Native Valve and Native Neo-Sinus Remodeling Following Transcatheter Aortic Valve Replacement

Abstract

BACKGROUND: Transcatheter aortic valve replacement (TAVR) pushes aside the diseased native aortic valve and creates a native neo-sinus bordered by the aortic root wall and the displaced native valve. There are limited data on the progression of native valve disease post-TAVR and no previous analysis of the native neo-sinus. METHODS: Native aortic valves and native neo-sinus explants obtained post-TAVR were evaluated histologically (hematoxylin and eosin, Movat pentachrome, and Martius Scarlet Blue stains) and by immunohistochemistry (TGF-β1 [transforming growth factor-beta 1], FAP [fibroblast activation protein], and ALP [alkaline phosphatase]) to assess disease mechanisms. RESULTS: Native aortic valves were obtained from 20 patients from 0 to 2583 days (7.08 years) post-TAVR. Native leaflets showed persistent calcific aortic stenosis-like disease activity with positivity for ALP and FAP. Native valve remodeling was observed as changes in architecture evident in explants >1.5 years, which was observed as crumpling of the leaflets. Disease activity was also present in native neo-sinuses with transcatheter heart valve implant durations >1 year with positive staining for TGF-β1, FAP, and ALP. Extensive native neo-sinus remodeling occurred with replacement and filling-in of this space with contiguous extracellular matrix, calcific deposits, and microvessels. CONCLUSIONS: Following TAVR, there is ongoing calcific aortic stenosis-like disease with architectural changes to native leaflets and extensive remodeling of the native neo-sinus, evidenced by replacement and contiguous filling-in of the native neo-sinus blood pool space with increasing implant duration. The dynamic nature of these tissues has potential implications for neo-sinus flow, valve degeneration, and re-intervention.