Five-year follow-up of the endothelial progenitor cell capturing stent versus the paxlitaxel-eluting stent in de novo coronary lesions with a high risk of coronary restenosis.

OBJECTIVES: To assess the long-term safety and clinical efficacy of the Genous endothelial progenitor cell capturing stent (ECS) compared with the TAXUS Liberté paclitaxel-eluting stent (PES) in lesions with a high risk of restenosis. BACKGROUND: Instead of the use of cytotoxic or cytostatic drugs in drug-eluting stents, a "pro-healing" approach in ECS may overcome impeded healing response due to delayed functional endothelialization of the stent struts. METHODS: In the prospective, randomized TRIAS pilot study 193 patients with coronary artery lesions carrying a high risk of restenosis were included (ECS: n = 98, PES: n = 95). The primary focus of this analysis was target vessel failure (TVF) at 5 years. Dual antiplatelet therapy was prescribed for ≥1 month after ECS and for ≥6 months after PES. RESULTS: At 5 years follow-up, no significant differences were found in TVF (ECS 24% vs. PES 29%, risk difference 95% confidence interval (RDCI) -17.3% to 7.4%). Between 2 and 5 years after the index procedure, low numbers of TVF were observed in ECS compared with PES (ECS 4% vs. PES 16%, RDCI -20.8% to -2.3%). There was no definite stent thrombosis in ECS compared with four patients in the PES group. CONCLUSION: This is the first randomized study providing very long-term clinical efficacy and safety of the ECS in lesions carrying a high risk of restenosis. At 5 years follow-up, TVF rates in ECS group are numerically lower compared with PES due to an increase of events between 2 and 5 years after the index procedure.

In situ Endothelialization: Bioengineering Considerations to Translation.

Improving patency rates of current cardiovascular implants remains a major challenge. It is widely accepted that regeneration of a healthy endothelium layer on biomaterials could yield the perfect blood-contacting surface. Earlier efforts in pre-seeding endothelial cells in vitro demonstrated success in enhancing patency, but translation to the clinic is largely hampered due to its impracticality. In situ endothelialization, which aims to create biomaterial surfaces capable of self-endothelializing upon implantation, appears to be an extremely promising solution, particularly with the utilization of endothelial progenitor cells (EPCs). Nevertheless, controlling cell behavior in situ using immobilized biomolecules or physical patterning can be complex, thus warranting careful consideration. This review aims to provide valuable insight into the rationale and recent developments in biomaterial strategies to enhance in situ endothelialization. In particular, a discussion on the important bio-/nanoengineering considerations and lessons learnt from clinical trials are presented to aid the future translation of this exciting paradigm.

Successful treatment of aortic root rupture following transcatheter aortic valve implantation in a heavily calcified aorta: a novel approach to a serious complication.

Aortic root rupture during transcatheter aortic valve implantation (TAVI) is an uncommon but almost uniformly fatal complication. We describe a novel surgical management of this complication using a combination of pledgeted sutures and prolonged direct digital compression with biomatrix and lattice adjuncts. Furthermore, our patient underwent percutaneous coronary intervention with endothelial progenitor cell-capturing stents, which facilitated TAVI to be performed off clopidogrel therapy. We believe the use of these stents reduced the severity of hemorrhage following aortic root rupture and helped maintain vessel patency following prolonged hypotension.

Endo/exo-genous dual-stimuli responsive gold nanotetrapod-based nanoprobe for magnetic resonance imaging and enhanced multimodal therapeutics by amplifying·OH generation.

Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) can produce high-toxic hydroxyl radicals (·OH) to kill cancer cells, but the limited concentration of endogenous hydrogen peroxide (H2O2) seriously restricted its application. Herein, using endo/exo-genous dual-stimuli, a novel nanoprobe with enhanced ·OH generation was developed for magnetic resonance (MR) imaging and multimodal therapeutics, in which gold nanotetrapod (AuNTP) with photothermal therapy (PTT) performance was coated with mesoporous silica (mSiO2) and loaded with cisplatin (CDDP), then a thin layer of manganese dioxide (MnO2) was deposited to construct AuNTP@mSiO2@CDDP@MnO2 nanoprobes. In TME, endogenous H2O2, CDDP-triggered self-supplying H2O2 produced via cascade reaction and the exogenous photothermal effect of AuNTPs together enhanced the ·OH generation of Mn2+ induced by glutathione (GSH) responsive degradation of MnO2. The prepared AuNTP@mSiO2@CDDP@MnO2 nanoprobes possessed perfect core@shell structure, good biocompatibility and GSH-dependent MR performance, in which the relaxation rates increased from 0.717 mM-1·s-1 to 8.12 mM-1·s-1. Under the multimodal therapeutics of CDT/PTT/chemotherapy, the developed AuNTP@mSiO2@CDDP@MnO2 nanoprobes demonstrated good antitumor efficacy. Our work provided a promising strategy for constructing TME-responsive nanoprobes with endo/exo-genous stimuli, achieving enhanced visualized theranostics of tumors. STATEMENT OF SIGNIFICANCE: Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) can produce high-toxic hydroxyl radicals (·OH) to kill cancer cells, but the limited concentration of endogenous hydrogen peroxide (H2O2) seriously restricted its application. Using endo/exo-genous dual-stimuli, AuNTP@mSiO2@CDDP@MnO2 (AMCM) nanoprobe was constructed, in which endogenous H2O2, CDDP-triggered self-supplying H2O2 and the exogenous photothermal effect of AuNTPs together enhanced the ·OH generation. Under the multimodal therapeutics of CDT/PTT/chemotherapy, the developed AuNTP@mSiO2@CDDP@MnO2 nanoprobe demonstrated good antitumor efficacy, and provided a promising strategy for constructing TME-responsive nanoprobes with endo/exo-genous stimuli, achieving enhanced CDT of tumors.

The Adverse Events Rate of Endothelial Progenitor Cell Capturing Stent in the Treatment of CAD Patients.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) have regenerative capacities and play an important role in vessel wall homeostasis. When attracted to the site of vessel wall injury, EPCs rapidly differentiate into a functional layer as part of the healing process. The Genous TM endothelial progenitor cell (EPC) capturing stent is coated with anti-human CD34+ antibodies which combine with circulating EPCs from the peripheral blood to the stent surface. OBJECTIVE: This meta-analysis aims to explore the Genous TM endothelial progenitor cell capturing stent in coronary artery disease (CAD) adverse event rate after one-year follow-up. METHODS: PubMed, EMBASE and, Google Scholar databases were searched for eligible studies. CAD survival data and clinicopathological features were analyzed by expected shortfall (ES) and 95% CI. Fixed-effect model and random-effect model are used for summary statistics. RESULTS: 12 studies, including 15985 coronary artery disease (CAD) patients who received PCI treatment were included in this study. After 1-year follow-up, the rate of adverse event showed that the target vessel failure (TVF) was 8.5% (7.6%-17.4%), target vessel revascularization was 4.1% (TVR, 0-15.6%), target lesion revascularization was 4.2% (TLR, 3.7%-22%), myocardial infarction was 2.0% (MI, 1.8%-5.2%), major adverse cardiac events was 8.7% (MACE, 6.4%-28%), and the all-cause death was 4.0% (0-9.2). CONCLUSION: After one-year follow-up, the incidence rate of Genous stent adverse events was stable in CAD patients. The study showed a better evaluation of Genous stent, and it provides a better reference for CAD clinical treatment.

Antiplatelet theRapy after Genous EPC-capturing coroNary stenT implantatiOn: the ARGENTO study: a prospective, multicenter registry.

BACKGROUND: To investigate the safety and efficacy of Genous Bio-engineered R stent (GRS) with ≤ 15-day or >15-day dual antiplatelet therapy (DAT), in patients undergoing percutaneous coronary intervention (PCI), with known or expected low compliance to long-term DAT (Antiplatelet theRapy after Genous EPC-capturing coroNary stenT implantatiOn--ARGENTO study). METHODS: Consecutive patients without ≤ 12-month revascularization history, known statins allergy, known hypersensitivity reaction or previous or concomitant monoclonal and/or recombinant antibodies therapy, treated with single- or multivessel PCI plus GRS, were prospectively enrolled, at four PCI centers. Major adverse cardiac events (MACEs), the composite of cardiac death, any myocardial infarction (MI) and target vessel revascularization (TVR), and stent thrombosis (ST) cumulative incidences were evaluated. RESULTS: Between March 2008 and March 2010, 384 patients (70.3% male, 423 lesions) were enrolled. At follow-up (22.8 ± 13.6 months), 8.6% MACEs, 3.4% cardiac death, 3.4% any MI, 4.7% TVR and 2.3% overall ST (definite/probable ST 1.3%) rates were reported, without differences between ≤ 15-day and >15-day DAT groups. At Cox multivariable-adjusted regression analysis (Hosmer-Lemeshow statistic, p=0.50) female sex, diabetes, previous PCI history, <45% left ventricular ejection fraction at admission and lesion length were identified as independent MACE predictors. DAT time duration (hazard ratio 1.98; 95% confidence interval 0.57-6.80, p=0.27) was not independent risk factor for MACEs. CONCLUSIONS: In consecutive, prospectively enrolled patients with PCI indication and known or supposed low compliance to long-term DAT, GRS implantation might be a safe and effective option regardless of DAT duration after stenting (≤ 15 days or >15 days).

Safety and effectiveness of the Genous™ endothelial progenitor cell-capture stent in the first year following ST-elevation acute myocardial infarction: A single center experience and review of the literature.

PURPOSE: The Genous™ stent (GS) is designed to accelerate endothelization, which is potentially useful in the pro-thrombotic environment of ST-elevation acute myocardial infarction (STEMI). We aimed to evaluate the safety and effectiveness of the GS in the first year following primary percutaneous coronary intervention (PCI) and to compare our results with the few previously published studies. METHODS AND MATERIALS: All patients admitted to a single center due to STEMI that underwent primary PCI using exclusively GS, between May 2006 and January 2012, were enrolled. The primary study endpoints were major adverse cardiac events (MACEs), defined as the composite of cardiac death, acute myocardial infarction and target vessel revascularization, at one and 12 months. RESULTS: In the cohort of 109 patients (73.4% male, 59 ± 12 years), 24.8% were diabetic. PCI was performed in 116 lesions with angiographic success in 99.1%, using 148 GS with median diameter of 3.00 mm (2.50-4.00) and median length of 15 mm (9-33). Cumulative MACEs were 2.8% at one month and 6.4% at 12 months. Three stent thromboses (2.8%), all subacute, and one stent restenosis (0.9%) occurred. These accounted for the four target vessel revascularizations (3.7%). At 12 months, 33.9% of patients were not on dual antiplatelet therapy. CONCLUSIONS: GS was safe and effective in the first year following primary PCI in STEMI, with an apparently safer profile comparing with the previously published data. SUMMARY: We report the safety and effectiveness of the Genous™ stent (GS) in the first year following primary percutaneous coronary intervention in ST-elevation acute myocardial infarction. A comprehensive review of the few studies that have been published on this subject was included and some suggest a less safe profile of the GS. Our results and the critical review included may add information and reinforce the safety and effectiveness of the GS in ST-elevation in acute myocardial infarction.