Thanks a lot, Nolan. Good morning to those of you in the U.S., including everyone here on campus at Irvine. Welcome to those of you listening from around the world on our video webcast. I'm Mark Wilterding, Vice President of Investor Relations and Treasurer here at Edwards Lifesciences. On behalf of everyone at the company, I wanna welcome you to our 2021 Investor Conference. We really appreciate you taking the time to learn more about the company today. You know, leading up to today's event, we solicited input from many of you, and the feedback we received has been incorporated into the agenda, which can be found online in the conference section. Some of you here today in Irvine.
What you'll see is that includes more physician cameos, additional product detail, more time for Q&A, and again, all of which I think will be appreciated and consistent with the feedback that you provided ahead of the meeting. For those of you online, please note the presentation slides will be available on the Edwards Investor Relations website following the conclusion of the prepared remarks and prior to the Q&A. Until then, please feel free to follow along online. Finally, I wanna take a minute just to mention the steps we've taken to ensure the safety of our in-room participants. As you can see, for those of you who are here, we are in a 10,000-sq ft conference room.
We've got plenty of space for all of you, appropriately distanced, I think, both in terms of the people in the room and on stage, as you'll see when we start getting into the presentations. Just know that the safety of our employees and our guests is paramount, and we take it very seriously. It remains a top priority. Just two additional items from me. Just take a minute to familiarize yourself with the important slide behind me. During today's events, we'll be making forward-looking statements. It's possible that actual results can differ from our expectations. The company's forward-looking statements speak only as of the date on which they are made, and the company does not undertake any obligation to update any forward-looking statement to reflect events or circumstances after the date of the statement.
For more information, please refer to our investor relations presentation and our SEC filings. We'll also discuss non-GAAP financial measures regarding our performance. Our SEC filings, along with our reconciliations of any non-GAAP financials, measures utilized to the most comparable GAAP measures are available on our website at ir.edwards.com. With that, thank you once again for your interest in Edwards Lifesciences. We really hope you enjoy today's event. With that, let me hand it over to our Chairman and CEO, Mike Mussallem, for some opening remarks. Mike?
Thanks, Mark. Let me add my warm welcome to all of you joining us here in person as well as those online. It's a real treat for us to be able to tell you our story and appreciate your sincere interest in our company. I've forgotten my little clicker here. Excuse me. We've got a lot that we're gonna cover, and we hope that you enjoy what we have prepared for you. Just to start out, one of the things that I'm most proud of is the culture of our company. We get this. We get a lot of feedback from our employees. The centerpiece of our culture is our credo. You can see it on the walls when you walk in, and you'll see it prominently displayed in all of our facilities. We talk about it.
We talk about it a lot when I visit with employee groups around the world. It's where we start the conversation. I can take you through it in detail, but it closes with the most important part, which is helping patients is our life's work, and life is now. There's an urgency to the work at Edwards Lifesciences. This focus on patient, patients is an incredible glue across this company, regardless of what kind of job you're in, whether you're sewing a heart valve or you're in one of the big R&D jobs or everything in between. It really guides us. When we go through moments of uncertainty and shock, like we did over the last couple of years with COVID, the culture shines through. I couldn't be more proud of our employees who put patients first throughout this entire thing.
We stood behind our employees, and our employees stood behind us. We're very proud of this. When in times of uncertainty, we say, "Just live the credo," it works for us. Let me take you a little bit deeper. The other part of our culture is our aspirations. We're always saying, "Well, how do we get this just right? What do we aspire to be?" We do aspire to be a global leader that transforms patients' lives through breakthrough medical technologies. I like to say that's easy to say. It's hard to do. It's inspiring for us. It's how we attract some of the best and brightest with that kind of goal in mind.
It's one of those special things that says, "You know, if I'm gonna dedicate my life to a particular endeavor, I wanna do something important with it." That's part of our aspiration. We would say we'd like to excel as a trusted partner through our distinguished quality and integrity. You know, this idea that changing the practice of medicine is a team sport, we cannot do this alone. We need to bring a lot of others along with us. To be a true trusted partner on that journey and to really be distinguished in terms of the way we behave, we think is an important aspiration for us. We wanna foster an inclusive culture where all employees have an opportunity to grow and thrive.
You know, we're pretty vast across the world, and to be able to create that kind of climate is something that we're constantly striving to do. Always opportunities for improvement on that, but Billy and Sal that we keep that right in front of us is something that's an important aspiration. We passionately, and I don't know how to use that word around our employees, passionately engage in the communities where we live and work. With the idea that we're gonna be givers to our communities, not takers. That people are gonna say, "I'm glad Edwards is in the community because they contribute more to our community than they take from it. We're a better community because of it." To try and be those kind of citizens. It fits, you know, our aspirations been around for a while.
It fits very nicely with this whole idea of what kind of a corporate citizen you are. Finally, if you get all those right, then we should deliver exceptional shareholder value. That's kind of the way we think about it, is get the other right, and the shareholder value will follow. We think it's a formula that works for us, and we continue to strive for these aspirations. Now, just to give you Edwards at a glance, if you will. We're so proud of the number of patients' lives that we get a chance to touch. We're very proud of the fact that almost everything Edwards does, we're in a global leadership position. At the center of all this is our employees. We're over 15,000 employees at this point. You might see some things there that are kind of interesting.
We got a lot of really smart technical people in this company that really helps us. We have this very cool sort of mix of very experienced people, but also many people that are newer to the company. Those of you that are on campus, maybe you saw the wall of our champions for life. These are employees that have worked for the company for 50 years or more, and it's extensive. At the same time, we have all these new young minds that are joining the company, stretching our thinking and encouraging us to dream big about what's possible in the future. It makes for a really cool dynamic, and it is global in nature and why I'm excited about what lies ahead. Now let's get into our strategy. We call it our patient-focused innovation strategy. It's different than other companies.
It starts with this idea that we're gonna pioneer breakthrough technologies. Now, pioneering breakthrough technologies sounds really great and really inspirational. It's got a lot of risk associated with it. Even the best ideas have a lot of things that can go wrong along the way. It's an inspiring kind of component to our strategy, and we think it's one that is ultimately the most valuable. We're not saying we're just gonna go. Everybody says they innovate. We're not talking about small innovations. We're talking big, bold, change the practice of medicine kind of innovations. That's core to our strategy. We also know that the practice of medicine does not change unless you show up with big evidence.
Yeah, it’s great that you have this super cool technology or new idea, but why do we know the new way is better than the old way? We know that we’re in a very long journey, and we’re gonna have to lay down evidence to get that practice to change. The other thing we say as a strategy is we like to go first. We like to be the leader. Sounds nice. Actually, it’s lower risk if you go second or third and find out what mistakes that others make. If you go first, there is no road. It’s not apparent what’s the best way to go. You don’t know where the problems are. It has struggles and challenges and risks associated with it. The other thing that goes along with it is you learn fast.
You learn faster than anybody else, and you're also in the room with the other future decision-makers about how to shape that future course of medical care. Being part of that decision-making process with other thought leaders, and actually setting the course is something that we consider a valuable part of our strategy. How do we manage all that risk associated with pioneering breakthroughs and going first? It's by staying focused. We believe that there are big unmet needs within the patients that we serve. If we stay singularly focused on those unmet needs, then we can excel at this. We think that if we were to diversify and to go into other areas, we wouldn't be nearly as capable of doing these bold innovations and going first. That's how the strategy comes together.
We believe that there are large numbers of patients that can be helped. If we say, "Oh, boy, maybe that limits the opportunity," we don't think so. We're just scratching the surface in terms of the number of patients we actually reach today. We think this is a robust strategy. It's been our strategy for a while, and we have no reason to think this isn't gonna be a very valuable strategy as we move ahead. Just to look backwards on whether it's delivered results, it's done okay. Now, the key is that there's a group of patients that need our innovations, and we're gonna talk about that more today. It is a large number. We're only reaching a small percentage of the patients that could be helped. What we strive to do are these triple wins, right?
Just think if you could have a new therapy that extended life and was a better quality of life and saved the system money. Now that's a winner. That's the triple win. That's what we constantly strive to do, and we get that right, we get an opportunity to ring the bell. It also gives you a sense for what kind of long-term planners we need to be. When we start on a journey, it's gonna take us years. There's no question in our mind, the reason that we're having a success in 2021 is because of the seeds that were planted years and years ago, right? Some a few years ago, some many years ago. The reason we're gonna be successful in the future is the seeds that we're planting today.
It's the nature of our strategy and why we feel so confident in this as we move ahead. We're gonna talk about a number of things at the conference. We feel proud that we're delivering results in 2021, and we'll go deeper on that. We think 2022 is gonna be an exciting year of achievement, and not just the numbers, but in the milestones we achieve. We're gonna talk about how big we think this opportunity is and that it's only getting larger. Finally, you'll get a chance to observe Edwards' leadership team, where I'm very proud of. You'll get a chance to hear from a number of those during the course of the day.
Just to reflect on 2021, it's gonna be a year of significant sales growth and earnings growth, and we're pleased to be able to deliver that. I'm also proud to say that we feel like each one of our four businesses got stronger, and exited 2021 stronger than we entered it. We stayed focused on driving the business. Our employees were incredibly dedicated throughout the course of the year, whether it was people that went into hospitals every day or people in our global supply chain, they just showed up and got things done. They achieved their milestones.
Across the board, whether it was continued expansion in TAVR or the transformation of technology that's going on in critical care or surgical, moving people to much higher quality premium products than ever before or the bold agenda of TMTT, we made progress on all those. While we had a nice year of earnings, what I was pleased of is we made big investments in our future. On the R&D side, on the infrastructure side, we invested big because we plan to have a bright future, and we think we're set up well, and we'll talk more about this as we move ahead. There we go. 2022 is gonna be a year that we're also gonna not only deliver double-digit sales and earnings growth, but deliver on a lot of important milestones.
We've got a lot of plans for ourselves, whether it's what's gonna happen in TAVR pursuing these big, bold expansions of treatment, the new therapies that you're gonna see in TMTT, innovations that are just starting to roll out in surgical and critical care also are compelling. We'll talk much more about each of those, but we think 2022 is not only gonna be a compelling year where we repeatedly have new launches, we have new data sets that are presented, we have regulatory accomplishments along the way that all set us up for the future that is equally bright. Now when we look ahead, we talked about this idea that there's a large group of underserved patients. We really believe that this is gonna grow significantly as we move ahead.
If we look at the markets that Edwards serves today, it's probably around $10 billion. By 2028, we think that'll approximately double. It's because each one of our businesses have an opportunity to serve people that are not served today. Big one there is gonna be the continued expansion of transcatheter aortic valve therapy. We think although it's been fantastic in the past, we're not nearly where we could be and should be with the treatment of this progressive and deadly disease. TMTT, we're just scratching the surface. These patients really have not had solutions in the past, and this counts on the fact that we're gonna be successful with many of our innovations and be able to treat them.
In surgical and critical care, we know that we can deliver better care than we ever have in the past, and we've got really exciting bold innovations to be able to do that. You look ahead and say, "Yeah, it's been a nice run, but what's the future look like?" We feel like we're just getting started. This is why I have so much confidence about the future and why I'm just pumped about what's ahead. Here's what our agenda looks like. You're gonna get a chance to hear from each of our leaders of the global business. Larry Wood in TAVR, Daveen in surgical structural heart, Bernard in transcatheter, Michael in tricuspid, Katie in critical care.
Scott will update you on our financial outlook, and then we'll close it out and have a chance for a robust Q&A at the end of the conference, and we'll take plenty of time for that. With that, I just thought that I didn't wanna close here without introducing Edwards' executive leadership team. This is a group of subject matter experts. I've been doing this for a long time. I've never been around a team more talented and more dedicated than this group. These folks are each world-class in terms of what they do, and it's a highly collaborative, real team that works together. We have fun together, and hopefully you get a chance to see that yourself. We're highly aligned, and when shareholder wins, our team wins as well.
That's the way we look at it, and we're motivated to be successful as a team every day. You're gonna hear from a number of speakers, but I'd also ask some people in the audience that aren't gonna be speaking. Would each of the members of the executive leadership team please stand? If you get a chance to bump into any of these folks and have a conversation with them, please do. All right. With that, we're gonna start the real meat of the presentation. It's my pleasure to introduce Larry Wood. Larry has been part of creating transcatheter aortic valve therapy from the very beginning, and he and his team have done a remarkable job, and I know that you're gonna love hearing from him, and we all love working with him.
Just to start it out, we're gonna show a little video that highlights where we've come from.
A huge breakthrough for heart patients. In fact, Dr. Oz says for cardiologists, it's the equivalent of putting a man on the moon. It's on the order of what penicillin did for infectious disease. The most revolutionary thing in heart surgery, in the 27 years I've been in practice.
This is a historic moment, and all of us here should recognize it as such. We're gonna remember it. We're gonna talk to our grandchildren, great-grandchildren, that we were there at the time these incredible advances in the care of patients with aortic stenosis was presented. Congratulations.
Since this new valve, my life has turned around completely.
The day I got out, I went to my daughter's basketball game. Just amazing.
After two months, I've been hiking in the Himalayan mountains.
I am alive, and I feel 100% better.
When we were talking before, I said to Marty, "Well, the PARTNER era is over." Marty smiled and turned to me and said-
The TAVR era has just begun.
Wow. All right. I still get chills when I hear Eugene Braunwald talk about advances in patients, so it's exciting. You know, it's been 10 years since we launched TAVR in the United States, and it is a big milestone, and it's a great time to reflect back and look at where we started. When we started, we had a 24 French device. About half of our procedures were done transcatheterically, which is really the surgical procedure. You look at the outcomes, and they were really impressive, but we were working on strictly inoperable patients when we first got started. To the point where we are with TAVR 3 now, it's about 93% of our patients are done transfemorally, and even patients that are done transfemorally often can get an interventional approach to having this done.
The number of patients that require surgery is actually quite small now. It's an amazing advancement with over 600,000 patients treated. If you look at the data where we are today, this is a PARTNER 1 trial, which is obviously very few patients, and this is the PARTNER 3 trial. It's impressive how far the data's come. What was more impressive is those are the 30-day results versus the one-year outcomes in PARTNER 3. In PARTNER 3, 99% of the patients were one and well at a year, and they were average age of 63 years old at the time of their procedure. It's been a remarkable journey to see how far this technology has advanced, and it's advanced in ways that are really meaningful. The mortality rate has steadily fallen. Stroke rate has steadily fallen. Paravalvular leakage has consistently gotten better.
Remember, we started in about 20 hospitals in the United States in the original PARTNER trial, and we've expanded now to about 850 hospitals. There was a lot of concern for, especially from the medical societies and from the physician community, as you expanded, you would actually see the results degrade. You'd see all of these results get worse because you'd have less skilled centers and people with less experience and do less volume. What we've been able to show is, you know, we can take this technology, we can take it to these hospitals, and we can continue to deliver these outstanding results, which is huge because it improves access for patients.
Now we're seeing SAPIEN 3 valve. We've taken millimeter precision to get paravalvular leak down to less than 1%, and that now accounts for about 92% of our sales globally. Big advancements that we've done and that we're very, very proud of. Other things that really, really matter that we don't talk about as much. Median procedure time now is under an hour. It's about 45 minutes. Next day discharge is about 80% of our patients go home the next day after having their aortic valve replaced, and that was something that was unthinkable a decade ago. 96% of our patients are discharged home, and this is actually a huge issue.
One of the things that when we talk to patients, you know, we focus so much in our world on mortality and stroke and these hard critical endpoints, but when you talk to patients, living independently is one of the most critical things. They're scared about undergoing some procedure and not going back home. They're scared that they're gonna end up in a nursing home, and then they'll never get back out of there. The fact that 96% of our patients went home to the home they came from is a really big deal. The fact that they did it in a day and they're up and moving around is amazing. I gotta say, this has been such a multifactorial win. Some of it's the technology for sure. The technology's advanced and that's gotten better.
The way that physicians have trained on this procedure, the way that they've disseminated it, the way that they've shared best practices across the community, the way that regulators have engaged and really enabled a lot of these things to happen, it's really been a win for everybody in this ecosystem. I couldn't be more proud of our teams, also the clinicians that we interact with, and frankly, the regulators that we've interacted with that's made this all possible, because if any part of that stakeholder group wasn't on board, I don't think we have these kind of outcomes, and we have these kind of results. I think one of the things that's most remarkable though is this is a study that recently came out that talked about the impact of TAVR on patients.
Basically what it showed was the life expectancy of patients with aortic stenosis has almost doubled during this TAVR era. That's because more patients are able to get treated, and they're getting spectacular outcomes. When you think about the impact on society for doing that, it's a really big deal. Now, the question that always comes up, though, is the cost to me of this. Does this make sense? There was a lot about that. I will tell you that a lot of people thought, well, yeah, maybe in the really high risk patients, but when you get into low risk patients, those patients tend to do really well from surgery. They tend to have shorter lengths of stay. It can be very difficult for you to demonstrate that this is a cost-effective procedure.
We have this data come out at ACC, and it showed we end up in the dominant quadrant, meaning the outcomes are actually better and it saves the system money. It's very rare for new technologies to land in that quadrant. Usually new technologies, they help more people, and it's great, but they also cost more money. In this case, we actually help people. We can save the system money. It's really, really a huge win. Where do we go from here? When we think about our next generation TAVR platforms, we think about optimizing valve sizing, especially in complex cases, right? That's something that we think about a lot. Expanding durability. Durability has become a bigger and bigger issue. When we were treating 83-year-olds, we didn't think as much about durability. I think Dr. Thomas put it somewhat eloquently last night.
We worry about getting them off the table. We worry about getting them out of the cath lab. That's really where long-term durability starts, is getting them out of the room. Now we're treating patients who are in their 60s. We're treating hypertensive patients. We're treating much younger patients. The durability is really, really important. Paravalvular leak. You know, while we see significant paravalvular leak less often, we still see some of it, and I think we can do better. I think we can further reduce that even from what we've done on Ultra. The other thing is sort of this lifetime management issue, which is to further enhance future coronary access. When we were treating 80-year-olds, coronary disease was probably behind them. It was probably something that was in their past.
Now, when we're treating patients in their sixties, coronary disease could very well be in front of them, which means that we fix their aortic stenosis, but we take away future options. That's not a good option for these patients. We have to make sure that we preserve all of their options for the future. It really is about this lifetime management of this patient. As it relates to that, I think we're just getting started. I think there's so much innovation that we can still apply to that. When you look at our portfolio, we have our SAPIEN 3 platform. We have our SAPIEN 3 Ultra platform, which again is about 93% of our sales globally. We have our SAPIEN X4 valve, and we're getting ready to start the Alliance trial.
We expect the IDE approval before the end of the year, and that's going to enable us to begin that trial, and we'll begin enrollment next year. We're very excited about that platform. It's going to have our RESILIA tissue on it, so we think that that's going to be a big enhancement as it relates to durability. It also has a number of other features that we think are going to be very important for clinicians and patients. We always have future platforms in development. We have at least one, usually two future platforms in development at any given time. It takes years to develop these platforms and do all the work that's necessary. As Mike said, our success five years from now is based on what we do today, not what we do five years from now.
Making sure we always have these platforms in development is huge. We have a short video here of two of our physicians, Tamim and Dr. Rahul Sharma, and they're going to talk a little bit about the X4 valves and the Alliance trial that we're getting ready to run.
TAVR has really evolved from a niche procedure that we only deployed in the higher risk or inoperable patients to a procedure that we use on a routine basis, even in younger, lower-risk patients. We've moved from a focus on immediate procedural complications to more long-term issues that are important in the lifetime management of these patients.
I think the X4 poses an opportunity to further improve upon already excellent clinical outcomes. We're looking at further reducing the rates of paravalvular leak from mild to trace or none. When we look at further reducing the rates of permanent pacemaker implantation, when we look at improving and optimizing coronary reaccess even further than the platform today allows us to. When we look at future durability and valve durability as we treat these younger and lower-risk patients.
It addresses some of these long-term challenges. There are enhancements that really focus on hemodynamic and durability, things like valve sizing, so that we can size the right valve for the patient every time. The ability to allow for future procedures, things like coronary reaccess and valve in valve procedures.
I think that the Alliance trial and the SAPIEN X4 platform is really the first step towards evaluating personalized precision medicine. I hope that the trial will be able to shed light on how we can best optimize that index procedure, how we can maintain coronary access in these patients who are younger and lower risk, who are likely to develop coronary-related issues in the future. How do we extend the longevity and the durability of the valve, and how do we future-proof these patients for a potential future valve in the valve procedure?
To me, this is an important step forward that will allow us to bring this new technology to our patients.
We talk a lot about how much younger our patients get, but look how much younger our principal investigators have gotten. It's really exciting. We're excited to get this trial started. We expect to get approval before the end of the year, and we'll start that trial next year. Switching gears a little bit from technology to talk about the disease. The way we treat aortic stenosis is different than how we treat any other disease. Philippe Généreux first started talking to me about this. The first person I heard talk about it. Just think about how we treat cancer. Think about in your own personal lives when you meet someone or you hear about someone, and they say they have cancer. The first question you ask is what stage?
They say stage two, and you say, "Oh, that's good news. You caught it early. You can do things about it." Somebody says, "Oh, stage four." You say, "Oh, that's not so great. That's really not good." Aortic stenosis, by the way we approach it, we only go after stage four. We wait till it gets to stage four before we even think about doing anything about it. But even that's not enough. It has to be stage four, and you have to start feeling bad before we're willing to do anything about it. That's what the guidelines say. All of the work we've done, all three PARTNER trials, all the work we've done in the last 20 years in this space has all been focused on, in essence, what is stage four.
It's that end-stage aortic stenosis disease when the person's already at that severe level and they feel bad from the disease. That's where we've been spending all of our time. We just have to say, does that still make sense? One of the questions is how did we get here? Why did we wait so long to treat aortic stenosis? On the surface, it doesn't seem to make sense. Part of the reason is the procedure was open-heart surgery. Patients are concerned about having open-heart surgery. Another key factor in it, though, is the difference between getting a mechanical valve or a tissue valve. If you get a mechanical valve, you're gonna be Coumadin. If you take Coumadin, it's going to restrict your lifestyle, and you're not going to be able to do all the things you used to do.
A lot of patients tried to wait, and they wanted to get a tissue valve. They wanted to wait as long as they could get it in the hopes that the tissue valve would outlive them. Because if a tissue valve failed at any point, the only way to fix it was a second open-heart surgical procedure. If patients don't want to have one, they certainly don't want to have two. It created this whole scheme, basically, of waiting as long as possible before you get intervention, waiting till the disease is severe, and waiting till you feel really sick. We're just not sure in a modern TAVR era that that still makes sense. When you look at our PARTNER 3 data, 99% of our patients are alive and well at a year.
80% of the patients come next day, they're being discharged home. Does it really make sense? Is it really benign? Is it really benign that you can go from this moderate disease to severe and not do damage for the rest of your heart? We don't think it is. We think you're doing damage to your heart during that period of time, much the same way cancer does damage to your body when you're moving from stage two to stage three or to stage four. We also have this unique ability to do a TAVR procedure. If you get a tissue valve and it fails at some point down the road, it's not a surgery to replace it. It's a second interventional procedure.
We think that this lead opens the door to think about this disease very differently and to treat it very differently. To do that, we're gonna have to bring the evidence. To change guidelines and to change really 60 years of clinical practice, we're gonna have to develop the evidence. I will tell you, when we went to power this trial for EARLY TAVR, and we reviewed all the literature. Yes, we can make estimates about what percentage of the population is asymptomatic. I will tell you there's no great studies on this because everybody approaches it a slightly different way. Even this issue of symptoms is really hard to ascertain. Patients, as Dr. Thomas said last night, a patient said he was asymptomatic, but he doesn't walk to the pub anymore. Living within your symptoms doesn't mean you don't have symptoms.
It just means you've adapted your lifestyle to where you don't really have them. A lot of patients say they're asymptomatic, but if you really tested them or you really had them walk uphill, they actually would have symptoms. One of the things that we're gonna learn from this trial is what percentage of patients are truly asymptomatic. When subjected to a protocolized stress echo, what percentage of patients are truly asymptomatic? We'll definitively be able to answer that question. We'll also be able to answer the question, how fast does it progress? Can somebody stay asymptomatic for three or four years and nothing bad happens to them? Or did they progress much more quickly than that? For the first time, when this data is available, we'll be able to answer that question. We'll also understand what damage happened during that asymptomatic period.
During that asymptomatic period, did something bad happen to their heart? This trial, we completed enrollment in this recently, which was a huge trial still for the team. I think we all understand how difficult it was to enroll trials, especially in this COVID environment. I'm just proud that the team had a role on that. It's a randomized trial. It has a two-year endpoint. All we do now is we wait for the patients to come to their two-year endpoint. I've gotten the question a lot. I'll just answer it now. People say, "Well, is there any chance you're gonna get to look at that data sooner?" We do not expect to look at that data sooner. When we designed this trial, we committed to the endpoint timeframe.
The most important thing is that we have a high-quality study, and if that's gonna take a little more time, then we think it's worth it. We think two years was the right timeframe for that study. To talk a little bit more about Early TAVR and kind of the basis for it, I have Philippe here, who really is a world expert in this and has really been a leader in thinking about how we should treat this disease.
The current guidelines recommend aortic valve replacement or surgical aortic valve replacement only if you have either symptoms or signs of heart failure or cardiac damage. One of the problems that we've seen often with patients is it's difficult to elicit symptoms from patients. On the other hand, patients sometimes really have difficulty to describe to the doctors in terms of symptoms of fainting or symptoms of repositioning and symptoms of heart failure or aortic stenosis. Really the rationale of the EARLY TAVR trial is to determine if there's a role for TAVR, either by SAPIEN platform compared to medical surveillance in improving outcome of patients, but also in preventing the onset of the cardiac events. The question is, why are we doing this now?
Before, the only option was open heart surgery, which was pretty aggressive and invasive, and patients with no symptoms were rarely considered this approach because of the invasiveness of the procedure. The less invasive approach with TAVR allowed us to push boundaries and to try to come to helping patients before they became completely symptomatic or before there's sign of cardiac damage. The EARLY TAVR trial could really be a game changer and a revolution to the management of patients with severe AS who come to us. The EARLY TAVR trial will try to investigate whether early intervention with TAVR could be beneficial for patients compared to medical and closer surveillance.
Even with that trial, though, we're still dealing with severe disease. We're still dealing with this stage four. We're still waiting for the disease at that severe point before we do anything. We're just asking the question, can we take this whole symptom assessment thing out of the equation and just focus on the hemodynamic results of the patient rather than having to do this whole gymnastics around symptoms. The next step in that process is really to look at moderate disease and does it make sense to let the disease progress from this moderate stage to the severe stage? We think with TAVR and the results that we have now, we're now enabled to go study this in a high quality way and say whether this makes sense. There's a large study that was done, primarily in Australia from Dr.
Chang, who we had speak a couple of years ago, I think, at our investor conference. What he showed in a population study that he did is, at least directionally, it appears that moderate patients have a trajectory that's more similar to severe patients than they are to mild patients. If that, in fact, turns out to be true, then moderate disease really isn't benign, and we probably shouldn't be waiting for it to progress. We're embarking on the PROGRESS trial. We got approval for this trial earlier this year. We've already started enrollment in this trial. Again, it's another randomized trial. It's 750 patients.
It's gonna take us some time to enroll, but we're going to do for the first time ever really understand what happens to people when they progress from moderate to severe, how fast do they progress from moderate to severe, and what damage is getting into the heart during that period of time. This trial is definitively going to answer those questions, and we're pretty excited about it. I asked Dr. Généreux here to talk a little bit about that trial and what he thinks that'll mean for patients.
Regarding moderate AS, there's not really any indication for aortic valve replacement. On the other hand, if you need another type of open heart surgery, you're entitled to replace the aortic valve. The rationale of the PROGRESS trial is really to challenge this paradigm related to this cut-off of severe AS, AVA less than 1, and really, is there a patient that maybe doesn't need to get severe aortic stenosis with an aortic valve area less than 1 and is labeled as moderate but could benefit from early intervention, especially if you use a TAVR platform which has excellent outcome. I would say that, with all the learning of the PARTNER trial, we realized that we probably intervene too late in the process of the disease.
We wait for patients who have either symptoms, who have heart dysfunction, who have other diseases associated. It may be the time to see this disease as, we said, the cancer of the heart. We all know that when you have a cancer, you don't wait for expansion of the disease, you don't wait for symptoms. You really preventively remove the cancer. The advantage of TAVR technology at this time for us maybe is that ideology to see this disease as progressive and deadly disease. Both the EARLY TAVR trial and the PROGRESS trial give us the opportunity to really better define the optimal timing of intervention, whether it is based on symptoms or not, or whether it's based on the evidence of cardiac damage for any given level of aortic stenosis severity.
We're super excited about these trials. What's gonna be nice is at the end of these studies when we have all this data, this is a body of evidence we're gonna have around aortic stenosis that just completely doesn't exist today. Between our series of PARTNER trials, which looked at everything from a risk level perspective, to our EARLY TAVR trial, where we'll be able to really understand symptoms and progression to the moderate AS trial, where we'll be able to understand the progression from moderate to severe, we're gonna be able to combine all that data together, and we should really be able to understand when is the optimal time to intervene for any given patient. It may not be the same for every patient. We really just get into this personalized precision medicine that we should be able to deliver.
This body of evidence is great capabilities to really understand that at a level that we've never understood it before. That's one of the things that's really exciting. Now, in terms of how many moderate patients are out there, we believe there's 2 moderate patients, moderate AS patients, out there for every severe patient that's out there. Now, that doesn't mean every one of them should get an intervention, and we need to run the trial to prove when the right time to intervene is. It's a large population of patients. If moderate disease really is doing damage to the heart, then it represents a significant opportunity. Last year we talked about a lot of milestones at our investor conference, a lot of good things.
We were kind of expecting last year that COVID was gonna be kind of in the rearview mirror by this time. Clearly that didn't really happen. You know, we dealt with COVID just longer than we expected. I gotta tell you, I couldn't be more proud of our team. We put some big milestones out there last year. Getting the low-risk approval in Japan and getting reimbursement for that. Enrolling the EARLY TAVR trial, the PROGRESS trial, getting that trial approved by the FDA and getting it started. Getting the IDE for the X4, which we expect to have before year-end, and the Alterra prestent for our congenital patients. We also expect to have that PMA approval before the end of the year.
I can't say enough about how well our team executed in a very, very difficult environment to meet milestones that are really, really important for the patients we serve. Very exciting. I'm very proud of the team. Now, we've talked a lot about how do we get patients off the sideline. We only take about 1 in 10 severe aortic stenosis patients each treatment day, and we know it's a struggle to get them off the sideline. Frankly, COVID did not make this easier. Patients were told to stay home, especially if they were compromised, and almost all aortic stenosis patients are immunocompromised. We've taken a unique step now where for the first time ever, we decided to go that next step and go a little bit direct to consumer.
We created a commercial to try to go direct to patients, and we'll play that for you now.
Andy, is everything okay?
I just found out I have aortic stenosis, and I need to have open heart surgery.
Andy, I'm sorry. I had severe aortic stenosis. I had TAVR. It doesn't require open heart surgery. Most people go home the next day to have their valve replaced, and I never missed our weekly golf date.
I had no idea. I'm gonna call my doctor and ask him about TAVR.
Order your free TAVR information kit at justgettingstarted.com.
No, it's not branded. It's not a heavy sell on SAPIEN 3. It's not any of those things. We get asked a lot, why do we wait so long to do anything direct to consumer? A couple of reasons. One, not inexpensive, but a much bigger reason is we have just deep respect for the physician-patient relationship. Stepping in the middle of that is something that you don't take on lightly. That's why the whole point of this is really to make patients aware this is another option and for them to ask their physician about it and to reengage that conversation. We're just trying to give patients the knowledge so that they know to ask their doctor about it and just know that the option exists. We believe the fundamentals of TAVR remain really strong.
We see the global TAVR opportunity by 2028 to be around $10 billion. We continue to see this opportunity grow. More importantly, we think there's growth drivers beyond that horizon. When we think of the PROGRESS trial, the Moderate AS trial, that probably doesn't hit in that 2028 window, just because the sheer endpoint and the time it's going to take to enroll. We think that this opportunity has legs well beyond that, and we do see this as being a $10 billion opportunity by 2028. If we turn to 2022, you know, we picture our growth to be in that 12%-15% range. The headwinds, you know, overall healthcare spending, there's always pressure on that.
The COVID recovery, there's still some uncertainty there as it relates to variants, and we're expecting that to stabilize largely. We think the benefits of TAVR are really strong, and we think they really showed strong during COVID with the next-day discharge and the other things that we're able to do. We think those groups remain strong. We were just getting started with low risk in a lot of markets. We think that that continues, especially as COVID begins to wane, and we get back to a little bit more business as usual. We're very excited about our future. With that, I'm gonna turn it over to my good friend, Daveen Chopra. He runs our surgical structural heart business.
He's a great partner for me, and we have a short video to play on his surgical business unit, and then he'll participate and talk about it. Thank you very much.
A lot of patients go and see a surgeon, and they say, "You are having mechanical valve because you are 30 times. Period." They come crying to me saying, "I do not want a life on warfarin." They want to do contact sports. They want to go skiing. They want to do activities where warfarin would be dangerous.
You okay?
The development of RESILIA tissue has created an extreme amount of confidence in our utilization of bioprosthetic valves in surgical patients. I've always been impressed by Edwards' focus on developing products that not only improves patients' quality of life but extends their lives. That's what's important to us as surgeons.
Tissue valves are here to dominate, and the more durable they are and the lower risk and less invasively we can put them in, the more they're here to stay.
Good morning. It is a real pleasure to be here with you all, talking a little bit about the surgical business. My name is Daveen Chopra. As you heard in the video from Doctors Ackland and Young, surgical patients are looking for the best technologies out there. Here at Edwards Surgical Structural Heart, we continue to really understand the unmet needs of those surgical patients and invent the life-saving technologies that are critical all the time while partnering with the cardiac surgeon. If you start off by first looking at our overall market, we believe that the surgical structural heart market will grow in the mid-single digits to over $2 billion in 2028. What's driving this is a couple different things. First, we see that across the world we know that patients are generally aging.
In emerging markets, we see increased access to both wealth and awareness of the disease that's helping this tailwind. We saw that during COVID, these life-saving surgeries were prioritized generally across the world. Additionally, we see a big tailwind, as Larry talked about, coming from structural heart disease awareness, diagnosis, and referral to heart team overall. With that, as patients get to the heart team, there is a certain number of those patients that are best treated surgically. Those patients include patients that are the younger, more active patients whose anatomy or etiology requires a surgical treatment, and those patients with heterogeneous disease, which when you have to do your surgery, you're treating more than one thing at that time in your heart. We hear from patients all the time that the unmet need they have is to live longer and live a better life.
For us, we think we've helped do that with our transformational innovation, the RESILIA tissue. This is a tissue in a technology that we think has an opportunity to help patients all around the world. What is the RESILIA tissue? We see that the major way that valves deteriorate over time, tissue valves deteriorate over time is through calcification. What happens is there are gradual increase in calcification as patients get older. What RESILIA does is that, especially if there is not a pathway mechanism, it effectively stops the formation of that pathway so that calcification never occurs. This is a technology that's actually taken a long time to invent. It didn't happen overnight. We actually started the technological development of this 17 years ago. We started the pre-market human clinical trials now over 10 years ago.
Now in the post-market, we have undertaken over 10 post-market studies that are planning to enroll nearly 5,000 patients to really continue to get that large body of evidence for RESILIA. The data we've seen so far has been impressive. If you look at the two pre-market studies, we enrolled over 800 patients. We now have five-year follow-up with those patients. Those patients had zero structural valve deterioration or SVD at 5 years. A great sign about the promise of RESILIA. With this information, we now see RESILIA tissue as an evolution of previous leaflet materials. We've taken this RESILIA tissue and now built three different surgical valve platforms across the aorta and the mitral.
What the RESILIA tissue does with these platforms is it really allows patients to thrive without the quality of life compromises that usually come from having a mechanical valve and its lifelong Coumadin that comes along with it. We've actually seen very strong physician preference to this value proposition and actually very strong patient preference to this value proposition. It's best to demonstrate this value proposition of RESILIA and the INSPIRIS product to actually share the story of Jake Anderson. Jake's the epitome of that patient and what a surgical AVR patient wants to get from their valve. He's late 30s, Jake's a rock climber, a dedicated father, a former nationally ranked swimmer. When his cardiologist recommended a surgical valve replacement, picking the right valve actually makes all the difference. Let's hear Jake's story.
The cardiologist said, "You have a bicuspid aortic valve with stenosis. You have an aortic aneurysm, and you will need an open heart surgery.
I stayed up all night reading everything I could get my hands on. What I learned about valves was that with mechanicals, you're less likely to have another surgery.
I would be on blood thinners. That would have meant the end of the hardcore Jake, the Jake who is not afraid to take risks. I was gonna have to really rethink who and what I was.
The INSPIRIS RESILIA valve is a tissue valve that is going to last much longer.
The possibility that the next valve that I need will simply be replaced using a transcatheter procedure. It seemed absolutely to be the game changer that I needed. When I woke up, the first words that Rosa said to me were, "You have a perfect heart." I then said to her, "I can breathe.
24 hours later, Jake is able to stand up on his own, and he's got people laughing in the ICU.
As soon as I could, I got in the water at six weeks and was swimming again. Today, I feel better than I did in my twenties. You know me, the guy who just had heart surgery. My life is defined by my ability to be in the outdoors and be athletic. Now I look at my life with a limitless possibility.
What a great story of Jake that touches your heart. I love how the RESILIA tissue and the INSPIRIS valve he had helped him get back to his outstanding quality of life. As I said, Jake received the INSPIRIS valve, which was the catalyst into RESILIA tissue for our two other RESILIA platforms as well that I'll talk about. For us today, INSPIRIS is the leading surgical aortic valve globally. In addition to having RESILIA tissue, you heard that it also has this VFIT technology. What the VFIT technology means is that if in the future you need to have another valve procedure and you want to then have a transcatheter valve-in-valve procedure, you can actually expand the surgical valve with a transcatheter valve to allow you to get the largest possible transcatheter valve in the patient to meet the best possible clinical outcome.
It's an amazing feature that helps really line you up in case you need that second procedure in the future. Our second RESILIA technology is our KONECT, which is the first and only ready to implant a tissue aortic valve conduit. This is really for patients who need not only aortic valve replacement, but also aortic root replacement. This is a very complex procedure. It's one of those procedures you don't wanna have, and the patients unfortunately don't have the transcatheter option. However, this is a subsection of the overall surgical AVR market, which continues to grow very quickly. Actually, nearly double-digit growth in this subsection of the market growth in the U.S. We launched this product in 2020 in the U.S., and we've seen physicians have a very rapid uptake of this very exciting innovation.
What we're hearing from physicians is that this product really helps streamline their procedures. What I mean by that is previously before they'd have this product, they had to take several different products off the shelf and almost help create their own product in the operating room while the patient is on pump. With this product, they're able to reduce the time on pump, streamline the procedure, and really help to make it a better patient outcome. It's been a very exciting product for both physicians as well as for patients. Our third RESILIA product is our MITRIS mitral valve, which is really designed to improve durability with higher pressure mitral valve. We really believe that this product successfully has that improved durability and has increased ease of use.
We actually got a chance to launch this product in the first market in the world of Japan in 2021. We got a chance to work very closely with the Japanese market to actually get Japanese approval first for this product, which is awesome feat. Within six months after launch, this is the leading surgical mitral valve already in Japan. With this exciting clinical result we're seeing so far in Japan, we're excited to launch this product in the U.S. in 2022. This is actually a big long-term growth opportunity. If you look globally right now at the mitral valve, nearly 60% of the world's surgical mitral valves are mechanical. So for patients, this offers an amazing opportunity. If you look overall at the emerging markets, we believe there's actually a great opportunity for surgery in the emerging markets.
As we know, as emerging markets continue to grow in wealth, we see that countries continue to want to spend a greater % of their GDP on health care. Patients continue to want to look for better solutions. As a result of that, we see that cardiac surgery procedures are actually continuing to grow at a much faster rate in emerging markets. We see that patients and physicians who would have primarily put in mechanical valves, if that's what's been available, are now looking for more premium innovations and are often looking to the Edwards premium tissue innovation as an upgrade to patient care. For us, we see a great opportunity in emerging markets. Moving for a second beyond actually the valve replacement market, I'm going to talk about surgical mitral repair for just one minute.
Surgical mitral repair right now is the standard of care for the low risk degenerative MR patient, where physicians put in an annuloplasty ring surgically. This is a group of patients, again, the low risk degenerative MR patients, that we think will continue to be surgical for many years in the future, and it's actually continuing to grow in overall numbers. It's one of those areas where if you can do the surgery well, you can actually get the patient back on their normal life expectancy. It's amazing. It's awesome for patients. However, we've seen that even in the best centers in the world, having consistent results is very hard to do. We see that as an opportunity for Edwards.
How do we continue to bring new innovation in the surgical mitral repair market where patients can get consistent results no matter what physician they go to or where in the world that they go? For that, we've actually invested in two different technologies in this space. One of them is the HARPOON beating heart mitral valve repair technology that's done transapically in a very minimally invasive approach for a subsection of those DMR patients. Additionally, we're in the development stage of a mitral adjustable repair system that actually allows you both on and off pump adjustability in size of the mitral product. It allows you to maximize mitral valve coaptation for the best possible results. We think these are great two future opportunities that we're working on for the surgical mitral repair patient.
If you move forward to 2022, we see that we continue to be excited about what's going to happen. We see headwinds of continued TAVR conversion, especially in those developed markets. As Larry talked about, we're always thinking about COVID recovery and how the world is changing, different variants, et cetera. We see some really exciting tailwinds where we see that the opportunity for continued adoption of our RESILIA products is a great tailwind potentially for us, along with this continued mechanical to tissue conversion that I talked about. For us in 2022, we're forecasting underlying growth rates in the mid-single digits and a total revenue range of $870 million-$950 million. In conclusion, we still continue to believe that the surgical structural heart markets will grow mid-single digits for many years in the future.
This includes growth in the surgical AVR market. For us in 2022, we are super excited about adoption of our transformative innovation with RESILIA. As you look to the future, even beyond RESILIA, we see there's a lot of opportunities to identify the unmet needs in cardiac surgeon patients and invest in life-saving technology. Thank you so much. I'm very excited next to actually call out one of my colleagues, Bernard Zovighian, from our TMTT. He's going to tell you all the exciting things going on in TMTT, and it's been a real pleasure to work with Bernard all the time. As he comes on stage, let's learn a little bit about the TMTT business.
Good morning. This video is a great recap to show, you know, how fortunate I feel about being able to build upon the very rich history of Edwards Lifesciences. You know, bringing us years of experience in surgical, about 10 years or more, you know, in the transcatheter world to mitral and tricuspid. You know, I feel like, you know, this is, you know, putting us in a very unique position to be able to achieve our vision to transform, you know, patient care. Indeed, you know, there are so many patients in need. You know, this disease, you know, mitral and tricuspid is very prevalent.
You know, for instance, in the U.S., there are more than 4 million, you know, patients, and only a very small percentage of these patients are treated today, less than 2%. These patients are sharing, you know, some similarities with the aortic patients, but not necessarily all of them. Now think about it. What's similar to aortic patient is they have a very poor quality of life. You know, there is a high mortality rate at 1 year, you know, between 20% and 40% between MR and TR. Unlike aortic patients, they are clinically diverse, and this is why, you know, we believe, you know, we need a portfolio to treat all of these patients.
By implementing our strategy, our broad strategy, our, you know, comprehensive, you know, strategy to treat all of these patients, we expect this opportunity to grow from what it is to today, you know, $1 billion globally to $5 billion in 2028. If you look at this number, you know, $5 million might sound, you know, a big number, but $5 billion is also only about, you know, a 5% adoption. We believe there are huge opportunity to grow beyond, you know, 2028. If you step back, you know, it is truly, you know, the reason why we are making bold investments in TMTT, you know, to change, you know, patient care, to change, you know, the practice of medicine, the same way we did it with TAVR in the last, you know, 10 years.
If by doing so, you know, we will also, you know, for sure, you know, be a major growth driver for the company in the years to come. Now, when you have, you know, such a bold vision, you need. It is very important to define how you are going to execute your plan. For us, you know, in TMTT it is about a couple of things. One is about, you know, focusing on three key drivers of success, having a differentiated portfolio, bringing world-class evidence, you know, to change the guidelines to equip, you know, physicians to treat the patients, and being able to achieve the real world outcome, you know, a favorable one, a great one. So that's one. The second one is being able to focus short-term and long-term.
Yeah, I have to tell you know, 2021, it gave me great confidence. We achieved already, or we are on track to achieve everything we committed to in 2021. Let me give you know, some highlights. We are on track to complete, you know, the enrollment of the CLASP IID trial by the end of the year this year. This puts us on track for a late 2022 U.S. approval for the DMR patient population. We completed the enrollment of a TRISCEND study with EVOQUE tricuspid, and this is going to give us, you know, all of the evidence to be able to achieve a late 2022 approval for EVOQUE in Europe. We are on track to double our revenue compared to last year and achieve our revised guidance.
I look at this one, you know, for sure, you know, this gives me confidence that we are on track to achieve our vision and we will keep executing year over year, you know, until we are there. The way we are organizing our presentation is in two parts, you know, mitral and tricuspid. Let me start with mitral first. I want to start with, you know, you watching a video from one of our true, you know, clinical partner, Dr. Firas Zahr.
Mitral valve disease is found in up to 10% of people older than 65 years old. It is thought to be two or even three more times more prevalent than aortic valve disease. As the population in the United States gets older, this problem is becoming more and more prevalent. In the last few years, there was a significant body of evidence started surfacing about the importance of treating mitral regurgitation. Unfortunately, with the current devices, not a lot of patients will be eligible or benefit from this therapy. Therefore, there is a huge gap in data that is available and the treatment option that is available for these patients. The current pivotal trial that is undergoing in Edwards Lifesciences will definitely generate the body of evidence that will help us choose the right therapy for the right patients.
We are extremely excited to see this data come out and fill the huge gap that we have in our knowledge in severe mitral regurgitation and provide therapeutic options for those patients who currently have no options.
What we heard, you know, from Firas is that, you know, mitral patients are very complex, you know, diverse. You know, this disease is very, you know, prevalent and few options. There are two big needs, you know, basically. Portfolio and, you know, more evidence. Let me stick to our, you know, mitral portfolio starting with PASCAL. We have gained a lot of confidence in this PASCAL platform. We are treating, you know, thousands of patients today. You know, more than 4,500 patients. The majority of them, you know, 3,800 and more than that, have been reported by a physician at major medical conventions so far, and very successfully. Many of them, you know, more than 450 patients, have reached a one-year follow-up or even more.
You know, what we can say is today, you know, physicians can achieve, you know, great acute outcome with PASCAL together with long-term outcomes. And the two randomized studies, CLASP IID for DMR patient population, CLASP IIF for the SMR patient population, will help close, you know, the gap Dr. Zahr was talking about. Now, you know, we are also committed, you know, to a rapid cadence of innovation. You know, I am very pleased, you know, as you have seen on my previous slide about, you know, the current generation of PASCAL. It is designed to safely navigate even in challenging anatomy, and we know it is very common for mitral patients. Physicians have the ability to reposition the device, you know, many times if they need to achieve, you know, the best patient outcome.
That's super important to be able to do that in a smooth manner. The stent valve is flexible, which is respecting, you know, the anatomy of a patient. All of these key attributes are, you know, super important. We are very pleased with the current gen. At the same time, we know that sometimes, you know, TEER, it can be complex. With that in mind, you know, we developed in the past couple of years, you know, the next gen PASCAL, you know, PASCAL Precision, to elevate efficiency, safety, and ease of use of PASCAL together with enabling a broader adoption of TEER. Being able to treat, you know, more patients. We already gained, you know, throughout, you know, 2021, you know, clinical experience with Precision. We got, you know, very positive feedback.
We anticipate that, you know, Precision is going to have a major impact on the customer experience. You know, we are not sitting here. You know, like, you know, Larry was talking about, you know, we have also a next gen after Precision. We are, you know, ready, you know, by next year to start some clinical trials. I'm not, you know, ready today, you know, to show you what the next gen is going to be, but, you know, you can expect in the next year, you know, for me, you know, to talk more about this position, to talk about it, you know, from the podium. Again, you know, we believe in this, you know, platform, you know, very much.
Now, you know, from a commercial standpoint, we are on track, like I said, you know, for a late 2022 approval in the U.S. in the DMR patient population. Let me tell you how we are thinking about the launch. We will bring our 50 years of experience in the space. You know, our experience, you know, from Europe with PASCAL and the 4,500, you know, patients we already treated. We will bring our, you know, best technology, PASCAL Precision, in the U.S. We will also, you know, bring, you know, all the evidence from CLASP IID. Now from a team standpoint, you know, we are going to build and we are building as we speak, you know, a team, dedicated team, you know, for the U.S. organization to be able to implement our high touch model like we have in Europe.
We will be implementing a controlled launch. What do I mean by controlled is that we are going to have many waves of site activation across, you know, the U.S. You know, we will conduct, you know, comprehensive physician training. We will help physicians, you know, screen patients to make sure, you know, they can achieve, you know, the best outcome. We will support every case. By the way, that's super important for us. Even, you know, this year and the last year during COVID in Europe, we were able to support, you know, all of the cases, having in mind, again, you know, patient outcome. Talking more about, you know, patient outcome, I'd like you to hear from one of Dr. Zahr's patients.
My dad loved the Oregon State Beavers. He would go to games, and he would have a really hard time getting up to our seat.
I would be dizzy, and I'd just lose my balance sometimes. Geez, I don't even know if I want to go to a game.
Larry's anatomy was extremely complicated. The leak was coming from part of the mitral valve where there is a lot of chordae that attach the valve to the ventricle. We got into this procedure day, and it was going to be tricky to get the device where we want it to be. PASCAL has a lot of CC features that allow us to optimize exactly where you want the device to be placed on the leaflet. Consistently had improvement in Larry's mitral regurgitation.
Approximately two weeks after the procedure, I started noticing a change in his energy. I was like, "Man, this is better than we expected.
I don't have to worry about breathing. I don't have to worry about shortness of breath. I don't have any trouble walking over to the stadium. In fact, sometimes he tells me to slow down 'cause I'm walking too fast. I think it's the best thing that's ever happened to me.
As you heard, you know, from this patient, Larry, you know, PASCAL can have a big impact. This is what drives us. This is what drives, you know, everyone in TMTT, you know, to do what we do. You know, obviously, you know, given the complexity of this disease, you know, TEER alone is not sufficient in our mind to treat all the patients and unlock, you know, this very large, you know, market opportunity. It is why the mitral replacement will be an important solution for patients. You know, it will, you know, complement, you know, PASCAL platform for non-TEER eligible patients. Yesterday night, you know, Dr. Feldman, you know, talked about that. The replacement has the ability to achieve, you know, superior efficacy in a very consistent manner. TEER, you know, stands for transcatheter edge-to-edge repair.
The big question with replacement, you know, has been and is. Can replacement achieve, you know, TEER safety level? That's, you know, a question that, you know, physicians are asking, you know, themselves, you know, for quite some time now. This is why we decided a long time ago, obviously informed by a long, you know, history in TAVR, and we moved, you know, you remember, I'm sure, you know, from our TEER approach to our, you know, transcatheter approach. We decided a long time ago to forgo invasive devices, invasive concepts like transseptal or like, you know, large, you know, frame sizes to focus on developing transfemoral 30 French. The objective is to offer, you know, the best of both worlds. The safety of TEER and the efficacy of replacement.
Now, you know, this kind of undertaking is a big innovation that, you know, very much aligned with what, you know, Mike was talking about in his opening, correct? It has some big innovation that's complex. This is what we love to do. This is why, you know, we are investing in two concepts, very different concepts in mitral replacement. You know, one, you know, M3, which is, you know, leveraging the well-established SAPIEN platform. We believe we are on track, you know, to have M3, you know, the first, you know, sub-30 French transfemoral transseptal commercial device in the MR indication. At the same time, you know, we have EVOQUE Eos, which has been specifically designed for the mitral anatomy. We've started our clinical experience already. We are very pleased. You know, physicians are super excited. We presented our first data at TCT this year.
You will hear, you know, more updates in 2022 about, you know, both, you know, platform. Let me now wrap up, you know, on the mitral franchise. From a technology standpoint, next year we are going to start the initial clinical experience of a next-gen PASCAL, you know, the one after PASCAL Precision. We are going to expand on our TEER experience, mitral replacement. On the evidence side, we will submit to FDA the CLASP IID data in the mid of 2022. You know, expect, you know, presentation of this CLASP IID data in the second half of 2022, prior to approval. We will continue to enroll, you know, the CLASP IIF and the TRISCEND clinical studies. Commercially, you know, we expect, you know, Precision DMR U.S. approval in late 2022.
In terms of revenue, we don't expect revenue in 2022. Think about a controlled launch in 2023, and an approval of PASCAL Precision in Europe late 2022 also. As you can see, 2022 will be another year of meaningful progress on the mitral front. Now let me turn to tricuspid and let's hear from three physicians. Volker Rudolph, Professor Lurz from Germany, and Dr. Patterson from the U.S.
Tricuspid regurgitation is the most underrated of all valve disorders that exist, and the patients have a very high risk for surgery.
Tricuspid valve regurgitation can come in several flavors. Some of it is due to the leaflets not coming together very well. Others are due to damaged leaflets or damaged valvular apparatus that supports the actual valve itself.
Every patient is individual, so you can't treat them with only one device. You need several devices and technologies.
It's pretty great to have access to the whole portfolio of Edwards, which gives us the opportunity to catheter-based leaflet repair, annuloplasty, and now also valve replacement. What we learned is that eliminating tricuspid regurgitation really has a major impact on the well-being of the patients.
They reported that the reduction in TR changed their lives, they feel much better. That created the awareness for the opportunity to help these patients and a lot of excitement. We are now in a situation where tricuspid therapy is almost clinical routine.
I look for the day when this is available in many hospitals around the country. Many physicians will be able to perform the procedures. If we do these trials right, and we're very rigorous on how we collect and analyze the data, we can change the paradigm for the treatment of tricuspid valve regurgitation.
What you heard from these three great panelists is a common message. Tricuspid is even more complex and more diverse than mitral. For sure, it needs for year two a portfolio and evidence to treat this patient population. For a long time, tricuspid has been the forgotten valve. I'm very pleased and proud about all the progress we have made in the last two years. In 2021 has been an amazing year in terms of progress. To date, we treated successfully more than 1,500 patients across our three modalities. Cardioband, PASCAL, and EVOQUE. We are seeing positive long-term data. More than 150 patients have a one-year follow-up or more.
We are starting to see, you know, some data acute and long term. This give us, you know, confidence in our potential to have a significant impact on these patients. Even though, you know, we all, you know, recognize that there is still a lot to learn. In the two pivotal randomized studies, CLASP II TR with PASCAL and TRISCEND II with EVOQUE, we provide, you know, very important evidence to achieve approval by adoption. All of this together will help physicians address, you know, this large, you know, patients and unmet need. We are innovating, you know, having in mind, you know, all what we learned about, you know, the tricuspid valve. You know, this valve is having, you know, dense chords. The leaflets are very thin and very fragile, and the imaging is quite of a challenge.
You heard about that, you know, yesterday night too, you know, from Dr. Ten, you know Tenma. Let me start with PASCAL. You know, our partner physicians are telling us today that the current gen of PASCAL is providing a very powerful solution for tricuspid patients. It is a diplomatic implant which is very helpful, you know, given the fact that the tricuspid leaflets are thin and fragile. You can safely navigate, you know, through chords. It is a flexible one. We believe that PASCAL Precision will provide an even greater confidence to physicians. Now, you know, let's turn to EVOQUE. Super exciting. You know, the year 2021 has been an amazing year, you know, for this platform. You know, we saw great benefit on the shark. Low-profile design, a sensitive range.
We have a wide range of valve sizes. The physicians are able to treat a very broad, you know, patient population. You know one of the early sign of this success is that, you know, every time, you know, we talk to a physician, they want the device. They call us, they want the device. There is a true excitement on this platform. When we open an account, you know, very typically, you know, the physician, you know, they need some time, you know, to find, you know, patients. You know, they spend just, you know, 5, 10, 15, 20 patients at first in a few weeks. For sure, you know, there is a lot of excitement given, you know, the benefit, the potential benefit of this platform.
All of that led to, you know, I don't know if you attended or you watched, you know, TCT. You know, TCT was kickoff with a live case with EVOQUE. It was, you know, a very calm, you know, procedure. You know, you saw that, you know, the patient was. The team, the efficiency was very relaxed. You know, the patient was very calm too. So they achieved a great outcome in about an hour. Later during TCT, Dr. Patrizio Lancellotti, who is PI for TRISCEND, has presented the six-month data at the late-breaking time presentation. Amazing results. Basically, you know, the efficacy, look at the efficacy. 100% had mild or less TR six months. Probably more exciting from the patient standpoint is the more significant reduction in mortality, re-hospitalization, and the quality of life.
You know, KCCQ, 27-point improvement. When we achieve 10 points, we believe it is a huge achievement. 27 points here. We are very encouraged. We are very excited, you know, like, you know, the physician community. At the same time, you know, it is still early. You know, TRISCEND II pivotal study is going to tell us more about, you know, the true benefit of this platform. You know, what patient is going to be eligible, you know, all of that. Yes, excited here. Let me summarize, you know, my tricuspid portion now. From a technology standpoint, year two, we are going to have, you know, initial clinical experience with the next gen PASCAL. You know, the one after Precision. Today, you know, I have not spent a lot of time talking about Cardioband.
Let me tell you, though, I have high expectation. You know, annular reduction in our minds has a very important role to play. It is effective for many patients. It will be an important option. You know, today, you know, this platform has one issue. One big issue, but one issue. It is way too long. You know, we are developing, you know, the next gen platform. Next year, we are going also to start, you know, some initial clinical experience with, you know, the next gen, you know, Cardioband. And we talk more, you know, during the year next year.
With regards to evidence, you know, we are going to continue enrolling, you know, the TRISCEND II pivotal study with EVOQUE, CLASP II TR pivotal study with PASCAL, and you are going to see the number of publication, you know, presentation, you know, throughout the year. From a commercial standpoint, you know, we are partnering with regulators in Europe to be able to navigate, you know, this new process, MDR process in Europe to be able to achieve CE mark for the EVOQUE platform by the end of the year next year. Now, you know, putting the mitral and tricuspid together.
You know, the range, the revenue range for next year is between, you know, $140 million and $170 million, which is about, you know, 18% growth, you know, from if you put it at the midpoint. After having doubled the revenue this year and achieve our revised guidance. Of course, you know, we could have some headwinds. You know, MDR, we believe MDR is going to be great for patients long term. Like any new regulation, any new process, you know, this may take some time on the part of both, you know, companies and the regulators to establish a new process. This is very important for us as we are bringing, you know, two new therapy, you know, next year to Europe.
COVID, obviously we made some assumptions, difficult to predict, you know, how, you know, the pandemic is going to progress. We see also some potential tailwinds of, European mitral market was soft in Q2, Q3. And a more, you know, a rapid return to solid growth next year can have a positive impact to our revenue. And then, you know, the body of evidence continue to expand. You know, mitral, tricuspid, you know, all what we do, all what the physician are doing, initiated, you know, by them. Can this be a bigger tailwind as early as 2022? Nevertheless, you know, 2022 will be another strong year, for TMTT. As I close, you know, let me remind you where we started today.
You know, we are very committed to our long-term vision, but also to deliver year over year, like we did this year. I am very pleased about how this year we were able to navigate COVID and still be able to be on track to deliver everything we committed to. You can expect, you know, 2022 to be even more impactful every year. With very important, you know, milestone. Late next year being able to achieve, you know, three approval, one in the US, two in Europe, sorry. The revenue growth of about, you know, 80%. Our progress in 2022 in my mind will set the stage for a stronger 2023 and beyond.
I am very proud about, you know, the progress that we made, you know, with all of the TMTT crew, you know, talented people, you know, passionate people. I feel we are on track to achieve our vision of leading and transforming care for mitral and tricuspid patients. Thank you so much. It is now, you know, my great pleasure to introduce, you know, Katie Szyman, who bring a lot of passion to the critical care business and has been a very successful leading, you know, this business unit. Katie, come on stage. Let's watch a video to talk about the critical care business.
Good morning, everyone, and as the video says, welcome to Critical Care. I'm gonna talk to you today about our vision, which is to improve the quality of care for millions of patients every year. We do it really with three key things. One is innovation, the second is evidence, and the third is how to drive the adoption of our technologies. Many people ask, "How does Critical Care products work? How do you improve the quality of care for patients?" We thought we'd start today with a video sharing the story of Raul, who is a patient who actually was hospitalized with COVID early during the pandemic. He was in the hospital for 47 days, and he was monitored for most of those days with our technologies. Let's roll the video of Raul.
Raul was the first patient that rolled in that looked like all of my coworkers and I. He could be any one of us. He was so young and so sick that you just go and say, you know, "You're doing well." Sorry. "And we're all pulling for you." Raul was so unstable at that point that we gave large amounts of sedatives. We were continuously looking at the monitors to make sure that the patient's blood pressure was high enough to where blood was being adequately perfused to his brain and his vital organs. He had to have a TruWave.
All my nurses, doctors, therapists were lined up there.
Ring the bell.
Thank you for providing the tools and data to my ICU nurses for keeping me safe and for me to be able to come back home. Thank you.
We love that tradition of ringing the bell. I don't know if you've been how close you've been to someone in the ICU, but as you often walk out, you ring the bell, and it's such a fantastic moment to see. That's really why all of us in Critical Care are so passionate about continuing to improve the quality of care for millions of patients throughout the world. If you think about Raul was monitored with our core monitoring technology. Using arterial line to provide continuous blood pressure information so that the clinicians can give him the care that he needs. As we look to the future of critical care, the majority today of our revenues continue to be from that core monitoring business, monitoring millions of patients. When we think about the future, we wanna shift that mix more towards smart monitoring.
What we mean by smart monitoring is adding advanced analytics so that we can actually improve the care and get patients home to their families faster. The shift to Smart Recovery, what does that actually mean? If you look at our market size today, it's roughly $1.1 billion. As we look out over into the future, the next seven years, we see that growing to $1.8 billion. You see there that the majority of the growth comes from smart monitoring actually growing faster because it's a higher value to clinicians and to hospitals, so it's going to grow faster.
How we're gonna do it is really by thinking about the 14 million patients today that are just monitored with plain blood pressure monitoring and saying, "I think of those 14 million that we could actually add smart monitoring and help them get home to their families faster." Today, in terms of Smart Recovery, we believe it's roughly 5% penetrated of the 14 million patients, and we think we can get to 15%-20% penetration over the next seven years, and that's gonna drive the majority of our growth. How are we gonna do that? Because it's hard to change practice in medicine, as we know. Really technology, evidence, and adoption, and I'll walk you through each of those three key areas. The first is just let's talk about how our technology is built.
We have our smart monitoring platform, which is the HemoSphere. We have algorithms that build on top of that, and then we have the sensor that is directly connected to the patient. In the future, we're gonna wrap all around that our connectivity solution. Let me talk about each of those things a little bit more. The HemoSphere platform has just been an incredible platform for us. We started rolling it out in 2018, and we started with the Cardiac Smart Recovery, which includes Swan-Ganz, FloTrac sensor, and the ForeSight sensor on it. Cardiac Smart Recovery rollout is about 50% complete today. This year, we're really starting the non-cardiac Smart Recovery rollout. What's included in non-cardiac Smart Recovery is the FloTrac, Acumen IQ, the ForeSight, and then our non-invasive ClearSight technology. We're just starting that rollout in the future.
About algorithms and sensors, and to kind of take it up a level and say, what are we doing in critical care? We're really smartifying everything. We've kinda made this word up, but it's really what we're doing is saying we today do sensors that will connect to the patient to tell you how the patient is doing right now. What we want to do with smartification is to add machine learning, data analytics, and kind of put it all together and actually then deliver IQ sensors that actually are then capable to deliver algorithms that are predictive in nature, that can tell the clinician not how the patient is doing today, but how they're going to be doing in the future. For example, HPI, hypotension prediction, we launched that in 2018.
It can tell clinicians up to 15 minutes in advance how their patient is going to be doing. Let's quickly talk about connectivity. Connectivity is getting all of the data off the HemoSphere, up to the cloud, through the EMR, and back down onto a clinician's cell phone. This is super important for anesthesiologists in particular because they often supervise two to four rooms at a time. Let's hear about that from Dr. Michael Scott from UPenn.
Although anesthesia uses a lot of technology to deliver what we do, what we're really lacking at the moment is a piece of technology that gives us situational awareness in our other rooms that we're supervising. With the increasing complexity of patients that are undergoing complex surgery, we really need some sort of device which gives us real-time situational awareness. That's what Viewfinder does. We're getting proactive, so we can suddenly improve the quality of delivery of care to patients in multiple rooms.
We got approval for the Viewfinder back in July, and I'm super happy to say that we actually monitored the first patient on a clinician's cell phone this week. Believe it or not, it takes time to work with the hospitals, get it all up and running, but we're very excited because we think this is gonna really improve care for patients going forward. Talking about clinical evidence, last year we talked about our MPOG study, where we studied whether using HPI could reduce the duration of hypotension experienced during long surgeries. In a database of 20,000 patients at 11 major academic centers, they found key finding is roughly 28 minutes. Imagine that you have a 3-hour surgery. In 28 minutes of that surgery, your mean arterial blood pressure is gonna be at a dangerously low level below 65.
With use of HPI in a prospective study, we were able to demonstrate that we could get it down to 12 minutes. We believe that as clinicians get more comfortable with the technology, we could see that coming down even further. What this can reduce, as clinicians begin to believe and change their practice, then we'll see the shift in our sensors moving more towards our Acumen IQ sensors than PUFFs. Why does hypotension matter? Why do we care? This is an amazing study that was published in The Lancet in 2019 that showed that if perioperative mortality was to be considered a disease state, it would actually be the third leading cause of death. There's a lot of things that happen to patients in that 30-day perioperative period, and hypotension is highly associated with the risk of postoperative mortality.
If we can actually get clinicians to focus on reducing hypotension, we believe that's going to be associated with a reduction in mortality in that 30-day period. We are actually going to start a new study, and we just announced this week that we have enrolled the first patient this past week in the HPI Smart-BP study. What we're gonna be studying is not only can we reduce the duration of hypotension during a procedure, but can we actually see if it impacts patient outcomes. It's gonna be a 1,500 patient study across 20 centers here in the U.S. We anticipate full enrollment by the end of Q3 2023, and we think that's gonna show that we can actually impact outcomes.
To hear more about it, we have Kamal Maheshwari from Cleveland Clinic, who's our PI, who's gonna speak about it.
Hi, everyone. I'm Kamal Maheshwari. I'm an anesthesiologist and researcher at the Cleveland Clinic. We are excited to start Smart BP trial at Cleveland Clinic because we believe it's gonna improve patient care. HPI software not only predicts hypotension or low blood pressure, but it's gonna also help treat the blood pressure for safety. That is a huge improvement in current care. Looking forward to the collaboration across the United States and can't wait to see the results.
Normally in our space with monitoring, people don't do a lot of these landmark studies, so this is a really big deal for us to make this investment. What we believe is that if we can build the clinical evidence, people will start to adopt more of these predictive technologies. Because you know how we all are. It's difficult to adopt something unless you truly believe, because it means changing how you've always done things. That's really gonna help change the world. The final area to talk about adoption is that CMS actually adopted intraoperative hypotension this past year as a quality measure, and the ASA also endorsed the quality measure. In fact, they're creating a database, and when they get their first 200,000 patients in that database, they plan to publish their baseline levels of hypotension.
The other thing that we continue to do to help with adoption is to do baseline studies at large IDNs and then get them to compare that when they implement HPI, do you really see a significant improvement in patient care? We're sort of doing bottom-up and top-down analysis as you think about adoption. This next year, we are estimating that we would have growth in the mid-single digits. You might say, "Well, you had higher growth this year, so why would it slow down?" It's really because this year we had a big surge in capital spending coming from hospitals as they released their capital budgets, going from 2020 where it was frozen to 2021 where we saw a big release.
As we go into next year, we think that won't repeat entirely, so we see our growth slowing down slightly due to that. We also have planned to discontinue some non-strategic products, and that will probably reduce our growth rate by 1%-2%. That's allowing us to focus more and more on Smart Recovery. In summary, I'd just like to say that we are very excited about the impact that we can have with Smart Recovery. We all get up every day excited about the impact that we have on millions of patients around the world, and I guarantee you that the best is yet to come for critical care. Thank you very much. It's my pleasure now to give you all a break because I'm sure you're really looking forward to that. We are going to reconvene at 10:25.
Thanks, everybody. The bathrooms are back here. There's coffee out there. If you're online, we'll see you at 10:25. Thanks, everybody.
Okay. Welcome back from the break. The second part of this program is gonna be so good. We don't even need a video or music or anything. We're just gonna dive right in. You heard how excited we are about the future of Edwards Lifesciences in the presentations earlier this morning. We're also really excited about the opportunity to help improve treatment for patients. We're enthusiastic about the opportunity to create value for shareholders, and we're gonna talk about how we intend to do that right now. There are three priorities that we think about in terms of financial objectives for Edwards Lifesciences: strong sales growth, healthy profitability, and smart capital allocation. The first and foremost of these is sales growth. At Edwards, that means organic sales growth. Durable, sustainable, and really driven by long-term investments in research and development and advancements of interest breakthrough therapies.
In 2021, we've had a good year, better than we guided to at this investor conference one year ago in December of 2020. In fact, the guidance that we gave during our third quarter earnings call in October is unchanged. We are reaffirming it today. That guidance is for sales of $5.2 billion-$5.4 billion or mid- or high-teens growth, rather than mid-teens growth, which we'd originally guided to for this year. EPS growth of over 20%, so still getting nice leverage out of our P&L. That strength in the business and better than guidance that we provided last year is really reflected in better performance in all four of our business units, TAVR, TMTT, Surgical, and Critical Care.
Turning to 2022, our expectation or plan is based upon the assumption that we have a gradual recovery from COVID, and we're assuming no significant impact from new variants. To make it clear, if we have a longer than expected recovery from COVID, or if we do have a significant impact from Omicron or any other, variants, then that would be a negative to the guidance that we're providing. We're expecting growth across all major regions in 2022. Foreign exchange is gonna be a factor. Because of the strengthening of the dollar, especially relative to the euro and the yen, we're expecting that 2022 sales outside of the U.S. when translated into dollars will be about $120 million lower than they would be at 2021 rates. That's about 2% of sales.
We expect a pretty high variability quarter to quarter in terms of year-over-year growth rates because of the impact that COVID had during the course of 2021. Overall, we're expecting low double-digit sales growth in 2022, $5.5 billion-$6 billion. By business unit, starting with TAVR, we're expecting double-digit growth across all major regions. We are planning on stable average selling prices and competitive positions. Now in 2022, we have another feature to the P&L, which is the expiration of a royalty revenue stream that we've received for many years now. It expires in April, and so instead of the typical $40 million annual run rate, we'll probably get about $12 million into 2022 before that royalty expires. Overall for TAVR, 12%-15% growth to $3.7 billion-$4 billion.
In TMTT, Gerard talked about his plans to continue to expand PASCAL in Europe, and that will be the biggest driver of commercial revenues in TMTT in 2022. We're looking forward to PASCAL coming to the U.S. and both Acuspis coming to Europe. Those approvals will happen in 2022. The real sales contributions won't start in earnest until 2023. Overall, we expect revenues of $140 million-$170 million for TMTT in 2022. In surgical structural heart, we're planning on the continued adoption of our products based on the RESILIA platform. We're looking forward to the launch of MITRIS, our new mitral valve here in the United States. A lot of the growth is gonna come from this continuing conversion from mechanical to tissue valves.
Overall, mid-single digit growth rate in surgical to $870 million-$950 million in 2022. Finally, in critical care, we're really excited about the acceleration of the adoption of Smart Recovery and the expansion of our hypotension prediction index technology. That combined with the launch of Viewfinder and other things that are going on in critical care, we believe will generate mid-single digit growth to $820 million-$900 million for critical care in 2022. Okay, turning to the second financial priority, profitability. Building healthy profitability for us starts with high gross margins that reflect the value that our products provide, also being able to fund expansion that we need to produce our products around the world and provide the ability to be able to support the growth in our field force.
For example, to support the continued growth in TAVR. For example, building the field force in the U.S. to support the launch in 2023 of PASCAL. Putting some more specificity on that, we expect our gross profit margin in 2022 to be 78%-79%. This is two percentage points higher than our guidance for 2021 of 76%-77%. Most of that increase, about 75% of that increase in gross margin guidance, is attributable to foreign exchange. I mentioned before that there will be a headwind to sales. We have an option program in place to offset that impact to the top line, and as a result, we'll have hedging revenues that come in at a 100% margin rate that contributes to a higher gross profit margin percentage.
We're also gonna see some operational efficiencies that make up the rest of that increase in gross margin rate. It'll be offset partially by investments that we're continuing to make in manufacturing capacity and the expiration of the TAVR royalty that I mentioned before. In terms of operating expenses, we're expecting selling, general, and administrative expenses as a percentage of sales to be 28%-30%. Research and development as a percentage of sales of 17%-18%. On the positive side, the expenses that we incur outside of the U.S. translate into lower dollars as a result of the same FX dynamic I mentioned before. We are still leveraging our scale. As the platform grows, as our global position grows, we get more benefits of the shared administrative and overhead and back office type expenses. We expect a nominal impact from inflation.
Certainly, we're seeing the same kinds of headwinds and pressures on wage rates in our production facilities and our salaried employee ranks as well. We expect that those impacts can be managed within the guidance that you're seeing right now. On the negative side, which is a little bit of a positive side, we're spending a lot of money getting ready for the TMTT launch in the U.S., and you'll see it's showing up in our operating expenses. We're also continuing to invest aggressively in enrolling clinical trials, and there's an expense that comes with that, but we think about it as an investment that's really important to bolster one of our top-line growth opportunities. Okay. Overall, it gets us to an adjusted operating margin of 53%-54%, up from about 51% in 2021.
Again, this reflects the benefit of FX. If you just take the midpoint of that 31%-34% range, call it 32.5, about a percentage point of that is attributable to FX. On an adjusted basis, it's more like 31 to 31.5 if you were to pick numbers in this range for modeling purposes. In terms of earnings per share, it's going to be a nice growth year for EPS. We expect this year EPS to be the high end of that $2.07-$2.47 range. Most of the increase in EPS to $2.50-$2.65 is coming from growth and operations improvements. That's 29-36 cents of the improvement. You do get some of that benefit from FX that falls to the bottom line.
It's partially or maybe even more than offset by some of the increasing tax pressures that we expect, not related to the Congressional tax action. We'll talk about that later, but just natural increase in our tax rate, partly because we're expecting less benefit from this ETB or the excess tax benefit we get from the deductibility of option expense. Turning to the third financial priority, capital allocation. Our intention is to continue to fund expansion in our production facilities while also being able to fund external investments. I'll talk a little bit about that in a second. Adjusted free cash flow in 2022, we're expecting to be $1.2 billion-$1.5 billion, up from year to date this year, $1.1 billion.
There's an important change that is hitting us in 2022 along with other companies. As part of the 2017 Tax Act, on January 1 is the expiration of our ability to deduct all of our research and development expenses for the current year against our current year tax expense. This doesn't affect our book P&L. This is just a tax item. Effectively, we have to defer the benefit of the R&D expense deductions over time rather than getting them all up front. The impact is about $200 million in 2022. We invest capital in a number of different places. We've got manufacturing resiliency representing about half of our total capital investment.
The balance is a combination of infrastructure investment and research capacity like you've seen for those of you in the room walking around our headquarters campus here. We have a lot of investments that we've made in supporting the growth of Edwards Lifesciences both here and in Israel, as Todd talked about last night, and other places around the world. We have an active business development effort underway, and a lot of the transactions that we do and investments that we make don't ever get reported publicly, but they're an important part of augmenting the activities we have underway internally. Our focus continues to be on structural heart, generally early-stage pre-revenue companies and startup efforts.
We do make investments in our intellectual property, and ultimately, we really think more carefully about what's a strategic fit for Edwards and how much cash flow can we put against acquisitions. We're not intending to change our strategy based upon how much cash flow the company is generating. We're also looking carefully on a regular basis at our product portfolio, and we're discontinuing getting out of products that are non-strategic or have lower growth potential. Here's just a summary of all the guidance that I just mentioned. Now I'd like to turn to the longer-term guidance. Between now and 2028, you heard Mike talk about this, expansion of the markets that we serve from nearly $10 billion today to nearly $20 billion in 2028. Here's how we get there.
TAVR, we expect to go from $5 billion-$10 billion by 2028. It's driven by really three things: greater awareness, label expansion, and geographic expansion of the TAVR footprint, and then third, new technologies like X4. With TMTT, the current market opportunity is about $1 billion in size, and we expect that to grow to about $5 billion by 2028. In the case of Edwards, it's going to be driven by three things. Differentiated portfolio technologies that Bernard talked about, positive clinical results from these different clinical trials that we're enrolling, and the third one is just continuing excellent real-world outcomes from patients who are benefiting from our TMTT therapies.
In surgical, current $1.5 billion market opportunity growing to something like $2 billion by 2028, supported by the adoption of our RESILIA technology for tissue, the mitral opportunity, the introduction of MITRIS in the U.S., for example, and emerging markets which continue to transition from mechanical valves to tissue valves. Finally, critical care growing from about $1.1 billion today to $2 billion in 2028, lifted by a shift to smart monitoring. The artificial intelligence and new technologies that Katie mentioned just before the break and more favorable clinical evidence. We're investing more now than we ever have before in evidence generation to support growth in critical care. Beyond sales, here's some other things to keep in mind and guidance that you can consider for the longer term P&L for Edwards.
We don't give specific numerical guidance, but here are some themes that can help you understand where we're going. Sales, you know, for gross profit, we're gonna continue to see the mix benefit of our higher margin products growing faster than our lower margin products. That's gonna lift our gross margin even as we invest in capacity expansion and even as we bring online new products that typically see the lower gross margin until we get to higher volumes and scale. In terms of SG&A, we're gonna get some leverage out of SG&A, but we're also gonna continue to invest in the field force that we have in place around the world to support physicians and make sure that we are helping deliver the best care possible for patients.
For research and development, you know, eventually the law of big numbers will work to our benefit, but for the foreseeable future, we're gonna continue to invest in multiple different clinical trials because that's really the future of Edwards Lifesciences. Remember, our number one financial priority is strong organic sales growth, and R&D is the big driver of that. Probably the biggest pressure point on our P&L is on taxes. You've all been following what's happening in Congress. We're following it closely. We do believe that any kind of tax change is probably gonna be a headwind to us over time.
So far, the discussions underway do not suggest any change for 2022, so it would not be an impact to our 2022 guidance, but it could impact our profitability and bottom line in the future, at least during the transition, if there's a reset in the tax rate for companies like Edwards. Overall, for earnings per share, we're gonna continue to buy back shares to offset dilution and to work down our net shares outstanding over time when we make opportunistic share repurchases. Overall, we're really excited about the future of Edwards. We're excited about the financial plan we have in place and how well integrated it is with our strategy. We've got a lot of confidence with where the company is going. With that, Mike, over to you for closing comments before we turn to questions and answers.
All right. Thanks, Scott. Scott is a fantastic partner to me personally and the rest of the ELT, and puts us in a great position for us to be poised for success in the future. I'll just do a quick wrap up here. You know, at its essence, our strategy is unchanged. We're really pleased with this strategy. We go in a different direction than many others in med tech who think that bigger is better. We believe that better is better, and this idea of being singularly focused and going for big, bold innovations that change practice and going first is the right way for us to behave. We got a lot of confidence that when we actually create really meaningful value is when we transform care for these patients that we serve, and there sure are a lot of them.
2022, we think, is gonna be a big year. You just had a chance to hear the details of that. Now, of course, it'll be nice sales growth and earnings growth, but more importantly, there's all the progress we're making toward our big, bold innovations. It'll be a year of continuing to collect and share powerful clinical data. We'll be launching some brand-new things that were never launched in the past. We'll be introducing and trying some things that we've never tried before in 2022. Overall, I think just advancing the state of the art for all the patients that we decide that we're gonna serve.
You know, there are a lot of milestones that happen during the course of the year and things that happen during meetings, and so we're excited about what's ahead in the near term and sets us up very well for the long term. I think it's an appropriate time to mention our board. Our board is fantastic. It's been a steady hand that's been extraordinarily supportive of us along the way. This is a group of people that are deeply experienced leaders, that really come from very different perspectives that are helpful to us. They constantly modernize our governance practices to make sure that we're shareholder-friendly and there's some good listening to all the constituencies that we serve.
They hold us on the management team accountable for our performance to make sure that we deliver in near term and the long term consistent with our strategy. One of the things that I'm most pleased about our board is they have stayed engaged. At a time when I know a lot of boards have gone virtual and so forth, our board of course showed up and found a way to be able to meet together safely, and we continually engaged, and we even visited some sites outside the U.S. together. I couldn't say enough about this group. Sustainability, we know we all get a chance to talk about. At Edwards, I just wanna make clear that sustainability is truly integrated into our culture and into the ways we run the business, into our strategy.
We don't sit here, run the business over here, and pursue those long-term goals and then try and be sustainable over here. We try and have it fully integrated so that it is part of the way we run the business. We have the privilege of doing that. We're obviously do all the things we can that I just mentioned to have strong governance practices. Separate from that, very socially engaged in all the communities that we engage with and try and be a positive force and a real positive citizen to all those around us. Also, because we're growing and we have a healthy balance sheet and we need new facilities, we're able to create our new facilities that are highly aligned with a positive environment. We're pleased with where we're positioned on sustainability.
We get recognition for some of what we do, but that's not why we do it. We do it because it just suits us well. Speaking of the social side of things, we're fortunate to be a successful company and to be profitable, and we're very committed to giving back. We do much of this work through the Edwards Lifesciences Foundation. Just this past year, we supported more than 250 charities around the world. We have fabulous charitable partners. The work of the foundation comes in two pieces. One is our big signature strategic effort, which we call Every Heartbeat Matters. We achieved our goal in 2020 and set a new bold goal for 2025 that said we're gonna improve the lives of 2.5 million underserved structural heart and critical care patients.
COVID doesn't make this easier, but we've got more than 50 dedicated strategic partners that are helping us pursue this, and we continue to be committed. The other part is to just support the communities where our employees live and work. We listen a lot to our employees and take our cue from them. We do a lot of special efforts, particularly around COVID, but we support all the communities. One of the things that I'm most proud of is that our employees actually get engaged in charitable activities. More than 80% of our employees in the past year did something charitable that they cared about over the past year, which tells you it's kinda in the DNA of our group to be able to give back, and I'm very proud of that.
Just in summary, I am very, very optimistic about the long-term prospects for our company. We're gonna create value. Why do I think so? Number one, the patient populations that we serve are underserved. Are we any better than our parents or our grandparents in terms of options? Yes. How about what's possible in the future? We think there are huge advancements that are possible with technology for this group of patients.
We think that because of the way we've behaved in the past, we've earned a certain amount of credibility and trust, which gives us the ability to think boldly and to go after these big, bold innovations, and that we're able to have strong partnerships with all the people that are so important to us that do our work, whether it's clinicians or the regulators or the payers, or the patients, who've been entrusted to do our work. We've got a heck of an R&D machine. We have some very, very talented folks that are so committed. They've worked hard through all the challenges along the way, and they are energized by the opportunity for them to do big, bold things. It gives me a great feel of confidence when I get to look into their eyes.
What our strategy is about is not necessarily acquiring the growth, but through our own efforts to generate true organic sales growth that's sustainable. What makes me probably feel best about the whole thing is this superstructure that's right in the center. This patient-focused culture. I wanna read one to you because I didn't wanna get this question. We do a lot of surveying of employees and ask them about how they feel about various things. One of the questions we ask, "At Edwards, we consider what's best for patients when making decisions." Over 90% positive. It's the kinda thing that gives me great confidence that we're well-positioned for a bright future. With that, thanks very much for your time. We're gonna transition to Q&A. We'll take a five-minute break. We'll put some chairs on the stage.
We'll bring up all the speakers, and then we'll jump into it.
All right. Hey, welcome back, everybody, to the Q&A portion of the investor conference. As Mike mentioned, as you can see from your agenda in front of you, we've allotted about an hour for Q&A, so we'll do our best to get to as many of the questions as possible from both of you in the room as well as those of you on the phone. For those of you on the phone, please just make sure you mute your computer audio before asking a question, and please use the dial-in that was included at the bottom of the press release we issued this morning. At the conclusion of the Q&A session, we'll ask Mike to make some brief closing remarks before signing it off. We'd like to give a little presentation video that you guys will enjoy.
With that, let me kick it off and open it up to some questions in the room while our operator, Diego, compiles a list of callers. Robbie, go ahead.
Robbie Marcus, J.P. Morgan. First off, thanks for putting this great event together. It's really helpful. Two questions from me. Maybe first on TMTT. It's real impressive revenue more than doubling through next year or almost doubling. You know, how do you think about the drivers to get there? 'Cause it seems like some of the new product approvals come later in the year. Is it increased sites? Is it trial revenue? Something else?
Yeah. Why don't I start out, and then Bernard, you can jump in. It's gonna primarily be a year of Europe sales next year, so that's where most of the sales are gonna come from. It's gonna be primarily the expansion of PASCAL in Europe. Although we do expect to have a U.S. approval by the end of the year for PASCAL, we really haven't modeled much impact for 2022. Bernard, you can provide a little bit more color there now.
Yeah. It is going to continue what we are doing in Europe. You know, it is about, you know, activating more sites across Europe. We have been doing that in the last, you know, couple of years. You know, we have even many more sites, you know, to opening up. We do that in a very meaningful fashion to make sure that we do it with a high-touch model of that. Site activation, number one. Number two is I talked about, you know, the market, you know, the micro market in Europe in Q3 was, you know, softer than expected. We are, you know, expecting that, you know, the micro market is going to recover in the next year.
Great. Thank you. Just to follow up, Mike, with evidence building around asymptomatic and over the next few years moving more into TMTT and hopefully over time moderate, you know, what are you doing to prepare the market and patients for the next five years of growth? You're gonna need probably a lot more doctors, more capacity at centers, also a lot more awareness and buy-in. What are the things you could do today to prepare the market for five years from now?
It's a great question. We don't have perfect control over that. One of the things that we can do is to do these big transformative clinical studies. There's something that really gets the attention of clinicians and systems broadly, is when we do this transformative work that has an opportunity to be published in prestigious journals and talked about from the podium, it sends a signal to where the growth is gonna come from. Our customers around the world, they wanna be where the puck is going. For them to get a signal of where the growth is gonna come from, you know, we obviously feel that way. We can see how well the market has reacted to TAVR over the years.
You know, we were able to send enough signals that TAVR is improving, it's expanding, and hospitals have capacity here. They say, "Wow, that's a growth opportunity for us." Actually, they know how to operate profitably within that sphere. We've been impressed in terms of the way that people have reacted. Do you have anything you want to add to that, Larry?
Yeah, sure. A lot of things that we can do is just help finish our best practices with each other and run programs for how we can be more efficient. Moving to concentration and moving to net discharge and making the procedure really efficient. I mean, it takes more time to turn over the room now than it does to actually perform the procedure. We have centers, you know, some of our top programs will do 7 TAVRs in a day. It shows you what kind of capability is there when the procedure is predictable and it works out well.
You're talking about programs like the Benchmark.
Right. Like our Benchmark program. You know, we'll run training programs on this. We'll do it at bigger meetings. It really helps centers advance. Even centers that are pretty well optimized.
They find there's still opportunities for them to get further optimized. We try to do that, you know, to create capacity for ourselves, but we also try to do that to create capacity for Bernard because as his innovations show up, they're gonna need that space. I think we try to talk to hospitals about the importance of training effective team. You know, one of the great things about TAVR is it's relatively de-skilled. You know, when we started it was the best operator in the hospital was doing TAVR. Now, you know, I go to cases and I think you can watch, you know, one of the KOLs and he's standing there talking to a fellow or actually teaching why the fellow has the case. That's just where the technology's gone.
Bernard is kind of more at the front end of that curve. We're still behind people, and the complementary imaging is still kinda coming online. I feel like he needs a lot of great capacity for his stuff showing up.
Yeah.
Thank you so much. Matt Miksic from Credit Suisse. One for Scott, and I have a follow-up, if I could. On the outlook, can you talk maybe a little bit about, you mentioned COVID obviously is a big question mark that can have an effect to the range that you've given. Can you talk maybe a little bit about some of the factors that sort of concentrated at the high end of your current range and some of the factors maybe at the low end of the range?
Matt, are you referring to 2021 or 2022?
2022.
Okay.
Yeah. You're right. COVID's a big wildcard, and our guidance is based upon the assumption that we do have this gradual recovery from COVID. There are no significant interruptions or dislocations resulting from variants. If one of those happens, like it's not a gradual recovery, it's an extended experience of COVID or there's a more significant impact, then that would negatively impact our guidance. If we're on this glide path to recovery from COVID, which is our plan, our guidance, then the real drivers to the high end of the range are more around the adoption of therapy. Therapy in the case of TAVR is, you know, relevant to what happens in Europe and the US.
The therapy in the case of TMTT is gonna be, as Mike and Bernard just said, more commercial sales of PASCAL in Europe. In surgical and in critical care, Katie and Daveen talked about the new products that are really helping to drive those sales. To the extent that adoption is faster than we're expecting then it's a higher end of sales range.
Great. Thanks. A follow-up for Bernard, if I could.
Yeah.
I know we've talked a lot about repair in mitral and TMTT driving next year's sales. Do you still have, it appears that you're gonna have a valve replacement approved by possibly the end of next year. I wanted you to talk a little bit about, you know, things like pace of enrollment of those studies and potentially what that tells you at this point about what the adoption and interest in that program could look like once you have a commercial product.
Yeah, no, sure. Great question. For sure. You know, like I share with you know, we see a lot of excitement. Excitement, you know, from the physicians, you know, involved in the TRISCEND study and the TRISCEND II clinical trial. We see that they are submitting a lot of patients. We see the cadence of patients being higher than usual. It is a true testament about the fact that, you know, they have no other solutions for these specific patients and, you know, the benefit of this technology, which is achieving a great outcome, you know, safe with a great efficacy. That we see that in a clinical study kind of things.
From when we get to our approval, you know, late next year in Europe, you know, we're still engaging to put together all the plan, but we are going to do it, you know, the way we do things, right. All the time. High touch model. We are going to have, you know, an activated site in high volume in 2023. So think about, you know, a value-add launch in 2023, because priority number 1 is to make sure. I think Larry talked about that, you know, earlier, you know, this morning where he said, "Look, yep, there is, you know, a big value in physician for their first, you know, three, five, 10, 20 cases have great outcome." So it is not about pace, it is about great outcome from patient number one, from patient 1,000. This is the way we are going to implement, you know, this launch.
Thanks. Well, I've got some other followers, so quick, yeah.
He's going down the wrong script.
Great. Larry Biegelsen Wells Fargo . Thanks. Great question. You know, one on PASCAL, one on early TAVR. Mike or Bernard on PASCAL. The price premium, are you signaling that you think you'll be able to show superiority in CLASP IID? If you don't show superiority, how much of an impediment do you think a price premium's gonna be to adoption? Just for Larry, how are crossovers handled in early TAVR? Do you think that'll be. Is there a lot of crossovers that you picture, you know, to show, you know, a significant benefit on the hard outcome? Why do you think you're gonna need a minimum of two years for all these patients?
The studies that are enrolling, you know, since 2017, you already have a lot of patients with a lot of accrual. Thanks.
Larry, you're best in class in getting four questions into one, I think. Let's start out with PASCAL. I think you can play these two different things. One is, do you think you'll have a premium and that you can command a premium? The other is do you think you'd be superior? We really look at that as two different things. Yes, we're operating at a premium, but no way to power this trial to be non-inferior. Bernard, why don't you take the first round?
Well, no, that's a good recap. The trial has been powered, you know, to demonstrate, you know, non-inferiority. And we are expecting that, you know, obviously, and this is what we have in our model. Now when it comes to value. The value for us means much more than that. You know, it is, you know, the value of the technology, our high touch model, where we train physicians, we are in the cave all the time. We help them screen the patient. And we believe, you know, we deliver value from a patient outcome standpoint. If you like, today, we are operating with this, you know, price premium in Europe. That's, you know, basically, you know, the way we are thinking about it, you know, Larry.
Yeah, Larry.
Larry, let me ask.
Yeah.
Larry's one two-part question. The issue of crossovers, you know, when a patient is asymptomatic, they're off guideline, and so they're not treated.
What? You know, just for those that aren't as deep, Larry, why don't you just back up and talk about what the crossover is rather than dive into the issue. Explain what the question is about.
Sure. In the EARLY CLAVAR trial, we take patients that are deemed asymptomatic. They've been studied for a stress echo, and they're confirmed to be asymptomatic. We randomize them 1 to 1. Half the group goes to CLAVAR, and half the group goes to medical therapy. For the group on medical therapy, there's no indication to treat them because they're truly asymptomatic, and so they're off guideline. Once they become symptomatic, now they're on guideline for therapy. There's no ethical way that we could say, "We're gonna deny a patient therapy just to prove a medical point." Right? Once they become on guideline, then they cross over and they get treated. Now in terms of, you know, the time it takes to enroll the trial, we account for that by making a modification to the sample size.
Because we're gonna have longer follow-up, we took a sample size I think from around 1,100 to 900 or something, 1,050 to 900 something in that ballpark. We accounted for that longer enrollment time. We wanna make sure that we capture a significant amount of patients. The fact is nobody knows how long it's gonna take patients to progress from asymptomatic to symptomatic. The risk of running a trial and saying, "Hey, just open the book to the year," and then finding out, "Oh, shucks, it didn't go the way we thought." You don't get to put the genie back in the bottle and run it for another year. To try to do this trial a second time, you know, think about what that would be for an investigation.
I'd rather make the investment up front, you know, by putting the two-year endpoint on it. I think we're gonna definitively show whether to treat the asymptomatic works or it does not. I think there's just more risk if you were to call that endpoint earlier.
Chris Pasquale.
Thanks. Chris Pasquale, Guggenheim. One for Bernard Zovighian and then one for Larry Wood as well. Bernard Zovighian, I just want to understand the regulatory timeline around PASCAL in the U.S. Did I hear you correctly that the trial has not yet completed enrollment but is on track by the end of the year?
Yes. You are correct.
Okay.
On track to complete. Go ahead.
Okay. We get the enrollment done in the next couple of weeks. You're talking about a mid-year submission, six months follow-up, and that's a pretty quick turnaround on the data. Approval by year-end is also a pretty quick turnaround for a PMA product. What gives you confidence you can actually get approval 12 months from now?
You know, one is. Yes. We are going to complete, you know, the study in the next, you know, few days. Obviously, you know, we are, you know, we have been running the study for quite some time now. You know, the team is ready to look at all the data. This is all about, you know, bringing now, you know, the patient for follow-up six months, and there is a window, correct? It is six months, you know, plus or minus, you know, few days, you know, few weeks. We are going to do our best, you know, together with the sites to bring the patient in, you know, the fastest we can. We are going to support them do that.
We are also, you know, talking to FDA to make sure they know it's coming, and it's on their agenda to be able to give us an approval, you know, 180 days, you know, by the end of the day.
Yeah. You know, it's also fair to say, Chris, you're right. There's risk involved in this. This isn't a no-brainer. This is an all success model if things go very well and that, you know, everybody, that the data falls in place and that everybody's properly motivated, and they have the time and the ability to move quickly. Yeah.
Okay. To what you said earlier, there's no guidance for this year. The guide slipped. There's no U.S. sales really in the guidance.
Correct.
That's right.
That's correct. Yeah.
Thank you. Larry, I was hoping you could just spend a minute on X4 and what the main benefits are there. Just color on PROGRESS, what patients you're looking at specifically. In the past, Moderate AS has been combined with heart failure symptoms as a population. It's not clear that that's what you're doing there, so I'm just looking for some insight on the patient side.
Well, good. Intentionally vague, so that's good. No. For X4, you know, I talked about adding RESILIA to the platform. For competitive reasons, I'm not gonna go into a whole bunch of other things about it. I think JD kind of clues where we're going. We think more can be done around paravalvular leaks, and we think more can be done to really optimize sizing. Patients, you know, don't come in 3-millimeter increments like everything else do. How do we really optimize valve performance for patients across the size range rather than just some very specific size range? I think, you know, PV leak, the optimal sizing. You know, obviously we wanna preserve coronary access or improve that when there's opportunities to do that.
The resilience issue around durability, I think is a big thing. You know, the PROGRESS trial is not like UNLOAD. It's moderate AS, and it's irrespective of symptoms. But practically, a patient has to come in and have an echo for some reason, which generally means they might have some sort of symptoms of some sort. Otherwise they're, you know, I don't think most healthy people just wander in and say, "I'd like to get an echo. I'm curious." They're coming in for some sort of reason, so I suspect we're gonna pick up some symptoms. What we didn't wanna do was have the hardcore symptomatic patient that we have in something like UNLOAD, which was a real barrier to enrollment. We just wanna focus it on primarily moderate AS.
We know the patients are in the system for a reason, and then randomize them very similarly to early CLAVAR. The one difference, you know, from early CLAVAR is Larry's issue on crossover. When a patient goes, has severe AS and then they go to symptomatic you have to cross them-
over because they're now on indication. A patient's symptoms getting worse in the moderate arm, they're still not indicated until they actually become severe. We're not gonna have that same sort of crossover issue. They can become severe, and once they become severe, we will have to cross them over. It's probably going to be a longer process depending on what range of moderate patients actually show up in the trial.
Thanks, Larry. Hey, Diego, it looks like there's some questions on the phone. Could you go to the phone to see if there. Our first caller.
Thank you. We do have a question from Vijay Kumar with Evercore ISI. Go ahead.
Hey, guys. Thanks for hosting this. Apologies I could not make it in person. You guys are looking great here. Mike, maybe a big picture question for you on mitral. I see there are a lot of numbers there. But high level, when you look at that high billion in a TAM, I shouldn't even call it TAM, the entire TAM. I think that's a real aggressive market in 2028. What goes into those numbers? Do you have obviously PASCAL is there. Do you have replacement in there as well? Do you have tricuspid in there? And what kind of share should this be, should Edwards take 50%, 60% of that market?
Thanks, Vijay. It's always kind of difficult here when you're trying to provide guidance that far into the future. But just to give you a sense of what's in our assumptions, yes, we believe that PASCAL is gonna be successful. That's in our assumptions. But again, we're talking about the market, not Edwards, right? But yes, we think that that's gonna be successful trials. Yes, we think that replacement products in the mitral and tricuspid product areas are going to be approved. And so that's in there. In terms of how much share we get, you know, time will tell. You know, we believe that the technology will advance. It will advance successfully. But in terms of how much share we get, that's really up for you all to estimate. Yeah.
Just maybe on this, Mike. I think one of the questions investors had was, you know, to buy into the Edwards long-term thesis, you know, we need to bet on mitral. Essentially, is Edwards just saying, "Look, we've solved mitral, and this is fairly de-risked." Is it that or what's the most you buy? And if I could want one from Larry. I think I heard a similar question on the TAM. Did you say it does not include moderate AS? If you could clarify on the $10 billion TAVR number.
Yeah. Thanks, Vijay. Those are really good questions. Let's just do that. Yes, we believe that we'll have success with replacement in tricuspid and replacement in mitral. Yes, we think that the TEER, the edge-to-edge therapy is gonna be successful in both tricuspid and in mitral. Some of those approvals are gonna come late in the cycle. It's not like they're gonna come in the next couple years. They'll come closer to 2028, so they'll have more or less moderate impact on 2028. As Bernard likes to say, we're just getting going in TMTT when we get to 2028. Hopefully that gives you a sense of what's in there. Bernard, feel free to add to that.
Larry, why don't you talk a little bit about what's in the TAVR assumptions, $10 billion by 2028 number.
Yeah, you know, yeah, I think you see all, you know, like, you know, basically, you know, the way to think about it is our five randomized study by then, you know, will be completed, finished, you know, presented. We will have evidence, some earlier, some later between now and 2028. Some will have a greater impact. You know, for sure we are expecting, you know, moving from today, which is a TAVR market to, you know, more replacements, tricuspid and mitral, you know, by 2028. This all together will basically is making, you know, this high billion.
Yeah. On the $10 billion for TAVR, the primary driver is severe symptomatic aortic stenosis patients. That's gonna be the primary driver. Continuing expand low risk and some of our global expansion, those are gonna be the things that primarily drive that. There is some asymptomatic in that number, but it comes later in that period. We probably don't think moderate shows up in that time period given it's a two-year endpoint on the trial and the time it'll take to analyze the data and the time it'll take to enroll. That's probably more out of scope. That's something that we think is a big driver beyond 2028.
in the core of your question, Vijay, is why should we believe it? You know, doesn't Edwards have to be successful with their innovations for that to happen? The answer is yes, that's true. We need to be successful. Not an all success model, but some serious success. Yeah.
Vijay, thanks so much for the questions. Diego, is there one other on the phone maybe that we can take a question from?
Yes. We do have a question from Danielle Antalffy with SVB Leerink. You can proceed with your question.
Hi, good morning, everyone. Thank you so much for hosting this event. I actually wanna start with critical care, and then I have one follow-up for Bernard on the mitral side of things. Katie, on critical care, where do you see the key technology advancements from here more specifically? And also curious how you think COVID has maybe changed hospitals' appetite to adopt this type of advanced technology.
Yeah. Thanks for the question. You know, where do we see future innovations around algorithms? With algorithm development, it's all about getting the data. Getting those baseline data sets helps us develop new algorithms to solve future problems, right? The first one that's coming out beyond hypotension detection is assisted fluid management. Assisted fluid management is a predictive indicator that recommends to clinicians when patients need fluid. That will be coming out in 2022. We're also working on algorithms around hypertension, so looking at the opposite end of hypotension. Really we think it's unlimited things that we can help with. To your question, during COVID, really everyone kind of goes back to basics. We saw everybody just going to basics with blood pressure monitoring.
As you saw in the example of Raul, just trying to ring the bell to get patients out and home to their families. Where they use the advanced and smart monitoring is mostly in cardiac surgery or cardiac ICU or in the longer high risk non-cardiac surgery and the non-cardiac ICU. To the extent that those procedures are coming back to normal again over time, that's where you're gonna see the growth.
Katie, when you've talked about it in the past, you've talked about the positives that have come, the things that critical care has been to help during COVID, but also some of the drags. Do you wanna describe that a little bit?
Yeah. We saw some increase in demand for capital and mostly significant increase in demand for our basic PPTs. What you see for us is if COVID surges, there's more of an increase in the core monitoring business, but then because procedures come down, then the smart monitoring come down, so it balances itself out a little bit. Over time, we're seeing actually a more stable, higher usage of our basic pressure monitoring. We're seeing regular procedures come back, and so smart monitoring is starting to come back to growth again. Thank you.
Got it. Okay. Thank you for that, Katie. Just one quick follow-up for Bernard and back to the guidance for TMTT for 2022. Just is there any more color you can give as far as you mentioned, you know, bridging us from 2021 to 2022 since you're activating new sites. How many new sites are going to be activated? Any color you can give that could give some comfort around the jump there that you guys expect to see? And are these gonna be competitive sites? Are you opening new sites entirely? Just a little more color there would be super helpful. Thanks so much.
No, thank you. Think about, you know, in the last, you know, couple of years, you know, where we have been deploying our sales force was, you know, we started in Germany. We have activated, you know, a lot of sites in Germany. We still have a way to go in Germany to activate, you know, more sites again because, you know, we go, you know, by quarter, and we see, you know, how many sites, you know, we can open. We also deploy our force in many countries outside of Germany, but we have not yet, you know, reached, you know, what we can do. I will say that, you know, we are opening a certain amount of sites, you know, by quarter.
We see that, you know, even in Q4, despite, you know, all of this, you know, COVID, you know, happening right now, we are still, you know, very active in opening new sites in Germany and outside of Germany. We are going to accelerate, you know, basically, you know, the site activation in Europe next year. This is one of the major driver of expansion next year in Europe.
Okay, great. Thanks for the questions. Maybe we'll transition back in the room then and see if there are any additional questions here. It looks like we're just going down the row. Joanne Wuensch, please.
Thank you. It's Joanne from Citi. I wanna clarify a couple of things on PASCAL, if that's okay. Are you assuming that a panel meeting will be needed in the United States?
No, we are not assuming that we will have a panel meeting. You know, this trial is a randomized trial against, you know, MitraClip. We are not assuming for a device in the second, you know, after MitraClip, you don't have a panel meeting. There's no panel meeting.
No panel meeting. Reimbursement will be in place when you get launched?
Reimbursement will be in place. You know, we have a current DRG in place today in the U.S.
A question in surgical heart valve. Talking a little bit more about headwinds as you know, sort of TAVR continues to take off. How do you think about incorporating that into your market assumptions?
No, definitely. Thanks for the question. Across our major markets, we continue to see the ratio out in the developed world especially. We can assume that the ratio of TAVR to SAVR continues to increase kind of based on where that healthcare system is in that ratio and patient care, which patients are getting a TAVR and which patients need a TAVR. We have that built into our model. If obviously that happens to a greater extent than we're assuming, that would be a headwind to our model next year.
Daveen, why don't you give a little bit more color on that? When we see these major approvals, you see sort of TAVR versus SAVR surge to some extent. You see it happen in different rates around the world. When you go big picture, do you think that aortics, surgical aortics will shrink, or do you think it'll grow? If so, why?
Yeah. There's two different factors you can always imagine, right? The AVR market, overall aortic valve replacements, are growing at a great rate, right? Within there, you see this conversion of SAVR to TAVR. We've now reached the point, especially in a market like the U.S., where the lower risk indication's been around for a few years, that there's been a bit of conversion where we've seen the surgical market for AVR continue to grow. How much it grows as part of that depends on the overall SAVR to TAVR kind of conversion.
We saw recently the last year as Larry's group got a great indication reimbursement for the low-risk indication in Japan, that TAVR-to-SAVR ratio started staying there, which still put a little bit of headwind to our business even though we're still slightly growing in the surgical market as a whole.
Just to build on that, you know, when we try to take TAVRs to a lot of emerging markets, they haven't even adopted tissue valves yet. They're still using mechanical valves. In places they're still using mechanical valves, there's probably today.
Go through the process of converting tissue, and then TAVR is gonna be further down the road. I think a lot of those emerging markets, there's still great opportunities for surgery to do that mechanical part of the pyramid for those mechanical valves is huge, and that's a great opportunity for us to win in those patients.
Thanks, Joanne. Anthony?
Thanks, Anthony Petrone from Jefferies. One on the $10 billion TAVR outlook, you know, and this dovetails on the discussion last time. What is in there for the percentage capture in the severe symptomatic category, specifically that $10 billion? I think last night you suggested 10%-15% referral rate. If you do that math, it really suggests that if you put a total available market on, it's about $68 billion. What is actually in there for the severe symptomatic capture rate? And then I have a follow-up on CapEx related to this for Scott.
Yeah. Well, it'd be kind of a doubling of the penetration rate, because if you look at the penetration rate now, it's still quite low. We're still probably in the low teens as it relates to penetration rate. Even if we double it was all severe symptomatic AS, you double it, you're still gonna be in the low twenties, low to mid-twenties, which still feels like a pretty low penetration rate for just severe symptomatic. I don't know.
You're even quoting the U.S. number, which is the highest number in the world.
Yes.
Globally, you go to other markets that, you know, 10%-15% is actually a lower number, so even more opportunity.
Yeah. You and I spend a lot of time looking at the total opportunity because we wanna make sure we don't double count, right? We create one model that we both live within. You know, it really does change depending on where you are in the world. You know, we quote the U.S. a lot because it's the largest opportunity, but even in the U.S., the treatment rates are surprisingly low when you consider how deadly this disease is.
The follow-up would be if you consider Early TAVR and then the PROGRESS initiatives and moderate, and now you have a DTC campaign, that may be, I think, you know, across all global markets, it would strike us that you would eventually need, you know, a growth CapEx cycle, right, in this 2028 horizon. If you really do unlock, let's say another 5% of severe symptomatic, will that require a growth CapEx cycle in that 2028 horizon? Thanks.
Well, we've been going through growth CapEx cycles, so you're right. What it's translated into is a combination of building new facilities and expanding the capacity of our existing facilities through things like retooling, lean initiatives, and the like. We're gonna continue to invest in both valve plants as well as delivery system production facilities around the world. Our objective is to really have a pretty broad footprint and to have redundancy in various different regions of the world to account for potential supply chain interruptions, potential regulatory interruptions, et cetera. We're gonna continue to invest in facilities.
You know, I just might add to that. We're not an overly capital-intensive business, and you can tell just by looking at our the amount of capital spending that we have on a traditional basis. When you talk about things like doing TV commercials, which we're just kind of experimenting with, I would say at this stage, probably not a capital expenditure. That puts pressure on our SG&A rate, and it's why we don't necessarily project ahead and say we're gonna get a lot of leverage because some of those costs, as even as the business grows, are gonna grow.
Thanks for the questions, Anthony. Maybe a couple more in room, and then we'll go back to the phone and then back in room. Jayson?
Thanks. Jayson Bedford from Raymond James. I'll ask the tough COVID question. It's amazing it took this long, but you've referred to COVID as a headwind in every segment of critical care. I know this is a dynamic situation, but at some point, COVID from a year-over-year growth perspective, I think, becomes a tailwind. Maybe can you talk to the COVID-related headwinds that you're seeing in the market today, and maybe just touch on the thought of tapping the backlog of patients.
You wanna go?
I think we can all kind of start. We can hardly wait until COVID is a tailwind. Right? I think we all can. For now, you know, the headwind is basically tied to various different hotspots. We've seen it in Europe as recently as just the second half of last month. We've seen it in how it relates to hospital staffing challenges. We're gonna work through this and try to be nimble and be prepared for whatever comes our way. We are expecting that we're gonna be living with COVID, especially as we get into the early part of 2022.
Yeah. I think maybe that's the point. When we give our forecast for 2022, we assume that, yes, it's a headwind, but it'll be a gradual recovery from COVID, and that we won't have any of these sharp impacts that come from a dramatic variant, for example, that came through. If that's wrong, then we'd be too optimistic in our 2022. Also, as Scott says, when we're thinking about calendarizing the year, probably more pressure in the front of the year than the back, just knowing that it's still winter and the system's still dealing with COVID and the variants that we're dealing with today, you know, with the idea that it's likely to be better, at least that's been our assumptions as the year goes on.
Comments on the backlog? Is that, you know, not worth mentioning?
No. It's worth mentioning, and it is there. It's a good point. For those that aren't closer to this, in Q2 of 2021, we saw a real boost in our sales, and we feel like there was a portion of that that was clearing of a backlog of fabrications, and we felt it in the U.S. and maybe even more broadly globally. Could that happen again? Yeah, it could happen again. We hesitate to predict it. We're certainly not feeling it at the moment, you know, we haven't put big numbers in our forecast related to that.
Okay. Just on PASCAL commercialization adoption in the U.S. will be impacted by a more narrow label versus your competitor out there. I realize you're also building a separate team for PASCAL, but can you talk about the potential synergies, selling synergies with your TAVR team if you think that's a factor as well?
Yeah. Bernard, you wanna go?
Yeah, sure. It will be, you know, for PASCAL, it will be a DMR approval, so we will be selling, you know,
You might wanna spend a section just explaining DMR.
Degenerative, you know, mitral regurgitation is, you know, one segment of the entire, you know, mitral patient segment. It is less than FMR, you know, functional. We will be selling only, you know, to the DMR, which is where we will get, you know, the approval. The year 2023 will be a full-blown launch, correct. We are going to start with, you know, a few sites. I don't know yet, you know, how many, but think about, you know, we have about, you know, 70 sites in our clinical study today. I believe we have a good target to start with. Then, you know, we will expand, you know, throughout the year.
In terms of synergy with Larry's organization, we are talking a lot. You know, Larry and I are talking, you know, every day. Yeah, sometimes, you know, multiple days. You know, our different people are talking on a regular basis. I think, you know, dedication is key to success. This is the only way for the high touch model. This is the only way to do, you know, the things the way we want to do it, to bring value to physicians and achieve, you know, optimal outcomes. Yes, the team will talk, but, you know, we are not going to obviously sell both together. The two teams are going to have, you know, different objectives.
Yeah, I think that's a really good point that you know, Larry, you can build on this as well, but remember when we launched TMTT, we could have leveraged the best transcatheter aortic valve team in the world in our opinion. We said, "You know what? That opportunity is so big, we want that team to stay focused, and tricuspid and mitral transcatheter valves are such a big opportunity, we want a dedicated team." That's why we went after it. We know when we get approval in the U.S., it'll just be the degenerative patients. We're in it for the long run. You know, Bernard has a trial going for the functional patients, and that'll come at some point. It will progress over time.
Ironically, there were more procedural synergies eight years ago. Eight years ago, we were doing all of our patient pre-op TEEs in the middle of their procedure. Our people were doing echo. We were using echo for sizing and for approaches and those things, and our procedures took a couple hours. This procedure takes a couple hours. It was much more similar. Now, if you look at where TAVR is, it's a 45-minute procedure. It's mostly under fluoro. You know, a patient can get done faster under echo, but all of the sizing is done on CT, which is very different than what's happening in the mitral procedures. You know, like we have.
You know, our whole goal is to how do we get better, faster procedures, how to do five a day and do them in one setting and do them very efficiently. The mitral technology is just not there place now where they can do that kind of staffing. I think it's pretty different. I think having focused teams really driving each thing makes the most sense now. There are a lot of synergies, though, in terms of how do we share account information, how do we share physician interests. You know, our council approach means, say, Kevin really interested in this, and so we go to Bernard, and sometimes we go to Naveen. The three of us all, you know, ignore Kevin, but the three of us all have very nice relationships and work closely together.
I don't think anybody could ignore Kevin there.
It's more important than just consensus, John. It's just about the field forces in the field, right? The coordination that happens on account with separate presentations from us when it's separate primary customers. The coordination between Bernard and Larry's organization in the U.S. now happens down the field. Our reps are talking to her, managers are talking to her about how to approach accounts by detecting who's the right person you should go to for different things. That's just important. I think it's a synergy we all have in Structural Heart with our scale.
It came back to you, but actually we work really closely with Katie as well because we're desperate sometimes to get any of the algorithmic work she's doing to be susceptible to AF. Katie and I work really closely together and say, "Hey, you know, is there some way to move away from echo diagnosis?" We pretty much spend a tremendous amount of time together in different ways and just trying to figure out how, you know, we can all partner together to make this thing go.
Jayson, thanks. Brandon?
Hi, Brandon Vazquez from William Blair. It seems like one of the main growth drivers at this point for TAVR is gonna be sort of getting these patients into the funnel. That's just step one. Seriously, even getting them into their heart failure team. We had one or two slides on this kind of dynamic. I feel like maybe you guys could probably done an entire session on just this dynamic. Could we just get a few minutes talking about that? What are the efforts you guys are investing in? Are you increasing those efforts or those investments as we're getting to kind of the next leg of patients?
Yeah. We're certainly increasing those efforts. We're, you know, we focus a lot on digital. We focus a lot on social media. We focus a lot on our presence on the Internet, and how do we, you know, reach out to people, how do we make people more aware of the disease, and also where can they find a heart team. The patient goes through this traditional pathway, if you will, of going to their GP and getting a referral to a cardiologist, and then getting diagnosed and running through. It takes the average patient more than like six months from the time that they first get diagnosed till the time they actually get their procedure. When you have a disease that's this deadly, that's just really not good.
Part of what we're trying to do is how do we jump over that a little bit and how do we get patients flowing more directly to a heart team? I mean, what a patient ultimately wants is they wanna see one of our heart teams that has the surgical options, the mitral options, the TAVR options the patient and say what's best for them. We really try to push the heart team concept, and we try to push patients to seek out a heart team, where they can get all the options for them. Not every patient is a good TAVR patient. You know, there's some patients that are better served in surgery, and I think product like KONECT are an excellent example of that. Somebody might have aortic and root pathology.
They come and ask you about TAVR because they maybe heard about it. If you're not a good candidate for it's just a great place for a handoff. This is just the stuff we continue to drive and continue to bring that. That's again why we work closely together. You know, the DTC commercial was a big leap for us. We thought about it deeply. We cared about it deeply, and we just felt it was the right time for us to do this. I think it'll take us a while to figure out how effective it is, but we're just committed one way or the other.
If something doesn't work, we just move on to the next thing, and we're just gonna keep going until we get these patients off the sideline and get them the care they need and deserve.
Got it. Thank you. Then one other one maybe on international. I think a couple of years ago in the 2019 analyst day, we spent a lot of time talking about under-penetrated markets in TAVR within international key markets. We didn't talk too much about it today. You can appreciate COVID kind of made that a little difficult. Where do you kind of sit with international penetration today? Is it still under-penetrated relative to the U.S.? And how big of an opportunity is there for investment there to set that up?
Yeah. I'll start here, and I encourage others to jump in here. Clearly, there's an under-penetration outside the U.S. compared to the U.S. The U.S. is the most penetrated, and we've just talked about how little the U.S. is penetrated, and it's a far bigger opportunity outside the U.S. It seems as though it primarily correlates to where they are in terms of the growth of their own economy. You know, GDP per capita kind of matters. We almost see as GDP per capita increases, healthcare spending increases, and the adoption of our technologies increases along with it. We still tend to see Europe and Japan, the biggest users of our technology outside the U.S. The emerging markets, although they're still smaller, are the ones that are growing the fastest.
Even mature technologies like the ones that Katie and Daveen are managing are still big growth opportunities. Feel free to jump in.
Yeah. That's why I think we highlighted and talked a little about it. At least in terms of that opportunity for, I think, you know, 60% of the world's mitral valves are mechanical, primarily coming from emerging markets. Huge opportunity to help those patients out with premium tissue technologies. I think, we can get excited about it. And I think as Mike says, we see these patients in self-pay markets, and you see a country get wealthier, people are living longer. The first thing they do is automatically say, "How can I spend some more on healthcare? How can I live a longer, better life?" You see their awareness of disease and their willingness to spend, go up and generally our end-use technologies matches along with that pretty well.
Even in Europe, and Europe's not homogeneous. If the penetration rates in Germany are very different than the penetration rates in the UK, there's still tremendous opportunity even when you look at greater Europe to improve these penetration rates. I think we look across Japan is still, you know, a rich opportunity, I think. You know, we're just getting started with low risk. We got the low-risk approval right in the middle of COVID. I just think there's a lot of international expansion that's still out in front of us.
Great. Thanks for the questions. Diego, it looks like we've got a few more online here. Maybe we could transition back to the phones before coming back in room and closing out a couple more questions there. Diego, go ahead if you're ready.
Thank you, Mark. Our next question comes from Matt Taylor with UBS. Go ahead with your question.
Hi, guys. Thanks for taking the question. So I wanted to ask you kind of one, I think it's really for Scott and maybe others can jump in just on the assumptions for next year before we get to the gradual COVID recovery. I think that makes sense to start out with. I was wondering if you could give us some thoughts on the big topics of staffing and supply chain. It sounds like you're relatively sanguine about supply chain, so just wanted some more detail there in terms of inflation impact. Then staffing is something a lot of clients are concerned about.
I was hoping you could provide some insights as to how you think that could resolve, you know, if COVID cases come down, do you think that largely resolves the staffing issues or could you see some tension in a hospital's ability to deliver care next year?
Well, I'll tackle global supply chain and leave the staffing for hospitals issue to somebody else. Global supply chain, it's a relative situation. In 2020, we ended up incurring a lot of additional expense, keeping our plants open, keeping our employees safe, keeping our supply chains resilient, supporting our suppliers. Those expenses actually come down during the course of 2021, and we're getting back to a more normalized expense environment for global supply chain, which is why we're not feeling as much of an increase as we hear other companies talk about.
Not to say there's not an impact, there's definitely headwinds, there's wage pressure, there are materials price pressures, but those are really pretty manageable at this point, and it's baked into that guidance that we gave of 78%-79% gross margins.
Matt, I'll just pile on a little bit. I'm extremely proud of our global supply chain. They've done a remarkable job of continuing to maintain supply during all kinds of challenges. A lot of it is not only their commitment to patients, but also the fact that the doctors have been very forward-leaning from a strategic point of view. They have built resilience in advance so that we were able to handle some of the shocks that we put on. As Scott said, it's a better situation right now, but if you were to actually get in there with those supply chain guys, they're fighting fires every day. They're constantly fighting, you know, price increases or disruptions to technology, and they found a way to maneuver through it. It's been impressive thus far, and it really hasn't shown up in our financials.
Now, the other part of your question is related to hospital staffing. We hear about that a lot from our customers, but, you know, maybe some of you guys wanna comment on that now.
I can jump real quick. From Scott's standpoint, obviously, I think that's the number one thing I hear from my customers in the U.S. and Europe more recently. I think, at least we saw during COVID that, surgeries were generally prioritized. I think, there are always some hits here or there. It's an overview problem for everyone. Everyone's got it, and they're kinda going hand to mouth across the board. In general, we've seen with surgeries that, there's some hits here or there, but across the board they're making it happen. It's tight. It's very tight. Pressure. They're waiting for the patient to get out of the ICU so they can finish the surgery and everyone in.
It's definitely top of mind, and they're hoping that as we move on from COVID, there's more optimism that we'll get to more staffing models, the normal models. If you guys wanna comment.
Yeah, I mean, a lot of hospitals, I think people have been frustrated, you know, whether it's kind of been in this or whether it's just people just stepping out of the field, it's causing frustration. I know hospitals are super active about trying to figure out how to backfill these positions. I know one of my hospitals, they hired 35 nurses, and they're all going through the training program now to kind of backfill this. I know they're being really aggressive in this all, but I think we're seeing the pendulum swing. I mean, I'd say how long ago was it? Maybe eight, 10 years ago, there was a real nursing shortage, and it was a big constraint. Then, you know, don't know how the nursing thing, it took years to go, but it backed up again, and it took care of itself.
I think, you know, one positive is I think nurses have been underpaid for a long time, and I think this is probably gonna be a little bit of a reset to nursing pay. I think that's probably a little bit of a positive because I was expecting, I don't know exactly when, but I think it'll return.
Thanks for the question. Diego, it looks like we've got a couple more on the phones. Maybe take those two next.
The next question comes from Adam Maeder with Piper Sandler. Please take your question.
Hey, good morning. Thanks so much for taking the questions. The first one for me is on TMTT and mitral repair, specifically. Timelines for CLASP IID study and DMR are pretty clear-cut, and I think kind of well discussed at this meeting. I didn't hear much on CLASP IIF for FMR. Was hoping you guys could share just a little bit more on the trial progress there or just broad strokes how we should be thinking about US commercialization. I had a follow-up. Thanks.
You know, thanks. You know what we did last year or maybe 18 months ago, when COVID hit, we look at all of our studies and we prioritized the studies. We said, you know, look, you know, the TRISCEND study, you know, what the most important for us, you know, to be able, you know, to bring, you know, this study along. We talked to all of our clinical sites around the nation and for them, you know, to prioritize, you know, the study. We did that well. They did that well within partnership. TOF was, you know, basically, you know, not on the top priority study.
Right now we are changing the priority as we speak, you know, given the fact that study is very close, you know, to be completed. Obviously, you know, IIF has been impacted. You know, CTR has been impacted, you know, because of this reason. You know, we see now, you know, an acceleration. We are seeing an acceleration, you know, this year, you know, on these two studies. I'm not ready to comment on exactly the timeline, you know, when we are going to complete, you know, these two studies. But this is, you know, basically you know where we are here.
Adam-
Yeah. Thanks for the color. Yeah. Thanks, Mark. For the follow-up, just wanted to ask about China and, you know, the opportunity for TAVR there. I think you've had an approval now for high-risk patients for 18 months or so. Just latest update today, how do you think about the future revenue ramp in the coming years? And then what is contemplated in that $10 billion TAVR market estimate for 2028 for China? Thanks so much.
I can start, Larry, and then you can jump into some specifics. The good news about China, it's a very big market and potentially a big market opportunity. What's been tough is getting our approval last year is that we're trying to launch during COVID. As you can imagine, there is exactly zero travel into China. Our ability to bring KOLs in or even visit ourselves has been severely limited. It just hasn't been possible. We're really not overly concerned about the short term. We're more focused on the long term there.
We think China's gonna be a nice opportunity, but when you consider how big TAVR is at this point, and how big TAVR is likely to be in 2028, that's probably still small, compared to the overall where the sales and sales growth is gonna come from then.
Yeah, I mean, I think China's gonna be important long term and what's gonna be short term, what's gonna be long term, who knows? You know to maximize the opportunity, Larry, you have to establish your footprint, you have to establish your brand. You know, we need to really establish our premium brand there. As spending increases, you know, we wanna make sure we get our fair share of that. It's a very different market than other places we compete. You have local Chinese competitors who don't follow the same regulatory process that we do. We don't deal with that really anywhere else in the world. It's largely self-pay, which also is a different dynamic, and there's a distributor aspect to it, so it's pretty different.
I think what we're really focused on right now is kinda like what Bernard talked about when bringing his therapy forward, is how do we make sure patients get an amazing experience? How do we bring our high touch model there? How do we establish our brand as we are a premium TAVR product, you know, in the region and make sure that we establish that and that we drive in patients who are best known to ask for it. I think that's our focus right now. It's much bigger focus on that because we think those are long-term drivers than focused on short-term revenue growth, which I think would be drivers to different things that I don't think would be as strategic over the long haul.
Adam, thanks again for the question. Diego, maybe one more on the phone and then we'll come back in room.
Your next question comes from Rick Wise with Stifel. Please go ahead.
Good afternoon, everybody. Thanks, Mark. Larry, just to kick it off, a question for you. You sort of touched on this in passing just a moment ago. It sort of at the end of your comments, you indicated that you I think your quote was, "We're just getting started with low risk in many markets." Japan, I'm guessing, is one. But maybe help us better understand why that comment. Is this geographic? Is this still in the U.S.? And maybe just help us think about current penetration of low risk and especially the growth contribution to your near- to medium-term growth outlook.
Sure. Well, Japan is probably the biggest opportunity for low risk. You know, Japan is different than other places we've been. Most places we started inoperable, then we went high risk, and we went intermediate risk, and we did low risk. There was just sort of this gradual step down. In Japan, we went right from high risk to low risk. It's a different step and kind of requires a little bit of a different education model. But again, having low risk, just taking a step back, this whole risk scheme is a regulatory artifact. It's not something that makes any sense to patients.
When you talk to an AS patient, regardless of their age, you say, "If you don't get your valve fixed, you're gonna die." Then they go, "Okay, well, can I get TAVR?" They go, "No, you can't. You're low risk." "I thought you just said I was gonna die." Well, yeah, you're gonna die. You're high risk from AS, but you're low risk of dying from surgery. That's really what low risk means. It doesn't mean you're low risk of dying. It just means you're low risk of dying from surgery. Now that we don't have that risk scheme there in these markets, people can just talk about, you know, commonly, what's the best solution for you and everything. It just changes the conversation rather than this artificial risk algorithm that we applied. So that's part of it.
Even when you look across Europe, remember, getting the approval in a lot of markets doesn't get you reimbursement. Getting an approval without reimbursement is fascinating, but not terribly productive. We continue to see reimbursement expanding, we continue to see those things expand, and that's what's gonna still drive some places in Europe. There's just a lot of international destinations where low risk is still terribly underpenetrated. They're still operating pretty much in the high and intermediate risk.
Larry, you know what I was thinking about is, remember the comment from Philippe Généreux, who I think is this doctor at Philippe Généreux who's involved in a lot of the new technologies we're talking about. It's funny the way that adoption has somewhat lagged the actual approvals.
Yeah, no, it's a great point. I mean, you know, we talk about getting the intermediate risk approval and how important that was for an intermediate risk, but it was probably even more important for high risk because people, when you just had the high-risk indication, people were debating surgery or TAVR in high risk. Once you got the intermediate risk, it almost killed the debate in high risk. And so as you get that next approval, what it does is it just sort of ends the discussion on whatever the previous approval was, and that's probably one of the biggest benefits you get from expanding those indications. I thought it was a really smart point from obviously somebody who's thought enough about it.
Obviously, right.
Hey, Rick, thanks for the question. Let's come back to the room. I understand there's some people typing in chat. Let me go to Suraj next from Oppenheimer, please. Suraj, could you raise your hand? Thank you.
Hello, everyone. Suraj Kalia, Oppenheimer. Mike, one question for you, and I'll throw in one for Larry. Mike, one of the topics that has been on TAVR that has been discussed is about access inequity, socioeconomic and race and whatnot. When you look at $10 billion for 2028, where does access figure into that picture? Larry, if I could quickly throw in a question for you. Yes, you will weigh on Alliance, and it just means thinking, you know, if it's gonna be on personalized medicine, right? You can think about providers and deviation protocols, patient characteristics, device site. What is the ultimate goal for SAPIEN X4 Alliance? Is it incremental benefits of what we are seeing today? Increase in patients? If you could just kinda give us some tangential goalposts to start thinking about. Thank you.
The question of access for some of those underserved populations is a complex one, but let me just try and get to the bottom line. In TAVR, like many other parts of medicine, it's a real problem. There really is an access issue. We find there are underserved communities that just don't get access to technology. As this market more or less doubles between now and 2028, we will make some nice progress in that regard. We will not have resolved the problem, but we will have been able to reach a much greater group, and it is a key part of our focus.
Yeah, just touching on that. It's just a little bit of a personal passion of mine. When you look at the penetration rates or the adoption rates of TAVR in white communities, the line, you know, that's really what's driving the curve. When you look at communities of color, it's almost flat. It's really disappointing to see how poor the adoption rates are. You know, it's multifactorial. We tried to run a study where we really focused on centers that wouldn't otherwise have access to TAVR. We put those centers in a community, we put another in IDE. We'll give away valves. We'll open up these hospitals. You know, we'll solve the problem.
We had a very difficult time enrolling that, and it's just so much more multifactorial than just free valves or having a hospital nearby. It's how patients move through the system. I just had a program last weekend where I was talking to local communities here in communities of color on how do we make this information available and how do we go to churches and barber shops and other sorts of places where communities of color get a lot of their trusted information. It's just. It's so disappointing that we've made such little progress in this area with technology that is so helpful to patients. It's just an area we continue to focus on, but it's complicated.
We're just gonna keep having to swing away at it and find out a way to solve it because what's going on just, you know, it's just fundamentally just not okay.
No, I know we're running short of time. You had a second question. Will you repeat it, please?
Yeah, the X-four. The other question about the X-four. I think it all works in concert. When I talk about the precision personalized medicine, part of that is about technology itself. It is what we're gonna do with EARLY TAVR and what we're gonna do with PROGRESS and what we do long term. Having an algorithm where you can plug all the patient characteristics in and then say, "For you, this is the right time to intervene, and this is the right way to do it." I think that's really what we're trying to drive a long-term play. That's not something that's gonna happen overnight or even in the next year or so, but we think the valve technology can be part of helping to enable that.
Okay. An hour of Q&A goes quickly. Maybe time for one more, and I would just remind you, for those of you who are able to stay, we'll have a lunch hosted with management right after this, so you can ask your questions then. Chris, I know we've heard from you already, so I wanna just spread it around a little bit more. How about Cecilia from Morgan Stanley?
Cecilia Furlong from Morgan Stanley. I'll just ask a quick question, but wanted to ask a little bit about your thoughts on longer term R&D investments. You talked about Cardioband being a focus for redesign going forward, but you talked also historically about heart failure, and that's been an area you've looked at. So just curious as you think about some of the longer term TMTT heart failure opportunity, what you're looking at, say, longer term, just the optimal portfolios you invest going forward.
Yeah. Maybe two different questions in there. Are you more of a question what the rate might be or more what the area of focus for R&D might be?
Really more the focus.
Yeah. Thanks for that. We've got the treasure of just having a target-rich environment. When you hear Larry talk about how much ground there is to cover in TAVR, it says, wow, we need to continue to invest because we know that's a winner. When you think about what Bernard is working on here in terms of unlocking therapies for transcatheter mitral and tricuspid, we're just getting started. You think about what Katie's doing to transform critical care medicine with technology or what Daveen's doing to offer some great solutions for people that are underserved today. Those are all big. At the same time, we've got teams looking at, you know, this giant population of heart failure that says, wow, that's the biggest expense item, biggest killer. Maybe that's a natural adjacency.
We as an executive team spend a lot of time talking about exactly that. I can't really project where we're gonna go out. We try and make right decisions along the way. You know we're long-term planners and always thinking.
Sometimes we fight about it. I mean, look
All right. I think we'll wrap things up at this point. Thank you so much for joining us. We never like to end a session without reminding all of ourselves why we're here and the impact that we have on patients. Let's run that video right now. Again, thanks for your interest in Edwards Lifesciences.
All right. I'll give you two bars in.
Okay.
One, two. One, two, three, four.
My name is Ed Murray, and I play wind instruments.
He plays the saxophone. He plays a flute and the clarinet.
I've been doing it for over 60 years professionally.
Music is very important in my dad's life. It's more than just a job. It's part of his identity. It brings him joy.
The most important thing about being a wind instrument musician is breath, adequate breath to develop a good sound. Without that, you don't play. When I first encountered shortness of breath, I was 73 or 74. My stomach was an empty. I was fatigued all of the time.
We went on a family vacation, and walking from the house to the beach was a very slight incline, but he was very challenged by that.
I contacted my PCP, and it was determined that my tricuspid valve was leaking. It looked like I might be facing open heart surgery. That was frightening to me.
The surgeon actually sent him to me and said, you know, "What can you do?" He had tricuspid regurgitation, and the right side of his heart was failing. Given the anatomy of his valve, replacement was absolutely the best option.
When I heard about the EVOQUE valve, I was very excited because I knew it was going to be much less time required for my recuperation. I said, "Where do I sign?
Despite the fact that it was our first case, Ed's procedure went very smoothly. We positioned the valve, deployed the valve. Everything was as expected and predicted by the Edwards screen.
When I woke up, I think I was smiling.
The next day, he was up walking around the floor.
On my third day, I was able to climb a flight of stairs, and I was told, "You can go home.
Welcome back, my Papa.
Good to see you.
Give me a kiss.
Oh.
All the color was back in his face. He was playful and joking with Grace, and I was so relieved to see my dad looking like himself again.
Within a couple of weeks, I was able to resume walking, and then I worked my way up to three miles a day. Now, as we like to say in the music world, I'm back in the groove. Get ahead, boogaloo. Rocking. When I picked up my instruments, the breathing I had been used to all my life came back to me. It made a huge difference in my life. Everybody, ladies and gentlemen. Let's hear it for Ed. Okay. Your turn. I'm back to teaching again, and I'm also teaching a very special student. No, you don't.
When we breathe in, our stomachs fill up with air, and then when we breathe out, the air all comes out like a balloon.
She's a quick learner.
B-flat. It sounds like, "Bee, my friend.
She can have a music career someday if she chooses. Come on, everybody. One more time for Ed Murray.
Ed has zero shortness of breath. The swelling is gone, and he completely came off of his diuretics. Most importantly to him is he's performing professionally and living his life the way that he had always hoped to.
My bond with my granddaughter is very, very important to me.
A few weeks ago, they were having a lesson, and I heard them marching. I overheard him say, "Hey, that was our first jam session.
I'm very excited about the future of EVOQUE. It's giving us a minimally invasive way of treating our patients and having them start living their lives.
To the employees at Edwards, I am so grateful to you. This innovative device has saved my dad's life.
The EVOQUE system is really providing an option for patients that really did not have one previously. We're making patients' lives better.
Thank you. Thank you so much for bringing me back to life.
Thank you for making my papa healthy again.
That's all, folks.