TRILUMINATE trial may pave the way for FDA clearance for tricuspid valve clip device

Paul Sorajja, MD, director, Center for Valve and Structural Heart Disease, Minneapolis Heart Institute, Abbott Northwestern Hospital, was the principal investigator for the late-breaking TRILUMINATE pivotal trial at the American College of Cardiology (ACC) 2023 meeting and explains details of this landmark trial. 

TRILUMINATE was a randomized study of transcatheter tricuspid valve edge-to-edge (TEER) repair for tricuspid regurgitation (TR). Surgical outcomes in these patients are not the best and only about 500 tricuspid surgical replacements are performed each year in the United States, Sorajja explained. This has left most patients to be treated medically, and interventions for this valve have largely been absent.[1]

With the success of the MitraClip device over the past decade for mitral regurgitation, a similar device, the TriClip, was developed for the tricuspid position. The positive data from this trial will be used for U.S. Food and Drug Administration (FDA) device review. 

"It's an exciting therapy, to be honest, because when you look at these patients with TR, they have had very few options for so many years," Sorajja explained. "For the first time we now have a solution that works. It is highly effective, it is safe and leads to a lot of improvement in quality of life."

The data show TR was reduced using TriClip from the categories of severe, massive and torrential, down to moderate or below in 87% of patients. The reduction in the control group who were treated with medical therapy alone was only 4.8%. 

The safety in the procedure was also a big improvement over surgical risks in these patients. The overall major adverse cardiovascular event (MACE) rate was 1.7%, with a death rate of 0.6% and a pacemaker rate of 0.6%.

"This is an incredibly safe procedure, and that is really important because the alternative of surgery in these patients really carry significant risk," Sorajja explained. 

Tricuspid regurgitation is not the same as MR or AR 

The surgical risk is much higher in these patients, unlike the much better surgical valve replacement outcomes seen in mitral and aortic valve replacements. Many times physicians make comparisons with the mitral regurgitation (MR) and aortic regurgitation (AR) to the tricuspid, but it has much different functionality and its own specific traits on the right side of the heart.

For example, Sorajja said unlike residual MR or AR, tricuspid patients can endure residual TR levels much better. For this reason, any improvement in TR, even with residual regurgitant jets, make the patient feel much better. 

"Residential TR is actually something that patients tolerate in a much different way, and we need to get away from trying to extrapolate that what we see on the left side of the heart is what we should see on the right side, because it is not. There are a lot of patients that live with moderate or severe TR for many years, and our data actually sheds light on the fact that when they are well managed medically, they can also go a long time as well.," Sorajja said.

With the higher risks associated with tricuspid valve replacement, repair now looks like the best option in TR patients.

"It is always better to have what nature gave you and try to work with that rather than replace everything," he explained. 

Use of 4D ICE to navigate tricuspid procedures

Five to seven years ago most interventional operators and echiocardiographers did not have any idea of how to get the best transesophageal echo (TEE) views of the tricuspid valve, and a lot has been learned in the just the past few years. Since the valve is on the side of the heart closest to the chest wall, TEE has to image through a lot of tissue and blood to view the valve and its surrounding anatomy, which is not ideal. Transgastric TEE views have also been developed to help image the valve. 

Another advancement helping transcatheter tricuspid valve procedures is intra-cardiac echo (ICE). With the introduction of 3D/4D ICE imaging catheters over the past few years, this technology has been very helpful to guide TriClip procedures. 

"I think this is one of the most amazing things that we teach the field of medicine is how to image the tricuspid valve in ways that we haven't been able to before," Sorajja said. "ICE is a really interesting way to look at the valve. When coming up from the IVC, the ICE catheter is right on top of the tricuspid valve."

He said right now he does not believe 4D ICE can replace TEE completely, but said it is an "amazing" complement to TEE.

"We have had a lot of experience with ICE, and it has saved us in a number of cases where the TEE could not see what we needed to see," Sorajja said.

What TriClip means to the future of tricuspid regurgitation patients

He said quality of life appears to be much more of a factor for patients with right side valve disease that in left side valve diseases. From that standpoint, he does see TEER as a major step forward to help these patients. 

"It would be one thing if the safety and effectiveness in the trial were just marginal. But the effectiveness and safety were out of this world, and the improvements for the quality of life were highly meaningful. So while we did not see differences in survival or hard endpoints, to me it fits with what these patients want," Sorajja explained. "The average age of these patients is 79. They do not come in asking to live longer, they ask about feeling better tomorrow." 

The complexity of the anatomy and treating the tricuspid valve is also much easier that that of the mitral valve. After the success of transcatheter aortic valve replacement (TAVR), there was wide expectation that the mitral valve was going to be the next great frontier. While that is how things started out several years ago, tricuspid valve device therapies and trials have been able to speed past mitral devices in development. The TriClip and a couple other tricuspid valve now appear to be of the verge of regulatory clearance in the next couple years. The fact that they are few treatment options for tricuspid patients and surgical outcomes are poor also has raised interest in finding new tricuspid solutions.

"Tricuspid valve therapies will likely pass mitral in that way, because there is no good alternatives. In mitral, we have great alternatives. Recent surgical data for mitral shows it has a mortality risk of just 0.6%, I mean, who can argue with that safety margin," he said.

Sorajja said transcatheter mitral valve repair and replacement still has a ways to go to catch up with surgical outcomes, but the story is very different in the tricuspid valve. 

"The surgical risks in tricuspid are so much higher, but transcatheter tricuspid is so much different and the alternatives with medical therapy are just not there," Sorajja concluded. 

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