Enhanced Endothelialization Using Resveratrol-Loaded Polylactic Acid-Coated Left Atrial Appendage Occluders in a Canine Model

Left atrial appendage occlusion (LAAO) is a well-established alternative to anticoagulation therapy for patients with atrial fibrillation who have a high bleeding risk. After occluder implantation, anticoagulation therapy is still required for at least 45 days until complete LAAO is achieved by neoendocardial coverage of the device. We applied a polylactic acid-resveratrol coating to the LAAO membrane to enhance endothelialization with the goal of shortening the anticoagulation therapy duration. Eighteen dogs were randomly divided into the experimental group (coated occluders) or the control group (noncoated occluders). The dogs were sacrificed in cohorts at days 14, 28, and 90 for anatomical and pathological examination to evaluate endothelialization and thrombus formation. Transesophageal echocardiography (TEE) was performed before sacrifice to evaluate device-related adverse events. According to the anatomical and pathological examinations, all except one LAAO cover exhibited larger or thicker tissue or neoendocardial coverage in the experimental group compared with the control group at the same sacrifice time points. All connection hubs were densely covered by endothelial cells at 90 days and completely covered at 28 days in the experimental group, while all connection hubs were thinly covered at 90 days and two connection hubs were exposed at 28 days in the control group. Pathological examination revealed no thrombus formation in the experimental group, while a small amount of thrombus was observed in one dog at 90 days and in two dogs at 28 days in the control group. Finally, TEE showed no peri-device leakage (PDL) in the experimental group, whereas a small amount of PDL was detected in one dog (3.2 mm) at 28 days and in one dog (3.7 mm) at 14 days in the control group. The resveratrol-loaded polylactic acid-covered LAAO device enhanced endothelialization and reduced thrombus formation and PDL. This effect could possibly reduce the anticoagulation therapy duration.