Appropriate use of bioresorbable vascular scaffolds in percutaneous coronary interventions: a recommendation from experienced users: A position statement on the use of bioresorbable vascular scaffolds in the Netherlands

Percutaneous coronary interventions (PCI) have become a reliable revascularisation option to treat ischaemic coronary artery disease. Drug-eluting stents (DES) are widely used as first choice devices in many procedures due to their established good medium to long term outcomes. These permanent implants, however, do not have any residual function after vascular healing following the PCI. Beyond this initial healing period, metallic stents may induce new problems, resulting in an average rate of 2 % reinterventions per year. To eliminate this potential late limitation of permanent metallic DES, bioresorbable coronary stents or ‘vascular scaffolds’ (BVS) have been developed. In a parallel publication in this journal, an overview of the current clinical performance of these scaffolds is presented. As these scaffolds are currently CE marked and commercially available in many countries and as clinical evidence is still limited, recommendations for their general usage are needed to allow successful clinical introduction.     

Why and how to avoid stenting during brachytherapy

Intracoronary radiation is a promising therapy to reduce restenosis after percutaneous coronary intervention. It may be anticipated that radiation and intracoronary stents - the current standard coronary revascularization procedure - have a synergic antirestenosis effect. However, this potential benefit has not been proven in the clinical scenario. Indeed, this combined approach (stenting plus brachytherapy) may even be harmful. Delayed endothelialization and late stent malapposition are important drawbacks of implanting a metallic prosthesis in the setting of radiation therapy. Owing to the relatively high frequency of late thrombosis after stenting irradiated coronary arteries, the Food and Drug Administration required that the labeling of both gamma- and beta-radiation devices recently approved for clinical use explicitly advise avoidance of the placement of new stents. The pathophysiologic aspects as well as the clinical implications of the implantation of a new stent in association with radiation delivered by radioactive stents or catheter-based systems are discussed in this paper.     

Dorsal column stimulation in multiple sclerosis: effects on bladder and long term findings.

The effect of dorsal column stimulation on bladder function in 15 patients with established multiple sclerosis was analysed by urodynamic tests. Significant improvement in flow rate and urethral sphincter pressure was recorded in about two thirds. Of 31 patients examined over five years only 13 showed initial benefit from stimulation and were given permanent stimulators; of these, only three appeared to receive lasting benefit. Early complications occurred in nine patients and five had a relapse of their disease. These results suggest that at present stimulation of the dorsal column does not have a place in the routine management of multiple sclerosis.     

Stent implantation in acute myocardial infarction using a heparin-coated stent: a pilot study as a preamble to a randomized trial comparing balloon angioplasty and stenting

Preliminary experience with primary stenting in myocardial infarction has suggested a greater benefit in clinical outcome than has been obtained with direct balloon angioplasty. However, subacute thrombosis (SAT) remains a limitation for this new mode of therapy. In the BENESTENT II Pilot and main trials, the incidence of SAT with the heparin-coated Palmaz-Schatz stent was only 0.15%. Therefore, as a preamble to a large randomized trial, the feasibility and safety of the use of the Heparin-Coated Palmaz-Schatz trade mark Stent in Acute Myocardial Infarction (AMI) was tested in 101 patients enrolled between April and September 1996 in 18 clinical centres. In 101 stent-eligible AMI patients, as dictated by protocol, a heparin-coated stent was implanted. The primary objectives were to determine the in-hospital incidence of major adverse cardiac events (MACE: death, MI, target lesion revascularization) and bleeding complications, while the secondary objectives were the procedural success rate and the MACE, the restenosis and reocclusion rates at 6.5 months. Stent implantation (n 3 129 stents) was successful in 97 patients of the 101 who were included in this trial. During their hospital stay, two patients died and no patient experienced re-infarction, ischaemia prompting re-PTCA or CABG. Four patients suffered a bleeding complication, three major and one minor, of whom three required surgical repair. At 210 days follow-up, 81% of the patients were event free. At 6.5 months restenosis was documented in 18% of the 88 patients who underwent follow-up angiography, including three total occlusions. The results, both with respect to QCA and the occurrence of MACE, compare favourably with studies using elective stenting in both stable and unstable angina patients. As a result of this pilot study, a large randomized trial comparing direct balloon angioplasty with direct stenting in 900 patients with AMI was initiated in December 1996.     

New Cerebral Lesions at Magnetic Resonance Imaging after Carotid Artery Stenting Versus Endarterectomy: An Updated Meta-Analysis

Background

Carotid endarterectomy (CEA) or stenting (CAS) are associated with a relatively low rate of clinical events, but diffusion-weighted imaging (DWI) is increasingly being used to compare the incidence of new ischemic lesions. Therefore, we conducted an updated meta-analysis on the occurrence of post-procedural new DWI lesions after CAS versus CEA.

Methods and Results

MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched and 20 studies (2 randomized and 18 non-randomized) with a total of 2104 procedures (CAS = 989; CEA = 1115) were included. The incidence of new DWI cerebral lesions was significantly greater after CAS than CEA (40.3% vs 12.2%; 20 studies; 2104 patients; odds ratio [OR] 5.17; 95% confidence interval [CI], 3.31-8.06; p<0.00001). Also peri-procedural stroke (17 studies; 1833 patients; OR 2.01; 95% CI, 1.14-3.55; p=0.02) and stroke or TIA (17 studies; 1833 patients; OR 2.40; 95% CI, 1.42-4.08; p=0.001) were significantly increased after CAS. This latter clinical advantage in the CEA group over CAS was tempered when CEA procedures were performed with shunting in all instead of selective shunting or when CAS was performed with only closed cell stents instead of both closed and open cell stents, however, no significant differences between subgroups emerged.

Conclusions

CAS is associated with an increased incidence of post-procedural brain DWI lesions. This greater amount of ischemic burden may also reflect a higher rate of cerebral events after CAS. However, whether recent technical advances mainly for CAS could potentially reduce these ischemic events still remains to be evaluated.     

Long-term outcome after coronary stenting

The present review assesses the data on long-term outcome after coronary stenting. Histological, angiographical and intravascular imaging data have shown that the insertion of stents constitutes only a transient stimulus to lumen renarrowing, that this process is almost complete at 6 months and that a certain degree of neointima regression is also possible after this time. Clinical data have confirmed the sustained benefit of stenting in the long term. Careful selection of optimal stent designs and application of the recent advances in adjunctive pharmacological therapy are currently effective strategies to improve both short-and long-term results with coronary stenting. However, further efforts are needed and are ongoing to combat restenosis, a process that counters the excellent short-term results of stenting in the long term.     

Comparison of computational modelling techniques for braided stent analysis

Abstract

Braided stents are associated with a number of complications in vivo. Accurate computational modelling of these devices is essential for the design and development of the next generation of these stents. In this study, two commonly utilised methods of computationally modelling filament interaction in braided stents are investigated: the join method and the weave method. Three different braided stent designs are experimentally tested and computationally modelled in both radial and v-block configurations. The results of the study indicate that while both methods are capable of capturing braided stent performance to some degree, the weave method is much more robust.     

Behaviour of implantable coronary stents during magnetic resonance imaging

BACKGROUND: Magnetic resonance imaging (MRI) becomes more and more a routine diagnostic tool in clinical cardiology. In patients undergoing MRI, metallic implants may be harmful by motion or heating under certain circumstances. Many cardiac patients have implanted intracoronary stents. However, the safety of these metallic implants and especially their temperature behaviour during MRI has not been sufficiently tested. METHODS: This study investigated motion and temperature changes of 14 different stents for intracoronary application in two clinical scanners at field strengths of 1.0 and 1.5 T. At 1.5 T these studies were repeated after implantation of the stents into the coronary arteries of excised porcine hearts. Furthermore, the clinical status of 33 patients was assessed after a cardiac MR study and compared with a group of 33 patients matched for age, sex and risk factors for restenosis. RESULTS: No visible motion of the stents was observed. Furthermore, using a highly sensitive infrared camera any significant heating of the stents during MRI could be excluded. The rate of clinical events was not different in patients after MRI as compared with the control group. CONCLUSION: It is concluded that MRI is safe in patients with the currently available intracoronary stents.     

Methods to improve dose uniformity for radioactive stents in endovascular brachytherapy

Intravascular brachytherapy (IVBT) has rapidly gained acceptance as a new treatment modality for reducing restenosis and improving the success rate of percutaneous transluminal coronary angioplasty (PTCA). Recent clinical results on patients treated with beta-emitting 32P stents suggest that radiation reduces in-stent restenosis but may exacerbate neointimal growth at the edges of the stents. This has been referred to as the "candy wrapper effect." It is well known that radioactive stents yield extremely inhomogeneous dose distributions, with low doses delivered to tissues in between stent struts, at the ends of the stent, and also at depth. Some animal model studies suggest that low doses of radiation may stimulate rather than inhibit neointimal growth in an injured vessel, and it is hypothesized that dose inhomogeneity at the ends of a stent may contribute to the candy wrapper effect. We present here a theoretical study comparing dose distributions for beta stents vs. gamma stents; "dumbbell" radioactive loaded stents vs. uniformly loaded stents; and stents with alternate strut design. Calculations demonstrate that dose inhomogenieties between stent struts, at the ends of stents, and at depth can be reduced by better stent design and isotope selection. Prior to the introduction of radioactive stents, criteria for stent design included factors such as trackability, flexibility, strength, etc. We show here that if stent design also includes criteria for strut shape and spacing that improved dose distributions are possible, which in turn could reduce the candy wrapper effect.     

Liposome coated stents: a method to deliver drugs to the site of action and improve stent blood-compatibility

A method to correct stent related complications non-invasively, is the local delivery of therapeutic agents. Different drugs have been delivered on stents, after being either dispersed or encapsulated in polymeric materials, and placed on stents to form drug-eluting-stents (DE-stents). Investigation of possibility to cover polymer - coated metallic stents, with liposomal drugs, for preparation of novel DE-liposome-coated-stents, has been initiated few years ago. In this context our research has been focused on answering the following questions: (i) Can liposomes be applied as coatings on polymer covered stents? (ii) Can drug release from liposome coated-stents be controlled? And: (iii) how is haemo-compatibility of stents affected? The results of the experiments carried out demonstrate that liposomal formulations of drugs can be used as coating systems of polymer covered stents for achieving sustained release of drugs at the site of interest. By modifying liposome characteristics, different amounts of drugs may be placed on the stents and their release rates can be adjusted for maximum therapeutic benefit. Finally, haemocompatibility of stents is highly improved (mainly in terms of cell adhesion and activation of coagulation system), when stents are coated with heparin-encapsulating -DRV liposomes.     

Effects of bifurcation-specific and conventional stents on coronary bifurcation flow. An experimental and numerical study

Our paper builds on existing research into conventional bare metal stents in order to assess new devices specifically designed for coronary bifurcation angioplasty. The first aim is to validate the numerical model against data from in vitro experiments on stented coronary phantoms. A surface mesh was built in accordance with micro-computed tomography images obtained from coronary stents implanted in silicone models and used for numerical analysis. Computational simulations for steady and unsteady cases generally agreed with their experimental counterparts. A second objective is to compare the hemodynamic performance of one of these new devices (Stentys) to that of conventional devices and stenting techniques in a simplified coronary bifurcation model. Four different coronary bifurcation stenting techniques were analyzed. We have focused on factors contributing to restenosis, such as wall shear stress (WSS), oscillatory shear index (OSI), pressure loss, and local normalized helicity (LNH). It was found that bifurcation-specific stents implanted in the side branch led to increased malapposition. This effect has proved to be more important than stent specific design characteristics such as strut size (different for conventional and Stentys stent). This conclusion is confirmed by means of drop in pressure and mechanical energy loss rate calculation; for the latter, the increase ranged from 9% to 17%, depending on the stenting technique, when dedicated stents were implanted in the side branch. The behavior patterns presented in this study should be double-checked against those obtained in more realistic geometries.     

Late thrombosis in cypher stents after the discontinuation of antiplatelet therapy

Drug-eluting stents, since their approval in the United States, have become the treatment of choice for de novo coronary artery narrowing due to their ability to reduce restenosis and the need for repeat revascularization. We present two patients who underwent percutaneous coronary intervention for the treatment of multivessel coronary artery disease; both patients were treated with sirolimus-eluting stents (SES) and bare metal stents (BMS).     

Bacterial biofilm and clogging of biliary stents

Endoscopic biliary stenting has become a standard palliative treatment for obstructive jaundice due to malignancies of the pancreas and the hepatobiliary system. Despite the high initial success rate in achieving biliary drainage, durable endoscopic stenting has been limited by the clogging of biliary stents, usually after 4–5 months, due to formation of an adherent bacterial biofilm. Various methods have been investigated for the prevention of bacterial adhesion and prolongation of stent patency. These include: 1) prophylactic use of antimicrobial agents and bile salts; 2) testing of new stent material and new designs for these biliary stents; and 3) the recent introduction of self-expandable metal stents. Each method has its own merits as well as specific problems. This article reviews the pathogenesis of biofilm formation on the biliary stents and the latest status of research in avoiding the problem of stent occlusion.     

Malignant Ureteral Obstruction: Functional Duration of Metallic versus Polymeric Ureteral Stents

Background

Ureteral obstruction caused by extrinsic compression is often associated with intra-abdominal cancers. Internal drainage with ureteral stents is typically the first-line therapy to relieve such obstructions. Novel designs of ureteral stents made of different materials have been invented to achieve better drainage. In this study, we described the functional outcomes of a Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) in patients with malignant ureteral obstruction and compare the functional duration of Resonance stents with regular polymeric stents in the same cohort.

Methods

Cancer patients who received polymeric stents and subsequent Resonance stents for ureteral obstruction between July 2009 and November 2012 were included in a chart review. Stent failure was detected by clinical symptoms, imaging studies, and renal function tests. The functional durations of each stent were calculated, and possible factors affecting stent patency were investigated.

Results

A total of 50 stents were successfully inserted into 50 ureteral units in 42 patients with malignant ureteral obstruction. There were 7 antegrade stents and 43 retrograde stents. There were no major complications. Stent-related symptoms were similar in both kinds of stents. After polymeric stents were replaced with Resonance metallic stents, hydronephrosis subsided or remained stable in 90% (45/50) of the ureteral units. Serum creatinine decreased or remained stable in 90% (38/42) of these patients. The Resonance stent exhibited a mean increase in functional duration of 4 months compared with the polymeric stents (p<0.0001), and 50% (25/50) of the Resonance stents exhibited a significant increase in functional duration (more than 3 months). Pre-operative serum creatinine < 2 was associated with a substantial increase in stent duration.

Conclusions

Resonance stents are effective and safe in relieving malignant ureteral obstructions after polymeric stents failure. Resonance stents can provide a longer functional duration than polymeric stents and should be offered as an option for internal drainage.     

载基因洗脱支架防治再狭窄的研究进展

药物洗脱支架(DES)在冠状动脉疾病的治疗中起到巨大作用,不但能机械支撑血管狭窄区,而且可以通过持续释放药物显著降低病灶处再狭窄率。然而,长期临床研究表明,载药DES在后期有引发血栓的风险。在DES表面载入基因药物,通过表面涂层输送系统局部缓慢释放治疗基因,能针对引起再狭窄的细胞过程进行修改。选择合适的治疗基因,可以抑制内膜增生,促进再内皮化,提高洗脱支架的有效性和安全性,是非常有前途的抗再狭窄方法。同时,良好的涂层材料不仅改善了支架表面的生物相容性,更能通过不同的基因药物输送系统有效控制治疗基因的释放速率。本文首先介绍了一部分针对再狭窄的治疗基因,在此基础上,综合阐述了基因缓释系统中使用的材料和技术,分析提炼了基因缓释系统的释放机理,举例分析了载基因洗脱支架的研究进展,并展望了该领域的发展前景。     

Discolored Ureteral Stents: Findings in Urinalysis and Urine Culture

Objective

Discolored ureteral stents are sometimes encountered in daily clinical practice; however, the mechanism(s) underlying the development of discolored ureteral stents remain unknown. In this study, we retrospectively analyzed the characteristics of discolored ureteral stents based on the results of a urinalysis and urine culture.

Materials & Methods

We identified a total of 26 patients with discolored ureteral stents and compared the findings in the urinalyses and urine culture in 21 discolored versus 45 non-colored ureteral stents.

Results

The median and mean (±SD) duration of stenting time was 78.0 and 81.3 (± 21.3) days for the discolored ureteral stents and 69.0 and 74.9 (± 19.8) days for the non-colored ureteral stents, respectively (P = 0.25). The discolored ureteral stents were associated with a higher mean urine pH than the non-colored ureteral stents (mean: 6.4 vs 6.0, P< 0.05). There were no significant differences between the two groups in the RBC (P = 0.51) and WBC (P = 0.35) counts in the urinalyses. In addition, the rate of a positive culture in the patients with discolored stents [20 of 21 (95.2%)] was significantly (P <0.01) higher than that observed in the patients with non-colored ureteral stents [33 of 45 (73.3%)].

Conclusions

In this study, the subjects with discolored ureteral stents showed a significantly higher likelihood of having a positive urine culture and also demonstrated higher pH values in the urinalyses. However, no clear cut-off point to predict discoloration was indicated.     

Medical Grand Rounds: refractory hypertension and renal insufficiency in a patient with renal artery stenosis.

Renal artery stenosis has become increasingly common as a cause of refractory hypertension and renal insufficiency. There is a high prevalence of bilateral disease and the lesions tend to progress over time. Newer, less invasive, imaging modalities such as doppler ultrasound, magnetic resonance angiography, and spiral CT scanning are evolving technologies in the diagnosis of renal artery stenosis. Advances in surgical technique, particularly the development of extra-anatomical procedures such as spleno-renal and hepato-renal by pass, have significantly lowered surgical morbidity and mortality and provides revascularization options for patients with complex vascular disease that would previously not have been considered because of their high surgical risk. Improvements in angioplasty technique and the use of stents are broadening the types of lesions that can be successfully approached with these techniques and may be particularly helpful for patients with more severe cardiac or cerebrovascular disease. The benefits of revascularization may be even greater for preservation of renal function than for control of blood pressure in properly selected patients. It is difficult to predict which patients will benefit from surgical revascularization versus medical management of RAS. Knowledge of the progressive nature of RAS, the high prevalence of bilateral disease, and the clinical characteristics that correlate with progression (e.g., decreasing renal size) are helpful in guiding clinical decisions regarding intervention. Additional studies to determine the predictive value of non-invasive tests such as CRS, doppler ultrasound before and after administration of angiotensin converting enzyme inhibitors, and other tests, are needed to assist the clinician in identifying who will benefit most from revascularization both in terms of renal function and blood pressure control.     

Molecular insight in cancer treatment and prevention

This article explores the impact of new insights in the biology of cancer on the treatment and the prevention of this disease. There are two types of targeted cancer treatment, afforded by the molecular profile of cancer. One concerns the use of agents targeted on a specific component of the cancer cells (e.g., CD20 in lymphoma) or on a specific survival function of the cancer cell (growth-factor-receptor interaction; transduction cascade). The other concerns the recognition of tumors that are more or less likely to benefit from cytotoxic chemotherapy according to their genomic or proteomic profile. Cancer prevention may benefit from new molecular insight in cancer biology as these processes allow early diagnosis of cancer, identification of patients at risk for cancer, and may provide intermediate markers for chemoprevention studies.     

内镜下逆行胰胆管造影置放胆道支架治疗恶性梗阻性 黄疸98 例疗效分析

目的:探讨内镜下逆行胰胆管造影置放胆道支架对恶性胆道梗阻的疗效及并发症的防治。方法:选择2008年2月至2011年9月我院收治的无法手术切除或不愿手术的恶性胆道梗阻患者98例,通过放置内置支架引流观察其操作成功率、支架通畅期和退黄效果、并发症发生情况及其防治效果和患者生存期等。结果:98例患者中有88例成功通过置入胆道内置引流管,成功率为89.8%,并发症发生率为11.22%,所有成功患者术后1周黄疸明显减退,支架平均通畅期137天,患者平均生存期为163天。结论:行胆道内置支架引流创伤小,并发症少,通畅性能好,可持久有效地控制黄疸,有效缓解病情,改善全身情况,明显延长恶性胆道梗阻患者的生存期。     

Economic evaluation of sirolimus-eluting stents

Background

Sirolimus-eluting stents have recently been shown to reduce the risk of restenosis among patients who undergo percutaneous coronary intervention (PCI). Given that sirolimus-eluting stents cost about 4 times as much as conventional stents, and considering the volume of PCI procedures, the decision to use sirolimus-eluting stents has large economic implications.

Methods

We performed an economic evaluation comparing treatment with sirolimus-eluting and conventional stents in patients undergoing PCI and in subgroups based on age and diabetes mellitus status. The probabilities of transition between clinical states and estimates of resource use and health-related quality of life were derived from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Information on effectiveness was based on a meta-analysis of randomized controlled clinical trials (RCTs) comparing sirolimus-eluting and conventional stents.

Results

Cost per quality-adjusted life year (QALY) gained in the baseline analysis was Can$58 721. Sirolimus-eluting stents were more cost-effective in patients with diabetes and in those over 75 years of age, the costs per QALY gained being $44 135 and $40 129, respectively. The results were sensitive to plausible variations in the cost of stents, the estimate of the effectiveness of sirolimus-eluting stents and the assumption that sirolimus-eluting stents would prevent the need for cardiac catheterizations in the subsequent year when no revascularization procedure was performed to treat restenosis.

Interpretation

The use of sirolimus-eluting stents is associated with a cost per QALY that is similar to or higher than that of other accepted medical forms of therapy and is associated with a significant incremental cost. Sirolimus-eluting stents are more economically attractive for patients who are at higher risk of restenosis or at a high risk of death if a second revascularization procedure were to be required.Restenosis is a major limitation to the long-term success of percutaneous coronary intervention (PCI). It is estimated that 14% of patients who undergo PCI with stent implantation require a second intervention within a year to manage restenosis.¹ A second coronary procedure carries a significant risk of death or impairment in health-related quality of life (HRQOL).² Moreover, given that approximately 21 200 PCIs with stenting were performed in Canada in 1999, restenosis has major economic implications.³Drug-eluting stents are the most recent technologic advance in restenosis prevention. To date, 4 randomized controlled clinical trials (RCTs) have compared the efficacy of sirolimus-eluting stents (the first available drug-eluting stent) and standard uncoated stents in the treatment of de novo native coronary artery disease and published their findings: RAVEL⁴ (RAndomized study with the sirolimus-eluting VELocity balloon-expandable stent), SIRIUS⁵ (study of the SIRolImUS-eluting stent), and C-SIRIUS⁶ and E-SIRIUS,⁷ the Canadian and European arms of SIRIUS. These trials all found notable reductions in the incidence of radiographic evidence of restenosis and symptomatic restenosis with the use of sirolimus-eluting stents. However, the overall survival rate was not affected. Currently, the cost of sirolimus-eluting stents (about Can$2900 per stent) is nearly 4 times that of conventional stents.⁸ Given the volume of PCIs performed annually, decision-makers must determine their optimal use.Using a subset of the cohort in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH),⁹ we estimated clinical event rates, HRQOL and health care costs for patients undergoing PCI with implantation of a conventional stent. Combining this information with data from the 4 RCTs, we estimated the cost per quality-adjusted life-year (QALY) gained by using sirolimus-eluting stents rather than conventional stents for such patients.