Percutaneous treatment of a coronary aneurysm by stent graft and drug-eluting stent implantation: a potential method to reduce stent graft restenosis

Coronary artery aneurysms (CAAs) can occur congenitally or secondary to specific disorders such as Kawasaki disease or atherosclerosis. Apart from a surgical approach, CAA can be treated by coronary stent graft (CSG) implantation. However, restenosis is frequent after CSG placement, precluding a wider use of this technique. We hypothesized that implantation of a drug-eluting stent (DES) within a CSG could be of use to avoid CSG restenosis. We report the case of a patient with a large aneurysm of the right coronary artery who underwent CSG implantation followed by DES placement. The immediate angiographic result showed complete exclusion of the aneurysm. Intravascular ultrasound confirmed good apposition of both the CSG and DES. Follow-up angiography after 23 weeks demonstrated a good long-term result without restenosis. The patient has remained asymptomatic during 12 months of follow-up. In conclusion, the present case suggests that CSG placement followed by DES implantation is a safe and effective approach to treat coronary aneurysms interventionally.     

The role of optical coherence tomography in coronary intervention

Optical coherence tomography (OCT) is an optical analog of intravascular ultrasound (IVUS) that can be used to examine the coronary arteries and has 10-fold higher resolution than IVUS. Based on polarization properties, OCT can differentiate tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identify thin-cap fibroatheroma. Because of the strong attenuation of light by blood, OCT systems required the removal of blood during OCT examinations. A recently developed frequency-domain OCT system has a faster frame rate and pullback speed, making the OCT procedure more user-friendly and not requiring proximal balloon occlusion. During percutaneous coronary intervention (PCI), OCT can provide detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition [ISA]). At follow-up examinations after stent implantation, stent strut coverage and ISA can be assessed. Several OCT studies have demonstrated delayed neointimal coverage following drug-eluting stent (DES) implantation vs. bare metal stent (BMS) placement. While newer DESs promote more favorable vascular healing, the clinical implications remain unknown. Recent OCT studies have provided insights into restenotic tissue characteristics; DES restenotic morphologies differ from those with BMSs. OCT is a novel, promising imaging modality; with more in-depth assessments of its use, it may impact clinical outcomes in patients with symptomatic coronary artery disease.     

冠状动脉小血管病变中药物球囊的应用进展

既往研究表明,冠状动脉小血管病变在植入药物洗脱支架后容易发生支架内再狭窄和支架内血栓,因此成为近年来冠状动脉介入领域的难题.药物涂层球囊(DCB)作为冠状动脉介入领域中的一种新兴技术,可在不植入支架的情况下将抗增殖药物快速和均匀地释放到血管壁,抑制新生内膜的过度增生.越来越多的研究表明DCB对冠状动脉小血管病变有较好的...     

Sirolimus-eluting stents for the prevention of restenosis in a worst-case scenario of diffuse and recurrent in-stent restenosis.

For recurrent in-stent restenosis (ISR), surgical revascularization or brachytherapy is still the principal therapeutic options. The present investigation explores the efficacy of a sirolimus-eluting stent to prevent restenosis in these lesions with a high risk of recurrence. In 22 consecutive patients with a recurrent and diffuse ISR, a sirolimus-eluting stent was implanted to cover the restenotic lesion. All patients were followed clinically for at least 1 year and underwent a repeat angiography after 7 months. A quantitative coronary angiographic analysis was done. The target vessel failure was 14% in the sirolimus-eluting stent group, with an angiographic late loss of only 0.39 +/- 0.54. No subacute stent thrombosis was observed, and the 1-year event-free survival was 86%. The three cases with restenosis were all focal and could be successfully treated by additional drug-eluting stent implantation. This study showed the efficacy of a sirolimus-eluting stent for the prevention of restenosis in a worst-case scenario of recurrent and diffuse ISR. The observed restenosis rate is lower than that reported after brachytherapy and suggests that sirolimus-eluting stents are a promising treatment option for ISR.     

药物洗脱支架置人术后断裂导致支架内再狭窄的临床分析

目的 探讨药物洗脱支架(DES)置入术后支架断裂与再狭窄的关系及支架断裂的特点.方法 回顾性分析冠状动脉支架置人术后行冠状动脉造影复查的536例患者,实验分为DES组(N=397)和裸金属支架(BMS)组(n=139).分析支架置入术前、术后及复查时的冠状动脉造影图像,找出支架内再狭窄和支架断裂的病例,分析支架断裂和再狭窄的关系以及支架断裂的病变特征及形态特征.结果 DES组和BMS组再狭窄分别为31例和30例(P＜0.01),其中5例发生支架断裂,断裂的支架均为DES,BMS组未见支架断裂,两组差异有统计学意义(P＜0.05).发生支架断裂的5例靶病变均为扭曲病变,支架断裂均发生在血管扭曲成角处.结论 支架断裂是DES置入术后发生再狭窄的原因之一,扭曲病变置入长的DES后可能容易发生支架断裂.     

Brachytherapy for restenosis after stenting for coronary artery disease: its role in the drug-eluting stent era

PURPOSE OF REVIEW: Recent years have brought remarkable changes to the field of interventional cardiology. The need for repeat intervention due to restenosis, the most vexing long-term failure of percutaneous coronary intervention, has been significantly reduced owing to the introduction of two major advances, the vascular brachytherapy (VBT) and the drug-eluting stents (DES). RECENT FINDINGS: Vascular brachytherapy has demonstrated its efficacy in limiting recurrence of existing in-stent restenosis. The past 2 years have sealed its reputation, with a variety of studies demonstrating its superiority over conventional therapy in challenging patient subsets with high risk for restenosis recurrence. Moreover, the long-term follow-up confirmed durability of this therapy, and the failures of VBT were characterized as easy to treat. Conversely, DES have shown spectacular efficacy at primarily preventing the first restenosis episode following the initial stent placement. Consequently, the role of VBT may be minimized, as the overall need for repeat revascularization is diminished as a result of the wide acceptance of DES. Furthermore, if the capacity of DES to treat in-stent restenosis is confirmed in randomized trials, they may eventually supersede VBT as the therapy of choice for in-stent restenosis. SUMMARY: At present, VBT is the proven and durable therapeutic choice for patients with complex, diffuse in-stent restenosis who would otherwise have a very poor prognosis for long-term event-free survival. DES have emerged as remarkably effective in minimizing the first restenosis occurrence; they also represent a promising and competitive alternative to VBT for the treatment of in-stent restenosis.     

Usefulness of coronary pressure measurement for functional evaluation of drug-eluting stent restenosis

Despite the widespread adoption of drug-eluting stent (DES) implantation, the optimal treatment of DES failures remains challenging. The present study evaluated the relation between quantitative angiography and the fractional flow reserve (FFR) in restenotic lesions after DES implantation and the efficacy of FFR in determining whether to treat these lesions. To assess their functional significance, the coronary pressure-derived FFR was measured in 50 DES restenotic lesions (49 patients). Additional intervention was performed in lesions with a FFR <0.8. Major adverse cardiac events were assessed at 12 months after the reintervention procedure. The mean percent diameter stenosis (%DS) was 58 ± 13%. Of the 50 lesions, 20 (40%) were deferred without additional intervention. The FFR and %DS had a negative correlation (r = -0.61, p <0.001). However, when only the lesions with diffuse-type restenosis (15 lesions) were analyzed, the degree of correlation decreased (r = -0.56, p = 0.12). Although most lesions (89%) with a %DS of ≥70 had significant functional ischemia, among 41 lesions with a %DS <70, only 20 (49%) had demonstrated functional patency. The incidence of adverse events during the 12 months of follow-up after FFR-guided treatment was 18.0% (23.3% in the FFR <0.80 group and 10.0% in FFR ≥0.80 group). In conclusion, a discrepancy was found between functional ischemia measured by the FFR and the angiographic %DS, in particular, in moderate- or diffuse-type restenotic lesions after DES implantation. The outcome of FFR-guided deferral in patients with DES in-stent restenosis seems favorable.     

Influence of stent design and deployment technique on neointima formation and vascular remodeling

A variety of different stent types is available for the treatment of coronary stenosis. However, in-stent restenosis remains the major limitation for the use of these devices. Intracoronary ultrasound (ICUS) in addition to coronary angiography provides precise measurements of coronary wall dimensions during stent implantation and of intimal hyperplasia during follow-up. The extent of coronary injury during stent implantation was shown to play an important role in neointima formation. It is characterized by endothelial exposure, intima laceration, and media permeation. Stent-induced coronary injury has been considered to depend on stent design and stent strut size with consecutive deep wall laceration. ICUS analysis showed a correlation between the stent design and the amount of neointimal tissue proliferation. The role of adventitial remodeling in the process of restenosis is discussed controversially. Post-procedural stent expansion may provoke adventitial remodeling. The stent design and stenting strategy determines the extent of peri- and post-procedural coronary injury. Post-procedural coronary morphologic changes and changes of the stent geometry depend upon the stent design. Beside further modifications as the use of drug-eluting stents the decrease of stent-related vessel injury should be an important criterion for the development of future stent design.     

Late-acquired incomplete stent apposition: morphologic characterization

Incomplete stent apposition (ISA) is a lack of contact between stents and the underlying vessel wall, best described by intravascular ultrasound (IVUS). Late acquired incomplete apposition, defined as complete stent apposition at the time of procedure but ISA at follow-up, is an unusual IVUS finding reported in intracoronary brachytherapy, bare-metal stent (BMS), and drug-eluting stent (DES) implantation. Late-acquired ISA is observed relatively more frequently with DES implantation compared with BMS implantation. Possible mechanisms of this phenomenon include focal/extensive vascular remodeling and dissolution of thrombus. While there are conflicting reports regarding the possible impact of this IVUS finding on clinical outcomes, recent reports of DES have suggested its possible association with late adverse cardiac events including late stent thrombosis. In this paper, we review the incidence, location, underlying pathology, and possible clinical sequelae of late-acquired ISA, primarily focusing on that of DES.     

Bioabsorbable and biocompatible stents. Is a new revolution coming?

With the introduction of drug-eluting stents (DES) the problem of restenosis after percutaneous stent implantation was partially resolved. In the first generation of DES a stainless steel platform was coated with a durable polymer eluting and controlling the release of an active restenotic drug. The impairment of re-endothelization after DES implantation, one of the causes of late stent thrombosis, was to some extent attributed to the properties of the durable polymer and/or drug that it eluted. The introduction of biodegradable platforms and biocompatible polymers may potentially address this issue. Modern technologies are being applied to improve the characteristics of biodegradable stents and find new active pharmacological agents or combinations of standard antirestenotic and antithrombotic drugs that can be eluted from the stents, in order to improve their safety profile and clinical utility.     

Observations and outcomes of definite and probable drug-eluting stent thrombosis seen at a single hospital in a four-year period

Stent thrombosis (ST) is a major safety concern after drug-eluting stent (DES) deployment, resulting in significant morbidity and mortality. The goal of this study was to examine the incidence, timing, clinical correlates, and outcomes after DES thrombosis in a real-world population. A retrospective analysis of 8,402 patients who underwent percutaneous coronary intervention and received a DES was performed. After DES implantation, 84 definite (DST) and 127 probable ST events occurred. The incidence of early DST was 0.8%, late DST was 0.4%, and very late DST was 0.4%. Multivariate analysis showed that a history of diabetes mellitus, myocardial infarction during admission, number of stents, and DES placement in a restenotic lesion were independently associated with DST. The incidence of early definite or probable ST (DPST) was 1.9%, late DPST was 1.4%, and very late DPST was 0.7%. Multivariate analysis showed that a history of diabetes, myocardial infarction during admission, cardiogenic shock, number of stents, and DES use in a restenotic lesion were independently associated with DPST. Both types of ST were associated with significantly higher rates of all-cause death, Q-wave myocardial infarction, and revascularization up to 24 months after DES implantation. In conclusion, ST after DES implantation in contemporary practice continues to occur from 30 days to 2 years at a rate > or =0.36%/year and is associated with high rates of morbidity and mortality. Diabetes mellitus, myocardial infarction, and DES use in a restenotic lesion were strongly associated with DST; therefore, careful consideration should apply when deploying a DES in these populations.     

血管内超声在冠状动脉药物洗脱支架晚期血栓研究中的应用

药物洗脱支架与金属裸支架相比,减少了再狭窄的发生率,但其长期安全性却引起了人们的注意。支架置入30 d以后出现的晚期支架内血栓问题成为目前介入心脏病学的研究热点。晚期支架内血栓发生率低,但一旦发生后果严重。有研究显示其发生的原因可能包括动脉的延迟愈合、动脉瘤形成及支架贴壁不良等。现就血管内超声在冠状动脉药物洗脱支架晚期血栓研究中的应用进展做一评述。     

Classification and Current Treatment Options of In-Stent Restenosis

Coronary stent implantation is currently performed in > 80% of percutaneous coronary interventions. Its main late complication is the development of in-stent restenosis (ISR), occurring in 10-80% of lesions treated in daily practice. The classification by Mehran et al. is most commonly used. Current therapeutic options to treat ISR include repeat balloon angioplasty, repeat stenting, cutting balloon angioplasty, directional coronary atherectomy, rotational coronary atherectomy, brachytherapy, and drug-eluting stents (DES). DES have been effective in reducing binary restenosis in de novo lesions in randomized controlled trials. The novel use of DES to treat ISR has been shown to be safe and effective in multiple studies involving sirolimus- and paclitaxel-eluting stents. As DES implantation becomes more widespread, ISR in DES is emerging as a new problem. The use of debulking techniques to treat ISR in DES is to be cautioned against. In this new era, the optimal treatment of this new problem is currently unknown. We await further data to see whether repeat DES implantation may help solve this vexing clinical problem.     

Coronary stent strut fracture after drug-eluting stent implantation: a newly recognized complication

Stent strut fracture (SSF) after drug-eluting stent (DES) implantation may be an important complication after DES implantation particularly in patients undergoing sirolimus eluting stent implantation. Since SSF is a highly relevant adverse event which can result in in-stent restenosis and thrombosis, we believe that DES with flexible stent platform or biodegradable DES may be needed to prevent this potential catastrophic complication.     

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.     

Opportunities and limitations of drug-coated balloons in interventional therapies

Drug-coated balloons (DCB) represent a novel clinical treatment modality for coronary and peripheral artery disease. Advantages over standard angioplasty and stent technologies including homogeneous drug delivery to the vessel wall, immediate drug release without the use of a polymer, the option of using balloon catheters alone or in combination with a bare metal stent, no foreign object that remains in the body, the potential of reducing antiplatelet therapy, and lower restenosis rates in some indications. As with drug-eluting stents (DES), one cannot assume a class effect for DCB. So far, data from randomized clinical trials identify the treatment of coronary in-stent restenosis (ISR) and of de novo and restenotic lesions in peripheral artery disease as viable options. Furthermore, treatment of de novo lesions in small coronary vessels, bifurcation lesions, long lesions, pediatric interventions, and cerebrovascular applications are potential beneficial indications. In the coronary application, a strategy of DCB angioplasty with provisional spot-stenting in the case of severe dissections may become a better alternative in long and complex lesions, bifurcations, or in patients with contraindications for DES.     

Comparison of bare metal stents versus drug-eluting stents on clinical decision making in patients with previous percutaneous coronary intervention admitted for suspected acute coronary syndrome

To determine whether the decreased rate of restenosis observed with drug-eluting stents (DES) has changed the treatment of patients with recurrent symptoms after stent placement, we compared patients hospitalized with presumed cardiac symptoms within 1 year after placement of either a DES or a bare metal stent (BMS). In this retrospective, single-center study, cases were identified from consecutive patients who received a DES from March 2003 to July 2004 or a BMS from August 2001 to June 2002. No differences were noted in the rate of hospitalization, hospitalization for presumed cardiac symptoms, use of coronary angiography in patients hospitalized for presumed cardiac symptoms, or average interval to hospitalization. In contrast, restenosis and the need for additional revascularization procedures were higher in the BMS group. The primary indication for additional revascularization was restenosis in the BMS group and progression of coronary artery disease in the DES group. In the DES group, the need for revascularization was significantly higher in patients with multi- versus single-vessel coronary artery disease (26% vs 7%, p < 0.05). In conclusion, the rate of hospitalization and use of coronary angiography in patients with recurrent symptoms were similar in patients who received a BMS or DES, despite the decreased rates of restenosis and additional revascularization procedures observed with DESs.     

Drug-eluting stents: What is the balance of risks and benefits?

Restenosis following bare metal stent (BMS) implantation has been the Achilles heel of percutaneous coronary intervention. When randomized trials showed dramatic reductions in restenosis and target-lesion revascularization in favor of drug-eluting stents (DES), they were widely embraced and soon used in 80% of percutaneous coronary interventions in the United States and some European centers. Consequently, the indications for stenting were pushed into uncharted territories. DES confirmed significant improvements in short-and mid-term outcomes as compared with BMS in real world registries. As the penetration of DES continued into patient and lesion subsets not formally tested in randomized trials, an entity characterized by sudden occlusion of the DES with an associated acute clinical syndrome was occasionally detected. The term late stent thrombosis was introduced to define this relatively new phenomenon, sometimes described with BMS as well. The absolute risk of stent thrombosis appears to be less than 2% throughout the first 3 years after stent implantation. DES thrombosis has provided a moment for pause to reconsider how to best use these new devices and what to expect from future ones.     

Intravascular ultrasound characterization of the "black hole" phenomenon after drug-eluting stent implantation

An intraluminal echolucent tissue, dubbed "black hole," has been identified by intravascular ultrasonography after intracoronary brachytherapy. This study reports the characteristics and incidence of the black hole in patients treated with drug-eluting stent implantation using a sirolimus-eluting stent (SES). We included intravascular ultrasound data from the Compassionate Use of Sirolimus-Eluting Stent (SECURE, n = 61 lesions) registry, a study involving patients in whom previous brachytherapy had failed, and the DIABETES trial (n = 165 lesions), a multicenter, randomized study comparing SES versus bare metal stents in diabetic patients. Intravascular ultrasound follow-up was scheduled at 8 months (SECURE trial, post-brachytherapy population) and 9 months (DIABETES trial). In the SECURE population, a black hole was observed in 10 patients (19.6%). Seven black hole segments had significant intimal hyperplasia (> 10%). A black hole accounted for 27% of total intraluminal tissue. In the DIABETES trial, 2 patients (2.5%) in the SES group and none in the bare metal stent group showed echolucent intimal hyperplasia. In conclusion, a black hole occurred frequently after implantation of a SES in patients in whom intracoronary brachytherapy had previously failed. Black holes were also identified in a nonirradiated population, although the incidence was lower than in the post-brachytherapy patients. Bare metal stents were not associated with this phenomenon.     

An intravascular ultrasound analysis of the mechanisms of restenosis comparing drug-eluting stents with brachytherapy

There are treatment failures after de novo drug-eluting stent (DES) implantation and after treatment with DESs or vascular brachytherapy (VBT) of in-stent restenosis (ISR) lesions. We studied 38 patients who presented with DES failure (26 patients after de novo DES implantation and 12 patients after DES treatment of ISR) and 30 patients who presented with VBT failure (all after treatment of ISR). Standard clinical data were collected and volumetric intravascular ultrasound was measured. Patients who presented with DES failures were 58.8 +/- 9.6 years of age and those who presented with VBT failures were 59.8 +/- 8.7 years of age; 60.5% of DES and 58.6% of VBT failures were in men; 31.5% of DES failures and 46.6% of VBT failures occurred in diabetic patients; and times to presentation were 210 +/- 101 days in DES failures and 510 +/- 527 days in VBT failures (p = 0.001). Minimal stent area was significantly larger in VBT than in the 2 DES failure groups (de novo DES implantation and DES treatment of ISR, p <0.0001); this was associated with more neointimal hyperplasia in VBT failures (p <0.0001). After it was normalized to stent length, intimal hyperplasia was diffusely distributed in VBT failures; conversely, DES failures were associated with less intimal hyperplasia and the intimal hyperplasia was mostly focal, with greater accumulation in the proximal and mid segments. In conclusion, VBT failures were caused by significant, recurrent, and diffuse intimal hyperplasia in the setting of adequate stent expansion, whereas DES failures were caused by only modest, but focal, intimal hyperplasia in the setting of DES underexpansion.