Masashi - Outcome After Acute Incomplete Sirolimus-eluting Stent Apposition As Assessed By Serial Intravascular Ultrasound

Outcome After Acute Incomplete Sirolimus-Eluting Stent Apposition as Assessed by Serial Intravascular Ultrasound Masashi Kimura, MD, PhD, Gary S. Mintz, MD, Stéphane Carlier, MD, PhD*, Hideo Takebayashi, MD, PhD, Kenichi Fujii, MD, Koichi Sano, MD, PhD, Takenori Yasuda, MD, Ricardo A. Costa, MD, Jose R. Costa, Jr., MD, Jie Quen, MD, PhD, Kaoru Tanaka, MD, PhD, Joanna Lui, BA, Giora Weisz, MD, Issam Moussa, MD, George Dangas, MD, PhD, Roxana Mehran, MD, Alexandra J. Lansky, MD, Edward M. Kreps, MD, Michael Collins, MD, Gregg W. Stone, MD, Jeffrey W. Moses, MD, and Martin B. Leon, MD We investigated the fate of postprocedural incomplete stent apposition (ISA) after sirolimus-eluting stent (SES) implantation by evaluating long-term intravascular ultrasound findings in 168 consecutive patients (182 de novo lesions). Postprocedural ISA was defined as >1 stent strut that was clearly separated from the vessel wall with evidence of blood speckle behind the strut without overlapping a side branch. After SES implantation, there were 61 ISA sites in 46 stents in 31 patients (23 at the proximal edge, 7 at the distal edge, and 31 within the stent body). There were no clinical, procedural, or intravascular ultrasound measurement differences between patients and lesions with versus without ISA. At follow-up, 15 acute ISA sites (25%) in 11 patients completely resolved and 40 sites (75%) in 20 patients persisted, although 32 of 46 persisting ISA sites (70%) decreased. There was a greater decrease in effective lumen area and a greater increase in peristent plaque area in the complete-resolution group than in the persistent-ISA group. No lesion developed stent thrombosis or in-stent restenosis (angiographic diameter stenosis >50%). Six acute ISA sites were also associated with new, late acquired ISA, only 1 of which resulted in aneurysm formation. Although most ISAs after SES implantation do not resolve completely, the incidence of restenosis or thrombosis is not affected. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006;98:436 – 442) Serial intravascular ultrasound (IVUS) studies have shown that sirolimus-eluting stents (SESs) decrease restenosis by inhibiting neointimal hyperplasia.1–3 However, questions remain, including the frequency and effect of incomplete stent apposition (ISA) at the time of stent implantation. Retrospective studies have suggested a relation between postprocedural ISA and stent thrombosis or between postprocedural ISA and underdosing at the tissue level due to a lack of stent–vessel wall contact, leading to in-stent restenosis.4 –11 This study examined the natural history of ISA after SES implantation and its relation to neointimal hyperplasia. •••

From our clinical and core IVUS laboratory databases, we identified 168 consecutive patients with 182 de novo lesions treated with SES implantation in whom IVUS imaging was performed at index and at follow-up (6.7 ⫾ 2.5 months). This study was approved by the institutional review board; written informed consent was obtained from all patients. All patients were premedicated with 325 mg of aspirin, which Columbia University Medical Center and Cardiovascular Research Foundation, New York, New York. Manuscript received November 8, 2005; revised manuscript received and accepted February 27, 2006. * Corresponding author: Tel: 212-851-9371; fax: 212-851-9330. E-mail address: [email protected] (S. Carlier). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.02.050

was continued indefinitely. A loading dose of 600 mg of clopidogrel was administered in the catheterization laboratory, and 75 mg/day of clopidogrel was recommended for ⱖ12 months. IVUS imaging was performed, after intracoronary administration of 0.1 to 0.2 mg of nitroglycerin, using motorized transducer pullback and a commercially available scanner (Boston Scientific, Natick, Massachusetts) that incorporated a 40-MHz, single-element, beveled transducer rotating at 1,800 rpm. The ultrasound catheter was advanced ⬎10 mm beyond the stent into the distal vessel, and the transducer was withdrawn at a pull-back speed of 0.5 mm/s to a point ⬎10 mm proximal to the stent. Images were recorded onto 0.5-in, high-resolution s-VHS tapes for offline analysis. All IVUS images were reviewed and quantitative and qualitative IVUS analyses were performed with computerized planimetry (TapeMeasure, Indec Systems, Mountain View, California). ISA was defined as ⱖ1 stent strut that was clearly separated from the vessel wall with evidence of blood speckle behind the strut without overlapping a side branch. Late-acquired ISA was defined as ISA that was present at follow-up but not at baseline. Aneurysm formation was defined as an increase in external elastic membrane and lumen cross-sectional area ⬎150% of the proximal reference. The following measurements were performed (Figures 1 and 2): (1) ISA angle (degrees); (2) ISA depth www.AJConline.org

Coronary Artery Disease/Outcome of Incomplete SES Apposition

Figure 1. Schematic of circumferential distribution of vessel, lumen, plaque/media, neointimal, struts, and superficial calcium postprocedural ISA. Schema shows the maximum angle of the ISA, superficial calcium behind the ISA, and measurements of maximum depth of the ISA.

(millimeters); (3) stent, lumen, external elastic membrane, peristent plaque and media, and ISA cross-sectional area (square millimeters); (4) neointimal hyperplasia cross-sectional area and percent neointimal hyperplasia obstruction (neointimal hyperplasia divided by stent cross-sectional area) at the site of ISA; (5) maximum neointimal hyperplasia cross-sectional area and percent neointimal hyperplasia obstruction at any location within the stent; (6) ISA length (millimeters); (7) arc of superficial calcification (degrees); and (8) number of malapposed struts. Effective lumen crosssectional area was defined as intrastent lumen plus ISA cross-sectional area. Statistical analysis was performed with StatView 5.0 (SAS Institute, Cary, North Carolina). Continuous variables were reported as mean ⫾ 1 SD. If data were normally distributed with a F test, continuous variables were compared with unpaired Student’s t test or regression analysis. Otherwise, a Mann-Whitney U statistic test was used. Categorical variables were reported as frequencies and compared with chi-square statistics. Variables with a p value ⬍0.2 were entered into the multivariate model to find inde-

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pendent predictors of persistent ISA and new late ISA. Statistical significance was set at p ⬍0.05. After SES implantation, there were 61 acute ISA sites in 46 stents in 31 patients. ISA location was at the proximal edge in 23, the distal edge in 7, and within the stent body in 31. Overall, average postprocedural ISA cross-sectional area was 2.01 ⫾ 1.95 mm2 and ISA length was 2.83 ⫾ 2.02 mm. As presented in Table 1, there were no significant clinical differences between patients with acute ISA versus those without. During follow-up, there were no episodes of stent thrombosis in either group. At follow-up, of the 31 patients, 18 were symptomatic or had a positive stress test result (ultimately determined to be related to other lesions), whereas the others were asymptomatic (follow-up angiography and IVUS imaging were performed for protocol reasons). Symptomatic patients (n ⫽ 18) had more neointimal hyperplasia (1.55 ⫾ 1.62 vs 0.25 ⫾ 0.59 mm2, p ⫽ 0.04) at the minimum lumen area position in the stent (not the ISA position). Fifteen of 61 postprocedural ISA sites (25%) in 11 patients completely resolved and 46 sites (75%) in 20 patients persisted, although 32 of 46 persistent ISA sites (70%) shrank. Table 2 presents a comparison of clinical and procedural differences between patients and lesions with complete stent apposition resolution versus ISA resolution. There were no differences between groups. Table 3 presents a comparison of IVUS findings between lesions with complete stent apposition resolution versus ISA resolution. Persistent ISAs had a larger angle of superficial calcium at the ISA site, and a higher frequency of persistent ISAs had an arc of superficial calcium that was larger than the ISA angle. There were no other baseline differences between groups, including all baseline measurements of ISA and location, baseline external elastic membrane, and peristent plaque/ media cross-sectional area. The only univariate predictors of persistent ISA (at p ⬍0.2; Tables 2 and 3) were longer ISAs, body ISA location, increased percentage of calcium, and angle of superficial calcium at an ISA site. However, there were no independent predictors of persistent ISA in the overall cohort. In the overall cohort, change in ISA cross-sectional area correlated with changes in peristent plaque/media crosssectional area and external elastic membrane cross-sectional area (Figure 3). At follow-up, there was a greater decrease in effective lumen cross-sectional area and a greater increase in peristent plaque/media cross-sectional area in the complete resolution group than in the persistent ISA group, but there was no difference in change in external elastic membrane cross-sectional area (Table 3). Six sites of acute ISA were also associated with new, late-acquired stent ISA, only 1 of which resulted in aneurysm formation. Table 4 presents a comparison of these 6 acute ISA sites (group 1) with the acute ISA sites that were not associated with new, late stent ISA (n ⫽ 55, group 2). Group 1 sites (those associated with new, late stent ISA) had an increase in all measurements of ISA and a greater in-

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Figure 2. Typical longitudinal IVUS images of patients who had segments with complete resolution, persistent ISA, and new, late ISA after the procedure at follow-up and IVUS measurements (ISA cross-sectional area [CSA] and ISA longitudinal length) of cases.

crease in external elastic membrane cross-sectional area and effective lumen cross-sectional area compared with group 2 sites. All group 1 ISA sites became larger. Conversely, 15 group 2 sites completely resolved, and 40 group 2 sites persisted. The only independent predictor of persistent ISA in group 2 was the arc of superficial calcification at the ISA site (odds ratio 1.022, 95% confidence interval 1.002 to 1.043, p ⫽ 0.03). In group 1 sites, a change in effective lumen crosssectional area correlated strongly with a change in external elastic membrane cross-sectional area but not with a change in peristent plaque/media cross-sectional area; a change in ISA cross-sectional area also correlated strongly with a change in external elastic membrane cross-sectional area but not with a change in peristent plaque/media crosssectional area (Figure 4). Conversely, in group 2 sites, a change in effective lumen cross-sectional area correlated with a change in peristent plaque/media cross-sectional area but not with a change in external elastic membrane cross-sectional area; a change in ISA cross-sectional area was also correlated with a change in peristent plaque/

media cross-sectional area but not with a change in external elastic membrane cross-sectional area (Figure 5). There was no independent predictor of late-acquired ISA in this analysis. •••

The main findings of our analysis were as follows: (1) most SES ISAs resolved or shrank secondary to an increase in peristent plaque/media cross-sectional area without causing stent thrombosis or contributing to in-stent restenosis; (2) superficial calcium deposits inhibited ISA resolution; and (3) acute ISAs had a totally different natural history if associated with new, late-acquired ISA in the same stent and shrank as a result of an increase in external elastic membrane cross-sectional area (rather than shrinking as a result of an increase in peristent plaque/media cross-sectional area). In our study, the incidence of postprocedural ISA was 18% (31 of 168 patients). ISA was more frequently observed at 6-month follow-up in the SES group than in the control group in the Randomized Study with the Sirolimus-

Coronary Artery Disease/Outcome of Incomplete SES Apposition Table 1 Baseline and procedural characteristics Variable

Age (yrs) Men/women Cigarette smoking Diabetes mellitus Unstable angina pectoris Interval (mo) Location of coronary lesion Left anterior descending Left circumflex Right No. of stents Stent diameter (mm) Total stented length (mm) Direct stenting After inflation Balloon size (mm) Maximal inflation pressure (atm)

Acute ISA Yes (n ⫽ 31)

No (n ⫽ 151)

59.6 ⫾ 10.8 21/10 6 (19%) 7 (22%) 1 (3%) 7.0 ⫾ 2.3

62.4 ⫾ 10.4 99/52 27 (18%) 51 (34%) 5 (3%) 6.5 ⫾ 2.6

22 (71%) 5 (16%) 4 (13%) 1.5 ⫾ 0.7 3.17 ⫾ 0.38 28.9 ⫾ 15.3 39% 57% 3.27 ⫾ 0.38 16.5 ⫾ 3.3

94 (62%) 29 (20%) 27 (18%) 1.6 ⫾ 0.8 3.05 ⫾ 0.33 26.8 ⫾ 12.7 67% 67% 3.26 ⫾ 0.42 17.8 ⫾ 2.9

p Value

0.9 0.12 0.7 1 0.3 0.9 0.07

Values are means ⫾ SDs or numbers of patients (percentages).

Table 2 Baseline and procedural characteristics between patients with complete resolution of acute incomplete stent apposition versus persistent incomplete stent apposition Variable

Age (yrs) Men/women Cigarette smoking Diabetes mellitus Unstable angina pectoris Follow-up (mo) Location of coronary lesion Left anterior descending Left circumflex Right ISA location Proximal edge In-stent body Distal edge No. of stents Stent diameter (mm) Total stented length (mm) Direct stenting After inflation Balloon size (mm) Maximal inflation pressure (atm)

Complete Persistent ISA p Resolution (n ⫽ 46) Value of acute ISA (n ⫽ 15) 61.3 ⫾ 9.4 4/1 2 (13%) 3 (20%) 0 (0%) 7.4 ⫾ 1.4

59.2 ⫾ 12.8 35/11 10 (22%) 12 (26%) 1 (2%) 6.9 ⫾ 2.5

11 (73%) 2 (13%) 2 (13%)

30 (65%) 8 (17%) 8 (17%)

0.8 0.7 0.3 1 1 0.53 0.9

0.2 10 (67%) 4 (27%) 1 (6%) 1.7 ⫾ 0.9 3.3 ⫾ 0.4 27.4 ⫾ 16.4 5 (33%) 9 (60%) 3.3 ⫾ 0.3 16.9 ⫾ 3.2

15 (31%) 27 (60%) 4 (9%) 1.5 ⫾ 0.6 3.2 ⫾ 0.4 29.2 ⫾ 13.7 16 (35%) 25 (54%) 3.3 ⫾ 0.3 15.9 ⫾ 3.1

Table 3 Intravascular ultrasound findings between sites of complete resolution of versus persistent incomplete stent apposition Variable

0.3 0.7 0.9 0.3 1 0.8 0.4

0.7 0.59 0.9 0.9 0.7 0.6 0.3

Values are means ⫾ SDs or numbers of patients (percentages).

Eluting Velocity Balloon-Expandable Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions (RAVEL).12 However, the true incidence of acute ISA was unclear, because no IVUS imaging after stenting was performed.12 Completed serial IVUS analysis from the Sirolimus-Eluting Stent in De Novo Coronary Lesions

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Complete Persistent ISA Resolution (n ⫽ 46) of acute ISA (n ⫽ 15)

External elastic membrane CSA (mm2) After stenting 18.6 ⫾ 5.7 20.0 ⫾ 5.2 Follow-up 18.8 ⫾ 5.6 20.6 ⫾ 5.1 ⌬ 0.2 ⫾ 0.6 0.6 ⫾ 1.7 Effective lumen CSA (mm2) After stenting 10.0 ⫾ 1.9 10.5 ⫾ 3.2 Follow-up 8.3 ⫾ 1.4 10.6 ⫾ 3.1 ⌬ ⫺1.7 ⫾ 1.3 ⫺0.5 ⫾ 1.4 Peristent plaque/media CSA (mm2) After stenting 8.6 ⫾ 4.7 9.5 ⫾ 3.2 Follow-up 10.3 ⫾ 4.8 10.0 ⫾ 3.3 ⌬ 1.7 ⫾ 0.9 0.5 ⫾ 1.5 Stent CSA (mm2) After stenting 8.2 ⫾ 1.3 8.4 ⫾ 1.9 Follow-up 8.4 ⫾ 1.4 8.4 ⫾ 2.0 ⌬ 0.2 ⫾ 0.4 0.0 ⫾ 0.4 Calcium at ISA site* 6.7% 65.2% Arc of superficial calcium (°) 12.0 ⫾ 24.0 135.1 ⫾ 104.1 ISA CSA (mm2) After stenting 1.8 ⫾ 1.2 2.0 ⫾ 1.2 Follow-up 0.0 ⫾ 0.0 2.2 ⫾ 2.4 ⌬ ⫺1.8 ⫾ 1.2 0.1 ⫾ 2.2 ISA length (mm) After stenting 2.2 ⫾ 1.2 3.1 ⫾ 2.2 Follow-up 0.0 ⫾ 0.0 4.0 ⫾ 3.7 ⌬ ⫺2.2 ⫾ 7.6 0.9 ⫾ 2.7 Arc of ISA (°) After stenting 155 ⫾ 76 154 ⫾ 73 Follow-up 0.0 ⫾ 0.0 147.3 ⫾ 81.7 ⌬ ⫺155 ⫾ 76 ⫺7 ⫾ 87 ISA depth (mm) After stenting 0.5 ⫾ 0.2 0.6 ⫾ 0.4 Follow-up 0.0 ⫾ 0.0 0.6 ⫾ 0.4 ⌬ ⫺0.5 ⫾ 0.2 0.0 ⫾ 0.2 No. of malapposed struts After stenting 1.9 ⫾ 1.3 2.1 ⫾ 1.2 Follow-up 0.0 ⫾ 0.0 2.2 ⫾ 1.3 ⌬ ⫺1.9 ⫾ 1.3 0.2 ⫾ 1.5

p Value

0.4 0.2 0.3 0.5 0.007 0.006

0.4 0.9 0.006 0.7 1 0.1 ⬍0.0001 ⬍0.0001 0.6 0.0007 0.002 0.2 ⬍0.0001 ⬍0.0001 1 ⬍0.0001 ⬍0.0001 0.2 ⬍0.0001 ⬍0.0001 0.5 ⬍0.0001 ⬍0.0001

Data are means ⫾ SDs or percentages. * Superficial calcium behind stent struts with an angle larger that the angle of ISA. ⌬ ⫽ change; CSA ⫽ cross-sectional area.

(SIRIUS) trial showed 13 cases (16.2%) of postprocedural ISA after 80 SES implantations.13 The incidence of ISA in this study is similar to that previously reported. In our study, 25% of postprocedural ISAs after SES implantation resolved completely, and 70% of persisting ISAs shrank during follow-up. In the SIRIUS trial, 7 of 13 ISAs observed at baseline were resolved and were not present at follow-up (resolved ISAs). In the TAXUS-II, 11 of 19 postprocedural ISAs in the bare metal stent group resolved at 6 months; 8 of 13 resolved in the slow-release group, and all postprocedural ISAs in the moderate-release group resolved.14

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Figure 3. Overall change (⌬) in effective lumen CSA correlated with changes in (A) peristent plaque/media CSA (p ⬍0.001, R2 ⫽ 0.499) and (C) external elastic membrane CSA (p ⬍0.001, R2 ⫽ 0.518). Change in ISA CSA correlated with changes in (B) peristent plaque/media CSA (p ⬍0.001, R2 ⫽ 0.460) and (D) external elastic membrane CSA (p ⬍0.001, R2 ⫽ 0.517). Abbreviation as in Figure 2.

Figure 4. In acute ISA lesions associated with additional new, late-acquired ISAs (group 1, n ⫽ 6), ⌬effective lumen CSA correlated strongly with (B) ⌬external elastic membrane CSA (p ⬍0.001, R2 ⫽ 0.999) but not with (A) ⌬peristent plaque/media CSA (p ⫽ 0.56, R2 ⫽ 0.091); ⌬ISA CSA also correlated strongly with (D) ⌬external elastic membrane CSA (p ⬍0.001, R2 ⫽ 0.988) but not with (C) ⌬peristent plaque/media CSA (p ⫽ 0.42, R2 ⫽ 0.168). Abbreviations as in Figures 2 and 3.

Coronary Artery Disease/Outcome of Incomplete SES Apposition Table 4 Intravascular ultrasound findings between sites of acute incomplete stent apposition that do or do not also develop an additional site of new, late incomplete stent apposition Variable

EEM cross-sectional area (mm2) After stenting Follow-up ⌬ Effective lumen cross-sectional area (mm2) After stenting Follow-up ⌬ Peristent plaque/media crosssectional area (mm2) After stenting Follow-up ⌬ Stent cross-sectional area (mm2) After stenting Follow-up ⌬ Calcium at ISA site* Arc of superficial calcium (°) ISA cross-sectional area (mm2) After stenting Follow-up ⌬ ISA length (mm) After stenting Follow-up ⌬ Arc of ISA (°) After stenting Follow-up ⌬ ISA depth (mm) After stenting Follow-up ⌬ No. of malapposed struts After stenting Follow-up ⌬

Without New, With New, Late ISA Late ISA (n ⫽ 55) (n ⫽ 6)

p Value

19.8 ⫾ 5.4 19.9 ⫾ 5.3 0.1 ⫾ 0.6

18.7 ⫾ 5.0 22.7 ⫾ 4.0 4.1 ⫾ 2.5

0.6 0.2 ⬍0.0001

10.5 ⫾ 3.0 9.7 ⫾ 2.7 ⫺0.8 ⫾ 1.5

9.7 ⫾ 1.2 13.9 ⫾ 2.0 4.2 ⫾ 2.4

0.6 0.0001 ⬍0.0001

9.3 ⫾ 3.6 10.2 ⫾ 3.7 0.9 ⫾ 1.5

9.0 ⫾ 4.0 8.9 ⫾ 4.0 ⫺0.1 ⫾ 0.1

0.6 0.4 0.09

8.4 ⫾ 1.8 8.3 ⫾ 0.8 8.5 ⫾ 1.9 8.1 ⫾ 0.6 0.1 ⫾ 0.4 ⫺0.1 ⫾ 0.3 35.7% 33.3% 106 ⫾ 106 68 ⫾ 60

0.9 0.7 0.3 0.9 0.4

2.1 ⫾ 2.0 1.2 ⫾ 1.8 ⫺1.8 ⫾ 1.2

1.5 ⫾ 0.8 5.7 ⫾ 1.9 4.2 ⫾ 2.4

0.5 ⬍0.0001 ⬍0.0001

2.7 ⫾ 2.0 2.2 ⫾ 2.5 ⫺0.6 ⫾ 1.5

3.9 ⫾ 1.9 10.3 ⫾ 4.3 6.4 ⫾ 3.5

0.17 ⬍0.0001 ⬍0.0001

156 ⫾ 76 93 ⫾ 76 ⫺64 ⫾ 84

136 ⫾ 30 0.5 280 ⫾ 90 ⬍0.0001 144 ⫾ 107 ⬍0.0001

0.6 ⫾ 0.3 0.4 ⫾ 0.4 ⫺0.2 ⫾ 0.3

0.5 ⫾ 0.2 0.9 ⫾ 0.2 0.4 ⫾ 0.1

0.7 0.01 ⬍0.0001

2.0 ⫾ 1.2 1.4 ⫾ 1.1 ⫺0.7 ⫾ 1.2

1.7 ⫾ 0.8 4.5 ⫾ 1.4 2.8 ⫾ 2.1

0.5 ⬍0.0001 ⬍0.0001

Data are means ⫾ SDs or percentages. * Superficial calcium behind stent struts with an angle larger than the angle of ISA. EEM ⫽ external elastic membrane; other abbreviation as in Table 3.

These discrepancies can be attributed to different patient inclusion criteria and different pharmacologic agents because resolution depended on an increase in plaque behind the stent (presumably peristent intimal hyperplasia) and not on negative vessel remodeling (smaller vessel area). The report from TAXUS-II did not include predictors of postprocedural ISA resolution. However, in the present report, the persistent ISA group had a greater frequency and a larger angle of superficial calcium. One previous study demonstrated that calcium influenced neointimal growth.15 In that study, the neointimal volume index was significantly

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lower on the calcified side than on the noncalcified side. These results support our findings that superficial calcification inhibits ISA resolution by inhibiting peristent neointimal hyperplasia. However, it is also possible that calcium inhibits inward vessel remodeling by limiting vascular responsiveness. In the present study, late-acquired ISA was observed in 8 cases (5.3%), similar to previous studies that reported a rate of 5.4% to 14.3% for late-acquired ISA after drug-eluting stenting.13,14,16 Acute ISAs associated with new, late ISA in the same stent had a totally different natural history, i.e., they grew as a result of an increase in external elastic membrane cross-sectional area (rather than shrinking as a result of an increase in peristent plaque/media cross-sectional area). As shown by Mintz et al17 and Hong et al18 in bare metal stents and Tanabe et al14 in paclitaxel-eluting stents, an increase in external elastic membrane cross-sectional area is the mechanism of new, late ISA. Thus, as suggested by the present study, positive remodeling not only caused new, late-acquired ISA but also affected the entire length of the lesion by enlarging the acute ISA area. Although aneurysms have been reported with drug-eluting stents, in our cohort only 1 patient with a new, late ISA manifested a coronary aneurysm. The number of ISA lesions was small. This is a consecutive but retrospective study. Follow-up analysis was limited by patients who returned to the catheter laboratory for follow-up angiography. The duration from procedure to follow-up angiography was 2.0 to 10.4 months. 1. Sousa JE, Costa MA, Sousa AG, Abizaid AC, Seixas AC, Abizaid AS, Feres F, Mattos LA, Falotico R, Jaeger J, et al. Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimuseluting stents in human coronary arteries. Circulation 2003;107:381– 383. 2. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, et al, on behalf of the RAVEL Study Group. Randomized study with the sirolimuscoated Bx Velocity balloon-expandable stent in the treatment of patients with de novo native coronary artery lesions. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773–1780. 3. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, et al, on behalf of SIRIUS Investigators. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315–1323. 4. Fujii K, Carlier SG, Mintz GS, Yang YM, Moussa I, Weisz G, Dangas G, Mehran R, Lansky AJ, Kreps EM, et al. Stent underexpansion and residual reference segment stenosis are related to stent thrombosis after sirolimus-eluting stent implantation. J Am Coll Cardiol 2005;45:995– 998. 5. Alfonso F, Suárez A, Angiolillo DJ, Sabate M, Escaned J, Moreno R, Hernandez R, Banuelos C, Macaya C. Findings of intravascular ultrasound during acute stent thrombosis. Heart 2004;90:1455–1459. 6. Singh H, Singh C, Aggarwal N, Dugal JS, Kumar A, Luthra M. Mycotic aneurysm of left anterior descending artery after sirolimuseluting stent implantation: a case report. Catheter Cardiovasc Interv 2005;65:282–285.

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Figure 5. In acute ISA lesions not associated with additional new, late-acquired ISAs (group 2, n ⫽ 55), ⌬effective lumen CSA correlated strongly with (A) ⌬peristent plaque/media CSA (p ⬍0.001, R2 ⫽ 0.783) but not with (B) ⌬external elastic membrane CSA (p ⫽ 0.50, R2 ⫽ 0.008); ⌬ISA CSA was also correlated with (C) ⌬peristent plaque/media CSA (p ⬍0.001, R2 ⫽ 0.73) but not with (D) ⌬external elastic membrane CSA (p ⫽ 0.68, R2 ⫽ 0.003). Abbreviations as in Figure 2 and 3. 7. Vik-Mo H, Wiseth R, Hegbom K. Coronary aneurysm after implantation of a paclitaxel-eluting stent. Scand Cardiovasc J 2004;38:349 – 352. 8. Stabile E, Escolar E, Weigold G, Weissman NJ, Satler LF, Pichard AD, Suddath WO, Kent KM, Waksman R. Marked ISA and aneurysm formation after sirolimus-eluting coronary stent implantation. Circulation 2004;110:e47– e48. 9. Uren NG, Schwarzacher SP, Metz JA, Lee DP, Honda Y, Yeung AC, Fitzgerald PJ, Yock PG, for the POST Registry Investigators. Predictors and outcomes of stent thrombosis. An intravascular ultrasound registry. Eur Heart J 2002;23:124 –132. 10. Shah VM, Mintz GS, Apple S, Weissman NJ. Background incidence of late ISA after bare-metal stent implantation. Circulation 2002;106: 1967–1971. 11. Balakrishnan B, Tzafriri AR, Seifert P, Groothuis A, Rogers C, Edelman ER. Strut position, blood flow, and drug deposition: implications for single and overlapping drug-eluting stents. Circulation 2005;111: 2958 –2965. 12. Serruys PW, Degertekin M, Tanabe K, Abizaid A, Sousa JE, Colombo A, Guagliumi G, Wijns W, Lindeboom WK, Ligthart J, et al, for the RAVEL Study Group. Intravascular ultrasound findings in the multicenter, randomized, double-blind RAVEL (RAndomized study with the sirolimus-eluting VElocity balloon-expandable stent in the treatment of patients with de novo native coronary artery Lesions) trial. Circulation 2002;106:798 – 803.

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