factors and functional capacity have been used to assess
peri-operative risk; however, recent evidence suggests
that these may be suboptimal.1 Consequently, clinicians
often rely on pre-operative non-invasive testing;2 how-
ever, the utility and incremental value of imaging tests
has been challenged.3
The VISION-CTA study was an international mul-
ticenter study of 955 patients, which was designed to
determine the value of pre-operative coronary computed
surgery in predicting MACE.4 Although the study
confirmed that CCTA measures of coronary artery
disease (CAD) severity were an independent predictor
MACE, many patients classified by CCTA as high risk
never experienced peri-operative MACE. Thus the use
of CCTA in this population could lead to the inappro-
priate overestimation of risk.4 Thus further refinement of
peri-operative risk is needed.
The objective of this VISION-CTA sub-study is to
understand the correlation between CAD on CCTA with
ischemia on nuclear myocardial perfusion imaging
(MPI) to determine if CCTA and nuclear MPI are
complementary in prediction of peri-operative MACE.
METHODS
Study Design
Stable pre-operative patients awaiting elective non-car-
diac surgery were enrolled in the VISION-CTA study.4 Of
these, patients who also had nuclear MPI performed as part of
the pre-operative assessment were included. The nuclear MPI
studies were performed within 3 months of the CCTA to be
included. VISION-CTA patients were C 45 years of age who
underwent elective vascular, orthopedic, thoracic, or abdom-
inal surgery requiring hospitalization and had one of the
following: (i) a history of CAD, (ii) risk factors for CAD, and
iii) history of congestive heart failure. Patients were excluded
from VISION-CTA study if there was a history of percuta-
neous coronary intervention (PCI), creatinine
clearance \ 35 mL
min, contrast allergy, pregnancy, persis-
tent atrial fibrillation or C 2 atrial or ventricular premature
beats on pre-operative 12 lead electrocardiogram (ECG),
weight [ 300 lb, inability to achieve heart rate \ 70 bpm
(single-source scanner) or \ 90 bpm (dual source scanner),
did not undergo non-cardiac surgery within 6 months follow-
ing CCTA, more than four non-evaluable segments on CCTA
(non-diagnostic scan), or if pre-operative CCTA demonstrated
significant left main stenosis.

Coronary Computed Tomography

Figure 1. Proposed algorithm for employing initial CCTA
and subsequent nuclear MPI for risk stratification for cardiac
events in high-risk non-cardiac surgery. Positive predictive
value (PPV) and negative predictive value (NPV) included at
each stage.
Angiography (CCTA)
The details of the protocol that was employed for CCTA
are described previously in the VISION-CTA.4 Each partici-
pating center employed C 64-MDCT and images were
analyzed by level 3 expert readers (radiologist or cardiologist)
Journal of Nuclear CardiologyÒ Dowsley et al 1333
Volume 27, Number 4;1331–7 Complementary pre-operative risk assessment using coronary computed tomography angiography

who were blinded to the patients’ clinical factors. Each
angiogram was read using a 17-segment model of the coronary
arteries.5 A common imaging protocol was employed at each
center that specified the use of heart rate control medications,
nitroglycerin, and image reconstructions.4
representing normal uptake (perfusion). The scores for each
segment were summed for a total score for the stress [summed
stress score (SSS)] and rest [summed rest score (SRS)] images.
The summed difference score (SDS) was calculated as SSS-
SRS. Each study was scored by one expert reader blinded to all
clinical and outcome data.

CCTA Image Analysis

For each vessel analyzed, the nature of atherosclerotic
plaque and degree of luminal narrowing were reported.
Degree of luminal stenosis for each vessel was categorized as
(1) normal—no evidence of atherosclerotic plaque, (2) mild
non-obstructive plaque (no plaques C 50% stenosis), (3)
moderate obstruction—at least one plaque with 50%-69%
stenosis (no plaques C 70% stenosis), and (4) significantly
obstructive (at least one plaque with C 70% stenosis). CCTA
findings for each patient were then classified as one of the
following: (1) normal, (2) non-obstructive CAD, (3) moderate
(50%-69%) obstructive CAD, (4) 1-vessel significantly
obstructive CAD, (5) 2-vessel significantly obstructive
CAD, and (6) high-risk anatomy (left main coronary artery
C 50%), 3 vessel CAD or 2 vessels with involvement of the
proximal LAD.
Nuclear Myocardial Perfusion Imaging
(MPI)
Myocardial perfusion images and reports were reviewed
from the three participating centers. Source images were
available for 47 of the 55 patients. A single expert reviewer
who was blinded to all clinical data and CCTA results
reviewed all available images and reports of the MPI studies.
Rest and Stress SPECT MPI
Cardiac Events
Patients were followed post-operatively at 30 days. Pri-
mary outcomes were all-cause death and non-fatal MI. Patients
had troponin measured at 6, 12 hours following surgery and on
postoperative days 1-3. MI was defined using the universal
definition of MI used in the VISION-CTA study. This required
a typical rise in troponin associated with one of (i) ischemic
signs or symptoms, (ii) ischemic changes by ECG, and (iii)
new imaging abnormalities suggestive of infarction. All events
were adjudicated by study personnel from the VISION-CTA
study.4
Statistical Analysis
To compare SSS and SDS values between patients with
and without obstructive CAD, a Mann-Whitney test was used.
Categorical data were expressed as percentages and the
Fisher’s Exact Ratio test was used to evaluate the predictive
capacity of ischemia and obstructive CAD in predicting
cardiac events. Statistical significance was designated at
P \ .05.
RESULTS
A total of 55 patients (mean age 68.5 ± 8.4 years,
80.0% male) were analyzed in this sub-study (Table 1).

Either rest/stress Tc-99m (47 patients) or stress/redistri-

bution Tl-201 (Thallous chloride; Lantheus Medical Imaging)
(8 patients) was performed as per local clinical routine abiding
by the American Society of Nuclear CardiologyÒ guidelines.6
Briefly, patients underwent a 1-day or a 2-day rest/stress Tc- Table 1. Baseline patient characteristics
99m, or a stress/redistribution Tl-201 SPECT. Stress was
performed with either symptom-limited treadmill exercise or N = 55
pharmacologic stress.7 Rest and stress images were acquired
on the same dual-headed cameras using low-energy high- Age 68.5 ± 8.4
resolution collimators with 15% energy window centered on Men 44 (80.0%)
the 140-keV photopeak for Tc-99m or 30% energy window Body mass index (kg
m2) 29.2 ± 5.0
centered on the 70-keV peak and 15% centered on the 167-keV Cardiac risk factors
energy peak for Tl-201.6 ECG-gated SPECT data were Smoker/ex-smoker 50 (90.9%)
acquired and reconstructed using a 64 9 64 matrix. SPECT Hypertension 46 (83.6%)
images were reviewed by expert observers using a standard Diabetes 17 (30.9%)
reporting template.8
Family history of CAD 15 (27.3%)
Medication
SPECT Image Analysis ACE inhibitor 25 (45.5)
Beta-blockers 34 (61.8)
Perfusion images were analyzed using standard 17-seg-
Statin 51(92.7)
ment model. For each segment, the severity in reduction in
tracer uptake was graded using a scale from 0 to 4 with 0
1334 Dowsley et al Journal of Nuclear CardiologyÒ
Complementary pre-operative risk assessment using coronary computed tomography angiography July/August 2020

SPECT Myocardial Perfusion (P \ .05). The odds ratio for severe CAD in predicting
ischemia was 8.47 (P \ .05).
Abnormal myocardial perfusion was present in 17
(31%) patients. Significant myocardial ischemia (SDS
C 2 or significant ischemia by report) was present in 14 Prediction of Cardiac Events by MPI
(25%) of patients. In the 47 patients in whom the MPI and CCTA
images were available, 13 (28%) patients had SSS C 4
At 30 days, there were a total of 8 (14.5%) MACE
and 10 (21%) patients had SDS C 2. Left ventricular
(1 death and 7 non-fatal MI). Two MACE occurred in
ejection fraction was normal in 54 (98%) patients.
patients without severe CAD (7.7%) 1 patient had
moderate stenosis by CCTA, and on MPI had SSS = 10,
Coronary CT Angiography SRS = 10, and SDS = 0 while the other patient had non-
obstructive atherosclerosis on CCTA and normal
A total of 17 (31%) patients had non-obstructive
myocardial perfusion. The rate of MACE was higher
CAD, 9 (16%) patients had moderate CAD, and 29
in patients with severe CAD (20.7%) and all those that
(53%) had severe CAD (1VD (18 patients), 2VD (8
had an event also had significant ischemia on MPI. Four
patients) or high-risk CAD (3 patients).
patients had severe single vessel CAD, 1 patient had
severe 2VD, and one patient had severe 3VD. There was
Correlation Between Severity of CAD a trend towards severe CAD (at least 1 vessel with
and Abnormal Perfusion C 70% stenosis) being a predictor of events with an
odds ratio of 3.13 (P = .19, Table 4).
The number of patients in each category of SSS and
Significant myocardial ischemia was predictive of
SDS and their corresponding severity of CAD by CTA is
MACE on univariate analysis with an unadjusted odds
outlined in Table 2. Patients with non-obstructive CAD
ratio of 14.63 (P = .003) and had a sensitivity, specificity,
or moderate stenosis had relatively low SSS and SDS,
positive predictive value, and negative predictive value of
whereas patients with severe CAD had a greater number
75.0% (CI 34.9 to 96.8), 83.0% (CI 69.2 to 92.4), 42.9%
of patients with significant perfusion abnormalities. The
(CI 17.7 to 71.1), and 95.1% (CI 83.5 to 99.4), respec-
mean SSS in all patients with severe CAD was
tively (Table 5). The predictive capacity of MPI
4.88 ± 1.22 which was significantly higher than that in
improved further when only those patients with severe
patients without severe CAD (1.30 ± 0.62, P \ .05,
CAD were analyzed (odds ratio increased from 14.63 to
Table 3). Similarly, the mean SDS was higher in
33.00 with a sensitivity, specificity, positive predictive
patients with severe CAD, 1.33 ± 0.46 vs 0.17 ± 0.17
value, and negative predictive value of 100% (79.4 to
(P \ .05, Table 3). Finally, the percentage of patients
100.0), 72.7% (49.8 to 89.3), 50.0% (21.1 to 78.9), and
with ischemic myocardium (SDS C 2) in patients with
100% (79.4 to 100.0), respectively (P = .023, Table 5).
severe CAD was 41.38% vs 7.70% for non-severe CAD

Table 2. Number of patients in different categories of abnormal perfusion depending on severity of

obstructive CAD

Summed stress score

0 1-3 4-8 9-13 > 13
CAD severity
Non-obstructive CAD 13 0 1 0 0
Moderate stenosis 7 0 1 1 0
Severe stenosis 8 5 7 3 2
Summed difference score
0 1 2 >2
CAD severity
Non-obstructive CAD 14 0 0 0
Moderate stenosis 9 0 0 0
Severe stenosis 14 1 4 6
Journal of Nuclear CardiologyÒ Dowsley et al 1335
Volume 27, Number 4;1331–7 Complementary pre-operative risk assessment using coronary computed tomography angiography

Table 3. Correlation between CCTA and nuclear myocardial perfusion

Percentage of patients
SSS SDS ischemic (SDS ‡ 2)
Severe CAD (at least 1 vessel 4.875 ± 1.216* 1.333 ± 0.461* 41.38*
with C 70% stenosis, N = 29)
Non-severe CAD (no vessels 1.304 ± 0.627 0.174 ± 0.174 7.70
with C 70% stenosis, N = 26)

*Significantly different than non-severe CAD, P \ .05

Table 4. Frequency of abnormal MPI and CTA results in patients with and without cardiac events

Events (N = 8) No events (N = 47) Odds ratio P-value

(1) Significant ischemia 6 (75%) 8 (17%) 14.63 .003
(2) Severe CAD (C 70% stenosis) 6 (75%) 23 (49%) 3.13 .188
Events (N = 6) No Events (N = 22) Odds ratio P-value
(3) Significant ischemia in 6 (100%) 6 (27%) 33.00 .023
patients with severe CAD
The number and frequency of significant ischemia and severe CAD on CTA (1 and 2) in patients with and without cardiac events
as well as odds ratios of ischemia and CTA in predicting events are shown. The number and frequency of significant ischemia in
the subset of patients with severe CAD (3) in patients with and without events and corresponding odds ratio of ischemia in
predicting events in this subset are shown

Table 5. Diagnostic accuracy of MPI and CCTA in predicting peri-operative MACE

Sensitivity Specificity PPV NPV

Significant 75.0% (34.9 to 96.8) 83.0% (69.2 to 92.4) 42.9% (17.7 to 71.1) 95.1% (83.5 to 99.4)
ischemia
Severe CAD 75.0% (34.9 to 96.8) 51.1% (36.1 to 65.9) 20.69% (8.0 to 39.7) 92.3% (74.9 to 99.1)
Significant 100.0% (54.1 to 100.0) 72.7% (49.8 to 89.3) 50.0% (21.1 to 78.9) 100% (79.4 to 100.0)
ischemia in
patients with
severe CAD

DISCUSSION MACE post-operatively.1 The use of clinical risk indices

may underestimate the true peri-operative risk.1 This has
This hypothesis generating sub-study suggests that
led to the use of pre-operative non-invasive testing with
(i) there is a strong correlation between degree of
hopes of better estimating each patient’s risk of MACE.
obstructive disease on CCTA and perfusion abnormal-
However, a meta-analysis has questioned the value of
ities on nuclear MPI in patients undergoing elevated risk
stress echocardiography and nuclear MPI suggesting
surgery, and (ii) nuclear MPI may be complementary to
that these tests have only moderate predictive value.3
CCTA and improve the identification of patients at risk
They demonstrated that one-third of patients who
of peri-operative MACE, and may play the greatest role
suffered a major cardiovascular event had a negative
in stratifying patients with severe CAD detected on
test and only strongly positive tests with moderate to
CCTA.
large areas of ischemia had significant positive predic-
More than 200 million non-cardiac surgeries are
tive value.3
performed annually worldwide and patients are at risk of
1336 Dowsley et al
Complementary pre-operative risk assessment using coronary computed tomography angiography
The results of the VISION-CTA study demonstrated
that CCTA measures of CAD severity were a predictor
of peri-operative MACE, but there were concerns that it
might inappropriately reclassify a large population into
the high-risk category.4 The lack of MACE in patients
with obstructive CAD underscores the complex nature
and likely multiple mechanisms of peri-operative MI.1
Currently, there may be difficulty in assessing the
hemodynamic consequences of stenotic lesions and the
‘vulnerability’ of atherosclerotic coronary plaque.9 This
discordance between anatomy and function has been
previously highlighted.
As the literature has suggested only moderate
predictive capacity of nuclear MPI and results of the
VISION-CTA study although predictive of MACE
would inappropriately classify a large percentage of
patients as high risk, the value of either of these tests in
isolation pre-operatively is questionable. Yet, identify-
ing those patients at highest risk of MACE is paramount
particularly for high-risk non-cardiac surgery. Our data
suggest that the two modalities are complementary in
risk stratification. In our study, only 7.7% of patients
without severe CAD experienced an event. This demon-
strated the excellent negative predictive capacity of
CCTA in this population. Nearly half of the patients in
our study could be reliably identified as low risk based
on the CCTA results (Table 3). Similar to the VISION-
CTA study, in our subgroup of patients, there would be a
large percentage of patients misclassified as high risk
based on results of CCTA alone (Table 4). By employ-
ing nuclear myocardial perfusion in the subset of
patients with severe CAD, significant ischemia was a
strong discriminator for predicting MACE (Table 4).
These data suggest utility of a strategy for pre-operative
risk assessment with the use of an initial CCTA with
further refinement by nuclear MPI in patients with
severe CAD (Figure 1).
Employing this strategy would result in the use of
two non-invasive tests in just over half of the patients in
our study which represents a high-risk group. This is
warranted given that the use of clinical risk predictors
alone, or single non-invasive testing cannot reliably
predict cardiac events. In a high-risk population, this
potentially leads to a relatively high rate of MACE,
inappropriate cancelation of surgery, or coronary
angiography with revascularization which can result in
delays either with CABG or PCI. Moreover, data do not
support pre-operative revascularization in most cases, a
notable exception is patients with significant left main
disease.4 It is important to note that patients that had
significant left main disease by CCTA were unblinded
and excluded from the trial VISION-CTA study and
hence from our sub-analysis. The initial use of CCTA
can identify these patients with left main disease upfront
Journal of Nuclear CardiologyÒ
July/August 2020
that are clearly at high risk without the need for further
non-invasive testing. Our data also suggest that signif-
icant risk of events occurs in patients without left main
disease and these events can be predicted with the
combined use of CCTA and nuclear MPI.
The mechanism of peri-operative MI is poorly
understood.1 A proposed mechanism relates to myocar-
dial supply-demand mismatch which may be associated
with fluid shifts, catecholamine surges, hypotension,
anemia, and hypoxia. These changes can increase
myocardial oxygen demand suggesting that ischemia
testing may indeed identify patients who could be most
susceptible. Alternatively, plaque rupture causing acute
coronary syndrome can occur in either lesions with or
without significant stenosis. Since ischemia and signif-
icant stenosis by CCTA were predictive of events, our
data suggest that supply-demand ischemia may have
been the predominant mechanism of MI. It is important
to acknowledge that our results differ from those of two
large meta-analyses that assessed the ability various
non-invasive modalities to predict peri-operative cardiac
events.3,10 The first assessed both nuclear MPI and stress
echocardiography and demonstrated moderate predictive
value of nuclear MPI in predicting events.3 However,
this meta-analysis studied a lower risk population with
MACE rates of 7.5% and 8.1% for stress echocardio-
graphy and nuclear myocardial perfusion, respectively,
as compared with 14.5% in our study. Our study
included a high percentage of vascular surgery patients
(69%) which likely explains the higher MACE which in
turn may have contributed to the higher predictive
capacity of ischemia testing. The second meta-analysis
compared the use of six different stress modalities in
vascular surgery patients.10 The meta-analysis demon-
strated a sensitivity of 83% and specificity of 40%. The
reason for the lower specificity in this prior study may
have been related to the fact that any fixed or reversible
defect was considered positive as compared with our
study, which used ischemia as the predictor of outcome.
The results of these studies may have suffered from false
positive test results. The results of our study suggest that
CCTA could be used as an initial test to exclude severe
CAD, however, MPI would be used to further refine risk
only in those with severe CAD. Further studies are
needed to understand if this is a feasible diagnostic
strategy.
It was unexpected that the SSS and SDS were
slightly lower in the high-risk CAD than patients with
severe single- and double-vessel CAD. A potential
explanation could be that 3 vessel disease can result in
‘‘balanced ischemia’’ and potentially appear normal on
MPI. More likely, however, is that the small number of
patients with high-risk anatomy in our study does not
Journal of Nuclear CardiologyÒ
Volume 27, Number 4;1331–7 Complementary pre-operative risk assessment using coronary computed tomography angiography
reflect an accurate assessment of myocardial perfusion
in this subset.
LIMITATIONS
A limitation of the present investigation is that due
to the relatively small sample size, the study was not
powered to assess the predictive capacity of CCTA and
nuclear MPI in predicting peri-operative MACE in
multivariable analysis. In addition, the small percentage
of female patients suggest that the results may not be
applicable to this group. Our study also had higher
MACE rate than the VISION-CTA study likely due to
selection of higher risk patients who would be more
likely to meet the requirement of additional pre-opera-
tive testing with nuclear MPI. Hence, results may be
more applicable to this higher risk cohort than to the
general population. Our results are encouraging however
and indicate a need for further investigations to deter-
mine the complementary value of CCTA and nuclear
MPI in predicting peri-operative MACE and whether
there is significant incremental value above traditional
clinical predictors.
Another limitation was that an accurate assessment
of the predictive capacity of high-risk anatomy on
CCTA could not be ascertained. A greater number of
patients with high-risk anatomy would be required to
determine the likelihood of events in this subgroup.
However, in our study, a significant number of events
occurred in the absence of high-risk anatomy (7/8).
Using high-risk anatomy as a predictor of events would
seem to have a low sensitivity, however, to determine
the specificity and positive predictive value of high-risk
anatomy for predicting peri-operative events would
require further studies.
NEW KNOWLEDGE GAINED
In conclusion, the present investigation suggests
that CCTA may be a useful initial test for pre-operative
prediction of cardiac events with normal or minor
findings portending a very low risk of events. In patients
with significant obstructive disease, nuclear MPI may be
complementary for further refining risk assessment.
Disclosures
Benjamin Chow holds the Saul and Edna Goldfarb Chair
in Cardiac Imaging Research. He receives research support
from CV Diagnostix and educational support from TeraRecon,
Inc. All other authors have no conflict of interests to disclose.
Dowsley et al 1337
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