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bioRxiv · 10.1101/2024.09.16.613284

Tricuspid valve maladaptation in sheep with biventricular heart failure: The posterior and septal leaflets

Kostelnik, C. J.·Meador, W. D.·Lin, C.-Y.·Mathur, M.·Malinowski, M.·Jazwiec, T.·Malinowska, Z.·Piekarska, M. L.·Gaweda, B.·Timek, T. A.·Rausch, M. K.
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Abstract

Tricuspid valve leaflets are dynamic tissues that can respond to altered biomechanical and hemodynamic loads. Each leaflet has unique structural and mechanical properties, leading to differential in vivo strains. We hypothesized that these intrinsic differences drive heterogeneous, disease-induced remodeling between the leaflets. Although we previously reported significant remodeling changes in the anterior leaflet, the responses among the other two leaflets have not been reported. Using a sheep model of biventricular heart failure, we compared the remodeling responses between all tricuspid leaflets. Our results show that the anterior leaflet underwent the most significant remodeling, while the septal and posterior leaflets exhibited similar but less pronounced changes. We found several between-leaflet differences in key structural and mechanical metrics that have been shown to contribute to valvular dysfunction. These findings underscore the need to consider leaflet-specific remodeling to fully understand tricuspid valve dysfunction and to develop targeted therapies for its treatment and more accurate computational models. STATEMENT OF SIGNIFICANCEOur study is significant as it advances our understanding of tricuspid valve remodeling by providing a comprehensive analysis of all three leaflets in a sheep model of biventricular heart failure. Unlike prior works that focused primarily on the anterior leaflet or generalized leaflet changes, we integrated morphological, histological, immunohistochemistry, biaxial mechanical testing, and two-photon microscopy to quantify differences between all three tricuspid valve leaflets (anterior, posterior, and septal) across multiple functional scales. This comprehensive approach highlights the unique remodeling response of each leaflet. Our findings offer critical insights for developing targeted therapeutic strategies and improving computational models of disease progression. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/613284v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1e8efaforg.highwire.dtl.DTLVardef@1cfee04org.highwire.dtl.DTLVardef@136956org.highwire.dtl.DTLVardef@68c488_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kostelnik, C. J., Meador, W. D., Lin, C.-Y., Mathur, M., Malinowski, M., Jazwiec, T., Malinowska, Z., Piekarska, M. L., Gaweda, B., Timek, T. A., Rausch, M. K.. 2024-09-20. Tricuspid valve maladaptation in sheep with biventricular heart failure: The posterior and septal leaflets. https://doi.org/10.1101/2024.09.16.613284

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