(Circulation. 1997;96:816-820.)
© 1997 American Heart Association, Inc.
Articles |
From the Division of Cardiology, Department of Clinical and Experimental Medicine and the Department of Cardiac Surgery (D.C.), University of Padua (Italy).
Correspondence to R. Scognamiglio, MD, Cattedra di Cardiologia, Policlinico Universitario, Via Giustiniani 2, 30100 Padova, Italy.
| Abstract |
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Methods and Results Eighty-four consecutive candidates for bypass surgery with chronic multivessel coronary artery disease were screened, and 60 were included in this prospective study. Preoperative evaluation of a reversible contractile dysfunction in asynergic myocardial regions was performed by dobutamine infusion at 5 (low dose) and 10 (intermediate dose) µg·kg-1·min-1 with each stage lasting at least 5 minutes; postextrasystolic potentiation (PESP), with a coupling interval ranging from 500 to 300 ms with a progressive 10-ms decrease; or a combination of both dobutamine infusion and PESP. Sensitivity (92% versus 86%) and predictive accuracy (89% versus 84%) were higher with PESP than dobutamine (P=.009 and P=.001, respectively), but the combination did not improve sensitivity or accuracy. Dobutamine induced ischemic dysfunction in 15% of patients at the intermediate dose; however, the low dose resulted in loss of sensitivity.
Conclusions PESP echocardiography is a useful and cost-effective method to identify viable myocardium in patients with multivessel coronary disease undergoing revascularization and is more sensitive and accurate than dobutamine infusion.
Key Words: dobutamine contractility coronary disease echocardiography revascularization
| Introduction |
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| Methods |
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70% stenosis by
selective coronary angiography and the presence of wall motion
abnormalities in at least two adjacent segments by 2D
echocardiography, (2) suitability for surgical
revascularization of all significant
stenosis (
70%) of the coronary arteries subtending
the asynergic areas, (3) echocardiogram to assess wall motion and
thickening in every LV myocardial segment, and (4) informed consent.
Patients were excluded because of any of the following reasons: (1)
angina during the echocardiographic study, (2) acute
myocardial infarction or unstable angina within 6 months of the study,
(3) LV aneurysm, (4) significant valvular heart
disease, (5) history of sustained ventricular
tachycardia or atrial fibrillation, (6)
perioperative myocardial infarction, (7) early graft
closure assessed by coronary arteriography at the time of
follow-up echocardiography performed in all 84
patients, and (8) silent ischemia detected by 48-hour
ambulatory ST-segment monitoring preceding preoperative and
postoperative echocardiography because silent
ischemia is a factor causing both stunned
myocardium and loss of myocardial viability over
time.4 5 The study was approved by the Institutional
Review Board, and informed consent was obtained from all
participants. Of the 84 patients screened, 2 refused to participate, 7 (8.9%) had technically inadequate echocardiograms, 2 developed angina and ST changes during the echocardiographic study, 2 had early bypass closure, 7 (5 in the preoperative study and 2 in the postoperative study) had silent myocardial ischemia, 2 suffered intraoperative myocardial infarction, and 2 died perioperatively. The final group of 60 patients consisted of 54 men and 6 women, ranging in age from 40 to 72 years (mean, 58±9 years). Thirty-five patients (58.3%) had histories and ECG evidence of previous myocardial infarction (36 anterior and 24 inferior). Thirty-eight had three-vessel disease, and 22 had two-vessel disease. None of the patients included in this study had received a ß-blocker, an inotropic agent, or a calcium channel blocker 48 hours before the echocardiographic assessment of myocardial viability; nitrates were stopped 12 hours before the test; and no patients received ACE inhibitors.
Dobutamine Echocardiography
Dobutamine echocardiography was
performed the same day as the surgical procedure, 1 hour after PESP.
Echocardiographic examinations were performed by use of
a Hewlett-Packard 77030A phased-array ultrasonoscope and a 2.5- or
3.5-MHz transducer; images were digitized on-line with an ECG R
wavetriggered mechanism. A quad-screen, continuous-loop display was
used to simultaneously compare resting with low and
intermediate doses and recovery images (5 minutes after
dobutamine infusion). Patients underwent continuous ECG
monitoring. Dobutamine was infused
intravenously by an infusion pump at 5 (low dose) and 10
(intermediate dose)
µg·kg-1·min-1.
The minimum duration of each stage of the infusion was 5 minutes. Blood
pressure and heart rate were recorded at the end of each stage.
Standard echocardiographic views were recorded in
the left lateral position before, during, and for 5 minutes after
dobutamine infusion. LV wall motion score, volumes, and
LVEF were calculated at each stage of dobutamine infusion.
After the test, the patient was observed with continuous ECG monitoring
for an additional 15 minutes. Criteria for stopping the
dobutamine infusion included hypotension, angina,
significant ventricular or supraventricular
arrhythmias, attainment of 85% maximal predicted heart rate,
or a new or worsened abnormality in systolic wall thickening in
at least two segments.
Postextrasystolic Potentiation
PESP was performed the same day as the surgical procedure, 1
hour before dobutamine testing. The basic heart rate was
the patient's own intrinsic sinus rate; PESP was recorded after an
atrial induced extrasystole to obtain a completely noninvasive
approach. Although the phenomenon is usually recorded after a
ventricular extrasystole, it appears to be equally manifest
after an atrial extrasystole.6 7 8 A quadripolar electrode
catheter was passed through the nares into the distal esophagus. The
lead was secured when the unipolar electrogram, recorded from the
middle electrodes, exhibited the greatest amplitude and the most rapid
deflection. In this position, consistent and constant atrial
capture was achieved by means of a programmable stimulator with a pulse
width and amplitude of 10 ms and 15 mA, respectively. A single atrial
extrastimulus was delivered every 10th sensed, spontaneous sinus beat,
and the induced extrasystole was progressively decreased by 10 ms,
obtaining a coupling interval varying from 500 to 300 ms. The
postextrasystole was then allowed to occur spontaneously, according to
the patient's intrinsic rhythm. During the procedure, LV dimensions
were monitored by 2D echocardiography, and we
considered for analysis only beats without significant changes
in LV dimensions evaluated as LV area in the corresponding view during
induction of PESP. This condition is necessary to avoid significant
changes in LV preload associated with the compensatory pause after the
extrasystole. A coefficient of variation of 5% was present for
both interobserver and intraobserver variations. Thus, a 10% increase
in LV dimensions represents the 95% confidence level for
detecting significant changes.
PESP was repeated in parasternal long-axis, midventricular parasternal short-axis, apical four-chamber, and apical two-chamber views. PESP images with different coupling intervals, in each echocardiographic view, were arranged in a split-screen, continuous-loop display to be compared directly with the baseline. Regional systolic wall thickening was assessed according to the recommendation of the American Society of Echocardiography with a 16-segment model,9 and then WMSI was calculated. To study changes in LVEF, volumes were calculated at each coupling interval by a biplane, area-length method by use of apical four- and two-chamber views of postextrasystolic beats. For analysis, we considered only potentiated beats with similar duration of the interval between the extrasystole and postextrasystole for a given coupling interval.
PESP During Dobutamine Infusion
PESP, with a coupling interval ranging from 400 to 300 ms with
10-ms changes every 10th sinus beat, was repeated at the fifth minute
of dobutamine (10
mg·kg-1·min-1)
infusion. LV volumes, LVEF, and wall motion score were calculated for
any given coupling interval.
Echocardiographic Analysis
LV function was studied by 2D
echocardiography at rest (preoperatively and
postoperatively) to assess changes induced by coronary bypass
revascularization and during dobutamine
infusion and PESP to predict preoperatively any improvement in regional
systolic wall thickening after successful
revascularization. Digitized echocardiograms were
coded and read by two independent observers blinded to the patient's
identity and the order of the studies. Wall motion and myocardial
thickening were analyzed by dividing the left ventricle into 16
segments, and a semiquantitative scoring system (1=normal,
2=hypokinesis, 3=akinesis, and 4=dyskinesis) was used.9
Agreement of interobserver analysis for segmental asynergy was
seen in 98% of the segments visualized. Discrepancies were resolved by
consensus with a third observer. Improved segmental wall motion during
dobutamine infusion or PESP or at follow-up study was
defined as endocardial excursion and wall thickening in akinetic or
dyskinetic segments at baseline or normalization of endocardial
excursion and wall thickening in hypokinetic areas at baseline. A
change from dyskinesia to akinesia was considered to be unchanged
segmental wall motion. Reversible dysfunction was defined as improved
wall motion in at least two contiguous abnormal segments; this
criterion was chosen to minimize the potential influence of tethering
of an abnormal segment by adjacent normal or hyperkinetic segments. LV
volumes were calculated by an ellipsoid biplane area-length
method.10 EF was derived as EF=EDV-ESV/EDV, where EDV and
ESV were the end-diastolic and end-systolic
volumes. In our laboratory, the degree of interobserver and
intraobserver correlations for serial measurements of LV area
(r=.98 and r=.97, respectively) and of LV length
(r=.98 and r=.96, respectively) is
reasonable.11 The interstudy variability of resting LVEF
was assessed by echocardiographic examination twice
within half an hour and calculated by averaging the absolute
differences between the two measurements. Changes in LVEF were
considered significant if they were outside the 95% confidence limit
of interstudy variability.
Follow-up Study
Follow-up echocardiograms were obtained in all 60 study patients
who underwent successful and complete coronary bypass
revascularization. All patients had
echocardiographic follow-up 4 to 6 weeks after their
procedures. At this time, coronary angiogram to exclude
patients with early bypass closure and 48-hour ambulatory ST-segment
monitoring to exclude patients with silent myocardial ischemia
were repeated in the 64 patients enrolled after the preoperative
evaluation who survived the surgical procedure without
perioperative myocardial infarction. Postoperative
resting WMSI, LV volumes, and EF were determined in a blinded
fashion.
Statistical Analysis
All data are expressed as mean±SD. Comparisons of continuous
variables were made by one-way ANOVA and Bonferroni's corrected
t test.
2 analysis was used to
compare categorical data. A value of P
.05 by two-tailed
test was considered statistically significant. Linear regression
analysis was used to correlate changes in LVEF with the
corresponding coupling interval during PESP. Sensitivity of a test was
calculated as true positive (number of asynergies correctly identified
as reversible by the test) divided by the number of myocardial segments
showing improvement after revascularization of the
related stenotic coronary artery. Specificity was
determined as true negative (number of asynergic segments correctly
identified as not reversible) divided by the number of segments showing
no improvement after revascularization of the
related coronary artery. Accuracy was determined as true
positive plus true negative divided by the total number of
asynergies.
| Results |
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Dobutamine Echocardiography
Dobutamine stress echocardiography
correctly identified contractile reserve in 348 of the 749 asynergic
segments (46%). The dobutamine dose at which regional wall
thickening first showed improvement was variable: 216 (62%)
asynergic segments increased at 5
mg · kg-1 · min-1
for 5 minutes, and 132 increased at 10
mg · kg-1 · min for 5 minutes. In 9
patients (15%), 24 myocardial segments improved after the first
dobutamine infusion and did not improve after the second
infusion.
Mean LVEF increased from 48±10% to 54±8% (P<.001) after
5
mg · kg-1 · min-1
of dobutamine infusion per 5 minutes and to 58±12
(P<.001) after 10
mg · kg-1 · min-1
of dobutamine infusion per 5 minutes, respectively. During
the low-dose test, LVEDVI did not change significantly (84±21 versus
80±20, P=NS), and heart rate increased from 69±18 to
82±16 bpm (P<.001). During the intermediate-dose test,
LVEDVI tended further to reduce but not significantly (78±22
mL/m2, P=NS), and heart rate increased (86±18
bpm; P<.001).WMSI for the group at the completion of
dobutamine test improved from 2.26±0.29 to 1.82±0.24
(P<.001; Fig 1
).
Specifically, 414 myocardial segments manifested contractile reserve during dobutamine infusion, 348 of which subsequently showed improved regional wall thickening after coronary revascularization. In contrast, 279 of 345 myocardial areas that had no significant improvement during dobutamine infusion failed to improve after revascularization. Thus, the sensitivity of the test was 86.1%, the specificity was 80.8%, and the accuracy in predicting reversibility of asynergies after bypass was 83.7%.
Postextrasystolic Potentiation
PESP adequately predicted the reversal of contractile dysfunction
in 372 of the 749 asynergic segments (49.6%). The number of asynergic
myocardial areas that first reversed the baseline contractile
dysfunction progressively increased as the interval between the normal
systole and the extrasystole became shorter: 22 asynergic segments
(6%) improved with a coupling interval of 500 to 450 ms, 37 asynergies
(10%) showed improvement of myocardial function between 450 and 400
ms, 204 segments (55%) improved between 400 and 350 ms, and 109 (29%)
improved between 350 and 300 ms. All these myocardial segments reversed
their contractile dysfunction at a coupling interval of 400 to 300 ms,
independent of the time of first improvement. No myocardial segments
showed deterioration of contraction during PESP induction. LVEDVI in
the postextrasystolic beats used for
analysis did not differ from baseline values (88±29 versus
84±21 mL/m2, P=NS), whereas LVEF increased
significantly (68±10% versus 48±10%, P<.001). The
maximum increase in LVEF (Fig 2
) by PESP was
significantly greater than the maximum increase by both low- and
intermediate-dose dobutamine infusion (P<.001
for both). A significant negative linear correlation (Fig 3
) existed between potentiated LVEF and the
corresponding coupling interval (r=-.5962,
P<.001). WMSI for the entire group improved significantly
by PESP from 2.26±0.29 to 1.64±0.29 (P<.001; Fig 1
). PESP
determined a significantly greater decrease in WMSI than
dobutamine (P<.001). Specifically, 421
myocardial segments manifested recruitable contractile reserve by PESP,
372 of which subsequently showed improved regional wall thickening
after bypass. In contrast, 296 myocardial areas of 345 segments without
significant improvement by PESP failed to improve after myocardial
revascularization. Thus, the sensitivity of the
test was 92%, the specificity was 85.7%, and the accuracy in
predicting reversibility of regional myocardial dysfunction after
bypass was 89.2%.
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Prolongation of the coupling interval because of spontaneous intranodal delay did not allow us to consider for analysis 142 of 5040 stimulations (2.8%). No complications occurred during PESP procedure; the total mean duration of the study was 28 minutes.
Association of Dobutamine Infusion and PESP
The association of dobutamine and PESP correctly
predicted the presence of a reversible contractile dysfunction in 370
of the 749 asynergic myocardial areas (49.3%). Specifically, 425
myocardial asynergic segments showed significant improvement during
PESP associated with dobutamine infusion, 370 of which
subsequently improved the pattern of contraction after coronary
artery bypass revascularization. However, 290 of
324 asynergic areas that did not significantly improve during the
combined test failed to improve after
revascularization. Thus, the sensitivity was
91.5%, the specificity was 84.0%, and the accuracy in predicting the
postbypass reversibility of asynergies was 88.1%. WMSI reduced
significantly from 2.26±0.29 to 1.69±0.27 (P=.006). This
reduction was significantly greater than that induced by
dobutamine infusion alone (P=.006), but it did
not differ from changes obtained by PESP (P=NS). In 9 of 60
patients (15%), 24 asynergic areas improved after the first infusion
and did not improve after the second one; PESP restored a normal
contraction in 20 of these areas (83.3%).
LVEF significantly increased from 48±10% to 66±9% (P<.001). The improvement in LVEF by PESP during dobutamine infusion was significantly greater than the increase by dobutamine alone (P<.001), but it did not differ from changes induced by PESP alone (P=NS).
Of the 2640 stimulated beats, 64 (2.4%) were not considered for analysis because of spontaneous intranodal delay.
| Discussion |
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This study shows that echocardiographic assessment of a reversible contractile dysfunction in hibernating myocardium by dobutamine infusion or PESP is predictive of improvement after coronary bypass. The results of both methods are highly acceptable for clinical application. Nevertheless, PESP may be more useful because it has higher sensitivity (92% versus 86%, P=.009) and accuracy (89.2% versus 83.7%, P=.001), whereas specificity is similar for both methods. The combination of the two methods does not improve the capability of PESP alone to predict restoration of contractile function after revascularization.
Several observations may explain the superiority of PESP. In this study, 15% of patients showed deterioration of regional myocardial function at an intermediate dose of dobutamine after an early improvement at a low dose. However, low-dose dobutamine infusion is able to identify only 62% of reversible myocardial asynergies detected by the overall test. Low doses of dobutamine reduce the risk of inducing myocardial ischemia, but the intensity of inotropic stimulation is not enough to restore a normal contractile function in hibernating myocardium in most patients. The possibility of a dobutamine-induced ischemia has also been stressed in previous studies.18 19 The susceptibility of hibernating myocardium to ischemia and the large variability in the intensity of inotropic stimulus necessary to restore contractile function may explain the results of PESP. In fact, inotropic stimulation by PESP is of increasing intensity because it reduces the coupling interval without the risk of inducing myocardial ischemia because it is instantaneous. Interestingly, the power of inotropic stimulus by PESP was enough to improve myocardial function in most LV areas (83.3%) with an ischemia-induced deterioration at intermediate doses of dobutamine. A potential limitation of PESP may derive from the modality of transesophageal stimulation that requires careful control of the effective coupling interval. Spontaneous delay of intranodal conduction may prolong the value of the programmed coupling interval and reduce the expected intensity of inotropic stimulus. In our study, this occurred in a small percentage (2.6%) of 7680 extrasystoles induced during PESP studies. However, echocardiographic monitoring of LV avoids some important limitations of PESP during contrast ventriculography, which offers a minimal number of beats for analysis and may cause changes in LV contractility and load by contrast medium.
Other methods of detecting viable myocardium such as positron tomography and thallium allayed imaging have also been shown to predict recovery of function after revascularization.8 9 These methods that do not allow direct visualization of contractile improvement have the potential of indicating the presence of viability even in the absence of residual contractile reserve, as in the presence of small islands of viable myocytes within a predominantly scarred region.20
In conclusion, echocardiography during dobutamine infusion or PESP can accurately identify the presence of viable hibernating myocardium in patients with coronary artery disease and may be helpful in predicting functional recovery after coronary artery bypass. Even though the best approach depends on the individual patient and the expertise of a particular institution in a specific technique, PESP is more useful than dobutamine in allowing maximal contractile recruitment without inducing ischemia.
| Selected Abbreviations and Acronyms |
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Received July 1, 1996; revision received February 18, 1997; accepted February 24, 1997.
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