So good morning everyone, and welcome to Medistim's Capital Markets Day. I'm very happy to see also people here in the room in the conference center in London, but I know that we have a lot of people following following us online. And we have a packed agenda for you today. We will see that the first half of our meeting here will concentrate on the cardiac market and tell you more about our new launch of the Intui software and what that will mean for us and for the surgeons in this space.

Then we will have a Q and A session, and we will continue with the talking about the vascular market. And we will learn about the new patent study that is just starting. Okay. But first I will start with sharing some comments about where Medistim is today and put this into the complex of next steps and innovations for accelerated  growth.

Medistim's journey, as you probably know, started already 40 years ago where we was we were a distributor of heart valves in the Norwegian market. And shortly after, the company started to develop its first proprietary product, the first flow meter, the Cardio Med, which was put on European market in 1994.

And since then, we have stayed committed to, to develop and refine these technologies for the surgeons out there in the world. And today we can say that we are a truly global organization with subsidiaries and direct sales and support teams in the USA Canada, China, Germany, Spain, uk, Denmark, Sweden, and Norway.

Let's also remind ourselves a little bit about the medical need and the technology. So metastatic help treat cardiovascular disease and cardiovascular disease continues to be the leading cause of death globally. And the target applications that metastatic is  serving is coronary bypass surgery.

It is also peripheral bypass surgery and carotid endarterectomy as some of the most important application areas. In all of these spaces and in CABG surgery, it's always been this big question. So when a patient needs revascularization, what is the optimal treatment? Should it be a percutaneous coronary intervention using stents, or is the patient benefiting more from open CABG surgery?

So we will have comments from  surgeons here today, which will put more light on this question, but it's a fact that 80 to 90% of patients in need of revascularization are referred for a PCI still, more than 700,000 patients are getting a CABG surgical procedure annually, and it's been a pretty stable number over the years.

And when we are putting patients through this pretty invasive procedure, it is very important that we are making sure that the patent or  that the graft are patent. And here is where medicine's technology, the transit flow measurement technology comes in. The beauty of this technology is that it really gives instant feedback on graft functionality.

So it provides the surgeon with the opportunity to correct and to revise while the patient is still on the operating table. So at right here we can see indications on the top right of suboptimal graft. We see a very spiky flow curve here, and we see a low flow. So in this this example, the surgeon decides to revise the anastomosis and we see a much better flow result.

So fixing the problem there and then. Okay, but if the flow is low there's not always a technical issue with the anastomosis that can be fixed. So that's also very important. And medicine felt that, we should develop a tool that could help investigate these  instances. And that's why we came out with the high frequency ultrasound modality and putting that into the same device.

And today, we are then delivering an expanded value proposition. It's a new workflow, and we are working and believing that this in the future will become the new standard of care.

The use of our technology are extensively documented. We have more than 600 clinical papers with medicine's technology, and we have also received endorsement from a number of clinical guidelines, both on the cardiac procedures, vascular procedures, both for flow and for imaging. And the miracle, this is the latest generation.

This can be purchased as a flow only system, or you can have it as a flow and imaging system, or you can actually upgrade it to imaging later on if that is of preference. The probes, so the TTFM flow probes, that's the sensors of this technology. They're sold as consumables and are reusable. And on the slide here, we can also see our imaging probe, which is unique in being approved for direct contacted cardiac tissue.

It provides  really excellent resolution in the near field, and it has a small probe head that allows for use in small incisions, and that's important. We are trying to provide our products in the most flexible way We are using alternative business models here. So the systems can be bought as capital.

We are also offering a paper procedure type of model in the United States and in the uk. And they're also providing lease options. Let's take a little look at the market. So starting with the coronary artery bypass graft market. So I already mentioned that we are counting more than 700,000 CABG procedures being performed.

Every year it's somewhere between 700,000 and a million. And based on the number of probes that we are selling, we are estimating that we are serving about 37% of these 700,000 procedures. Then we are also estimating that competition may serve about 8%. So let's say around 45% of the market is then  supported.

It means that more than half of the procedures are not assisted with any type of technology and are supported only with finger palpation. It means that we are looking at the total addressable market for the company based on flow only of 1 billion, no annual sales per year. And if we are counting in the high frequency ultrasound modality as well, that addressable market is double the size looking at the TTFM adoption in CABG.

So I think this is still a very interesting map. We see that Japan has been, the leader is still the leader and most of the procedures being performed in Japan is served with medicine's technology. This is also the situation for most of Europe, so Central Europe and the Nordic countries I would say more than 80% of procedures are served.

And we can also see that in the United States things are moving. Based on the probe sales, we can now estimate that we're serving about 35% of these 200,000 procedures. Then in the future, of course, markets like India with a growing population and also growing number of CABG procedures being performed.

This is an important future market for metastatic. It is also interesting to see that following this increasing adoption, we are seeing increasing number of publications coming out there. So the last 15 years we've seen a tremendous growth in publications. And I think this talks to the relevance and the importance of the technology and the interest from the surgical community to investigate further its value.

And of course CABG surgery is dominating here, but we're also seeing increased number of publications on vascular applications and transplant as well. So surgical guidance and quality assessment is needed in vascular surgery as well. And this market is actually larger than the CABG market, both in terms of number of procedures being  performed annually, and also then providing a larger market opportunity for medicine.

We will talk a lot about peripheral bypass surgery later today. And as you can say, see that market research wa that was performed last year found that it's more than 500,000 peripheral bypass surgery procedures being performed every year globally. Quick look at the financial performance, we see that over time and over the past two decades, we've seen strong revenue and profit growth from the company. Last year, we delivered 526 million NOK's in revenues. And 69% of this is what we call recurring revenue. So it comes from probe sales, from sales of paper procedure procedures, and also from lease income.

The EBIT margin last year was at 25%. I think it's a solid margin, but a bit lower than we have been used to seeing. So we would like to take that up to the  more normal levels. On the balance sheet, we see a strong cash flow, high equity ratio, and no long-term interest bearing debt. A solid position.

Taking a look, look at the year to date numbers per September. So last year we actually delivered growth in Norwegian currency, but due to the weak Norwegian Krone versus both US dollars and euro, we, if it, we compensate for that. We actually had a slight decline on our sales revenues last year.

And we are pointing to the sort of macroeconomic headwinds with the high interest rates and the, and inflation as one of the components for actually making purchasing and investment decisions a bit harder. We've seen this lightning up through the, this year, so we had a growth since the first quarter and a higher growth as the quarters has combined.

So after three quarters, we are looking at 5.3, 5.3%  revenue growth in Norwegian currency, and the currency adjusted this correlates to 3.7%. So still in the lower range compared to what we have used to see so thereof cur the current topic for today, how to accelerate growth going forward.

So we'll come back to that. I think it's great to see that the America's region, of course with us being the most important market came back very strongly in the third quarter with 17% occurrence in neutral growth. So that is a sign of  recovery. The Europe middle East Africa is doing well at 6.8% growth and Asia Pacific has been influenced by the transition of going from a distributor to a direct operation in China and also some challenges in Japan.

Third party products had a really strong year so far this year with 14% growth, which is actually untypical. Sales revenues, of course, has an impact also on EBIT, but we also know that we are now running the operating expense level at a higher level due to these  new direct countries and also because we introduced a double shift in our pro production.

EBIT margin has been a bit lower than we have been used to seeing, but it has been recovering. And the 25.6% EBIT at of the three quarters I think is is decent. We need to talk about our growth strategy and we remain committed to converting the high penetrated flow only CABG markets to flow and imaging.

And the request study, as I think many are familiar with will continue to be a very important tool in achieving this goal. Further growing adoption in underpenetrated markets. I have pointed to several regions of the world where the use of TTFM is still in the early days.

And product innovation for ease of use is central to get some traction there. I pointed to flexible pricing and business models and we that we are building a position in vascular surgery and we will continue to expand our direct market coverage. Also,  but let's go into the pro product innovation part here.

As I think many companies in this space has experienced over the past several years regulatory requirements has really made it yeah. It's a bit hard to allocate as much resources to innovation and product development. Compared to earlier days, we've seen that a lot of our resources has gone into maintenance and really being able to keep the products on the market.

So we found that we had to actually reimagine our innovation process. We wanted to create a team that could to work looser so in, in a more agile way. And very much in close collaboration with users. And we also wanted to ensure that the voice of customers are also meeting the voice of technology.

So let's also ask, with the new technologies available to us, how can we exploit them and how can we put them into action, into our own products? So with the,  with this group, we have been able to de deliver more defined concepts and handing this over to the engineering team so that their job becomes more effective.

At the same time, we had to also increase the capacity, so the number of heads in our product development, and it's been double since the pre covid time. So just reminding ourselves on the, sort of the history here. So we launched TTFM in the mid nineties. We have had several generations of the flow meter.

Then launched a new paradigm of adding high frequency ultrasound in 2010. And we are now working on the sixth generation, which is in development. And going forward, of course, we will continue to work on the hardware side of things. So we will continue to develop the systems, the devices, and the probes as well.

But I do believe that we will be seeing a lot of innovation where we're adding value from data from the systems and data from the clinical  cases as well. And that's what we are going to learn more about today. The I two software. And I will just say that based on this platform, we will also see imaging upgrades.

We will see increased con connectivity both to the patient Jo Journal and to enabling us to do remote servicing. And a little bit later we will also see hopefully interpretation guidance based on machine learning. I'm using my time here and the intuitive software. So Twitter, my good colleague will talk more about this, but what it is, first and foremost, it's a response to users' requests.

So it is really point by point trying to address what they have told us. More intuitive use interface. They want the reference values, more context data. So we will learn more about that, but it's also a fact that the old software has created some type of technology depth for the company. So we took the opportunity in this project to actually revamp the whole software a architecture.

And we are  now looking at the cutting edge future-proof software, a architecture that will help us shorten the development time for the next innovations. And, on the vascular side, we will also today learn about the patent clinical study. Very important because there is a lack of interpretive guidance and completion control for peripheral bypass surgery.

And the timing for this study is really good because here as in CABG, there is a debate on what is the best procedure. Is it endovascular alternatives or open surgery? And a recent study the best CLI trial is concluding that endovascular treatment is today it's the first choice, but the recent study has shown that the open surgery provides better results.

So is really timely to investigate further how our technologies can help manifest this. And I'm very proud to present the investigator team for the patent study. Here we have Professor Michael Conte as the lead investigator who's also the first  author of the Global Guidelines. In this space, we have the secretary General from the European Society of Vascular Surgery, moderate Venal, which we will also hear from later in this presentations Today, we have the President of the Japanese Society of Vascular Surgery Professor Azuma.

We have Professor Alik Farber, which was the first author of this Bests CLI trial. And we have Professor Clement Darling and Professor Joseph Mills, who are both past presidents of the American societies of vascular surgery. So a great group of people and it's going to be very interesting how this study will yeah, both start and continue and we will see what it will lead to.

To summarize why should revenue growth accelerate? So this is really the big question, right? And first of all, I will say that I believe market dynamics is getting back to a more normal state. In the USA, we see that macro improvements with inflation stabilizing at the lower level. This should lead to continued relief and  greater investment capacity.

So this is also already what we are seeing signs from in our own sales processes in Asia Pacific. We expect to being passed the transition time in in China, and we also expect Japan to normalize. And then of course these new in initiatives that we've just mentioned. And we will learn more about the software on the cardiac side.

And the patent study on the vascular side will help us spur interest and awareness and thereby also adoption of these technologies. Continuous improvement is always important for us. And we will definitely continue to concentrate on that. The EBIT is also expected to come back to more normal levels, although I'm not ashamed of the EBIT margins that we are currently delivering either, but with higher growth in own products compared to the third party products that will drive EBIT margin.

Higher growth of the imaging will drive the same. And also seeing higher margin sales  from us and other direct markets will help us in this direction. And we are also working on automating our. Manufacturing process or probes, and that will in the little bit longer term, help us also. So with this I've spent all my time and more so thank you very much for listening to that.

Now I will give the word to the product and business manager for our cardiac business. And he's, the title of his talk will be introducing Intui our new software platform, -, an intuitive solution, optimized, to provide data interpretation, guidance, and enhancing surgical decision making for better patient outcomes.

Thank you, Kari. That is right. That is the title of my presentation. I took the liberty of shortening a little bit in this sense of type. But yes, I'll be here to introduce the new MiraQ Intui software platform. I am  very excited and very proud of this and I'm glad to have the opportunity to talk to your people about this.

But what is this MiraQ Cardiac Intui software platform? As Kari said, we have been focusing our innovation lately with into collaboration with the surgical communities. And this software platform is developed in collaboration with surgical communities worldwide. And that has been very important for us that this is something that is developed in accordance and in incorporate collaboration with these surgical teams.

This is not something that a bunch of engineers have cooked up in a corner in a corporate building. This is useful stuff, and our focus has been on improving the system interactions and providing better support for interpretation of flow measurements. To make it easier to use for the users and in the end to create a wider adoption and more routine use of our systems in the markets.

We have already a well established market base. We've already sold all the early adopters. Now we need to reach the normal surgeons and the normal surgical teams to do we need  to remove all of the hurdles and the barriers of entry, and this is a software that we believe does that. With that said Intui has for us, been about simplification and in the sense of simplifying things.

I'm gonna, we've done a bunch of changes. There's a lot of changes in the software, but I'm gonna boil it down to four main points. We have been improving on our dual modality setup, so our system does two things. Having a system do one thing really good is a lot easier than having a system do two things really good.

So we have doubled down on that. We have, as you'll see modernized the user interface quite radically. We have added context for the decisions with some graphical elements that I'll show you. And we have greatly improved the reporting functionality as well. Go first to the merging of the ultrasound imaging and the transit time flow measurements.

In medicine we believe that these two modalities go perfectly well together. They are fantastic in the way that they provide different types of data  that are useful for the surgeon. So the ultrasound imaging gives you the contextual information. It gives you a picture, a map if you want, of what is actually going on.

And then you get the hard data from the transit time flow measurement that gives you actionable numbers that you can correlate with your previous knowledge. And now with the Intui software, you can have some guidance in there as well. We need to do this. And the improvements we've made to these two modalities in the two-way software is that we made the interactions smoother, so there are less button presses.

Ultrasound imaging is a complicated modality. We have boiled it down to the minimum amount of button presses so that it's easy for the operating team in a stressful environment to correctly set up the system and use it optimally.

Now, the user interface has been greatly modernized throughout the whole software. But where it's most apparent is probably here in the ultrasound sorry, in the transit time flow measurement live measurement  screen. The top illustration here is the current software, which is perfectly functional, but when you compare it to the bottom version, which is the new and Intui software, that there's a lot of changes.

And we've kept all the good things. Of course, the flow curve is essential. The mean pulsatility index diastolic failing, all of these things that are important for how you interpret the transit time flow measurement, all of that information is still there, but now it's grouped in a logic way on the top of the screen so that you add one glance can take in all of these parameters and see everything you need to see quickly.

You don't have to search around the screen to find the numbers. They're all up there very easily identifiable. Also, on the right side of the Intui screen, that we have added a work list as we call it that tells you where you are in your procedure. There is a graphical representation of your grafts instead of just a text that tells you which components you've used.

And this type of information makes it much more obvious for the  rest of the surgical team where you are in the procedure. If a more expert surgeon needs to come and help a less expert surgeon he will quickly know where the procedure stands just by looking at the screen very quickly. Like in this example case, this is a relatively bad flow curve.

If somebody needs to come in and rescue a day, they will take one look at the screen, they'll know where they are and they'll understand the problem quickly. And also with the graphical representation of the graphs instead of using words. This was a complex problem for us to solve 'cause there was no standardized way of naming these graphs.

And that was a problem if we want to create a large set of data because you need that data to be standardized and anodized correctly if you want to do some further analysis on it. Now, with this graphical representation with the drawings or the subway maps as we like to call them it is standardized, meaning that we can collect data from large sources and, start actually crunching these numbers and hopefully get some interesting findings. I've been promising context for decisions. What I've been talking about is, of course, the gauges or the dials on the top of the flow measurements here it's very colorful. We're using the traffic light convention, red, yellow, green.

These are all user configurable so that every surgical team every surgeon can input their own values that they like to use for their decisions. These are numbers that the surgeon will previously have had to keep in their mind all the time. They'll have to read them, memorize them, and remember them during high pressure situations like surgery.

This can be difficult in a pressured situation, so we just put them on screen for them instead. It's a very simple fix, but it's a very important one. And. The values they want to use can be individual or they can be set up by institution or they can be tweaked to the different types of measurement steps as well.

It's very flexible and this will be a great tool for lesser experienced surgeons. They can  have these values input they can read publications, put them in there, and they'll always be there and help them. We also improved our reporting. Bottom left picture here is Dr. John Puskas that is reading, proudly reading his report after trying the system.

The reporting was previously just a printout of whatever you'd measured. Now in this new and improved reporting scheme, you get a one pager that summarizes your whole procedure and shows you at one glance what you've done, all the graphs you've performed, the measurements you've done in a, like a small thumbnail that captures the most important characteristics of the measurement.

And then of course in the subsequent pages you have the actual measurements. So this front page the feedback on this from our early access sites have been that this will actually save the surgeons a lot of time. 'cause a lot of time they'll have to hand draw this picture of the heart. Instead, now you get a beautiful illustration created by the system that can be used to communicate with your peers at the hospital or even maybe patients and relatives if you choose to do  and this is, this Intui software is just the first step is the start of the Intu e experience. This will be the software platform that medicine will use to continue innovating on building new features, introducing new functionality in the future. And as Kari said, we've redone the whole thing.

It makes it easier for us to innovate quicker, be faster to the market with new features. And I, as a product manager, I'm very much looking forward to releasing a bunch of new and exciting features on this platform in the relatively short future. So thank you. That was all from you today.

I am very happy to being able to introduce the next speaker that is Professor Puskas. Who is the Chief of the Cardiothoracic Surgery at Emory University Hospital, Midtown in Atlanta, Georgia. And he's also one of the founders of a very important organization, the cus organization and the ICC meeting that has just  celebrated, I would say the 10th anniversary of the inception.

And John Puskas have a lot of experience with our technology and I would say he's absolutely one of the most influential voices in cardiac surgery today. Please, John, the stage is yours. Thank you Kari. And thank you for the opportunity to address this important group of people who are helping to lead.

And I imagine also fund a technology that is focused on improving the quality of coronary bypass surgery in, at least in my world, I know you have focus on vascular surgery and other things that are not part of my day-to-day life. But we at the International Society for Coronary Artery Surgery live and breathe coronary surgery, and we rely on the Medistim portfolio of products to help us be sure that at the end of each operation we've done the excellent job that we that every patient deserves.

So my topic is the role of Medistim  and quality improvement ectomy for coronary bypass surgery. These are my disclosures. The most important of which is that I am a consultant to Medistim. For training and also new product development. I was privileged to have a small role in helping the engineering team refine the Intui software.

And also participate in some of the ongoing efforts towards improvement in hardware. I agreed to serve as a consultant to Medistim because the corporate mission of Medistim, Medistim and the corporate mission or the academic mission of for my own career and for the International Society for Coronary Surgery are perfectly aligned, namely to improve the quality of care of coronary bypass patients globally.

So what is coronary bypass? Just for the newcomers, perhaps Coronary bypass surgery is the only surgical treatment for coronary artery disease, which is the number one killer of human beings. Blood vessels from elsewhere in a patient's body are harvested and  redeployed to the heart, becoming conduits to deliver blood supply beyond blockages in the arteries that normally feed the working muscle of the heart.

And what future will this surgical procedure or this set of surgical procedures have? I believe it's a bright and growing future. It will require ongoing collaboration between innovative surgeons and innovative corporations to improve coronary bypass surgery. But as Abraham Lincoln said, the best way to predict the future is to create it.

And I think it's important to focus or to realize that Medistim addresses the value imperative in surgical therapy in general. That is that we must provide value by improving quality at a reasonable cost. Now coronary bypass surgery is expanding worldwide and adoption of the transit time flow meter technology that Medistim has introduced is also expanding worldwide.

We anticipate the number of global coronary bypass operations rising towards 1  million in the next year or two. And this is largely due to growth in China and India. It's also due to an aging population in the developed world and the rapid remarkable expansion of what we think of now as a pandemic of cardiometabolic syndrome which is a combination of obesity diabetes and systemic inflammation.

This produces coronary artery disease and peripheral vascular disease, both of which are the two primary disease processes that Medistim addresses. I. Another important concept. And I will say without going into a very long discussion of the new pharmaceuticals that have been brought to the market in the most wealthy portions of the world the Ozempic-like medicines are having an impact on primary care.

But if you measure simply the proportion of human beings on this planet who have access to those drugs presently it's minuscule almost, very difficult to measure. It's so  small compared to the total number of patients globally with coronary artery disease. And another seismic change that's coming is an evolution away from the role of the interventional cardiologists performing an invasive diagnostic coronary angiogram to function as a gatekeeper to assign patients to have either.

Stenting or percutaneous coronary intervention or coronary bypass surgery. The very fact that the ratio of PCI or stenting to coronary bypass surgery varies by 10 fold among different practitioners, different cities and different countries, tells you that there is a great deal of influence on that decision making that is not evidence-based.

And frankly probably not appropriate or in the patient's best interest. This is fundamentally possible because the person doing the in diagnostic test presently is an interventional cardiologist who can simply proceed with a stent procedure  without further delay or discussion or involvement of a coronary surgeon.

That gatekeeper role is changing and I think it will change fundamentally over the next two to five years throughout the developed world. And I mentioned the epidemic of diabetes and Cardiometabolic syndrome. India has the distinction of being the diabetes capital of the world with we're now approaching 60 million diabetic patients in India, 40 million in China, and a little over 20 million in the United States.

These numbers are rapidly rising with no end in sight, and that leads to an accelerating burden of cardiovascular disease with India now outstripping all other nations on earth. And I think that's to a degree because we're not able to measure it as well in China. But suffice it to say that this burden of cardiovascular disease is ramping up globally with no end in sight.

And coronary bypass surgery  subsequently is also rising. After a dip, during the pandemic, coronary bypass cases in India continue to rise and we now. Have clear evidence that India is the nation and that performs the largest number of coronary bypass operations globally at about 200,000 individual cases.

Why does that matter? Because coronary bypass surgery works better for patients with diabetes than stenting does. And this is the data from the Freedom Trial published in the New England Journal actually a decade ago, which randomized patients to have multi-vessel stents or coronary bypass surgery.

And all of these patients were diabetic. And you can see that for the hard endpoint of death, stroke, and myocardial infarction, cornea bypass, beat stenting and the curves really began to diverge at about two and a half years and continued to diverge through the first five years with a striking benefit of cornea bypass.

Over Multivessel stenting for patients with diabetes. Again, the  epidemic of diabetes is very relevant. When we follow those same patients in that trial through seven years of follow-up, the curves continue to diverge further in favor of coronary bypass. And why is that? It's because cornea bypass protects patients not just from the effects of a present flow, limiting upstream blockage in a coronary artery, but also protects patients against acute events caused by non flow limiting lesions, which can rupture and have an acute thrombosis in the future.

So coronary bypass surgery benefits patients more than stenting because it protects against future myocardial infarction. It does so at the expense of more invasion and more perioperative risk. And the number one thing that we think about. Is stroke. These are also data from the Freedom Trial showing you that the risk of stroke is about twice as high in coronary bypass compared to stenting.

But there are things that can be done to mitigate against that risk. And primary among them is ultra use of ultrasound at the time of surgery to interrogate the aorta and to decide exactly where to put cannulas and how to apply clamps to the aorta to safely accomplish the operation while re reducing the risk of stroke, because most strokes come from athero embolism.

That's to say embolism of atherosclerosis from the aorta itself during the operation and the Medistim. High frequency ultrasound or epi cardiac ultrasound probe is especially useful in this regard. And you can see images that we can get from this kind of tool to interrogate the aorta and plan where we're going to apply a clamp because we don't want to apply it over an image or rather over a fungating atheroma that you see there in this aorta.

Even this kind of thickened aortic wall can  spill debris into the bloodstream if a clamp is applied at that spot. So my favorite operation involves completely avoiding any manipulation of the aorta. And here you see an image of that where two internal thoracic arteries are used for inflow and there is no manipulation of the aorta at all.

This is also ensconced within the European guidelines, recommending minimization of aortic manipulation and prior to aortic manipulation, the use of epi aortic ultrasound, again, one of the key technologies that media stem brings to the operating room for us. The other key technology is the transit time flow meter tool that was described earlier and shown these.

This is the device that measures by an ultrasonic technology a flow meter technology. The actual flow within the bypass grafts, the resistance, the flow, the characteristics of the pulsitivity of the wave form of that flow. And it helps us understand the quality of the bypass graft and the accomplishment of our  goal for that patient.

It also allows us to do it again, to revise a bypass graft if we see. With immediate feedback in the operating room that the bypass graph we've constructed is not doing the job we expected it to do. And Kari mentioned earlier the request registry or clinical study. I was privileged to participate in this.

And it was, and is I think a landmark study of a thousand patients from seven sites in Europe and North America. Having first time coronary bypass surgery. We used the medias stem transit time flow meter, and epic cardiac ultrasound imaging probes to study the grafts and to document the quality of the graphs with the older Medistim technology.

But even with the previous generation of software, this tool was extremely useful. In fact, 26% of patients had at least one change or adjustment in surgical strategy. Driven and guided by  the information the surgeons received from the Medistim tools and the adjustments were where to manipulate the aorta, where to bypass the, a actual coronary target whether to revise the bypass anastomosis and to interrogate the quality of the conduits themselves.

So 10% of patients had a change in planned aortic manipulation based on the identification and detection of atherosclerosis in the ascending aorta. So to adjust for that potential risk, the ultrasound guides the surgeon to, to individualized the application of cannulas in clamps to the aorta to minimize risk.

About 20% of patients had a change in that anticipated site on the coronary artery where the anastomosis would be constructed to ensure that the bypass graft goes beyond not in front of the blockage in the artery that is visualized on the angiogram. About 3% of bypass grafts were  revised.

That means to say redone at the time of surgery because the flow of the TTFM was unsatisfactory. And typically after they were revised, the flow was much improved. And that, of course, is the primary purpose. Now, until recently, we hadn't a peer review publication that said that makes patients live longer.

But this paper from Italy actually does exactly that. This is an analysis published in December of 23, presented last year at the American Association for Thoracic Surgery by Dr. Ally and her colleagues, an analysis of a multicenter registry. Evaluating the role of TTFM or transit time flow metric in coronary artery bypass surgery.

So this is 1600 patients who had coronary bypass surgery at nine sites. And basically they sought to identify whether there was a cutoff point in the TTFM that would predict poor outcomes for patients. And they determined that accepting an  inadequate, that is to say less than 15 MLS per minute flow to the LAD was in fact predictive of adverse events during clinical follow up.

And here you see that the mace the likelihood of death, stroke, or macro infarction was about 3.5 times higher in patients who were left with a flow to the LED, less than 15, compared to those whose LED flow was greater than 15. Moreover, as you can see in the lower panel, when graph flow was poor and the graph was subsequently revised, the later graph flow was much improved.

And similarly, the Pulsatility Index or PI, which was too high before revision was suitably lowered after revision. So these are direct measures that the Medistim technology guides surgeons to make appropriate changes in the operating room. And those changes improve graft function as measured by the Medistim device,  and that improved function correlates to better clinical outcomes for their patients.

This is an important three step logic that validates the utility of the mid stem technology and coronary surgery. So I'm gonna show you a couple of cases because it relates to that LAD flow. What should one do with a skeletonized left internal thoracic artery graft? The typical conduit we use to bypass the LAD if it has poor inflow.

So we had a resident learning to harvest skeletonize ITA's. And the ITA had mediocre flow. We assessed it with the ultrasound probe and  identified a portion of that arterial conduit, which was damaged during the harvest. It had what's called a dissection, so we excised that segment, reconstructed it, and then used it to, for the bypass graft, resulting in a good outcome for the patient.

Now, what to do if you've already done the anastomosis to the LED and the flow is not so good? Of course, we measure the  flows. Here's an lead ITA to the LAD, that, that looked visually to be just fine, but had a flow of only five ccs per minute and a Pulsatility Index that was much too high at eight.

We were guided by the TTFM and ultimately made the decision to redo the left internal thoracic artery graft to the LAD. And then after repeating the TTFM, we see that the flow is now 23. The pulse deal index is less than three, and the patient did well. So I will confess that I assisted my junior to do that anastomosis, and I thought he was doing a perfectly good job.

So apparently I wasn't doing such a good job supervising him. And I will confess that this is, I've done this for 30 years. It's apparently I missed a maneuver that he performed that limited the flow at the toe of that anastomosis. And when I personally redid it, the flow was, five times higher.

I wouldn't have noticed that in the absence of using TTFM, I thought that I had seen him, watched him adequately,  and the graft was fine, but in, in fact, it was not. So this is why the European guidelines recommend routine intraoperative graft flow and I think it's bizarre to perform coronary surgery.

Without that, I'm gonna segue before closing to a new technology that, as I mentioned earlier, we'll change the gatekeeper role for the interventional cardiologist and I believe will lead to a higher portion of patients having coronary bypass surgery rather than multi-vessel stenting that is inappropriate for them.

And that new technology is an imaging technology, not a surgical technology. This technology allows a non-interventional cardiologist or even a radiologist to perform a study that will reveal and document the existence and location of blockages in the coronary arteries without. Involvement of an interventional cardiologist so that one can imagine a family  practitioner or non-interventional cardiologist subsequently deciding whether the patient should have coronary bypass surgery, multi-vessel stenting, or just medical therapy.

These are the kind of images that are available with that they can be produced with commonly available CAT scanners. Today the numbers represent the nomenclature of the branches of the coronary artery. This is actually a patient of mine, and here you see blockages in the right coronary artery.

Very carefully identified. They're exact location pinpointed. Here are blockages in the left anterior descending or LAD, again, with bright calcium specs indicating where the blockages are tight and where they are calcified. And the left circumflex the other artery of the heart, again, demonstrating the exact location and tightness of the blockages.

This particular patient has a syntax score of 66. Now, a syntax score is a way of quantitating the complexity and degree of coronary artery disease.  Anything over 33 is considered severe. This patient has extremely severe coronary disease and this technology also tells us a fractional flow reserve derived from CAT scan F-F-R-C-T.

Any number less than 0.8 indicates a blockage that is flow limiting. And you can see this patient has numerous branches of those three coronary arteries where that hemodynamically calculated flow blockage is significant. So the functional index score is also extremely high. We plan to do this operation, a complex double mammary artery operation with radial artery outflows to five targets based on the non-invasive imaging.

This is, we did exactly that operation we planned, and then a month later. We did another CAT scan demonstrating that all of these graphs are open. And I'm, I'll just jump through some of these, but each of the graphs can be carefully documented in a follow up and demonstrated to be open with a residual syntax  score.

That's only two. So from 66, we've got it down to two. And this is without an interventional cardiologist doing a diagnostic test. Therefore, the, this, in this case, the role of the interventional cardiologist as gatekeeper was eliminated. And I think this will change the pattern of coronary disease allocation to the alternative therapies of multi vessel PCI medicines or coronary bypass surgery.

And in fact, this could even be truly unbiased with AI algorithms. The syntax score 2 20 20 is actually an AI algorithm which incorporates characteristics of the coronary angiogram, the CAT scan angiogram with clinical features of the patient. To predict the 10 year mortality risk or five year major adverse cardiac event for that particular individual patient if they are assigned to have coronary bypass surgery versus multi-vessel stenting.

And I think this is the kind of thing that will  ultimately drive more patients towards surgical revascularization and fewer patients, or a lower percentage of patients towards multi-vessel stenting. This is a, an analysis of the syntax score 2020 as it applies to the old syntax score. They retrospectively looked at that dataset and determined that only about 20% of patients in the syntax trial we're better off in terms of 10 year predicted survival with PCI rather than CABG.

So I think we're gonna see an increase in the volume of coronary surgery and that will be aided and embedded, I think, by the Medistim technology. I'm not gonna go through in detail these in two e slides. You've seen them before, but this is truly an intuitive way. Of providing the feedback for the surgeon in real time so that she or he can revise graft when appropriate to ensure that the patient leaves the operating room with a perfect revascularization.

That's the goal of the International Society for Coronary Artery Surgery. We had our  10th annual meeting just these last few days here in London. One of the sessions was this one. Intraoperative quality assessment in CABG should be mandatory, and you can see that this really focused on TTFM and high frequency ultrasound evaluation of Coronagraphs.

This was a well attended session with leaders from America, from Israel, from Japan, from Italy, and from Edinburgh all addressing the utility of the mid STEM technology. We will do a similar session at our next meeting in New York in 2025. Thank you for your attention.

Thank you so much John for that very insightful presentation. Now, I'm very proud also to being able to introduce associate Professor Gianluca Torregrossa coming from the vascularization program at LA now in Philadelphia. And he is a guy who is really passionate for minimal invasive and robotic surgeries and has also been one  of the early exercise for the Intui software.

So please, we would like to hear about your experience and your thoughts about this. Thank you so much.

Good morning everyone. My name is Gianluca Torregrossa, and I am currently Associate Professor in Philadelphia. As you can hear, my background are definitely not from United States of America. I'm from Italy where I completed my training and left for the US when I was a fellow after spending one year in Africa.

John Puskas, you heard him, is my most important mentor in my own journey, in my own career. And it's always, it's a pleasure to be here in front and giving a lecture to people that are not physicians. And for me is a extremely new type of feedback. When you have to start to give up a lecture, it's always complex to engage the interest of an audience that  you don't know.

Someone of you are not even in this room, and most of you are not in this room. So telling you a story has a power to bring you back to a very special moment in your way, in your life where someone was putting you to bed and telling you something that was nice and making you comfortable. So the words of once upon a Time.

Have a special act as a special power, a special reflect in your own brain. So let me start with a story. Once upon a time, there was a company that was named Nokia, and Nokia was the fourth of the fifth most valuable brand in the world, making billion of dollars in revenue capital. And in less than eight years, Nokia failed the analysis of Nokia.

Was extensive, but most of the analysts agreed with the last words of the CEO during the last day in  which he closed and file 11 Nokia that was then acquired by Microsoft. We didn't do anything wrong, but somehow we lost. And the reason why Nokia lost, and the reason why I bid that every one of you has, or 95% of you has a different type of brand phone in their pocket, and I know which phone do you have is because Nokia did not innovate enough.

They didn't do anything wrong, but they were not fast enough in providing innovation. Their competitor were innovating faster than they were. And that what disrupt the fifth most valuable brand of Nokia, you can be sitting on a phenomenal technology leading the market, but if you don't innovate. You lose your market and I this message has a lot to say in each one of our work for you industry, for you investors, for  me, as a surgeon, and these rules, it's applicable to the life of each one of us.

It's applicable to me as a cardiac surgeon. If I don't innovate, I will lose my job. I will lose what I can do. We are in a very incredible moment facing challenging minimally invasive PCI. We are always checking this number, medical therapy, but the reality is that coronary artery bypass grafting is evolving itself, is evolving towards a new level of minimal invasive that can provide something incredibly new, the exactly long-term quality of life that bypass software respect of PCI, without the burden of a sternotomy, without the burden of an aggressive, invasive procedure.

So let me bring you to a journey. The journey. Start with this picture and the journey. Start with a picture that show you the two system, one beside the other one,  the new and old system, the new and old software that can allow us to pivot around this new technology of coronary artery bypass grafting.

And here we are. You are about to sit to the console of a robotic surgical system, and we are about to enter inside the chest of a human being and to perform what we call a robotic bypass surgery. Come with me. You are seeing the heart from the left side of the chest. We are opening the sac that contain the heart.

I hope that your breakfast has always, has already been digested. We are looking inside of the pericardium. That is one of our coronary target. And now you're looking into the chest wall where these arteries that we call internal thoracic artery leaves serving the chest wall and they can be reroute deployed to the heart.

And you see how this magnification you see how beautiful we can see,  connect and operate to the art itself even more. Come with me and see how we can connect these arteries together. You see these are you're seeing a heart moving. An LAD One of the target that we are doing is suture and up there the internal thoracic artery previously harvested.

So a truly pure, minimally invasive approach to assess and address coronary artery bypass grafting. And more than my words, more than what I can tell you, more than what I can convince you. I'm a retired physician. Listen to the words of the physician. Very much knew what my apprehension was, my remembering of my experiences, training at the Cleveland Clinic and people undergoing open heart surgery.

Even you made me feel very relaxed with our preoperative visit and with the anticipated procedure that you wanted to perform, and I felt very  confident with how many days you have been in the hospital. I was discharged 26 hours after the procedure. How did you felt back then? I felt really comfortable once all the chest tubes and the arterial lines and the IJ line was removed, I felt very comfortable.

I was able to walk in the hallways on the surgical floor or on the postoperative floor. But you were telling me about the dental procedure. Oh yeah. I've had dental extractions that. We're more uncomfortable than this procedure. Literally no exaggeration. If anybody has had a root canal, they know what I mean.

A physician who had a double bypass two memory artery, deployed to the best target of the left coronary system, twenty six hours after his at home. This is innovation. This is the future. So where do you sit has? TTFM? TTFM sits here, and I want to go  a little bit fast on these slides, but TTFM sits here, medicine sits here, sits at the center at the key point of all of this, there is no way I can innovate.

There is no way I can perform a robotic bypass. I can perform this level of surgery, I can discharge a patient one day, 26 hours after a surgery if I don't have the opportunity to test those graft inter operative and know that for sure those graft are nice, are patent, and they're serving this patient well.

I feel confident to send this patient home because I can perform an assessment intraoperatively more. I can teach how to perform this surgery to someone else. As you heard from Dr. John Puskas, he told me how to perform bypass surgery and robotic bypass surgery. He was feeling comfortable to let me take in the ownership and the responsibility  to perform something that has a huge impact, the most important impact in the 10 years life survival of an individual, of a father, of a husband, of a grandfather, of someone.

And you can let this huge responsibility in the ends of the next generation because I can test the bypass that my trainee nowadays does in my operating room. That is training, that is the key point technology that the most important stone of that Roman arch that sustain innovation, education, and of course patient safety.

So the gold standard and the key co corner point is Medistim. In this sense, the innovation that you are bringing in become essential. And this innovation becomes essential because we are now with this new software, not only able to have a  more clear and a more important view, but we are also able to create reports.

Reports that now can be spread around, can be spread to patient, can be spread to family, can be spread to referring physician, creating a culture around these numbers, around these values that we have seen. These numbers means a lot to people like me, Dr. John Puskas, and even to people that, that has spent all of their life with Medistim personally embracing this technology as industry, as partners.

But there is still a lot to do. There are a lot of physician, there are a lot of cardiologists out there that take care of patients. And then when you tell them, I have done a triple bypass and I check the graft, and these were the flow of your own patients, they still don't know what exactly it means.

And it's in our important mission to educate. Everyone the general practitioner,  the patient's family, but providing a report, providing a physical copy of something that can be intuitively seen, they, that has a graphics in their pictures that depict what type of surgery they receive. That has a huge impact.

And I want to go to the, this video showing you some of the feature of this device. That we can now address and draw the type of and measure the type of devices that we do. We can check and drawing the pictures of the bypass that we are doing. We can teach thanks to a very intuitive level of red, green, and yellow.

What type of flow you should expect. I can put my eight years old daughter and tell me if she wants green, yellow, red, I'm sure what color she will decide to pick. So that is intuition. That is Intui. That's the software that allow us  to really re bring back interest, bring back culture, bring back new technology and education for the next generation of surgery.

And you see the opportunity here that we have to literally create graphics. A graphic that explained to a patient you now see in something that get printed. At your own home after your own surgery, what really happened during that six hours when your chest was open or when someone was operating, you robotically and indeed a series of bypass.

You understand graphically what happened to you, has a level of comfort, and add a level of comfort for yourself, for your families. That has a huge important element, even in the care, even in the success recovery for that patients. And again, most importantly, we educate the people around us. We educate cardiologists, we educate general practitioner,  distributing and spreading the news of what medicine has done in the last 30, 40 years of successful story.

And you see these are some of the results. These are the value, these are the report, these are the picture that can be printed and come home with the patients itself. And again, a system that provide in a very simple color coded understanding of all of the flow that has been taken and all of the picture and images modality that we can acquire for.

And here you see more from a, an open case. There is a heart beating still not lunchtime guys. And one of the bypass there and the probe that is positioned on the graft to connect and detect the flow. In this side screen, you see me moving around the probe on the heart of the patient and check the flow and making sure that all of the parameters are in line with what I expect.

And this is innovation. This is  future. This is what we need for our patient. In conclusion, you guys are the keystone, the elements of an arch that extend from innovation to education and patient safety. And all of this is possible because we can check the results of what we are doing. Innovation is the most important element that push

us to be better, to be relevant, and to maintain the benefit of the best treatment for coronary artery disease that is coronary artery bypass grafting in the next 20 plus years to stay strong and be relevant. I'm extremely excited for the future of coronary bypass grafting. Have, as you heard from Dr.

John Puskas, the future is bright. The future is bright. Because new imaging technology will reassign  patients, AI will reassign patients, decreasing the disproportion between PCI and cab. The future is bright because you have a new generation of surgeons interested in minimally invasive robotic approaches that will be able to guarantee the same quality of the work that our mentors have done in revolutionizing the post-op recovery for our patients.

The future is bright because we can educate and education is the only element in which we can bring innovation and continually to build up on innovation. And we can educate because we can assess that the trainee has done is the same perfect job that I would've done if I were sewing the bypass grafting on my grandmother, on my father, on a someone of my own family.

Thank you so much and I'm happy to take any question from the audience.  We will change the subject a little bit and we will now, I will now introduce our vice president of the medical department, talking about the patent, a new clinical study on the use of flow and imaging in peripheral bypass surgery for treating critical limb threatening ischemia, CLTI, the stages you are.

Thank you so much Kari, and good morning. Yes, the patent study is another bypass study in the lower limb in patients with critical limb threatening ischemia. And CLTI is the most severe stage of patients who have peripheral arterial disease. So it's a subset of these patients with PID that get CLTI.

But still it's a large population because the  number of patients with PID is over 200 million new cases per year, and around 10, 11% of them progress to  CLTI. It's the symptoms of  CLTI is pain at rest. It's non it's non-healing ulcerations and it's necrosis or gangrene.

And without being treated, these patients do really bad and round up to 20%, 25% of them die within the first year of diagnosis. And it's also associated with a high risk of amputation. So unless these patients get revascularized either by endovascular treatment with balloon, with their, without the stent, or they get open surgery they have a poor, very poor prognosis.

So why? Have we initiated the patent study? We have initiated it because it's a large and severely deceased patient population  with more than 500,000 bypasses done per year, and many of these bypasses fail. So we have numbers indicated that around 20% of these fail within the first year. So how can TTFM and high frequency ultrasound add value?

This is a it is a bypass, they have a proximal and they have a distal anastomosis, and several things can happen. Been to the anastomosis. It could be a stenosis, which is basically a narrowing, it could be caused by a misplaced stitch or some other course. Or it could be an intima flap, which is a injury of the vessel wall.

Or it could be a thrombus, which is a clock formation. And none of these can be seen by the visual visually or detected by palpation. But  TTFM can easily detect a flow limiting impact. And you can study, see with ultrasound what is causing this. And this image below shows a, an intima flap with a thrombus.

Between the anastomosis, you have the graft, in this case, the vein graft, and you want this to be opened or a patent and if it's twisted, that will impact flow. And also if it is a kink, that will impact flow. Or you could have a small or large leakage if you have a kink or a twist. You could see it if you use an open surgical technique like you see at at the bottom here.

But if you use a bridged technique and that is very common, you can't really see the kink or the twist, or if you have an open vein branch is similar. If you don't see it, you can't detect  it. And if you have a, for certain techniques, you need to take out the vein valves, and they are small and tiny, but can be very important.

And all of this, if it has an impact on flow, you can easily detect it with TTFM and you can study it and see what is causing it by high frequency ultrasound. Here you are probably very familiar with the curves. If the flow is high, like in this first case. You have a repetitive curve with a low pi.

In the middle you have an obstructed bypass and with a lowly low flow spiky curve, high pi, and that was revised and flow got much better. And you have here, you see these TTFM probes. This is without an handle. And this is the type of probes that is used during robotic surgery. So there, there are very small, easy to  place here.

They are snapped on the vessel and then you see ultrasound both in the longitudinal and the transverse view. So we think that the combination of using flow and imaging complement each other. They're a perfect match and you can, TTFM can rapidly detect flow related issues and ultrasound can describe what the problem is.

And you may wonder, aren't there any other techniques that could be used to detect these problems? And there are a variety of techniques that can be used. It's duplex, ultrasound, angiography, doppler and our, and, but we think that but there are no standardized method recommended.

And you will hear more from Professor Venermo talking about the advantages and the disadvantages of these different types. And also, as Kari mentioned, there have been recent studies  showing that some patients. Benefit more from having a bypass as their first choice instead of endovascular treatment.

And Professor Conte will talk more about this in his presentation. So the gold of the patent study is several fold. It's to tech, tech technical issues that can be identified and corrected. Interoperatively. It's to identify the grafts that has a high risk of failure and separate those from the graft that has a low risk.

And we also want to collect data for later health economic analysis. So the design of the study is prospective, it's international. Multicenter. We expect the enrollment of patients to take around two years, and then we will follow up each patient for one year and then you will have the analysis and publications.

So we plan on enrolling  450 CLTI patients in 15 sites in the us, in Europe and in Asia. So that's a short introduction to the patent study. So thank you for your attention.

And then the time has come to to listen to a prerecorded presentation from Professor Michael Conte Professor at division of Vascular and Endovascular Surgery at the University of California San Francisco. And Professor Conte will be the lead investigator of the patent study. Good afternoon.

I'm Mike Conte, Chief of Vascular Surgery at the University of California San Francisco. I'm pleased to join you today to speak about the clinical value of completion assessment and leg bypass surgery, and the rationale for the patent study that we are now launching with Medistim.

These are some disclosures I have relevant to this talk.

Peripheral artery disease or atherosclerosis affecting the arteries of the lower extremities is a growing global health problem due primarily to aging of the world's population, as well as the ongoing epidemic of diabetes. Estimates are that currently more than 200 million people in the world are affected with peripheral artery disease.

It increases significantly with age and it affects. All socioeconomic strata and has grown by almost 25% over the first two decades of the current century. Indeed, PAD is a major global health problem.

Revascularization is a cornerstone of treatment for advanced PAD to relieve symptoms,  improve quality of life, and avoid major amputation. Traditionally, open bypass surgery of the leg has been an effective and durable treatment option for many patients, and is well established in the surgical literature.

Over the last number of decades, increasingly technologies of the endovascular arena have allowed us to cross open and dilate a wide range of lesions in the lower extremity, such that endovascular therapies now are the dominant form of treatment for PAD. However many patients will either not be good candidates for endovascular intervention or have failed endovascular intervention, and there remains an open question, which patients are best served by which type of revascularization, lower extremity bypass is best performed using an autogenous great saphenous vein.

This is something that's been well established over many years in the surgical literature. This is a study looking, a typical  study looking at a single center large retrospective series of autogenous, lower extremity bypass grafts performed at my prior institution in Boston. 75% of these bypasses were done for an indication of chronic limb threatening ischemia or critical ischemia to preserve limb function.

What's evident from this graft patency curve is that there's essentially three phases of graft failure. It in the first 30 days, there's a failure rate of between five and eight or 10%. That is largely deemed due to technical factors. This is a range of issues related to performance of the procedure, including the quality of the actual conduit, the size of the target artery, and also technical defects within the graft are at the anastomosis.

The largest drop in patency of bypass grafts occurs in the first two years secondary to a process that we call intimal hyperplasia, which is the development of  stenosis within the conduit, often at focal sites, perhaps at valve sites, and sometimes at the anastomosis. This is a process of scarring that occurs within the graft, but may also have relationships to the initial technical treatment of the bypass, including retained valve sites and hemodynamic effects.

And then at subsequent time points the. Graft stabilizes and the failure rates reduce over time, largely related to what we believe to be atherosclerosis development in the inflow and outflow arteries and also within the graft. But these two this two is related to the preexisting m animal hyperplasia that occurs within the conduit, which may be the soil for the atherosclerosis that develops later.

All in all, the initial implantation time is a critical time for the adaptation of the vein graft, and may set the stage that only for immediate technical events, but for downstream events.

In the early two thousands I was a lead investigator of a large clinical trial that tested a novel drug that was a molecular therapy that was targeted to reduce graft failure by reducing scar tissue formation. This is a study of over 1400 patients with critical limb ischemia who underwent lower extremity bypass grafts with a primary endpoint of non-technical graft failure.

This study importantly included duplex ultrasound imaging of the bypass over time so that we could accurately monitor what was happening in these bypass graphs. In this study, which was a landmark study, we found that the overall primary trial endpoint occurred in 25% of patients in both groups. And if we looked at primary patency in the first year, there was about a 40% loss of patency, primarily due to the development of focal lesions that were treated successfully by reinterventions  to maintain secondary patency.

So this trial establishes that a technical failure, while relatively low in this trial is potentially a downstream surrogate for later events. The goal of completion assessment at the time of the procedure is to ensure the technical adequacy of the bypass. We want to make sure that there are no significant anastomotic defects, no problems within the conduit itself, such as a routine valve or a damaged segment with underlying pathology.

Wanna make sure there are no tunneling errors in the leg or compressions, areas of kinks or twists. And also we want to examine the runoff in the leg itself. There are several approaches to achieve this that are in common use and standard of care is really unclear. Different vascular surgeons and different institutions tend to have their own patterns of use angiography by placing a needle or catheter in the graft.

And injecting contrast with x-ray imaging  is a common modality. Duplex ultrasound is another common modality, and some surgeons just perform a simple handheld doppler and pulse exam. With that background, it's important to know that in recent years we have seen several new large clinical trials trying to help determine which is the most effective way to revascularize patients with advanced PAD or chronic limb threatening ischemia.

And the largest of these trials is the best CLI trial, which was reported in 2022 in the New England Journal of Medicine. This is a trial that basically randomized patients who were felt to be good surgical candidates and who had a reasonable option for either open or endovascular intervention to bypass or endovascular treatment upfront.

The trial was intentionally divided into two parallel studies based on a preoperative assessment of whether or not the patient had a good quality gray saphenous vein,  so that in these two parallel trials, there were actually two separate hypotheses. In the larger cohort with a good vein hypothesis was that the vein would outperform endovascular therapy.

Whereas in, in the cohort two patients who did not have a good vein, the hypothesis was that endovascular therapy would outperform bypass. In the end, what was found was that in cohort one, patients who had their bypass performed with a good quality saphenous vein had a significantly better long-term clinical effectiveness as demonstrated across multiple endpoints, but including important, this primary endpoint of major vascular reintervention, amputation, or death.

You can see that surgical patients had a much lower event rate over time that these curves separate early and continue to separate over the course of the first year, after which they remain relatively parallel. Importantly, that's just a  time to the first event. But the value of a well done bypass surgery is evident also by the total number of repeat procedures that these patients receive over time.

In fact, less than half the incidence of additional procedures was less than half in the surgical group of the patients with the good vein compared to the endovascular arm suggesting a much higher burden of re-treatment for patients who received endovascular therapy. What about just doing the bypass after the endovascular treatment fails?

Why isn't that just an okay way to practice? And in, in many places, that is an approach that is undertaken, but many studies have shown that secondary bypass works, but it's simply inferior. This was a recent systematic review that re looked at a number of papers, pulling data from nearly 12,000 patients and showing that patients who had a primary bypass.

Had about a 60% reduction in or improvement in amputation free  survival compared to patients who had their bypass only after a failed previous catheter therapy. We looked at this same question within the best CLI trial and found the same exact finding. This was recently presented at the European SVS meeting.

This is data that shows the major amputation rate for patients in the trial who had a primary bypass in the solid line versus those who underwent a secondary bypass after failed endovascular. And you can see that the this is a significant reduction for the patients who had a primary bypass that's nearly half within the first year.

In reality we know that these two therapies both have important and comp complimentary roles, and that there are certain patient and anatomic factors that are more favorable for one versus the other. Hence, a the decision making really hinges on a number of important factors. Patients who are higher surgical  risk, patients who have less complex lesions in their arteries, and patients who don't have a good quality vein are gonna always be favored for endovascular intervention.

However, patients that present with more severe limb threatening conditions, such as extensive gangrene, who have more complex lesions, who have had previous failed multiple endovascular treatments. And especially those who have a good quality vein and are good surgical risk may do better with a bypass first.

And this is what the data is increasingly showing. And in fact, recent practice guidelines, including what that from the European Society for Vascular Surgery, for example, show a expert opinion suggesting that if a patient has long occlusions, is fit for surgery and has a saphenous vein, they should preferentially get a bypass first.

The global vascular guidelines published in 2019 suggests that one should have a selective process of deciding  between open bypass and endovascular based on the patient's overall risk. The degree of limb threat or limb severity was shown on the X axis here and the anatomic complexity as well, such that patients who have advanced limb threat and complex lesions.

Are probably best served by an open bypass first, whereas many other patients are good candidates for endovascular first. In reality, how often is open bypass being used in patients with CLTI? That's a difficult number to come upon, but if you look at a number of recent large registries, national registries and other large multidiscipline multicenter studies, it looks like between 25 and 35% of patients are generally getting an open bypass for CLTI.

And based on my own personal experience, I think the number of between 20 and 30% is probably about appropriate given the types of  patients and complexities that we see with CLTI. So that brings us to the current importance of the Peyton trial, which really is an opportunity for us to. Define the best approach to completion assessment after open bypass surgery to raise the quality and the consistency of open bypass surgery for CLTI.

In this trial, we aim to test both transit time flow measurement, and high frequency ultrasound imaging in patients needing a vein bypass or below the knee target in CLTI. This will give us an opportunity to develop and essentially confirm or validate certain flow measurement criteria as validated criteria to confirm high likelihood of technical success and sustained one year patency.

I think that this trial will be an outstanding opportunity for us to elevate the field of vein bypass surgery for CLTI to get  more vascular surgeons comfortable and familiar with. The use of TTFM and also to raise more attention to the importance of completion assessment in bypass surgery. Thanks very much.

I really appreciate the opportunity to participate in the conference, and I would hope to be available to you as needed for any questions in the future. Thank you.

Yes. And then we'll have the next speaker as well. And then we'll have a q and a session on this topic. I hope we will be able to connect with the Professor Maarit Venermo, who is the Professor of Vascular Surgery at Helsinki University. So she will be live with us over Zoom and yeah, available for questions.

Maarit please the stage is yours.

Yeah. Thank you very much and good morning. My name is Maarit  Vernermo. I'm a Professor of Vascular Surgery in Helsinki University Hospital, and I'm very happy to present our practice in Helsinki for completion control after a lower limb bypass surgery and don't have any conflicts of interest related to this topic.

So here you can see the most important risk factors for arterial disease. Many treatment of hypertension and hypocholesterolemia has improved and prevalence of smoking decreased the one circle with green. At the same time, the prevalence of diabetes has increased and is increasing, and the number of elderly people as well as we live longer in the health university hospital.

We do a lot of. Procedures. We are the biggest surgical unit and Nordic countries. Our catchment area is 1.7 million inhabitants, the primary one, and  here you can see the evolution in the number of endovascular and open surgical procedures in seventies. Nowadays we do about 2,500 endovascular and one 1,600 open surgical procedures.

In seventies, smoking was the most important risk factor and pipe surgery to prevent amputations was not yet routine procedure as it is today. In the end of eighties, bypass surgery started to increase in numbers, and in nineties the prevalence of diabetes studies started to increase increasing also the number of procedures for arterial disease today.

The prevalence of diabetes continues increasing, but at the same time, people live longer increasing the prevalence of arterial disease even further. And you can see the role  leading countries in terms of prevalence of diabetes to five being Mexico, Turkey, Spain, US, a, and China. In the right in turn is the development of the number of population with diabetes and its prevalence and it's growing.

Patients who undergo stop bypass surgery usually have advanced peripheral art disease, and the procedure is limb saving. In most of the cases, the question is bypass or amputation. We have done a lot of studies on CLTI and health in several doctoral thesis. And here's a picture from one of those. So if we use autologous vein, we can achieve excellent limbs after bypass surgery.

Here's the curve from one of these showing the limbs for 600 patients after bypass  surgery. This is from another thesis on a living status five years after either bypass or amputation for patient who originally is living independently at home. In the right, you can see that amputation for a patient living at home in the beginning Majority of the patients live at institution after five years.

When in turn, if they undergo, bypass and save their leg, majority of the patients are able to continue independent living at home. And of cost saving is obvious for society as because of the fact I showed that after amputations, patients usually have to go to institution. These leads to significantly higher costs compared to bypass surgery.

The reasons to do completion control are obvious.  We want to prevent graft failure and optimize long-term patency. As the best bypass graft is out, autologous vein and it's availability is limited. We do not want to lose a good bypass with single segments and greater veins because of problems, which we could fix in the first place.

One individual has about two meters of saphenous vein, not more. This is a paper on the causes of primary graft failure after saphenous when bypass published already in 92, and it included over 450 bypass operations. Primary graft failure rate was 20% and in 63%. The reason for graft failure was related to problem with graft itself.

And you can see the reasons for graft failure here in the left,  and almost all these problems leading to graft failure can be distinguished with completion control, and they can be fixed at the first place before patient leaves operating theater. The most common completion control methods are ultrasound angiogram, or transit time flow meter.

There are still places that are not doing any kind of completing control because we don't yet have proper recommendations in our guidelines. There's no scientific data for comparing these methods. In Helsinki, we use transit time flow meter in all cases as called completion control. If any problems are suspected, we first make ultrasound scan the graft to distinguish the problem.

We do  angiogram if ultrasound is inconclusive or when we suspect info or outfall problem, which we fix immediately. However, we do angio in less than 10% of the cases. Angiogram is not good because it, we have to give patient toxic or nephrotoxic contrast media. We made several studies in early 2000 showing that flow measurement can distinguish with graft related problems as well as compromised inflow and outflow compared to ultrasound and routine angiogram as complete in control method transit time flow meter is significantly quicker to perform and non-invasive and safe.

Furthermore, you can always use these methods as additional component, if any suspicion if TTFM  and here I saw you, a video on our routine case. So first we measure flow two to five centimeter, restart the proximal graft and take a look to a contact to a probe, and also the curve of the. The shape of the curve.

Here we can see that the curve is good, but the diastolic flow is a little bit low, which means that there is resistance in the restart part. And this is why we then want to dilate the distal vessels by giving some Papaverine. And then we see the reaction of the Papaverine, how the end diastolic flow will increase, and it shows that we don't have any problems in the graft itself.

If it doesn't increase, then we can suspect that there is some stenosis after the distal anastomosis,  and we can be for first ultrasound and then an fix the problem, and also a pulse. That index is important and we want it to decrease less than two. And here we can see that actually the flow itself almost increased four times from the baseline.

And here is another procedure where we do have some kind of problem. The first one was really good. Again, two centimeters after proximal anastomosis, and you can see clearly that the curve is a little bit flat and also flow nine, seven. It's okay, but it's not really good. And then we do ultrasound, high frequency ultrasound, and again,  measure the flow there with the probe.

And you can see that the curve is pretty much similar a little bit. Flat and velocity is flow because we didn't see any problems in the proximal anastomosis, we made angiogram and we saw stenosis in the IAC part and made stenting to the external I artery. And after the procedure, after the stenting, the cure you saw was good after Papaverine.

Very nice reaction. And the flow increases to four times, and index also decreases below two.

We made analysis to our 700 in complete bypass graft. And divided the patients  according to the flow interterritorials. 71% of the grafts were single segment saphenous veins, and overall occlusion rate at one year was 19.6, and we could clearly see, and you can see here actually limb salvage rates were 93, 86 and 77 and survival of the patients 8 1 76 and 71 at one year.

And here you can see the proportional hazard model adjusting with graft material, and we can see significantly higher graft failure rate in the crops with the lowest territorial flow and the failure occurs during the first year and it's relative equal meter crops thereafter.

I also analyzed how Papaverine response predicts graft failure and indeed responds to  Papaverine, further predicts graft failure irrespective of the primary flow measurement. You

So yeah, transit time flow meter and high frequency, the ultrasound are used in Helsinki all areas of vascular surgery, in bypass surgery, and other lower limb revascularization procedures of open aortic surgery and also cardiac surgery. We due to 150 cardiac operations annually and this is really nice to see the flow and also the anastomosis or the patch area with HF US.

The reasons are it's quick, it's non-invasive. It gives very valuable information on the inflow and outflow as well as possible graft problems. And we use angiogram only when we suspect problems in  TTFM or HFUS, and it's, as I already told, it's less than 10% of the cases. And patent is prospective trial.

We will investigate the possible benefit of completion control with TTFM and HFUS in patients with CTI who undergo below the knee and bypass surgery. Civil Centers of excellence in Europe, USA and a CR are joining to this unique and important trial. Our aim is to create evidence. Which we use to build a clear standard for completion control after bypass surgery, and have recommendations at guidelines level to improve patient care and limb sage globally.

Thank you very much. So then I will just take the opportunity  to, of course thank our speakers and participants very much for their insightful contributions. And thank you all who has joined us here in the room today and also online. So thank you very much.