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

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.

Déclaration de conflit d'intérêts

Financial • Two US patents awarded related to the research presented in this manuscript, and a third University of Louisville (UofL) invention disclosure was filed February 1, 2021, but is not presented in this manuscript Slaughter MS, Giridharan GA, Sobieski MA, Soucy KG, and Koenig SC. Atrial appendage closure device and related methods (US Patent 10,531,878 awarded January 14, 2020) Slaughter MS, Giridharan GA, Sobieski MA, Soucy KG, and Koenig SC. Atrial appendage closure device and related methods (US Patent 10,898,202 awarded January 26, 2021) Slaughter MS, Monreal G, Koenig SC, Jimenez J, Tompkins L. Left Atrial Appendage (LAA) device, delivery tool, and related methods (UofL Invention Disclosure no. 21038, filed February 1, 2021) • Research presented in this manuscript was funded as an internal project subaward (PI: Guruprasad Giridharan) from a 5-yr Coulter Foundation grant awarded to University of Louisville (PIs: Robert Keynton, PhD and Mark Slaughter, MD) • Co-authors Jimenez, Koenig, Slaughter are co-founders of Cor Habere (Louisville KY), and are continuing the research and development of the StrokeShield system (LAA device) presented in this manuscript. Note: Cor Habere was founded after the research and development presented in this manuscript had been completed. • Cor Habere was awarded a NIH SBIR phase I grant (R43HL142337-01) to continue development of the StrokeShield system (LAA device, delivery tool) but none of the work supported by the SBIR phase I grant is presented in this manuscript. Co-authors (Giridharan, Koenig, Slaughter) were awarded US Patent 10,531,878 (January 14, 2020) and US Patent 10,898,202 (January 26, 2021). All of the co-authors are continuing with the development of the StrokeShield device and are listed as co-inventors on our recent UofL invention disclosure (no. 21038, filed Feb 1, 2021) and co-investigators of NIH SBIR phase I grant (R43HL142337-01, awarded Sep 30, 2019). This information does NOT alter our adherence to PLOS ONE policies on sharing data and materials.