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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 1, January/February 2018
20
AFRICA
disease in the FAME [Fractional Flow Reserve (FFR) versus
Angiography in Multivessel Evaluation)] study.
13
However, FFR
is limited by its invasive nature, and non-invasive approaches
such as CT-FFR, SPECT and CMR are needed.
More recently, CT-FFR was described in the DISCOVER-
FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via
Noninvasive Fractional FlowReserve) study.
6
Although the study
results have been encouraging, this technique requires much time
as well as analysis on a parallel supercomputer. By contrast,
TAG can be applied to any CCTA study in daily practice. This
technique does not require any modification of CCTA protocols
and involves a relatively simple analysis without the need for
complicated software, therefore suggesting the possibility of a
non-invasive functional assessment of coronary stenosis.
7
Contrast opacification on single-shot CCTA with wide-area
detector CT is homogenous along the length of a normal coronary
artery, but exhibits a linear drop-off in luminal HU along
the length of the artery in the presence of haemodynamically
significant coronary artery stenosis.
14
Choi
et al
. reported a low
sensitivity but high specificity for TAG measured in 64-detector
row CCTA that, when added to CCTA percentage stenosis
information, significantly increased the area under the receiver
operating characteristic curve for the detection of an abnormal
invasive FFR
<
0.8.
15
However, an earlier study of TAG was
performed using a 64-slice multi-detector row scanner,
8,15
which
had a limitation of temporal heterogeneity in coronary artery
opacification.
Wong
et al
.
7
reported that TAG independently predicted
FFR
<
0.8 and increased both the sensitivity and specificity of
information on CCTA percentage stenosis. That study used a
320-detector row CT scanner, but performed rest CCTA without
stress CCTA. Thereafter, another study compared the diagnostic
accuracy of combined CTP and TAG320.
9
Both stress and rest
CCTA were performed using 320-detector row CT scanner, but
an initial rest CCTA scan was followed by a stress CCTA scan.
As a result, cross-contamination of contrast during the second
acquisition (stress CCTA) might have led to false negatives.
We used a CCTA protocol in which the stress phase is
followed by the rest phase during a single examination, which
differs from the protocols used in previous studies. Performing
a stress phase acquisition first could allow a ‘clean’ acquisition,
thus optimising the detection of haemodynamically significant
coronary artery stenosis by avoiding contrast contamination.
16
This protocol is suitable for patients with an intermediate to high
pre-test probability of CAD, patients with high calcium scores
(> 400 mg/dl), and patients with known CAD. We used a CT
protocol in which the stress phase was followed by the rest phase
because our patients had exhibited moderate coronary artery
stenosis during ICA.
Interpretation of TAG may be limited by multiple heartbeat
acquisition algorithms and coronary calcification. The use
of a wide-area detector allows a longitudinal axis of 16 cm,
which in most instances enables the entire heart volume to be
imaged in a single gantry rotation with a short breath-hold
time. This is ideal for TAG functional assessments of coronary
arterial stenosis because this modality would enable non-invasive
quantitative assessment of coronary contrast changes with
temporal uniformity,
7,14
and eliminate step registration artifacts.
Radiation dose is a major issue concerning the clinical
application of stress CCTA. To determine the optimal
enhancement time, a 10-s stress CCTA scan was performed,
causing a relative increase in the radiation dose of our protocol
(10.6
±
2.6 mSv) relative to the doses of previous studies. The
radiation dose may decrease with a static scan or dynamic stress
CCTA with a shorter scan duration. Although dynamic scanning
results in higher radiation doses, its advantages includes the
ability to determine the optimal enhancement time or to generate
dynamic data sets for the visual analysis of serial dynamic
images. Further studies are needed to reduce the radiation doses
from dynamic CT scans before implementing widespread use.
To our knowledge, we have compared for the first time the
diagnostic accuracy of TAG of stress CCTA using a wide-area
detector CT with that of stress perfusion CMR as a reference
standard. In many studies, invasive FFR is becoming more
widely accepted and is selected as the reference standard, but
FFR has disadvantages such as its invasive nature, the associated
radiation exposure, and high costs.
17
Stress perfusion CMR has been established as a non-invasive
diagnostic modality with a high diagnostic accuracy for inducible
perfusion defects. This modality has the advantage of no
radiation exposure or attenuation artifacts. The diagnostic
accuracy of stress perfusion CMR is significantly greater than
that of SPECT,
18
and a qualitative visual analysis of CMR
versus FFR identified an excellent diagnostic accuracy for the
detection of functionally significant CAD, using a FFR cut-off
value
<
0.75 for discriminating haemodynamically significant
from non-significant stenosis.
19,20
CMR has become an important
non-invasive diagnostic modality for the clinical work-up of
patients with significant coronary artery stenosis.
In five (9%) coronary arteries (one LAD, two LCX and two
RCA), the TAGs of stress CCTA were not consistent with the
findings of stress perfusion CMR. Two RCAs were hypoplastic,
and one LCX exhibited diffuse atherosclerotic changes. On the
TAGs of these vessels, the transverse graph axis, which represents
the distance from the ostium to the distal coronary artery, was
relatively short, and the diameters of the coronary arteries were
small, and TAG indicated a false positive. On the other hand, the
TAG of one LCX and one LAD indicated a false negative. The
LCX had stenosis of the far distal portion of the coronary artery,
and the LAD had stenosis of the coronary ostium. The stenotic
portion of the coronary artery was the beginning or end-point
on the transverse graph axis, and therefore the intraluminal
attenuation gradient of these vessels was not affected by HU in
the stenotic portions of the coronary arteries.
Limitations
This study has some limitations. First, this was a single-centre
study with a small sample of patients who underwent ICA.
Larger, multi-centre studies are needed to provide further
functional information and confirmation, using stress perfusion
CMR as a reference. Second, the radiation dose incurred during
stress CCTA was relatively high. A 10-s scan duration was used
to determine the optimal enhancement time for dynamic stress
CCTA. Therefore, a shorter dynamic stress CCTA scan duration
should be adopted to reduce the radiation dose.
Third, the TAG is influenced by the scanner hardware and the
measurement technique. There is no standardised measurement
method, and obtaining TAG remains time consuming. Although
a semi-automated programme has been introduced, currently