CARD11: Polymeric Endoluminal Paving for Prevention of Paravalvular Leak in Transcatheter Aortic Valve Replacement

Abstract

Background: Calcific aortic valve disease and associated aortic stenosis is increasingly common, with prevalence across the age spectrum. Transcatheter aortic valve replacement (TAVR) has emerged as a life-saving, non-surgical alternative for replacement of diseased aortic valves, restoring non-obstructive blood flow from the heart. While effective, current TAVR technology remains limited by adaptability to patient-specific anatomy, leading to incomplete deployment and non-conformal fit resulting in paravalvular leak. Polymeric endoluminal paving was previously developed as a methodology allowing deployment of polymeric materials on tissue surfaces, serving as structural materials and barriers. Here we adapt the paving methodology to fill gaps and defects resulting from incomplete TAVR valve deployment to limit paravalvular leak. Specifically, we assess the efficacy pf polymeric paving in vitro as a means of gap filling and leak reduction in valves deployed in 3-D physical models of severely stenosed aortic valves. We hypothesize that applied polymeric biomaterials will fill and conform to irregular aortic valve geometries acting as a sealant to reduce paravalvular leak. Methods: Polymeric hydrogels were prepared from ABA block copolymer macromers composed of diacrylate terminated by PLA-b-PEG-b-PLA. Hydrogel networks were prepared by swelling these macromers, following the addition of free radical initiators. Hollow tubular constructs were formed via melt-processing in PDMS molds to fit as a “sleeve” around deployed PolyV® nitinol stent (Fig 1A). The sealing efficacy of polymers was examined using a silicone replica of CAVD aortic root with deployed stent + polymer construct (Fig 1B). A rubber stopper was used to fully occlude aortic lumen and restrict flow to paravalvular areas for quantitative analysis. To test sealing against hydrostatic pressure, valve construct was connected to Tygon tubing and water was added at equivalent 10 mmHg increments at 5-minute intervals. Volume from paravalvular flow was measured at each step. Experiments were performed with N = 4 polymeric sleeves. Results: We found significant reduction in paravalvular leakage with polymer sleeves compared to no polymer at all pressures tested. Figure 1C shows the mean ± standard deviation volume of water leaked over 5 minutes of corresponding hydrostatic pressure. No leakage was detected up to 60mmHg for all polymer sleeves tested. At approximately 85-90 mmHg, the rubber stopper failed, however the polymer sleeve remained intact. Conclusions: Polymeric paving utilized with TAVR is a promising combinative therapy for preventing paravalvular leakage. Our results indicate that potential polymeric biomaterials are capable of conforming to non-physiologic aortic valve morphologies, filling and sealing paravalvular gaps, while withstanding physiologic trans-aortic pressures. With further translation, polymer paving can be useful in improving TAVR outcomes.