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557
lACC Vol. 10. NO.3
September 19X7:557-67
Positron Emission Tomography Detects Tissue Metabolic Activity in
Myocardial Segments With Persistent Thallium Perfusion Defects
RICHARD BRUNKEN, MD, FACC, MARKUS SCHWAIGER, MD,
MALEAH GROYER-McKAY, MD, FACC, MICHAEL E. PHELPS, PHD,
JAN TILLISCH, MD, HEINRICH R. SCHELBERT, MD, FACC
Los Angeles, California
Positron emission tomography with uN-ammonia and
(SF -2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments
with a stress thallium defect in 12 patients. Myocardial
infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial
ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51
segments studied, 36 had a fixed thallium defect, 11 had
a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with
a fixed defect and 4 (36%) of the 11 segments with a
partially reversible defect exhibited myocardial infarction on study with positron tomography.
Stress planar thallium-20l scintigraphy has been used extensively in clinical practice to assess myocardial perfusion
in a variety of circumstances (l). Perfusion deficits that
persist on serial images have usually been attributed to irreversible scar formation whereas deficits that improve or
resolve on delayed images have been associated with viable
tissue (2,3). For example, prior clinical studies (4,5) have
From the Division of Nuclear Medicine and Biophysics, Department
of Radiological Sciences, the Division of Adult Cardiology, Department
of Medicine, UCLA School of Medicine, and the Laboratory of Nuclear
Medicine, Laboratory of Biomedical and Environmental Sciences. * University of California, Los Angeles, California 90024.
*Operated for the U.S. Department of Energy, Washington, D.C.. by
the University of California under Contract DE-AC03-76-SFOOO12. This
work was supported in part by the Director of the Office of Energy Research, Office of Health and Environmental Research, Washington D.C..
by Grants HL 29845 and HL 33177 from the National Institutes of Health,
Bethesda, Maryland, and by an Investigative Group Award from the Greater
Los Angeles Affiliate of the American Heart Association, Los Angeles.
California. It was presented in part at the 58th Annual Scientific Sessions
of the American Heart Association, November II to 14. 1985. Washington.
D.C.
Manuscript received September 29, 1986: revised manuscript received
March 24, 1987, accepted April 10, 1987.
Address for reprints: Richard Brunken, MD, Division of Nuclear Medicine and Biophysics, UCLA School of Medicine, Los Angeles. California
90024.
<D 1987by tbe American College of Cardiology
In contrast, residual myocardial glucose utilization
was identified in the majority of segments with a fixed
(58%) or a partially reversible (64%) thallium defect.
All of the segments with a completely reversible defect
appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did
not distinguish segments with ischemia from infarction.
Thus, positron emission tomography reveals evidence of
persistent tissue metabolism in the majority of segments
with a fixed or partially resolving stress thallium defect,
implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.
(J Am Coil CardioI1987;10:557-67)
suggested that myocardial segments with resting wall motion abnormalities and a fixed thallium-20l defect rarely
exhibit functional improvement after revascularization,
whereas segments with a reversible thallium-20l defect typically improve after revascularization.
Other observations, however, suggest that viable but
functionally impaired tissue may exist in some ventricular
segments with a persistent thallium-20 I perfusion defect.
Some myocardial segments with a fixed thallium-201 defect
do exhibit improved function after revascularization (4,5).
Liu et al. (6) noted that 75% of myocardial segments with
a persistent thallium-20 I defect on stress scintigraphy exhibited a normal thallium pattern after angioplasty of the
culprit lesion. In the series of patients undergoing coronary
revascularization reported on by Gibson et al. (7), 45% of
myocardial segments with a persistent defect on preoperative stress scintigraphy exhibited a normal thallium perfusion pattern and normal washout kinetics after coronary
artery bypass surgery. The clinical problem is to distinguish
hypoperfused but viable tissue from regions with extensive
scar formation.
Previous experimental studies (8-13) have demonstrated
that hypoperfused, ischemic tissue may retain the ability to
0735-1097/X7/$3.50
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BRUNKEN ET AL.
METABOLISM IN PERSISTENT THALLI UM DEFECTS
metabolize glucose . Residual tissue perfusion may allow
aerobic or anaerobic glycolysis, and glucose utilization will
be enhanced relative to blood flow. Because myocardial
regions with extensive scar formation are metabolically inactive, the presence of metabolic activity distinguishes ischemic tissue from regions of extensive scar formation.
With the advent of positron emission tomography and
labeled tracers of blood flow and metabolism, it is now
possible to noninvasively assess relative myocardial perfusion and glucose utilization in humans. Relative myocardial perfusion is assessed with 1JN-ammonia ( 14, 15), and
relative glucose utilization is assessed with the glucose analog, 18F-2-deoxyglucose (16,17) . Criteria for myocardial
ischemia and infarction have previously been reported (18).
In ischemia , 18F-2-deoxyglucose tissue concentrations are
augmented relative to those of UN-ammonia; in infarction,
concentrations of both UN-ammonia and IXF-2-deoxyglucose are concordantly reduced. Persistence of metabolic
activity in hypoperfused segments correlates well with the
histologic presence of viable tissue ( 19) and is predictive
of functional improvement after restoration of blood flow
(20 ,2 1). Because thallium-20 I and UN-ammonia have previously been shown to correlate closely as markers of perfusion (15,22), we postulated that some myocardial segments that exhibited stress scintigraphic criteria for myocardial
fibrosis (persistent or only partially resolving stress thallium
defects) might exhibit residual glucose metabolism on study
with positron tomography. The purpose of this study was
to assess myocardial perfusion and glucose utilization with
positron tomography in segments with a persistent or partially resolving stress thallium defect.
Methods
Study patients. Twelve consecutive patients, II men
and I woman, with a persistent defect on stress thallium
scintigraphy were studied; their mean age was 56.3 ± 8.9
years. Ten patients had a clinical history of previous myocardial infarction; in these patients there was a total of 14
antecedent infarctions. Congestive heart failure was noted
in seven. Angina was present in six patients and an additional patient had atypical chest discomfort. Four patients
had a history of ventricular tachycardia, two had chronic
atrial fibrillation, two had left bundle branch block and one
had a permanent pacemaker for trifascicular block.
Eleven of the 12 patients had coronary angiography: 7
had triple vessel disease, 2 had double vessel disease and
2 had single vessel disease. Nine patients had one or more
vessels with :;:;::90% diameter narrowing. Two patients had
had remote coronary bypass grafting; all grafts were closed
on angiographic study in one patient and the other patient
did not have graft angiography . Left ventricular ejection
fraction, as determined by radionuclide ventriculography
(n = 9), left ventricular angiography (n = 2) or echocardi-
lACC Vol. 10. No, 3
September J 987:557-67
ography (n = I), averaged 32. 1 ± 13.7%. At our institution, an ejection fraction > 50% on left ventricular angiography or radionuclide ventriculography or > 55% on
echocardiography is considered normal. At the time of study
10 patients were receiving nitrates (for angina or atypical
chest discomfort in 7 and congestive heart failure in 3); 6
each were receiving digoxin and diuretics; 4 were receiving
calcium channel blockers; 3 each were receiving beta-receptor blockers, type I antiarrhythmic drugs and other vasodilators; and I was receiving amiodarone.
Stress thallium scintigraphy. All subjects underwent
graded treadmill exercise with heart rate and blood pressure
monitoring utilizing either the Bruce, Kattus or Naughton
protocol. Exercise was terminated when 85% of the maximal
predicted heart rate for age was achieved, when ST segment
depression exceeded baseline by > 2 mm or when moderately severe symptoms or abnormal blood pressure response
precluded further exercise. Leads II, V2 and Vs were continuously monitored during exercise and in the early recovery period; 12 lead electrocardiograms (ECGs) were obtained before and immediately after exercise. The mean
achieved rate-pressure product was 17,377 ± 5,186; the
mean percent of maximal predicted heart rate achieved was
78.8 ± 14.7%. Three patients achieved > 85% of their
maximal predicted heart rate. Two patients had ST-T changes
diagnostic of ischemia; the remainder had nonspecific
ST-T changes.
Thallium-201 chloride ( 1.5 to 2.0 mCi) was administered
intravenously I minute before termination of exercise. Imaging was begun within 10 minutes of isotope administration
and was performed for 600 seconds in the anterior, 45° left
anterior oblique and left lateral projections using a Technicare series 100 camera equipped with a low energy, parallel-hole all-purpose collimator. Delayed images were obtained 4 hours after thallium administration in similar projections. Patients were allowed to ambulate and to drink
clear liquids between the postexercise and delayed images.
Count recovery was 600,000 to 800,OOO/image for the immediate postexercise and 400,000 to 600 ,000/ image for the
redistribution views. Acquired images were stored on floppy
disks as 128 x 128 matrices. Image processing was performed utilizing a Technicare 560 computer; each study was
photographed at varying intensities directly from the computer CRT display. The mean interval between thallium
scintigraphy and positron tomography was 10.6 ± 11 .6
days (range I to 33).
Thallium image interpretation. Three experienced nuclear medicine physicians independently assessed thallium
uptake in each of seven myocardial segments on both the
postexercise and redistribution images (Fig. I) using the
following scale: 0 = normal, I = mild but definite defect,
2 = moderately severe defect and 3 = complete defect
(background level). Scores on multiple views were averaged
to give a mean value for the following anatomic segments:
lACC Vol. 10. No.3
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METABOLISM IN PERSISTENT THALLIUM DEFECTS
September 1987:557-67
Ant
LAO
La t
Figure 1. Diagrammatic anterior (Ant), 45° left anterior oblique
(LAO) and left lateral (Lat) planar thallium-20l images, illustrating
assignment of anatomic ventricular segments. I and II = Anterobasilar segment; 2 and 12 = anterolateral segment; 3, 8 and 13
= apical segment; 4 and 14 = inferior segment; 5 and 15 =
posterobasilar segment; 6 and 7 = anteroseptal segment; 9 and
10 = lateral segment.
anterobasilar, anterolateral, apical, inferior, posterobasilar,
anteroseptal and lateral. A thallium defect was defined by
a mean segmental score 2:0.66 on the postexercise study;
that is, at least two graders agreed that a defect was present.
Defects were classified as fixed if the difference between
the postexercise and redistribution scores was <0.5. Partial
redistribution was defined by an improvement in the mean
score of 2:0.5 but a failure to achieve a score of sO.33 on
the redistribution study. A thallium defect was said to be
completely reversible if the mean score on the redistribution
study was sO.33 (that is, two observers agreed that the
defect normalized). Simple analysis of variance did not reveal any significant difference between mean segmental scores
for each observer (F = 2.64, P = NS) and scores differed
by s I in 87% of the segments examined.
Positron emission tomography. Tomographic imaging
was performed with an ECAT II (CT!, Inc.) tomograph,
559
utilizing previously published methods (18). Six contiguous
cross-sectional transmission images 1.0 to 1.5 ern apart were
initially obtained to allow correction for photon attenuation.
After the intravenous bolus administration of 15 to 20 mCi
of the flow tracer 13N-ammonia, corresponding images of
relative myocardial perfusion were obtained in the same
cross-sectional planes. The specific activity of the 13N_
ammonia was 100 to 200 Ci/mmol. After acquisition of the
perfusion images, 10 mCi of the metabolic tracer 18F_2_
deoxyglucose was administered as a single intravenous bolus.
Acquisition of the metabolic images was begun 40 minutes
after 18F-2-deoxyglucose administration to allow sufficient
time for myocardial uptake and phosphorylationof the tracer
(23). Identical positioning for each set of images was achieved
by marking each subject's chest with washable ink and
aligning the marks with a reference low power laser beam
from the tomograph. The specificactivity of the 18F-2-deoxyglucose was 2 Ci/mmol (24). Subjects were studied I to
2 hours after a carbohydrate-containing meal and were given
a 25 to 50 g oral glucose load I hour before the administration of the 18F-2-deoxyglucose. This served to enhance
myocardial glucose utilization relative to that of free fatty
acids (25). Total body radiation dose for a complete study
was 0.08 rad (26,27). Each subject gave written consent on
a form approved by the University of California at Los
Angeles Human Subject Protection Committee.
Analysis of tomographic images. An operator-interactive computer program was used to analyze the data (18).
The normalizedcircumferentialcount profilesof both tracers
for each tomographic plane were displayed as a function of
the angle from a line from the mid-apex through the center
of the ventricular cavity. The data were then referenced to
~ Anteroseptal
D Anterobasilar
o
Apex
Q Lateral
~ Posterobasilar
Figure 2. Diagrammatic representation of six crosssectional tomographic planes, illustrating the assignment of the seven anatomic ventricular regions.
~ Anteroseptal
o
Apex
o
Anterolateral
~ Inferior
Q
Lateral
~ Posterobasilar
~
Anteroseptal
D Anterolateral
Q
Lateral
fZi] Inferior
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BRUNKEN ET AL.
METABOLISM IN PERSISTENT THALLIUM DEFECTS
JACC Vol. 10. No, 3
September 1987:557-67
established normal laboratory values for each 30° sector of
each tomographic plane (18). This dual isotopic technique
eliminates concerns about the partial volume effect because
any segmental anatomic differences in the myocardium will
equally affect count recoveries for both tracers. Hypoperfused regions were identified on the 13N-ammonia study by
13N activity <2 SD below normal. Recovered F-18 activity
in these regions discriminated between the absence or persistence of tissue metabolic activity. Myocardial infarction
was defined by a concordant reduction in recovered 18F
counts in three or more contiguous sectors (18). Myocardial
ischemia was defined by an 18F, 13N count difference >2
SD above normal in two or more contiguous sectors (18).
Anterobasilar, anterolateral, apical, inferior, posterobasilar,
anteroseptal and lateral ventricular segments were defined
(Fig. 2).
Statistical analysis. Values reported are mean values
± I SD. Segmental thallium scores were analyzed using
simple analysis of variance, followed by the F test for statistical significance. Comparisons between sets of clinical
interest (for example, thallium scores for segments with
tomographically defined ischemia versus infarction, or postexercise thallium scores versus delayed thallium scores) were
performed with Student's t test for unpaired data. The characteristics of patients with and without tomographic ischemia were compared using the chi-square test (with Yates'
correction when appropriate). Probability (p) values <0.05
were considered statistically significant.
Results
Thallium scintigraphy. Fifty-five segmental thallium
defects were identified on the postexercise images in the 12
patients. Two fixed septal defects were excluded from analysis because of associated left bundle branch block (28).
Two anterobasilar segments with a thallium defect were not
imaged with positron tomography and these segments were
also excluded from analysis. Of the remaining 51 segmental
Table 1. Classification and Location of 51 Segmental
Thallium Defects*
Anterobasilar
Anterolateral
Apical
Inferior
Posterobasilar
Anteroseptal
Lateral
Total
Fixed
Defect
Partially
Reversible
Defect
Completely
Reversible
Defect
I
0
7
8
4
2
5
7
4
0
I
1
0
0
0
I
I
36
II
4
4
2
I
2
*Excludes two anterobasilar defects (one fixed, one partially reversible)
that were not imaged with positron tomography.
2.5
r p = NS 1
rpeO.Ol1
r P < 0.01 1
Partially
Reversible
n = 11
Completely
Reversible
n=4
2.0
G)
~
0
0
rn
1.5
E
::J
III
1.0
s:
I-
0.5
0.0
Post
Exercise Delayed
Fixed
Defects
n = 36
Figure 3. Immediate postexercise and 4 hour delayed segmental
thallium scores for the fixed, partially reversible and completely
reversible thallium defects. Thallium defects were assessed by
three independent graders on a scale of 0 (normal) to 3 (complete
defect, equivalent to background). The number of segments analyzed is given beneatheach classification. There was no significant
difference between the postexercise and delayed studies in mean
segmental thallium score for the fixed defects; in contrast, both
partially reversible and completely reversible defects had significantly better delayed thallium scores.
thallium defects, 36 were fixed, 11 were partially reversible
and 4 were completely reversible. The number of defects
in each thallium category is listed by ventricular segment
in Table 1. In the segments with a fixed thallium defect,
there was no significant difference between the mean postexercise and delayed thallium scores. Mean delayed scores
for both partially reversible and completely reversible defects were significantly better than the mean postexercise
scores (Fig. 3).
Mean segmental thallium scores are listed according to
stress scintigraphic and tomographic classification in Table
2. On the postexercise studies, segments with a partially
reversible defect had a significantly higher mean score than
did segments with either a fixed or a completely reversible
defect. On the delayed studies, however, the mean scores
for segments with a fixed or partially reversible defect were
equally poor; both were significantly worse than the score
for segments with complete redistribution.
Correlation with positron tomography. Of the 36
myocardial segments with a fixed thallium defect, only 15
(42%) fulfilled the criteria for tomographic infarction (Fig.
4). In contrast, criteria for tomographic ischemia were present in 9 segments (25%), and 12 segments (33%) appeared
normal on tomographic study (Fig. 5). Similarly, of the 11
segments with a partially reversible thallium defect, only 4
(36%) exhibited tomographic criteria for myocardial infarction; criteria for tomographic ischemia were present in
4 segments (36%) (Fig. 6), and 3 segments (27%) were
JACC Vol. 10. No.3
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METABOLISM IN PERSISTENT THALLI UM DEFECTS
September 1987:557- 67
561
Table 2. Segmental Thallium Scores by Scintigraphic and Tomographic Classification
Postexercise
Delayed
p Value'
1.23 ::: 0.60
1.1I ::: 0. 52
0. 16 :!: 0. 13
< 0.0 \
< 0.0 1
0.57 ::: 0.58
0.76 ::: 0.56
1.27 ::: 0.70"
NS
NS
NS
Stress Scintigra phy
Fixed defects (n = 36)
Part ially reversible defects (n
II )
Completely reversible defects (n = 4 )
1.41 ::: 0.59
1.87 ::: 0.52t
1.04 ::: 0.35
NS
Positron Tomographyt
0.78 ::: 0.65
1.11 ::: 0.66
1.52 ::: 0.79\
PET norm al (n = 39)
PET ischemia (n = 17)
PET infarct (n = 22)
Summary of postexercise and 4 hour delayed mean thallium scores for myocardial segments when classified
by stress thallium scintigraphic and positron emission tomograph ic (PET ) criteria. Thallium de fects were visually
assessed and graded by three independent observers . PET class ifications are those of Marsh all et al. ( 18): PET
normal = norm al perfu sion and glucose utilization ; PET infarct = concordant reduction in both perfusion and
glucose utilizati on ; PET ischemia = preserved glucose utilization despite diminished perfu sion. See text for
details. Analy sis of variance revealed a statistically significant difference in mean scores on both the postexercise
and dela yed studies. when class ified either by stress sc intigraphic or by positron tomograph ic criteria .
*Probability of delayed score as compared with postexe rcise score ; t p < 0.025 as compare d with fixed
defe cts; p < 0.02 as co mpared with co mpletely re versible defec ts: t Exci udes the anterobasi lar segments in
four patient s in which positron tomographi c imaging was inco mplete : \ p < 0.00 I as co mpared with PET normal:
0.05 < P < 0.10 as co mpared with PET ischemia: li p < O.()()) as compared with PET norma l; p < 0.02 as
compared with PET ischemi a .
norm al. Thu s. residual tissue metabolic activity was identified in the majority of segments with a fixed (58%) or only
a partially reversible (64%) thall ium defect. All segments
with a completely reversible thallium defect were normal
on positron tomography. The tomographi c finding s in the
seg ments with fixed , partially reversible and completely
rever sible thallium defects are summarized in Figure 7.
LAO
Positron emission tomo graph y detected seven myocardial
segments with rest abnormalities of perfu sion that were not
appreciated on thallium scintigraphy . Three segments (one
Figure 4. A, Postexercise and delayed thallium-20l images from
a 66 year old woman who sustained a myocardial infarction 4 years
before study. Fixed thallium-20l defects are noted in the anterolateral. apical and septal segments. 8, On study with positron
tomography, concordant reductions in blood flow and glucose utilization are noted in the corresponding ventricular segments on the
UN-ammonia and I~F-2-deoxyglucose studies, respectively, signifying tomographic infarction. Abbreviations as in Figure I .
Ant
Lat
A
Post
Exercise
Delayed
B
Blood
Flow
Glucose
Metabolism
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BRUNKEN ET AL.
METABOLISM IN PERSISTENT THALLIUM DEFECTS
lACC Vol. 10, No.3
September 1987:557-67
LAO
Ant
Lal
A
Post
Exercise
Delayed
Figure 5. A, Postexercise and delayed thallium images from a 44
year old man who sustained a myocardial infarction 7 months
before study, demonstrating fixed defects in the anterolateral, apical and septal segments of the ventricle. B, On positron tomography, perfusiondeficits are noted in the corresponding ventricular
segments on the '3N-ammonia study (left). In addition, another
perfusion defect is noted in the posterobasilar segment. On the
'8F-2-deoxyglucose study (right), however, glucose utilization is
well preserved in these ventricular segments, indicating tomographic ischemia. Abbreviations as in Figure I.
anterolateral, one inferior and one posterobasilar) exhibited
tomographic criteria for myocardial infarction, and four segments (one inferior, one posterobasilar and two lateral) exhibited tomographic ischemia.
When mean thallium scores of all ventricular segments
were compared according to positron tomographic classification, segments that were normal on tomographic study
had significantly better scores than did segments with tomographic infarction on both the postexercise and delayed
thallium studies (Table 2). On the postexercise studies, segments with tomographic ischemia had a mean score as poor
as the score for segments with tomographic infarction. On
the delayed study, however, the mean score for ischemic
segments was significantly better than the score for segments
with tomographic infarction. There was no significant difference between the scores for ischemic segments and normal segments on either the postexercise or delayed studies.
None of the three tomographic classes exhibited a significant
difference in mean score between the postexercise and delayed thallium study.
B
Blood
Flow
Glucose
Metabolism
Clinical correlation. Nine patients had one or more
segments with tomographic ischemia. In two, ischemia was
identified adjacent to segments with tomographic infarction.
In the other seven patients, either ischemia was identified
at sites remote from infarction or all of the hypoperfused
segments in a vascular distribution exhibited tomographic
ischemia. Patients with ischemia were as likely to experience chest pain (five of nine versus two of three), have triple
vessel disease (six of nine versus one of two) or require
treatment for congestive heart failure (six of nine versus one
of three) or ventricular ectopic activity (three of five versus
two of five) as were those without ischemia. Mean treadmill
rate-pressure product (17,844 ± 4,801 versus 16,133 ±
7, lIS) and left ventricular ejection fraction (32.0 ± 14.8%
versus 32.3 ± 12.5%) were similar in both groups. Two
patients had ischemic ST-T changes while on the treadmill;
lACC Vol. 10, No.3
BRUNKEN ET AI.
METABOLISM IN PERSISTENT THALLIUM DEFECTS
September 1987:557-67
563
LAO
Ant
Lat
A
B
Post
Exercise
Delayed
both had rest tomographic ischemia in one or more corresponding myocardial segments, On stress thallium scintigraphy, improvement or normalization of the defect was not
correlated statistically with uptake of '8F-2-deoxyglucose
(II of 15 versus 21 of 36).
Discussion
On study with positron tomography, only 15 (42%) of
36 fixed and 4 (36%) of II partially resolving segmental
thallium defects exhibited tomographic infarction. In contrast, residual metabolic activity was detected in the majority
of segments with a fixed (58%) or partially resolving (64%)
thallium defect. All segments with a completely reversible
thallium defect were normal on positron tomography. In this
patient group, neither the clinical presentation nor improvement in the thallium defect 4 hours later was statistically
associated with '8F-2-deoxyglucose uptake on study with
positron tomography.
Technical considerations. Fifteen (32%) of 47 segments with a persistent stress thallium defect had normal
perfusion at rest when assessed with positron tomography.
Relative 13N-ammonia tissue tracer concentrations were within
the normal range, thereby failing to meet previously established definitions of ischemia or infarction. The mean value
± 2 SO had previously been chosen to define the normal
range because it is the criterion used by many clinical laboratories to define normal values. The spatial resolution of
the ECA T II tomograph is 1,8 em and count recovery reflects
the sum of all activity in a relatively large anatomic region
(each 30° sector could represent as much as 4.3 crrr'). Al-
Blood
Flow
Glucose
Metabolism
Figure 6. A, Postexercise and delayed thallium images from a 59
year old man who sustained a myocardial infarction I year before
study. On the postexercise images, thallium-201 deficits are noted
in the inferior, apical. anterolateral and septal segments. These
improve but fail to normalize completely on the delayed study and
were considered partially reversible defects. B, On study with
positron tomography, diminished perfusion is noted in corresponding myocardial segments on the UN-ammonia images (left). On
the 'RF-2-deoxyglucose study (right), however. glucose utilization
is well preserved in these same segments, indicating tomographic
ischemia. Abbreviations as in Figure 1.
though a rim of subendocardial fibrosis or multiple small
foci of fibrosis might diminish count recovery, if the sum
of all activity in a given sector fell within 2 SO of the mean,
this would result in a normal tomographic classification and
could explain why some segments with a persistent visual
thallium defect were classified as normal on positron tomography.
Tomographic ischemia and infarction were additionally
defined by the extent of anatomic involvement; for example,
ischemia was defined by the presence of the '8F-2~deoxy­
glucose/Plv-arnmonia mismatch in two or more contiguous
30° sectors. In this way, subtle differences in patient position
or level of tomographic plane did not result in a false positive
study. However, a segment with a relatively small thallium
defect could have been classified as normal with positron
tomography. Because of these factors, the current tomographic technique may have a higher specificity than sensitivity for the detection of myocardial ischemia and infarction. However, this same technique has proved useful
in predicting improvement in segmental function after coro-
564
BRUNKEN ET AL.
METABOLISM IN PERSISTENT THALLIUM DEFECTS
Fixed
Defects
50
III
C
CI>
E
58%
Partially
Reversible
42%
40
Ol
'''I
Completely
Revers ible
36%
100%
4
4
CI>
en
'0
30
C
Q)
0
20
~
Q)
a.
12
9
15
10
o
PET
Figure 7. Summary of the positron emission tomographic (PET)
findings in the myocardial segments with fixed, partially reversible
and completely reversible thallium defects. The number of segments in each classification is indicated by the figure on the appropriate bar. Segments normal on positron tomography are indicated by vertical lines, ischemic segments by cross-hatched
lines and infarcted segments by the open bars. The majority of
segments with a fi xed or partially reversible thallium defect exhibited persistent tissue metabolic activity on study with 18F_2_
deoxyglucose.
nary revascularization (2 1); thus the normal or ischemic
tomographic classification of a myocardial segment with a
persistent thallium perfusion defect is of practical clinical
importance, despite the possibility that small amounts of
fi brosis might exist in that segment and be visually detectable on the thallium study.
Exercise versus rest studies for tissue viability. Comparing stress thallium scintigraphy, which assessed myocardial perfusion after exercise and at 4 hours delay, with
positron tomography, which assessed rest myocardial perfusion and metabolism, also poses some difficulties. A previous report (29) has suggested that thallium redistribution
may be delayed longer than 4 hours in vascular beds subserved by vessels with stenosis :::::90%. Given that most of
the patients in the current study had one or more vessels
with :::::90% stenosis, we cannot exclude the possibility that
some of the persistent defects noted on the 4 hour thallium
images may have exhibited some degree of redistribution
had more delayed images been obtained. Several other reports have also compared rest and redistribution thallium
images. In the series of patients with coronary artery disease
reported on by Blood et al. (30),45 (73%) of 62 patients
with signifi cant coronary artery disease had rest thallium
images that were identical to the 4 hour redistribution images. In the report of Ritchie et al. (3 1), 25 of 27 patients
with exercise-induced thallium defects had complete or at
least partial redistribution on imaging at 4 to 5 hours. Thus,
lACC Vol. 10, No.3
September 1987:557- 67
it is unlikely that more delayed imaging would have significantly altered the outcome of this study.
Planar thallium versus positron tomographic imaging. Althoughthere are difficulties in comparing ventricular
segments derived from planar and tomographic imaging
techniques, we attempted to minimize these inherent differences by having experienced observers assess segmental
thallium activity on multiple planar views and using the
resultant average score for each anatomic segment. In an
independent study (21), utilizing the same seven segment
ventricular analysis technique, positron tomography successfully predicted functional improvement in asynergic
myocardial segments after coronary revascuIarization . In
that study, segmental wall motion was also assessed with
planar techniques (for example, radionuclide ventriculography), and thus we believe that it is possible to achieve a
good correlation between segments derived from planar imaging and those derived from positron tomography.
More recent advances in thallium imaging, like single
photon emission computed tomography or the analysis of
thallium washout rates, or both (32-36), have been reported
to enhance the sensitivity of thallium imaging for the detection of occult coronary artery disease and the identification and localization of antecedent myocardial infarction.
Neither of these methods was available at our institution
when this study was performed. Although the advantages
of single photon emission computed tomography and thallium kinetic analysis for the detection of coronary artery
disease and antecedent infarction are clear, it is less certain
how useful the application of these techniques to this study
would have been. The purpose of this study was to assess
relative glucose metabolism in segments with persistent,
readily identifiable thallium deficits. The aim was not to
detect coronary disease, but to determine whether tissue
metabolic activity was present in segments that exhibited
persistent thallium defects. Abnormal thallium washout rates
would have been anticipated in most of the segments with
a persistent thallium defect. Also, others (22) have previously shown a good correlation between tomographic thallium defects and 13N-ammonia defects noted on positron
tomography. Thus, it is unlikely that the use of a tomographic thalliumtechnique or analysis of segmental thallium
washout rates, or both, would have signifi cantly contributed
to this study.
Effect of dietary state. Positron tomography was performed in the postprandial state, increasing myocardial glucose utilization relative to that of free fatty acids (25) . Although the factors regulating glucose utilization in ischemic
myocardium are poorly understood. glucose uptake may
persist despite a systemic metabolic milieu favoring fatty
acid utilization (37). In the current study, tracer concentrations were normalized to maximal activity in the myocardium. In the fastingstate, normal myocardium preferentially
utilizes free fatty acids and glucose uptake is low (25) . As
l ACC Vol. 10. No.3
September I'JX7:557-67
a result, 1KF-2-deoxyglucose uptake in ischemic myocardium is increased relative to that in normal myocardium.
In the postprandial state, augmented utilization of glucose
by normal myocardium would tend to result in a relative
decrease in I ~F-2-deoxyglucose uptake in ischemic regions
that could result in a classification of infarction and underestimate the extent of tissue viability. Although the quality
of the ' ~F-2-deoxyglucose study is enhanced by imaging in
the postprandial state, this may have resulted in an underestimation of the extent of viable tissue.
Correlation with thallium scintigraphy. Preservation
of tissue metabolic activity and, thus, evidence of tissue
viability, was noted in the majority of myocardial segments
with a fixed or partially reversible thallium defect. The data
in this study are consistent with the study of Gibson et al.
(7), in which 45% of persistent thallium defects on preoperative stress scintigraphy exhibited a normal thallium
perfusion pattern and normal washout kinetics after coronary
artery bypass surgery; improvement in segmental function
provided additional evidenceof tissue viability in these myocardial segments.
Four (36%) of 11 of the segments with partial redistribution exhibited criteria for myocardial infarction on study
with positron tomography, indicatingthat apparent improvement in a thallium defect docs not exclude the possibility
that extensive scar formation may exist in that myocardial
segment. Although this may reflect observer error or the
possibility that exercise-induced ischemia may have occurred in tissue adjacent to scar tissue, other investigators
(38) have argued that thallium redistribution is a complex
process that must be interpreted with caution. The findings
of our study would similarly suggest that partial thallium
redistribution on 4 hour delayed images must be interpreted
with caution if taken to be an indicator of the presence of
substantial amounts of viable tissue.
Becauseof the entry criteria employed in this study, there
were only four myocardial segments with a thallium perfusiondefect that exhibited complete redistribution. Because
a good correlation has previously been demonstrated between thallium-201 and N-13 ammonia as markers of myocardial perfusion (15,22), it was expected that positron tomography (performed in the rest state) would demonstrate
a normal perfusion pattern. Although there were relatively
few segments for analysis. all were normal on positron
tomography.
Additional perfusion defects noted with positron tomography. Positron tomography detected a perfusion defect that was not detected on thallium imaging in seven
segments. Six of the seven defects were in inferior, posterobasilar or lateral segments. that is. in the distribution of
the left circumflex or the right coronary artery, for which
the sensitivity of planar thallium imaging is relatively low
(39), and in segments for which interobserver agreement is
poorest (40). Although positron tomography does have the
BRUNK EN ET AL.
METABOLI SM IN PERSIST ENT TH ALLI UM DEFECTS
565
advantage of being a tomographic imaging technique, adequate assessment of the anterobasilar segment was not
achieved in four patients. Future developments in tomographic instrumentation, including the ability to image or
format the cross-sectional images of the ventricle along the
long or short axis in multiple, interdigitating planes, will
more reliably enable complete visualization of the myocardium.
Thallium scores of segments classified by positron tomographic criteria. When the thallium scores of myocardial segments were analyzed according to positron tomograph ic classification, neither normal, ischemic, nor
infarcted segments exhibited statistically significant differences between the postexercise and delayed scores (Table
2). Normal segments remained normal, and infarcted segments had scores that remained equally poor with time.
Ischemic segments did exhibit the largest change in mean
thallium score (0.35 or 32%), but this was not statistically
significant. Although statistical significance might have been
achieved had more segments been analyzed. it is also possible that some of these segments may have had such a
severe perfusion defi cit at rest that exercise failed to enhance
the relative magnitude of the deficit suffi ciently for visual
detection.
On the delayed thallium images, ischemic segments had
a mean thallium score that was significantly better than the
score for infarcted segments (p < 0.0 I). Although a similar
trend was observed on the postexercise images, this was not
statistically significant. These data suggest that ischemic
segments have a less severe reduction in perfusion than do
infarcted segments and these findings are consistent with
previous observations (4 1). ln patients with chronic ischemic heart disease, mean relative tissue concentrations of
l3N-ammonia are significantly less in regions with tomographic infarction than in regions with ischemia (41). However, in both the current and the previous study (4 \), relatively large standard deviations were present in the measured
segmental values, denoting considerable overlap between
values for ischemic and infarcted segments. Thus, assessment of relative perfusion in any given myocardial segment,
panicularly one with a moderately severe reduction in flow
(41), would be unlikely to be successful in predicting the
presence or absence of glucose utilization.
Clinical significance of findings. As a readily available,
noninvasive method of assessing myocardial perfusion, thallium-20 I scintigraphy has proved invaluable for detecting
coronary artery disease ( I), for assessing the severity of
coronary stenoses (42.43) and the response to therapeutic
procedures (44-48 ) and for stratifying risk in patients with
ischemic heart disease (49-52). As such, it will likely remain in the clinician's armamentarium for many years to
come. However, the results of the current study, in conjunction with previous reports (6,7), would indicate that the
reliance on perfusion markers alone for assessment of tissue
566
BRUNKEN ET AL.
METABOLISM IN PERSISTENT THALLIUM DEFECTS
viability in segments with persistent abnormalities of myocardial blood flow might lead to underestimation of the
extent of salvageable tissue. Myocardial regions associated
with a large thallium-201 defect may contain only small
amounts of fibrosis (53) and, conversely, some investigators
have argued that the accumulation of thallium-20l is a passive process, depending on blood flow rather than on tissue
viability (54). Thus, use of an independent marker of tissue
viability like 18F-2-deoxyglucose would appear to be clinically helpful in these situations.
Myocardial infarction is a heterogeneous process and the
degree of myocardial fibrosis occurring as a result of an
ischemic injury varies considerably (55-57). Because the
spatial resolution of the ECAT II tomograph utilized in this
investigation was 18 mm, it is possible that the observed
uptake of '8F-deoxyglucose in the myocardial segments appearing hypoperfused on thallium scintigraphy might, in
some instances, have represented accelerated glucose utilization in a rim of viable epicardial myocardium adjacent
to a dense subendocardial infarct. In such a situation the
extent of functional recovery of segmental wall motion after
coronary revascularization would depend on the amount of
viable myocardium remaining in the epicardium. Although
a previous report from this laboratory (21) noted that segments that demonstrated preserved myocardial uptake of
18F-deoxyglucose had an 85% probabilitiy of improved wall
motion after coronary revascularization, future studies with
positron tomography should be able to provide even more
information about the extent of tissue viability in hypoperfused myocardial segments. With the advent of the next
generation of tomographs offering better spatial resolution
and higher efficiency, noninvasive quantitative measurements of myocardial blood flow and glucose utilization should
be feasible, allowing more accurate determination of the
amount of viable but jeopardized tissue in hypoperfused
myocardial segments.
Conclusions. In this study, positron emission tomography with 13N-ammonia and 18F-2-deoxyglucose revealed
persistent tissue metabolic activity in the majority of myocardial segments with a fixed or partially reversible thallium
defect, implying the presence of viable tissue in these segments. Neither the severity of the thallium defect nor apparent improvement in the defect 4 hours after exercise
reliably distinguished tomographically identified segments
with ischemia from those with infarction. Thus, reliance on
markers of perfusion alone for the assessment of tissue viability in segments with persistent abnormalities of blood
flow may underestimate the extent of salvageable myocardium.
We thank N. S. MacDonald, PhD and the Cyclotron Staffforthe production
of the isotopes. The tomographic studies were performed by the following
dedicated nuclear medicine technologists: Francine Aguilar, Cynthia Whitt,
Lawrence Pang and Ron Sumida. M. Lee Griswold, Cynthia Whitt and
Ron Sumida assisted with the illustrations and Kerry Engber prepared the
manuscript.
lACC Vol. 10, No.3
September 1987:557-67
References
I. Iskandrian AS, Hakki AH. Thallium-201 myocardial scintigraphy. Am
Heart 1 1985;109:113-29.
2. Pohost GM, Zir LM, Moore RH, McKusick KA, Guiney TE, Beller
GA. Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-20 I. Circulation
1977;55:294-302.
3. Berman DS, Garcia EV, Maddahi J, Rozanski A. Thallium-201 myocardial perfusion scintigraphy: redistribution. In: Freeman LM, ed.
Freeman and Johnson's Clinical Radionuclide Imaging. 3rd ed. Orlando, FL: Grune & Stratton, 1984:481-2.
4. Rozanski A, Berman DS, Gray R, et al. Use of thallium-201 redistribution scintigraphy in the preoperative differentiation of reversible
and nonreversible myocardial asynergy. Circulation 198 I;64:936-44.
5. Iskandrian AS, Hakki AH, Kane SA, et al. Rest and redistribution
thallium-201 myocardial scintigraphy to predict improvement in left
ventricular function after coronary arterial bypass grafting. Am 1 CardioI1983;51:1312-6.
6. Liu P, Kiess MC, Okada RD, et al. The persistent defect on exercise
thallium imaging and its fate after myocardial revascularization: does
it represent scar or ischemia') Am Heart J 1985;110:996-1001.
7. Gibson RS, Watson DD, Taylor GJ, et al. Prospective assessment of
regional myocardial perfusion before and after coronary revascularization surgery by quantitative thallium-201 scintigraphy. J Am Coli
CardioI1983;1:804-15,
8. Brachfeld N, Scheuer J. Metabolism of glucose by the ischemic dog
heart. Am J Physiol 1967;2 I2:603-6.
9. Opie LH, Owen P, Riemersma RA. Relative rates of oxidation of
glucose and free fatty acids by ischaemic and nonischaemic myocardium after coronary artery ligation in the dog. Eur 1 Clin Invest 1973;3:
419-35.
10. Neely JR, Whitmer JT, Rovetto MJ. Effect of coronary blood flow
on glycolytic flux and intracellular pH in isolated rat hearts. Circ Res
1975;37:733-41.
I I. Opie LH. Effects of regional ischemia on metabolism of glucose and
fatty acids. Circ Res 1976;38(suppl 1):1-52-74.
12. Marshall RC, Nash WW, Shine KI, Phelps ME, Ricchiuti N.Glucose
metabolism during ischemia due to excessive oxygen demand or altered coronary flow in the isolated arterially perfused rabbit septum.
Circ Res 1981;49:640-8.
13. Liedtke Al. Alterations of carbohydrate and lipid metabolism in the
acutely ischemic heart. Prog Cardiovasc Dis 1981;23:321-36.
14. Schelbert HR, Phelps ME, Hoffman El , Huang SC, Selin CE, Kuhl
DE. Regional myocardial perfusion assessed with N-13 labeled ammonia and positron emission computerized axial tomography. Am 1
Cardiol 1979:43:209-18.
15. Schelbert HR, Wisenberg G, Phelps ME, et al. Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilation. VI. Detection of coronary artery disease
in human beings with intravenous N-13 ammonia and positron computed tomography. Am 1 Cardiol 1982;49: 1197-207.
16. Gallagher BM, Fowler 15, Gutterson NI, MacGregor RR, Wan CN,
Wolf AP. Metabolic trapping as a principle of radiopharmaceutical
design: some factors responsihle for the biodistribution of rIRF j-2deoxy-2-fluoro-D-glucose. J Nucl Med 1978;19:1154-61.
17. Ratib 0, Phelps ME, Huang SC, Henze E, Selin CE, Schelbert HR.
Positron tomography with deoxyglucose for estimating local myocardial glucose metabolism. 1 Nucl Med 1982;23:577-86.
18. Marshall RC, Tillisch lH, Phelps ME, et al. Identification and differentiation of resting myocardial ischemia and infarction in man with
positron computed tomography, 18F-Iabeled fluorodeoxyglucose and
N-13 ammonia. Circulation 1983;67:766-78.
19. Sochor H, Schwaiger M, Schelbert HR, et al. Assessment of tissue
viability in reperfused canine myocardium by a multiple radiotracer
techinque (abstr). 1 Am Coli Cardiol 1985;5:451.
20. Schwaiger M, Schelbert HR, Ellison D, et al. Sustained regional
10, No. 3
September 1987:557- 67
lACC Vol.
abnormalities in cardiac metabolism after transient ischemia in the
chronic dog model. J Am Coli Cardiol 1985;6:336-4 7.
21. Tillisch J, Brunken R, Marshall R, et al. Reversibility of cardiac wall
motion abnormalities predicted by positron tomography. N Engl J
Med 1986;314:884-8.
22. Tamaki N, Senda M, Yonekura Y, er al. N-13 ammonia myocardial
positron computed tomography: ( I ) Comparative study with thallium201 SPECT. Kaku Igaku 1985;22:185- 91.
23. Krivokapich J, Huang SC, Phelps EM, et al. Estimation of rabbit
myocardial metabolic rate for glucose using fluorodeoxyglucosc. Am
J Physiol I982;243:H884-95.
24. Bida GT , Satyamurthy N, Barrio JR. The synthesis of 2-lF- 111 I fluoro2-deoxy-D-glucose usingglycals: a reexamination. J Nuel Med 19S4:25:
1327-34 .
25. Drake-Holland AJ. Substrate utilization. In: Drake-Holland AJ, Noble
MIM, eds. Cardiac Metabolism. Chicester: John Wiley, 1983:195-213
26. Lockwood AH. Absorbed doses of radiation after an intravenous injection of N-13 ammonia in man: concise communication. J Nucl Med
1980:21:276- 78.
27. Jones Sc. Alavi A, Christman D, Montanez I, Wolf AP, Reivich M.
The radiation dosimetry of 2-lF-1SI fluoro-2-denxy-D-glucose in man.
J Nuel Med 1982;23:6 13- 7.
28. Hirzel HO, Senn M. Nuesch K, et al. Thallium-201 scintigraphy in
complete left bundle branch block. Am J Cardiol 1984;53:764- 9.
29. Gutman J, Berman DS, Freeman M, et al. Time to completed redistribution of thallium-201 in exercise myocardial scintigraphy: relationship to the degree of coronary artery stenosis. Am Heart J 1983:106:
989-95 .
30. Blood OK, McCarthy OM, Sciacca BR, Cannan PJ. Comparison of
single-dose and double-dose thallium-20 I myocardial perfusion scintigraphy for the detection of coronary artery disease and prior myocardial infarction. Circulation 1978;58:777- S8.
31. Ritchie JL, Albro PC, Caldwell JH, Trobaugh GB, Hamilton GW.
Thallium-201 myocardial imaging: a comparison of the redistribution
and rest images. J Nuel Med 1979;20:477- 83.
32. Ritchie JL, Williams OL, Harp G, Stratton JL, Caldwell JH. Transaxial tomography with thallium-201 for detecting remote myocardial
infarction: comparison with planar imaging. Am J Cardiol 19S2:50:
1236-41.
33. Kirsch CM, Doliwa R, Buell U, Roedler D. Detection of severe
coronary heart disease with TI -20I: comparison of resting single photon emission tomography with invasive arteriography. J Nucl Med
1983:24:761- 7.
34. Tamaki N, Yonekura Y, Mukai T, et al. Stress thallium-201 transaxial
emission computed tomography: quantitative versus qualitative analysis for evaluation of coronary artery disease. J Am Coll Cardiel
1984;4:1213- 21.
35. Garcia EV, Van Train K, Maddahi J, et al. Quantification of rotational
thallium-201 myocardial tomography. J Nuel Med 1985:26:17- 26.
36. Abdulla A, Maddahi 1. Garcia E, Rozanski A. Swan HJe. Berman
OS. Slow regional clearance of myocardial thallium-20 I in the absence
of perfusion defect: contribution to detection of individual coronary
artery stenoses and mechanism for occurrence. Circulation 19S5:71:
72-9 .
37. Brunken RC, Schwaiger M, Schelbert HR. PET detection of residual.
viable tissue in acute MI. J Appl Radiol 1985:14:82- 6.
38. Bergmann SR, Hack SN, Sobel BE. "Redistribution" of myocardial
thallium-20 I without reperfusion: implications regarding absolute
quantification of perfusion. Am J Cardiol 1982;49:1691- S.
39. Rigo P, Bailey IK, Griffith LSC, Pill B. Wagner HN. Becker i.c .
Stress thallium-2ot myocardial scintigraphy for the detection of individual coronary arterial lesions in patients with and without previous
myocardial infarction. Am J Cardiol 1981;48:209-16.
BRUNK EN ET AL.
METABOLI SM IN PERSISTENT THALLIUM DEFECTS
567
40. Atwood JE. Jensen O. Froelicher V, et al. Agreement in human
interpretation of analog thallium myocardial perfusion images. Circulation 1981:64:60 1-9.
41. Brunken RC. Schwaiger M. Tillisch JH , Marshall RC, Phelps ME,
Schelbert HR. Relation between blood flow and glucose metabolism
in hypoperfused ventricular segments in chronic ischemic heart disease
(abstr). J Am Coli Cardiol 19S6;7:202A.
42. Reisman S. Berman O. Maddahi 1, Swan HJe. The severe stress
thallium defect: an indicator of critical coronary stenosis. Am Heart
J 1985:110:12S- 34.
43. Kalil V. Kelly MJ. Soward A, et al. Assessment of hemodynamic
significance of isolated stenoses of the left anterior descending coronary artery using thallium-20 I myocardial scintigraphy. Am J Cardiol
1985:55:342-6 .
44. Iskandrian AS. Haaz W, Segal BL, Kane SA. Exercise thallium-201
scintigraphy in evaluating aortocoronary bypass surgery. Chest 1981 ;80:
11-5.
45. Greenberg BH. Hart R. Botvinick EH, et al. Thallium-201 myocardial
perfusion scintigraphy to evaluate patients after coronary bypass surgery. Am J Cardiol 1975:42:167- 76.
46. Scholl JM. Chaitman BR. David PRoet a!' Exercise electrocardiography and myocardial scintigraphy in the serial evaluation of the results
of percutaneous transluminal coronary angioplasty. Circulation 1982:66:
380-90.
47. Okada RO. Lim YL. Boucher CA, Pohost GM, Chesler OA. Block
Pc. Clinical. angiographic. hemodynamic. perfusional and functional
changes after one-vessel left anterior descending coronary angioplasty.
Am J Cardiol 19S5;55:347- 56.
48. Wijns W. Serruys W. Reiber JHC. et al. Early detection of restenosis
after successful percutaneous transluminal coronary angioplasty by
exercise-redistribution thallium scintigraphy. Am J Cardiol 1985;55:
357-6 1.
49. Becker LC. Silverman K1. Bulkley BH, Kallman CH, Mellits ED,
Weisfeldt M. Comparison of early thallium-201scintigraphy and gated
blood pool imaging for predicting mortality in patients with acute
myocardial infarction. Circulation 1983;67: 1272- 82.
50. Gibson RS, Watson 00. Craddock GB, et a!' Prediction of cardiac
events after uncomplicated myocardial infarction: a prospective study
comparing predischarge exercise thallium-201 scintigraphy and coronary angiography. Circulation 1983;611 :321-36.
51. Iskandrian AS, Hakki AH. Kane-Marsch S. Prognostic implications
of exercise thallium-20 I scintigraphy in patients with suspected or
known coronary artery disease. Am Heart J 1985;110:135-43 .
52. Ladenheim ML. Pollock BH. Rozanski A, et al. Extent and severity
of myocardial hypopcrfusion as predictors of prognosis in patients
with suspected coronary artery disease. J Am Coli Cardiol 1986;7:
464- 71.
53. Bulkley BH. Silverman K. Weisfeldt ML. Burow R, Pond M, Becker
LC. Pathologic basis of thallium-20 I scintigraphic defects in patients
with fatal myocardial injury. Circulation 1979:60:7115- 92.
54. Forman R, Kirk ES. Thallium-20J accumulation during reperfusion
of ischemic myocardium: dependence on regional blood flow rather
than viability. Am J Cardiel 19S4:54:65Y-63.
55. Stinson EB. Billingham ME. Correlative study of regional left ventricular histology and contractile function. Am J Cardiol 1977:39:
37S- R.1.
56. Hameng W, Suy R. Schwarz F, et al. Ultrastructural correlates of
left ventricular contraction abnormalities in patients with chronic ischemic heart disease: determinants of reversible segmental asynergy
post-rcvascularization surgery. Am Heart J 1981;102:S46-57.
57. Freifeld AG, Schuster EH. Bulkley BH. Nontransmural versus transmural myocardial infarction . A morphologic study. Am J Med 1983:75:
423- 32.