Endothelial Progenitor Cell Capture Stent Research Articles

Three-Year Clinical Follow-Up of an Unselected Patient Population Treated with the Genous Endothelial Progenitor Cell Capturing Stent

We assessed the 3-year clinical outcome in our single-center cohort of mainly unselected patients treated with the endothelial progenitor cell capturing stent (ECS). The ECS is coated with CD34+ antibodies specifically targeting the circulating endothelial progenitor cells population to accelerate endothelialization that in turn may prevent the occurrence of in-stent restenosis and stent thrombosis (ST). All patients in our study had coronary artery lesions that were treated with an ECS. The majority of patients had complex lesions with an estimated high risk of restenosis. A total of 405 patients were enrolled. The primary end-point of target lesion failure (TLF) was defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR). At 3 years, TLF was 18.3% and TLR was 14.2%. Early ST occurred in 2 patients. No cases of late and very late definite ST were reported. This single-center study demonstrates the safety at 3 years of the ECS in an unselected patient population, including a fair number of patients with complex lesions, reflecting daily practice. Our data compare well with drug-eluting stent and bare metal stent registries enrolling unselected patient populations. Importantly, in our analysis, no cases of late or very late definite ST were reported.

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

To study the effect of endothelial progenitor cell (EPC) capture on the vascular response to coronary stenting. 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. 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. 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.

Final results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody coated stent (Genous™Stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients

ObjectiveTo assess the safety and efficacy of the Genous™ endothelial progenitor cell (EPC) capturing stent in conjunction with HmG-CoA-reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions. Methods and resultsThe HEALING IIB study was a multi-center, prospective trial, including 100 patients. The primary efficacy endpoint was late luminal loss by QCA at 6-month follow-up (FU). Although statin therapy increased relative EPC levels by 5.6-fold, the angiographic outcome at 6 month FU was not improved in patients with an overall in-stent late luminal loss of 0.76±0.50mm. The composite major adverse cardiac events (MACE) rate was 9.4%, whereas 6.3% clinically justified target lesion revascularizations (TLRs) were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified in-stent thrombosis. At 12 month FU, MACE and TLR increased to 15.6% and 11.5% respectively and stabilized until 24 month FU. 18 Month angiographic FU showed a significant decrease in late luminal loss (0.67±0.54, 11.8% reduction or 10% by matched serial analysis, P=0.001). ConclusionThe HEALING IIB study suggests that statin therapy in combination with the EPC capture stent does not contribute to a reduction of in-stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it did not improve the angiographic outcome of the bio-engineered EPC capture stent. Remarkably, angiographic late loss was significantly reduced between 6 and 18 months.

Prospective randomised trial evaluating a paclitaxel-coated balloon in patients treated with endothelial progenitor cell capturing stents for de novo coronary artery disease

BackgroundPercutaneous coronary intervention with stent implantation is limited by the occurrence of re-stenosis and the risk of stent thromboses.ObjectiveTo define the impact of paclitaxel-coated balloon angioplasty plus endothelial progenitor cell...

Effectiveness and Safety of the Genous Endothelial Progenitor Cell-Capture Stent in Acute ST-Elevation Myocardial Infarction

The endothelial progenitor cell (EPC)-capture stent promotes endothelialization and preliminary studies have suggested its safety and feasibility in ST-elevation myocardial infarction (STEMI). Detailed late clinical follow-up and angiographic analyses are, however, limited. We sought to determine late angiographic and clinical outcomes of the Genous EPC-capture stent in primary angioplasty. EPC-capture stents were implanted during primary angioplasty in 489 consecutive patients presenting with STEMI from 2004 through 2008. The first 100 consenting patients undergoing successful stent implantation scheduled to undergo relook coronary angiography at 6 to 12 months were enrolled. Ninety-five patients with 96 lesions were analyzed independently. Mean duration of follow-up coronary angiography was 245 days. In-stent late luminal loss measured 0.87 ± 0.67 mm. Binary restenosis (defined as >50% diameter stenosis) was 28%, with diffuse in-stent restenosis (Mehran class II) as the predominant pattern. Of 27 patients with binary restenosis, 14 (52%) were symptomatic, with 10 patients undergoing target lesion revascularization. Asymptomatic patients had significantly larger reference vessel and in-stent minimal luminal diameters (2.77 ± 0.39 vs 2.54 ± 0.44 mm, p = 0.040; 2.74 ± 0.34 vs 2.31 ± 0.72 mm, p = 0.004, respectively). Follow-up late loss and diameter stenoses were also in favor of the asymptomatic group. Major adverse cardiac event rate was 16% at a mean follow-up of 34 months. There were no cases of Academic Research Consortium-defined stent thrombosis. In conclusion, implantation of the EPC-capture stent during primary angioplasty is associated with a favorable late clinical outcome but with higher than anticipated angiographic late loss.

Coronary revascularisation with Genous stent helps reduce the waiting time for lung resection

Patients suitable for lung resection for primary lung cancer and with myocardial ischaemia due to significant coronary artery stenosis, despite optimal medical therapy, are considered for either percutaneous or surgical revascularisation prior to thoracic surgery. Percutaneous coronary intervention (PCI) with bare metal stent (BMS) requires patients to initially receive dual anti-platelet therapy of clopidogrel and aspirin for at least 6 weeks, which delays the waiting time for curative lung resection. We report the successful use of the Genous endothelial progenitor cell (EPC) capture stent in two patients requiring PCI for significant coronary artery disease prior to lung resection. Following PCI with Genous stent implantation, both patients received dual anti-platelet therapy for 1 week. Clopidogrel was then discontinued and a week later both safely underwent curative lung resection receiving aspirin alone. At 6 months' follow-up, neither patient had symptoms or electrocardiograph changes suggestive of angina. Our report suggests that in patients requiring PCI prior to lung resection the Genous EPC capture stent is suitable and reduces their waiting time for surgical resection to 2 weeks instead of 6.

Endothelial progenitor cell capturing stent and short dual antiplatelet therapy in patients on chronic anti-vitamin k regimen undergoing percutaneous coronary interventions: long-term outcomes of a single centre registry

To evaluate outcomes of the endothelial progenitor cell (EPC) capture stent in patients on chronic anti-vitamin K (AVK) regimen, requiring percutaneous coronary intervention (PCI). Between February 2007 and February 2008, 78 consecutive patients under chronic AVK treatment undergoing PCI were enrolled in the registry and received an EPC capture stent. The incidence of comorbid conditions was analysed by the Charlson index. Dual antiplatelet therapy (DAT, aspirin and clopidogrel) was prescribed for one month only together with the AVK treatment, after PCI. Major adverse clinical events (MACE) rate, included death, acute myocardial infarction (MI) or target lesion revascularisation (TLR), incidence of stent thrombosis and rate of haemorrhagic events were collected. A?Charlson index >3 was present in 89% of patients. At 14±8 months the cumulative rate of MACE was 22%: 10 deaths (six cardiac deaths), and six TLR. No MI or definitive/probable stent thromboses occurred during follow-up. Four major haemorrhagic episodes occurred during follow-up, all of them after the first month. Patients on AVK treatment represent a highly comorbid population with a high event rate after PCI. The strategy of PCI with an EPC capture stent and short duration of DAT may be used in patients who need a short-term DAT.

Percutaneous coronary interventions with an endothelial progenitor cell capture stent (EPC) for high risk patients with no option for drug eluting stents: long term clinical outcomes of a single centre registry

Drug eluting stents (DES) are currently considered the gold standard for reducing restenosis of coronary artery lesions. Owing to their effect on the healing process, DES use requires mandatory prolonged dual antiplatelet therapy (DAT). The endothelial progenitor cell (EPC) capture stent, attracting circulating EPCs, promotes vascular healing and allows a short post-procedural period of DAT. The aim of the present study was to evaluate the short and long term clinical outcomes of the use of the Genos R stent™ in a selected high risk population with "no option" for DES. From December 2005 to October 2008, 61 high risk patients with clear contraindications to a prolonged period of DAT who underwent PCI with EPC capture stent implantation in our institution were prospectively selected and analysed. Technical success rate was 100%. Procedural success rate was 95.1%. After two years, major adverse cardiovascular events (MACE) free survival was 80.6%. According to the Academic Research Consortium definitions, cardiac death occurred in 1.6% of patients, and re-infarction, target lesion revascularisation (TLR), and target vessel revascularisation (TVR) occurred in 6.6%, 9.8%, and 11.5% of patients, respectively. Definite stent thrombosis occurred in one patient (specifically at 0 days). In patients who underwent surgery, no post-procedural MACE and no stent thrombosis were recorded. EPC capture stent implantation in high-risk patients with no option for DES seems encouraging, with satisfactory clinical outcomes both at short and at long term follow-up.

Replay to the article by Wendel HP et al.: Endothelial progenitor cell capture stents — Hype or hope?

We are grateful to Wendel et al. for their article elucidating mechanisms and problems about cell capturing stents. This interesting paper give rise to some remarks regarding the beneficial impact of new devices and drug on reducing the incidence of the most important complication associated with stent implantation during percutaneous coronary intervention (PCI).

One-year clinical outcome after provisional T-stenting for bifurcation lesions with the endothelial progenitor cell capturing stent compared with the bare-metal stent

Objective Currently no data exists regarding the outcomes after the novel endothelial progenitor cell capturing stent (EPCcS) placement in bifurcation lesions using a provisional T-stenting. This study evaluates the 1-year clinical outcome in patients treated with the EPCcS for a bifurcation lesion using a provisional T-stenting technique and compared these to a historical control group treated with an identical bare-metal stent (BMS). Methods In single-center study, 178 consecutive patients with a de novo bifurcation lesion treated with an EPCcS and 465 consecutive patients treated with an equivalent BMS were included. Multivariate and propensity-score analyses were performed to adjust for differences in clinical and angiographic characteristics between the EPCcS group and the BMS group. Results At 1-year, the cumulative rate of the primary end point (cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR)) was 12.4% in the EPCcS group and 17.2% in the BMS group (hazard ratio [HR] 0.70; 95% confidence interval CI, 0.44–1.12; P = 0.13). The 1-year cumulative rate of TLR was lower among patients treated with EPCcS compared with the control stent as a result of fewer coronary artery bypass grafting, 10.7% vs. 12% respectively (HR 0.88; 95% CI, 0.53–1.49; P = 0.64). The cumulative rate of definite ST was 0.6% in the EPCcS as compared with 0.4% in the BMS group. Conclusions Although, the EPC stent shows favorable outcomes in the treatment of bifurcation lesions, the reduction in the cumulative rate of cardiac death, MI, or TLR as compared with the BMS was statistically non-significant.

Successful use of endothelial progenitor cell capture stents in a coronary artery disease patient with aspirin hypersensitivity who failed initial aspirin desensitization

A 56-year-old man with history of G6PD deficiency and aspirin-induced asthma presented with acute coronary syndrome. He complained of sudden onset of chest pain on the day of admission. Electrocardiography revealed dynamic ST changes in lead V1 and V2; troponon-I level was elevated at 7.05ng/mL (normal: <0.04ng/mL); creatinine phosphokinase level was normal. His clinical condition was stabilized with a course of subcutaneous injection of low-molecular-weight heparin (LMWH), clopidogrel, and statin.

Two‐Year Clinical Registry Follow‐up of Endothelial Progenitor Cell Capture Stent Versus Sirolimus‐Eluting Bioabsorbable Polymer‐Coated Stent Versus Bare Metal Stents in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction

Endothelial progenitor cell (EPC) capture stent is designed to promote rapid endothelization and healing and is potentially useful in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We studied the intermediate-term efficacy and safety of EPC stent and compared that with sirolimus-eluting bioabsorbable polymer stent (CURA) and bare metal stent (BMS) in AMI patients. Patients presenting with AMI who underwent primary PCI with the respective stents between January 2004 and June 2006 were enrolled in the single-center clinical registry. The study end-points were major adverse cardiac events (MACE) and stent thrombosis. A total of 366 patients (EPC = 95, CURA = 53, BMS 218) were enrolled. Baseline demographics including age, gender, diabetes, renal impairment, predischarge left ventricular ejection fraction, and creatinine kinase level were comparable among the groups. Procedural success rate was 99.5%. Post-procedural thrombolysis in myocardial infarction (TIMI) 3 flow was achieved in EPC 91.6%, CURA 96.2%, and BMS 88.5% (P = 0.209). At 2 years, the MACE rate was EPC 13.7%, CURA 15.1%, and BMS 19.7% (P = 0.383). Target vessel revascularizations (TVR) were EPC 4.2%, CURA 9.4%, and BMS 6.0% (P = 0.439). Nonfatal myocardial infarctions were EPC 1.1%, CURA 3.8%, and BMS 4.1% (P = 0.364). One patient in the EPC group had acute stent thrombosis. There was no late stent thrombosis in the EPC group. EPC stent appeared to be safe and had comparable clinical efficacy with a BMS when used in the AMI setting. At 2-year follow-up, the EPC group showed favorable, single-digit TVR rate and stent thrombosis remained a low-event occurrence.

Endothelial progenitor cell capture stents: will this technology find its niche in contemporary practice?

Drug-eluting stents (DES) have significantly reduced rates of restenosis; however, elution from their surface of cytotoxic and cytostatic drugs, together with the presence of non-erodable polymers, is associated with impaired endothelialization, allergic reactions, inflammation, and vascular dysfunction, factors which have all been implicated in the most prominent safety concern with DES today —stent thrombosis (ST).1–3 The development of newer DES with polymers that are either more biocompatible, biodegradable, or completely absent, together with completely biodegradable stents has been an important step forward to minimize the potential risk of ST. Despite this, however, the rapid restoration of a functional endothelium appears, in theory at least, to be one of the most intuitive ways of minimizing the risk of ST and excessive neointimal proliferation.4 Therefore, it comes as no surprise that soon after the discovery of endothelial progenitor cells (EPCs),5 a novel coronary stent, the Genous™ EPC capture stent (OrbusNeich, Florida, USA), was developed which had a proprietary coating that contained anti-human CD34 antibodies ( Figure 1 ). These antibodies were able to capture circulating EPCs, such that the EPC capture stent was considered a potential solution to many of the problems of coronary stenting. Figure 1 Schematic diagram illustrating the underlying principal behind the EPC capture stent. The CD-34 antigen on the EPC binds to the anti CD-34 antibody on the stent's surface to promote rapid endothelialisation. Six years on, and Beijk et al. 6 report the 1-year outcomes of the TRIAS HR study, the first randomized study comparing the Genous™ EPC stent with a conventional DES (the Taxus Liberte stent). This study adds to the paucity of data already available on the EPC stent, and disappointingly reaffirms the disparity between technological promise and real-life clinical results. Prior to the completion of 1-year follow-up this single-centre study was transformed into … *Corresponding author. Tel: +31 10 7035260, Fax: +31 10 4369154, Email: p.w.j.c.serruys{at}erasmusmc.nl

Endothelial progenitor cell capture stent implantation in patients with ST-segment elevation acute myocardial infarction: one year follow-up

The Genous endothelial progenitor cell (EPC) capture stent is a bioengineered R stent coated with immobilised antibodies on its stent struts to allow for the capture of circulating EPCs to promote rapid endothelisation. We assessed the impact of this stent in the primary percutaneous coronary intervention (PCI) of patients with acute ST-elevation myocardial infarction (STEMI) and examined its long term clinical outcomes. All patients with acute STEMI without cardiogenic shock who underwent primary PCI between January 2005 and April 2007 and received the stent were enrolled in the study. The study endpoints were major adverse cardiac events (MACE) defined as death, MI and target vessel revascularisation (TVR) at 30 days, six months and one year. A total of 321 enrolled patients received 357 EPC capture stents during the study period. The cohort comprises 81.0% males with mean age of 54.6+/-11.6 years. The mean stent length used was 20.98+/-5.50 mm and mean stent size was 2.99+/-0.32 mm. Ninety-four percent of patients achieved Thrombolysis in Myocardial Infarction (TIMI) 3 flow post-procedurally. The cumulative MACE rate was 8.1% at 30 days, 10.0% at six months and 12.2% at one year. There was one patient who developed acute stent thrombosis and another two with subacute stent thromboses. No late thrombosis or late cardiac mortality was observed in our cohort. The need for TVR was 4.4% at one year. The use of EPC capture stents in patients who underwent primary PCI for STEMI is safe and showed good clinical outcomes, with low rates of TVR and no late stent thrombosis.

Successful use of endothelial progenitor cell capture stent in a de novo lesion previously covered by vascular brachytherapy

New lesion developed in an area which had received vascular brachytherapy poses a clinical dilemma. We report the successful use of endothelial progenitor cell capture stent implantation to treat this lesion sub-type, with no observed adverse event after withdrawal of clopidogrel.

Late Stent Thrombosis After Drug-Eluting Stent

Following the inspiration of Dr S. Windecker, the team from Bern, Switzerland, has contributed >30 studies on drug-eluting stent efficacy and safety, several of which represent essential pieces in the puzzle. The article in this issue of Circulation by Cook et al1 belongs to that select group of key references. The series of robust and detailed reports on the Bern-Rotterdam cohort studies have coined the 0.6% yearly linear rate of definite late stent thrombosis associated with the permanent coronary implantation of first-generation drug-eluting stents.2 Intravascular ultrasound imaging of the thrombosed stents has revealed the strong association of incomplete strut apposition with the event.3 At the same time, collective analysis of all the available evidence4 demonstrated that a reduction in restenosis with drug-eluting stents prevented adverse events caused by the treatment of the more frequent recurrences with bare metal stents. With the former compensating for the latter, the net result of this balancing act between safety and efficacy resulted in no difference in death and myocardial infarction rates up to 4 years after the initial procedure. Article see p 391 In the present study, late hypersensitivity reaction was identified as a cause for late stent thrombosis, in association with stent malapposition caused by necrotizing vasculitis around the stent struts. Histopathological analysis of aspirated thrombus showed eosinophilic infiltration typical for type IVb hypersensitivity reaction following implantation of sirolimus-eluting stents. Macrophage infiltration typical for type IVc hypersensitivity was seen with paclitaxel-eluting stents. The biomarker gradient between coronary and peripheral blood was significant for high-sensitivity C-reactive protein and myeloid-related protein 8/14, both markers of local inflammatory reaction. These patterns were not observed with early drug-eluting stent thrombosis, early …

Endothelial progenitor cell capture stents — hype or hope?

The first report of late stent thrombosis leading to acute myocardial infarction in patients receiving the new CD34 antibody coated endothelial progenitor cell (EPC) capture stent may cast doubts on this technology. In our letter we review the potential risks and benefits of these stent types and give a short overview of recent alternative stent coatings for in vivo self endothelialization by using peptides, magnetic molecules or aptamers. Drawbacks with EPC capture stents should not lead to condemning this strategy in general, but rather stimulate research efforts to develop more suited capture molecules and more sophisticated coatings for the post-DES era towards more biological coatings which mimicry progenitor cell homing factors for rapid vascular wall regeneration.

Genous™ endothelial progenitor cell-capturing stent system: a novel stent technology

Drug-eluting stents have been demonstrated to significantly reduce clinical and angiographic restenosis in patients with coronary artery disease compared with bare-metal stents. Intuitively, however, a prohealing approach for the prevention of in-stent restenosis by promoting accelerated re-endothelialization is favored over the aggressive pharmacologic cytotoxic and cytostatic approach of the drug-eluting stents. The endothelial progenitor cell-capturing stent attracts circulating CD43+ progenitor cells that bind to the stent surface and differentiate into a functional endothelial layer. It is theorized that the accelerated establishment of the endothelial layer covering the stent struts will reduce the risk of neointimal hyperplasia and smooth muscle cell proliferation. The safety and efficacy have been demonstrated in the nonrandomized Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth (HEALING) studies, and the device received a CE mark in 2005. This article reviews the realization of the endothelial progenitor cell-capturing stent, its relevance compared with other stent types, current evidence on clinical performance, and future perspectives. At present, the larger randomized Tri-stent Adjudication Study (TRIAS) that is ongoing will directly compare the clinical usefulness of this new endothelial progenitor cell-capturing stent with bare-metal stents and drug-eluting stents.

Successful use of endothelial progenitor cell capture stents in two cases of acute coronary syndrome complicated by major bleeding episodes

We report on the successful use of endothelial progenitor cell (EPC) capture stents in 2 cases of acute myocardial infarction (MI) that was complicated by major bleeding episodes requiring blood transfusion and necessitating early discontinuation of anti-thrombotic/anti-plaletet agents.

AS-4: Routine Use of a New Endothelial Progenitor Cell Antibody-Coated Stent in Patients with Primary PCI for ST-Elevation Myocardial Infarction: A Prospective Registry

Although endothelial progenitor cell (EPC) capture stent may be safe in theory and may even prevent stent thrombosis and restenosis, there are only limited data on its use in primary percutaneous intervention. This study was intended to assess the safety of routine use a new EPC antibody-coated stents in patients with primary PCI for ST-elevation myocardial infarction (STEMI).