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Comparison of Dilatation Mechanism and Long-Term Vessel Remodeling Between Directional Coronary Atherectomy and Balloon Angiopla
June 2002
Although acute and late results of coronary intervention have been obtained by coronary angiography and this method might be sufficient for daily practice, angiography is a luminology1 and cannot reveal changes in vessel and plaque volume. On the other hand, use of intravascular ultrasound (IVUS) allows transmural, tomographic imaging of coronary arteries in humans in vivo, providing insight into the pathology of coronary artery disease. Furthermore, the time course of vessel remodeling after directional coronary atherectomy (DCA) has recently been evaluated by volumetric analysis with IVUS.2,3 Volumetric analysis has the potential to evaluate the longitudinal morphology and redistribution of plaque after coronary intervention. However, no data are available for long-term follow-up of coronary interventions using IVUS. In the present study, we evaluated the mechanisms of dilatation by plain old balloon angioplasty (POBA) and DCA as well as long-term changes in plaque and vessel volume using the Netra 3-dimensional (3-D) IVUS system in non-restenosed lesions at 6-month follow-up.
Methods
Study patients. The study group consisted of 25 patients, including 10 patients who underwent DCA in 10 lesions and another 15 patients who underwent POBA in 15 lesions between February 1995 and November 1996. All lesions met the following criteria: 1) no severe bending either proximal to or within the lesion; 2) no superficial calcification of > 1 quadrant as determined by IVUS; 3) reference diameter > 3 mm for DCA group by quantitative coronary angiography (QCA); 4) initially successful lesions; 5) no angiographic restenosis at 6-month follow-up; 6) evaluation by IVUS pre- and post-intervention, at 6-month follow-up, and at over 1-year follow-up. Patients who had acute myocardial infarction (MI), cardiogenic shock or non-protected left main trunk lesions were excluded from this study. The study was approved by the Medical Ethical Committee of our institution. All patients provided informed written consent to undergo the procedure and return to follow-up angiography and IVUS.
Interventional procedures. All patients received oral aspirin (81 mg/day), ticlopidine (200 mg/day) and intravenous heparin (10,000 U) before the procedure; heparin was subsequently administered to maintain activated clotting time > 300 seconds. The percutaneous transluminal angioplasty procedures were performed using 10 French (Fr) femoral artery sheaths and 10 Fr guiding catheters for the DCA group and 8 Fr for the POBA group. The DCA procedure was performed according to standard protocols using an average number of 23.7 ± 7.8 cuts. Final balloon pressure during the cut was 34.4 ± 13.3 psi. The DCA device was 7 Fr G in 7 patients and 7 Fr GTO in 3 patients. The endpoint of atherectomy was percent plaque area of Angiographic analysis. All cineangiograms were analyzed by two experienced cardiologists who were blinded to the results of clinical and IVUS data using a QCA with an edge detection algorithm (CMS, MEDIS, The Netherlands).4 The outer diameter of the contrast-filled catheter was used for calibration. The minimal lumen diameter (MLD), reference diameter, percent diameter stenosis (%DS) and lesion length (shoulder to shoulder) were measured for one projection showing the most severe stenosis; measurements were recorded pre- and post-intervention, at 6-month follow-up (FU1) and at longer-term follow-up (FU2). Reference diameter was defined as the mean of the proximal and distal reference diameters. Acute gain, late loss and loss index were calculated from the measurements described above. All lesions were qualitatively classified according to the modified American College of Cardiology/American Heart Association classification.5
IVUS imaging protocol. All IVUS imaging runs were performed after administration of 100–200 µg intracoronary nitroglycerin. The imaging system incorporated a single-element, 30 MHz, beveled transducer within a 2.9-Fr long monorail catheter that had a common distal lumen design which accommodated the guidewire or transducer, but not both (Cardiovascular Imaging Systems, Inc., San Jose, California). The imaging catheter was advanced beyond the target lesion, and the transducer was slowly withdrawn within the stationary imaging sheath using a motorized pullback device at a constant speed of 0.5 mm/s. The accuracy of the motorized transducer pullback device has been validated in vivo.6 All IVUS studies were recorded on 0.5´´ (1.27 cm), high-resolution s-VHS tape for offline analysis. Three-dimensional volumetric analysis3,7–9 was performed for the entire stenotic lesion with a Netra IVUS system.10 The 2-D imaging data were directly transferred to a computer workstation for 3-D imaging. The frame acquisition rate was 30 frames/s, and 3-D images were constructed by surface rendering. A maximum of 200 image slices were digitized and stacked in cylindrical format. For individual cross-sectional image slices, the cross-sectional contours can be edited manually as needed. Final mean cross-sectional area measurements were made from the entire data set of planar images. Final volumes were calculated using Simpson’s rule. Reference vessel was not included in the analysis. The reference segment was analyzed by 2-D IVUS, and plaque thickness (total of maximal and minimal plaque thickness) was always Definitions. Procedural success was defined as final %DS 50% at follow-up by QCA.
Data analysis. Baseline patient and lesion characteristics in the DCA and POBA groups were compared. Changes in QCA and 2-D IVUS data parameters were also compared between the two groups pre-intervention, post-intervention, at FU1 and FU2. In 2-D and 3-D IVUS analyses, the serial changes in area at the MLD site and vessel volume within the lesion for lumen, plaque and vessel were evaluated. Measurements of volumetric variables post-intervention, at FU1 and FU2 were normalized to those at pre-intervention because of variability in vessel size and lesion length on 3-D IVUS analysis.
Statistical analysis. Quantitative data are given as mean values ± 1 standard deviation; qualitative data are presented as frequencies. Continuous variables among baseline characteristics were compared using the non-paired student’s t-test; categorical variables were compared with the Chi-square test or Fisher’s exact test. Serial changes in continuous variables in each group were compared by repeated analysis of variance and Dunnett’s post hoc test. p-values Baseline clinical and angiographic characteristics. There was no difference in baseline clinical characteristics between the DCA and POBA groups (Table 1). DCA was performed for the left anterior descending coronary artery in 7 patients and for proximal lesions in 8 patients (Table 2). The lesions were all eccentric in the DCA group. However, there was no significant difference in angiographic characteristics between the two groups.
QCA results (Table 3). Reference diameter was larger in the DCA group than in the POBA group. Lesion length was similar in the two groups. There was no difference in pre-intervention MLD between the two groups, but MLD was significantly larger in the DCA group then in the POBA group at post-intervention, FU1 and FU2. The same tendency was observed for %DS change in the two groups, except that %DS was similar in the two groups at FU2. Although acute gain was larger in the DCA group than in the POBA group, loss index was similarly low in both groups.
IVUS results. Two-dimensional IVUS data are shown in Table 4. There were no differences in vessel, lumen or plaque (intima + media) areas at the reference site between the two groups. In the DCA group, increase in lumen area at the MLD site by the procedure was explained by increase of vessel area in 18.1% of all increase in lumen area and decrease of plaque area in 81.9% in the DCA group. In the POBA group, increase in lumen area was explained by increase in vessel area in 42.5% of all increase of lumen area and decrease of plaque area in 57.5%. These proportions did not differ significantly between the two groups (p = 0.1855).
Three-dimensional IVUS data revealed that mean length analyzed was 14.9 ± 3.0 mm in the DCA group and 20.4 ± 4.8 mm in the POBA group. All lumen volume, plaque volume and vessel volume data were normalized to control values at pre-intervention to eliminate variability in vessel size and lesion length in the DCA and POBA groups.
Serial changes of vessel area at MLD site and vessel volume throughout the entire lesion (Figures 1 and 2). Vessel area at MLD increased just after the procedure, and was maintained at FU1 in the POBA group. On the other hand, in the DCA group, vessel area increased for the first time after a longer duration (at FU2). Volumetric analysis (Figure 2) yielded findings similar to those of 2-D IVUS analysis (Figure 1). Vessel volume increased just after POBA and was sustained throughout the study period. Vessel enlargement was detected at FU1 in 3-D analysis earlier than in 2-D analysis in the DCA group.
Serial changes of lumen area at MLD site and lumen volume within the entire lesion (Figures 3 and 4). The two methods revealed the same change in lumen size. In both groups, lumen increased significantly post-intervention, and the increase persisted until FU2. In the present study, vessel volume increased during the period between 6-month follow-up (FU1) and over 1-year follow-up (FU2) in 5/10 lesions (50%) in the DCA group and in 8/15 lesions (53%) in the POBA group.
Serial changes of plaque area at MLD site and plaque volume within the entire lesion (Figures 5 and 6). Although plaque at the MLD site significantly decreased post intervention, and this decrease was sustained until FU2 in both groups as determined by 2-D IVUS (Figure 5), plaque volume within the lesion did not change at all in the POBA group. In contrast, plaque volume decreased significantly after debulking, and no significant proliferation was observed in the DCA group at follow-up (Figure 6).
Relationship between degree of positive vessel remodeling and DCA procedures. The patients with positive vessel remodeling at follow-up exhibited small percent plaque volume, similar to those without positive remodeling. Thus, this remodeling was actually vessel enlargement, and not “positive remodeling”. Luminal volume after DCA and the incidence of subintimal resection were similar in the two groups with and without vessel enlargement (60% versus 80%, respectively).
Discussion
We delineated the difference in mechanism of dilatation between DCA and POBA and time course of vessel change after these procedures in non-restenosed lesions utilizing 3-Dand 2-D IVUS.
Mechanism of dilatation by POBA and DCA evaluated for MLD site by 2-D IVUS and for entire lesion by 3-D IVUS. The principal mechanism of dilatation in DCA has been reported to be debulking of plaque, and acute luminal gain was obtained by debulking in 76–85% of all lumen gains and was obtained by vessel stretch during balloon inflation in 15–24%.11,12 On the other hand, POBA decreases less plaque volume than DCA, and causes more vessel stretching to increase luminal area compared with DCA.13 These findings are based on 2-D IVUS analysis at the MLD site, and the present study confirmed these results. However, few data are available on mechanisms of dilatation as evaluated by volumetric analysis. Interestingly, plaque volume in the entire lesion did not change post-balloon angioplasty even though plaque area decreased at the MLD site after POBA in the present study. This difference in the results of 2-D and 3-D IVUS analyses suggests the possibility that longitudinal plaque distribution, but not plaque compression in the POBA group, caused the decrease in plaque area at the MLD site without decrease in a total plaque volume within the lesion. Thus, as determined by 3-D IVUS analysis for non-restenosed lesions, the principal mechanism of dilatation for the POBA group was vessel stretching and longitudinal plaque redistribution. In contrast, plaque debulking was the principal mechanism of dilatation in the DCA group.
Mechanism and time course of vessel remodeling after coronary intervention. IVUS has been utilized to reveal the mechanisms of restenosis after coronary intervention, which include acute elastic recoil post-procedure, chronic vessel remodeling and neointimal hyperplasia. According to Mintz et al., 73% of late lumen loss was explained by vessel remodeling and only 27% was explained by neointimal hyperplasia in an IVUS study where results of POBA, DCA and laser angioplasty were analyzed together.14 However, the principal mechanism of restenosis by each new device was not clarified in that study. It is possible that each device has a different mechanism. In the present study, neither chronic vessel remodeling nor neointimal hyperplasia was recognized at longer-term follow-up in lesions that exhibited no restenosis at 6-month follow-up. DCA revealed late vessel enlargement at FU1 and FU2 in the present study, although neither vessel stretching nor positive remodeling appeared to be the causative factor, since plaque volume did not increase during follow-up.
There was no deep intimal cut or resultant aneurysmal formation. The increase in arterial volume may be the result of a loss of the usual constrictive force of elastic elements in a vessel as a consequence of the interventional procedure, with passive expansion of the artery with lower compliance under the influence of arterial pressure. Mintz et al.3 reported that greater early increases in plaque area were associated with greater late decreases in arterial area, especially in restenotic lesions after DCA. The early increase in arterial area within 1 month was not sustained. During the subsequent 5 months, there was a decrease in arterial area in almost all lesions. The late decreases in arterial area were inversely correlated with the early increases in plaque and arterial area.
Even if a common trigger was present, i.e., vessel injury during intervention, it did not cause the late decrease in arterial area in the non-restenosed lesions observed in the present study. As a possible adjunctive mechanism, we speculated that some neurohumoral factors participated in vessel enlargement.15 In response to hemodynamic forces after revascularization, there would be increased synthesis and release of endothelium-derived growth factor, platelet-derived growth factor, tissue-plasminogen activator, and tissue growth factor-b1 when endothelial cells recover in non-restenosed lesions.15–17 On the other hand, in the POBA group, vessel enlargement occurred just after the procedure and persisted at FU1, and the vessel had shrunken slightly at FU2, unlike DCA. This might be due to the presence of a relatively large amount of resultant plaque suppressing the flow-mediated vessel enlargement.
Superiority of 3-D IVUS to 2-D IVUS. A limitation in the comparison of serial ultrasound studies is the virtual impossibility of examining exactly the same ultrasonic cross-section in each study. In previous studies, anatomic landmarks such as sidebranches or deep calcification were used to define corresponding images in serial studies.2 Use of the proposed 3-D IVUS analysis system offers a more reliable solution to this problem, because a long arterial segment can be examined. Minimal differences in the start and end points of repeated studies are unlikely to impair the accuracy of determination of changes in lumen and plaque volume measurements assessed for an entire arterial segment.7 Matar et al.18 recently reported an intraobserver study that yielded a correlation coefficient of 0.98 for automated threshold-based measurements of lumen volume in vivo, a result confirmed by the high reproducibility of volumetric measurement observed in a previous study.7
One study limitation is that differences in vascular tone could have contributed to measurements of arterial and lumen dimensions. However, all patients were studied only after administration of significant doses of intracoronary nitroglycerin.
1. Topol EJ, Nissen SE. Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease. Circulation 1995;92:2333–2342.
2. de Vrey EA, Mintz GS, von Birgelen C, et al. Serial volumetric (three-dimensional) intravascular ultrasound analysis of restenosis after directional coronary atherectomy. J Am Coll Cardiol 1998;32:1874–1880.
3. Mintz GS, Kumura T, Nobuyoshi M, Leon MB. Intravascular ultrasound assessment of the relation between early and late changes in arterial area and neointimal hyperplasia after percutaneous transluminal coronary angioplasty and directional coronary atherectomy. Am J Cardiol 1999;83:1518–1523.
4. Hausleiter J, Nolte CWT, Jost S, et al. Comparison of different quantitative coronary analysis systems: ARTREK, CAAS, and CMS. Cathet Cardiovasc Diagn 1996;37:14–22.
5. Ellis SG, Vandormael MG, Cowley MJ, et al. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease: Implications for patient selection. Circulation 1990;82:1193–1202.
6. Fuessl RT, Mintz GS, Pichard AD, et al. In vivo validation of intravascular ultrasound length measurements using a motorized transducer pullback device. Am J Cardiol 1996;77:1115–1118.
7. von Birgelen C, di Mario C, Li W, et al. Morphometric analysis in three-dimensional intracoronary ultrasound: An in vitro and in vivo study performed with a novel system for the contour detection of lumen and plaque. Am Heart J 1996;132:516–527.
8. von Birgelen C, Mintz GS, de Feyter PJ, et al. Reconstruction and quantification with three-dimensional intracoronary ultrasound: An update on techniques, challenges, and future directions. Eur Heart J 1997;18:1056–1067.
9. von Birgelen C, Mintz GS, Nicosia A, et al. Electrocardiogram-gated intravascular ultrasound image acquisition after coronary stent deployment facilitates on-line three-dimensional reconstruction and automated lumen quantification. J Am Coll Cardiol 1997;30:436–443.
10. Kaneko T, Nakao A. Three-dimensional imaging of intraportal endovascular ultrasonography for pancreatic cancer. Gastrointest Endosc 1998;48:1–2.
11. Umans VA, Baptista J, di Mario C, et al. Angiographic, ultrasonic, and angioscopic assessment of the coronary artery wall and lumen area configuration after directional atherectomy: The mechanism revisited. Am Heart J 1995;130:217–227.
12. Matar FA, Mintz GS, Farb A, et al. The contribution of tissue removal to lumen improvement after directional coronary atherectomy. Am J Cardiol 1994;74:647–650.
13. Tenaglia AN, Buller CE, Kisslo KB, et al. Mechanisms of balloon angioplasty and directional coronary atherectomy as assessed by intracoronary ultrasound. J Am Coll Cardiol 1992;20:685–691.
14. Mintz GS, Popma JJ, Pichard AD, et al. Arterial remodeling after coronary angioplasty. A serial intravascular ultrasound study. Circulation 1996;94:35–43.
15. Dzau VJ, Gibbons GH. Vascular remodeling: Mechanisms and implications. J Cardiovasc Pharmacol 1993;21:S1–S5.
16. Sumpio BE, Banes AJ, Levin LG, Johnson G. Mechanical stress stimulates aortic endothelial cells to proliferate. J Vasc Surg 1987;6:252–256.
17. Resnick N, Dewey CF, Atkinson W, et al. Shear stress regulates endothelial PDGF-B chain expression via induction of novel transcription factors. FASEB J 1992;6:1592A.
18. Matar FA, Mintz GS, Douek P, et al. Coronary artery lumen volume measurements using three-dimensional intravascular ultrasound: Validation of a new technique. Cathet Cardiovasc Diagn 1994;33:214–220.
