LAUSR

The objective of this work was to determine whether tricuspid valve leaflets maladapt to functional regurgitation as they do in the mitral valve. If they did, pharmacological control of the underlying mechanisms could open opportunities to support tricuspid valve surgery and improve currently poor outcomes. To this end, we used a biventricular heart failure model to induce functional tricuspid valve regurgitation in sheep. We sacrificed animals once they showed signs of heart failure (with in 2-3 weeks). In those animals (and controls), we measured tricuspid anterior leaflet area and thickness, collagen content via ELISAs, tissue stiffness via mechanical testing, and cellular changes via immunohistochemistry. We found a statistically significant increase with disease in leaflet area (p=0.004), thickness (p=0.037), collagen content (p=0.001), circumferential leaflet stiffness (p=0.001), and SMA (p=0.030), Figure 1. Our findings imply that in approximately 2-3 weeks of biventricular heart failure and associated functional tricuspid regurgitation, tricuspid valve leaflets underwent substantial remodeling. Specifically, it appears that activation of valvular interstitial cells increased collagen syntheses resulting in leaflet growth, thickening, and stiffening. No other previous study has demonstrated tissue maladaptation on all functional scales in the tricuspid valve. Our work is relevant as it implies that pharmacological control of this maladaptive response could allow for the promotion of the positive effects (e.g., area increase) while suppressing negative effects (e.g., fibrosis).