Peri-Stent Reference Segment Plaque Burden Is Associated With Disease Progression in Saphenous Vein Grafts (A Serial Intravascular Ultrasound Assessment)

Peri-Stent Reference Segment Plaque Burden Is Associated With Disease Progression in Saphenous Vein Grafts (A Serial Intravascular Ultrasound Assessment)

Peri-Stent Reference Segment Plaque Burden Is Associated With Disease Progression in Saphenous Vein Grafts (A Serial Intravascular Ultrasound Assessme...

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Peri-Stent Reference Segment Plaque Burden Is Associated With Disease Progression in Saphenous Vein Grafts (A Serial Intravascular Ultrasound Assessment) Young Joon Hong, MDa, Gary S. Mintz, MDb, Sang Wook Kim, MDa, Teruo Okabe, MDa, Li Lu, MSa, Anh B. Bui, MDa, Augusto D. Pichard, MDa, Lowell F. Satler, MDa, Ron Waksman, MDa, Kenneth M. Kent, MD, PhDa, William O. Suddath, MDa, and Neil J. Weissman, MDa,* We are aware of no studies of peri-stent disease progression or luminal compromise in saphenous vein graft (SVG) lesions. We used serial intravascular ultrasound (IVUS) to assess disease progression in peri-stent saphenous vein bypass graft reference segments. We studied 37 peri-stent SVG reference segments in 21 patients; 16 were proximal and 21 were distal to the stent. The same anatomic image slice was analyzed after the intervention and at follow-up; this site was 3.68 ⴞ 2.22 mm from the stent edge. Graft age was 10.1 ⴞ 5.4 years, and mean follow-up duration was 13 months (range 3 to 61). Overall, change in SVG area, change in lumen area, and change in plaque burden correlated with postintervention plaque burden (r ⴝ 0.448, p ⴝ 0.005; r ⴝ ⴚ0.584, p <0.001; and r ⴝ 0.507, p ⴝ 0.001, respectively). For the proximal edge, change in lumen area correlated with change in plaque area (r ⴝ ⴚ0.951, p <0.001), but not with change in SVG area (r ⴝ ⴚ0.337, p ⴝ 0.201). For the distal edge, change in lumen area correlated more strongly with change in plaque area (r ⴝ ⴚ0.982, p <0.001) than with change in SVG area (r ⴝ ⴚ0.624, p ⴝ 0.003). When peri-stent reference segments were divided into 2 groups according to postintervention plaque burden (>50% [n ⴝ 20] vs <50% [n ⴝ 17]), there was a greater decrease in lumen area (ⴚ1.12 ⴞ 0.81 vs ⴚ0.33 ⴞ 0.26 mm2, p <0.001) and greater increases in SVG area (0.26 ⴞ 0.29 vs 0.09 ⴞ 0.09 mm2, p ⴝ 0.027), plaque area (1.37 ⴞ 0.96 vs 0.42 ⴞ 0.30 mm2, p <0.001), and plaque burden (8.2 ⴞ 5.6% vs. 2.8 ⴞ 1.6%, p <0.001) in segments with a plaque burden >50%. In conclusion, peri-stent reference segment SVG disease progression and lumen loss were more significant in segments with a greater postintervention plaque burden after implantation of a bare metal stent or drug-eluting stent. © 2007 Elsevier Inc. All rights reserved. (Am J Cardiol 2007;100:1233–1238)

With intravascular ultrasound (IVUS) imaging, stent edge and reference segment effects can be separated into an increase or decrease in vessel area and/or an increase or decrease in plaque area.1–7 Previous serial IVUS studies have reported that significant lumen loss occurs at a peristent reference segment after implantation of a bare metal stent (BMS)1– 6 or drug-eluting stent (DES).6,7 Serial IVUS studies have also reported a relation between plaque burden after stent implantation and peri-stent reference segment lumen loss after implantation of a BMS or DES in native coronary arteries.8,9 However, to the best of our knowledge, no study has examined the relation between postintervention plaque burden and peri-stent reference segment changes in saphenous vein graft (SVG) lesions. Therefore, the purpose of the present study was to use serial IVUS studies (after intervention and at follow-up) to assess SVG a Cardiovascular Research Institute/Medstar Research Institute, Washington Hospital Center, Washington, DC; and bCardiovascular Research Foundation, New York, New York. Manuscript received February 14, 2007; revised manuscript received and accepted May 22, 2007. *Corresponding author: Tel: 202-877-0223; fax: 202-877-0206. E-mail address: [email protected] (N.J. Weissman).

0002-9149/07/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2007.05.042

disease progression in reference segments adjacent to stent edges. Methods Patient population: Between October 4, 2000, and August 20, 2002, 209 patients underwent IVUS-guided SVG interventions at the Washington Hospital Center. Patients were included if they had ⱖ1 de novo target lesion (⬎50% diameter stenosis by visual estimate) localized in a diseased SVG with a reference vessel diameter ⬎2.5 and ⬍4.0 mm. We excluded patients with ST-segment elevation myocardial infarction, documented left ventricular ejection fraction ⬍25%, impaired renal function (creatinine level ⬎3.0 mg/ dl), totally occluded SVGs, or restenotic SVG lesions, and patients in whom adequate IVUS images could not be obtained. We identified 21 patients who underwent postintervention and follow-up IVUS. Fourteen patients had a single lesion treated with ⱖ1 BMS and 7 patients had 8 lesions treated with ⱖ1 DES. Among these 22 lesions, 6 segments proximal to the proximal stent edge were excluded because of their ostial location and 1 segment distal to the distal stent edge was excluded because of its location at anastomosis. Therefore, there were 37 peri-stent reference segments available for analwww.AJConline.org

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Table 1 Baseline clinical characteristics (n ⫽ 21) Characteristic Age (yrs) Men Unstable angina pectoris Non–ST-segment elevation myocardial infarction Diabetes mellitus Hypertension Smoker Hypercholesterolemia (⬎220 mg/dl) Graft age (yrs) Distal protection device use Bivalirudin use Left ventricular ejection fraction (%) Discharge medications Aspirin Clopidogrel Statins ␤ blockers Angiotensin antagonists

Table 2 Coronary angiographic findings and procedural results (n ⫽ 22) Value 69.4 ⫾ 11.4 18 (86%) 15 (71%) 6 (29%) 10 (48%) 18 (86%) 10 (48%) 18 (86%) 10.1 ⫾ 5.4 5 (24%) 19 (91%) 40 ⫾ 12 21 (100%) 21 (100%) 17 (81%) 20 (95%) 10 (48%)

Data are presented as means ⫾ SD and number (percent).

ysis; 16 segments were proximal to the proximal stent edge and 21 segments were distal to the distal stent edge. Hospital records of all the patients were reviewed to obtain information on clinical demographics and medical history. Quantitative coronary angiographic analysis: Quantitative analysis (CAAS II; Pie Medical, Maastricht, The Netherlands) was performed using standard protocols.10 With the outer diameter of the contrast agent-filled catheter as the calibration standard, the minimal lumen diameter, reference diameter, and lesion length were measured in diastolic frames from orthogonal projections. IVUS imaging protocol: IVUS examinations were performed after the intervention and at follow-up after administration of 200 ␮g nitroglycerin into the SVG using a commercially available IVUS system (Boston Scientific/ SCIMed, Minneapolis, Minnesota). The IVUS catheter was advanced distal to the target lesion, and imaging was performed retrograde to the aorto-ostial junction at an automatic pull-back speed of 0.5 mm/s. IVUS analysis: Qualitative analysis was performed according to the American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of IVUS studies.11 The same anatomic image slice was analyzed after intervention and at follow-up using planimetry software (TapeMeasure; INDEC Systems, Mountain View, California). The SVG area was measured by tracing the outer border of the entire SVG as has been previously described.12 By using the proximal or distal stent edge as an axial landmark and a known pullback speed, identical cross-sectional image slices on serial studies could be identified for comparison. The anatomic image slice selected for serial analysis had an axial location within the 5-mm-long peri-stent reference segments at the smallest postintervention lumen area; if there were multiple image slices within the same lumen area, the image slice with the largest SVG area and plaque area was selected to

Finding

Value

Diseased vessel SVG to left anterior descending artery SVG to left circumflex artery SVG to right coronary artery Lesion location Ostial Proximal Middle Distal Distal anastomosis Initial TIMI flow grade 0 1 2 3 Stent type Bare-metal stents Drug-eluting stents Stent diameter (mm) Stent length (mm) Direct stenting Deployment pressure (mm Hg) Stent-implanted segments Reference diameter (mm) Preprocedural minimal lumen diameter (mm) Postprocedural minimal lumen diameter (mm) Lesion length (mm)

6 (27%) 8 (36%) 8 (36%) 7 (32%) 7 (32%) 5 (23%) 2 (9%) 1 (5%) 0 (0%) 0 (0%) 2 (10%) 19 (91%) 14 (64%) 8 (36%) 3.58 ⫾ 0.60 19.3 ⫾ 6.4 14 (64%) 14 ⫾ 3 3.68 ⫾ 0.82 0.73 ⫾ 0.44 3.19 ⫾ 0.61 14.2 ⫾ 7.6

Data are presented as means ⫾ SD and number (percent). TIMI ⫽ Thrombolysis In Myocardial Infarction.

Table 3 Postintervention and follow-up intravascular ultrasound findings Finding Peri-stent minimum lumen site Saphenous vein graft area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Stent edge Stent area (mm2) Intimal hyperplasia area (mm2) Intimal hyperplasia (%)

Postintervention

Follow-up

p Value

14.34 ⫾ 4.12

14.52 ⫾ 4.22

⬍0.001

6.91 ⫾ 2.55 7.43 ⫾ 3.44 50.8 ⫾ 15.7

6.16 ⫾ 2.87 8.37 ⫾ 4.09 56.5 ⫾ 18.8

⬍0.001 ⬍0.001 ⬍0.001

8.6 ⫾ 3.3 NA

8.7 ⫾ 3.6 5.3 ⫾ 2.9

1.0

NA

59.7 ⫾ 23.6

Data are presented as means ⫾ SD. NA ⫽ not applicable.

compare the postintervention and follow-up SVG area, lumen area, plaque (i.e., SVG minus lumen) area, and plaque burden (i.e., plaque area divided by SVG area). We also measured minimum stent area, SVG area, and intimal hyperplasia area at the site of the smallest stent area within 5 mm from each stent edge. Statistical analysis: Statistical analysis was performed using SAS software (version 9.1; SAS, Cary, North Carolina). Continuous variables were presented as the mean

Coronary Artery Disease/SVG Disease Progression

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Figure 1. Correlations between postintervention peri-stent plaque burden and change in peri-stent SVG area (A), change in peri-stent lumen area (B), change in peri-stent plaque burden (C), and percent neointimal hyperplasia (D).

value ⫾ 1 SD and compared by paired or unpaired Student’s t test or nonparametric Wilcoxon test if the normality assumption was violated. Discrete variables are presented as percentages and relative frequencies and compared using chi-square statistics or Fisher’s exact test as appropriate. Pearson’s correlation coefficient was used to evaluate the associations between postintervention peri-stent plaque burden and change in SVG area, change in lumen area, change in plaque area, change in plaque burden, and percent neointimal hyperplasia and among change in lumen area and change in SVG area and change in plaque area. A p value ⬍0.05 was considered statistically significant. Results Patient characteristics and angiographic and procedural results: Baseline characteristics are listed in Table 1. Graft age was 10.1 ⫾ 5.4 years and distal protection devices were used in 24% of patients (n ⫽ 5). Sixty-two percent of patients were treated with statins, 71% of patients with ␤ blockers, 52% of patients with angiotensin antagonists, and 67% of patients with clopidogrel from the postintervention

period to follow-up. Angiographic findings and procedural results are listed in Table 2. Predilation was performed in 8 lesions (36%). Balloon size was 3.18 ⫾ 0.47 mm and balloon length was 17 ⫾ 7 mm. All balloons were shorter than the stents. IVUS results: No stent edge dissections were noted at the postintervention study. IVUS follow-up was performed at a mean of 13 months after stent placement (range 3 to 61). Postintervention peri-stent reference segment minimum lumen sites were 3.68 ⫾ 2.22 mm from their respective stent edges. Overall, SVG area and plaque area increased and lumen area decreased from the postintervention study to follow-up (Table 3). Change in SVG area, change in lumen area, and change in plaque burden all correlated with postintervention plaque burden (r ⫽ 0.448, p ⫽ 0.005; r ⫽ ⫺0.584, p ⬍0.001; and r ⫽ 0.507, p ⫽ 0.001, respectively). However, intrastent neointimal hyperplasia did not correlate with postintervention plaque burden (r ⫽ 0.289, p ⫽ 0.083; Figure 1). There were no correlations between change in SVG area, change in lumen area, change in

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Figure 2. Correlations between change in lumen area and change in plaque area (A), change in lumen area and change in SVG area (B), and change in SVG area and change in plaque area (C).

plaque area, and change in plaque burden versus the follow-up interval. Overall, change in lumen area correlated with change in plaque area (i.e., disease progression, r ⫽ ⫺0.971, p ⬍0.001) and with change in SVG area (i.e., remodeling, r ⫽ ⫺0.491, p ⫽ 0.002; Figure 2). Although there were no significant differences in change in SVG area, change in lumen area, change in plaque area, and change in plaque burden between proximal and distal stent edges, the relation between change in lumen area versus remodeling was different for proximal and distal edges. For 16 proximal stent edges, change in lumen area correlated with change in plaque area (r ⫽ ⫺0.951, p ⬍0.001), but not with change in SVG area (r ⫽ ⫺0.337, p ⫽ 0.201). For 21 distal stent edges, change in lumen area correlated more strongly with change in plaque area (r ⫽ ⫺0.982, p ⬍0.001) than with change in SVG area (r ⫽ ⫺0.624, p ⫽ 0.003). Overall, change in SVG area correlated with change in plaque area (r ⫽ 0.684, p ⬍0.001, Figure 2) at both stent edges. DES- versus BMS-treated lesions: For BMS-treated lesions (24 stent edges), SVG area and plaque area increased and

lumen area decreased from the postintervention study to follow-up (SVG area, 15.09 ⫾ 3.53 to 15.31 ⫾ 3.67 mm2, p ⫽ 0.001; lumen area, 7.09 ⫾ 1.80 to 6.22 ⫾ 2.40 mm2, p ⬍0.001; and plaque area, 8.00 ⫾ 3.28 to 9.08 ⫾ 4.00 mm2, p ⬍0.001), and change in SVG area, change in lumen area, and change in plaque burden all correlated with postintervention plaque burden (r ⫽ 0.607, p ⫽ 0.002; r ⫽ ⫺0.732, p ⬍0.001; r ⫽ 0.555, p ⫽ 0.005, respectively). For DES-treated lesions (13 stent edges), SVG area and plaque area increased and lumen area decreased from the postintervention study to follow-up (SVG area, 12.95 ⫾ 4.89 to 13.07 ⫾ 4.92 mm2, p ⫽ 0.002; lumen area, 6.58 ⫾ 3.62 to 6.03 ⫾ 3.69 mm2, p ⫽ 0.002; and plaque area, 6.38 ⫾ 3.60 to 7.04 ⫾ 4.09 mm2, p ⫽ 0.001), but change in SVG area and change in lumen area did not correlate with postintervention plaque burden (r ⫽ 0.396, p ⫽ 0.181 and r ⫽ ⫺0.532, p ⫽ 0.061, respectively), suggesting an effect of the eluted drug. Change in lumen area correlated more strongly with change in plaque area than with change in SVG area in DES-treated lesions (r ⫽ ⫺0.990, p ⬍0.001 and r ⫽ ⫺0.641, p ⫽ 0.018, respectively) and BMS-treated lesions (r ⫽ ⫺0.967, p ⬍0.001 and r ⫽ ⫺0.454, p ⫽ 0.026, respectively).

Coronary Artery Disease/SVG Disease Progression Table 4 Postintervention and follow-up intravascular ultrasound findings according to postintervention peri-stent plaque burden Finding

Postintervention Saphenous vein graft area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Edge stent area (mm2) Follow-up Saphenous vein graft area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Change in measurements Saphenous vein graft area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Edge neointimal hyperplasia (%)

Plaque Burden ⬍50% (n ⫽ 17)

Plaque Burden ⬎50% (n ⫽ 20)

p Value

13.51 ⫾ 3.94

15.04 ⫾ 4.23

0.266

8.41 ⫾ 2.24 5.11 ⫾ 2.32 37.0 ⫾ 9.8 7.4 ⫾ 1.7

5.64 ⫾ 2.10 9.40 ⫾ 2.99 62.6 ⫾ 8.3 9.6 ⫾ 3.9

⬍0.001 ⬍0.001 ⬍0.001 0.028

13.60 ⫾ 3.98

15.30 ⫾ 4.37

0.229

8.08 ⫾ 2.14 5.53 ⫾ 2.54 39.7 ⫾ 10.4

4.52 ⫾ 2.37 10.78 ⫾ 3.61 70.8 ⫾ 10.5

⬍0.001 ⬍0.001 ⬍0.001

0.09 ⫾ 0.09

0.26 ⫾ 0.29

0.027

⫺0.33 ⫾ 0.26 0.42 ⫾ 0.30 2.8 ⫾ 1.6 53.8 ⫾ 29.1

⫺1.12 ⫾ 0.81 1.37 ⫾ 0.96 8.2 ⫾ 5.6 64.8 ⫾ 16.8

⬍0.001 ⬍0.001 ⬍0.001 0.160

Data are presented as means ⫾ SD.

IVUS results according to postintervention plaque burden: We divided the reference segments into 2 groups according to the postintervention peri-stent reference segment plaque burden (⬎50% [n ⫽ 20, 62.6 ⫾ 8.3%] vs ⬍50% [n ⫽ 17, 37.0 ⫾ 9.8%]). Baseline SVG area was similar, but lumen area was smaller and plaque area was larger in segments with a plaque burden ⬎50% (Table 4). At follow-up, there was a greater decrease in lumen area and greater increases in SVG area, plaque area, and plaque burden in segments with a postintervention plaque burden ⬎50%. Discussion The present IVUS study showed that peri-stent reference segment SVG disease progression and lumen loss were greater in segments with a greater postintervention plaque burden, especially in SVG lesions treated with BMS, and lumen loss was more strongly correlated with an increase in plaque area than with change in SVG area. Several studies have demonstrated peri-stent edge lumen loss after BMS implantation in native coronary arteries. Hoffmann et al2 performed serial IVUS analysis at (1) the most normal-looking cross sections within 10 mm proximal or distal to the stent, (2) another cross section midway between this slice and the stent edge, and (3) at the proximal or distal stent edge and found that late lumen loss correlated more with remodeling (r ⫽ 0.809, p ⬍0.0001) than with tissue growth (r ⫽ 0.283, p ⫽ 0.0014) at the most remote cross sections, whereas late lumen loss correlated less with remodeling (r ⫽ 0.283, p ⫽ 0.0014) than with tissue growth (r ⫽ 0.636, p ⬍0.0001) closer to the edge of the stent. Mudra et al3 reported that there was no relevant disease

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progression immediately adjacent to the stent despite a considerable plaque burden (46 ⫾ 11% and 48 ⫾ 11% at the proximal and distal reference sites, respectively). Weissman et al4 performed serial IVUS analyses of 10-mm-long reference segments proximal and distal to the stent edge in a cohort with predefined, protocol-driven follow-up IVUS and had similar findings as Hoffmann et al.2 Hoffman et al8 also evaluated predictors of restenosis at the margins of Palmaz-Schatz stents using IVUS performed after intervention and at follow-up (5.4 months) in 161 stent-implanted lesions. In this study, the dominant periprocedural predictor of stent margin restenosis in a mixed population of native arteries and SVGs (32%) was the plaque burden of the contiguous reference segment. Several IVUS studies have also reported serial edge analysis after DES implantation. In the Asian PaclitaxelEluting Stent Clinical Trial (ASPECT),13 there were no significant changes at either edge. In the study of the QP2eluting polymer stent system by Honda et al,7 there was significant lumen loss at the distal edge. In the TAXUS-II trial,6 there was an increase in vessel area, an increase in plaque area, and a decrease in lumen area within the first 1 mm proximal and the first 3 mm distal to slow- and moderate-release Taxus stents (Boston Scientific, Natick, Massachusetts). In the Diabetes and Sirolimus-Eluting Stent (DIABETES) trial,5 there was net lumen enlargement at the proximal and distal edges after sirolimus-eluting stent implantation because of a significant increase in vessel volume. In the present study, lumen loss correlated more strongly with plaque growth than with remodeling at a point 3.68 ⫾ 2.22 mm from the stent edge, suggesting that SVGs may not undergo remodeling changes as easily as native coronary arteries, at least adjacent to stent edges in SVGs with a significant baseline plaque burden. This would result in a greater impact of stent edge disease progression or intimal hyperplasia on lumen dimensions in SVGs than in native arteries. However, the present study did not examine cross sections more remote from the stent edges. Sakurai et al9 analyzed IVUS parameters in 317 edges of 167 stents from the Sirolimus-Coated BX Velocity BalloonExpandable Stent in the Treatment of Patients with De Novo Coronary Artery Lesions (SIRIUS) trial. Eighteen edges were restenosed, and a larger reference plaque burden and a larger edge stent area/reference minimum lumen area were associated with edge stenosis. In the present study, if the edge plaque burden was ⬎50%, the decrease in lumen area was quite significant. Lumen loss more strongly correlated with postintervention plaque burden after implantation of a BMS compared with a DES. Several angiographic studies have assessed SVG disease progression. Domanski et al14 reported that maximum SVG stenosis and minimum SVG lumen diameter on baseline angiography were predictive of angiographic disease progression. Campos et al15 presented long-term follow-up data of normal and minimally diseased SVGs; more than half of these grafts remained normal or minimally diseased. Data from Mehta et al16 also suggested a favorable outcome if SVGs were normal at baseline. We are aware of no previously published data on IVUS assessment of progression of SVG disease.

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The presence of remodeling within the SVG is controversial. Nishioka et al17 showed a lack of remodeling in SVGs, but this conclusion was disputed by other authors.12,18,19 In a study by Ge et al,19 lesion-site SVG area was significantly greater than those of the proximal and distal reference segments and SVG area increased in accordance with the increase in plaque area, which are evidence of remodeling. Although the present study analyzed only SVG cross sections near the stent edge, the increase in plaque area was accompanied by an increase in SVG area consistent with positive remodeling. There are several limitations to be mentioned. First, this study is based on a small sample size and was retrospective in nature. Second, the study population came from a single center, raising the possibility of selection bias. Third, we did not demonstrate the effects of medications, cholesterol level, and blood pressure on disease progression. Fourth, we did not assess the changes in SVG, lumen, and plaque areas that were more distant from the stent edges because these segments were not affected by the stent or balloon. 1. Hoffmann R, Mintz GS, Popma JJ, Satler LF, Pichard AD, Kent KM, Walsh C, Mackell P, Leon MB. Chronic arterial responses to stent implantation: a serial intravascular ultrasound analysis of PalmazSchatz stents in native coronary arteries. J Am Coll Cardiol 1996;28: 1134 –1139. 2. Hoffmann R, Mintz GS, Dussaillant GR, Popma JJ, Pichard AD, Satler LF, Kent KM, Griffin J, Leon MB. Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study. Circulation 1996;94:1247–1254. 3. Mudra H, Regar E, Klauss V, Werner F, Henneke KH, Sbarouni E, Theisen K. Serial follow-up after optimized ultrasound-guided deployment of Palmaz-Schatz stents. In-stent neointimal proliferation without significant reference segment response. Circulation 1997;95:363–370. 4. Weissman NJ, Wilensky RL, Tanguay JF, Bartorelli AL, Moses J, Williams DO, Bailey S, Martin JL, Canos MR, Rudra H, et al. Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population. Am J Cardiol 2001;88:248 –252. 5. Jimenez-Quevedo P, Sabate M, Angiolillo DJ, Costa MA, Alfonso F, Gomez-Hospital JA, Hernandez-Antolin R, Banuelos C, Goicolea J, Fernandez-Aviles F, et al. Vascular effects of sirolimus-eluting versus bare-metal stents in diabetic patients: three-dimensional ultrasound results of the Diabetes and Sirolimus-Eluting Stent (DIABETES) Trial. J Am Coll Cardiol 2006;47:2172–2179. 6. Serruys PW, Degertekin M, Tanabe K, Russell ME, Guagliumi G, Webb J, Hamburger J, Rutsch W, Kaiser C, Whitbourn R, et al. Vascular responses at proximal and distal edges of paclitaxel-eluting stents: serial intravascular ultrasound analysis from the TAXUS II trial. Circulation 2004;109:627– 633.

7. Honda Y, Grube E, de La Fuente LM, Yock PG, Stertzer SH, Fitzgerald PJ. Novel drug-delivery stent: intravascular ultrasound observations from the first human experience with the QP2-eluting polymer stent system. Circulation 2001;104:380 –383. 8. Hoffmann R, Mintz GS, Kent KM, Satler LF, Pichard AD, Popma JJ, Leon MB. Serial intravascular ultrasound predictors of restenosis at the margins of Palmaz-Schatz stents. Am J Cardiol 1997;79:951–953. 9. Sakurai R, Ako J, Morino Y, Sonoda S, Kaneda H, Terashima M, Hassan AH, Leon MB, Moses JW, Popma JJ, et al. Predictors of edge stenosis following sirolimus-eluting stent deployment (a quantitative intravascular ultrasound analysis from the SIRIUS trial). Am J Cardiol 2005;96:1251–1253. 10. Gronenschild E, Janssen J, Tijdens F. CAAS. II: a second generation system for off-line and on-line quantitative coronary angiography. Cathet Cardiovasc Diagn 1994;33:61–75. 11. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, Pinto FJ, Rosenfield K, Siegel RJ, Tuzcu EM, Yock PG. American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS): a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001;37:1478 –1492. 12. Hong MK, Mintz GS, Hong MK, Abizaid AS, Pichard AD, Satler LF, Kent KM, Leon MB. Intravascular ultrasound assessment of the presence of vascular remodeling in diseased human saphenous vein bypass grafts. Am J Cardiol 1999;84:992–998. 13. Hong MK, Mintz GS, Lee CW, Song JM, Han KH, Kang DH, Song JK, Kim JJ, Weissman NJ, Fearnot NE, Park SW, Park SJ. Paclitaxel coating reduces in-stent intimal hyperplasia in human coronary arteries: a serial volumetric intravascular ultrasound analysis from the Asian Paclitaxel-Eluting Stent Clinical Trial (ASPECT). Circulation 2003;107:517–520. 14. Domanski MJ, Borkowf CB, Campeau L, Knatterud GL, White C, Hoogwerf B, Rosenberg Y, Geller NL. Prognostic factors for atherosclerosis progression in saphenous vein grafts: the postcoronary artery bypass graft (Post-CABG) trial. Post-CABG Trial Investigators. J Am Coll Cardiol 2000;36:1877–1883. 15. Campos EE, Cinderella JA, Farhi ER. Long-term angiographic follow-up of normal and minimally diseased saphenous vein grafts. J Am Coll Cardiol 1993;21:1175–1180. 16. Mehta I, Zaret B, Weinberg J, Kopf G, Elefteriades J. Should diseasefree saphenous vein grafts be replaced at the time of redo CABG? Circulation 1996;94(suppl I):I-412–I-413. 17. Nishioka T, Luo H, Berglund H, Eigler NL, Kim CJ, Tabak SW, Siegel RJ. Absence of focal compensatory enlargement or constriction in diseased human coronary saphenous vein bypass grafts: an intravascular ultrasound study. Circulation 1996;93:683– 690. 18. Mendelsohn FO, Foster GP, Palacios IF, Weyman AE, Weissman NJ. In vivo assessment by intravascular ultrasound of enlargement in saphenous vein bypass grafts. Am J Cardiol 1995;76:1066 –1069. 19. Ge J, Liu F, Bhate R, Haude M, Gorge G, Baumgart D, Sack S, Erbel R. Does remodeling occur in the diseased human saphenous vein bypass grafts? An intravascular ultrasound study. Int J Cardiol Imaging 1999;15:295–300.