(Circulation. 1995;91:1419-1426.)
© 1995 American Heart Association, Inc.
Articles |
Improvement of Subendocardial Myocardial Perfusion After Percutaneous Transluminal Coronary Angioplasty
A Myocardial Contrast Echocardiography Study With Correlation Between Myocardial Contrast Reserve and Doppler Coronary Reserve
From the Unité de Recherche U.400 de l'Institut National de la Santé et de la Recherche Médicale and Département d'Ultrasonologie de l'Université Paris Val-de-Marne, Service des Explorations Fonctionnelles and Service de Cardiologie, Hôpital Henri Mondor, Créteil, France.
Correspondence to Jean-Luc Dubois-Randé, MD, PhD, Service de Cardiologie, Hôpital Henri Mondor, 51 avenue du maréchal De Lattre de Tassigny, 94010 Créteil, France.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background After angioplasty coronary reserve improves but does not normalize in most patients. The purpose of this study was to examine before and after angioplasty coronary reserve and transmural myocardial blood flow distribution using myocardial contrast echocardiography.
Methods and Results Twelve patients with left anterior descending coronary artery stenosis were investigated before and immediately after angioplasty. A Doppler catheter was placed in the proximal segment. Myocardial contrast echocardiography was performed by imaging the septum in M mode in a parasternal view using a 3.0-mL bolus of sonicated amidotrizoate sodium meglumine through the guiding catheter. The gray level before injection was subtracted from the gray level after injection to maximize contrast time-intensity curves. The area under the curve was used as an indicator of myocardial blood flow, and subendocardial/subepicardial ratios were measured. After baseline measurements were obtained, Doppler and echographic data were recorded after a bolus infusion of papaverine into the left main coronary artery. The same protocol was performed in patients after angioplasty and in five control subjects with normal coronary arteries. Before angioplasty, echocardiographic and Doppler coronary reserve were 2.57±0.48 and 2.54±0.57, respectively. Both increased after angioplasty to 3.65±0.57 and 3.36±0.70, respectively (P<.05). Coronary reserve values obtained in patients with these two methods under the different conditions and in control subjects were correlated (r=.81; P=.0001). Before angioplasty, subendocardial/subepicardial septal ratios decreased from 0.80±0.48 to 0.60±0.27 after papaverine (P<.05). However, after angioplasty, these ratios tended to increase, from 0.72±0.27 to 0.92±0.45 after papaverine, but they did not change in control subjects (1.11±0.23 to 0.92±0.11).
Conclusions These results show that myocardial contrast echocardiography yields flow reserve values that correlate with values obtained using intracoronary Doppler. This technique may be considered as an accurate tool to assess coronary reserve in humans.
Key Words: angioplasty • echocardiography • myocardial perfusion
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Experimental studies using radiolabeled microsphere techniques have shown that myocardial ischemia predominantly affects the subendocardial layer of the myocardium.1 2 3 4 5 Recently, myocardial contrast echocardiography (MCE) has been proposed as a new technique for assessing coronary circulation and transmural myocardial perfusion.6 7 8 9 10 11 12 13 14 Experimental studies have demonstrated that in comparison to radiolabeled microspheres, MCE is an accurate technique for assessing coronary reserve in dogs with critical stenoses.12 Moreover, MCE is a sensitive technique for detecting changes in myocardial flow induced by dipyridamole in the various layers of normal segments as well as segments supplied by a critical stenotic coronary artery.15
The intracoronary Doppler technique has shown that in patients with coronary stenoses, the coronary reserve remains abnormal even after successful coronary angioplasty.16 17 18 19 20 21 Recent studies have suggested that myocardial echocardiography could be useful in assessing the functional success of angioplasty.10 12 13 22 Using MCE, Lim et al11 showed that in patients with coronary artery stenosis there was a decrease in the subendocardial/subepicardial gray-level ratio in the segment supplied by a stenotic coronary artery, thus indicating the occurrence of subendocardial myocardial ischemia. However, the effects of angioplasty on the various myocardial layers have not yet been studied in humans.
The present study was designed to assess the accuracy of MCE measurements of coronary reserve compared with intracoronary Doppler measurements and to investigate the effect of angioplasty on transmural blood flow distribution. Accordingly, we examined the effect of angioplasty on myocardial blood flow distribution and coronary reserve in patients with a proximal left anterior descending coronary artery stenosis using MCE. This study was done at rest and after papaverine coronary infusion in order to assess the coronary reserve.23
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Selection
The study population consisted of 12 patients (10 men and 2 women; mean age, 58±9 years) selected from a population of patients scheduled for percutaneous transluminal coronary balloon angioplasty of proximal left anterior descending coronary artery stenosis. Patients were included if they had ischemia as demonstrated by exercise testing or thallium-201 imaging; a good acoustic window for the visualization of the interventricular septum; single-vessel disease of the proximal left anterior descending coronary artery (stenosis >70%); no angiographic evidence of collateral circulation (grade 0); normal wall motion as assessed by both two-dimensional echocardiography (fractional shortening, 35±6%) and left ventriculography (left ventricular ejection fraction, 64±6%). Patients with unstable angina, recent or previous myocardial infarction, previous percutaneous transluminal coronary angioplasty procedure, or clinical evidence of heart failure were not included. No patient had myocardial hypertrophy or valvular heart disease. Vasoactive therapy, including calcium channel blockers, angiotensin-converting enzyme inhibitors, and long-acting nitrates, was discontinued at least 24 hours before catheterization. No patient received ß-adrenergic blockers within 48 hours before the study. All patients received aspirin 100 mg/d for 48 hours before the study, and the use of short-acting sublingual nitroglycerin was allowed up to 1 hour before the study. Written informed consent was obtained from all patients before inclusion. The study protocol was approved by the local ethics committee.
Control Group
Five patients (4 men and 1 woman; mean age,
47±5 years)
undergoing coronary angiogram for diagnosis of atypical chest pain and
fulfilling the following inclusion criteria were considered as control
subjects in this study: normal coronary angiogram with luminal smooth
coronary arteries; no evidence of ischemia as demonstrated by exercise
testing and thallium-201 imaging; no risk factors for atherosclerosis;
no evidence of heart disease and no myocardial hypertrophy on
echocardiography; normal left end-diastolic ventricular
pressures (<10 mm Hg) assessed before performing coronary angiogram;
coronary blood flow reserve above 3 as assessed by intracoronary
papaverine administration. None of these patients used medications.
MCE Study
Septal M-mode images were obtained by a
commercially available
phased-array system (CFM 750 Vingmed) with a 3.25 MHz transducer. MCE
was performed by imaging an M-mode parasternal axis view just above the
midpapillary muscle level with a proximal depth, focusing only on the
right ventricle and interventricular septum during left main
intracoronary injection of sonicated amidotrizoate sodium meglumine
76%. Gain settings were adjusted at the beginning of the protocol and
were not changed.
Numerical echocardiographic data were directly
transferred to a
Macintosh IIci microcomputer and stored on an optical hard disk (300
MB). These data had spatial and temporal samplings of 
d=total
depth/256 and t=5 ms, respectively, on 256 gray levels. The
maximum
size of each data set was 256 pixels in depth and 2048 pixels in time.
Data handling, processing, display, and analysis were performed on
the microcomputer by using the ECHODISP program (Vingmed
Sound).
Our aim was to obtain the maximum information (number of pixels) on the interventricular septum. However, it was not possible to analyze the posterior wall with enough spatial precision to explore the subendocardial and subepicardial perfusion.
Echocardiographic Analysis
To quantify the intensity of
echocardiographic signals in
the septal segments, the CINEPROBE program (Vingmed
Sound) was used with 256 gray levels. On the M-mode septum,
end-diastolic bands 10 pixels wide were the regions of
interest. End diastole was defined as being coincident with the
upstroke of the electrocardiographic R wave. Each segment was divided
by the operator into two halves, corresponding to epicardial and
endocardial layers, and gray levels were measured for the entire
segment as well as for each layer. Epicardial and endocardial septal
interfaces were automatically detected on the gray-level profile traced
with the CINEPROBE program (Fig 1
).
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The four
end-diastolic preinjection contrast frames
were averaged to produce a mask frame either for the entire septum or
for both endocardial and epicardial halves. Digital subtraction was
performed by subtracting the gray-level values in the mask frame data
points from the corresponding gray levels in all postinjection frames.
Subtracted time-intensity curves were then generated by using the
diastolic data for the entire septum and for both the endocardial and
epicardial layers (Fig 2). Several measurements could be
made from the time-intensity curves and used as indices of myocardial
perfusion. In agreement with previous
studies,9 10 11 12 15
peak
intensity and the area under the curve were chosen. Two ratios were
used to define myocardial reserve as assessed by MCE: peak intensity
after papaverine coronary infusion over the baseline peak intensity and
area under the gray-level curve after papaverine infusion over the
baseline area. Finally, the subendocardial/subepicardial gray-level
ratio was calculated and defined as the ratio of the area under the
gray-level curve for the endocardial half over the area under the
gray-level curve for the epicardial half.
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Sonification and
Injection of the Contrast Solution
Sonification of the contrast
solution was done as
described by Keller et al12 using an Ultrasonic Atomizer
(Model VC50 AT). Briefly, 7 mL of amidotrizoate sodium meglumine 76%
was sonicated for approximately 30 seconds until a homogeneous and
slightly turbid solution was generated. Before injecting sonicated
material, the catheter was purged by opening the distal coronary
angioplasty catheter Y connector leading to
fill the catheter with blood. Three milliliters were rapidly injected
by hand into the catheter, and echocardiographic recordings were
obtained simultaneously until the contrast medium disappeared from the
myocardium. Because the dead space of the catheter is approximately 1
mL, only 2 mL of sonicated material entered the myocardium. All
sonifications and injections were performed manually by the same
investigator.
Wall-Motion Analysis
Measurements of
septal fractional shortening were made in a
cardiac cycle preceding the contrast injection at baseline and at peak
papaverine-induced hyperemia.
Intracoronary Doppler Study and Assessment of Coronary Artery
Stenosis
An 8.0F guiding catheter was positioned in the ostium of the
left coronary artery. A 3.0F Doppler catheter (NuVel, Nu Med Inc) with
a side-mounted crystal of 20 MHz was advanced through the guiding
catheter into the proximal left anterior descending coronary artery
prior to the stenosis. The Doppler signal was transmitted to a
velocimeter (MDV 20, Millar Instruments Inc). The position of the
catheter and the range of the sample volume were adjusted to obtain a
high-quality signal as assessed by both audio and graphic controls.
Mean and phasic Doppler velocity signals were recorded, and coronary
flow reserve was calculated as the quotient of the peak mean blood flow
velocity after papaverine administration over mean resting blood flow
velocity.
Coronary stenosis and the results of coronary angioplasty were assessed in two orthogonal views by quantitative coronary angiography as described.24
Hemodynamic Measurements
Since
load changes may influence coronary reserve, left
ventricular pressures and the first derivative of the left ventricular
pressure (peak positive and negative left ventricular dP/dt) were
monitored in seven patients with a 5F microtip Millar catheter (Millar
Industries) placed through the other femoral artery into the left
ventricle. Aortic pressure was monitored through the guiding catheter,
and ECG was continuously monitored throughout the study. ECG, Doppler
velocity, and pressure tracings as well as derivatives were read on a
multichannel recorder and recorded on a Gould recorder (Gould TA
2000).
Experimental Protocol
Before coronary angioplasty,
intraventricular and aortic
pressures, intracoronary Doppler velocity, septal thickening, and
contrast echocardiographic measurements were recorded at rest and 30 to
45 seconds after a bolus infusion of 12 mg papaverine into the left
main coronary artery to assess coronary myocardial reserve.
Video frames showing the Doppler catheter placement were recorded to ensure its correct repositioning after angioplasty. The Doppler catheter was then exchanged for a balloon angioplasty catheter, and the lesion was dilated. The size of the balloon was calculated on the basis of the normal segment proximal to the site of the lesion to be dilated. Three inflations of 90 seconds each were performed, and the result of the angioplasty was assessed quantitatively. In case of significant residual stenosis and to obtain the best angiographic result, a larger balloon was used, and repeated inflations were performed until a residual stenosis <30% was obtained.
After coronary angioplasty, a 5-minute period was observed to ensure that angiographic results were stable. At this point, the coronary Doppler catheter was advanced proximal to the dilated region and placed in a position similar to that in the preangioplasty study. The same parameters measured before coronary angioplasty were recorded again at rest and after papaverine infusion. After withdrawal of the intracoronary guidewire and Doppler catheter, angiograms were obtained in the same projections as those taken before the angioplasty to assess the final coronary angioplasty result.
Statistical Analysis
All data are expressed as
mean±SD. A paired t test
was used to compare reserve values (MCE and intracoronary velocity)
before and after angioplasty and the subendocardial/subepicardial
gray-level ratios measured before and after papaverine intracoronary
bolus injection both before and after angioplasty. Correlations between
coronary blood flow reserves as assessed by Doppler analysis and
MCE were performed by the linear regression method. Coronary flow
reserve using the intracoronary Doppler technique was calculated by an
independent investigator unaware of the echocardiographic data.
Statistical significance was accepted at P<.05.
Assessment of Reproducibility
The reproducibility for the
measurements of peak intensity, area
under the curve, and subendocardial/subepicardial gray-level ratio was
assessed in six other patients with stenosis of the left anterior
descending coronary artery undergoing routine coronary diagnosis
angiography. In these patients, injections of sonicated contrast medium
were repeated twice. Results are expressed as the mean±SD difference,
and correlations were calculated by the linear regression method.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Of the 12 patients initially studied, 3 had noninterpretable MCE data. After angioplasty, a right ventricular contrast enhancement was observed in these patients following the intracoronary injection of microbubbles during the assessment of coronary blood flow reserve. Consequently, since a correct determination of the septal contrast intensity was not possible, these 3 patients were excluded from the current study.
Angioplasty was successful for the remaining 9 patients, with a mean decrease in coronary stenosis from 84±21% to 27±18%, P<.01.
Hemodynamic Conditions and Septal Thickening
Systemic
hemodynamic parameters at rest and 30 to 45 seconds after
papaverine administration (peak effect on coronary blood flow) both
before and after coronary angioplasty are shown in Table 1. No
significant hemodynamic changes occurred after
papaverine infusion. End-diastolic pressure tended to
increase after papaverine, but the trend was similar before and after
angioplasty. Before angioplasty, septal thickening decreased from
43±6% to 30±6% after papaverine administration
(P<.05)
and tended to increase after angioplasty (39±6% to 42±9%,
P=NS).
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Coronary Reserve After Angioplasty
Individual values of
coronary reserve assessed either by
Doppler or MCE before angioplasty are shown in Table 2.
Coronary blood flow velocity at baseline (before coronary reserve
assessment) was similar before and after coronary angioplasty
(4.23±0.3 versus 4.34±0.45 kHz, P=NS). Compared
with
values measured before angioplasty, coronary reserve as assessed by
Doppler and transmural MCE (area under the curve) increased by 33±21%
and 42±15%, respectively (both P<.05).
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Regional Assessment of Coronary Blood Flow
Before
angioplasty, subendocardial coronary reserve (2.23±0.36)
was lower than subepicardial coronary reserve (2.99±0.87,
P<.05) (Table 3). Subendocardial/subepicardial
gray-level
ratio was 0.80±0.48 at rest and decreased to 0.60±0.27
(P<.05) after papaverine infusion (Fig 3). After
angioplasty, subendocardial coronary reserve
increased significantly, but no change was observed in
subepicardial coronary reserve. In contrast to conditions before
angioplasty, subendocardial coronary reserve was higher than the
subepicardial reserve. At rest, the subendocardial/subepicardial
gray-level ratio was 0.72±0.27 and tended to increase
(0.92±0.45,
P=NS) after papaverine infusion in contrast to conditions
before angioplasty. Individual data are given in Fig 3.
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Coronary Blood Flow Reserve in Control Subjects
At baseline,
heart rate and mean aortic blood pressure were 67±18
beats per minute and 95±12 mm Hg, respectively. No significant
changes in these parameters were observed after papaverine
administration, and septal thickening remained unchanged (46±7%
versus 45±7% at baseline, P=NS). Coronary blood flow
reserve as assessed by Doppler and transmural MCE of the entire septum
(area under the curve) were 3.78±0.63 (range, 3.1 to 3.9) and
3.58±0.28 (range, 3.3 to 4), respectively.
Subendocardial coronary reserve (3.14±0.11) was significantly (P<.05) lower than subepicardial coronary reserve (4.35±0.84).
The subendocardial/subepicardial level ratio at
rest was 1.11±0.12, a
value not significantly different from patients before angioplasty
(P=.12). After papaverine infusion, the
subendocardial/subepicardial level ratio did not change significantly
(0.91±0.09, P=NS). Individual data are shown in Fig
3
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Relation Between Coronary Reserve As Assessed by MCE and Doppler
Measurements
Coronary reserve values obtained at rest and after
papaverine
administration using both methods were correlated (r=.81,
P=.0001; Fig 4). No correlation was found
with data from peak intensity (r=.39, P=.11)
and
Doppler coronary reserve.
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Correlations between the coronary reserve of the subepicardium and subendocardium as assessed by MCE and the coronary reserve as assessed by Doppler were r=.77, P=.0001 and r=.55, P=.0064, respectively (all P<.05).
Reproducibility of Results
Peak
intensity curve, area under the curve, and
subendocardial/subepicardial gray-level ratio showed reproducible
results between the same observer. The mean differences for the two
analyses were 0.035±0.199 (2.7%) for peak intensity and
0.092±0.229
(3.5%) for area under the curve. The mean subendocardial/subepicardial
gray-level ratios measured in the two sequential injections were
0.83±0.044 and 0.88±0.052. The mean differences for the two
analyses
were 0.052±0.021 (6.2%). For each variable, the two serial
measurements were correlated: r=.92 (P=.002),
r=.91 (P=.003), and r=0.93
(P=.008) for peak intensity, area under the curve, and
subendocardial/subepicardial gray-level ratio, respectively.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The present study shows that coronary reserve measured by the area under the curve as assessed by MCE is correlated to coronary reserve as measured by the Doppler technique. This study also shows that percutaneous transluminal coronary angioplasty improves the coronary reserve of the subendocardial region and increases the subendocardial/subepicardial gray-level ratio. These results suggest that coronary angioplasty improves the perfusion of the subendocardial region.
Assessment of Regional Blood Flow by MCE
MCE was initially
proposed as a method of identifying myocardial
regions supplied by the injected coronary artery. Experimental data
first demonstrated the ability of this method to visualize accurately
myocardial segments perfused by the vessels filled with the contrast
solution.6 7 8 MCE can also be
successfully applied to
estimate perfusion zones of coronary artery during cardiac
catheterization.9 10 11 12 13 14
Quantification rather than the
presence or absence of enhanced contrast was investigated, showing that
MCE allowed the assessment of coronary blood flow reserve and
transmural myocardial blood flow distribution. Indeed, this technique
was validated for the measurement of blood flow reserve against the
method of radiolabeled microspheres in dogs. In particular, Keller et
al12 showed that the ratios of areas under the curves
derived from time-intensity plots generated during MCE were well
correlated with coronary blood flow reserve using radiolabeled
microspheres. Cheirif et al15 showed that MCE was a
sensitive technique to detect changes in myocardial flow induced by
dipyridamole in the various layers of normal segments as well as in
segments supplied by a critically stenotic coronary artery. In humans,
regional measurements of myocardial contrast intensity before and after
papaverine infusion were obtained, showing that MCE was able to
differentiate regions with normal hyperemic response from those with
abnormal response due to the presence of an obstructive lesion as
determined angiographically.10 Recently, Lim et
al11 measured transmural myocardial blood flow
distribution in patients with or without coronary artery stenosis using
MCE. They found no significant difference in the
subendocardial/subepicardial gray-level ratio before rapid pacing among
anteroseptal, posterolateral, and inferior segments in patients without
coronary artery disease, indicating that transmural myocardial blood
flow distribution was homogeneous from endocardium to epicardium in all
areas of the left ventricular short-axis image. However, the
subendocardial/subepicardial gray-level ratio significantly decreased
after rapid pacing in segments supplied by stenotic coronary artery,
indicating a subendocardial ischemia after pacing but not at rest.
In
the present study, another methodology was used to detect
regional myocardial blood flow perfusion. M mode was chosen to focus on
an accurate temporal resolution. To avoid or to minimize translation
between end-diastolic frames, patients were asked to hold
their breath during the injections and the echographic data
acquisition. On-line digital capture of scan line echo data avoided
many problems of image degradation. Furthermore, subsequent digital
subtraction processing seemed to reduce the effects of instrument
settings and facilitated the study of spatial distribution of
perfusion. The ability of digital subtraction echocardiography to
provide high-quality and contrast-enhanced radiographic images is
accepted. The digital subtraction processing techniques applied to
echocardiography in this study were similar. In studies in which
coronary flow was reduced, measurements from the washout phase of the
curve, such as T
, were well correlated
with changes in coronary artery blood flow and not myocardial
perfusion.8 25 However, when the experimental
protocol
included a hyperemic stimulation, the results were more accurate with
peak intensity9 10 11 15 and
area under the
curve12 15 than with measurements of the
T. In the present study and in
agreement with
other human studies, correlation with Doppler coronary blood flow
velocity was found using area under the curve and not peak
intensity.26 However, using the area under the curve, a
coefficient correlation of only .81 indicates that echocardiographic
measurements account for 65% of the variability of the Doppler
measurement.
Coronary Blood Flow Reserve After Coronary Angioplasty
Several investigators have reported an improvement of the coronary
blood flow reserve after percutaneous transluminal coronary
angioplasty. However, it has been shown that coronary blood flow
reserve remains depressed in approximately half of the patients despite
angiographic and hemodynamic improvement in the epicardial
artery.13 16 21 27 Recovery
of normal coronary reserve
responses may be expected in most patients some months later. Previous
studies have demonstrated good correlation between the measurements of
coronary flow reserve as assessed by Doppler technique and
MCE.9 Additionally, using MCE, Reisner et
al27 showed a marked improvement in peak contrast
intensity after coronary angioplasty, and Porter et al28
found a marked improvement in area under the curve, demonstrating that
MCE was able to assess quantitatively the immediate results of coronary
angioplasty. However, no study comparing the results of coronary
angioplasty with both Doppler and MCE techniques had been made. In the
present study, after coronary angioplasty, both techniques showed
an increase in coronary blood flow reserve, which tends to normalize.
In agreement with a previous report,9 the present
study shows that changes in Doppler epicardial flow velocity after
papaverine administration are correlated with the changes in area under
the curve in the entire septum as measured by MCE. Interestingly,
analysis of regional reserve showed that in contrast to conditions
before coronary angioplasty, coronary reserve of the subendocardium
increased after coronary angioplasty. However, if an improvement of
subendocardial perfusion is expected after coronary angioplasty, the
reasons why coronary reserve was higher after coronary angioplasty in
the subendocardium compared with the subepicardium remain unclear. We
cannot exclude that regional wall-motion changes may have participated
in changing regional blood flow since septal thickening was different
after angioplasty during the measurement of coronary blood flow.
Subendocardial/Subepicardial Gray-Level Ratio
In addition to
regional coronary reserve assessment, MCE allows
the measurement of endocardial/epicardial gray-level ratios. In the
present study, the subendocardial/subepicardial ratio at rest was
below 1 and lower than the findings of Lim et al,11 who
had an at-rest subendocardial/subepicardial ratio nearly equal to 1 in
patients with coronary artery stenosis. However, since there was no
significant difference of the subendocardial/subepicardial ratio
compared with that found in our control population, we cannot ascertain
that there was a subendocardial ischemia at rest. Indeed, experimental
studies have demonstrated that severe coronary stenosis produces
myocardial underperfusion or perfusion defect even at
rest.13 During papaverine infusion, a significant decrease
in subendocardial/subepicardial ratio was shown before angioplasty in
patients with coronary stenosis, but no change was observed in control
subjects. After coronary angioplasty, this ratio tended to increase.
These results suggest that patients with coronary artery stenosis may
have subendocardial hypoperfusion without at-rest wall-motion
dysfunction. These data agree with experimental data that show
subendocardial ischemia.17 19 Recently, using both
the
microsphere method and MCE, Cheirif et al15 showed that
dipyridamole administration resulted in a significant reduction in
endocardial/epicardial flow ratio in an ischemic region due to a
critical stenosis of the circumflex artery. A similar change in the
subendocardial/subepicardial ratio was observed by contrast
echocardiography with the use of the area under the curves of the
subendocardial and subepicardial layers. These data are also consistent
with those of Lim et al,11 who demonstrated that the
subendocardial/subepicardial ratio decreased after pacing in patients
with coronary stenosis.
Limitations of the Study
All injections and sonifications
were performed by the same
investigator to decrease the variability in the rate of injection and
in the number and size of the bubbles generated. Nevertheless,
limitations included the absolute size and number of microbubbles
injected and their volume of distribution, gain and reject settings in
the echocardiographic system, depth of penetration, degree of
attenuation, exact angle of incidence, axial resolution, and gray-scale
compression settings. Therefore, although relative blood flow could be
measured, it might not be feasible to measure absolute myocardial blood
flow. For these reasons, it seems important to focus on the results of
subendocardial/subepicardial ratios calculated during the same
injection.
We used amidotrizoate sodium meglumine because of the current use of this agent in other studies,10 12 22 although this contrast medium may influence myocardial contractility and consequently coronary blood flow. However, we monitored ventricular pressure and derivatives, and we did not observe any significant negative inotropic effect during contrast medium injections. This is probably due to the small quantities of contrast agent injected into the coronary circulation. Although new contrast agents appear promising,29 the results found in the present study are unlikely to have been affected by the choice of meglumine.
The present results concerning transmural blood flow distribution must be considered very carefully since we could not validate this technique with microspheres in humans. However, animal studies have validated MCE as a tool for assessing transmural blood flow, and our findings concerning the effect of angioplasty on transmural blood flow distribution agree with other studies.30 Additionally, there is indeed no "gold standard" for assessing transmural coronary flow reserve in humans, and other promising techniques, such as nuclear studies, have not yet been validated.31
Clinical Implications
The ability to assess changes in blood
flow in the different
myocardial layers is a major advantage of MCE. In patients with
coronary stenosis, MCE shows that perfusion of the subendocardium was
altered, and our data suggest that it may be reversed by angioplasty.
Application of this technique could be considered for patients with
known altered coronary reserve, as in hypertrophy, and the results may
improve our understanding of myocardial perfusion in different
pathological states.
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Acknowledgments |
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This study was supported in part by a grant of the Fédération Française de Cardiologie.
Received June 20, 1994; revision received September 20, 1994; accepted October 3, 1994.
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