Intracoronary stents reduce restenosis compared with balloon

Treatment of In-Stent Restenosis With Excimer Laser Coronary Angioplasty Versus Rotational Atherectomy Comparative Mechanisms and Results Roxana Mehran, MD; George Dangas, MD, PhD; Gary S. Mintz, MD; Ron Waksman, MD; Alexandre Abizaid, MD; Lowell F. Satler, MD; Augusto D. Pichard, MD; Kenneth M. Kent, MD, PhD; Alexandra J. Lansky, MD; Gregg W. Stone, MD; Martin B. Leon, MD Background Atheroablation yields improved clinical results for balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA) in the treatment of diffuse in-stent restenosis (ISR). Methods and Results We compared the mechanisms and clinical results of excimer laser coronary angioplasty (ELCA) versus rotational atherectomy (RA), both followed by adjunct PTCA; 119 patients (158 ISR lesions) were treated with ELCA PTCA and 130 patients (161 ISR lesions) were treated with RA PTCA. Quantitative coronary angiographic and planar intravascular ultrasound (IVUS) measurements were performed routinely. In addition, volumetric IVUS analysis to compare the mechanisms of lumen enlargement was performed in 28 patients with 30 lesions (16 ELCA PTCA, 14 RA PTCA). There were no significant between-group differences in preintervention or final postintervention quantitative coronary angiographic or planar IVUS measurements of luminal dimensions. Angiographic success and major in-hospital complications with the 2 techniques were also similar. Volumetric IVUS analysis showed significantly greater reduction in intimal hyperplasia volume after RA than after ELCA (43 14 versus 19 10 mm 3, P 0.001) because of a significantly higher ablation efficiency (90 10% versus 76 12%, P 0.004). However, both interventional strategies had similar long-term clinical outcome; 1-year target lesion revascularization rate was 26% with ELCA PTCA versus 28% with RA PTCA (P NS). Conclusions Despite certain differences in the mechanisms of lumen enlargement, both ELCA PTCA and RA PTCA can be used to treat diffuse ISR with similar clinical results. (Circulation. 2000;101:2484-2489.) Key Words: stents restenosis lasers ablation angioplasty revascularization Intracoronary stents reduce restenosis compared with balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA). 1,2 However, in-stent restenosis (ISR) remains an important clinical problem. ISR is caused by intimal hyperplasia (IH). 3,4 Intravascular ultrasound (IVUS) imaging has shown that the mechanism of lumen enlargement during PTCA of ISR is a combination of additional stent expansion and tissue extrusion outside the stent segment. 5 Although ISR can be treated with PTCA, the recurrence rate, especially in diffuse ISR, is very high. 5,6 In a comparative study of ISR therapy, we showed better long-term clinical outcome with excimer laser coronary angioplasty (ELCA) plus adjunct PTCA than with PTCA alone. 7 The long-term outcome after rotational atherectomy (RA) has also been reported to be superior to historic controls of PTCA treatment of ISR. 8 However, differences in ablation efficiency and clinical efficacy between these atheroablative techniques have not been studied. In the present study, we compared the mechanism, atheroablative efficiency, and clinical results of ELCA versus RA (both followed by adjunct PTCA) for the treatment of diffuse ISR. Methods This study included 249 patients with diffuse ( 10 mm in length) ISR in tubular slotted or multicellular stents. Interventional techniques were either ELCA PTCA (n 119 patients, n 158 lesions) or RA PTCA (n 130 patients, n 161 lesions). This represents a consecutive series of patients with diffuse ISR treated at our institution over a period of 3 years. The decision to perform atheroablation with ELCA versus RA was made by the operator. Exclusions were limited to patients participating in brachytherapy protocols (n 273), focal ISR (n 401), and saphenous vein graft ISR (n 83). Procedure In lesions treated with ELCA Vitesse catheters (Spectranetics/ Advanced Interventional Systems), the mean value of the largest Received August 5, 1999; revision received November 22, 1999; accepted December 12, 1999. From the Cardiovascular Research Foundation, Lenox Hill Heart & Vascular Institute, New York, NY (R.M., G.D., A.J.L., G.W.S., M.B.L.), and the Intravascular Ultrasound Imaging and Cardiac Catheterization Laboratory, Washington Hospital Center, Washington, DC (G.S.M., R.W., A.A., L.F.S., A.D.P., K.M.K.). Correspondence to George Dangas, MD, PhD, Cardiovascular Research Foundation, 55 E 59th St, 6th Floor, New York, NY 10022. E-mail gdangas@compuserve.com 2000 American Heart Association, Inc. Circulation is available at http://www.circulationaha.org 2484

Mehran et al ELCA vs RA for Diffuse In-Stent Restenosis 2485 laser fiber catheter used was 1.81 0.18 mm in diameter; the maximum catheter size was 1.4 mm in 19 (12%), 1.7 mm in 59 (37%), and 2.0 mm in 80 (51%) cases. The laser catheter to artery ratio was 0.72 0.21. A single-pass technique was used in 52%. Energy densities were 35 to 55 mj/mm 2 (mean 45.7 5.5 mj/mm 2 ). A saline flush technique was used in all cases. Adjunct PTCA was performed with nominal balloon size 3.6 0.6 mm, balloon-to-artery ratio 1.3 0.3, and maximum inflation pressure 17 3 atm. Additional stents were placed in 41 (25.6%) lesions. RA was performed with the use of 1.50- to 2.15-mm diamondcoated metal burrs (Boston Scientific). The mean value of the largest burr used was 1.89 0.18 mm in diameter; maximum size was 1.5 mm in 15 (9.5%), 1.75 mm in 48 (30%), 2.0 mm in 86 (53%), and 2.15 mm in 12 (7.5%) of cases. The burr-to-artery ratio was 0.74 0.20. Adjunct PTCA was performed with nominal balloon size 3.2 0.4 mm, balloon-to-artery ratio was 1.4 0.4, and maximum inflation pressure was 14 5 atm. Additional stents were placed in 48 (26.2%) lesions. Angiographic Analysis Quantitative coronary angiographic analysis was performed by a core angiographic laboratory blinded to the results of the IVUS analysis and clinical follow-up. A previously validated system (ARTREK, Quantitative Cardiac Systems) was used with the contrast-filled catheter as the calibration standard. Minimal lumen diameter, reference diameter, and percent diameter stenosis were measured before atheroablation and after atheroablation plus adjunct PTCA (final) from multiple projections; the results from the single worst view were recorded. Ostial lesions begin at 3 mmofthe major coronary artery ostium. 9 IVUS Imaging Protocol Studies were performed with 1 of 2 commercially available systems. The first system (CVIS/Inter Therapy Inc) incorporated a singleelement, 25-MHz transducer and an angled mirror mounted on the tip of a flexible shaft, which was rotated at 1800 rpm within a 3.9F short monorail polyethylene imaging sheath to form planar crosssectional images in real time (used in 15 [4.7%] cases). The second system (Boston Scientific Corp/Cardiovascular Imaging Systems Inc) used a single-element, 30-MHz beveled transducer mounted on the end of flexible shaft and rotated at 1800 rpm within a 3.2F short monorail imaging sheath (used in 304 [95.3%] cases). With both systems, the transducer was withdrawn automatically at 0.5 mm/s to perform the imaging sequence. IVUS imaging 10 was performed after administration of 0.2 mg intracoronary nitroglycerin. The ultrasound catheter was advanced 10 mm beyond the target lesion, and an imaging run was performed at the aorto-ostial junction. Studies were recorded only during pullback onto half-inch, high-resolution s-vhs for off-line analysis. IVUS imaging was routinely performed before atheroablation and after atheroablation plus adjunct PTCA (final). Quantitative Planar IVUS Measurements Two-dimensional, cross-sectional area (CSA), and length measurements by IVUS have been validated. 11 18 Area measurements were performed with the use of a commercially available program for computerized planimetry (TapeMeasure, Indec Systems Inc) at the image slice with the smallest lumen CSA and included stent, lumen, and IH (stent minus lumen) CSA. When the plaque encompassed the catheter, the lumen was assumed to be the physical size of the imaging catheter. The proximal and distal references were defined as the most normal-looking cross section (largest lumen with the least plaque) within 10 mm proximal and distal to the ISR lesion but before side branches. ISR length was the axial length of the stent (mm) in which IH CSA was 75% stent CSA. If the ISR lesion continued into the contiguous reference segment, the ISR length included the length of the reference segment whose lumen CSA was 25% of the adjacent stent margin CSA. At a pullback speed of 0.5 mm/s, 2 seconds of the videotape playback is equal to 1 mm of axial stent length. Volumetric IVUS calculation of ablation efficiency. Optimal device with 100% ablation efficiency should ablate all plaque within theoretical cylinder with length equal to target lesion length and diameter equal to outer diameter of device. Formula provided does not account for theoretical possibility that a degree of stent expansion may occur after atheroablation (such effect was not observed in present study). Volumetric IVUS Analysis This analysis included all patients who had complete IVUS imaging before intervention, after atheroablation, and after adjunct PTCA (final). Baseline characteristics of this subset were similar to the entire cohort. All lesions included in this subset were ISR within Palmaz-Schatz stents and were treated with 2.0-mm ELCA catheters or 2.0-mm RA burrs. IVUS imaging was performed with the 3.2F system. On playback of the recorded studies, IVUS images were measured every 1 mm of axial ISR length. Stent, lumen, and IH volumes were calculated by means of Simpson s rule. 3,4,7 The impact of atheroablation on lumen enlargement was assessed by comparing postatheroablation and preatheroablation measurements; the effect of adjunct PTCA was evaluated by comparing final and postatheroablation measurements. 7 Ablation efficiency was normalized to the maximum ablation catheter size and was calculated as the ratio of the lumen volume after ablation divided by the theoretical cylinder with CSA equal to the area of the maximum ELCA catheter or RA burr used and with length equal to the ISR length with a preablation lumen area smaller than the ELCA catheter or RA burr (Figure). Clinical Data and Follow-Up Patient charts were reviewed, and clinical, demographic, and laboratory data were entered prospectively into the database by a dedicated Data Coordinating Center. Clinical follow-up was performed with telephone contacts or office visits at 1, 3, 6, and 12 months. Major late clinical events were source documented and adjudicated, including death, Q-wave myocardial infarction, and ischemia-driven target lesion site revascularization (TLR; percutaneous or surgical). Statistical Analysis Statistical analysis was performed with the use of StatView 4.02 (Abacus Concepts) or SAS (Statistical Analysis Systems, SAS Institute Inc). Categorical data were presented as frequencies and compared with Fisher s exact test. Continuous data were presented as mean SD and compared with paired and unpaired Student s t tests. We conducted multivariate logistic regression analysis to investigate a potential difference in TLR between the 2 groups, controlling for baseline variables with significant between-group differences. A value of P 0.05 was considered significant; probability values 0.10 are reported as not significant. Results Baseline characteristics are shown in Table 1. More left anterior descending lesions were treated with ELCA PTCA than with RA PTCA (38% versus 23%, P 0.01). The groups had similar percentages of lesions 20 mm in length (60% in both groups) and of total occlusions (7% in the ELCA PTCA versus 5% in the RA PTCA group, P NS). Each group included 58 (36%) lesions with recurrent ISR.

2486 Circulation May 30, 2000 TABLE 1. Baseline Characteristics TABLE 3. Planar (2D) IVUS Results Patients/lesions, n 119/158 130/161 Age, y 63 11 62 13 NS Male/female, n 81/38 88/42 NS Hypertension 83 (66) 99 (71) NS Diabetes mellitus 40 (32) 51 (36) NS Hyperlipidemia 93 (74) 114 (82) NS Rest angina 32 (25) 38 (27) NS Previous infarction 62 (50) 54 (40) NS Previous bypass surgery 46 (39) 49 (35) NS Chronic renal insufficiency 14 (11) 16 (12) NS Peripheral vascular disease 26 (21) 29 (21) NS Left ventricular ejection fraction, % 0.43 0.11 0.48 0.13 0.01 Lesion location Left anterior descending 60 (38) 40 (23) 0.01 Right coronary artery 58 (37) 65 (38) NS Left circumflex 40 (25) 56 (35) 0.04 Ostial position 16 (10) 18 (11) NS Variables are n (%) or mean SD. Procedural Results We observed no perforations, 1 (0.6%) abrupt closure in the ELCA PTCA group, and 2 (1.1%) no-reflow cases in the RA PTCA group (P NS for angiographic complications). Major in-hospital complications were also similar in the 2 groups: 1 (0.7%) death in each group and 4 bypass surgery operations in the ELCA PTCA group (3.3% versus 0%, P NS). There were no Q-wave myocardial infarctions in either group. We documented postprocedure elevation of creatine kinase-mb 5 normal in 11% (n 14) with ELCA PTCA versus 8% (n 11) with RA PTCA (P NS); creatine kinase-mb 2 normal occurred 28% and 23%, respectively (P NS). There were no differences with respect to preprocedure and final luminal dimensions by quantitative angiography (Table 2). The acute gain was 1.50 0.38 mm with ELCA PTCA and 1.53 0.41 mm with RA PTCA (P NS). TABLE 2. Quantitative Angiographic Results No. of lesions 158 161 Before intervention Lesion length, mm 16.98 12.93 17.52 13.35 NS Reference lumen 2.60 0.57 2.62 0.68 NS diameter, mm Minimum lumen diameter, mm 0.64 0.50 0.75 0.46 NS Diameter stenosis, % 74 22 70 16 NS Final postintervention Reference lumen 2.78 0.48 2.79 0.44 NS diameter, mm Minimum lumen diameter, mm 2.17 0.62 2.26 0.44 NS Diameter stenosis, % 22 16 18 13 NS Variables are mean SD. No. of lesions 158 161 Before intervention Lesion length, mm 18.4 11.8 19.5 10.1 NS Reference lumen CSA, mm 2 6.93 2.20 7.06 2.18 NS Minimum stent CSA, mm 2 6.94 2.16 7.19 2.36 NS Minimum lumen CSA, mm 2 1.80 1.38 1.85 1.29 NS IH CSA, mm 2 5.09 1.17 5.69 1.78 NS Final Minimum lumen CSA, mm 2 5.51 2.27 5.39 1.92 NS Minimum stent CSA, mm 2 7.42 2.52 7.63 2.91 NS IH CSA, mm 2 2.03 0.92 2.30 1.35 NS Changes (final pre) Change in stent CSA, mm 2 0.54 1.39 0.47 0.16 NS Change in lumen CSA, mm 2 3.72 1.78 3.64 1.58 NS Change in IH CSA, mm 2 2.92 1.71 3.38 1.08 NS Variables are mean SD. Both groups had similar preatheroablation and final dimensions by quantitative planar IVUS analysis as well (Table 3). There was a trend toward a smaller reduction in IH CSA with ELCA PTCA than with RA PTCA (2.92 1.01 versus 3.38 1.08 mm 2, P 0.09). The contribution of stent expansion to the final luminal gain was 15% in the ELCA PTCA group versus 13% in the RA PTCA group (P NS). Volumetric IVUS Analysis This analysis included only those patients with routine preatheroablation, postatheroablation, and final IVUS imaging. After both ELCA and RA, lumen gain was entirely due to atheroablation/extrusion; we observed no additional stent expansion. In the ELCA subgroup, 27% of the overall luminal gain (final-preatheroablation) was due to ELCA, and 73% was due to adjunct PTCA (54% additional stent expansion and 46% tissue extrusion). In the RA subgroup, 46% of the luminal gain (final-preatheroablation) was due to RA and 54% was due to adjunct PTCA (52% additional stent expansion and 48% tissue extrusion). Ablation efficiency was higher with RA compared with ELCA: 90 10% versus 77 12% (P 0.004) (Table 4). However, adjunct PTCA was responsible for 50% of the overall lumen gain in both groups and equalized the final lumen dimensions (by both quantitative angiography and IVUS) in the 2 groups. One-Year Clinical Outcome Long-term results are shown in Table 5. No significant difference was documented between the 2 groups; TLR rates were almost identical (26.2% with ELCA PTCA versus 27.9% with RA PTCA, P NS). TLR was also similar in both groups when patients with additional stent implantation were excluded: 29.8% ELCA PTCA versus 26.3% RA PTCA (P NS). By multivariate analysis, controlling for baseline between-group differences (lesion location), the selection of interventional technique (ELCA PTCA versus RA PTCA) still was not predictive of TLR.

Mehran et al ELCA vs RA for Diffuse In-Stent Restenosis 2487 TABLE 4. Volumetric IVUS Results No. of lesions 16 14 Before intervention IH length, mm 17.1 10.4 19.5 11.9 NS Stent volume, mm 3 140 25 148 30 NS Lumen volume, mm 3 44 18 31 25 NS IH volume, mm 3 96 23 123 33 NS After atheroablation Stent volume, mm 3 140 25 148 29 NS Lumen volume, mm 3 63 14* 72 13* NS IH volume, mm 3 77 20* 79 25* NS Change post pre Change in stent volume, mm 3 0.5 0.2 0.5 0.3 NS Change in lumen volume, mm 3 18 9 41 15 0.001 Change in IH volume, mm 3 19 10 43 14 0.001 Ablation efficiency, % 77 12 90 10 0.004 After adjunct PTCA Stent volume, mm 3 166 26 174 23 NS Lumen volume, mm 3 114 26 121 14 NS IH volume, mm 3 55 11 52 9 NS Changes final post Change in stent volume, mm 3 28 11 26 10 0.06 Change in lumen volume, mm 3 51 13 50 12 NS Change in IH volume, mm 3 22 10 26 11 NS Changes final pre Change in stent volume, mm 3 28 11 26 8 NS Change in lumen volume, mm 3 70 15 91 14 0.06 Change in IH volume, mm 3 40 13 71 15 0.001 Variables are mean SD. *P 0.03 compared with before intervention; P 0.03 compared with both after atheroablation and before intervention. Discussion Atheroablative techniques have been advocated for the treatment of diffuse ISR in response to the poor long-term results achieved with PTCA alone (restenosis rates 54% to 85%). 5 7 The superior results reported after atheroablation plus adjunct PTCA have been attributed to the greater reduction of in-stent neointimal tissue. If atheroablation per se was a strong determinant of clinical outcome, then differences between atheroablative devices with respect to ablation efficiency and the amount of IH removed should translate into improved TABLE 5. One-Year Follow-Up Results Patients/lesions, n 119/158 130/161 Death 10 (8) 6 (5) NS Q-wave myocardial infarction 1 (1) 2 (2) NS Repeat percutaneous intervention 38 (24) 42 (26) NS Coronary bypass surgery 5 (3) 3 (2) NS Overall target lesion revascularization 41 (26) 45 (28) NS Variables are n (%). long-term clinical benefit. In the present study of diffuse ISR, both ELCA PTCA and RA PTCA improved lumen dimensions by a combination of tissue ablation, tissue extrusion, and additional stent expansion. Although RA achieved greater IH ablation, this was not accompanied by improved 1-year clinical outcome. Mechanistic Comparison of ELCA PTCA Versus RA PTCA In vitro and in vivo animal models originally suggested that excimer lasers precisely cut through atheroma, including calcium, without harmful thermal injury. 19 24 Conversely, IVUS has indicated that the mechanism of lumen enlargement after ELCA of nonstented lesions was a combination of tissue ablation (76% of lumen enlargement) and vessel expansion (24% of lumen enlargement) with no evidence of calcium ablation. 24 In the present study, volumetric IVUS analysis showed that all of the lumen enlargement during ELCA treatment of ISR was the result of tissue ablation. This was probably related to the absence of calcium in ISR lesions and to the scaffolding effects of endovascular stents that may limit laser-induced vessel expansion. As with ELCA, we found luminal enlargement after RA to be exclusively due to tissue ablation. This was similar to a previous volumetric IVUS study assessing tissue ablation after RA of nonfibrocalcific plaque. 25 We found 77% ablation efficiency for ELCA, which is similar to the theoretical ablation capacity of the 2.0 Vitesse ELCA catheter and to previous in vitro data with the same catheter. 26 Similar ablation efficiency has also been reported for the 1.7 Vitesse ELCA catheter. 26 Newer-generation optimally spaced ELCA catheters have been shown in vitro to increase ablation efficiency by 20% compared with the currently approved concentric catheters, 26 with a potential to equalize the difference that we observed in ablation efficiency between ELCA and RA. These catheters were not available at the time of the present study. The 90% ablation efficiency we found for RA was similar to previous reports in non-isr lesions. 27 29 The marginal differences may reflect different elastic properties of lesions within a stent as compared with the previous reports on RA in de novo lesions. 29 In the present volumetric IVUS analysis, only 2.0-mm burrs were studied. Ablation efficiency has not been shown to differ among different burr sizes in experimental conditions (D. Dillard, Boston Scientific Engineering Department, Seattle, Wash; personal communication). The mechanism of adjunct PTCA was similar in both groups, through an almost equal magnitude of tissue extrusion and stent expansion. The magnitude of additional stent expansion during adjunct PTCA (15% and 19% in the 2 groups) was similar to stand-alone PTCA in previous volumetric IVUS studies as reported by us and others. 5,7 Short-Term Clinical Results Despite these mechanistic observations, both ELCA PTCA and RA PTCA achieved similar final lumen dimensions by angiography and planar IVUS analysis. Thus, the greater ablation efficiency of RA was

2488 Circulation May 30, 2000 balanced by a relatively smaller contribution of adjunct PTCA to the final lumen dimensions. However, the current study also showed the limitations of these techniques. First, the mean final angiographic residual diameter stenosis measured 18% to 22%. Second, despite ablation with both ELCA and RA, there was still significant residual neointimal tissue within the stent (27% after ELCA PTCA and 29% after RA PTCA. Long-Term Clinical Results In a previous study comparing ELCA PTCA versus PTCA alone, we reported superior long-term results with ELCA PTCA, but the use of ELCA per se was not an independent predictor of TLR. 7 The independent determinant of late outcome was the final procedural luminal gain, whether by ablation, by tissue extrusion, or by additional stent expansion. 7 In the present study, the similar final lumen dimensions after ELCA PTCA and RA PTCA were accompanied by similar long-term results (Table 5). Atheroablation per se may not offer a specific long-term advantage over tissue extrusion or stent expansion as long as final lumen dimensions were maximized. One possible explanation is that diffuse ISR may, in some patients, represent a biologically aggressive response that cannot be counteracted by the simple approach of atheroablation regardless of the efficiency. On the other hand, we cannot exclude the possibility that catheters with greater ablation efficiency might have yielded greater reduction in IH hyperplasia and possibly incur an additional clinical benefit. The 2 interventional techniques had a 26% to 28% TLR rate. This relatively low TLR may be explained by 2 factors. (1) The 1-year mortality rate was 5% to 8%; these patients might otherwise have presented with recurrence. (2) A significant number of patients were excluded from this analysis because of participation in vascular brachytherapy protocols; these patients may have represented a higher-risk group. The placebo arm of the Washington Radiation In-Stent Restenosis Trial had a clinical recurrence rate of 60%, whereas the active treatment arm ( 192 Ir) had a markedly lower recurrence rate. 30 Study Limitations This study was a retrospective analysis of lesions treated with ELCA PTCA or RA PTCA; lesions were not randomized to the 2 treatment strategies. The operators were not blinded to any of the IVUS imaging runs. The volumetric IVUS methods used to separate IH tissue ablation from extrusion was available only in the subset of patients with IVUS imaging after atheroablation (before PTCA). Since final IVUS imaging was routinely performed immediately after completion the intervention, this study was unable to investigate the recently reported time-dependent effect of tissue reintrusion within the treated segment. 31 Although the type and length of the initially restenosed stents were unavailable, we have previously documented that the length of IH (measured by IVUS) rather than the stent length is a predictor of recurrent ISR. 32 We do not believe that stent recoil contributed significantly to the results because tubular-slotted and multicellular stents do not recoil. 33,34 It is possible that with more aggressive tissue ablation, the final procedural result might have been improved in both groups. However, the anticipated (but not yet proven) clinical benefit from even more aggressive atheroablation should be carefully evaluated against the risk of procedural complications, which were very small with the present approach. Conclusions Despite the higher ablation efficiency of RA compared with ELCA, ELCA PTCA and RA PTCA yield similar longterm clinical results in the treatment of diffuse ISR in native coronary arteries. References 1. Fischman DL, Leon MB, Baim DS, et al, for the Stent Restenosis Study Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in treatment of coronary artery disease. N Engl J Med. 1994;331:496 501. 2. Serruys PW, de Jaeger P, Kiemeneij F, et al, for the Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary heart disease. N Engl J Med. 1994;331:489 495. 3. Dussaillant GR, Mintz GS, Pichard AD, et al. Small stent size and intimal hyperplasia contribute to restenosis: a volumetric intravascular ultrasound analysis. J Am Coll Cardiol. 1995;26:720 724. 4. Hoffman R, Mintz GS, Dussaillant GR, et al. Patterns and mechanisms of in-stent restenosis: a serial intravascular ultrasound study. Circulation. 1996;94:1247 1254. 5. Mehran R, Mintz GS, Popma JJ, et al. Mechanism and results of balloon angioplasty for the treatment of in-stent restenosis. Am J Cardiol. 1996; 76:618 622. 6. Gordon PC, Gibson CM, Cohen DJ, et al. Mechanism of restenosis and redilatation within coronary stents: quantitative angiographic assessment. J Am Coll Cardiol. 1993;21:1166 1174. 7. Mehran R, Mintz GS, Satler LF, et al. Treatment of in-stent restenosis with excimer laser coronary angioplasty: mechanisms and results compared with PTCA alone. Circulation. 1997;96:2183 2189. 8. Sharma SK, Duvvuri S, Dangas G, et al. Rotational atherectomy for in-stent restenosis: acute and long-term results of first 100 cases. JAm Coll Cardiol. 1998;32:1358 1365. 9. Popma JJ, Bashore TD. Qualitative and quantitative angiography. In: Topol E, ed. Textbook of Interventional Cardiology. Philadelphia, Pa: WB Saunders; 1994:1052 1068. 10. Pandian NG, Kreis A, Brockway B, et al. Ultrasound angioscopy: real-time, 2-dimensional, intraluminal ultrasound imaging of blood vessels. Am J Cardiol. 1988;62:493 494. 11. Hodgson JM, Graham SP, Sarakus AD, et al. Clinical percutaneous imaging of coronary anatomy using an over-the wire ultrasound catheter system. Int J Cardiac Imaging. 1989;4:186 193. 12. Gussenhoven EJ, Essed CE, Lancee CT, et al. Arterial wall characteristics determined by intravascular ultrasound imaging: an in vitro study. JAm Coll Cardiol. 1989;14:947 952. 13. Nishimura RA, Edwards WD, Warnes CA, et al. Intravascular ultrasound imaging: in vitro validation and pathologic correlation. J Am Coll Cardiol. 1990;16:145 154. 14. Potkin BN, Barorelli AL, Gessert JM, et al. Coronary artery imaging with intravascular high-frequency ultrasound. Circulation. 1990;81: 1575 1585. 15. Nissen SE, Grines CL, Gurley JC, et al. Application of a new phased -array ultrasound imaging catheter in the assessment of vascular dimensions: in vivo comparison to cineangiography. Circulation. 1990;81: 660 666. 16. Tobis JM, Mallery JA, Gessert J, et al. Intravascular ultrasound crosssectional arterial imaging before and after balloon angioplasty in vitro. Circulation. 1989;80:873 882. 17. Nissen SE, Gurley JC, Grines CL, et al. Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease. Circulation. 1991;84:1087 1099. 18. Fuessl RT, Mintz GS, Pichard AD, et al. In vivo validation of intravascular ultrasound length measurements using a motorized transducer pullback system. Am J Cardiol. 1996;77:1115 1118.

Mehran et al ELCA vs RA for Diffuse In-Stent Restenosis 2489 19. Sharma SK, Kini A, Duvvuri S, et al. Randomized trial of rotational atherectomy vs balloon angioplasty for in-stent restenosis (ROSTER): interim analysis of 100 cases. Circulation. 1998;98(suppl I):I-511. Abstract. 20. Grundfest WS, Litvack F, Forrester JS, et al. Laser ablation of human atherosclerotic plaque without adjacent tissue injury. J Am Coll Cardiol. 1985;5:929 933. 21. Litvack F, Grundfest WS, Papaioannou T, et al. Interventional cardiovascular therapy by laser and thermal angioplasty. Circulation. 1990; 81(suppl IV):IV-109-IV-116. 22. Shelton ME, Hoxworth B, Shelton JA, et al. A new model to study quantitative effects of laser angioplasty on human atherosclerotic plaque. J Am Coll Cardiol. 1986;7:909 915. 23. Rosenfeldt FL, Chi L, Black AJR, et al. Excimer laser angioplasty in the atherosclerotic rabbit: comparison with balloon angioplasty. Am Heart J. 1992;124:349 355. 24. Mintz GS, Kovach JA, Saturnino SP, et al. Mechanisms of lumen enlargement after excimer laser coronary angioplasty: an intravascular ultrasound study. Circulation. 1995;92:3408 3414. 25. Dussaillant GR, Mintz GS, Pichard AD, et al. Effect of rotational atherectomy in noncalcified atherosclerotic plaque: a volumetric intravascular ultrasound study. J Am Coll Cardiol. 1996;28:856 860. 26. Lippincott R, Bellendir J, Taylor K, et al. Optimally spaced fiber catheter for excimer laser coronary angioplasty (ELCA). In: Proceedings of the International Society for Optical Engineering. In press. 27. Reisman M. Efficiency of rotational atherectomy. In: Reisman M, ed. Guide to Rotational Atherectomy. Birmingham, Mich: Physicians Press; 1997: 14 16. 28. Safian RD, Freed M, Lichtenberg A, et al. Are residual stenoses after excimer laser angioplasty and coronary atherectomy due to inefficient or small devices? Comparison with balloon angioplasty. J Am Coll Cardiol. 1993;22:1628 1634. 29. Mintz GS, Potkin BN, Keren G, et al. Cross-sectional and 3-dimensional intravascular ultrasound analysis of coronary artery geometry after rotational atherectomy. Circulation. 1994;90(suppl I):I-203. Abstract. 30. Waksman R, Chan RC, Porazzo MS, et al. Intracoronary gamma radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis. Circulation. 2000;101:2165 2171. 31. Shiran A, Mintz GS, Waksman R, et al. Early lumen loss after treatment of in-stent restenosis: an intravascular ultrasound study. Circulation. 1998;98:200 203. 32. Mehran R, Dangas G, Mintz, GS, et al. Patterns of in-stent restenosis: angiographic classification and implications for long-term clinical outcome. Circulation. 1999;100:1872 1878. 33. Painter JA, Mintz GS, Wong SC, et al. Serial intravascular ultrasound studies fail to show evidence of chronic Palmaz-Schatz stent recoil. Am J Cardiol. 1995;75:398 400. 34. Hong MK, Park SW, Lee CW, et al. Intravascular ultrasound comparison of chronic recoil among different stent designs. Am J Cardiol. 1999;84: 1247 1250, A8.