Dr Patrick Serruys

So I'm Patrick Washington Serruys. I'm an established Professor of Interventional Medicine and Innovation in Galway, and I'm a Consultant of the Advanced Centre for Imaging in the CORRIB lab.

What is the current research landscape for treating patients with symptomatic aortic valve stenosis?

I think that by saying symptomatic you reduce the landscape because I think we have published last year the textbook on aortic valve, on TAVR with the late Alain Cribier and John Webb, Raj Makkar, Helene Eltchaninoff, usual suspect. And then in that book there is a big chapter on prevention of aortic stenosis. So there are now four, five drugs who can slow down the calcification of the valve, so I have to mention that.

Then you have the big block of symptomatic and then what is the field moving to is the asymptomatic. This morning we had beautiful lectures and LBT from Philippe Genereux at PCR and it's all about asymptomatic patients. But about the symptomatic, you could say that we are moving to what we call the moderate aortic stenosis. So it's a little bit technical but if you have a velocity of the jet above 4 and 40 millimetre of mercury you are severe, but if you are between 3.1 and 3.9, then you are moderate.

The problem of the moderate is that it's a mixed bag. Its patient are moderate but going to the severe, but there is also moderate, will remain moderate because they low flow, low gradient, because of fibrosis—it's already too late. But that's a big field: the asymptomatic, symptomatic and some prevention that will come.

Could you describe the study design and key findings?

Yeah, I mean you have to go back to 2019. You have two giants: Edwards and Medtronic. There are other people coming, but basically, they are the two golden standards. So I've been working with the Indian people since the year 2000 on stent and many other things—a slow process. But at some point, they had a good domestic product and how to introduce that in the world, you know.

So what we did, we said we are going to compare their valve, called Myvalve, versus the golden standard: [illegible] versus the Medtronic Evolute and versus the Sapien Edwards. The point which was difficult is that everybody make iteration in the valve. So we said okay, we'll take everything. Whatever comes as a new iteration will be in the so-called contemporary group, the two golden standard.

So it's a randomised trial between these two groups. So first, we take severe aortic stenosis—symptomatic. Yeah, that's point number one. Point number two: the decision to treat the patient is basically the decision of the heart team. That's something new because we don't have really inclusion / exclusion criteria. What we have is according to the ESC guideline of 2021. Finally, is the heart team who say I want to do something for this patient That's point number one.

Then we randomise Myvalve versus the contemporary group which is a combination of Sapien and Evolute of Medtronic. And then there are two phases in this trial and we have to talk about the two phase because everything is done according to the VARC-3. You know, VARC-3 is the Bible of the cardiologist. Now if you are a trialist and an investigator, you follow the recommendation of VARC-3. And VARC-3 said, at 30 days we look to the safety and the efficacy, but the safety.

So there is seven components there, of course death, of course stroke, but then bleeding, kidney failure, damage of the vasculature, pacemaker, conduction disturbance—all kind of thing acute related to the safety. And that's 30 days.

And then VARC advised at one year something different: you still look at death and stroke, but then you look at rehospitalisation. And the reason for rehospitalisation are huge, huge. It could be some structural deterioration of the valve, some hemodynamic deterioration of the valve or complete failure of the valve you have to replace. Yeah, so that's the two phase. The first phase, we achieve non-inferiority versus the two others.

Then we make a little bit the detail in a publication, ergo intervention on specifically Myvalve Evolute, Myvalve Sapien—quite instructive. And then in the things that I have present this morning, the outline of this morning, was about the one year.

And again, we see that there is non-inferiority a little bit on everything. So if you look at the number of deaths, for instance, the ultimate criteria: 27:27. You cannot argue with that. You don't need statistic. If you look at the stroke, okay, 21:13, but not significant. If you look at rehospitalisation, 16:20, not significant and sometimes going in different direction. So if you combine these three date events, because they are date event—there is a date for the death, there is a date for a stroke, there is a date for hospitalisation—completely neutral freedom is around 80, 89% in both groups.

What are the clinical implications of these results?

It's a difficult question. I think the big novelty of that technology from India is what we call the intermediate nominal size. They are the first one. If you take Edwards, you have jump of 3 millimetre between the nominal size—so 20, 23, 26, 29. If you take the Medtronic, it's also jump of 3 millimetres, but then suddenly 5 millimetres between the 29 and the 34. And people forgot that the surgeon have also jump of not 3 millimetre but 2.5. So he has a jump of 1.5. So when you come in the lab and you see the valve, the multispan CT scan, and they tell you the diameter is 21.5, if you work with the conventional valves, you have to take either 20, underestimate, or 23, overestimate.

And then there is always the risk of ruptures and all these things. So that's the novelty, but today, to be completely honest, we have not yet extracted in a significant way the value of that. We have trend because the number in the study is not major, maybe I did not mention 768, 384 in each group. So it's still small numbers.

Okay, it's good for a composite endpoint but not for that kind of subtility. We have created a fitting index because basically, if you need the shoes 20, 21.5 or 23, you need to have the right nominal size. So the fitting index has been created and we will explore with the other trial, COMPARE-TAVI, which has been done in Denmark. We are going to pool the patient and see if really this possibility, the spectrum of size, has a clinical impact on pacemaker, on regurgitation. That will be important.

Now one thing you should not underestimate, it's a little bit tricky to talk about that, is the clinical cost benefit. Okay, I mean obviously, technology coming from United States was expensive. Medtronic was always mitigating the price somewhat. Okay, that explained that some of the people have been attracted by the self-expanding and then suddenly you have outsider which is India. They have changed in three years, they have made three iterations.

You know, India is teaching and producing 10 million engineer per year. Per year! Okay, so you see valve very stable over the years of moving deterioration as slow, this guy in three years, bang, bang, bang. They changed drastically, you know, from a hexagon to an octagon. Very amazing. So I think that it's already there in 82 countries in the world. And I think that the simplicity is now a very short valve: 18, 21 millimetres. The shortening is really minimum: 12%. So it's maybe a valve for Mr. Everybody. You know, you don't need to be a prima donna in TAVR to do these things, you know.

What further research is needed, and what are the next steps for the Myval THV platform?

What I've learned in trial that I did in the previous decade, that the 10 years follow up is essential. It's only after 10 years that you really get the answer. Curve can diverge and converge. Curve can diverge forever. That's a serious signal. But when they diverge and converge, there is a moment of vulnerability and then it disappear. That's point number one.

Point number two: long-term follow-up is important. And then the issue is to go to do what we call preemptive treatment. You don't wait for the damage of the myocardium, you treat the patient. He has the disease, he has the gradient, but not yet the damage. That's the moment to do something. Because when the damage is there, it's irreversible, it's fibrotic, there's nothing to do. So I think we are going to go in the direction of preventive treatment. Pre-emptive and preventive treatment, both. That's what is going to happen.