So my name is Gagan Singh. I'm an interventional cardiologist and structural cardiologist at the University of California, Davis Health in Sacramento, California. I kind of specialise predominantly in structural heart procedures involving the mitral and tricuspid valves, and then also left atrial appendage closure.

What is the importance of this study?

To back up a little bit, TRILUMINATE is looking at therapy for patients with tricuspid regurgitation, and tricuspid regurgitation has always been this, you know, bastard stepchild if you will. You know, it's a disease, we don't really have anything for it so we'll just not bother with it.

And I think having a therapy now for a heart valve disease really allowed us to look into it and to see, hey, what is their anatomy and anatomical considerations, what are the clinical considerations and then how does it impact patients? And we see these patients and they're suffering, they have really bad right-sided heart failure, they have cross chronic symptoms, they live just a miserable life.

So TRILUMINATE, the early series, showed that you know, hey listen, it was safe, we could put it on successfully, these clips, and patients did okay. And then the pivotal trial, which you're referring to, was really the first of its kind. It really was a groundbreaking, landmark clinical trial that really has now paved the way for a huge multi-billion dollar industry for tricuspid valve disease.

And so TRILUMINATE is now for the first time, it answers the question, if you just leave these patients alone versus if you put clips on them, can you impact their quality of life, can you keep them out of the hospital? And that's what this trial answered.

Could you explain the study design and patient population in the TRILUMINATE pivotal trial?

The study design was a randomised trial. So it was patients who had severe, symptomatic tricuspid regurgitation who had been optimised on medical therapy. And this is adjudicated by heart failure physicians. So a lot of patients had to be on diuretics, high doses of diuretics, they had to be on mineralocorticoid receptor antagonists, they had to be on Jardiance or SGLT2 inhibitors. And after all of that, they underwent hemodynamic studies and these patients could not be decompensated, they had to be fully optimised and then they had to undergo transesophageal echoes to make sure that they had anatomy that was suitable for the clip procedure.

And after you went through this very rigorous screening process, then basically those patients were then randomised to either medical therapy or they received the clip procedure. On average, patients were in their 70s to 80s, 90% plus of them had atrial fibrillation, at least a third of them had prior pacemaker leads. So overall, a very sick cohort, many of them with class III, class IV heart failure symptoms.

What were the key findings from the two-year outcomes data?

Yeah, the two-year data is really just, I think, something that's again groundbreaking. When we looked at the one-year data, what we saw was that there was quality-of-life improvement, and you know, there was a lot of debate about that. Is that meaningful? Does that really impact the patient? Does that really impact payers, especially, you know, insurance companies?

And so that was a lot of debate, and now fast forward a year later, not only do we have sustained improvement of quality-of-life metrics, not only do we have sustained reduction in tricuspid regurgitation, but now we actually have reduction in heart failure hospitalisations which is, I think, a big deal because we come from the aortic world, the mitral world.

We're expecting changes within the first six months to one year. This is a very different group of patients. They're not immediately dying from tricuspid regurgitation, they're just living a chronically miserable life and it's a very, very slow process. So at two years, the trial now shows that these patients, actually, we can keep them out of the hospital if they're treated with the tricuspid clip procedure.

There was a 28% reduction in heart failure hospitalisation. And what we focused on in the presentation here at EuroPCR was predominantly looking at the control patients. A lot of these control patients, if you leave them alone, and this is for the first time ever, we now have natural history data on tricuspid regurgitation in a clinically adjudicated and an echo adjudicated manner — nobody's ever done that before.

And what we're finding is that if you leave patients with tricuspid regurgitation alone that they do progress even as early as one year and their TR regurgitation gets worse, their symptoms get worse and you want to catch them before they get too far gone.

What implications do your results have for current guideline recommendations?

You got to take TR seriously. If you have tricuspid regurgitation and the patients have symptoms, you can't just sit on it — that's kind of the key take-home messages. What we're also learning now, with five-plus years of experience in the tricuspid space, we're not just targeting patients to just moderate regurgitation or less: we really need to get them down as low as possible; we need to identify these patients faster; we need to get them on medical therapy sooner, and then if they are candidates, to offer them therapy sooner. And I think those are some of the key messages, key clinical implications, is that we just can't sit on these patients for that long.

What further research is needed, and what are the next steps in advancing T-TEER techniques?

Yeah, that's actually the million-dollar question, which is , clinically, what are these patients going to look like? So in the TRILUMINATE clinical trial, the pivotal trial, patients either got treated with the device right at time point zero, and those are going to be followed out to five years. So we'll continue to analyse those patients and follow those patients and see how they're doing.

At one year, patients were allowed to cross over. Of the cross-over patients, about a quarter of them, of the patients that crossed over, a quarter of them had heart failure hospitalisations, three quarters of them had progression of symptoms.

So now these patients have been treated and we're going to follow them out for another two, three years. The question is, can we restore them to the same level as these patients who were originally treated with a device or did we lose precious time in that one year? So that's going to tell us on that if we can actually get to these patients ahead of time.

And then there's about a little under 50 patients that are so far still in the control arm and are not treated. So the question is, how do they do at year two, year three, year four, year five? I think this is going to be important because there's not just TEER therapy, there's replacement therapy, there's all these other non-alternative, non-repair or replacement therapies that people are working on. And I think people are recognising that A: it's a problem and you cannot sit on these patients. And that's what the ongoing research will help us identify.