Discordant
viability techniques
Ullrich Schricke, Markus Schwaiger
Klinik und Poliklinik für Nuklearmedizin, Klinikum rechts der
Isar,
Technische Universität München, Germany
Correspondence: Dr Ulriche Schricke, Klinik und Poliklinik für
Nuklearmedizin,
Klinikum rechts der Isar, Technische Universität München, Ismaninger
Strasse 22,
81675 München, Germany (schricke@dhm.mhn.de)
Introduction
Previous studies have demonstrated that myocardial dysfunction
characterized by an absence of wall thickening is not necessarily
caused by scar tissue, as it can also occur in viable myocardium
in instances of stunning or hibernation. The term “stunned myocardium”
refers to a reversible form of contractile dysfunction that occurs
after restoration of coronary blood flow, following a period of
transient ischemia.[1] The duration of stunning can vary between
hours and weeks, but its resolution is spontaneous without the
need for treatment.
Hibernation describes a state of decreased function caused by
an acute (short-term hibernation) or chronic (long-term hibernation)
reduction of myocardial blood flow. By definition, the contractility
of hibernating myocardium returns after successful revascularization.[2] The concept of short-term hibernation is based on the hypothesis
that the metabolic demand of ischemic cells can adapt to the reduced
perfusion, establishing a new level of “perfusion-contraction
matching” which prevents myocytes from necrosis.[3] Long-term
hibernation is also associated with ultrastructural changes such
as disorganization and reduction of the myofibrils, and an increase
in extracellular collagen and myocardial glycogen content, which
may limit or delay functional recovery after revascularization.[4,5]
Identification of viable myocardium
The identification of viable myocardium is an important clinical
task. In patients with severely impaired left ventricular function,
surgical intervention is associated with a higher risk of perioperative
complications. Selecting patients with severely depressed myocardial
function for revascularization therapy on the basis of prior viability
detection significantly lowers the rate of perioperative complications.
Furthermore it enables prediction of functional recovery and therefore
suggests decreased long-term mortality.[6,7] Thus, major efforts
have been made to develop noninvasive methods for detecting viable
myocardium.
The information required to assess viability varies between the
methods used, but includes measurement of cell metabolism, cell
membrane integrity, mitochondrial function and contractile reserve
under b-adrenergic stimulation.
Myocardial energy metabolism assessed
by PET
Cardiac myocytes metabolize a wide variety of substrates. Under
normoxic conditions, the heart preferentially metabolizes free
fatty acids. Their oxidation accounts for about 60% to 70% of
total myocardial oxygen consumption in the fasting state.[8] However,
in ischemically compromised myocardium the utilization of free
fatty acids decreases whereas the use of exogenous glucose is
preserved or accelerated.[9,10] This finding is the rationale
for the use of 18F-2-fluoro-2-deoxyglucose (18FDG)
as a radiolabeled tracer of exogenous glucose metabolism in PET
to measure viability. In combination with a flow tracer, such
as 13N-ammonia, a visual “mismatch” with augmented
uptake of glucose relative to blood flow is indicative of hibernating
myocardium.[11,12] Dysfunctional areas with preserved blood flow
and preserved uptake of glucose may reflect stunned myocardium.
As exogenous glucose utilization of myocytes can be increased
by a high-carbohydrate meal or insulin infusion, current viability
protocols include standardization of metabolic conditions during
examination.[13,14]
Recent studies have also demonstrated the accuracy and feasibility
of 18FDG and SPECT in the detection of viable myocardium.[15] Despite the fact that SPECT is widely available and less expensive
than PET, the method is rarely used for detecting viable myocardium.
The need for an ultra-high-energy collimator has limited its routine
use. Other groups have used 11C-acetate, a tracer of
tricarboxylic acid cycle flux, with PET. This tracer allows assessment
of myocardial oxygen consumption, which is known to be preserved
in hibernating myocardium.[16,17] However, the short half-life
of the tracer (about 20 min) limits its use to PET centers that
have a cyclotron on site.
Cell membrane integrity assessed by SPECT
Since the 1970s 201Tl has been widely used as a single-photon
tracer for myocardial perfusion imaging. 201Tl is a
monovalent, heavy metal, cation crystal with a crystal radius
similar to that of K+. The cellular uptake of 201Tl,
like that of K+, involves the active transport of the ion by Na-K-ATPase
and therefore maintains cell membrane integrity.[18] The high
first-pass extraction by the myocardial tissue of approximately
85% and the linear relationship of tracer uptake and myocardial
blood flow over a wide range make this tracer a suitable agent
to assess coronary blood flow, providing images are acquired soon
after tracer injection.[19] After initial uptake of 201Tl,
there is a continuous exchange of 201Tl between perfused,
viable myocardium and the blood pool. This process of continuous
exchange forms the basis of 201Tl redistribution, identifying
in a second set of images regions with hypoperfused viable myocytes
3 to 4 h after tracer injection by delayed defect resolution.[20] Several animal studies have shown that the redistribution noted
in delayed images represents an absolute reduction in thallium
concentration in regions with normal perfusion, along with an
absolute increase in the concentration in hypoperfused regions.[21,22] A variety of protocols have been proposed to further improve the
sensitivity of the method. Some authors have suggested late acquisition
18 to 24 h after tracer injection, because some regions with viable
myocardium have shown a further resolution of 201Tl
defect compared with images acquired 3 to 4 h after injection.[23] Others have suggested the administration of a first dose of 201Tl
under stress conditions to detect stress-induced ischemia, and
the administration of a second dose after 3 to 4 h imaging at
rest (stress-redistribution-reinjection imaging).[24] Obviously,
the reinjection of thallium immediately after redistribution imaging
facilitates the 201Tl uptake in hypoperfused but viable
myocytes by augmentation of the blood concentration of the tracer.
Mitochondrial function assessed by SPECT
Further research resulted in the development of 99mTc-labeled
cations including the isonitrile sestamibi and the phoshine compounds
tetrofosmin and furofosmin. The 140 keV photon energy peak of
99mTc is optimal for imaging with a gamma-camera and
produces higher quality images than those produced by 201Tl.
Moreover the short half-life of 99mTc permits administration
of higher doses than those used by 201Tl, yielding
better imaging quality in a shorter acquisition time. By far the
best validated tracer in this group is 99mTc sestamibi.
As in the case of 201Tl, the tracer uptake in myocytes
is linear to myocardial blood flow over a wide range.[25] The
complex is sequestered within mitochondria by the large negative
transmembrane potential, after it has been passively transported
across plasma and mitochondrial membranes, and shows no significant
redistribution.[26,27] Therefore, 99mTc sestamibi accumulation
in myocytes reflects mitochondrial function, which parallels cellular
viability. Recent studies suggested that the specificity of this
method can be improved by the administration of nitrates prior
to examination.[28,29]
Systolic wall thickening assessed by
dobutamine echocardiography
The idea of using dobutamine stress echocardiography for the detection
of viable myocardium is based on the hypothesis that hibernating
as well as stunned myocardium retains the ability to respond to
ß-adrenergic stimulation, resulting in augmented contractility.
The technique involves stepwise administration of dobutamine.
A variety of protocols have evolved. Typically the administrated
dose increases in 3- to 5-min stages and ranges from 2.5 to 10
µg kg–1 min–1 dobutamine for the established
low-dose protocols.[30] High-dose protocols with administration
of up to 40 µg kg–1 min–1dobutamine are
currently under clinical investigation. In this approach a biphasic
response was noted with an initial augmentation of contractility
during low-dose administration of dobutamine and a loss of contractility
during administration of higher doses. This was found to be of
high prognostic value in the prediction of functional recovery
after revascularization in a given segment.[31] However, the use
of this method is dependent on the investigator’s experience as
well as on the echogenic build of the patient.
Systolic wall thickening assessed by
dobutamine MRI
MRI has proved to be highly accurate for the assessment of cardiac
anatomy and ventricular function. Its high spatial and temporal
resolution combined with its independence from the investigator’s
experience and the anatomical build of the patient allows the
assessment of systolic wall thickening and end-diastolic wall
thickness with higher accuracy and better reproducibility than
echocardiography.[32] However, the method has not yet entered
general clinical use and only a few studies exist assessing the
impact of dobutamine MRI on the measurement of myocardial viability.[33,34]
Another promising new MRI technique, not yet validated for clinical
use, is the differentiation of viable myocardium and irreversible
cell damage by patterns of contrast enhancement. Rogers et al
[35] studied 17 patients after reperfusion therapy following their
first acute myocardial infarction. A first-pass acquisition, combined
with a delayed acquisition about 7 min after administration of
nonionic gadolinium (Gd-HP-DO3A), was made. They found that a
normal first-pass signal followed by a hyperenhanced signal on
delayed images indicates viability, whereas the absence of both
signals suggests irreversible cell damage. Kim et al [36] used
gadolinium DTPA, an ionic contrast agent, to measure viability
following acute and chronic infarction in animal models. They
concluded that hyperenhancement 20 to 30 min after administration
of the contrast agent indicates irreversible cell damage. However,
in both studies viability was assessed after restoration of coronary
artery blood flow. Further studies must clarify whether viable
myocardium can also be identified prior to revascularization by
this method.
Discordant information
Myocardial viability detection is a field of ongoing research.
When considering the accuracy of the methods currently available
for the detection of viability in clinical routine, it should
be recognized that the number of patients currently examined by
the varying methods is relatively small and heterogeneous. Moreover
the techniques adopted for examination and revascularization,
as well as the selection of thresholds for differentiating viable
from nonviable tissue, vary with each method. Finally, differences
in the accuracy of the methods may also be explained by the varying
study endpoints used to assess myocardial viability, including
regional and global functional recovery after revascularization
and detection of viable myocardium, compared with a varying “gold
standard”.
However, several studies comparing two or more currently employed
modalities have shown that, depending on the different intracellular
processes measured, findings concerning viability are under certain
circumstances somewhat discordant.[15] For example, the presence
of a severe perfusion defect on either 4-h 201Tl redistribution
or 201Tl reinjection images did not preclude the possibility
of residual tissue viability, as was shown by a direct comparison
with PET using 18FDG metabolic imaging. Residual “metabolic”
viability was demonstrated in 50% of severe defects on redistribution
images and 25% of severe defects on reinjection images.[37] The
same laboratory compared the results of stress-redistribution-reinjection
201Tl SPECT imaging with 99mTc sestamibi
imaging in a group of 54 patients. The investigators reported
that in 36% of segments demonstrating irreversible defects on
99mTc sestamibi imaging, 201Tl images indicated
viable myocytes.[38]
Several discrepancies can be found, especially if findings regarding
contractility under b-adrenergic stimulation are compared with
nuclear tracer uptake. In a recent publication, dobutamine echocardiography,
PET and 201Tl
SPECT were compared with the histopathological finding of fibrosis
in explanted hearts. The study revealed that contractile response,
as assessed by dobutamine echocardiography, requires at least
50% viable myocytes in a given segment, whereas scintigraphic
methods identify segments with about 25% viable myocytes.[39] This suggests that nuclear techniques may be highly sensitive
for the detection of viable myocardium. A negative finding almost
excludes a significant number of myocytes in a given segment being
viable. This finding is in keeping with a recent study from Pagano
et al.[40] who compared the predictive value of dobutamine echocardiography
and a combined 13N-ammonia/18FDG PET protocol
in identifying patients with reversibility of left ventricular
dysfunction prior to coronary artery bypass surgery. Thirty patients
with coronary artery disease and severely decreased left ventricular
function were studied. The authors concluded that dobutamine echocardiography
and PET have similar positive predictive values (68% vs 66%) in
the identification of hibernating myocardium, but dobutamine echocardiography
has a significantly lower negative predictive value than PET (54
vs 96%; P < 0.0001). Selected studies with a head-to-head comparison,
demonstrating discordant viability information are shown in Table
1.
Table 1. Studies with a head-to-head comparison,
showing discordant viability information in patients with severely
depressed left ventricular function. Sensitivity and specificity
given for the study by Baumgartner et al.39 are related to detection
of segments containing more than 25% viable myocytes. In all other
studies sensitivity and specificity are given for the prognosis
of regional functional recovery after revascularization.
In clinical decision-making, one has to be aware of such discordant
information. If the decision whether a patient with severe myocardial
dysfunction should undergo revascularization therapy or heart
transplantation is based on the amount of viable myocardium detected,
the method chosen to measure viability may be of critical importance.
One might argue that dobutamine echocardiography is the method
of first choice for specific prediction of regional functional
recovery in patients with depressed myocardial function in whom
revascularization is contemplated, because pooled data suggest
that this method has the highest specificity.[15] One might further
argue that regions of the heart which are viable according to
metabolic PET or 201Tl studies, but not viable according
to dobutamine echocardiography, are unlikely to improve soon after
successful revascularization, because of the small amount of viable
myocytes detected by nuclear techniques.[44] However, if regions
with such discordant viability information are identified as being
viable, patients may benefit from revascularization of these regions
in terms of delayed improvement of regional contractility,[40,44] modification of the remodeling process, and prevention of adverse
cardiac events.[39,45–47]
Conclusion
Current methods for the assessment of myocardial viability identify
viable myocardium with varying accuracy mostly as a result of
the different intracellular processes measured. Methods assessing
contractility under b-adrenergic stimulation are less sensitive
than metabolic PET imaging or 201Tl scintigraphy in
detecting small amounts of viable myocytes. Even if discordant
viability information generally refers to regions with only a
limited number of viable myocytes, patients may benefit from revascularization
of such regions with regard to long-term outcome.
Acknowledgment
We would like to thank Ms Leishia Tyndale-Hines for her assistance
in editing this manuscript.
REFERENCES
Myocardial 'stunning' in man.
Bolli R.
Department of Medicine, Baylor College of Medicine, Houston,
Tex. 77030.
Publication Types:
PMID: 1451239 [PubMed - indexed for MEDLINE]-
Comment in:
The hibernating myocardium.
Rahimtoola SH.
Department of Medicine, University of Southern California
School of Medicine.
The hibernating myocardium refers to resting LV dysfunction
due to reduced coronary blood flow that can be partially or
completely reversed by myocardial revascularization and/or by
reducing myocardial oxygen demand. It is different from the
stunned myocardium. Methods for its detection are not yet
perfect. Hibernating myocardium has been demonstrated to be
present in several clinical subgroups of patients; however,
currently its full clinical presence and impact are not
adequately defined.
PMID: 2783527 [PubMed - indexed for MEDLINE]-
Development of short-term myocardial
hibernation. Its limitation by the severity of ischemia and
inotropic stimulation.
Schulz R, Rose J, Martin C, Brodde OE, Heusch G.
Abteilung fur Pathophysiologie, Universitatsklinikums Essen,
FRG.
BACKGROUND. Short-term hibernating myocardium is characterized
by a decrease in contractile function in proportion to the
reduced myocardial blood flow. Myocardial creatine phosphate
content, initially decreased during the first minutes of
ischemia, returns to near-control values, the ischemia-induced
net lactate production is attenuated, and the myocardium
remains viable despite ongoing hypoperfusion and contractile
dysfunction. Hibernating myocardium after 85 minutes of
ischemia maintains an inotropic reserve and responds to
short-term intracoronary dobutamine infusion with increased
work; however, this inotropic response is at the expense of
metabolic recovery. We therefore hypothesized that the
development of myocardial hibernation is a delicate process
that is easily disturbed by unfavorable alterations in the
oxygen-supply demand balance. METHODS AND RESULTS. To study
the impact of prolonged inotropic stimulation on the
development of myocardial hibernation, the left anterior
descending coronary artery was cannulated and hypoperfused at
constant flow in 12 enflurane-anesthetized swine. The
reduction of coronary inflow was followed by a reduction of
regional myocardial work (sonomicrometry) from 248 +/- 59 mm
Hg.mm to 73 +/- 35 mm Hg.mm (P < .05) at 5 minutes of
ischemia. Dobutamine (2.5 +/- 1 micrograms/min) was then
infused for an additional 85 minutes. Work was increased at 5
minutes of dobutamine to 139 +/- 34 mm Hg.mm (P < .05
versus 5 minutes of ischemia). However, this increase was only
transient, and after 85 minutes of dobutamine, work was
decreased below the initial ischemic value (42 +/- 34 mm
Hg.mm). At 5 minutes of ischemia, creatine phosphate content
was reduced from 8.80 +/- 1.97 to 6.21 +/- 3.87 mumol/g wet wt,
and myocardial ATP content was decreased slightly from 4.75
+/- 0.92 to 4.12 +/- 1.29 mumol/g wet wt (both, P = NS). After
5 minutes of dobutamine, further reductions in creatine
phosphate content to 3.11 +/- 0.76 mumol/g wet wt and in ATP
to 3.14 +/- 0.81 mumol/g wet wt were observed (both, P <
.05 versus control). During the remainder of the continuous
dobutamine infusion, creatine phosphate content remained
unchanged, whereas ATP further decreased significantly to 1.68
+/- 0.96 mumol/g wet wt. The beta-adrenoceptor density of the
left anterior descending coronary artery-perfused myocardium
was 36.5 +/- 5.8 fmol (-)-[125I]iodocyanopindolol/mg protein
under control conditions, and this was unchanged during
ischemia and the subsequent dobutamine infusion. Following 90
minutes of ischemia with 85 minutes of dobutamine and 2 hours
of reperfusion, infarct size (triphenyl tetrazolium chloride
staining) was 26.3 +/- 7.5% of the area at risk. With constant
hypoperfusion, dobutamine redistributed blood flow away from
the subendocardium (0.20 +/- 0.08 versus 0.11 +/- 0.04 mL.min-1.g-1)
toward the subepicardium (0.45 +/- 0.13 versus 0.51 +/- 0.21
mL.min-1.g-1) as well as to the right ventricle (0.26 +/- 0.08
versus 0.32 +/- 0.09 mL.min-1.g-1). Therefore, in two other
groups of six and five swine, the severity of ischemia was
increased to achieve an 80% or a 90% reduction in regional
function, respectively, and the importance of the severity of
blood flow reduction per se for the development of myocardial
infarction was studied. The infarct size in the animals
undergoing 85 minutes of dobutamine (26.3 +/- 7.5%) was
increased above the level expected from the blood flow
reduction alone (6.3 +/- 6.4%, P < .01). CONCLUSIONS. Both
the increased severity of ischemia and the enhanced energy
expenditure induced by dobutamine impair the development of
myocardial short-term hibernation and precipitate myocardial
infarction.
PMID: 8393390 [PubMed - indexed for MEDLINE]-
Ultrastructural correlates of left
ventricular contraction abnormalities in patients with chronic
ischemic heart disease: determinants of reversible segmental
asynergy postrevascularization surgery.
Flameng W, Suy R, Schwarz F, Borgers M, Piessens J, Thone
F, Van Ermen H, De Geest H.
The relationships between structural alterations and left
ventricular (LV) contraction abnormalities were studied in
patients with coronary artery disease (CAD). Transmural
biopsies of the LV anterior free wall were taken during
aortocoronary bypass surgery (CABG) in 62 patients. When
preoperative anterior wall motion (AWM) was reduced,
significant myocardial cell degeneration was found in patients
with as well as without previous anterior infarction (MI). The
amount of myocardial fibrosis was increased only in patients
with ECG evidence of previous anterior MI (p less than 0.001).
In a second series of 139 CAD patients, cineventriculograms
performed before and 8 months after CABG were examined. In
patients with patent grafts to the LV anterior wall not
previously infarcted, reduced AWM became normal. In patients
with previous anterior MI the outcome of AWM was unpredictable
(usually unimproved). Thus the histologic correlate of reduced
AWM in segments not previously infarcted was progressive loss
of contractile material in otherwise viable myocardial cells.
Some reversibility was suggested by restoration of resting
function after CABG. Unpredictable results in segments
associated with pathologic Q waves appear related to the
fibrous component of these previously infarcted areas.
PMID: 6975559 [PubMed - indexed for MEDLINE]-
Multivariate analysis of angiographic,
histologic, and electrocardiographic data in patients with
coronary heart disease.
Flameng W, Wouters L, Sergeant P, Lewi P, Borgers M, Thone
F, Suy R.
In 61 consecutive patients undergoing aortocoronary bypass
grafting, angiographic and electrocardiographic (ECG) changes
were studied. Histologic delineation of myocardium was
obtained by analysis of transmural biopsy specimens acquired
at the time of surgery. The use of principal-component
analysis revealed three definite groups of patients. Group I
comprised patients with histologic findings associated with
severe left anterior descending coronary artery (LAD) stenosis,
without abnormal wall motion or ejection fraction. ECG
abnormalities were limited to ST changes. Group II comprised
patients with severe myocardial cell degeneration with only
modest fibrosis associated with severe LAD stenosis and
severely impaired wall motion. The incidence of infarction on
the ECG was low. Group III patients had important myocardial
cell degeneration with severe fibrosis associated with severe
LAD stenosis, severely depressed wall motion, and
significantly impaired ejection fraction. In this group there
was a high incidence of infarction apparent on the ECG.
Postoperative follow-up (24 months) showed a total survival of
94.4% in group I, 92.8% in group II, and only 72.7% in group
III. This identification of subtypes of coronary artery
disease seems to be helpful in estimating patient prognosis
after coronary surgery.
PMID: 6609785 [PubMed - indexed for MEDLINE]-
Late results of surgical and medical
therapy for patients with coronary artery disease and
depressed left ventricular function.
Pigott JD, Kouchoukos NT, Oberman A, Cutter GR.
Late survival and freedom from myocardial infarction were
determined for 192 patients with coronary artery disease and
depressed left ventricular ejection fraction at rest (less
than or equal to 35%) determined by biplane angiography who
were evaluated between 1970 and 1977. Seventy-seven patients
had coronary artery bypass grafting and 115 patients were
treated medically and were considered surgical candidates. The
medical and surgical groups were comparable in all baseline
characteristics examined except frequency of three vessel
disease and angina pectoris, which occurred in a significantly
greater percent of the surgically treated patients (p less
than 0.01). Only three medically treated patients (2.6%)
underwent coronary bypass grafting in the follow-up period.
Seven year actuarial survival was 63% in the surgical and 34%
in the medical group (p less than 0.001). Ninety-three percent
of patients in the surgical group and 81% of those in the
medical group were free of nonfatal myocardial infarction (p =
0.01), and 62 and 33%, respectively, were alive and free of
myocardial infarction (p less than 0.001) at 7 years.
Significant differences in survival favoring surgical
treatment were observed for the subsets of patients with an
ejection fraction of 25% or less (p = 0.0002) and 26 to 35% (p
= 0.01), and for the subsets with three vessel coronary
disease (p less than 0.001), normal left ventricular
end-diastolic volume (less than or equal to 100 ml/m2) (p =
0.005) and elevated end-diastolic volume (greater than 100
ml/m2)(p = 0.001). After adjustment for other important
prognostic variables, the type of treatment remained
significant in predicting the relative risk (medical to
surgical) of mortality at 5 and 7 years (2.58 and 2.12,
respectively). These data corroborate the trends observed in
several randomized trials of medical and surgical therapy in
patients with abnormal left ventricular function. If hospital
mortality for coronary artery bypass grafting is less than 5%,
substantial benefit can be anticipated for the majority of
patients with depressed ventricular function.
PMID: 3872896 [PubMed - indexed for MEDLINE]-
Comment in:
Preoperative positron emission tomographic
viability assessment and perioperative and postoperative risk
in patients with advanced ischemic heart disease.
Haas F, Haehnel CJ, Picker W, Nekolla S, Martinoff S,
Meisner H, Schwaiger M.
Department of Cardiovascular Surgery, Deutsches Herzzentrum
Munchen, Munich, Germany.
OBJECTIVES: This study sought to investigate whether
determination of tissue viability by means of positron
emission tomography (PET) before coronary artery bypass graft
surgery (CABG) affects clinical outcome with respect to both
in-hospital mortality and 1-year survival rate. BACKGROUND:
Patients with coronary artery disease (CAD) and severe left
ventricular (LV) dysfunction are at higher risk for
perioperative complications associated with CABG. Therefore,
the selection of patients who will benefit from CABG is an
important clinical issue. METHODS: This study retrospectively
evaluated 76 patients with advanced CAD and LV dysfunction (LV
ejection fraction < or = 0.35) who were considered
candidates for CABG. Thirty-five patients were selected for
CABG on the basis of clinical presentation and angiographic
data (group A), and 34 of 41 patients were selected according
to extent of viable tissue determined by PET (group B) in
addition to clinical presentation and angiographic data.
RESULTS: There were four in-hospital deaths (11.4%) in group A
and none in group B (p = 0.04). After 12 months, the survival
rate was 79% in group A and 97% in group B (p = 0.01).
Postoperatively, group B patients had a less complicated
recovery (p = 0.05). They required lower doses of
catecholamines (p = 0.002) and demonstrated a significantly
decreased incidence of low output syndrome (p = 0.05).
CONCLUSIONS: This retrospective data analysis suggests that
selection of patients with impaired LV function on the basis
of extent of viability supplementary to clinical and
angiographic data may lead to postoperative recovery with a
low early mortality and promising short-term survival.
Therefore, viability studies permit selection of patients who
are at low risk for serious perioperative complications.
PMID: 9385895 [PubMed - indexed for MEDLINE]
8. Opie L. Fuels: aerobic and anerobic metabolism. In: Opie L,
ed. The Heart. Physiology, from cell to circulation. Philadelphia,
PA: Lippincott-Raven, 1998; 295.
Relative rates of oxidation of glucose and
free fatty acids by ischaemic and non-ischaemic myocardium
after coronary artery ligation in the dog.
Opie LH, Owen P, Riemersma RA.
PMID: 4772338 [PubMed - indexed for MEDLINE]-
Effect of coronary blood flow on glycolytic
flux and intracellular pH in isolated rat hearts.
Neely JR, Whitmer JT, Rovetto MJ.
The rate of coronary blood flow was varied in isolated working
rat heart preparations to determine its influence on the rate
of glocose utilization, tissue high-energy phosphates, and
intracellular pH. A 60% reduction in coronary blood flow
resulted in a 30% reduction in oxygen consumption, an
accelerated rate of glusoe utilization, lower tissue levels of
high-energy phosphate, and higher tissue levels of lactate and
H+. Ventricular performance deteriorated as reflected by a
decrease in heart rate and peak systolic pressure. Further
reductions in coronary blood flow resulted in inhibition of
glycolysis, a greater decrease in tissue levels of high-energy
phosphates, and higher tissue levels of both lactate and H+.
These changes in glycolytic flux, tissue metabolites, and
ventricular performance were proportional to the degree of
restriction in coronary blood flow. The importance of coronary
blood flow and washout of the interstitial space in the
maintenance of accelerated glycolytic flux in oxygen-deficient
hearts is emphasized. It is concluded that acceleration of ATP
production from glycolysis can occur only in the marginally
ischemic tissue in the peripheral area of tissue supplied by
an occluded artery. The central area of tissue which receives
a low rate of coronary blood flow will have a reduced rate of
ATP production due to both a lack of oxygen and an inhibition
of glycolysis.
PMID: 156 [PubMed - indexed for MEDLINE]-
Reversibility of cardiac wall-motion
abnormalities predicted by positron tomography.
Tillisch J, Brunken R, Marshall R, Schwaiger M, Mandelkern
M, Phelps M, Schelbert H.
Positron emission tomography (PET) can be used with
nitrogen-13-ammonia (13NH3) to estimate regional myocardial
blood flow, and with fluorine-18-deoxyglucose (18FDG) to
measure exogenous glucose uptake by the myocardium. We used
PET to predict whether preoperative abnormalities in left
ventricular wall motion in 17 patients who underwent
coronary-artery bypass surgery were reversible. The
abnormalities were quantified by radionuclide or contrast
angiography or both, before and after grafting. PET images
were obtained preoperatively. Abnormal wall motion in regions
in which PET images showed preserved glucose uptake was
predicted to be reversible, whereas abnormal motion in regions
with depressed glucose uptake was predicted to be irreversible.
According to these criteria, abnormal contraction in 35 of 41
segments was correctly predicted to be reversible (85 percent
predictive accuracy), and abnormal contraction in 4 of 26
regions was correctly predicted to be irreversible (92 percent
predictive accuracy). In contrast, electrocardiograms showing
pathological Q waves in the region of asynergy predicted
irreversibility in only 43 percent of regions. We conclude
that PET imaging with 13NH3 to assess blood flow and 18FDG to
assess the metabolic viability of the myocardium is an
accurate method of predicting potential reversibility of
wall-motion abnormalities after surgical revascularization.
PMID: 3485252 [PubMed - indexed for MEDLINE]-
Regional myocardial metabolism in patients
with acute myocardial infarction assessed by positron emission
tomography.
Schwaiger M, Brunken R, Grover-McKay M, Krivokapich J,
Child J, Tillisch JH, Phelps ME, Schelbert HR.
Positron emission tomography has been shown to distinguish
between reversible and irreversible ischemic tissue injury.
Using this technique, 13 patients with acute myocardial
infarction were studied within 72 hours of onset of symptoms
to evaluate regional blood flow and glucose metabolism with
nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose,
respectively. Serial noninvasive assessment of wall motion was
performed to determine the prognostic value of metabolic
indexes for functional tissue recovery. Segmental blood flow
and glucose utilization were evaluated using a circumferential
profile technique and compared with previously established
semiquantitative criteria. Relative N-13 ammonia uptake was
depressed in 32 left ventricular segments. Sixteen segments
demonstrated a concordant decrease in flow and glucose
metabolism. Regional function did not change over time in
these segments. In contrast, 16 other segments with reduced
blood flow revealed maintained F-18 deoxyglucose uptake
consistent with remaining viable tissue. The average wall
motion score improved significantly in these segments (p less
than 0.01), yet the degree of recovery varied considerably
among patients. Coronary anatomy was defined in 9 of 13
patients: patent infarct vessels supplied 8 of 10 segments
with F-18 deoxyglucose uptake, while 10 of 13 segments in the
territory of an occluded vessel showed concordant decreases in
flow and metabolism (p less than 0.01). Thus, positron
emission tomography reveals a high incidence of residual
tissue viability in ventricular segments with reduced flow and
impaired function during the subacute phase of myocardial
infarction. Absence of residual tissue metabolism is
associated with irreversible injury, while preservation of
metabolic activity identifies segments with a variable outcome.(ABSTRACT
TRUNCATED AT 250 WORDS)
PMID: 3489746 [PubMed - indexed for MEDLINE]-
Comment in:
Euglycemic hyperinsulinemic clamp and oral
glucose load in stimulating myocardial glucose utilization
during positron emission tomography.
Knuuti MJ, Nuutila P, Ruotsalainen U, Saraste M, Harkonen R,
Ahonen A, Teras M, Haaparanta M, Wegelius U, Haapanen A, et
al.
Department of Clinical Physiology, University of Turku,
Finland.
To enable assessment of myocardial viability, myocardial
glucose utilization has commonly been stimulated by oral
glucose loading. To compare the effects of glucose loading and
insulin and glucose infusion (insulin clamp) on PET
fluorodeoxyglucose ([18F]FDG) myocardial scan image quality
and regional myocardial glucose utilization rate (rMGU), eight
patients with angiographically documented coronary artery
disease and previous myocardial Q-wave infarction were studied
twice, once during insulin clamp and once 1 hr after oral
glucose loading. The rMGU rates were derived by graphic Patlak
analysis in 33 normal, 10 scar and 6 "hot spot"
myocardial segments. Infusion of insulin and glucose gave
stable plasma-glucose and serum-insulin levels during imaging.
In contrast, glucose loading caused marked changes in
plasma-glucose and insulin concentrations. The image quality
was clearly superior and the fractional utilization rates of
[18F]FDG were twice as high during insulin clamp than after
glucose loading (p less than 0.0001). Due to the higher
plasma-glucose levels after glucose loading, the calculated
rMGU in normal, scar and hot spot myocardial segments was
comparable between the two protocols. The insulin clamp
technique makes it possible to adjust and maintain a metabolic
steady state during the PET study. It does not alter [18F]FDG
uptake patterns in different myocardial areas when compared to
the standard glucose loading protocol, but this technique
results in superior image quality and permits the use of
smaller [18F] FDG patient doses.
PMID: 1613561 [PubMed - indexed for MEDLINE]-
Enhancement of myocardial [fluorine-18]fluorodeoxyglucose
uptake by a nicotinic acid derivative.
Knuuti MJ, Yki-Jarvinen H, Voipio-Pulkki LM, Maki M,
Ruotsalainen U, Harkonen R, Teras M, Haaparanta M, Bergman J,
Hartiala J, et al.
Turku Cyclotron-PET Center, Finland.
Recently, the euglycemic hyperinsulinemic clamp technique was
shown to give excellent image quality during metabolic
steady-state conditions. Acipimox is a new potent nicotinic
acid derivative that rapidly reduces serum free fatty acid (FFA)
levels by inhibiting lipolysis in peripheral tissue. METHODS:
To compare the effects of acipimox administration and insulin
clamp on [18F]fluorodeoxyglucose ([18F]FDG) uptake and
myocardial glucose utilization, five nondiabetic and seven
type II diabetic patients who had had previous myocardial
infarctions were studied twice: once during a clamp study and
once after the administration of acipimox (2 x 250 mg orally).
All patients also underwent resting SPECT perfusion imaging
prior to PET scans. RESULTS: The patients tolerated acipimox
well. Although fasting plasma glucose levels were higher in
diabetic patients (9.2 +/- 3.4 versus 5.5 +/- 0.3 mM, p =
0.03), they were decreased both during clamping and after
acipimox; during imaging, no significant differences between
the groups and approaches were detected. By visual analysis,
the image quality and myocardial [18F]FDG uptake patterns were
similar during clamping and after acipimox. Compared with the
relative [18F]FDG uptake values obtained during clamping,
acipimox yielded similar results in normal, mismatch and scar
segments (r = 0.88, p = 0.0001). Similar rMGU values were also
obtained during both approaches. CONCLUSION: Thus, PET imaging
with [18F]FDG after the administration of acipimox is a simple
and feasible method for clinical viability studies both in
nondiabetic and diabetic patients. It results in excellent
image quality and gives rMGU levels similar to the insulin
clamp technique.
PMID: 8195886 [PubMed - indexed for MEDLINE]-
-
Accuracy of currently available techniques
for prediction of functional recovery after revascularization
in patients with left ventricular dysfunction due to chronic
coronary artery disease: comparison of pooled data.
Bax JJ, Wijns W, Cornel JH, Visser FC, Boersma E, Fioretti
PM.
Department of Cardiology, Academic Hospital, Leiden, The
Netherlands. bax@cardio.azl.nl
OBJECTIVES: This study evaluated the relative merits of the
most frequently used techniques for predicting improvement in
regional contractile function after coronary revascularization
in patients with left ventricular dysfunction due to chronic
coronary artery disease. BACKGROUND: Several techniques have
been proposed for predicting improvement in regional
contractile function after revascularization, including
thallium-201 (Tl-201) stress-redistribution-reinjection,
Tl-201 rest-redistribution, fluorine-18 fluorodeoxyglucose
with positron emission tomography, technetium-99m sestamibi
imaging and low dose dobutamine echocardiography (LDDE).
METHODS: A systematic review of all reports on prediction of
functional recovery after revascularization in patients with
chronic coronary artery disease (published between 1980 and
March 1997) revealed 37 with sufficient details for
calculating the sensitivity and specificity of each imaging
modality. From the pooled data, 95% and 99% confidence
intervals were also calculated. RESULTS: Sensitivity for
predicting regional functional recovery after
revascularization was high for all techniques. The specificity
of both Tl-201 protocols was significantly lower (p < 0.05)
and LDDE significantly higher (p < 0.01) than that of the
other techniques. CONCLUSIONS: Pooled analysis of 37 studies
showed that although all techniques accurately identify
segments with improved contractile function after
revascularization, the Tl-201 protocols may overestimate
functional recovery. The evidence available thus far indicates
that LDDE appears to have the highest predictive accuracy.
Publication Types:
PMID: 9362401 [PubMed - indexed for MEDLINE]
-
Functional recovery after coronary
revascularization for chronic coronary artery disease is
dependent on maintenance of oxidative metabolism.
Gropler RJ, Geltman EM, Sampathkumaran K, Perez JE,
Moerlein SM, Sobel BE, Bergmann SR, Siegel BA.
Division of Nuclear Medicine, Edward Mallinckrodt Institute of
Radiology, Saint Louis, Missouri 63110.
OBJECTIVES. This study was performed to define the importance
of maintenance of oxidative metabolism as a descriptor and
determinant of functional recovery after revascularization in
patients with left ventricular dysfunction attributable to
chronic coronary artery disease. BACKGROUND. Although
myocardial accumulation of 18F-fluorodeoxyglucose indicates
the presence of tissue that is metabolically active, it may
not identify those metabolic processes required for
restoration of myocardial contractility. Experimental studies
suggest that, under conditions of ischemia and reperfusion,
maintenance of myocardial oxidative metabolism is an important
metabolic determinant of the capacity for functional recovery.
METHODS. In 16 patients positron emission tomography was
performed to characterize myocardial perfusion (with H(2)15O),
oxidative metabolism (with 11C-acetate) and utilization of
glucose (with 18F-fluorodeoxyglucose). Dysfunctional but
viable myocardium was differentiated from nonviable myocardium
on the basis of assessments of regional function before and
after coronary revascularization. To define the importance of
coronary revascularization on myocardial perfusion and
metabolism, tomography was repeated in 11 patients after
revascularization. RESULTS. Before revascularization,
perfusion in 24 dysfunctional but viable myocardial segments
and 29 nonviable segments averaged 79% and 74%, respectively,
of that in 42 normal myocardial segments (both p less than
0.01). Dysfunctional but viable myocardium exhibited oxidative
metabolism comparable to that in normal myocardium. In
contrast, in nonviable myocardium, oxidative metabolism was
only 66% of that in normal (p less than 0.01) and 69% of that
in reversibly dysfunctional myocardium (p less than 0.003).
Regional utilization of glucose normalized to regional
perfusion in dysfunctional but viable myocardium was greater
than that in normal myocardium (p less than 0.01). However, in
both reversibly and persistently dysfunctional myocardium,
utilization of glucose normalized to relative perfusion was
markedly variable. CONCLUSIONS. The results indicate that
preservation of oxidative metabolism is a necessary condition
for recovery of function after coronary recanalization in
patients with chronic coronary artery disease. Consequently,
approaches that measure myocardial oxygen consumption, such as
dynamic positron emission tomography with 11C-acetate, should
facilitate the identification of those patients most likely to
benefit from coronary revascularization.
PMID: 1512335 [PubMed - indexed for MEDLINE]-
Functional recovery after coronary
revascularization for chronic coronary artery disease is
dependent on maintenance of oxidative metabolism.
Gropler RJ, Geltman EM, Sampathkumaran K, Perez JE,
Moerlein SM, Sobel BE, Bergmann SR, Siegel BA.
Division of Nuclear Medicine, Edward Mallinckrodt Institute of
Radiology, Saint Louis, Missouri 63110.
OBJECTIVES. This study was performed to define the importance
of maintenance of oxidative metabolism as a descriptor and
determinant of functional recovery after revascularization in
patients with left ventricular dysfunction attributable to
chronic coronary artery disease. BACKGROUND. Although
myocardial accumulation of 18F-fluorodeoxyglucose indicates
the presence of tissue that is metabolically active, it may
not identify those metabolic processes required for
restoration of myocardial contractility. Experimental studies
suggest that, under conditions of ischemia and reperfusion,
maintenance of myocardial oxidative metabolism is an important
metabolic determinant of the capacity for functional recovery.
METHODS. In 16 patients positron emission tomography was
performed to characterize myocardial perfusion (with H(2)15O),
oxidative metabolism (with 11C-acetate) and utilization of
glucose (with 18F-fluorodeoxyglucose). Dysfunctional but
viable myocardium was differentiated from nonviable myocardium
on the basis of assessments of regional function before and
after coronary revascularization. To define the importance of
coronary revascularization on myocardial perfusion and
metabolism, tomography was repeated in 11 patients after
revascularization. RESULTS. Before revascularization,
perfusion in 24 dysfunctional but viable myocardial segments
and 29 nonviable segments averaged 79% and 74%, respectively,
of that in 42 normal myocardial segments (both p less than
0.01). Dysfunctional but viable myocardium exhibited oxidative
metabolism comparable to that in normal myocardium. In
contrast, in nonviable myocardium, oxidative metabolism was
only 66% of that in normal (p less than 0.01) and 69% of that
in reversibly dysfunctional myocardium (p less than 0.003).
Regional utilization of glucose normalized to regional
perfusion in dysfunctional but viable myocardium was greater
than that in normal myocardium (p less than 0.01). However, in
both reversibly and persistently dysfunctional myocardium,
utilization of glucose normalized to relative perfusion was
markedly variable. CONCLUSIONS. The results indicate that
preservation of oxidative metabolism is a necessary condition
for recovery of function after coronary recanalization in
patients with chronic coronary artery disease. Consequently,
approaches that measure myocardial oxygen consumption, such as
dynamic positron emission tomography with 11C-acetate, should
facilitate the identification of those patients most likely to
benefit from coronary revascularization.
PMID: 1512335 [PubMed - indexed for MEDLINE]-
The interrelationship between thallium and
potassium in animals.
Gehring PJ, Hammond PB.
PMID: 6017338 [PubMed - indexed for MEDLINE]-
The extraction of thallium-201 by the
myocardium.
Weich HF, Strauss HW, Pitt B.
The concentration of thallium-201 in the myocardium
immediately following injection of tracer is the result of
both blood flow delivering tracer to the heart and extraction
by the myocardium. In these studies, the extraction of
thallium-201 by the canine myocardium was determined as a
function of heart rate, coronary blood flow, hypoxia, changes
in pH, and following administration of propranolol, insulin,
and strophanthin. Under basal conditions, extraction fraction
measured 88 +/- 2.1%, following pacing to a rate of 195
beats/min extraction fraction remained unchanged at 88.5%.
Similar results were found with changes in pH, propranolol,
insulin, and strophanthin. Hypoxia caused a significant
decrease in extraction fraction to 77.9%. When coronary blood
flow was increased in excess of demands by drugs, extraction
fraction fell logarithmically.
PMID: 872309 [PubMed - indexed for MEDLINE]-
Thallium redistribution in dogs with severe
coronary artery stenosis of fixed caliber.
Pohost GM, Okada RD, O'Keefe DD, Gewirtz H, Beller G,
Strauss HW, Chaffin JS, Leppo J, Daggett WM.
PMID: 7460217 [PubMed - indexed for MEDLINE]-
Differentiation of transiently ischemic
from infarcted myocardium by serial imaging after a single
dose of thallium-201.
Pohost GM, Zir LM, Moore RH, McKusick KA, Guiney TE, Beller
GA.
Myocardial 201Tl uptake and regional blood flow by the
microsphere technique were determined in anesthetized dogs
undergoing either 20 min of coronary occlusion and 100 min of
reperfusion (N = 10) or 120 min of occlusion (N = 4). In both
groups, 201Tl was injected intravenously after 10 min of
occlusion. In transiently occluded dogs, regional flow at the
time of 201Tl administration was reduced to 8 +/- 3% of normal
flow in endocardial layers of the central ischemic zone. After
100 min of reperfusion, flow values were not significantly
different from normal. 201Tl activity after reperfusion rose
to 56 +/- 5% of normal, demonstrating that redistribution of
the radionuclide occurred during the reflow period. In animals
with persistent occlusion, there was a significant
relationship between 201Tl uptake and flow (r = 0.95) and no
evidence of redistribution of 201Tl during the two hour
occlusion period. In another five dogs receiving 201Tl, serial
gamma camera images obtained during reperfusion showed
increasing uptake of the tracer in apical defects which
returned to normal by 4 hours of reflow. Thirteen patients
with stable angina received 2 mCi of 201Tl intravenously at
peak exercise, and multiple gamma camera images obtained
serially. All demonstrated zones of diminished 201Tl uptake 10
min after exercise. Defects which partially or completely
disappeared within 1-6 hours postexercise corresponded to
areas supplied by coronary arteries with significant stenoses.
Persistent defects were present in regions of old myocardial
infarction. Six additional patients with acute myocardial
infarction demonstrated 201Tl myocardial defects which showed
no significant change over 6 hours. Thus, redistribution of
201Tl into ischemic myocardium was demonstrated during
transient coronary occlusion in dogs and after exercise stress
in man. Sequential imaging after a single dose of 201Tl at the
time of exercise may provide a means for distinguishing
between transient perfusion abnormalities or ischemia and
myocardial infarction of scar.
PMID: 832345 [PubMed - indexed for MEDLINE-
Time course of thallium-201 redistribution
after transient myocardial ischemia.
Beller GA, Watson DD, Ackell P, Pohost GM.
PMID: 7357722 [PubMed - indexed for MEDLINE]-
Late reversibility of tomographic
myocardial thallium-201 defects: an accurate marker of
myocardial viability.
Kiat H, Berman DS, Maddahi J, De Yang L, Van Train K,
Rozanski A, Friedman J.
Department of Medicine (Division of Cardiology), Cedars-Sinai
Medical Center, Los Angeles, California 90048.
Twenty-one patients were studied who underwent thallium-201
stress-redistribution single photon emission computed
tomography (SPECT) both before and after coronary artery
bypass grafting (n = 15) or transluminal coronary angioplasty
(n = 6). All patients underwent thallium imaging 15 min, 4 h
and late (18 to 72 h) after stress as part of the
preintervention thallium-201 scintigram. In a total of 201
tomographic myocardial segments with definite post-stress
thallium-201 perfusion defects in which the relevant coronary
arteries were subsequently successfully reperfused, the 4 h
redistribution images did not predict the postintervention
scintigraphic improvement: 67 (85%) of the 79 4 h reversible
as well as 88 (72%) of the 122 4 h nonreversible segments
improved (p = NS). The 18 to 72 h late redistribution images
effectively subcategorized the 4 h nonreversible segments with
respect to postintervention scintigraphic improvement: 70
(95%) of the 74 late reversible segments improved after
intervention, whereas only 18 (37%) of the 48 late
nonreversible segments improved (p less than 0.0001). The
frequency of late reversible defects and the frequency of
postrevascularization improvement of late nonreversible
defects are probably overestimated by this study because of
referral biases. The cardiac counts and target to background
ratios from late redistribution studies resulted in
satisfactory cardiac images for visual interpretation. For
optimal assessment of the extent of viable myocardium by
thallium-201 scintigraphic studies, late redistribution
imaging should be performed when nonreversible defects are
observed on 4 h redistribution images.
PMID: 3263995 [PubMed - indexed for MEDLINE]-
Comment in:
Enhanced detection of ischemic but viable
myocardium by the reinjection of thallium after
stress-redistribution imaging.
Dilsizian V, Rocco TP, Freedman NM, Leon MB, Bonow RO.
Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, Md 20892.
BACKGROUND. The identification of ischemic but viable
myocardium by thallium exercise scintigraphy is often
imprecise, since many of the perfusion defects that develop in
ischemic myocardium during exercise do not "fill in"
on subsequent redistribution images. We hypothesized that a
second injection of thallium given after the redistribution
images were taken might improve the detection of ischemic but
viable myocardium. METHODS. We studied 100 patients with
coronary artery disease, using thallium exercise tomographic
imaging and radionuclide angiography. Patients received 2 mCi
of thallium intravenously during exercise, redistribution
imaging was performed three to four hours later, and a second
dose of 1 mCi of thallium was injected at rest immediately
thereafter. The three sets of images (stress, redistribution,
and reinjection) were then analyzed. RESULTS. Ninety-two of
the 100 patients had exercise-induced perfusion defects. Of
the 260 abnormal myocardial regions identified by stress
imaging, 85 (33 percent) appeared to be irreversible on
redistribution imaging three to four hours later. However, 42
of these apparently irreversible defects (49 percent)
demonstrated improved or normal thallium uptake after the
second injection of thallium, with an increase in mean
regional uptake from 56 +/- 12 percent on redistribution
studies to 64 +/- 10 percent on reinjection imaging (P less
than 0.001). Twenty patients were restudied three to six
months after coronary angioplasty. Of the 15 myocardial
regions with defects on redistribution studies that were
identified as viable by reinjection studies before angioplasty,
13 (87 percent) had normal thallium uptake and improved
regional wall motion after angioplasty. In contrast, all eight
regions with persistent defects on reinjection imaging before
angioplasty had abnormal thallium uptake and abnormal regional
wall motion after angioplasty. CONCLUSIONS. These data
indicate that the reinjection of thallium improves the
detection of ischemic myocardium and that myocardial regions
with improved thallium uptake on reinjection imaging represent
viable but jeopardized myocardium.
PMID: 2362606 [PubMed - indexed for MEDLINE]-
Quantification of area at risk during
coronary occlusion and degree of myocardial salvage after
reperfusion with technetium-99m methoxyisobutyl isonitrile.
Sinusas AJ, Trautman KA, Bergin JD, Watson DD, Ruiz M,
Smith WH, Beller GA.
Department of Internal Medicine, University of Virginia Health
Sciences Center, Charlottesville 22908.
Serial myocardial imaging with technetium-99m methoxyisobutyl
isonitrile (99mTc-MIBI) has been proposed for evaluating
myocardial salvage after reperfusion. To define 99mTc-MIBI
uptake before and after reperfusion, 17 open-chest dogs
underwent 3 hours of left anterior descending artery occlusion
and 3 hours of reperfusion. 99mTc-MIBI was injected during
occlusion (group 1) or after 90 minutes of reperfusion (group
2). Myocardial 99mTc-MIBI activity was correlated with
microsphere flow during occlusion and reperfusion. Anatomic
risk area and infarct area were defined by postmortem vital
staining and correlated with the perfusion defects defined by
analysis of 99mTc-MIBI macroautoradiographs and gamma camera
images of myocardial slices. The left ventricle was divided
into 96 segments for gamma well counting. Flow and 99mTc-MIBI
activity were normalized to nonischemic values. Myocardial
segments were grouped, based on occlusion flow, into zones:
severely ischemic (less than or equal to 30% nonischemic),
moderately ischemic (greater than 30%, less than or equal to
60% nonischemic), mildly ischemic (greater than 60%, less than
or equal to 90% nonischemic), and nonischemic (greater than
90%, less than or equal to 120% nonischemic). Among dogs
injected with 99mTc-MIBI during coronary occlusion (group 1),
myocardial 99mTc-MIBI activity correlated linearly with
occlusion flow for both endocardial (r = 0.91) and transmural
(r = 0.91) segments. The risk area defined by 99mTc-MIBI
autoradiography (group 1) correlated with the postmortem risk
area (rho = 0.94) but was 29% smaller than the anatomic risk
area (p = 0.03), reflecting the contribution of collateral
flow. Among dogs injected with 99mTc-MIBI after reperfusion (group
2), myocardial 99mTc-MIBI did not correlate with reperfusion
flow in either endocardial or transmural segments. Among group
2 dogs, myocardial 99mTc-MIBI activity was significantly less
than reperfusion flow at the time of injection in the severely
ischemic (25 +/- 5% versus 74 +/- 24% nonischemic, p = 0.002),
moderately ischemic (54 +/- 12% versus 96 +/- 15% nonischemic,
p = 0.001), and mildly ischemic (84 +/- 6% versus 93 +/- 3%
nonischemic, p = 0.002) zones. The defect area defined by
99mTc-MIBI autoradiography (group 2) correlated very closely
with the postmortem infarct area (rho = 0.98). Thus, the
myocardial uptake of 99mTc-MIBI during coronary occlusion
correlates with occlusion flow and reflects the "area at
risk." When 99mTc-MIBI was given after 90 minutes of
reperfusion following 3 hours of coronary occlusion, the
myocardial activity was significantly reduced compared with
reperfusion flow in both necrotic and perinecrotic regions,
reflecting myocardial viability more than the degree of
reperfusion.
PMID: 2401074 [PubMed - indexed for MEDLINE]-
Uptake and retention of hexakis
(2-methoxyisobutyl isonitrile) technetium(I) in cultured chick
myocardial cells. Mitochondrial and plasma membrane potential
dependence.
Piwnica-Worms D, Kronauge JF, Chiu ML.
Department of Radiology, Harvard Medical School, Brigham and
Women's Hospital, Boston, MA 02115.
The fundamental myocellular uptake and retention mechanisms of
hexakis (2-methoxyisobutyl isonitrile) technetium(I) (Tc-MIBI),
a technetium-99m-based myocardial perfusion imaging agent, are
unresolved. Because of the lipophilic cationic nature of
Tc-MIBI, it may be distributed across biological membranes in
response to transmembrane potential. To test this hypothesis,
net uptake and retention of Tc-MIBI in cultured chick embryo
ventricular myocytes were determined under conditions known to
alter mitochondrial and plasma membrane potentials. Isovolumic
depolarization of plasma membrane potentials in 130 mM
extracellular K (Ko) 20 mM extracellular Cl buffer reduced net
accumulation of Tc-MIBI from 171 +/- 16 (control) to 29 +/-
3.3 fmol intracellular Tc-MIBI/mg protein.nM extracellular
Tc-MIBI. Unidirectional influx of Tc-MIBI in cells depolarized
in 30 mM Ko buffer was also reduced; a resting plasma membrane
potential of -87 +/- 6 mV was calculated from the Goldman flux
equation using normal Ko/high Ko Tc-MIBI influx ratios.
Addition of the potassium ionophore valinomycin to cells
incubated in 130 mM Ko buffer to additionally depolarize
mitochondrial membrane potentials further reduced net uptake
of Tc-MIBI to levels comparable to that found in nonviable
freeze-thawed preparations ([Tc-MIBI]i/[Tc-MIBI]o = 1). By
depolarizing mitochondrial (and in part plasma membrane)
potentials with the protonophores 2,4-dinitrophenol and
carbonyl cyanide m-chlorophenylhydrazone (CCCP) Tc-MIBI was
rapidly depleted from 181 +/- 16 (control) to 16 +/- 2.6 and
31 +/- 4.2 fmol/mg protein.nMo, respectively, with kinetics
that did not correlate with loss of cellular ATP content. CCCP
alone inhibited 90 +/- 3% of net accumulation or 66 +/- 3% of
unidirectional influx of Tc-MIBI in a concentration-dependent
manner. By hyperpolarizing mitochondrial membrane potentials
with the K+/H+ ionophore nigericin or the ATP synthase
inhibitor oligomycin, net uptake and retention of Tc-MIBI were
increased by 60 +/- 9% and 375 +/- 20%, respectively. Caffeine,
as well as the respiratory chain electron transport inhibitor
rotenone, did not significantly alter net cell uptake (p
greater than 0.2). These data indicate that the fundamental
myocellular uptake mechanism of Tc-MIBI involves passive
distribution across plasma and mitochondrial membranes and
that at equilibrium Tc-MIBI is sequestered within mitochondria
by the large negative transmembrane potentials.
PMID: 2225379 [PubMed - indexed for MEDLINE]-
Effect of mitochondrial and plasma membrane
potentials on accumulation of hexakis
(2-methoxyisobutylisonitrile) technetium(I) in cultured mouse
fibroblasts.
Chiu ML, Kronauge JF, Piwnica-Worms D.
Department of Radiology, Brigham and Women's Hospital, Harvard
Medical School, Boston, Massachusetts.
Hexakis(2-methoxyisobutylisonitrile) technetium(I) (Tc-MIBI)
is representative of a class of 99mTc-based lipophilic
cationic myocardial perfusion imaging agents. To test the
hypothesis that the mechanism of cellular uptake may involve
distribution across biologic membranes in response to membrane
potential, Tc-MIBI net uptake and retention were determined in
cultured mouse BALB/c 3T3, NIH 3T3, and v-src transformed NIH
3T3 fibroblasts as well as in cultured chick embryo heart
cells. Isovolumic depolarization of plasma membrane potentials
with 130 mM K 20 mM Cl buffer decreased Tc-MIBI net cell
uptake in all preparations. In BALB/c 3T3 cells, depolarizing
mitochondrial membrane potential with valinomycin in high K
buffer or with the protonophore CCCP inhibited net uptake and
retention of Tc-MIBI while hyperpolarizing mitochondrial and
plasma membrane potentials with the K+/H+ exchanger nigericin
increased Tc-MIBI net uptake. These results indicated that net
cellular uptake and retention of Tc-MIBI in fibroblasts were
determined by both mitochondrial and plasma membrane
potentials; the gamma-emitting properties of Tc-MIBI may
therefore raise the possibility of monitoring membrane
potential in vivo.
PMID: 2213187 [PubMed - indexed for MEDLINE]-
Rest technetium-99m sestamibi tomography in
combination with short-term administration of nitrates:
feasibility and reliability for prediction of
postrevascularization outcome of asynergic territories.
Bisi G, Sciagra R, Santoro GM, Fazzini PF.
Department of Clinical Pathophysiology, University of
Florence, Italy.
OBJECTIVES. This study investigated the role of nitrate
technetium-99m sestamibi imaging in predicting the
postrevascularization outcome of chronically hypoperfused
asynergic territories. BACKGROUND. Rest technetium-99m
sestamibi myocardial scintigraphy underestimates the presence
of viable myocardium in asynergic territories. Stimulation
that improves coronary blood flow could increase tracer uptake
in hibernating territories. METHODS. Nineteen patients with a
previous myocardial infarction and left ventricular
dysfunction scheduled for revascularization underwent
quantitative technetium-99m sestamibi tomography under
baseline conditions and during isosorbide dinitrate infusion.
Global and regional function were assessed, respectively,
before and after revascularization by radionuclide
angiocardiography and two-dimensional echocardiography.
RESULTS. Seven patients (group A) showed postrevascularization
regional function recovery, and 12 (group B) showed no
significant changes. In group A, nitrate infusion induced a
decrease in the extent of the global uptake defect ([mean +/-
SD] -37.4 +/- 21.6% of baseline value); in group B, no change
or a slight increase was observed (+5.8 +/- 8.4%, p <
0.0005 vs. group A). The nitrate-induced changes in the extent
of uptake defect correlated with postrevascularization changes
in ejection fraction (r = -0.94, SEE 7.6). After
revascularization, 11 asynergic vascular territories showed
improvement (hibernating), and 34 remained unchanged (fibrotic).
With administration of nitrates, 10 hibernating territories
had a decrease in the extent of uptake defect, whereas only 4
of 34 of the fibrotic territories showed a nitrate-induced
uptake improvement. CONCLUSIONS. Short-term administration of
isosorbide dinitrate immediately before injection of
technetium-99m sestamibi increases tracer uptake in some
chronically hypoperfused asynergic territories. This finding
correlates with the observation of post-revascularization
functional recovery. Nitrate technetium-99m sestamibi
myocardial scintigraphy could be a promising method for the
noninvasive detection of viable hibernating myocardium.
Publication Types:
- Clinical Trial
- Controlled Clinical Trial
PMID: 7930251 [PubMed - indexed for MEDLINE]-
Enhanced detection of viable myocardium by
technetium-99m-MIBI imaging after nitrate administration in
chronic coronary artery disease.
Maurea S, Cuocolo A, Soricelli A, Castelli L, Nappi A,
Squame F, Imbriaco M, Trimarco B, Salvatore M.
Nuclear Medicine Department, University Federico II, Naples,
Italy.
The aim of this study was to assess whether nitrate
administration improves the imaging capabilities of 99mTc-MIBI
tomography in detecting viable myocardium in coronary artery
disease (CAD). METHODS: Thirty-one patients with
angiographically proven CAD and chronic LV dysfunction (ejection
fraction 39% +/- 9%) underwent two 99mTc-MIBI studies on
separate days: one under rest conditions and the other after
nitroglycerine (0.005 mg/kg per os) administration. Within 1
wk, all patients also underwent rest-redistribution 201Tl
imaging. Eight patients were also studied by echocardiography
before and 5 +/- 3 mo after coronary revascularization.
RESULTS: On resting 99mTc-MIBI images, 302 segments had normal
uptake, 183 segments had moderately reduced uptake and 197 had
severely reduced uptake. Of the segments with severely reduced
uptake, 54 (27%) had increased uptake after nitroglycerine and
were viable on 201Tl images. Of the 143 (73%) segments with
severely reduced 99mTc-MIBI uptake and no change after
nitroglycerine, 81% were nonviable on 201Tl images. In the
eight patients studied before and after revascularization, 87%
of segments with reversible 99mTc-MIBI defects and abnormal LV
function demonstrated functional recovery after
revascularization, whereas 89% of segments with irreversible
99mTc-MIBI defects did not. CONCLUSION: In patients with
chronic ischemic LV dysfunction, nitrate administration
improved the detection of severely hypoperfused but still
viable myocardium on 99mTc-MIBI images.
PMID: 7472580 [PubMed - indexed for MEDLINE]-
Echocardiography for the assessment of
myocardial viability.
Lualdi JC, Douglas PS.
Charles A. Dana Research Institute, Beth Israel Deaconess
Medical Center, Boston, MA 02215, USA.
The identification of viable myocardium in the setting of
acute myocardial infarction or chronic coronary artery disease
with reduced left ventricular function has important
prognostic and therapeutic implications. Many noninvasive
methods have been used to assess viability, and recently,
dobutamine stress echocardiography has been studied for this
purpose. Dobutamine stress echocardiography is a safe,
accessible, and relatively inexpensive technique. Moreover,
its accuracy for detecting viability approaches that of
positron emission tomography and thallium scintigraphy. In
addition to dobutamine stress echocardiography, other
echocardiographic techniques, such as myocardial contrast
echocardiography and dipyridamole stress echocardiography, are
being developed to delineate viability. In the future,
echocardiographic methods may identify viability with enough
accuracy to allow us to better select patients for
revascularization procedures when the indications are
otherwise unclear.
Publication Types:
PMID: 9339433 [PubMed - indexed for MEDLINE]-
Comment in:
Dobutamine echocardiography in myocardial
hibernation. Optimal dose and accuracy in predicting recovery
of ventricular function after coronary angioplasty.
Afridi I, Kleiman NS, Raizner AE, Zoghbi WA.
Department of Medicine, Baylor College of Medicine, Methodist
Hospital, Houston, Tex. 77030.
BACKGROUND: Myocardial hibernation is a condition of chronic
left ventricular dysfunction associated with severe coronary
artery disease whereby significant recovery of function occurs
after revascularization. Identification of hibernating
myocardium has important prognostic and therapeutic
implications. The presence of contractile reserve as assessed
by dobutamine echocardiography may be promising in the
detection of hibernation. We designed a prospective study to
evaluate the accuracy and optimal dose of dobutamine
echocardiography for predicting recovery of ventricular
function after angioplasty in patients with stable coronary
artery disease and ventricular dysfunction. METHODS AND
RESULTS: Twenty patients with stable coronary artery disease
and segmental ventricular dysfunction scheduled for coronary
angioplasty underwent dobutamine echocardiography before
revascularization using incremental doses of 2.5, 5, 7.5, 10,
20, 30, and 40 micrograms/kg per minute every 3 minutes.
Digital images of all eight stages were displayed
simultaneously (two quad screens side by side) and interpreted
using a 16-segment ventricular model and a 6-grade scoring
system. Serial resting echocardiograms before, early (< 1
week), and late (> or = 6 weeks) after angioplasty were
digitized and randomized in a quad-screen format for the
assessment of recovery of function. Wall motion score index in
the revascularized regions decreased from 2.86 +/- 0.76 before
angioplasty to 2.12 +/- 1.03 late after angioplasty (P <
.05). Of 320 ventricular segments, 148 had abnormal wall
motion at baseline and 114 were revascularized. Recovery of
function (> or = 2 grades) occurred in 25% of
revascularized segments early and in 33% late after
angioplasty. Of the 34 abnormal segments not revascularized,
recovery of function occurred in only 1. During dobutamine
echocardiography, abnormal segments exhibited one of four
responses: biphasic (improvement at low dose and worsening at
high dose) in 28% of segments, sustained improvement
(persistent improvement till peak dose) in 18%, worsening in
15%, and no change in 39%. A biphasic response had the highest
predictive value (72%) for recovery of function followed by
worsening only (35%), while the lowest was seen with a "no-change"
or sustained improvement response (13% and 15%). Combining
biphasic and worsening responses resulted in a sensitivity of
74% and specificity of 73% for assessment of recovery of
individual segments and 90% and 60%, respectively, for
functional recovery of individual patients (n = 10). In
segments with a biphasic response, the low dose at which
improvement in wall motion was most prevalent (84%) was 7.5
micrograms/kg per minute and increased to 94% when the 5 and
7.5 micrograms/kg per minute doses were displayed. The
reworsening phase of the biphasic response was usually seen
with doses > or = 20 micrograms/kg per minute but was also
observed as early as the 7.5 micrograms/kg per minute dose.
CONCLUSIONS: The wall motion response during dobutamine
echocardiography is useful in the prediction of recovery of
ventricular function after revascularization in patients with
stable coronary artery disease and ventricular dysfunction.
The administration of low as well as high doses of dobutamine
is needed for optimal evaluation.
PMID: 7828291 [PubMed - indexed for MEDLINE]-
-
Comparison of dobutamine transesophageal
echocardiography and dobutamine magnetic resonance imaging for
detection of residual myocardial viability.
Baer FM, Voth E, LaRosee K, Schneider CA, Theissen P,
Deutsch HJ, Schicha H, Erdmann E, Sechtem U.
Klinik III fur Innere Medizin, Universitat zu Koln, Germany.
A dobutamine-induced contraction reserve in akinetic but
viable myocardium, observed by echocardiography or magnetic
resonance imaging (MRI), is a reliable indicator of myocardial
viability. However, the comparative diagnostic accuracy of
these 2 techniques is unknown. Therefore, 43 patients with
myocardial infarction (infarct age > or = 4 months) and
regional akinesia underwent dobutamine transesophageal
echocardiography (TEE) and dobutamine MRI (10 microg
dobutamine/ min/kg). Both imaging techniques were compared
with the reference standard 18F-fluorodeoxyglucose positron
emission tomography (FDG PET). An infarct region was
considered viable if a dobutamine contraction reserve could be
assessed visually by TEE or quantitatively by MRI in > or =
50% of segments graded "a" or dyskinetic at rest.
Infarct regions were graded viable by PET if FDG uptake was
> or = 50% of the maximal FDG uptake in a region with
normal wall motion by left ventriculography. A dobutamine
contraction reserve was found in 21 of 43 patients (49%) by
TEE and MRI. A viable infarct region by FDG PET was diagnosed
in 26 of 43 patients (60%). FDG uptake and dobutamine TEE were
concordant in 36 of 43 patients (84%) and dobutamine MRI and
FDG PET were concordant in 38 of 43 patients (88%).
Sensitivity and specificity of dobutamine TEE and dobutamine
MRI for FDG PET-defined myocardial viability were 77% versus
81% and 94% versus 100%, respectively. Both imaging techniques
yielded similar results for the detection of myocardial
viability as defined by FDG uptake, with a slightly higher
sensitivity and specificity for the quantitatively evaluated
dobutamine contraction reserve by MRI.
PMID: 8752185 [PubMed - indexed for MEDLINE]
-
Assessment of residual viability in
patients with myocardial infarction using magnetic resonance
techniques.
Sechtem U, Voth E, Baer F, Schneider C, Theissen P, Schicha
H.
Klinik III fur Innere Medizin, Universitat zu Koln, Germany.
Magnetic resonance techniques have only recently been employed
to assess residual myocardial viability after myocardial
infarction. Three approaches have been described to achieve
this purpose: First, the use of signal intensity changes on
spin-echo images with and without the application of contrast
media to define irreversible injury to the myocardium in acute
and subacute infarcts; second, measurement of metabolite
concentrations within the infarct area using magnetic
resonance spectroscopy, and third, quantitation of myocardial
thickness and systolic wall thickening in chronic infarcts.
This paper reviews the pertinent literature and compares MR
techniques with other imaging techniques used in the diagnosis
of myocardial viability.
Publication Types:
PMID: 8409542 [PubMed - indexed for MEDLINE]-
-
Comparison of low-dose
dobutamine-gradient-echo magnetic resonance imaging and
positron emission tomography with [18F]fluorodeoxyglucose in
patients with chronic coronary artery disease. A functional
and morphological approach to the detection of residual
myocardial viability.
Baer FM, Voth E, Schneider CA, Theissen P, Schicha H,
Sechtem U.
Klinik III fur Innere Medizin, Universitat zu Koln, Germany.
BACKGROUND: There have been conflicting reports of whether
substantial myocardial thinning alone as an indirect sign of
myocardial scarring is sufficient evidence to exclude the
presence of viable myocardium in patients with previous
myocardial infarction and persisting regional left ventricular
akinesia. Demonstration of a dobutamine-induced contraction
reserve in postischemic viable but akinetic myocardium may
serve as a direct indicator of myocardial viability. In the
present study, end-diastolic wall thickness at rest and
dobutamine-induced systolic wall thickening assessed by
magnetic resonance imaging (MRI) were compared with
corresponding [18F]fluorodeoxyglucose uptake as assessed by
positron emission tomography (FDG-PET). METHODS AND RESULTS:
Thirty-five patients with myocardial infarction (infarct age,
> 4 months) and regional akinesia or dyskinesia assessed by
left ventriculography underwent rest and dobutamine MRI
studies (10 micrograms dobutamine.min-1.kg-1) and FDG-PET
followed by segmental analyses of end-diastolic wall thickness,
systolic wall thickening, and FDG uptake in corresponding
short-axis tomograms. Two definitions of viability, as
assessed by MRI, of a segment akinetic at baseline were used:
(1) end-diastolic wall thickness of > or = 5.5 mm (the mean
minus 2.5 SD of a healthy control group [n = 21]) and (2)
evidence of dobutamine-induced systolic wall thickening >
or = 1 mm. Segments were graded as viable by FDG-PET if FDG
uptake was > or = 50% of the maximum uptake in a region
with normal wall motion as assessed by left ventriculography.
Preserved end-diastolic wall thickness in akinetic regions was
found in 17 of 35 (48%) patients at rest, and functional
recovery within the infarct region was found in 19 of 35 (54%)
patients during dobutamine infusion. Viability of the infarct
region was indicated by FDG-PET in 23 of 35 patients (66%),
yielding a diagnostic agreement between FDG uptake and
myocardial morphology in 29 of 35 (83%) and between
dobutamine-induced contraction reserve and FDG-PET in 31 of 35
(89%). Of 2200 segments, 482 (22%) were akinetic at rest. Of
these akinetic segments, 234 (48%) had preserved end-diastolic
wall thickness, 251 (52%) had a dobutamine-induced contraction
reserve, and 299 (62%) were graded as viable by FDG-PET.
Correlations of FDG uptake with end-diastolic wall thickness
at rest (r = .48) and with dobutamine-induced wall thickening
(r = .42) were similar. Comparison of segmental MRI and
FDG-PET gradings indicated that dobutamine-induced wall
thickening was a better predictor of residual metabolic
activity (sensitivity, 81%; specificity, 95%; positive
predictive accuracy, 96% than was end-diastolic wall thickness
(sensitivity, 72%; specificity, 89%; positive predictive
accuracy, 91%). However, grading a segment as viable if at
least one of both MRI parameters fulfilled viability criteria
improved the sensitivity (88%) of MRI for FDG-PET-assessed
metabolic activity without a major decrease in specificity
(87%) or positive predictive accuracy (92%). CONCLUSIONS:
Viable myocardium is characterized by preserved end-diastolic
wall thickness and a dobutamine-inducible contraction reserve.
Both parameters should be taken into account to maximize the
sensitivity of MRI in the detection of regions with signs of
viability on FDG-PET images.
PMID: 7850935 [PubMed - indexed for MEDLINE]
-
Comment in:
Early contrast-enhanced MRI predicts late
functional recovery after reperfused myocardial infarction.
Rogers WJ Jr, Kramer CM, Geskin G, Hu YL, Theobald TM, Vido
DA, Petruolo S, Reichek N.
Division of Cardiology, Department of Medicine, Allegheny
General Hospital, Pittsburgh, PA 15212, USA.
BACKGROUND--We have observed 3 abnormal patterns on
contrast-enhanced MRI early after reperfused myocardial
infarction (MI): (1) absence of normal first-pass signal
enhancement (HYPO), (2) normal first pass signal followed by
hyperenhanced signal on delayed images (HYPER), or (3) both
absence of normal first-pass enhancement and delayed
hyperenhancement (COMB). This study examines the association
between these patterns in the first week after MI and late
recovery of myocardial contractile function by use of magnetic
resonance myocardial tissue tagging. METHODS AND RESULTS--Seventeen
patients (14 men) with a mean age of 53+/-12 years were
studied after a reperfused first MI. Contrast-enhanced images
were acquired immediately after bolus administration of
gadolinium and 7+/-2 minutes later. Tagged images were
acquired at weeks 1 and 7. Circumferential segment shortening
(%S) was measured in regions displaying HYPER, COMB, or HYPO
contrast patterns and in remote regions (REMOTE) at weeks 1
and 7. At week 1, %S was depressed in HYPER, COMB, and HYPO
(9+/-8%, 7+/-6%, and 5+/-4%, respectively) and were less than
REMOTE (18+/-6%, P<0.003). However, in HYPER, %S improved
at week 7 from 9+/-8% to 18+/-5% (P<0.001 versus week 1).
In contrast, HYPO did not improve significantly (5+/-4% to
6+/-3%, P=NS) and COMB tended to improve 7+/-6% to 11+/-6%
(P=0.06). CONCLUSIONS--HYPER has partially reversible
dysfunction and represents predominantly viable myocardium.
COMB shows borderline improvement and likely contains an
admixture of viable and necrotic myocardium. HYPO shows little
functional improvement at 7 weeks, presumably because of
irreversible myocardial damage.
PMID: 9989958 [PubMed - indexed for MEDLINE]-
-
Relationship of MRI delayed contrast
enhancement to irreversible injury, infarct age, and
contractile function.
Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti
O, Bundy J, Finn JP, Klocke FJ, Judd RM.
Northwestern University Medical School, Feinberg
Cardiovascular Research Institute, Department of Medicine,
Chicago, IL 60611-3008, USA.
BACKGROUND: Contrast MRI enhancement patterns in several
pathophysiologies resulting from ischemic myocardial injury
are controversial or have not been investigated. We compared
contrast enhancement in acute infarction (AI), after severe
but reversible ischemic injury (RII), and in chronic
infarction. METHODS AND RESULTS: In dogs, a large coronary
artery was occluded to study AI and/or chronic infarction (n =
18), and a second coronary artery was chronically instrumented
with a reversible hydraulic occluder and Doppler flowmeter to
study RII (n = 8). At 3 days after surgery, cine MRI revealed
reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal,
P<0.001). In RII, wall thickening before, during, and after
inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%,
and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and
56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming
occlusion, transient ischemia, and reperfusion.
Gd-DTPA-enhanced MR images acquired 30 minutes after contrast
revealed hyperenhancement of AI (294+/-96% of normal,
P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight
weeks later, the chronically infarcted region again
hyperenhanced (253+/-54% of normal, n = 8, P<0.001).
High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated
that the spatial extent of hyperenhancement was the same as
the spatial extent of myocyte necrosis with and without
reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R =
0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97,
P<0.001). CONCLUSIONS: In the pathophysiologies
investigated, contrast MRI distinguishes between reversible
and irreversible ischemic injury independent of wall motion
and infarct age.
PMID: 10556226 [PubMed - indexed for MEDLINE]
-
Comment in:
Regional thallium uptake in irreversible
defects. Magnitude of change in thallium activity after
reinjection distinguishes viable from nonviable myocardium.
Dilsizian V, Freedman NM, Bacharach SL, Perrone-Filardi P,
Bonow RO.
Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20892.
BACKGROUND. Thallium reinjection immediately after
stress-redistribution imaging identifies ischemic but viable
myocardium in as many as 50% of the regions characterized by
conventional redistribution imaging as irreversibly injured.
However, we have previously shown that some regions in which
irreversible defects persist despite reinjection are
metabolically active, and hence viable, by positron emission
tomography. In the current study, we determined whether the
severity of reduction in thallium activity within irreversible
defects on redistribution images and the magnitude of change
in regional thallium activity after reinjection can further
discriminate viable from nonviable myocardium in such defects.
METHODS AND RESULTS. We studied 150 patients with coronary
artery disease by exercise thallium tomography using the
rest-reinjection protocol. The three sets of images (stress,
redistribution, and reinjection) were then analyzed
quantitatively. The increase in regional thallium activity
from redistribution to reinjection was computed, normalized to
the increase observed in a normal region, and termed "differential
uptake." Of the 175 myocardial regions designated to have
irreversible thallium defects on conventional 3-4 hour
redistribution images, 132 had only mild-to-moderate reduction
in thallium activity (51-85% of normal activity), and 43 had
severe reduction in thallium activity (less than or equal to
50% of normal activity). Thallium reinjection resulted in
enhanced relative activity in 60 of 132 (45%) of the
mild-to-moderate irreversible defects and 22 of 43 (51%) of
the severe irreversible defects, leaving roughly half of these
defects remaining irreversible after reinjection. However, in
regions that appeared to remain irreversible despite
reinjection, the magnitude of differential uptake differed
between mild-to-moderate (74 +/- 14%) and severe (35 +/- 16%)
irreversible defects (p less than 0.001). All regions with
mild-to-moderate defects demonstrated greater than 50%
differential uptake after reinjection. In contrast, all except
two of the regions with severe irreversible defects
demonstrated differential uptake of less than 50%. Fifteen
patients also underwent positron emission tomography at rest
with 18F-fluorodeoxyglucose (FDG) and 15O-water. FDG uptake
was present in 91% of regions with mild-to-moderate reduction
in thallium activity, and the results of differential uptake
and FDG data were concordant in 81% of these regions.
CONCLUSIONS. These data indicate that the magnitude of
thallium uptake after reinjection differs between
mild-to-moderate and severe irreversible defects on standard
3-4 hour redistribution images. The substantial differential
uptake of thallium (greater than 50%) after reinjection in
mild-to-moderate defects, even when relative thallium activity
does not increase appreciably (and the defect appears to
remain irreversible), coupled with preserved metabolic
activity by positron emission tomography, supports the concept
that such mild-to-moderate irreversible defects represent
viable myocardium.
PMID: 1735157 [PubMed - indexed for MEDLINE]-
Erratum in:
- Circulation 1995 Jun 15;91(12):3026
Myocardial viability in patients with
chronic coronary artery disease. Comparison of 99mTc-sestamibi
with thallium reinjection and [18F]fluorodeoxyglucose.
Dilsizian V, Arrighi JA, Diodati JG, Quyyumi AA, Alavi K,
Bacharach SL, Marin-Neto JA, Katsiyiannis PT, Bonow RO.
Cardiology Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, MD 20892.
BACKGROUND: 99mTc-sestamibi and thallium imaging have similar
accuracy when used for diagnostic purposes, but whether
sestamibi provides accurate information regarding myocardial
viability in patients with chronic coronary artery disease has
not been established. Since there is minimal redistribution of
sestamibi over time, it may overestimate nonviable myocardium
in patients with left ventricular dysfunction, in whom blood
flow may be reduced at rest. METHODS AND RESULTS: We studied
54 patients with chronic coronary artery disease with a mean
ejection fraction of 34 +/- 14%. Patients underwent stress/redistribution/reinjection
thallium tomography and, within a mean of 5 days, same-day
rest/stress sestamibi imaging using the same exercise protocol
and with patients achieving the same exercise duration. Of the
111 reversible thallium defects on either the redistribution
or reinjection study, 40 (36%) were determined to be
irreversible on the rest/stress sestamibi study, whereas only
3 of 63 irreversible thallium defects despite reinjection (5%)
were classified to be reversible by sestamibi imaging. The
concordance regarding reversibility of myocardial defects
between thallium stress/redistribution/reinjection and same
day rest/stress sestamibi studies was 75%. A subgroup of 25
patients also underwent positron emission tomography (PET)
studies with 15O-labeled water and [18F]fluorodeoxyglucose (FDG)
at rest after an oral glucose load. As in the overall group of
54 patients, there was concordance between thallium and
sestamibi imaging regarding defect reversibility in 51 of 73
regions (70%). In the remaining 22 discordant regions (30%),
18 (82%) appeared irreversible by sestamibi imaging but were
reversible by thallium imaging. Myocardial viability was
confirmed in 17 of 18 regions, as evidenced by normal FDG
uptake (10 regions) or FDG/blood flow mismatch (7 regions) on
PET. These regions were present in 16 of the 25 patients
studied (64%). We then explored methods to improve the
sestamibi results. First, when the 18 discordant regions with
irreversible sestamibi defects were further analyzed according
to the severity of defects, 14 (78%) demonstrated only
mild-to-moderate reduction in sestamibi activity (51% to 85%
of normal activity), suggestive of predominantly viable
myocardium, and the overall concordance between thallium and
sestamibi studies increased to 93%. Second, when an additional
4-hour redistribution image was acquired in 18 patients after
the injection of sestamibi at rest, 6 of 16 discordant
irreversible regions (38%) on the rest/stress sestamibi study
became reversible, thereby increasing the concordance between
thallium and sestamibi studies to 82%. CONCLUSIONS: These data
indicate that same-day rest/stress sestamibi imaging will
incorrectly identify 36% of myocardial regions as being
irreversibly impaired and nonviable compared with both
thallium redistribution/reinjection and PET. However, the
identification of reversible and viable myocardium can be
greatly enhanced with sestamibi if an additional
redistribution image is acquired after the rest sestamibi
injection or if the severity of reduction in sestamibi
activity within irreversible defects is considered.
PMID: 8313546 [PubMed - indexed for MEDLINE]-
-
Assessment of myocardial viability by
dobutamine echocardiography, positron emission tomography and
thallium-201 SPECT: correlation with histopathology in
explanted hearts.
Baumgartner H, Porenta G, Lau YK, Wutte M, Klaar U, Mehrabi
M, Siegel RJ, Czernin J, Laufer G, Sochor H, Schelbert H,
Fishbein MC, Maurer G.
Department of Cardiology, Vienna General Hospital, University
of Vienna, Wien, Austria.
OBJECTIVES: We examined the relationship among viability
assessment by dobutamine echocardiography (DE), positron
emission tomography (PET) and thallium-201 single-photon
emission computed tomography (TI-SPECT) to the degree of
fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to
be sensitive in identifying viability of asynergic myocardium.
However, PET and TI-SPECT indicated viability in a significant
percentage of segments without dobutamine response or
functional improvement after revascularization. METHODS:
Twelve patients with coronary artery disease and severely
reduced left ventricular function (EF 14.5+/-5.2%) were
studied with DE prior to cardiac transplantation: 5 had
additional PET and 7 had TI-SPECT studies. Results of the
three techniques were compared to histologic findings of the
explanted hearts. RESULTS: Segments with >75% viable
myocytes by histology were determined to be viable in 78%, 89%
and 87% by DE, PET and TI-SPECT; those with 50-75% viable
myocytes in 71%, 50% and 87%, respectively. Segments with
25-50% viable myocytes showed response to dobutamine in only
15%, but were viable in 60% by PET and 82% by TI-SPECT.
Segments with <25% viable myocytes responded to dobutamine
in 19%; however, PET and TI-SPECT demonstrated viability in
33% and 38%, respectively. Discrepant segments without
dobutamine response but viability by PET and SPECT had
significantly more viable myocytes by pathology than did those
classified in agreement to be nonviable but had significantly
less viable myocytes than those classified in agreement to be
viable (p < .001). CONCLUSIONS: These findings suggest that
contractile reserve as evidenced by a positive dobutamine
response requires at least 50% viable myocytes in a given
segment whereas scintigraphic methods also identify segments
with less viable myocytes. Thus, the methods may provide
complementary information: Nuclear techniques appear to be
highly sensitive for the detection of myocardial viability,
and negative tests make it highly unlikely that a significant
number of viable myocytes are present in a given segment.
Conversely, dobutamine echo may be particularly useful for
predicting recovery of systolic function after
revascularization.
PMID: 9822099 [PubMed - indexed for MEDLINE]
-
-
Predictive value of dobutamine
echocardiography and positron emission tomography in
identifying hibernating myocardium in patients with
postischaemic heart failure.
Pagano D, Bonser RS, Townend JN, Ordoubadi F, Lorenzoni R,
Camici PG.
Cardiothoracic Surgical Unit, Queen Elizabeth Hospital,
Birmingham, UK.
OBJECTIVE: To compare the predictive value of dobutamine
echocardiography (DE) and positron emission tomography (PET)
in identifying reversible chronic left ventricular (LV)
dysfunction (hibernating myocardium) in patients with coronary
artery disease (CAD) and overt heart failure. PATIENTS: 30
patients (four women) with CAD and heart failure undergoing
coronary artery bypass grafting (CABG). METHODS: Myocardial
viability was assessed with DE (5 and 10 micrograms/kg/min)
and PET with [18F] 2-fluoro-2-deoxy-D-glucose (FDG) under
hyperinsulinaemic euglycaemic clamp. Regional (echo) and
global LV function (MUGA) were assessed at baseline and six
months after CABG. RESULTS: 192 of the 336 (57%) dysfunctional
LV segments improved function following CABG (hibernating) and
the LV ejection fraction (EF) increased from 23(7) to 32(9)%
(p < 0.0001) (in 17 patients > 5%). DE and PET had
similar positive predictive values (68% and 66%) in the
identification of hibernating myocardium, but DE had a
significantly lower negative predictive value than PET (54% v
96%; p < 0.0001). A significant linear correlation was
found between the number of PET viable segments and the
changes in EF following CABG (r = 0.65; p = 0.0001). Stepwise
logistic regression identified the number of PET viable
segments as an independent predictor of improvement in EF >
5%, whereas the number of DE viable segments, the baseline
LVEF, and wall motion were not. CONCLUSIONS: DE has a higher
false negative rate than PET in identifying recoverable LV
dysfunction in patients with severe postischaemic heart
failure. The amount of PET viable myocardium correlates with
the functional outcome following CABG.
PMID: 9602663 [PubMed - indexed for MEDLINE]
41. Gerber BL, Vanoverschelde JL, Bol A et al. Myocardial blood
flow, glucose uptake, and recruitment of inotropic reserve in
chronic left ventricular ischemic dysfunction. Implications for
the pathophysiology of chronic myocardial hibernation. Circulation
1996; 94: 651–659.
-
Assessment of myocardial viability in
chronic coronary artery disease using technetium-99m sestamibi
SPECT. Correlation with histologic and positron emission
tomographic studies and functional follow-up.
Maes AF, Borgers M, Flameng W, Nuyts JL, van de Werf F,
Ausma JJ, Sergeant P, Mortelmans LA.
Department of Nuclear Medicine, K. U. Leuven, Belgium.
OBJECTIVES: The value of 99mTc-sestamibi (2-methoxy-isobutyl
isonitrile [MIBI]) as a viability tracer was investigated in
patients undergoing coronary artery bypass graft surgery.
BACKGROUND: Initial studies claim that rest MIBI single-photon
emission computed tomographic (SPECT) studies can be used to
assess myocardial viability. METHODS: Thirty patients with a
severely stenosed left anterior descending coronary artery and
wall motion abnormalities were prospectively included. The
patients underwent a MIBI rest study, a positron emission
tomographic (PET) flow (13NH3) and metabolism
(18F-deoxyglucose) study and nuclear angiography before
undergoing bypass surgery. A preoperative transmural biopsy
specimen was taken from the left ventricular anterior wall.
Morphometry was performed to assess percent fibrosis. After 3
months, radionuclide angiography was repeated. RESULTS:
Statistically significant higher MIBI values were found in the
group with myocardial viability as assessed by PET than in the
group with PET-assessed nonviability (p < 0.01).
Significantly higher MIBI values were found in the group with
enhanced contractility at 3 months (76 +/- 13% vs. 53 +/- 22%,
p < 0.01). A linear relation was found between MIBI uptake
and percent fibrosis in the biopsy specimen (r = 0.78, p <
0.00001). When maximizing the threshold for assessment of
viability with MIBI by using functional improvement as the
reference standard, a cutoff value of 50% was found, with
positive and negative predictive values of 82% and 78%,
respectively. CONCLUSIONS: 99mTc MIBI uptake was significantly
higher in PET-assessed viable areas and in regions with
enhanced contractility at 3 months. A linear relation was
found between percent fibrosis and MIBI uptake. An optimal
threshold of 50% was found for prediction of functional
recovery.
PMID: 8996296 [PubMed - indexed for MEDLINE]
43. Vanoverschelde JL, AM DH, Marwick T et al. Head-to-head comparison
of exercise-redistribution-reinjection thallium single-photon
emission computed tomography and low dose dobutamine echocardiography
for prediction of reversibility of chronic left ventricular ischemic
dysfunction. J Am Coll Cardiol 1996; 28: 432–442.
Comment on:
Metabolic imaging and contractile reserve
for assessment of myocardial viability: friends or foes?
Vanoverschelde JL, Melin JA.
Publication Types:
PMID: 10461613 [PubMed - indexed for MEDLINE]-
Comment in:
Clinical outcome of patients with advanced
coronary artery disease after viability studies with positron
emission tomography.
Eitzman D, al-Aouar Z, Kanter HL, vom Dahl J, Kirsh M, Deeb
GM, Schwaiger M.
Department of Internal Medicine, University of Michigan
Medical Center, Ann Arbor 48109-0028.
OBJECTIVE. The aim of this study was to determine the
prognostic significance of perfusion-metabolism imaging in
patients undergoing positron emission tomography for
myocardial viability assessment. BACKGROUND. Positron emission
tomography using nitrogen-13 ammonia and 18fluorodeoxyglucose
to assess myocardial blood flow and metabolism has been shown
to predict improvement in wall motion after coronary artery
revascularization. The prognostic implications of metabolic
imaging in patients with advanced coronary artery disease have
not been investigated. METHODS. Eighty-two patients with
advanced coronary artery disease and impaired left ventricular
function underwent positron emission tomographic imaging
between August 1988 and March 1990 to assess myocardial
viability before coronary artery revascularization. RESULTS.
Forty patients underwent successful revascularization.
Patients who exhibited evidence of metabolically compromised
myocardium by positron emission tomography (decreased blood
flow with preserved metabolism) who did not undergo subsequent
revascularization were more likely to experience a myocardial
infarction, death, cardiac arrest or late revascularization
due to development of new symptoms than were the other patient
groups (p less than 0.01). Concordantly decreased flow and
metabolism in segments of previous infarction did not affect
outcome in patients with or without subsequent
revascularization. Those with a compromised myocardium who did
undergo revascularization were more likely to experience an
improvement in functional class than were patients with
preoperative positron emission tomographic findings of
concordant decrease in flow and metabolism. CONCLUSIONS.
Positron emission tomographic myocardial viability imaging
appears to identify patients at increased risk of having an
adverse cardiac event or death. Patients with impaired left
ventricular function and positron emission tomographic
evidence for jeopardized myocardium appear to have the most
benefit from a revascularization procedure.
PMID: 1512333 [PubMed - indexed for MEDLINE]
46. Lee KS, Marwick TH, Cook SA et al. Prognosis of patients with
left ventricular dysfunction, with and without viable myocardium
after myocardial infarction. Relative efficacy of medical therapy
and revascularization. Circulation 1994; 90: 2687–2694.
Erratum in:
- Circulation 1999 Oct 5;100(14):1584
Prognostic value of myocardial ischemia and
viability in patients with chronic left ventricular ischemic
dysfunction.
Pasquet A, Robert A, D'Hondt AM, Dion R, Melin JA,
Vanoverschelde JL.
Divisions of Cardiology and Nuclear Medicine, University of
Louvain Medical School, Brussels, Belgium.
BACKGROUND: Previous studies showed that thallium scintigraphy
and dobutamine echocardiography were accurate, noninvasive
ways of predicting contractile recovery after
revascularization in patients with left ventricular (LV)
dysfunction. However, the prognostic impact of such methods
remains uncertain. METHODS AND RESULTS: We prospectively
studied 137 consecutive patients with coronary disease and LV
dysfunction who underwent exercise-redistribution-reinjection
thallium scintigraphy and dobutamine echocardiography to
identify myocardial ischemia and viability. A total of 94
patients subsequently underwent revascularization, and 43
underwent medical treatment. The primary endpoint was cardiac
mortality, and mean follow-up was 33+/-10 months. Twenty-four
patients died of cardiac causes. By Cox's regression analysis,
long-term survival was related to the extent of coronary
disease, the presence of diabetes, type of treatment, the
presence of ischemic myocardium as determined by thallium
scintigraphy, and the presence of viable myocardium as
determined by both tests. Three-year survival was greater in
patients with ischemic myocardium (as determined by thallium
scintigraphy) or viable myocardium (as determined by both
tests) who underwent revascularization than in the other
groups (P=0.018 with thallium; P<0.001 with dobutamine).
Subgroup analyses indicated that among patients with 1- or
2-vessel disease, only those with ischemic or viable
myocardium improved survival after revascularization, whereas
in patients with 3-vessel or left main diseases,
revascularization always improved survival, albeit more in the
presence of ischemic or viable myocardium. CONCLUSIONS: Among
the parameters commonly available in patients with LV ischemic
dysfunction, the presence of ischemic myocardium (as
determined by thallium scintigraphy) and that of viable
myocardium (as determined by dobutamine echocardiography) are
independent predictors of subsequent mortality. These
observations may be useful in the preoperative selection of
patients for revascularization.
PMID: 10402443 [PubMed - indexed for MEDLINE]
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