Serial intravascular ultrasound comparison of the extent and distribution of intimal hyperplasia six months after stent implantation for de novo versus in-stent restenosis lesions

The aim of this study was to compare intimal hyperplasia (IH) growth at 6 months in patients with de novo lesions treated with stents versus IH regrowth in patients with treated in-stent restenosis. Intravascular ultrasound was performed after intervention and at the 6-month follow-up visit as part of a standardized protocol across several clinical trials. At 6 months, the lumen was larger in the de novo group (mean lumen cross-sectional area [CSA] 6.31 +/- 2.2 vs 4.48 +/- 1.9 mm(2), p = 0.0001; minimum lumen CSA 4.2 +/- 1.8 vs 2.59 +/- 1.5 mm(2), p = 0.0001). However, the total increase in the mean IH CSA volume was the similar in the de novo and ISR groups (2.89 +/- 1.6 vs 2.64 +/- 1.94 mm(2), respectively; p = 0.11). We found that IH regrowth in restented in-stent restenosis lesions was similar to that in de novo stent implantation and that the final lumen CSA was an important component of in-stent restenosis recurrence.     

Thiazolidinedione treatment attenuates diffuse neointimal hyperplasia in restenotic lesions after coronary stent implantation in type 2 diabetic patients: an intravascular ultrasound study

OBJECTIVES: Thiazolidinedione treatment reduces neointimal tissue proliferation after coronary stent implantation in diabetic patients. However, in-stent restenosis still persists in patients treated with thiazolidinedione. The effect of thiazolidinedione treatment on the pattern of in-stent restenosis remains unclear. This study investigated whether thiazolidinedione treatment attenuates diffuse neointimal hyperplasia in restenotic lesions after coronary stent implantation in diabetic patients. METHODS: Volumetric intravascular ultrasound was performed at 6 months after coronary stent implantation in 76 patients with restenotic lesions who received either conventional anti-diabetic treatment (control group, n = 56) or thiazolidinedione treatment (thiazolidinedione group, n = 20). RESULTS: There were no significant differences between the two groups in stent volume (99 +/- 32 vs 90 +/- 20 mm3, respectively, p = 0.26) or in minimal lumen area in the stent (1.4 +/- 0.6 vs 1.6 +/- 0.5 mm2, respectively, p = 0.11). However, there were significant reductions in neointimal volume (56 +/- 25 vs 36 +/- 11 mm3, respectively, p < 0.01)and neointimal index (56 +/- 11% vs 41 +/- 8%, respectively, p < 0.01) in the thiazolidinedione group. Coefficient of variation of neointimal tissue accumulation was greater in the thiazolidinedione group (45.5%) than in the control group (25.2%). CONCLUSIONS: Intravascular ultrasound study demonstrated that together with reduction of overall neointimal tissue proliferation, thiazolidinedione treatment caused greater point-to-point heterogeneity in the neointimal tissue accumulation in restenotic lesions after coronary stent implantation. This finding strongly suggests that thiazolidinedione treatment attenuates diffuse in-stent restenosis in diabetic patients.     

Two-year follow-up intravascular ultrasound analysis after bare metal stent implantation in 120 lesions.

The objective of this study was to examine long-term changes after bare metal stent implantation in a relatively large number of patients. There are few reports of intravascular ultrasound (IVUS) studies performed on stented and nonstented (reference) segments beyond 6 months after bare metal stenting. Using IVUS, we evaluated serial changes in stented and reference segments between 6 and 24 months after stent implantation in 110 patients with 120 lesions. Serial IVUS images were acquired at five equidistant intrastent sites and at two different reference segment sites. Measurements were made of the external elastic membrane (EEM), stent, lumen, and intimal hyperplasia (IH = stent - lumen) area. For the whole patient group, between 6 and 24 months, the mean IH area in stented segments decreased from 2.6 +/- 1.0 to 2.3 36+/- 0.9 mm2 (P < 0.001), and the mean lumen area increased from 6.2 +/- 2.0 to 6.5 +/- 1.9 mm2 (P < 0.001). The mean IH area decreased in 91 lesions (76%) and increased in 29 lesions (24%) between 6 and 24 months. There were no significant changes in EEM or lumen area in the reference segments. Late angiographic restenosis (diameter stenosis > or = 50%) occurred in three lesions between 6 and 24 months. A late target lesion revascularization was performed for one lesion. In the period of time between 6 and 24 months after stenting, IH regression occurred in most (76%) stent lesions, resulting in late lumen increase. However, IH progression was observed in 24% of in-stent lesions. No significant changes of EEM or lumen area occurred in the reference segments.     

Intravascular ultrasound assessment of expansion of the sirolimus-eluting (cypher select) and paclitaxel-eluting (Taxus Express-2) stent in patients with diabetes mellitus

Patients with diabetes have a higher risk for in-stent restenosis after coronary stent implantation. Drug-eluting stents (DES) are highly effective in reducing in-stent restenosis. Once neointimal hyperplasia is suppressed with DES, the impact of stent underexpansion becomes magnified. The aim of this study was to evaluate DES expansion in patients with diabetes. Ninety-five patients with diabetes were randomized to Cypher Select (n = 48) or Taxus Express-2 (n = 47) stent implantation. Intravascular ultrasound was performed after stent implantation. Stent expansion was defined as the ratio of measured to predicted minimum stent diameter. There was a trend for lower stent expansion in the Cypher Select stent group (0.74 +/- 0.08 vs 0.78 +/- 0.11 in the Taxus Express-2 stent group, p = 0.061). Cypher Select stents achieved a final minimal stent cross-sectional area of 5.5 +/- 1. 8 mm2, compared with 6.4 +/- 1.9 mm2 for Taxus Express-2 stents (p = 0.015). For stents with nominal diameters > or =2.75 mm (Cypher Select n = 40, Taxus Express-2 n = 38), 42.5% of the Cypher Select stents and 10.5% of the Taxus Express-2 stents did not achieve a final minimum stent area of 5 mm2 (p = 0.002). Insulin treatment (relative risk 0.31, 95% confidence interval 0.10 to 0.95, p = 0.041) and stent type (relative risk 0.15, 95% CI 0.04 to 0.53, p = 0.003) were independent predictors of not achieving a minimum stent area >5.0 mm2. In conclusion, an important percentage of DES in patients with diabetes fail to achieve the manufacturers' predicted final minimal stent diameter. Cypher Select stent and insulin treatment were independent predictors of not achieving a minimum stent area >5.0 mm2.     

Usefulness of minimum stent cross sectional area as a predictor of angiographic restenosis after primary percutaneous coronary intervention in acute myocardial infarction (from the HORIZONS-AMI Trial IVUS substudy)

HORIZONS-AMI was a prospective dual-arm randomized trial of different antithrombotic regimens and stent types in patients with ST-segment elevation myocardial infarction. A formal intravascular ultrasound (IVUS) substudy enrolled 464 patients with baseline and 13-month follow-up at 36 centers. Of them, 318 patients with 355 lesions were evaluated for this study. Angiographic restenosis occurred in 45 of 355 lesions (12.7%). Bare-metal stent use (45.5% vs 21.2%, p <0.001) and diabetes mellitus (29.5% vs 10.9%, p <0.001) were more prevalent in patients with versus without restenosis. Postprocedure IVUS minimum lumen area (5.6 mm(2), 5.0 to 6.1, vs 6.7 mm(2), 6.5 to 6.9, p <0.001), minimum stent area (5.7 mm(2), 5.1 to 6.3, vs 6.9 mm(2), 6.6 to 7.1, p <0.001), and reference average lumen area (7.7 mm(2), 6.8 to 8.6, vs 9.7 mm(2), 9.3 to 10.1, p <0.001) were smaller in restenotic versus nonrestenotic lesions. By multivariable analysis, minimum stent area was an independent predictor of angiographic restenosis (odds ratio 0.75, 95% confidence interval 0.61 to 0.93, p = 0.009) in addition to diabetes, bare-metal stent use, and longer stent length. Attenuated plaque behind the stent struts had a trend to predict less binary restenosis (p = 0.07). In conclusion, a smaller IVUS minimum stent area was an independent predictor of angiographic restenosis after primary percutaneous intervention in patients with ST-segment elevation myocardial infarction, similar to patients with stable coronary artery disease.     

Intravascular ultrasound parameters associated with stent thrombosis after drug-eluting stent deployment

Drug-eluting stent (DES) thrombosis (ST) can be devastating. The study aim was to evaluate intravascular ultrasound (IVUS) predictors for DES thrombosis by comparing IVUS studies after implantation in 13 patients with 14 DES thrombosis lesions with a group of controls (30 lesions in 27 patients) matched for history of chronic renal failure and type of DES. Five patients (38%) discontinued dual antiplatelet therapy at the time of ST. There were 3 in-stent restenosis lesions (21%) treated using DESs in the ST group compared with 0 in the control group (p <0.05). Compared with the control group, IVUS studies in the ST group showed a smaller minimum stent area (4.6 +/- 1.1 vs 5.6 +/- 1.7 mm(2), p = 0.0489). In the ST group, 11 of 14 stents had a minimum stent area < or =5.0 mm(2) compared with 12 of 30 in the control group (p = 0.0392). Minimum stent area in patients who stopped clopidogrel therapy and developed ST (5.30 +/- 1.15 mm(2)) tended to be larger compared with that in patients who developed ST while using clopidogrel (4.24 +/- 0.96 mm(2), p = 0.091). Within the 5-mm-long proximal and distal reference segments analyzed, the ST group had larger proximal reference maximum plaque burdens and smaller minimum lumen areas, along with a tendency toward similar findings in the distal reference segments. In conclusion, IVUS findings at the time of DES implantation in patients who subsequently developed ST showed a smaller minimum stent area (especially in patients who developed ST while using clopidogrel) and more residual disease at the stent edges.     

Factors predictive of cardiac events and restenosis after sirolimus-eluting stent implantation in small coronary arteries.

OBJECTIVES: Predictors of cardiac events and restenosis after sirolimus-eluting stent (SES) implantation in small coronary arteries were evaluated. BACKGROUND: Although SES implantation has markedly reduced the risk of restenosis, small vessel disease remains a major cause of SES failure. METHODS: We prospectively investigated the factors predictive of cardiac events and restenosis in 1,092 consecutive patients who received SES implantation for 1,269 lesions in small coronary arteries (< or = 2.8 mm). Follow-up angiography at 6 months was performed in 751 patients with 889 lesions (follow-up rate 70.3%). RESULTS: Restenosis (diameter stenosis > or = 50%) was angiographically documented in 65 patients with 77 lesions (8.7%): 55 focal (71.4%), 8 diffuse (10.4%), 2 diffuse proliferative (2.6%), and 12 total (15.6%). Lesion length, stent length, reference artery size, and in-stent restenotic lesions were univariate predictors of restenosis. By multivariate analysis, lesion length (OR 1.04; 95% CI 1.02-1.05; P < 0.001) and in-stent restenotic lesions (OR 3.38; 95% CI 1.80-6.35; P < 0.001) were significant independent predictors of restenosis. During follow-up (23.2 +/- 7.9 months), there were 17 deaths (5 cardiac and 12 noncardiac), 5 nonfatal Q-wave myocardial infarctions, and 42 target lesion revascularizations. The cumulative probability of survival without major adverse cardiac events (MACE) was (96.6 +/- 0.6)% at 1 year and (95.1 +/- 0.7)% at 2 years. In multivariate analysis, lesion length (HR 1.04; 95% CI 1.01-1.07; P = 0.004) and in-stent restenotic lesions (HR 3.29; 95% CI 1.58-6.86; P = 0.001) were independently related to MACE. CONCLUSIONS: SES implantation in small coronary arteries is safe and effective, with lesion length having a major impact on restenosis and MACE.     

Intravascular ultrasound assessment of lesions with target vessel failure after sirolimus-eluting stent implantation

Intravascular ultrasound (IVUS) evaluation was performed in 33 lesions with sirolimus-eluting stent (SES) failure: 4 thromboses, 26 in-stent restenoses (including 6 edge stenoses), 4 new stenoses >5 mm proximal to the stent, and 1 patient with no evidence of the implanted SES (presumably because of embolization). A minimum stent area <5.0 mm(2) (stent underexpansion) was observed in 67% of all SES failures (in particular, 67% of intrastent restenosis); negative remodeling was observed in 4 of 6 stent edge restenoses, and new lesions were secondary to an increase in plaque area.     

Outcome of percutaneous hybrid coronary revascularization: bare metal stents jeopardize the benefit of sirolimus-eluting stents in the real world

BACKGROUND: In an effort to contain procedural costs while limiting the risk of in-stent restenosis, hybrid percutaneous revascularization (ie, stenting with at least one sirolimus-eluting stent [SES] and at least one bare metal stent [BMS] in the same patient) is felt to be a cost-effective alternative to exclusive SES use. OBJECTIVE: To describe the outcome of hybrid percutaneous revascularization for the treatment of patients with multiple coronary artery lesions. METHODS AND RESULTS: Fifty-six patients (42 men; mean age [+/- SEM] 64+/-2) underwent hybrid stenting (average of 1.2 SES/patient and 1.3 BMS/patient). SES were used to treat lesions at higher restenotic potential, including longer lesions, smaller target vessels and bifurcation lesions (mean stent length [+/- SEM] was 21.1+/-1.2 mm for SES and 16.0+/-0.6 mm for BMS; stent diameter mean [+/- SEM] was 2.9+/-0.0 mm for SES and 3.1+/-0.1 mm for BMS; bifurcation lesions were 43% for SES and 7% for BMS; all P<0.01). At nine months of clinical follow-up, no death or myocardial infarction was reported. Twenty-one patients underwent clinically driven repeat coronary angiography at a mean (+/- SEM) of 8+/-1 of months (range two to 12 months) follow-up. Target lesion revascularization procedures were recorded in six patients (11%) for nine lesions (6%). Of these lesions, seven were categorized after blinded analysis as due to in-BMS restenosis and two to in-SES restenosis (P=0.01); three patients (5.4%) underwent reangioplasty for de novo lesions. There was one case of acute in-SES thrombosis. SES showed significantly less neointimal hyperplasia (late lumen loss was 0.4+/-0.1 mm for SES and 1.3+/-0.1 mm for BMS; loss index was 0.15+/-0.05 for SES and 0.48+/-0.05 for BMS; all P<0.001). CONCLUSIONS: The use of SES resulted in less neointimal hyperplasia even when used to treat lesions at higher risk for restenosis based on angiographic characteristics. BMS implantation significantly limits this beneficial effect, compromising the outcome of hybrid percutaneous coronary revascularization.     

Restenosis and stent fracture following sirolimus-eluting stent (SES) implantation.

BACKGROUND: Restenosis still occurs, even with the sirolimus-eluting stent (SES), and the precise mechanisms and the impact of stent fracture on restensosis have not yet been elucidated. METHODS AND RESULTS: Intravascular ultrasound (IVUS)-guided SES implantation was performed in 184 lesions in 151 patients with stable and unstable angina. Serial (pre-, post- and follow-up) quantitative coronary angiography analysis was obtained in 169 lesions in 138 patients (angiographic follow-up rate: 91%) and 12-month clinical follow-up was done in all patients. Restenosis occurred in 13 (7.7%) of 169 lesions. Stent fracture occurred in 4 (2.4%) of 169 lesions at follow-up. Of the 13 restenotic lesions, 8 had intimal hyperplasia, 4 had stent fracture, and 1 had late stent thrombosis at 7 months. Although multivariate logistic regression analysis revealed that minimal lumen area (min-LA) post (p=0.027), total stent length (p=0.003) and diabetes (p=0.032) were significant independent predictors of restenosis, univariate analysis showed that stent fracture was more common in the restenosis than in the non-restenosis groups (p=0.001). CONCLUSIONS: Although min-LA post by IVUS, total stent length by QCA and diabetes are independent predictors for angiographic restenosis, stent fracture occurred in 4 lesions (2.4%) and all of them resulted in restenosis (31% of the restenosis). The impact of stent fracture and its potential role in the development of restenosis deserves further study.     

Comparison of vessel response following sirolimus-eluting stent implantation as assessed by serial 3-D intravascular ultrasound study

Recent sirolimus-eluting stent (SES) studies have suggested higher rates of restenosis in non-left anterior descending (LAD) artery lesions. The aim of this study was to evaluate differential vessel response (LAD versus non-LAD) to SES implantation using serial intravascular ultrasound (IVUS). A total of 94 patients who underwent SES implantation and serial (post-PCI and 8 months) 3-dimensional IVUS were enrolled from our database. Volumetric analysis was performed throughout the stent as well as the adjacent reference segment (up to 5 mm). Volume index (volume/length) was calculated for vessel (VVI), lumen (LVI), and plaque (PVI). Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). With respect to the in-stent segment, VVI, PVI, and LVI at post-PCI were not significantly different between the LAD (n = 41) and non-LAD (n = 53) lesions. At follow up, however, maximum CSN was significantly greater in the non-LAD lesions (18.3 +/- 15.2% versus 12.2 +/- 10.0%; p = 0.029). At the proximal reference segment, the non-LAD lesions showed a significantly greater LVI decrease than the LAD lesions (p <0.05), primarily due to mild vessel shrinkage observed in the non-LAD lesions. There were no significant differences at the distal reference segment between the LAD and non-LAD lesions. This detailed IVUS analysis suggests that there are minimal differences in the vessel responses following SES implantation. These findings may have potential implications for mechanical and pharmacokinetic properties of next-generation drug-eluting stent technology.     

The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS)

OBJECTIVES: We assessed the safety and effectiveness of the sirolimus-eluting stent (SES) in treating single de novo long lesions in small native coronary arteries compared to an identical bare metal stent (BMS). BACKGROUND: The SES was previously demonstrated to reduce restenosis significantly. However, patients with long lesions in small vessels have not been well studied and may define a group at very high risk. METHODS: The Canadian Study of the Sirolimus-Eluting Stent in the Treatment of Patients With Long De Novo Lesions in Small Native Coronary Arteries (C-SIRIUS) was a multicenter, randomized, double-blind trial comparing SES versus identical BMS. The primary end point was in-stent minimal lumen diameter (MLD) at eight months. Secondary end points included angiographic restenosis at 8 months, target lesion revascularization (TLR), and major adverse cardiac events (MACE) at 270 days. RESULTS: A total of 100 patients were enrolled at eight Canadian sites. The in-stent MLD at eight months was 2.46 +/- 0.37 mm in the SES compared with 1.49 +/- 0.75 mm in the BMS (a 65% increase, p < 0.001). Angiographic restenosis occurred in 1 of 44 SES patients (2.3%, with no in-stent restenosis) and in 23 of 44 BMS patients (52.3%, p < 0.001). At 270 days, there were two clinically driven TLRs in the SES (4%) and nine in the BMS (18%, p = 0.05). The Kaplan-Meier estimate of freedom from MACE at 270 days was 96.0% for SES patients and 81.7% for BMS patients (p = 0.029). CONCLUSIONS: Patients with long lesions in small vessels are at very high risk of restenosis. In these patients, the SES dramatically reduces the risk of restenosis at eight months, translating into an excellent clinical outcome at nine months.     

Mechanism of cutting balloon angioplasty for in-stent restenosis: an intravascular ultrasound study.

We investigated by intravascular ultrasound (IVUS) the mechanism of action of cutting balloon (CB) angioplasty in patients with in-stent restenosis. Seventy-one consecutive restenotic lesions of 66 patients were studied by quantitative coronary angiography (QCA) and IVUS before, immediately after, and, in 20 cases, at 24-hr time interval after CB. CB was selected according to 1:1 CB-to-stent ratio and inflated at 8 atm for 60-90 sec. Both IVUS planar and volumetric (Simpson's rule, 25 patients) analysis were carried out. IVUS measurements included external elastic membrane area (EEMA), stent area (SA), minimal lumen area (MLA), and restenosis area (RA). Following CB, QCA analysis showed increase of minimal lumen diameter (1.17 +/- 0.46 vs. 2.45 +/- 0.51 mm; P < 0.0001) and decrease of diameter stenosis (64% +/- 13% vs. 21% +/- 9%; P < 0.0001). IVUS measurements showed a significant increase of MLA (2.18 +/- 0.80 vs. 7.31 +/- 1.8 mm(2); P < 0.0001), SA (9.62 +/- 2.6 vs. 10.7 +/- 2.75 mm(2); P < 0.0001), and EEMA (17.27 +/- 5 vs. 18.1 +/- 5 mm(2); P < 0.0001) and a decrease of RA (7.43 +/- 2.63 vs. 3.45 +/- 1.39 mm(2); P < 0.0001). No significant change was observed in the original plaque + media area (7.65 +/- 3 vs. 7.38 +/- 2.9 mm(2); P = NS). Thus, of the total lumen enlargement (5.13 +/- 1.85 mm(2)), 23% was the result of increase in mean SA, whereas 77% was the result of a decrease in mean RA. These changes were associated with a 5% increase in EEMA. IVUS volumetric changes paralleled planar variations. Angiographic and IVUS changes were well maintained at 24 hr. CB enlarges coronary lumen mainly by in-stent tissue reduction associated with a moderate degree of additional stent expansion. Favorable QCA and IVUS acute results are maintained at 24 hr.     

Frequency and characteristics of incomplete stent apposition during and after sirolimus-eluting stent implantation

OBJECTIVES: Incomplete stent apposition (ISA) is frequently observed after sirolimus-eluting stent (SES) implantation. This study investigated the incidence, morphological features, and possible mechanisms of this phenomenon. METHODS: Fifty-two lesions in 47 eligible patients were treated with SES and serial intravascular ultrasound (IVUS) assessment at the time of post-intervention and 8-month follow-up. ISA was carefully identified from the IVUS images of these lesions. Specifically, quantitative two dimensional IVUS analysis was performed if the lesions demonstrated ISA, including routine IVUS parameters as well as other measurements related to ISA. RESULTS: Overall, ISA was observed in 13 lesions (25.0%) at follow-up. Persistent ISA (n = 6, 11.5%), defined as ISA consistently observed both at post-intervention and follow-up, and late-acquired ISA (n = 7, 13.5%)were systematically compared. Eighty-three percent of cases of persistent ISA were located around the stent edges, whereas all cases of late-acquired ISA were in the stent body. In the persistent ISA group, no serial changes were observed in the lumen area or external elastic membrane area (EEMA) from post-intervention to follow-up. However, in the late-acquired ISA group, EEMA and lumen area significantly increased from post-intervention to follow-up (EEMA: 13.4 +/- 3.2 vs 17.6 +/- 3.3 mm2, respectively, p < 0.0001 ; lumen area: 6.7 +/- 1.4 vs 9.2 +/- 1.8 mm2, respectively, p = 0.004). No adverse clinical events were observed in either group. CONCLUSIONS: ISA was frequently observed during and after SES implantation in clinical practice. No clinical disadvantages were observed during 16 month clinical follow-up periods. Positive remodeling may potentially cause late-acquired ISA.     

Comparison of paclitaxel-eluting stent and sirolimus-eluting stent expansion at incremental delivery pressures

OBJECTIVES: We sought to compare the adequacy of paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) expansion based on intravascular ultrasound (IVUS) imaging criteria at conventional delivery pressures. METHODS: Forty-six patients underwent SES implantation and 42 patients underwent PES implantation for de novo native coronary lesions<33 mm in length with reference lumen diameters of 2.5-3.5 mm. Stents were serially expanded with gradual balloon inflations at 14 and 20 atm. IVUS imaging was performed prior to intervention and after each balloon inflation. Stent expansion (minimal stent cross-sectional area/reference lumen cross-sectional area) was measured. Inadequate stent expansion was defined using the MUSIC criteria (all struts apposed, no tissue protrusion, and final lumen cross-sectional area>80% of the reference or >90% if minimal lumen cross-sectional area was <9 mm2). RESULTS: The baseline characteristics of the two groups were similar except for shorter lesion length, larger mean lumen cross-sectional area, larger lumen diameter, and lower plaque burden in the PES group. Stent expansion was inadequate in 80% of patients with SES versus 63% of patients with PES at 14 atm, although this was not statistically significant. After 20 atm, 48% of patients with SES remained underexpanded as compared with 35% of patients with PES. CONCLUSION: Drug-eluting stents showed significant underexpansion by MUSIC criteria at conventionally used inflation pressures. Higher balloon inflations are required especially during deployment of a SES. IVUS guidance is recommended to ensure optimal results and outcomes with both stents.     

Sirolimus- and paclitaxel-eluting stents in comparison with balloon angioplasty for treatment of in-stent restenosis.

This study evaluated the acute and follow-up effectiveness of sirolimus-eluting stents (SESs) and nonpolymer-based paclitaxel-eluting stents (PESs) in comparison will balloon angioplasty for treatment of complex in-stent restenosis (ISR) lesions. Drug-eluting stents have been demonstrated to be highly effective for treatment of de novo lesions. The use of drug-eluting stents for treatment of complex ISR is less well defined. Eighty one lesions with in-stent restenosis (lesion length < 30 mm in a native coronary artery) were treated with either PTCA alone (n = 26 lesions in 25 patients), PES (n = 27 lesions in 24 patients; Achieve, Cook; 3,1 mug paclitaxel/mm(2) nonpolymer-based coating), SES (n = 28 lesions in 28 patients; Cypher, Cordis; 140 mug sirolimus/cm(2) metal surface area). Nine-month MACE rates were 32%, 8%, and 14% (all due to repeated revascularization procedures, except one death in the SES group) in the PTCA, PES, and SES group, respectively. Postintervention minimal lumen diameter in stent was significantly greater in the SES and the PES group in comparison with the PTCA group (2.37 +/- 0.26, 2.54 +/- 0.42, 1.78 +/- 0.23 mm; P < 0.001). At 6-month angiographic follow-up, late loss in stent was 0.77 +/- 0.45, 0.43 +/- 0.53, and 0.29 +/- 0.52 mm for the PTCA, PES, and SES group, respectively (P = 0.005). In-lesion restenosis rate was 61% for the PTCA group, 20% for the PES group, and 13% for the SES group (P = 0.042). The implantation of SES as well as nonpolymer PES proved to be effective for treatment of ISR. The combination of improved acute gain and reduced late loss results in a significantly improved angiographic follow-up result in comparison with PTCA.     

Mechanisms and predictors of carotid artery stent restenosis: a serial intravascular ultrasound study.

OBJECTIVES: The aim of this study was to determine the mechanisms and predictors of carotid artery restenosis after carotid artery stenting (CAS) using serial intravascular ultrasound (IVUS) imaging. BACKGROUND: Carotid artery stenting is increasingly used to treat high-grade obstructive carotid disease, but our knowledge of carotid in-stent restenosis and remodeling remains limited. METHODS: Post-procedural and 6-month (median 6 months) follow-up quantitative carotid angiography and IVUS were performed after self-expanding stent deployment in 50 internal carotid arteries (ICA). The IVUS measurements at multiple designated sites included minimal luminal diameter, lumen area, stent area (SA), and neointimal hyperplasia area (NIH). RESULTS: Late stent enlargement at follow-up was found at all segments, and the percentage increase was greatest at the ICA lesion site (mean +/- SD, 48.9 +/- 35.3%). The NIH, expressed as a percentage of SA, was seen within all segments of the stent and was greatest at the ICA lesion site (37.3 +/- 23.3%). There was a strong positive correlation between the amount of NIH and late stent enlargement (r = 0.64; p < 0.001). Immediate post-procedural minimum ICA SA (r = -0.37; p < 0.01) and stent expansion (r = -0.44; p = 0.001) correlated negatively with the percentage restenotic area at follow-up. CONCLUSIONS: Although self-expanding carotid stents generate considerable neointimal hyperplasia, the process is balanced by marked late stent enlargement. Small stent dimensions immediately post-procedure were associated with a higher risk of restenosis.     

Late intravascular ultrasound findings of patients treated with brachytherapy for diffuse in-stent restenosis.

This study aimed at evaluating long-term (24-month) effects of beta-irradiation (188Re-MAG3-filled balloon) using intravascular ultrasound (IVUS) in patients with in-stent restenosis (ISR). Long-term effects of beta-irradiation on intimal hyperplasia (IH) within the stented segment and vessel and lumen dimensions of nonstented adjacent segments in patients with ISR have not been sufficiently evaluated. Two-year follow-up IVUS was performed in 30 patients with patent ISR segments at 6-month follow-up angiography. Serial IVUS images were acquired at five equidistant intrastent sites and at three different reference segment sites. IH burden (%) was defined as 100 x (IH/stent area). Mean intrastent IH area and IH burden significantly increased between 6 and 24 months, from 2.1 +/- 1.1 to 2.6 +/- 1.4 mm2 (P < 0.001) and from 26% +/- 10% to 33% +/- 14% (P < 0.001), respectively. There was a significant decrease of mean external elastic membrane (from 10.1 +/- 3.9 to 9.7 +/- 3.9 mm2; P = 0.015) and lumen area (from 5.6 +/- 2.3 to 5.1 +/- 2.3 mm2; P = 0.021) within distal reference segments between 6 and 24 months. Target lesion revascularization (TLR) was performed in six patients (20%) between 6 and 24 months after beta-irradiation therapy. There were no significant differences between TLR and non-TLR groups except for a smaller minimum lumen area at 24 months in the TLR group. Because of a small amount of late loss between 6 and 24 months, most irradiated ISR vessel segments remained stable for up to 2 years. However, quantitative evidence of late catch-up was evident in most patients and was significantly associated with 24-month TLR in some patients.     

Efficacy and feasibility of helixcision for debulking neointimal hyperplasia for in-stent restenosis.

The Helixcision system is a novel 6 Fr-compatible catheter designed to debulk tissue for in-stent restenosis lesions. The purpose of this study was to determine the efficacy and feasibility of this new system for removing neointimal hyperplasia. A total of 32 in-stent restenosis lesions in 32 patients were treated with helixcision followed by balloon angioplasty. Debulking efficacy was assessed with serial baseline intravascular ultrasound (IVUS) in a subset of 18 lesions. To investigate longitudinal efficacy, 3D analysis was also performed in 12 lesions with automated pullback to calculate average cross-sectional areas across the stent. Prior to procedure, the angiographic reference diameter was 2.60 +/- 0.46 mm. Immediately after procedure, minimum lumen diameter improved from 0.84 +/- 0.33 to 2.19 +/- 0.41 mm (P < 0.0001). IVUS showed a significant reduction of intimal area (IA) after helixcision (from 4.95 +/- 2.04 to 2.88 +/- 1.48 mm(2); P < 0.001). Adjunctive balloon angioplasty further improved lumen area (LA) mainly by stent expansion rather than IA reduction at the site of minimum lumen area. The degrees of IA reduction and LA improvement were closely similar in volumetric analysis. Thirty-day and 6-month clinical follow-up were available in 97% (n = 31) and 72% (n = 23) of the enrolled patients, respectively. At 30-day follow-up, no major adverse cardiac event was reported except for periprocedural CK elevation in two patients (6%). Target legion revascularization within 6 months was performed in six patients (26%). Preliminary results of helixcision indicate that this system is safe and feasible for the treatment of in-stent restenosis. The concordant results between 2D and 3D IVUS analyses suggest that this unique technology can achieve uniform longitudinal debulking throughout the stent. The long-term outcomes appeared to be favorable, considering the relatively diffuse lesion morphology.     

Procedural results and distal embolization after saphenous vein graft stenting and angioplasty for in-stent restenosis of grafts

Saphenous vein graft (SVG) angioplasty is associated with frequent periprocedural complications due to distal embolization and a high risk of restenosis. The purpose of this single-center, retrospective study was to determine the distal embolization incidences and outcomes of stenting for SVG lesions and percutaneous angioplasty for in-stent restenosis of these SVGs. We studied 48 consecutive patients (mean age, 62 +/- 7 years, 92% men) who had prior CABG and underwent stent deployment to SVG lesions detected at our institution over a period of 4 years. Mean lesion length was 12.4 +/- 3.2 mm. The minimal lumen diameter increased from 0.7 +/- 0.3 mm to 3.2 +/- 0.4 mm after stenting. Distal embolization as no reflow/slow flow phenomenon occurred in 5 (10%) patients. Angiographic success was achieved in 98% of the patients. Procedural success was achieved in 96% of the patients. No reflow/slow flow phenomenon was observed, particularly in patients with acute coronary syndrome. During the follow-up, 11 patients (23%) had angiographic evidence of restenosis. Lesions were treated with balloon angioplasty and the minimal lumen diameter increased from 2.6 +/- 1.1 mm to 3.1 +/- 0.3 mm. The angiographic and procedural success rates were both 100%. There were no cases of "no" reflow/slow flow. Restenosis was particularly frequent in patients with diabetes mellitus, hypercholesterolemia, and acute coronary syndrome. Stent implantation in patients with de novo SVG lesions can be achieved with a high rate of angiographic and procedural success. The distal embolization risk is lower during angioplasty of in-stent restenosis lesions of SVGs compared to de novo SVG lesions.