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NEW ORLEANS -- Transcatheter edge-to-edge repair (TEER) of severely regurgitant tricuspid valves improved outcomes, largely in terms of quality of life, the TRILUMINATE Pivotal trial showed.

Compared with medical therapy alone, the percutaneous placement of an investigational TriClip device to hold the leaflets together was favored in a Bayesian analysis with a win ratio of 1.48 (95% CI 1.06-2.13, P=0.02), reported Paul Sorajja, MD, of the the Valve Science Center at Minneapolis Heart Institute Foundation, at the American College of Cardiology (ACC) annual meeting. The findings were simultaneously published in the (NEJM).

That primary endpoint was a hierarchical composite of death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and at least a 15-point improvement in quality of life on the 100-point Kansas City Cardiomyopathy Questionnaire (KCCQ) scale at 1 year.

The only component with a significant difference between groups was KCCQ improvement, with a mean gain of 12.3 points after TEER versus 0.6 points with medical therapy alone (P<0.001).

Trial Implications

"For patients with tricuspid regurgitation who are at too high a risk for surgery or at intermediate risk, it's great to have an option," said ACC late-breaking trial session panelist Ajay Kirtane, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York City.

However, he called it disappointing that there were no hard-outcome improvements as is commonly expected from reducing tricuspid regurgitation (TR). Indeed, TEER brought 87.0% of treated patients to no greater than moderate TR severity, compared with 4.8% of those in the control group (P<0.001).

"We all believe that the clip reduces TR, and then we all believe that pathologically TR severity affects outcomes -- so why is there no difference in any other outcome?" he posited.

Sorajja responded that while that relationship has held in left-heart failure, the evidence hasn't been established for right-heart failure. "The guidelines tell us look for those severe symptomatic patients and treat them, but unfortunately the American guidelines specifically do not have class I indications for TR because we do not know what the long-term benefit is for these patients."

"This is first randomized clinical trial to study and test the impact of TR reduction on long-term effects on survival," he said. "We have to start thinking about right-sided versus left-sided disease."

ACC press conference discussant Kendra Grubb, MD, of Emory Structural Heart and Valve Center in Atlanta, also expressed surprise at the lack of mortality impact, but suggested that such an impact might emerge as these patients are followed out longer-term in comparison to medical therapy, which is essentially diuretics in this group.

Until there are such benefits, or more than the moderate quality-of-life advantages shown in the trial, uptake might be low, suggested Joanna Chikwe, MD, of Cedars-Sinai Medical Center in Los Angeles.

However, there are other transcatheter devices in development for TR, including replacement akin to surgical annuloplasty, she pointed out in an interview with 木瓜直播. If those pan out in to more substantially reduce TR, they might be preferred.

Based on findings from the mitral space, when patients get a clip, it makes transcatheter replacement much more challenging, essentially limiting patients to one or the other percutaneous approach, she said.

Whichever technology emerges on top, an important message is treating earlier, when TR is severe, rather than massive or torrential, Grubb and Chikwe agreed.

Trial Details

The trial included 350 patients with severe TR and New York Heart Association functional class II, III, or IVa symptoms despite a stable guideline-directed heart failure medication regimen. They also had a pulmonary artery systolic pressure of less than 70 mm Hg.

Enrollment excluded patients with any other cardiovascular conditions in need of interventional or surgical correction, such as severe aortic stenosis or mitral regurgitation. Those with anatomy not suitable for the TriClip therapy, or for whom the device wasn't expected to reduce TR to moderate or less, were also not randomized. More complex anatomy patients were enrolled in a single-arm trial, the results of which were , showing high implant and procedural success, as well as at least a two-grade reduction in TR in most cases.

Patients had to be at intermediate or greater surgical risk as determined by their local heart team at the 65 participating centers in the U.S., Canada, and Europe.

They were randomly assigned to receive either TEER with the TriClip G4 delivery system within 14 days of randomization or medical therapy alone during the enrollment period from Aug. 21, 2019 through Sept. 29, 2021.

Procedure involved transfemoral delivery of the device with a 25-French catheter under echocardiographic and fluoroscopic guidance for the operator and general anesthesia for the patient.

The cohort averaged age 78, with 55% women and 94% having functional tricuspid regurgitation. Comorbidities included atrial fibrillation in 90%, hypertension in 81%, and a cardiac implantable electronic rhythm device in 15%. More than one-third had previous mitral or aortic-valve interventions, and a quarter had been hospitalized for heart failure within the year before enrollment.

Fully 71% had massive or torrential tricuspid regurgitation (grade 4 or 5). The left side was largely preserved with an average left ventricular ejection fraction of 59% (20% or greater was required for entry).

The primary endpoint win ratio calculation was described in NEJM as "forming all possible pairs of one patient from the TEER group and one patient from the control group and then dividing the number of pairs in which the patient in the TEER group has a better outcome than the patient in the control group (i.e., a win in the TEER group) by the number of pairs in which a patient in the control group has a better outcome than the patient in the TEER group."

Reduction in TR also evident and durable in paired analysis through 12 months, Sorajja noted. Residual TR was linked to quality of life, and change in severity was associated with better quality of life.

The hierarchical secondary points of 30-day freedom from major adverse events and reduction in TR severity to no more than moderate significantly favored, although change in 6-minute walk distance from baseline to 12 months didn't differ between groups.

Strengths of the study included use of an echo core lab to independently confirm TR severity before enrollment, but limitations centered on the lack of a sham treatment, which could have contributed to a Hawthorne effect.

KCCQ scores in the control group improved as well, Kirtane said, noting that patients brought back in an unblinded fashion told they had a TR reduction might be more likely to state that their quality of life is improved in some ways.

"We do not feel this is a placebo effect," countered Sorajja.

Importantly, the procedure was "remarkably safe," he added. While there was one case of cardiovascular mortality and one tricuspid valve surgery for persistent TR, there were no elective cardiovascular surgeries and no device-related adverse events. The permanent pacemaker rate was 1.6% in each arm, which Sorajja called "very, very low for a TR therapy."

One question is whether patient selection should target patients who have poor quality of life at baseline, Kirtane said, since there didn't appear to be a downside to waiting to treat patients in the trial in terms of hard outcomes. Another is what will be the best approach for younger and healthier patients, he added.

"Before we go to low risk," Sorajja responded, "we have to really understand what low risk is. It was relatively easy to enroll in this trial despite the pandemic because these patients did not have a good alternative out there," whereas low risk patients do have surgery as an option.

"We're learning lot, because this is a new therapy, there were a lot of new operators, a lot of the operators had never seen this device or done this procedure before," he said. "There is opportunity to do additional clips to reduce TR...I think like MitraClip, with time it will get better."

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