# Tricuspid Valve Maladaptation: Its Stimuli, its Effect on Valve Function, and its Response to Therapy

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $682,916

## Abstract

ABSTRACT. 1.6 million Americans suffer from functional tricuspid valve regurgitation (FTR); that is, tricuspid
valve leakage due to valve-extrinsic factors such as pulmonary hypertension-induced right ventricular
remodeling. Of those patients, only approximately 8-10 thousand are surgically treated. This undertreatment of
patients with FTR has been declared “a public health crisis”. While the reasons for undertreatment are multi-fold,
one is unarguably that available treatment options have suboptimal outcomes while being high-risk; thus, tilting
the risk-benefit scale toward conservative treatment. For example, FTR recurs in as many as 10-30% of patients
treated via the gold-standard surgical technique tricuspid valve annuloplasty. Additionally, mortality rates of re-
operation are exorbitantly high (>30%). Clearly, better therapeutic approaches are needed to treat FTR and to
stop undertreatment of a large patient population. Our collaborative team has recently shown in two separate
sheep models that the tricuspid valve leaflets grow and fibrotically remodel in FTR. The discovery of tricuspid
valve (mal)adaptation now raises the possibility to both harness the valve’s native ability to grow, and thereby
counteract disease, and to therapeutically target leaflet fibrosis. However, before being able to use our new
knowledge toward improving treatment of FTR and toward overcoming today’s massive undertreatment, tricuspid
valve maladaptation must be better understood: To date, we don’t know its stimuli, the mechanisms of its
detrimental effects on valve function, or how therapy may be used to suppress fibrosis. The objective of this
current proposal is to overcome these gaps in knowledge. To this end, we will test our central hypothesis that
disease-induced leaflet strains stimulate leaflet maladaptation which, in turn, hinders valve coaptation and
contributes to FTR, and that leaflet maladaptation may be halted by counteracting disease-induced stimuli. We
will pursue our objective in three aims: 1) Identify the stimuli of tricuspid valve maladaptation, 2) Delineate the
mechanisms through which maladaptation impedes valve function, 3) Test whether prophylactic intervention
halts maladaptation. To accomplish these aims, we will combine innovative, chronic sheep models with in-vitro
flow loop valve characterization using high-speed 3D imaging, and extensive mechanical, compositional, and
biological tissue phenotyping. Our team has a long collaborative track record of studying tricuspid valve function
and disease, and is supported by a senior colleague with 30 years of experience in in-vitro valve experimentation.
Upon conclusion of this work, we expect to have identified the stimuli for tricuspid valve maladaptation,
understand the mechanisms through which it impedes valve function, and have shown that it can be halted
through surgical intervention. Thus, we will have shed light on a recently identified disease mechanism of the
tricuspid valve and sugge...

## Key facts

- **NIH application ID:** 10841715
- **Project number:** 5R01HL165251-03
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** MANUEL Karl RAUSCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $682,916
- **Award type:** 5
- **Project period:** 2022-06-20 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841715

## Citation

> US National Institutes of Health, RePORTER application 10841715, Tricuspid Valve Maladaptation: Its Stimuli, its Effect on Valve Function, and its Response to Therapy (5R01HL165251-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10841715. Licensed CC0.

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