Impact of asymmetric stent expansion on neointimal hyperplasia following sirolimus-eluting stent implantation

To assess whether asymmetric stent expansion affects suppression of neointimal hyperplasia after sirolimus-eluting stent implantation, 64 patients in the SIRolImUS-coated Bx Velocity stent trial who underwent single 18-mm stent implantation and 3-dimensional intravascular ultrasonography at 8-month follow-up were enrolled. To assess the longitudinal stent asymmetric expansion, 2 cross sections with a maximal/minimal stent area were chosen in each patient. To assess for tomographic stent asymmetric expansion, stent eccentricity was determined by dividing the minimum stent diameter by the maximum stent diameter. At the 2 cross sections with a maximal/minimal stent area, a sirolimus-eluting stent reduced neointimal hyperplasia significantly with no interaction between the treatment and stent areas. A sirolimus-eluting stent also significantly reduced neointimal hyperplasia in the concentric and eccentric stent groups.     

Impact of intravascular ultrasound lesion characteristics on neointimal hyperplasia following sirolimus-eluting stent implantation

The effect of lesion characteristics on neointimal hyperplasia after sirolimus-eluting stent implantation was examined in 45 patients who underwent successful preinterventional intravascular ultrasound. There were no differences in neointimal hyperplasia between the moderate/severe calcified lesion group (calcium arc >120 degrees ) and the non/mild calcified lesion group or between the positive vessel remodeling group (external elastic membrane area at the minimal lumen area site larger than that at the proximal reference site) and negative vessel remodeling group. No correlation between preinterventional plaque burden and neointimal hyperplasia was found. In patients who have coronary artery disease, sirolimus-eluting stents continue to demonstrate striking suppression of neointimal proliferation, irrespective of lesion characteristics previously associated with greater restenotic risk.     

Influence of plaque calcium on neointimal hyperplasia following bare metal and drug-eluting stent implantation.

OBJECTIVES: To examine the influence of vessel wall calcium on neointimal hyperplasia (NIH) following bare metal stent (BMS) and drug-eluting stent (DES) implantation. BACKGROUND: While procedural complications with coronary stenting in calcified lesions are well reported, little is known about subsequent NIH on plaque calcium following either BMS or DES implantation. METHODS: In the Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial, 6 months follow-up volumetric intravascular ultrasound data were available for 41 lesions (BMS, 19; DES, 22). NIH thicknesses on superficial, deep, and noncalcified plaque were calculated at every 0.5 mm intervals over the stented segment. Calcified and less-calcified cross-sections were defined as those containing arcs of plaque calcium > or = 90 degrees and < 90 degrees , respectively. RESULTS: In BMS, mean NIH thickness on both superficial (0.24 +/- 0.23 mm) and deep calcium (0.25 +/- 0.21 mm) was significantly smaller than that of noncalcified plaque (0.31 +/- 0.22 mm) (P < 0.0005). NIH area was significantly smaller in calcified cross-sections compared to less-calcified cross-sections (2.1 +/- 1.2 mm2 vs. 3.1 +/- 1.9 mm2, P < 0.0001). While in contrast, in DES, mean NIH thickness was similar, irrespective of the presence or location of calcium (0.03 +/- 0.05 mm vs. 0.03 +/- 0.06 mm vs. 0.03 +/- 0.05 mm, superficial vs. deep vs. noncalcified plaque, P = NS). NIH area was also similar between calcified and less-calcified cross-sections (0.3 +/- 0.6 mm2 vs. 0.3 +/- 0.6 mm2, P = NS). CONCLUSIONS: These results suggest that while plaque calcium may influence NIH following BMS implantation, NIH suppression using DES does not appear to be affected by the presence or location of calcium.     

Distribution pattern of neointimal hyperplasia following sirolimus-eluting stent implantation assessed by 3-dimensional intravascular ultrasound

Sirolimus-eluting stents (SES) have been shown to reduce intimal hyperplasia (IH) within the stent. Although angiographic studies have suggested focal distribution of IH, these data are limited by its spatial resolution and the minimal amount of IH. Therefore, the exact distribution pattern of SES IH remains unclear. Ninety-six SIRIUS trial patients who underwent SES (51) or bare metal stent (45) implantation and three-dimensional IVUS at 8 months follow-up were enrolled. Neointimal area (stent-lumen area) was obtained at every 0.5-mm interval throughout the stented segment. The length of each stent with IVUS-detectable neointima was determined and divided by the stented length in each case to normalize the data. Even with IVUS, IH was detectable in very limited SES stented segments (median 8% of total stented length) compared to the diffuse nature of IH within BMS with only 5 stented lesions having segments free from IH. In 25% (13 of 51) of patients, no IH was detectable within whole SES stented segments. In conclusion, SES has reduced not only the total amount of IH, but also limited the distribution. These data suggest that local conditions (heterogeneity of biological responses of particular plaques, pharmacokinetics, or their combination) may play a role in IH following SES implantation.     

Overview of pharmacology and clinical trials program with the zotarolimus-eluting endeavor stent

Despite considerable benefits associated with current drug-eluting stents (DES), continued attention to the safety, efficacy, and deliverability of first-generation DES has led to the development of new antiproliferative agents with alternative stent platforms and different drug carrier systems. Zotarolimus is a recently developed pharmacologic agent with both antiproliferative and anti-inflammatory properties. The Endeavor drug-eluting stent (Medtronic Vascular, Santa Rosa, CA) represents the combination of zotarolimus, a low-profile cobalt alloy stent platform, and a biocompatible phosphorylcholine drug carrier system. At present, four clinical trials examining the safety and efficacy of the Endeavor stent have been performed. Although these studies have enrolled patients with similar clinical and angiographic characteristics, they have differed in trial design and study population size and have been performed across a broad geographic and physician distribution. Despite these differences, the results of these trials demonstrate consistently low rates of angiographic restenosis and repeat revascularization in addition to a favorable safety profile, with no occurrences of late stent thrombosis through 1 year of follow-up. This review describes the pharmacology and design on the Endeavor stent, summarizes results from recent clinical trials evaluating the Endeavor stent, and provides an overview of ongoing and future directions for clinical investigation.     

国产西罗莫司洗脱支架与紫杉醇洗脱支架抑制血管内膜增生的血管内超声比较研究

目的利用血管内超声（IVUS）方法比较国产西罗莫司洗脱支架（Firebird^TM）与紫杉醇洗脱支架（Taxus^TM）对冠心病患者新生内膜增生的抑制作用。方法自2003年5月至2007年6月,203例冠心病患者（283处病变）行药物洗脱支架术并在术后1年行冠状动脉造影和血管内超声（IVUS）检查。其中136例患者（185处病变）置入Firebird^TM支架（Firebird组）,67例患者（98处病变）置入TaxusTM支架（Taxus组）。结果203例患者（283处病变）中168例患者（236处病变）接受了一年随访造影和血管内超声检查,其中Firebird组108例患者（147处病变）,Taxus组60例患者（89处病变）。两组患者基础临床情况及造影特征相似。Firebird组支架内晚期管腔丢失（0.17±0.29mm比0.43±0.51mm,P〈0.0001）和节段内晚期管腔丢失（0.18±0.36mm比0.38±0.33mm,P=0.003）明显小于Taxus组,而两组近端参考血管晚期管腔丢失（0.11±0.27mm比0.15±0.32mm,P=0.321）和远端参考血管晚期管腔丢失（0.08±0.10mm比0.09±0.16mm,P=0.483）差异并无统计学意义。IVUS分析显示,两组间平均支架面积、平均管腔面积、最小支架面积、平均支架体积、平均管腔体积比较,差异均无统计学意义。但Firebird组平均内膜增生面积（0.35±0.58mm^2比1.29±1.26mm^2,P〈0.0001）、平均内膜增生面积百分数（5.45%±9.26%比17.38%±13.75%,P〈0.0001）、内膜增生最大面积百分数（9.41%±14.15%比31.56%±20.99%,P〈0.0001）、平均内膜增生容积（2.09±5.46mm^3比13.43±18.59mm^3,P〈0.0001）和平均内膜增生容积百分数（1.68%±5.84%比8.62%±9.90%,P〈0.0001）较Taxus组均明显减少。结论国产西罗莫司洗脱支架（Firebird^TM）置入术后再狭窄发生率较低,与TaxusTM支架相比,抑制内膜增生作用更显著。     

动静脉瘘所致的高剪切力减轻支架置入术导致的新生内膜增生

目的 研究动静脉瘘(AVF)所致的高剪切力(WSS)对动脉支架植入术后内膜增生(NIH)的影响.方法 将36 只雄性新西兰大白兔随机分为3 组,每组12 只.支架组:右颈总动脉(CCA)植入支架;支架+动静脉瘘(AVF)组:右CCA植入支架并行右颈AVF;对照组:未行处理.21天后,取支架段CCA标本用于组织学染色和蛋...     

Relation between vascular morphologic changes during stent implantation and the magnitude of in-stent neointimal hyperplasia

Intimal hyperplasia usually occurs after balloon overstretch injury or wire coil stimuli to coronary arteries. We examined whether the degree of vessel wall stretch during coronary stent placement could predict the amount of in-stent neointimal hyperplasia after a 6-month follow-up. Serial (preintervention, postballooning, poststent implantation, and a follow-up after 6 months) intravascular ultrasound (IVUS) was used to study 457 consecutive cross-sectional areas in 28 patients. IVUS imaging, using a motorized pullback system at 0.5 mm/s, allowed 1-mm axial increment measurements of the total vascular, stent, and lumen cross-sectional areas. The mean total vascular area changed from 10.89 +/- 2.50 mm2 before to 11.27 +/- 2.49 mm2 after ballooning, to 12.80 +/- 2.59 mm2 after stenting, and to 12.58 +/- 2.41 mm2 at follow-up (p < 0.0001). The mean lumen area changed from 3.36 +/- 1.95 mm2 before to 4.21 +/- 1.65 mm2 after ballooning, to 5.16 +/- 1.09 mm2 after stenting, and to 3.57 +/- 1.23 mm2 at follow-up (p < 0.0001). The mean stent area decreased from 5.25 +/- 1.17 mm2 after stenting to 5.09 +/- 0.90 mm2 at follow-up (p < 0.0001). Stepwise logistic regression analysis showed that delta total vascular area (after stent implantation - before intervention) was a strong predictor of the amount of intimal hyperplasia (r = 0.57, p < 0.0001). Vascular overstretch caused by the stenting procedure promotes intimal hyperplasia in proportion to the degree of sectional vascular stretch.     

Effects of gold coating of coronary stents on neointimal proliferation following stent implantation

Experimental studies suggest a reduced neointimal tissue proliferation in vascular stainless steel stents coated with gold. This prospective multicenter trial evaluated the impact of gold coating on neointimal tissue proliferation in patients undergoing elective stent implantation. The primary end point was the in-stent tissue proliferation measured by intravascular ultrasound at 6 months comparing stents of identical design with or without gold coating (Inflow). Two hundred four patients were randomized to receive uncoated (group A, n = 101) or coated (group B, n = 103) stents. Baseline parameters did not differ between the groups. Stent length and balloon size were comparable, whereas inflation pressure was slightly higher in group A (14 +/- 3 vs 13 +/- 3 atm, p = 0.013). Procedural success was similar (A, 97%; B, 96%). The acute angiographic result was better for group B (remaining stenosis 4 +/- 12% vs 10 +/- 11%, p = 0.002). Six-month examinations revealed more neointimal proliferation in group B. By ultrasound, the neointimal volume within the stent was 47 +/- 25 versus 41 +/- 23 mm(3) (p = 0.04), with a ratio of neointimal volume-to-stent volume of 0.45 +/- 0.12 versus 0.40 +/- 0.12 (p = 0.003). The angiographic minimal luminal diameter was smaller in group B (1.47 +/- 0.57 vs 1.69 +/- 0.70 mm, p = 0.04), with a higher late luminal loss of 1.17 +/- 0.51 versus 0.82 +/- 0.56 mm (p = 0.001). Thus, gold coating of the tested stent type resulted in more neointimal tissue proliferation.     

Strain differences in neointimal hyperplasia in the rat.

We performed an initial screen of 11 rat strains by use of a standard balloon injury to the left iliac artery to observe whether genetically determined differences existed in the development of neointimal hyperplasia. Neointimal hyperplasia was assayed 8 weeks after the vascular injury on coded microscopic sections. Statistically significant differences in the percentages of the vascular wall cross-sectional areas composed of intima (percentage intima) secondary to neointimal hyperplasia were noted among the different rat strains (P<0.02), with the Brown-Norway (BN), Dark Agouti, and Milan normotensive strain rats having the highest and the spontaneously hypertensive rats (SHR) having the lowest percentages of intima. In a separate experiment, F1 hybrids of SHRxBN strains and parental BN and SHR underwent the vascular injury, and the parental strains again showed a statistically significant difference from one another in the mean percentage of intima (P<0. 0001). The F1 hybrids showed an average percentage of intima intermediate between those of the parental strains. The average lumen size of the injured BN vessels were significantly smaller than that of the noninjured control vessels (P=0.044), but this significance disappeared when the circular areas of these vessels were calculated without taking neointimal growth into consideration (P=0.649). These results provide the groundwork for a genetic linkage analysis to identify the genes that influence the development of neointimal hyperplasia after vascular injury.