Enhanced Thromboresistance and Endothelialization of a Novel Fluoropolymer-Coated Left Atrial Appendage Closure Device.

BACKGROUND: Device-related thrombus (DRT) after left atrial appendage closure (LAAC) procedures is a rare but potentially serious event. Thrombogenicity and delayed endothelialization play a role in the development of DRT. Fluorinated polymers are known to have thromboresistant properties that may favorably modulate the healing response to an LAAC device. OBJECTIVES: The goal of this study was to compare the thrombogenicity and endothelial coverage (EC) after LAAC between the conventional uncoated WATCHMAN FLX (WM) and a novel fluoropolymer-coated WATCHMAN FLX (FP-WM). METHODS: Canines were randomized for implantation with WM or FP-WM devices and given no postimplant antithrombotic/antiplatelet agents. The presence of DRT was monitored by using transesophageal echocardiography and verified histologically. The biochemical mechanisms associated with coating were assessed by using flow loop experiments to quantify albumin adsorption, platelet adhesion, and porcine implants to quantify EC and the expression of markers of endothelial maturation (ie, vascular endothelial-cadherin/p120-catenin). RESULTS: Canines implanted with FP-WM exhibited significantly less DRT at 45 days than those implanted with WM (0% vs 50%; P < 0.05). In vitro experiments showed significantly greater albumin adsorption (52.8 [IQR: 41.0-58.3] mm2 vs 20.6 [IQR: 17.2-26.6] mm2; P = 0.03) and significantly less platelet adhesion (44.7% [IQR: 27.2%-60.2%] vs 60.9% [IQR: 39.9%-70.1%]; P < 0.01) on FP-WM. Porcine implants showed significantly greater EC by scanning electron microscopy (87.7% [IQR: 83.4%-92.3%] vs 68.2% [IQR: 47.6%-72.8%]; P = 0.03), and higher vascular endothelial-cadherin/p120-catenin expression after 3 months on FP-WM compared with WM. CONCLUSIONS: The FP-WM device showed significantly less thrombus and reduced inflammation in a challenging canine model. Mechanistic studies indicated that the fluoropolymer-coated device binds more albumin, leading to reduced platelet binding, less inflammation, and greater EC.

Nanoparticle-Mediated Cell Capture Enables Rapid Endothelialization of a Novel Bare Metal Stent.

Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic cell capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (Fe3O4) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled cells to 2205 SS stents. In this study, we show extensive endothelialization of magnetic 2205 SS stents (median 98.4% cell coverage) within 3 days, whereas the control 316L SS stents exhibited significantly less coverage (median 48.9% cell coverage, p < 0.0001). This demonstrates the ability of intracoronary delivery of magnetic nanoparticle labeled autologous endothelial cells to improve endothelialization of magnetized coronary stents within 3 days of implantation.

The fate of patients with clinical recurrence after sirolimus-eluting stent implantation (a two-year follow-up analysis from the SIRIUS trial).

Although clinical outcomes after sirolimus-eluting stents (SESs) have been previously described ("primary" success rates), the fate of patients whose SES implantation fail and who require ischemia-driven target lesion revascularization is poorly understood. The SIRIUS trial is a prospective, randomized, clinical trial that includes 533 evaluable patients with SESs. Twenty-two of these patients had adjudicated ischemia-driven target lesion revascularization (4.1%) within the first year of follow-up and comprised the study population of this analysis. Of these patients, 11 (50%) had diabetes, and restenotic lesions were focal and located at the proximal stent edge in 91% and 73% of patients, respectively. Restenosis was treated with bare metal stent implantation, balloon dilatation, or intravascular brachytherapy in 82%, 13.5%, and 4.5% of patients, respectively. At 1-year follow-up after the first recurrence (2-year follow-up after the index procedure), only 5 of these patients (23%) required a second repeat revascularization procedure. Risk factors for a second recurrence after treatment of SES restenosis were female gender, long lesions that required long stents at the index procedure, and an early first recurrence. In conclusion, SES failure treated with traditional percutaneous coronary intervention yielded good outcome at 1-year follow-up (secondary failure rate only 23%), perhaps due to the focal nature of the SES restenotic lesion. Future studies should evaluate other methods, including drug-eluting stents, to further optimize the outcome of treatment of SES failures.

The approach to small vessels in the era of drug-eluting stents.

The treatment of small-vessel disease will occupy an increasingly important part of interventional cardiology practice and this raises several issues. The definition of "small vessels" has great implications for device size selection, and knowledge of "normal" small-vessel dimensions is important. Stents have been applied in the setting of smaller-vessel disease and future iterations of small-vessel stents will need to address several design factors. Stent strut thickness might impact on subsequent restenosis as well as late lumen loss. There has been great interest in the use of drug-eluting stents for small vessels. Randomized clinical trials of sirolimus-eluting versus bare metal stents in the treatment of small-vessel disease have shown significant improvements in the rates of target lesion revascularization and restenosis with sirolimus-eluting stents. These improvements in restenosis rates are attributable to the low levels of late loss with the drug-eluting stent.

Creativity, ingenuity, serendipity.

Some of the earliest experiences of invasive cardiology centred on studying the physiology of congenital heart disease in a series of ongoing attempts to understand pathophysiology and anatomy, and then devising strategies to treat the lesion. Tremendous growth in the field and rapid advances in patient care have become possible due to the collaboration of early investigators, including pediatric cardiologists, cardiovascular pathologists, embryologists, physiologists and cardiovascular surgeons. This group has expanded to include radiologists, vascular biologists and engineers. Mason Sones' serendipitous encounter with a patient led to the thought that one patient's 'complication' might lead to another therapy and, as a result, studies were conducted. Early equipment was bulky, rigid and inflexible. Andreas Gruentzig was instrumental in the development of several new techniques. Throughout the development of invasive cardiology, great attention has been paid to the evaluation of both successful and failed outcomes. Over the intervening years, multiple advances in technology have improved procedures by making invasive cardiology easier, safer and more predictable and have expanded the patient population that could benefit from it. These advances included new devices, such as atherectomy transluminal extraction catheters, as well as with directional coronary atherectomy, rotational atherectomy and laser-based techniques. Interventional cardiology has soared with single-centre and multicentre randomized trials. Intracoronary stents have completely revolutionized therapy, becoming smaller, more flexible and more easily deliverable. With the introduction of drug-eluting stents, restenosis rates have been dramatically reduced. However, chronic total occlusion continues to be a problem in interventional cardiology due to increased risk of early and late complications and increased restenosis rates. New areas continue to be developed, combining the inventions and designs of collaborators. An increased knowledge of the basic pathophysiology of cardiovascular disease, combined with creative technology and imaginative operators, will continue to advance the field.