Low dose dobutamine echocardiography for predicting functional recovery after coronary revascularisation.

Abstract

To evaluate the effects of chronic coronary occlusion on the accuracy of low dose dobutamine echocardiography in predicting recovery of dysfunctional myocardium after revascularisation.
Retrospective study.
Tertiary referral centre.
53 consecutive patients with >/= 70% stenosis of the left anterior descending coronary artery (LAD) and regional ventricular dysfunction (group 1, non-occluded LAD; group 2, occluded LAD) who underwent dobutamine echocardiography.
26 patients underwent coronary artery bypass grafting and 27 had percutaneous transluminal coronary angioplasty.
Baseline studies before revascularisation included cross sectional echocardiography at rest and during dobutamine infusion (5-10 microgram), and coronary angiography. The dobutamine study was performed mean (SD) 35 (28) days before revascularisation. Echocardiography at rest was repeated 90 (48) days after revascularisation.
Of 296 dysfunctional segments, 63 in group 1 (43%; 63/146) and 69 in group 2 (46%; 69/150) (NS) improved at follow up. Mean (SD) regional wall motion score index decreased from 1.97 (0.48) (95% confidence interval (CI) 1.01 to 2.93) before revascularisation to 1.74 (0.52) (95% CI 0.70 to 2.78) at follow up in group 1 (p = 0.001), and from 2.12 (0.41) (95% CI 1.30 to 2.98) to 1.88 (0.36) (95% CI 1.16 to 2.60) in group 2 (p = 0.0006). In group 1, sensitivity (87% v 52%; p < 0.0001), negative predictive value (88% v 65%; p = 0.001), and accuracy (77% v 64%; p = 0.01) were all significantly higher than in group 2, despite the angiographic evidence of collaterals in patients with occluded vessels.
Dobutamine echocardiography shows reduced sensitivity in predicting recovery of dysfunctional myocardium supplied by totally occluded vessels. Thus caution should be used in selecting such patients for revascularisation on the basis of a viability assessment made in this way.

Full text

Page 1

Low dose dobutamine echocardiography for
predicting functional recovery after coronary
revascularisation
F Piscione, P Perrone-Filardi, G De Luca, M Prastaro, C Indolfi, P Golino,
S Dellegrottaglie, M Chiariello
Abstract
Objective—To evaluate the eVects of chronic coronary occlusion on the accuracy of low dose
dobutamine echocardiography in predicting recovery of dysfunctional myocardium after revascu-
larisation.
Design—Retrospective study.
Setting—Tertiary referral centre.
Patients—53 consecutive patients with > 70% stenosis of the left anterior descending coronary
artery (LAD) and regional ventricular dysfunction (group 1, non-occluded LAD; group 2,
occluded LAD) who underwent dobutamine echocardiography.
Interventions—26 patients underwent coronary artery bypass grafting and 27 had percutaneous
transluminal coronary angioplasty.
Main outcome measures—Baseline studies before revascularisation included cross sectional
echocardiography at rest and during dobutamine infusion (5–10 µg/kg/min),and coronary angio-
graphy. The dobutamine study was performed mean (SD) 35 (28) days before revascularisation.
Echocardiography at rest was repeated 90 (48) days after revascularisation.
Results—Of 296 dysfunctional segments, 63 in group 1 (43%; 63/146) and 69 in group 2 (46%;
69/150) (NS) improved at follow up. Mean (SD) regional wall motion score index decreased
from 1.97 (0.48) (95% confidence interval (CI) 1.01 to 2.93) before revascularisation to 1.74
(0.52) (95% CI 0.70 to 2.78) at follow up in group 1 (p = 0.001), and from 2.12 (0.41) (95% CI
1.30 to 2.98) to 1.88 (0.36) (95% CI 1.16 to 2.60) in group 2 (p = 0.0006). In group 1, sensitiv-
ity (87% v 52%; p < 0.0001), negative predictive value (88% v 65%; p = 0.001), and accuracy
(77% v 64%; p = 0.01) were all significantly higher than in group 2, despite the angiographic evi-
dence of collaterals in patients with occluded vessels.
Conclusions—Dobutamine echocardiography shows reduced sensitivity in predicting recovery of
dysfunctional myocardium supplied by totally occluded vessels. Thus caution should be used in
selecting such patients for revascularisation on the basis of a viability assessment made in this way.
(Heart 2001;86:679–686)
Keywords: dobutamine; coronary artery disease; viability; chronic occlusion
Dobutamine echocardiography is currently
used to predict recovery of regional and global
left ventricular systolic function in patients
with chronic coronary artery disease. Inotropic
stimulation with dobutamine results in a tran-
sient amelioration of contractile dysfunction in
viable myocardium which is highly predict-
ive offunctional
revascularisation.1–6
However, although the
specificity of the test is very high its sensitivity
has been reported to be suboptimal, especially
in the setting of severely dysfunctional myocar-
dium.4 7It has been shown that enhancement
of contractile function by dobutamine relies on
preservation of coronary flow reserve, leading
to an increase in blood flow in dysfunctional
myocardium.8 9However, coronary reserve is
correlated with the severity of coronary artery
stenosis and is greatly reduced in territories
supplied by occluded vessels.10 11Thus it is
conceivable that the accuracy of the test may
vary in relation to the patency of the vessel, but
very limited data evaluating such a hypothesis
have so far been reported.12
The aim of our present study was to evaluate
whether the accuracy of low dose dobutamine
echocardiography is influenced by the patency
recoveryfollowing
of coronary vessels and by the development of
a collateral circulation in patients with chronic
coronary artery disease. We selected patients
with left anterior descending coronary artery
(LAD) disease because revascularisation of the
LAD has a greater impact on left ventricular
function and prognosis,13–15and because it
minimises the source of overlap among diVer-
ent vascular territories.
Methods
PATIENT POPULATION
Our patient population was selected from a
consecutive group of 170 patients who formed
part of a prospective protocol at our institution.
The criteria for entering the study were first,
the presence of > 70% diameter stenosis in the
LAD; and second, regional wall motion abnor-
malities at rest in one or more myocardial seg-
ments belonging to the LAD territory, identi-
fied on both cross sectional echocardiography
and contrast ventriculography.
Patients with myocardial infarction, unstable
angina, or congestive heart failure occurring
within one month of the study were excluded;
additional exclusion criteria were: > 50%
left main stenosis, significant valvar disease,
Heart 2001;86:679–686 679
Division of Cardiology,
Federico II University,
Via Sergio Pansini 5,
I-80131 Naples, Italy
F Piscione
P Perrone-Filardi
G De Luca
M Prastaro
C Indolfi
P Golino
S Dellegrottaglie
M Chiariello
Correspondence to:
Dr Perrone-Filardi
fpperron@unina.it
Accepted 18 June 2001
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Page 2

previous coronary artery bypass graft surgery,
and technically inadequate echocardiographic
images.
One hundred and twenty nine patients (120
men and nine women) met the entry criteria,
and 110 of these (85%) had a history of previ-
ous myocardial infarction. In 90 of the latter
(70%), the infarct occurred in the LAD
territory. Among the 129 patients, an occluded
LAD was present in 51 and a significantly
stenosed LAD in the remaining 78. Sixty
patients belonging to this initial population
were revascularised. The decision to carry out
revascularisation was based on stable angina in
35 patients (58%), angina at rest in nine
(15%), a positive stress test in 11 (18%), and
worsening heart failure in the remaining five
(8%), but not on myocardial viability. Seven
patients refused to have echocardiographic
studies after revascularisation. Therefore the
remaining 53 patients (50 men and three
women, mean (SD) age 59 (7) years) represent
the study population. This was divided in
group 1 (non-occluded LAD; 27 patients;
mean stenosis 82 (12)%) and group 2 (oc-
cluded LAD; 26 patients). As detailed in table
1, the two groups did not diVer with respect to
age, history of anterior infarction, clinical
symptoms, prevalence of multivessel disease,
baseline left ventricular ejection fraction, or
preoperative global and regional (LAD terri-
tory) wall motion score index (WMSI).
STUDY PROTOCOL
Baseline studies before revascularisation in-
cluded cross sectional echocardiography at rest
and during dobutamine infusion. Forty six
patients also underwent
(single photon emission computed tomography)
according to the rest–redistribution protocol4
and had coronary angiography.
SPECT and dobutamine echocardiography
were performed on the same day in most
patients (95%).They were performed at a mean
of 35 (28) days before revascularisation. Echo-
cardiography at rest was repeated 90 (48) days
after revascularisation. In all patients, calcium
antagonists and oral nitrates were withdrawn for
at least 48 hours,? blockers for at least 72 hours,
201thallium SPECT
201Thallium
and transdermal nitrates for at least 12 hours
beforethestudy.Informedconsentwasobtained
from each patient before the study.
ECHOCARDIOGRAPHY
Cross sectional echocardiography was per-
formed with a 2.5 MHz transducer and a com-
merciallyavailablescanner
Hewlett–Packard Inc, Andover, Massachu-
setts,USA) under resting conditions and in the
last three minutes of each dobutamine infusion
level. Echocardiographic images were acquired
in the left lateral decubitus position and
recorded on 12.5 mm VHS videotape. Four
standard views of the left ventricle were
obtained for each acquisition: parasternal long
axis, short axis at mitral and papillary muscle
level, and apical four and two chamber views.
After baseline echocardiography had been
performed, low dose dobutamine echocardio-
graphy was begun, using a mechanical infusion
pump. The initial dose was 5 µg/kg/min for five
minutes, and the dose was then increased to
10 µg/kg/min for five more minutes. Blood pres-
sure was measured periodically, and a 12 lead
ECG was monitored continuously throughout
the study and during the recovery phase.
The total duration of the study did not
exceed 30 minutes.No patient reported angina
or developed life threatening arrhythmias or
hypertension during the test. In two patients,
dobutamine infusion had to be interrupted in
the last minute of the peak dose infusion
because of the development of ventricular
bigeminy; this subsided after the infusion of ?
blockers. Mean (SD) heart rate was 76 (10)
beats/min at baseline (95% confidence interval
(CI) 55 to 97) and increased to 95 (20) beats/
min (95% CI 55 to 135) at the end of peak
infusion (p < 0.0005). Systolic blood pressure
was 131 (20) mm Hg (95% CI 91 to 171) at
baseline and 136 (20) mm Hg (95% CI 96 to
176) at the end of the study (NS). Resting
echocardiography was repeated at follow up
using the same examination criteria.
(Sonos1000,
201THALLIUM IMAGING
After an overnight fast, patients underwent
quantitative SPECT after the administration of
3 mCi of
ing conditions. SPECT images were acquired
15–20 minutes and four hours after the
lium injection, as previously described.4Thirty
two images were acquired from a 30° right
anterior oblique to a 60° left posterior oblique
view in 6° increments.
201thallium intravenously under rest-
201thal-
CORONARY ANGIOGRAPHY
All patients underwent cardiac catheterisation.
Left ventriculography and coronary angio-
graphy were carried out by the Judkins
technique. The left and right coronary arteries
were imaged in multiple views, including
craniocaudal angulations. To minimise the
potential eVect of coronary vasoconstriction,
contrast injection was performed after intrac-
oronary administration of glyceryl trinitrate
(200 µg). The number of diseased vessels did
not diVer significantly between the two groups
of patients (table 1).
Table 1Characteristics of the patient population
Non-occluded LAD
(group 1,n=27)
Occluded LAD
(group 2,n=26)p Value
Clinical data
Age (years)
Male
Female
Hypertension
Hypercholesterolaemia
Previous anterior MI
Q wave
Non-Q-wave
Angiographic data
Multivessel disease
Proximal stenosis
Diameter stenosis (%)
Collateral channels to LAD
Echocardiographic data
LVEF (%)
WMSI
Regional WMSI
59 (6)
26
1
9 (31%)
11 (40%)
58 (7)
24
2
8 (28%)
10 (37%)
NS
NS
NS
NS
NS
16 (59%)
4 (15%)
16 (61%)
3 (11%)
NS
NS
21 (77%)
17 (63%)
77 (8)
1 (3%)
20 (78%)
16 (62%)
100
22 (85%)
NS
NS
p<0.001
p<0.001
44 (11)
1.68 (0.33)
1.97 (0.48)
41 (9)
1.9 (0.37)
2.12 (0.41)
NS
NS
NS
Values are mean (SD) or n (%).
LAD, left anterior descending coronary artery; LVEF, left ventricular ejection fraction; MI, myo-
cardial infarction; WMSI, wall motion score index.
680
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ECHOCARDIOGRAPHIC ANALYSIS
Undigitised echocardiographic images were
analysed oV line from the videotape playback
by continuous display. This was done by two
independent operators who were unaware of
the clinical and angiographic results. When
echocardiography was performed during fol-
low up, the operators were not aware of the
pre-revascularisation study results.
Regional wall motion was evaluated at the
chordal, papillary muscle, and apical levels,
and was assessed visually using both endocar-
dial motion and wall thickening. For analysis,
the left ventricle was divided into 16 segments
as recommended by the American Society of
Echocardiography.16
The
ventricular images at the cordal and mid-
papillary muscle levels were divided into six
myocardial segments, starting at the 3 o’clock
position and proceeding clockwise, represent-
ing posterolateral, inferior, posteroseptal, an-
teroseptal, anterior, and anterolateral myocar-
dium, respectively. Short axis images at the
apical level were divided into four myocardial
segments, starting at the half past one o’clock
position and proceeding clockwise, represent-
ing lateral, inferior, septal, and anterior apical
myocardium. The LAD territory was defined
as basal, mid, and distal segments of the left
anterior wall, basal and mid segments of the
anterior and posterior septum, and the distal
septum, the total number of segments being
eight (fig 1). To evaluate regional systolic func-
tion, wall motion and thickening were graded
semiquantitatively using a scoring system
short axismid-
where 1 = normal contraction, 2 = hypokinesia
(severely reduced wall thickening and inward
motion), 3 = akinesia (absence of wall motion
and of systolic thickening), and 4 = dyskinesia
(absence of wall thickening and outward
motion). Systolic function was scored at rest
and at each dobutamine dose.
Regional systolic dysfunction was defined
when a score of > 2 was assigned to a myocar-
dial segment in at least two diVerent echocar-
diographic views. Viable myocardium was
defined as an improvement of functional score
of > 1 grade in at least one segment with rest
hypokinesia or akinesia. Myocardial scarring
was identified in segments with resting dys-
function that did not show improvement
during low dose dobutamine echocardio-
graphy. Recovery in the LAD territory was
defined as improvement in functional score by
> 1 grade of one or more septal or anterior
segments compared with the preoperative rest
study. For both preoperative and postoperative
rest echocardiograms, a WMSI was derived
(the sum of individual wall motion scores
divided by the respective number of segments)
for the entire ventricle (global WMSI) and for
the LAD territory (regional WMSI).
The reproducibility
graphic analysis in our laboratory has been
reported previously.4In particular, exact agree-
ment in segmental scores (including function
at rest and during inotropic stimulation) was
82% (? value 0.62; p < 0.01), and in 97.5% of
all segments analysed the score diVerence
between two echocardiographic readings was
within 1 point.
Our interobserver and intraobserver repro-
ducibility of the global left ventricular ejection
fraction was analysed by the Bland–Altman
method. This analysis showed no significant
diVerence for either interobserver variability
(r = 0.37; NS) or intraobserver variability
(r = 0.3; NS). According to our variability
data, a cut oV point of 6% was chosen to
distinguish patients with or without a signifi-
cant improvement in postrevascularisation
ejection fraction.
of the echocardio-
201THALLIUM IMAGING
Ineach
ventricular slices from the short axis series were
considered.Tomograms were then divided into
six sectors of equal arc, representing the poste-
rolateral, inferior, posteroseptal, anteroseptal,
anterior, and anterolateral myocardium.4The
sectors from two consecutive three pixel thick
short axis tomograms were then grouped and
averaged. Thus 12 myocardial regions were
analysed for each patient. Of these segments,
six were assigned to the territory of the LAD,
four (two anterolateral and two posterolateral)
were assigned to the territory of left circumflex
coronary artery, and two inferior segments
were assigned to the territory of the right
coronary artery (fig 1). Alignment and analysis
of the studies were visually made by two opera-
tors unaware of the echocardiographic results.
A cut oV point of 65% was used to
distinguish viable from non-viable myocar-
dium.17
patient,fourconsecutivemid-
Figure 1
into 16 segments in short axis tomograms at chordal
(upper),mid-papillary (medium),and apical (lower)
levels.White segments were assigned to the left anterior
descending coronary artery (LAD) territory.
Pie chart showing the division of left ventricle
5
2
31
46
11
8
15
13
14 16
97
1012
Low dose dobutamine echocardiography and coronary revascularisation
681
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CORONARY ANGIOGRAPHY ANALYSIS
All coronary angiograms were analysed by an
investigator who had no knowledge of the
results of the echocardiograms.Each vessel was
visualised in multiple views, and the most
severe appearing lesion was selected for analy-
sis. Care was taken to avoid overlap of adjacent
branches. Vessel occlusion was defined as a
lesion with no anterograde distal flow. Collat-
eral circulation was graded according to the
classification of Rentrop and colleagues18: 0 =
no visible collateral, 1 = collateral filling of the
vessel branches without reaching the epicardial
artery,2 = partial filling of the epicardial artery,
and 3 = complete filling of the epicardial artery.
STATISTICAL ANALYSIS
Statistical analysis was performed with the
SPSSstatisticalpackage.19
paired t tests were used to compare continuous
variables. Values are reported as mean (SD)
and 95% confidence intervals. Bonferroni’s
correction was used for multiple group com-
parisons.
Unpairedand
Results
Angiographic collateral flow to the LAD was
present in one patient in group 1 without
occlusion (1/27; 3%) and in 22 patients in
group 2 (22/26; 85%) with an occluded LAD
(p < 0.00001). There were no significant
diVerences in clinical characteristics between
the two groups (table 1). The left ventricular
ejection fraction was 44 (11)% (95% CI 22%
to 66%) in group 1, and 41 (9)% (95% CI 23%
to 59%) in group 2 (NS).
Twenty seven patients underwent translumi-
nal coronary angioplasty (PTCA; 11 patients
in group 1 and 16 patients in group 2);
successful dilatation—defined as a diameter of
the residual stenosis not exceeding 30% of the
lumen diameter—was achieved in all cases.
The remaining 26 patients underwent coron-
ary artery bypass grafting (CABG; 16 in group
1 and 10 in group 2); in all these cases grafting
of the LAD was successful. The internal mam-
mary artery was used in 10 patients (six in
group 1 and four in group 2). No patients had
major complications associated with the revas-
cularisation procedure.
In all,we evaluated 424 myocardial segments
belonging to the LAD territory; 296 (70%) of
these were dysfunctional, including 146 in
group 1 and 150 in group 2.Figure 2 shows the
data on systolic function in the segments
evaluated.
SEGMENTAL ANALYSIS
In group 1 patients, 79 (54%) of 146 dysfunc-
tional segments were hypokinetic and 67
(46%) were akinetic. In group 2, 60 (40%) of
150 dysfunctional segments were hypokinetic
(NS v group 1) and 90 (60%) were akinetic
(p = 0.03 v group 1).
The number of dysfunctional segments
showing contractile reserve during low dose
dobutamine echocardiography
cantly higher in group 1 than in group 2
patients (81 of 146 (55%) v 57 of 150 (38%);
p = 0.002; fig 3). This diVerence was mostly
accounted for by the higher percentage of aki-
netic segments showing contractile reserve in
group 1 patients than in group 2 patients,
although this diVerence was not significant
(16/67 (24%) v 13/90 (14%), respectively) (fig
3).
A biphasic response was observed in only
three segments (1%),one in group 1 and two in
group 2).
Of 296 dysfunctional segments in the LAD
territory undergoing revascularisation, 132
(44%) improved at follow up. Recovery of
regional function was not aVected by the
patency of the coronary vessel,as it occurred in
63 (43%) of 146 dysfunctional segments in
group 1 and 69 (46%) of 150 dysfunctional
segments in group 2 (NS). In particular,
improvement was observed in 45 (57%) of 79
hypokinetic segments in group 1 and in 35
(58%) of 60 hypokinetic segments in group 2
(NS), as well as in 18 (27%) of 67 akinetic seg-
ments in group 1 and 34 (38%) of 90 akinetic
segments in group 2 (NS) (fig 4).
Sensitivity, specificity, accuracy, and positive
and negative predictive power for dobutamine
echocardiography and
predicting functional recovery after revascu-
larisation are reported in table 2. Low dose
was signifi-
201thallium SPECT in
Figure 2
percentage of segments showing normal contraction,
hypokinesia,and akinesia in patients with a non-occluded
left anterior descending coronary artery (LAD;white bars)
and an occluded LAD (black bars).The percentage of
akinetic segments was significantly higher in patients with
an occluded LAD.
Regional systolic function represented as the
50
40
30
20
10
0
p = 0.03
Number of segments (%)
Normal HypokineticAkinetic
Figure 3
contractile reserve on low dose dobutamine
echocardiography in patients with a non-occluded left
anterior descending coronary artery (LAD;white bars)
and an occluded LAD (black bars).
Percentage of dysfunctional segments showing
100
80
60
40
20
0
p < 0.002
Number of dysfunctional segments with
contractile reserve (%)
All
dysfunctional
HypokineticAkinetic
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dobutamine echocardiography showed a better
sensitivity (87% v 52%; p < 0.0001), accuracy
(77% v 64%; p = 0.01), and negative predic-
tive value (88% v 65%; p = 0.001) in group 1
than in group 2, respectively. These data were
confirmed when further analysis was restricted
to akinetic segments (table 3).
A further analysis was done by dividing
territories with or without Q wave myocardial
infarction in the two groups; this did not show
any significant diVerences (table 4).
To investigate whether the degree of the col-
lateral circulation influenced the dobutamine
echocardiography results, patients with an
occluded LAD were further subdivided into
group 2A with a well developed collateral
circulation (n = 18; Rentrop class III and II),
and group 2B with a less well developed collat-
eral circulation (n = 8; Rentrop classes I and
0). In group 2A, the sensitivity and accuracy
were significantly reduced compared with
group 1 patients (53% v 87%, p < 0.0001; and
65% v 77%, p = 0.036), but not diVerent from
group 2B (50% and 60%, respectively). No
significant diVerences in specificity were ob-
served among the three groups of patients. In
contrast, recovery of contractile function was
not aVected by the status of the coronary artery
before revascularisation, as regional wall mo-
tion improved to a similar degree in the three
groups of patients (table 5).
201Thallium SPECT data were available on
183 (62%) of 296 dysfunctional segments (93
of group 1 and 90 of group 2).In group 2 (table
2),
higher sensitivity than low dose dobutamine
echocardiography (72% v 52%; p < 0.05),
whereas in the same comparison in group 1
there was lower specificity (21% v 68%;
p < 0.0001), lower accuracy (59% v 77%;
p < 0.01), and reduced negative predictive
value (37% v 88%; p < 0.0001). These data
were also confirmed when further analysis was
restricted to akinetic segments (table 3).
201thallium SPECT showed a significantly
PATIENT ANALYSIS
In the whole group of patients, left ventricular
ejection fraction increased significantly from
43 (9)% (95% CI 25% to 61%) before
revascularisation to 47 (9)% (95% CI 29% to
65%) afterwards (p < 0.001). Left ventricular
ejection fraction improved similarly in patients
undergoing PTCA (from 43 (10)% (95% CI
23% to 63%) to 47 (10)% (95% CI 27% to
67%)) (p < 0.001) and in those subjected to
CABG (from 41 (11)% (95% CI 19% to 63%)
to 45 (11)% (95% CI 23% to 67%))
(p < 0.001).
Improvement in left ventricular ejection
fraction was more pronounced in group 2
patients (from 41 (9)% (95% CI 23% to 59%)
to 47(7)%(95%
(p < 0.001), whereas this did not reach signifi-
cance in group 1 patients (from 44 (11)%
(95% CI 22% to 66%) to 46 (10)% (95% CI
26% to 66%)) (NS).
We compared the accuracy of low dose dob-
utamineechocardiography
SPECT in predicting global left ventricular
function after revascularisation in patients with
single vessel revascularisation. These data are
reported in table 6. We found a threshold of at
least two viable segments conferring optimal
values of accuracy. In group 1, low dose
dobutamine echocardiography showed a simi-
lar value for sensitivity but a higher value for
accuracy than
group 2,
sensitivity (89% v 44%) and accuracy (60% v
57%) than low dose dobutamine echocardio-
graphy.
CI33% to 61%))
and
201thallium
201thallium SPECT, whereas in
201thallium SPECT showed better
Figure 4
function.The percentage of improved hypokinetic and
akinetic segments did not diVer between patients with a
non-occluded left anterior descending coronary artery
(LAD;white bars) and an occluded LAD (black bars).
EVects of revascularisation on regional systolic
80
60
40
20
0
Number of improved
segments (%)
HypokineticAkinetic
Table 2
SPECT in predicting functional recovery after revascularisation in patients with a
non-occluded (group 1) and an occluded (group 2) left anterior descending coronary artery
Accuracy of low dose dobutamine echocardiography (LDDE) and
201thallium
LDDE
201Thallium SPECT
Group 1Group 2 Group 1 Group 2
Sensitivity
Specificity
Accuracy
PPV
NPV
87% (55/63)
68% (57/83)
77% (112/146)
68% (55/81)
88% (57/65)
52% (36/69)***
74% (60/81)
64% (96/150)*
63% (36/57)
65% (60/93)**
80% (48/60)
21% (7/33)†††
59% (55/93)††
65% (48/74)
37% (7/19)†††
72% (39/54)†
64% (23/36)***
69% (62/90)
75% (39/52)
61% (23/38)
*p = 0.01; **p = 0.001; ***p < 0.0001 v group 1.
†p < 0.05; ††p < 0.01; †††p < 0.0001 v LDDE.
NPV, negative predictive value; PPV, positive predictive value; SPECT, single photon emission
computed tomography.
Table 3
SPECT in predicting functional recovery after revascularisation of akinetic segments in
patients with a non-occluded (group 1) and an occluded (group 2) left anterior descending
coronary artery
Accuracy of low dose dobutamine echocardiography (LDDE) and
201thallium
LDDE
201Thallium SPECT
Group 1Group 2Group 1 Group 2
Sensitivity
Specificity
Accuracy
PPV
NPV
72% (13/18)
94% (46/49)
88% (59/67)
81% (13/16)
90% (46/51)
26% (9/34)***
93% (52/56)
68% (61/90)**
69% (9/13)
67% (52/77)**
67% (10/15)
26% (5/19)†††
44% (15/34)†
42% (10/24)†
50% (5/10)†
79% (19/24)†††
60% (9/15)††
72% (28/39)*
76% (19/25)*
64% (9/14)
*p < 0.05; **p < 0.01; ***p < 0.001 v group 1.
†p > 0.05; ††p < 0.01; †††p < 0.001 v LDDE.
NPV, negative predictive value; PPV, positive predictive value; SPECT, single photon emission
computed tomography.
Table 4
recovery after revascularisation in the absence or presence of complete vascular occlusion
(groups 1 and 2) and in the absence (control) or presence of a Q wave anterior myocardial
infarct
Accuracy of low dose dobutamine echocardiography in predicting functional
Group 1Group 2
Q wave MIControlQ wave MI Control
Sensitivity
Specificity
Accuracy
PPV
NPV
89% (34/38)
71% (39/55)
78% (73/93)
68% (34/50)
90% (39/43)
84% (21/25)
64% (18/28)
73% (39/53)
68% (21/31)
82% (18/22)
52% (23/44)
74% (43/58)
65% (66/102)
61% (23/38)
67% (43/64)
52% (13/25)
74% (17/23)
63% (30/48)
68% (13/19)
59% (17/29)
Group 1, non-occluded left anterior descending coronary artery; group 2, occluded left anterior
descending coronary artery; MI, myocardial infarction; NPV, negative predictive value; PPV, posi-
tive predictive value.
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Discussion
ACCURACY OF LOW DOSE DOBUTAMINE
ECHOCARDIOGRAPHY IN PREDICTING
REVERSIBILITY OF REGIONAL DYSFUNCTION
Our main finding in the present study was that
low dose dobutamine echocardiography is not
very accurate in predicting recovery of dysfunc-
tional myocardium supplied by occluded cor-
onary arteries. In fact, only 52% of segments
supplied by an occluded LAD that improved
after revascularisation were identified by dob-
utamine echocardiography.In addition,35% of
the segments supplied by occluded vessels that
did not show contractile reserve improved after
revascularisation. Sensitivity further decreased
in severely dysfunctional myocardium, as only
26% of akinetic viable segments supplied by an
occluded LAD were identified by dobutamine
echocardiography. Low
echocardiography also showed a lower sensitiv-
ity in patients with occluded vessels when glo-
bal left ventricular functional recovery was
analysed.
Various pathophysiological mechanisms may
account for this finding. It has been reported
that transient amelioration of myocardial dys-
function during inotropic stimulation—the
hallmark ofviability
echocardiography—depends on the recruit-
ment of residual coronary reserve which allows
an increase of blood flow in the dysfunctional
myocardium.9However, when coronary re-
serve is compromised, recruitment of inotropic
reserve is rapidly followed by the development
of ischaemia and a deterioration in function,
even in the absence of completely occluded
coronary vessels.8This hypothesis is strength-
ened by our
showed a better sensitivity and accuracy than
low dose dobutamine echocardiography only in
the patients with occluded vessels.
dose dobutamine
using dobutamine
201thallium SPECT data, which
In patients with occluded coronary vessels,
flow reserve has been reported to be greatly
attenuated or completely lost during dypirida-
mole infusion.10 11It is conceivable that in this
case the increase in blood flow in the dysfunc-
tional myocardium may be inadequate to cause
transient contractile improvement, or it may
result in a very mild and transient functional
enhancement undetectable by our current
semiquantitative analysis of echocardiographic
images.
Experimental data further indicate that the
accuracy of dobutamine for identifying dys-
functional myocardium is decreased when a
substantial amount of necrotic myocardium
coexists in the same territory, even when blood
flow is restored at reperfusion.20In addition,
reversible degradation of the cellular contrac-
tile apparatus in long standing dysfunctional
myocardium may also contribute to the lack of
contractile reserve, generating a false negative
response.21
Thus it is conceivable that diVerent mecha-
nisms may contribute to reducing the accuracy
of dobutamine for identifying severely dysfunc-
tional viable myocardium.
PREVIOUS STUDIES
Despite the theoretical limitations of the test in
the setting of occluded coronary arteries, there
are few data on its use in such patients. In a
population of 12 patients with a chronically
occluded left anterior descending coronary
artery and a moderately depressed ejection
fraction, Afridi and colleagues reported a posi-
tive and negative predictive accuracies for dob-
utamine echocardiography of 100% and 86%,
respectively, for improvement in dysfunctional
myocardium after revascularisation, though
sensitivity and specificity were not reported.12
A high negative predictive accuracy is at
variance with our findings in the present study,
where a suboptimal value was observed,
indicating that many akinetic segments defined
as non-viable by dobutamine do recover after
revascularisation. The short (one month)
follow up evaluation in Afridi’s study may
partly explain this discrepancy, as it has been
reported that a longer time interval may be
required for dysfunctional myocardium to
recover completely.7Thus a longer period of
follow up in that study might have allowed
recovery of additional dysfunctional segments,
so reducing the observed negative predictive
value of the test.
VIABILITY IN COLLATERAL DEPENDENT
MYOCARDIUM
Another important observation of the current
study is that recovery of function occurs in
about half the dysfunctional segments supplied
by occluded vessels, and results in a significant
increase in global left ventricular ejection frac-
tion, that is one of the main determinants of
survival in patients with coronary artery
disease. However, the degree of collateral flow
did not predict the occurrence of functional
recovery, indicating that viability—at least in
terms of the possibility of recovery of contrac-
tile function at rest—is not always associated
Table 5
revascularisation in patients with a non-occluded left anterior descending coronary artery
(LAD) (group 1),an occluded LAD and collaterals of class II–III (group 2A),and an
occluded LAD and collaterals of class 0–I (group 2B)
Accuracy of low dose dobutamine echocardiography (LDDE) and the eVects of
Group 1 Group 2AGroup 2B
LDDE sensitivity
LDDE specificity
LDDE accuracy
Regional WMSI
Pre-
Post-
Regional WMSI change (%)
87%
69%
77%
53%**
73%
65%*
50%
75%
60%
1.97 (0.48)
1.74 (0.53)††
12
2.26 (0.33)
2.01 (0.30)††
9
1.81 (0.52)
1.59 (0.36)†
12
*p < 0.05; **p < 0.0001 v group 1.
†p < 0.05; ††p < 0.01 v regional WMSI pre-revascularisation.
WMSI, wall motion score index.
Table 6
SPECT in predicting global left ventricular functional recovery after single vessel
revascularisation for either a non-occluded (group 1) or an occluded (group 2) left anterior
descending coronary artery
Accuracy of low dose dobutamine echocardiography (LDDE) and
201thallium
LDDE
201Thallium SPECT
Group 1Group 2 Group 1Group 2
Sensitivity
Specificity
Accuracy
PPV
NPV
100% (4/4)
28% (2/7)
54% (6/11)
44% (4/9)
100% (2/2)
44% (4/9)
66% (4/6)
57% (8/15)
66% (4/6)
44% (4/9)
100% (4/4)
14% (1/7)
44% (5/11)
40% (4/10)
100% (1/1)
89% (8/9)
16% (1/6)
60% (9/15)
62% (8/13)
50% (1/2)
NPV, negative predictive value; PPV, positive predictive value; SPECT, single photon emission
computed tomography.
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with the presence of a collateral circulation on
angiography.
This finding supports the observation of Di
Carli and colleagues,22who reported that
viability evaluated by positron emission tomog-
raphy is detectable in only 58% of dysfunc-
tional regions supplied by an occluded vessel
where there is angiographic evidence of collat-
erals. It is also consistent with the data of Sabia
and associates,23who showed a lack of correla-
tion between the degree of wall motion
improvement after revascularisation and blood
flow supply before revascularisation in patients
with recent myocardial infarction.
Taken together, these data indicate that
angiographic evaluation of collateral circula-
tion should not be used to predict myocardial
viability in patients with chronic coronary
artery disease and occluded coronary arteries
who are candidates for revascularisation.
STUDY LIMITATIONS
Repeat coronary angiography was not per-
formed in the present study. Thus restenosis at
the time of follow up cannot be excluded with
certainty. However, no
symptoms or had evidence of ischaemia on
investigation,which minimises the likelihood of
restenosis. In addition, the observation that
most segments with unchanged function after
revascularisation were in the same vascular ter-
ritories as segments that showed improved
function reduces this possibility still further.
Another limitation of the study is that recov-
ery of viable dysfunctional segments may not
have been complete by three months after
revascularisation. However, this would tend to
reduce the negative predictive value further,
making our results understated.
Visual analysis of regional function may rep-
resent a limitation of the echocardiographic
technique, especially
whereas in the present study left ventricular
function and dimensions were preserved or
were only moderately abnormal.
Currently, there are no reliable quantitative
methods for evaluating regional function, and
such methods as there are do not represent gold
standard analyses at present. In addition, visual
analyses from videotapes might impair repro-
ducibility. However, data from our laboratory
indicate excellent reproducibility for videotape
analysis, especially for akinetic myocardium.4
In the present study only low dobutamine
doseswere used. However, the
contractile response induced by high dob-
utamine doses, while being very specific, is less
sensitive at predicting functional recovery than
the low dose response.5 24By not using high
doses, we might have missed a deterioration in
the function of akinetic segments that showed
improvement at low dosage;in this way we may
have included among the viable myocardial
segments both those showing sustained im-
provement (for which the positive accuracy is
reduced) and those with a potential biphasic
response (for which the positive accuracy is
very high). This would tend to maximise sensi-
tivity while reducing specificity. However, the
sensitivity of dobutamine was suboptimal in
patientdeveloped
in large ventricles,
biphasic
the present study, so the use of only low doses
would only diminish the impact of our findings
rather than exaggerate it. Moreover, our nega-
tiveaccuracy in akinetic
65%—in other words, 35% of akinetic seg-
ments that did not improve with dobutamine
recovered after revascularisation. As demon-
strated by Afridi and colleagues and Panza and
associates,5 25the vast majority of segments
showing transient improvement do so at
dobutamine doses of < 10 µg/kg/min. Thus it
is very unlikely that the 35% of segments clas-
sified as negative using low doses would
improve at higher doses. This gives further
support to our conclusion that the use of low
dobutamine doses did not aVect the main find-
ings of the study.
Finally a factor that may hamper the evalua-
tion of segmental motion is the presence of
postsurgical paradoxical septal motion. We do
not believe that this could have hampered our
results as more than half our patients were
treated by PTCA and as a combination of both
inward motion and myocardial wall thickness
was used in evaluating regional function.
segmentswas
CLINICAL IMPLICATIONS AND CONCLUSIONS
Our study shows that recovery of function
occurs in a sizeable number of revascularised
dysfunctional segments supplied by occluded
coronary arteries. Identification of such myo-
cardial territories remains a problem,as neither
the presence of collaterals nor the response to
inotropic stimulation using dobutamine echo-
cardiography is suYciently accurate in predict-
ing the functional eVects of revascularisation
under these circumstances. However, the
limited number of such patients so far reported
emphasises the need for further confirmation
of our findings.
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IMAGES IN CARDIOLOGY
An unusual hyperkalaemia induced block
The tracing below was recorded from a patient
with a DDD pacemaker and hyperkalaemia
(7.8 mEq/1) caused by acute renal failure. The
atrial mechanism is sinus at a rate of 110/min.
Every sinus P wave is followed by a ventricular
spike, but several of these fail to depolarise the
myocardium. The paced QRS complexes are
extremely wide, measuring about 0.38 seconds.
There is a basic 2:1 block of artificial stimuli;
following a ventricular capture, the ensuing
spike falls at the apex of the T wave during the
refractory period. This is caused by the extreme
prolongation of the ventricular depolarisation
and repolarisation process.In addition,spike-to-
QRS intervals show a gradual lengthening, end-
ing in block of two consecutive stimuli.
The association of 2:1 block with progressive
prolongation of the conduction intervals up to
block of two or three consecutive impulses is
known as “alternating Wenckeback periodic-
ity”. This phenomenon is well recognised in
atrioventricular conduction, particularly in
atrial flutter, but has not been hitherto
observed in conduction between an artificial
pacemaker and the ventricular myocardium.
Correction of the hyperkalaemia was fol-
lowed by normal ventricular capture and
narrowing of the QRS complexes.
FRANCESCO LUZZA
SCIPIONE CARERJ
GIUSEPPE ORETO
oretogmp@tin.it
50 Hz 0.08–35 Hz112/minMan 25 mm/s 10 mm/mU SAD50 Hz 0.08–35 Hz155/min
04 Feb 01 20:3604 Feb 01 20:36 GE marquette GE marquette
I
II
III
I
II
III
I
II
III
U2.22 MAC 500
686
Piscione,Perrone-Filardi,De Luca,et al
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