PATHOMORPHOLOGICAL PATTERNS OF DYSFUNCTIONS OF XENOPERICARDIAL BIOPROSTHESES OF HEART VALVES OF THE “UNILINE” MODEL

Highlights Prosthetic endocarditis (PE) was the main cause of dysfunctions of biological prosthetic heart valves of the UniLine model that occurred during the first 4 years of operation. The main factor in the development of PD insolvency in the later time period was structural valvular degeneration (SKD). The key macroscopic signs of SCD included calcification and ruptures of the valve apparatus. At the microscopic level, PD with SCD was characterized by moderate cellular infiltration with a predominance of macrophages. In turn, for valves with PE, thickening of the valves and the formation of vegetation were noted, the development of which was accompanied by aggressive invasion of neutrophils. The results of cluster analysis of data on 46 key clinical and pathomorphological features supported the division of the studied PD sample into 2 stable clusters corresponding to the patterns of CD and PE. Abstract Aim. This study aimed to comprehensively evaluate the pathomorphological changes in “Uniline” bioprosthetic heart valves (BHVs) explanted due to dysfunction. Methods. A total of 44 “Uniline” BHVs, retrieved from an equal number of recipients during valve re-replacement procedures were examined. To determine cellular composition and assess biomaterial microstructure, valve leaflets were sectioned and stained using hematoxylin and eosin, Russell-Movat pentachrome, Oil Red O, and Alizarin Red S. Bacterial colonies were identified using Gram staining. Immunohistochemistry was performed with the NovoLink Polymer DS detection system and antibodies against the pan-leukocyte marker (CD45), T-lymphocytes (CD3), B-lymphocytes (CD19), macrophages (CD68), neutrophils (MPO), and platelets (CD62p). Stained sections were scanned on an MT5300L microscope, and the resulting histological slides were analyzed using QuPath and Fiji software. Cluster analysis was performed to identify pathomorphological patterns of BHV dysfunction. Results. Clinical and pathomorphological data confirmed PE and SVD as the underlying causes of dysfunction within the cohort. Patients in the PE and SVD groups showed no significant clinical or demographic differences. The mean duration of BHV function was 30 months for PE and 74 months for SVD. Valves explanted due to SVD exhibited leaflet calcification and tears. Most BHVs with PE were characterized by the presence of vegetations on the leaflets. SVD-affected valves displayed moderate macrophage infiltration, whereas PE cases showed aggressive neutrophil invasion. Cluster analysis algorithms identified two stable patterns of dysfunction: the first was characterized by features typical of SVD, including chronic inflammation and calcification, while the second corresponded to persistent acute inflammation associated with PE. Conclusion. PE and SVD are key pathomorphological patterns of dysfunction in “Uniline” BHVs, treated with ethyleneglycol diglycidyl ether. The identified patterns are the same as the main causes of degeneration in BHVs treated with glutaraldehyde. This underscores fundamental limitations in using chemically cross-linked xenopericardium for BHV manufacturing and, consequently, highlights the necessity for developing new materials and methods aimed at improving the durability of artificial heart valves.