(Circulation. 1995;91:1944-1951.)
© 1995 American Heart Association, Inc.
Articles |
Relation Among Stenosis Severity, Myocardial Blood Flow, and Flow Reserve in Patients With Coronary Artery Disease
From the Division of Nuclear Medicine and Biophysics, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, University of California, Los Angeles, and the Laboratory of Nuclear Medicine, Laboratory of Biomedical and Environmental Sciences.
Correspondence to Marcelo Di Carli, MD, Positron Emission Tomography Center, Department of Radiology, Children's Hospital of Michigan, 3901 Beaubien St, Detroit, MI 48201-2196.
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Abstract |
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Background Coronary arteriography is considered the "gold standard" for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography.
Methods and Results We studied 28 subjects: 18 patients with coronary artery disease (66±8 years) and 10 age-matched healthy volunteers (64±13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non–infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4±0.4 versus 2.6±0.7, respectively; P=NS). Quantitative PET estimates of hyperemic blood flow (r=.81, P<.00001), flow reserve (r=.78, P<.00001), and an index of the "minimal coronary resistance" (r=.78, P<.00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4±0.4 versus 1.8±0.5, respectively; P=.04).
Conclusions In patients with coronary artery disease, noninvasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.
Key Words: coronary disease • blood flow • myocardium • tomography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Coronary arteriography is the current "gold standard" for evaluating the severity of a coronary stenosis. Angiographic stenosis severity is usually expressed in percent diameter stenosis. However, this approach is limited because it does not include other lesion characteristics such as length, shape, and eccentricity that may also affect the impedance to blood flow. Accordingly, Gould, Kirkeeide, and colleagues1 2 proposed and validated the use of a single measure of coronary flow reserve on quantitative arteriography as a parameter that reflects all the various anatomic factors influencing stenosis severity. Similarly, other investigators also reported a close correlation between coronary flow reserve measured with intracoronary Doppler probes and luminal stenosis by quantitative arteriography.3
The evaluation of the physiological significance of coronary lesions may also be assessed noninvasively with myocardial perfusion imaging during pharmacologically induced coronary vasodilation.4 5 6 7 8 Most previous reports9 10 comparing myocardial perfusion imaging and angiographic findings, however, examined both imaging and angiographic results in terms of sensitivity and specificity rather than as a continuous spectrum of severity. Quantification of myocardial blood flow and flow reserve with N-13 ammonia and positron emission tomography (PET) has been validated extensively in animals and humans.11 12 13 Furthermore, this technique has been used successfully for diagnosis of coronary artery disease,8 14 for assessing the significance of coronary stenosis,5 and for evaluating the results of interventions such as coronary revascularization.15
We hypothesized that myocardial flow reserve based on quantitative measurements derived from N-13 ammonia PET imaging is related to luminal area stenosis on coronary angiography. Accordingly, this study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by N-13 ammonia and PET and percent area stenosis on quantitative coronary arteriography.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Study Group
The study group consisted of 28 subjects: 18 patients with chronic coronary artery disease undergoing coronary angiography for evaluation of chest pain and 10 age-matched healthy volunteers (7 men and 3 women; mean±SD, 64±13 years of age) with a low probability (<5%) of coronary artery disease based on the absence of symptoms and coronary risk factors, a normal resting ECG, and a normal submaximal treadmill test.16 In the healthy control volunteers, no regional flow defects were noted both at rest and during hyperemia by visual inspection and by polar mapping after comparison to a database of healthy individuals as described previously.17 The homogeneous N-13 ammonia uptake argues further that these healthy volunteers were indeed free of significant coronary artery disease.14 The patients with coronary artery disease (14 men and 4 women; mean age, 66±8 years) had a mean left ventricular ejection fraction of 45±14%. None had a history of hypertension, aortic stenosis, or hypertrophic cardiomyopathy. Six patients had a history of previous myocardial infarction based on clinical history, the presence of pathologic Q waves on the resting ECG, and the presence of regional wall motion abnormalities on contrast left ventriculography. Infarct-related coronary arteries were excluded from analysis. In addition, 7 vessels were excluded from analysis owing to the lack of adequate visualization on coronary angiography. The mean time interval between the PET study and coronary angiography was 3.7 months (range, 2 days to 5 months). All patients were clinically stable between the PET study and the angiographic procedure. Of the 18 patients with coronary artery disease, 10 had three-vessel disease, 6 had two-vessel disease, and 2 had single-vessel disease. These 18 patients had 41 diseased coronary arteries that were unrelated to prior infarction. If a vessel was affected by several stenoses in series, only the most severe stenosis was considered for analysis. Each subject signed an informed consent form approved by the Human Subject Protection Committee of the University of California, Los Angeles.
Positron Emission Tomography
All subjects refrained from
caffeine-containing beverages or
theophylline-containing medications for 24 hours before the PET study.
Myocardial blood flow at rest and after administration of 0.56 mg/kg
dipyridamole IV infused over 4 minutes was quantified noninvasively
with N-13 ammonia and dynamic PET imaging.
The whole-body tomograph (Model 931/8, CTI/Siemens) used in this study acquires 15 transaxial planes with an in-plane spatial resolution of 6.5-mm full-width half-maximum (FWHM), has an interplane spacing of 6.75 mm, and covers a 10-cm axial field of view. The images were reconstructed with a Shepp filter with a cutoff frequency of three cycles per pixel, resulting in an effective in-plane resolution of 11-mm FWHM.
A 20-minute transmission scan was acquired for correction of photon attenuation. Beginning with the IV bolus administration of N-13 ammonia (15 to 20 mCi), serial images were acquired for 19 minutes (12 frames of 10 seconds each, 2 frames of 30 seconds, 1 frame of 60 seconds, and 1 frame of 900 seconds). Forty-five minutes later, after physical decay of N-13 ammonia, 0.56 mg/kg dipyridamole IV was infused over 4 minutes. A second dose of N-13 ammonia (15 to 20 mCi) was injected 4 minutes after dipyridamole infusion, and images were recorded in the same acquisition sequence. Patient motion was minimized by fastening a Velcro strap across the patient's chest. Arterial blood pressure and ECGs were recorded continuously throughout the study.
Quantification of Blood Flow
Transaxial images were
reoriented on a Macintosh IIci personal
workstation (Apple Computer Inc) into six contiguous short-axis slices
of the left ventricle, progressing from the apex to the
base.17 To quantify regional myocardial blood flows at
rest and during hyperemia, three short-axis slices of the rest and the
hyperemic studies were selected in each patient. With the first of the
serially acquired images that clearly visualized the left ventricular
myocardium, sectorial regions of interest encompassing the myocardial
segments supplied by each non–infarct-related coronary artery were
assigned to each of the three midventricular short-axis slices. Within
each vascular territory, the regions of interest were placed to the
area that on visual inspection had the lowest N-13 ammonia
concentration on the dipyridamole-stress images. The size of each
sectorial region of interest was adjusted to the individual coronary
anatomy, eg, the size of the stenosed vessel, the anatomic location of
the stenosis, and the dominance as defined on the coronary angiograms.
In coronary artery territories with normal N-13 ammonia activity on the
stress images, the region of interest was assigned to the entire
vascular territory. In each territory of stenosed arteries, an attempt
was made to assign rather large regions of interest (typically
encompassing >36° of the myocardial circumference of a given short
axis cross section) to minimize statistical noise. The regions of
interest were then copied to the first 2 minutes of serially acquired
N-13 ammonia images, and regional myocardial tissue time-activity
curves were obtained. In each vascular territory, a single
time-activity curve was then obtained by averaging of the corresponding
N-13 ammonia data in adjacent ventricular planes. A 25-mm2
region of interest (10 pixels) was placed in the left ventricular blood
pool and copied to the first 12 frames of the serially acquired images
to obtain the arterial input function.
Partial volume effects were corrected with a recovery coefficient that assumed a homogenous myocardial wall thickness of 1 cm. The myocardial N-13 activity curves also were corrected for spillover of activity from the blood pool to the myocardium and for physical decay of N-13. The time-activity curves were then fitted with a previously validated two-compartment tracer kinetic model.18 The arterial input function was not corrected for N-13 metabolites because the degree of metabolite contamination in humans during the initial 2 minutes after tracer administration is rather small.18 Because myocardial blood flow at rest is related to the rate-pressure product, an index of cardiac work,19 resting flow values were normalized to the corresponding rate-pressure product in each patient by dividing the resting flow value by the rate-pressure product multiplied by a linear factor of 10 000 in each individual patient.
The approach yields reproducible measurements of blood flow as demonstrated previously in 20 healthy volunteers studied at an average time interval of 3 to 7 days. Flow values at rest and during hyperemia in each major vascular territory differed randomly between the two measurements by an average of 10% to 15%.20
Quantitative Coronary Arteriography
The stenosis severity was
quantified on the coronary
arteriograms as described by Brown et al.21
Cineangiographic frames of orthogonal views were digitized as an
interlaced television image (512x512 pixels, 256 shades of gray) and
stored in a Gould-DeAnza IP-8500 image processor, interfaced to a
Digital Equipment Corp VAX 11/780 computer. A range of coronary
stenoses (from 18% to 97% luminal narrowing) involving major coronary
arteries was outlined with an automated edge detection algorithm using
a two-dimensional (2D) search. All traced lesions were corrected for
pin-cushion and magnification distortion. Lesion cross-sectional area
was estimated with a geometric method using biplane orthogonal views of
each lesion. In this study, quantitative measurements of luminal
stenosis are reported in terms of percent reduction in cross-sectional
area rather than absolute values of percent diameter to minimize errors
in the evaluation of eccentric lesions.
Statistical Analysis
Data are presented as mean±SD. A
one-way ANOVA was used to
compare estimates of myocardial blood flow, flow reserve, and
"minimal coronary resistance" between groups with different
degrees of luminal stenosis (ie, <50%, 50% to 70%, 70% to 90%,
and >90%). Hemodynamic and myocardial blood flow results before and
after dipyridamole in patients and volunteers were compared with
Student's t test for paired or unpaired data as
appropriate. Regression analysis used a Loess smoothed fit of the
data.22 A probability value of <.05 was used to define
statistical significance.
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Results |
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In the 18 patients, a total of 41 non–infarct-related coronary vessels were analyzed. Eleven coronary arteries had <50% stenosis, 9 arteries had 50% to 69% stenosis, 10 arteries had 70% to 90% stenosis, and 11 arteries had >90% stenosis. Of the 41 coronary stenoses analyzed, there were 16 left anterior descending coronary arteries (10 proximal and 6 middle), 7 left circumflex coronary arteries (5 proximal and 2 middle), 5 proximal obtuse marginal coronary arteries, 1 proximal first diagonal coronary artery, and 12 right coronary arteries (3 proximal, 7 middle, and 2 distal). Five coronary arteries had 2 stenoses in series and 1 coronary artery had 3 stenoses in series.
Hemodynamics Findings
None of the patients had a history of
hypertension. Two patients
had a basal blood pressure of 160/85 mm Hg but no evidence of
ventricular hypertrophy on ECG or 2D echocardiography. In the remaining
16 patients, blood pressure was <140/80 mm Hg. Table 1
summarizes the hemodynamic findings at rest and after dipyridamole in
the patients with coronary artery disease and in the age-matched
healthy volunteers. After dipyridamole, both groups of subjects
demonstrated a significant increase in heart rate and rate-pressure
product, whereas no significant change was observed in systolic,
diastolic, or mean aortic blood pressure. No significant difference was
observed in any hemodynamic parameter between the patients and the
healthy volunteers.
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Changes in Myocardial Blood Flows and Stenosis Severity
At
rest, myocardial blood flows in regions supplied by vessels
with 
70% area stenosis were lower than in those regions supplied by
vessels with <50% area stenosis (0.7±0.2 versus 0.9±0.2
mL · g-1 · min-1,
P<.01; Table 2). However, resting blood
flows were similar in all groups of coronary stenoses when they were
normalized to the rate-pressure product (Table 2).
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Myocardial blood flows in regions supplied by minimally stenosed
coronary arteries (<50% area stenosis) in patients with coronary
artery disease were similar to those of the age-matched healthy
volunteers, both at rest and after dipyridamole (0.9±0.2 versus
0.9±0.2
mL · g-1 · min-1,
P=NS, and 2.3±0.6 versus 2.3±0.5
mL · g-1 · min-1,
P=NS, respectively; Table 3). As a result,
the mean myocardial blood flow reserve was similar in both groups
(2.4±0.4 versus 2.6±0.7, P=NS; Table
3).
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After dipyridamole, myocardial blood flows in
regions supplied by
arteries with <50% area stenosis increased significantly by an
average of 2.4 (0.9±0.2 to 2.3±0.6
mL · g-1 · min-1,
P<.001; Fig 1). Blood flows in regions
supplied by vessels with 50% to 70% area stenosis showed a similar
response to coronary vasodilatation, increasing by an average of 2.3
(0.9±0.2 to 2.0±0.4
mL · g-1 · min-1,
P<.001; Fig 1). In contrast, reductions in
hyperemic flows
were observed in regions supplied by vessels with 70% to 90% area
stenosis, which on average increased by 1.8 (0.7±0.2 to 1.2±0.4
mL · g-1 · min-1,
P<.001; Fig 1). Blood flows in regions supplied by
arteries
with >90% area stenosis showed an attenuated response to
dipyridamole, achieving an average ratio of hyperemic to rest blood
flow of only 1.4 (0.7±0.2 to 1.0±0.3
mL · g-1 · min-1,
P<.05; Fig 1).
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Correlation Between Myocardial Blood Flow and Coronary Stenosis
Severity
Myocardial Blood Flow
Hyperemic blood flows
were inversely and nonlinearly related to
the percent cross-sectional area stenosis on coronary arteriography
(r=.81, P<.00001; Fig 2).
Importantly, despite the relatively large variability, these
measurements distinguished between 50% to 70% and 70% to 90%
luminal stenoses (2.0±0.4 versus 1.2±0.4
mL · g-1 · min-1,
P<.01; Table 2
). Moreover, hyperemic blood flows
were
significantly lower in regions supplied by vessels with lesions >90%
than in those supplied by vessels with lesions <50% (1.0±0.3 versus
2.3±0.6
mL · g-1 · min-1,
P<.001; Table 1).
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Myocardial
Flow Reserve
Estimates of myocardial flow reserve were significantly
correlated
with the cross-sectional area stenosis (r=.78,
P<.00001; Fig 3) and with the percent
diameter stenosis (r=.77, P<.00001; Fig
4). Importantly, coronary lesions with 50% to 70% area
stenosis had a significantly higher myocardial flow reserve than those
with 70% to 90% area stenosis (2.4±0.4 versus 1.8±0.5,
P<.05; Table 2), suggesting a different vasodilator
reserve
among coronary lesions with a moderate degree of luminal obstruction
(Fig 4). Furthermore, measurements of myocardial flow reserve
were
significantly lower in myocardium supplied by arteries with >90% area
stenosis than those supplied by vessels with <50% area stenosis
(1.4±0.4 versus 2.4±0.4, P<.001; Table
2).
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Minimal Coronary Resistance
To
relate the hyperemic blood flow to one of its major
determinants, the coronary driving pressure, the mean aortic blood
pressure was divided by the hyperemic blood flow, and an index of the
minimal coronary resistance was obtained. A significant correlation was
observed between the estimated coronary resistances and the percent
area stenosis on angiography (r=.78, P<.00001;
Fig 5).
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As expected, minimal hyperemic coronary
resistances increased
significantly with increasing stenosis severity. Estimates of minimal
coronary resistances were equally as effective as hyperemic blood flows
and flow reserve measurements for distinguishing mild to moderate
degrees of stenosis severity (Table 2). In addition, these
estimates
also discriminated between lesions with 70% to 90% area stenosis from
those with >90% area stenosis (84±28 versus 125±52
mm Hg · mL-1 · min-1 · g-1,
P<.05; Table 2).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The present study demonstrates that in patients with coronary artery disease, noninvasive estimates of myocardial blood flow and flow reserve made with N-13 ammonia and PET imaging are correlated closely with quantitative measurements of luminal stenosis severity on coronary arteriography. Importantly, our results indicate that noninvasive measurements of myocardial flow reserve by N-13 ammonia and PET imaging can differentiate coronary lesions of 50% to 70% stenosis from lesions of 70% to 90% on coronary arteriography.
Comparison With Previous Studies
Our results demonstrate that
hyperemic blood flows and flow
reserve measurements are inversely and nonlinearly related to stenosis
severity on quantitative coronary arteriography. A progressive loss in
vasodilator capacity, resulting in reductions in hyperemic blood flows
and flow reserve with increasing stenosis severity, has been
demonstrated in the animal model.23 24 Of note, the
plots
in Figs 2 through 4 are virtually
identical to previously published
data in animal models,23 confirming the universality of
these relations using different species and different methodologies for
assessment of blood flow and arteriographic measurements. Despite the
considerable scatter in these relations, hyperemic blood flows and
estimates of flow reserve discriminated between mild, moderate, and
severe stenosis severity on coronary arteriography (Table 2).
In
humans, Wilson et al3 reported significant correlations
between coronary flow reserve as measured by intracoronary Doppler
techniques and stenosis severity on coronary angiography. In the same
study, coronary flow reserve was estimated from flow velocities rather
than from myocardial blood flows as determined in the present study
by N-13 ammonia and PET imaging. Our results are in agreement with
those of Uren et al25 using O-15 water and PET. They
reported that resting blood flow remains unchanged regardless of the
severity of coronary stenosis and that myocardial flow reserve declines
with increasing angiographic stenosis.
The observed variability in hyperemic blood flows and flow reserve measurements for any given degree of luminal area stenosis may be related to physiological and angiographic variables and to limitations in some of the methodologies applied in this study. The effect of some of these factors on hyperemic blood flows and flow reserve was addressed by Czernin et al,19 including the effect of heart rate,26 27 28 resting blood flows (ie, the denominator of the myocardial flow reserve calculation), left ventricular end-diastolic pressure,29 contractility,30 and the magnitude of dipyridamole-induced hyperemia.31
The magnitude of the blood flow response to
dipyridamole-induced
vasodilatation depends to a large extent on the coronary perfusion
pressure.32 In this study, we estimated the minimal
coronary resistance to normalize the hyperemic blood flows to the
coronary perfusion pressure. Fig 4 demonstrates that this
normalization
resulted in a significant reduction in data scatter, at least between
20% and 80% area stenosis, suggesting that the coronary driving
pressure was an important determinant of these relations. The reason
for the larger variability in the minimal coronary resistances observed
for lesions with >80% area stenosis is unknown but may relate to
geometric factors not accounted for in this study such as shape,
eccentricity, and entrance and exit angles, all of which are known to
modulate vascular resistances. Nevertheless, these observations are
consistent with the results of Wilson and colleagues3
using a minimal coronary vascular resistance index.
In this study, we
observed that myocardial regions supplied by coronary
arteries with minimal obstruction (<50% area stenosis) had an average
flow reserve of 2.4, which was not statistically different from the
estimates of flow reserve in our age-matched control population (Table
3). These findings contrast with those of Uren et
al.33
They suggested that in patients with coronary artery disease, normal
myocardial regions indeed have an abnormal perfusion reserve. Previous
studies34 showed that a diffuse atherosclerotic process
affecting the endothelium-dependent vasodilator
capability may result in a decreased myocardial flow reserve in
apparently normal vessels on the arteriogram. However, our measurements
of flow reserve in patients with coronary artery disease were similar
to those of our age-matched control population. Moreover, our findings
are further supported by previously published reports demonstrating
that myocardial perfusion reserve declines with
age.19 35
The apparent discrepancy between our findings and those of Uren et al
might be explained by the fact that in Uren et al's study, the flow
values of patients with coronary artery disease were compared with
those obtained in significantly younger volunteers. Thus, these
apparently incongruent results may reflect methodological differences
rather than contradictory findings.
Arteriographic factors also may have contributed to the variability in the correlation between myocardial flow reserve and the anatomic severity of individual stenosis. Fedele et al36 showed in experimental animals that maximal coronary blood flows in luminal stenoses with similar cross-sectional areas were significantly lower in "complex" (multilumen) as opposed to "simple" coronary stenosis. Although the prevalence of such complex lesions in humans is unknown, it may be relatively high in the setting of acute coronary syndromes where the prevalence of thrombus is high.37 Because patients with unstable angina or recent myocardial infarction were not included in this study, this is unlikely to account for the interindividual variability in hyperemic blood flows and flow reserve. An additional potential factor to consider is the presence of vasospasm, which is known to exist in coronary lesions.38 Indeed, small, dynamic changes in stenosis severity during hyperemia may occasionally affect the resistance to blood flow and result in a variable flow reserve at any level of luminal stenosis.3 Although theoretically possible, it is unknown to what extent the presence of vasospasm might have affected our results. Important angiographic geometric considerations not evaluated in this study such as shape, stenoses in series, or eccentricity may also affect flow resistance and might account for some of the variability in myocardial flow reserve measurements for a given degree of luminal stenosis.
Study Limitations
Several potential methodological
limitations might have influenced
the results of this study. First, to correct for the partial
volume-related underestimation of true myocardial N-13 ammonia
concentrations, the left ventricular wall thickness was assumed to be
uniform and 1 cm in all subjects. Of note, although two patients had a
baseline blood pressure of 160/85 mm Hg, none of the subjects included
in this study had a history of hypertension, aortic valve stenosis, or
hypertrophic cardiomyopathy. Moreover, the data analysis was
restricted to the non–infarct-related coronary arteries with normal
regional wall motion. Therefore, we do not anticipate a significant
difference in myocardial wall thickness among the myocardial regions
analyzed in this study. Three patients developed chest pain during
dipyridamole infusion; however, this was not associated with an actual
decline in myocardial blood flow.
Second, important angiographic geometric considerations not evaluated in this study such as shape, stenoses in series, or eccentricity may also affect flow resistance and might account for some of the variability in myocardial flow reserve measured at a given degree of stenosis severity. Nevertheless, our results showed a significant correlation between hyperemic blood flows, flow reserve, and area stenosis, a major determinant of lesion resistance. Furthermore, the methods used in this study to quantify the angiographic coronary lesions have been shown to reflect stenosis severity accurately.39 Previous studies40 suggested that relative rather than absolute estimates of myocardial perfusion reserve might be a more sensitive descriptor of the physiological consequences of angiographic stenosis severity. Indeed, in the 8 patients with one- and two-vessel disease in this study, there was a significant correlation between the relative flow reserve (flow reserve in the diseased coronary vessel/flow reserve in the normal coronary vessel) and the degree of angiographic coronary stenosis (r=.89, root mean square error=0.13, P<.00001). However, this quantitative technique was not feasible in all our study patients because it assumes the presence of at least one myocardial region supplied by a normal vessel in each patient; in this study, 10 patients had three-vessel disease. The resistance to blood flow in the five vessels with stenoses in series may have not been accurately assessed. Because stenoses in series do not necessarily behave as additive resistances and because criteria for quantitative analysis of such lesions have not been established, only the most severe stenosis in each coronary artery was used for analysis. Nevertheless, the exclusion of the vessels with serial stenoses from analysis resulted in similar correlations between stenosis severity and measurements of myocardial blood flow and flow reserve, making it unlikely to account for the observed variability in hyperemic blood flows.
Clinical Implications
In patients with coronary artery
disease, noninvasive measurements
of myocardial blood flow and flow reserve by N-13 ammonia PET imaging
are inversely and nonlinearly related to stenosis severity as defined
by quantitative coronary arteriography. Importantly, coronary lesions
of intermediate severity have a differential myocardial flow reserve
that decreases with increasing stenosis severity. These differences can
be detected noninvasively by N-13 ammonia PET imaging, thus allowing
better definition of the functional importance of known coronary
stenoses. Additionally, measurements of regional myocardial blood flow
can define functional consequences of an anatomically characterized
coronary stenosis. Thus, the scatter of the data about the regression
line between stenosis severity and flow reserve or hyperemic flows may
indeed be attributable to a possible discrepancy between structure and
function.
Accurate assessment of the physiological severity of coronary stenoses may have an important role as an aid for more objective determination of medical versus mechanical treatment of coronary artery stenosis and for assessment of the results of such treatments, especially because more readily available clinical tools such as chest pain are poorly related to stenosis severity. Although relative rather than absolute measurements of flow reserve may be equally accurate in defining stenosis severity, the validity of such relative measurements hinges on the presence of normally perfused myocardium. However, such normal myocardium may not always be available for comparison in patients with three-vessel coronary artery disease, as was the case in this study. In addition, these measurements may be clinically useful in patients with silent coronary artery disease as the only basis for choosing medical or mechanical intervention to prevent sudden death and myocardial infarction and for monitoring progression or regression of coronary artery disease.
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Acknowledgments |
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This work was supported in part by the director of the Office of Energy Research, Office of Health and Environmental Research, Washington, DC; by Research Grants HL-29845 and HL-33177 from NIH, Bethesda, Md; and by an Investigative Group Award from the Greater Los Angeles (Calif) Affiliate of the American Heart Association. This work was finished during Dr Di Carli's tenure of a Research Fellowship Award from the Greater Los Angeles Affiliate of the American Heart Association. The Laboratory of Biomedical and Environmental Sciences was operated for the US Department of Energy by the University of California under contract DE-FC03-87ER60615. We are indebted to Ron Sumida, Lawrence Pang, Francine Aguilar, Marc Holgan, and DerJenn Liu for their expert technical assistance in performing the PET studies; Jeffrey A. Gornbein, DrPH, for his statistical assistance; and Diane Martin for preparing the artwork.
Received August 18, 1994; revision received October 10, 1994; accepted October 31, 1994.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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