My name is Susheel Kodali, I'm an interventional cardiologist at Columbia University in New York.
1. What is the TRISCEND Study and what does it aim to address?
So, the TRISCEND Study is looking at studying the sort of, the safety and feasibility of transcatheter tricuspid valve replacement with the EVOQUE System. And part of the rationale is I think over the last several years in the last decade, we've seen that severe TR and transcatheter options for the treatment of severe TR is an unmet need. We're seeing more and more patients that present with symptomatic TR, that are not good surgical candidates, that don't have options. And even the guidelines don't really address the issue of options for treatment of tricuspid regurgitation, and you know, guideline-directed medical therapy is the management of left-sided heart disease and diuretics. So, there's a lot of patients with symptoms and, you know there are different devices that are looking at it. You know transcatheter repair technologies with either Triluminate and PASCAL have done some early feasibility studies showing that it's feasible. But they also demonstrated a lot of the limitations of repair. You know, there are a lot of anatomies that aren't suitable. You can't get, you know, getting a predictable reduction of TR to moderate or less is not always feasible in many patients. And so transcatheter replacement from a femoral approach, in a way, in a manner similar to TAVR, would potentially be an ideal option. And the EVOQUE system from Edwards is designed to replace the tricuspid valve in a native tricuspid annulus via a transfemoral percutaneous approach.
2. What was the design, patient population, and endpoints?
So, this was a prospective, single-arm, multicentre study. You know, there was a fair amount of trial oversight. There was a central screening committee, made up of people from the company, but also physician leaders, an echocardiographic core lab, the clinical events committee, and a data safety monitoring board. The population was basically patients with symptomatic, moderate, or greater TR, although the majority, more than 90% had severe and you know, and 50% had massive or torrential TR. These were patients that were seen by their local heart team and felt to have symptoms despite optimal medical therapy. And so, then they underwent screening with the TEE and a CTA, and if they were anatomically suitable, they were eligible to receive the EVOQUE valve replacement system. The endpoints were device and procedural success, you know, device success was the valve deployed and the delivery system retrieved in the intended position. And the procedural success was basically device success without significant PVL at the end of, my discharge. And then the other endpoint was major adverse events at 30 days.
3. What are the key findings to date?
So, we've, the key findings, basically, in an elderly population with a median age of 79 that was sort of high risk for surgery, with a lot of co-morbidities, including Afib, and more than 90% ascites, and more than 20% chronic kidney disease in two-thirds of the patients and, you know patients who had prior surgery, and prior CABG, in 14% prior valve surgery, and 40% that the transfemoral replacement was feasible. You know, the valve was deployed in all but one patient successfully. Procedural success was 94%. And this was done in a percutaneous manner in all patients. You know these were patients that had a median length of stay post-procedure of three days. And the vast majority, 89% were discharged to home. Another 5% were discharged home with services, and only 5% were discharged to a nursing facility or another hospital. And so it was a feasible approach in this elderly, highly comorbid population. Now there were, you know, adverse events, which is not unexpected. The major adverse event rates were 22.6%. The majority of these were bleeding events as defined by MVR criteria. And none of the bleeding events was life-threatening or fatal. Many of them were not related to the procedure. There was one vascular site or access site bleeding. There were four vascular bleedings, sort of non-access site, but the rest were not related to the EVOQUE valve replacement procedure. There was some epistaxis, there were two GI bleeds. There was haematuria, there were two patients that had blood loss during a follow-up surgical tricuspid valve intervention. But there, you know, in this elderly population with high bleeding risk, and as I said 20% ascites, the bleeding rates were not surprising. There was one cardiovascular mortality. This was a patient that had an EVOQUE procedure that was where the valve was deployed low. They required a SAPIEN in it. And the patient just sort of had persistent right heart failure after and died at around three weeks. There was one other mortality which was not cardiovascular. A patient died from a carcinoid that was pre-existing within 30 days. As I said there were two patients that ended up having surgical reintervention. And this was for, you know, valve embolization, or valve migration, or valve malpositioning. And so, these two patients went to surgery, got their valve explanted, and then they were discharged successfully. So, the other important finding is the device worked well in reducing TR. When we look at matched echoes, as I said 44% had massive or torrential TR at baseline. At 30-day follow-up, all but one patient had mild or non-TR. Two-thirds of patients had none or trace TR. So, the valve was effective. And one, and there was also evidence of, you know, sort of remodelling post valve replacement. RV mid-diastolic diameters and IVC diameters got smaller between baseline and 30 days. One important concern that we all have with transcatheter replacement is how does the RV handle it? And how does RV function work? And what we noticed was after the procedure at discharge there was some worsening of RV function. You know, patients with severe RV dysfunction were excluded from the trial, but at discharge, there was some worsening in RV function with, you know, about a quarter of the patients having moderate or severe RV dysfunction. But we noticed by 30 days that this had started to improve. And so that's something that we need to look at more closely as we go forward. Importantly, these patients got a tremendous clinical benefit. There was a significant improvement in six-minute walk distance by about 46 meters from a very, sort of, inhibited baseline of around 200 meters. They improved significantly. KCCQ scores improved by 19 points, which is dramatic. And this is the same level of improvement that we've seen with other transcatheter valve therapy, such as MitraClip or TAVR.
4. What conclusions can be made?
So these patients do benefit and fixing TR does help these patients clinically as well. I mean, I think the conclusions are that transcatheter tricuspid valve replacement is feasible. It is effective at reducing TR. There's a clinical benefit. You know, the device is, it can be done in the vast majority of patients safely. And even sort of based on these results we've started the randomized pivotal trial TRISCEND 2, to really demonstrate that in this population of high-risk patients with TR, that treatment does improve both clinical and other long-term outcomes