麻豆传媒

SAN FRANCISCO -- Tricuspid transcatheter edge-to-edge repair (T-TEER) performed better than anticipated in patients expected to have only a modest benefit due to more complex anatomy, the TRILUMINATE trial showed.

After receiving the investigational TriClip device to hold the leaflets together, most patients enrolled in the single-arm portion of the trial as a result of their complex anatomies -- presumed to preclude a reduction in tricuspid regurgitation (TR) to moderate or less -- actually achieved that grade of regurgitation.

At 30 days, 40% dropped from severe or worse TR to moderate TR and 40% had trace or mild TR. "Equally remarkable," those rates were maintained (43% and 38%, respectively) at 1 year, David Adams, MD, of the Icahn School of Medicine at Mount Sinai in New York City, reported at the Transcatheter Cardiovascular Therapeutics (TCT) meeting.

"In retrospect, we're not very good at predicting the magnitude of TR reduction in tricuspid TEER in more complex scenarios," he said at the session.

TriClip probably isn't the answer for everyone, he said. "I'm hoping that one day we will have a portfolio of ways to do repair and replacement of the tricuspid valve in these patients. But I think our pool of potential clip candidates has expanded based on the data I've shown today."

The proportion achieving moderate or less TR in the single-arm trial (81%) was similar to the 89% in TriClip-treated patients in the randomized portion of the trial with more favorable anatomy, although the latter group achieved more mild or trace TR.

Quality of life score improvements on the Kansas City Cardiomyopathy Questionnaire (KCCQ) were similar as well.

Survival through 12 months with at least a 10-point gain over baseline in KCCQ score met the primary endpoint performance goal in that arm with a rate of 46.2% (P=0.0008) despite the more anatomically complex population in the single-arm cohort.

Adams also presented outcomes for the full 589 patients randomized in the trial, with similar findings compared with the data on the first 350 that was released earlier this year. One change was that the improvement in 6-minute walk distance achieved significance in imputed and paired analysis it didn't have in the smaller dataset.

TriClip still didn't improve 12-month freedom from mortality or tricuspid valve surgery (90.1% vs 90.3%). But the proportion with at least a 15-point gain in KCCQ score was preserved, so the additional patients strengthened the primary endpoint of those endpoints plus heart failure hospitalization in a Bayesian analysis with a win ratio of 1.53 compared with medical therapy alone (95% CI 1.14-2.05).

"Data from all randomized subjects in the TRILUMINATE pivotal trial strengthen the conclusions of the previously reported primary cohort analysis," Adams said.

In a separate analysis of the initial 350 randomized patients diving deeper into the quality of life findings, Suzanne Arnold, MD, MHA, of Saint Luke's Mid America Heart Institute and the University of Missouri-Kansas City, reported a number needed to treat of 3.5 for one additional patient to be alive and well at 12 months.

"Exploratory analyses suggested that much of the health status benefit of T-TEER could be explained by TR reduction and that improvement in health status after T-TEER was strongly correlated with reduced 1-year mortality and heart failure hospitalization," her group wrote in a paper simultaneously released in the .

Still, TCT session study discussant Gorav Ailawadi, MD, of the University of Michigan in Ann Arbor, noted that these findings didn't quite measure up to what might have been expected from mitral valve TEER with MitraClip.

"We were overwhelmed by how good COAPT was; we're not quite seeing that same level of overwhelming success although we're now starting to see a signal [of benefit with TEER]," he said. "Obviously the results with functional TR, as most of these patients are with TEER therapies, are not the same with tricuspid as they are with mitral."

Adams agreed that it's becoming clear that right sided valve disease is very different than left sided valve disease. "And we probably were a bit naive in thinking we would see mortality benefits at 1 year," he said. "We don't take a patient to the operating room and promise them they'll live longer in 1 year if we do a tricuspid valve operation. And by the way, survival is not mentioned in the ACC/AHA [American College of Cardiology/American Heart Association] guidelines indication for tricuspid valve intervention. So I think we've got to sort of start rethinking the expectation."

Arnold agreed but acknowledged one challenge: "Even if we're not seeing clinical hard endpoints, I think that making patients feel better is an incredibly important goal. And so I think with some of these open label trials, we just have to figure out how do we prove that it's real? How do we prove that improving patient's health status is not just a placebo effect?"

One big concern is that there's no information about the blinding of the patient to their echocardiographic finding at the time of completing the KCCQ, as the echo and KCCQ likely happened at the same visit.

"I'm concerned about those correlations and the unblinding of a patient knowing that their echo looks good. The tech might tell them, 'Oh, the echo looks good. You have less.' And then they take the KCCQ," said TCT press conference moderator Roxana Mehran, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

"If we want to validate these patient-reported outcomes, they have to be separated from other endpoints that could unblind or bias the results of a KCCQ," she said.

One thing that is reassuring in that respect was that patients who had the most reduction in tricuspid regurgitation garnered the greatest benefit in terms of quality of life, commented Wayne Batchelor, MD, of the Inova Heart and Vascular Institute in Falls Church, Virginia, a panelist at the press conference.

"We're starting to peel the onion a little bit and get a glimpse of how this could be biologically connected," he said. "I think the missing pieces now are the mechanistic links. So it'd be very interesting to see how this relates to changes in RV [right ventricular] modeling."