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Objective The purpose of this study was to determine combination of perfusion and WM increased from 31.40 to
whether regional wall motion (WM) abnormalities 50.71 (P < 0.001) compared to perfusion. The sensitivity of
by rest-only 99mtechnetium-sestamibi (99mTc-MIBI) combination of perfusion and WM for detecting obstructive
electrocardiogram (ECG)-gated single-photon emission CAD in patients with multivessel disease was higher than
computerized tomography (SPECT) myocardial perfusion single-vessel disease (56.1% vs. 25.0%; P < 0.001), with
imaging (MPI) had incremental diagnostic value for similar specificity.
detecting obstructive coronary artery disease (CAD) in
Conclusion Regional WM abnormalities at rest, as
suspected CAD patients.
shown by rest-only 99mTc-MIBI ECG-gated SPECT MPI,
Methods This study retrospectively studied 255 have additional diagnostic value over perfusion alone for
consecutive suspected CAD patients who underwent detecting obstructive CAD in suspected CAD patients.
rest-only ECG-gated SPECT MPI and were performed Nucl Med Commun 42: 276–283 Copyright © 2020 Wolters
coronary angiography within 3 months. Obstructive CAD Kluwer Health, Inc. All rights reserved.
was defined as ≥70% narrowing of the inner diameter of Nuclear Medicine Communications 2021, 42:276–283
the left anterior descending coronary artery, left circumflex
Keywords: coronary artery disease, electrocardiogram-gated,
coronary artery and right coronary artery or their main myocardial perfusion imaging,
branches and ≥50% narrowing of the left main coronary single-photon emission computerized tomography, wall motion
artery. QPS and QGS were used to assess rest perfusion a
Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow
and WM. Summed rest score ≥4 and summed motion University, bChangzhou Key Laboratory of Molecular Imaging, Changzhou,
score ≥2 exhibited in two consecutive segments in one Jiangsu Province, cDepartment of Nuclear Medicine, Affiliated Beijing Chaoyang
Hospital of Capital Medical University, Beijing, dDepartment of Cardiology, The
territory was considered abnormal. Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province
and eDepartment of Nuclear Medicine, The First Hospital of Shanxi Medical
Results The sensitivity of the combination of perfusion University, Taiyuan, Shanxi Province, China
and regional WM abnormalities was significantly higher Correspondence to Yuetao Wang, MD, Department of Nuclear Medicine,
than perfusion alone for detecting obstructive CAD The Third Affiliated Hospital of Soochow University, No.185, Juqian Street,
(46.8% vs. 30.9%; P < 0.001), with similar specificity Changzhou, Jiangsu Province 213003, China
Tel: +86 013852040196; fax: +86 519 86621235; e-mail: yuetao-w@163.com
(91.9% vs. 95.0; P = 0.063). The global chi-square value of
Received 23 August 2020 Accepted 26 October 2020
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Incremental value of regional wall motion abnormalities Liu et al. 277
MPI can provide information on perfusion, global and minutes later. Acquisitions were performed using a dual-
regional function through one-step station with high head 90° gamma camera (Symbia T16; Siemens Medical
reproducibility and repeatability [6–8]. Previous stud- Systems, Erlangen, Germany) equipped with a paral-
ies [9–12] have shown that regional wall motion (WM) lel-hole collimator with low energy and high resolution.
changes after stress add incremental diagnostic value for A 20% symmetric energy window around the 140-KeV
detection of severe CAD. photopeak and eight frames per R-R cycle were used for
image acquisition. Sixty-four images covering 180° were
However, stress testing cannot be applied to all patients, obtained with a 64 × 64 matrix and 1.45 magnification.
especially in patients with suspected acute coronary syn- The ‘beat-length acceptance window’ was ± 20% of the
drome (ACS), or other people with exercise and drug expected R-R duration. Projection data were filtered
test contraindications such as severe heart failure. There with a Butterworth filter (order, 5; cutoff frequency, 0.4)
are about 2.5 million patients with ACS [13] and a large and then reoriented to obtain left ventricle (LV) short-
number of suspected ACS patients in the real world of axis, horizontal long-axis, and vertical long-axis images
China every year. It is especially important to improve through filtered back projection. No attenuation correc-
the ability of rest-only SPECT MPI to detect obstructive tion was used in this study.
CAD. In addition, our previous research [14] has found
that reduced wall thickening exists in normal perfusion Quality control
segments on resting MPI in patients with MI. Previous We performed quality control procedures in the pro-
studies have found that 30% of suspected CAD patients cess of original image acquisition, reconstruction, and
have abnormal resting perfusion [15] and a decrease of image quantification, including observing whether the
10–20% in subendocardial blood flow would be adequate myocardial radioactive uptake was good, whether there
for inducing severe regional dysfunction [16]. Therefore, was leakage of imaging agent injection, and whether
the goal of the present study was to determine whether there was a radioactive focus outside the heart. We
regional WM abnormalities based on rest-only 99mTc- also checked the original image to see if there was any
MIBI ECG-gated SPECT MPI had incremental diag- movement and checked the gated quality control curve,
nostic value for detecting obstructive CAD in suspected sinogram and linogram in the tomographic processing.
CAD patients. Patients who did not meet the above quality control
requirements were excluded. The adjustment of the
Methods tomographic axis was performed automatically, supple-
Patient enrollment mented by manual adjustment. The long-axis direction
We retrospectively studied 2038 consecutive patients should be parallel to the longest axis of the LV. Image
who performed ECG-gated SPECT MPI at the Third quantification was performed automatically by the soft-
Affiliated Hospital of Soochow University between ware. When the automatic delineation was not good,
March 2015 and November 2018. Inclusion criteria: sus- we would make appropriate manual adjustments to
pected CAD patients, rest-only 99mTc-MIBI ECG-gated ensure accurate sampling of the myocardial boundary
SPECT MPI was performed, coronary angiography was contours.
performed within 3 months of SPECT MPI. Three hun-
dred eleven patients were initially enrolled. Exclusion Image analysis
criteria were severe valve disease (n = 9), hypertrophic or A 17-segment model of the LV was used for scoring
dilated cardiomyopathy (n = 15), significant arrhythmia resting perfusion by a dedicated software package
(n = 21) and poor overall image quality (n = 11). Finally, (QPS 2009; Cedars-Sinai Medical Center, Los Angeles,
there were 255 patients with suspected CAD in this California, USA), with a five-point scoring system for
study. The enrolled population all had stress contraindi- defect severity (0 = normal perfusion; 1 = mildly reduced;
cations [17], including 62 patients with suspected ACS, 2 = moderate reduction; 3 = severe reduction; 4 = absent
61 patients with asthma, 53 patients with systolic blood perfusion) [18].The summed rest score (SRS) was the
pressure >200 mmHg before examination, 41 patients sum of all perfusion scores on the rest scan. The QGS
with limb movement disorders also combined with software package was used to quantitatively measure
second- or third-degree atrioventricular block without end-diastolic volume, end-systolic volume, LV ejection
a functioning pacemaker, 38 patients with decompen- fraction (LVEF) and summed motion score (SMS) from
sated heart failure. This was an observational study and resting ECG-gated SPECT MPI. A scale of 0–5 was used
the data were analyzed anonymously, so there was no for grading WM (0 = normal, 1 = mildly hypokinetic,
informed consent. 2 = moderately hypokinetic, 3 = severely hypokinetic,
4 = akinetic, 5 = dyskinetic) [19]. To allow for statistical
Resting image acquisition correlation with angiographic findings, the 17 segments
99m
Tc-MIBI (740–925 MBq) was injected intravenously for both perfusion and WM were divided into the terri-
at rest, and ECG-gated SPECT MPI was initiated 60–90 tories of left anterior descending coronary artery (LAD),
Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
278 Nuclear Medicine Communications 2021, Vol 42 No 3
Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Incremental value of regional wall motion abnormalities Liu et al. 279
patients with abnormal perfusion and WM, 44 territo- (P < 0.001) compared to perfusion and the specific-
ries showed abnormal perfusion. Among the 44 abnor- ity was slightly reduced (94.7% vs. 98.1%; P = 0.016)
mal perfusion territories, 42 (95.5%, 42/44) territories (Fig. 3).
also showed abnormal WM, showing good consistency.
In addition, combination of regional WM and perfu- Incremental value of combination of regional wall
sion abnormalities had 13 (8.1%, 13/161) misdiagnosed motion and rest perfusion for detecting obstructive
patients which stenosis <70%. The clinical and coro- coronary artery disease in patients with multivessel
nary angiography results of these patients are exposed disease
(Table 3). The association of WM and perfusion abnormalities had
higher sensitivity (56.1% vs. 25.0%; P < 0.001) for detect-
Incremental value of regional wall motion ing obstructive CAD in patients with multivessel disease
abnormalities to rest perfusion alone for detecting than in patients with single-vessel disease, with similar
severe coronary stenosis in overall, left anterior specificity. Combination of WM and perfusion abnormal-
descending coronary artery, left circumflex coronary ities correctly identified 37 (56.1%, 37/66) patients with
artery and right coronary artery territories multivessel disease and seven (25.0%, 7/28) patients with
The sensitivity for detecting severe coronary stenosis single-vessel disease (Fig. 4). A patient example is shown
was higher for association of perfusion and WM than for (Fig. 5).
perfusion alone in overall territories (36.7% vs. 20.4%,
respectively, P < 0.001), with slightly reduced specificity
(94.7% vs. 97.2%; P < 0.001). In LAD territories, the sen-
Discussion
The present study confirmed that combination of
sitivity of combination WM and perfusion for detecting
regional WM abnormalities and perfusion by rest-only
severe coronary stenosis increased from 27.6% to 40.2% 99m
Tc-MIBI ECG-gated SPECT MPI had incremen-
(P = 0.001) compared to perfusion, with no significant
tal value for detecting obstructive CAD in suspected
difference in specificity (92.3% vs. 95.2%; P = 0.063). In
patients. The sensitivity of the association of regional
LCX territories, the sensitivity of association WM and
WM and perfusion abnormalities was significantly
perfusion was higher than perfusion (22.6% vs. 11.3%;
higher than perfusion for detecting obstructive CAD
P = 0.016), with no significant difference in specificity
(46.8% vs. 30.9%; P < 0.001), without a significant loss in
(96.9% vs. 97.9%; P = 0.500). In RCA territories, the sen-
specificity. The global chi-square value of combination
sitivity of combination WM and perfusion for detecting
of perfusion and regional WM abnormalities increased
severe coronary stenosis increased from 19.1% to 48.9%
Fig. 2
Fig. 1
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280 Nuclear Medicine Communications 2021, Vol 42 No 3
Table 3 Individual analysis of abnormal wall motion/perfusion in patients without obstructive coronary artery disease (n = 13)
CAD, coronary artery disease; CMD, coronary microvascular dysfunction; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; RCA, right
coronary artery; WM, wall motion.
Fig. 3
The sensitivity and specificity of perfusion alone and combination of perfusion and WM for detecting severe coronary stenosis in overall, LAD,
LCX and RCA territories. LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; RCA, right coronary artery; WM, wall
motion. *P < 0.05 compared with perfusion alone.
from 31.40 to 50.71 (P < 0.001) compared to perfusion with stress contraindications cannot perform stress ECG-
alone. The sensitivity of combination of perfusion and gated SPECT MPI. Taban Sadeghi et al. [15] evaluated
WM for detecting obstructive CAD in patients with the value of resting MPI in suspected CAD with atypical
multivessel disease was higher than in patients with chest pain in the emergency room and found that 30%
single-vessel disease (56.1% vs. 25.0%; P < 0.001), with of the enrolled patients had abnormal resting perfusion.
similar specificity. Similar to this research, our study found that 30.9% of
obstructive CAD patients had abnormal resting MPI and
It is well known that SPECT MPI is a widely used
the sensitivity of combined regional WM abnormality was
noninvasive method for detecting myocardial ischemia.
further increased to 46.8%. On the other hand, despite the
Abnormal (reduced perfusion/defect) stress MPI and
combined regional WM, the sensitivity of resting MPI to
resting MPI partially or completely returned to normal
diagnose obstructive CAD was not high. Therefore, we
indicate myocardial ischemia. At rest, even if the cor-
still advocate that suspected CAD patients without stress
onary arteries are significantly narrowed, myocardial
contraindications need to perform stress MPI.
blood flow can still be normal. The increase in myocar-
dial blood flow under stress is limited by the reduction Shirai et al. [12] have proved that the combined assess-
of coronary flow reserve of the diseased blood vessel, ment of worsening of LV regional WM and perfusion data
showing abnormal perfusion. However, many patients in exercise 201Tl gated SPECT MPI had incremental
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Incremental value of regional wall motion abnormalities Liu et al. 281
value for detection of multivessel CAD. We have found multivessel disease than in patients with single-vessel
that combination of WM and perfusion abnormalities by disease, with similar specificity. First, the possible mech-
rest-only 99mTc-MIBI gated SPECT MPI had higher sen- anism was that the territories of abnormal WM were
sitivity for detecting obstructive CAD in patients with increased with the growth of the number of severe cor-
onary stenosis, although multivessel disease was prone
Fig. 4 to balanced ischemia. Second, single-vessel disease may
have collateral circulation to maintain normal perfusion
and WM, while patients with multivessel disease have
reduced myocardial blood flow in multiple territories and
insufficient collateral circulation compensation, resulting
in abnormal perfusion or WM.
Fig. 5
A patient example. A 60-year-old patient was admitted to the hospital with repeated chest pain for half a month. Each pain lasted for 3–5 minutes.
The examination showed that the high-sensitivity cardiac troponin I (hs-cTnI) was slightly increased (0.0520 ng/ml; normal standard: 0–0.0400 ng/
ml) and the electrocardiogram (ECG) was normal. The patient was diagnosed with suspected acute coronary syndrome (ACS) and received rest-
only ECG-gated single-photon emission computerized tomography (SPECT) myocardial perfusion imaging (MPI). (a) Rest ECG-gated SPECT
MPI images, the three rows from top to bottom are left ventricular (LV) short-axis, vertical long-axis and horizontal long-axis images, respectively.
There are no abnormalities in resting MPI. (b) Rest perfusion score map shows the score of left anterior descending coronary artery (LAD) territory,
left circumflex coronary artery (LCX) territory and right coronary artery (RCA) territory are 2, 1 and 0, respectively, which are considered as normal
perfusion. (c) Wall motion score map shows the score of LAD, LCX and RCA territories are 12, 0 and 1, respectively, indicating an abnormality in
LAD territory. (d) Subsequently coronary angiography was performed: LAD, 90% narrowing of the near-mid (black arrow); left main coronary artery
(LM), negative; LCX, negative; RCA, 50–70% narrowing of the near-mid. This figure shows the incremental value of regional wall motion abnormal-
ities for detecting obstructive disease in suspected CAD patients, while the rest perfusion is normal. CAD, coronary artery disease.
Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
282 Nuclear Medicine Communications 2021, Vol 42 No 3
would be adequate for inducing severe regional dysfunc- that regional WM abnormalities based on rest-only 99mTc-
tion. Third, previous studies [22–24] have confirmed that MIBI ECG-gated SPECT MPI has the potential to help
myocardial ischemia in patients’ daily lives may cause perfusion to identify high-risk CAD in patients with con-
myocardial stunning, which leads to normal perfusion but traindications to stress testing.
reduced regional WM. Lastly, the compensation of coro-
nary blood flow can maintain normal perfusion in some Limitation
territories supplied by stenotic vessels at rest. In addition, Several limitations of this study should be considered.
95.5% abnormal perfusion or abnormal WM vascular ter- First, all enrolled patients had stress contraindications
ritories were consistent in 26 obstructive CAD patients and were only a small part of patients in clinical work.
with abnormal perfusion and WM. The possible mecha- We still maintain that suspected CAD patients without
nism was that severe stenosis leads to long-term chronic stress contraindications need to undergo stress MPI.
ischemia in the dominated territories, leading to abnor- Second, the enrolled population included multiple
mal perfusion and WM. stress contraindications and we did not perform sub-
group analysis due to the number limitation. Third, we
Lewis et al. [25] reported that WM abnormalities detected
did not implement regadenoson or dobutamine stress
by resting echocardiography were associated with severe
MPI in 61 asthma patients, because regadenoson is
(≥70%) coronary artery stenosis in 252 patients who had
not available and dobutamine stress MPI is rarely con-
no history of MI. In 77 abnormal WM separate regions,
ducted in China. Other than that, the sample size of this
60 regions (78%) were supplied by coronary vessels with
study was small, a large sample and prospective research
≥70% stenosis. Similar to this study, Pärkkä et al. [26]
is needed.
showed that abnormal WM obtained from resting mag-
netic resonance cine imaging can be used to detect CAD.
By analyzing regional WM, 11 out of 30 subjects were Conclusion
determined to have CAD. However, echocardiography Regional WM abnormalities at rest, as shown by rest-only
99m
relies on the operator’s skills and conventional echocardi- Tc-MIBI ECG-gated SPECT MPI, has incremen-
ography cannot obtain myocardial perfusion parameters. tal diagnostic value over perfusion alone for detecting
MRI is expensive and contraindicated in patients with obstructive CAD in suspected CAD patients.
claustrophobia and pacemakers. ECG-gated SPECT
MPI can obtain perfusion and regional function param- Acknowledgements
eters noninvasively through one-step station, with high This research was supported by the National Natural
reproducibility and repeatability. Science Foundation of China (81871381, PI: Y.W.), Key
Laboratory of Changzhou High-tech Research Project
Gallagher et al. [27] reported that the sensitivity of com- (CM20193010, PI: Y.W.), Chinese National Natural
puted tomography (CT) coronary angiography was 86%, Science Foundation for Young Scholars (81701737, PI:
and the specificity was 92% for the detection of ACS J.W.), Social Development Foundation of Changzhou
in low-risk chest pain patients. According to the latest Science and Technology Bureau, Jiangsu Province,
ESC guidelines, both CT coronary angiography and China (CE20175029, PI: J.W.), Chinese National Natural
MPI are class I recommendations for people with sus- Science Foundation for Young Scholars (81701734, PI:
pected CAD. CT coronary angiography is considered for X.S.), Chinese National Natural Science Foundation for
patients with contraindications to stress MPI. However, Young Scholars (81901777, PI: F.Z.), and Science and
CT coronary angiography requires the use of iodinated Technology Project for Youth Talents of Changzhou
contrast agents, which is related to the risk of allergies Health Committee (QN201920, PI: F.Z.).
and nephrotoxicity. In addition, extensive coronary cal-
cification, irregular heart rate, severe obesity, inability Conflicts of interest
to cooperate with breath-holding, etc. may affect the There are no conflicts of interest.
image quality of CT coronary angiography. Therefore,
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