# Tricuspid valve adaptation to right heart disease: A multiscale, histomechanical study in sheep

> **NIH NIH F31** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $16,276

## Abstract

PROJECT SUMMARY
Approximately 1.6 million Americans suffer from leakage of their right atrioventricular heart valve, which is
referred to as tricuspid valve (TV) regurgitation (TR). This is noteworthy as TR is not only a significant source of
morbidity but also an independent predictor of mortality. Furthermore, treatment options for severe TR are
suboptimal, with as many as 30% of patients developing recurrent TR within five years of surgery. TR is in most
cases considered secondary to other conditions, implying that its causes are valve-extrinsic. Specifically, it is
thought that right ventricular remodeling due to pulmonary hypertension, for example, causes papillary muscle
(PM) displacement and annular dilation. PM displacement subsequently radially strains and immobilizes the TV
leaflets via chordal tethering, while TV annular dilation circumferentially strains the leaflets. Together, PM
displacement and annular dilation prohibit proper coaptation, rendering the TV regurgitant. Interestingly, studies
on the left side of the heart have shown that mitral valve (MV) tissue grows and remodels in response to
pathological mechanical (patho-mechanical) stimuli from left ventricular (LV) disease, e.g., due to leaflet strains
following PM displacement and annular dilation. Although at first believed to be a positive adaptation to a
changing mechanical environment, this maladaptation also causes the MV leaflets to thicken and become stiffer,
further compromising valve function. The TV, on the other hand, is severely understudied. Therefore, it is
unknown whether the TV similarly remodels in response to patho-mechanical stimuli, and if remodeling
contributes to improper valve function. This finding would render TR not entirely valve-extrinisic and thus call into
question current treatment strategies as well as potentially explain poor outcomes. To fill this gap in our
knowledge, the proposed project aims to demonstrate TV remodeling in vivo in response to leaflet strain in an
ovine disease model at the micro-scale (Aim 1) and the tissue-scale (Aim 2). The aims utilize state-of-the-art
techniques in morphometric analysis, microstructural imaging, mechanical testing, and quantitative protein
analysis and are based on a well-established tachycardia-induced cardiomyopathy sheep model. Our current
lack of knowledge is potentially withholding better treatment strategies for TR, which could otherwise improve
the currently poor outcomes of TV therapy. Thus, my ultimate goal is to inspire pharmacological strategies to
modify the underlying biological events that lead to TV remodeling and optimize the tissue’s response to patho-
mechanical stimuli. Such efforts are underway for the MV where Losartan is tested as a pharmacological
treatment of MV regurgitation. Along with the research strategy, the fellowship training plan is organized to offer
the applicant professional development toward an independent research career in a top tier institutional
environment at ...

## Key facts

- **NIH application ID:** 10249361
- **Project number:** 5F31HL145976-03
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** William D Meador
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $16,276
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-01-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249361

## Citation

> US National Institutes of Health, RePORTER application 10249361, Tricuspid valve adaptation to right heart disease: A multiscale, histomechanical study in sheep (5F31HL145976-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10249361. Licensed CC0.

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