LAA closure is evolving: are you ready? PCR London Valves 2025

Good afternoon and welcome to this session of on left atrial appendage closure. Is it evolving? It is. And are

closure. Is it evolving? It is. And are

you ready for that? Your primary

interest might be valves, but there's a lot of your valve patients that will also have atrial fibrillation and some of them will not tolerate anti-coagulation and left atrial

appendage closure might be an option for them.

>> [snorts] >> We just had in the main auditorium uh session on combined uh mital valve repair and left atrial appendage closure.

So this is a summary slide uh showing that we now uh within the field of LAC have got uh four randomized clinical

trials LAC versus anti-coagulation.

The first one were prevail and protect that was LAC versus Warin. Uh now we also have P 17 an option which is uh

against DOAX and you can see the signal from those randomized trial are that uh LAC has the same uh stroke preventative

effect like anti-coagulation but there are less major bleeding uh when you do LAC and there's also a

signal for reduced mortality when you go for LAAC.

So probably those data have transitioned into an increasing LAC activity and you can see the upper curve is from the US

registry on LAC and uh at now there are more than 500,000 LA closure procedures done in US. If you look back in last

year it was 125,000 procedures and in Europe 25,000. So this

is definitely a highly increasing activity for lift atrial appendage closure. So in this session we'll try to

closure. So in this session we'll try to address what are the unmet needs in stroke prevention for patients having AF and how can we evaluate the latest

clinical evidence and what do the guidelines say about left atrial appendage closure and what are really the patient population that can derive

the greatest benefit from left atrial appendage closure. And we have a very

appendage closure. And we have a very esteemed faculty here uh with professor John Cam from London uh Dr. Philip Guo Baris

Casper Cors Denmark Apostle Sikas from Greece and it's now a honor for me uh to invite

professor John Cam here from London. um

he's really a pioneer uh within the field of atrial fibrillation and really the father for all of us in this field.

So please professor Cam unmet meets need in stroke prevention.

>> Thank you very much y and good afternoon everyone. It's my job merely to set the

everyone. It's my job merely to set the scene.

I'm not an implant of the LAAC, but I'm very interested in atrial fibrillation. I'm very interested in

fibrillation. I'm very interested in stroke and atrial fibrillation. And I

would like to cover the field for you very briefly against which we can assess the evolution of left atrial appendage

closure. So let me start by pointing out

closure. So let me start by pointing out that as usual I do have some conflicts of interest. Most of these conflicts are

of interest. Most of these conflicts are related to professional societies, editing roles and so on. But I certainly have been paid by various companies.

Here they are and amongst them is Boston Scientific. So please be aware of that

Scientific. So please be aware of that as I speak. Let me start with some wellknown issues just to set the scene.

Stroke five times more common in patients with atrial fibrillation.

Warerin reduces the stroke rate by 66% and mortality [snorts] by 26%.

DOAX such as a pixaban further reduce strokes major bleeding and mortality.

But there is a residual risk of strokes and bleeding.

We can further help the stroke rate by treating co-orbidities such as heart failure, diabetes and hypertension.

We have on the horizon new anti-coagulants.

And it's becoming increasingly obvious that the more we reduce the burden that is the total time duration in which a

patient is in atrial fibrillation the less likely it is that a stroke will occur.

Now most patients of course are treated with an anti-coagulant warrin or a DOAC predominantly doax but there are problems with anti-coagulants.

They're not completely effective. They

do cause major bleeding such as intraraanial bleeding. They do have drug

intraraanial bleeding. They do have drug drug and food drug interactions, particularly the vitamin K antagonists.

They do have reversal agents, but they're expensive or slow. And

importantly, many patients do not adhere to therapy. Many

physicians do not prescribe anti-coagulants and often the dose is not the correct dose. All major problems

with warerin and other anti-coagulants.

Here's an FDA commissioned survey of DOAC drugs in the context of prevailing warin therapy. And you can see that

warin therapy. And you can see that thrombboic strokes are significantly reduced.

You can see also that intraanial hemorrhage is reduced by half. Major

extraraanial bleeding is increased with some doax, reduced with others. And the

death rate is reduced by doax in comparison with warrin but the residual risks are significant. A 1% peranom

thrombboic stroke rate intraraanial hemorrhage in half a percent that's one in 200 patients of course major extranial bleeding in two to 3% and

death in 2% of our patients. So with

this in mind, often patients are never prescribed an anti-coagulant.

There are common reasons for this which we all understand. They may be actively bleeding. They may have

bleeding. They may have hyperensitivities.

They may have severe liver disease. They

may be pregnant. They may have severe thrombocytoenia or severe renal impairment. And then

there are less absolute reasons such as prior intraraanial hemorrhage or major bleeding, uncontrolled hypertension or pep active peptic ulcer, concurrent

medications such as NSAIDs or dual antiplatlet therapy. They may have a

antiplatlet therapy. They may have a high risk of falling particularly those with traumatic falls and they may have extremes of body weight for which we're

very uncertain about the dose of the anti-coagulant.

Here are some data from Garfield AF. The

largest of the international surveys, 55,000 patients, 30% of these patients

were never given an anti-coagulant despite having a Chadvas score of two or more. You can see that the more the

more. You can see that the more the health care expenditure in countries the more likely they were to have anti-coagulants and the opposite the

less the healthcare expenditure the less likely to have anti-coagulants. If we

look specifically at the causes, we have paroxismal atrial fibrillation rather than permanent history of bleeding, primary care settings, old age,

dementia, cerosis and vascular disease.

And around the world, even within Europe, you can see there are major differences in the utilization of anti-coagulation.

patients, even if they're prescribed anti-coagulants, often fail to take the medication. There are all sorts of

medication. There are all sorts of relevant factors, particularly medication related, such as adverse events from the medication, just having

too big a pill. medical condition

related such as asymptomatic patients or patients who have conccomittent problems with depression, anxiety, people who don't think the problem is important.

Social and economic related issues such as a low level of uh literacy and education, a high cost of medication and

living in rural areas and uh unstable living conditions. patient related

living conditions. patient related things such as knowledge, poor understanding and so on. The fear of side effects, forgetfulness, cognitive

impairment common in atrial fibrillation and mistrust, lack of support, poor provision with the health care system.

So all sorts of reasons why lack of adherence may occur. What about dosing?

Here are some more data from Garfield at the point when 35,000 patients had been enrolled. And you can see that if you

enrolled. And you can see that if you look specifically at the patients on the left hand side who were treated with the correct dose, the orange bars is between

70 and 80%. You can see low dosing. The

blue bars is common between 20 and 30% and a few patients overdose. On the

right hand side, you can see the consequences of this. If you have high doses or low doses or nonrecommended doses, you can see there's a major

deviation with adjusted data or raw data from the line of imunity. What happened

with patients who took the appropriate dose?

Now, how quick does a thrombus form?

Many of us may think it takes months or years for a thrombus to form, but it can take only minutes. I just want to emphasize that by showing this case

report. If you look at 3:57 p.m., the

report. If you look at 3:57 p.m., the

left atrial appendage arrowed on the slide is has no clock within it. Half an

hour later at 4:27, there's a clock forming and it's even more dense at 4:31.

So 30 minutes and a clot can form. So

people who neglect their anti-coagulation are at high risk.

Now what about people who discontinue medication? Actually in the Garfield

medication? Actually in the Garfield study it was only 30%. It can increase as much as 40 or 50%. You can see that

only three reasons kept patients on the drug. It was either they were old, they

drug. It was either they were old, they had already had a history of stroke or they had permanent atrial fibrillation.

Discontinuation was very common particularly with kidney disease and with events such as bleeding events. The

consequences of the discontinuation you can see on the right hand side and you can see that discontinuing the drug just for seven days is associated with very

substantial outcome events in these patients.

So let me conclude with this slide.

Stroke prevention therapy is often either ineffective, unsafe, not prescribed, not continued,

used wrongly or rejected by patients or physicians. We can do much to improve

physicians. We can do much to improve our ability to select the patient and select the right therapy. Importantly,

we can treat the comorbidity and increasingly we're interested in how we can treat any atrial cardiammyopathy.

But there are three major relatively new treatments. more effective

treatments. more effective anti-coagulants such as abalis abalismab or milvexian a reduction of AF burden which I've

already described with uh ablation techniques or left atrial appendage closure or excision these either in

alone or as part of a hybrid therapy are the modern context of the evolution of prevention of stroke for atrial fibrillation and it is in this setting

that we want to discuss particularly what happens and how the left atrial appendage closure device is evolving.

Thank you very much. [applause]

Thank you very much Professor Cam for setting the scene for us. You will be able to ask questions for the speakers and the panel here using the app. Uh we

can uh read your questions up here.

You pointed out uh Professor Cam uh some of the major problems with all anticogants adherence.

Do you think in order to get uh effective drugs, we need some drugs that could actually have a duration of weeks or months because apparently it's a very

difficult task for us all all of us to remember taking our pills and and be adherent. Yes, I I I think we do need

adherent. Yes, I I I think we do need drugs which are long acting and some of the new anti-coagulants

which are uh monoconal antibodies can be injected and they'll last for a month. So you can get a month's worth of

month. So you can get a month's worth of treatment and then you can be sure that the next injection is given. So that is a possibility to have long acting

medication and that's certainly in the mind of the drug developers of these new anti-coagulants. Others are oral drugs

anti-coagulants. Others are oral drugs that you have to take once or twice a day but several are monoconal antibodies

but expensive of course.

So one of the other options uh to go for a continuous stroke prevention would be to put put in an occludder because it will it will be there and it will it

will be there uh in the future as well and there will not be those adherence issues and it might also solve some of

our uh bleeding uh problems. So uh I would say thank you for your uh presentation uh professor cam and then I

will invite you Philillip uh to speak about LAC. Is it a safe procedure? Is it

about LAC. Is it a safe procedure? Is it

an effective procedure? Can it solve some of the problems highlighted by uh professor Cam?

>> Thank you very much uh Yanser K. Uh so

uh balancing efficacy and safety for left atrial appendage closure.

These are my disclosures.

As you know uh left atrial appendage closure is a one-time procedure. It's a

one-time implant that do not need to be replaced. It's a minimally invasive

replaced. It's a minimally invasive procedure that we can performed under general anesthesia or a catlab ep suit by a hard

team.

The average time procedure has been one hour. It's now less in many centers and

hour. It's now less in many centers and the average hospital stay has been one day and it's now performed as a same day

discharge procedures in many centers.

You all know the watchman that is the most common and the best studied device for left atrial appendage closure.

More than 10 years experience with watchman. So we have a lot of data. We

watchman. So we have a lot of data. We

have a lot of studies and that will be my task to go through these studies. As

we mentioned already, more than half million patients have been treated with Watchmen. And as you can see from the

Watchmen. And as you can see from the Pinele Flex study uh that was performed in 2018, we can see that the safety end points

was crucially low and very reassuring with Watchman Flex. Only two patients on 400 had an eskeemic stroke. No all

because there's no ambolism, no device or procedure related uh major events.

What about the efficacy? You can see that periprocedure adverse events were far less below the performance goal that was expected in this trial.

We had data from Surpass Pro and you can see that with Watchman Flex Pro. The events were very similar

Flex Pro. The events were very similar at 45 days to what we had with Flex in Pinele. So very low rate of events, less

Pinele. So very low rate of events, less major bleeding. We will potentially

major bleeding. We will potentially discuss why, but this is very reassuring regarding the use of Watchman Flex uh

worldwide. So what about watchman flex

worldwide. So what about watchman flex pro I mentioned you know that it's the last generation of watchman flex the

heel LA study was uh performed to show about the primary safety endpoint you can see the composite of all cause mortality all stroke systemic amisolism

and major bleeding at 6 months and this safety endpoint was far less below the performance goal that was expected to be

21% % it was less than a half of that and it was very very similar to that that we observed with the pineal flex study.

More recently we had the results of the option study trial. You know that the option study is a major trial involving

1,600 patients treated with AF ablation and then who were randomized to watchman flex or to oral anticoagulant with a follow-up of three years. The primary

efficacy on point was all cause death stroke or systemic amolism and the primary safety was nonprocedural major bleeding or clinically relevant non-

major bleeding at 36 months.

This is the efficacy that we observe in the two harms and you can see that the non-inferiority was met with watchman 5.3%

rate of composite efficacy and point at 3 years compared to 5.8 with anti-coagulant with doax. So this

is very reassuring that in the modern era with the most modern drugs that we have in a context of a randomized

control trial where pills are given and counted in every patient that the device do as well as the latest generation anti-coagulant.

What about safety? You can see that the number of bleeding was half with watchmen compared to

patients treated with anti-coagulants which is I would say very surprising to me because these patients were not high bleeding risk patients. They were low

bleeding risk patients with a hospital blood score of 1.2. So even with these patients at low bleeding risk, the difference between watchman and

anti-coagulation was very very significant at three-year follow-up. And

then we had the good surprise that this efficacy and safety uh endpoints were still consistent across all

subgroups of the trial. What about

whatever patient's age, sex, shatzva score, haz blood score, AF type, every single patient, every single group at

least benefited from the trial. So in

this context, we had last week in AHA the closure AFR trial that was presented.

And what is the closure AF? It's a

randomized control trial that was driven and conducted in Germany in Europe where patients with a chazva score more than two at increased bleeding risk because

of a house score more or equal three a history of bleeding or very severe chronic kidney disease were randomized to catheterbased left atrial upon

disclosure or to physician directed best medical care and the primary end point of this study at three years was a composite of stroke, systemic embolism,

cardiovascular death or major bleeding.

So the community was surprised that in this trial the left atrial appendage closure procedure failed to met to meet the

non-inferiority compared to best medical treatment.

And we have to say that in this group more than 80% of the patients were treated with doax.

So we don't want to hide behind our finger. I think we have to talk about

finger. I think we have to talk about that and we have to better understand what happened with the trial. There's a

lot to say and to learn from this trial and I think interpretation of the trial should be very cautious. We don't have the study

very cautious. We don't have the study published at the moment. We just had preliminary result that were presented during AHA last week. So we've heard

that yes the trial might be underpowered.

The rate of per procedure complications rate was far higher than it is in contemporary practice and trials.

But to me what is obvious is that in this trial highly selected patients were recruited.

These patients were far older and sicker than patients that we treat in real life.

And if you look at the annual mortality rate in these patients in this study, it was 15% per year.

So these patient were not consecutive just one number the number of patients recruited per year and per center was 1.5.

So these patients were highly selected, high risk for procedure and this is probably what was the problem, what was the issue, what was

the difference with different trials that I previously mentioned. I think it's very helpful to

mentioned. I think it's very helpful to go through that. It will probably us help us to identify patients who fail to derive benefit from

the procedure. This is what we called

the procedure. This is what we called futile in the field of tavi. And we here at the PCR London valve, we know that this we

had a lot of fuel tavi in the past and we were very very uh dedicated to find the good population

that benefit from the from the procedure and I think that with closure AF we have a futile lack population.

So that being said, what are the mechanisms underlying higher efficacy and safety across patients and in our uh procedures and

practice? I think pre-procedure imaging

practice? I think pre-procedure imaging and intraprocedure imaging are key and really in the modern uh practice and in

our hospital today we have a lot and we have learned a lot from 3D imaging and multiple planner reconstructions.

We learn a lot together. We share

knowledge and we have a lot of meetings like this one today to to share best clinical practice and to learn one from the others.

Of course we have device technology and delivery sheet technology that helped a lot decreasing the number of procedures and finally we are shifting away

progressively from general anesthesia with mini probes and with ice and patients in conscious sedation. So now I think that lack is nowadays a safe

procedure in line with modern interventional cardiology like we do with PVI with PCI. It's a same day discharge procedure

in ambulatory care sensitive units and it's a procedure that we would like to expand through conccomant therapy. We

talked about PVI but also TMVR. We had a great nice case in main arena 1 hour ago. Ter patients may benefit from that

ago. Ter patients may benefit from that because they have high bleeding risk and more than onethird of them have h in summary I think that we can say that

lack with watchmen is both safe and effective procedure. We have a number of

effective procedure. We have a number of very important trials with a large number of patients.

As you know, the number of cases have grown at an astounding rate, especially in the US and it's increasing now in Europe. In this context, I think that

Europe. In this context, I think that closure AF should be interpreted as a signal to better stratify clinical

indications and avoid futile lack in patients with a low expected uh life expectancy.

Of course, operator skills, imaging, next generation, new generation device and delivery technology have substantially contribute to higher

efficacy and safety and nowadays a post-implant anti-thrombotic regimen is evolving to a simplified regimen thanks to the the work of Jenser and

Casper especially and this has to be adapted to patients bleeding and thrombotic risk. Thank you.

thrombotic risk. Thank you.

Thank you very much, Phipe. I I think we will have to move on because we're we're running out of time already. Having said

that, let me introduce our next speaker who is Casper Corome from Arus in Denmark and he's going to tell us why anti-coagulation

isn't always enough. Casper,

>> thank you, John.

Um okay these are my disclosures. First

of all as John already mentioned we know that DOAG is not perfect. The efficacy

and safety is already established. But

we also know that the risk of stroke despite of anticoulation is around 2% per year. This is from the randomized

per year. This is from the randomized studies. So this is in a controlled

studies. So this is in a controlled randomized setting where we control that the patients actually take medication.

So it might be even higher in real life.

And as you see on the graph, it depends on the vascular risk profile of the patient. But the strongest predictor of

patient. But the strongest predictor of stroke and recurrent stroke is having already had a stroke. And that that's regard regardless of whether it's on

therapy or whether it's the first presentation of atrial fibrillation. You

see that the the two lines up here are patients with prior stroke history and it's regardless of the chat score.

We also know that patients with a history of stroke are at increased risk of major bleeding events. This is also from the one of the randomized DOA

trials and we see it across the other DOAC trials as well.

So these patients may particularly benefit from uh other therapies or add-on therapies. And further to

add-on therapies. And further to highlight that we we see from stroke registries on the left hand side you

have from swish uh stroke registry where 21% had pre-existing AF diagnosis upon admission and uh on the right hand side you see

Danish data from our Danish AF registry from 2024 that 65% of patients admitted with a stroke and AF had redeemed a prescription of

anti-coagulation in the in the three months before admission.

So why do these patients experience stroke? And as John also mentioned, some

stroke? And as John also mentioned, some of them is due to insufficient anti-coagulation, wrong dosing, uh compliance issues or uh

that we stop DOG due to interventions and so forth. But quite a significant proportion have competing risks or a emolic stroke despite of anticogulation.

And we know from the studies that changing the strate strategy or adding antiplatlet therapy or increasing the RNR value doesn't help anything. It does

not modify the risk of recurrent stroke and it's strongly discouraged in the guidelines.

Then the layers free trial despite being a surgical trial it actually taught us quite a lot and for many years we've been citing uh imaging studying saying

that the left atrial appendis is the nidis for thrombus and it is but the the layers free trial highlighted that the left atrial

appendage has a causal role for AF related strokes. So eliminating the left

related strokes. So eliminating the left atrial appendage decreases stroke risk and here by 2.2% in absolute risk reduction after uh four years of

follow-up but we do not know whether it's patients have to continue anticoulation or whether it's regardless of anticoulation. This is a sub study from

anticoulation. This is a sub study from the layers trial showing that the benefit of left atrial appendage inclusion surgically was consistent

regardless of doag use or not.

We also have some observational data.

These are um from um European sites left atrial appendage acclusion and they were propensity matched to a cohort receiving

anti-coagulation primarily DOA and there was a comparable see over here comparable stroke risk this is from the Danish study and the amate observational

registry and on this uh slide you see patients with stroke on therapy where there was a huge benefit benefit of left appendage acclusion. This is

appendage acclusion. This is observational data.

I think one of the main questions and I I think uh Aposttolo will also go into that is how should we treat these patients after closing the appendage and

if we look at other trials in secondary stroke prevention we have uh the eases trials all four of them showed no

benefit of anti of doc therapy when there is no atrial fibrillation and um so so perhaps we could actually

leave patients on aspirin after closing the appendage because we believe that we take AF related strokes out of the equation and what we see is that many

people site that the bleaching risk on doic is comparable to aspirin and I don't believe that's true we have data

from the um articia and no AF trials and subclinical AF significantly increased bleeding risk the hazard ratio of 1.6%

6% uh 1.6 so 60% increased major bleeding risk on DOE compared to aspirin and despite not being significant when

you combine all the EUS trials the hazard ratio is completely the same 1.6 six. So I think that DA will likely

six. So I think that DA will likely cause more bleeding than aspirin therapy.

So to conclude I think these patients having stroke regardless of whether it's on therapy or whether it's history of stroke without do therapy or

anticolation there's a huge question how should we actually treat them should it be dak continued I don't think that is a good solution for those having failure on

stroke on therapy should we combine left atrial penetrusion with dak or should we combine left atrial penetrusion with single antiplatlet therapy. Luckily, we

have four randomized trials ongoing and we should include patients and randomize them so we can get good data to support our continued strategies. Thank you very much.

>> Thank you very much, Casper. Just one

quick question. Are you then advocating for a hybrid approach, anti-coagulation plus LAAC or LAAC alone in patients that

don't tolerate or don't take anti-coagulants?

I I I would advocate for left atrial appendage occlusion in combination with a platelet inhibitor because I think then patients are covered for the AF

related strokes and we do not have any studies showing that if you do not have AF there's a benefit of dank but leaving them on a platelet inhibitor will cover

uh other causes like small vessel and large vessel disease.

>> Thank you very much Casper. Thank you.

>> Let's move now to our next speaker who is Apostles Sikus who is from Thessalonica in Greece and he's going to talk about post-procedural medication

pathway. Apostle

pathway. Apostle >> thank you. I'm very glad uh to be here uh with this um exceptional panel and I will try briefly to um talk about um

what we do after LA closure. But before

doing that just wanted to present to you a slide uh I presented in TCT 2016 at that time talking about LA closure. We're worried

about complications and uh I think we still need to know the device that we're using. We still need to master the

using. We still need to master the technique and of course we need to know the patient but the topic I will talk about is more to do with the patient itself or herself himself or herself.

Right now we are talking about performing an optimal LA closure. We're

not worried so much about complications and we need to look carefully and to understand uh what is the patient we're

we're dealing with. This is a case I was asked to do LA closure. The patient is under general anesthesia. This is how this patient looks h when he's asleep.

And then we increase the heart rate. We

increase the blood pressure and you have a totally different image. So there are still many things to learn for each individual patient. And the patients are

individual patient. And the patients are not the same.

H medicine sometimes at least in the ancient times was considered art and this is sometimes the indication here the the the scenario here because when

we we offer these patients stroke prevention strategies they come from all over the place and I will briefly present to you what we think about when

we talk uh when we decide what to do after LA closure. So it it depends uh did the patient has previous bleeding was it minor major? Did the patient had

a stroke on anti-coagulation? This is a totally different patient population.

Did he had a thrombus or based on the history does the patient have another reason to take anti-throotic therapy like coronary artery disease or deep vein thrombosis? Is he or he she

vein thrombosis? Is he or he she compliant?

The anatomy is very important. the the

appendix and the heart has various a very variable anatomy. We have may have a dilated appendix, dilated left atrium.

We may have um spontaneous contrast as you saw before. We may have mitral regurgitation, low ejection fraction. So

every patient has its own or her own uh characteristics. The implant quality is

characteristics. The implant quality is very important. We h it depends the

very important. We h it depends the medication that we will give later on may depend on the on the per device leak or it may depend on uh the the the

device size that we have put. And

finally there are some regulatory and guidelines issues because if you choose not to prescribe the I per IFU or per regulatory um requirements medication

you may face some uh you know questions later on. So, and this is I mean these

later on. So, and this is I mean these are the options that you might give later on. It's all over the place. So,

later on. It's all over the place. So,

so far I I have more questions than answers for you. Uh there are a few things that we have learned. We recently

published this meta analysis based on uh data from uh several studies and showed that a leak over 3 mm is not benign. So

if a patient has a leak of more than 3 mm uh we need to reconsider our antagulation therapy and thrombotic therapy later. And the second part is

therapy later. And the second part is the device related thrombosis partially this was related to uh as uh to the

definition of what is uh the um DRT. We

now know that the left side of the image based on the work of also of Janzeric is not DRT is healing. H and we have learned that we should not do very deep

implantation of devices because what we have seen uh in studies is that uh we pro we may um expose the patient to less uh flow conditions and we have a

thrombus. Uh that being said, there is

thrombus. Uh that being said, there is new technologies coming up uh the Watchman Flex Pro with a special coating on on the PTFE that at least in Alma

studies has has shown superiority for the cloth formation on the device and the DRT as you see here. This remains to be proven of course in in large and larger studies. In the meantime, I will

larger studies. In the meantime, I will just show you this meta analysis that was just accepted in European heart journal h about this particular topic

and we um investigated approximately uh 7,000 uh 70,000 people patients in several studies and uh these were the eligibility criteria and the

outcomes was major bleeding, thrombboism, DRT and all cause mortality. H so 49 observational studies

mortality. H so 49 observational studies and three randomized clinical trials and this is the comparison uh between lowd doax

versus other options uh with these four uh outcomes and this may look like a busy slide but I can tell you that the uh take-home message and the final uh

considerations the results the conclusions that we had is that we have a trend towards dax and the trend is towards halfd dose noax as the best

option. But still there are things uh

option. But still there are things uh for us to learn and hopefully the results of the simplify study that is now now running uh sponsored by Boston

scientific withman flex pro will give more definite answers to this question but what is very important is to go from numbers to individual patients. This is

this is all about modern medicine I think. Thank you very much.

think. Thank you very much.

>> [applause] >> Thank you very much apostles. A quick

question again. Uh you say lowd doak following uh implantation of an LAC.

Does it matter which DOAC?

>> The more data we have is with a Pixaban but uh the the trend was the same in different kind of DAX.

>> Thank you very much.

So let's move now to the last of the formal talks and that will be given by Yenzeric who is going to who's from our in Denmark and he's going to talk about

perspectus from the international guidelines. Over to you Yan Zerk.

guidelines. Over to you Yan Zerk.

>> Thank you very much. So we have guidelines. We have ESC guidelines and

guidelines. We have ESC guidelines and we have US guidelines. The most recent ESC guidelines is from uh 2024. And as

you can see uh we do have um a class 2B level C evidence recommendation and it's so it's not a very very strong

recommendation in the ESC guidelines and it's addressing patients that have a contraindication for long-term anticoulation and they may be considered

for LAA closure. So the uh low level C uh is probably related to the fact that we still need more randomized data and

we have many trials coming up in near future. If you look on the American

future. If you look on the American guidelines, uh they are more liberal. Uh

they are also addressing patients that have a contra indication to long-term oral anticoulation and they recommend left atrial appendage occlusion with a

2A classification level of evidence B and they use um the phrase is reasonable to do LAAC.

They also address people that do not have a strict contraindication but that have a high risk of bleeding and consider LAC as a reasonable alternative.

We do have abundant new data coming up and you can see during the years this is a number of publication about LAA closure and there's really a lot of

observational study but there's also an increasing amount of randomized clinical trials. So hopefully we can get a

trials. So hopefully we can get a stronger recommendation in upcoming uh guidelines.

There's also a new 2025 US guideline coming from Sky and Heart rhythm society

and you can see uh here that uh if you have AF and a contra indication the panel here also suggests LAO but you

have to involve your patient you have to explain the patients about the risk that are with the procedure and also the risk that are related to uh all

contraindication and also those guidelines consider LAAC as an alternative to all anti-coagulation just

that you have AF and even though you are able to tolerate OAC it can be an alternative again if you want to

understand the procedural risks and the risk with anti-coagulation we also have a position paper published in Europeace last year. This was a large

group of interventional cardiologists, EPS, but also neurologists, nefologist and gastro people were involved in

creating uh those more practical guidelines on when to do left atrial appendage occlusion or when to consider

it. And you can see that if you have

it. And you can see that if you have mild a mild uh to moderate risk of major

bleeds uh you have also to um be aware of is the patient actually adherent to all anti-coagulation. Is there a failure

all anti-coagulation. Is there a failure for this patient or is there even uh in the history also unacceptable bleeding

or there might be also stroke events uh during all anticoulation and all these factors uh would motivate uh physicians to consider LAC and

especially if you have a high risk of bleeding and you are predictable not a very good candidate for anti-coagulation you should consider consider LAC and

this is a population of patients that we actually treat now. Those are the ones that have recurrent bleeds very often.

We have patients have suffering recurrent gastronm bleeding. We have

patients suffering bleeding in the brain. We have uh patients uh where

brain. We have uh patients uh where neurologists are really afraid that have they have a lot of microbleleeds in the brain. We have uh patients where we

brain. We have uh patients where we isolate the left atrial appendage and are leaving just a very hypo contractile appendage with a high risk of stroke. We

have renal failure patients that do not tolerate doax very well. So all these uh patients are very very difficult to

treat in clinical practice with doax and those are the patients that we actually get referred for left atrial appendage

closure and offer this therapy. [snorts]

The guidelines are not at the moment addressing the data that we have from the most recent trials. For instance,

you have seen Philip showed us the option trial data. So this is after ablation. You can the usual standard way

ablation. You can the usual standard way is to go for full doag after ablation.

But there's now this alternative of LAC where we have proved that you can have the same degree of stroke prevention

with LAC than with DOAX but you have the advantage of an reduced bleeding risk long-term. Here was nonprocedial

long-term. Here was nonprocedial bleeding uh reduced by 56%. And even

though you also count procedural bleeds, there's a major difference in the bleeding as verse events uh with uh the two regiments here in favor of LAC. You

get much less bleeding with that concept.

We still have trials out there. Closure

AF was mentioned. We don't uh have the full paper yet. We have other papers on contraindicated patients coming up uh in

the future and especially I want to highlight the champion AF. has been

mentioned. It's a really large trial, more than 3,000 patients like a general AF population having Chadvas 2 or three

and randomized either to Watchman Flex or to DOAC and this trial uh will be presented in March next year. So uh we

are very very close to having the largest trial ever on left atrial appendage closure and a little bit later the catalyst trial this is with the

amulet device will follow and give us even then more information uh and randomized data we have I want to highlight this as well because it's it's

a very very good surgical trial you see that it's a very large group of patients there's more and 2,390 patients that comes for cardiac surgery

in addition to bypass or valve surgery they get closure surgically of their LAO and both groups here the group that have

no surgical closure and those that have closure are on all anticoulation after surgery and you can see here that with

left atrial appendage surgical closure they do much better in terms of their stroke risk because after three year stroke rate was one/ird lower in the

group with surgical closure. So this is now has been transitioned into a class one recommendation for surgeons to close

the left atrial appendage and we have the layers four study running now. We

will try to replicate those data with a perccutaneous uh procedure. So this is also a very

uh procedure. So this is also a very large trial 4,000 patients and again here you do both lift atrial appendage

occlusion and on top of this also do treatment. So this is for the very

treatment. So this is for the very high-risk patients with chadf four or more

so thank you for your attention.

[applause] Thank you very much and Zeric why don't you come back to us here and I think we could start with some general questions.

I'm struck uh apostulous by the fact that the implant rate in the US is very much higher than it is in Europe even though

we had in many ways a head start in terms of using LAAC.

What do you think is the reason? Is it

because uh interventional cardiologists are not doing many implants here in Europe or is it because of any other reason financing or

>> whatever >> there there are several reasons for that uh it's a different health system and Europe we have in Europe have we have different health systems I think part of

it has to do with the reimbursement of medication for the noax in patient population with AF as compared to zero uh cost for a patient who under goes

early closure in the US but that's a question also for me to be honest and especially for the patients that are not adherent or that they are not taking anything and just have a

stroke this is a big question for me uh I don't know Philip if you have something else I haven't answered on this question yet but um what I would like to comment if I may have one second

is that we are here in London val and I believe that LA closure is here to stay and I believe that interventional cardiologists who especially those who

do structural heart disease procedures should be familiar with this therapy and most probably you will have to do it at some point in your medical practice

especially younger physicians I mean it's growing and it's here to stay so we're very I'm very happy that we're here in London valves discussing these topics what do you think

>> no I I agree agree. I mean probably the main difference between Europe and and the US for the numbers of procedure is

driven by the fact that we should take care of we should hear patients and we should uh have really in mind that

patient choice is crucial. Uh of course it's not driving everything. Uh I agree there's some reimbursement issues, there

are finances issues, uh healthcare organization but um it's a pity that as you said a lot of patients have nothing

and we are comparing patients with doax to patients treated with the procedure.

But in the real life we have a lot of patients who have no doax or doax sometimes two times or something else and it's really a problem.

I think uh we are also seeing more and more ablation activity and that's also part of the discussion that if you can restore sinus rhythm for a period that

will also help to prevent uh strokes.

But many of those patients that come for ablation they really have a desire to come off oral anticoulation. They are

younger many of them are physically active and they are afraid of oral anti-coagulation. So it has also to do

anti-coagulation. So it has also to do about quality of life because if you at the same time as the ablation can get your device and get lifelong strong uh

stroke prevention and don't need to think about all anticogulation I I think that's a major benefit uh for the patient. Yes and recently we have the

patient. Yes and recently we have the insights of the alone AF trial showing that in lowrisk population they may potentially benefit only from AF

ablation. So we have and we will

ablation. So we have and we will probably in the near future more understand more what happened in this population. We have a broader spectrum

population. We have a broader spectrum of patients from lowrisk patients. We

had in the past chva zero one now we have a two but then in these patients some of them may benefit from AF ablation as a risk prevention stroke

prevention procedure at least for few day few years potentially. Then the

large population of patients having advantage of left atrial appendage closure and potentially futile lag patients as I mentioned.

>> Are there questions from the audience and we really must give you a chance please sir. Yes.

please sir. Yes.

>> Can I ask a question to the audience?

How many have you implanted a device in your practice here in the room? One at

least one device. How many implanters here? Okay. Zero devices. Zero. Never

here? Okay. Zero devices. Zero. Never

never done but you would like to do.

Okay. Thank you. Just understand please.

>> Right. Um my question is what is your approach to somebody with contraindications to OAC and you do a a closure device and then

incidental finding of a PFO patient who had a stroke.

>> Yeah, I think this is very clear. Sorry,

I will take that. The patient who has a atrial fibrillation does not have a cryptogenic stroke by definition. H they

the the problem is already on the left side. So I don't think we're justified

side. So I don't think we're justified to do PFO closure unless there is special circumstances. I don't know Jan

special circumstances. I don't know Jan Eric. No, I I think that's the same

Eric. No, I I think that's the same concept and I mean for PFO closure we are talking about also typically a

younger age group below uh 65 or below 60 and uh the the typical scenario are they have sinus rhythm and come in with

a stroke. Uh but

a stroke. Uh but I mean if you have a younger patient with atrial fibrillation and you have what you could call a high-risisk PFO

you probably have to uh deal with both both factors at some time point and I think we are we are also moving towards

not only treating one I mean risk factor for stroke uh it doesn't make sense so in the interest of the patient we really

have to also So treat things like like PFO if it's if it's young age. I think

>> yes. Yes.

>> This the surgical data is quite striking that the surgical data if you're on or and your data possess if you're on an oral antiquagulant plus a device you

probably do better than a device alone.

And then I I'm just struck because a cardiac surgeon once told me that unless you get the device the entry point absolutely smooth surgically there will

always be a risk and it just strikes me that maybe we're just dealing with reduced risk. So maybe a NOAC plus

reduced risk. So maybe a NOAC plus device closure offers you the best protection. Then the next phase is

protection. Then the next phase is maybe, you know, a no device alone and then just going down because I I don't see how aspirin is going to be protective personally because it's a

relatively low pressure environment and stasis. I'm just hypothesizing here, but

stasis. I'm just hypothesizing here, but maybe the best solution is to have both if you can tolerate it and then escalate down. I I'll let everybody else answer

down. I I'll let everybody else answer it. But just to remember, not all

it. But just to remember, not all strokes in people who have atrial fibrillation are due directly to the atrial fibrillation. So there is a role

atrial fibrillation. So there is a role for aspirin in that in that sense. But

um apostles >> well the last three trial was phenomenal because it really told us that the left rattal appendis is a problem. Now either

excise or close it with a device. We

have to deal with that now and see how well we can do it. But it's there and it's randomized and it's very strong. I

don't know if we have much time to talk about it.

>> I think not. I think it's >> I think we have to >> thank you very much.

>> Come to an end and I just have uh some key points here because um I hope that you have seen that LAC can be a

valuable solution for AF patients who do not get effective anti-coagulation for various reasons. It can be bleeding,

various reasons. It can be bleeding, non-adherence etc. and Philillip showed us that we now have a procedure that has become very safe

and effective and I believe that it can be compared to what we are doing normally in the Kath lab with PCI and PVI as well and also uh post-procedural

medication we have learned a lot we started out with a watchman device with all anticoulation in the beginning and quite intensive regimens but we have

data that sed and reduce those though are actually probably effective just to avoid DIT but we are also awaiting here randomized

data.

Our ESC guidelines uh do not give us very strong evidence. uh but there will be more RCTs coming very soon and uh

especially also we have uh the combined ablation LAC approach which is not covered in the guidelines but I think we have a very large nicely uh performed

randomized trial the option trial that have told us that this can be a alternative for patients coming for ablation to get either a combined

conccommittant procedure or also a sequential uh procedure and in that way give uh stroke prevention.

So uh thank you very much for coming and listening to LAC uh and uh I think this will be hopefully also a topic for the years to come on

London valves and and I I think and foresee we'll also see much more combined studies with mital intervention

LAC and also it's relevant for the tavi population but I hope you are inspired

to go home and prepare for LAC. Uh it

will probably become a very uh demanding not demanding but it will be there will be a lot of request for this procedure also from patients in the

future. So thank you for coming.

future. So thank you for coming.

[applause]