Drug‐eluting stent fracture: Incidence,contributing factors,and clinical implications

Stent fracture has been observed in noncoronary vessels, especially in the superficial femoral and popliteal arteries and with bare metal stents in saphenous vein grafts of coronary arteries. Since the introduction of drug‐eluting stents, stent fractures have also been reported in small studies and case reports. We reviewed these publications to assess what is known regarding the incidence, contributing factors, and clinical implications of drug‐eluting stent fracture in coronary arteries. The reported rate of drug‐eluting stent fracture in coronary arteries ranges from 1 to 8%, although much of the available literature is derived from single‐center studies that are heterogeneous in their study methods. A higher risk of stent fracture may be associated with the right coronary artery location, excessive tortuosity or angulation of the vessel, overlapping stents, and longer stents. The closed‐cell design of the Cypher stent has been associated with increased rigidity that may increase the risk of stent fracture, although these studies did not assess the overall outcomes between the Cypher and Taxus stents in a head‐to‐head comparison. Stent fracture has been shown by most studies to be associated with a statistically increased incidence of focal in‐stent restenosis, and some have shown an increased risk of target lesion revascularization. Other complications observed with stent fracture include stent thrombosis, coronary aneurysms, myocardial infarction, and sudden death. © 2009 Wiley‐Liss, Inc.     

Long‐term complication after LM bifurcation treatment

Two months after left anterior descending (LAD) artery and left circumflex (LCx) artery bare metal stent implantation, a proliferative subocclusive in‐stent restenosis in LCx coronary with severe LM coronary (LM) involvement developed. The present clinical case describes a simplified strategy for unprotected LM percutaneous coronary intervention using two bioabsorbable biolimus‐eluting stents without involvement of the LAD coronary using an “L” technique. © 2010 Wiley‐Liss, Inc.     

Late acute thrombosis after implantation of sirolimus‐eluting stent to treat in‐stent restenosis

Drug‐eluting stents (DES) have significantly reduced the incidence of in‐stent restenosis (ISR) compared to bare metal stents (BMS). However, recent randomized trials comparing DES with BMS reported few cases of late DES thrombosis. We report the case of late sirolimus‐eluting stent thrombosis occurring 22 months after its elective implantation in a restenotic BMS and soon after the interruption of combined anti‐platelet therapy with aspirin and Clopidogrel.     

Acute coronary syndrome due to early multiple and complete fractures in sirolimus‐eluting stent: A case report and brief literature review

Despite drug eluting stents (DES), as compared to bare metal stents, have reduced in‐stent restenosis, complex and long lesions remains a challenge for interventional cardiologist. Their treatment is often associated with an unfavorable outcome, related to in‐stent restenosis, stent thrombosis, and target lesion revascularization. These complications may derive from the contact between metallic structures and coronary artery endothelium, and consequent overexpression of platelet activating factors, growth factors, and inflammatory cytokines. Recently, an additional mechanism has emerged as new cause of these complications: “stent fracture.” Several factors are involved in this phenomenon including material and stent platform, target vessel features, stent implantation technique, and implant duration. We reported a case of 69 years old man with rare early and complex DES fractures on right coronary that caused acute coronary syndrome 36 hr after a previous percutaneous coronary intervention.© 2012 Wiley Periodicals, Inc.     

Clinical outcomes of drug‐eluting versus bare‐metal in‐stent restenosis

In‐stent restenosis (ISR) is a challenging syndrome that affects drug‐eluting stents and bare‐metal stents. However, data comparing the outcomes of drug‐eluting versus bare‐metal ISR are limited. Our objective was to evaluate the long‐term clinical outcomes of drug‐eluting versus bare‐metal ISR. Patients who underwent percutaneous coronary intervention at Cleveland Clinic for ISR from 05/1999 to 06/2007 were included. Unadjusted outcomes were tested using Kaplan‐Meier curves followed by multivariable adjusted Cox proportional hazards analyses. Twenty seven variables, including type of stent used to treat ISR and procedural date, were included. The primary end point was a composite of death, myocardial infarction (MI), or target lesion revascularization (TLR). The secondary endpoints were components of the primary endpoint. Of 931 patients identified, 225 had drug‐eluting ISR and 706 had bare‐metal ISR. There were 279 cumulative events for a median follow‐up of 3.2 years. The primary endpoint was not different between drug eluting and bare‐metal ISR (22% versus 33%, adjusted hazard ratio [HR] 1.14; 95% confidence interval [CI], 0.79–1.66; P = 0.49). The secondary endpoints of death (8% versus 16%, adjusted HR 1.05; 95% CI, 0.56–1.98; P = 0.88), MI (4% versus 5%, adjusted HR 1.48; 95% CI, 0.54–4.04; P = 0.45), and TLR (15% versus 16%, adjusted HR 1.30; 95% CI, 0.81–2.11; P = 0.28) were also not different. This study represents the largest analysis comparing drug‐eluting to bare‐metal ISR. On multivariable Cox proportional hazard analyses, drug‐eluting and bare‐metal ISR have similar long term outcomes. © 2009 Wiley‐Liss, Inc.     

Rotational atherectomy for fibro‐calcific coronary artery disease in drug eluting stent era: Procedural outcomes and angiographic follow‐up results

Objectives: The aim of this study was to examine the binary re‐stenosis rates, procedural success, and in hospital outcomes following treatment of fibro‐calcified coronary lesion with rotational atherectomy in drug eluting stent era. Background: Binary restenosis rates have remained high with the use of bare metal stents following rotational atherectomy in calcified lesions. There is limited data available following rotational atherectomy in drug eluting stent era. Methods: We evaluated the procedural and angiographic outcomes following a consecutive series of 516 procedures treated with rotational atherectomy followed by stenting. We compared the results between Rota + Drug eluting stent (DES) and Rota + bare metal stent (BMS) groups. Results: Procedural success was achieved in 97.1% of the lesions with overall low in hospital adverse events (death in 1.1%, Q MI in 1.3%, Non Q MI in 5.3%, and urgent repeat PCI in 0.4%). There was significant reduction in the binary restenosis rates following Rota + DES use as compared to Rota + BMS use (11% vs. 28.1%, P < 0.001; OR = 3.17, 95% CI: 1.76–5.93) and similar reduction was seen in the target lesion revascularization (10.6% vs. 25%, P = 0.001; OR = 2.81, 95% CI: 1.53–5.14). We have identified ostial lesions, chronic total occlusion lesions, and use of bare metal stents as independent predictors of restenosis in this group of patients. Conclusions: Rotational atherectomy can be performed with high success rates and low complications, and rotational atherectomy followed by drug eluting stent implantation significantly reduces binary restenosis rates in fibrocalcific lesions as compared to rotational atherectomy and bare metal stents. © 2010 Wiley‐Liss, Inc.     

Stent fracture associated with drug‐eluting stents: Clinical characteristics and implications

Objective : To evaluate the clinical characteristics and implications of stent fracture in drug‐eluting stents. Background : Approximately 2.5 million drug‐eluting stents are implanted every year worldwide. In 10 randomized controlled trials involving 2,602 patients, no incidence of stent fracture was recognized or reported. Methods : From April 2003 to December 2005, 2,728 patients underwent drug‐eluting stenting. The angiograms of all 530 patients who underwent repeat angiography were analyzed to identify the presence of stent fracture. We then documented the incidence of adverse events associated with drug‐eluting stent fracture and systematically analyzed the clinical, procedural, and structural factors, which might predispose to stent fracture. Results : Stent fracture was identified in 10 patients. None of these fractures were detectable at the time of stent placement. The median time interval from stent implantation to detection of fracture at repeat angiography was 226 days (range, 7–620 days). Adverse clinical outcomes associated with stent fracture occurred in 7 patients (6 patients had binary restenosis and 1 patient had stent thrombosis), all necessitating repeat intervention. Analysis of potential predisposing clinical, procedural, and structural factors revealed that 4 patients had excessive tortuosity in the proximal segment, and overlapping stents were used in 5 cases. All fractures occurred in sirolimus‐eluting stents. Conclusions : Stent fracture may represent a new potential mechanism of restenosis and stent thrombosis in drug‐eluting stents. Predisposing clinical and procedural factors may be vessel tortuosity and use of overlapping stents. The most important predisposing factor, however, may be stent structure, since all fractures occurred in sirolimus‐eluting stents. © 2006 Wiley‐Liss, Inc.     

Percutaneous therapy of bifurcation lesions with drug‐eluting stent implantation: the Culotte technique revisited

INTRODUCTION: The most effective strategy for bifurcation stenting is currently undefined. The Culotte technique was developed as a method that ensures complete bifurcation lesion coverage. However, it went out of favour due to a high rate of restenosis when utilizing bare metal stents. Drug‐eluting stents reduce the rate of restenosis and need for repeat lesion revascularization compared with bare metal stents; we re‐evaluated this technique with drug‐eluting stent implantation. METHODS: Between April 2002 and October 2003, 207 patients were treated for at least one bifurcation lesion with drug‐eluting stent implantation to both the main vessel and side branch. Of these, 23 were treated with the Culotte technique (11.1%) for 24 lesions. Sirolimus‐eluting stents were used in 8.3%, and paclitaxel‐eluting stents in the remaining 92.7%. RESULTS: Clinical follow‐up was obtained in 100%. One patient had a myocardial infarction at 14 days (maximum rise in creatine kinase 872IU/L) related to thrombosis occurring in another lesion, and underwent repeat revascularization. There were no episodes of stent thrombosis in the Culotte lesions. At eight months follow‐up, there were no deaths and no further myocardial infarction. One patient required target lesion revascularization (TLR), and a second underwent target vessel revascularization. The cumulative rates of survival‐free of TLR and major adverse cardiac events were 94.7% and 84.6% respectively. Angiographic follow‐up was obtained in 16 patients (69.6%) at a mean period of 8.3±4.3months. The late lumen loss for the main vessel and side branch were 0.48±0.56?mm and 0.53±0.33?mm respectively, with binary restenosis rates of 18.8% and 12.5%.

CONCLUSIONS: In this small study of bifurcation stenting utilizing the Culotte technique with drug‐eluting stent implantation, there was a low rate of major adverse events and need for target lesion revascularization at eight months, when compared with historical data of bifurcation stenting with bare metal stents. Further re‐evaluation of this technique utilizing drug‐eluting stents, is warranted in the setting of larger randomized studies.     

Estrogen‐eluting stent implantation inhibits neointimal formation and extracellular signal‐regulated kinase activation

Objectives : The goal of this study was to evaluate the efficacy and the mechanism of 17β‐estradiol‐eluting stents on inhibiting neointimal formation of abdominal aortas in rabbits fed with high fat diet. Background : Animal experiments have shown that local delivery of estrogen reduced neointimal formation after coronary angioplasty. Preliminary trial of estrogen‐eluting stent implantation in patients with coronary disease also suggests a reduction in restenosis. Methods : We implanted 17β‐estradiol‐eluting stents, or control phosphorylcholine‐ coated stents, or bare metal stents of abdominal aortas in rabbits fed with high fat diet. Histology, immunohistochemistry, and Western blot analysis were used to assess the efficacy and mechanism of inhibiting neointimal formation of 17β‐estradiol‐eluting stents. Results : Western blot analysis revealed marked increase in ERK phosphorylation in 30 min after deployment of phosphorylcholine‐coated or bare metal stents, indicating activation of MAP kinase pathway. Immunohistochemistry showed intense staining of phospho‐ERK in the medial smooth muscle cells in stent‐implanted region. Extensive neointimal hyperplasia developed 12 weeks after stenting. In contrast, we observed significant inhibition of ERK phosphorylation and neointimal thickening in estrogen‐eluting stent‐implanted animals. Immunohistochemistry of factor VIII‐related antigen demonstrated an accelerated reendothelialization as compared with the bare metal stent or phosphorylcholine‐coated stent‐implanted controls. Conclusions : Current study suggests that estrogen‐eluting stents reduce neointimal formation and hence prevent restenosis after angioplasty possibly by inhibiting ERK activation in smooth muscle cells and promoting reendothelialization. © 2007 Wiley‐Liss, Inc.     

Particle debris from a nanoporous stent coating obscures potential antiproliferative effects of tacrolimus-eluting stents in a porcine model of restenosis.

Polymer stent coatings may not be suitable for drug elution because of inherent proinflammatory effects. A previous study suggested a beneficial effect of a stent eluting tacrolimus from a nanoporous ceramic aluminum oxide coating in a rabbit restenosis model. We investigated whether this stent is effective in preventing in-stent restenosis in a porcine restenosis model. Thirty-four juvenile swine underwent balloon overstretch injury and were subjected to implantation of either stainless steel (bare) stents, bare stents coated with nanoporous aluminum oxide alone, and coated stents eluting 50 and 180 mug of tacrolimus (FK506). In-stent restenosis was quantified at 1 and 3 months after stent placement by histomorphometry. A significant increase of neointimal hyperplasia was noted with the stents coated with aluminum oxide alone compared with bare stents (2.92 +/- 1.02 and 1.38 +/- 0.51 mm(2), respectively; P < 0.02). In all arteries containing coated stents, particle debris was found in the media and neointima, resulting in augmented vascular inflammation. In the group of stents coated with aluminum oxide, FK506 elution at a dose 180 mug reduced neointimal hyperplasia vs. no drug elution (1.66 +/- 0.49 vs. 2.92 +/- 1.02 mm(2); 180 mug vs. ceramic alone; P < 0.03). At a dose of 50 mug stent-based delivery of FK506, no reduction of neointimal hyperplasia was found (2.88 +/- 1.31 and 2.92 +/- 1.02 mm(2), respectively; P = NS; FK506 vs. ceramic alone). In summary, particle debris shed from a drug-eluting aluminum oxide coating of a stainless steel stent counteracts potential antiproliferative effects of stent-based tacrolimus delivery in a porcine model of restenosis. We propose that stent coatings eluting drugs need to be routinely tested for being tightly anchored into the stent surface. Alternatively, omission of any coating used as a drug reservoir may eliminate inflammatory particle debris after placement of drug-eluting stents.     

Late restenosis following placement of a sirolimus eluting stent for in-stent restenosis

Drug eluting stents (DES) are rapidly replacing intravascular brachytherapy for the treatment of bare metal in-stent restenosis (ISR). To date, there are no long-term follow up data supporting this practise. We report symptomatic repeat in-stent restenosis occurring 27 months after sirolimus eluting stent deployment for de novo in-stent restenosis. This case suggests that in a subgroup of patients with ISR, as with brachytherapy, the drug eluting stent may be simply delaying rather than inhibiting the restenotic process.     

Kissing drug eluting balloons for in‐stent restenosis complicating bifurcations treated with drug‐eluting stents

The management of in‐stent restenosis (ISR) complicating bifurcation lesions is technically challenging and implant of further stents may not be feasible. The use of drug‐eluting balloons provides an attractive option for treatment of such lesions allowing a technically simple procedure without the need for further complex stenting. The SeQuent Please paclitaxel‐eluting balloon (B. Braun, Berlin, Germany) has been shown to be superior to a paclitaxel eluting stent or balloon angioplasty for ISR complicating a bare‐metal stent. However, there is no data on the efficacy of the SeQuent Please in ISR complicating drug‐eluting stents or bifurcation lesions. We report two cases where the SeQuent Please was used in this setting with angiographic success and freedom from target vessel failure and angina at 24 months. In both cases the Sheathless Eau Cath guide (Asahi Intecc, Japan) was employed to perform a kissing‐balloon dilatation with the SeQuent Please, so allowing treatment via radial access. © 2012 Wiley Periodicals, Inc.     

A completely fractured zotarolimus‐eluting stent in an aortocoronary saphenous vein bypass graft

Drug‐eluting stents (DES) have significantly improved the rate of target vessel revascularization in comparison with bare metal stents. DES fracture was not reported in multicenter randomized clinical trials, but several case reports of DES fracture have been published, mostly with sirolimus‐eluting stents. DES fracture is associated with stent restenosis and thrombosis. We report a zotarolimus‐eluting stent fracture in an aortocoronary saphenous vein graft (SVG) bypass. The patient presented with chest pain and a non‐ST‐elevation myocardial infarction. He underwent cardiac catheterization that showed a complete fracture of a zotarolimus‐eluting stent in the ostium of a sequential SVG to the diagonal and obtuse coronary arteries. His management included coronary angioplasty and retrieval of the proximal fractured segment. We discuss the potential causes for this stent fracture and suggest caution when using a DES in an ostial location of a SVG bypass, especially in a highly mobile vessel. © 2012 Wiley Periodicals, Inc.     

Stent thrombosis after complex multivessel stenting in an elderly patient

We report a challenging case in terms of procedural difficulty as well as long‐term patency. Multivessel stenting procedures for long subtotal occlusions in the right coronary artery (RCA) and left anterior descending coronary artery (LAD) were successfully performed in an 84‐year‐old female who had complications of severe left ventricular dysfunction and a recent history of gastric ulcer bleeding. Two bare‐metal stents were successfully deployed in the mid and distal RCA. A drug‐eluting stent could only be deployed in the proximal RCA. Two drug‐eluting stents were deployed in the proximal LAD and LMT. Late stent thrombosis in the proximal RCA occurred about 3 months later. We speculated that a lack of aspirin and bare metal stent restenosis were the reasons for the late stent thrombosis. This case was very challenging in terms of balancing the risk of ischemia and bleeding after coronary stent deployment. © 2010 Wiley‐Liss, Inc.     

Drug-eluting stent implantation for treatment of recurrent renal artery in-stent restenosis.

Percutaneous renal artery stenting has become the treatment of choice for renal artery stenosis. In-stent restenosis (ISR) still remains a persistent problem. Drug eluting stents have significantly reduced the incidence of ISR in coronary arteries. We report a case in which recurrent renal ISR was successfully treated with paclitaxel-eluting stent implantation, using intravascular ultrasound guidance, with maintained stent patency at 6 months.     

雷帕霉素涂层支架预防血管内再狭窄的研究进展

如何防治冠状动脉介入治疗术后再狭窄形成已成为当今介入心脏学界面临的一大挑战 ,近年来的研究表明雷帕霉素涂层支架可有效预防再狭窄形成 ,为解决这一难题提供了新的治疗手段。本文就目前雷帕霉素涂层支架在临床防治再狭窄研究的最新进展作一综述。     

冠状动脉介入治疗后造影复查支架再狭窄结果分析

目的:分析不同类型支架置入术后冠状动脉(冠脉)造影复查的影像学特点.方法:入选行冠脉介入治疗后进行造影复查的577例患者的846处病变,根据置入支架类型及方式不同分别分析其临床资料及冠脉造影资料.结果:冠脉造影随访率为22.62%;药物支架虽然病变更复杂,但其冠脉造影复查再狭窄率明显低于裸支架(20.29%VS 42.56%,P=0.000);裸支架重叠、药物支架重叠、裸支架与药物支架重叠时再狭窄率分别为53.49%,25.55%,35.29%.药物支架在支架内弥漫性、支架内弥漫性累及两端及支架内局限性再狭窄率明显低于裸支架,差异均有统计学意义(P=0.001,P=0.013,P=0.031),药物支架支架近端局限性再狭窄率高于裸支架,差异有统计学意义(P=0.000);不同药物支架冠脉造影复查再狭窄率没有统计学差异(P=0.193);药物支架和裸支架在糖尿病患者中冠脉造影复查再狭窄率为23.85%和42.65%(P=0.012).结论:①长病变需要重叠支架时尽量使用药物支架重叠;②药物支架改变了支架再狭窄类型,由弥漫型再狭窄转为局限型;③不同种类药物支架效果良好;④药物支架对糖尿病患者同样有效.     

Metal allergy to everolimus‐eluting cobalt chromium stents confirmed by positive skin testing as a cause of recurrent multivessel in‐stent restenosis

A 54‐year‐old woman treated with cobalt‐chromium everolimus eluting stents (CoCr‐EES) for her left distal circumflex and diagonal branch lesions suffered from repeated in‐stent restenosis in both lesions. Neointimal proliferation occurred rapidly and almost simultaneously in the two lesions. The cause was established to be metal allergy, as determined by patch tests which were strongly positive for bare metal stents and weakly positive for CoCr‐EES. Following the third successive angioplasty, we initiated treatment with prednisolone (30 mg daily) and the anti‐allergic and anti‐proliferative drug tranilast (300 mg daily). An elective angiogram performed 3 months later showed no evidence of in‐stent restenosis in any of the stented lesions. Furthermore, the patient has remained angina‐free for 15 months. The unique features of this case include: (1) near‐simultaneous repeated multivessel in‐stent restenosis in a patient with skin test‐documented metal allergy to cobalt‐chromium stents; (2) adjunctive systemic medical therapy with prednisolone and tranilast appeared to terminate the malignant restenotic cycle. © 2015 Wiley Periodicals, Inc.     

The genous™ endothelial progenitor cell capture stent accelerates stent re‐endothelialization but does not affect intimal hyperplasia in porcine coronary arteries

Objectives : To study the effect of endothelial progenitor cell (EPC) capture on the vascular response to coronary stenting. Background : The introduction of drug‐eluting stents has reduced the need for target lesion revascularization, but their effect on delayed healing, inflammation, and vascular dysfunction has emphasized the need to design strategies that improve current DES. One such strategy is to improve endothelialization by capturing CD34‐positive cells (EPC) by the stent surface. The first human clinical trial using coronary EPC capture stents showed stent safety but neointimal thickness (NIT) was not reduced compared to bare metal stents (BMS). To understand these responses we studied the coronary response to the EPC capture stent in swine. Methods and Results : The stent, coated with murine antihuman monoclonal CD34 antibodies, was assessed with QCA guided stent implantation in normal swine coronary arteries for early endothelialization at 2 and 5 days, and NIT at 28 and 90 days in comparison to control stents carrying a non‐specific murine antibody or to BMS. The main finding was that while the EPC capture stent significantly improved early endothelialization it did not reduce NIT at 28 and 90 days. Conclusions : The EPC capture stent improves early endothelialization in swine but this does not affect neointimal thickness as compared to control stents at 28 and 90 days. © 2011 Wiley Periodicals, Inc.     

Aneurysm formation after drug‐eluting balloon treatment of drug‐eluting in‐stent restenosis: First case report

A 55‐year‐old male underwent paclitaxel‐eluting stent implantation in a bifurcation lesion of his left anterior descending artery (LAD) during an episode of unstable angina in 2008. A late in‐stent restenosis developed 15 months after implantation of the drug‐eluting stent (DES) and was treated with paclitaxel eluting balloon. Two months later, during angiography for functional assessment of the significance of lesions in the circumflex artery, an aneurysm at the place of drug‐eluting balloon (DEB) inflation was observed. The patient was left on double antiplatelet therapy and scheduled for clinical observation after 3 months and control coronary angiography after 6 months for aneurysm progression follow‐up. © 2012 Wiley Periodicals, Inc.