In-Vitro Assessment of the Effects of Transcatheter Aortic Valve Leaflet Design on Neo-Sinus Geometry and Flow.

Transcatheter aortic valve (TAV) leaflet thrombosis is a clinical risk with potentially fatal consequences. Studies have identified neo-sinus flow stasis as a cause of leaflet thrombosis. Flow stasis is influenced by the TAV leaflets, which affect the local fluid dynamics in the aortic sinus and neo-sinus. This study evaluated the effects of TAV leaflet features on the neo-sinus flow as a measure of leaflet thrombosis risk. Five TAVs of varied leaflet length and insertion height were tested in a simulator. Hydrodynamics and leaflet kinematics through en-phase imaging were quantified. Velocity fields were assessed using high-speed particle image velocimetry. Regions of flow stasis and particle residence times (PRTs) were quantified. TAVs with shorter leaflet length exhibited larger orifice areas and lower transvalvular pressure gradients. Shorter leaflet length and increased leaflet insertion TAVs additionally exhibited lower neo-sinus PRTs (0.44 ± 0.21 vs 2.83 ± 0.48 cycles, p < 0.05) and higher neo-sinus peak velocities (0.15 ± 0.009 vs 0.07 ± 0.005 m/s, p < 0.05) than TAVs with longer leaflet length and lower leaflet insertion. The average neo-sinus volume positively correlated with PRT(r = 0.810, p < 0.001), and extent of flow stasis (r = 0.682, p < 0.05). These results suggest that a small neo-sinus volume may reduce flow stagnation and particle residence, potentially reducing the risk of leaflet thrombosis. We propose that leaflet design features might be proactively controlled in the design of future transcatheter aortic valves.

Biomechanics of Endothelial Tubule Formation Differentially Modulated by Cerebral Cavernous Malformation Proteins.

At early stages of organismal development, endothelial cells self-organize into complex networks subsequently giving rise to mature blood vessels. The compromised collective behavior of endothelial cells leads to the development of a number of vascular diseases, many of which can be life-threatening. Cerebral cavernous malformation is an example of vascular diseases caused by abnormal development of blood vessels in the brain. Despite numerous efforts to date, enlarged blood vessels (cavernomas) can be effectively treated only by risky and complex brain surgery. In this work, we use a comprehensive simulation model to dissect the mechanisms contributing to an emergent behavior of the multicellular system. By tightly integrating computational and experimental approaches we gain a systems-level understanding of the basic mechanisms of vascular tubule formation, its destabilization, and pharmacological rescue, which may facilitate the development of new strategies for manipulating collective endothelial cell behavior in the disease context.