Percutaneous tricuspid valve replacement improves patient outcomes

Xiaoping Li¹, Jianshe Yang^2*

1. University of Electronic Science and Technology of China, Chengdu, China

2.Tongji University School of Medicine, Shanghai, China

*Corresponding author:

Professor Xiaoping Li, MD, University of Electronic Science and Technology of China, Chengdu, China,E-mail: lixiaoping@uestc.edu.cn

Professor Jianshe Yang, Ph.D, Tongji University School of Medicine, Shanghai 200072, China. Tel: +86-21-66302721, E-mail: 2305499@tongji.edu.cn

Tricuspid valve regurgitation is a type of heart valve disease. The valve between the two right heart chambers doesn't close as it should. Blood flows backward through the valve into the upper right chamber. If you have tricuspid valve regurgitation, less blood flows to the lungs. The heart has to work harder to pump blood.

Some people are born with heart valve disease that leads to tricuspid regurgitation. This is called congenital heart valve disease. But tricuspid valve regurgitation also may occur later in life due to infections and other health conditions.

Mild tricuspid valve regurgitation may not cause symptoms or require treatment. If the condition is severe and causing symptoms, medicine or surgery may be needed.

Tricuspid valve regurgitation often doesn't cause symptoms until the condition is severe. It may be found when medical tests are done for another reason.

Symptoms of tricuspid valve regurgitation may include: extreme tiredness, shortness of breath with activity, feelings of a rapid or pounding heartbeat, pounding or pulsing feeling in the neck, swelling in the belly, legs or neck veins. To understand the causes of tricuspid valve regurgitation, it may help to know how the heart and heart valves typically work.

The tricuspid valve is between the heart's two right chambers. It has three thin flaps of tissue, called cusps or leaflets. These flaps open to let blood move from the upper right chamber to the lower right chamber. The valve flaps then close tightly so blood doesn't flow backward.

In tricuspid valve regurgitation, the tricuspid valve doesn't close tightly. So, blood leaks backward into the upper right heart chamber. Causes of tricuspid valve regurgitation may include following possible reasons.

A heart problem you're born with, also called a congenital heart defect. Some congenital heart defects affect the shape of the tricuspid valve and how it works. Tricuspid valve regurgitation in children is usually caused by a rare heart problem present at birth called Ebstein anomaly. In this condition, the tricuspid valve does not form correctly. It also is lower than usual in the lower right heart chamber.

Marfan syndrome. This condition is caused by changes in genes. It affects the fibers that support and anchor the organs and other structures in the body. It's occasionally associated with tricuspid valve regurgitation.

Rheumatic fever. This complication of strep throat can cause permanent damage to the heart and heart valves. When that happens, it's called rheumatic heart valve disease.

Infection of the lining of the heart and heart valves, also called infective endocarditis. This condition can damage the tricuspid valve. IV drug misuse increases the risk of infective endocarditis.

Carcinoid syndrome. This condition occurs when a rare cancerous tumor releases certain chemicals into the bloodstream. It can lead to carcinoid heart disease, which damages heart valves, most commonly the tricuspid and pulmonary valves.

Chest injury. An injury to the chest, such as from a car accident, may cause damage that leads to tricuspid valve regurgitation.

Pacemaker or other heart device wires. Tricuspid valve regurgitation might happen if wires from a pacemaker or defibrillator cross the tricuspid valve.

Heart biopsy, also called an endomyocardial biopsy. Heart valve damage can sometimes happen when a small amount of heart muscle tissue is removed for examination.

Radiation therapy. Rarely, radiation therapy for cancer that is focused on the chest area can cause tricuspid valve regurgitation.

There are many risk factors that can increase the risk of tricuspid valve regurgitation, such as, an irregular heartbeat called atrial fibrillation (AFib), being born with a heart problem, called a congenital heart defect, damage to the heart muscle, including heart attack, heart failure, high blood pressure in the lungs, also called pulmonary hypertension, infections of the heart and heart valves, history of radiation therapy to the chest area, use of some weight-loss drugs and medicines to treat migraines and mental health disorders.

Tricuspid valve regurgitation complications may depend on how severe the condition is. Possible complications of tricuspid regurgitation include:

An irregular and often rapid heartbeat, called atrial fibrillation (AFib). Some people with severe tricuspid valve regurgitation also have this common heart rhythm disorder. AFib has been linked to an increased risk of blood clots and stroke.

Heart failure. In severe tricuspid valve regurgitation, the heart has to work harder to pump enough blood to the body. The extra effort causes the lower right heart chamber to get bigger. Untreated, the heart muscle becomes weak. This can cause heart failure.

Right heart system disease currently lacks effective clinical treatment methods. With the progress of interventional valve technology, minimally invasive interventional surgery has also entered the "three-valve era". Earlier, the TRILUMINATE study initially confirmed that percutaneous tricuspid margin repair could significantly reduce tricuspid regurgitation and improve the quality of life. However, given that clamp surgery may still have some degree of residual reflux, with a potentially detrimental impact on prognosis. Valve replacement may better repair valve function, bring a more stable prognosis. Recently, NEJM published the TRISCEND II study results to initially verify the clinical efficacy and safety of a percutaneous tricuspid valve replacement. 

In this international multicenter trial, 400 patients with symptomatic severe tricuspid regurgitation were randomized at a 2:1 ratio to receive transcatheter tricuspid valve replacement plus medication (valve replacement group) or medication alone (control group). The stratified composite primary endpoints included rate of death from any cause, rate of RV AD or heart transplantation, rate of postoperative tricuspid intervention, hospitalization rate of heart failure, percentage increase of total score (KCCQ-OS), at least one grade of New York Heart Association (NYHA), and at least 30 m. The win rate (Win Ratio) of the primary outcome was calculated starting from the first event in the hierarchy.

The win rate (Win Ratio) of the primary outcome was calculated starting from the first event in the hierarchy. The results showed that a total of 267 patients were assigned to the valve replacement group and 133 patients to the control group. At 1 year, the odds for the valve replacement group were 2.02 (95% confidence interval [CI], 1.56 to 2.62; P <0.001). In patient paired comparisons, the valve replacement group won more than the control group in death from any cause (14.8% vs 12.5%), postoperative tricuspid intervention (3.2% vs 0.6%), and improved KCCQ-OS score (23.1% vs 6.0%), NYHA cardiac rating (10.2% vs 0.8%), and 6 minutes increased walking distance (1.1% vs 0.9%).

The valve replacement group won less than the controls in annual heart failure hospitalization rates (9.7% vs 10.0%). The incidence of severe bleeding was 15.4% in the valve replacement group and 5.3% in the control group (P=0.003); the proportion of new permanent pacemaker was 17.4% and 2.3%, respectively (P <0.001).

This study demonstrated that in patients with severe tricuspid regurgitation, percutaneous tricuspid valve replacement significantly improved the overall outcomes of patients. Furthermore, tricuspid valve replacement may bring more bleeding risk and implantation of a permanent pacemaker. Overall, this study provides important supporting evidence for clinical use of tricuspid regurgitation replacement. However, the statistical analysis of Win Ratio does put the clinical practical significance of the results into doubt. From a classical statistical perspective, there was little significant change between the two groups in the incidence of mortality events and HF readmission rate. The improvement in the subjective assessment of patients' symptoms and quality of life, but the non-blinded design of this study is flawed in the subjective scale assessment. In fact, one of the main findings of this study was that 95% of patients in the device group could improve from severe tricuspid regurgitation to less than mild tricuspid regurgitation, but how long such hemodynamic improvement can translate into the benefit of a clinical hard end point, we look forward to more long-term follow-up data.

Reference

1. Hahn RT, Makkar R, Thourani VH, Makar M, Sharma RP, Haeffele C, et al. Transcatheter Valve Replacement in Severe Tricuspid Regurgitation. N Engl J Med. 2024 Oct 30. doi: 10.1056/NEJMoa2401918. 

2. Huynh, K. Transcatheter repair for severe tricuspid regurgitation. Nat Rev Cardiol 20, 284 (2023). https://doi.org/10.1038/s41569-023-00859-1