Left Ventricular Dyssynchrony Parameters Measured by Phase Analysis of Post-stress and Resting Gated SPECT Myocardial Perfusion Imaging

Abstract

Phase analysis has been validated to measure left ventricular (LV) dyssynchrony from resting gated SPECT myocardial perfusion imaging (MPI). In 1-day rest/stress protocols, often only post-stress gated data are acquired. The purpose of this study was to determine whether LV dyssynchrony parameters measured at post-stress significantly differ from those measured at rest. Sixty normal subjects, 40 patients with stress-induced ischemia but normal LV function, and 29 patients with LV dysfunction were included in this study. All patients were scanned using a 2-day Technetium-99m sestamibi (MIBI) MPI protocol, where gated SPECT data were acquired at 60 min post injection of the radiotracer. LV dyssynchrony parameters at post-stress and at rest were calculated and compared using paired t-test. There were no significant differences in the LV dyssynchrony parameters between post-stress and resting in all cohorts. No patient showed differences in the LV dyssynchrony parameters between the post-stress and resting scans significantly greater than the reported variations in these parameters between serial resting scans. There was no significant difference in dyssynchrony parameters measured at rest and 60 min after stress on MPI gated images.

Full text

World Journal of Nuclear Medicine/Vol 12/Issue 1/January 2013 3
Introduction
Phase analysis has been developed to assess left
ventricular (LV) dyssynchrony based on gated single
photon emission computed tomography (SPECT)
myocardial perfusion imaging (MPI).[1] It has been shown
that the LV dyssynchrony parameters (phase standard
deviation (PSD) and phase histogram bandwidth (PHB))
measured by phase analysis correlate well with those
measured by tissue Doppler imaging,[2‑4] and predicted
response to cardiac resynchronization therapy (CRT) in
heart failure (HF) patients.[5] Recently, phase analysis has
shown to be able to identify the site of latest mechanical
activation as the optimal LV pacing lead position.[6] In
the above validation studies, all gated SPECT images
were acquired using resting Technetium‑99m (Tc‑99m)
gated SPECT MPI protocols.
In practice, most of the Tc‑99m MIBI SPECT MPI
scans are performed using same‑day resting/stress
protocols, where the resting data are acquired using
a relatively low dose as compared to the stress data,
and many centers only acquire gated SPECT data at
stress. Presumably, the high‑count gated SPECT data
acquired post‑stress can provide better quantication
of LV function. However, it has been shown that in
patients with an earlier myocardial infarction, LV
function post‑stress might not represent the true resting
LV function.[7] Consequently, this study suggested the
stratication of patients before starting gated SPECT
MPI, meaning in patients with an earlier myocardial
infarction, the gated acquisition should be performed
during the resting study. In another study, post‑stress
LV ejection fraction (LVEF) reduced and end‑systolic
Left Ventricular Dyssynchrony Parameters Measured
by Phase Analysis of Post‑stress and Resting Gated
SPECT Myocardial Perfusion Imaging
Yanli Zhou1, Dianfu Li1,2, Jianlin Feng2, Donglan Yuan2, Zenic Patel3, Kejiang Cao1, Ji Chen3
1Departments of Cardiology, 2Nuclear Medicine, The First Afliated Hospital of Nanjing Medical University, Nanjing,
Jiangsu, China, 3Department of Radiology, Emory University, Atlanta, GA, USA
Abstract
Phase analysis has been validated to measure left ventricular (LV) dyssynchrony from resting gated SPECT myocardial
perfusion imaging (MPI). In 1‑day rest/stress protocols, often only post‑stress gated data are acquired. The purpose of
this study was to determine whether LV dyssynchrony parameters measured at post‑stress signicantly differ from those
measured at rest. Sixty normal subjects, 40 patients with stress‑induced ischemia but normal LV function, and 29 patients
with LV dysfunction were included in this study. All patients were scanned using a 2‑day Technetium‑99m sestamibi (MIBI)
MPI protocol, where gated SPECT data were acquired at 60 min post injection of the radiotracer. LV dyssynchrony
parameters at post‑stress and at rest were calculated and compared using paired t‑test. There were no signicant differences
in the LV dyssynchrony parameters between post‑stress and resting in all cohorts. No patient showed differences in the
LV dyssynchrony parameters between the post‑stress and resting scans signicantly greater than the reported variations in
these parameters between serial resting scans. There was no signicant difference in dyssynchrony parameters measured
at rest and 60 min after stress on MPI gated images.
Keywords: Left ventricular dyssynchrony, myocardial perfusion imaging, phase analysis
Address for correspondence:
Dr.DianfuLi,DepartmentofCardiology,TheFirstAfliatedHospitalofNanjingMedicalUniversity,300GuangzhouRd,Nanjing,Jiangsu210029,
China.E‑mail:lidianfu@gmail.com
Original Article
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DOI:
10.4103/1450-1147.113931
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4 World Journal of Nuclear Medicine/Vol 12/Issue 1/January 2013
Zhou, et al.: Left ventricular dyssynchrony
volume and end‑diastolic volume increased in patients
with stress‑induced ischemia.[8] However, the effect
of ischemia on the difference between post‑stress and
resting LV function measurements was modest and
rarely exceeded the condence limits in normal patients
undergoing 2‑day protocols.[9] There is a recent study
enrolling 20 patients with reversible perfusion defects
involving >10% of the LV myocardium and 20 normal
subjects to show that there was no signicant change
from rest to stress in the LV dyssynchrony parameters
between the two groups.[10] It is important to note that
all of the subjects in this study had normal LVEF. The
impact of stress on LV dyssynchrony parameters was
not evaluated in patients with LV dysfunction.
The purpose of this study was to determine whether LV
dyssynchrony parameters (PSD and PHB) measured at
post‑stress signicantly differ from those measured at
rest in normal subjects, patients with stress‑induced
ischemia but normal LVEF, and patients with LV
dysfunction.
Materials and Methods
Patients
The study retrospectively analyzed gated SPECT
MPI data acquired from July 2008 to January 2010.
Sixty normal subjects (30 underwent exercise stress
and 30 underwent adenosine stress), 40 patients
with stress‑induced ischemia but normal LV
function (LVEF >50%, 20 underwent exercise stress and
20 underwent adenosine stress), and 29 patients with LV
dysfunction (LVEF <50%, 19 underwent exercise stress
and 10 underwent adenosine stress) were included in
this study. Table 1 summarizes the characteristics of the
three cohorts. Stress‑induced ischemia was considered
in the presence of reversible myocardial perfusion defect
at stress. Among the 29 patients with LV dysfunction,
14 had ischemic cardiomyopathy (including 10 patients
with myocardial infarction) and 15 patients had
non‑ischemic cardiomyopathy. The study protocol
was approved by the institutional review board (IRB).
Acquisition and processing
A 2‑day MIBI SPECT MPI protocol was used in this
study. Patients who had exercise stress underwent a
symptom‑limited treadmill test using standard Bruce
protocol. MIBI was intravenously injected when a ≥85%
heart rate was achieved. Exercise was continued at the
workload for 1.5‑2.0 min when possible. Patients who
had adenosine stress were infused with adenosine at
140 µg/kg/min for 5 min and MIBI was injected at
the end of the second minute. Tc‑99m Sestamibi doses
ranged from 25 to 30 mCi depending on the patients’
weight or body mass indices.
A Philips CardioMD system (Philips Medical Systems,
Milpitas, CA, USA) was used to acquire all post‑stress
and resting scans with 20% energy windows around
140 keV. A total of 64 projections (24 sec/projection,
total acquisition time of 14 min) were obtained over a
180° circular orbit. The gated SPECT data were acquired
as eight frames per cardiac cycle. Data were stored in a
64–64 matrix with 6.4 mm/pixel.
All of the gated SPECT data were reconstructed using
a manufacturer‑provided filtered backprojection
program (AutoSPECTPlus™, Philips Medical Systems).
All reconstructed data were reoriented to generate gated
short‑axis images and then submitted to phase analysis
to calculate PSD and PHB.[1] The post‑stress and resting
images were processed side‑by‑side by an experienced
technologist, who was blinded from this research project.
Statistical analysis
Paired t‑test (two‑tailed) and Bland–Altman plot were
used to compare the post‑stress and resting PSD and
PHB in the three cohorts, respectively. A P < 0.05 was
considered statistically signicant.
Results
Table 2 shows the LV dyssynchrony parameters in the
three cohorts. In normal subjects, although it showed
a trend that LV dyssynchrony parameters acquired
from stress scans were smaller than those from resting
Table 1: Patient characteristics
Normal subjects (
n
=60) Patients with ischemia (
n
=40) Patients with LV dysfunction (
n
=29)
Age (years) 60.3±18.3 60.9±10.2 61.8±9.5
Male (%) 55 67.5 82.5
Diabetes mellitus (%) 8.9 17.5 12.5
Hypertension (%) 45 63 57.5
MI/non‑MI (%) NA 7.5/92.5 34.5/65.5
Ischemic/non‑ischemic (%) NA NA 48.2/52.8
QRS duration (msec) 100±18.7 101.5±20.9 102.5±20.9
SSS NA 6.1±3.9 13±12
SDS NA 4±2.9 1.9±2.1
MI: Myocardial infarction; SSS: Summed stress score; SDS: Summed difference score
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World Journal of Nuclear Medicine/Vol 12/Issue 1/January 2013 5
Zhou, et al.: Left ventricular dyssynchrony
scans, the differences were not signicant. Figure 1a‑c
shows the Bland–Altman plots that compared the LV
dyssynchrony parameters between the post‑stress and
resting scans in the three cohorts. The mean differences
in the LV dyssynchrony parameters were very small,
indicating there were no systemic differences in these
parameters between the post‑stress and resting scans.
There were no outliers that showed clinically important
differences in the LV dyssynchrony parameters between
the post‑stress and resting scans, indicating the two
scans yielded equivalent results. Figure 2a and b
shows two example patients with anterior and inferior
ischemia post‑stress, respectively. Both patients
had comparable LV synchrony at post‑stress and at
rest. Figure 3 shows an example patient with severe
LV dysfunction (LVEF = 24%) and myocardial
infarction (summed stress score = 33). Even though
severe reduction in perfusion uptake in the infarct
region might impact the phase measurement, the global
LV dyssynchrony parameters were not signicantly
different between the post‑stress and resting scans,
indicating that phase analysis was a robust tool to
measure LV dyssynchrony in patients with severe LV
dysfunction and myocardial infarction.
Discussion
This study compared LV dyssynchrony parameters
measured by phase analysis of gated SPECT MPI
between post‑stress (either adenosine or exercise)
and resting scans. No signicant differences in these
parameters were observed in normal subjects, patients
with stress‑induced ischemia but normal LV function,
and patients with LV dysfunction. As the majority
of clinical MPI data are acquired using 1‑day Tc‑99m
protocol, where usually gated SPECT data are acquired
only at post‑stress, this nding supports the application
Table 2: Post‑stress and resting LV function
parameters
Normal
subjects
(n=60)
Patients with
ischemia
(n=40)
Patients with
LV dysfunction
(n=29)
Stress Rest Stress Rest Stress Rest
PSD
Mean 9.3 9.3 8.9 8.8 28.5 29.9
SD 2.0 1.9 2.9 2.4 17.1 18.8
P value 0.89 0.82 0.05
PHB
Mean 28.5 29.5 28.4 28.8 95.6 99.9
SD 5.9 5.7 8.3 8.3 70.4 74.0
P value 0.23 0.74 0.06
EF
Mean 76.1 76.2 61.5 64.8 33.5 35.4
SD 6.4 6.4 9.7 7.5 10.1 10.9
P value 0.83 0.004 0.12
PSD: Phase standard deviation; PHB: Phase histogram bandwidth; SD: Standard
deviation; LV: Left ventricular
Figure 1: Bland‑Altman plots for comparisons of the post‑stress and resting LV dyssynchrony parameters in the (a) normal subjects,
(b) patients with stress‑induced ischemia but normal LV function, and (c) patients with LV dysfunction
c
b
a
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6 World Journal of Nuclear Medicine/Vol 12/Issue 1/January 2013
Zhou, et al.: Left ventricular dyssynchrony
of phase analysis to post‑stress Tc‑99m gated MIBI
SPECT MPI data to measure LV dyssynchrony, which
is equivalent to that measured at rest.
Stress‑induced ischemia is associated with post‑stress
reduction in LVEF and increased post‑stress EDV and
ESV.[11] Stress‑induced severe ischemia may lead to
myocardial stunning and transient LV dilation, and
possibly LV dyssynchrony. A few studies showed that
physical effort might further increase LV dyssynchrony
in patients with HF assessed by echocardiography
during exercise.[12‑14] However, a recent study reported
that even a large reversible perfusion defect does not
alter the indices of mechanical dyssynchrony by phase
analysis in patients with coronary artery disease and
normal LVEF, when all post‑stress data were acquired
60 min post injection of Tc‑99m Sestamibi.[10] This study
conrmed that nding, and indicated that the post‑stress
LV dyssynchrony was equivalent to that at the resting
state in patients with LV dysfunction.
For Tc‑99m Sestamibi, the post‑stress image acquisition
minimum delay is 15‑20 min for exercise stress, 45‑60 min
for resting, and 60 min for pharmacologic stress,[15] in
order to avoid the inuence of liver and gut uptake. We
uniformly acquire the stress imaging 60 min after tracer
injection. As we all know, the parameters of the wall
motion and dyssynchrony are derived from the gated
images that are acquired at the time of imaging, not at
the time the tracer injection. So, the timing of acquisition
may affect the function and dyssynchrony parameters.
There are two limitations of this study. First, there are
only 14 ischemic and 15 non‑ischemic HF patients in
this study, which may suggest limited statistical power.
Secondly, to clarify the difference of LV dyssynchrony
parameters between the post‑stress and resting scans,
different stage post injection of Tc‑99m Sestamibi will
be observed in our further study.
Conclusion
The LV dyssynchrony parameters measured at 60 min
after stress did not significantly differ from those
measured at rest in normal subjects, patients with
stress‑induced ischemia but normal LV function,
and patients with LV dysfunction, in a 2‑day Tc‑99m
MPI protocol. Phase analysis can be applied to
post‑stress Tc‑99m gated SPECT MPI data to measure
LV dyssynchrony, which is equivalent to that measured
at rest.
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comparable LV synchrony at post‑stress and at rest
b
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World Journal of Nuclear Medicine/Vol 12/Issue 1/January 2013 7
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How to cite this article: Zhou Y, Li D, Feng J, Yuan D, Patel Z, Cao K,
Chen J. Left Ventricular Dyssynchrony Parameters Measured by Phase
Analysis of Post‑stress and Resting Gated SPECT Myocardial Perfusion
Imaging. World J Nucl Med 2013;12:3‑7.
Source of Support:ThisstudywassupportedinpartbythePublic
HealthSupportProgramofJiangsuProvince,CHINA(ZX07200907)
andbyanNIH‑fundedresearchproject(1R01HL094438‑01A1,PI:
JiChen,PhD).Thetermsofthisarrangementhavebeenreviewedand
approvedbyEmoryUniversityinaccordancewithitsconict‑of‑interest
practice.Conict of Interest:Nonedeclared.
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