New York Valves 2024 Symposium - Anteris Technologies

[Music] all right everybody we're going to go ahead and kick off our session here and uh thank you for the enthusiasm uh and the line I think uh from a food perspective hopefully we'll have enough

for everybody um but we're really excited to have everybody here today and I think you know fortunately I'm amongst friends here on this panel uh in this conversation but what we really want to talk about today is I

think is really a different technology what we've talked about a lot of times in the tavern space we're not looking at just replacing the valve but really restoring the native valve and so I'm Chris maduri and I'm going to really kick off this session today but the goal

today is to really give you a better understanding of derar which again is a new class of Taver R valve that's really designed to restore native

float all right let's get this moving here can we put the slides up please perfect so I'm Chris maduri I'm at Carolin University Hospital in Stockholm

Sweden and I'm also the uh CMO at an terorist Technologies so I think really to start the conversation we have to go backwards because we have to ask our what have we

been doing for the last 15 to 20 years and to be honest the goals and when you look around the other Tavern devices that are being developed the target has been how do we make a better version of

a bioprosthetic valve and personally as we started this quite a few years ago we asked ourselves a different question how do we actually design a valve that actually instead mimics the native valve

instead of actually trying to mimic a bioprosthetic valve and I think that's fundamentally the difference you're going to see here today as we look forward and we see all the initial results with this technology so for some

important background this wasn't just kind of a convoluted idea by a bunch of friends this was actually built off of a company and terce that has a long history of the development of

bioprosthetic or bi or tissue technology so this cuttingedge tissue technology has actually been around since 2014 being FDA approved and has been used in over 55,000 patients now globally in the

cardiac space and as well as a vascular patch and it's been clinically proven to be calcium free up to 10 years and there's a long long source of literature that really supports this conversation now I think it's important

because if we're going to talk about building a backbone of trying to mimic a native valve want to make sure we have the right right platform to be able to do that and so first anteras who had been selling this tissue for a while asked themselves listen what is another

space we could be moving into there seems to be a lot of opportunity in the Taver space but again the question was not how do we make another bioprosthetic valve is what is the unet need in the tavern space how do we ask ourselves

different questions and that question really was well if we're going to go after a new Target what does a healthy aortic valve perform like and then after that we ask ourselves okay if this is what it performs L and we've now

established those benchmarks how do we actually try to mimic that valve then we have to put it on a stent and lastly we have to actually be able to deliver it pretty effectively so that wasn't just done now I think those are important

questions but they weren't done in a silo by a group of Engineers and some people in Industry it was actually done by a company that said you know what these are important ideas but we actually want to engage the key leaders

in the globally and ask them how to actually find the unmet needs and how to actually build them so that point some of which are on the podium today including myself or initially engaged and asked that question what are the

unmet needs in the tavern space What are the compromises what are younger patients need and to be honest it took us a few years to get there I mean we had a lot of times we're looking at designs and trying to sort this out and

it was a struggle but eventually we think we landed on The Sweet Spot that you'll see today really is transformative and what we identified was that if we wanted to mimic the native aortic valve we couldn't do the

same thing everybody else does we couldn't take a piece of tissue and cut it into three pieces sew it onto a stent and try to mimic the bioprosthetic valves exist today we have to look at it differ say how do we mimic what a

healthy valve looks like the only way that's done is by taking that single piece of tissue just like the body's valve itself is and molding it to the shape of the Native aortic valve and

that hence allows us to actually have native healthy like performance now we said all that was important well of course we have already mentioned the backbone is having an incredibly durable

tissue with these important anti calcification and the the ftic tissue properties but the design of valve that also reduced had long coaptation length to reduced stress there was balloon expanable because it was felt to be

important at the time that people wanted an easy to use valve the struggle was we were trading off when we're using an easy to use valve because there was a compromising hemam performance we also wanted to be able to have commis

alignment as well as coronary access so building on that then we took this adap tissue and molded now I think it's important to understand why haven't other people done this why is it not you know people thought of it this way well

it's important to understand that this unique adapt tissue process allows this tissue to be molded you cannot just take a normal bioprosthetic you know Bine paric cardio tissue and go mold it into

this shape you have to have the unique securely IB based properties of this tissue to actually provide this unique shape and I think it's important to recognize what this tissue actually has

in it this tissue has undetectable levels of GL of of free alides which is a big driver in the gassification process but Additionally you find no

alphal no DNA or RNA remnants and no phospholipids and again these are all part of that inflammatory response that contributes to degeneration now that's great you have a great tissue you've molded it but I

think it's important to understand that by building this biometic design of it again it really does normalize flow and reduce leaflet stress and what you can see here is that unlike a bioprosthetic

valve that typically has a couple Mill coaptation length at best what you see is it's incredibly long coaptation length and what that allows this valve to do and Mike will talk about it a little bit more is it allows you to

avoid any pin wheeling and additionally significantly reduces leaflet stress I think these are all again key components to durability and you can see this here this valve as it open closes is really

what you want a surgical aortic valve repair to look like when it open closes this is what you want a healthy aortic valve to look like as I already mentioned and Sushi will get into more it is an incredibly

to use easy to use balloon stable system this valve is in and out of the body within a few minutes of putting it in through the sheath it's that easy and intuitive to use it's a very robust 14 French expandable sheath system and

again Su shei will get to that a little bit more but I think lastly what I want to touch on before I pass this off to my friends and colleagues here is you know sorry we built a valve and you'll see

the hemodynamics are really unparalleled clinically as well um but what we think is also important is not just how wide it opens but how it opens and this is something that hasn't often been looked about in the field but I think it's

going to be a really important topic in the near future and that's the word we use kinematics of the leaflet so how does it actually open and if you actually watch here in slow motion what you'll see is this so in a traditional

threepiece valve as it opens it really hinges like a door so it is three different leaflets and they essentially are swinging open and closed like this conversely when you watch how this derar

is built it allows you to to build native like flow in because you end up puffing as you can see in the durav our leaflets in the middle here and then popping open so there's not this turbulent flow that's coming out here

and there so as you watch this move slowly you can see that this just goes from puffing to popping open versus this kind of door opening appearance in the other ones so I'll let it play one more

time but I think you can appreciate here that there's distinct differences in the leaflet kinematics to allow you to have a more native like valve function

so in summary you know we can talk about a lot of things here but I think what's important to understand is this valve with a incredible history of tissue technology with the company was built

not to make another bioprosthetic valve but it was built to mimic the native valve which is what could be a better Target when we're talking about best possible therapies for our patients it is made not just by a group of Engineers

but you'll see about the intuitiveness of it and you'll hear in our conversations today this was Physicians who we talk weekly or every other week with Engineers embedded to to figure out what two users need to get the right

results and it has incredible coaptation length as well as tissue technology we think will provide benefits from a durability perspective acutely and longterm and opens and closes

differently than other valves thank you all right shall we uh start with some of the discussion maybe um basically you you introduce new terminology ology you mentioned this

biomatic valve um Michael is this truly a different class of valve technology or is this more of the same what is your opinion on that I think this is a different valve design I mean you know

when we look at our Valves and we wonder how they're going to work how long they're work we we look at valve design and tissue science and and this has really Incorporated both of those one in the valve design using a single molded

piece with fairly High commissures which allows it to spread the struss across the leaflet um it it's going to leave it's going to lead to a better not a better opening but a better closing force and it's also going to lead to

better valve durability I think so I think I think this is something that's completely different I mean we know that at least in the world of surgery there's only one operation for a stenosis that get you back to a normal lifespan and

that's the Ross because I give you a normal valve and so the closer I can mimic an aortic valve the more biomic you become the longer the valve is going to last and and I think that this will

translate into clinical out comes which we've seen I think in other trials based on hemam and durability yeah great Point go no I was really going to ask a question to Vinnie

because I always learn so much about surgical Valves and song from Vinnie so Vinnie you know up until maybe a year yeah two years ago when Chris approached

me I had not heard of in teras uh and then I suddenly find out they have this long history of actually making tissue and of having a special treatment for

for antic calcification maybe you want to give us some comments cuz you've seen a whole array of different Technologies for valve tissue so in in surgery we use pericardium patch or pericardium in many

places I think the commonest two places you can associate easily with is one is rvot patch or in pulmonic side and many times it's not just the patch you can

make a unicas speed Val as well and the second which is now very common is root enlargement and in both these sides one of the things we learn is when we

reoperate is these can become calcified and then they pose a big hazard in terms of managing it at that point and that is the reason this particular tissue

technology has been used on the pulmonic side in over 50,000 patients and has shown hardly any calcification so although one may say that it's less

Dynamic at that point but the duration it has been used is long and that I think points us that this anti-calcification works abolutely and I I I was going to toss it

to Nita because I mean I think your comment Mike about the Ross procedure and I know Nita you have experienced with a lot with that from your Center and the MRI perspective and and I mean do you think that's I mean as we've talked about biomedic and the benchmarks

I mean what do you think when you've seen this valve obviously in use in your own practice and the importance of trying to you know have a percutaneous Ross essentially procedure right yeah I mean I think the the Ross is really the

gold standard and so we have quite a large population of those patients we do a lot of um adult congenital a lot of these young bicuspid patients that are getting Ross procedures you know one of the things we've seen on on CMR is how

the you know the Dynamics or the hemodynamics of these valves are essentially like a native valve you know and I think that is the gold standard that's what we're all looking for to replace a valve with a valve that

behaves like your own I mean and Joel is going to talk to us a lot about what he's seen in CMR but I think it's really exciting times for patients who are going to need aortic valve replacement by by the way what is the importance of

the cooptation length because it was clear from from your slides that you see the there's a longer quotation length with this technology is this something relevant or is this a trivial finding if

you go back to to ER Valve Repair valve sparing Roots one of the things that they teach early on is that your valve should look like a pair of preying hands with the heel of your palm at or above the anulus and with at least 8 millimeters of fingers touching and and

the more more cooptation not only does it relieve the stress but it gives you more leeway if it starts to expand in anyway to prevent AI as as time goes on so if you look look at this that was over 8 millimet and if you looked at the

heel of the praying hands they're above the anus those are exactly what we look for after a revolve repair so so what is a typical cooptation yeah so 8.4 millimeters has been the main 8.4 8.4 yeah which a normal trans cath or

surgical valve is usually just a couple millimeters yeah so you know what struck me today as well is that our terminology when it comes to Tava has changed I mean we never spoke about coaptation length

for over 20 years right so now we're talking about coaptation length and the other topic or the other new terminology that we talking a lot more that you mentioned is pen Wheeling um suil how

important is pen Wheeling maybe you want to explain what P pin Wheeling is for for the audience and how important it is sure so I mean I think when we talk about a lot of extra tissue we're always

worried that the valve won't expand and and so the if you have an underexpanded valve a tri leaflet valve and you're going to see pin Wheeling where the leaflets are are sort of rotated as they

close and and whether that's going to lead to leaflet thrombosis or early degeneration has always been a concern that's especially in a lot of these terms came up when we're doing valve and

valve with h sapiens in in Prior surgical valves where you're not fully expanding the valve and in the engineers have from have always taught us that you

know to get a proper hemodynamics and not only just opening but closing you have to you know fully expand the valve and I and I think part of the challenge

is that you know in in a lot of these you know it's not we have three sizes and the ranges are broad that you implant these sizes in so you you don't fully expand a valve because the anatom is going to limit you or you're going to

injure the root whereas in surgery they're taking it out we're sort of limited by the anatomy and so when the first time I saw this I actually was worried about it because my notion of

redundant tissue and extra cation I was worried that that's not the the right approach and I know what Mike is saying and this is more like you see the closing it's it's the coaptation but

it's not rotating or or pin wheeling and I think it's a great point because what we've seen is that on the bench studies that unlike most valves that you have like a 1 to 2 millimet sweet spot from a

size perspective there's no pin willing around 6 to 7 millimet in size because these praying hands stop the valve from rotating on each other because it's like a blanket holding it straight up so one

last question before we move to the next one azim I mean you use all sorts of valves all the time I mean where is this need or where are the trade-offs today

and what what is the need still in the space yeah absolutely sometimes wonder why do we need so many valves but I I think we do and I think that that need is becoming more and more impar as we

start treating patients who are younger with longer life expectancies our our standard of what we'll accept in a young patient is just has has to be very high

it has to be as good as when Vinnie and Mike put in a surgical valve we have to be able to give is without exception you know low pacemaker rates no pvl but more

importantly is we need to start as we talk about this lifetime management it shouldn't be only about oh what typ of valve we going to put in when that fails we need to start talking about can we choose a valve and find a valve that's

going to last the patient even longer so maybe we don't have to worry about what's the second or third valve down the road and to me I think that's the part I'm I'm most interested in is can

we find a valve for a younger patient that's going to last them as long as possible yeah absolutely so sui you want to take it

next so chil did a cool live case earlier today in a by kuspit Valve but he he was still relying on te guidance what what's the story about that I I I

don't do any Echo anymore because we we we focus on excellent results ouch ouch patient- centered care not phys centered

sorry um so um moving on thank you very much uh so it's my pleasure to sort of present some of the initial experience with the davar system these are my disclosures most relevant as a

consultant for ENT ter and did some of the uh First cases uh with the device with Chris and the rest of the team um so you know dvar has a reasonable experience it's over 50 patients 56

patients uh the first in Human Experience outside the US was 41 patients a US EFS study of 15 patients these were single arm studies and just to get the initial experience understand

the the uh sort of the system and get some safety and feasibility of the and allow us to iterate the system during this process and I think that's what EFS is for and I think we we've iterated

this device from the first inh human and the way the balloon works the way the device tracks all the different components because we learned during the course of an EFS which is what what really was important and and I think

that's sort of the feedback that I think was important for me and that was sort of to be a Chris's point that there was a team that was sort of giving feedback and the engineers were trying to make

those changes was is really quite relevant um and then there are Core Labs to look at sort of the obvious important endpoints with trans thasc Echo CT CMR and try to really understand is there

differences how can we optimize this further uh and obviously there will be ongoing followup the the outside the US is just one year but the EFS is out to 10 years uh you see the sort of the

Baseline demographics is just a limited demographics what you know there were sort of intermediate to higher risk patients um the SDS is were three in the

first inum and 5.8 in the EFS uh important to note the area derived annular diameter uh was under 23 it was 20 roughly in the low 22s that's because

right now there was at this time there's only one valve size and and that sort of dictated obviously some of the the sizing so that's why you see most of the experience and when you look at the gradients and you look at the hemodynamics it's important to keep that

in mind um and you see the typical sort of risk factors that we see in Taver patients I think Chris mentioned this a bit um you know it's it's a balloon expandable valve it's sort of what we're

familiar with um but the balloon is different it it has been iterated uh to provide stability um and part of it is and we're going to talk here is there's there's commiss alignment with this

device there's a knob in the back that allows you to to rotate to get commissioner alignment but one one of the challenges that we noticed in the initial EFS is no when we first the

first iteration of the device when you rotated you you inflated it was somewhat unpredictable you you lined it up but as you inflated the balloon characteristics or the valve would rotate and so you didn't end up where you where you

thought you were and that's where there's a lot of time spent on the balloon uh that that is now St that the valve is stable now in terms of its rotation as you inflate um it's a

steerable catheter single you know single Direction steering to help you navigate the arch and then there's a 14 French uh expandable sheath now uh to help with the vascular

access um this is typical you see it's a 14 French um but you know these are these what as a physician I you know these seem very simple and it would be frustrating why things didn't work and

um you know it seems like you know we've been used to the E sheath for a long time I know there's with the ice seve and things and uh there are challenges with this and it took some time but you know the initial cases were done through

much larger seats either a 22 French Gore or uh other various commercial sheaths so it you know it had to iterate down but now it's through a 14 French e sheath um you see here there is a uh

there's flexion typical to what we see with the current balloon with the Edwards balloon expandable system um but the valve is crimped on the balloon um there's no uh you know no withdrawing the balloon the valve is crimped onto

the balloon and and the balloon is different different it's got these uh and I think that that was a lot of the engineering and you know I'm not I I can't really explain about part of the characteristics was you needed to be

able to be reliably crimp at the same spot and you wanted the balloon to expand reliably because I think we learned from their early partner days uh that there was a lot of asymmetric

expansion of the balloon and when you get asymmetric expansion of the balloon you see motion of the valve up or down uh and during deployment and I think that's one of the concerns so you wanted to

you know like a dog bone typee expansion which helps stabilize the valve during deployment and that they were reliable for shortening because part of the Simplicity of balloon expandable is you put it in the position you want you

inflate the balloon and it it it sort of locks into where you want it to be but if if the balloon characteristics aren't optimized that won't happen I think there was there was a lot of learnings and you know from early iteration of

balloon to where we are now is quite different as I said part of it is about the rotational characteristics as well so then U you you L you use these tabs uh these sort of figure don't if I can

point here you can when you rotate the back handle you you based on CT uh and by your initial anagram you know where the where the commers are where the coordinators are um and again we can

talk about commiss alignment or alignment to coronaries obviously it's very different when you're doing bicuspid valve do you align to what commer or do you align to a coronary I think for a lot of us what we're talking about with commissional alignment is

coronary access so we tend to more align to coronary but you can rotate uh and you and you align these in a manner that you when as the valve inflates you'll

get commiss or coronary alignment and then again I'll let this play a few times and what you see and and I'll and we'll let it play the first time and what you want is and what you

see sometimes is frustrating is as you're starting to inflate you see the balloon sort of slide on the valve um and what we wanted to do was avoid that and there are these Stoppers here that are um night all

um that hold the valve in place but I the easiest way to look at is look at this marker and it the the valve stays very stable on the balloon during

deployment um and and obviously this is one case but the experience more recently has been that with multiple cases this is this is what happens and I think that's an important feature and I guess you know over you're going to have

to learn that over you know hundreds of times in cases I think the other thing I'd add on that one to is I mean this is in the right left of you and so you can the the commisural post or on the uh outer curve there the two overlapping

ones and then you have one that you don't see on the inner curve uh right and so I think what's important to recognize is like you said it it doesn't rotate and that was a lot of work to do that but you see this goes straight out

and also it's proba nice is the commissional post actually stay in place during inflation as well so actually for valve and valves actually we did a tab and Tav and Tav recently and um you know you can use the commisural post to put

it on node five pretty easily and identify your spot as well yeah and I think that's the the feature that you know the first I remember in the beginning the cases that we did you know this these would rotate and it wouldn't

stay stable and I think this was this took some time and it's really about balloon characteristics right you can align but if the balloon is going to rotate uh the valve as it inflates

that's obviously a challenge so uh real quick these are the initial safety uh results um you know the from a primary safety end point there was one mortality in the EFS uh

data um and then you look at the other events uh one stroke um pacemaker rates um in the initial first in human around 5% typical what we see with Bloon

expandable no Pacers in the initial us experience uh there were some vascular complications early on and again as I said early on we use a 22 French Gore

sheath um and and so it's you know obviously plays a role in some of it um and the the rest of the events you see here are pretty pretty low and pretty typical what we see with current

commercial experience and then there's been a lot of talk about hemodynamics and obviously that's been the main focus and so this is again a valve in a mean anular size

of about 22 millimet you you get eoas of 2.2 uh mean gradients of eight and what's important is I I've started focus a lot more on DVI and this DVI is a lot

point 6 is is a lot more than we typically see we typically see DVI is.

35445 uh but this is quite remarkable again measure to the hemodynamics you see here again this cor lab data the uh DVI as well as the valve areas

consistent valve varies over two uh with this valve for this uh annular size and the mean gradient less than 10 around 8 to n that stayed consistent this is the

initial first in human experience this is the data for the um the the US EFS experience and again you see in this data one one pacemaker um at 6.7 no

other mortality here that you saw then again hemodynamics quite similar reproducible 2.2 mean gradients around 7 and A2 and again DVI above 6 um

no significant pvl uh in the previous experience again no significant mod pvl as well um and again you see the hemodynamics again this is only 30-day data but you see the results here so you

know this is initial data it's 50 patients there's been iteration of the of the valve over the course of these first uh 50 cases uh in terms of not only the not the valve as much but the delivery

system to get these consistent results the hemodynamics has been excellent with a single valve size um it's a you know predictable balloon expandable delivery system um and the the global pivotal

trial is going to be starting next year and so we'll get get some data and comparison to existing Valves and see how it performs so I'll stop there thank you very much Anita I mean you want to comment I

mean you used it now quite a few times in valve inv valve and um just talk about the ease of use because I think it's a you know we're all busy operators and maybe a lot of people who come to these meetings are very experienced in

Tavor uh but I think it's important to make sure the Technologies as they translate are pretty intuitive I mean what was your experience yeah so we've done five cases we're going to be presenting our data tomorrow in a session so I encourage you to to come

see that you know essentially we decided to do these cases under special access for particular reasons for these patients so they were patients who did have bypass grafts even though they had an AVR um and they had con we had

concerns about leaving them with high gradients and so we chose durar and so you know we had never done a case when we did our first valve and valve in July of last year it's varied intuitive I

mean it's like the technology that we already know how to use the commissional alignment was easy and that was sort of the earlier generation that we did on our first case and so I think it really does utilize the skills that you already

have and the knowledge that you already have to be able to to deploy a valve it I think Crossing the valve was hard in a couple of our cases more than actually putting the valve in place because the gradients were so high but um you know

it's it's easy to use I mean there's nothing you know very foreign about this at all and Vinnie you've been in a ton of the cases now I think as many as me almost I mean the last time we did what

13 12 13 just uh last month and I mean we were flying through what was your experience I think uh suil highlighted the changes which is important um you

know any new device you start device delivery system both have to be you know married together well as well and the last trip was phenomenal in terms of

seeing the changes not just on the second generation wall but the delivery system and the sheath yeah and hence the procedure has become very streamlined now and uh again the duration of the

procedure despite you know multiple checklist is really short so as Anita said here it's something which we already do a balloon expander it's no

different anymore is is predil mandatory no no your predil and I think I would congratulate the engineers on that I would say that

uh the features of the nose cone and the delivery the catheter and the balloon is such that the predilation in in a very horizontal basped like Anatomy calcified

it's still easy to cross so I think it's interesting so a few of us have spent years on calls talking through this and you know a lot of times we do a lot of things in practice and we think we understand how things work and why they

work but then when you dig deeper on the engineering side you realize maybe you didn't really understand it the way you thought so one thing that we spent a lot of time was on the the nose cone actually distal stop and actually interestingly the first time they

mentioned to me can we have a tightly woven nightl distal stop I was like why would we use nightl to hold something in placees you know and it's actually quite fascinating because the way it works is unbelievable I mean it lets you smooth

out your frame as you're crossing the arch it lets you have just enough enough give as you actually crossing the valve and as you're actually pushing through the expandable sheath it really allows you to track those Contours a bit easier

as well so I think credit to them that they have done a great job really getting a creative solution to some of the things we see clinically well and the other important feature and that seems um simple but it

isn't is the short the short stand frame yeah so I I am very much in favor of avoiding stand frames in front of the coronaries and SOI already mentioned commissional alignment or coronary

alignment but basically if you have a short stand frame you don't need to B bother about a coronary alignment you just want to focus on commissional alignment because that might affect your

hemodynamic valve performance so um so then you don't need to make any concessions in terms of your commissional alignment if you have a stand frame in front of the coronaries

that's where you may want to opt for coronary alignment to make sure that you that you will be able to re access the coronaries if need it so I think that is

also an an important very simple but very important feature of the I do think sorry I was just going to say that you know when you're doing this size valve

in these annuli even balloon expandable is going to be to the sinus in many and that's where I think the coronary alignment and a large open cell I think is valuable so I think that the top

cells are open because the the it's a short frame but when you when you're doing 26 and 29 valves you often are below the cornay but I would say a lot of the especially in women lot of these

23 valves um you're end up above the corner are so getting the alignment and getting the having a large open cell for corn access I think is important and you know the next generation is going to be through this right now is a little bit taller than a 23 sapen and the next

generation is going to be I think three or four millimet shorter so it's going to be comparable to the no now it is the new generation is actually now yeah but but when you talk about commure and Corner alignment you got to remember that even if you have a Buy customer

with 180 coronaries cories are never behind the commer they can't be they can be above it they can be to the side of it and so unless it unless your post goes above your normal commer no matter

how your corner are if you line up post to post your Corners are gonna be okay yeah I I think it's a great point I know I think I saw roxan in here earlier and I know Mike's here from the smart trial

data and looking at I think we talk about annual size and looking at some of the hemon namic results of Z I mean you I've seen you talk on this before but I mean you know this really I think goes

back to a different because we've just talked about the short frame right and we've consistently seen Short frames or balloon spals that we are compromising H Mak maybe there's some Mild improvement

now but still not normalization of hos and it seems like now at least with this design that we're able to really get the evolute if not better he D Performance but what is kind of your thoughts looking at that compared to maybe some

of the smart data I guess what I take away when I look at all this data is that we all have to accept except that not all valves are created equally that not all

Tava valves are the same not all self-expandable valves give you the same hemodynamics or can be um put in the same class and similarly with balloon

expandable valves we're now coming into a world where I think in the next few years we'll see in the United States multiple balloon expandable Valves and because we deploy it on a balloon

doesn't mean they're all the same and I think that's going to be really the important discussion right is what are the differences between different Technologies and it's going to come to

because I think when when you talk about balloon expandable es of use and reproducibility are really the goal standard and why many people like the valve then it's going to come down to

frame height do you have commercial alignment how reliable the commercial alignment is what is your tissue made of and how long that's going to last and because you know not all of us are going

to be here 20 years from now um still doing valves you also want to look at are there any early changes as regards to hemodynamics gradients valve areas

and maybe some unique features that jaia will tell us about later that we'll be able to say maybe one valve has some advantages over another valve um so I

think you know this area is still um a very important and wide open area and I'm I'm glad smart came out because it's forcing us to to address the fact and

talk about the fact that we can't use one valve in every patient every Anatomy that certain valves do better and that there are other factors that are important to our patients uh in making a

choice and so we're going to have to get better at choosing the right valve for the right patient yeah no absolutely Mike ready I think it's up to you now well I know a lot of the people in

this room but for for those you that don't know me I'm Michael R I'm a cardiac surgeon from Houston and I've been doing cardiac surgery for a little over 40 years now and and I and my clinical and research interest has been

cardiac valve disease particularly aortic valve disease and so I've been very interested in hemodynamics and why hemodynamics matter we already mentioned earlier that the Ross procedure is the only thing that gets you back to a

normal uh lifespan because it it mimics your re or valve and the closer you get the longer you're going to live we have lots of growing data that any level of aor nois even mild shortens your life

the echo database from from Australia shows us that so we really want to get back to to as close to normal as we can and you've already seen this this uh

slide uh Shi showed you this so if you look at the first in man and EFS so EAS 2.2 2.18 both very good the problem with EA is it's fraught with air because of

measurement in fact when we started core valve my echol laab would not even give you an eoa for a surgical valve because the because measuring the lvot was so hard they only give you a DVI because that's the only thing they thought was was acran in fact if you look at the

literature and you you read two different studies with the same valves one have an EA of 1.8 and one have an EA of two because they're read by different Cor laabs in fact we've looked at Echo cor laab versus sites for the Paragon

trial and and one of the things that doesn't correlate is eoa eoa is fraught with error mean gradient mean gradients do correlate between Echo cor labs and sites the problem is they're flow dependent and so if you don't know the

flow you don't know one thing that's independent of both of those is Doppler velocity index DVI so why is DVI important well DVI is important because it just comes from the

continuity equation that flow below the valve equals flow at the tip of the the opening of the valve the EA and the flow below the valve is the lvot area times the lvot velocity times index that

envelope you see an echo that summarizes all instantaneous velocities across syy and that equals the eoa the TIC valve opening times the aortic velocity time index you don't have to measure any links for your lvot you're not going to

lose by the square there because you don't measure you're just measuring vtis and vtis are pretty easy to measure measure so if you divide the lvot vti by the oric vti what that equals that do V

index is the ratio of that individual patient effective orice area to that individual patient's left uh lvot area at that individual patient's flow so it's normalized to flow and it's

normalized to to to size why because little people have little LS and big people have big LS so if you go back and you look at like Becky hans's work you'll see that no matter what valve size the DVI is the same because it's

not an actual number for the OA it's a percentage of the OA to the lvot and of course you'd like to be as close to one as you possibly can get so if you look

at DVI here durv 64 evolute 61 that comes from Becky hans's work when Becky went back and looked at the core laab echoes in the uh evolute uh uh trials

and the partner trials and saping 3 was 042 so that's 64% of that patient's lvot 61% of that patient's lvot or 42% of that patient's lvot in the evolute trials when we did this I went back and

looked at the mean surgical mean surgical was 05 and and that's why I think when you looked at the evolute trial the durability turned out to be better and the survival turned out to be

better because it's clearly better hemodynamics now we've talked about this coaptation length if you look at this again I I tell you when when you look at this we know from AIC Valve Repair because we do a lot of those now that

you want to see your your praying hands the heel of your hands at or above the anulus and you'd like to see at least 8 millimeters coaptation that cooptation allows you to even overexpanded valve

without developing AI it spreads the stress out across that and it does c that does not cause you to pin wheel pin wheel is the length of the leaflet not the amount of of cooptation you have what this does is reduce stress and it

should make it last longer and because the way it's folded Chris has already shown you that it opens up better it opens up in a better fashion and it opens up more fully and that's why you're seeing the DVI that we're

seeing now there's really no pin Wheeling I'm not going to go over this again you've already seen this once but pinwheeling so I'm grateful for pinwheeling because when I was a young surgeon there was a valve called I es

you shy everybody but maybe abart is Too Young Too Old too young to know this but it was one of the first tissue valves ever remember because we're we're getting up there it was a tissue valve and it

failed why because they put in these very long leaflets to try to prevent leakage and they pin wheeled and they all failed and so I spent a lot of my early surgical career taking out inq shyy valves and people learn from that

that P Wheeling is a bad thing because the leaflets lengthwise fold on themselves and they twist and they fail because that creates stress points now we also see with this valve and I'm not going to say much about this

because this is really going to be for Gile to talk about is more laminer flow laminer flow is crucial anytime you get turbulent flow you lose energy and what the heart cares about is how much work

it has to do to get the blood out of the heart and around the body and work is is force times distance and force is mass times acceleration and if you get laminer flow there's less energy

expended getting that blood forward than if you have chaotic flow now you can measure this with Echo because in because in laminer flow the velocity changes from the wall to the Midstream whereas in turbulent flow the means are

the same across there but you're losing energy you can do this with that but it's much better done with with CMR and I'm I'll let J comment on that but I do think that when we when you look at this and one of the things that we're

starting to look at as a field is not just how big the valve opens but how does the blood flow across the valve and laminer flow is one of the key things and that's one reason why tissue valves in some ways are a little bit better

than some of the older mechanical valves we had that had single dis because the single disc cause very turbulent flow where central openings start to lend themselves to laminer flow but not all of them end up

laminer and again this is just an echo show I'm going to skip over this you can do this with Echo it's not really the way to do it the real way to do it is do it with 4D CMR and it it it shows it

very nicely so hamic per performance matters hemodynamics affect your survival hemodynamics affect your ability to recover and do what you want to do we know that severe patient prostetic mismatch impedes your ability

to exercise and and the and the smaller your valve the smaller eoa the harder you're going to have doing the things you want to do particularly As you move

to younger more active patients and DVI really is the metric I think we ought to all be looking at I mean it's much more important than eoa which is fraught with errors it's much more important than me in gradients which are important but

they're all flow dependent whereas this is independent of flow and independent of patient size and it gives you a good valve to valve patient-to-patient metric to look at Pin will and cooptation Link

can also be seen Echo these are really early signs of what I think are going to be increased durability things that we know of from AIC valve repair and laminina flow can be seen on Echo through all levels of the valve and it

may explain some of the hamic performance you when you look at the CMR you'll really see this you look at a normal valve and you look at a dur valve and what you see is you get the same type of laminer flow and again the

closer you can get to the valve God gave you when it was working the better off you are so I'm going to stop there and we'll move on uh to either questions for the next one well said Mike I think for the sake of want to have more conversation thank you uh let's jump to

joal because he's going to build on that in the flow perspective and then we can really kind of settle in on some of these other uh clinically relevant differences well thank you so much Chris

uh and and terce for this opportunity presenting here work that has uh been done by a colleague as well panash gar uh from Norwich in UK as well that helped us tremendously in the

development of this some disclosures that get Consulting from entas so set the stage that aortic valve we're talking about thetic stenosis but this is not just the disease of

obviously the valve it's the disease of the valve of The ventricle and of the arteries we're talking about arteries too yes so in a patient with sosis

obviously there has to be some compensatory U increase in the wall thickness to accommodate the increase wall stress and by doing that it comes at the expense of obviously having

fibrosis scar that you see here by late Gat after you do AVR provided that there's no prosthesis paent mismatch and there is good control of hypertension

and you have a healthy arteries you're going to regress this hypertrophy you're going to regress even some of the interstitial expansion which is by the collagen that we can measure by MRI so a

good artery good artery should be pulsatile they should be able to accommodate the blood flow and in diast they should continue to propagate their flow so that profusion continues in dio

as well so what happens with the ortic stenosis normal tic flow should be lamina so the Vmax the peak the highest velocity should be at the very center of the vessel not touching the walls and

obviously with the ortic stenosis we're going to distort that blood flow and so the flow gets erratic it gets distorted there's turbulence and there's going to be more wall sheer stress because it's going to hit the wall at the arteries

well these arteries are not going to like and eventually they're going to become stiff and that stiffness is going to create obviously some reflection of these waves and even in syy bounces in

the wall and it travels back again so you wasting energy and this ventricle is wasting even more work so it doesn't like that so this is a non-lam this is a

laminar flow and this is a nonlaminar turbulent flow is that true well this has been done with the 4D flow MRI as you can see from healthy here the

bullseye it starts to move into the periphery as we get more stenotic different groups of patients and some other Concepts they are going to be important how far are you from the

center that's called the displacement ratio the distance from the centroid of the vessel in this systolic flow reversal ratio that is that reflection

that comes back even in syy so it's that that turn around because of the reflection of the Waves well there's a easy solution let's fix the valve we tried that we do that

with surgery and this is some work that we had done together with the group at pen pre and post cardiac MRI and it turns out that actually after you fix the eortic valve with surgery you

increase your aortic stiffness maybe you are unmasking because now The ventricle is talking directly with the arteries there's no more impeding Force like the TIC valve so the compliance goes down

the stiffness goes up and this reflection which is that countert talk between The ventricle and the arteries the pushback is called the reflection magnitude was inversely correlated with

kccq that is the patients that had the highest reflection of the magnitude had the worst cases G Improvement and that was seen well surgery did not work how

about Taver let's go to Tav all right so we do this looking at 4D flow severe aortic stenosis with 4D flow MRI you can see that the flow is quite not laminar

it's eccentric it's turbulent it hits the outer curvature you put a Sapient here but you could say it could be other valve it could be a surgical valve as well and you still have not restored lemon of flow that is a cross-section of

the order looking at exactly that flow displacement at 10:00 ideally you like to have the flow down the center right well we have learned through this publication from

Philip Geno looking at the changes of eortic stage and now we're fixing this either with surgery or with Taver there's not a significant Improvement you improve obviously some of the

symptoms but the changes of the heart that should occur within a one-year time span did not happen only 15% had Improvement it's pretty much a lateral

move for most patients and some of them worsening is that because are we true simplistic to think that one valve would fix everything are we doing a small benefit to these patients is that because there could be some other

culprits and one of them here that unfortunately discover is hypertension as well that was one of the causes of lack of cardiac stage Improvement and

that is that again importance of flow that might be um related to that when we look into both Surgical and Tav valves

again for 4D flow Central flow is normal with M eccentricity severe eccentricity this is in balloon Expendable valves we could see that whether we look at surgery or Taver we could see that

eccentricity seems to be even greater with Tav of devices and greater for displacement and that might have also some implications into increase in wsh

stresses we talked about continuation of hypertension amplification of that in increase uh W stre stress so is there a way that we could do this without

causing a compromise to the arteries so we took this work um at the Republic of Georgia and I want to again give cudas to pgar good friend and colleague who uh

working together with the group there has been able to apply not only to the face contrast as you see here but even 4D flow as we have now looking at the

post CMR flow pattern of Jar so this is a normal heiva there's no as as you can see in syy it comes it fills out nicely here the cross-section of the order flow

displacement is minimal and flow reversal ratio is pretty much minimal here have five patients of davar you can see again same lamina flow contrast now obviously with severe s that's how they

would start with before they got into the durar you see this very displaced flow with sapen you can see the same magnitude not too different from

actually severe as um that's from the FL perspective evolute we can see also some flow displacement and even surgical valves here with Edwards Magna e so

there was no significant difference between what you see post with this device versus even a normal healthy aortic valve so restoration of

potentially normal flow which might have Downstream implications to the valve to The ventricle into the arteries now looking at this bomatic design again

just put into bar graphs this uh flow displacement comparing Health tic valves with durav VAR and other competitors you can see that there's greater displacement and greater reversal ratio

with other devices versus What was seen with this biomatic but so we are talking about different languages and Concepts and uh really lexicon here we're talking about

cooptation lamp we're talking about how we can optimize the uh delivery of this balloon Expendable valve and now introducing the flow I think it's quite a lot so let's actually dial back down

and understand maybe that's great you can show colors but so what right so I mean show me that there is actually some benefit beyond what this colors would show so what is the impact of actually

doing something after restoring Flow To The ventricle so we need to look at the left ventricle and again this is a construct that cardiac MRI is considered

the gold standard for precise quantification here we have 12 paired patients pre and six months post there is also some Echo data obviously done by

um Taver Valves and Brian Lyon who is here in the audience as well looking at Echo but the Precision of measurement of the e is difficult because it relies on assumptions on the formulas and a lot of

that has to do with also the dimensions of the ventricle but nonetheless with MRI with 12 patients we could see here that there is an important LV Mass regression which ultimately speaks for

how did you unload that ventricle and also Improvement on left mass index as well by 29% and if you can do this Delta here you can see this is almost 20

points whereas you know in the this recent meta analysis that was published nine Publications 246 patients the average left Mass regression was about 15 of course we're talking about one

valve size versus across of the spectrum but needless to say that that benefit that was seen with also the gradients and the echo DVI that was presented by

Dr weiron and others might have also some implications Into The ventricle and we are very excited to see also the continuation of this data now here in US

this is the data from the EFS um there was 15 patients and we have cardiac amri in a handful of them uh this is to be expanded now we can see this pre-imposed

cardiac amri there is Improvement of the global launch no strain the ejection fra is already super good so you cannot make it better you could make it worse but did not get worse but you can make

strain better you can make the RV strain better you can make also left ventricular Mass substantially reduced and more importantly again the restoration of the flow as you can see

the red column of blood is the red down Center uh which um was again something that we have restore from this obviously severe eortic cenotic turbulent flow so

my final thoughts is that you know in the post Imaging analys that we have seen so far demonstrates that this long coaptation length um similar to a native aortic valve might have some very

favorable benefits not only from Echo gradients but also hioa and DVI there is some some very favorable early reverse remodeling that now has been seen by

cardiac MRI and obviously importantly the restoration of this normal Lina flow and obviously the jury still out whether these U findings would have obviously

some Downstream impact into LV remodeling arterior stiffness that will be um prospectively evaluated now with the ongoing future studies and also the

pivotal sub study thank you [Applause] provocative stuff Joel thank you um thoughts from anybody immediate comments

well I just want to say one thing but I mean I've been doing this a long time you know we've always relied on Echo and I have nothing against Echo but you know the mass regression on Echo is is fraught with errors because of the

formula MRI is is to me the gold standard and and and the use of MRI for for lamin or flow for for extra set expansion early on for midwall fibrosis

and we're learning so much about this that really affects I think that the the early signs of what's going to happen long term to these patients clinically which we never really thought about before and and I think Imaging is is

really helping to drive this forward and I think the things that g just showed you are all markers for something that that you're getting more heart recovery you're going to end up with less fibrosis as long as you do it early enough and and the heart's going to be

having to to deal with less work now one comment about why after a valve replacement your a walls stiffer I put a big cut on it and I sew it up you know that makes it very stiff yep

so so obviously I haven't done it for such a long time but I'm I'm also very impressed with the MRI data is is this going to be incorporated in the next trial yeah a great question yeah joah yeah so we are very fortunate I mean

talking about differentiating also in the way that we take science and take that seriously from the very Beginnings you know bringing everybody together there was this impetus you know and thanks for listening because it's

through this observations if you know if it was known you know that's why we do research we don't know the answers right so let's explore by cardiac MRI you know we were looking at you know how could we be much more precise in this uh reverse

remodeling early on but then let's add flow because that might be quite unique as we start to see some of the preliminary Echo data showing very high dvis and very um you know increased um

valve areas it's like there has to be some cross talk between The ventricle and the arteries that we need to explore but but but there are quite some logistic challenges with implementing an

MRI study so is it is it is it the ambition to incorporate that in a in in a sub study yeah so in a substudy from the pivotal trial there will be obviously selected size that will be

trained uh that will be able to do 4D flow MRI um but that's the beauty of a method like that that is precise you don't need a huge number of patients to show a difference because of the precis I'm building up my fourth hybrid room

that's going to have a 1.5 Tesla magnet attached to the room I can literally take your your your lab bed roll it in because we'll have a non-m 1.5 Tesla is

outdated it's Tesla these days no but actually I have I have suck yeah no you don't want to go high Tesla a high magnetic F because that

comes with more problems with artifacts so 1.5 is what we saw here that's beautiful that that delivers you know what's important is

now tavers established for 22 years every trial has taken us to the next level m in terms of indication in terms of flow so I think this is probably the

next level right is stop worrying just at fixation and function but is it adequate function yeah and I think that's going to help us a lot if those of us remember old campaigns in the US

it's the economy stupid it's the flow stupid everything is flow and it's how you measure a flow and and that's and when you look at how we treat these patients the Mantra should be it's the

flow stupid so J is there any long-term data correlating with this flow I mean I see the LV Mass regression is there anything else out there or are we rewriting now how this is going to be

done in the future yeah there is some preliminary actually work on Ross procedure and Ford flow in Ross that is the one that restores the L flow and and showing that it's with better outcomes

it actually when you do a Ross procedure you are able to restore complete lamina flow from a severe lar and you can show that on CMR amazing so you know whether this would have better implications to

unloading the ventricle making some benefit to the arteries and eventually durability it's that's why we're excited about what the future will show we don't know yet so so maybe one more question

to you and Chris because when you show the different valves and you guys at Minneapolis have also shown that with balloon expandable valves valve

expansion is important right for flow for outcomes for preventing Hal so that kind of flow we see is it dependent on getting maximal expansion of the valve

and what impact is valve expansion going to have on flow yeah I mean I think it's a great question that I I will say from some of the things we've seen from our earlier

learnings and now I I think it's there's probably some role of both but I think the design of the leaflets themselves play a much bigger role than the frame expansion itself there there's learning from the history of surgery so we had a

valve that we don't have anymore it's called the Toronto stentless valve and it was a subcoronary valve but it was and it was pliable so you can basically put any size valve into any size hole and some of these valves came out and had higher gradients much higher than

you'd expected and you went back looked and the surgeon put in a valve that was matched to a a larger lvot than the anulus and so what happened is they had this extra tissue in there and that leads to increased gradients and it'll

lead to pin wheeling again pin Wheeling is the length of the leaflets I mean underexpanded valves of any type are bad yeah yeah with underere expansion obviously comes more pin willing uh even

the the the suturing of the leaflets you show on those very nice nematic renderings that you could see that there is some real estate that is lost by just the virtal of the commissure posts these leaflets they open completely and they

open very freely so that might have an implication of what we are seeing as the flow uh measure by by CC MRI is there a question is there yes go

ahead hello yes hello okay good morning I wanted to ask about uh if durav has good potential for uh like a to evolve disease and romatic heart disease

patients especially young population uh because we were like designing a trial for uh people who like patients who have romatic heart disease and they

have their Metro aortic valve affected and you know most of them are women and they want to they seek for pregnancy and sadly if they made open heart surgery

warin is theogenic so we were like seeking for giving them an alternative option so we we had a choice on uh Evol

yeah and so I'm just asking you do you think davar is has a good potential for this are we talking about young women that want to have children and and because because the because no matter

what kind of valve we put in this tissue it's going to fail and it's nothing but a bridge to either a mechanical or a Ross so the only thing you can put in it's not going to fail is a Ross I don't care what tissue valve a young woman it particularly in the mital position is

worse but the when we look at these these are all bridges to allow you to have children to some event other procedure which is not such a bad idea in these countries right because then

maybe you take the 24y old to 34 and she's had of two kids and then she get some so some of the poly marage valves are now being tested over in India and young women who have mitro valve disease

who need to have children and if those valves last even five years that's going to be a real plus because they a mitol and a young woman wears out in in no time at all but having said that this is

very important and this has been already done with other devices so I think in childbearing age group means I operated in Philippines Indonesia Malaysia is

they still off for surgical vales which are bioprosthetic so why not replace it with something which will give you equivalent or maybe even more durability

maybe it is five becomes eight or maybe eight becomes 10 and I think this is going to be a important conversation going ahead and all these patients are small anuli so let's not forget that

either so as a surgeon I don't want to do root enlargement in a 20year old I would rather you know reoperate at that time do a mechanical so very very good

question yeah and yeah congratulations on your study that's very important for another question sorry um do you think that apart from women like men for example do you think that jar would be

like stable in young uh population because we know that in like young population there is no enough time for calcification so like there is no like I I I was amazed that it has secure

deployment over the balloon so I believe maybe it has a good potential it would be life-changing third world hard countries time will yeah we need to do the clinical studies and prove to the

rest of you that the durability is good thank you so much question thank you for the questions so one last question is we're wacking up just uh back to joal and I think you know just summarizing things today maybe I'll just summarize

instead of tossing your question but I think first of all thank you to everybody in the audience and really appreciate it and thank you to the panel I think the takeaway is that you know um this valve uh with the credit to the

people in the company really decided to build something different right it wasn't just to make another bioprosthetic valve but to mimic the native aortic valve I think we've seen that was able to be done not only do it

but do it with a really easy to use delivery system and uh which is important the clinical results are is good if not better than anything from a hamic perspective and further I think

there's really exciting evidence on the restoration of flow uh being laminer flow and Jo I me congratulates that lb Mass regression is remarkable on MRI and I think it's be really exciting to see

where those things go a lot of us will be helping or everybody here is going to be is heavily involved in the global pivotal trial there were a few spots left actually for that so if you're extremely eager and think you can crush

it uh come find a few of us but uh it's almost uh tapped out so um otherwise thank you for coming today and uh we look forward to showing you more than

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