Demonstration of proof-of-concept of StrokeShield system for complete closure and occlusion of the left atrial appendage for non-valvular atrial fibrillation therapy

Abstract

In the US, the most significant morbidity and mortality associated with non-valvular atrial fibrillation (NVAF) is embolic stroke, with 90% of thrombus originating from the left atrial appendage (LAA). Anticoagulation is the preferred treatment for the prevention of stroke in NVAF patients, but clinical studies have demonstrated high levels of non-compliance and increased risk of bleeding or ineligibility for anticoagulation therapy, especially in the elderly population where the incidence of NVAF is highest. Alternatively, stroke may be preventing using clinically approved surgical and catheter-based devices to exclude or occlude the LAA, but these devices continue to be plagued by peri-device leaks and thrombus formation because of residual volume. To overcome these limitations, Cor Habere (Louisville, KY) and the University of Louisville are developing a LAA closure device (StrokeShield) that completely occludes and collapses the LAA to minimize the risk of stroke. The StrokeShield device is a collapsible occluder (nitinol reinforced membrane) that completely covers the LAA orifice with an expandable conical coil anchor that attaches to the myocardium. The device is designed for catheter-based delivery and expands to completely occlude the LAA orifice and collapse the LAA. The primary advantages of the StrokeShield system are a completely sealed LAA (no peri-device flow or residual space) and smooth endothelialized connection to the left atrial wall with minimal risk of cardiac bleeding and tamponade. We tested proof-of-concept of a prototype StrokeShield device in acute (n = 2) and chronic 60-day (n = 2) healthy canine models. Acute results demonstrated that the conical coil securely attached to the myocardium (5N pull-out force) and the Nitinol umbrella fully deployed and covered the LAA ostium. Results from the chronic implants demonstrated long-term feasibility of device placement with no procedural or device-related intra- or post-operative complications, secure placement and correct positioning of the device with no device migration. The device successfully occluded the LAA ostium and collapsed the LAA with no interference with the mitral valve, circumflex coronary artery, or pulmonary veins. Necropsy demonstrated no gross signs of thrombus or end-organ damage and the device was encapsulated in the LAA. Histology demonstrated mature neointima covering the device with expected foreign body inflammatory response. These early positive results will help to guide the iterative design process for the continued development of the StrokeShield system.

Fig 1. StrokeShield device.

The two primary components of the StrokeShield device (22 mm width, 6 mm height) include conical anchor which screws into the LAA myocardium to secure the device, and a Dacron-covered Nitinol umbrella membrane that unfolds following deployment to occlude and collapse the LAA. The upper (A1-A4) and lower (B1 = B4) photos show device with bare Nitinol wire and Dacron-covered umbrella frame, respectively, for isometric (A1,B1), front (A2,B2), back (A3,B3), and side (A4,B4) views.

Fig 2. In vivo deployment of the StrokeShield device.

Fluoroscopic images from 60-day chronic animal study showing in vivo deployment of the StrokeShield device. Panels A-E were obtained at baseline/implant and panel F at day-60 (terminal study). A, contrast dye injection into the LA showing the LAA. B, Direct surgical approach via the LA dome for placement of the StrokeShield device. The device is loaded on the tip of the delivery tool with partial exposure of the conical coil. C, StrokeShield device screwed into the LAA myocardium with delivery tool pullback in progress. D. Partial opening of the StrokeShield Nitinol umbrella. E. Complete opening of the StrokeShield Nitinol umbrella in place in the LAA ostium. F, StrokeShield device at day-60. Contrast dye injected via a ventriculogram catheter into the LA chamber shows no dye flow into the collapsed LAA. Panel F, originally obtained in right lateral decubitus position, has been flipped horizontally to match the left lateral decubitus position (right thoracotomy) of panels A-E.

Fig 3. StrokeShield device in situ.

The StrokeShield device in the LAA at necropsy (day 60) in the chronic canine model demonstrating tissue encapsulation and freedom from interference with the mitral valve and pulmonary veins.

Fig 4. Histology performed on 60-day chronic canine myocardium and StrokeShield device.

At left, Elastic Trichrome (ET) stain demonstrating healed and mature neointima covering the Dacron and nitinol struts (dark black shapes) of the closure device (black dotted line), fully mature fibrovascular connective tissue filling the closure device cavity (red asterisk), and occlusion point at the contact between closure device disc and atrial wall with normal healing (red arrowhead). The black box is further detailed in the upper right image (ET stain). Here, the dotted line indicates healed and mature neointima covering the closure device with irregular edges and microtears indicative of handling artifact. The black double arrow is mature fibrocellular neointima lining the Dacron cover. At lower right, Hematoxylin and eosin stain (H&E) (lower right) showing healed and mature neointima (dotted line) covering the closure device with irregular edges and microtears indicative of handling artifact. The black double arrow shows mature fibrocellular neointima lining the Dacron cover and the single arrow shows Dacron with expected minimal to mild foreign body inflammatory response [18].