So, we'll just move right along to Dr. John Thompson, who was initially practiced, did his training in the United Kingdom, and then as of two years ago, he moved to be the director of the Pediatric Cath Lab at Johns Hopkins in Baltimore, and he's a national PI for a pivotal study of the venous P valve. So, he'll give us a summary of this valve that's not yet available in the U.S., but maybe at some point in the future. This is a talk of a slightly different type, because I'm very aware that most of you will not have any experience with this valve. You may have seen it if you attend international meetings and it's been implanted in other countries, but by and large, I think this is a valve that will be new to you. So, I'm simply going to try and give you an overview of the valve, what it is, how it behaves, how it's implanted, and some context, but I'm not going to try and do any sort of comparison between valves. I'm not sure that would be appropriate based on the state of data at the moment, but what I would say is that I think that all of the self-expanding valves, all three of them, if we include P valve alongside Altera and Harmony, are best suited to certain types of anatomy. I think they all like the same type of anatomy, whether it's length to the outflow tract and a slight choke point, et cetera. So, I'm not sure that we're going to bring in a new valve that will suddenly allow you to successfully treat difficult anatomy that the other valves don't cope with. So, what is this valve? It's obviously self-expanding. It's built on a nitinol frame. There's a porcine pericardial tri-leaflet valve, which is sewn inside. So, the cover, if you like, isn't in fact a cover. It's an interior and it's made of the porcine material rather than there being cloth involved in covering any of the valves. In common with Harmony and Altera, it's a cotton reel type shape. It flares at both ends. The distal ends are very large loops of nitinol with virtually no capacity to obstruct anything. And proximally you have two little clasps, which are the mechanisms by which it attaches to the delivery sheath. So, new kid on the block. Well, I mean, that's really made me chuckle. This is far from a new kid on the block. The first human implant was in 2013, a decade ago. That was in China, followed rapidly by the first implant in the EU, which was in London. That was Shaq Qureshi. Subsequently, a CE mark study, very similar to a FDA pivotal study, and that led to approval. This is now approved for routine clinical implant right the way across the EU and is used accordingly. The current status is that, as I say, the approved at the top left of that little square, the EU, China and Argentina have full approval. There are, in fact, other nations in Asia, Southeast Asia, where the valve is used routinely, which don't have the same approval mechanisms as most other countries. There are ongoing trials in Australia, stroke, New Zealand, Canada and India. And as Constantine mentioned, the plan is for there to be a pivotal trial, which has been approved by the FDA, which will, with luck and a good wind, should start, I would think, realistically, at the beginning of 2024. Worldwide, there are 600 implants, more than 600 implants, but 600 for sure. The longest clinical follow-up is more than 10 years. So how does it differ from the other valves? Well, I mean, I've used all three by the fortune of working both in Europe and the States. And what I would say is that the P-valve, I think, has a softer frame than either Altera or Harmony. And whether that's to do with the nature and gauge of the nitinol, or the lack of a fabric stroke cloth covering, I'm not sure. But it does mean that this valve behaves differently. It doesn't come in one size, or in Harmony's case, two sizes. In fact, it comes in 10 different sizes and lengths. And so this red bar refers to the middle segment, the width of the valve. And it's from 28 to 36 millimeters in either a 25 or 35 millimeter length, referring to the middle. So that's 10 different options. So that makes it very different to the existing valves in the US. It means that, one, a substantial amount of stock needs to be carried if you're implanting this valve. And it means that there is a different way of sizing and positioning this valve. It requires a grip. So I will say sometimes to people that I think with P-valve, the anatomy grips the valve, whereas with the other self-expanding valves, I think by their slightly stiffer nature, they grip into the anatomy. And I think that although that may sound like semantics, I think it does explain the difference in behavior. Sizing, I'd like to say that P-valve has the same exquisite sizing protocols that we have for Harmony and Altera in that you send a CT and come back with all those beautiful images that Amy was showing, which are absolutely fabulous. By the time the report is through and it's been looked at, you know pretty much that you're going to be able to implant or not one of those two valves. There is pre-implantation image planning available for P-valve. It's actually based on either CT or MRI because MRI is used more liberally in countries outside of the US and is of a sufficient standard, I think, to make reasonable judgments about what you may or may not be able to implant. But it certainly doesn't reliably assess tissue compliance to tell you whether you will achieve a grip with the tissue on the valve. And as the anatomy is absolutely essential and means that as well as the cross-sectional imaging and geography, you also need balloon sizing for this valve. So every case goes into the cath lab with the intention of sizing the outflow tract using usually a big sizing balloon, occasionally a relatively compliant balloon, a non-sizing balloon. But I tend to use the NewMed PTSX, which goes up to really big sizes. And the original protocols included a concomitant angio to show that you've got a seal. And then the waste on the balloon is your, it's not the only piece of information that you use to select the valve size, but I would say it's the most important. And from that, you select a valve. And as a general rule, you're normally working on the balloon diameter plus four millimeters or so. And it depends, of course, on the anatomy, but that's the rule of thumb, meaning that the 36 valve is generally, you're able to deal with outflow tracts that are around the 32 to 34 millimeter mark. If you get beyond that, then it becomes, it can be a slightly emotional experience implanting one of these valves in a bigger outflow tract. The length is nearly always 25 millimeters. The longer length is rarely required. And I would say that 95% of my implants have been at 25 millimeter length. You've got a load of length related to the flares on either side, and having an extremely long valve is not generally necessary. And it's mounted into its own delivery system, and it's mounted under ice cold saline, which allows the nitinol to be folded up using a little compressor device that comes with it. And it folds into something akin to the capsule that you see on the Ensembl device. So it has a capsule and a delivery handle. And then really it's advanced usually through a 26 dry seal sheath. Originally with this valve, it was, before we all worked out that the dry seal was useful, it was taken up without a dry seal, but there were instances of the valve perforating the sheath. And I would say that always in my practice, I would use a dry seal to safely take this up to the target using a stiff wire, either a Lundquist or similar. And the choice of PA for delivery is very much like the other valves based on how you think the valve will cant as it uncovers. And this is the delivery sequence. You start high with the P valve, usually well into the pulmonary artery of choice. The flares at the distal end are uncovered and large, so there's very rarely a problem with obstruction. And the issue is almost always being sure that the valve won't fall backwards into the RV. So the dry seal is removed once you're into the target position. And then you use the delivery handle, which is in the bottom right, which has a little knob that you twist, which then brings back the capsule, which is recapturable probably to about 50 or 60%. So you can go back if you're not happy, and you leave a pigtail or whatever angiographic catheter you like in the distal anatomy to make sure that you're in the correct position and you unsheath. It's a two-man job. Somebody needs to control the position while somebody turns the capsule remover. And so this is the distal end with probably about 40 or 50% out. And then you move on to releasing the thing, which is a relatively quick... Once you're in position and you're happy and the distal end is right, then you unsheath quite quickly and deploy the device, making sure that the eyelets on the proximal end are free from the little metal end of the delivery sheath, which holds them. So you've got to make sure that's free before you start to remove the carrot, etc. And then it's a case of tidying up as per other valves, angiography for position, standard hemodynamic checks, ice if it's within your practice. Increasingly, since I've been in the US, although I dislike ice for atrial septal defect, I really do like it for valves. And I think it gives you a huge amount of information and stops the need to interact with a freshly implanted valve. So that really, I decided to focus on the nuts and bolts of implanting this valve. And I think that in my 10 minutes, I don't have time to summarize the CEMark study, which included 81 cases. There's now 70% of these at three-year follow-up and data collection is nearly complete for them. All I will say is that in common with Matt's presentation, with P-valve in this study, which was set up very much like the Ulterior and Harmony study, there were no major adverse events, all patients survived, procedures were successful. There have been no revalvings of P-valves or major valve dysfunction, and no more than mild PI as per this graph in all of these cases. There is one case with moderate pulmonary incompetence at two-year follow-up. That case hasn't made it out to three years yet, but everyone else is in the trivial to mild category. And so the valve seems to perform nicely as per the other valves. It's functioning with no major adverse events. So in summary, this actually is an old timer on the block. It's been around for a long, long time, and it's been, I think, shown to be reliable and safe for native outflow track revalving. I think once you get used to implanting it, it has its own tricks, but I think it performs very predictably. I do think it's different in nature to the other US valves. I think it has a slightly softer frame. I think it requires a grip rather than benefiting from a grip. And I guess that we'll find out in time how that will translate to clinical choices and algorithms. That's something that we'll need to see. And I think we're now entering an era where proof of concept for these self-expanding valves has long since been proven. It's now going to be about digging deep into how they behave and what suits what type of anatomy and of course their long-term function. So with that, I'll thank you and hand you back to Constantine.

Pediatric Cath Lab

venous P valve

self-expanding valve

nitinol frame

porcine pericardial tri-leaflet valve