Transcatheter Options Best for Tricuspid Regurgitation in Matched Registry Analysis

SAN FRANCISCO, CA—In patients with severe, symptomatic tricuspid regurgitation (TR), a comparison pitting a range of different transcatheter interventions against medical therapy suggests that the these approaches are associated with a lower risk of death and hospitalization for heart failure, as well as a lower risk of all-cause mortality.

The new propensity-matched analysis, which was presented at TCT 2019 and published simultaneously in the Journal of the American College of Cardiology, suggests that the rate of survival free from heart failure at 1 year was 51.3% among patients treated with medical therapy and 68.4% among those treated with a transcatheter option (P = 0.0003).  

The analysis drew on registry numbers that included outcomes for several devices currently being used for tricuspid disease under compassionate use. The MitraClip (Abbott Vascular) was used in approximately 80% of patients, but also employed in smaller numbers were the Forma and Pascal tricuspid repair systems, the Trialign annuloplasty system, and Cardioband (all from Edwards Lifesciences), as well as the TriCinch repair technology (4TECH) and NaviGate valve bioprosthesis (NaviGate Cardiac Structures). 

“The prevalence of tricuspid regurgitation in the cardiology population, as well as in the general population, is high,” said lead investigator Maurizio Taramasso, MD, PhD (University Hospital of Zurich, Switzerland). “We’ve known for several years that the presence of significant TR is associated with an increased risk of adverse events, including reduced survival and increased heart failure hospitalization. Still, there is some uncertainty with regard to what we can do for the patient by reducing TR. We don’t know if reducing TR by an intervention is a good goal.”

Jeroen Bax, MD (Leiden University Medical Center, the Netherlands), who moderated the late-breaking science session, called the transcatheter treatment of TR the next frontier in cardiovascular medicine. Commenting on the buzz that’s surrounded TAVR for the past several years, Bax said that while the field of transcatheter tricuspid valve interventions is still in its relative infancy, there is a growing interest in treatments targeting dysfunctional tricuspid valves.

“Most people go to the aortic sessions, but this is where the field is going to go,” he said. “We are taking care of the aortic valve problems and we are taking care of the left atrium problems, such as atrial fibrillation and left atrial appendage [closures]. These diseases, like the tricuspid, are difficult and are challenging, but this is what we’re going to be doing in the next couple years.”

Paul Fiorilli, MD (Penn Medicine, Philadelphia, PA), who was not involved in the study, said he was impressed by the propensity-matched analysis, noting that it’s one of the first to compare clinical outcomes among patients treated with transcatheter tricuspid valve therapy with individuals who receive standard medical therapy.

“There’s the obvious caveats, including that medical therapy isn’t standardized,” he told TCTMD. “At first glance, the data look very good in terms of procedural success, which obviously can be improved, although the success rate is reasonable. The outcomes associated with the patients who did have procedural success and a reduction in their TR are excellent. It clearly shows a reduction in hard outcomes.”

The next step, he said, will be to confirm these data in a randomized controlled trial. “But they’re very encouraging,” said Fiorilli. “In patients where you can obtain a reduction in TR with the transcatheter approach, those patients are likely to do much better than those treated with medical therapy. It basically tells me going forward that this is where the field is headed.” 

The TriValve Registry From Leiden and Mayo

In the absence of randomized trial data, the researchers turned to the TriValve Registry, which includes data on transcatheter tricuspid valve interventions performed in patients with severe or greater symptomatic TR at 22 heart centers in Europe and North America.

The decision to perform the intervention under a compassionate use protocol was made by institutions’ heart teams following clinical and anatomical assessment. The overall population included 472 patients undergoing transcatheter valve interventions and 1,179 patients treated with medical therapy. The propensity-matched analysis, which paired patients according to age, surgical risk, and systolic pulmonary arterial pressure, ultimately included 268 patients in the transcatheter intervention and medical therapy arms, but even after matching, the patients treated with transcatheter tricuspid interventions were significantly sicker. For example, they were more likely to have NYHA class III/IV heart failure, mitral regurgitation, atrial fibrillation, and a pacemaker or defibrillator. 

In the unadjusted propensity-matched analysis, a transcatheter intervention for the treatment of TR was associated with a 40% reduction in death or hospitalization for heart failure and a 44% reduction in all-cause mortality. In an adjusted model that accounted for sex, NYHA class, atrial fibrillation, and right ventricular dysfunction, transcatheter tricuspid valve therapy was associated with a 61% lower risk of death or heart failure hospitalization and a 59% lower risk of all-cause mortality.

Investigators observed a significant difference in clinical outcomes among individuals who underwent a successful transcatheter intervention—defined as residual TR less than grade 3+ and successful retrieval of the device—and those who did not. Risk of death/hospitalization for heart failure and all-cause mortality were similar for patients with an unsuccessful transcatheter procedure and those treated with medical therapy.

“If you don’t reduce TR, basically the outcome is similar to the control group,” said Taramasso. “If you don’t reduce TR, what you see when you look at the curves is that survival and the composite endpoint is pretty much comparable to the natural history of the disease.”

Successful Procedure in 85% of Cases

Of the 268 patients treated via a transcatheter intervention, procedural failure occurred in 14% of patients. This number likely doesn’t reflect real-world practice given the experience of operators at these high-volume institutions, said Taramasso. In the overall population of 472 patients treated with transcatheter valve interventions, procedural success was approximately 75%. Achieving a success rate of 85% and higher, said Taramasso, is “not so easy.”

For years physicians have focused on left-sided valvular disease, atrial fibrillation, and mitral regurgitation; the tricuspid valve has sometimes, in the past, been “lost in the mix,” said Fiorilli. Additionally, physicians are aware that mortality with tricuspid valve surgery is relatively high, and there are no data showing that intervening to reduce TR with surgery improves clinical outcomes. In fact, a recent analysis published in the Journal of the American College of Cardiology showed that surgery was not associated with improved survival compared with medical therapy in patients with severe TR.

At their institution, the current treatment course for such patients is mainly diuretics, said Fiorilli. “This analysis encourages us that there are some good options available, obviously on [an investigational] trial basis,” he said. “The results look reasonable. It may shift our practice a little bit to more aggressively enroll patients in tricuspid trials.”     

These new data emphasize the unmet treatment needs of patients with severe TR, agreed panelist Mayra Guerrero, MD (Mayo Clinic, Rochester, MN). While Guerrero believes transcatheter interventions for severe symptomatic TR will prove to be the right approach for patients, “we have to find the right therapy,” she said.

Robert Bonow, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), who spoke with the media, said that one of the goals with patients with severe or greater symptomatic TR is earlier treatment. “We’re often seeing these patients late in the game when they come for surgery,” said Bonow. “It’s a struggle sometimes, and these data show that replacing the tricuspid valve does lead to a better outcome and perhaps that can be done with a transcatheter approach.”

Bax agreed. “We need to go in earlier,” he said. “That’s my view in almost everything we do in cardiology. These things don’t get better if you don’t treat them. You can delay the process a bit with medical therapy, but at the end of the day you need to cure it. For that reason, I think we need to step in earlier. This is a specific issue with tricuspid regurgitation.”

Speaking with the media, Taramasso said one of the goals of the TriValve Registry, which is a collaboration between Leiden University and the Mayo Clinic, is to identify specific patients with severe TR would benefit from the transcatheter intervention, as well as provide information on technical success and feasibility of the procedures. “Of course, we need more patients and longer follow-up, but the idea is that based on the data we’re collecting we’ll able to know when is too late [for an intervention], which patients should not be treated, and what are the predictors of worse outcomes,” he said.