(Circulation. 1995;92:3436-3444.)
© 1995 American Heart Association, Inc.
Articles |
Quantitative Relation Between Myocardial Viability and Improvement in Heart Failure Symptoms After Revascularization in Patients With Ischemic Cardiomyopathy
From the Division of Nuclear Medicine, Department of Medical and Molecular Pharmacology, Laboratory of Nuclear Medicine, Laboratory of Biomedical and Environmental Sciences; the Crump Institute for Biological Imaging; and the Division of Cardiothoracic Surgery (H.L.), Department of Surgery, University of California at Los Angeles, School of Medicine.
Correspondence to Marcelo F. Di Carli, MD, Positron Emission Tomography Center, Children's Hospital of Michigan, 3901 Beaubien Blvd, Detroit, MI 48201-2196. E-mail: mdicarli@pet.wayne.edu.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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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 
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
(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.
Key Words: cardiomyopathy • myocardium • revascularization • tomography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Symptomatic left ventricular dysfunction is associated with frequent hospitalizations and poor survival in patients with coronary artery disease. Previous studies1 2 indicate that myocardial revascularization in selected patients improves survival and may also improve heart failure symptoms. Alleviation of heart failure symptoms is of utmost importance in deciding the appropriate treatment strategy. Indeed, it is the primary reason that patients with left ventricular dysfunction seek medical attention. However, because surgical mortality in these patients is high, preoperative assessment of the amount of myocardial viability is crucial to identify patients who will benefit most from revascularization both prognostically and symptomatically.
PET with FDG has been used successfully to distinguish viable from infarcted myocardium.3 4 Increased glucose uptake in segments with reduced blood flow (flow-metabolism mismatch) indicates the presence of viable myocardium. A flow-metabolism mismatch identifies myocardium with a potentially reversible impairment of contractile function, average literature positive and negative predictive accuracies being 83% and 84%, respectively.5 6 7 8 9 10 Studies with either rest11 12 13 or exercise14 15 16 201Tl imaging protocols also demonstrated that they can provide clinically relevant information with respect to myocardial viability in patients with regional or global systolic dysfunction. In addition, previous clinical data acquired by use of resting 201Tl scintigraphy11 13 or metabolic imaging5 17 indicate that improvement in global LV systolic function is related to the anatomic extent of myocardial viability as assessed preoperatively. However, a quantitative correlation between the measured extent of viable myocardium and the change in heart failure symptoms has not been established.
The present study tested the hypothesis that improvement in heart failure symptoms after CABG in patients with ischemic cardiomyopathy would be related to the extent, magnitude, and location of viable myocardium, as determined by quantitative analysis of preoperative PET images.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Study Group
Forty-one consecutive patients with coronary artery disease and ischemic cardiomyopathy (mean LV ejection fraction, 27±7%; range, 15% to 42%) referred for assessment of myocardial viability and subsequent CABG were enrolled in the study. Global LV ejection fraction was obtained from contrast left ventriculography in 33 patients and echocardiography in 8 patients. Four patients died during the in-hospital postoperative period and 1 patient died suddenly before follow-up. The remaining 36 patients constitute the study cohort. Twenty-six of these 36 patients were part of a previous study in which we reported that patients with blood flow–metabolism PET mismatches have a survival benefit if they are revascularized.18 In the present study, we focused the analysis on the relation between the extent, intensity, and location of PET mismatches and the magnitude of heart failure symptom improvement after CABG. There were 31 men and 5 women, 49 to 81 years of age (mean, 66±8 years). Twenty-eight patients (78%) had a history of previous Q-wave myocardial infarction. None of the individuals had recent clinical infarctions. Nine patients (25%) had previous CABG. Thirty patients had >70% luminal narrowing of all three major epicardial coronary arteries, and the remaining 6 had two-vessel disease. The mean LV diastolic dimension by echocardiography was 64±7 mm (range, 50 to 75 mm).
Assessment of Functional Status
Functional status of patients
was assessed before and after CABG
(mean follow-up, 25±14 months) by use of a Specific Activity Scale
previously described and validated by Goldman et al.19 The
Specific Activity Scale is based on approximations of the
metabolic costs of a variety of personal care, housework,
occupational, and recreational activities.20 21
Goldman et
al19 demonstrated a 68% agreement between the Specific
Activity Scale system and exercise treadmill performance, which
was significantly higher than that of the Canadian
Cardiovascular Society system (59%) and New York Heart
Association estimates (51%). Furthermore, in the same
study,19 the Specific Activity Scale had a reproducibility
of 73%. This was similar to the reproducibility observed with the
Canadian Cardiovascular Society system but
significantly higher than that obtained by use of the New York Heart
Association criteria. Using a previously validated interview
protocol,19 we determined whether specific activities were
performed and, in particular, what symptoms were provoked by them. A
patient was considered able to perform a given number of METS if the
appropriate activity was performed to completion, with or without
symptoms. Conversely, if the activity was not performed because of
symptoms, fear of symptoms, or habit, and if no other activity of
approximately equal or higher metabolic cost was performed,
the patient was considered unable to attain the given
metabolic load. Patients were placed into a Specific
Activity Scale functional class according to the metabolic
load associated with the most strenuous activity performed before and
after myocardial revascularization.19
In each patient, the functional status before and after CABG was
determined by interviews conducted either personally or by telephone
contact with the patient by an investigator who was blinded to the PET
data.
Positron Emission Tomography
Resting regional myocardial
perfusion and glucose uptake were
assessed with 13N-ammonia, FDG, and PET. Imaging was
performed on a whole-body positron emission tomograph (model
931-108, Siemens-Computer Technology, Inc). Studies were acquired in
the glucose-loaded state, after oral administration of 50 g
glucose. A 20-minute transmission scan was recorded for correction
of photon attenuation. Fifteen transaxial emission images were then
obtained for 20 minutes, beginning 7 minutes after an intravenous
injection of 20 mCi of 13N-ammonia. Then, 10 mCi of FDG was
injected intravenously and, after 30 minutes (to allow for decay of
13N-ammonia and for metabolic trapping of FDG
in the myocardium) another set of transaxial images was
acquired for 20 minutes.
Image Analysis
Transaxial images were reoriented on a
Macintosh IIci personal
workstation (Apple Computer Inc) into six contiguous short-axis and
three modified apical slices of the LV.22 23
Analysis of relative myocardial perfusion, glucose uptake, and
their relation was performed by use of a method described previously in
detail.22 Briefly, volume-weighted polar maps were
generated from circumferential profiles of the maximal myocardial count
activity obtained along 60 equally spaced radii generated from the
center of the LV cavity. The circumferential profiles were constrained
by elliptical regions of interest encompassing the LV
myocardium on each of the six short-axis slices. The
"raw" 13N-ammonia and FDG polar maps were normalized
to myocardial regions with the highest 13N concentration.
Extent of a perfusion abnormality was computed as the number of pixels
with relative myocardial 13N-ammonia activity below the
lower limit of normal (mean-2 SD) in the entire LV. Severity of a
perfusion abnormality was assessed by computing the average percent
reduction of the relative myocardial 13N-ammonia uptake
below the lower limit of normal (mean-2 SD). To identify myocardial
regions with increases in glucose uptake relative to blood flow, the
FDG polar maps were then compared with the 13N-ammonia
maps, resulting in a difference polar map. These difference maps were
subsequently compared with a database of normals. Depending on the FDG
uptake, hypoperfused regions were categorized into PET mismatch and PET
match. A concordant reduction in FDG and 13N activities was
defined as a flow-metabolism match, whereas an
FDG/13N difference of >2 SD above the normal mean was
defined as a flow-metabolism mismatch. Scintigraphic
extent of a PET mismatch was expressed as percent of the entire LV and
of each coronary vascular territory (LAD, left circumflex
artery, and right coronary artery territories). Average
severity of a PET mismatch (FDG/13N difference) in the
entire LV myocardium and in each vascular territory was
expressed as the average number of SD above the normal mean.
Statistical Analysis
All continuous data are presented as
mean±SD. Survival
probability of the entire patient population was estimated by use of
the Kaplan-Meier method. Paired comparisons between preoperative and
follow-up data were performed with Student's t test or
Fisher's exact test as appropriate. Multiple groups were compared with
a single-factor ANOVA and the F test. For significant F values, the
Tukey test (with correction for group size) was used to identify
differences between pairs of groups. Linear regression analysis
was performed by least-squares fitting. The effect of covariates on
heart failure symptom improvement was assessed by use of multiple
logistic regression analysis.24 ROC curves were
derived according to the method described by Metz.25 A
probability of less than .05 was considered significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Coronary Artery Bypass Grafting
All patients underwent complete revascularization that was based on the anatomic distribution of coronary stenosis and review of operative reports. The mean number of grafts per patient was 4±0.8. In addition, no patient had mitral valve replacement or aneurysmectomy. Four of the 41 patients died during the in-hospital postoperative period (30-day operative mortality of 10%). Two of these 4 patients had ECG changes compatible with a postoperative infarction. All postoperative deaths were primarily due to worsening of heart failure. In patients who died within the 30-day postoperative period, preoperative PET imaging demonstrated flow-metabolism mismatches extending from 29% to 54% of the LV in 3 of 4 patients and a predominantly matched defect in 1 patient. In addition, 1 patient died suddenly before follow-up (20 months after CABG). In this patient, preoperative PET imaging demonstrated a flow-metabolism mismatch of 22%. The Kaplan-Meier estimate of the 2-year survival probability for the entire study group was 87%. The remaining 36 patients were free from ischemic events (nonfatal myocardial infarction or unstable angina); however, all patients had some degree of functional limitation during follow-up, as assessed by the Specific Activity Scale.
Relation Between Preoperative Symptoms and PET Imaging
Findings
At the time of hospitalization leading directly to CABG, all
patients had symptoms of congestive heart failure. Thirty-two
patients were in class III and 4 patients were in class IV heart
failure according to the Specific Activity Scale
classification.19 Thirteen patients also had angina
pectoris. Thirty-four patients (94%) were receiving
angiotensin-converting enzyme inhibitors,
30 patients (83%) furosemide, 28 patients (78%) digoxin, 20 patients
(56%) oral nitrates, 12 patients (33%) calcium channel blockers, and
5 patients (14%) ß-blockers.
Preoperative findings in the 36
patients with LV dysfunction are
summarized in Table 1
. For the entire study group, the
mean perfusion defect size was 63±13%, whereas the mean perfusion
defect severity was 33±12%. Similarly, the extent of
flow-metabolism match was 41±23%, indicating
extensive areas of myocardial infarction. However, despite the presence
of class III or class IV (Table 1, patients 4, 9, 31, and 35)
heart
failure on the Specific Activity Scale, preoperative PET imaging
demonstrated significant areas of flow-metabolism
mismatch averaging 23±22% of the LV, suggesting that advanced heart
failure symptoms do not exclude the presence of significant myocardial
viability.
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Average extent and mean severity of preoperative resting
perfusion
defects were similar in patients with and without angina (Table
1
). Of
note, the extent of flow-metabolism mismatch in the 13
patients with angina did not differ from that of the 23 patients
without angina (15±22% versus 27±21%, P=NS). Thus, the
presence of angina was not associated with more extensive areas of
viable but hibernating myocardium.
Correlation Between Postoperative Specific Activity Scale and
Exercise Tolerance
Fig 1 depicts the correlation
between postoperative
Specific Activity Scale classification and exercise capacity in 15
patients who performed treadmill exercises concurrently with the
interviews. All patients were clinically stable between both
assessments, and there were no changes in heart failure medications.
There was a significant correlation between the METS of activity
estimated by use of the Specific Activity Scale and those
calculated by use of exercise treadmill data
(y=2.3+0.5x, r=.73, SEE=1.02,
P=.002).
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Preoperative PET Findings and Change in Heart Failure
Symptoms
Univariate analysis. Results of
univariate analysis relating the extent and
severity of a perfusion defect, the extent and severity as well as the
product of the extent and severity (mismatch index) of a PET
mismatch, LV size, LV ejection fraction, and age are given in Table
2. Total scintigraphic extent of a PET mismatch was
related linearly to percent improvement in functional status after CABG
(r=.87, P<.0001, Fig 2); patients with
larger mismatches had the greatest improvement in symptoms of heart
failure. Furthermore, the anatomic location of a PET mismatch also
correlated with the change in functional status after CABG. The extent
of a PET mismatch in the territory of the LAD (r=.61,
P=.0001, Table 2) and the severity of a PET mismatch in
the
territory of the right coronary artery (r=.62,
P=.0001, Table 2) showed the highest correlations with
the change
in functional status after CABG.
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Multivariate analysis. To determine the independent contribution of each variable for predicting a change in functional status after CABG, a multivariate analysis that used a stepwise procedure was performed. Results indicated that total extent of a PET mismatch (F=40.2, P=.0001) and age (F=4.1, P=.05) were the only two independent predictors of the change in functional status after CABG. Of note, neither the severity of a mismatch nor the mismatch index (product of its extent and severity) added information once the extent of mismatch was entered into the model. The regression equation for the predicted improvement in METS was -0.86+0.0356 · total extent of PET mismatch+0.0308 · age.
To further correlate the anatomic location of mismatches on PET imaging with the degree of heart failure symptom improvement after CABG, the extent and intensity of a mismatch and their interaction in the three major coronary territories (LAD, left circumflex artery, and right coronary artery) were investigated in a separate multivariate model. Results indicated that the combination of the extent and severity of a flow-metabolism mismatch in the LAD territory (F=22.39, P=.0001) and the severity of a flow-metabolism mismatch in the right coronary artery territory (F=12.04, P=.002) were the only two independent predictors of change in heart failure symptoms after CABG.
Flow-Metabolism PET Mismatch for Predicting Improvement
in Symptoms of Heart Failure
As shown in Fig 2, the
greatest improvement in heart failure
symptoms occurred in patients with the largest mismatches on
quantitative analysis of the blood flow and glucose
metabolism PET images. To determine the total extent of a
PET mismatch that best predicted an improvement in functional class of
at least one grade, a ROC analysis was performed. On the basis
of this analysis, the optimum operating point on the curve
corresponded to or was greater than an 18% PET mismatch on
quantitative analysis. This operating point was associated with
a sensitivity of 76% and a specificity of 78% for predicting an
improvement in functional class of at least one grade (Fig 3).
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Accordingly, patients were divided into three groups. Group A consisted
of 11 patients with minimal (<5%) or no PET mismatch before CABG
(mean, 1.5±1.4%). Group B consisted of 8 patients with modest
preoperative mismatches involving between 5% and 17% of the LV (mean,
13±4%). Group C comprised 17 patients with large mismatches involving
18% of the LV myocardium (mean, 41±19%). Fig 4
demonstrates that all groups of patients exhibited
some improvement in heart failure symptoms after CABG. Patients in
group C (18% mismatch) achieved a modest but significantly higher
functional state compared with patients in groups A and B (5.7±0.8
METS in group C versus 4.9±0.7 and 4.9±0.5 METS in groups A and
B,
respectively, P=.009). More importantly, the higher level of
estimated METS achieved by patients in group C after CABG resulted in
an average improvement of 107% (2.8±0.7 METS to 5.7±0.8 METS,
P<.001, Fig 4). In contrast, patients without significant
mismatches (<5%) or with relatively small mismatches (5% to 17%)
exhibited only relatively small improvements in METS of activity after
CABG of 34% and 42% compared with baseline, respectively (ANOVA,
P<.001) (Fig 4).
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Patients in groups A, B, and C did
not differ with respect to age,
prior CABG, prior myocardial infarction, LV
end-diastolic diameter, LV ejection fraction, and
extent of angiographic coronary disease. Furthermore, the three
groups of patients did not differ with respect to medications affecting
the severity of heart failure symptoms after CABG (Table 3).
However,
patients in group C had more severe symptoms of heart failure before
CABG than those in groups A and B (2.8±0.7 versus 3.7±0.6 and
3.6±0.7 METS, P<.05, Fig 4), presumably due to the
presence of larger resting perfusion abnormalities (68±9% versus
59±10% and 58±8%, P<.05) and
flow-metabolism mismatches (Fig 4).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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An accurate, noninvasive determination of myocardial viability is clinically important to identify coronary artery disease patients with severely depressed LV function who will benefit most from revascularization. Previous studies indicate that preoperative imaging with myocardial perfusion, metabolism, or both can provide clinically useful information for identifying patients with coronary artery disease and LV dysfunction who will benefit from revascularization both functionally5 6 7 8 9 10 11 12 13 14 15 16 17 and prognostically.18 26 27 28 Nonetheless, the question of whether revascularization will alleviate heart failure symptoms in these patients, which is often the primary functional limitation, remains an important concern for patients and physicians. The findings in the present study suggest that the magnitude of improvement in heart failure symptoms after CABG in patients with ischemic cardiomyopathy is related to the quantitative extent of myocardial viability as determined preoperatively. Furthermore, our results also suggest that the beneficial gain in functional capacity after CABG is related to the preoperative extent, magnitude, and anatomic location of a mismatch between blood flow and metabolism on PET imaging.
Significance of a Flow-Metabolism PET
Mismatch
In humans, the combined evaluation of regional myocardial
blood
flow and glucose metabolism allows identification of
specific metabolic patterns that occur in ischemic
but viable as well as in infarcted
myocardium.3 4 Increased glucose uptake in
segments with reduced blood flow (flow-metabolism
mismatch) indicates the presence of viable myocardium.
Conversely, a segmental concordant reduction in glucose utilization and
blood flow reflects necrosis and scar tissue formation. Previous
studies have confirmed extensively that a
flow-metabolism mismatch on PET imaging successfully
identifies potentially reversible myocardial dysfunction after
revascularization.5 6 7 8 9 10 17
Moreover,
the study by Tillisch et al5 reported a correlation
between scintigraphic extent of preoperative mismatch, as assessed
qualitatively, and improvement in LV ejection fraction after CABG. For
example, LV ejection fraction remained unchanged in patients with one
or fewer of eight anatomic segments with PET mismatch. In contrast, in
patients with two or more segments with mismatch before CABG, LV
ejection fraction improved from 30±11% to 45±14% 6 weeks after
CABG.
Observations
Our results suggest that the preoperative extent
of a
flow-metabolism mismatch is correlated linearly and
significantly with the magnitude of
postrevascularization improvement in heart
failure symptoms (Fig 2). Patients with large mismatches
(18%),
particularly in the LAD territory, had the greatest clinical benefit,
improving their functional status by 107%, which had an important
impact on the patients' quality of life. Before CABG, these patients
generally were not able to shower without experiencing significant
functional limitation; after CABG, they were able to walk at a rate of
4 miles per hour on level ground without significant functional
limitation. This change in functional status was significantly greater
than the improvement observed in patients without significant (<5%)
or with relatively small preoperative flow-metabolism
mismatches (5% to 17%), whose improvement was only 34% and 42%,
respectively. Although the absolute level of METS achieved by patients
in group C after CABG was statistically higher than that observed in
patients in groups A and B, the difference was only modest. Thus, the
greater improvement of patients in group C also was due to their lower
preoperative functional capacity (Fig 4). This difference may
relate to
the fact that patients in group C had significantly larger areas of
flow-metabolism mismatch, which likely influenced their
preoperative functional state. Nonetheless, our findings suggest that
patients presenting with advanced heart failure symptoms as the
primary functional limitation should not be presupposed as not having
clinically relevant areas of myocardial viability and thus be kept from
realizing a significant symptomatic (and probably
prognostic) benefit of revascularization. The
selected threshold of 18% of the LV with a
flow-metabolism mismatch was associated with the best
trade-off between sensitivity (76%) and specificity (78%) on the
ROC curve for predicting a change in functional capacity after CABG
(Fig 3). Our results agree with previous
reports1 2
demonstrating a significant improvement in heart failure symptoms after
CABG in patients with severely depressed LV function. However, our
findings contrast with those reported in the Coronary Artery
Surgery Study (CASS).29 In the CASS registry, the
percentage of patients presenting with predominant heart failure
symptoms who were alive and free from severe functional limitation at
5-year follow-up was not statistically different between medical
therapy and revascularization. Of note, in the CASS
study, patients were not categorized according to the absence or
presence of myocardial viability. The latter might explain the lack of
significant improvement in symptoms of heart failure in the surgical
group.
Although the overall relation between scintigraphic extent of a
flow-metabolism mismatch and functional improvement
after CABG was statistically significant, our data show that change in
heart failure symptoms can vary appreciably among patients with
comparable extent of flow-metabolism mismatch.
Additionally, there was some degree of improvement in heart failure
symptoms in patients without significant (<5%) or with relatively
small (<18%) mismatches (Fig 4). Of note, use of cardiac
medications
affecting the severity of heart failure symptoms was similar in groups
A, B, and C (Table 3). The reason for this variability
is unknown but may relate to physiological
limitations and/or limitations in some of the methodologies applied in
the present study. One possible explanation for the variable
postoperative change in heart failure symptoms among individual
patients with large mismatches may be the lack of effective improvement
in tissue perfusion despite a successful grafting of the
stenotic arteries, due to the presence of target vessels with
poor distal runoff. Indeed, in the study by Ragosta et
al,13 there was substantial improvement in the accuracy of
rest-redistribution thallium-201 scintigraphy for
predicting an improvement in systolic ventricular
function after adjusting for the adequacy of
revascularization, as assessed by postoperative
perfusion imaging. Another possible explanation for this variable
response to revascularization may be that our
definition of PET mismatch (preserved FDG activity in a region with
reduced perfusion) may have underestimated the presence of stunned
myocardium. Indeed, repetitive bouts of silent or
symptomatic ischemia superimposed on hibernating
myocardium or regions with normal or nearly normal blood
flow at rest, which went undetected by our definition of PET mismatch,
may have led to myocardial stunning with further impairment of
contractile function and worsened heart failure.30 Thus,
improvement in ventricular function due to stunning may
have contributed to the variable improvement of heart failure
symptoms among patients with comparable mismatches and to the observed
functional improvement in patients without significant or with
relatively small mismatches. A third possible explanation is that
improvement in LV diastolic function also may have
contributed to the observed interindividual variability in functional
status after CABG among patients with comparable extent of
flow-metabolism mismatches. LV diastolic
function is markedly impaired in chronic heart
failure31 32 and has been shown to improve after
successful myocardial
revascularization.33 34 35 In addition,
improvement in LV diastolic function, systolic
function due to stunning, or more likely a combination of both may
account for the improvement in heart failure symptoms observed in
patients with relatively small or no mismatches before CABG.
Unlike previous studies, which have concentrated on the functional outcome of hibernating myocardial regions after revascularization,5 6 7 8 9 10 11 12 13 15 16 17 the present study did not include a systematic assessment of LV function after CABG. Rather, the present study focused on the relation between myocardial viability as assessed preoperatively by FDG imaging and the postoperative change in heart failure symptoms by use of a readily accessible, valid, and reproducible clinical scale. Nevertheless, the linear relation between the change in functional status after CABG and the scintigraphic extent of a flow-metabolism mismatch on FDG imaging suggests an improvement in LV function as a possible mechanism. This hypothesis is supported by previous observations demonstrating an improvement in ventricular function after CABG only in patients with extensive areas of flow-metabolism mismatch (approximately 20% of the LV).5 17 Further support is provided by the results of Ragosta et al,13 who demonstrated a positive and significant correlation between improvement in systolic LV function and extent of myocardial viability as determined by rest-redistribution 201Tl imaging.
In the
present study, patients with heart failure and angina did
not exhibit more extensive areas of viable myocardium as
assessed by the flow-metabolism mismatch pattern. In
fact, our data showed that the extent of
perfusion-metabolism mismatches tended to be larger in
patients without angina. A flow-metabolism mismatch
refers to dysfunctional myocardium that, at rest, exhibits
reduced blood flow but preserved metabolic activity, a
pattern that many believe represents the metabolic
expression of hibernating myocardium. The clinical
manifestation of angina in patients with coronary artery
disease and LV dysfunction reflects a transient imbalance between
supply and demand in viable but not necessarily hibernating myocardial
regions. Alternatively, the presence of angina in these patients may
represent residual inducible ischemia in regions with
prior nontransmural infarction (which will be matched on PET) or in
regions with normal blood flow and metabolism at rest
(which will be normal on PET). Although it is conceivable that regional
blood flow in mismatched regions may worsen during stress and be
manifested clinically as angina, previous observations from our
laboratory36 suggest that only a fraction (49% in our
experience) of mismatched segments will display such a worsening in
regional perfusion during stress. Furthermore, our findings agree with
those of Ragosta et al13 in patients with coronary
artery disease and depressed LV function. They reported a lack of
correlation between the presence of angina and improvement in global LV
function after CABG. Our data also showed that advanced symptoms of
heart failure did not exclude the presence of extensive areas of
myocardial viability (Table 1). However, because only four
patients
were in class IV heart failure, definitive inferences regarding the
relation between the severity of heart failure and the presence of
viable myocardium must be limited.
Because the aim of the present study was to define the physiological relations between the response of heart failure symptoms to myocardial revascularization and the preoperative extent and magnitude of myocardial viability, no other imaging approaches were considered in the study design. For example, rest-redistribution thallium-201 scintigraphy alone,11 12 13 14 in combination with radiolabeled synthetic fatty acid imaging,37 or perhaps FDG,38 and single photon emission computed tomography have been shown to be useful in detecting clinically relevant myocardial viability. Although it seems conceivable that a similar relation between heart failure symptoms and myocardial viability could be found with different imaging modalities, this needs to be investigated further.
Study Limitations
Several potential methodological
limitations might have influenced
the results of the present study. First, the study population was a
selected group referred for assessment of myocardial viability and
subsequent CABG and not a consecutive group of patients with
ischemic cardiomyopathy. The applicability
of our findings to a cohort of patients with ischemic
cardiomyopathy who were not considered primarily
for CABG is less certain. Furthermore, due to the relatively small
number of patients, especially with class IV heart failure, definitive
inferences regarding the relation between the severity of heart failure
symptoms and myocardial viability must be limited.
Second, the functional status of patients was assessed by use of a Specific Activity Scale rather than more objective descriptors of exercise tolerance such as treadmill exercise or estimates of oxygen consumption. However, the Specific Activity Scale used in the present study has been shown previously to be a simple, reproducible, and valid system to assess the functional status of patients when compared with treadmill exercise data, even more so than widely adopted systems such as the New York Heart Association and Canadian Cardiovascular Society classifications.19 Moreover, the significant linear correlation between postoperative functional capacity as assessed by the Specific Activity Scale and the treadmill exercise data in the present study further supports the validity of the Specific Activity Scale as a measure of the patients' functional status. Third, the present report did not include a systematic assessment of regional or global LV function after CABG. Although the observed linear relation between improvement in heart failure symptoms and quantitative extent of a flow-metabolism mismatch on FDG imaging suggests an improvement in systolic LV function as an important mechanism, the relation between systolic function and heart failure symptoms after CABG needs to be investigated further.
Conclusions
The present study demonstrates that in coronary
artery
disease in patients with depressed LV function, preoperative
quantification of the extent and magnitude of myocardial viability is
predictive of the degree of improvement in heart failure symptoms after
CABG. Importantly, our results suggest that the beneficial gain in
functional capacity after CABG is related to the preoperative extent of
viable myocardium, magnitude of glucose uptake, and
anatomic location of a flow-metabolism mismatch on PET
imaging. The linear relation between the preoperative extent of viable
myocardium and improvement in functional status after CABG
suggests that the magnitude of functional improvement can be predicted.
These findings may be clinically useful for assessing the
risk-to-benefit ratio of myocardial
revascularization in patients with coronary
artery disease, severe LV dysfunction, and heart failure symptoms.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported in part by the Director of the Office of Energy Research, Office of Health and Environmental Research, Washington, DC, and NIH research grant HL-29845, Bethesda, Md. This work was completed during Dr Di Carli's tenure of a Research Fellowship Award from the American Heart Association, Los Angeles, Affiliate. The authors are indebted to Ron Sumida, Lawrence Pang, Francine Aguilar, Marc Holgan, and DerJenn Liu for their technical assistance in performing the PET studies; to Jeffrey A. Gornbein for his statistical assistance; and to Diane Martin for preparing the artwork.
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Footnotes |
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The Laboratory of Nuclear Medicine is operated for the US Department of Energy by the University of California under contract No. DE-FC03-87ER60615.
Received January 23, 1995; revision received June 12, 1995; accepted August 1, 1995.
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R. J. Kim, R. M. Judd, E.-L. Chen, D. S. Fieno, T. B. Parrish, and J. A. C. Lima Relationship of Elevated 23Na Magnetic Resonance Image Intensity to Infarct Size After Acute Reperfused Myocardial Infarction Circulation, July 13, 1999; 100(2): 185 - 192. [Abstract] [Full Text] [PDF]
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J. J. Bax, D. Poldermans, A. Elhendy, J. H. Cornel, E. Boersma, R. Rambaldi, J. R. T. C. Roelandt, and P. M. Fioretti Improvement of left ventricular ejection fraction, heart failure symptoms and prognosis after revascularization in patients with chronic coronary artery disease and viable myocardium detected by dobutamine stress echocardiography J. Am. Coll. Cardiol., July 1, 1999; 34(1): 163 - 169. [Abstract] [Full Text] [PDF]
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M. A. Auerbach, H. Schoder, C. Hoh, S. S. Gambhir, S. Yaghoubi, J. W. Sayre, D. Silverman, M. E. Phelps, H. R. Schelbert, and J. Czernin Prevalence of Myocardial Viability as Detected by Positron Emission Tomography in Patients With Ischemic Cardiomyopathy Circulation, June 8, 1999; 99(22): 2921 - 2926. [Abstract] [Full Text] [PDF]
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R. Senior, S. Kaul, and A. Lahiri Myocardial viability on echocardiography predicts long-term survival after revascularization in patients with ischemic congestive heart failure J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1848 - 1854. [Abstract] [Full Text] [PDF]
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The CHRISTMAS Study Steering Committee and Investi, J. G.F. Cleland, D. Pennel, S. Ray, G. Murray, P. MacFarlane, A. Cowley, A. Coats, and A. Lahiri The Carvedilol Hibernation Reversible Ischaemia Trial; Marker of Success (CHRISTMAS) Eur J Heart Fail, June 1, 1999; 1(2): 191 - 196. [Abstract] [Full Text] [PDF]
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T. H. Marwick, C. Zuchowski, M. S. Lauer, M.-A. Secknus, M. J. Williams, and B. W. Lytle Functional status and quality of life in patients with heart failure undergoing coronary bypass surgery after assessment of myocardial viability J. Am. Coll. Cardiol., March 1, 1999; 33(3): 750 - 758. [Abstract] [Full Text] [PDF]
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K.F. Fox, M.R. Cowie, D.A. Wood, A.J.S. Coats, P.A. Poole-Wilson, and G.C. Sutton New perspectives on heart failure due to myocardial ischaemia Eur. Heart J., February 2, 1999; 20(4): 256 - 262. [PDF]
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S. Firoozan, K. Wei, A. Linka, D. Skyba, N. C. Goodman, and S. Kaul A canine model of chronic ischemic cardiomyopathy: characterization of regional flow-function relations Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H446 - H455. [Abstract] [Full Text] [PDF]
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M. F. Di Carli, J. Maddahi, S. Rokhsar, H. R. Schelbert, D. Bianco-Batlles, R. C. Brunken, and B. Fromm LONG-TERM SURVIVAL OF PATIENTS WITH CORONARY ARTERY DISEASE AND LEFT VENTRICULAR DYSFUNCTION: IMPLICATIONS FOR THE ROLE OF MYOCARDIAL VIABILITY ASSESSMENT IN MANAGEMENT DECISIONS J. Thorac. Cardiovasc. Surg., December 1, 1998; 116(6): 997 - 1004. [Abstract] [Full Text] [PDF]
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