# Development of a Porcine Model of Severe Tricuspid Regurgitation

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $639,763

## Abstract

Specific Aims
Tricuspid regurgitation is a very common etiology of valvular cardiomyopathy. In the United States alone, there
are an estimated 1.3 million patients with severe tricuspid regurgitation. Severe tricuspid regurgitation carries
an ominous prognosis as observational data demonstrate 1-year mortality rates are as high as 46%. At
present, there are no effective therapeutics that counteract the cardiac effects of tricuspid regurgitation, and
treatment consists of diuretics for volume overload or surgical correction. Surgical treatment is both high risk
and quite costly. The in-hospital mortality for surgical repair of tricuspid regurgitation remains at 8-10%, and the
average cost of hospitalization is >$80,000. Both medical and surgical treatment of tricuspid regurgitation is
difficult because tricuspid regurgitation compromises both right atrial and right ventricular function due to
continual volume overload, but the mechanisms underlying the pathological changes in each chamber are
undefined. These key unanswered questions will be addressed in this proposal.
One barrier to understanding the detrimental molecular effects of tricuspid regurgitation on the right atrium and
right ventricle is the lack of robust animal models of severe tricuspid regurgitation. Rodent models of valvular
cardiomyopathy are limited because it is technically challenging to induce valve disease due to the small size
of the animals. In addition, evaluation of right atrial and ventricular structure and function in rodents can be
quite challenging even with the most experienced echocardiographer. Finally, mice and rats do not provide
sufficient tissue to perform multi-omics studies, which has further hampered our ability to gain mechanistic
insights. Large animal models may circumvent some of these challenges, and offer additional advantages, as
they are widely believed to better recapitulate human physiology. However, a large animal model of severe
tricuspid regurgitation is lacking, but our supplement will close this important knowledge gap.
In our preliminary studies, we show endovascular-mediated damage of the tricuspid valve results in significant
tricuspid regurgitation and right heart remodeling. When comparing right atrial and ventricular volumes of two
pigs to our historic controls, we observed significant right heart remodeling with increased right atrial and right
ventricular end-diastolic volumes. Thus, we provide proof of principle data that we have generated a large
animal model of severe tricuspid regurgitation, and this lays the groundwork for further mechanistic and multi-
omic exploration of this highly translational model.
In this supplemental proposal, we will further refine our porcine model of severe tricuspid regurgitation and
then perform a deep molecular phenotypic evaluation of both the right atrium and right ventricle to delineate
the molecular underpinnings of right heart remodeling. Then, we will compare and contrast the effects of right...

## Key facts

- **NIH application ID:** 11076420
- **Project number:** 3R01HL162927-03S1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Kurt W Prins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $639,763
- **Award type:** 3
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11076420

## Citation

> US National Institutes of Health, RePORTER application 11076420, Development of a Porcine Model of Severe Tricuspid Regurgitation (3R01HL162927-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11076420. Licensed CC0.

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