New era for aortic regurgitation: how new guidelines & AR-dedicated devices will redefine treatment

Good morning everyone. Uh welcome to this session in the forum. Hopefully

some of you have been in this room before. We aim to deliver a different

before. We aim to deliver a different kind of session. We're not going to have lots of didactic presentations. We want

to have a lot of discussion and that means audience discussion as well. So

we're going to get these microphones and Martin my colleague here will explain to you how that's going to work. So I'm an interventional cardiologist in Leeds in the UK and we've got a stellar faculty

here trader cardiac surgeon from Mines.

We've got Matty Adam who's been a pioneer of AR treatment with Tavy in Cologne and my colleague and compatriate Muhammad Al Khalil from Newcastle. And

then Martin Gilar um who is our spokesperson and Martin you can maybe tell the audience here how we can get them involved.

>> I think we are pleased to to have you and very welcome much welcome. So the

goal is that you have to comment if you have some comments some question do not hesitate it because we are here for you

and uh you can ask by this way I can send you the the cube but also you go you you my friend caps >> tell us who you are and where you're from.

>> Uh uh my name is Ken Mloud um and actually I'm one of the board of directors of Yenoval. So I'm not going to say very much today at all.

[laughter] >> Okay, we we better do a good job. He's

marking out at work, Martin.

>> And and you have also the application if you prefer. So do not hesitate to ask

you prefer. So do not hesitate to ask question to make comments.

>> But even if you don't want to ask questions, you may not get a choice like our friend here because the microphone might come your way. So be be aware if you go on your phone, we're going to be throwing microphones at you because they can't do injuries. So we're not at risk

of litigation. Okay. Well, let's get

of litigation. Okay. Well, let's get into the session. So you know what we're here to do to talk about today is trans catheter treatment of aortic regurgitation and we're going to look at

the guidelines and how dedicated devices specifically the yanaval trilogy system will define treatment. So our learning objectives are to understand the challenges of tav and the treatment of

aortic regurgitation to find out more about the yaval trilogy system which currently in Europe is the only approved device for treating pure aortic regurgitation. We're going to

aortic regurgitation. We're going to we're going to embrace the new guidelines and and see what they tell us about transa management of aortic regurgitation and then we're going to

dive deep into the evidence base and clinical performance of Yanaval system.

We're going to do that by basing the session around two real life cases of Yanaval for pure aortic regurgitation.

So I'm going to hand over with no further ado to Mac and he's going to present the first case. back.

>> Thanks Dan for the introduction and thanks [clears throat] for the invite.

Yeah, so these are two real cases we've done recently at the Freeman Hospital um in Newcastle which is north of England.

Um those are my conflict of interest. So

this is a 77 years old gentleman who [clears throat] had an exertional breathlessness NHA class 2. He had a background of coronary artery bypass graft and had a recent coronary

androgram in terms of as part of his workup and he had a patented lema graft and a vein graft to his diagonal. He has

also a background of hypertension and atrial fibrillation. He's being

atrial fibrillation. He's being breathless. He underwent an echo

breathless. He underwent an echo cardiogram which showed that he has a severe triate aortic regurgitation which we believe was secondary to a right coronary cusp prolapse. To be fair, his

trans thoracic echo was not really cut that it's severe and he subsequently underwent a transovial echo to confirm the severity. As you could see here, the

the severity. As you could see here, the jet is quite eccentric but it's quite broad and it's hugging majority of the LVT. Uh we were satisfied from our

LVT. Uh we were satisfied from our imaging colleague that this is actually severe aortic regurgitation combined with his symptoms. We think that maybe aotic valve intervention is indicated in

terms of the hemodynamic um effect on the left ventricle. The left ventricle was actually normal in size and function. Index was fine. His antibimp

function. Index was fine. His antibimp

is slightly elevated as 1300 as part of his workup giving his previous chronic art bypass graft. So we

thought we will maybe do a tavic to assess suitability for trans catheter approach. And as you could see here on

approach. And as you could see here on the right side that there is no calcium on his aortic valve leaflet. His area is 538 perimeter of 83. I've put the lvot

here on purpose because for those who continue to do conventional tavi conventional devices for iotic regurgitation this is important and um this is what we have in terms of uh the

work cup subsequently went for a heart team discussion and then I'm going to hand over to >> yeah so so I think we have this type of

patient very very often in our cat lab so it's a patient with a pure artic regation So I think the first question is for for

our surgeon because uh uh for you is it a place for TV or is it a place for surgery for this kind of patient?

Well, you know, if you just look at the anatomical features, it would be a surgical candidate would be an easy I I would say rather agic replacement. There

is a non-coronary cusp prolapse that's the reason for the AR. You could think about repairing the valve, but the the person is 76 years old and that doesn't

make sense to be honest. Why would I take a risk if I implant a surgical good biological valve then the outcome for like 15 years is predicted and that's fantastic. So I would not think about

fantastic. So I would not think about repair. I could think about replacement

repair. I could think about replacement but honestly uh if I would have access to a dedicated device in this whole setting of um elevated risk patient I

would clearly vote towards Tavi but with a dedicated device.

>> And what about the previous GPHS Hrik? I

mean let's say this patient was 67 with previous grafts. Is is that a big factor

previous grafts. Is is that a big factor for you? The previous graft you know to

for you? The previous graft you know to steers you away from surgery.

>> Sure. every redo is an increased risk operation especially when they're patent grafts. Um but 67 then of I have to tell

grafts. Um but 67 then of I have to tell you then we don't have long-term data on on these dedicated devices. So with 67 I would rather think first about surgery and then if there are endomical

restrictions that would prevent surgery then yes go for >> but with 76 totally you know the other way around this is a clear candidate for me.

>> What about our audience? Um, can we get a show of hands? Who will manage this patient by surgical aotic valve replacement?

No takers. 77 with previous grafts and and and tavy with a conventional device for this patient. We'll come back to this.

Come on. So, has everyone in the room got access to a dedicated device? Okay.

Well, that's a discussion we're going to come on to. So Hendrickk maybe we can see what the guidelines tell us about the role of TAVI for patients with aortic regurgitation.

>> Yeah, definitely. So you all know the new guidelines have come out and for sure uh we all know that surgery surgical replacement mainly is a life-saving treatment. If you have AR in

life-saving treatment. If you have AR in an operable patient and you operate on him, the outcome is much better than not operating on him. We have data out on that for a long time. But what we also know and this is the reason why we're

here actually talking alternatives to surgery is that there's significant undertreatment of sour in this patient population. Um and if you just look at

population. Um and if you just look at those who who showed up with severe AR only nearly half of the patients underwent an operation while the other half just didn't get a treatment at the

time and if it was moderate to CVR it was only 20% who had access to surgery.

So there is a clear need for an alternative to surgery and this is very important because if you leave the patients with AR you know what the outcome will be depending on the degree

of AR the results are very bad over time so mortality is high if you have sever but it's also elevated if you just have moderate or even mild AR so we have to do something about this and this is

shows us that in this in the picture often having patients so much undertreated that we are need an alternative to surgery And what are the patient groups that really profit from

an alternative surgery? And uh this shows it very nicely. Basically the

patients with female gender got much less access to the O than male patients.

The higher risk patients in the older age groups, the frail patients, all those did not get surgical treatment and for them we definitely need at least an alternative to surgery. But if you look

at the guidelines and these are the new guidelines that have just recently been published. This is all surgical

published. This is all surgical indications and this is TAVER indications. Now, if you go get a closer

indications. Now, if you go get a closer look on that, there is still a clear indication gap between SAR and Tavi in favor of Sabur and we only got a 2B

recommendation for TAR and this is clearly restricted still clearly restricted to symptomatic patients ineligible for surgery and we've later on we're going to discuss why it is like this and and hopefully it's going to

change but at this stage if you just look at the guidelines this is where we are.

Yeah, it's interesting the word the the the the the precise language ineligible for surgery in interestingly in the UK where we're not known for kind of

leaping ahead in terms of uh uh where we go with new technologies the guidance from NICE is high risk or ex or or in unsuitable for surgery. So what do you

think about that Hendrickk? I mean cuz there's patients you I think we've been treating AR with conventional devices for a long time when the surgeon won't operate that's the only option right but

what about are we now with dedicated valves are going to come onto the data in a place where high-risisk surgical candidates so you would operate but they're high risk now maybe tav is a better option if you've got access to a

dedicated device what do you what do you think is it still just inoperable or is it high risk or inoperable >> no it's also high risk it's maybe even moderate risk I have to say but because what we know so far and we're going We'll go through the data later on, but

we know so far the results of the dedicated device is so good basically that you can look at these patients like we do looking at patients with noises with the exception that we don't have

long-term data. So I would not you know

long-term data. So I would not you know age wise I would not go too far down but let's say a lowrisisk patient 80 years old to me is a clear candidate for a dedicated device. I would not even think

dedicated device. I would not even think about surgery in this patient group anymore since we have access to it. But

if you don't have access to it, it would not necessarily be the same when it comes to non-dedicated device. They

would rather think about surgery first because more predictable results.

>> So, so do you think uh in your center if you have a a dedicated valve or a a classical valve, what do you think for this kind of patient if you want to take

it to treat it by podenos?

>> Thanks for the question. I'm Mat from Liblia. Um uh we have we have

Liblia. Um uh we have we have opportunity to use to use dedicated device. Uh but so far in the last year

device. Uh but so far in the last year we are gaining to find suitable patients but they're not so frequent as you mentioned earlier. Uh but uh we we have

mentioned earlier. Uh but uh we we have some urgent semi-urgent cases that were treated with nonedicated devices like kidds. There were some slips we have to

kidds. There were some slips we have to add another part. Therefore we very cautious uh in picking the patients and we we are temporary on surgical side.

Maybe we can get a show of hands. Who in

the audience has access in their center to a dedicated device?

Okay.

So, let me have a volunteer who is treating Tavy with aki.

>> Are you what are you doing in your I believe that you don't have access in your center.

>> So, what do you do when you've got pure AR cases in >> Nottingham? Thank you uh Dan and

>> Nottingham? Thank you uh Dan and congratulations on becoming the president of BIS. Uh what we do we write to leads and we say we've got this patient who's got severe aortic

regurgitation. We don't have a dedicated

regurgitation. We don't have a dedicated device. So we refer to the centers we've

device. So we refer to the centers we've got the most experience. If we had to do a non dedicated device it would be an oversized sapion or or or that down that

route. And there are certain centers in

route. And there are certain centers in the region that use the the um octaore as well. So those are the other

as well. So those are the other alternatives.

Hope that answered the question.

>> Yeah, it's interesting. I I'll I'll bring you in in marking the case presentations for Euro PCR this year. We

could have had three sessions on balloon expanded valves in the left ventricle which were used for pure AR. So but

we'll come on to that when we see some data. Yes. What's your view?

data. Yes. What's your view?

>> Yeah.

>> Well, just a question about the dedicated devices. I mean there's

dedicated devices. I mean there's there's still quite a bit of I mean this is a great case, right? It's a prolapse case. fits great and you clearly in the

case. fits great and you clearly in the presentation commented that it's a trileaflet valve but a lot of these valves are not trileaflet like a lot of bicuspits have significant AI and I'm

just wondering in terms of the population that we're capturing that would be candidates for the valve >> yeah well we're going to come on to a discussion of the anatomical suitability

for ya but I mean Hendrickk I think I've heard you talk about this how common is it for a bicuspid valve to have pure AR in your experience >> it's pretty common actually so I have to

say also the not maybe not the majority but at least half of the patients with pure are by hospitals and this is not the patient population fortunately enough they show up younger age and they

most of them are surgical candidates so this is why we don't have a problem there and if this symmetric by kuspot valve it's even easy to repair so it's not a patient population I care so much about what we still see and this is the

experience we have and maybe Mati can also comment on that since we have know the dedicated treatments available. We

see those patients, you know, not really overflowing our um ambulances, but many patients now show up and they just haven't been presented before because there was a lack of treatment. And this

is what happens and and Mat will also see the same thing once you, you know, offer it. Then all of a sudden the

offer it. Then all of a sudden the patients come, right, Marty, what do you think?

>> I I absolutely agree, Henrik. And and I think it's it's worth mentioning that there are two different public, as you said, two different um populations of patients. We have the younger ones by

patients. We have the younger ones by cuspit ones and we have an older cohort of patients that has aotic regurgitation and those are not mainly bicuspit and and the more you talk about it's a little bit like like tricuspid

regurgitation right the more you talk about the more you will see those patients um and we'll we'll show you with data later on I think that that it's not only as you know my impression

is you can see picking up numbers all over the world if you have access to dedicated systems >> okay well we should move on in the interest of time. So we, you know, we're coming on now. I think we all agree there's a clear consensus in the room.

This is a patient for trans catheter approach. So then the question is what

approach. So then the question is what device and are we going to use? And it's

worth reflecting on where we've been up until recently in terms of access to conventional devices. So this was a very

conventional devices. So this was a very early registry study um with which included 331 patients from 40 centers retrospective data collection who were

treated for a dominant aotic regurgitation. It's worth noting when

regurgitation. It's worth noting when you we come to the outcomes of this study that calcification was not an exclusion. Um and there were some AR

exclusion. Um and there were some AR specific devices included. Um these were transapical uh J valve valve engager at that time. But if you look at the

that time. But if you look at the outcomes and I've highlighted the key ones in the red boxes that we had a 3% procedural mortality. We had 16.6% of

procedural mortality. We had 16.6% of patients having a second valve implanted and we had 10% of patients with with at least modic regurgitation. So these are

pretty awful outcomes. And you might say, well, this is 2017, so you know, have we got any better? So more recent data came from this registry, the Pantheon registry, um, which again was a

retrospective multic-enter registry collecting data on patients with uh, dominant aortic regurgitation. But

again, you'll see from my red box there that some of these patients had calcification. I think we'll all agree

calcification. I think we'll all agree that if there's moderate calcification, then conventional devices are fine. Um

and about just under twothirds of these patients had no calcification. These are

the ones that we we really worry about with dedic uh with non-dedicated devices. And there was a mixture of

devices. And there was a mixture of self-expanding and balloon expandable.

And you can see here again there were still some dedicated devices there.

There were some Yanav valve uh patients included in the self what they categorized in this study as self-expanding.

So let's look at the outcomes and it's easy to look at the bar chart there. TVM

is embleization. So we've got an embleization rate between 10 and 15%.

And it is a horrible thing and I'm sure many of you will experience it. When you

get an embleization, you know that you're you're in trouble. Uh about 10 to 15% of cases needing a second valve.

About 10% still having moderate aortic regurgitation and the all cause mortality in hospital 5%. So this is kind of what we're looking at. Even when

we kind of try to make the results look a bit better by including some calcified cases, including some dedicated devices, we're still looking with conventional devices, 10% embleization, 10% second

valves, 10% residual moderate aortic regurgitation. So really outcomes that I

regurgitation. So really outcomes that I think you know are not acceptable and should only be used for um for when we

don't have another option. So Hrik I've clicked on. So let's maybe we'll move on

clicked on. So let's maybe we'll move on to to just discuss what if anything the guidelines tell us about conventional versus dedicated devices.

>> Yeah and you know there's not so much in the guidelines though this is on the the excerpt that I gave you here. So the

guidelines give Tavi overall just a 2B indication as we just discussed. And if

you go into the topic of nicated versus dedicated devices clearly the use of nonicated devices is turned out to be off label due to the increased risk of

malpositioning and residual. So this is uh nothing you would really go for but the dedicated devices appear to minimize the risk of migration and residual AR but they come up with a high pacemaker

implantation rate. But also this is

implantation rate. But also this is questionable. So at the time the the

questionable. So at the time the the guidelines came out the AIR trial was published. So they knew the data still

published. So they knew the data still they only gave it a 2B indication that may have also something to do with the fact that those non-dedicated devices are not really available for all of you.

Maybe that was one of the reasons why they did not increase the indication here to at least a 2A. Um but this is of course going to change in the future and I'm I'm 100% sure with the next edition

of the guidelines we will see an easy indication with the use of dedicated devices but this is what the guidelines say today and the only thing we can present you. Yeah, I mean I did I did

present you. Yeah, I mean I did I did ask Fabian PR about this actually, you know, and he and he he said exactly what you said that they didn't want to say that you should only treat AR with

dedicated devices until those dedicated devices are available to to the whole community, you know, because they, you know, they didn't want to say, look, you shouldn't be treating AR unless you've got these devices because obviously

sometimes patients are inoperable when we need to. But but maybe Matty we can come on to you because what we and you can show us why dedicated devices make all the difference with some of the data

that might apply to a max case.

>> Absolutely. I think the biggest difference with the dedicated device is my heart rate and that's all what's missing in these tables from the Pantheon trials. My heart rate is

Pantheon trials. My heart rate is definitely above 120 if I do non-dedicated devices and non-calified annuli and and I'm hope I'm not the only

guy. But so what is special about the

guy. But so what is special about the dedicated system we're talking uh about today, the trilogy system? Um I mean the the item that's that stands out

obviously are these three locators. And

the locators are supposed to go into each designated um coronary cusp. They

will help you with uh deploying the valve absolutely u coronary or commercial aligned. They will help you

commercial aligned. They will help you in preventing u dislocation into the left ventricle and once you deploy the valve they will also form a seal and

they will also hold the valve in place.

So the trick is the three locators and the self-expanding stand frame will work together to prevent um dislocation and also give you better ceiling.

Um and we'll see later with Mac um that you know the um there are certain um things you can do with the delivery system and the valve itself um and the

steps you will go through is you will first while only the locators are exposed you will first align the valve with the native cusps then you will go

forward advance the system interact with the native leaflets and then deploy the valve. the system is fully ro you know

valve. the system is fully ro you know has full rotation so you can actually uh actively commercial align which is very

important of course um for this um the study that has been around um we mentioned it already has been the aligned AR study trial um and this is a

slide from um actually the just recent publication yesterday from Lancet because the the study was designed as a multic-enter non-bladed single army evaluation of patients with AI R3 plus

and more. Um, and it you looked at three

and more. Um, and it you looked at three day 30-day primary safety and one year primary efficiency endpoint and it had continuous access. Um, and and that's

continuous access. Um, and and that's important because we were talking about I my feeling about picking up the speed in which I see those patients with AR.

You can also see that in in in this study it's 180% in the pivotal trial population and 520 continuous access population. So, I think that's an

population. So, I think that's an important thing. The the continuous

important thing. The the continuous access was so fast that now we're talking about 700 patients with a 2-year follow-up. Um, the patient baseline

follow-up. Um, the patient baseline characteristics are are are shown here.

I mean, it's a very typical population.

I think it's 79 year old um population with 45% female. Um, SDS promis 3.8. um

they all had a little bit of history of AIB and there was left bundle branch and right bundle branch block quite commonly and I think you know maybe we can touch on this later with the pacemaker issues

something that I think is important um AI AR severity was obviously severe or moderate to severe and the mean annual perimeter was 80 so um on you know I

think it's on the upper end of what you'd think in terms of perimeters but very doable in the with the system obviously because it was the trial uh technical success rates were strikingly

high. I mean technical success during

high. I mean technical success during procedure was 95% almost with a device success at 30 days with 97% um good hemodynamic performance gradients below

21 100% moderate or severe AR or PVL 0.5%. So I think really really promising

0.5%. So I think really really promising results with a procedural death of 0%. I

mean and again talking about heart rate while performing non-dedicated devices I think that's very reassuring what we see here um as we now have access to two

more to to more follow up and to two-year data you'll see mean aortic valve gradient effective orifice area um and PVL are consistently

very good over one or two years with you know almost no moderate AR which is also in contrast to non-dedicated devices Um I'll just quickly show you the

primary safety endpoint at 30 days.

Again, why am I doing this? Because

there's something important that we can learn from this slide and the next slide. New pacemaker impl for for

slide. New pacemaker impl for for example overall was 21.6%.

Let's take this as an example and move to the next slide. Sorry.

[clears throat] You'll see that you have sorry different endpoints uh on the on the bottom left primary composite endpoint new pacemaker

any bleeding any vascular complication and you have the turtle like the the in recruitment or the enrollment over time in turtles on the right hand side of the

screen. You will see that significantly

screen. You will see that significantly over time with recruitment and experience all of these end points came down. Vascular complication came down,

down. Vascular complication came down, bleeding came down and especially pacemaker rate came down from 26% to 16%. So there is something we can learn

16%. So there is something we can learn here and I think we can also improve techniques with these dedicated devices.

Um again as is already significantly shown in the slide before but the procedure date is actually affecting um the predictors of new pacemaker as of

course is right bundle branch block and the large valve sizes. So so much for the dedicated data from the align trial.

>> Yes. So congratulations. So I think we we we saw that with this all this result that it's there is a place for this dedicated valve if we compare the the

the complication presented by D just before. So I think it's very important

before. So I think it's very important now to go to the result of the case.

>> Yeah no pressure no pressure at all.

Yeah. So yeah as you all discussed we went for the MDT discussion. We had the chat and we thought that probably perccutaneous option um with large uh trilogy valve 27 mm will be there I

think and I share the heart rate bit with Matty exactly you know prior to the trilogy your heart rate will go through the roof you are with your body's on a speed dial because you know that the

valve could imolize um so basically what we've done um this is the setup how we do it uh basically you have a a right radial right fmeral uh and you put a two

pigtail usually with any tavi device we usually put it in the non-cornary but with this you need to really align the annulus and understand particularly the anatomy. So we put another pigtail in

anatomy. So we put another pigtail in the right coronary and you try to delineate where exactly is the annulus and try to understand each of those cusps. Um and from there basically you

cusps. Um and from there basically you you put a long sheath which is a curved sheath and you could see it up all the way to here. So you could see the sheath here all the way and goes all the way

down to the femoral and from there you insert the uh transat device. You could

see the um the locators here and it is important to screen those to make sure that they are not bent. Now I'm sure you all had a lot of experience. I haven't

seen it Dan have you seen it before?

Have you seen it Matty without those bend? But it is a good practice to to

bend? But it is a good practice to to screen this to make sure that actually uh what happened here? Sorry. So go back and you screen it. And then from there

you bring the device and you line up the ceiling uh the ceiling marker of the device with the with the sheath and then you track the sheath back to the

descending aorta. And now that will open

descending aorta. And now that will open the locator slightly. And this is the first step how we do it. We still high up at the STJ junction. We're quite far

from the annulus. And this is the first step.

From there we will push the controller slightly in and by doing this the locator will open more. You could see it now the locator are now far more spread

than before by advancing the locator.

And subsequently what we need to do we need to make sure that those locator are actually align anatomically with the cusp. So we need to make sure that the

cusp. So we need to make sure that the right cusp is actually at the front. And

what we need to do then is doing an ARO sweep. So the front locator will appear

sweep. So the front locator will appear anteriorly and this will give us confidence that actually we are aligned within the anatomy of the aortic valve

and subsequently we slow advance the controller until we are above the cusps and historically when we do this with

any dedicated valve you will be really really worried. This is very control

really worried. This is very control environment. The patient is completely

environment. The patient is completely stable. The operator is completely

stable. The operator is completely stable. There's no issue so far.

stable. There's no issue so far.

Everything's under control. Everything

could be done again. There's no problem.

Now, the most important part is we need to make sure that each locator are actually at the right cusp you want it.

And that's where you have to use probably different catheters. So, this

is a multi-purpose. And we here you could see that the locator is exactly at the none. So we

are confident we are above the none.

Subsequently we check the left and this is a good confirmation. We engage the left coronary. You could see exactly the

left coronary. You could see exactly the locator again at the bottom of the left corneary cusp.

And the last bit which is sometimes challenging is the right. You could

sometimes engage the right corneary archery and then trying to slip the caster in and trying to check and again you'll be happy here that actually I am engaging with the right cornea cusp

and from there you could potentially check the depth but the most important thing here is you deploy it under rapid pacing and it literally like this

and you could see sometimes the catlab team saying having that gasp like oh god what's going to happen because they are familiar with AR cases that things could potentially go And then the final check and

so as the guy said you know the good seal the actual intrinsic leaflet they act they act as a sealing mechanism plus the actual skirt. So this patient did

angographic quite well he was keen to go home on the same day and I had to stop him from going home. I just thought it's too much you know to send him home on the same day. We sent him home on the following day. He came back after 3

following day. He came back after 3 months for his echo cardiogram. And this

is exactly what's happening with the echo. Um no AR maybe trace of AR. You

echo. Um no AR maybe trace of AR. You

could see it just a whiff there just for the um for the keen eye but significant clinical improvement which I think we've seen in the align AR data. It's much

better clinical symptomatic benefit than aotic stenosis patient in terms of QCQ.

>> All right.

>> So M I mean great case, beautiful result, perfect, you know, which in our experience it is every time. I mean I think I'm right in saying this was your first case. I mean you know

first case. I mean you know >> tell us about how it was doing this for the first time you know was it challenging to do it >> um what was the kind of response of the team and the you know the operating team

and the rest of the catalab team to the your first ever >> so this was yeah so that is something probably I should declared this was the ever first case I've done myself and at the Freeman hospital historically we've

always been concerned and worried about AR as I said you know there will be two or three operators on a speed dial that there is an AR case happening in the kath lab things could potentially go wrong. We need actually probably a

wrong. We need actually probably a self-expanding we use it with evolute and then probably you have to have a backup with an Edward to slip it in and always all these going in your mind. We

walked in there. I to be honest, you know, when we looked through the process how we do it, you'll be like, well, it looks like straightforward, but I don't know how exactly it will be inside the cat lab. But I have to say it's a very

cat lab. But I have to say it's a very wellont controlled deployment. There's

literally I didn't actually felt at all that there is an an invasive procedure.

The cat lab team were very impressed with how things were because it's very controlled. Everything stepwise you

controlled. Everything stepwise you could see Dan particularly proctor me on this case and he was telling me go left, go right, check this, check that. I

literally was a puppet just doing this and doing that. So it wasn't it wasn't difficult for me. And the end result to be honest when we deployed I wasn't looking at the valve. I was looking at the actual deployment which I think is the right thing to do. So you when you

deploy it on the rapid pacing and then you look you'll be like wow the valve is already in. Uh I missed that. And

already in. Uh I missed that. And

actually that's what it should be. You

should focus on how to deploy it and you will miss the valve deployment and your team will be very happy with the result at the end because you don't have to get another valve. You don't have to fuff

another valve. You don't have to fuff around with cardiac you know CPR all of this. So yeah. So, so Mac we have a

this. So yeah. So, so Mac we have a couple question a question. Yeah.

>> Yeah.

>> Yeah. It's a wonderful case with excellent results.

>> So I just wanted to know whether do you use eco cardiography during the positioning or is just only the fluoscopy which you use and what was the time duration for the usual procedure

how long does it take?

>> Yeah very good question. So we don't use echo cardiogram. We use only

echo cardiogram. We use only fluoroscopy. That's at least our

fluoroscopy. That's at least our practice. I think maybe people might use

practice. I think maybe people might use toe or might use transthoracic. seen

some cases people try to see they grasp the leaflets actually this case particularly was relatively straightforward it was my first case but we've done it within 35 minutes I think that was done from the start to the end

um with deployment of the valve >> another question here um yeah I mean just to come back briefly I mean I think on the TOE it's common fairly common practice in North America I mean from my perspective been Matty you've got the most experience it's completely

unnecessary I mean it you can do it very controlled with confidence with fluuro guidance >> absolutely I mean you can you see if you want to be sure in a very um exciting

case and you know a lot of prolapse or difficult anatomy um maybe a little bit of bicuspit in there yes no and and so in cases like this when it's really challenging te is an option but we never

use it actually >> another question I have >> yeah are there any concerns about not being coaxial like for example vertical annuli etc etc because ideally obviously you want those to engage symmetrically

correct >> yeah that's I think that is a good setup for the next case. Exactly. Right. So,

I'll hand over to Dan.

>> This guy is is on.

>> So, yeah, there is concern when it's actually um >> No, that's that that it's a great question and that really nicely leads us on to the next. We got one more comment before we do and then we're going to move on.

>> Really very interesting case um regarding the pacing rate is high.

What's the reason? Is it because of the interaction with the conduction system or >> um >> I think from the surgical data we know that about you Henry you go first.

>> Yeah this is a good question actually we cannot answer that question completely at this stage. Uh we know also from surgery that pacemaker rates are higher in our patients compared to as patients.

Um we looked at the you know when the first pacemaker rates have been coming out of course I was concerned we looked into all the CT based morphology data.

We did not find yet that that sign that shows us. But then as Mati showed a long

shows us. But then as Mati showed a long time with changing a little bit the procedure, changing the degree of oversize, not pushing so far again to bring that valve deeper as it supposed

to be. And then we came back to a 15%

to be. And then we came back to a 15% pacemaker rate these days. So that is still higher than we used from Tavi. It

may have something to do that the very often as we've seen in that last case too the LVT is also stretched due to the you know um the uh degree of AR patients have and maybe the stretching of the LVT

and of the membrane septum is a prerequisite for higher pacemaker rates because the conduction system is also stressed already before the procedure.

This may play a role but I I can't give you the final answer. Maybe Dan you can I don't know. [snorts]

No, I mean I you know I think AR we AR patients we know have a higher pacemaker rate as you said and you know this there is relative o oversizing a little bit more than the average self-expanding

device but interestingly the data analysis so far don't seem to indicate any association between oversizing and pacemaker a or indeed depth of implantation. So so I think

implantation. So so I think >> that's a very great point and I I just want to say exactly we don't have evidence that oversizing is actually affecting this. I mean we have been

affecting this. I mean we have been coming down a little bit in the sizing algorithm with oversizing and we have improved pacemaker rates but if you look at very detailed it's not the oversizing

it's the bigger valves that have higher pacemaker rates and it's the most stretched analy and it is the patients with right bundle branch AV and left bundle branch block. So I think to

Henrik's point, I think that might be a good explanation. For example, SNTR, the

good explanation. For example, SNTR, the more stretched out we have with these reg regurgitant valves, the more stretched out we already have the

anatomy, maybe we even affecting the conduction system through that dilation so much that we have higher pacemaker rates.

>> So I think we should move on. Yeah. I

mean, so I think we've seen a case which would have been a complex case with a conventional device, but actually anatomically was pretty favorable for yay valve, but we know that patients with a regurgitation often have very

complex anatomy. So Matt, you know, let

complex anatomy. So Matt, you know, let me hand back to you for your second case. I don't know if this was your

case. I don't know if this was your second ever case or your third.

>> The second one actually, I think it was on the same day.

>> Was a bit more challenging.

>> It was on the same day. I think we've done those. Uh so yeah, so not always

done those. Uh so yeah, so not always it's nice anatomical. Um so this is a second case uh to touch on complex anatomy. Um this is a a younger patient

anatomy. Um this is a a younger patient 74 um lady with recent admission of heart failure and um she was transferred from a district hospital. She had a

underwent trans thoracic echo cardiogram which showed that she has a severe triaflet aortic regurgitation which is secondary to a a very large ascending aortic aneurysm. She has a background of

aortic aneurysm. She has a background of hypertension, hypoglycemia, but she was relatively frail and this is important for the decision-m which we're going to discuss.

This is her echo cardioardiogram. As you

could see from echo actually the aortic root is quite dilated. Her regurgiton

volume was measured as 127 mil that is severe is more than 60. Um although her pressure half time is in the moderate range she did have severely dilated left

ventricle with impaired function.

her antiprob was okay prior to her um procedure and that is to reflect that well diuretes patient

she underwent her uh CTV which showed good uh trans femoral again you could see there's a there's a gap uh due to the stretch of the aorta um importantly

the non-coronary cusp is relatively small compared to the right which I think it will come into um into what what we've done during the procedure and she has a very large um ascending

aneurysm I think it was measure 5.8 8 cm.

Um, so she was discussed in the MDT and I will ask Hendrick, what would you have done? She's 74. You haven't seen the

done? She's 74. You haven't seen the patient. Uh, but I just need to

patient. Uh, but I just need to emphasize that she's frail.

>> Yeah. Well, first I have to say, why didn't she show up earlier? I mean, this is really sad because, you know, this degree of AR is really tremendous and

and with earlier treatment that would be maybe an easy operation. Now she has 38% ejection fraction. She is very frail but

ejection fraction. She is very frail but anyhow I mean this is and I'm a surgeon you know um so I have to apologize for not jumping right away into the taravi business here with this root dilation

and and this was not ascending or auto dilation or root dilation right and we have a 58 mm root here already and I think the ascending might be even like 7

cm already. It's dramatic. I would first

cm already. It's dramatic. I would first really check every option to do a nice bental on her. That solves the problem because just placing the valve on such a dilated route that carries a risk that

the root pathology is ongoing and that the patient unluckily comes back with type A dissection at a certain time. So

that would be my concern. But of course, if she's inoperable or very high risk for surgery, then we could do something about it and just place a valve. But

forgive me that I, you know, feel intrigued to operate her the way we would usually do.

>> You're not a fan of why I said the smash and grab surgical approach. Just replace

the valve, leave.

>> No, that is stupid. I mean, why why should if I would just do surgical val replacement? Then I'd rather do T with

replacement? Then I'd rather do T with dedicated device. It's much lower risk

dedicated device. It's much lower risk and not put the patient on her lung machine, arrest the heart and all that.

So that that wouldn't make sense. If I

treat that patient, I treat it properly with a bentile and that would be my solution. Right.

solution. Right.

>> Maybe we can Martin.

>> Okay. So in the audience who treat this patient by a packetous way and which valve if they have no uh a dedicated

valve use in this type of case. So who

treat this patient with a packetous wave we >> let's have a show of hands then s you haven't met this patient but frail surgery. Hands up for surgery.

surgery. Hands up for surgery.

>> Yeah there's a few there.

>> Okay.

>> And trans catheter with conventional device.

I think it's the answer is very clear.

Nobody nobody from do you want comment this type of case? Um yeah no absolutely we would we would um we would be using Yenna valve here and we we've used 10

now in in our uh patients with pure a regurgitation in sarco but obviously you know I'd agree with Henrik that you've got to make sure that that surgery is not an option because clearly you know

she's got a dilated descending aorta but if you have thoroughly explored surgical options and absolutely transcend valve is is absolutely the correct uh

treatment. Can I just ask a question

treatment. Can I just ask a question whilst whilst I've got the box and it's really about deployment and um I was at the meeting earlier in the year and u and and the question really is about

deployment and burst pacing. So I

certain notices that Mac use burst pacing and and I just want to hear Matty and Dan's view and and Rick what they're doing regarding deployment. I always use burst pacing short run. I think it keeps

things stable but I'd like to hear your views.

Well, um, to be honest, I only use accelerated pacing. Heart rate 120, 130,

accelerated pacing. Heart rate 120, 130, 140, depending on how, you know, how good the pressure reacts to pacing, but usually it's 120. Um, I'm a bit weird

because I keep pacing on while I move the system out of the valve. Um, I like this because I still I'm I'm under control. I'm focusing on getting the

control. I'm focusing on getting the system out of uh of, you know, the the delivery system out of the deployed valve. So, I can focus on that. Then I

valve. So, I can focus on that. Then I

turn pacing off and then if I have 15% pacemaker, you know, if I have something low heart rate, I can then take care of that after I remove the system. So

that's my workflow. I just want, you know, I'm the guy one thing at a time. I

really like to be controlled in that. I

think you don't need rapid pacing. I

think it helps. Uh I think accelerated pacing also does the trick. It's a

self-expanding valve, so you uh would would think that that would be sufficient. But I mean I think I think

sufficient. But I mean I think I think the answer is whatever works best for you, right? And how do you do it?

you, right? And how do you do it?

>> Yeah, I mean I I don't think you need fast rapid pacing. It's a it's a it's an instantaneous deployment. You know,

instantaneous deployment. You know, there are other systems that are deployed rapidly. You know, Acurate was

deployed rapidly. You know, Acurate was was similar in some ways, but it's so much more so much faster and so much more stable. So, you know, I wonder

more stable. So, you know, I wonder whether we need pacing at all, but we do pace about 120 usually.

>> That's a great question. I mean, we should >> after the session we should try. Okay.

Listen [laughter] we should move on. But I think you know because this case is about complex anatomy and you know Saga has said and we would be exactly the same and this is why we always say to with Yaval with

these horrible cases when they say this is a tough case but we say yeah but it's still by far the best option so we're going to do it you know are you going to help us you know this case would you take this case on? And you know we had

the question from our colleague over here from the US. What are the anatomical factors that mean maybe it's not possible? Canada sorry

not possible? Canada sorry >> Canada okay that's an important difference um well I think um we would we would definitely do the case if you know hard team discussion is

interventional option we would go for a dedicated device um I think there are some considerations um with that you know interaction with the root where do

you put the sheath where you pull the sheath back all that but I think uh hopefully uh you shows that this might be a very doable case and that we have a good result in in this patient

Um things we might want to not tackle right now are super calcified bicuspits.

Um you know it's a valve that's designed for a triricuspit oric valve. Um and

while we have done quadricuspit and bicuspit I think it really depends on the anatomy of the valve. So you want to have interactions of three locators with

three cusps. Um and I think that's

three cusps. Um and I think that's important. we can push further after we

important. we can push further after we settled this but right now um I think you know that that's my considerations to that >> and there's I guess size that's the other thing you know so the maximum

perimeter is 90 I mean we've don't know where you've been to we've been to 92 so that's about 28.6 six millimeters by perimeter. Yeah. So we need

perimeter. Yeah. So we need >> we need and we will get a bigger device but um that that that's maybe another >> point. So I will have the um the

>> point. So I will have the um the information about Matty about what what happens for the the real life and I do a

registry I use some data about the uh in the real world not only in all AR.

>> All right let's see if we have something there. surprise we have but I'm not sure

there. surprise we have but I'm not sure if I include Mac because if that's a second case giving the trajectory I'm not sure what his 50th case will be so not sure if you [laughter] can register

[snorts] um so what what we did is like I mean a line is a super control setup core lab uh screening committee and that's great because these trials will help us push the guidelines but also on

the other hand I think we need to uh document and show what we do in real world in real life and what we did is like we put eight European centers all super experienced together and we

collected 360 patients with pure AR and you can see that the baseline characteristics actually fit the align trial um pretty accurate. I mean our

patients are a little bit older but overall I mean it's clearly a high um or a pure AR with severe AR population. Um

to be honest technical success in our patients and there were some crazy cases in this registry. I can promise you technical success rate is 98%. So um

it's it's a really high rate of of technical success. We had second valve

technical success. We had second valve implantations in you know centers that were beginning centers that were super experienced like overall in our clinical cohort of 360 patients 0.8% if you

compare that to the non-dedicated devices I think that's a huge difference uh vascular compilations were low with 5% stroke rate was also very low 0.6% 6%

and and meanic valve gradient and valve area were favorable. We had overall permanent pacemaker implantations of 22% but a little higher than the last cohort

of of a line but again I think this is due to the complexity of our cases.

mortality stayed low over the follow-up.

We had follow-up um a little bit more of 3 years from from some of the patients, but overall the best endpoint I think in terms of the most patients was one year

and valve area stayed above two. Mean

gradient stayed below four and you'll see there's technically no moderate uh PVL, no moderate AR after uh one year and longer. So I think those are very

and longer. So I think those are very promising results. So 99% less than

promising results. So 99% less than moderate and and something we you know I think is super important to judge also is the improvement in functional class

in these patients as um we discussed aortic mutation we sometimes wonder about symptoms it's not as clear as anortic stenosis it's not shortness of breath so much it's not angina it's not

syncopy like these patients need a little bit more of questioning and a little bit more of interacting with them to understand if they actually improving Um so KCCQ and all this is super

important as well but also you know these patients with this they improve a lot. So New York Heart Association class

lot. So New York Heart Association class one and two and 85% of our patients. So

I think overall we can say even in in a real world cohort the treatment of AR with TABI is challenging with non-medicated but yes if we have dedicated devices I think we have a very good outcome.

>> Marty thanks and that's the first time those data have been shown. I think I'm right in saying and >> absolutely >> we we were lucky enough to contribute our learning curve to that you know our first 25 cases I think and there was

some there really was everything that we did all the horrible anatomy so so I mean before we go on to the case and we see how Matt got on with this pretty nasty case you know it is a

transformative difference it's a 10-fold change in the bad outcomes right less than 1% embleization compared to 10% at least given you know because there was some calcified cases in that and we saw with the non-calcified it was worse

How do we get dedicated devices out there? Should every center that does

there? Should every center that does TAVI have a dedicated AR device in your opinion or do we need to have referral centers? Can the procedure be done uh if

centers? Can the procedure be done uh if you're doing 10 or 15 a year or do you need to be a high volume? What's your

perspective on that? Because to help the whole overall population of patients with their AR, we need to make this technology available to all of them.

>> Very good question. I mean being a high volume center I might be biased a little bit so take this with a grain of salt but I mean the guidelines give a little bit little bit of advice on hardware

units hardware centers how we should structure our our you know vascular heart disease programs or our our structural programs overall um I do think that you know if you're a low

volume center you should stick to the valves that you know best if that's a dedicated system then I think it's good um but Overall, I think we should work together and find centers that have

experience in those dedicated devices and then build a referral network around that. Um, so I mean there's always a

that. Um, so I mean there's always a good correlation between the numbers you do and the outcomes you get. So I think also here we have to keep that in mind, right? But again being a high volume

right? But again being a high volume center I might be biased on that. Right,

>> Kendrick?

>> Yeah, I think I I have to challenge you a little bit with this Mati because I wish we had that discussion about mitro intercusp therapies. Yeah, I'm a clear

intercusp therapies. Yeah, I'm a clear fan of dedicated centers who deliver best perfect quality, but here I mean we've done several hundreds of cases

now. It is after a while just a regular

now. It is after a while just a regular ti procedure and the risk profile is so low so that I I cannot find arguments uh why not every let's say tavi center that

is a proper tavi center should do it. I

don't even necessarily see the need for cardiac surgery on site because nothing is happening there. So for to me it's a bit different. I would say once that is

bit different. I would say once that is out there's a bit of learning curve but it's not much. We send our proctors around and then you learn how to do it.

I see this in all of your hands when the company is available and and and able to produce as many devices are needed. But

I see this really coming. And then one maybe one more point and I'm we in an AR session but if you use it just for pure AR and non-calified AR you would not see so many patients right away but you can

use that valve in every patient who has predominant AR but calcification. You

can either use it in a stenosis patient.

It's very it's a very good valve for stenosis when you for example have low coronary because you will never see a chronic occlusion with the valve. So if

you want to use a valve more more often, you can use it even cases in tricuspid cases of course. Um and then you go from there. So I'm I'm you know I'm not so

there. So I'm I'm you know I'm not so much >> I'm not going to challenge you on this opinion. I'm happy to support everybody

opinion. I'm happy to support everybody who wants to do this well because it's a lot of fun. Um and I just want to you know a little bit um follow up on your point of vortex because it's a great

point. I mean you have by by definition

point. I mean you have by by definition commercial alignment. Um we did um a

commercial alignment. Um we did um a series of cases in the beginning and the pacemaker rate for example is in in the aortic stenosis patient with this valve

is low singledigit numbers. So clearly a regation is different from a stenosis.

We do see consistently low gradients in artic stenosis as well. So I mean once we I think have used this device as a dedicated device for AR there might also be a trajectory to push this even

further in mixed disease and maybe even extinotic cases.

Yeah, that's great. And I have to say I'm going to side with Hendrickk as well. I mean, I think, you know, this is

well. I mean, I think, you know, this is what I find with his devices, there are more steps, but it's so controlled and so predictable and you get a perfect result every time. So, I I think to get

to the patients, I mean, I like Hendrickk, I wish we had referral centers and we have some um we have some centers like Nottingham who refer patients, but we also have plenty of centers, you know, I know centers in London, they won't refer them up the

road. They'll do it with a conventional

road. They'll do it with a conventional device. So, I think our best way of

device. So, I think our best way of helping the overall population is to get this device into every center if we can.

Martin, you got another comment before we we see the case. If

>> I could just just offer an opinion on that, we've done 10. We are one of the 35 centers in the UK. Um, and I have to say that I think that it's really important and I would agree with with

Dan and and and Henrik that this ought to be available in every center that it's doing, you know, a sizable number.

It's relatively easy technology to use.

It's not really super complicated and I think there's a horrible disease amongst cardiologists that we are reluctant to refer to other centers and if we want to remove that obstacle and get patients treated that we must make it available.

So as soon as this technology is scaled up as it soon will be then it must be made available to really every center that is doing tab in my humble opinion.

>> So Martin on that note should we see how Mac on his second ever third which um very horrible case Yeah, Saga, hold that thought with this case. I'm not sure it's always straightforward. So anyway,

to go back to the uh decision. So the

patient was seen actually by two surgeon and she was turned down for a frailty reason. They thought that it's too much

reason. They thought that it's too much high risk. It's probably one of them

high risk. It's probably one of them said prohibitive risk. Um so we agreed to go ahead with a trans femoral with a trilogy medium 25 mm. Now unlike the

first case as you could see here there's a significant AR but we despite all our effort to delineate the cusp anatomy we

weren't able to get this right we tried right radial we had to get bifirmal access we use different catheters and I have to say we weren't able to get where

we want to do so that was the first challenge we had is we don't understand exactly the anatomy we have impression that look it it probably is a vertical

kind of annulus um but we we couldn't particularly see the none and this was the really challenge we think all those catheter are sitting in the right which we've seen it actually on CT it's

relatively large but we couldn't really appreciate the none at all she has no option she's not surgical candidate the team are already ready we had a brief discussion I said you know what sold it

we're going to do it anyway so here we go uh I'm not going to go through the same Yep. Uh so again you put a long

same Yep. Uh so again you put a long sheath 18 in French you pull it way back uh you advance the controller uh and then you'll advance it further and there you could see the locator now is open

and what we've done despite all our effort to put the catheter in each particular sinus or cusp sorry we weren't able to appreciate the none. So

what we've decided to do is a sinus injection to try to understand a bit more hoping that the valve actually would separate those and despite the effort of advancing the

controller we were not really aligning the valve properly and as you could see the the the aortas are relatively horizontal. So what we've done with this

horizontal. So what we've done with this this time is we advanced the actual delivery system rather than the controller. So we pushed on the whole

controller. So we pushed on the whole system and the wire and as you could see now the valve is actually hugging the outer curve and now you start to appreciate that the aorta is actually

more horizontal than when initially checked. And from here we start to

checked. And from here we start to appreciate actually where the annulus might be.

And from there we thought okay well now we are start to win. Now we start to understand the anatomy a bit more. we

probably will be able to appreciate all the the cusps. So from here, I'm sure you all agree you could appreciate the left.

And as you could see, the valve is literally horizontal.

So we got one cusp. We need to get the other two.

So what we've done, we sweep into the isolated left and we were able to separate the right from the none.

And we were able to appreciate that this will be the right cusp.

And with the same technique, we sweep to the none to the isolated nun and we've checked again and we are comfortable that this is

actually touching the base of the nun.

From there we check the implant depth.

At that point, we were pacing on the Safari wire and I'm sure you could see here there's a temporary wire going in.

So on that particular occasion, the pacing failed. So we had to put a

pacing failed. So we had to put a temporary wire and I'm not sure whether you remember that case, Dan. Even the

temporary wire was [laughter] was very difficult to implant.

And the rest is deployed under pacing.

I was literally worried that this valve will go up into the aorta.

And this is the engine.

>> Yeah, it's I mean I was there.

>> I feel a [laughter] bit ill just watching it back. But you know this was a second case and I think you know on the same day >> what what I'd also say when that conversation about you might say well you shouldn't be doing this case unless you've got an expert and obviously you

had me there as a proctor but actually you know we were you get incredible support from the company and this was a tough case we had Malta the most experienced uh field clinical specialist

of Yaval doing this case and so he helped us to kind of navigate this the the challenges and get as we always do a perfect result.

>> So Martine I think we're running out of time unfortunately. Yes, I think it I I

time unfortunately. Yes, I think it I I I hope you enjoyed this session because we learn a lot. Uh we know that Arctic regidation is is not so rare. There is a

rate of 10% but also valular disease arctic disease with predominant of articidation. So with the conventional

articidation. So with the conventional conventional uh valve it's difficult to to treat this artic regidation uh related to the difficulty for the

anchoring the valve and the the rate of paralular league as we show in in the data. So for me the place of this

data. So for me the place of this dedicated valve that would seems so easy to to to use if we uh uh learn to be

expert it will be a great advance for our patient and allow us to treat by a perccutaneous way. So and uh I I am very

perccutaneous way. So and uh I I am very happy and I would like to thanks all the our expert Dan it is a pleasure and you

because with your interaction unfortunately it's the end but we we can you can ask a question to to the experts just now. Thank you so much. Thank you.

just now. Thank you so much. Thank you.