Abstract
Over 1.6 million Americans suffer from significant tricuspid valve leakage. In most cases this leakage is designated as secondary. Thus, valve dysfunction is assumed to be due to valve-extrinsic factors. We challenge this paradigm and hypothesize that the tricuspid valve maladapts in those patients rendering the valve at least partially culpable for its dysfunction. As a first step in testing this hypothesis, we set out to demonstrate that the tricuspid valve maladapts in disease. To this end, we induced biventricular heart failure in sheep that developed tricuspid valve leakage. In the anterior leaflets of those animals, we investigated maladaptation on multiple scales. We demonstrated alterations on the protein and cell-level, leading to tissue growth, thickening, and stiffening. These data provide a new perspective on a poorly understood, yet highly prevalent disease. Our findings may motivate novel therapy options for many currently untreated patients with leaky tricuspid valves.
Highlights
The tricuspid valve regulates blood flow between the right atrium and right ventricle
Based on our hypothesis that anterior leaflet tissue remodels in disease, we investigated the presence of four cellular markers frequently associated with remodeling via immunohistochemistry: (i) a-smooth muscle actin, (ii) Ki67, (iii) matrix metalloproteinase 13 (MMP13), and (iv) transforming growth factor b1 (TGF-b1)
We investigated the tricuspid valve’s propensity toadapt to tricuspid regurgitation (TR), which was motivated by research on mitral valveadaptation to physiological (Pierlot et al, 2015) and pathological stimuli (Dal-Bianco et al, 2016; Levine et al, 2015; Stephens et al, 2008; Beaudoin et al, 2017)
Summary
The tricuspid valve regulates blood flow between the right atrium and right ventricle. Its function as a check-valve depends on the well-orchestrated interplay between the three leaflets and the valve’s annular junction with the surrounding myocardium. The three leaflets coapt and seal the valve orifice, while, during diastole, they open to allow for blood to pass. Leaflet coaptation is further ensured through fibrous cords which connect the leaflets to the papillary muscles of the ventricular myocardium, akin to parachute cords that prevent leaflet prolapse into the atrium (Silver et al, 1971; Smith et al, 2020; Meador et al, 2020a). In tricuspid regurgitation (TR), leaflet coaptation is incomplete allowing for retrograde leakage through the valve (Mangieri et al, 2017). In 85% of severe cases, TR is considered functional or secondary to right ventricular remodeling and left-sided heart
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
