(Circulation. 1995;91:2748-2752.)
© 1995 American Heart Association, Inc.
Articles |
From the Thoraxcenter, Departments of Cardiology (M.A., J.H.C., A.S., A.E., F.J.T.C., D.K., A.H.M.M.B., J.R.T.C.R., P.M.F.) and Cardiac Surgery (A.P.W.M.M.) and the Department of Nuclear Medicine (A.E.M.R.), University Hospital Rotterdam-Dijkzigt and Erasmus University, Rotterdam, Netherlands.
| Abstract |
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Methods and Results Thirty-eight patients with severe chronic LV
dysfunction (ejection fraction
40%, one or more akinetic [Ak] or
severely hypokinetic [SH] segments on resting echocardiogram) who
underwent uncomplicated coronary artery bypass graft surgery were
studied with simultaneous dobutamine stress echocardiography and
poststress reinjection 201Tl single-photon emission
computed tomography (SPECT) before surgery. The Ak or SH segments were
considered viable by LDDE when wall thickening improved during the
infusion of 10
µg · kg-1 · min-1
dobutamine. Scintigraphic definition of viability was the presence of
normal 201Tl uptake, totally reversible defect, partially
reversible defect, or moderately severe fixed defect. The postoperative
improvement of dyssynergic segments was determined with a rest
echocardiogram 3 months after surgery. Of 608 LV segments, 169 were
classified as Ak and 51 as SH on resting preoperative echocardiography.
Of these, 170 were successfully revascularized. Wall motion during LDDE
improved in 33 severely dyssynergic segments and was more frequent in
SH than in Ak segments (19 of 44 versus 14 of 126,
P<.0001). Viability was detected by 201Tl SPECT
criteria in 103 SH or Ak segments. Thirty-two of the 33 segments from
LDDE responders were judged viable on 201Tl SPECT, whereas
201Tl viability was also detected in 71 of 137 segments
from LDDE nonresponders. The sensitivity and the specificity for the
prediction of postoperative improvement of segmental wall motion were
74% (95% confidence interval [CI], 67% to 81%) and 95% (95% CI,
92% to 98%) by LDDE and 89% (95% CI, 84% to 94%) and 48% (95%
40% to 56%) by 201Tl SPECT, respectively. Positive
predictive value of LDDE was higher than that of 201Tl
SPECT (85%, [95% CI, 80% to 90%] versus 33% [95% CI, 26% to
40%]). Thirty-six patients had angina before and only 1 had angina 3
months after revascularization. High-dose dobutamine echocardiography
demonstrated significant reduction in stress-induced ischemia (new or
worsening of preexisting wall motion abnormalities) after surgery (from
163 to 23 LV segments).
Conclusions In patients with severe chronic LV dysfunction, LDDE is a good predictor of the improvement of dyssynergic segments after revascularization. Because 201Tl SPECT overestimates the probability of postoperative improvement of dyssynergic segments, LDDE should be the preferred imaging technique for preoperative assessment of these patients.
Key Words: dobutamine myocardium bypass echocardiography scintigraphy
| Introduction |
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Both 201Tl single-photon emission computed tomography (SPECT)2 3 4 5 and low-dose dobutamine echocardiography (LDDE) have been proposed as effective techniques for the evaluation of myocardial viability.6 7 8 9 10 11 Although LDDE is more widely available, it is unknown whether its efficacy and reliability equal those of 201Tl SPECT, which is more established in this role.2 3 4 5
To determine the relative merits of the two imaging techniques, we compared 201Tl SPECT and LDDE in the prediction of functional recovery in 38 patients with left ventricular dysfunction who were undergoing coronary artery bypass graft surgery. Postoperative resting echocardiography at 3 months was used to determine left ventricular improvement.
| Methods |
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40% on contrast
ventriculography, history of previous (>3 months old) myocardial
infarction, one or more akinetic (Ak) or severely hypokinetic (SH)
segments on preoperative resting echocardiography (16-segment left
ventricular model), absence of recent episodes of unstable angina,
absence of significant (>50%) left main stem stenosis, and absence of
(hemodynamically) significant valvular disease. Five patients were withdrawn from the study because of perioperative myocardial infarction (3 patients), resection of all dyssynergic segments (1 patient), or inability to graft any of the Ak or SH segments (1 patient). Thirty-eight patients constituted the final study population. Mean patient age was 59 years (range, 36 to 73 years), and 26 were men. All patients were symptomatic36 had angina pectoris and 20 had dyspnea on effort. Mean angiographic left ventricular ejection fraction was 31% (range, 18% to 40%). One-vessel disease, defined as diameter stenosis of a major coronary artery of >50%, was present in 3 patients; 16 patients had two-vessel disease; and 19 patients had three-vessel disease. Four patients had undergone previous coronary artery bypass graft surgery. Four patients were on ß-blockers during the preoperative diagnostic work-up.
Dobutamine Stress Echocardiography
The dobutamine stress test
was performed as follows. A
two-dimensional transthoracic echocardiogram in standard views and a
12-lead ECG were recorded with the patient at rest. Dobutamine was
infused through an antecubital vein at dosages of 5 and 10
µg · kg-1 · min-1, for 3
minutes at each dose. Subsequently, three other steps from 20 to 40
µg · kg-1 · min-1 (3
minutes each)
were added. Finally, atropine (up to 1 mg) was injected when 85% of
the maximal heart rate had not been reached.12 The
echocardiogram was monitored during the test, and the last minute of
each stage was recorded on videotape. The echocardiographic images were
also digitized (on optical disk [Vingmed CFM 800] or on floppy disk
[Esaote Biomedica SIM 7000]) and displayed side-by-side in
quadscreen
format to facilitate the comparison of images at rest and after
dobutamine with subsequent postoperative images. A 3-lead ECG was
monitored continuously, and a 12-lead ECG was recorded every minute.
Blood pressure was measured by sphygmomanometer at each 3-minute
stage.
Postoperative Echocardiography
To assess the functional
outcome of the dyssynergic segments, we
obtained resting two-dimensional echocardiograms in all patients 3
months after cardiac surgery. In addition, high-dose
dobutamine/atropine stress echocardiography was obtained in 32
patients.
Analysis of Preoperative and Postoperative Echocardiograms
The interpretation of echocardiograms was performed by two
experienced observers who were blinded to the clinical, angiographic,
and previous echocardiographic results of the individual patients. In a
subset of 11 patients (176 segments), the interobserver and
intraobserver variabilities of the classification of resting wall
motion and the response to LDDE were also assessed. The assessment was
based on both the digitized images displayed in a quadscreen format and
a review of the images recorded on the videotape. The assessment was
semiquantitative, and a 16-segment model13 was used. The
wall motion, including wall thickening, of every segment was scored
with a 5-point scoring system, where 1 is normal wall motion and
thickening, 2 is moderately hypokinetic, 3 is SH, 4 is Ak, and 5 is
dyskinetic. We defined a segment as SH in the presence of minimal wall
thickening with a limited inward motion of <2 mm; as Ak in the absence
of systolic wall motion and thickening and, whenever possible,
confirmed by M-mode tracing; and as dyskinetic in the presence of
systolic outward wall motion with thinning.
Wall thickening was
primarily used for the classification of wall
motion, preventing the problem of postoperative paradoxical septal
motion. Also, to reduce the confounding effect of tethering from
adjacent segments, segmental wall thickening was analyzed
frame-by-frame during the first half of systole. Myocardial viability
was judged to be present in a dyssynergic (either Ak or SH) segment
when wall motion improved during the infusion of low-dose dobutamine by
at least one point of the scoring system. Thus, a severe hypokinesis
becoming moderately hypokinetic or systolic myocardial thickening
becoming apparent in a previously Ak segment was considered a marker of
viability. Myocardial ischemia was judged to be present when there
was worsening by
1 of the segmental score. Ak and dyskinetic segments
were not evaluated for this purpose.
Follow-up echocardiograms were compared with the corresponding preoperative resting images. For each segment, improvement of function was defined as a decrease of one or more grades. Moreover, we used the preoperative and postoperative wall motion score indexes (WMSIs) to evaluate the effect of revascularization on global LV function. WMSI was defined as the sum of the degrees of each segment divided by the total number of segments analyzed.
201Tl SPECT Imaging
Briefly, as described
previously,14 15 16
201Tl (2 mCi) was injected intravenously 1 minute before
the termination of the infusion of high-dose dobutamine (up to 40
µg · kg-1 · min-1, with
the
addition of atropine if there were no signs of ischemia and if 85% of
the maximal heart rate had not been reached). The acquisition of the
poststress SPECT imaging was started within 10 minutes after the
interruption of the dobutamine infusion. All images were acquired with
a Siemens Gammasonics single-head Rota Camera (Orbiter) and a
low-energy, all-purpose collimator. Thirty-two projections were
obtained, from left posterior oblique to right anterior oblique, with
an acquisition time of 45 seconds for each projection. A Gamma 11
computer system was used to process the tomographic data. Four hours
after the stress imaging, a second acquisition was performed 20
minutes following the reinjection of 1 mCi of 201Tl.
As previously described,15 16 the interpretation of the images was based on six short-axis slices, three longitudinal slices, and three transverse long-axis slices (both stress and after reinjection). The analysis was performed visually with the assistance of quantitative measurement (circumferential profiles). The same 16-segment model used for interpretation of the echocardiograms was applied for the interpretation of the SPECT images. Scintigraphic images from the short-axis and the long-axis views were matched with the echocardiographic images. Each defect was classified as fixed, partially reversible, or totally reversible. A myocardial segment was considered nonviable in the presence of a severe irreversible defect. A defect was classified as severe if the 201Tl uptake of a segment was <50% of the uptake of the "normal" segments on the quantitative circumferential profile analysis and if it was consistent with a severe visually assessed defect. Scintigraphic definition of viability was based on the presence of normal 201Tl uptake, totally reversible defect, partially reversible defect, or moderately severe fixed defect.
Statistical Analysis
Continuous data are expressed as
mean±SD. Univariate
analysis for categorical variables was performed using the
2 test with Yates' correction. Differences were
considered significant if the null hypothesis could be rejected at the
.05 probability level. Sensitivity, specificity, and positive and
negative predictive values were based on their standard definitions and
are reported with the corresponding 95% confidence interval (CI). The
interobserver and intraobserver variabilities of regional wall motion
pattern were assessed as percent agreement and
value.
| Results |
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Low-Dose Dobutamine Echocardiography
Only 14 of the 126 Ak
segments that could be successfully
revascularized showed the presence of wall thickening during low-dose
dobutamine on preoperative echocardiogram. These 14 Ak segments were
detected in 8 patients.
Wall thickening improved during the infusion of dobutamine in 19 of the 44 SH segments. These 19 segments were present in 9 patients. Thus, viability was detected more frequently in SH than in Ak segments (P<.0001).
The interobserver and intraobserver concordances
of resting wall motion
analysis were 84% (
, 0.79) and 87% (
, 0.82), respectively.
The interobserver and the intraobserver concordances of the response of
wall motion during LDDE also were excellent: 92% (
, 0.84) and 94%
(
, 0.86), respectively.
High-Dose Dobutamine Echocardiography
At peak stress, new or
worsening of preexisting wall motion
abnormalities was detected in 163 of 576 segments (in 32 of 36
patients). Angina occurred in 28 patients during the test.
201Tl SPECT
201Tl SPECT imaging
indicated the presence of viable
myocardium in 49 of 112 Ak regions not responding and in 14 of 14 Ak
regions responding to dobutamine and in 22 of 25 SH regions not
responding and in 18 of 19 SH regions responding to dobutamine (Table
1
). From these data, it is clear that 201Tl
SPECT indicates viable myocardium more frequently than LDDE
(P<.001). The Figure
displays the
distribution of perfusion patterns by 201Tl SPECT according
to the different LDDE results.
|
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Postoperative Clinical and Echocardiographic Data
At 3 months
after surgery, only 1 patient had angina and 10
patients still complained of dyspnea on effort.
Improvement of Regional Wall Motion
Resting echocardiograms
at 3-months postoperative follow-up
revealed an improvement of wall motion in 38 (22%) of the 170
dyssynergic segments. The improvement was found in 22 (17%) of the 126
Ak segments (change to SH in 6 segments, to moderate hypokinesis in 13
segments, and to normal in 3 segments) and in 16 (36%) of the 44 SH
segments (change to moderate hypokinesis in 8 segments and to normal in
8 segments) (P=.02).
Reduction in Dobutamine-Induced Myocardial Ischemia
Of 32
patients who underwent a high-dose dobutamine stress
test during follow-up, 3 had angina at peak stress. New or worsened
wall motion abnormalities were detected in 10 patients and in 23 of 512
LV segments.
Prediction of Regional Improvement
Postoperative improvement
occurred in 28 of 33 segments that
improved during LDDE and in only 10 of 137 segments that did not
improve (Table 1
). Of the segments judged to be viable by LDDE,
postoperative improvement occurred in 79% of SH segments and in 93%
of Ak segments.
201Tl SPECT detected the presence of viable
myocardium in
32 of the 33 matched segments considered viable by LDDE. Despite the
frequent indication of viability by 201Tl SPECT in the Ak
segments unresponsive to dobutamine (44%), improvement after
surgery was found in only 8% of these segments. Similarly, wall
thickening improved after revascularization in only 1 of the 25 SH
regions unresponsive to dobutamine, despite signs of viability by
201Tl SPECT in 22 of these 25 segments. Table 2
shows the predictive accuracy with 95% CI of the two
methods for the postoperative improvement of SH and Ak segments.
|
Global Left Ventricular Function
The WMSI revealed that there
were no significant differences
before and after coronary artery bypass graft surgery in either the
subset in whom myocardial viability was predicted by LDDE (13 patients)
(2.6±0.5 versus 2.4±0.4) or in the entire study population
(2.3±0.5
versus 2.3±0.5).
Coronary Angiography
A routine coronary angiogram independent
of the recurrence of
symptoms was undertaken in 14 patients at 3-month follow-up. Sustained
patency of the grafts to the Ak or SH segments was demonstrated in all
of these patients.
| Discussion |
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We prospectively studied a group of patients with severe chronic LV dysfunction who were candidates for surgical revascularization (1) to assess the prevalence of regional improvement of Ak and SH segments after surgical revascularization and (2) to evaluate the roles of LDDE and 201Tl SPECT for predicting such improvement. In addition, the reversibility of stress-induced myocardial ischemia was assessed by clinical judgment and high-dose dobutamine stress test.
In this series of patients, improvement of regional function after revascularization was found in 22% of Ak and SH segments. This percentage is lower than that of other series7 9 10 and might be related to the selection of patients with severely impaired LV function in a tertiary referral center with an ongoing heart transplantation program.
We have demonstrated that preoperative LDDE is both a sensitive (28 of 33 segments) and a specific (127 of 137 segments) predictor of postoperative outcome of regional myocardial function. The pattern of improvement of wall thickening in severely dyssynergic regions during the infusion of low-dose dobutamine was found to be a reliable predictor of functional recovery of wall motion after successful and uncomplicated surgical revascularization, with a positive predictive value of 85% (95% CI, 80% to 90%), whereas the pattern of Ak or SH unresponsive to low-dose dobutamine is indicative of nonviable tissue and has a negative predictive value of 93% (95% CI, 89% to 97%).
201Tl SPECT (matched for echocardiographic segments)
indicated the presence of viable myocardium more frequently than LDDE
(103 of 170 versus 33 of 170). However, this imaging technique appears
to be less suitable than LDDE to predict the postoperative improvement
of regional wall motion in patients with severe LV dysfunction. In
particular, the high prevalence of viability detected before surgery by
201Tl SPECT and the low prevalence of postoperative
functional improvement result in a low specificity and in a low
positive predictive value (Table 2
).
Overestimation of myocardial viability by perfusion scintigraphy may relate to several factors. First, scintigraphy may detect islands of jeopardized vital myocardial cells of inadequate size to revert LV dysfunction despite successful revascularization. Second, tethering by scar tissue may restrict the improvement in wall motion of adjacent viable segments. Third, functional recovery may not be complete by 3 months ("embalmed myocardium").17 Finally, since subendocardial layers play a major role in wall motion, a necrosis limited to the subendocardium may result in severe dyssynergy despite the presence of viable myocardium in the subepicardial layers.18
In our study group, there was no significant postoperative improvement of global LV function; however, bypass surgery alleviated myocardial ischemia, since the number of patients with angina and the extent of stress-induced ischemia were greatly reduced. This is consistent with the high postoperative patency rate of bypass coronary grafts and confirmed the usefulness of dobutamine stress echocardiography in the assessment of stress-induced myocardial ischemia after coronary revascularization.12
Previous Studies
Although several
studies6 7 8 11 19
have addressed the
role of dobutamine echocardiography for the assessment of LV functional
recovery in patients with recent myocardial infarction, few data are
available regarding its predictive value for postrevascularization
functional improvement.9 10 In two previous studies
on
postrevascularization recovery, Marzullo et al9 and
Cigarroa et al10 reported a higher incidence of wall
thickening during low-dose dobutamine in Ak regions (47% and 39%,
respectively, compared with 11% in the present study). This
discrepancy may relate to different methodologies (absence of
subclassification for SH segments in their studies) and patient
selection (inclusion in the present study of patients with more
severe and more long-standing ventricular dysfunction, where stunned
myocardium is less likely to be present). Considering the value of
LDDE in predicting postoperative functional outcome, our findings are
in agreement with those of the two previous reports.
Study Limitations
First, the number of viable Ak and SH
segments identified in the
present study was limited despite our analysis of 608 segments
both before and after coronary artery bypass graft surgery. This,
however, reflects our stringent inclusion criteria and our strict
method of analysis (panel review with simultaneous, quadscreen
format).
Second, we arbitrarily timed the outcome of dyssynergic segments 3 months after surgical revascularization. However, it cannot be excluded that functional improvement can also occur later.
Finally, we focused on the postoperative phase of regional wall motion. We are aware that the improvement in a limited area of myocardium can be clinically not relevant to global LV function. However, this was not the primary aim of the study.
Conclusions
Our observations in the setting of severe chronic
LV dysfunction
indicate that (1) wall thickening during low-dose dobutamine in Ak
segments is infrequent, (2) responsiveness of Ak and SH segments to
low-dose dobutamine is both a specific and a sensitive predictor of
postrevascularization functional improvement, and (3) compared with
LDDE, 201Tl SPECT has an equivalent sensitivity for the
prediction of postoperative myocardial functional improvement but a
lower specificity. Thus, LDDE should be the preferred imaging technique
for predicting the functional outcome of patients with severe LV
dysfunction who are under consideration for coronary artery bypass
graft surgery.
| Acknowledgments |
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| Footnotes |
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Received October 18, 1994; revision received December 8, 1994; accepted December 18, 1994.
| References |
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I. Iglesias-Garriz, F.e. Corral, M. A. Rodriguez, C. Garrote, M. Montes, and E. Sevillano Pre-infarction angina elicits greater myocardial viability on reperfusion after myocardial infarction: a dobutamine stress echocardiographic study J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1846 - 1850. [Abstract] [Full Text] [PDF] |
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K. Yoshinaga, K. Morita, S. Yamada, K. Komuro, C. Katoh, Y. Ito, Y. Kuge, T. Kohya, A. Kitabatake, and N. Tamaki Low-Dose Dobutamine Electrocardiograph-Gated Myocardial SPECT for Identifying Viable Myocardium: Comparison with Dobutamine Stress Echocardiography and PET J. Nucl. Med., June 1, 2001; 42(6): 838 - 844. [Abstract] [Full Text] [PDF] |
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R Sicari, A Ripoli, E Picano, A.C Borges, A Varga, W Mathias, L Cortigiani, R Bigi, J Heyman, S Polimeno, et al. The prognostic value of myocardial viability recognized by low dose dipyridamole echocardiography in patients with chronic ischaemic left ventricular dysfunction Eur. Heart J., May 2, 2001; 22(10): 837 - 844. [Abstract] |