Nicholas van Mieghem:
Welcome to the view from the ThoraxCentre for Radcliffe Cardiology. My name is Nicholas van Mieghem. Next to me as always my good friend and colleague Joost Daemen. And today we're going to preview the ESC 2025 meeting that is coming up in Madrid end of the month of August. Let's start Joost with one of the TAVI trials, that is DOUBLE-CHOICE that will be presented by our good friend Mo Abdel Wahab from Leipzig. And this is an open label randomised controlled trial with a 2x2 factorial design. Basically they're looking at a comparison of the acurate valve with the self expanding Evolut system and then also comparing anaesthesia protocols with conscious sedation versus local anaesthesia. Basically this trial is following up on the SOLVE trial that was another randomised controlled study from Holger Thiele and his group in Leipzig where they recently published a five year data. They compared Evolut or the core valve with Sapien valve at five years. No difference between the two platforms but there was a difference when they were comparing general anaesthesia with conscious sedation and conscious sedation was outperforming general anaesthesia on the long run with lower mortality in the conscious sedation arm. So it makes total sense to come with a follow up trial that is now comparing two different valve platforms but also two different anaesthesia protocols. And this is the DOUBLE-CHOICE. 836 patients from 10 centres in Germany and yeah, we'll see what's going to happen. In terms of the one year data, I'm particularly interested in the comparison between the local anaesthesia and the conscious sedation because we in Rotterdam, we are proponents of local anaesthesia so no sedatives to our patients. We have the impression that it expedites the, the procedures but also in our own data set we saw a difference in favour of local anaesthesia over conscious sedation with less delirium and less infections and also abbreviated hospital stay. So an interesting study to watch out for. Unfortunately it's comparing Acurate also with the Evolut valve and accurate is no longer on the market but it may also shed light further light on the Acurate IDE trial that basically was the end of the Acurate story.

Joost Daemen:
Yeah, that's it, right? I mean if the Acurate would outperform Evolut or show better gradients without a difference in clinical endpoints, I mean that would be a bitter pill to swallow for Boston, I guess, but I mean, that's what it is. And obviously a trial that started a couple of years ago and I agree with you that another trial showing a potential benefit of consciousness sedation would be, most welcome.

Nicholas van Mieghem:
Well, this is not conscious sedation. It is looking at local anaesthesia that would outperform. So it's even a step further.

Joost Daemen:
Yeah.

Nicholas van Mieghem:
All right. Another study, that we wanted to highlight is the VANTAGE trial. This is a prospective study, that I, have the privilege to present at the ESC that is evaluating the Navitor platform, which, is an intraannular functioning self expanding valve system with also a circuit sealing fabric. But now it's looking at patients at low and intermediate risk. So at this point in time, Navitor only has a label for high risk patients. So this is exploring also this platform in low and intermediate risk patients. We're talking about approximately 500 patients, not randomised, but there is a core lab involved. So it's high quality data and we're going to see whether this platform is ready to be used also in low and intermediate risk patients who have a longer life expectancy. And this valve platform, on paper at least, has all the elements for lifetime management. It should, have a low rate of paravalvular leaks. It should also have a very good hemodynamic valve performance that we also see already in our practise. And that has been, replicated again and again in studies, using this platform. And we'll see what's going to happen. Obviously we are all familiar with, the pacemaker rates that are also associated with this technology. Let's look at the results. So the primary effectiveness endpoint is PVL, more than mild. And the safety endpoint is a composite of mortality and stroke at one year.

Joost Daemen:
Yeah, let's see.

Nicholas van Mieghem:
All right, let's go to the heart failure.

Joost Daemen:
Yeah. So this is ESC, and as, you guys all know, like ACC, ESC is obviously a general cardiology meeting with a lot of focus on, heart failure, in which a lot of, drugs that emerged in the last decade have brought a lot of colour to the heart failure space and really changed the scope on how we treat those patients. Along those lines, a couple of trials that we briefly would like to highlight. One is VICTOR, which is a large multicenter randomised controlled trial designed to test if vericiguat reduces cardiovascular disease and cardiovascular death and heart failure. Hospitalisation versus placebo in patients with heart failure and reduced ejection fraction who have not been previously hospitalised. Really stable patients in New York class 2 plus 2 or higher heart failure on guideline directed medical therapy. Ejection fraction below 40%. The trial will enrol or has enrolled over 6,000 patients from 519 sites across the globe. So vericiguat is not a drug that is well known, in, I would say the Netherlands. That's currently not, being reimbursed. It's a soluble guanylate cyclase stimulator designed to restoring impaired nitric oxide, signalling showing positive effects on left, ventricular hypertrophy and fibrosis, and also reduces afterload by decreasing pulmonary artery pressures. The drug is not that new. It recently proved to work in patients with worsening heart failure in the VICTORIA trial. This is VICTOR now also showing the potential effect of vericiguat in patients at a somewhat lower risk. So the more stable, heart failure patients, so to speak, talking about, VICTORIA. This was the large randomised controlled trial that initially was published in New England now already five years ago, showing a 10% reduction in CV death in MI in patients with worsening heart failure and ulcer, ejection fractions below 45% at 32 months. at this meeting, Javed Butler will present more data. I'm not sure what that exactly will entail but, I think it will at least lead to some discussion at the meeting because this trial showed a 10% reduction, which is not the 30% reduction that we see with the SGLT2s. It is reimbursed in many countries now in Europe, but not in all. Also not in the Netherlands, simply because the effect size was not that, overwhelming as compared to the SGLT2s. And that's why I think, the results of VICTOR and also perhaps this subgroup analysis, will have the potential to change, how popular this drug is in the heart failure space specifically, since obviously in the VICTORIA, no patients were on SGLT2 inhibitors. Whereas in the newer trial VICTORIA, I assume that at least half of them will be on SGLT2.

Nicholas van Mieghem:
Well, you said it. I think that's going to be very essential in the discussion. How many patients were on ARNIs and how many patients were on SGLT2 inhibitors? Those are the new pillars of heart failure therapies these days. So that will also, I think, help drive the uptake of this new medical therapy in the field.

Joost Daemen:
So one other trial, that is quite interesting is the DIGIT HF. It's a large multicenter randomised control trial from Hanover.

Nicholas van Mieghem:
On Digoxin?

Joost Daemen:
Digitoxin. Yeah, it's not digoxin, but it's digitoxin and that's actually a brother of digoxin. But it's potentially a little bit less cardiotoxic, but more importantly is excreted by the liver instead of the kidneys. So from that perspective it's perhaps a little bit more patient friendly. It is interesting because this drug obviously is terribly old and has no clear recommendation in current guidelines. It has a 2B recommendation now in current heart failure guidelines in Europe, for patients with heart failure with reduced ejection fraction and in sinus rhythm. But now this drug is again tested, or not again is finally tested in a large outcome trial, enrolling patients with advanced systolic chronic heart failure. So those in New York class 3 or 4 or those in New York class 2 with an ejection fraction below 30%. And I've heard some positive rumours about the trial. I think it's interesting because it may add something that has been on the shelf for a very long time and may now, change a little bit the way how we use it. Also in the Netherlands, the DIGI HF trial is currently ongoing. Basically the same trial. So, yeah, let's see.
Nicolas Van Mieghem:
Well, it's a group of patients with not a lot of alternatives. Right. Less than 30%. So that has been an exclusion of a lot of trials. And you know, there are several med tech companies exploring, this specific set of patients. Whether we can do something with LV reconstruction or more aggressive treatment of mitral regurgitation, I'm not so sure. So my bet would be that this will become a negative study because these patients, they are very tough to handle.

Joost Daemen:
True. But I have a lot of events and in that perspective, a little help could make a relatively large difference. So let's see.

Nicolas Van Mieghem:
Yeah, well, speaking of treatment of patients of heart failure patients, but then HFrEF patients with an acute episode of heart failure, that is the DAPA Act HF TIMI 68. This is a trial, I think, an important trial that is evaluating the use of SGLT2 inhibition after stabilisation of an acute heart failure event. More 2,400 patients, with acute heart failure were included in this trial, regardless of the ejection fraction. So the median age was 69 years old. One in five of the patients were black. So there's quite diverse, patient population. Ejection fraction was less than 40% in 72% of the patients. And ARNIs were being used in a quarter of the patients. Type 2 diabetes in 35%. Also of interest, the follow up is only two months. So this is really the acute treatment of these patients and the primary endpoint at two months is death or worsening heart failure. I am very interested in the results of this trial because if this would end up being a positive trial, that really is then a very strong argument to put all the patients on all heart failure patients on SGLT2 inhibitors. Because it's so elusive how the effect of SGLT2 inhibitors is. Right. The mechanism is so unclear. But if it really hits already early on, then I think this is an important signal that, this is definitely one of the pillars, one of the true pillars of contemporary heart failure, therapy.

Joost Daemen:
Yeah, to me it's a very provocative design with an endpoint at two months in a population that eventually I would guess 90% of those patients will anyway get these SGLT2. So, yeah, let's see, what this trial shows. But given the fact that the, yeah, the price to pay with this drug in terms of side effects and specifically early side effects is very low. So it may be positive. But let's see.

Nicolas Van Mieghem:
Yeah, well, talking about the pillars of heart failure therapy, what about the beta blockers? Since I think multiple decades, we know that beta blocking agents are one of the cornerstones of heart failure therapy. And there are now several trials coming up that looking into this, beta blocking agents. Is it still needed in light of all the other therapies that we have? And so we have one trial from, Spain and Italy, which is the REBOOT study. REBOOT study, is including more than 8,500 patients in a randomised study testing the benefits of beta blocker maintenance therapy in patients who are discharged after a myocardial infarction. And that can be a STEMI or a non STEMI with a proven ejection fraction above 40%. Patients, will be randomised at discharge of the index event. So that is of interest. And obviously you want to know, okay, how many of those patients will be on an SGLT2 inhibitor? What is the uptake of ARNIs Are these patients on high doses of statins? So it's basically where heart failure and ACS therapies come together. The Primary outcome is, at five years and it's the incidence of major, adverse cardiac events, which is a composite of all cause, mortality, reinfarction and heart failure admission. I think an important study that might change, the way we are treating, heart failure patients, especially the patients with ischemic heart disease. Moving forward.

Joost Daemen:
Yeah, I'm not so sure about this one. Right. Because. Ejection fraction above 40%. So what do you think? You think it's going to be? I'm not. I don't think you're going to. You believe that we will continue using beta blockers? No, I don't think so. I think it will be negative. I think it will be negative in patients with a normal EF and a drug that is likely not the most popular agent among patients. So, I'm not so sure this one will, make it. But let's see.

Nicholas van Mieghem:
Well, I'm with you. And there is another trial more or less on the same topic, and that is the DANBLOCK. This is another randomised, controlled study now from the Nordics, from denmark. More than 20, 2,700 patients, included in this trial, where they're also looking at the value of keeping patients on beta blockers, when they are discharged. After a STEMI or a non STEMI with an ejection fraction above 40%, the randomization again is at discharge. Again, you want to know, are these patients on SGLT2 inhibitors? What about high doses of statins? What about ARNIs And the primary composite endpoint is all cause death, recurrent MI, revascularization with PCI or CABG, ischemic stroke, heart failure admissions, and so on. So, a little bit a different primary, endpoint than the other trial. But at the same time, I think a relevant study, the trial had, some issues with its enrollments, slow enrollments. So at one point they were, gearing up with also, the BETAMI study. This is another trial in the, in the Nordics. More, it's in Norwegia, in Norway. Sorry, Norway. And then obviously they're pooling the data because they had more or less the same, trial design. And we're going to see whether they're going to present just the data, or the pooled analysis. So that's going to be of interest to follow up. But I think this might also become a trial that demonstrates that probably these patients, after their ischemic event, will no longer need, beta blocking therapy on top of all the other medical therapies that work.

Joost Daemen:
So you're saying that trial enrollment was really hit by COVID 19. Well, that, that suggests that a lot of patients will not be on SGLT2.

Nicholas van Mieghem:
So that, so that's going to be very important for the interpretation of this and the other trials. Right? Yeah, yeah.

Joost Daemen:
So more controversial stuff in heart failure is the REFINE-ICD.

Nicholas van Mieghem:
Yeah. So obviously there is a relatively low threshold for use of ICDs in patients with ischemic and non ischemic cardiomyopathies. But the guidelines are changing and the way we are using ICDs, in the Netherlands really has moved on. It's becoming more and more restrictive. This is a trial of 700 patients in the US, Canada and Europe. Patients are post MI, again post STEMI or non STEMI, and they are at least two months out with an ejection fraction between 35 and 50%. I think the inclusion criteria are enriched, with also holter evaluation where they are looking at the heart rate turbulence or T wave alternate. So if that is present, then patients will become eligible for participation. I think that makes total sense. So you will look for a more vulnerable set of patients and then patients are randomised to an ICD or no icd. And the primary endpoint is very simple. All cause death at a minimum of 18 months. So I think if this is a negative trial, then it really is basically underscoring the current trends to become more and more restrictive in patients with ischemic cardiomyopathy. And I think this is a clinically very relevant study.

Joost Daemen:
I agree. And honestly I would be highly surprised if this trial is going to end up positive. I mean, you know that patients with an EF above 35% post specifically non STEMI, and perhaps having had a small infarct, their risk of dying within within 18 months is about 1 to 2%. So in 700 patients I would be highly surprised if this trial.

Nicholas van Mieghem:
But there is a little nuance. And that is, they are looking for the high risk patients. Right. At higher risk for vts and sudden cardiac with this holter criteria.

Joost Daemen:
Yeah, that's correct. It's not. But it's a screening.

Nicholas van Mieghem:
Yeah, that's, that's absolutely correct. All right, now let's move on to the antithrombotic therapy after an ACS.

Joost Daemen:
Yeah, well, not, not yet. We first wanted to discuss the OPTION STEMI trial.

Nicholas van Mieghem:
This is STEMI, not an ACS.

Joost Daemen:
Yes, but not DAPT.

Nicholas van Mieghem:
Okay, what is this..

Joost Daemen:
You said antithrombotics.

Nicholas van Mieghem:
Yeah.

Joost Daemen:
Okay, we'll move to the antithrombotics in a second. But first, OPTION STEMI. So OPTION STEMI is a multicenter randomised controlled trial from, South Korea, randomising a bit less than 1,000 patients with STEMI, and multivessel disease too. And you will not be surprised either. Direct complete revascularization versus staged complete revascularization with a primary endpoint of death, MI and unplanned revascularization at one year. So this concept is not that novel, but it's an interesting design because first, the comparative arm is a staged procedure that is not as per routine practise, done within two to four weeks, but is done in the same hospital sitting. So that means likely within 24 to 72 hours, which is a little bit unconventional. What also is interesting is that in the assessment of multivessel disease, there's a basically use of FFR I.e. protocol mandated, which is a little bit awkward as this is definitely not per current routine clinical practise guidelines for stemi, given the conflicting data of the use of physiology in non culprits in stemi. So a lot of questions in respect to this trial. Then obviously if you do the stage procedure within 24 to 48 hours, what will that do to the assessment of peri-procedutal MIs? Either, or from the. From the stage procedure. So a lot of unknowns. But again, it's an interesting concept and what I think is good about this trial is that it is again another trial that actually shows the potential of immediate complete revascularization in patients with STEMI, following the BIOVASC, trial that was run here from Rotterdam and the MULTISTARS AMI trial that also hinted to a direction of superior outcomes with immediate complete revascularization.

Nicholas van Mieghem:
Yeah, I totally agree. I think the, the main difference between BIOVASC and MULTISTARS AMI and OPTION STEMI is the timing of the staging. Right. And the staging has had to be done within the index hospitalisation, in the OPTION STEMI trial. I think from from a practical point of view, it doesn't make so much sense. Right. Also from a financial incentive for, for sites to where it, where it matters. I think the rehospitalisation makes it more attractive than doing everything in a, same hospitalisation. So. Yeah.

Joost Daemen:
Yeah. All right, now we go to the antithrombotics. The dual ACS trial is a very large or yet another trial assessing differences in short versus long term DAPT in patients with acute coronary syndrome. It's a trial that is now basically the first again after two trials that are ongoing. First LEGACY and the Other one is COMPARE-STEMI 1 and 9 published randomised controlled trials on the topic. But this one is a little bit different. It's a multicenter trial, randomised control to test the difference in 3 versus 12 month DAPT in patients with a type 1 MI. So that also includes non STEMI, I guess in 18,000 patients in the UK with the primary endpoint of all cause mortality. So that makes the trial little bit different. It also has a design that given the sample size, uses electronic health record linkage to track the duration of therapy and outcome, which is likely somewhat different than the other trials that really used patient approaches, critical event committees, etc. How this trial would do that is not yet completely clear to me. I also have no clue on what type of agents will be studied. So I guess it will be a more or less real world study that randomises patients but is not that dogmatic about what type of agents to use. So, a lot of unknowns but it's definitely a huge trial that I think is worthwhile to look out for.

Nicholas van Mieghem:
It's indeed it's a huge trial but maybe a little too late because we have walked away from 3 months versus 12 months. We are comparing 1 month versus 12 months or even 0 months of DAPT versus 12 months of DAPT. So I think the relevance of this trial might end up being limited. Although it's a huge number of patients and the primary endpoint is very pure. It's all cause death. So that brings us to two other trials that are definitely looking into other regimens of antithrombotic therapy. And this is the NEO-MINDSET from our good friend Pedro Lemos, also alumni from Erasmus University Medical Centre here in Rotterdam. And he has designed a randomised controlled trial in Brazil on early withdrawal of aspirin after PCI for ACS. More than 3,400 patients were randomised and patients required also complete revascularization if they had multivessel Coronary artery disease. What is still unclear to me is is it non stemi or does it also include STEMI? So we're going to look out for that piece of information and basically what they are comparing is conventional Dual antiplated therapy with aspirin in combination with ticagrelor or prasugrel for one year versus dropping aspirin within four days after the index procedure and then continue with single antiplatelet therapy with ticagrelor or prasugrel Primary endpoint at one year is death, stroke, MI or urgent target vessel revascularization. This is an important trial that more or less has the same design as the LEGACY trial that we are still, running together with, our colleagues from Amsterdam at UZ Henriques. That is the LEGACY study. This is a trial that is focusing on patients with non STEMI and unstable angina. So excluding patients with STEMI. And those patients are being randomised to a DAPT for one, year versus single antiplatelet therapy with the potent antiplatelet drugs ticagrelor prasugrel for more than one year. So it's going to, well, it will add to, the scientific background of simplifying antithrombotic therapies. As a matter of fact, there is yet another one, another trial that is the TARGET FIRST, and this is by my good friend Giuseppe Tarantini from Padua. A randomised trial comparing one month of DAPT versus one year of DAPT. After, ACS, more than 2,200 patients enrolled across Europe, Italy, Portugal, Netherlands, Spain and France. And, again patients had to undergo complete revascularization in case of multivessel disease. But this trial was enrolling STEMI and non STEMI patients. So again, one month versus one year of DAPT therapy. And the primary endpoint at one year was death, MI stent thrombosis, stroke, but also including major bleeding. I think this trial is, also overlapping, with COMPARE STEMI one that also is a randomised Study focusing on STEMI patients, where patients will be randomised to one month of DAPT versus one year of DAPT. I think a lot of trials coming our way that will help refine and maybe simplify antithrombotic therapies for all patients, not only for patients who are at a high bleeding risk, but every patient simplified. Keep it simple. Maybe one antiplatet drug will suffice.

Joost Daemen:
Yeah, it's interesting because I mentioned nine randomised trials have been done already on the topic. All a little bit different, but at the end essentially studying the same thing. And, the guidelines are relatively clear that if you stratify patients per bleeding risk category, you can safely decrease the DAPT duration to, let's say three months double, and then the rest single. But I have to say in our practise and also in the region and hearing from colleagues, most still get one year DAPT. And that's where I think with these specific trials, they may finally move the needle.

Nicholas van Mieghem:
I hope so. And most trials on this topic were on the so called high bleeding risk patients, but there was never a true penalty and never a true penalty of dropping aspirin. So why would we not consider that then in patients who without a high bleeding risk? Okay, let's move on to blood pressure.

Joost Daemen:
Yeah, so blood pressure and patient adherence, and that's a topic close to my heart, having performed a lot of renal denervation studies in the past decade, and this is OUTREACH. So OUTREACH is a multicenter randomised controlled trial designed to test whether compliance testing in patients on hypertensive therapy will increase blood pressure control adherence and healthcare costs. So this is a hot topic because, as you know, interventional therapies for blood pressure control are being explored studies and approved across the globe. But the issue with drugs is that approximately 50% of patients are 30 to 50% are non compliant. And that makes the results of these studies difficult to interpret. That also makes from a clinical perspective the value of the need for these interventional therapies perhaps, somewhat, let's say, disputed, but it's a thing. And you know, if you see 100 patients on your outpatient clinic and you know that 50% is non compliant, I mean there are 3, 4, 5 taking 3, 4, 5 antihypertensive meds, that's an issue. And this is a study of a topic that has been started here also in Rotterdam. In the RHYME study, 100 patients randomised to compliance, testing and then confronting the patient with the result of the compliance testing versus control. So simply doing the compliance testing without any, let's say disclosure to the patient. And what we found is that the compliance increased to above 90% in patients who were confronted with the result, but no significant effects on blood pressure control. And this trial is basically doing the same thing. 200 patients, who need to have at least two antihypertensive mats in 12 sites in the UK. Primary endpoint here was blood pressure control at three months. So also a study that, I mean if it follows the results of RHYME, you would expect that it may just reach a significant P value. And I think it's interesting if you can, yeah, by stimulating patients show a difference at three months that could be of interest. Conversely, what we also found in RHYME is that at 12 months the result was faded away. So it is an interesting topic. But yeah, whether this will do the trick remains uncertain.

Nicholas van Mieghem:
I think this is why we will keep looking for medtech alternatives to medical therapy. And this is for heart failure. This is also true for hypertension. So that's why I also hope that renal denervation at one point will become more like mainstream.

Joost Daemen:
Mainstream. Absolutely. I totally agree. Simone Biscaglia, another friend, will present the three year results of the FIRE trial. So this is a little bit of a different trial. It was an international multicentre randomised controlled trial to assess what a complete physiology guided PCI is superior to culprit only PCI in patients aged 75 years or higher presenting with acute coronary syndrome. It was a study that enrolled almost 1500 patients from 35 sites in Italy, Spain and Poland and was already published in the New England a couple of years ago reporting a 27% reduction in the primary endpoints of death, MI, stroke or ischemia driven revascularization. A difference that was quite striking I have to say and was particularly driven by a significant difference in death and MI. Yeah, I had three issues at the time with the trial. One was that it was actually studying three concepts in one trial. And that to me is always a little bit that raises some questions. So the study assessed whether complete was better than Culprit only PCI whether physiology guided approach was better than angio-guided approach and whether physiology with either FFR, non-hyperemic indices or angio-based FFR was better than angiography. There are a lot of questions within one trial with a striking endpoint we have to admit. But now the three year results will be presented. I think it's quite interesting because these pertain to patients 75 years or older and the benefit in terms of death in MI may slightly fade away up to 3 years. I would not be surprised to see that. But let's see.

Nicholas van Mieghem:
Well, to me this is a trial about complete revascularization and whether you do it coronary physiology guided or not, you need to do, you need to achieve complete revascularization. So yeah, this, this control arm of culprit only PCI, that is something from the past.

Joost Daemen:
Yeah, I agree. Even, even in patients age 75 years or older because that's what we learned already from a lot of these trials. There was no heterogeneity in the treatment effect in those above or below 75. So that perspective. Yeah, let's see then. AI GATEKEEPER, also an interesting trial, a little bit out of the box concept. So this is a multicenter, open label, randomised control trial from Korea, enrolling 450 patients. So basically this trial really focused on AI and it was designed to determine the efficacy, safety and cost effectiveness of AI Gatekeeper software. So really a software based AI solution to assist clinicians in the diagnosis of coronary artery disease by, predicting coronary artery disease, which was defined as the, presence of lesions of 50% or higher on either CTA or angio, from a multimodality AI technology that integrates clinical risk factors and baseline blood tests, including a chest X ray, EKG and echocardiogram in patients with suspected coronary artery disease. So you would say, well, what is the value in this in a population, by the way, that should be at low to intermediate risk? Well, I think it is interesting because we learn from a lot of these patients that underwent ct, which is very popular these days in patients at low to intermediate risk is also per current treatment, guidelines is that only 10% of these patients actually go to the cath lab. 90% has no relevant coronary artery disease. So that's a lot of patients and a lot of CT scanning. And if algorithms like this would be able to predict with a reasonable degree of certainty, patients that have a extremely low risk of lesions, I think that could help in how we use these technologies in referring, patients from either CT or angio.

Nicholas van Mieghem:
Well, it's another trial to promote artificial intelligence, in our practise. But a randomised controlled trial on this topic, including only 450 patients, that probably will be a hypothesis generating at best.

Joost Daemen:
That's also true if you consider that, yeah, about only 40%, 40 of these patients will have disease. Now let's see. I don't know.

Nicholas van Mieghem:
Okay, so then maybe the last trial is a trial on the value of LAA closure and this now we're talking about surgical LAA closures. This is a randomised controlled study that looks at the value of surgical LAA closure on top of surgical aortic valve replacement with or without mitral surgery and CABG. More than 1,000 patients were included in this study. Finnish trial that also included one site from the Netherlands, Nieuwegein. And the interesting part here is that patients had a CHA2DS2–VASc of equal or above 2, but no atrial fibrillation. So there was no history of atrial fibrillation. And patients were still randomised to LAA closure or control. The primary endpoint at five years, a composite of stroke, cardiovascular embolization and cardiovascular death. I think this is a very interesting, trial. It's also following up on the LAAOS trial by Richard Whitlock a couple of years ago in the New England Journal, where they looked at more than 4,800 patients with atrial fibrillation that were randomised to cardiac surgery with LAA closure or cardiac surgery without LAA closure. And basically that was a positive trial because the LA closure reduced stroke or cardiovascular embolization. This is a different patient population, so we're talking about patients who did not have or do not have a history of, atrial fibrillation. And what is then the value of LAA closure? So can you protect these patients upfront from, the issues related to atrial fibrillation, potential atrial fibrillation that might, arise down the line? I think an interesting, study that might end up being positive. So, let's see. And let's also see whether LAA closure, comes at, a technical price. Right? Does it make the surgery more complex or not? Our surgeons keep telling us no. This is almost, a trivial additional procedure during, a sternotomy. So let's see. I think this is an interesting one that might also, be adopted very fast because our surgeons are very keen on, introducing new stuff, in their procedures.

Joost Daemen:
Yeah, I agree. And I also would bet that this one is positive. I mean with endpoint at five years, a lot of patients who may have afib but never recognised afib, or as you say, develop afib, down the road they will have the same benefit. So, I would not be surprised if also this one will make it. But, we will know within two weeks. So good thinking of our Finnish colleagues.

Nicholas van Mieghem:
So with that, I think we are at the end of our preview. Thank you very much for being with us and we'll keep you posted on, what's happening at ESC and then come back with our wrap up of ESC 2025. Goodbye.

Joost Daemen:
Thank you.

Nicholas van Mieghem:
Bye bye.