»» Good morning, welcome. My name is Joan Michaels, I'm the Program Manager for the STS, ACC, TBT Registry. I have a better half. Her name is Carol Cron. She manages the STS, part of the STS and ACC TBT Registry. She's coming off the AQO meeting that they hosted last week if any of you had participated in that. So she's in a coma state right now. But no, she's fine. But she wished us really well and sent some really good thoughts. So she and I collaborate and work collaboratively together with both Dr. Vino Terani who's the surgeon part of the STS, ACC, TBT Registry, and Dr. Wayne Batchelor is the ACC part of the STS, ACC, TBT Registry. So there's a lot of people to blame if you don't like anything about the STS, ACC, TBT Registry. We just happen to be the two people who are here today. So we're very excited that you're here. Thank you. Thank you for coming. My plane had a problem. I don't like to fly. We had to get off and sit in the airport yesterday before we got back on. So I can imagine a lot of you had to deal with some of the same issues or making sure your dogs and cats and kids are fed. But we're all here. This is going to be a great three days. We're starting off with Dr. Batchelor sort of giving the idea of kind of where we were, where we are, and where we're going with the TBT Registry. So exciting data, exciting news. And then we'll have some time for some interactive questions. So think about what's your pain point? What's your problem point? What do you want us to look at when we're doing our upgrade for next year? In introducing Dr. Batchelor, he has way too long of a resume. But what I do know of him is he's my personal concierge physician and also the referral for anybody at the ACC. We call Dr. Batchelor. So he's well taken care of and we have to be nice to him today. But he's marvelous, marvelous and so helpful with the TBT Registry. He is the Director of Interventional Cardiology at the Inova Heart and Vascular Center as well as the Associate Director of the Heart Center. He's the Director of Interventional Cardiology and Associate Director of the Full Heart Center. Also he's a professor at Duke. He's also in the process of getting his Executive MBA program currently at NYU. He's busy. He travels all over the country and the world. He is involved in about 160 clinical trials. And besides being my personal concierge physician, he's also in charge co-chair with Dr. Tarani as I said of the TBT Registry. We meet every Friday morning to go over questions. And we meet monthly with the full Steering Committee to decide the future of the registry involving again, everything you'll talk about today. But he's very involved in the registry and also in personal interest with structural heart, disparities of care, cardiac shock, cardiogenic shock, complex PCI patients. So we're very happy and lucky that, you know, he could have gone both directions, either in the PCI world or structural heart. We're very lucky to have him with structural heart. So if I forgot anything, oh, and he has a dog. That was the first time I met him I said, so all right, you have a dog. And he said, yeah. So he checked the box. And I would like to introduce Dr. Wayne Batchelor to the podium now. Thank you very much. »» Thanks so much, Joan. I'm glad I didn't answer. Cat, maybe I wouldn't have gotten the job. I don't know. But you're a dog lover obviously. It's really a pleasure to be here amongst you all. And my task over the next sort of 30 to 45 minutes is to recap a little bit about how did we actually get here with regards to the TBT Registry? What was the backdrop? Where are we now? What is the current sort of state of the art? And where are we headed? I can't promise you I'm going to answer all your questions addressing those three arenas. But I think we can touch on some really interesting points. And then hopefully in the time where we have questions go over some additional comments. Those are my disclosures. So where did this all come from, the TBT Registry, transcatheter valve therapy in general? It really has its origins based on our interest in aortic valve stenosis, aortic valve disease. Aortic stenosis is a condition that afflicts patients more often as you get older. At age 75 you have a 2% chance of having severe aortic stenosis. It goes up to 8% by age 85. We know that when you're diagnosed with aortic stenosis, there's a latent period. Your heart tolerates it actually quite well, it compensates. And then over time, once you get symptoms, your survival basically drops off the map. You can see here on this paper from Eugene Braunwald back in the 1960s that it was very clear that once you were symptomatic with aortic valve stenosis, your survival was about one and a half years. It was a lethal condition. So historically the surgeons have really dominated this arena. They were clever. They came up with a wonderful technique that was predictable, that was effective. And if you got an aortic valve replacement, you did very well. The challenge was getting through the surgery. The valve functioned well. But periprocedurally it was a difficult task, especially for older patients. So as we went along, we started to recognize that up to 30-40% of patients who are actually eligible for a valve replacement never got it. The question was why? And it's largely because patients were often older. This tracks with age, the incidence of aortic valve disease. They were frail and they had comorbid conditions that would often preclude them from going through the open heart surgery necessary to get the valve. So therein lies the impetus for the research and investigation to figure out a less invasive option to aortic valve disease. And we really should pay tribute to Henning Rudd Anderson, the gentleman who really came up with the first valve prototype that would allow us to place a valve through a transcatheter approach. He was from Denmark and he did a lot of work in an animal model and developed a prototype and presented this at the American Heart Association meeting in 1992. And it was a poster presentation at that time. It didn't even make it to the oral presentation. And then later on he published this. But it caught a lot of attention of a lot of folks, where at that time we were developing coronary stent technology. And he was taking it a step further to mount a valve on a balloon expandable prosthesis that could be delivered through the groin. Fast forward a decade with more research, Alain Cribillet in Rouen, France, and his group came up with the first procedure done in a human being. He had a 57-year-old man who had a very low ejection fraction, severe refractory heart failure. He was hospitalized multiple times. The balloon dilated his valve and it recoiled. He had severe aortic stenosis and he was too sick for surgery. So at that time the first valve technology was just being developed in follow-up to Anderson's work, something called percutaneous valve therapies, PVT, a company that had its origins from the Anderson valve. They developed a valve, Alain Cribillet and his team had the courage to go ahead and try it on this 57-year-old gentleman who was dying. Suffice it to say, they succeeded. Alain Cribillet placed the valve, the patient survived the procedure, and four months later he died of other causes because he was sick and he had peripheral vascular complications. But the procedure went very smoothly. And at the time when he went to his grave, he had a working bioprosthetic valve. That disrupted the therapy. This is the valve actually that they implanted. It was an anterograde approach. So they went through the vein, did a transeptal through the left atrium, left ventricle and implanted it in an anterograde fashion, the opposite direction that we do now. But that was disruptive. I mean, it completely shattered everything that we had essentially believed about aortic valve stenosis, that it was purely a surgical procedure, it was the domain of the surgeons and interventional cardiology really had no place. Now of course, we do this routinely with relative impunity and with phenomenally high success rates. So it's been 20 years. And what's happened in that 20 years? Well first of all, there's been a good basis for randomized clinical trials in this space. The partner study was really the first and perhaps one of the most important ones where patients with severe symptomatic aortic valve stenosis were considered in two groups. If you were inoperable, where the surgeons felt that you were too high risk to even try, then you were randomized to get a TAVR procedure versus standard therapy, which was basically medical therapy for heart failure. Now if you were deemed to be high risk but not prohibitive, you were also randomized to get a TAVR versus surgical aortic valve replacement. So there were these two arms and the TAVR could be done either transapically or through the transfemoral approach. Suffice it to say that in the high risk cohort, TAVR came out on par at 24 months in terms of mortality versus open aortic valve replacement. And in fact, in the early 6-12 months there was a higher hazard of mortality in surgery versus transcatheter aortic valve therapy. This was the first generation valve, very primitive valve, often 24 French sheaths, very large sheaths. And it still came out to be slightly safer and over time equivalent to surgery. Now in the inoperable patients, there was a dramatic reduction in mortality. There was a 20% absolute reduction in the likelihood of dying in the next 24 months if you got a TAVR valve. Remember aortic valve stenosis was a lethal condition. And we knew that the natural history would be that most patients would be dead in one to two years. What we didn't know is how much we could change that trajectory with this new technique. This was earth shattering and when it was presented in meetings it really got a standing ovation. It was a big, big development. To see that we had a number needed to treat of five to prevent one death with a new procedure was something fantastic. I can remember exactly where I was the first time we did and who I did my first procedure on. It was like, you know, if you ask any interventional cardiologist about their first TAVR, everyone can remember it. It was a very, very distinct event. So at the time I was practicing in northern Florida, we had a 91-year-old patient who was relatively healthy other than her age. She was at home, but she kept on getting admitted with heart failure. Normal ejection fraction, normal coronary arteries, just in and out of the hospital with heart failure because of refractory aortic stenosis. The surgeon just didn't want to operate because of age. So we decided to provide her with this therapy that's me doing that procedure. We deployed the first Edward Sapien valve that was available, Gen 1. And 22 French sheath, 7-millimeter sheath in this lady. She went home 72 hours later. This is the team. She's standing there in the middle. Did great. She lived to 98. And so, you know, this is when you sort of have that moment of awe when you recognize that you're a part of medical history where there's a clear delineation that's going to be significant in terms of a disruptive therapy. So let's fast forward a little bit there. We had all these publications that showed that this worked in prohibitive and high risk. And then of course the Medtronic self-expanding processes followed soon thereafter. Now we had all this terrific data and we're high-fiving it. We're saying, okay, we've got something new for our patients to offer them less invasion of their body to get a good therapy. The question was, what next? How do we take this, how do we disseminate it safely across the United States, the largest market where people are going to be consuming these products? How do we ensure that they're safe? How do we track that? And how do we iterate and reevaluate over time when new valve therapies come out, newer versions of the same valve come out in the commercial setting? And this is really how the TPT registry was born. And I think most of us paid tribute to these three individuals, Dr. David Holmes on the left, Dr. Bram Zuckerman from the FDA, and Dr. Michael Mack on the right. Dr. Holmes was the president of the American College of Cardiology at the time. Dr. Michael Mack was president of the STS. And of course the regulatory body, the FDA, was crucial to ensure that we could construct a registry that was a post-market surveillance registry that would track how this actually fared in the real world. And it's because of these three individuals and many others that we're actually here today to talk about this registry and its importance. The purpose of the STS ACC TPT registry was to look at what happened in the real world when all these therapies were brought to bear. And this was really important because remember, these were only clinical trials, carefully selected patients. We weren't sure exactly how this would pan out when new sites were brought on, sites across the entire nation, and new patients were being treated. And this was sort of unleashed in a commercial setting. So the TPT registry really, when it was started, was crafted basically based on the case report form used for the partner trial. It basically just crosswalked most of those variables into the registry, recognizing that it really showed very good effectiveness for determining the safety and efficacy in the clinical trial space. Let's just use the same variables for the most part for the registry. So it was a seven-page CRF that included 30-day and one-year outcomes, including quality of life measurements, echo data, and clinical data. And of course, the linkage of this to reimbursement through the national coverage decision with Medicare was really important. It was required for sites to be reimbursed from Medicare, from CMS, it was required that they enroll their patients in this registry so that there could be ongoing coverage and evidence-based development as we studied the technology as years passed. So we've really come a long way. This is the original CREBIE valve that was on the left. There have been multiple iterations that are much more effective. These valves now have basically skirts that prevent aortic regurgitation. They're now down to 14 French sheaths, which are much smaller than the original 20 to 24 French sheaths we used. And the predictability in deploying these valves has gone way up, such that we're now seeing 96 percent deployment from the femoral. We rarely have to go through any other avenue for accessing the heart. Now one of the other things that's come out of this whole process, including the TBT registry and the clinical trials leading up to it, is the central role of the multidisciplinary heart team. The national coverage decision also required that patients be assessed by a multidisciplinary team. And these are folks who bring to bear all their relative expertise to help the patient get through the procedure. The nursing staff, the PAs, the APPs and nurse practitioners, the radiologists, the anesthesiologists, everybody has got to provide their expertise. And that will ultimately lead to what we call shared decision-making. Because at the end of the day, we're talking about a very high-risk group of patients, often old, who have to make decisions about their willingness to take on risk relative to a particular amount of benefit. Those are sometimes nuanced decisions, especially as you get into the higher-risk cohort. So we really needed to have a proper evaluation, and this is where the multidisciplinary heart team comes into play and is so central to the way that we treat our patients and make sure that we're doing the right thing. Now what about the current state? Where have we gone? And the next set of slides are going to just highlight the growth of TAVR and how we've fared in terms of outcomes. And luckily, because of the TPT registry, we've really got our finger on the pulse from month to month of how we're actually doing with regards to this therapy and others. So in 2013, we had a little over 200 sites. We've grown to 834. I think the count was 834, Joan, we were going over this this morning. And that's just tremendous growth in sites. Just think of how difficult it is to scale a high-risk procedure across the country that involves a completely new therapy and a completely new procedure. Not easy. Kudos to the folks who trained sites and opened up new sites. So the TPT registry now is covered. Sites are in every single state. We have three in Puerto Rico. We just launched one in Brazil as the first international site. And we're ongoing and growing. A couple of things you can see from this map that shows the sites. The sites are concentrated where the population is concentrated. One of the challenges that we continually have had was how do we ensure that patients have access to this therapy? We just got Wyoming up. When did Wyoming come up, Joan? A few years ago. Is Casper in the house? We were very excited. People at the ACC were really running around saying, yes, Wyoming. Those folks used to have to go all the way down to Denver for the most part. So it's flourishing right now. So you can imagine, you know, these are often older patients who wants to travel outside their state and well beyond the confines of their family, et cetera, to get a procedure done on strange sites, strange doctors they've never met, et cetera. So one of the challenges is constantly weighing this balance between opening up new sites that might have lower volume and balancing quality and outcomes, because there's a relationship between volume and outcomes. The good news is, as the technology has advanced and gotten more predictable, more effective and safer, I think we can do that a little bit better than we could at the beginning of this when it was really a much more dangerous and difficult procedure. So here are the TAVR submitted to the registry. Look at this growth. We started off with a little over 4,000 in the first year of cases being done. We now are doing about 100,000 cases a year. Tremendous growth. I wanted to just show this slide comparing our growth to the growth of the iPhone, the world's most successful company, a $3 trillion company that has basically scaled and been extremely effective in leveraging tremendous resources in the distributing and selling its product. Well, in 2012, when TAVR started, there were 125 million iPhones sold. They basically have doubled this over the last decade, about almost 100 percent, 80 to 100 percent growth to 225 million. Well, we took TAVR and started with 4,000 and 4,600, and we scaled and ramped up to 100,000. That is 2,000 percent growth over 20 years. That's 25 times the growth of the sale of iPhones. I know it's not a fair comparison, but I just like comparing ourselves to Apple to make us look better than, hopefully, than we would otherwise. But really, it's a testament to the entire team, and honestly, multiple stakeholders, sites, the folks who enter the data, many of whom are in this room, the physicians, the nursing staff, the hospital administrators, the regulators, CMS, all these folks had to be involved to make this work effectively, and they also had to have this done in a coordinated fashion, which we know in healthcare is not easy to do. It's not perfect, but I think we should just pause and think just how much has been done and accomplished, and how many lives have been saved by this registry, and the information garnered from the registry over the last two decades. So what's happened in the aortic valve universe since TAVR has been unleashed? You know, the surgeons were exceedingly nervous. We had a lot of surgeons in the interventional cardiologist's office asking questions, what's gonna happen, what are you guys doing? Well, what's interesting is, as TAVR has grown almost exponentially, surgical volumes have only dropped modestly. So the blue graph here shows that surgical volumes have dropped, but they didn't go all the way to the bottom. It dropped from 70,000 to sort of 50,000 to 60,000. TAVR's gone from 4,000 to almost 100,000. So that just tells me that what we were doing was meeting an unmet need, where of all those patients who were not getting surgery, who now could get a safe procedure and go home usually the next day. The median age has dropped a bit from 80s to now sort of 70s to 80. If you're high risk, the median age in the TAVR, in the TBT registry is 81. If you're low risk, it's 76. Race is shown here, and the reason I put this up here is the demographics are interesting with the TBT registry. African Americans make up about 12% of the US population, but only about 4% of the TAVR population. So this speaks volumes to me and tells us that we're not disseminating this therapy as equitably as we would like, and there's a lot of work that needs to be done, and Joan knows how near and dear to my heart this particular topic is, and we're gonna be doing some work to see if we can change that data. In terms of TAVR procedure location, it's shifting from hybrid labs and ORs more to cath labs. Now it's about 21% of these procedures are done in cath labs, about a third in hybrid cath labs, and then about 40 to 45, 6% in hybrid ORs. This can be done now safely in cath labs, and I think we're gonna see that trend continue. TAVR access has really changed since its inception. It used to be that about 60, 70% were done transfemoral in the early sort of 2012, 2013 range. Now it's about 96% through the femoral, and that is just largely due to the miniaturization of the catheters now that are much smaller, about half in size as they were to begin with. TAVR risk categories have changed because we've actually now, since getting the high-risk indication, we now have an intermediate and a low-risk indication for TAVR. So now we're seeing more and more patients who are choosing to have TAVR rather than open-heart surgery. Our challenge now is what to do with the very young patient who's 50 years old and who's gonna need maybe two or three more bioprosthetic valves during their lifetime. Do they go for TAVR now? Do they get surgery now and TAVR later? TAVR now, surgery later? I mean, these are unanswered questions, and I can tell you we spend a lot of time in our valve clinic trying to address those issues in the younger cohort because they're now approved, and we get these 50, 60-year-old patients saying, I don't wanna go through surgery. It's not an easy question, and a lot of it depends on their anatomy and other factors, but we're having to engage in these shared decision-making scenarios more and more with young, low-risk patients. How have we done? The next few slides will talk about outcomes over the last two decades. TAVR mortality, I wanna show, you know, this is an interesting slide. Our TAVR mortality at one year was 26% when we first started doing this procedure. It's dropped down to 11% nationwide. Our in-hospital mortality is now at 1.2%. I mean, that's just absolutely amazing to me. We're getting close to what it is for a PCI procedure. It's really, really a very low-mortality procedure, all comers. Doesn't mean that everyone can do this in every single scenario, in every state, in every site, but it does show that properly trained sites can do this with very good mortality. Median length of stay is now a day. Almost everybody goes home the next day after a TAVR. It's unusual that we have patients stay two days now. They would be the exception to the rule rather than the rule. Mortality has drifted down in terms of the high-risk cohort and in the low-risk cohort, but this is just showing high-risk alone. Mortality in hospital for high-risk patients is 2%. Remember, high-risk usually in the STS model would portend about an 8% plus risk of 30-day mortality. So to get these folks out of the hospital and at 30 days have 3.4% mortality is really very good. Our low-risk cohort has also dropped in terms of their mortality over time. Remember, low risk just kind of came into play really around in the last few years, but we're now seeing fractions of a percent mortality for in-hospital mortality in this, and that's what it needs to be because that's what the surgeons get. They can get less than 1% mortality in a low-risk patient. So we have to be at that level to compete with the best gold standard historically. What about stroke? This is a really important endpoint for patients. We're now at a, we've dropped down from about 3% stroke to 1% to 2%. So if you look at 30-day stroke, which I think is most relevant, it's 2% right now in the registry, and it used to be close to 3%. It's dropped a bit. It hasn't plummeted. And unfortunately, embolic protection has not provided a complete answer. Some people favor using it, but the vast majority of procedures are not done with embolic protection because the randomized trial, looking at that, wasn't as positive as most of us would have expected. So we'll have to see how that plays out, but it's gonna be very hard to change 2% down to 1% and 0%. It's in sort of a sporadic event that is not easy to anticipate and predict. Bleeding has dropped significantly as sheath size has come down. We were at around 4% to 5% in the early part of our experience, and we're down to 1% to 2% for major bleeding and life-threatening or disabling. Life-threatening and disabling is less than 2%. Pacemakers have been one of the challenges we've had to deal with when you implant this valve, you're very close to the conducting tissue in the heart, the bundle branches, and you can get a left bundle, and if you have a preexisting right bundle in particular, you can go into complete heart block. And so we're seeing, with the early valves, we saw about 15% of patients would need a pacemaker at 30 days. That's dropped to about 10%, and in hospital, it's down to 7%. Pretty good numbers. It's gonna be hard to get that below 5% just because of the natural anatomy of the heart relative to the aortic valve, the heart conducting tissue related to the aortic valve. This is an interesting slide that shows 30-day changes in New York Heart Association. So how symptomatic are the patients? On the left is baseline. You can see the vast majority of patients, over 85% are NYHA Class III or IV. Then after the procedure, the vast majority are I to II, who've had a significant impact on their symptoms. This does make patients feel better. It's one of the more rewarding aspects of treating these patients. They come into the office usually saying that they're feeling better. So that's TAVR. That's the history of TAVR. Now, what is the registry doing otherwise? Well, I can tell you there is a ton of other work that we need to do and we need to track. We're looking closely at mitral and tricuspid procedures, and I don't have time to go into a ton of detail on the tricuspids, for example. I'm gonna walk you through a little bit of mitral information. So transcatheter edge-to-edge repair has also come up as a means to repair the mitral valve, a much more complicated valve. It has papillary muscles, cords, leaflets. And it's not just a tube like the aortic valve is with the valve in it. It's a complex part of the ventricle that runs contiguous with the left ventricle and has multiple dimensions to it. So repairing that valve is not as easy as repairing or replacing the aortic valve. Taking a little longer to get really good therapy, but the best therapy out there right now is transcatheter edge-to-edge repair. So I'll speak on this a little bit. This is where we go through the right femoral vein to the right atrium, cross over from right to left, steer down to the mitral valve, and then place clips on the valve. And that actually creates apposition of the edges of the leaflet in the area of regurgitation. You could put one, two, or three clips on, and without overly narrowing the valve, you can get rid of a lot of the regurgitation. This is an example of a case. This is an echocardiogram, and all this jet of abnormal flow going backwards in the heart. I don't know if this is gonna work. We'll see. There, right, that's all mitral regurgitation, that mosaic of colors on echo. You can see that the patient has actually a little bit of prolapse of that leaflet. This is a three-dimensional image. We're now in the F atrium looking down at the valve on FOSS. So this is the anterior leaflet and the posterior leaflet. You can see these posterior leaflets billowing out and sort of prolapsing up toward the image, the TEE probe. And then after the clip goes in, so we put in two clips here, you can see one clip, two clip, where this was all redundant and the regurgitation was we've repaired with these two clips. There's still opening of the valve on the other sides of the clip. We've gotten a very nice result, and we've gone from all that regurgitation and now just a trace degree of residual regurgitation in this 88-year-old patient. Went home the next day, heart failure improved, symptoms improved. Again, a very rewarding procedure in the right patient. So we had this parallel sort of movement of transcatheter repair of the mitral valve after TAVR, and we had to also figure out how to ensure the safety and efficacy of this particular development also in the community. And so the TVT registry has played a very important role in determining the safety of these procedures. Now, there are clinical trials have really shown dramatic improvement in outcome with mitral valve repair using the transcatheter approach. So this is the COAP trial. This is a randomized trial taking patients who had heart failure, reduced LV function, and secondary mitral regurgitation where the mitral valve was regurgitant not because of primary valve disease but because of an enlarged ventricle where the leaflets are being pulled apart and there's usually a central degree of regurgitation. So the CLIP therapy was evaluated relative to just medical therapy, and this was really an out-of-the-ballpark home run for the CLIP. There was a marked reduction in heart failure hospitalizations and a marked reduction in mortality, and to the point where you could look at the p-value. It's unusual in a clinical trial. You get a p-value where you can't count all the zeros. So this was a strongly statistically positive study and a strongly clinically positive study with a nearly 20% reduction in heart failure hospitalizations, absolute reduction. So we've actually now been tracking mitrals as well, just like TAVR. We're up to 542 sites across the United States. This is the heat map of where the sites are geographically located. Sort of mimics TAVR to some extent. We've gone from 99 sites to 14,000, I'm sorry, from 99 sites to 542 sites, and then procedures have gone up to now close to 15,000 procedures a year for this particular procedure. Now how has the mitral valve universe changed in terms of surgery versus transcatheter therapy? You can see here the growth of transcatheter edge-to-edge repair from 1,200 to 15,000 nearly, and what has it done to the open mitral valve surgical volume? It's only modestly impacted. Again, suggesting we're reaching patients who probably weren't good surgical candidates. This is very important, because I think the surgeon's concern that we were gonna steal all their business was largely over-exaggerated. Certainly, there are some patients who are gonna have these procedures done instead of surgery, but what's happening is we're opening up the therapy to a lot more patients who actually needed it and deserved it, but were just too high risk for surgery. Now the median age, as you can imagine, has dropped as we've sort of opened this up more and more over time. It used to be 82. It's down to about 79 for transcatheter edge-to-edge repair. Median length of stay is also, this is an overnight stay. Used to be several days. It's now down to one for the median time. How have we done with mitral regurgitation? At 30 days, your likelihood of having residual mitral regurgitation after this procedure is 7% in the registry. It used to be upwards of 13%. It's dropped significantly as experience has been gained by operators and technology has been advanced. We're now onto the fourth generation of the MitraClip, for example, and we've seen that play out quite nicely. Stroke is not as common after mitral interventions compared to aortic interventions. So you can see here, stroke is now at 1% or less, and that's what it should be for a mitral procedure for repair. And then you can see here, the one year is in green, mortality, and then in hospital blue, and 30 day in red. You can see the mortality here. Overall has dropped over time, but not as much as we saw it drop in TAVR, but it was low to begin with. And this one year is largely reflective of the patient population we're treating. So we can get them through the procedure, and then what's happening is, they are succumbing to heart failure for other reasons. That's because a large number of these patients are patients who have really bad ventricles, and we're treating the mitral valve to try to reduce the volume load on the ventricle, but we're not inherently treating the ventricle. They still have heart failure from ventricular dysfunction. So we're seeing higher one year mortality rates than we might see, for example, after TAVR. How are patients feeling? Well, this is important to track, and this is why that one year data is so, so important. And I know that there are some folks who are entering data for the registry in this room, and I know the bane of your existence is trying to just get the physicians and the other members of the team to make sure that the patients are seen, they're followed up, and that data is entered. It's crucial, because we really need to understand how people are doing at one year to understand the full impact of any technologic advance. And so right now, our challenge is trying to get those one year follow-ups done, especially the echo and the visits. And we're hovering around 50% for that, and we really ought to be at 80, 90%. And that's perhaps a topic for conversation. I know Joan has some ideas on that, and Kim has a lot of experience discussing this topic. But it's really important. So for the folks in the room, we appreciate everything that you're doing. Don't give up. This is really important. Just going back to this, this is showing that most patients are in class three to four and after they get the clip, most end up in class one to two. So we're having a positive impact on symptoms at 30 days, and we have to still continue to track that out. So there are lots of other things that we're doing with the registry. You're gonna hear more about transcatheter, tricuspid valve replacement and repair. The Trilubinate pivotal trial has finished. It showed an improvement in quality of life relative to transcatheter edge-to-edge repair on the tricuspid side. Right now, that's in the FDA under consideration for commercialization. We'll hear probably in the next six months, we hope, on whether or not that gets approved. And then of course, we have transcatheter mitral valve replacement, particularly in patients who have a bioprosthetic valve. It's a very good way to have your mitral valve treated by just simply putting an aortic valve, reversing it and putting it in the mitral position, which is a nice way to deal with bioprosthetic valve failure on the mitral side. Lots of data. Lots of discussion around how the technology advanced, the clinical trials. I'm trying to give you some relevance in terms of understanding how important it is to connect the dots between the clinical trials, what's happening in the real world. It's not a guarantee that we're gonna mimic the clinical trials. The TVT registry was really paramount for us to understand exactly how this was playing out. It also has done other things to add value to us. And that's in terms of feeding back this information to regulators, to sites, to other stakeholders to understand number one, how can we predict risk? Number two, how can we compare sites and feedback site information to the site so that they can use this in their QI processes to improve their care that they deliver to their patients? And how can we also give patients information on the site that they're going to to have their procedure performed? The TVT registry can check all those boxes and this is some of the important things that we've been working on. For example, the risk model. Through all this data, and we have, remember, hundreds of thousands of patients now in the registry between TAVR and mitral cleavage. I think it's over 500,000 now we have. So we have tons of statistical ability to develop predictive models to understand who's gonna fare better or worse. So we have an in-hospital mortality model that we've published. We have a 30-day predictive model that was published. And the 30-day incorporated quality of life in that model and that's an important learning that the patient's baseline status, not only in terms of their age and their clinical factors, but their frailty and their quality of life factors in to their ultimate risk. This is an important thing for us to consider and that's why filling out these KCCQ questionnaires are so important. So we've also developed a composite score. We basically looked at all of the outcomes that were most important in determining mortality. And basically, obviously mortality's important, but stroke is important, bleeding, AKI, which is acute kidney injury, paravalve, there are leaks, or paravalve, there are regurgitation. Those are all important endpoints for patients that actually also predict mortality. So we actually created a composite model where if you had any one of those in a hierarchical fashion that was considered an important endpoint. So we can track that and actually feed that back to sites and actually grade sites based on their adjusted risk of having one of those composite outcomes happen. And so we now have a system for reporting this back to sites and sites can voluntarily publicly report and we're seeing more and more sites do that. I think we're at what, 40% reporting? 46%. 46% of sites are now voluntarily, this is not mandated, but voluntarily publicly reporting. In order to publicly report, you have to have been participating in the registry for three years, done at least 60 cases in the past three years, have good KCCQ questionnaire completion, five meter walk test completion, and 30 day status. And if you do that for rolling three years, you can publicly report voluntarily. That can really help the sites and also the community and patients understand how things are faring across multiple sites across the country. This is kind of what the public reporting looks like. You get the report back, it's got your name, your volume, the risk adjusted TAVR composite, so all those endpoints I just pointed out in a composite fashion, zero is the average, and you can see where you are relative to zero, minus or plus, and that can give you a lot of information on how your site's performing. At the end of the day, you're also given a star rating from one to three, one being less than average, two being average, and sorry, three being above average. It's hard to get above average on the star rating. This is the distribution of where the 435 sites fared. It's only 5% get three stars. The vast majority of really good sites get two stars, so if you have two stars, don't sweat it, and one star is down here, and a couple of other pieces of information to understand. You can move and shift from one to another, and you can see that the vast majority are gonna be in here, so it's very hard to get up here, but you could drop down here and move back up here. You can stay here for a period of time, and then the next rolling three, you might drop down, so remember that all of this is moving. You're being compared relative to the rest of the sites in the country, so if you stay stagnant and you have the same mortality and everyone else is dropping their mortality or their strokes, you're actually gonna look worse over time, so these are complicated phenomenon, but we've tried to simplify it in terms of this star rating, and it's nothing that you have to sort of rest the future of your site on. A lot of sites will be two stars, but it is valuable information for sites and for patients. So what else? Where else are we going with the registry? There are some things that we still need to work on. We're updating the appropriate use criteria that's being worked on as we speak so that we can understand what is considered appropriate use of these therapies. What kind of guidance can we give to sites and operators and patients to understand what's an appropriate deployment of this therapy across the nation? Aortic regurgitation. We now have the Jena valve that's been approved by the FDA, so we're gonna have to create a module to track how the Jena valve and other valves perform in pure aortic regurgitation. We have a mitral risk model that's being developed. We're just on the last legs of that. It's pretty well finished, and we're gonna be able to apply that same modeling to the mitral valve and provide perhaps a composite endpoint and be able to do the same thing that we've done with TAVR for the mitral side. And then there's interactive dashboard that will give the site and the operators a lot more clarity and ability to evaluate their own data within their own site. At the end of the day, really when you think about it, the most important stakeholder is gonna be the site and the patient in this TBT registry if you really think about it. So we've gotta make sure that the sites have their own information, and they can query their information and find out how they're doing in terms of particular demographics and particular outcomes for their own site over time. So I'll finish up here with just a couple more slides. I just wanna let you know that the TBT registry is the world's largest repository of transcatheter valve therapy. It is an exceedingly important database that really gives us tremendous information on what we're doing and helps evaluate new technologies as they roll out from the pre-market to the post-market phase. The registry tracks outcomes and safety of all patients, just about all patients who get aortic valve TAVR right now and the vast majority of mitrals. We are now over half a million patients into this journey. This is of value to multiple stakeholders. When you think about it, this is important to patients. They need to know and understand how sites are doing and how this data is, what their risks are. This is important to providers. This is important to hospitals, researchers, regulators, and payers. So there are multiple stakeholders who play an important role in ensuring that there's still value to the TBT registry. And as an interventional cardiologist and as a researcher, I can tell you that given that there's been about 65 to 70 manuscripts created in the last several years, 10 to 15 years, from the TBT registry, it is extremely important for us as people who are interested in understanding research and outcomes and how to better our therapies. The TBT registry informs us tremendously in that regard. So the challenge is moving ahead. We have some headwinds. Site burden, it's not easy. It's not easy to enter the data. There's a lot of data to enter. There are cost implications to this. How do we evaluate new technologies? Do we create new modules for new technologies? Well, that costs time and money and effort. Site development, should we open up new sites? If so, where? Should they, at what point do we sort of say that this site's not gonna have enough volume? This volume versus access relationship is a very tricky one. It's kind of a difficult needle to thread. How do we improve the diversity of the patients that we serve? There are large swaths of patients who are not getting access to this therapy. These variables run along race and ethnicity and where you live. If you're in rural America, you're much less likely to get TAVR than if you're in a metropolitan area. What about data quality? How do we ensure completeness of data? How do we just make sure that we get those one-year data elements entered? The echoes done, the patient seen, and of course, the 30-day as well. How can we get five-year data? Well, we can link through CMS to get mortality data and that's one thing that we just accomplished, but we do that through a grant mechanism and that grant will run out. How is there a way to sort of get this baked in so that we get long-term data more readily? And then finally, we should be able to use the TVT registry as a robust research database. We're collecting all this data. It would be a shame not to be able to use it for research purposes in terms of nesting a randomized clinical trial within the registry and garnering all that valuable information. So how do we do that? How do we develop a lean case report forms that we can perhaps add to the registry or use the existing registry data to use some experimental designs to answer some questions that we really need to answer within interventional cardiology? These are all some of our headwinds and some really challenging questions that we're gonna face to maintain the value of the registry over the next several years. So this is just a few of our compadres working at the registry, the Steering Committee and Publications Committee and I wanna thank you all for just hearing me out and listening to this long journey that we've been on with the registry. I wanna thank Joan in particular for her insistence that I come here and present and it's just wonderful to talk to you all and I'm really looking forward to the question period because I'm sure you'll have good questions. I just hope that we'll be able to answer them all. There's lots of questions to be answered. So thank you for your time and I'll stop at that point and we can entertain questions. Thank you. Thank you, Dr. Gresham. So I'm gonna scoot over there. I think that's where I'm supposed to get the questions but a couple of things. I wanna recognize Dr. Kim Gabon in the room. Are you here, Kim? Raise your hand. She is also on our Steering Committee as an APP at Beth Israel and so if there's anything you wanna complain about, she'll take it. But just to tie in with what Dr. Batchelor was saying about how interactive and how fast-paced moving the registry is, if you've been in this game for a little bit, you understand that you send us the questions, you give us the complaints, the concerns, we take it to the physicians and this group of physicians has been so flexible, understanding, willing to answer. Case in point, at a valve coordinator meeting many years ago, I said, show me a raise of hands who's doing PFTs, not a raised hand. And Kim was kind enough to say, Joan, we stopped doing those two years ago. That's ridiculous. It's causing the delay in getting the patient to the table. Hospitals don't have the equipment. You're bumping the patients that really need the PFTs done. That information allowed me to bring it back to this group and certainly now you see, you do PFTs if you need to do PFTs, but it's something, again, pulled over from partner and there have been a couple other examples. But just so that you know, we constantly are trying to pivot and do it right. And just one big thank you to all of you. I know we tried to meet you last year in person. This is certainly so great to see you all. Thank you, thank you so much. I will say as nurses, you give us a snowstorm, you give us COVID, you give us whatever else. We were able to pivot either virtually or y'all didn't miss a beat. And I get chills when I say it, but I mean it. I mean, the data didn't drop. I've heard all kinds of stories about sneaking the patients in the back way, setting up special rooms for them so that your TAVR volume pretty much continued for the most part during these past few horrible years. So that's a big thank you. Now while I go over there, I'm just gonna ask Dr. Batchelor. So kind of in the what's next era, what scares me I think is when you said, oh, TAVR mortality rate, PCI rate, pretty good. If you're an administrator in the room, you might be thinking we could carve down the resources and the staffing. And what concerns me is what's about to come with Mitral and even more so with tricuspid. What words of wisdom or what can you arm everybody to go back and say, no, no, no, don't cut that. We actually might need more resources. And as I understand it, it'll take a year before you see a tricuspid patient skipping down the road like you see your TAVR patient. So be ready, be wary, and we're not done yet is what I'm saying with what'll happen with the Mitral tricuspid. Yeah, I mean, that's a really, really important point. There are multiple things that are happening simultaneously right now. We're getting better at what we do. The risk profile of the patient is changing. But we've developed a well greased machine that deals with a tremendous volume. At Inova, we're probably gonna do more than 450 TAVRs this year. And in order to get the mortality rates where they should be, remember, it's not an absolute number we should be looking at, it's a relative number. So if we're gonna continue to deploy this therapy, which most people want over surgery, we have to be able to look them in the eye and say, you will do as well or better than surgery. So it's not a 1% mortality we should be looking at, it is what's the expected mortality for that patient for that particular disease. And as risk profiles go down, you have to drop your expected mortality and your observed mortality. And in order to do that, you need this well greased team approach to do it. It's actually as much a travesty to double mortality in the low risk group who are younger patients who wanna live a long life and should be able to live a long life. And if you stop supporting the programs and deploying those resources, to go from one to three or 4% is a huge problem. And it's also a very disingenuous approach to younger folks who are coming to you with the expectation of the low mortality. So mortality, we have to be a little bit careful about how we interpret it. And it doesn't mean that less resources are necessary, I would argue the opposite. You have to maintain your resources to make sure that that mortality is kept low in a situation where it should be low. So that's number one. Number two, the tricuspid field is really going to be wide open. Much more difficult anatomically, anatomic valve, big valve, three leaflets, often four. And it's going to be tough to get the same, the kinds of patients that we're seeing in the tricuspid side, they're sick. They're old, they have kidney disease. And we're seeing that we can get their valve repaired from the transcatheter edge-to-edge repair and replacement. The challenge is just keeping them at a hospital for heart failure. That's been a challenge. So we're going to have to innovate. We're going to have to use a team approach, great imaging, high skilled operators, and then industry's going to have to come up with some clever and better solutions and redesigns for their existing technology. But that is a huge population. Just by way of comparison, there are about four to five million people out there with severe, with significant mitral valve disease, mitral valve regurgitation. There are probably about maybe one and a half to two million aortic valve stenosis patients. There are another 1.5 million patients with tricuspid valve disease. And the tricuspids we're doing almost minimally. You know, there are five to 600 isolated surgical procedures for that 1.5 million. And now we're just scratching the surface with our transcatheter therapies. So the floodgates are going to open as soon as we have better technologies. We have transcatheter edge to edge repair, and we have replacement following soon thereafter in terms of the regulatory process. So that's going to be brought to bear on the tricuspid population soon. And what valve centers are going to see is this huge influx and demand for these untreated patients because the surgeons are not treating these folks. In fact, the gap between the unmet need for tricuspid is, in my opinion, equal or greater than it was for mitrals. So we're going to see a floodgate, and we're going to have to be smart about how we treat these patients, how we get them evaluated. And we're going to absolutely have to track how they're doing in the registry to make sure that it's safe and efficacious. Nobody cut any staff. A couple housekeeping, Pat's asking about the length of stay metric. And so just a housekeeping issue, the length of stay executive metric has been suppressed. Why? Because this is kind of stymied me. It's like, why do we care? Everybody's at one day. Well, I think it's an accreditation, and it's an important metric that people want to, understanding it's one day, they want to count hours. Until we do the upgrade, and until we could ask you to collect date and time of admission, we can't calculate the length of stay. So if you follow that, it's with all the registries. So it's been suppressed. We will reintroduce it when we do the upgrade. To the downside of asking for one more data element, well, we'll have to collect not only the date of admission, but also the time. And then we'll be able to show that. The slides, a lot of the data slides that Dr. Batchelor showed are available twice a year or updated on the TVT website. If you don't know where that is, or if you can't find it, my phone number and my email is in the app. And I'm happy to shoot those out to you. But we collect the data, and it's with a snapshot of everything that's been done. And then the physicians scrub it and decide how they want to display it. And then we post that twice a year. But that would go through all four modules. Again, tricuspid being off-label, don't hang your hat on that data. But definitely with mitral and aortic. And you could certainly show this at your meetings. With the Power BI dashboard that we will be launching, a nice interactive tool will be, you'll be able to sort of splice and dice the, if your team wants to say how many patients within this age cohort raised sex and how many have had this procedure, you'll be able to collect that data and then just print a button. And you'll get your customized slides printed. So that's a very nice tool with Power BI. So stay tuned for that. We're working on that. Someone asked about AUC. The AUC that we're working on, another reason why we're holding back on the upgrade is with the AUC data elements, we'll probably have to add a few more to the new version. And they'll all be highlighted, included in what we're considering our basic data set. So we're not sure how many data elements, but the AUC is being changed and updated from when, I think 2017, or it's been a while. So that'll be updated. Pacemaker, your thoughts on if you know the patient has a conduction issue, in your practice, do you put the pacemaker in table side during TAVR prior to, or watch them and send them home with a temporary wire, a temporary loop, and then decide what to do? How do you handle pacemakers? Yeah, so this is where clinical discretion and judgment play an important role, as well as Medicare and CMS guidance. The challenge is if you put a pacemaker in prophylactically and the patient has maybe, let's say, an existing right bundle branch block and maybe a first degree block, and you're worried that they're gonna develop a left bundle and a complete heart block situation, you can't really justify putting in a pacemaker prophylactically unless you get an EP consult and someone saying that this is warranted and indicated, and they have to provide some sound evidence for that. Be careful about putting them in prophylactically because CMS might have issues with that, and it's probably not good medicine unless you're confident that they're gonna need it. Luckily, our technique has really gotten more refined. So if I know that a patient has a very high risk of needing a pacemaker, valve selection can make a difference. Generally speaking, balloon expandables may offer a little bit more advantage there in terms of pacemaker rates, and a really superficial, really high deployment. So we can often avoid a pacemaker just by some technical things that we do in the procedure. So most of the time we would, if it's really a high risk patient, I'd have an EP physician see the patient in consultation beforehand. If it's just like a right bundle and you're concerned that they could have a problem by developing a left bundle during the procedure, I would just do the procedure with the technique that would give the patient the lowest risk of developing a left bundle, high deployment. And then if there's a new bundle branch block, like a left bundle in the first degree, for example, we might put those patients on a monitor afterwards, an MCOT, and then we can pick up signs of a more advanced heart block and then get them in for a pacemaker. And most of those patients we would have afterwards seen by an electrophysiologist before they go home. So different sites have different ways of dealing with this. It's a common problem, but just be careful. You can't get ahead of the game and start prophylactically putting in pacemakers. I think CMS will have an issue with that, payers. Maybe. A good question that I would want to address, even if it wasn't asked, but it was asked, was the face-to-face evaluation, the public health emergency, PHE, that we all lived through for the past three years, expired, terminated, stopped, whatever you want to call it, as of May 11th. So the clear instructions that we've been given is that after, since May 11th, that we're back to the NCD requirements of face-to-face evaluation. And I know that's difficult and that's sort of turning the Titanic around from a very nice way of doing the evaluation prior to that, not face-to-face, but that's back to the pre-COVID exemption rules as of right now. Are there any, does anyone want to come up and ask any questions or any questions? Go ahead, just yell. Tell us who you are. The other thing is everybody make buddies and yes. »» Oh, okay. My pushback is why. So everybody's mad at us for the vascular complications. And smarter people than me have said, why are people so, it's not in the risk model. But it makes it important. And we talked about this this morning, yes, it is important because that sort of leads into the bleeding, which is important, it is in the risk model. And there's a lot of information, and I could share the manuscript that was written when the physicians who developed the TAVR risk model looked at all of the variables in the TVT registry to say what sort of made the cut, what was a high enough hazard ratio that actually showed it affected the patient's one-year mortality, right? And all of those that Dr. Batchelor showed, kidney, PVL, which I wonder if they'll take that out with the skirt now. Is there, PVL used to be, you're dead with PVL. Not so much anymore with the new valves. But bleeding, stroke and mortality, certainly. So the question is, vascular complications and pacemaker did not hit a high enough hazard ratio to be in that game. And that's why you don't find them as an endpoint. So the discussion when we did that metric was, minor and major, whatever, the way we have vascular complications, what we will do in the update is to align with the way they do in the cath registry, vascular complications requiring treatment. Because you have folks that are, oh, yes, yes, yes. You have folks that every little bubble, every little mark that I dare you to find it after the patient leaves the table, but they've still collected that as a vascular complication. So does it really matter? It matters if you had to require treatment after that vascular complication, right. So it's going to take away one, and I don't know if they're in the room, but the analogy that somebody gave me is, when you put a piece of tape on an onion-skinned 88-year-old, you pull that off, that's a complication, right. And so that's more important than maybe just kind of a little thing that we're asking you to collect that we don't do anything with. So the new world will be vascular complications requiring treatment aligning with PCI. »» I think it's an important distinction between what variables in the model translate independently or add independent predictive power to mortality versus which are important for the program and the patient. So a vascular complication that leads to a procedure is important to the patient. It's also important to the program. But it may have nothing to do with one-year mortality. Because if they get through the procedure and they do fine, it doesn't actually have a lot of relevance. I really am looking forward to the update because I think as a clinician, we should be capturing the things that are important to the patient and the program and not just important to the model, you know, the mortality model. »» And I'll leave you with this one thing, but we could talk about this all day, stroke. Patients would rather die than have a stroke. That's when Dr. Batchelor talked about the shared decision making and what are the patients concerned about. We all know they don't want to have a stroke. They lived a long life. They're ready to die. But they don't want that stroke. So Michigan's in the house here, I know, and they think they're all that in a bag of chips. But they did a good study in all the programs that are in Michigan and looked at if you in fact were a stroke center, you had a higher stroke rate. Well, duh, right? Of course. If you look for it, you will find a stroke probably in me right now. So what the Steering Committee is working on right now is evaluating the Michigan experience. And we're looking at the sites of all 834 that are actually, are you a certified stroke center? There's a lot of different delineations of a stroke center, right, three main ones and then another one I don't really understand. But what the Steering Committee is evaluating now is a huge research project to duplicate the Michigan project to all 834 sites. And why would we want to do that? We would want to look at if that falls out same, same, that if you're a stroke center, you in fact have a higher stroke rate. And so what that then will leave the Steering Committee to look at is, should we not define stroke differently? But is a stroke, is a stroke, is a stroke? Or do we want to maybe perhaps just collect strokes that are debilitating, that caused you to have an altered life situation? You cannot go home. You cannot work. So again, that's a very sensitive nuance. I don't know if Dr. Batchelor wants to end with that. But stay tuned and pay attention when we come out with that, because that will be a major shift. »» Yeah. This is going to be really important that we actually get this right. When you think about it, and from the Michigan paper, and congratulations to the Michigan folks. It was really actually very good work. And Dr. Deeb and his counterparts did an excellent job with this analysis and this publication. It basically showed that a lot of stroke centers are actually very good centers. And the message unfortunately, if we're not careful, is that they're getting penalized for actually just being more careful at detecting a very, very important outcome. That's the last thing that we want to leave behind. So we're going to have to do very good work. And we'll expand this to the entire database and look at stroke centers within the TBT registry that are certified versus not certified. I suspect we'll find a difference, but we'll wait and see. But that's going to be important work. And then from that, we'll actually revamp how we look at stroke within the registry. So whether or not it's a stratified analysis based on stroke certification, or we just look at major strokes that lead to significant debility, because a lot of the gap is probably in picking up more subtle strokes. You know, if someone's hemiparetic, most stroke centers, stroke certified or non-certified centers are going to get that right. It's the sort of the transient, more sort of minor residual deficit patients that can be missed sometimes. But we have to get this right, because we're actually penalizing centers that are trying to do their very best. And that's the last thing that we want to do. That's right. So I want to end. Sorry, we went over. Thank you. Thank you so much, Dr. Batchelor. You really did a fantastic presentation. Thank you. Thank you. Great job.

STS

ACC

TBT Registry

transcatheter valve therapies

TAVR

TMVR

registry growth

mortality rates

heart failure hospitalizations

data quality