Tricuspid Valve Leaflet Remodeling in Sheep with Biventricular Heart Failure: A Comparison between Leaflets

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.

Note:
Funding Information: The research reported in this publication was partially supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Numbers 1R01HL165251-01 and R21HL161832 (MKR), F31HL145976 (WDM), the American Heart Association for their support under Award Number 18CDA34120028 (MKR), and internal grants from Meijer Heart and Vascular Institute at Corewell Health.

Declaration of Interests: Manuel K. Rausch has a speaking arrangement with Edwards Lifesciences. The other authors have no conflicts to declare.

Ethics Approval Statement This research complied in accordance with the Principles of Laboratory Animal Care, formulated by the National Society for Medical Research, and adhered to protocols outlined in the Guide for Care and Use of Laboratory Animals, published by the National Institutes of Health. Additionally, this protocol was developed, reviewed and performed in accordance with the approval of a local Institutional Animal Care and Use Committee at Corewell Health. The specific approval numbers are 2017-357, 2018-402, 2018427, and 2018-439.

Keywords: Leaflet-specific Remodeling, Tachycardia-induced Cardiomyopathy, Biaxial Testing, Histology, Two-photon Microscopy