Predictors of Paravalvular Regurgitation Following Implantation of the Fully Repositionable and Retrievable Lotus Transcatheter Aortic Valve (From the REPRISE II Trial Extended Cohort)

Paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR) is associated with worse long-term outcomes. The Lotus Valve incorporates an innovative adaptive seal designed to minimize PVL. This analysis evaluated the incidence and predictors of PVL following implantation of the Lotus transcatheter aortic valve. The REPRISE II study with Extended Cohort enrolled 250 high-surgical risk patients with severe symptomatic aortic stenosis. Aortic regurgitation was assessed by echocardiography pre-procedure, at discharge and 30 days by an independent core lab. Baseline and procedural predictors of mild or greater PVL at 30 days (or at discharge if 30-day data were not available) were determined using a multivariate regression model (N=229). Among 229 patients, 197 (86%) had no/trace PVL, 30 had mild, and 2 had moderate PVL; no patient had severe PVL. Significant predictors of mild/moderate PVL included device:annulus area ratio (odds ratio [OR]: 0.87 (95% CI: 0.83-0.92); P<0.001), LVOT calcium volume (OR:2.85;(1.44-5.63); P=0.003), and annulus area (OR:0.89(0.82-0.96); P=0.002). When the device:annulus area ratio was <1, the rate of mild/moderate PVL was 53.1% (17/32). The rates of mild/moderate PVL with 0-5%, 5-10%, and >10% annular oversizing by area were 17.5% (11/63), 2.9% (2/70), and 3.2% (2/63), respectively. Significant independent predictors of PVL included device:annulus area ratio and LVOT calcium volume. When the prosthetic valve was oversized by ≥5%, the rate of mild or greater PVL was only 3%. In conclusion, the overall rates of PVL with the Lotus Valve are low and predominantly related to device/annulus areas and calcium; these findings have implications for optimal device sizing

mRNA localization in polarized intestinal epithelial cells

An important feature of enterocyte maturation is the asymmetrical distribution of cellular functions including protein localization. mRNA sorting is one mechanism for establishment and maintenance of this process in other systems, and we have previously demonstrated differential localization of mRNAs in human enterocytes. To study regulation of mRNA sorting, we established a model in polarized Caco-2 cells. Proxy cDNA constructs containing β-galactosidase (β-gal)/green fluorescence protein (GFP) and the 3′-untranslated region (3′-UTR) of either human sucrase-isomaltase or villin were transfected transiently or stably. A control construct contained poly-A sequence in place of 3′-UTR. Expression of GFP was observed by confocal microscopy; intracellular location of the construct mRNA was imaged by in situ hybridization. The sucrase-isomaltase mRNA proxy localized to an apical position in Caco-2 cells as in native enterocytes; the villin mRNA proxy did not show significant localization. The control construct was not localized and was found diffusely throughout the cell. Proxy GFP proteins tended to localize with their mRNA proxies, but with less precision. This study establishes a valuable model for the investigation of mRNA localization in intestinal epithelial cells. Mechanisms controlling asymmetrical distribution of intestinal mRNAs can be now be elucidated