Impact of preinterventional arterial remodeling on in-stent neointimal hyperplasia and in-stent restenosis after coronary stent implantation.

BACKGROUND: Patterns of arterial remodeling during the course of plaque development have been shown to play an important role in both the progression of de novo atherosclerosis and in the restenotic process following coronary intervention. The aim of the present prospective study was to evaluate the effect of pre-interventional arterial remodeling on in-stent neointimal hyperplasia (NIH) and in-stent restenosis (ISR) after stenting. METHODS AND RESULTS: Pre-interventional arterial remodeling was assessed in 85 native coronary lesions by using intravascular ultrasound (IVUS). The remodeling index (RI) was 1.09+/-0.20 in the positive remodeling (PR)/intermediate remodeling (IR) group and 0.84+/-0.12 in the negative remodeling (NR) group. The plaque plus media cross sectional area (P&M CSA) at pre-intervention and NIH CSA at follow-up in the minimal lumen CSA were significantly larger in the PR/IR group (9.2+/-2.9 mm2 vs 6.2+/-1.8 mm2, 3.3+/-1.2 mm2 vs 1.5+/-0.9 mm2; p = 0.001, p = 0.001, respectively). On 3-dimensional analysis of IVUS images at follow-up, the lumen volume was significantly smaller in the PR/IR group than that in the NR group (62+/-15 mm3 vs 75 +/-20 mm3; p = 0.001), and neointima hyperplasia volume was significantly larger in the PR/IR group than that in the NR group (46+/-15 mm3 vs 26+/-10 mm3; p = 0.001). A significant positive correlation was found between pre-interventional RI and follow-up NIH CSA (r = 0.25, p = 0.022). The incidence of ISR and repeat intervention was significantly higher in the PR/IR group (30.8% vs 18.2%, 28.8% vs 15.2%; p = 0.032, 0.035, respectively). CONCLUSION: Measuring pre-interventional arterial remodeling patterns by IVUS may be helpful to stratify lesions at high-risk of ISR.     

辛伐他丁对支架新生内膜的作用

目的观察他丁类调脂药物对支架再狭窄和支架内新生内膜的影响.方法对单支冠脉病变行支架植入术的患者随机接受或不接受调脂药物的治疗,10月后复查冠脉造影和血管内超声检查.结果 65位患者随机接受辛伐他丁10mg治疗.辛伐他丁组患者在接受降脂治疗后血清总胆固醇降低15%,低密度脂蛋白胆固醇下降了26%,高密度脂蛋白胆固醇增加12%.辛伐他丁组和对照组支架再狭窄率无差异(分别为30.3%和37.5%,P>0.05).定量冠脉造影结果两组比较,两组参考段血管直径、支架最小管腔直径以及直径狭窄率均无明显差异.血管内超声发现辛伐他丁组参考段血管内膜腔截面积、最小血管内膜腔截面积以及最小支架截面积均无显著性差异.新生内膜截面积两组比较对照组大于辛伐他丁组,但无统计学意义.结论辛伐他丁长期治疗能够有效降低血中致动脉粥样硬化的脂蛋白.但10 mg/日的辛伐他丁对支架的再狭窄率以及支架内膜增生无明显影响.     

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.     

Sex differences in neointimal hyperplasia following endeavor zotarolimus-eluting stent implantation

Inconsistent results in outcomes have been observed between the genders after drug-eluting stent implantation. The aim of this study was to investigate gender differences in neointimal proliferation for the Endeavor zotarolimus-eluting stent (ZES) and the Driver bare-metal stent (BMS). A total of 476 (n = 391 ZES, n = 85 BMS) patients whose volumetric intravascular ultrasound analyses were available at 8-month follow-up were studied. At 8 months, neointimal obstruction and maximum cross-sectional narrowing (CSN) were significantly lower in women than in men receiving ZES (neointimal obstruction 15.5 ± 9.5% vs 18.2 ± 10.9%, p = 0.025; maximum CSN 30.3 ± 13.2% vs 34.8 ± 15.0%, p = 0.007). Conversely, these parameters tended to be higher in women than in men receiving BMS (neointimal obstruction 36.3 ± 15.9% vs 27.5 ± 17.2%, p = 0.053; maximum CSN 54.3 ± 18.6% vs 45.6 ± 18.3%, p = 0.080). There was a significant interaction between stent type and gender regarding neointimal obstruction (p = 0.001) and maximum CSN (p = 0.003). Multivariate linear regression analysis revealed that female gender was independently associated with lower neointimal obstruction (p = 0.027) and maximum CSN (p = 0.004) for ZES but not for BMS. Compared to BMS, ZES were independently associated with a reduced risk for binary restenosis in both genders (odds ratio for women 0.003, p = 0.001; odds ratio for men 0.191, p <0.001), but the magnitude of this risk reduction with ZES was significantly greater in women than men (p = 0.015). In conclusion, female gender is independently associated with decreased neointimal hyperplasia in patients treated with ZES. The magnitude of risk reduction for binary restenosis with ZES is significantly greater in women than in men.     

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。     

Relationship between stent malapposition and incomplete neointimal coverage after drug-eluting stent implantation

Background: Using optical coherence tomography (OCT), we evaluated the relationship between malapposed and uncovered struts following implantation of drug‐eluting stents (DESs). Methods: A total of 271 patients with 306 lesions who underwent DES implantation and follow‐up OCT were included in the study. The lesions were grouped based on the presence of malapposition and then by the median value of the percentage of malapposed struts (1.3%) to produce 3 groups: lesions without malapposition (group I, n = 232) and those with percentage of malapposed struts <1.3% (group II, n = 37) or ≥1.3% (group III, n = 37). Percentages of malapposed and uncovered struts were calculated as percent ratio of malapposed or uncovered to total struts in the defined cross‐sections, respectively. We compared percentage of uncovered struts in all analyzable struts and in the residual struts without malapposed segments among the 3 groups. Results: Group III showed a significantly larger percentage of uncovered struts among all the struts (group I, 3.7 ± 6.4 vs. II, 5.5 ± 5.6 vs. III, 17.6 ± 15.9%, P < 0.001) and among residual struts without malapposed segments (3.7 ± 6.4 vs. 5.2 ± 5.7 vs. 15.0 ± 14.4%, respectively, P < 0.001). There was a significant correlation between malapposed and uncovered struts in group III (r = 0.393, P = 0.016), but not in group II (r =?0.007, P = 0.965) among residual struts without malapposed segments. Conclusion: The percentage of uncovered DES struts was quite different depending on the presence and extent of malapposed struts. (J Interven Cardiol 2012;25:270–277)     

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.     

Probucol inhibits in-stent thrombosis and neointimal hyperplasia by promoting re-endothelialization

BACKGROUND: Evidence suggests that delayed re-endothelialization is responsible for in-stent thrombosis. Probucol inhibits neointimal thickening in animals via enhanced re-endothelialization and is the only oral drug that consistently inhibits restenosis after coronary angioplasty in humans. Here, we examined the effects of probucol on re-endothelialization and neointimal formation in a stent model. METHODS AND RESULTS: New Zealand White rabbits were fed a hypercholesterolemic diet with probucol (1%) or without (control) (n=11 each) for 6 weeks. At 2 weeks, endothelial denudation and stenting of the iliac artery was performed. Iliac arteries were harvested at week 6, and stented segments sectioned and analyzed. Compared with control, probucol increased in-stent re-endothelialization (74+/-6% in controls versus 93+/-3% in probucol-treated; P=0.008), and decreased average luminal stenosis (58+/-27 versus 31+/-16%; P=0.01) and stent depth (619+/-310 versus 314+/-158 microm; P=0.009). Compared with control, probucol also decreased accumulation of macrophages in the neointima. Furthermore, none of the probucol-treated rabbits had in-stent thrombosis, whereas four of eleven control rabbits showed thrombosis (P=0.04). CONCLUSIONS: Probucol demonstrates anti-restenotic and appears to have anti-thrombotic properties that are likely related to its ability to promote in-stent re-endothelialization.     

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.     

Impact of the cross-sectional geometry of the post-deployment coronary stent on in-stent neointimal hyperplasia: an intravascular ultrasound study.

To establish the relationship between the cross-sectional geometry of the post-deployment stent and the degree of in-stent neointimal hyperplasia (INH), intravascular ultrasound (IVUS) was used to examine cross-sections of the coronary arteries from 23 patients with coronary stents 6 months after implantation. Stent cross-sectional area (Sa) and stent perimeter (Sp) from 200 stent cross-sections, and the stent radius (Sr) and thickness of INH (Id) of 2,880 radial axes, were measured, and the mean degree of roundness (Rd) of stent cross-section was calculated for each stent as Rd=4piSa/Sp2. The degree of deformity (Df) of the stent cross-section was also calculated by comparing it with a hypothetical circle (the area of this hypothetical circle was equal to the Sa): Df=Sr/R, where R is the radius of the hypothetical circle. The area of INH was significantly larger in the Rd<0.87 group (n=84) than in the Rd> or =0.87 group (n=116) (3.83+/-1.26 vs 3.16+/-1.32 mm2, p<0.0005). There were significant differences in the thickness of INH among the 3 groups classified by the value of Df (Df<0.95: n=425, 0.21+/-0.12mm; 0.95< or =Df<1.05: n=2008, 0.29+/-0.15mm; Df> or =1.05: n=447, 0.34+/-0.15mm, overall p<0.0001). These data suggest that in-stent neointimal proliferation is more likely to occur in stented coronary arteries with a more oval than rounded cross-section, and particularly within the more pronounced and curved portion of the oval.     

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...     

Clinical outcomes for sirolimus-eluting stent implantation and vascular brachytherapy for the treatment of in-stent restenosis.

The purpose of this study was to compare the mid-term clinical outcome of sirolimus-eluting stent (SES) implantation and vascular brachytherapy (VBT) for in-stent restenosis (ISR). We assessed the 9-month occurrence of major adverse cardiac events (MACE) in 44 consecutive patients with ISR treated with SES implantation and 43 consecutive patients treated with VBT in the period immediately prior. Baseline clinical and angiographic characteristics of the two groups were similar. During follow-up, three patients (7%) died in the VBT group and none in the SES group. The incidence of myocardial infarction was 2.3% in both groups. Target lesion revascularization was performed in 11.6% of the VBT patients and 16.3% of the SES patients (P = NS). The 9-month MACE-free survival was similar in both groups (79.1% VBT vs. 81.5% SES; P = 0.8 by log rank). The result of this nonrandomized study suggests that sirolimus-eluting stent implantation is at least as effective as vascular brachytherapy in the treatment of in-stent restenosis.