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.

Histopathologic description of Wingspan stent in acute ischemic stroke.

OBJECTIVE AND IMPORTANCE: We report the histopathologic examination of Wingspan stent in acute ischemic stroke. CLINICAL PRESENTATION: A 75-year-old female presented with acute left-hemiplegia due to right carotid terminus occlusion. Mechanical embolectomy was unsuccessful. INTERVENTION: A Wingspan stent was placed from the distal intracranial carotid artery to the proximal middle cerebral artery stem and established partial antegrade flow. The patient died of malignant infarction on post-stroke day 7. At autopsy, embolized calcified atherosclerotic plaque fragments were noted within a non-occlusive thrombus over which the Wingspan stent was deployed. There was no evidence of intimal or media dissection or perforator ostium occlusion. CONCLUSION: Our case provides a rare pathological description of intracranial stent placement in the setting of acute ischemic stroke.

Comparison of inflammatory response after implantation of sirolimus- and paclitaxel-eluting stents in porcine coronary arteries.

BACKGROUND: Although both sirolimus (CYPHER) and paclitaxel (TAXUS) drug-eluting stents have demonstrated efficacy and safety in clinical trials, human autopsy data have raised concerns about long-term healing and the potential for local inflammatory reactions. METHODS AND RESULTS: Overlapping stents (CYPHER drug-eluting stents, Bx SONIC bare metal stents, TAXUS drug-eluting stents, and Liberté bare metal stents) were implanted in noninjured coronary arteries of 58 domestic swine. Histopathological evaluation of proximal, overlapped, and distal stented segments was determined with emphasis on inflammation at 30, 90, and 180 days. Circumferential granulomatous inflammation in all stented segments was defined as inflammation consisting of macrophages, multinucleated giant cells, lymphocytes, and granulocytes, including many eosinophils, adjacent to almost all struts. Circumferential granulomatous inflammation was more prevalent in CYPHER (9 of 23, 39%) compared with TAXUS (1 of 21, 5%; P=0.01) and control bare metal stents (0 of 44) in the combined 90- and 180-day cohorts. Only CYPHER specimens showed marked adventitial inflammation (P=0.0025) and fibrosis (P=0.0055) accompanied by extensive remodeling. Fibrin deposition within neointima and medial smooth muscle cell death were greater (both P<0.001) in TAXUS than CYPHER at 30 days, with more fibrin in TAXUS than CYPHER through 90 days (P<0.05). CONCLUSIONS: Although these data cannot be directly extrapolated to humans, the high prevalence in this porcine model of diffuse granulomatous inflammation seen with CYPHER stents, persisting at 180 days and associated with extensive remodeling of the artery, and persistent para-strut fibrin deposition with TAXUS stents emphasize the need for further investigation of biocompatibility with these and other novel combination drug/polymer drug-eluting stents.