Manuel Rausch, an assistant professor with appointments in the Department of Aerospace Engineering and Engineering Mechanics and the Department of Biomedical Engineering, has received a prestigious R01 grant from the National Institutes of Health in the amount of $3.9 million. He will use the funding to lead a study of the heart’s tricuspid valve to better understand functional tricuspid valve regurgitation (FTR) – a condition that causes leakage of the valve located between the right atrium and the right ventricle of the heart.

It is estimated that 1.6 million Americans will suffer from significant FTR and that of those patients, only approximately 8-10 thousand are surgically treated, leaving a large number patients who are untreated. If left untreated, severe FTR can cause pressure to rise in the right chamber of the heart and in worst case scenarios, might eventually result in heart failure.

The main function of the tricuspid valve is to avoid backflow of blood when the heart contracts, Rausch said.

“When the heart contracts, the right ventricle contracts, and then it should propel the blood into the lungs. The blood, which comes from the body’s systemic circulation, should not be pushed back from where it came from,” Rausch said. “And that’s where the tricuspid valve comes in – it prevents the blood from being pushed back. It does so through small leaflets or flaps that come together to seal the passage between right atrium and right ventricle.”

Until recently, it was believed that when the tricuspid valve fails, it does so without showing any damage to the leaflets themselves. However, Rausch and colleagues showed over the past few years that this may not be so. In fact, they showed that the valve leaflets stiffen and thicken when they leak. These changes may contribute to FTR; thus, rendering tricuspid valve regurgitation not so functional after all.

“The research supported by this grant is essentially trying to identify what causes the thickening and stiffening on these leaflets,” Rausch said. “We want to look into the stimuli and demonstrate that stiffening and thickening of the valves actively contributes to their dysfunction. Neither for the tricuspid valve, nor for other heart valves has this been directly shown.”

The team also aims to show that early intervention might prevent this phenomenon from happening in the first place.

Currently, the standard treatment for FTR involves a surgical approach known as tricuspid annuloplasty, which is invasive, does not have a great long-term success rate and fails approximately one third of the time. Rausch’s work could motivate earlier intervention with less invasive procedures and treatments, such as drug-based therapeutics or catheter-based technology.

“Ultimately, it’s our hope is that we are able to identify a mechanism that contributes to the progression and severity of the disease, and that this motivates a reason for early intervention,” Rausch said.