Contemporary stent treatment of coronary bifurcations.

Treatment of coronary bifurcation lesions represents a challenging area in interventional cardiology. The introduction of drug-eluting stents (DES) reduced restenosis in the main branch (MB). However, restenosis at the ostium of the side branch (SB) remains a problem. Although stenting the MB with provisional SB stenting seems to be the prevailing approach, in the era of DES various two-stent techniques emerged (crush) or were re-introduced (V or simultaneous kissing stents, crush, T, culottes, Y, skirt) to allow stenting in the SB when needed. This review describes in detail various techniques used for implantation of two stents by intention to treat.     

Contemporary stent treatment of coronary bifurcations

Treatment of coronary bifurcation lesions represents a challenging area in interventional cardiology. The introduction of drug-eluting stents (DES) reduced restenosis in the main branch (MB). However, restenosis at the ostium of the side branch (SB) remains a problem. Although stenting the MB with provisional SB stenting seems to be the prevailing approach, in the era of DES various two-stent techniques emerged (crush) or were re-introduced (V or simultaneous kissing stents, crush, T, culottes, Y, skirt) to allow stenting in the SB when needed. This review describes in detail various techniques used for implantation of two stents by intention to treat.     

Drug-eluting stents for coronary bifurcations: bench testing of provisional side-branch strategies.

The objective of this study was to bench-test provisional bifurcation stenting strategies to provide insights on how best to perform these with drug-eluting stents (DESs). Bifurcation stenting with DESs reduces restenosis compared with bare metal stents (BMSs). Outcomes with a single DES are better than with two DESs but if the main branch is stented, there needs to be a reliable strategy for provisionally stenting the side-branch with full ostial scaffolding and drug application. Stents were photographed in a phantom after deployment with different strategies. With provisional T-stenting, placement of the side-branch stent without gaps is difficult. The internal (or reverse) crush strategy fully scaffolds the side-branch ostium but is experimental. The culotte technique providing excellent side-branch ostial coverage is easier to perform with open-cell or large-cell stent design. In general, kissing balloon post-dilation improves stent expansion, especially at the ostium, and corrects distortion. However, a main-branch kissing balloon of smaller diameter than the deploying balloon causes distortion. Final main-branch postdilatation or sequential postdilatation prevents distortion after the internal crush strategy.     

Drug-Eluting Stent Restenosis: Incidence, Predictors, Mechanisms, and Treatment

Drug-eluting stents (DES) represent a major advance in percutaneous coronary intervention (PCI). Clinical trials have shown significant reductions in restenosis with both sirolimus- and paclitaxel-eluting stents, with subsequent revascularization rates in the single digit range in most studies. Predictors of restenosis and target lesion revascularization include diabetes, prior restenosis, smaller post-PCI minimal lumen diameter and complex lesion features, such as long lesions, smaller vessels, ostial lesions, and bifurcations. DES restenosis is most commonly focal (or multifocal) within the stent and less commonly is manifest as a diffuse or proliferative narrowing. The mechanisms of DES include stent under-expansion, nonuniform stent strut distribution or stent malapposition, polymer disruption due to difficult stent delivery, stent fracture, and possibly drug resistance or failure. Although only limited data are available regarding treatment of DES restenosis, reintervention appears to be associated with relatively low subsequent recurrence rates and repeat DES implantation is generally accepted as the treatment of choice for DES restenosis.     

Coronary restenosis after implantation of drug-eluting stents

Randomized trials comparing drug-eluting stents (DES) with bare-metal stents have shown that the former significantly reduce the incidence of angiographic and clinical restenosis into an unprecedented low, one-digit, range. However, post-DES restenosis is not zero. Next to incomplete coverage with DES of the vessel segment injured by balloon angioplasty, factors such as stent underexpansion, stent overexpansion, and nonuniform distribution of stent struts have been associated with post-DES restenosis. Current evidence suggests that inadequate, though predominantly focal, delivery of the antiproliferative agent (sirolimus or paclitaxel) into the vessel wall is likely the common cause of post-DES restenosis. There is no consensus at present on how to treat post-DES restenosis. Long-term results reported to date on small numbers of patients undergoing interventional treatment for post-DES restenosis appear to be worse than outcomes observed after the index intervention, regardless of whether another DES was implanted or not, and warrant further study.     

Can we afford to eliminate restenosis? Can we afford not to?

Over the past decade, coronary stenting has emerged as the dominant form of percutaneous coronary revascularization. However, bare metal stents remain limited by a high incidence of restenosis, leading to frequent repeat revascularization procedures and substantial economic burden. Antiproliferative drug-eluting stents (DES) have recently demonstrated dramatic reductions in rates of restenosis, compared with conventional stenting, but important concerns about their costs have been raised. In this article, we summarize current evidence on the economic impact of restenosis and explore the potential benefits and economic outcomes of DES. In addition to examining the long-term costs of this promising technology, we consider the potential cost-effectiveness of DES from a health care system perspective and the impact of specific patient, lesion, and provider characteristics on these parameters.     

Drug-eluting stents: a critique

Despite advances in the design of balloons and stents, restenosis remains a major drawback of coronary angioplasty. Multiple randomised trials have demonstrated that drug-eluting stents (DES) can significantly reduce rates of restenosis by 60-75% across both lesion and patient subsets. In recent years there has been an exponential increase in the worldwide use of DES. This expansion has occurred as a result of an enthusiastic extrapolation of results from randomised trials leading to "off-label" use of DES in anatomical or clinical high-risk scenarios, or both. However, emerging medium- to long-term follow-up data have raised concerns about the safety of DES. A number of analyses have recently shown increased rates of late stent thrombosis in patients with DES. The exact mechanisms leading to stent thrombosis remain unclear. This article critically reviews the available efficacy and safety data on DES and discusses the factors influencing our current practice and perception of the net value of DES.     

The risks and benefits of drug-eluting stents in the setting of STEMI

Primary percutaneous coronary intervention (PCI) represents the treatment of choice in patients with ST-segment elevation myocardial infarction (STEMI). In randomized trials excluding STEMI patients, using drug-eluting stents (DES) significantly reduced angiographic restenosis and target vessel revascularization compared with bare metal stents (BMS); however, concerns exist regarding an increased follow-up incidence of stent thrombosis after DES implantation. This complication, which is associated with higher mortality and morbidity rates, may be more frequent among STEMI patients receiving DES versus BMS. Various registries, randomized trials, and two recent meta-analyses on patients undergoing primary PCI have shown that using DES is safe and is associated with significantly reduced rates of restenosis and repeat intervention without an increased risk of myocardial infarction or stent thrombosis at intermediate-term follow-up. However, large trials with hard clinical end points and longer follow-up are needed before routine DES use can be recommended in patients undergoing primary PCI.     

Kissing drug-eluting balloons for the treatment of unprotected distal left main bifurcation drug-eluting stent restenosis

The advent of drug-eluting stents (DES) associated with improvements in interventional techniques, encouraged the use of percutaneous coronary intervention (PCI) for unprotected left main (ULM) stenosis because of the lower need of repeat revascularization compared to the bare-metal stents (BMS). Nevertheless, ULM DES in-stent restenosis (ISR) continues to occur. The choice of treatment strategy (medical treatment, repeated PCI, or coronary artery bypass graft) for ULM DES-ISR depends primarily on several clinical and angiographic factors, making optimal patient selection crucial in the appropriate treatment of ULM-ISR lesions and achievement of favorable long-term outcomes. We describe in this report a successful modern approach to manage a distal ULM DES-ISR following a 2-stent strategy, consisting in the kissing inflation of two DEBs in both branches of the bifurcation.     

Review of randomized clinical trials of drug-eluting stents for the prevention of in-stent restenosis

Drug-eluting stents (DESs) have shown significant promise at reducing rates of restenosis and subsequent revascularization compared with bare metal stents (BMSs). The purpose of this report is to provide a systematic review of the randomized clinical trials that have evaluated the efficacy and safety of DESs. A total of 28 randomized clinical trials were identified: 21 comparing a DES (sirolimus, paclitaxel, ABT-578, actinomycin, everolimus, or 7-hexanoyltaxol) with a BMS and 7 comparing a DES with another DES (sirolimus vs paclitaxel). Early sirolimus and polymeric paclitaxel studies in low-risk populations demonstrated marked reductions in restenosis according to angiographic and clinical parameters, compared with BMSs. These promising findings led to the more recent evaluations of DESs in higher risk patients in controlled and head-to-head comparisons. In these subsequent trials, sirolimus and paclitaxel DESs continued to exceed the therapeutic potential of BMSs, with a slight but consistent angiographic advantage being observed with the sirolimus DESs.     

How to approach drug-eluting stent restenosis

Drug-eluting stents (DES) have been a major advance in percutaneous coronary intervention reducing restenosis and repeat revascularization. The application of DES to the treatment of complex lesion and patient subsets has resulted in significant rates of DES restenosis or failure. Though predominantly focal, substantial rates of non-focal DES restenosis are being observed. Non-focal disease most likely represents a resistant process that will remain a therapeutic challenge. An understanding of the causative mechanical and biological factors is essential for the prevention and treatment of DES restenosis. Robust data relating to the treatment efficacy for this problem is lacking. At present, repeat DES or vascular brachytherapy appear to the best available options. Evidence from randomized controlled trials and large registries is required to establish a formal treatment approach. We provide guidelines based on current available evidence.     

Bifurcation lesions.

The introduction of drug-eluting stents has significantly improved the immediate and long-term results following treatment of bifurcation coronary lesions. Despite these improvements, few questions are still without a clear answer. Among them the most important one is the need to use two stents vs provisional side branch stenting in true bifurcations. At present time the approach most frequently applied is to stent the main branch stenting to the side branch only for suboptimal results. In situations when the operator needs two stents as intention to treat we suggest the usage of the "Crush" or "V" technique. These two approaches have been utilized with good immediate and long-term results with sirolimus-eluting stents and with polymer-based paclitaxel-eluting stents. The usage of the "Crush" technique followed by final dilation of the side branch and with kissing balloon inflation has decreased. We recently evaluated results with this technique in 70 patients treated with sirolimus-eluting stents. The 6-month angiographic follow-up was available in 83% of the lesions and restenosis rate was 33% (7% main and side branches and 26% only side branch). No difference was observed in the restenosis rate on the main branch between lesions treated with final kissing balloon inflation and lesions without final kissing inflation (4% in the final kissing group vs 8% in the no final kissing group, p = 1.00). The restenosis rate on the side branch was lower in the final kissing group (17%) in comparison to the no final kissing group (42%) (p = 0.046). Similar results are achieved with polymer-based paclitaxel-eluting stents. The introduction of drug-eluting stents with selective usage of stenting the main and side branches applying the "Crush" or "V" techniques has significantly improved the results compared to bare metal stents in bifurcation lesions.     

Drug-eluting stents: caution and concerns for long-term outcome

Recent publications on drug-eluting stents (DES) report a significant reduction in restenosis rates as compared to bare metal stents in patients mostly with single vessel disease. We have recently observed however, late stent thrombosis following CYPHER DES implantation. The patient developed a hypersensitivity reaction around stent struts limited to the polymer with aneurysmal dilatation and extensive inflammation of the arterial wall in the absence of vascular healing. This incidence promotes a cautionary view and perhaps supports the use of DES only in high-risk patients.     

应用双药物洗脱支架治疗分叉病变的近远期临床疗效

目的探讨应用双药物洗脱支架（DES）治疗分叉病变的临床疗效。方法选择分支开口有严重狭窄且分支口径≥2．50mm的分叉病变患者为本研究的入选对象。2003年10月至2005年6月共入选应用双DES治疗分叉病变的患者112例,113处病变。分叉病变的类型为前降支／对角支62例（54．9％）,左冠状动脉主干分叉病变32例（28．3％）,回旋支／钝缘支18例（15．9％）,右冠状动脉远端分叉病变1例。113处分叉病变中采用Crush技术64处,“T”型支架置入27处;改良“Y”型支架置入11处;对吻支架置入5处;“V”型支架置入和Culotte技术置入各3处。结果入选112例患者113处分叉病变中（226处病变）使用Cypher或Cypher select DES 91个,TAXUS DES 74个,Firebird DES 67个。64处分叉病变采用Crush技术置入双支架后60处（93．7％）完成了最后的对吻球囊扩张技术。手术成功率为100％。住院期间1例发生亚急性血栓致急性心肌梗死（AMI）,再次介入治疗成功。住院期间心脏事件发生率（MACE,包括死亡、AMI、再次血管重建）为0．89％（1／112）。112例均完成了9个月的临床随访,无死亡发生,1例发生AMI由晚期血栓形成所致。48例完成了9个月的冠状动脉造影随访（42．9％）,8例发生了支架内再狭窄,其中1例进行了冠状动脉旁路移植术,5例再次行介入治疗,总再狭窄发生率为16．7％（8／48）。随访期间MACE发生率为8．04％（9／112）。结论本研究结果显示对于分支口径≥2．5mm且口部有严重狭窄性病变的分叉病变,采用双DES治疗是安全的,近、远期临床疗效是满意的。与Cypher DES相比较,TAXUS DES的再狭窄发生率有增加的趋势。     

Drug-eluting stents: towards new endpoints

Drug-eluting stents (DES) have significantly reduced the rates of in-stent restenosis (ISR). As previously observed with bare-metal stents (BMS), either patient's clinical characteristics and lesion morphology may influence the risk of recurrence even with DES. In this review we will focus on the most recent available data on clinical settings where DES efficacy on long-term outcomes are largely unknown. In particular, we report on very complex lesions (bifurcations, small vessels, chronic total occlusions, in-stent restenosis) myocardial infarction, multivessel disease, treatment of bypass graft and of unprotected left main disease. Several issues are still open on DES routinary use for these indications, mainly as far as stent thrombosis is concerned. Recent pathological studies show that DES are characterized by chronic inflammatory infiltrates and delayed endothelialization. Therefore, this effect could translate in a 'vulnerable period' for thromboses longer than with BMS. Even though large meta-analysis have excluded higher rates of stent thrombosis with DES rather than with BMS, few cases of unusual very late stent thrombosis have been described, pointing out that this problem seems to be still unsolved. Although DES provide better angiographic outcomes in each clinical setting, further randomized studies are running to assess their safety and efficacy on currently off-label indications.     

Titanium-nitride-oxide-coated Titan-2 bioactive coronary stent: a new breakthrough in interventional cardiology

The introduction of drug-eluting stents (DES) has revolutionized the field of interventional cardiology, since it has reduced the incidence of restenosis by 50% to 70%. However, recent worrisome data from registries and meta-analyses emphasized higher rates of late and very late stent thrombosis associated with DES. The recently introduced titanium-nitride-oxide-coated stent bioactive stent (Titan-2) was manufactured by a proprietary process to coat titanium-nitride-oxide on the surface of the stainless steel stent, based on a plasma technology using the nano-synthesis of gas and metal. This late-breaking stent has demonstrated an excellent biocompatibility, as reflected by lower rates of platelet aggregation and fibrin deposition, and better endothelialization. Preclinical and clinical trials and registries involving real-life unselected populations have shown a low rate of major adverse cardiac events at long-term follow-up. Restenosis rates were comparable with those of DES, with very rare stent thrombosis. Equally favorable results have been obtained in patients at high-risk of in-stent restenosis, such as diabetics and those with small coronary arteries. Results in patients presenting with acute coronary syndrome have been again comparable to those of DES, with tendency to lower rates of myocardial infarction and stent thrombosis. Comparisons with second generation drug-eluting stents have also been promising.     

The fine balance of quality and quantity: the time has come to define quality of PCI!

Drug‐eluting stents (DES) have revolutionized the treatment of coronary bifurcation lesions. Among different DES types, sirolimus‐eluting stents (SES) showed better outcomes than paclitaxel‐eluting stents. Because novel sirolimus analogues have been implemented in DES, a prospective observational comparison was undertaken to compare major mammalian target of rapamycin inhibitor‐eluting stents in the treatment of bifurcation lesions according to the provisional T‐stenting and small protrusion (TAP) technique. Overall, 187 patients (165 men, 65 ± 10 years) were enrolled in the study: 80 patients received a SES, whereas zotarolimus‐eluting stents (ZES) were implanted in 53 patients and everolimus‐eluting stents (EvES) in 62 patients. Primary end‐point of the study was the 12‐month incidence of target bifurcation failure (TBF) defined as occurrence of cardiovascular death, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR) or angiographic documentation of >50% restenosis on the main vessel or TIMI flow <3 on the side branch. Groups were homogeneous according to main clinical and angiographic characteristics. Overall, 17 (9.1%) patients had TBF: 4 (2.1%) patients had nonfatal non‐ST‐segment elevation MI, 9 (4.8%) patients underwent TVR, and 6 (3.2%) patients had an angiographic restenosis. The rate of TBF was statistically different among the three groups (7.9% in SES group, 18% in ZES group, and 3.3% in EvES group, P = 0.024). Previous MI was associated with a worse outcome (P = 0.025), whereas final kissing balloon was associated with a better outcome (P = 0.045). In conclusion, in this prospective registry, significant differences between DES were found in the outcome of patients treated for coronary bifurcation lesions according to provisional TAP technique. Thus, prospective randomized trials in this field are needed. © 2010 Wiley‐Liss, Inc.     

Safety of drug-eluting stents in the coronary artery in ST-elevation myocardial infarction at a single high-volume medical center

Several trials have shown the effectiveness of drug-eluting stents (DES) in reducing restenosis. Acute ST-elevation myocardial infarction (STEMI) has been an exclusion criterion in most trials evaluating the safety and efficacy of DES. There is recent randomized trial data evaluating the use and safety of DES for acute myocardial infarction. However, there is a need for "real world" data on the efficacy and safety of DES in STEMI. A single-center retrospective analysis was performed on 188 consecutive patients with STEMI treated with primary or rescue coronary angioplasty between March 2004 and July 2005. The study consisted of 3 groups: 115 patients treated with paclitaxel-eluting stents, 55 with sirolimus-eluting stents, and 18 with bare metal stents. Outcomes were assessed from 12 to 28 months (mean 20, median 19) for major adverse cardiac events (MACEs) including myocardial infarction, in-stent thrombosis, clinical restenosis, and death. There were 4 in-stent thromboses in the paclitaxel group (3.4%) and 2 in-stent thromboses in the sirolimus group (3.6%). The thromboses ranged from acute (within 24 hours) to as late as 8 months. Clinical restenosis occurred in 4 patients (3.4%) in the paclitaxel group and in 2 patients (3.6%) in the sirolimus. None of the 18 patients with bare metal stents had thrombosis or clinical restenosis. There were 7 total deaths, all related to complications from the index STEMI: 1 in the bare metal group, 1 in the sirolimus group, and 5 in the paclitaxel group. The postdischarge MACE rate was 7% with no deaths. In conclusion, the use of DES in acute STEMI is associated with a low postdischarge MACE rate and a 3.5% in-stent thrombosis rate, which is similar to reported rates in earlier randomized trials.     

Focal in-stent restenosis and in-stent thrombosis within the same bare-metal stent 5 years after deployment in a saphenous vein graft

Complications of percutaneous coronary intervention include in-stent restenosis (ISR) and in-stent thrombosis (IST) which have different underlying pathophysiological processes and different treatment strategies. ISR is primarily due to excessive neointimal growth and occurs in 20-30% of bare-metal stents (BMS). Drug-eluting stents (DES) have decreased the rates of ISR (< 10%), but are potentially associated with increased IST related to delayed arterial healing and stent strut exposure. ISR of BMS typically occurs within 6 months of stent deployment. IST usually occurs within 12 months of DES deployment. We present a case of focal ISR and IST within the same BMS, confirmed with intravascular ultrasound, 5 years after deployment in a saphenous vein graft.     

药物洗脱支架引起的去内皮化与支架内血栓形成机制的研究新进展

药物洗脱支架(DES)因其显著的低支架再狭窄(ISR)发生率,在动脉粥样硬化性疾病中广泛应用。但是,大量研究发现,置入DES的患者发生支架内血栓形成的风险呈上升趋势。相关研究表明,支架内血栓形成的发生与支架血管内皮损伤紧密相连。损伤的内皮层可引起血小板黏附聚集、支架梁异位或支架内新生动脉粥样硬化形成。因此,本文就DES引起的内皮损伤和支架内血栓形成的具体相关机制以及目前研究的生物可降解支架对防御支架内血栓形成的作用做一简要概述。