Author + information
- Received March 5, 1997
- Revision received June 27, 1997
- Accepted July 10, 1997
- Published online November 1, 1997.
- ↵*Dr. Thomas R. Porter, Section of Cardiology, University of Nebraska Medical Center, 600 South 42nd Street, Box 982265, Omaha, Nebraska 68198-2265.
Objectives. We sought to determine the effect of multivessel as opposed to single-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging and intravenous perfluorocarbon-exposed sonicated dextrose albumin contrast injection.
Background. Intermittent harmonic imaging has permitted the detection of myocardial perfusion abnormalities with an intravenous ultrasound contrast agent. The effect of multivessel disease on inducibility of these perfusion abnormalities is unknown.
Methods. In 10 dogs, intravenous injections of contrast agent were given at rest and during dobutamine stress echocardiography when a single coronary artery stenosis was present (≥50% diameter by quantitative angiography) and again when a second stenosis (range 44% to 92% diameter) was present in the vessel supplying the adjacent perfusion bed. The peak myocardial contrast was visually and quantitatively assessed in the mid and lateral regions of the perfusion bed of the first stenosis (original stenosis zone) in the presence of one- and two-vessel stenosis.
Results. Peak myocardial contrast defects in both the mid and lateral segments of the original stenosis zone during dobutamine stress echocardiography was significantly lower when two-vessel stenosis was present (p = 0.015), especially in the lateral segment. The spatial extent of the perfusion defect in the original stenosis zone risk area increased significantly when two-vessel stenosis was present, and correlated closely with actual risk area (r = 0.99). Previous total occlusion followed by reperfusion of the vessel supplying the original stenosis zone significantly increased the amount of collateral activity between perfusion beds.
Conclusions. Collateral flow limits the spatial extent of inducible ischemia within the risk area of single-vessel stenosis. Restoring blood flow to one perfusion bed reduces the extent of a perfusion abnormality that can be induced in an adjacent stenosed bed.
The myocardial contrast produced with intermittent harmonic imaging after intravenous perfluorocarbon ultrasound contrast injection has been shown to correlate with both coronary blood flow and myocardial blood flow changes [1, 2]. More recently, it has been shown to be capable of quantifying absolute myocardial blood flow . These validation studies have primarily been done in the absence of coronary artery disease (CAD) or with only single coronary artery narrowing. In a routine clinical setting, however, noninvasive imaging technicians are often asked not only to detect whether significant CAD is present, but also to discriminate between single-vessel and multivessel CAD. The myocardial contrast produced with intermittent imaging in an experimental setting of both single-vessel and multivessel CAD, therefore, may give a better understanding of how sensitive this technique is in discriminating between these two settings and how much global myocardial perfusion is affected by significant coronary artery narrowing in more than one vessel. The purpose of this study was to compare the effects of two-vessel versus one-vessel stenosis on the severity of a contrast defect that can be induced during stress echocardiography when using an intravenous ultrasound contrast agent and intermittent harmonic imaging.
1.1 Preparation of Perfluorocarbon-Exposed, Sonicated Dextrose Albumin
Perfluorocarbon-exposed sonicated dextrose albumin (PESDA) was prepared similar to previously described methods . Briefly, 8 ml of perfluorobutane was hand-agitated with a 3:1 mixture of 5% dextrose and 5% human albumin. This mixture then underwent electromechanical sonication for 80 s. The mean microbubble size of PESDA using this method has been shown to be 4.7 ± 0.2 μm, with a mean concentration of 1.3 × 109microbubbles per milliliter. The dose of intravenous PESDA for all comparisons of myocardial contrast enhancement was 0.0025 ml/kg in seven dogs, 0.005 ml/kg in two dogs and 0.01 ml/kg in one dog.
1.2 Animal Preparation
The study involved 10 mongrel dogs. The entire study was approved by the Institutional Animal Care and Use Committee and was in compliance with the “Position of the American Heart Association on Research Animal Use,” adopted by the Association in November 1984. Each dog was placed under general anesthesia with intravenous sodium pentobarbital, intubated and placed on a respirator. A left lateral thoracotomy was performed and the heart was suspended in a pericardial cradle. Two-millimeter transit-time ultrasound coronary flow cuffs (S-series, Transonics, Inc.) were placed around the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCx) to monitor coronary blood flow. A 7F pulmonary artery catheter and a 7F pigtail catheter were used to monitor pulmonary artery and left ventricular pressures, respectively. Then 2-0 silk ligatures were placed around the LAD and LCx for subsequent creation of stenoses. Ultrasound images were obtained using a harmonic transducer supplied by either Hewlett Packard (2.0 MHz fundamental frequency) or Advanced Technology Laboratories (1.7 MHz fundamental frequency). The transducer was placed in a warm water bath overlying the anterior surface of the heart and positioned to produce a short-axis view of the left ventricle at the mid-papillary muscle level. The region of interest for comparing peak myocardial videointensity (PMVI) was either the midanteroseptal and midseptal segments (LAD perfusion bed) or midlateral and midposterior segments (LCx perfusion bed). Intermittent imaging was performed by triggering ultrasound transmission to just one point every one to three cardiac cycles.
Background-subtracted PMVI from the LAD and LCx perfusion beds was measured off-line at end-systole from high fidelity videotape images. Gray-scale software (Tom-Tec Review Station), which quantitates videointensity (0 to 255 scale) versus time, was used to measure the contrast intensity. Instrument settings and triggering intervals were kept constant in each dog for each comparison. The region of interest (∼100 square pixels) was placed at the midmyocardial level of each segment analyzed and kept at this position for comparisons of PMVI when one- and two-vessel stenoses were present. For the purpose of analysis, the perfusion bed supplied by the first stenosis was termed the original stenosis zone(SZ). This SZ was also subdivided into a middle segment (mid-SZ) and a lateral segment (lat-SZ) (outer 25% of the risk area). Then PMVI was measured in each of these regions under baseline conditions and during dobutamine stress echocardiography. The perfusion bed supplied by the second stenosis was termed the adjacent perfusion bed(APB).
1.3 Measurements of Regional Wall Thickness Inside and Outside the Ischemic Zone
Regional left ventricular wall thickening in the SZ and APB was measured at each setting using videotape analysis of the end-diastolic and end-systolic frames (defined as the largest and smallest left ventricular chamber sizes in the cardiac cycle, respectively). The average regional wall thickness from three equally spaced measurements of end-diastolic and end-systolic wall thickness within the LAD and LCx perfusion beds was taken after each intervention.
1.4 Creation of One- and Two-Vessel CAD Before and After Abrupt Occlusion
In the first six dogs, a 2-0 silk ligature was first tightened around the LAD (n = 4) or LCx (n = 2). As previously stated, the perfusion bed supplied by this vessel was called the SZ. Intravenous injections of PESDA were then administered, and contrast images from intermittent imaging were transferred to videotape. Conventional (>30 Hz) frame rate images were also recorded for wall thickening measurements. After these baseline injections, a second stenosis was then made in the second coronary artery supplying the APB. Repeat intravenous injections of PESDA were then performed in the setting of two-vessel stenosis. Coronary blood flow measurements in both vessels were also recorded with both one- and two-vessel stenoses.
Coronary angiography was then performed to assess the severity of stenosis. This was accomplished with a 7F Amplatz catheter, which was placed into the left main coronary artery under fluoroscopic guidance for injections (2 to 3 ml) of radiographic contrast agent. The images from these injections were stored on cine film and used to confirm angiographic stenosis severity after reperfusion with an automated border-detection computer program (ARTREK, ImageComm). The flow probe was removed before angiography so that both proximal and distal reference points could be used for quantitative angiography. The coronary catheter was used for calibration. Both percent diameter stenosis and minimal lumen diameter (MLD) were measured for each stenosis.
After this, incremental dobutamine infusion was performed starting with 5 μg/kg body weight per min for 7 min and increasing if needed to 10, 20, 30 and 40 μg/kg per min. Peak stress was considered present if the heart rate increased by 20 beats/min over baseline levels or a new wall motion abnormality developed. At peak stress, contrast enhancement with the same dose of intravenous PESDA as that used for baseline measurements was repeated using the same triggering interval. Coronary blood flow from the transit-time flow meters was also measured in each coronary vessel.
Then, the second stenosis supplying the APB was removed while the peak dobutamine dose was still at peak infusion. Once coronary flow reached a steady state in this vessel, contrast enhancement was reassessed with two more intravenous PESDA injections.
In four dogs, this same experimental protocol was performed after 1.6 ± 0.9-h occlusion of the vessel supplying the SZ (SZ-vessel) to assess the effect of previous coronary occlusion on the amount of collateral recruitment. After reperfusion, a stenosis (≥50% diameter) was again placed in the SZ-vessel. After intravenous PESDA injections in the setting of one-vessel stenosis, a second stenosis was placed in the vessel supplying the APB. After baseline PESDA injections, dobutamine infusion was initiated up to 10 μg/kg per min, and contrast injections were repeated with two-vessel and then one-vessel stenosis as described earlier.
In dogs in which a visually evident contrast defect was present in the SZ, the defect was planimetered during dobutamine stress echocardiography when two vessels were stenosed, and again after the stenosis supplying the APB was removed. These measurements were compared with the total spatial extent of the SZ perfusion bed (risk area), which was determined by injecting intravenous PESDA after total occlusion of the vessel at the end of the experiment. Finally, 40 ml of 3% Monastral Blue was then administered into the left atrial appendage, and the dog was subsequently killed. The heart was excised and sliced in views that corresponded to the short-axis echocardiographic image. A transparency was overlaid onto the myocardium for tracing of the myocardial regions that were stained by Monastral Blue and the areas that were not stained (area at risk). These risk area measurements were correlated with the spatial extent of the contrast defect determined with PESDA during total occlusion of the SZ-vessel. Triphenyltetrazolium chloride staining was performed in the four dogs that had prolonged coronary occlusion before performing the one-vessel versus two-vessel study.
1.5 Statistical Analysis
Peak myocardial videointensities in the SZ (mid and lateral segments) with two-vessel compared with one-vessel stenosis during dobutamine stress echocardiography were compared using the paired ttest. Analysis of variance (Student-Newman-Keuls multiple comparisons procedure) was used to compare PMVI at peak dobutamine stress echocardiography in the mid and lateral segments of the SZ during one- and two-vessel stenosis. This was also used to compare coronary blood flow and wall thickening at peak dobutamine stress echocardiography in the SZ and APB during one-vessel and two-vessel CAD.
Comparisons of PMVI in the SZ during dobutamine stress echocardiography in dogs with two-vessel stenosis and a previous coronary occlusion compared with those with no previous occlusion were made using the unpaired ttest. This was also used to compare the SZ-MLDs in dogs that had a visually evident contrast defect with those of dogs that did not exhibit a contrast defect. A correlation between the MLD of the stenosis supplying the APB and the degree of improvement in myocardial contrast in the lat-SZ after releasing the stenosis supplying the APB during dobutamine stress echocardiography was made using the Pearson correlation coefficient. Interobserver variabilities in PMVI measurements between two independent reviewers were also compared using the Pearson correlation coefficient. Injection to injection variability in PMVI was also measured with the same coefficient.
The range of MLDs in the SZ-vessel was 0.51 to 1.47 mm (mean 0.93), whereas the range of percent diameter stenoses was 50% to 82% (mean 61%). The range of MLDs supplying the APB was 0.21 to 1.5 mm (mean 0.97). Mean percent diameter of the vessel supplying the APB was 70 ± 11%.
Although the four dogs that were studied after prolonged coronary ischemia had only a 10 μg/kg per min dose of dobutamine, they also had a chronotropic response during dobutamine infusion. The mean heart rate under rest conditions in the six dogs that had studies before coronary occlusion was 129 ± 19 beats/min and increased to 163 ± 7 beats/min during dobutamine stress echocardiography. In the four dogs that were studied after reperfusion, the rest heart rate was 102 ± 18 beats/min and increased to 131 ± 16 beats/min during dobutamine infusion. Left ventricular systolic pressure also increased significantly from 111 ± 15 mm Hg under baseline conditions to 139 ± 28 mm Hg during dobutamine stress echocardiography in all dogs.
2.1 Coronary Blood Flow and Wall Thickening Responses in the Setting of One-Vessel and Two-Vessel Stenoses
Table 1demonstrates the changes in wall thickening and coronary blood flow to both the SZ and APB under rest conditions and during dobutamine stress echocardiography in the presence of one- and two-vessel stenoses. Coronary blood flow in the vessel supplying the APB during dobutamine stress echocardiography in the setting of two-vessel stenosis was 45 ± 31 ml/min and increased significantly to 61 ± 26 ml/min when this stenosis was released (p < 0.05) (Table 1). Release of the stenosis supplying the APB did not increase anterograde flow in the SZ-vessel (Table 1), but there was a significant improvement in PMVI in the lat-SZ, indicating collateral flow from the APB (see later discussion).
In three of the six dogs studied during dobutamine stress echocardiography (without previous occlusion), wall thickening was abnormal (<30%) in the SZ when two-vessel stenosis was present. When the stenosis supplying the APB was removed, only one dog had abnormal wall thickening. In the four dogs studied after prolonged coronary occlusion of the SZ, wall thickening during dobutamine stress echocardiography was normal (≥30%) in all dogs in the setting of two-vessel stenosis.
2.2 PMVI Measurements After Intravenous Contrast Injection with Intermittent Harmonic Imaging in the Setting of One- Versus Two-Vessel Stenosis
During dobutamine stress echocardiography, PMVI was significantly lower in the mid-SZ and lat-SZ when a second stenosis was present in the vessel supplying the APB (Table 1). Table 2demonstrates the individual changes in PMVI in the mid-SZ and lat-SZ during dobutamine stress echocardiography when one- and two-vessel narrowing was present. In one dog (dog 7, Table 2), baseline measurements of PMVI in each segment were not obtained when both one- and two-vessel stenoses were present. In dogs with >50% diameter stenosis supplying the APB (8 of 10 dogs), the magnitude of the increase in PMVI in the lat-SZ perfusion bed when going from two-vessel to one-vessel stenosis during dobutamine stress echocardiography was linearly related to the MLD of the stenosis of the vessel supplying the APB (r = −0.85, p < 0.05) (Fig. 1). The increase in PMVI in the lat-SZ during dobutamine stress echocardiography after removal of the stenosis supplying the APB was also affected by the severity of stenosis supplying the original SZ. As can be seen from Table 2the greatest increases in PMVI in the lat-SZ during dobutamine stress echocardiography after removal of the APB stenosis occurred in dogs that had eithera MLD <1.0 mm supplying the APB ora MLD <0.70 mm supplying the SZ. The increases in PMVI in the remaining dogs were of lesser significance (range 4% to 24%) and were only slightly higher than injection to injection variability or interobserver variability (see later discussion).
A significant increase in PMVI during dobutamine stress echocardiography was also observed in the mid portion of the risk area of the SZ in five of the 10 dogs after removal of the APB stenosis. In all five of these dogs, anterograde coronary blood flow to the SZ decreased during dobutamine stress echocardiography, whereas coronary blood flow increased or stayed the same in the dogs that did not exhibit a change in PMVI in the mid portion of the SZ when the stenosis supplying the APB was removed.
2.3 Differences in Peak Myocardial Contrast in SZ of Dogs with Previous Occlusion
As can be seen in Table 2dogs in whom studies were performed after prolonged coronary occlusion demonstrated similar responses in the lat-SZ during dobutamine stress echocardiography when compared with those that had comparisons between one-vessel and two-vessel disease without previous occlusion (dogs 1 to 6) (Table 2). Despite similar stenosis severity (67 ± 15% in the inducible ischemia only group vs. 60 ± 8% in the coronary reperfusion plus induced ischemia group), PMVI in the mid-SZ and lat-SZ during two-vessel stenosis was significantly higher during dobutamine stress echocardiography in the dogs that had previous occlusion (81 ± 37 U in dogs with previous occlusion vs. 41 ± 28 U in dogs without previous occlusion) (p < 0.05).
2.4 Spatial Measurements of Contrast Defect Within SZ During Dobutamine Stress Echocardiography During One- and Two-Vessel Stenosis
In six of the dogs, the contrast defect in the SZ was visually evident by both observers during dobutamine stress echocardiography and could be spatially measured in the presence of both one- and two-vessel stenosis (Fig. 2). The MLD of the SZ-vessel of these six dogs tended to be smaller than that in the other four dogs in whom a visually evident defect could not be spatially measured (0.8 ± 0.2 mm in those with a visually evident defect vs. 1.1 ± 0.3 mm in those without a visually evident contrast defect in the SZ during dobutamine stress echocardiography) (p = 0.056). In the six dogs with a visually evident defect, the size of the contrast defect within the risk area of the SZ increased significantly when a stenosis supplying the APB was present (Fig. 3), with the increase in size occurring mainly at the lateral margins of the SZ risk area. The contrast defect size with two-vessel stenosis at peak dobutamine stress echocardiography closely approximated total risk area for the SZ (r = 0.99, p < 0.005).
Fig. 3⇓is a short-axis image from one dog during dobutamine stress echocardiography that demonstrates the effect of two-vessel stenosis on the size of the contrast defect in the SZ (LAD in this dog). Fig. 4is a second example where the LCx was the original stenosis, again showing the marked increase in size of the contrast defect within the circumflex risk area when two-vessel stenosis was present during dobutamine stress echocardiography.
There was a close correlation between the risk area determined by contrast echocardiography during total occlusion of the coronary artery and Monastral Blue–derived risk area (r = 0.93, p = 0.008). In the four dogs that were studied after coronary reperfusion, the infarct area within the SZ determined with triphenyltetrazolium chloride was 25 ± 14%.
The interobserver variability in PMVI measurements between two independent observers was 19% (r = 0.96, p < 0.005, SE 13 U). Injection to injection variability in PMVI measurements both at rest and during dobutamine stress echocardiography (total of 14 comparisons) was 16% (r = 0.97, p < 0.001, SE 9 U).
Previous experimental investigations studying collateral blood flow with intracoronarycontrast echocardiography have demonstrated the dynamic interaction between two APBs when anterograde myocardial blood flow to one of the regions becomes reduced [5, 6]. The lateral zone of the risk area in these studies became highly dependent on collateral blood flow from the APB when rest anterograde myocardial blood flow was reduced . Other investigators have demonstrated using intracoronary contrast echocardiography that collateral perfusion in dogs played a role in determining whether recovery of function in the infarct zone would occur. More extensive collateral flow resulted in a smaller infarct size . Experimental studies using radiolabeled microspheres have demonstrated that a decrease in subendocardial blood flow in the LAD perfusion bed occurs during acute LCx ischemia .
In this study, we demonstrated a similar dynamic interplay between LAD and LCx perfusion beds during dobutamine stress echocardiography with intravenous ultrasound contrast and intermittent harmonic imaging. The size of a dobutamine-induced contrast defect in the perfusion bed of a vessel that had a stenosis was influenced by whether there was also a significant stenosis in the APB. A second coronary stenosis broadened the lateral extent of the contrast defect in the original SZ during dobutamine stress echocardiography. There was a linear relation between the severity of the stenosis supplying the APB and severity of the contrast defect observed in the SZ (Fig. 1). When this second stenosis supplying the APB was removed, the size of the perfusion defect in the original SZ was reduced and quantitatively resulted in a significant increase in PMVI in the lateral segment of the SZ perfusion bed.
Although the increase in PMVI in the original SZ after removal of the stenosis supplying the APB during dobutamine stress echocardiography was significantly greater in the lateral than in the mid segment of the SZ, we also observed an increase in PMVI in the mid segment in five of the 10 dogs. It was in these five dogs that coronary blood flow to the SZ actually decreased during dobutamine infusion, indicating a functionally more severe stenosis when compared with the remaining dogs in whom no change in PMVI in the central segment of SZ occurred after removal of the APB stenosis. Previous observations have also shown that even central segments of a perfusion bed can receive flow from adjacent perfusion beds when anterograde blood flow becomes severely reduced .
3.1 Clinical Implications of the Study
Clinical studies using intracoronarymyocardial contrast echocardiography in humans have shown that greater collateral flow to the perfusion bed of an occluded infarct vessel results in lower peak creatine kinase levels and better recovery of function within the infarct zone after restoration of anterograde flow . These studies also demonstrated the superiority of contrast echocardiography in identifying collateral blood flow when compared with angiography. Other investigators have demonstrated that contrast enhancement from collateral blood flow disappears immediately after successful angioplasty of the coronary artery supplying anterograde flow to the recipient perfusion bed .
Although there are differences in the amount of epicardial and endocardial collateral connections between dogs and humans , the findings of this study may indicate that collateral flow from APBs reduces the amount of inducible ischemia that occurs when only one-vessel CAD exists. This may explain why the sensitivity of stress perfusion imaging techniques is consistently lower in detecting angiographically significant single-vessel CAD compared with multivessel disease . In our study, perfusion defects were significantly larger in the original SZ only when a second stenosis was present in the APB. This interaction between perfusion beds is also important to consider when revascularization is being considered in patients. Even if only one vessel could be revascularized in a patient with multivessel CAD, it may improve blood flow to regions outside the distribution of this vessel during periods of stress.
In our study, we found that dogs with a previous coronary occlusion had a sustained increase in collateral flow to the SZ during dobutamine stress echocardiography when compared with dogs that did not have a previous coronary occlusion. Previous ischemia may increase collateral flow to this region and hence reduce the amount of ischemia that can be induced after reperfusion. This may explain why patients who have a previous history of angina, even if it occurred just 48 h before acute myocardial infarction, have less myocardial damage and a lower complication rate than patients with no antecedent angina before infarction .
3.2 Study Limitations
One limitation of our study is that the coronary lesion was a discrete stenosis in an acute setting. Although this is different from the more chronic and diffuse development of a coronary stenosis in the human setting, there is evidence that this dynamic interaction between perfusion beds may be even more prominent in the chronic setting. Intermittent ischemia in chronic CAD may elicit release of growth factors that promote development of coronary collateral vessels . Total occlusion of the LAD has been shown to only minimally affect left ventricular systolic function in patients with a long history of angina before occlusion . It is therefore likely that the results of this study may only indicate the minimal impact that collateral vessels play in preserving blood flow to a perfusion bed with reduced anterograde flow reserve.
Second, although an increase in PMVI in the lat-SZ was observed when going from two- to one-vessel stenosis during dobutamine stress echocardiography, we could visually identify a perfusion defect in the SZ in only six of the dogs. One reason for this is the poor ability of gray-scale imaging, even with intermittent harmonic imaging, to detect smaller regional differences in microbubble concentration within the myocardium. This problem was aggravated during two-vessel ischemia, because the APB contrast enhancement was also decreased. Recent developments in digital processing, such as subtraction of precontrast images, combined with color-coding algorithms that allow better visual discrimination of regional differences in videointensity [17, 18], should improve our ability to detect the spatial extent of ischemia.
Third, the range of videointensity gray scale for the off-line analysis of myocardial contrast enhancement used in this study was from 1 to 255. Adding background myocardial videointensity, maximal myocardial videointensity reached 200 U in some dogs before background subtraction. These higher values may have been in the nonlinear portion of the videointensity versus microbubble concentration curve. Other investigators have shown that the relation between videointensity and bubble concentration remains linear at the lower end of this scale , and most videointensities within the myocardium in our study were in this lower range.
Finally, intermittent harmonic imaging with intravenous ultrasound contrast injection is limited when compared with selective intracoronary contrast injections, because the former cannot quantify how much one vessel is supplying in terms of collateral channels to an adjacent bed. Furthermore, we do not have knowledge of where the mid and lateral portions of the risk area are located in a clinical setting. In our study, however, we could rapidly determine how much restoration of blood flow to one vessel resulted in improvement in contrast to the APB. By assessing contrast enhancement before and after revascularization, intermittent imaging with intravenous contrast injection could rapidly and noninvasively identify how much myocardial blood flow is improved to all perfusion beds after revascularization of one vessel.
The size and severity of myocardial contrast defects in one perfusion bed observed with intermittent imaging and intravenous contrast injections during dobutamine stress echocardiography are significantly affected by the presence of a stenosis in the APB. In contrast, removing the stenosis in this APB results in a significant improvement in perfusion to the original risk area during periods of stress. The ability of intermittent harmonic imaging to observe these phenomena must still be tested in a noninvasive transthoracic setting. Nonetheless, this dynamic interplay between APBs should be considered when assessing what effect multivessel CAD has on global myocardial perfusion.
☆ This study was supported in part by research funding obtained from the Department of Internal Medicine, University of Nebraska.
- adjacent perfusion bed
- coronary artery disease
- left anterior decending coronary artery
- lateral segment of stenosis zone
- left circumflex coronary artery
- middle segment of stenosis zone
- minimal lumen diameter
- perfluorocarbon-exposed sonicated dextrose albumin
- peak myocardial videointensity
- vessel supplying the stenosis zone
- Received March 5, 1997.
- Revision received June 27, 1997.
- Accepted July 10, 1997.
- The American College of Cardiology
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