Reoperations after failed aortic valve neocuspidization: Histopathological analysis of explanted leaflet material

OBJECTIVES: Aortic valve neocuspidization (AVNeo) provides favorable mid-term outcomes, yet the histological mechanisms of valve failure requiring reoperation remain incompletely characterized. We performed histopathological and immunohistochemical analysis of explanted leaflet material from failed AVNeo valves to analyze their modes of failure at the histological level. METHODS: Leaflet specimens explanted during reoperation for failed AVNeo between January 2021 and December 2025 underwent routine processing with hematoxylin and eosin staining. Additional staining for connective-tissue remodeling and calcification was performed according to local protocols. Immunohistochemistry included CD31 to assess endothelialization and vascular response, CD45 to characterize inflammatory infiltration, and vimentin to identify fibroblast-like mesenchymal cellular infiltration. Prespecified endpoints included inflammation, fibrin/fibrinopurulent deposition, degeneration, fibrosis, calcification, surface endothelialization, fibroblast-like infiltration, angiogenesis/angiomatosis, and restoration of fibrous architecture. RESULTS: Specimens from six patients were analyzed. Indications for reoperation were IE in three patients, structural degeneration with aortic regurgitation in two GTAP valves, and leaflet perforation in one xenopericardial valve. Reoperation occurred earlier in IE cases than in non-IE cases. IE specimens showed severe inflammation, prominent fibrinous/fibrinopurulent surface deposits, absent CD31-positive surface endothelialization, absent fibroblast-like infiltration, and no vascular remodeling. In contrast, late non-IE GTAP specimens demonstrated partial surface endothelialization, fibroblast-like infiltration, mild angiogenesis/angiomatosis, fibrosis, mild calcification, and partial restoration of fibrous architecture. The xenopericardial specimen showed limited integration. CONCLUSIONS: Failed AVNeo leaflets demonstrate heterogeneous degeneration and time-dependent host integration. Late non-IE GTAP failures demonstrated histological evidence of tissue integration, including endothelialisation, cellular and vascular ingrowth, whereas early IE-related failures lack these features. Larger standardized studies are required.