Intermediate Disease May Be the ‘Sweet Spot’ for T-TEER Survival Benefit

For patients with tricuspid regurgitation (TR), the extent of disease appears to influence 1-year mortality following tricuspid transcatheter edge-to-edge repair (T-TEER), confirm new prospective European registry data.

Specifically, for those at extreme ends of the spectrum—early or advanced stage disease—there was no survival advantage with T-TEER.

“We know that when it comes to symptoms, patients almost always benefit, irrespective of whether they present very early, mid, or late stage of disease,” senior author Philipp Lurz, MD, PhD (University Medical Center of the Johannes Gutenberg-University Mainz, Germany), told TCTMD. “But when it comes to survival, it makes sense that that ‘sweet spot’ of intermediate disease stage might be the one where the biggest mortality benefits can be achieved.”

That doesn’t mean patients should be selected based on their disease stage, he cautioned.

“Because even when they present very late, they benefit symptomatically, and when they present early, they not only benefit symptomatically, but it might also be that they have the highest benefit in terms of lifetime management,” Lurz said.

Suzanne Arnold, MD (Saint Luke’s Mid America Heart Institute/University of Missouri-Kansas City), who commented on the findings for TCTMD, agreed it’s intuitive that there would be an ideal stage of tricuspid disease in which to intervene with T-TEER and acknowledged an inherent limitation of the major trials in this space.

“It has been a very attractive concept,” she said. “A lot of us who have participated in the TRISCEND and TRILUMINATE trials almost felt like the patients were too early in the [disease] stage and maybe that’s why they did [not see a mortality difference]. I think that we’ve had this idea that there may be a group of patients who benefit beyond just health status.”

The EuroTR study, led by Florian Schlotter, MD (University Medical Center of the Johannes Gutenberg-University Mainz), was published in the February 10, 2025, issue of JACC: Cardiovascular Interventions.

EuroTR Results

Approved in the US last year, T-TEER with the TriClip device (Abbott) has been shown to reduce the incidence of heart failure hospitalizations and improve quality of life compared with medical therapy alone. One criticism of the TRILUMINATE study that led to regulatory approval, however, was that treatment did not improve survival. This led to arguments over the optimal timing of this procedure, especially with regard to the sickest patients who might have irreversible disease.

For the EuroTR study, researchers prospectively evaluated patients (mean age 79 years; 47% male) with significant TR who underwent T-TEER (n = 1,300) with either TriClip or the Pascal system (Edwards Lifesciences) at one of 12 European centers or were managed conservatively at a single institution (n = 585). The disease stage was classified as early (21%), intermediate (62%), or advanced (17%) based on left and right ventricular function, renal function, and natriuretic peptide levels.

Mortality rates increased from 6% in those with early disease to 15% in the intermediate cohort and 31% for those with advanced-stage disease.

There was no difference in 1-year mortality risk between T-TEER and conservative management for patients with early (HR 0.78; 95% CI 0.34-1.80) or advanced stage disease (HR 1.06; 95% CI 0.71-1.60). There was a survival benefit in the intervention arm versus medical therapy among patients with intermediate stage disease (HR 0.73; 95% CI 0.52-0.99).

Defining Disease Stage

Lurz acknowledged that classifying the stage of TR disease can be subjective and that the methods used in their study are not the final word. With further refinement, future research studies might aim to enroll more patients with middle-stage disease, he suggested.

For Arnold, the current analysis is limited by the fact that the controls receiving medical therapy were enrolled at a single center, adding that the findings should be considered “hypothesis-generating.” She agreed that they should be used to help design future studies in this space, acknowledging that there is “no perfect way” to define disease stage.

“Trying to really drill down on defining the stages of disease, I think, would be really interesting and important because some of the factors that they included in here may be related to the TR, but also are just related to increased mortality from other things,” Arnold said, adding that she would like to see more focus on RV function and pulmonary pressure.

In general, though, the study findings are “good news for the field because it indicates where the biggest survival benefits might be,” Lurz said. “It should not be forgotten that we don't only do these procedures to prolong life, but we also do these procedures to ameliorate symptoms.” There are ongoing T-TEER studies in sicker patients, such as those with liver or renal dysfunction or prior heart failure hospitalizations, and these may potentially show a survival benefit, he added.

In an accompanying editorial, Firas Zahr, MD, and Scott Chadderdon, MD (both Oregon Health & Science University, Portland), say the identification of a survival benefit among intermediate disease stage patients in the study is a “salient finding.”

The study “adds to the evidence that key clinical factors—heart failure with preserved ejection fraction, mildly reduced right ventricle function, moderately reduced estimated glomerular filtration rate, and moderately elevated N-terminal pro–B-type natriuretic peptide—may indeed define this optimal treatment zone.”