Download Detection of Subendocardial Ischemia in the Left Anterior

JACC: CARDIOVASCULAR IMAGING
VOL. 1, NO. 3, 2008
© 2008 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER INC.
ISSN 1936-878X/08/$34.00
DOI:10.1016/j.jcmg.2008.02.004
CLINICAL RESEARCH
Detection of Subendocardial Ischemia in the Left
Anterior Descending Coronary Artery Territory With
Real-Time Myocardial Contrast Echocardiography
During Dobutamine Stress Echocardiography
Feng Xie, MD, Saritha Dodla, MD, Edward O’Leary, MD, FACC,
Thomas R. Porter, MD, FACC
Omaha, Nebraska
O B J E C T I V E S The purpose of this study was to test whether the transmural delineation of
myocardial perfusion during dobutamine stress imaging with real-time myocardial contrast echocardiography (RTMCE) might permit visualization of dobutamine-induced subendocardial ischemia.
B A C K G R O U N D Significant coronary artery disease can be present despite normal transmural wall
thickening (WT) responses during dobutamine stress echocardiography (DSE). One potential reason is
dobutamine-induced recruitment of epicardial WT in the presence of subendocardial ischemia.
M E T H O D S Myocardial perfusion and WT were examined with RTMCE during DSE with a continuous
infusion of ultrasound contrast in 94 patients with normal resting WT. Fifty-five of the patients had a ⬎50%
diameter stenosis in the left anterior descending coronary artery (LAD). The WT was visually assessed by a
blinded reviewer at 2 time periods: initially after a high mechanical index impulse before myocardial contrast
replenishment (MCR), and again during MCR. Subendocardial %WT was measured during MCR, if a subendocardial
perfusion defect was visually evident, whereas transmural WT was quantified on the pre-MCR images.
R E S U L T S Fifty patients (91%) with LAD stenoses exhibited a myocardial contrast defect at peak stress,
with 45 defects being subendocardial. Transmural WT pre-MCR appeared normal in 35 of the 45 patients with
subendocardial perfusion defects (78%). However, a subendocardial WT abnormality was apparent during
MCR in 18 of these 35 patients, even though transmural WT was not different from the 17 patients with
normal subendocardial WT (33 ⫾ 15% vs. 36 ⫾ 14%). Quantitative measurements of WT within the subendocardium were significantly less in the patients with visually evident subendocardial WT abnormalities,
when compared with those who seemed to have normal WT during MCR (17 ⫾ 8% vs. 25 ⫾ 10%, p ⬍ 0.01).
C O N C L U S I O N S In patients with significant LAD disease, RTMCE during DSE detects subendocardial
ischemia even when transmural WT appears normal. Real-time myocardial contrast echocardiography should
be the preferred ultrasound imaging method when using contrast to detect coronary artery disease during
DSE. (J Am Coll Cardiol Img 2008;1:271– 8) © 2008 by the American College of Cardiology Foundation
From the Department of Internal Medicine, Section of Cardiology, University of Nebraska Medical Center, Omaha, Nebraska.
This work was supported by the Theodore Hubbard Foundation, Omaha, Nebraska. Dr. Porter has received grant support from
Bristol-Myers Squibb Medical Imaging, ImaRx Therapeutics, Inc., and Siemens Medical Solutions and has served as consultant
to ImaRx Therapeutics, Inc., Acusphere Inc., and Point BioMedical. Dr. Xie has served as consultant to Acusphere Inc.
Manuscript received December 21, 2007; revised manuscript received February 20, 2008, accepted February 28, 2008.
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Detection of Subendocardial Ischemia
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R
eal-time myocardial contrast echocardiography (RTMCE) has become a useful tool to
detect coronary artery disease during dobutamine and dipyridamole stress echocardiography (1–5). The low mechanical index (MI) pulse
sequence scheme significantly reduces microbubble
destruction, allowing the examination of myocardial
perfusion while simultaneously improving endocardial border delineation. This can be especially
helpful during dobutamine stress echocardiography
(DSE), where the assessment of perfusion might
add to the value of wall motion analysis in detecting
significant coronary artery disease (6). Detection of
ischemia (i.e., wall thickening [WT] abnormalities)
during dobutamine stress might be made more
difficult, because of the ability of dobutamine to
recruit the epicardial layers to contract (7). This
might mask WT abnormalities that are confined to
the subendocardial layers. We hypothesized that a
subendocardial perfusion defect delineated
with RTMCE might permit one to detect
ABBREVIATIONS
subendocardial ischemia despite normal
AND ACRONYMS
transmural thickening. This hypothesis
CI ⴝ confidence interval
was tested in patients with known left
DSE ⴝ dobutamine stress
anterior descending stenoses, by examinechocardiography
ing transmural and subendocardial apical
LAD ⴝ left anterior descending
WT with RTMCE during dobutamine
coronary artery
stress.
MCR ⴝ myocardial contrast
replenishment
See page 279
MI ⴝ mechanical index
RTMCE ⴝ real-time myocardial
contrast echocardiography
METHODS
WT ⴝ wall thickening
Study population. Fifty-five patients with
normal resting wall motion and normal resting
myocardial contrast enhancement underwent DSE
with RTMCE and had quantitative angiography
performed at a mean of 2.4 ⫾ 2.8 weeks of the
stress test documenting the presence of a ⬎50%
diameter stenosis in the left anterior descending
coronary artery (LAD). Thirty nine patients without significant LAD stenoses (or with bypassed
LAD arteries) who underwent dobutamine stress
with RTMCE over the same time period served as
control subjects. Mean age of the patients was 61 ⫾
13 years (47 women). Other demographic characteristics are listed in Table 1.
RTMCE. The contrast agent used for RTMCE was
the commercially available lipid-encapsulated microbubble Definity (Bristol-Myers Squibb Medical
Imaging, Inc., North Billerica, Massachusetts).
This agent was administered as a 3% intravenous
continuous infusion at 4 to 6 ml/min under resting
conditions and during dobutamine stress. The infusion was adjusted to optimize myocardial opacification while minimizing attenuation from left
ventricular cavity contrast.
The RTMCE was performed with ultrasound
scanners equipped with low-MI real-time pulse
sequence schemes, which use either interpulse amplitude modulation (Power Modulation; Sonos
5500, Philips Medical Systems, Bothell, Washington) or interpulse phase and amplitude modulation
(Contrast Pulse Sequencing; Siemens Acuson Sequoia, Mountain View, California). The MI was
kept at ⱕ0.25, and frame rate was kept at 25 to 30
Hz during dobutamine stress imaging. Time gain
compensation and 2-dimensional gain settings were
adjusted to suppress any nonlinear signals from
tissue before contrast injection and remained unchanged throughout the study. Contrast-enhanced
images from apical views (4-, 2-, and 3-chamber)
were obtained and digitized at rest and at maximal
stress after the patients had achieved a test end
point.
Dobutamine stress. Patients were instructed to discontinue beta-blocker drugs at least 24 h before the
stress test. Intravenous dobutamine was infused at a
starting dose of 5 ␮g/kg/min, followed by increasing doses of 10, 20, 30, 40, up to a maximal dose of
50 ␮g/kg/min, in 3- to 5-min stages. Atropine (up
to 2.0 mg) was injected in patients not achieving
85% of the predicted maximal heart rate (220 ⫺ age
in years). The end points of stress tests were:
achievement of the target heart rate (85% of predicted maximal heart rate), maximal dobutamine/
atropine doses, ST-segment elevation ⱖ2 mm at an
interval of 80 ms after the J point in non–Q-wave
leads, sustained arrhythmias, severe chest pain, or
intolerable adverse effects considered to be due to
dobutamine or atropine. Hypotension was defined
as a fall of systolic blood pressure below 80 mm Hg
or a reduction ⱖ20 mm Hg from baseline. A
hypertensive response was defined as blood pressure
ⱖ230/120 mm Hg.
Image analysis. Apical WT and contrast enhancement was analyzed on the first cardiac cycle after a
brief (5 to 25 frames for the Philips Sonos 5500 or
1 to 3 cardiac cycles for Siemens Acuson Sequoia)
high (1.4 to 1.9) MI impulse before any myocardial
contrast replenishment (MCR). These were referred to as pre-MCR images. The second analysis
of WT occurred during a cardiac cycle 1 to 2 s after
the high MI impulse (referred to as MCR images).
Digitized loops of these images were examined in
the apical windows. A subendocardial perfusion
Xie et al.
Detection of Subendocardial Ischemia
JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008
MAY 2008:271– 8
defect was defined as one in which an evident
decrease in contrast enhancement within the inner
one-half of the myocardial wall was visualized
during the replenishment phase of contrast (Online
Video 1). A transmural perfusion defect was one in
which decreased contrast enhancement was observed through the entire wall of the segment
during the replenishment phase in the apical segments despite normal myocardial contrast enhancement in other segments (Online Video 2).
For each patient, 2 separate files were digitized
and created for blinded analysis (total of 188 image
loop files in the 94 patients). The images were
randomly mixed with other studies and analyzed
separately from one another. One file was the
immediate post– high-MI impulse pre-MCR, in
which the reviewer analyzed transmural WT when
no contrast was present in the myocardium and only
contrast-enhanced endocardial border delineation
was present. The second analysis, done at a separate
time from a separate independent file, was the
examination of WT during MCR. At this time, if a
subendocardial perfusion defect was present, the
reviewer determined whether WT within the region defined by the perfusion defect was abnormal,
with both the contrast-enhanced endocardial and
transmural border. Subendocardial WT was graded
as normal when it appeared to be thickened beyond
approximately 30% of its end-diastolic thickness
during systole and abnormal when no or reduced
thickening within the subendocardial defect was
perceived.
Quantitative measurements of WT. The end diastolic and end systolic wall thickness for transmural
WT was measured on the pre-MCR images (the
first cardiac cycle after the high MI impulse) by
using the endocardial border delineated with left
ventricular cavity contrast and the epicardial border.
Transmural WT (%) ⫽
End-systolic thickness 共mm兲 ⫺
End-diastolic wall thickness 共mm兲
⫻ 100%
End-systolic defect thickness 共mm兲
The subendocardial WT measurement was only
possible if a subendocardial perfusion defect was
present during MCR images. This was measured
with the endocardial border delineated with cavity
contrast and the transmural border delineated by
the subendocardial perfusion defect. (see example in
Fig. 1). The formula for subendocardial WT was
then determined as follows:
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Table 1. Clinical Characteristics of Patients With Known LAD Stenoses
Variables
n
Patients Without
LAD Disease
Patients With
LAD Disease
39
Age (yrs)
Male
p
Value
55
60 ⫾ 13
61 ⫾ 14
0.669
17
30
0.402
History of smoking
12 (31%)
24 (44%)
0.294
Hypertension
33 (85%)
50 (91%)
0.516
Hyperlipidemia
30 (77%)
42 (76%)
0.854
Diabetes
22 (56%)
30 (55%)
0.975
No. of patients achieving 85% PMHR
34 (87%)
46 (84%)
0.856
Rate-pressure product (mm Hg/min)
22,794 ⫾ 5996
21,343 ⫾ 5911
0.273
Previous MI outside LAD territory
Previous PCI or CABG
Previous PCI to LAD
Previous CABG to LAD
No. of patients with RCA/LCX disease
Also with LAD stenosis
Concentric remodeling
1 (3%)
4 (7%)
0.399
17 (44%)
16 (29%)
0.218
3
5
5
3
13 (33%)
35 (64%)
0.007
16 (29%)
0.679
0
9 (23%)
CABG ⫽ coronary artery bypass graft; LAD ⫽ left anterior descending coronary artery; MI ⫽ mechanical
index; PCI ⫽ percutaneous coronary intervention; PMHR ⫽ predicted maximum heart rate; RCA ⫽ right
coronary artery.
Figure 1. Example of Measurements for Subendocardial WT
Apical 4-chamber view of real-time myocardial contrast echocardiography
with contrast pulse sequencing (Siemens Acuson Sequoia, Mountain View,
California) was obtained from a patient with significant left anterior
descending coronary artery disease during dobutamine stress. Subendocardial wall thickening (WT) within the apex was measured off-line with commercially available software. The end-diastolic and -systolic wall thickness for
transmural WT was measured on the pre-MCR images (the first cardiac cycle
after the high mechanical index impulse; left panels) as the distance
between the endocardial border (arrow) delineated with left ventricular cavity contrast and the epicardial border (arrow). Subendocardial WT was measurable only if a subendocardial perfusion defect was present (arrows)
during the replenishment period (MCR; right panels). See the text for calculation formula. ED ⫽ end-diastole; ES ⫽ end-systole; MCR⫽ myocardial contrast replenishment.
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Table 2. Sensitivity, Specificity, and Accuracy of Visual WMA During
the Pre-MCR and MCR Time Periods in Detecting a Significant Coronary Stenosis
WMA Pre-MCR
WMA During MCR
Myocardial Perfusion
Sensitivity
27%
59%*
91%†
Specificity
87%
74%
49%‡
Accuracy
52%
65%
73%*
Myocardial perfusion analysis is also shown. *p ⬍ 0.02 compared with pre-MCR; †p ⬍ 0.001 compared with
other groups; ‡p ⬍ 0.05 compared with other groups.
MCR ⫽ myocardial contrast replenishment; WMA ⫽ wall motion analysis.
Subendocardial WT (%) ⫽
End-systolic defect thickness 共mm兲 ⫺
End-diastolic defect thickness 共mm兲
⫻ 100%
End-systolic defect thickness 共mm兲
End-diastole was defined as the largest left ventricular cavity size and end-systole was defined as
the smallest left ventricular cavity size.
Statistical analysis. All data are expressed as mean
values ⫾ SD. For clinical characteristics of patients,
2-tailed unpaired Student t tests were used for
inter-group comparison. A chi-square test was used
for comparisons of proportions, unless proportions
were low, in which case a Fisher exact test was used.
The sensitivity, specificity, and accuracy of WT
analysis (transmural and subendocardial) as well as
perfusion analysis were computed for detecting a
⬎50% diameter stenosis in the LAD. Proportional
differences between the visual analysis of WT and
perfusion were compared with McNemar tests or
Fisher exact tests if expected cell frequencies were
low. Multi-group means were compared by analysis
of variance (ANOVA). One-way ANOVA was
used for comparisons of quantitative WT measurements. The inter-observer agreement on both
transmural and subendocardial WT analysis was
compared by analyzing the agreement with a second
reviewer in 25 patients randomly selected from the
study group. Kappa values were used to determine
interobserver agreement. A p value ⬍ 0.05 was
considered significant.
RESULTS
Patient characteristics. The LAD stenoses ⬎50%
diameter were present in 55 of the patients (32 with
multi-vessel coronary artery disease, 23 with singlevessel LAD disease). The range of stenosis diameters was 50% to 100%. Table 1 lists the demographic data of the patients examined, comparing
those with and without LAD disease. There were
no differences in these 2 groups in cardiac risk
factors, prior revascularizations, or rate pressure
product achieved. Four patients with LAD stenosis
had a history of a previous myocardial infarction in
a non-LAD territory, 12 (22%) patients had previous percutaneous coronary intervention (5 of the
LAD), and 4 (7%) patients had previous coronary
artery bypass grafting surgery (3 of the LAD).
Visual subendocardial and transmural myocardial perfusion analysis. Table 2 depicts the sensitivity, spec-
ificity, and accuracy of perfusion imaging versus
WT analysis (pre-MCR and during MCR). Of the
55 patients with a significant LAD stenosis, 45
exhibited a subendocardial perfusion defect and 5
exhibited a transmural perfusion defect. Diagnostic
accuracy of visual analysis of perfusion imaging with
Figure 2. Dynamic Changes of Subendocardial WT on Apical 4-Chamber View With RTMCE
A 65-year-old woman presented with shortness of breath. Apical 40-chamber view of real-time myocardial contrast echocardiography
(RTMCE) with contrast pulse sequencing was obtained during dobutamine stress. On the pre-MCR images, WT was normal, whereas during MCR an apical subendocardial WT abnormality was evident, because of the subendocardial perfusion defect. Subendocardial WT
measured 20%, whereas transmural WT was measured to be 50%. At complete replenishment (4 s after high MI impulse), the defect
disappeared. Abbreviations as in Figure 1.
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RTMCE was 73% (95% confidence interval [CI]
65% to 79%); sensitivity was 91% (95% CI 84% to
96%); and specificity was 49% (95% CI 39% to
56%). Figure 2 demonstrates an example of a
subendocardial perfusion defect seen during MCR
in the apical 4-chamber view (Online Video 3).
Of the 45 patients with subendocardial apical
defects, 10 (22%) exhibited abnormal WT on the
pre-MCR images. Of the 35 remaining patients, 18
exhibited a subendocardial WT abnormality on the
MCR image, whereas 17 seemed to have normal
subendocardial WT during MCR. Figures 2 and 3
demonstrate examples in 2 patients where subendocardial WT appeared abnormal during MCR,
whereas transmural WT on the pre-MCR images
appeared normal (Online Videos 4 and 5). Interobserver agreement for visual subendocardial and
transmural myocardial WT analysis was 88%,
Kappa values 0.76.
Table 3 demonstrates the rate pressure product,
mean and range of % diameter stenoses in the
LAD, and frequency of left circumflex or right
coronary stenoses in the patients who had ⬎50%
diameter LAD stenoses and had 1) abnormal transmural WT on the pre-MCR images, 2) normal
transmural WT but abnormal subendocardial WT
and abnormal subendocardial perfusion, and 3)
normal transmural and subendocardial WT but
abnormal subendocardial perfusion. Note that there
were no differences in any of these variables between the 3 groups.
Quantitative subendocardial and transmural myocardium analysis. Table 4 summarizes the subendocar-
dial and transmural WT measurements in the
patients who had subendocardial perfusion defects
at peak stress without transmural WT abnormalities
on the pre-MCR images. Measured WT within the
subendocardium was significantly less in the patients with visually evident subendocardial WT
abnormalities, when compared with those who
seemed to have normal WT during MCR (17 ⫾ 8%
vs. 25 ⫾ 10%, p ⬍ 0.01). However, these 2 groups
did not show any differences in transmural WT
measured on the pre-MCR images (33 ⫾ 15% vs.
36 ⫾ 14%, p ⫽ 0.30)
DISCUSSION
Chronotropic doses of dobutamine have been
shown to increase transmural WT, even in perfusion beds subtended by coronary stenoses that range
from 30% to 80% in diameter (8). If the stenosis is
more severe or if higher doses of dobutamine are
used, WT becomes abnormal (2). Transmural myo-
Xie et al.
Detection of Subendocardial Ischemia
Figure 3. Example of Subendocardial Defects With
Normal Transmural WT on Apical 3-Chamber View With RTMCE
Apical 3-chamber view of RTMCE with power modulation (iE33, Philips Medical Systems, Bothell, Washington) during peak dobutamine stress in a
patient with a significant left anterior descending coronary artery stenosis.
Pre-MCR (left panels) WT was normal, as delineated by the blue arrows in
the left panels. On the MCR images (right panels), a subendocardial perfusion defect is evident and subendocardial WT appeared abnormal (red
arrows). Abbreviations as in Figures 1 and 2.
cardial blood flow responses, however, are different,
with decreases in myocardial blood flow observed
even in milder non-flow limiting stenoses (2). As
the stenosis becomes more severe, a marked decrease in subendocardial blood flow has been observed (9 –11), with a marked decrease in endocardial/epicardial flow ratios. In this study, RTMCE
detected this decrease in endocardial to epicardial
blood flow abnormality in 45 of the 55 patients with
LAD stenoses ⬎50%.
Another pertinent pharmacologic property of
dobutamine is its ability to recruit the subepicardial
layers to thicken. The subendocardium is responsible for over 40% of WT under resting conditions
(12,13), and thus resting WT might be abnormal
even when only a subendocardial infarction is
present. Dobutamine, in this setting, will nearly
normalize WT due to recruitment of the epicardial
layers (12). This finding has served as the basis for
the use of dobutamine to identify viable myocardium. In this study, however, we observed that this
recruitment of subepicardial layers might mask the
detection of subendocardial ischemia. Because
RTMCE is capable of delineating transmural perfusion abnormalities (14,15), the transmural border
created by the subendocardial perfusion defect was
able to delineate when a subendocardial WT ab-
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Table 3. Pertinent Variables in Patients With LAD Stenoses
Abnormal TM WT
(n ⴝ 10)
75 ⫾ 18%
% LAD diameter stenosis (range)
Normal TM WT,
Abnormal SE WT
(n ⴝ 18)
Normal TM WT,
Normal SE WT
(n ⴝ 17)
73 ⫾ 18%
74 ⫾ 17%
p Value
0.967
22,620 ⫾ 5,788
20,653 ⫾ 6,750
21,533 ⫾ 6,261
0.745
No. of patients reaching 85% predicted maximal heart rate
9 (90%)
15 (83%)
13 (76%)
0.666
No. of patients with RCA/LCX stenosis
6 (60%)
11 (61%)
12 (71%)
0.797
Rate-pressure product (mm Hg/min)
Pertinent variables in patients with left anterior descending coronary artery (LAD) stenoses who had subendocardial (SE) perfusion defects and: 1) abnormal
transmural (TM) wall thickening (WT); 2) normal TM WT but abnormal subendocardial WT and perfusion; or 3) normal TM WT and abnormal subendocardial perfusion
but normal subendocardial WT.
LCX ⫽ left circumflex coronary artery; RCA ⫽ right coronary artery.
normality was present. Of the 35 patients with
LAD stenoses who seemed to have normal transmural WT on the pre-MCR images, 18 exhibited
evidence of subendocardial ischemia when the
MCR images were examined.
We did not see differences between those with
subendocardial perfusion defects and visually abnormal subendocardial WT and those with visually
normal WT in terms of severity of the LAD
stenosis subtending the affected perfusion bed or
the rate pressure product achieved during dobutamine stress (Table 3). Furthermore, we did not see
any differences between these 2 groups in the
number of cases in which the collateral perfusion
beds were subtended by a significant stenosis. One
potential explanation is that the “ischemic cascade”
played a role (2), in that if we had prolonged the
duration of stress further in the patients with
normal subendocardial WT it would have eventually become abnormal. However, we did not attempt in this study to prolong the duration of
infusion, once we had achieved maximum dobutamine/atropine doses or ⬎85% of the predicted
maximum heart rate.
These findings have 2 important clinical implications. Conventional DSE relies on the induction
of a transient wall motion abnormality to detect
significant coronary artery disease. However, these
wall motion abnormalities might not occur in up to
40% of patients with significant coronary artery
disease (7,16). Although radionuclide imaging has
detected perfusion abnormalities in patients with
normal wall motion during dobutamine stress (7), it
is unable to delineate transmural differences in
myocardial blood flow and thus will not be able to
identify when subendocardial ischemia might be
present in those normal transmural WT at peak
stress. Real-time myocardial contrast echocardiography has sufficient resolution to identify transmural
differences in myocardial blood flow during stress
imaging and thus might improve the detection of
ischemia during dobutamine stress testing. Secondly, current ultrasound contrast agents are approved only for enhancing endocardial border delineation. This study indicates that enhancing
border delineation might not be sufficient to improve the detection of coronary artery disease during dobutamine stress testing. Real-time myocardial contrast echocardiography can be used to
improve both the endocardial and transmural border and thus should be the preferred ultrasound
imaging method when clinically using contrast
during dobutamine stress testing.
Study limitations. The ability of WT on the preMCR images (where only an enhanced endocardial
border is present) to detect significant LAD stenoses had lower sensitivity than what has been reported in published reports. There are several potential explanations for this. One is that we only
included patients with normal resting WT in this
study, whereas other studies looking at the ability of
dobutamine stress WT to detect LAD disease have
Table 4. WT Measurements in Patients With Subendocardial Perfusion Defects and Normal TM WT
TM WT at Rest
Subendocardial WT at Peak
TM WT at Peak
Subendocardial perfusion defects with normal WT
42 ⫾ 11% (23%–69%)
25 ⫾ 10% (8%–48%)
36 ⫾ 14% (20%–63%)*
Subendocardial perfusion defects with abnormal WT
39 ⫾ 11% (27%–55%)
17 ⫾ 8% (0%–30%)†
33 ⫾ 15% (14%–63%)*
TM perfusion defects
43 ⫾ 7% (33%–53%)
—
30 ⫾ 27% (7%–76%)
Patients without LAD disease
39 ⫾ 11% (20%–57%)
—
44 ⫾ 13% (22%–65%)
*p ⬍ 0.05 compared with patients without left anterior descending coronary artery (LAD) disease; †p ⬍ 0.01 compared with subendocardial perfusion defects with
normal wall thickening (WT).
TM ⫽ transmural.
Xie et al.
Detection of Subendocardial Ischemia
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included patients with resting WT abnormalities
(17). Secondly, it is possible that the ultrasound
contrast on some of our pre-MCR images (which
were obtained immediately after the high MI impulse) might have inadequately filled the endocardial border and prevented the detection of a transmural WT abnormality. Thirdly, we had a high
percentage of patients with concentric remodeling,
which might have reduced wall stress and the
frequency of inducible transmural WT abnormalities (18). In these patients, it is possible that WT
might have become abnormal during the recovery
phase, which was not analyzed in our study.
Fourthly, the use of real-time perfusion usually
requires frame rates that are 22 to 25 Hz. This
lower frame rate might have prevented the detection of tardokinesis in zones supplied by ⬎50%
diameter stenoses, which requires frame rates of 60
Hz using color kinesis (19). Finally, although we
reached 85% of predicted maximum heart rate in
nearly all patients, the rate pressure product
achieved might have been insufficient to induce a
WT abnormality (Table 3).
Although there was visually no detectable WT
abnormality in a large percentage of pre-MCR
images in the patients with subendocardial perfusion defects, quantitative measurements of transmural WT were not augmented when compared
with baseline WT (Table 4). We did note that there
was a trend toward worsening quantitative measurements of WT in patients with visually normal
subendocardial WT to those with visually abnormal
subendocardial WT to those with transmural WT
abnormalities. Augmentation of WT would not be
expected in patients with inducible subendocardial
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Real-time myocardial contrast echocardiography with
a continuous infusion of ultrasound contrast permits
the detection of subendocardial ischemia in a significant number of patients that have apparent normal
transmural WT during dobutamine stress. Because
this technique can detect subendocardial perfusion
abnormalities, it improves the detection of ischemia by
creating both a transmural and endocardial border and
thus should be the preferred ultrasound imaging
method when using contrast during DSE.
Acknowledgments
The authors thank Stephanie Lyons and Stacey Kearney for their help in the preparation of the manuscript.
Reprint requests and correspondence: Dr. Thomas R. Porter, University of Nebraska Medical Center, 981165
Nebraska Medical Center, Omaha Nebraska 681981165. E-mail: [email protected].
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APPENDIX
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