Plaque Removal Prior to Stent Implantation in Native Coronary Arteries: Why? When? and How?

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1 IAGS 1998 Proceedings Plaque Removal Prior to Stent Implantation in Native Coronary Arteries: Why? When? and How? Issam Moussa, MD, Carlo Di Mario, PhD, MD, Antonio Colombo, MD From the Centro Cuore Columbus, Milan Italy. Presented at the Fifth Biennial International Andreas Gruentzig Society Meeting, Punta del Este, Uruguay. Address reprint requests to: Antonio Colombo, MD, Centro Cuore Columbus, Via M. Buonarotti 48, Milan, Italy. Prospective randomized clinical trials have demonstrated the superiority of coronary stents in reducing angiographic restenosis and clinical events compared to PTCA in focal de novo lesions in native coronary a r t e r i e s. 1 3 However, restenosis remains a significant problem when stents are implanted in complex lesion subsets, such as: long lesions, 4 ostial lesions, 5 7 chronic total occlusions, 8, 9 bifurcational lesions 10 and calcified lesions. 11 Restenosis after implantation of slotted tube stents is mainly due to neointimal proliferation. 12 It has been postulated that the degree of neointimal hyperplasia after stenting is proportional to the degree of vessel wall stretch. 13 The stretching force needed to expand the vessel is proportionate to the vessel wall resistance manifested by the absolute amount and consistency of the plaque. Therefore, it is logical that the maximal stretching force will need to be applied where the plaque is most severe to achieve an adequate lumen gain. Theoretically, this stretching effect would lead to more propensity for neointimal hyperplasia at the original plaque site. In fact, preliminary experimental data in animal models 13 support this concept. In humans, observational intravascular ultrasound data 14 i n d i c a t e s that a larger pre-intervention plaque burden leads to a higher rate of late lumen loss after stenting. In addition, observational angiographic data 15 indicates that, in patients who had stent implantation, restenosis tends to occur at the original lesion site (where the plaque burden is largest). Based on these observations it could be speculated that the removal of atherosclerotic plaque prior to stenting may lead to a reduction in neointimal hyperplasia (late lumen loss), therefore, reducing the incidence of restenosis. The efficacy of interventional devices in excising atherosclerotic plaque depends primarily on plaque consistency and composition (i.e., noncalcified versus calcified). Directional coronary atherectomy (Devices for Vascular Interventions, Temecula, California) has been shown to be the most effective device in removing fibrotic noncalcified plaque, 16 thus transforming the rigid atherosclerotic arterial wall to a more elastic structure that is amenable for dilatation. 1 7 H o w e v e r, despite the reduction in restenosis with optimal directional atherectomy compared to PTCA, restenosis remains about 30% with no difference in the need for repeat revascularization at 1 year. 18 On the other hand, rotational atherectomy has shown to be the preferred strategy to ablate calcified plaque. 1 9 However, despite high procedural success rates, high restenosis rates of 37 57% were observed after rotational atherectomy. 20, 21 A recent histopathologic study has demonstrated the relation of the presence of calcium to the amount of plaque burden. 22 In vivo intravascular ultrasound data have demonstrated that coronary calcium is an important determinant of decreased wall 36 The Journal of Invasive Cardiology

2 Plaque Removal Prior to Stent Implantation in Native Coronary Arteries: Why? When? and How? compliance, 23 thus leading to high incidence of dissections when these types of lesions are treated with PTCA. 24 Elective use of stents in calcified lesions has not been extensively applied due to the theoretical consideration of the inability to fully expand the stent because of lesion rigidity. However, when coronary stenting is utilized in this setting, incomplete and asymmetrical stent expansion occurs in up to 50% of cases. 25 With respect to the mechanism of restenosis after rotational and directional atherectomy, several investig a t o r s 2 6, 2 7 have shown, utilizing IVUS, a d e v i c e - s p e c i f i c mechanism for restenosis. The late lumen loss after rotational and directional atherectomy was mainly the result of pathologic arterial remodeling. Therefore, the failure of s t a n d - a l o n e debulking or stand-alone stenting in significantly reducing restenosis in complex lesion subsets and the mechanisms underlying this process, highlights the need to explore the possible synergistic role of combining both techniques in an attempt to reduce restenosis in these lesion subsets. In this report, we will review our experience in debulking prior to coronary stenting and its potential clinical applications. Directional coronary atherectomy prior to stent implantation. To examine the feasibility, safety and potential for reducing restenosis using this approach, we initiated a pilot prospective registry in February By February 1997, a total of 71 patients with 90 lesions were enrolled in this ongoing registry. The inclusion criteria targeted patients whom are historically known to be at high risk for restenosis, such as: patients with lesions that are located in vessels < 3.0 mm but accessible to DCA (31%), lesions longer than 15 mm (34%), bifurcational lesions (21%), ostial lesions (5%) and chronic total occlusions (9%). Directional atherectomy was performed using methods previously described (BOAT). The endpoint of the atherectomy procedure was to achieve a < 20% residual diameter stenosis by visual estimate. To achieve this, a 7 Fr GTO Cutter was used in 97% of cases with an average of 15 ± 10 cuts. Coronary stenting was performed with the goal to reach a near zero angiographic residual stenosis. Only slotted tube stents were used; modular AVE stents (Arterial Vascular Engineering, Santa Rosa, California) were used in situations where other stents could not be delivered. Intravascular ultrasound guidance was used after DCA and after stenting in a subset of pre-intervention patients. All patients were discharged on aspirin 325 mg orally, four times daily and ticlopidine 250 mg orally, two times daily for 2 weeks. Clinical follow-up was obtained in all patients at 1 month and 1 year after the procedure. Angiographic follow-up was performed in 62 out of 70 Table 1. Patients and lesions characteristics. Patients characteristics n = 71 Age (years) 57 ± 9 Male 66 (93%) Smoking (past or current) 56 (79%) Hypertension 28 (39%) Diabetes mellitus 10 (14%) Hyperlipidemia 42 (59%) Prior MI 34 (48%) Unstable angina 23 (33%) LIVEF 61±9% Number of vessels diseased 1 vessel 31 (44%) 2 vessel 24 (34%) 3 vessel 16 (22%) Lesions n = 90 Vessel treated LAD 54 (60%) LCX 14 (16%) RCA 20 (22%) LM2 (2%) Lesion location Ostial 8 (9%) Proximal 41 (45%) Mid 34 (38%) Distal 7 (8%) Values are expressed as the mean ± SD or as a percent of the total group; MI = myocardial infarction; LIVEF = left ventricular ejection fraction; LAD = left anterior descending; LCX = left circumflex; RCA = right coronary artery; LM = left main. eligible patients (89%) with 75 out of 89 eligible lesions (84%) at a mean duration of 5.6 months. Clinical follow-up was obtained in all patients at 9 months. R e s u l t s. Patient and lesion characteristics are shown in Table 1. Angiographic and intravascular ultrasound measurements are shown in Table 2. Clinical success was achieved in 96% of patients. Major procedural complications occurred in 3 patients: one patient (who had a guiding catheter-induced left main dissection that required bail-out stenting) underwent emergency bypass surgery and died 2 weeks post surgery; two patients (2.8%) had nonfatal Q-wave myocardial infarction. Non-Q wave myocardial infarction occurred in 8 patients (11.3%). Five patients (7%) had CK-MB elevation between 2 and 3 times the upper limits of normal, and 3 patients (4.3%) had CK- MB elevation between 3 and 5 times the upper limits of normal. No other major adverse cardiac events were reported at 1 month follow-up. At angiographic follow-up, loss index was 0.33 and binary angiographic restenosis (defined as 50% diameter stenosis) Vol 11 No 1 January

3 MOUSSA, et al. Table 2. Quantitative angiographic and intravascular ultrasound measurements Pre- Post Post Characteristics Intervention DCA Stenting Angiographic measurements n = 90 n = 90 n = 90 Reference diameter (mm) 3.27 ± ± ± 0.52 Minimum lumen diameter (mm) 0.87 ± ± ± 0.57 Percent diameter stenosis 74 ± ± ± 10 Lesion length (mm) ± 6.31 Acute gain (mm) 1.44 ± ± 0.65 IVUS measurements n = 56 n = 63 n = 73 Minimum lumen CSA (mm 2 ) 2.83 ± ± ± 1.96 Vessel CSA (mm 2 ) ± ± 3.79 DCA = directional coronary atherectomy; CSA = cross sectional area; values are expressed as the mean ± SD. i n t r a -stent or at stent borders occurred in 8 out of 75 (10.7%) lesions, but only 5 lesions (6.7%) had intrastent restenosis. All these restenotic lesions were focal and patients were treated with repeat balloon angioplasty with no further cardiac events at follow-up. Figure 1 illustrates angiographic measurements preintervention, post-dca, post stenting and at follow-up. Long-term clinical follow-up was obtained in all patients at a mean of 9 months. No patient had MI, CABG or death. Target lesion revascularization (TLR) was needed in 6 lesions (6.7%). Is the combination of directional atherectomy and stenting safe? When an alternative interventional approach is proposed to improve clinical outcome, safety has to be established first. In this study, major adverse cardiac events (death, CABG, Q-wave MI) in the first month occurred in 3 patients (4.2%). This rate of complications is not significantly different from what has been reported in trials utilizing stent alone or DCA alone strategy in a more selected patient population. In the STRESS trial, 2 M A C E occurred in 4.9% of patients (Q-wave MI in 2.9% of Figure 1. Frequency distribution curves for angiographic minimum lumen diameter pre-intervention, after direction atherectomy, after stenting, and at follow-up. patients and emergency bypass surgery in 2% of patients). In the recently reported OARS and BOAT optimal atherectomy trials, 16, 18 MACE occurred in 2.5% and 2.8%, respectively. This demonstrates that even though this combined approach was used in patients that are considered at high risk, the event rate was similar to other approaches. However, the issue of the high incidence of non-q wave MI remains of concern. In this study, non-q wave MI occurred in 11.3% of patients, a rate that is similar to what has been reported in both OARS and BOAT trials (14% and 16%, respectively). This is higher than what is encountered with PTCA or stenting alone. However, the impact of non-q wave MI following an otherwise successful procedure on long-term outcome is still the subject of ongoing investigations. Cutlip et al. 28 recently reported the results of prospective, randomized multicenter dataset of 3,387 patients treated with various interventional devices, pooled from the BOAT, STARS and STRATAS trials. In this analysis, the authors found no association between cardiac enzyme elevation and mortality at 1 year follow-up. On the other hand, Simoons et al. 29 also reported the results of a prospective, randomized multicenter dataset of 4,762 patients pooled from the CAPTURE, EPIC and EPILOG trials. In this analysis, the authors found an association between the degree of CK-MB rise and mortality at 6 month follow-up. Furthermore, in a subset analysis of the EPIC trial 30 the use of IIb/IIIa receptor antagonist (Reopro; Eli Lilly, Indianapolis, Indiana) has been shown to reduce the incidence of non-q wave myocardial infarction in patients undergoing directional atherectomy from 15.4% in the placebo arm to 4.5% in the Reopro arm. Use of IIb/IIIa inhibitors may lower the incidence of CK-MB rise, especially when long lesions are d e b u l k e d. Does directional atherectomy prior to stent implantation lower the need for repeat interventions? In the absence of a control arm of patients who 38 The Journal of Invasive Cardiology

4 Plaque Removal Prior to Stent Implantation in Native Coronary Arteries: Why? When? and How? Figure 2. Simple linear regression lines regression lines of late loss (LL) against acute gain (AG) for the atherectomy stent group (dotted line) and the stent alone group (solid line); note the downward shift in the regression line. had stent implantation without prior atherectomy, matching study patients to reference patients with similar characteristics may compensate for some of the limitations of a non-randomized study. Matching was performed with respect to the presence of diabetes mellitus, previous PTCA (restenotic lesions), reference vessel diameter, lesion length, lesion severity and number and type of stents implanted. All 75 lesions in 62 patients from the study group with angiographic followup were matched with 75 lesions in 71 patients who underwent stenting alone. Despite matching, the atherectomy plus stent group had a significantly higher number of lesions located at major bifurcations (20% vs. 7%; p = 0.03), and a slightly higher (but not statistically significant) number of chronic total occlusions (7% vs. 1.3%, p = 0.20) and ostial lesions (11% vs. 4%; p = 0.20). The directional atherectomy plus stent group had a loss index of 0.33 ± 0.33 which is significantly lower than the loss index in the stent alone group (0.46 ± 0.36; p = 0.03). This change in the biologic response of vessel wall to injury led to a restenosis rate of 10.7% in the atherectomy plus stent group compared to 21.3% in the stent alone group (p = 0.07). Subsequently, this difference in binary restenosis led to a significantly lower need for target lesion revascularization in the atherectomy plus stent group (6.7%) compared to the stent alone group (18.7%; p = 0.03). These findings strongly suggest that plaque removal prior to stenting attenuates the intensity of neointimal hyperplasia traditionally encountered with coronary stenting alone. This is better illustrated in Figure 2, where it appears that for every given amount of acute gain there is less late lumen loss (neointimal hyperplasia) when atherectomy is utilized prior to stenting (note the downward shift in the regression line). However, this relationship is not constant across all degrees of lumen gain. It appears that the regression line for the DS group intersects the regression line for the S group at a high level of lumen gain. This indicates that stenting procedures lose their leverage due to an exacerbated late loss response beyond a certain threshold of vessel wall stretching. However, an argument could be made that more plaque removal in these lesions might have kept the favorable balance between acute gain and late loss at a higher lumen gain threshold. How much debulking is needed to produce a favorable clinical outcome? Accepting the assumption that plaque removal prior to stent implantation does reduce late loss and the need for repeat revascularization, the question is how much debulking is necessary to produce this effect? A previous observational intravascular ultrasound study 14 has shown that coronary lesions with a small plaque burden (percent plaque area, < 0.6), compared to lesions with a large plaque burden (percent plaque area > 0.6), have lower late lumen loss after coronary stenting. In an attempt to answer this question, we evaluated the impact of the degree of residual plaque burden after atherectomy on loss index after coronary stenting in the patient cohort that underwent IVUS interrogation after atherectomy and had angiographic follow-up at 6 months. The loss index was 0.28 in the group with low residual plaque burden after atherectomy versus 0.52 in the group with large residual plaque burden after atherectomy (group II), p = This led to a trend towards lower restenosis rate in group I (4.4%) compared to group II (29%), p = This data indicates that there is a strong trend towards less neointimal hyperplasia after stenting in the group with small residual plaque burden (% plaque area, 0.6) after atherectomy. Rotational ablation prior to stenting in calcified and undilatable lesions. To examine the role of rotational atherectomy prior to stenting on the outcome of patients with calcified or undilatable lesions, we studied 75 consecutive patients with 106 lesions who underwent this combined approach between March 1993 and June Calcified or undilatable/uncrossable lesions were present in 90% of cases and lesions greater than 15 mm in 10% of cases. In this series, the majority of patients had intravascular ultrasound-guided stenting followed by antiplatelet therapy. Procedural success was achieved in 93% of lesions. Acute stent thrombosis occurred in 2 lesions (1.9%), and subacute stent thrombosis in 1 lesion (0.9%). Angiographic follow-up was performed in 83% of lesions at 4.6 ± 1.9 months with angiographic restenosis of 22.5%. Clinical follow-up was performed in all patients at 6.4 ± 3 months, target lesion revascularization was needed in 18% of lesions. Predictors of restenosis in this study were lesion length and post-procedure intra-stent minimum lumen area as measured by intravascular ultrasound. Vol 11 No 1 January

5 MOUSSA, et al. Since there was no control arm with stenting alone, we performed a comparative analysis between calcified lesions that underwent elective Palmaz-Schatz stenting with and without rotablation over the same time period. Stenting alone was used for shorter lesions (required lower number of stents) in larger vessels. After adjusting for vessel size, the rota-stent group had lower residual angiographic percent diameter stenosis and a higher ratio of minimal stent cross-sectional area to vessel cross-sectional area and higher symmetry index. In addition, three out of 41 patients (7%) in the stent alone group had to undergo emergency bypass surgery because of occlusive dissections after stenting. This data is consistent with prior observations suggesting that even balloon pressures exceeding 20 atm may be insufficient to overcome the limitations imposed by a severely calcified plaque, and attempts to obtain full expansion of a stent may cause vessel rupture instead of further enlarging the stent. Previous observations 3 2 have shown that the use of an oversized balloon to attempt to overcome this problem is associated with significant vessel complications such as vessel rupture. For these reasons we feel that the best approach to facilitate stent expansion in a calcified lesion is to modify vessel wall compliance by calcium ablation. The role of rotablation prior to stenting in calcified lesions has also been studied by other investigators. Comparing calcified lesions in vessels > 3.0 mm treated with rotational atherectomy and stenting to lesions treated with rotational atherectomy alone or stenting alone, Hoffmann et al. 11 showed a greater acute lumen gain (2.17 ± 0.60, 1.12 ± 0.61, 1.81 ± 0.66 mm; p < 0.01) and a lower target lesion revascularization rate in lesions treated with rotational atherectomy and stenting (12.2%, 31.6%. 24.5%; p < 0.05), respectively. However, it remains unclear whether more aggressive debulking would yield superior long-term results. Using rotational atherectomy alone, Kaplan et al. 3 3 showed a higher target lesion revascularization rate with burr/vessel ratio less than 0.6 or greater than 0.85 after rotational atherectomy. They explained their results by stating that the significant undressing of the burr might not ablate enough plaque or calcium to allow effective balloon expansion during adjunctive angioplasty. Meanwhile, the significant burr oversizing might increase the risk of vessel dissection or increase the stimulus for smooth muscle cell proliferation, leading to an increased restenosis rate. However, no data are available when rotablation is followed by stent implantation. In an attempt to answer this question we evaluated the short and long-term outcome of 126 consecutive patients (162 lesions) who underwent stenting following rotational atherectomy between May 1995 and February 1997 because of the presence of severe calcification on fluoroscopy or intravascular ultrasound (95%). Lesions were all type B2 or C; 39% were longer than 15 mm, necessitating a long stent or multiple stents. Lesions were divided into two groups: a group where aggressive rotational atherectomy was performed (defined as the use of a final burr size 2.25 mm and/or final burr/vessel ratio 0.8) in 56 lesions in order to decrease plaque mass; and a group where less aggressive rotational atherectomy was performed (106 lesions) with the objective to alter vessel wall compliance to allow better balloon expansion. Most of the patients underwent optimization of stent deployment with high-pressure final balloon dilatations and received antiplatelet therapy with ticlopidine and aspirin. Particular attention was paid to patients who had no reflow that did not resolve promptly. In these patients intra-aortic balloon pumping was initiated or abciximab bolus and infusion were started. Those may be important points to prevent subacute stent thrombus when stenting is performed following rotational atherectomy. 13 Patients in the aggressive rotational atherectomy group had higher incidence of procedural Q-wave (8.9% vs. 1.9%; p < 0.05) and non-q wave (11% vs. 1.9%, p < 0.05) myocardial infarction. Although there was no significant difference in minimal lumen diameter after the procedure (3.11 ± 0.68 vs ± 0.48 mm, NS) between the aggressive and less aggressive group, a greater minimal lumen diameter was observed at follow-up in the lesions treated with aggressive rotational atherectomy (2.12 ± 1.31 vs ± 0.89 mm; p < 0.01). Restenosis rates were 30.9% in the lesions treated with aggressive rotational atherectomy and 50.0% in those treated without aggressive rotational atherectomy (p < 0.05). In addition, lesions treated with aggressive rotational atherectomy had a lower incidence of diffuse restenosis compared to lesions treated with less aggressive rotational atherectomy (9.5% vs. 25.0%; p <0.05) despite similar lesion and stent lengths. The impact of aggressiveness of rotablation on acute safety. As with directional atherectomy, the incidence of CK-MB elevation with rotational atherectomy remains a concern. Procedural myocardial infarction occurred more frequently in lesions treated with aggressive rotational atherectomy. Coronary arteries that are treated with rotational atherectomy have calcifications and/or complex atherosclerotic plaques and myocardial infarction has been presumed to be caused by capillary plugging by atherosclerotic p a r t i c l e s. 3 4 Previous studies have shown that the incidence of non-q and Q-wave myocardial infarction after rotational atherectomy were 2 25% and 0 4.8%, r e s p e c t i v e l y. In the present study, although rotational atherectomy was performed with a stepped burr 40 The Journal of Invasive Cardiology

6 Plaque Removal Prior to Stent Implantation in Native Coronary Arteries: Why? When? and How? approach, paying particular attention to avoid any drop in rotational speed and avoiding long passes, higher incidences of non-q wave (11%) and Q-wave (8.9%) myocardial infarction with aggressive rotational atherectomy were observed. This finding may reflect the volume of microparticulate debris produced by the aggressive rotational atherectomy. A strategy to limit myocardial infarction is needed to make this aggressive technique more applicable. It is interesting to speculate that a more liberal prophylactic usage of abciximab have significantly decreased the occurrence of myocardial infarction. 35 Does aggressive rotablation prior to stenting have an impact on the incidence of angiographic restenosis? In the present study, although stenting following aggressive rotational atherectomy reduced the restenosis rate compared to stenting following less aggressive atherectomy, the restenosis rate after aggressive rotational atherectomy followed by stenting was still moderately high (30.9%). The fact that restenosis is lower in the aggressive atherectomy group despite the absence of a difference in the angiographic and IVUS dimensions immediately following stenting may suggest that plaque ablation has a favorable impact on late loss. It is possible that plaque removal may decrease the chronic arterial wall stretch following stent placement, removing a stimulus for intimal hyperplasia. Further large scale studies with follow-up IVUS evaluation may help to clarify this issue. Interestingly, the pattern of diffuse restenosis was significantly less frequent in lesions treated with aggressive rotational atherectomy followed by stenting (9.5%). Previous studies have shown that the need for repeat interventions after balloon angioplasty of lesions with diffuse restenosis is significantly higher than that of focal restenosis. 36, 37 Therefore, even though a number of lesions treated with aggressive rotational atherectomy followed by stenting needed a subsequent intervention, a second recurrence is probably less likely to occur because the restenotic lesions are frequently focal therefore more amenable to PTCA treatment. Clinical implications: Debulking prior to stent implantation. In summary, debulking prior to stenting is an approach that is based on sound theoretical, experimental and clinical observations. Preliminary non-randomized experience has shown the feasibility and favorable long-term outcome of selected patients undergoing this combined approach. However, two issues have to be addressed: 1) the risk of Q-wave myocardial infarction is unacceptably high when aggressive rotablation is used in severely calcified and long lesions, a fact that limits the clinical utility of this approach for these lesions; 2) the incidence of non-q wave myocardial infarction is moderately increased compared to PTCA or stent alone. Despite the controversy concerning the impact of this issue on long-term clinical outcome, this remains a limitation that has to be dealt with by the utilization of potent antiplatelet agents which may decrease these periprocedural ischemic complications and/or by development of new atherectomy devices that produce lower embolization rates; and 3) considering the increased procedural time and immediate costs, this approach has to be applied in selected patient subsets where debulking or stenting as a stand-alone strategy is associated with a high restenosis rate. Randomized clinical trials testing this approach using the various debulking devices are currently in progress. However, until the results of such randomized trials are available, the following algorithm for debulking and stenting might serve an important clinical purpose: Directional atherectomy prior to stenting. Lesions technically accessible to both DCA and stenting, non-calcified, located in vessels > 2.5 mm and with any of the following characteristics: Aorto-ostial lesions Bifurcational lesions Lesions that need two or more stents Chronic total occlusions Rotablation prior to stenting. Lesions located in native coronary arteries > 2.5 mm in diameter with any of the following characteristics: Uncrossable with low profile balloon catheters Unable to obtain full balloon expansion Moderate to severe calcifications REFERENCES 1. Serruys P, Jaegere P, Kiemeneij F, et al. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331: Fischman DL, Leon MB, Baim D, et al. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331: Macaya C, Serruys PW, Rygrok P, et al. for the Benestent study group. Continued benefit of coronary stenting compared to balloon angioplasty: One year clinical follow-up of the Benestent trial. J Am Coll Cardiol 1996;27: Itoh A, Hall P, Maiello L, et al. Coronary stenting of long lesions (greater than 20 mm): A matched comparison of different stents. Circulation 1995;92:SuppII:I Zampieri P, Colombo A, Almagor Y, et al. Results of coronary stenting of ostial lesions. Am J Cardiol 1994;73: Rocha-Singh K, Morris N, Wong SC, et al. Coronary stenting for treatment of ostial stenosis of native coronary arteries or aorto-coronary saphenous vein grafts. 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7 MOUSSA, et al. tive angiographic and intravascular ultrasound study. C i r c u l a t i o n 1996;94 Suppl I:I Goldberg SL, Colombo A, Maiello L, et al. Intracoronary stent insertion after balloon angioplasty of chronic total occlusions. J Am Coll Cardiol 1995;26: Moussa I, Di Mario C, Moses J, et al. Comparison of angiographic and clinical outcome of coronary stenting of chronic total occlusions versus subtotal occlusions. Am J Cardiol 1998;81: Colombo A, Maiello L, Itoh A, et al. Coronary stenting of bifurcational lesions: Immediate and follow-up results. 1996;27(Suppl A):277A. 11. Hoffmann R, Mintz GS, Kent KM, et al. Is there an optimal therapy for calcified lesions in large vessels? Comparative acute and follow-up results of rotational atherectomy, stents, or the combination. J Am Coll Cardiol 1997;29:68A. 12. Hoffmann R, Mintz G, Dussailant G, et al. Patterns and mechanisms of in-stent restenosis: A serial intravascular ultrasound study. Circulation 1996;94: Carter AJ, Farb A, Laird J, et al. Neointimal formation is dependent on the underlying arterial substrate after coronary stent p l a c e m e n t. J Am Coll Cardiol 1996;February special issue:320a. 14. Moussa I, Di Mario C, Moses J, et al. The impact of preintervention plaque area as determined by intravascular ultrasound on luminal renarrowing following coronary stenting. Circulation 1996;94: Corvaja N, Moses J, Moussa I, et al. Stent restenosis: where does it occur? An angiographic analysis (Abstr). Eur Heart J 1997;18(Suppl): Simonton CA, Leon MB, Baim DS, et al. Optimal directional coronary atherectomy: Final results of the Optimal Atherectomy Restenosis Study (OARS). Circulation 1998;97: Ibrahim A, Kronenburg M, Boor P, et al. Atherectomy and angioplasty improve compliance and reduce thickness of iliac arteries-an in vitro ultrasound study. Circulation 1994;90:I Baim DS, Cutlip D, Sharmin SK, et al. Final results of the balloon versus optimal atherectomy trial (BOAT). C i r c u l a t i o n 1998;97: Mac Isaac AI, Bass TA, Buchbinder M, et al. High speed rotational atherectomy: Outcome in calcified and noncalcified coronary artery lesions. J Am Coll Cardiol 1995;26: Warth D, Leon M, O Neill W, et al. Rotational atherectomy multicenter registry: Acute results, complications and 6-month angiographic follow-up in 709 patients. J Am Coll Cardiol 1994;24: Reifart N, Vandormael M, Krajcar M, et al. Randomized comparison of angioplasty of complex coronary lesions at a single center. Circulation 1997;96: Sangiorgi G, Rumberger J, Severson A, et al. Arterial calcificat i o n and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: A histologic study of 723 coronary artery segments using nondecalcifying methodology. JAmColl Cardiol 1998;31: Alfonso F, Macaya C, Goicolea J, et al. Determinants of coronary compliance in patients with coronary artery disease: An intravascular ultrasound study. J Am Coll Cardiol 1994;23: Fitzgerald P, Ports T, Yock P. Contribution of localized calcium deposits to dissection after angioplasty. An observational study using intravascular ultrasound. Circulation 1992;86: Fitzgerald P, STRUT registry investigators. Lesion composition impacts size and symmetry of stent expansion: Initial report from the strut registry (Abstr.). J Am Coll Cardiol 1995;February special issue:49a(902 2). 26. Mintz GS, Popma JJ, Hong MK, et al. Intravascular ultrasound to discern device-specific effects and mechanisms of restenosis. Am J Cardiol 1996;78(Suppl 3A): de Vrey E, Mintz GS, Kimura T, et al. Arterial remodeling after directional coronary atherectomy: A volumetric analysis from the Serial Ultrasound Restenosis (SURE) Trial (Abstr.). JAm Coll Cardiol 1997;February special issue:280a Cutlip DE, Chauhan M, Senerchia C, et al. Influence of myocardial infarction following otherwise successful coronary intervention on late mortality. C i r c u l a t i o n ; 9 6 : Simoons ML, Harrington R, Anderson KM, et al. Small, non- Q-wave myocardial infarctions during PTCA, are associated with increased 6 months mortality (Abstr). C i r c u l a t i o n ; 9 6 : Lefkovits J, Blankenship JC, Andersom KM, et al. Increased risk of non-q-wave myocardial infarction after directional atherectomy is platelet dependent: Evidence from the EPIC trial. J Am Coll Cardiol ; 2 8 : Moussa I, Di Mario C, Moses J, et al. Coronary stenting following rotational atherectomy in calcified and complex lesions: Angiographic and clinical follow-up results. C i r c u l a t i o n ; 9 6 : Nakamura S, Colombo A, Gaglione A, et al. Intracoronary ultrasound observations during stent implantation. C i r c u l a t i o n ; 8 9 : Kaplan BM, Safian RD, Mojares JJ, et al. Optimal burr and adjunctive balloon sizing reduces the need for target artery revascularization after coronary mechanical rotational atherectomy. Am J Cardiol ; 7 8 : Hansen DD, Auth DC, Vracko R, Ritchie JL. Rotational artereoctomy in atherosclerotic rabbit arteries. Am Heart J ; : Braden GA, Applegate RJ, Young TM, et al. Abciximab decreases both the incidence and magnitude of creatine kinase elevation during rotational atherectomy (Abstr). JAmColl Cardiol ; 2 9 : A Christophe B, Banos J, Belle EV, et al. Six-month angiographic outcome after successful repeat percutaneous intervention for in-stent restenosis. C i r c u l a t i o n ; 9 7 : The Journal of Invasive Cardiology

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