Metabolic
imaging in the evaluation of myocardial ischemia and
viability
Jeroen J. Bax1, Lucas J. Klein2,
Gerrit W. Sloof3, Frans C. Visser2
1Leiden University Medical Center, The Netherlands;
2Academic Hospital Vrije Universiteit Amsterdam,
The Netherlands;
3Amsterdam Medical Center, The Netherlands
Correspondence: Dr Jeroen J Bax, Leiden University Medical Center,
Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands (jbax@knoware.nl)
Introduction
The number of patients presenting with chronic heart failure secondary to coronary
artery disease and left ventricular (LV) dysfunction is increasing rapidly.
It has recently been estimated that 4.7 million patients in the USA have
chronic heart failure and the incidence of coronary artery disease in these
patients may be as high as 70%.[1]
The long-term prognosis of patients with heart failure is extremely poor; data
from the Framingham Heart Study documented a 5-year survival rate of 25% in
men and 38% in women who developed heart failure.
Therapeutic options in these patients include medical therapy, heart transplantation
or revascularization. Despite the optimization of medical therapy (diuretics,
digoxin, ACE inhibitors, beta-blockers, spironolactone), the long-term prognosis
remains poor. The long-term results with heart transplantation are excellent,
but the limited number of donor hearts is greatly exceeded by the increasing
demand. The third option (revascularization) can be an alternative, although
the procedure is accompanied by a much higher risk for (peri-)operative events
than in patients with normal LV function.[2] Data from the
Collaborative Study in Coronary Artery Surgery in 6630 patients, revealed a
(peri-)operative mortality of 1.9% in patients with a preserved LV function
(LV ejection fraction [LVEF] >50%) compared with 6.7% in patients with an LVEF <20%.[2]
Conversely, a substantial number of patients show an improvement in LVEF after
revascularization. Elefteriades et al[3] evaluated LVEF before
and after surgical revascularization in 68 patients with depressed LVEF and
demonstrated a significant improvement in LVEF in roughly 60% of these patients.
Since LVEF is an important prognostic parameter, improvement in LVEF may translate
into improved survival.
Based on these considerations, identification of patients who may potentially
benefit from revascularization is mandatory in order to justify the increased
risk of (peri-)operative events. The postoperative improvement in LVEF has
been related to the preoperative presence of viable myocardium.[4] Accordingly,
assessment of myocardial viability has become an important component of the
diagnostic and prognostic workup of patients with ischemic cardiomyopathy.
Over the past two decades a number of diagnostic modalities have been developed
for the identification of viable myocardium.[4] These modalities
are based on the detection of different characteristics of viable myocardium,
including residual metabolic activity, cell membrane integrity, intact mitochondria
or inducible contractile reserve. Residual metabolic activity (oxidative or
anaerobic) can be evaluated by labeling different myocardial substrates with
radionuclides (Figure 1).
 Figure 1. Schematic presentation of
metabolic pathways of myocardial substrate metabolism. Positron
emitting radionuclides such as 11C-palmitate, 11C-acetate and
18F-labeled deoxyglucose (FDG) are tracers of the metabolic
rate of important energy substrates such as free fatty acids
and glucose. In addition, the single-photon emitting agent
123I-labeled 15-(p-iodophenyl)-3-R,S-methyl- pentadecanoic
acid (BMIPP, not shown in this figure) also traces free fatty
acid metabolism. a GP, alpha-glyceryl phosphate; CoA, coenzyme
A; CPT-1, carnitine-palmitoyl-transferase; HK, hexokinase;
G3PDH, glyceraldehyde-3-phosphate dehydrogenase; PDH, pyruvate
dehydrogenase; PFK, phosphofructokinase; TCA, tricarboxylic
acid cycle; TG, triglycerides.(Reproduced from reference 53
with permission.)
The clinically most relevant radionuclides include 11C-acetate
(to assess oxidative metabolism), 123I-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic
acid (BMIPP, to assess free fatty acid utilization) and F18-fluorodeoxyglucose
(FDG, to evaluate glucose utilization).[4,5] Cell
membrane integrity can be evaluated using thallium-201, intactness
of mitochondria can be studied with technetium-99m sestamibi,
and contractile reserve can be probed with 2D echocardiography
or MRI during stepwise infusion of dobutamine.
In this article, the use of radionuclides for the noninvasive assessment of
myocardial metabolism will be reviewed. Following a brief summary on cardiac
metabolism, the role of the three radionuclides (11C-acetate, BMIPP
and FDG) will be discussed.
Cardiac metabolism
The heart has the ability to metabolize a wide variety of substrates such as
free fatty acids, glucose, lactate, pyruvate, ketone bodies and amino acids.
Under normal resting conditions, metabolism is mainly oxidative, with free
fatty acids and glucose being the major sources of energy. The preferred substrate
depends on arterial substrate concentrations (dietary conditions), hormonal
factors (mainly insulin) and workload. For example, in the fasting state free
fatty acids are primarily utilized for cardiac energy production, whereas in
the postprandial state glucose becomes the preferred substrate.
Under ischemic conditions with decreased oxygen delivery, oxidative metabolism
of free fatty acids is decreased and exogenous glucose becomes the preferred
substrate for the myocardium. Depending on the degree of residual oxygen availability,
glucose may predominantly be metabolized anaerobically as evidenced by increased
lactate release. The amount of energy produced by anaerobic glycolysis may
not be adequate to maintain contractility but may be sufficient to preserve
the cellular integrity. However, if perfusion is diminished below a critical
threshold level, tissue concentrations of lactate and hydrogen ions rise and
inhibit glycolysis.[6] This results in loss of ion concentration
gradients across the cell membrane, followed by cell membrane disruption and
cell death.
Accordingly, information on the use of different metabolic substrates is highly
valuable in evaluating the ‘viability status’ of the myocardium.
Assessment of oxidative metabolism: 11C-acetate
11C-acetate as a tracer
Acetate is easily labeled with 11C and in contrast to other metabolic
tracers, such as FDG and labeled fatty acids, 11C-acetate is directly
taken up by the tricarboxylic acid (TCA) cycle and metabolized to CO2 and water. 11C-acetate
used in nuclear medicine is usually labeled in the C-1 position to avoid metabolic
trapping in amino acid pools and the TCA cycle. Uptake of 11C-acetate
after intracoronary and intravenous administration is avid and fast, and dependent
on blood flow. Metabolism is in principle only dependent on TCA cycle activity.
The clearance rate of 11C activity from the heart after administration
of the tracer is a direct reflection of the activity of the TCA cycle. Because
TCA cycle activity is directly coupled to myocardial oxygen consumption (MVO2),
myocardial clearance rates of 11C-acetate reflect oxidative metabolism.
Clearance of 11C-acetate is almost independent from the substrate
that is used as the main fuel by the heart at the moment of administration
of the tracer, because there is only a variation of approximately 4% in production
of the reducing equivalents (NADH + H+ and FADH2) used in oxidative
phosphorylation when either glucose or free fatty acids are used as the substrate.
Time-activity curves obtained from regions of interest in 11C-acetate
studies consist of two parts: a build-up phase and a clearance phase. Usually,
the initial part of the study (the build-up phase of activity) lasts around
5 min, after which a steep decay occurs. Data of the uptake phase have been
used for determination of myocardial blood flow, either qualitatively by determining
peak myocardial values or quantitatively by modeling. Although blood flow and
metabolism are usually tightly coupled, there is still a variation in blood
flow at a certain level of metabolism, especially in patients with ischemic
heart disease.[7] This implies that peak myocardial values
after 11C-acetate injection are correlated, but not tightly, with
myocardial clearance rates of 11C-acetate.
Clearance of 11C-acetate from the heart is exponential and consists
of one exponential at low cardiac workloads and two exponents at higher workloads.
Because of the positron emission of 11C and the rapid clearance
of 11C-acetate from the myocardium, a study is best performed using
PET equipment when regional information is important; however, one study used
gamma-cameras equipped with high-energy collimators to determine global 11C-acetate
clearance from the myocardium.[8]
Relation of 11C-acetate clearance
to MVO2
Initial studies validating acetate as a measure of MVO2 were performed
with 14C-acetate and a direct relation was found between 14C-CO2
production and MVO2.[9] The clearance rate in the
venous effluent of 14C-CO2 was similar to that of externally measured
clearance from the myocardium of 11C-activity, measured with gamma-probes
after simultaneous injection of 14C- and 11C-acetate.[9]
The clearance rate was found to be independent of myocardial substrate usage.[10] In
later experiments, myocardial clearance rates measured with PET were related
to measured MVO2 and tight correlations were found,[10] as well
as with the rate-pressure product (RPP). In animals, a bi-exponential clearance
rate was usually found, whereas clearance was mono-exponential at rest in humans.[11] This
can be explained by the lower workload of the hearts of larger mammals (lower
frequency, but also lower wall tension). With dobutamine stimulation, clearance
rates usually become bi-exponential.[11,12] However, the
second exponential is extremely slow (0.005–0.01 min–1) and to determine
this rate adequately, scanning times of 1–3 h are necessary, which is impractical.
Therefore, in humans usually mono-exponential curve-fitting procedures were
used.
The RPP is usually used to determine cardiac work and thus the MVO2 in
humans. Mono-exponential clearance rates in humans were closely correlated
to the RPP.[11-16] The relationships determined are shown
in Table 1.
Table 1. Relation of mono-exponential
curve-fits of 11C-acetate clearance to the RPP in humans: results
from linear regression analysis.
 There is a rather large variation between the
different reports, limiting the universal use of 11C-acetate
clearance to determine oxygen consumption based on these relationships.
A probably more accurate approach to determine MVO2 from
the 11C-acetate clearance is the use of tracer kinetic
modeling. This has been validated by Sun et al.[17] ,
but needs confirmation in other studies.
11C-acetate in ischemia and
viability
Acetate has been extensively used in studies evaluating ischemia and myocardial
infarction. In animals, it was observed that myocardial TCA cycle activity
was reduced immediately after occlusion of a coronary artery and subsequent
release, but recovered in the following days to weeks.[18] There
was a significant correlation between the recovery of TCA cycle activity and
the recovery of function.[18,19] The effect of dobutamine
on stunned myocardium, showing recovery of TCA cycle activity, was found by
Hashimoto et al.,[20] together with recovery of function.
In humans, 11C-acetate clearance was reduced in the central area
of myocardial infarction, with gradual normalization of the clearance rates
in regions more distant from its center.[21] Also in patients
with reperfusion therapy after myocardial infarction a reduction in oxidative
metabolism could be demonstrated.[22] Relatively preserved 11C-acetate
clearance (in relation to perfusion) was associated with recovery of function.[22]
In patients with chronic LV dysfunction due to coronary artery disease or previous
infarction, recovery of function was found in areas with a relatively preserved 11C-acetate
metabolism.[23] In addition, dobutamine increased 11C-acetate
clearance in areas showing recovery of function after revascularization, in
contrast to areas that did not.[24] These observations led
to investigations to predict recovery of function based on 11C-acetate
clearance[25,26] (Table 2).
 Table
2. 11C-acetate to predict recovery of function post-revascularization.
These studies used absolute cut-off values of 11C-acetate
clearance to predict recovery of function, irrespective of
myocardial workload. Neither of the studies used 11C-acetate
clearance normalized to that of myocardium with normal wall
motion. Nevertheless, sensitivity and specificity of 11C-acetate
to predict recovery of function after revascularization were
81% and 61%, respectively. Compared with the sensitivity and
specificity of FDG PET (88% and 73% respectively, see below),[27] absolute 11C-acetate
clearance may not be as accurate for the prediction of recovery
of function after revascularization. However, additional studies
employing normalized clearance rates may improve the accuracy
of 11C-acetate imaging for the prediction of functional
recovery after revascularization.
Assessment of oxidative metabolism:
free fatty acids
Since long-chain non-esterified free fatty acids are the main energy source
for the normoxic myocardium, various radiolabeled free fatty acid analogues
have been developed for in vivo scintigraphy. 11C-palmitate in combination
with PET is considered to be the gold standard for noninvasive evaluation of
cardiac free fatty acid utilization. Following intravenous administration, 11C-palmitate
is avidly taken up by the myocardium. Therefore, 3–5 min after tracer administration,
myocardial distribution shows a good correlation with perfusion. In normal
myocardium, clearance shows a bi-exponential pattern, with a rapid early phase
corresponding to beta-oxidation of 11C-palmitate with release of 11C-O2
and after 20–30 min a slower second phase mainly reflecting incorporation of 11C-palmitate
into the lipid pool.[28] The complexity, high costs and the observation that
back-diffusion of non-metabolized 11C-palmitate during ischemia
contaminated the early clearance phase (and thus data interpretation),[28] have
limited widespread use of 11C-palmitate.
Alternatively, radioiodinated fatty acids have been advocated for the noninvasive
investigation of cardiac free fatty acid utilization in humans (see for an
overview ref 29).Iodine-123 has physical properties (peak
energy 159 keV, half-life 13.2 h) that allow acquisition with conventional
gamma-cameras and the iodine molecule resembles stereometrically a methyl group.
In the past two decades a variety of radioiodinated fatty acids have been developed
to study free fatty acid metabolism.
Initially, straight-chain iodinated fatty acids have been studied, in which
iodide or an iodinated phenylring was introduced at the terminal end of the
fatty acid chain. Because of the relatively rapid turnover, limiting the use
for SPECT imaging, the background activity and backdiffusion during ischemia,
these iodinated fatty acids are not used in clinical cardiology.
To increase myocardial retention, methyl-branching of free fatty acids was
introduced by Knapp et al.[30] The radioiodinated 3-monomethyl-substituted
analogue, BMIPP, exhibits myocardial clearance slow enough to permit regional
distribution studies by SPECT.
BMIPP as a tracer
Despite its modified structure, it was demonstrated in the initial biodistribution
studies[30] that myocardial uptake of BMIPP is similar to
that of natural free fatty acids. Fujibayashi et al.[31] observed
that in normal canine myocardium 74% of the intracoronary administered dosage
of BMIPP was extracted with a subsequent retention of 65%.
Following myocardial uptake, BMIPP is activated to BMIPP-CoA. Thereafter it
is mainly incorporated into triacylglycerols.[30] The remaining
(smaller) part is catabolized.[32] BMIPP metabolism also
depends on substrate availability.[32] Following fasting,
glucose plasma levels are diminished, while free fatty acid levels are high.
As a consequence, cardiac uptake of BMIPP is favored under these circumstances
and therefore BMIPP scintigraphy in patients is performed under resting and
fasting conditions.
BMIPP in ischemia and viability
The initial clinical studies with BMIPP by Dudczack et al.[33] using
planar imaging, confirmed the expected prolonged myocardial retention, providing
excellent delineation of the myocardium. Considering the advantages of tomography,
more recent BMIPP studies have exclusively used SPECT.
For the detection of ischemia and viability, BMIPP is used often in conjunction
with a perfusion tracer (thallium-201, technetium-99m sestamibi). In segments
with reduced resting perfusion, BMIPP uptake can be concordantly reduced (perfusion-BMIPP
match), more severely reduced (perfusion-BMIPP mismatch) or relatively increased
(reversed perfusion-BMIPP mismatch).
Matsunari et al[34] reported that areas with a perfusion-BMIPP
mismatch exhibited redistribution on stress-redistribution thallium-201 imaging
(indicating ischemically jeopardized viable tissue). Franken et al.[35] demonstrated
that patients with a recent myocardial infarction showed preserved contractile
reserve during low-dose dobutamine echocardiography in regions with a perfusion-BMIPP
mismatch, again indicating the presence of viable myocardium in these regions.
Conversely, none of the regions with a perfusion-BMIPP match exhibited contractile
reserve, suggesting that these regions represented scar tissue.
Subsequently, studies evaluated whether BMIPP SPECT could predict recovery
of LV function following reperfusion in acute myocardial infarction.[36,37] LV
function improved significantly in the patients showing a perfusion-BMIPP mismatch
during the acute stage; in contrast, no change in LV function was noted in
the patients with a perfusion-BMIPP match. Moreover, the extent of mismatch
was closely related to the extent of recovery at follow-up.
There are only a few studies to determine whether BMIPP imaging is also useful
to differentiate viable myocardium from scar tissue in patients with chronic
coronary artery disease and LV dysfunction. Two studies evaluated patients
with chronic coronary artery disease and LV dysfunction who underwent revascularization.[38,39] Taki
et al.[39] evaluated patients with chronic coronary artery
disease with BMIPP and resting thallium-201 (to assess perfusion) prior to
revascularization: wall motion was assessed before and after revascularization.
Improvement of function occurred in 17 of 20 regions with a perfusion-BMIPP
mismatch, compared with 1 of 4 regions with a perfusion-BMIPP match. Accordingly,
a sensitivity of 94% and a specificity of 50% to predict improvement of regional
function after revascularization were obtained (Figure 2).
 Figure
2. Bar graph demonstrating the sensitivity (blue bars)
and specificity (red bars) of BMIPP SPECT for the prediction
of improvement of regional and global LV function post-revascularization
(based on references 38 and 39).
Prediction of improvement of global LV function after revascularization was
also evaluated by Taki et al.[39] Six out of 10 patients who were classified
viable by BMIPP imaging improved in LVEF, whereas 6 of 9 patients who were
classified as nonviable did not improve in LVEF. Similar data were shown
by Hambije et al.[38] Pooling the data from these two studies yielded a sensitivity
of 81% and a specificity of 56% to predict improvement of LVEF after revascularization
(Figure 2). In addition, Hambije et al.[38] demonstrated that in patients
who continued to show an area of mismatch 6 months after revascularization,
a further increase in LVEF could be anticipated at 1-year follow-up.
Finally, Tamaki et al.[40] evaluated the prognostic significance
of areas showing a perfusion-BMIPP mismatch in a cohort of 50 patients with
chronic coronary artery disease, with a mean follow-up of 23 months. Nine patients
experienced a cardiac event during the follow-up period, including two cases
of nonfatal infarction, five cases of unstable angina and two cases of late
revascularization. Univariate analysis showed that the number of segments with
a perfusion-BMIPP mismatch was the best predictor of future cardiac events.
Thus, most of the currently available literature indicates that myocardium
showing a reduction in perfusion with a further reduction in BMIPP uptake (mismatch
pattern) indicates jeopardized but viable tissue that may recover spontaneously
(in acute myocardial infarction) or after revascularization (in chronic coronary
artery disease), whereas myocardium exhibiting a concordantly reduced perfusion
and BMIPP uptake is likely to represent scar tissue that does not have the
potential for recovery of function. Besides the matches and mismatches, a reverse
mismatch pattern (BMIPP uptake increased relative to perfusion) has been noted.
While this pattern is relatively scarce in patients with acute myocardial infarction,
it has been observed more often in patients with chronic coronary artery disease.
Sloof et al.[41] recently compared BMIPP and FDG imaging
in patients with chronic coronary artery disease and LV dysfunction. The authors
demonstrated that segments with a reversed perfusion-BMIPP mismatch frequently
exhibited a perfusion-FDG mismatch (see below), suggesting the presence of
viable tissue. Unfortunately, the patients did not undergo revascularization
and therefore functional outcome after revascularization could not be assessed.
Thus, the exact relevance of reverse mismatches remains unclear and awaits
further study.
Assessment of glucose metabolism: 18F-fluorodeoxyglucose
(FDG)
FDG as a tracer
FDG is a glucose analogue (one OH group has been replaced by F18) and the initial
trans-sarcolemmal uptake of FDG is identical to that of glucose. FDG competes
with glucose for uptake and phosphorylation to FDG-6-PO4, a process mediated
by the enzyme hexokinase. Unlike glucose-6-PO4, FDG-6-PO4 does not undergo
further metabolism and remains trapped in the myocyte. FDG uptake in the myocardium
is highly dependent on the presence of competing substrates (free fatty acid,
lactate, amino acids) and hormonal plasma levels (mainly insulin). Since low
free fatty acid levels and high glucose/insulin levels promote FDG uptake,
cardiac FDG studies are preferably performed following oral glucose loading.
To further standardize the metabolic circumstances, hyperinsulinemic-euglycemic
clamping has been advocated.[42] Although this approach results
in superb image quality (even in patients with diabetes mellitus), the procedure
is rather laborious and time-consuming. Recently, the use of nicotinic acid
derivatives (acipimox) has been suggested and the initial results are promising.[43,44] Oral
administration of these substances results in extremely low plasma free fatty
acid levels, and when administered in combination with a small meal (to stimulate
endogenous insulin production) the image quality of cardiac FDG studies was
comparable to that obtained following hyperinsulinemic-euglycemic clamping.[43,44]
FDG in ischemia and viability
As in BMIPP studies, FDG imaging is usually combined with perfusion imaging.
Similar to the BMIPP studies, different perfusion-FDG patterns can be observed:
viability on perfusion-FDG imaging is defined when either perfusion is normal
(consistent with [repetitive] stunning) or when increased FDG uptake is present
in perfusion defects (perfusion-FDG mismatch, probably reflecting hibernation).
Scar tissue is characterized by a concordant reduction in perfusion and FDG
uptake (perfusion-FDG match).
Since FDG is a positron-emitter, FDG imaging is traditionally performed using
PET equipment. However, due to the relatively long half-life of F18 (110 min)
on the one hand, and to the development of 511 keV collimators on the other,
FDG imaging is also feasible with SPECT. Over the past 5 years, substantial
experience with cardiac FDG SPECT imaging has been obtained.[45] Although
resolution of SPECT is inferior to that of PET, similar clinical information
(perfusion-FDG mismatches and matches) can be derived from FDG SPECT as with
FDG PET. An example of FDG SPECT showing a perfusion-FDG mismatch is given
in Figure 3.
 Figure
3. Two series of short-axis slices of a patient with
a perfusion-FDG mismatch; in the inferior wall, perfusion
(assessed by resting thallium-201, lower series) is absent,
whereas FDG uptake (upper series) is relatively preserved.
(Reproduced from reference 54 with permission.)
Several studies have directly compared FDG PET with FDG SPECT, and were consistent
in demonstrating a good agreement between PET and SPECT in the assessment
of viable myocardium. For example, Burt et al.[46] studied
20 patients with chronic coronary artery disease; all of these patients had
a defect on 4-h delayed resting thallium-201 imaging. Subsequently, these
patients underwent both FDG PET and FDG SPECT. Sixty-one segments exhibited
a defect on thallium-201 imaging, 11 segments showed preserved FDG uptake
on both PET and SPECT, and 45 showed absent FDG uptake on both PET and SPECT.
Accordingly, similar information concerning viability/-scar tissue was provided
in 56 of 61 (92%) segments. Hence, the available data indicate that FDG imaging
with PET and SPECT provide similar information considering tissue classification.
Over the past 15 to 20 years, numerous studies have used FDG imaging to evaluate
the presence of residual glucose utilization in patients with acute ischemic
syndromes and in patients with chronic coronary artery disease and LV dysfunction.[27] Most
clinical experience, however, has been obtained in patients with chronic ischemic
LV dysfunction. In these patients, FDG imaging, combined with perfusion imaging,
can detect residual viable tissue and predict improvement of LV function after
revascularization. Recently, the results of [12] FDG PET
studies were pooled to determine the value of FDG PET for the prediction of
improvement of regional LV function after revascularization.[27] Pooling
of the results yielded a sensitivity of 88% with a specificity of 73%. Studies
using FDG SPECT demonstrated similar results: Bax et al. evaluated 55 patients
with severe coronary artery disease and depressed LV function (LVEF 39 ± 14%)
with SPECT prior to revascularization.[47] Recovery of function
was observed in 94 segments, of which 80 were classified viable on FDG SPECT.
Alternatively, 187 segments did not improve in function and 141 of these were
classified non-viable by FDG SPECT. Thus, a sensitivity of 85% and a specificity
of 75% to predict improvement of regional LV function were derived.
Although the prediction of improvement of regional LV function is important,
the prediction of improvement of global LV function is probably more relevant
from a clinical point of view, since LVEF is an important prognostic parameter.
Several FDG PET studies have demonstrated that patients with viable tissue
are likely to improve in LVEF, in contrast to patients without viable tissue.[48]
In fact, 11 studies have evaluated LVEF before and after revascularization
and related the findings to the FDG PET data. In 10 of 11 studies, the average
LVEF improved significantly in patients with viable tissue on FDG PET (ranging
from 7% to 18% absolute increase in LVEF). In seven of these studies ‘non-viable
patients’ (according to the PET findings) were also included; none of these
studies demonstrated an improvement in average LVEF (from 4% absolute increase
to 12% absolute decrease in LVEF). The average LVEF improved by 10.6 ± 4.1%
in the studies with viable patients and decreased by –1.7 ± 2.1% in the studies
with the non-viable patients (Figure 4).
 Figure
4. Average changes in LVEF following revascularization
in studies with ‘FDG PET viable’ patients (left) and ‘FDG
PET non-viable’ patients (right) (based on references 48).
Frequently, the improvement in LVEF is accompanied by an improvement in heart
failure symptoms. Bax et al.[49] have recently evaluated
47 patients with ischemic cardiomyopathy (LVEF 30 ± 6%) with FDG SPECT prior
to revascularization. The patients were divided into three groups, according
to the number of dysfunctional but viable segments on FDG SPECT (using a
13-segment model). Group I consisted of 22 patients without substantial viability
(<3 viable segments), group II consisted of 17 patients with an intermediate
amount of viable tissue (3–5 segments) and group III consisted of eight patients
with a large amount of viable tissue (>5 segments). In group I, heart failure
symptoms (expressed in NYHA scores) did not change. In group II, a modest
improvement in heart failure symptoms was observed, but the largest improvement
NYHA score was observed in group III (Figure 5).
 Figure
5. Changes in heart failure symptoms (scored according
to the NYHA classification) following revascularization in
three groups of patients. Blue bars represent NYHA score
before revascularization, red bars represent NYHA score after
revascularization (based on reference 49).
Two FDG PET studies have also evaluated the change of symptoms and exercise
capacity
in viable and non-viable patients.[50,51] Marwick et al.[50] evaluated
patients with FDG PET, prior to revascularization. The results indicated that
patients with substantial viability demonstrated a significant improvement
in exercise capacity. Finally, the long-term prognostic value of FDG PET was
evaluated in five studies, with a total of 549 patients.[52] These patients
were grouped according to treatment (revascularization/medical) and viability
status (absent/present) (Figure 6).
 Figure
6. Pooled data from five FDG PET studies (549 patients)
evaluating the prognostic value of the technique. The bars
represent the event rate according to the treatment (revascularization
or medical therapy) and the absence (mismatch –) or presence
(mismatch +) of viable tissue on FDG PET. The highest event
rate was observed in the viable patients who were treated
medically (based on reference 52).
The mean follow-up varied from 12 to 29 months.
The highest event rate (42%) was observed in the viable patients
who were treated medically, whereas the lowest event rate (9%)
was observed in the viable patients who underwent revascularization
(Figure 6).
These results suggest that residual viability in patients with chronic coronary
artery disease and depressed LV function is an unstable situation prone to
future events. An important limitation of these studies is their retrospective,
non-randomized character. Prospective, randomized trials are needed to determine
the precise impact of viability in combination with treatment on long-term
survival.
Conclusion
Heart failure secondary to coronary artery disease is becoming one of the major
concerns in clinical cardiology. Besides medical therapy and heart transplantation,
coronary revascularization can be an alternative treatment. In order to justify
the higher risk of revascularization in patients with heart failure, detection
of viable myocardium has become an important issue. According to the many studies
in the literature, improvement of LV function, heart failure symptoms and prognosis
can only be anticipated in patients with substantial viable tissue. Metabolic
imaging using PET and SPECT in combination with a variety of radionuclides
allows noninvasive assessment of the “viability status” of the myocardium,
and provides a useful tool to guide patient management.
REFERENCES
Medical management of heart failure
secondary to coronary artery disease.
Challapalli S, Bonow RO, Gheorghiade M.
Division of Cardiology, Northwestern University Medical School, Chicago,
Illinois 60611, USA.
Publication Types:
PMID: 9894618 [PubMed - indexed for MEDLINE]-
Clinical and angiographic predictors
of operative mortality from the collaborative study in
coronary artery surgery (CASS).
Kennedy JW, Kaiser GC, Fisher LD, Fritz JK, Myers W,
Mudd JG, Ryan TJ.
Fifteen institutions participating in the Collaborative Study in Coronary
Artery Surgery (CASS) have performed isolated coronary artery bypass surgery
upon 6630 patients (1061 women and 5569 men) for coronary artery disease.
The overall operative mortality (OM) was 2.3% (range 0.3-6.4%). Mortality
increased with age, from 0 in the group 20-29 years old to 7.9% in the group
70 years and older. OM was higher for women in each group, ranging from 2.8%
for ages 30-39 years to 12.3% for age 70 years and older (0.8% and 5.8% for
men). Clinical manifestations of congestive heart failure were associated
with increased OM. Mortality was 1.4% in one-vessel, 2.1% in two-vessel and
2.8% in three-vessel disease (diameter narrowing greater than or equal to
70%). Among 1019 patients with left main coronary artery (LMCA) stenosis,
OM ranged from 1.6% in patients with mild stenosis and a right-dominant system
to 25% in patients with severe (greater than or equal to 90%) stenosis and
left dominance. OM varied with ejection fraction (EF) (1.9% for EF greater
than or equal to 50% to 6.7% for EF less than 19%) and left ventricular wall
motion score (1.7% for least abnormal to 9.1% for most abnormal). For elective
surgery, OM was 1.7%, for urgent surgery 3.5%, and for emergency surgery
10.8%. Mortality was 40.0% among 30 patients with severe LMCA stenosis who
underwent emergency revascularization. Advanced age, female sex, symptoms
of heart failure, LMCA stenosis, impaired left ventricular function and nonelective
surgery are associated with a higher OM. These factors should be considered
in the selection of patients for coronary artery surgery.
PMID: 6970631 [PubMed - indexed for MEDLINE]-
Coronary artery bypass grafting in severe
left ventricular dysfunction: excellent survival with improved
ejection fraction and functional state.
Elefteriades JA, Tolis G Jr, Levi E, Mills LK, Zaret
BL.
Section of Cardiothoracic Surgery, Yale University School of Medicine, New
Haven, Connecticut.
OBJECTIVES. The present study evaluated our experience with coronary artery
bypass grafting in patients with severe left ventricular dysfunction. BACKGROUND.
Despite the ominous prognosis of advanced ischemic cardiomyopathy, coronary
artery bypass grafting in this setting remains controversial because of concerns
over operative risk and lack of functional or survival benefit. METHODS.
We analyzed the data of 83 consecutive patients (69 men, 14 women, aged 42
to 83 years [mean 66.8]) with a left ventricular ejection fraction < or
= 30% who underwent isolated coronary artery bypass grafting (without aneurysmectomy,
valve replacement or other open heart procedures) performed by one surgeon
during a 6-year period. The ejection fraction ranged from 10% to 30% (mean
24.6%). Preoperatively, 49% of patients had angina, 52% had congestive heart
failure (17% with pulmonary edema) and 30% manifested significant ventricular
arrhythmia. The mean number of grafts was 2.7/patient. The internal mammary
artery was used in 82% of grafts to the left anterior descending coronary
artery. The intraaortic balloon pump was required therapeutically (for angina
or pump failure) in 19% of patients and was prophylactically placed preoperatively
in another 43% of patients. RESULTS. The hospital mortality rate was 8.4%
(7 of 83). The mortality rate was 3.3% (2 of 61) in those patients who did
not require admission to an intensive care unit immediately before operation.
Canadian Cardiovascular Society angina class improved postoperatively by
1.9 categories and New York Heart Association congestive heart failure class
by 1 category. Left ventricular ejection fraction (assessed postoperatively
in 68 of 76 hospital survivors) improved from 24.6% preoperatively to 33.2%
postoperatively (36% increase) (p < 0.001). At 1 and 3 years, respectively,
all-cause survival was 87% and 80% and freedom from cardiac death was 89.8%
and 84.5%. CONCLUSIONS. In patients with coronary artery disease and advanced
ventricular dysfunction: 1) coronary artery bypass grafting can be performed
relatively safely, 2) good medium-term survival is attained, 3) improvement
in left ventricular function can be documented objectively after bypass grafting,
4) quality of life is improved (as reflected by improvement in anginal and
congestive heart failure status), and 5) the internal mammary artery can
safely be used as a conduit. The use of coronary artery bypass grafting is
encouraged for this group of patients and may provide a viable alternative
to transplantation in selected patients.
PMID: 8227799 [PubMed - indexed for MEDLINE]-
Comment in:
The viable myocardium: epidemiology, detection, and
clinical implications.
Marwick TH.
Department of Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
The success of fibrinolytic and other therapies has reduced the mortality
of myocardial infarction. However, many survivors develop congestive heart
failure. Medical treatment of this disorder has limited efficacy, and cardiac
transplantation has limited availability. Contrary to previous teaching about
ischaemic injury, roughly 40% of segments involved in myocardial infarction
may subsequently recover, either spontaneously or after revascularisation.
The persistence of such viable myocardium means that previous approaches
to treatment of myocardial infarction must be reappraised. This review examines
the pathogenesis of this response, the techniques that may be used to identify
the salvageable tissue, and the clinical implications. Myocardial revascularisation
may improve symptom status, exercise capacity, and prognosis in selected
patients with viable myocardium.
Publication Types:
PMID: 9519973 [PubMed - indexed for MEDLINE]
5. Knapp FF Jr, Kropp J. Iodine-123-labeled
fatty acids for myocardial single-photon emission tomography:
Current status and future perspectives. Eur J Nucl Med 1995;
22: 361–381.
Effects of regional ischemia on metabolism
of glucose and fatty acids. Relative rates of aerobic and
anaerobic energy production during myocardial infarction
and comparison with effects of anoxia.
Opie LH.
The rate of coronary flow reaching the oxygen-linited heart appears to be
crucial in determining the myocardial tissue metabolic response. The tissue
metabolic response to anoxia, well studied in hearts perfused with anoxic
media, differs in many important ways from the response to ischemia. In regional
ischemia (developing infarction) there is still a residual oxygen uptake
which is reduced approximately to the same extent as the delivery of O2;
there is also decreased delivery of substrates and decreased removal of CO2,
H+, and lactate, with increased concentrations of these metabolites. Contents
of hexose monophosphates rise rather than fall in anoxia. Measurements of
glycolytic intermediates show an initial burst of accelerated glycolytic
flux lasting less than 1 minute after coronary artery ligation; thereafter
rates of flux decrease to control values or even less at 120 minutes. Relative
inhibition of phosphofructokinase (PFK) activity may be explained by a slow
rate of fall of ATP and a developing intracellular acidosis. In this model,
glucose accounts for a greater part of the residual oxidative metabolism
than does free fatty acid (FFA).
PMID: 5202 [PubMed - indexed for MEDLINE]-
Coronary circulation during heavy exercise
in control subjects and patients with coronary heart disease.
Holmberg S, Serzysko W, Varnauskas E.
PMID: 5149090 [PubMed - indexed for MEDLINE]-
Comment in:
Feasibility of planar myocardial carbon 11-acetate imaging.
Klein LJ, Visser FC, Nurmohamed SA, Vink A, Peters JH,
Knaapen P, Kruijer PS, Herscheid JD, Teule GJ, Visser CA.
Department of Cardiology, Institute for Cardiovascular Research of the Free
University Amsterdam, The Netherlands.
BACKGROUND: Myocardial oxygen consumption can be determined by using carbon
11-acetate (11C-acetate) and positron emission tomography (PET). The aim
of this study was to validate planar 11C-acetate scintigraphy in healthy
individuals by relating the myocardial clearance rate of dynamic 11C-acetate
scintigraphy with the rate-pressure product, which is used as a measure of
cardiac work. Also, the optimal curve-fitting procedure of the time-activity
curve and the intraobserver and interobserver variation of determining the
clearance rates were assessed. METHODS AND RESULTS: Six subjects were studied
at rest, and seven subjects were studied during dobutamine stimulation. Imaging
was performed with a planar camera equipped with high-energy collimators
for 45 minutes after the injection of 185 MBq of 11C-acetate. Myocardial
time-activity curves were corrected for decay. During the study, heart rates
and blood pressures were measured to calculate the rate-pressure product.
Myocardial time-activity curves showed a clear biphasic pattern. Clearance
rates were expressed in k values. The best fitting procedure, as assessed
by means of the lowest error of k and the best correlation with the rate-pressure
product, proved to be a monoexponential fit on the first part of the time-activity
curve (kmono). Subjects studied during dobutamine infusion had significantly
higher rate-pressure product (15.0 +/- 2.1*10(3) vs 8.6 +/- 1.2*10(3), P < .001)
and 11C-acetate clearance rates (kmono = 0.0657 +/- 0.0110 vs 0.0313 +/-
0.0056, P < .0001) than subjects studied at rest. There was low intraobserver
and interobserver variation in determining kmono values. A significant correlation
between the rate-pressure product and the monoexponential clearance rate
was found (kmono = 5.11*10(-6)*RPP-0.012; r = 0.94, P < .001). CONCLUSIONS:
The estimation of myocardial oxygen consumption is feasible with planar 11C-acetate
scintigraphy. Clearance rates and the relation with the rate-pressure product
are similar to those reported in PET studies. This technique may be used
for the assessment and follow-up of global myocardial metabolic abnormalities,
eg, in patients with hypertensive heart disease, cardiomyopathy, myocarditis,
and valvular disease.
PMID: 10888392 [PubMed - indexed for MEDLINE]-
Delineation of myocardial oxygen utilization
with carbon-11-labeled acetate.
Brown M, Marshall DR, Sobel BE, Bergmann SR.
Although positron-emission tomography (PET) with labeled fatty acid delineates
infarct size and permits qualitative assessment of fatty acid utilization,
quantification of oxidative metabolism is limited by complex alterations
in the pattern of utilization of fatty acid during ischemia and reperfusion.
Because metabolism of acetate by myocardium is less complex than that of
glucose or palmitate, we characterized kinetics of utilization of radiolabeled
acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit
buffer and performed a pilot tomographic study in man. Results of initial
experiments with carbon-14-labeled acetate (14C-acetate) indicated that the
steady-state extraction fraction of acetate averaged 61.5 +/- 4.0% in control
hearts (n = 4), 93.6 +/- 0.9% in hearts rendered ischemic (n = 4), and 54.8
+/- 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation
of 14C-acetate, assessed from the rate of efflux of 14CO2 in the venous effluent,
correlated closely with the rate of oxygen consumption under diverse metabolic
conditions (r = .97, p less than .001). In addition, no significant differences
were observed between rates of efflux of total 14C in all chemical species
(reflecting total clearance of tracer from myocardium) and efflux of 14CO2.
Clearance of 11C-acetate, measured externally with gamma probes in normal
and ischemic myocardium, correlated closely with clearance of 14C-acetate
measured directly in the effluent (r = .99, p less than .001) and with overall
myocardial oxygen consumption (r = .95, p less than .001). Accumulation and
clearance of 11C-acetate from human myocardium with PET demonstrated kinetics
comparable to those seen with radiolabeled acetate in vitro. Thus externally
detectable clearance of 11C-acetate provides a quantitative index of myocardial
oxidative metabolism despite variation in the patterns of intermediary metabolism
that confounds interpretation of results with conventionally used tracers
such as glucose and fatty acid.
PMID: 3113765 [PubMed - indexed for MEDLINE]-
Validity of estimates of myocardial
oxidative metabolism with carbon-11 acetate and positron
emission tomography despite altered patterns of substrate
utilization.
Brown MA, Myears DW, Bergmann SR.
Cardiovascular Division, Washington University School of Medicine, St. Louis,
MO 63110.
We recently demonstrated that the myocardial turnover rate constant (k) measured
noninvasively with positron emission tomography (PET) after intravenous administration
of [11C]acetate provides a reliable index of myocardial oxidative metabolism
(MVO2) theoretically independent of the pattern of myocardial substrate use.
However, because estimates of metabolism with other metabolic tracers are
sensitive to substrate use, we measured k in 12 dogs during baseline conditions
and again after infusion of either glucose (n = 8) or Intralipid (n = 4),
interventions that raised arterial glucose or fatty acids by more than fivefold
with concomitant changes in myocardial substrate use. Following glucose administration
k increased, but no difference was detected after compensation for changes
in hemodynamics and myocardial work induced by the infusion (0.18 +/- 0.03
min-1 (t1/2 = 3.9 min) at baseline compared with 0.22 +/- 0.06 min-1 (t1/2
= 3.2 min, p = N.S.). k was not affected by Intralipid infusion (k = 0.15
+/- 0.06 min-1 at baseline and 0.14 +/- 0.04 min-1 during infusion), and
correlated closely with MVO2 measured directly (n = 19 comparisons, r = 0.89).
The results indicate that estimates of MVO2 using [11C]acetate and PET are
valid despite changes in the pattern of myocardial substrate utilization.
PMID: 2786932 [PubMed - indexed for MEDLINE]-
Myocardial oxidative metabolism in normal
subjects in fasting, glucose loading and dobutamine infusion
states.
Tamaki N, Magata Y, Takahashi N, Kawamoto M, Torizuka
T, Yonekura Y, Nishizawa S, Sadato N, Tadamura E, Ono S,
et al.
Department of Nuclear Medicine, Kyoto University Faculty of Medicine, Japan.
Experimental studies indicated the clearance rate constant of 11C-acetate
as an index of regional myocardial oxygen consumption. To assess the response
of the clearance rate from the left ventricular (LV) myocardium to the change
in plasma substrate levels and to the increase in the cardiac work load in
normal subjects, a total of 18 dynamic positron emission tomographic studies
were performed at rest in the fasting state (control) (n = 7), after oral
glucose administration (n = 4), and during dobutamine infusion (n = 7) in
7 normal volunteers. The clearance rate constant (Kmono) was similar in the
control (0.065 +/- 0.017 min-1) and glucose loading states (0.059 +/- 0.008
min-1), whereas a significant increase in Kmono was observed during dobutamine
infusion (0.106 +/- 0.018 min-1) (p < 0.01) in relation to the increase
in the pressure-rate product with a correlation coefficient of 0.873 (p < 0.01).
When the LV myocardium was divided into 6 segments, there were no significant
differences among the segments in Kmono values in any condition. These normal
responses should be valuable for assessing oxidative metabolic reserve and
regional changes in oxidative metabolism in patients with coronary artery
disease.
PMID: 1489631 [PubMed - indexed for MEDLINE]-
Assessment of the effects of dobutamine
on myocardial blood flow and oxidative metabolism in normal
human subjects using nitrogen-13 ammonia and carbon-11
acetate.
Krivokapich J, Huang SC, Schelbert HR.
Department of Medicine, UCLA School of Medicine 90024-1679.
The dual purposes of this study with positron emission tomography were to
measure the effects of dobutamine on myocardial blood flow and oxidative
metabolism, and to compare carbon-11 (C-11) acetate versus nitrogen-13 (N-13)
ammonia in quantitating flow in normal subjects. Flow was quantitated with
N-13 ammonia at rest and at peak dobutamine infusion (40 micrograms/kg/min)
in 21 subjects. In 11 subjects, oxidative metabolism was also estimated at
rest and peak dobutamine infusion using the clearance rate of C-11 acetate,
k mono (min-1). A 2-compartment kinetic model was applied to the early phase
of the C-11 acetate data to estimate flow. The rest and peak dobutamine rate-pressure
products were 7,318 +/- 1,102 and 19,937 +/- 3,964 beats/min/mm Hg, respectively,
and correlated well (r = 0.77) with rest and peak dobutamine flows of 0.77
+/- 0.14 and 2.25 ml/min/g determined using N-13 ammonia as a flow tracer.
Rest and dobutamine flows estimated with C-11 acetate were highly correlated
with those determined with N-13 ammonia (r = 0.92). k mono increased from
0.05 +/- 0.01 to 0.18 +/- 0.02 min-1, and correlated highly with the increase
in flows (r = 0.91) and rate-pressure products (r = 0.94). Thus, the increase
in cardiac demand associated with dobutamine is highly correlated with an
increase in supply and oxidative metabolism. C-11 acetate is a unique tracer
that can be used to image both flow and metabolism simultaneously.
PMID: 8498380 [PubMed - indexed for MEDLINE]-
Oxidative metabolism in the myocardium
in normal subjects during dobutamine infusion.
Tamaki N, Magata Y, Takahashi N, Kawamoto M, Torizuka
T, Yonekura Y, Tadamura E, Okuda K, Ono S, Nohara R, et
al.
Department of Nuclear Medicine, Kyoto University Faculty of Medicine, Japan.
To assess the biventricular response of the clearance rate of carbon-11 acetate
as an index of myocardial oxidative metabolism to increase in work-load,
dynamic positron emission tomography was performed at rest and during dobutamine
infusion in 14 normal subjects. The clearance rate constant (Kmono) of the
left ventricular (LV) myocardium increased during dobutamine infusion (0.112
+/- 0.020 min-1 vs 0.065 +/- 0.015 min-1 at rest) (P < 0.001) in proportion
to the increase in the pressure-rate product. Kmono in the right ventricular
(RV) myocardium also increased (0.080 +/- 0.018 min-1 vs 0.034 +/- 0.013
min-1 at rest) (P < 0.001), with an excellent correlation with the LV
Kmono (r = 0.920). The fact that the increase in RV Kmono during dobutamine
infusion was greater (158% +/- 81%) than that in LV Kmono (79% +/- 39%) (P < 0.005)
indicates a greater increase in oxidative metabolism in the RV in response
to inotropic stimulation in normal subjects.
PMID: 8462612 [PubMed - indexed for MEDLINE]-
Hemodynamic and mechanical determinants
of myocardial O2 consumption in normal human heart: effects
of dobutamine.
Vanoverschelde JL, Wijns W, Essamri B, Bol A, Robert
A, Labar D, Cogneau M, Michel C, Melin JA.
Division of Cardiology, University of Louvain Medical School, Brussels, Belgium.
The relationship of myocardial O2 consumption (MVO2) to its potential hemodynamic
and mechanical determinants was investigated in eight healthy normal volunteers
at rest and during infusion of dobutamine (5-10 micrograms.kg-1.min-1). MVO2
was calculated from the monoexponential myocardial clearance of [1-11C]acetate
with positron emission tomography, and left ventricular mechanical function
was assessed by two-dimensional echocardiography. Infusion of dobutamine
increased heart rate by 53%, the tension-time index by 31%, and the rate-pressure
product by 116%. Cardiac output (+70%), left ventricular ejection fraction
(+24%), total mechanical energy [systolic pressure-volume area, (PVA) +84%],
and left ventricular pressure-work index (+100%) also increased during infusion
of dobutamine. During infusion of dobutamine, MVO2 increased from 96 +/-
17 to 233 +/- 19 J.min-1.100 g left ventricle-1, while myocardial efficiency
(the ratio of PVA to MVO2) decreased from 46 +/- 8 to 35 +/- 4% (P < 0.001
each). MVO2 was best correlated (P < 0.001) with the PVA (r = 0.92) and
the pressure-work index (r = 0.92). Infusion of dobutamine also resulted
in a significant parallel upward shift of the PVA-MVO2 relationship, indicative
of an increase in PVA-independent MVO2. Our data indicate that, in human
subjects, MVO2 is mainly related to systolic PVA and that inotropic stimulation
with dobutamine results in decreased efficiency of contraction, such as that
previously described in isolated hearts.
PMID: 8285227 [PubMed - indexed for MEDLINE]-
Regional myocardial oxygen consumption
determined noninvasively in humans with [1-11C]acetate
and dynamic positron tomography.
Armbrecht JJ, Buxton DB, Brunken RC, Phelps ME, Schelbert
HR.
Department of Radiological Sciences, UCLA School of Medicine 90024.
Experimental studies of animals have previously demonstrated the validity
of [1-11C]acetate as a tracer of oxidative metabolism for use with positron
emission tomography. The present study was undertaken to define in normal
human volunteers the relation between myocardial clearance kinetics of [1-11C]acetate,
and the rate-pressure product as an index of myocardial oxygen consumption.
Twenty-two studies were performed of 12 volunteers. The rate-pressure product
was increased with continuous supine bicycle exercise in six studies. Of
the 16 resting studies, seven were performed in the fasted state and nine
following an oral glucose load, to define possible effects of substrate availability
on the tracer-tissue kinetics. Myocardial tissue time-activity curves were
biexponential. Clearance of activity was homogeneous throughout the myocardium.
The rate constants k1, obtained from biexponential fitting, and kmono, obtained
by monoexponential fitting of the initial linear portion of the time-activity
curves, correlated well with the rate-pressure product. Although the correlation
coefficient was higher for k1 than for kmono (0.95 vs. 0.91), analysis on
a sectorial basis showed less regional variability in kmono. This suggests
that kmono, which is more practical than k1 because it requires shorter acquisition
times, may be more clinically and experimentally useful for detection of
myocardial segments with abnormal oxygen consumption. Overall, changes in
myocardial substrate supply were without significant effect on the relation
between the rate constants (k1 and kmono) and the rate-pressure product,
although a small decrease in kmono/rate-pressure product was observed following
oral glucose by paired analysis in four subjects. It is concluded that [1-11C]acetate
can be used for the noninvasive measurement of myocardial oxygen consumption
in humans with positron emission tomography, and, thus, has clinical and
experimental potential as a tool for the understanding and diagnosis of myocardial
disease.
PMID: 2791250 [PubMed - indexed for MEDLINE]-
Assessment of myocardial oxidative metabolic
reserve with positron emission tomography and carbon-11
acetate.
Henes CG, Bergmann SR, Walsh MN, Sobel BE, Geltman EM.
Cardiovascular Division, Washington University School of Medicine, St. Louis,
Missouri 63110.
We have previously demonstrated that positron emission tomography (PET) with
[11C]acetate allows noninvasive regional quantification of myocardial oxidative
metabolism. To assess the metabolic response of normal myocardium to increased
work (oxidative metabolic reserve), clearance of myocardial 11C activity
after administration of [11C]acetate i.v. was measured with PET in seven
normal subjects at rest and during dobutamine infusion. At rest, clearance
of 11C was monoexponential and homogeneous. The rate constant of the first
phase of 11C clearance, k1, averaged 0.054 +/- 0.014 min-1 at a rate-pressure
produce (RPP) of 7329 +/- 1445 mmHg X bpm. During dobutamine infusion, RPP
increased by an average of 141% to 17,493 +/- 3582 mm Hg Z bpm. Clearance
of 11C became biexponential and remained homogeneous. k1 averaged 0.198 +/-
0.043 min-1 with a mean coefficient of variation of 16%.. k1 and RPP correlated
closely (r = 0.91; p less than 0.001), and the slope of the k1/RPP relation
remained consistent in all subjects (1.48 +/- 0.42). These findings suggest
that PET with [11C]acetate and dobutamine stress may provide a promising
approach for evaluation of regional myocardial oxidative metabolic reserve
in patients with cardiac diseases of diverse etiologies and for assessment
of the efficacy of interventions designed to enhance the recovery of metabolically
comprised myocardium.
PMID: 2788722 [PubMed - indexed for MEDLINE]-
Simultaneous measurement of myocardial
oxygen consumption and blood flow using [1-carbon-11]acetate.
Sun KT, Yeatman LA, Buxton DB, Chen K, Johnson JA, Huang
SC, Kofoed KF, Weismueller S, Czernin J, Phelps ME, Schelbert
HR.
Department of Molecular and Medical Pharmacology, School of Medicine, University
of California, Los Angeles 90095-1735, USA.
[1-Carbon-11]acetate has been used as a tracer for oxidative metabolism with
PET. The aim of this study was to validate, in humans, a previously proposed
two-compartment model for [1-11C]acetate for the noninvasive measurement
of myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) with
PET. METHODS: Twelve healthy volunteers were studied with [13N]ammonia, [1-11C]acetate
and PET. Myocardial oxygen consumption was invasively determined by the Fick
method from arterial and coronary sinus O2 concentrations and from MBF obtained
by [13N]ammonia PET. RESULTS: Directly measured MVO2 ranged from 5.2 to 11.1
ml/100g/min, and MBF ranged from 0.48 to 0.88 ml/g/min. Oxidative flux through
the tricarboxylic acid cycle, reflected by the rate constant k2, which correlated
linearly with measured MVO2 [k2 = 0.0071 + 0.0074(MVO2); r = 0.74, s.e.e.
= 0.015]. With this correlation, MVO2 could be estimated from the model-derived
k2 value by MVO2 = 135(k2) - 0.96. The slope of this relationship was close
to that previously obtained in rats and implies that the tricarboxylic acid
cycle intermediate metabolite pool sizes are comparable. The net extraction
(K1) of [1-11C]acetate, measured by PET, from blood into myocardium correlated
closely with MBF by K1 = 0.15 + 0.73(MBF) (r = 0.93, s.e.e. = 0.033) and,
thus, provided noninvasively obtainable measures of blood flow. CONCLUSION:
The proposed compartment model for [1-11C]acetate fits the measured kinetics
well and, with proper calibration, allows estimation of absolute MVO2 rather
than only an index of oxidative metabolism. Furthermore, [1-11C]acetate-derived
estimates of MBF are feasible.
PMID: 9476935 [PubMed - indexed for MEDLINE]-
Quantitative assessment of prolonged
metabolic abnormalities in reperfused canine myocardium.
Buxton DB, Mody FV, Krivokapich J, Phelps ME, Schelbert
HR.
Division of Nuclear Medicine and Biophysics, Wadsworth Veterans Administration
Medical Center, Los Angeles, CA.
BACKGROUND. Prolonged metabolic abnormalities have been demonstrated previously
in postischemic myocardium, including relative increases in glucose uptake
and abnormal fatty acid kinetics. However, quantitative metabolic information
is limited, and the time course of changes in MVO2 in postischemic myocardium
is unknown. To address these issues, chronically instrumented dogs were studied
serially over 1 month after transient left anterior descending coronary artery
(LAD) occlusion, using positron emission tomography. METHODS AND RESULTS.
Dynamic imaging protocols were used in conjunction with tracer kinetic models
to quantify blood flow and metabolic rates. Myocardial sectors were defined
as normal, predominantly reversibly injured, and infarct-containing, based
on occlusion blood flow images and postmortem histochemistry. Myocardial
blood flow and metabolism were homogeneous at baseline. During LAD occlusion
for 3 hours, myocardial blood flow in reversibly injured and infarct-containing
sectors (determined with 13NH3) was decreased to 46% and 23%, respectively,
of blood flow in normal tissue. MVO2, determined with [1-11C]acetate, was
decreased less than myocardial blood flow, consistent with increased oxygen
extraction in the ischemic tissue. After reperfusion, blood flow normalized
rapidly in reversibly injured tissue but remained depressed in infarct-containing
sectors. Regional myocardial function, assessed by two-dimensional echocardiography,
was severely depressed during occlusion and did not improve significantly
until 1 week after reperfusion. MVO2 remained depressed after reperfusion
in both reversibly injured and infarct-containing sectors, did not improve
from occlusion levels until 1 week after reperfusion, and remained significantly
depressed 1 month after reperfusion even in reversibly injured sectors; [1-11C]palmitate
kinetics were also abnormal in postischemic tissue. As reported previously,
glucose metabolic rates were increased relative to baseline in normal but
not in postischemic tissue 3 hours after reperfusion. Subsequently, glucose
metabolism tended to be higher in postischemic relative to normal myocardium.
CONCLUSIONS. The results demonstrate decreased oxidative metabolism in postischemic
tissue, with concomitant abnormalities in palmitate kinetics and glucose
metabolism. Oxidative metabolism and regional function demonstrated a parallel
recovery with time.
PMID: 1572040 [PubMed - indexed for MEDLINE]-
Recovery of regional contractile function
and oxidative metabolism in stunned myocardium induced
by 1-hour circumflex coronary artery stenosis in chronically
instrumented dogs.
Heyndrickx GR, Wijns W, Vogelaers D, Degrieck Y, Bol
A, Vandeplassche G, Melin JA.
Cardiovascular Center, O.L.V.-Ziekenhuis, Aalst, Belgium.
Stunned myocardium produced by 1 hour of critical coronary artery stenosis
was evaluated for alteration in regional mechanical function and overall
oxidative and fatty acid metabolism by positron emission tomography (PET)
in chronically instrumented dogs. Twenty-seven dogs, chronically instrumented
for measurements of left ventricular pressure and regional myocardial wall
thickening in normal and ischemic zones, were subjected to a 1-hour period
of myocardial ischemia produced by graded left circumflex coronary artery
stenosis, resulting in minimal residual flow. Mean transmural myocardial
flow during 1-hour coronary stenosis decreased to 0.34 +/- 0.04 ml/min per
gram in the ischemic zones (normal zone transmural flow, 0.96 +/- 0.10 ml/min
per gram). Systolic wall thickening in the ischemic zone was almost completely
abolished (-97 +/- 4%). On reperfusion, systolic wall thickening immediately
resumed but remained depressed. Progressive recovery was noted with time.
At 24 hours, systolic wall thickening was still depressed (-20 +/- 6%, p < 0.01).
At 1 week, wall thickening had completely recovered and was no longer significantly
different from the control condition. In addition, the absence of necrosis
at the site of wall thickness measurements was confirmed at autopsy in all
dogs. No abnormalities were found by electron microscopy in four dogs undergoing
myocardial biopsies at the time of PET studies. Dynamic PET studies using
[1-11C]acetate tracer (performed at 6 hours, 1 week, and 2 weeks after reperfusion)
and [1-11C]palmitic acid tracer (performed at 6 hours, 12 hours, 24 hours,
1 week, and 2 weeks after reperfusion) allowed the computation of regional
tissue time-activity curves in different regions of interest at different
times during follow-up. Despite full reperfusion, abnormal [1-11C]acetate
and [1-11C]palmitic acid kinetics were observed in the posterior segments,
previously subjected to ischemia, as evidenced by a significant decrease
in the slope of the early 11C clearance curve component. Repeat PET studies
revealed progressive normalization of overall oxidative metabolism and fatty
acid metabolism, which paralleled the time course of recovery of mechanical
function. Thus, myocardial ischemia, produced by 1-hour coronary artery stenosis,
followed by full reperfusion is associated with a prolonged period of postischemic
mechanical and metabolic dysfunction. This transient reduction in oxygen
delivery induced a prolonged impairment in fatty acid beta-oxidation as well
as a reduction in overall oxidative metabolism despite full reoxygenation.
A similar time course for recovery of function and metabolism was observed.
PMID: 8443876 [PubMed - indexed for MEDLINE]-
Responses of blood flow, oxygen consumption,
and contractile function to inotropic stimulation in stunned
canine myocardium.
Hashimoto T, Buxton DB, Krivokapich J, Hansen HW, Phelps
ME, Schelbert HR.
Department of Molecular and Medical Pharmacology, University of California-Los
Angeles School of Medicine.
To examine the effects of inotropic stimulation on regional myocardial blood
flow (MBF), oxidative metabolism, and contractile function in stunned myocardium,
nine closed-chest dogs were studied 2 hours postreperfusion after a 25 minute
occlusion of the left anterior descending coronary artery (LAD). MBF was
determined with microspheres, and regional myocardial oxygen consumption
(MVO2) was estimated from the rate constant k1 of the rapid clearance phase
of [1-11C] acetate time activity curves, recorded with dynamic positron emission
tomography. Myocardium at risk was determined from [13N] ammonia images obtained
during occlusion. Wall motion, assessed by two-dimensional echocardiography,
was impaired in postischemic myocardium in all dogs 2 hours after reperfusion.
Dobutamine infusion increased the rate pressure product by 70% +/- 31% and
significantly improved contractile function in the postischemic region in
all dogs. In remote myocardium, MVO2 increased from 5.7 +/- 1.2 to 8.6 +/-
1.6 mumol/gm/min, and blood flow from 0.87 +/- 0.16 to 1.52 +/- 0.42 ml/gm/min
in response to dobutamine. In reperfused myocardium, MVO2 increased from
3.1 +/- 0.7 to 7.4 +/- 1.5 mumol/gm/min, and blood flow from 0.51 +/- 0.12
to 1.2 +/- 0.4 ml/gm/min. Oxygen extraction increased significantly in reperfused
myocardium relative to remote myocardium consistent with a flow-limited response
to dobutamine stimulation. The improvement in contractile function failed
to correlate significantly with relative increases in MBF or MVO2, suggesting
that mechanical function is not as tightly coupled as MBF and MVO2 in postischemic
myocardium during inotropic stimulation.
PMID: 8172053 [PubMed - indexed for MEDLINE]
- Noninvasive estimation of regional myocardial
oxygen consumption by positron emission tomography with
carbon-11 acetate in patients with myocardial infarction.
Walsh MN, Geltman EM, Brown MA, Henes CG, Weinheimer
CJ, Sobel BE, Bergmann SR.
Department of Internal Medicine, Washington University School of Medicine,
St. Louis, Missouri 63110.
We previously demonstrated in experimental studies that myocardial oxygen
consumption (MVO2) can be estimated noninvasively with positron emission
tomography (PET) from analysis of the myocardial turnover rate constant (k)
after administration of carbon-11 (11C) acetate. To determine regional k
in healthy human subjects and to estimate alterations in MVO2 accompanying
myocardial ischemia, we administered [11C]acetate to five healthy human volunteers
and to six patients with myocardial infarction. Extraction of [11C]acetate
by the myocardium was avid and clearance from the blood-pool rapid yielding
myocardial images of excellent quality. Regional k was homogeneous in myocardium
of healthy volunteers (coefficient variation = 11%). In patients, k in regions
remote from the area of infarction was not different from values in myocardium
of healthy human volunteers (0.061 +/- 0.025 compared with 0.057 +/- 0.008
min-1). In contrast, MVO2 in the center of the infarct region was only 6%
of that in remote regions (p less than 0.01). In four patients studied within
48 hr of infarction and again more than seven days after the acute event,
regional k and MVO2 did not change. The approach developed should facilitate
evaluation of the efficacy of interventions designed to enhance recovery
of jeopardized myocardium and permit estimation of regional MVO2 and metabolic
reserve underlying cardiac disease of diverse etiologies.
PMID: 2809744 [PubMed - indexed for MEDLINE]
-
Metabolic imaging by positron emission
tomography early after myocardial infarction as a predictor
of recovery of myocardial function after reperfusion.
Hicks RJ, Melon P, Kalff V, Wolfe E, Dick RJ, Popma
JJ, Topol E, Schwaiger M.
Department of Internal Medicine, University of Michigan Medical Center, Ann
Arbor, USA.
BACKGROUND: Myocardial ischemia leads to alterations in myocardial substrate
metabolism that have been shown to reflect severity of ischemic injury. The
purpose of this study was to correlate oxidative metabolism with recovery
of contractile function in patients with acute myocardial infarction. METHODS
AND RESULTS: Regional blood flow and oxidative metabolism were assessed by
dynamic positron emission tomography early after myocardial infarction treated
with thrombolytic therapy in 18 patients. The extent of myocardial perfusion
abnormally (carbon 11-labeled acetate uptake; relative amplitude < or
= 50%) was inversely correlated with the ejection fraction obtained within
8 hours of the onset of chest pain (r = -0.81; p - 0.01) but not clearly
with that at follow-up 1 week later (r = 0.64; p = 0.09). Oxidative metabolism
(carbon 11-labeled acetate; monoexponential clearance) was higher in periinfarct
territories with early or late recovery of contractile function than in those
without, but there was a large overlap in absolute values limiting the predictive
power of a single measurement. Relatively preserved oxidative metabolism
compared with perfusion in low-flow areas was predictive of early (day 1
to 1 week) and delayed (week 1 to beyond 1 month) recovery. Normal resting
perfusion with regionally decreased oxidative metabolism predicted early
recovery of contractile function. CONCLUSION: Thus in patients studied with
positron emission tomography early after myocardial infarction, comparison
of regional perfusion and oxidative metabolism was more predictive of recovery
in contractile function than was assessment of either one alone.
PMID: 9420679 [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]-
-
Noninvasive assessment of myocardial
viability by positron emission tomography with 11C acetate
in patients with old myocardial infarction. Usefulness
of low-dose dobutamine infusion.
Hata T, Nohara R, Fujita M, Hosokawa R, Lee L, Kudo
T, Tadamura E, Tamaki N, Konishi J, Sasayama S.
Department of Internal Medicine, Kyoto University Hospital, Japan.
BACKGROUND: When patients with severely depressed left ventricular function
are treated, it is crucial to know in advance how much functional recovery
is expected from coronary revascularization. METHODS AND RESULTS: We compared
the results of 11C acetate positron emission tomography (PET) with dobutamine
infusion with changes in regional wall motion evaluated by left ventriculography
in 28 patients with old Q-wave anterior myocardial infarctions. Dysfunctional
but viable myocardium (group A, n = 13) was separated from nonviable myocardium
(group B, n = 15) by echocardiographic assessments of regional wall motion
before and after successful coronary revascularization. 11C acetate PET was
performed to characterize normalized myocardial blood flow and oxidative
metabolism (the clearance rate constant, k mono). While the baseline k monos
of the infarct areas of the two groups were different with overlap, the responses
to dobutamine infusion were directionally different. In addition, relative
perfusion by 11C acetate PET could predict recovery of left ventricular function
as well as or better than dobutamine 11C acetate kinetics. The extent of
the increase in k monos of the infarct area with dobutamine infusion correlated
well (P < .01) with the degree of the increase in the percentage of systolic
segment shortening in the infarct area (left ventriculography) after coronary
revascularization. CONCLUSIONS: 11C acetate PET with dobutamine infusion
can predict not only the reversibility of dysfunctioning myocardium after
coronary revascularization but also the extent of improvement of regional
wall motion in patients with old Q-wave infarction.
PMID: 8873657 [PubMed - indexed for MEDLINE]
-
Comparison of carbon-11-acetate with
fluorine-18-fluorodeoxyglucose for delineating viable myocardium
by positron emission tomography.
Gropler RJ, Geltman EM, Sampathkumaran K, Perez JE,
Schechtman KB, Conversano A, Sobel BE, Bergmann SR, Siegel
BA.
Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology,
Saint Louis, Missouri 63110.
OBJECTIVES. This study was designed to determine in patients with advanced
coronary disease whether prediction of recovery of mechanical function after
coronary revascularization could be accomplished more effectively by positron
emission tomography (PET) with carbon-11 (11C)-acetate than by PET with fluorine-18
(18F)-fluorodeoxyglucose. BACKGROUND. Results of previous studies have demonstrated
that preservation of myocardial oxidative metabolism (measured by PET with
11C-acetate) is necessary for recovery of systolic function after coronary
revascularization. METHODS. Myocardial oxidative metabolism was quantified
before revascularization in 34 patients by the analysis of the rate of myocardial
clearance of 11C-acetate. Metabolism of glucose was assessed by analysis
of uptake of 18F-fluorodeoxyglucose. Receiver operating characteristic curves
for predicting functional recovery were derived for the measurements of oxidative
metabolism and glucose metabolism. In addition, criteria for prediction of
recovery of function based on measurements of oxidative metabolism and glucose
metabolism were developed and compared. RESULTS. Analysis of receiver operating
characteristic curves indicated that estimates of oxidative metabolism were
more robust in predicting functional recovery than were estimates of glucose
metabolism (p < 0.02). Moreover, threshold criteria with 11C-acetate exhibited
superior positive and negative predictive values (67% and 89%, respectively)
than did the criteria with 18F-fluorodeoxyglucose (52% and 81%, respectively),
p < 0.01. In segments with initially severe dysfunction, estimates of
oxidative metabolism tended to be more robust than estimates of glucose metabolism
in predicting functional recovery. Moreover, in such segments, the threshold
criteria with 11C-acetate tended to exhibit superior positive and negative
predictive values (85% and 87%, respectively) than did the criteria with
18F-fluorodeoxyglucose (72% and 82%, respectively), although statistical
significance was not achieved. CONCLUSIONS. In patients with advanced coronary
artery disease, the extent to which functional recovery can be anticipated
after coronary revascularization can be delineated accurately by quantification
of regional oxidative metabolism by PET with 11C-acetate.
PMID: 8227825 [PubMed - indexed for MEDLINE]-
-
Assessment of myocardial viability by
use of 11C-acetate and positron emission tomography. Threshold
criteria of reversible dysfunction.
Wolpers HG, Burchert W, van den Hoff J, Weinhardt R,
Meyer GJ, Lichtlen PR.
Department of Internal Medicine, Hannover Medical School, Germany.
BACKGROUND: Dual positron emission tomography (PET) imaging with a perfusion
tracer and 18F-fluorodeoxyglucose (FDG) can detect myocardial viability.
This approach may be replaced by a single 11C-acetate study, which enables
quantification of both regional blood flow and oxidative metabolism. The
significance of acetate-derived indexes for myocardial viability is examined.
METHODS AND RESULTS: Thirty postinfarct patients with akinetic ventricular
segments, a mean ejection fraction of 42 +/- 11%, and high-grade coronary
obstructions were studied with serial 11C-acetate PET scanning before and
7 +/- 5 months after coronary revascularization. Acetate PET was tested against
FDG and serial assessments of segmental wall motion. Sixty of 155 severely
dysfunctional LV segments improved postoperatively, and regional blood flow
increased. Flow estimates after revascularization suggested little fibrosis
in reversible segments. At baseline, blood flows differed between normal
myocardium, reversible dysfunction, and irreversible dysfunction (1.04 +/-
0.27, 0.73 +/- 0.18, and 0.43 +/- 0.18 mL.min-1.g-1, respectively; P < .001).
Oxidative metabolic rates were reduced only in irreversibly injured LV segments.
Multivariate analysis identified the acetate perfusion index as the only
independent predictor of postoperative recovery. Its predictive accuracy
was similar to that of FDG imaging but superior to indexes of flow-metabolic
mismatch or oxidative metabolism. CONCLUSIONS: After myocardial infarction,
quantitative indexes of perfusion and oxidative metabolism from acetate PET
indicate a critical threshold beyond which tissue is irreversibly injured.
Findings support the use of blood flow as a marker of myocardial viability
in chronic postinfarct patients with modestly reduced ejection fractions.
PMID: 9118508 [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]
-
Efflux of metabolized and nonmetabolized
fatty acid from canine myocardium. Implications for quantifying
myocardial metabolism tomographically.
Fox KA, Abendschein DR, Ambos HD, Sobel BE, Bergmann
SR.
It has generally been assumed, from assessment of myocardial metabolism with
[1(-11)C]palmitate and positron emission tomography, that clearance of the
radiolabel from the myocardium is attributable solely to efflux of the products
of oxidative metabolism. However, interpretations would differ if this assumption
were unfulfilled. Furthermore, efflux of metabolized and nonmetabolized tracer
has not been quantified. Accordingly, in this study, myocardium was perfused
extracorporeally in 21 open-chest anesthetized dogs, and the extraction and
clearance of [1(-11)C]palmitate were characterized under baseline conditions
(normoxia, n = 21), and, again, with ischemia (n = 6), with hypoxia (n =
9), or under control conditions (n = 6). After intracoronary bolus injection
of [1(-11)C]palmitate, myocardial time activity curves were measured with
a beta-probe, and the products of oxidative metabolism (11CO2) and efflux
of extracted but nonmetabolized fatty acid ("back-diffusion" of
[1(-11)C]palmitate) were measured directly from analysis of arterial and
regional coronary venous blood. Under control conditions, 45.2 +/- 3.8% (mean
+/- SD) of initially extracted [1(-11)C]palmitate was metabolized to 11CO2,
whereas 6.2 +/- 2.6% back-diffused in unaltered form in 1-10 minutes. In
contrast, with ischemia (perfusion of 26% of baseline), only 16.9 +/- 9.8%
of administered tracer evolved as 11CO2 (P less than 0.001 compared with
control) but 15.6 +/- 8.9% (i.e., almost half of the total amount cleared)
evolved unaltered as [1(-11)C]palmitate (P less than 0.05). Similarly, with
hypoxia, 15.1 +/- 8.4% evolved as 11CO2 (P less than 0.0001) and 18.8 +/-
11.7% back-diffused (P less than 0.001). Overall, from 1-40 minutes after
intracoronary injection of tracer, back-diffusion of [1(-11)C]palmitate contributed
40.6% of total radioactivity in the effluent with ischemia, 48.7% with hypoxia,
but only 8.9% under control conditions. Despite the increased back-diffusion
of [1(-11)C]palmitate seen with ischemia and hypoxia, the overall residue
of 11C activity in myocardium increased, consistent with the diminished clearance
observed in the myocardial time-activity curves and the increase in the tissue
content of triglyceride and nonesterified fatty acid. Our results indicate
that estimates of oxidative metabolism based upon clearance of radiolabeled
fatty acid must take into account the efflux of initially extracted but nonmetabolized
fatty acid. The findings apply to external determination of oxidative metabolism
of the heart with any imaging modality that delineates retention and clearance
of labeled fatty acids or their analogs.
PMID: 4017196 [PubMed - indexed for MEDLINE]
29. Bax JJ, Knapp FF, Visser
FC. Single-photon imaging of myocardial metabolism: the role
of iodine-123 fatty acids and fluorine-18 deoxyglucose. In:
Murray IPC, Ell PJ, Eds. Nuclear Medicine in clinical diagnosis
and treatment. 1998; 1497–1508.
New radioiodinated methyl-branched fatty
acids for cardiac studies.
Knapp FF Jr, Ambrose KR, Goodman MM.
The effects of 3-methyl substitution on the heart retention and metabolism
of 3-R,S-methyl-(BMIPP) and 3,3-dimethyl-(DMIPP) analogues of 15-(p-iodophenyl)-pentadecanoic
acid (IPP) were studied in rats. Methyl substitution considerably increased
the myocardial half-time values in fasted rats: IPP, 5-10 min; BMIPP, 30-45
min; DMIPP, 6-7 h. Because of the observed differences in the relative myocardial
uptake and retention of these agents, an evaluation of the subcellular distribution
profiles and the distribution of radioactivity within various lipid pools
extracted from cell components was performed. Studies with DMIPP in food-deprived
rats have shown high levels of the free fatty acid and only slow conversion
to triglycerides. These data are in contrast to the rapid clearance of the
straight chain IPP analogue and rapid incorporation into triglycerides, and
suggest that the prolonged myocardial retention observed with DMIPP in vivo
may result from inhibition of beta oxidation. Subcellular distribution studies
have shown predominant association of DMIPP and BMIPP with the mitochondrial
and microsomal fractions, while IPP was primarily found in the cytoplasm.
Because of the unique "trapping" properties and the high heart:blood
ratios, [123I]DMIPP should be useful for evaluation of aberrations in regional
myocardial uptake.
PMID: 3490376 [PubMed - indexed for MEDLINE]-
Metabolism and kinetics of iodine-123-BMIPP
in canine myocardium.
Fujibayashi Y, Nohara R, Hosokawa R, Okuda K, Yonekura
Y, Tamaki N, Konishi J, Sasayama S, Yokoyama A.
Department of Genetic Biochemistry, Faculty of Medicine, Kyoto University,
Japan.
The kinetics and metabolic fate of 123I-15-(p-iodophenyl)-3-(R,S)- methylpentadecanoic
acid (BMIPP) in canine myocardium were studied in an open-chest dog model.
METHODS: After left anterior descending artery injection of BMIPP, blood
samples were collected from the corresponding great coronary vein (V) and
femoral artery (A). On the basis of the A-V radioactivity difference as well
as the HPLC elution profile at various time points, myocardial extraction,
retention and metabolism of BMIPP were evaluated. RESULTS: BMIPP was instantly
extracted from the plasma into the myocardium (74% of the injected dose)
and was then retained (65.3%). Washout of the retained radioactivity was
low (8.7%) and most of the washout was as alpha- and beta-oxidation metabolites
(2.3 + 2.9 + 1.4%), with little loss of BMIPP itself (2.1 %). CONCLUSION:
BMIPP is suitable for static SPECT imaging of the myocardium, and its slow
washout appears to be due to metabolism through alpha- and beta-oxidation.
PMID: 8965141 [PubMed - indexed for MEDLINE]
.
Comment in:
Metabolism of iodine-123-BMIPP in perfused rat hearts.
Yamamichi Y, Kusuoka H, Morishita K, Shirakami Y,
Kurami M, Okano K, Itoh O, Nishimura T.
Central Research Laboratory, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Increased clinical use of 123I-labeled 15-(p-iodophenyl)-3-(R,S)-methyl-
pentadecanoic acid ([123I]BMIPP) revealed discordance between BMIPP uptake
and that of perfusion agents, which was inexplicable due to the uncertainty
of its myocardial metabolism. This study clarifies the metabolic fate of
BMIPP and its relation to substrates in isolated rat hearts. METHODS: Rat
hearts were perfused with 5 mmole/liter HEPES buffer containing various
energy substrates and 1% bovine serum albumin. The buffer was recirculated
for 4 hr after bolus injection of [123I]BMIPP. Heart time-activity curves
were monitored externally. After perfusion, the radioactivity in the heart
and recirculated buffer was measured. The metabolites in the buffer were
then extracted and analyzed by HPLC and TLC. RESULTS: when 0.4 mmole/liter
oleate was the energy substrate, more than eight radioactive BMIPP metabolites
were detected. The metabolites in the coronary effluent depended on the
energy substrate in the buffer. The radioactivity in the heart at the end
of the perfusion period was significantly higher when 0.4 mmole/liter oleate
(28.0% +/- 1.2% ID/g, mean +/- s.e.m.) or 10 mmole/liter glucose with 25
U/liter insulin (43.9% +/- 2.2% ID/g) were the substrates compared to when
5 mmole/liter acetate (8.5% +/- 0.4% ID/g) or 0.4 mmole/liter cold BMIPP
(6.2% +/- 0.3% ID/g) were the substrates. The distribution of metabolites
suggests that oleate stimulated both alpha and beta oxidations, whereas
glucose with insulin inhibited both. Acetate also stimulated alpha oxidation
but not beta oxidation. Cold BMIPP strongly inhibited both alpha- and beta-oxidations,
and little alpha oxidation occurred compared to beta-oxidation. CONCLUSION:
These results suggest that [123I]BMIPP is metabolized in the myocardium
and the metabolism is closely related to myocardial carbohydrate utilization.
PMID: 7769426 [PubMed - indexed for MEDLINE]
-
Structurally modified fatty acids: clinical
potential as tracers of metabolism.
Dudczak R, Schmoliner R, Angelberger P, Knapp FF, Goodman
MM.
Recently 15-p-iodophenyl-beta-methyl-pentadecanoic acid (BMPPA) was proposed
for use in myocardial scintigraphy, as a possible probe of metabolic processes
other than beta-oxidation. In 19 patients (CAD/15, St.p. Mi/7; control 4)
myocardial scintigraphy was carried out after i.v. I-123-BMPPA (2-4 mCi).
Data were collected (LAO 45 degrees/14; anterior/5) for 100 min in the fasted
patients. Organ to background (BG) ratios were calculated for the heart (H)
and liver (L), and the elimination (E) behaviour was analyzed from BG (vena
cava region) corrected time activity curves. In 10 patients plasma and urine
were examined. By CHCl3/MeOH extraction of plasma samples (90 min after injection),
both in water and in organic medium soluble catabolites were found. TLC fractionation
showed that those were co-migrating, compared to standards, with bencoic
acid, BMPPA and triglycerides. In the urine (0-2 h after injection, 4.1%
dose) hippuric acid was found. The mean t-max of BMPPA occurred at 15 min
in the heart and at 9 min in the liver (P less than 0.01), with H/BG and
L/BG ratios of 1.8 and 2.1, respectively. The elimination of BMPPA was slower
from the heart than from the liver (P less than 0.01). It was biexponential
from the liver in all cases (means: t/2 I, 11.4 min; t/2 II, 92 min; t/2
I uncor., 38 min) with the size of phase I smaller than that of phase II
(means: I/II, 0.57). From the heart BMPPA turnover was biexponential in 11
patients (means: t/2 I, 13.8 min; t/2 II, 187 min; t/2 I uncor., 65 min;
I/II, 0.34), but monoexponential in 8 (means: t/2, 218 min).(ABSTRACT TRUNCATED
AT 250 WORDS)
PMID: 3490377 [PubMed - indexed for MEDLINE]-
Kinetics of iodine-123-BMIPP in patients
with prior myocardial infarction: assessment with dynamic
rest and stress images compared with stress thallium-201
SPECT.
Matsunari I, Saga T, Taki J, Akashi Y, Hirai J, Wakasugi
T, Aoyama T, Matoba M, Ichiyanagi K, Hisada K.
Department of Radiology, Fukui Prefectural Hospital, Japan.
Myocardial kinetics of 123I-labeled 15-(p-iodophenyl)3R, S-methylpentadecanoic
acid (BMIPP) were evaluated with dynamic SPECT, and stress and rest BMIPP
images were directly compared in conjunction with stress 201Tl. METHODS:
We studied 26 patients with prior myocardial infarction. Two minutes after
injection of BMIPP, dynamic data acquisition with a three-headed SPECT was
started and continued for 12 min. Conventional SPECT images were obtained
at 20 min and 3 hr after injection. On a separate day, exercise, stress 201Tl
SPECT was performed at 10 min and 3 hr after injection. Exercise stress-BMIPP
imaging was performed in 15 of the patients, and static SPECT images were
obtained. RESULTS: With dynamic SPECT, early clearance of BMIPP from the
myocardium was observed in the segments with reversible 201Tl defects, suggesting
enhanced contribution of backdiffusion from BMIPP. In myocardial segments
with reversible 201Tl defects, 20-min BMIPP images showed a higher frequency
of reduced uptake when compared to 3-hr 201Tl (90/163) imaging. CONCLUSION:
With BMIPP dynamic SPECT, an enhanced contribution of backdiffusion in the
early phase from ischemic myocardium was suggested. When exercise stress
BMIPP images were obtained, a more severe defect was observed than on rest
BMIPP and stress 201Tl imaging, possibly due to decreased coronary blood
flow and impaired fatty acid uptake induced by ischemia during exercise.
PMID: 8046479 [PubMed - indexed for MEDLINE]-
Abnormal free fatty acid uptake in subacute
myocardial infarction after coronary thrombolysis: correlation
with wall motion and inotropic reserve.
Franken PR, De Geeter F, Dendale P, Demoor D, Block
P, Bossuyt A.
Department of Nuclear Medicine, University Hospital, Free University of Brussels,
VUB, Belgium.
Iodine-123-free fatty acid analogs, such as beta-methyliodophenylpentadecanoic
acid (BMIPP), allow for myocardial metabolic studies with SPECT. The goal
of this investigation was to determine whether BMIPP uptake can be used to
differentiate viable myocardium from scar tissue soon after coronary thrombolysis
for acute myocardial infarction. METHODS: BMIPP and 99mTc-sestamibi (MIBI)
myocardial distribution after injection at rest were analyzed in 22 patients
4 to 10 days after coronary thrombolysis. The relative uptake of the two
tracers was compared on a segmental basis to the regional wall motion and
to the inotropic reserve assessed by two-dimensional echocardiography and
low-dose dobutamine stimulation. RESULTS: Three segmental patterns were identified
in the infarct-related coronary artery territory. Segments with normal BMIPP
and MIBI uptake showed normal wall motion. Segments with more reduced BMIPP
uptake than MIBI uptake (mismatching) showed either normal wall motion or
demonstrated inotropic reserve during dobutamine stimulation. Segments with
matched defects always showed abnormal wall motion and did not demonstrate
inotropic reserve, regardless of the MIBI uptake. CONCLUSION: In patients
with subacute myocardial infarction, combined imaging of BMIPP and MIBI at
rest might be more sensitive than MIBI or wall motion at rest alone to demonstrate
myocardial areas that have been acutely ischemic. Mismatching is due to more
severely depressed fatty acid metabolism than expected on the basis of the
flow and is indicative of jeopardized, but viable myocardium. In dysfunctional
segments, mismatching may correspond either to stunned or to hibernating
myocardium. Matched defects are associated with scar tissue.
Publication Types:
- Clinical Trial
- Controlled Clinical Trial
PMID: 7965152 [PubMed - indexed for MEDLINE]
-
Recovery of impaired left ventricular
function in patients with acute myocardial infarction is
predicted by the discordance in defect size on 123I-BMIPP
and 201Tl SPET images.
Ito T, Tanouchi J, Kato J, Morioka T, Nishino M, Iwai
K, Tanahashi H, Yamada Y, Hori M, Kamada T.
Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan.
A discrepancy between myocardial perfusion defect and wall motion abnormalities
is frequently found early after coronary reperfusion in patients with acute
myocardial infarction. The purpose of this study was to assess recovery of
impaired left ventricular function by reference to the discordance in defect
size between myocardial fatty acid uptake and myocardial perfusion using
combined single-photon emission tomographic (SPET) imaging early after coronary
perfusion therapy. In 37 patients with acute myocardial infarction, iodine-123
15-(p-iodophenyl)-3(R, S)-methylpentadecanoic acid (BMIPP) and thallium-201
SPET scans were performed early after coronary reperfusion. A severity score
was determined from the extent of the imaging defect with each tracer. Left
ventricular wall motion score (WMS) and ejection fraction (EF) were obtained
at admission and at 4 weeks after the onset of infarction. In 32 of the 37
patients, discordance in defect sizes delineated with the two SPET studies
was found during the acute stage. The severity score for BMIPP was larger
than that for 201Tl during the acute stage (7. 7+/-2.4 vs 4.4+/-2.5, P <0.001).
There was a fair correlation between the severity score for BMIPP and WMS
(r=0.82, P <0.0001), but a poor correlation between that for 201Tl and
WMS. The extent of discordance in severity scores between BMIPP and 201Tl
during the acute stage correlated well with the extent of the improvement
in WMS (r=0.86, P <0.0001) and that of EF (r=0.85, P <0.0001). We conclude
that the discordance in defect size on BMIPP and 201Tl SPET images during
the acute stage of infarction is an early predictor of the viability of the
myocardium at risk of infarction.
PMID: 8753680 [PubMed - indexed for MEDLINE]-
Prediction of functional outcome after
myocardial infarction using BMIPP and sestamibi scintigraphy.
Franken PR, Dendale P, De Geeter F, Demoor D, Bossuyt
A, Block P.
Department of Nuclear Medicine, University Hospital, Free University of Brussels,
Belgium.
We determined the predictive value of combined beta-methyl iodophenyl pentadecanoic
acid (BMIPP) and sestamibi scintigraphy for the functional outcome after
myocardial infarction and compared the value of this approach with dobutamine
echocardiography. METHODS: Rest BMIPP, rest sestamibi and low-dose dobutamine
echocardiographic studies were obtained in 18 patients 4 to 10 days after
infarction (mean 6.7 +/- 2.0 days). Six months later, a rest echocardiographic
study was performed to assess functional outcome. RESULTS: Wall motion improved
in 27/33 segments (82%) which showed mismatching but not in 19/21 segments
(90%) with matched defects (p < 0.001). The accuracy of combined BMIPP
and sestamibi SPECT in predicting segmental functional outcome was higher
(85%) than that of sestamibi uptake alone (77%). Wall motion improved in
16/20 segments (80%) showing contractile reserve and not in 21/34 segments
(63%) with the negative dobutamine test, giving an accuracy of 69% for dobutamine
echocardiography. Combination of the two techniques resulted in higher positive
(94%) and negative predictive values (94%). CONCLUSION: Mismatching of BMIPP
and sestamibi uptake is predictive for long-term functional recovery after
acute myocardial infarction. In contrast, segments with matched defects contain
only scar tissue. Combined BMIPP and sestamibi scintigraphy offers increased
accuracy compared to dobutamine echocardiography.
PMID: 8965133 [PubMed - indexed for MEDLINE]-
BMIPP imaging to improve the value of
sestamibi scintigraphy for predicting functional outcome
in severe chronic ischemic left ventricular dysfunction.
Hambye AS, Dobbeleir AA, Vervaet AM, Van den Heuvel
PA, Franken PR.
Nuclear Medicine and Cardiology, Middelheim Hospital, Antwerp, Belgium.
Mismatching between beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) and
perfusion accurately predicts functional outcome after acute myocardial infarction.
The current investigation was aimed at evaluating the value of this method
to predict the evolution of global function according to the applied treatment
in patients with chronic ischemic heart disease. METHODS: Twenty patients
with infarction and chronic left ventricular dysfunction were studied (median
infarction age 12 wk, range 2 wk-15 y). Radionuclide angiography, two-dimensional
echocardiography and BMIPP and gated sestamibi scintigraphy were performed
with the patient at rest before and >6 mo after treatment (revascularization
in 13 patients and conservative therapy in 7 patients). In 7 patients, radionuclide
angiography was repeated after 1 y. RESULTS: On a patient basis, mismatching
with BMIPP less than sestamibi was noted in 15 patients at baseline. Of these
15 patients, 11 had significant functional improvement at follow-up versus
only 1 of the 5 patients with a matched decreased uptake. Hence, the combined
sestamibi/BMIPP was 73% positive and 80% negative in predicting functional
outcome, with a global accuracy of 75%. On a segmental basis, using an optimal
threshold of uptake defined by receiver operating characteristic curve analysis,
sestamibi was only 63% accurate in predicting regional outcome. Adding BMIPP
improved the accuracy to 80% (P = 0.001). At follow-up, significant mismatching
was still noted in 7 patients in the revascularized group and 1 in the medically
treated group. The mismatch was associated with a further increase in ejection
fraction at 1-y follow-up in only the revascularized group. CONCLUSION: In
patients with chronic left ventricular dysfunction after infarction, a mismatching
with BMIPP less than sestamibi reliably identifies jeopardized but viable
myocardium and predicts functional recovery with an accuracy similar to that
reported in the acute and subacute phases of the infarction.
PMID: 10492367 [PubMed - indexed for MEDLINE]-
Assessment of improvement of myocardial
fatty acid uptake and function after revascularization
using iodine-123-BMIPP.
Taki J, Nakajima K, Matsunari I, Bunko H, Takata S,
Kawasuji M, Tonami N.
Department of Nuclear Medicine, Kanazawa University School of Medicine, Japan.
We used beta-methyl iodophenyl pentadecanoic acid (BMIPP) to evaluate changes
in myocardial fatty acid utilization before and after revascularization and
the ability of BMIPP to predict functional recovery in patients with chronic
coronary artery disease. METHODS: Thirty-four patients with chronic coronary
artery disease (60 +/- 10 yr) underwent BMIPP and 201Tl SPECT (stress-reinjection
201Tl in 29 patients and resting 201Tl in 5 patients) before and 2-5 wk after
percutaneous transluminal angioplasty (n = 23) or coronary artery bypass
surgery (n = 11). Cardiac function was evaluated by gated blood-pool scintigraphy
(n = 26) or two-dimensional echocardiography (n = 8) before and after revascularization.
RESULTS: In 32 patients with reduced BMIPP uptake before revascularization,
scintigraphic findings with 201Tl improved in 28 patients after revascularization.
In these 28 patients, BMIPP uptake improved in 20 patients (71%). Wall motion
abnormality was observed in 16 of these 20 patients before revascularization,
with 15 showing wall motion improvement after revascularization. In eight
patients without improvement of BMIPP uptake, despite 201Tl uptake improvement,
wall motion abnormality was observed in four patients before revascularization;
after revascularization, one showed wall motion recovery, and three did not.
Ejection fraction (EF) improvement after revascularization correlated best
with the area of improved BMIPP uptake (r = 0.84, p < 0.0005). EF improvement
also correlated with the area of improved reinjection 201Tl uptake (r = 0.54,
p < 0.05) and improved 201Tl uptake at stress after revascularization
(r = 0.48, p < 0.05). The area of discordant uptake of BMIPP less than
reinjection 201Tl uptake before revascularization was a good predictor of
EF improvement after revascularization (r = 0.58, p < 0.01); however,
the area of reversible 201Tl defect was not (r = 0.34, p = 0.15). CONCLUSION:
In patients with chronic coronary artery disease, functional improvement
after revascularization is closely related to the recovery of BMIPP uptake.
Discordant BMIPP uptake less than reinjection 201Tl uptake is a potential
predictor of functional recovery.
PMID: 9379183 [PubMed - indexed for MEDLINE]-
Prognostic value of iodine-123 labelled
BMIPP fatty acid analogue imaging in patients with myocardial
infarction.
Tamaki N, Tadamura E, Kudoh T, Hattori N, Yonekura Y,
Nohara R, Sasayama S, Ikekubo K, Kato H, Konishi J.
Department of Nuclear Medicine, Hokkaido University School of Medicine, Kita-15,
Nishi-7, Kita-ku, Sapporo, 060, Japan.
This study was undertaken to evaluate the prognostic value of iodine-123
labelled 15-iodophenyl-3-R,S-methyl pentadecanoic acid (BMIPP) imaging in
patients with myocardial infarction. BMIPP is an iodinated methyl branched
fatty acid analogue which is trapped in the myocardium with little washout,
thereby reflecting fatty acid utilization in the myocardium. We previously
reported that in patients with myocardial infarction, regions are often observed
where reduced BMIPP uptake is seen relative to thallium-201 perfusion at
rest. However, the clinical significance of such discordant BMIPP uptake
remains unknown. Fifty consecutive patients with chronic myocardial infarction
referred for stress thallium scan and coronary arteriography underwent BMIPP
imaging at rest. Each patient was in a stable condition at the time of the
radionuclide study. Follow-up was performed at a mean interval of 23 months
to investigate the prognostic implications of the radionuclide studies. Nine
patients had cardiac events during the follow-up period. Univariate analysis
showed that the number of discordant BMIPP versus 201TL uptake segments was
the best predictor of future cardiac events (P=0.0245), followed by the presence
of discordant BMIPP uptake (P=0.0388) and the number of 201TL redistribution
segments (P=0.0444). When all the clinical and radionuclide variables were
analysed by Cox regression analysis, the presence of discordant BMIPP uptake
was the best, and an independent, predictor of future cardiac events (chi
2=8.5) followed by the number of coronary stenoses on angiography (chi 2=3.9).
These preliminary data suggest that decreased BMIPP uptake relative to 201TL
is a valuable predictor of future cardiac events in patients with myocardial
infarction. Areas with such discordant BMIPP uptake may contain jeopardized
myocardium where fatty acid utilization has been severely suppressed relative
to myocardial perfusion.
PMID: 8599958 [PubMed - indexed for MEDLINE]-
Comment in:
Increased uptake of iodine-123-BMIPP in chronic
ischemic heart disease: comparison with fluorine-18-FDG SPECT.
Sloof GW, Visser FC, Bax JJ, van Lingen A, Eersels
J, Knapp FF Jr, Teule GJ.
Department of Nuclear Medicine, Free University Hospital, Amsterdam, The
Netherlands.
To evaluate the potential role of 15-p-[123I]iodophenyl-3-(R,S)-methylpentadecanoic
acid (BMIPP) for the assessment of myocardial viability, the patterns of
BMIPP versus 18F-fluorodeoxyglucose (FDG) uptake were evaluated in patients
with chronic ischemic heart disease. METHODS: Twenty-one patients with
stable chronic coronary artery disease underwent resting TI SPECT to delineate
myocardial perfusion followed by FDG SPECT to detect residual viability
in regions showing perfusion defects. Resting BMIPP SPECT was obtained
on a separate day. SPECT images were displayed as polar maps (13 segments)
and analyzed semiquantitatively. A total of 273 segments were analyzed.
RESULTS: In 87 (32%) of the segments, a perfusion defect was observed.
In perfusion defects, the distributions of BMIPP/TI (mis)matches were significantly
different (p < 0.0001) between the FDG viable (n = 42) and nonviable
(n = 45) segments. A BMIPP/TI mismatch (BMIPP uptake higher than perfusion)
was found in 74% of FDG viable segments, whereas a BMIPP/TI match (BMIPP
uptake equal or lower than perfusion) was found in 69% of FDG nonviable
segments. Agreement between matching or mismatching of segments was assessed
to be 71%. Agreement was 81% when the data were analyzed on a patient basis.
The observed frequency of BMIPP/TI mismatches was significantly higher
(p < 0.05) in segments with an old myocardial infarction (20 of 36;
55%) than it was in subacute infarcted myocardium (5 of 21; 24%). CONCLUSION:
In chronically hypoperfused myocardium, an increased BMIPP uptake relative
to perfusion was detected, which is different from the decreased BMIPP
uptake often reported in (sub)acute myocardial ischemia. Therefore, the
interval from infarction may be an important factor in the interpretation
of BMIPP scintigraphic data. Increased BMIPP uptake was associated with
FDG/TI mismatches and may, therefore, confirm myocardial viability. Some
segments with a FDG/TI mismatch, however, revealed a BMIPP/TI match. These
segments may contain viable but more severely damaged tissue. Further studies
on functional recovery are warranted to assess the significance of a BMIPP/perfusion
(mis)match for tissue viability.
PMID: 9476931 [PubMed - indexed for MEDLINE]
42. Knuuti J, Nuutila P, Ruotsalainen
U et al. Euglycemic hyperinsulinemic clamp and oral glucose
load in stimulating myocardial glucose utilization during positron
emission tomography. J Nucl Med 1992; 33: 1255–1262.
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]
44. Bax JJ, Visser FC, Veening
MA et al. FDG SPECT image quality using acipimox; comparison
with oral glucose loading and hyperinsulinemic glucose clamping.
Eur J Nucl Med 1996; 23: 1051–1055.
Fluorine-18-fluorodeoxyglucose cardiac
imaging using a modified scintillation camera.
Sandler MP, Bax JJ, Patton JA, Visser FC, Martin WH,
Wijns W.
Department of Radiology and Radiological Sciences, Vanderbilt University
Medical Center, Nashville, Tennessee 37232-2675, USA.
Conventional 201TI and hexakis 2-methoxy-2-isobutyl isonitrile studies are
less accurate as compared to FDG PET in the prediction of functional recovery
after revascularization in patients with injured but viable myocardium. The
introduction of a dual-head variable-angle-geometry scintillation camera
equipped with thicker crystals (5/8 in.) and high-resolution, ultrahigh-energy
collimators capable of 511 keV imaging has permitted FDG SPECT to provide
information equivalent to that of PET for the detection of injured but viable
myocardium in patients with chronic ischemic heart disease. The development
of standardized glucose-loading protocols, including glucose-insulin-potassium
infusion and the potential use of nicotinic acid derivatives, has simplified
the method of obtaining consistently good-to-excellent quality FDG SPECT
cardiac studies. FDG SPECT may become the modality of choice for evaluating
injured but viable myocardium because of enhanced availability of FDG, logistics,
patient convenience, accuracy and cost-effectiveness compared to PET.
Publication Types:
PMID: 9867138 [PubMed - indexed for MEDLINE]
-
Direct comparison of fluorine-18-FDG
SPECT, fluorine-18-FDG PET and rest thallium-201 SPECT
for detection of myocardial viability.
Burt RW, Perkins OW, Oppenheim BE, Schauwecker DS, Stein
L, Wellman HN, Witt RM.
Department of Radiology, Richard L. Roudebush Veteran's Affairs Medical Center,
Indianapolis, Indiana.
Twenty consecutive patients were evaluated for presumptive myocardial viability
using rest TI-SPECT, FDG-PET and FDG-SPECT. The FDG studies were performed
after rest TI-SPECT to guide intervention or medical management. METHODS:
Twenty patients with proven coronary artery disease, either known or suspected
to have previous myocardial infarction and persistent perfusion defects shown
by rest reinjection TI-SPECT, underwent FDG-PET and subsequent FDG-SPECT
with a three-detector SPECT camera. FDG-PET and SPECT images were compared
by five observers to determine if any fixed thallium segments were visualized
by either FDG imaging method. RESULTS: Thirteen of 60 fixed segments were
shown probably viable by FDG-SPECT (8 of 20 patients) and 14 of 60 by FDG
PET (7 of 20 patients). Two patients had fixed thallium segments found probably
viable with FDG by SPECT alone and one by PET alone. CONCLUSION: FDG is shown
to provide additional information about myocardial viability. Both SPECT,
using a three-detector camera, and PET with a specialized instrument are
equally effective for imaging FDG in this application.
PMID: 7830109 [PubMed - indexed for MEDLINE]-
-
Prediction of improvement of contractile
function in patients with ischemic ventricular dysfunction
after revascularization by fluorine-18 fluorodeoxyglucose
single-photon emission computed tomography.
Bax JJ, Cornel JH, Visser FC, Fioretti PM, van Lingen
A, Huitink JM, Kamp O, Nijland F, Roelandt JR, Visser CA.
Department of Cardiology, University Hospital Leiden, The Netherlands.
OBJECTIVES: We evaluated the use of fluorine-18 fluorodeoxyglucose (FDG)
and single-photon emission computed tomography (SPECT) to predict improvement
of left ventricular ejection fraction (LVEF) after revascularization. BACKGROUND:
FDG SPECT has recently been proposed for assessment of myocardial viability.
However, FDG SPECT still awaits validation in terms of predicting improvement
of contractile function after revascularization in patients with poor left
ventricular (LV) function. METHODS: Fifty-five patients with contractile
dysfunction (including 22 with LVEF < 30%) underwent FDG SPECT during
hyperinsulinemic glucose clamping and early thallium-201 SPECT (to assess
perfusion). Improvement of LV function was evaluated 3 months after revascularization
with echocardiography and radionuclide ventriculography. RESULTS: The 55
patients were arbitrarily classified into two groups: 19 with three or more
viable, dysfunctional segments on FDG SPECT and 36 with less than three viable,
dysfunctional segments. LVEF increased significantly in the first group,
from 28 +/- 8% (mean +/- SD) before to 35 +/- 9% (p < 0.01) after revascularization.
In the second group, LVEF remained unchanged after revascularization (45
+/- 14% vs. 44 +/- 14%, p = NS). The 22 patients with severely depressed
LV function were similarly classified into two groups: 14 with three or more
viable segments on FDG SPECT in whom LVEF improved significantly (25 +/-
6% vs. 32 +/- 6%) and 8 with less than three viable segments in whom LVEF
remained unchanged (24 +/- 6% vs. 25 +/- 6%). CONCLUSIONS: This study shows
that FDG SPECT can identify patients in whom LV function improves after revascularization.
Because SPECT is widely available, this technique may contribute to more
routine use of FDG for determination of viability.
PMID: 9247508 [PubMed - indexed for MEDLINE]
48. Bax JJ, Patton J, Poldermans
D, Elhendy A, Sandler MP. FDG imaging with PET and SPECT. Cardiac
applications. Semin Nucl Med 2000; in press.
Comment in:
Relationship between preoperative viability and
postoperative improvement in LVEF and heart failure symptoms.
Bax JJ, Visser FC, Poldermans D, Elhendy A, Cornel
JH, Boersma E, Valkema R, Van Lingen A, Fioretti PM,
Visser CA.
Department of Cardiology, Leiden University Medical Center, Leiden, The
Netherlands.
The presence of myocardial viability is predictive of improvement in regional
left ventricular (LV) function after revascularization. Studies on predicting
improvement in global LV function are scarce, and the amount of viable
myocardium needed for improvement in LV ejection fraction (LVEF) after
revascularization is unknown. Moreover, whether the presence of viability
is associated with relief of heart failure symptoms after revascularization
is uncertain. Hence, the aims were to define the extent of viable myocardium
needed for improvement in LVEF and to determine whether preoperative viability
testing can predict improvement in heart failure symptoms. METHODS: Patients
(n = 47) with ischemic cardiomyopathy (mean LVEF +/- SD, 30% +/- 6%) undergoing
surgical revascularization were studied with 18F-FDG SPECT to assess viability.
Regional and global function were measured before and 3-6 mo after revascularization.
Heart failure symptoms were graded according to the New York Heart Association
(NYHA) criteria, before and 3-6 mo after revascularization. RESULTS: The
number of viable segments per patient was directly related to the improvement
in LVEF after revascularization (r = 0.79, P < 0.01). Receiver operating
characteristic curve analysis revealed that the cutoff level of four viable
segments (representing 31% of the left ventricle) yielded the highest sensitivity
and specificity (86% and 92%, respectively) for predicting improvement
in LVEF. Furthermore, the presence of four or more viable segments predicted
improvement in heart failure symptoms after revascularization, with positive
and negative predictive values of 76% and 71%, respectively. CONCLUSION:
The presence of substantial viability (four or more viable segments, 31%
of the left ventricle) on FDG SPECT is predictive of improvement in LVEF
and heart failure symptoms postoperatively.
PMID: 11197985 [PubMed - indexed for MEDLINE]
-
Prediction by postexercise fluoro-18
deoxyglucose positron emission tomography of improvement
in exercise capacity after revascularization.
Marwick TH, Nemec JJ, Lafont A, Salcedo EE, MacIntyre
WJ.
Department of Cardiology, Cleveland Clinic Foundation, Ohio.
The extent of ischemic and hibernating myocardium, which may be detected
by increased postexercise uptake of fluoro-18 deoxyglucose (FDG) using positron
emission tomography, may determine the degree of functional benefit after
revascularization. This study examined the influence of the amount of this
FDG-avid myocardium on changes in left ventricular function and exercise
parameters after revascularization. Echocardiography and exercise testing
were performed before and after intervention in 23 patients who had undergone
positron emission tomography for the evaluation of myocardial perfusion (using
rubidium-82), and postexercise FDG imaging in the fasting state. Follow-up
echocardiography (22 +/- 14 weeks after revascularization) was compared with
preoperative FDG activity in 7 myocardial regions per patient. Systolic function
improved after intervention in 19 of 26 malperfused, dysfunctional FDG-avid
regions (73%), and did not improve in 35 of 47 dysfunctional regions without
increased FDG uptake (74%). The influence of the amount of FDG-avid tissue
on changes in functional state was examined by comparing 9 patients with
multiple (greater than or equal to 2) FDG-avid regions with the remainder.
Those with multiple FDG-avid regions demonstrated improvement in peak rate-pressure
product (20 +/- 4 to 26 +/- 4 x 10(3), p less than 0.02), and percentage
of maximal heart rate achieved at peak (84 +/- 10% to 93 +/- 6%, p = 0.04),
neither of which changed significantly in the remaining patients. Exercise
capacity increased from 5.6 +/- 2.7 to 7.5 +/- 1.7 METS in the group with
multiple FDG-avid regions; this increase of 55 +/- 18% exceeded the increase
of 13 +/- 10% in the remainder (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 1550012 [PubMed - indexed for MEDLINE]-
-
Quantitative relation between myocardial
viability and improvement in heart failure symptoms after
revascularization in patients with ischemic cardiomyopathy.
Di Carli MF, Asgarzadie F, Schelbert HR, Brunken RC,
Laks H, Phelps ME, Maddahi J.
Department of Medical and Molecular Pharmacology, University of California
at Los Angeles, School of Medicine, USA.
BACKGROUND: Studies of patients with coronary artery disease and left ventricular
dysfunction have shown that preoperative quantification of myocardial viability
may be clinically useful to identify those patients who will benefit most
from revascularization both functionally and prognostically. However, the
relation between preoperative extent of viability and change in heart failure
symptoms has not been documented carefully. We assessed the relation between
the magnitude of improvement in heart failure symptoms after coronary artery
bypass surgery (CABG) and the extent of myocardial viability as assessed
by use of quantitative analysis of preoperative positron emission tomography
(PET) images. METHODS AND RESULTS: We studied 36 patients with ischemic cardiomyopathy
(mean left ventricular ejection fraction, 28 +/- 6%) undergoing CABG. Preoperative
extent and severity of perfusion abnormalities and myocardial viability (flow-metabolism
mismatch) were assessed by use of quantitative analysis of PET images with
13N ammonia and fluorine-18-deoxyglucose. Each patient's functional status
was determined before and after CABG by use of a Specific Activity Scale.
Mean perfusion defect size and severity were 63 +/- 13% and 33 +/- 12%, respectively.
Total extent of a PET mismatch correlated linearly and significantly with
percent improvement in functional status after CABG (r = .87, P < .0001).
A blood flow-metabolism mismatch > or = 18% was associated with a sensitivity
of 76% and a specificity of 78% for predicting a change in functional status
after revascularization. Patients with large mismatches (> or = 18%) achieved
a significantly higher functional status compared with those with minimal
or no PET mismatch (< 5%) (5.7 +/- 0.8 versus 4.9 +/- 0.7 metabolic equivalents,
P = .009). This resulted in an improvement of 107% in patients with large
mismatches compared with only 34% in patients with minimal or no PET mismatch.
CONCLUSIONS: In patients with ischemic cardiomyopathy, the magnitude of improvement
in heart failure symptoms after CABG is related to the preoperative extent
and magnitude of myocardial viability as assessed by use of PET imaging.
Patients with large perfusion-metabolism mismatches exhibit the greatest
clinical benefit after CABG.
PMID: 8521565 [PubMed - indexed for MEDLINE]
-
Comment on:
Fluorodeoxyglucose imaging to assess myocardial
viability: PET, SPECT or gamma camera coincidence imaging?
Bax JJ, Wijns W.
Publication Types:
PMID: 10565786 [PubMed - indexed for MEDLINE]
-
The clinical role of metabolic imaging
of the heart by positron emission tomography.
Schwaiger M, Hicks R.
Department of Internal Medicine, University of Michigan Medical Center, Ann
Arbor 48109-0028.
Publication Types:
PMID: 2013798 [PubMed - indexed for MEDLINE]
Prediction of improvement of ventricular
function after revascularization. 18F-fluorodeoxyglucose
single-photon emission computed tomography vs low-dose
dobutamine echocardiography.
Cornel JH, Bax JJ, Fioretti PM, Visser FC, Maat AP,
Boersma E, van Lingen A, Elhendy A, Roelandt JR.
Thoraxcenter, University Hospital Rotterdam-Dijkzigt, The Netherlands.
AIMS: To compare assessment of myocardial flow and glucose metabolism by
single-photon emission computed tomography (SPECT) with low-dose dobutamine
echocardiography in predicting improvement in regional and global left ventricular
function after coronary artery bypass grafting. METHODS AND RESULTS: Thirty
patients with regional wall motion abnormalities (mean ejection fraction
32 +/- 19%) were studied with low-dose dobutamine echocardiography (5 and
10 micrograms. kg-1 min-1) and thallium-201/ 18F-fluorodeoxyglucose(FDG)
SPECT prior to surgery. For comparative analysis, a 13-segment model was
used. Postoperative improvement was predicted if the echocardiogram showed
that wall motion abnormalities were reversible during the dobutamine infusion
and there was normal perfusion or relatively increased FDG uptake in perfusion
defects (mismatch) in dyssynergic segments on SPECT. After surgery, ventricular
function was reassessed. An echocardiogram was taken at the 3 month follow-up
with the patient at rest. Regional wall motion had improved in 62/168 (37%)
revascularized segments. In predicting functional outcome, low-dose dobutamine
echocardiography reached a sensitivity of 89% and a specificity of 82%, with
a positive predictive value of 74% and a negative predictive value of 93%,
whereas for thallium-201/FDG SPECT these values were 84%, 86%, 78% and 90%,
respectively. In patients with more than two viable segments on either technique,
the wall motion score index, a surrogate of global ventricular function,
improved significantly. CONCLUSION: For the optimal prediction of functional
outcome, combined assessment of flow and FDG imaging is needed. Both thallium-201/FDG
SPECT and low-dose dobutamine echocardiography appear comparable and similarly
accurate in predicting improvement of left ventricular function after surgical
revascularization.
Publication Types:
PMID: 9183585 [PubMed - indexed for MEDLINE]
|
Books,