Hello everybody, my name is Dr Goal. I'm one of the Interventional and Structional Cardiologists at Mount Sinai Heart in New York City, and I'm also Director of Structural Heart Disease at Mount Sinai South Nassau.

Which patient populations are at the highest risk for embolic events during TAVR?

You know, there have been population that have been studied so all the trials have looked at all-comers population.

But I think in general, people who are the higher risk are the people who have heavy calcification on the valve, people who are going valve-in-valve procedures, people who have bicuspid anatomy, that have heavily calcified annulus as well as the leaflets, also the patients who have previous history of stroke that puts them at a higher risk of having strokes in future, patients who have atrial fibrillation, patients with advanced age, people who are on dialysis, or people who have porcelain aorta.

Those are people who are at the higher risk of having a stroke in general, but particularly in patients who are going for a TAVR procedure that have the highest risk of having a stroke.

What strategies are currently used to minimise stroke risk during TAVR, and what are the current unmet needs?

So there are a lot of, you know, that's a good question. So majority of the stroke actually happened periprocedurally, either during the procedure or at the early time. As you can imagine, while you're passing wires and catheters and passing your devices, there is always a risk of embolism happening because of calcified valve where you're ballooning either pre-dilation or post-dilation. That's putting you at high risk of having an embolic debris going to the brain.

So based on that, there are a few devices available in the market. But the only FDA approved device here in the United States is the SENTINEL device, which is made out of two filters that protect the brachiocephalic as well as the left common carotid. It does not protect the left vertebral; however, the majority of the debris that falls in usually is captured by these two filters. And that was the basis of doing randomised studies with these devices.

There are other devices available in the market such as TriGuard. And the other strategies to reduce the stroke risk is like, you know, at our center usually what we have done, we have actually published this protocol that we do for people who have high risk of stroke, especially people who are elderly, has a history of AFib or previous stroke. We usually don't stop their anticoagulation, like three days or four days before if they're on Eliquis or Xarelto or Warfarin, we usually keep it until 48 hours, at least two days before. Plus we admit them a day before and we start them on IV heparin. So they are on IV heparin until they go into the cath lab, and we stop the IV heparin while they get into the lab. That has significantly reduced our stroke rates.

Plus people like the other risk factors, like people who have self-expendable valves that have a higher risk of recapture and scraping the aorta or people who have bicuspid anatomy, so pre dilation, post dilation—those are important things. So the pre-CT scan evaluation of looking at the people who are at a higher risk of having a stroke have a high calcification, so you have to be careful and then you choose your valve accordingly, plus do minimal pre and post dilation if you can avoid to have this embolic risk. And plus the filters, as I said, are very effective and that is where the SENTINEL device comes into use. So those are the things.

And the unmet needs are definitely a device that can cover all the brain, including the left vertebral. So TriGuard system is one of those and then looking at the patient subpopulation that actually would benefit from these devices, not everybody in my opinion needs the SENTINEL device based on the data we have available.

But definitely we can find people who are at a higher risk of stroke, and hopefully the future clinical trials and further sub analysis of the recent trials can give us a little bit better answer who would most benefit from these devices.

How do current guidelines or consensus statements address the use of embolic protection devices (EPDs) in TAVR?

I mean the guidelines are very ambiguous. There is no strong, so first of all there is no very, very strong data to support use of this filter devices. So the only device that has been studied, as I said, is SENTINEL which is studied extensively in the trials.

According to the ACC/AHA 2020 guidelines, the last guidelines we have for the valvular heart disease, actually gave it a 2B recommendation, saying that the embolic protection devices can be considered in high risk patients and then selective use, not all comers, but maybe selective use to prevent the periprocedural stroke rate. The ESC and the EACTS 2021 guidelines does not necessarily give any class recommendation but they support routine use is not really needed, but however, case by case basis can be considered. And the recent consensus by the [illegible] expert opinion also says that the tailored use of these devices can be considered for high-risk patients.

So in summary, I would say the current guidelines are ambiguous. They recommend in high population like patients who are at a higher risk of stroke. But again, defining this high-risk patient is very variable. It all depends on the center and the procedural list and, you know, the experience of the center. But we're still lacking a standardised definition of what is considered as the high-risk patients who benefit from this protection, EPDs, embolic protection devices.

Have the results of recent clinical trials influenced your practice?

It definitely has. There was a lot of buzz around the PROTECTED TAVR trial because the previous trials were very small. They were not powered to detect any clinical outcome like this, the stroke mortality or the disabling stroke.

So the previous trials, the CLEAN-TAVI trial, the MISTRAL-C trial and the SENTINEL IPD trial, they were pretty small. They had like 100, 200 or 300 patients; they were not really big. So the PROTECTED TAVR trial that came out in 2022 actually was a little bummer because everybody was expecting that this filter device would give us finally an answer and would justify the use of SENTINEL device.

However, the results were kind of neutral: there was no significant difference in all-cause stroke. There was a trend towards improvement in disabling stroke with the use of these EPD devices; however, the numbers were very small. There were eight strokes, I would say 0.5% in the use of sentinel and then 1.3%, then total of 20 strokes in around 1,500 patients.

So there was a 0.8% absolute difference with the number retreat of 125. So you can imagine using this device for 125 patients to justify one disabling stroke. Again the numbers were very small to make a decision whether to use this device or not.

And then the recent the BHF PROTECT trial that came out just killed it. It showed absolutely no difference in terms of total stroke, disabling stroke, PIA, or all-cause mortality. So that is why we took this meta analysis to actually totality of data because we want to combine all the patients together, and we have a total of 11,000 patients in this meta analysis. And we showed there is no difference either in all stroke, disabling stroke, non-disabling stroke, PIA, or all cause mortality—absolutely no difference statistically significant in 11,000 patients.

I think we've been more selective. Before we were using SENTINEL for all comers. Now we've moved away from that and we're using mostly in patients who have very calcified bicuspid anatomy, patients who have previous, if they're going valve-in-valve TAVR. We're more aggressive in using it in patients who are getting a self-expendable valve.

What advice would you give to cardiologists about incorporating embolic protection into TAVR practice?

Mechanistically, it makes sense. If you look at the previous data, it does show that it captured debris in almost 99% of the people. So you would imagine if it captured the debris and you're doing a device which is supposed to capture all this embolic debris while you're doing the procedure, it would give a difference in terms of heart rate points, but however it has not shown.

What it has shown is if you do the MRI before and after, there's definitely reduced lesions on the MRI. Does it translate into clinical outcomes? Maybe neurocognitive outcomes, which is yet to be seen. It's very variable and probably will see a difference maybe in a few years down the line in terms of their cognitive decline or not. With the use of devices, now we're moving towards younger patients and they're going to outlive their valves and they're going to live a longer period of time, so we might be able to see a difference.

Does it directly contribute with the SENTINEL protection device? It's yet to be seen but I would suggest, I don't think we have to throw it out of the window, this device completely, but I think we just have to wait and see and then maybe a little bit more data that comes in or a subgroup analysis of this recent trials, the PROTECTED TAVR trial and the BHF PROTECT-TAVI trial, will give us a little bit of an answer, which patient to use this device in.

Are there emerging technologies or techniques that might improve embolic protection during TAVR?

There are a few devices that are upcoming. There's a TriGUARD device, TriGUARD 3, which covers the whole ascending aorta including the arch and filters out any debris that goes in. There's [illegible] device. So there are a few devices that are coming to the market.

They're doing some small trials, feasibility studies, but it's going to take a little while to give us an answer. But again, I think more selective uses of these devices and identifying the patient population which are going to benefit from this embolic protection devices is the way to go.