(Circulation. 1997;96:2884-2891.)
© 1997 American Heart Association, Inc.
Articles |
Dependency of Contractile Reserve on Myocardial Blood Flow
Implications for the Assessment of Myocardial Viability With Dobutamine Stress Echocardiography
From the Cardiovascular Division, Department of Internal Medicine (H.H.L., V.G.D.-R., P.A.L., M.C., J.F.W., P.J.R., R.J.G.) and the Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology (D.A.D., R.J.G.), Washington University School of Medicine, St Louis, Mo.
Correspondence to Robert J. Gropler, MD, Mallinckrodt Institute of Radiology, 510 S Kingshighway Blvd, St Louis, MO 63110. E-mail gropler{at}mirlink.wustl.edu
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Abstract |
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Background Contractile reserve, improvement in contractile function during inotropic stimulation, is a proposed marker of viable myocardium. This study was designed to address, in patients with left ventricular dysfunction due to chronic coronary artery disease, whether contractile reserve depends on myocardial blood flow.
Methods and Results We studied 19 patients, at rest and during dobutamine, with 2D echocardiography for regional mechanical function and PET for regional myocardial blood flow ([15O]water) and oxygen consumption ([11C]acetate). Of 166 myocardial segments, 21 had normal systolic function, 56 were dysfunctional but contractile reserve–positive, and 89 were dysfunctional and contractile reserve–negative. Myocardial blood flow at rest was lower in contractile reserve–negative (0.41±0.18 mL · g-1 · min-1) than in contractile reserve–positive (0.50±0.22 mL · g-1 · min-1) and normal segments (0.55±0.20 mL · g-1 · min-1, P<.009). After dobutamine infusion, blood flow increased less in contractile reserve–negative (0.63±0.38 mL · g-1 · min-1) than in contractile reserve–positive (1.28±0.65 mL · g-1 · min-1) and normal segments (1.93±0.83 mL · g-1 · min-1, P<.0001). Likewise, myocardial oxygen consumption was lower at rest in contractile reserve–negative (clearance rate of [11C]acetate, 0.043±0.012 min-1) than in contractile reserve–positive (0.048±0.01 min-1) and normal segments (0.058±0.008 min-1, P<.02). Myocardial oxygen consumption with dobutamine increased less in contractile reserve–negative (0.060±0.013 min-1) than in contractile reserve–positive (0.077±0.016 min-1) and normal segments (0.092±0.024 min-1, P<.0001). Of segments defined as viable by PET, 54% were contractile reserve–negative and exhibited lower blood flow with dobutamine (0.72±0.36 mL · g-1 · min-1) than with viable, contractile reserve–positive segments (1.29±0.70 mL · g-1 · min-1, P<.0001).
Conclusions Contractile reserve depends, in part, on the level of myocardial blood flow at rest and during inotropic stimulation.
Key Words: tomography • myocardial contraction • echocardiography • coronary disease
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Introduction |
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Reversible left ventricular contractile dysfunction secondary to coronary artery disease has been well described.1 2 3 The presence of reversibly dysfunctional, or viable, myocardium has been used to determine the prognosis and treatment for patients with left ventricular dysfunction secondary to coronary artery disease.4 5 Several noninvasive imaging methods have subsequently been applied to differentiate viable from nonviable myocardium. These include 201Tl scintigraphy,6 PET with [18F]fluorodeoxyglucose7 or [11C]acetate,8 and dobutamine stress echocardiography.9 10 With dobutamine stress echocardiography, dysfunctional segments are identified as viable if they exhibit improvement in contractile function during inotropic stimulation, a phenomenon known as myocardial contractile reserve.11
Results of studies in experimental animals, however, suggest that contractile reserve is dependent on the level of myocardial blood flow at rest and during inotropic stimulation.12 13 14 15 The flow dependency of the contractile reserve phenomenon has important implications regarding the use of dobutamine stress echocardiography to assess myocardial viability, particularly when myocardial blood flow is reduced. It has been speculated but not yet proved that an impairment in myocardial blood flow may explain the lower negative predictive value of dobutamine stress echocardiography to detect viable myocardium in certain clinical scenarios.16 Accordingly, the purpose of this study was to examine in humans the extent to which the capacity of dysfunctional myocardium to exhibit contractile reserve is dependent on the level of myocardial perfusion at rest and during inotropic stimulation.
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Methods |
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Study Population
The study was approved by the Human Studies and the Radioactive Drug Research committees at the Washington University School of Medicine. All patients provided informed written consent before enrollment. Patients were screened for left ventricular contractile dysfunction with two-dimensional (2D) echocardiography and for coronary artery disease with coronary arteriography. Nineteen patients (17 men and 2 women; mean age, 60±8 years) were found to have left ventricular contractile dysfunction due to chronic coronary artery disease (ie, the severity of left ventricular dysfunction was concordant with the extent of coronary artery disease). Patients were excluded if they had clinical evidence of active or recent (<6 months) myocardial ischemia (eg, unstable angina, myocardial infarction, or pulmonary edema). The majority of patients had moderate-to-severe left ventricular dysfunction at rest (mean ejection fraction, 26±7%), with 15 of 19 patients having global ejection fractions estimated by 2D echocardiography at <25%. Eighteen of 19 patients had multivessel coronary artery disease as determined by coronary arteriography: one vessel (n=1), two vessel (n=2), and three vessel (n=16). Thirteen patients had suffered a remote myocardial infarction, and 12 had undergone previous coronary revascularization with either coronary artery bypass grafting (n=7) or percutaneous transluminal coronary angioplasty (n=5). ß-Blocker therapy was withheld for at least 24 hours before the study.
Imaging Protocol
The imaging protocol is outlined in Fig 1
. Under resting conditions, patients
underwent rest 2D echocardiography (Hewlett-Packard
Sonos 1500) in the standard imaging planes (parasternal long- and
short-axis, apical two- and four-chamber views) to measure regional
contractile function. This was followed by a PET scan (SP-3000E, PETT
Electronics) to measure regional myocardial blood flow and myocardial
oxygen consumption. A 2-minute scan, obtained with a rotating
68Ge/68Ga sector source, was acquired and
reconstructed to verify proper positioning. After the positioning scan,
a 15-minute transmission scan was performed for generation of
attenuation correction factors used in emission-image reconstruction.
The PET protocol to measure myocardial blood flow involved inhalation
of 40 mCi of [15O]carbon monoxide, with the immediate
collection of a 300-second scan, followed by a bolus of 0.40 mCi/kg IV
of [15O]water, with the immediate collection of a
150-second dynamic scan. To measure regional myocardial oxygen
consumption, a bolus of 0.40 mCi/kg IV of [11C]acetate
was given, followed by a 30-minute dynamic scan to determine
[11C]acetate myocardial kinetics. After the rest studies,
dobutamine (5, 10, 15, and 20 µg ·
kg-1 · min-1
IV) was infused during continuous monitoring of blood pressure, heart
rate, and regional contractile function (by
echocardiography) until maximal contractile
improvement was observed or the maximal dose of dobutamine
(20 µg · kg-1 ·
min-1) was reached. Dobutamine
infusion was stopped if the patient developed signs or symptoms of
myocardial ischemia, significant arrhythmias, and/or
symptomatic hypotension. If a decline in regional function
was observed, the dose of dobutamine was decreased to the
previous level, and regional function was reassessed. At the optimal or
peak dose of dobutamine, repeat measurements of myocardial
blood flow and oxygen consumption by PET were made. 2D
echocardiography was performed at the end of the
study (with the patient still on dobutamine) to ensure that
myocardial ischemia (defined as a decline in regional wall
motion) had not occurred. The echocardiographic images
were stored in a cine-loop, digital quad screen format (Tomtec Freeland
Systems) for side-by-side comparison of the rest and
dobutamine stress images.
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Image Analysis
Left ventricular segment model. The left
ventricle was analyzed by use of an 11-segment model adapted
from the American Society of Echocardiography
recommendations to allow image registration with the PET images (Fig 2).17 Several steps were
taken to minimize potential errors due to misalignment of the PET and
echocardiographic images. First, all PET images were
reformatted into short-axis, horizontal long-axis, and vertical
long-axis views, thus allowing direct region-to-region comparison with
the corresponding short-axis, apical four-chamber, and apical
two-chamber echocardiographic views. Second, PET
measurements were averaged over several midventricular
slices to obtain a representative sample of the
corresponding echocardiographic imaging plane. Finally,
only large regions of interest were analyzed, as previously
reported.8 The left ventricular septum was not
included in our analysis because a significant proportion of
our patients had previous coronary artery bypass graft surgery
causing paradoxical septal motion, which leads to difficulty in
analysis of this region. Myocardial segments were included in
the final analysis only if all three
physiological parameters (contractile
function, myocardial blood flow, and myocardial oxygen consumption)
could be quantified accurately.
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Echocardiography. Regional contractile
function was graded visually, and each myocardial segment was assigned
a wall motion score according to a modification of the recommendations
of the American Society of Echocardiography, where
1=normal (or hyperdynamic), 1.5=mild hypokinesis, 2=hypokinesis,
2.5=severe hypokinesis, 3=akinesis, and 4=dyskinesis.17
Left ventricular segments with a baseline wall motion score
of <1.5 were defined as normal; those with a baseline wall motion
score of 
2.0 were defined as dysfunctional. During inotropic
stimulation, dysfunctional segments in which contractile function
improved by at least one full grade (improvement in wall motion score
1.0) were classified as contractile reserve–positive. Segments with
improvements in wall motion score of less than one grade were
classified as contractile reserve–negative. All studies were reviewed
independently by two experienced echocardiographers who
were blinded to the clinical and PET data. Interobserver concordance
was 91%. Discrepancies in wall motion score between the two observers
were settled by consensus, and in no case was the disagreement greater
than a 0.5 grade. One observer reviewed all the studies twice, at least
2 weeks apart, with an intraobserver concordance of 94%.
PET. Regional myocardial blood flow was quantified by use of a parameter optimization method developed and validated previously at our institution.18 19 20 To permit better quantification at very low flow rates, the partial volume correction factor within this algorithm was fixed to a value calculated independently based on the transmission and [15O]carbon monoxide scans.21 Myocardial oxygen consumption was quantified from the myocardial turnover rate constant of acetate, which reflects the rate of clearance of 11C activity from myocardium after the administration of [11C]acetate and which correlates closely with myocardial oxygen consumption measured directly both in experimental animals and in humans.22 23 24 In addition, the perfusable-tissue index for each segment was calculated as the ratio of the partial-volume correction (determined with the parameter-optimization method) divided by the extravascular tissue density (determined from the transmission scan).25 The perfusable-tissue index has been shown recently by our group to reflect heterogeneity of perfusion across the myocardium, because it is a function of both intensity and transmural distribution of blood flow.25 Therefore, at a given level of transmural blood flow, if heterogeneity of perfusion is high, as in subendocardial infarction, perfusable-tissue index values are low (typically <0.6), and if heterogeneity is low (ie, flow is homogeneous), perfusable-tissue index values are high (approaching 1.0).
Coronary angiography. The extent of coronary artery disease was determined in patients (n=9) who had undergone cardiac catheterization within 6 months of this study but who had not undergone previous coronary artery bypass graft surgery (because of difficulty in determining whether blood flow to a myocardial segment is supplied by the native vessel or the bypass graft). An experienced interventional cardiologist who was blinded to the clinical, PET, and echocardiographic data measured the percent reduction in coronary artery diameter with standard caliper technique. The coronary artery distribution was correlated to the PET and echocardiographic regions of interest by a scheme described by Bourdillon et al.26
Statistical Analysis
Continuous data are presented as mean±SD. Comparison
between values for segments at rest and on dobutamine was
performed by paired t test. Comparisons between normal,
contractile reserve–positive, and contractile reserve–negative
segments were performed by ANOVA with appropriate post hoc testing
(Bonferroni/Dunn). A statistically significant difference was
considered to be present when P<.05.
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Results |
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Segmental Analysis of Contractile Function
Eighteen of the 19 patients completed the imaging protocol. One patient completed the rest PET and the rest and dobutamine stress echocardiograms, but was unable to undergo the dobutamine PET because of symptomatic hypotension; the data from this rest study were included.
Rest images of 209 myocardial segments were potentially available. Of these, 166 segments were of adequate technical quality for assessment of all three measurements of interest: contractile function, myocardial blood flow, and myocardial oxygen consumption. PET images of 43 segments were excluded because of poor quality (ie, low count statistics, myocardium out of the field of view, or patient movement between scans). Because the dobutamine stress data were not available in 1 patient and because of technical considerations in other segments, images of 137 segments during dobutamine infusion were adequate for analysis. An average of 8.7±1.5 segments per patient were analyzed (range, 6 to 11 segments per patient).
Of the 166 rest myocardial segments, 21 (from 5 patients) showed normal contractile function, 56 (from 14 patients) were dysfunctional but contractile reserve–positive, and 89 (from 19 patients) were dysfunctional and contractile reserve–negative. Fifteen of the 19 patients had at least two different types of myocardial segments; 4 patients had only contractile reserve–negative segments. Contractile dysfunction at rest was, by definition, least severe in the normal segments (1.1±0.2). The contractile reserve–negative segments had worse contractile function at rest (2.7±0.4) than the contractile reserve–positive segments (2.3±0.3, P<.0001). By definition, contractile function improved in the contractile reserve–positive myocardial segments during the infusion of dobutamine (wall motion score on dobutamine, 1.2±0.3).
The dobutamine dose at which the PET study was performed was similar in normal and contractile reserve–negative segments (11.7±2.9 µg · kg-1 · min-1 and 11.0±4.6 µg · kg-1 · min-1, respectively, P=NS) but was higher in contractile reserve–positive segments (14.1±4.5 µg · kg-1 · min-1, P<.0001 versus contractile reserve–negative segments).
Measurements of Myocardial Blood Flow
Myocardial blood flow measured at rest and during
dobutamine infusion and the absolute change in myocardial
blood flow for each class of myocardial segments are shown in Fig 3. Myocardial blood flow at rest was
lower in contractile reserve–negative segments (0.41±0.18 mL ·
g-1 · min-1)
than in either contractile reserve–positive (0.50±0.22 mL ·
g-1 · min-1)
or normal segments (0.55±0.20 mL ·
g-1 · min-1,
P<.009). During dobutamine infusion, myocardial
blood flow increased in all three groups of segments
(P<.0001). However, the level of myocardial blood flow
during inotropic stimulation remained lower in the contractile
reserve–negative (0.63±0.38 mL ·
g-1 · min-1)
than in contractile reserve–positive segments (1.28±0.65 mL ·
g-1 · min-1)
or normal segments (1.93±0.83 mL ·
g-1 · min-1,
P<.0001). Myocardial blood flow during
dobutamine in contractile reserve–positive segments was
also less than in normal segments (P<.0001). The increase
in myocardial blood flow from rest to dobutamine was
blunted in contractile reserve–negative segments (0.25±0.35 mL
· g-1 ·
min-1) compared with contractile
reserve–positive (0.80±0.59 mL ·
g-1 · min-1)
and normal segments (1.38±0.86 mL ·
g-1 · min-1,
P<.0001). The increase in blood flow was also less in
contractile reserve–positive segments than in normal segments
(P<.0001). Thus, in myocardial segments that are
dysfunctional at rest, the presence of contractile reserve is
associated with higher levels of myocardial blood flow at rest and
during inotropic stimulation.
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Measurements of Myocardial Oxygen Consumption
Measurements of myocardial oxygen consumption at rest and on
dobutamine and the absolute change in myocardial oxygen
consumption for each group of myocardial segments are shown in Fig 4. Commensurate with the reduction in
blood flow, myocardial oxygen consumption at rest was lower in the
contractile reserve–negative segments (0.043±0.012
min-1) than in either contractile
reserve–positive (0.048±0.01 min-1) or
normal segments (0.058±0.008 min-1,
P<.02). During dobutamine infusion, myocardial
oxygen consumption increased in all three groups (P<.0001).
The level of myocardial oxygen consumption on dobutamine
was lower in contractile reserve–negative segments (0.060±0.013
min-1) than in contractile reserve–positive
(0.077±0.016 min-1) or normal segments
(0.092±0.024 min-1, P<.0001).
Myocardial oxygen consumption on dobutamine was also less
in contractile reserve–positive compared with normal segments
(P=.0007). The increase in myocardial oxygen consumption
from rest to dobutamine was blunted in contractile
reserve–negative segments (0.018±0.011
min-1) compared with contractile
reserve–positive (0.030±0.014 min-1) and
normal segments (0.034±0.021 min-1,
P<.0001). Thus, as with blood flow, the presence of
contractile reserve is associated with higher levels of myocardial
oxygen consumption at rest and during dobutamine
infusion.
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Measurements of Percent Reduction in Coronary Artery
Diameter
Percent reduction in diameter for the coronary arteries
supplying each group of myocardial segments is shown in Fig 5. The percent reduction in
coronary artery diameter was more severe in contractile
reserve–negative segments (88%±24%) than in contractile
reserve–positive (67%±38%, P=.0056) or normal segments
(24%±39%, P<.0001). Also, the percent reduction in
coronary artery diameter was more severe in contractile
reserve–positive than normal segments (P=.0004). Therefore,
in concordance with the blood flow measurements, the absence of
contractile reserve is associated with more severe coronary
artery stenosis.
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Myocardial Blood Flow, Contractile Reserve, and Myocardial
Viability
To determine the extent to which differing admixtures of viable
and nonviable myocardium may have contributed to the
relationship between myocardial blood flow and contractile reserve, we
measured these parameters in dysfunctional segments
classified as viable or nonviable on the basis of rest levels of
myocardial oxygen consumption as measured by PET, according to
previously validated criteria
(Table).8 Of the 102
segments classified as viable, 55 (54%) were contractile
reserve–negative. These segments exhibited lower levels of myocardial
blood flow during dobutamine and a smaller increase in
myocardial blood flow from rest than that measured in viable,
contractile reserve–positive segments (P<.0001). Of the 43
segments classified as nonviable by PET, 34 (79%) were contractile
reserve–negative. In these segments, the level of myocardial blood
flow at rest and during dobutamine and the absolute
increase in myocardial blood flow were less than observed in nonviable,
contractile reserve–positive segments (P<.002). Thus, in
the presence of equivalent levels of myocardial oxidative
metabolism, contractile reserve is still associated with
higher levels of blood flow, making it unlikely that differences in the
extent of viable and nonviable tissue alone can fully account for the
observed relationship between the level of blood flow and contractile
reserve.
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Measurements of Transmural Flow Heterogeneity
Measurements of rest perfusable-tissue index normalized to rest
myocardial blood flow are shown in Fig 6
for contractile reserve–positive and contractile reserve–negative
segments. Because the perfusable-tissue index is sensitive to the
absolute level of blood flow, the normalized perfusable-tissue index,
rather than the absolute perfusable-tissue index, is more useful for
comparing transmural flow heterogeneity between
different myocardial segments. The normalized perfusable-tissue index
was similar at rest in contractile reserve–positive (1.71±0.62) and
contractile reserve–negative segments (1.78±0.94, P=NS),
suggesting that the degree of flow heterogeneity
between these segments was similar.
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Discussion |
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Reversible contractile dysfunction is thought to result from repetitive or prolonged ischemia (stunning) or from chronic hypoperfusion (hibernation).2 27 28 Differentiation of reversibly (viable) from irreversibly (non-viable) dysfunctional myocardium has been used to determine both prognosis and treatment for patients with ischemic cardiomyopathy. Improvement in contractile function of dysfunctional myocardium during inotropic stimulation, or contractile reserve, has been proposed as a marker of myocardial viability. The results of the present study demonstrate that in patients with moderate-to-severe left ventricular dysfunction due to chronic coronary artery disease, the capacity to exhibit contractile reserve probably depends on the level of myocardial blood flow both at rest and during inotropic stimulation.
Myocardial Blood Flow and Contractile Function
The dependence of contractile function on the level of myocardial
blood flow at rest is well established.29 30 The
importance of myocardial blood flow on the augmentation of contractile
function with inotropic stimulation has also been shown in several
animal models. McGillem et al12 studied acute
ischemia in dogs and demonstrated that dysfunctional myocardial
segments supplied by coronary arteries with the greatest
stenoses had the smallest augmentation in coronary flow
during dobutamine infusion (10 µg ·
kg-1 · min-1)
and lacked contractile reserve. Sklenar et al13 showed in
dogs subjected to acute ischemia and reperfusion that wall
thickening during dobutamine correlated with the extent of
myocardial necrosis except in segments supplied by totally occluded
arteries. In the latter segments, there was no contractile reserve
during dobutamine, despite histological
evidence of viable myocardium. A more recent study by
Sklenar et al14 , also in dogs subjected to acute
ischemia and reperfusion, showed that a residual
coronary stenosis that limits hyperemic flow
will attenuate the contractile reserve response. Chen et
al15 studied the response to low- and high-dose
dobutamine in porcine models of acute ischemia and
short-term hibernation (1.5 and 24 hours, respectively). They
demonstrated that at low doses of dobutamine (4.5±2.2
µg · kg-1 ·
min-1), coronary flow increased and
contractile function improved, but at higher doses (12.6±4.1 µg
· kg-1 ·
min-1), coronary flow was not
augmented and contractile function deteriorated. These experiments
provide compelling evidence for a flow dependency of the contractile
reserve phenomenon in acute and subacute myocardial
ischemia. The results of our study suggest that a similar
relationship between the level of myocardial blood flow and contractile
reserve is present in humans with chronic coronary artery
disease.
Previous work in humans to quantify the relationship between contractile reserve and myocardial blood flow is limited. Severi et al31 used MRI to measure the effects of dobutamine (5 to 40 µg · kg-1 · min-1) on regional contractile function while measuring myocardial blood flow with PET and [15O]water in patients with acute and chronic coronary artery disease. They showed that myocardial segments exhibiting normal contractile augmentation during dobutamine exhibited greater increases in myocardial blood flow than segments in which contractile function worsened with inotropic stimulation. This study differs from our own because Severi et al looked at worsening wall motion with dobutamine in patients with normal or mildly decreased left ventricular function, whereas we studied improvement in wall motion with dobutamine in patients with moderate-to-severe left ventricular dysfunction. Sawada et al32 showed, in patients with primarily chronic coronary artery disease, that contractile reserve occurred more commonly when rest perfusion (measured by [13N]ammonia and PET) was normal than when it was reduced. This study, although similar to our own, did not include quantitative measurements of blood flow, nor did it include measurements of blood flow during dobutamine infusion.
Composition of Dysfunctional Myocardium: Impact on
Contractile Reserve
Our data provide evidence for an association between myocardial
blood flow and contractile reserve, but other factors may be important.
It is possible that the extent of infarcted tissue within a myocardial
segment is a more critical determinant of contractile reserve. We
assessed the impact of varying admixtures of viable and nonviable
myocardium on the association between contractile reserve
and the level of blood flow in two ways. First, we examined the
association between contractile reserve and myocardial blood flow in
segments classified as viable and nonviable on the basis of the level
of myocardial oxygen consumption as measured by PET.8 33
In a similar patient population, we have shown previously that the
level of myocardial oxygen consumption can predict improvement in
contractile function after coronary
revascularization with a positive predictive value
of 85% and a negative predictive value of 87%.8 More
than half of the segments in the present study identified as viable
did not exhibit contractile reserve. These segments exhibited less
augmentation of myocardial blood flow during inotropic stimulation than
that observed in viable segments with contractile reserve. Therefore,
given an equivalent extent of metabolically viable
myocardium, adequate levels of myocardial blood flow appear
to be a prerequisite for the contractile reserve response. Similarly,
Iliceto et al34 compared dobutamine stress
echocardiography with myocardial contrast
echocardiography in humans after acute myocardial
infarction and showed that microvascular integrity may be a
prerequisite for the presence of contractile reserve. Our data extend
the hypothesis that contractile reserve may depend on myocardial blood
flow to patients with chronic coronary syndromes.
A second method used to assess the impact of varying admixtures of viable and nonviable myocardium on the association between contractile reserve and the level of blood flow was to estimate heterogeneity in the transmural distribution of blood flow in each myocardial segment. It has been shown that the subendocardium contributes the most to overall systolic thickening and that reductions in subendocardial blood flow have the greatest impact on segmental contractile function.35 36 Therefore, it is possible that in the contractile reserve–negative segments, the presence of subendocardial infarction accounted for the lower levels of myocardial blood flow observed. Although the limited spatial resolution of PET images precludes direct quantification of myocardial blood flow within specific layers of the myocardium, the perfusable-tissue index calculated from the PET images provides an indirect measure of the heterogeneity of transmural blood flow. The rest perfusable-tissue index normalized to the level of rest myocardial blood flow was similar in contractile reserve–positive and contractile reserve–negative segments, suggesting that flow heterogeneity at rest was similar in this group of segments. Therefore, the comparable values of normalized perfusable-tissue index in these segments, taken in sum with differing levels of blood flow in the contractile reserve–negative and contractile reserve–positive segments, despite similar levels of viable myocardium, make it unlikely that the admixture of viable and nonviable myocardial tissue is the sole determinant of contractile reserve in this study.
Other Determinants of Contractile Reserve
After myocardial infarction, contractile function of a myocardial
segment can be affected by the contractile function of adjacent
segments. Noninfarcted segments adjacent to infarcted segments often
exhibit abnormalities in circumferential shortening that are due, at
least in part, to changes in regional stress-strain relations and/or
availability of metabolic substrates.37 38
Therefore, contractile reserve is also likely to depend on the
contractile function of adjacent myocardial segments, overall left
ventricular geometry, and segmental stress-strain
relations.
The increase in myocardial oxygen consumption during dobutamine despite the absence of contractile reserve in myocardial segments with viable tissue by PET may be due to alterations in energy transduction. The oxygen cost of excitation-contraction coupling in patients with coronary artery disease is higher in patients with moderate-to-severe left ventricular dysfunction than in those with normal or mildly decreased systolic function.39 Thus, during inotropic stimulation, some dysfunctional but viable segments may be unable to augment contractile function.
Limitations
It cannot be concluded with certainty that the impaired blood flow
response during dobutamine resulted in blunting of
contractility as opposed to the reverse scenario.
Decreased contractility could account for the
impairment in blood flow secondary to decreased oxygen demand. However,
the findings of reduced blood flow at rest, more severe
coronary artery stenosis, and similar flow
heterogeneity in contractile reserve–negative segments
are in agreement with results of studies in experimental animals,
supporting the primacy of the dependence of contractile reserve on the
level of myocardial blood flow.
The dose of dobutamine administered to patients with contractile reserve–positive segments was slightly higher than that given to patients with contractile reserve–negative segments. Patients with a higher proportion of contractile reserve–negative segments may have been more susceptible to ischemia and thus were unable to tolerate higher doses of dobutamine. This difference, however, was small (3.2 µg · kg-1 · min-1) compared with the differences in augmentation of myocardial blood flow and oxygen consumption with dobutamine in the two groups and therefore was not likely to have been the primary determinant of which segments exhibited contractile reserve.
In our study, the severity of systolic dysfunction at rest was greater in the contractile reserve–negative segments than in the contractile reserve–positive segments. This may be secondary to different proportions of infarcted tissue within these segments; however, as discussed, it probably reflects lower levels of myocardial blood flow. Regardless, the difference in wall motion score at rest between the two groups was small (0.4) and unlikely to have been a major determinant of which segments exhibited contractile reserve.
In an attempt to show the dependency of contractile reserve on myocardial blood flow, we used the level of myocardial oxygen consumption to classify viable myocardium. The traditional "gold standard" of myocardial viability is the recovery of contractile function after coronary revascularization. However, the measurement of myocardial oxygen consumption with PET is an accurate marker of functional recovery after coronary revascularization, as shown by our laboratory8 and by others.33 Furthermore, the main focus of this study was not to determine which imaging technique best identified viable myocardium but rather to better elucidate the impact of myocardial blood flow on the contractile reserve response. Clearly, studies designed to determine the relative accuracy of blood flow measurements, contractile reserve, and myocardial metabolism to identify reversibly dysfunctional myocardium would require measurement of these parameters before and after coronary revascularization.
Implications of the Study
The presence of contractile reserve on the dobutamine
stress echocardiogram is currently used to detect viable
myocardium. It has been shown to be accurate in predicting
recovery of function after reperfusion9 10 40 but may have
reduced negative predictive value in certain clinical
settings.41 42 43 In this study, we have shown the blood flow
dependency of the contractile reserve phenomenon. These findings
provide a physiological explanation for why some
viable myocardial segments in which contractile function fails to
improve during inotropic stimulation may ultimately recover function
after coronary reperfusion.
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Acknowledgments |
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This work was supported in part by NIH grants HL-13581, HL-48906, and HL-54361 and by a Minority Scientist Development Award from the American Heart Association, Dallas, Tex, to Dr Dávila-Román. We would like to thank Edward M. Geltman, MD, and Julio E. Pérez, MD, for their thoughtful review of the manuscript.
Received January 9, 1997; revision received June 11, 1997; accepted June 19, 1997.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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