 Welcome to the Texas Heart Institute Educational Programs on Innovative Technologies and Techniques. The next topic that we are going to discuss today is current status of TAVR. I'm Zvonne McRayser, I'm an Interventional Cardiologist at the Texas Heart Institute and Baylor St. Luke's Medical Center in Houston, Texas. Join us today is Dr. Vino Turani, he's a Marcus Chair of Cardiovascular Surgery and Director or Marcus Valve of Piedmont Heart Institute. He also has multiple positions and accolades as you can see. He's the President of Southern Surgical Association and the President of Heart Valve Society, as well as the President of South Atlantic Cardiovascular Society and Co-Chair of SDS-ACC National Transcarriage Valve Therapy Database. In addition to being co-principal investigators on many TAVR clinical trials. It's a pleasure to have you here, Dr. Turani. Thank you, Dr. Craig. Here are our disclosures. I have no conflict of interest pertinent to this presentation and Dr. Turani states that he has no conflict of interest pertinent to this presentation. So, Dr. Turani, we recently saw this publication of the SDS-ACC-TVT Registry of Transcarriage-Triotic Valve Replacement and the trends in the United States with TAVR from 2011 to 2020. And you are one of the participants in this particular study but also you have tremendous experience from other studies as well, which is the base of this information. Can you share with us a little bit about this particular study? What are the new developments? And let's start with how many sites were performing TAVR that were included in this study and also a little bit about TAVR volumes. First of all, thank you to you and the Texas Heart Institute for the invitation to be with you for this session. And this is some of the latest data. It's not only part of the manuscript that we published with John Carroll in 2020, but also some additional data that's unpublished. And I'll go through those over the time period. You can see this slide really talks about the geographic distribution. The next slide will talk a little bit more about the volume. But you can see, for instance, in Texas, you see an epicenter in certain areas of Texas. And for those of you watching this, you'll see that there's a lot of sites in California. There are a lot of sites in Florida, a lot of sites in Texas, and then in the Northeast corridor around New York and Boston. And so this just gives you a geographic distribution with a paucity in the middle portion of the country that is west of the Mississippi. And you can see that there is a lot less sites. But this just gives you a glimpse of where the sites are. And on the next slide, what you're able to see is that the right-hand side, you can see they're now year-to-date for 2020. This was the first quarter of 2020. There are 701 sites doing TAVR in the United States. And you can see that the volume has gone up through in 2019. There were 73 isolated TAVRs performed. And you can see there was 4,492 valve and valve procedures performed. So we're just knocking on 78,000 cases. You can see Q1, 2020, they were already in Q1, they were 15,000. But remember, COVID came into play. So I'm not sure that we'll hit that number that we thought we would, that growth that we would see with the low-risk patients. It'll be interesting to see, Zinnabar, whether we're going to hit that number because of COVID. But you can see the trends are pretty impressive since 2012, since we've started the registry. So can you mention a little bit about what has happened to the outcomes as far as TAVR is concerned over the last decade or so? And particularly considering only overall mortality and mortality with different risk groups. Absolutely. So this just shows you the one-year mortality. So let's go through this a little bit. The blue line represents in-hospital mortality. The red line represents 30-day mortality. And the green line is the CMS-linked one-year mortality. So we're a little behind on the one-year CMS because it takes a while to get that data. So if we just concentrate on the one-in-hospital 30-day mortality, you can see that our original, when we had extreme risk patients in 2012, you can see the mortality was up to almost 8% in 30 days. And you can see how over time that has really dropped over this seven-year time period to 2.3%. This is all patients. It includes low-risk, intermediate-risk, high-risk, extreme risk. So it's a different patient population, but you can see overall, you can see that it's about 2.3% in 30 days. If I go to the first quarter of 2020, you can see that we're down to 1.1%. Now, I think that the next slide will really show you what we're talking about within the risk groups. It's very different. I think that just the previous slide showed you just generic numbers. I think it's not fair anymore to look at that. When you agree, it's in every way that you have to break it down into risk categories. So if you look at 2019, all patients had that 1.3 and that 2.3, what we talked about. But look at the differences. Low-risk patients had a under 1% 30-day mortality, a high and extreme risk-ribid patients out of 3.7%. So really, when I start to think about this, I think this slide is more important to me than is the previous slide, which is talking about today. And I can constantly tell my patients that are getting low-risk, low-risk tavers that they'll have a less than a 1% chance of mortality at 30 days. What are your thoughts? Do you agree that this is kind of what you're seeing in your populations? Oh, absolutely. I think this is absolutely remarkable, particularly when we start reviewing the data from the early experiences and you were co-principal investigator of the partner trials. And you remember the problems and issues related to mortality and also to morbidity. So I think it's a tremendous progress. Yeah, I think that another progress that we'll talk a little bit about in the future is that I was doing 45, when I did my first tavern in 2006, we were doing 45% of our patients were trans-apical. Remember, we've gotten away from that. And we'll talk a little bit, you and I will talk about that a little bit in a minute. So one interesting thing is, and maybe this is appropriate time to mention this, but it's related more to the future. We can see that we can reduce the mortality, hospital and 30 day mortality dramatically in patients that are so-called low-risk and intermediate risk. So it wouldn't be prudent therefore to be a little bit more aggressive in treating those patients earlier rather than waiting until they get to the critical condition. And then you have serious aspects as far as mortality and morbidity is concerned. No, I think you're right. And you're talking about sometimes asymptomatic patients, but also those patients that have maybe moderates and those patients that have worse and moderate but quite not severe. I think those are ongoing studies that are going on. There's an asymptomatic trial called the early tavern study that's currently enrolling patients. And there's a couple of companies that are working on a moderate AS trial also, moderate AS and normal EF, not the moderate AS and low EF. I'm talking about the moderate AS and normal EF. There's contemplation of starting those trials. So I think that over the next couple of years we're really gonna dive into that. But I think in the lower risk patients, we still need to look at long-term outcomes. I think 30 day mortality is probably not adequate for a 65 year old. I think we expect those patients to live over 15 years. So I think we still have a lot to figure out over the next five years. Very good. So one very important issue is a median length of stay. So what has happened in median length of stay? And this is a very important question because I actually was at your institution to learn how to do a fast track tavern. It means just a 24 hour stay. So you have tremendous experience in it. And one of the earliest publications in the United States related to this particular approach. Yeah, I mean, you know, resource utilization, I think for the physicality of an institution has become more and more important. And we did adopt that early on in the minimalist pathways that I did when I was in my prior institution and you can see the length of stays at 2014. You're looking at, again, high risk patients in green, red or intermediate risk patients in low or low risk patients are in the blue. You can see now over time, we've gone from four to five to six days all the way down to one to two days. So I think that for the most part, most of these patients now are, you would expect them to have a median length of stay after the procedure of less than two days. I think this becomes important. But what we needed to set out a little bit more clearly is we haven't stepped up from in-hospital mortality to 30-day mortality. I would rather a patient stay an extra day but decrease that gap of in-hospital to 30-day mortality. So I think we need to be cautious in not pushing patients out too fast. And we need to, in our own institutions, need to figure out how to close that gap of in-hospital in 30-day, even if it means that we keep the patient for one or the day. What are your thoughts about that? Well, I think for low risk patients, it's pretty straightforward that they can be shared within 24 hours. In great majority of instances, that's what we do practically routinely. It also depends on a patient's underlying condition, which plays a significant role as well. And many other factors, but I absolutely agree with you. We should not be discharging the patient just for the sake that we wanted to reduce the cost that we have to think of the patient's benefit first. Yeah. And it becomes more costly if they get reinvented, quite honestly. Right, that is absolutely true. But just one more comment relating to this shorter length of stay, which is like you say, minimalist approach that you've authorized and also what we call a fast track protocol for TAVR, which is not a topic of this presentation, but certainly it's doable for a lot of institutions and for a lot of operators, but you have to pass a certain learning curve. Yeah. And you have to know how to do it to avoid serious problems. You're right. I had done over 400 or 500 TAVRs before we started. I don't think we need to do that now anymore, but you probably need to have 40 or 50 under your belt so that you feel comfortable understanding where the snakes are underneath the rocks. All right, let's move forward. So another thing is that we would like to know what has happened with the trends as far as the age is concerned and time of procedures over a period of time. Yeah, this is great. So what I've elected to do is break it down into the different categories. I think that's important as we dissect these patients out. It's interesting to me, the intermediate risk and the high risk patients at the top haven't really changed in the last two or three years. They're still hovering around 80 to 81 as a median age. Look at what the low risk patients, you see some low risk patients in 2014, but that's all because what the team, the hard team designated that patient to be, but you see that we're down to 75. My prediction is that we'll be down to a median age of 70 by the end of 2020. So I think that this will continue to decrease. I think the high risk patients and intermediate risk patients will probably stay in the low 80s to upper 70s. Interesting. What is the hard team reason for the procedure? What has happened? Yeah, I mean, there's two ways to look at this, right? There's one which is the SDS score and then one is what the hard team designated that patient to be. And the SDS score sometimes don't match with what the hard team says. For instance, there may be a patient with a porcelain aorta that has a very low SDS score but is considered an extreme risk patient. So to me, this is a very, a better way to look at it is what did the hard team decide? Look at the growth of low risk patients in blue. It is now 26% of the tavers in 2020 of Q1. That blows me away. It's a faster increase than I had anticipated. Look at 2019, 12%. So if the rest of 2020 holds into place, I would guess that you're gonna have low and intermediate risk will be the dominant players for the reason for having a taver. And I think that we'll continue to see extreme risks and high risk, but the growth will be in low risk patients. Yeah, I agree with you. Nothing can replace the human factor and physicians experiencing, experiencing making the judgment. Who's at low risk? Who's at intermediate risk and who is at extreme or high risk? Yeah, that's great. And I do wanna show you what the SDS scores look like. So look at the high risk in green. It's about the same. It hasn't dropped as fast as I thought it would. You can see that in 2014, we had 6.7% as the median SDS score is now at 6%. If you look at intermediate risk, it has dropped from 5.3 to four. And already we're seeing low risk patients go from 3.1 to 2.3. But really if you look at the, from 2019 to 2020, it's really 2.3 and 2.3. So roughly we're seeing most of these patients, I think will be around the one to 2% range for low risk patients. Very good. And here, this is from the Jack article. You can see that the majority of these patients are going home now. Look at the difference in 2011 to 2013, only 2.3 of the patients were really going home, but now over 90%. This just shows you the reflection of moving from extreme risk prohibitive patients to lower risk patients in my opinion. Right. Another thing is that maybe it's not well represented here, but it's certainly true in your experience, in my experience, using the minimalist approach, local anesthesia and conscious sedation, for continuous approach, offers us the benefit to discharge patients sooner. No doubt about it. Have less complications, whether it's vascular or cardiac or whatever else. What we noticed that we actually early on, one of the things that drove us to do this is that when you have octogenarians who are intubated, they almost, most of them, greater than 2.3 of them, had some type of swallowing issues and they had silent aspiration. And you don't get that if you don't intubate the patient. Right. So let's talk a little bit more about some issues that have been a major problem in the past, particularly as far as access side preferences are concerned and reasons for those complications and what has happened in the last decade or so. And how has this affected the outcomes? So I think this is probably the number one reason that our outcomes have improved. You can see that a third of the patient, 30% of the patients were trans apical at that time in 2014. We only had trans aortic or trans apical. Subclavian was not that popular at that time. Look at, and you've seen our curves for mortality, they're absolutely inversely related to this. Look at the growth that in right now in the United States, 96% of patients have a transformer arterial access. And that I think is a large portion of YA patients are going home at one to two days afterwards. B, they're going home instead of going to a nursing facility. And three, I think our survival is better because of that. So there's no doubt in my mind that this is a very important reason of the improvement in the outcomes for trans catheter bowel therapies. I'm sure you would agree with that, Zenibir. Absolutely. Actually in the early trials, partner trials, the incidence of vascular complications was close to 16%. Yeah. And we have dropped down tremendously to definitely below 5%. 5%, yeah. Yeah. And I think that has been huge. And think about how that's happened over a decade. And to me, that's absolutely remarkable that the companies have been able to do that within a decade. And definitely the closure devices have helped us agree to do that as well. 100% agree. And so we did want to just tell you what are the different pathways for alternative access. So you can see trans apical has significantly decreased. I've done over 300 trans apical valves, TAVR valves, and that was my mainstay. But as you can see in the United States in 2019, only 200 were done in the entire United States. So a major decrease. Direct aortic cylinder has gone way down. Accelerate becomes a dominant so far, but the fastest rising is the transcarotid that we are able to publish the first paper in North America in doing that case when the valves were first available in 2014. So I've now done over almost 75 transcarotids. That's my second choice, but you can see the country across the board is doing more axular subclavian. And I think these are interesting. Other includes trans cables. So trans cable is also an alternative access that is being used, but not in huge amounts as you can see here. You know, interestingly, I was a little bit surprised to hear that your second approach is transcarotid. We do a significant number of TAVRs and I personally have not had any scenarios where I felt like I have no other option, but transcarotid. Part of the reason for it is, number one, we feel pretty comfortable with femoral acids and percutaneous closure devices. That's number one. I've been doing that for several decades for EVAR, T-VAR and so on. But also now with the advent of shockwave, we can treat those and gain access through the femoral artery. So I have not had a need really to use a carotid access. Occasionally we'll do a subclavian, but most of the time we are successful with a trans femoral and trans-cable. Yes, it's reasonable in certain scenarios, but the technology is not there to remedy the access sites. And then it adds a cost tremendously. I know it adds a cost. So our pathway as transform arterial, number two is shockwave to your point. But remember that was only available for the last year or so. Before that, we didn't have access very much to that. Our third choice is trans-cable. Our fourth choice is trans-carotid. So what I mean is our second choice, it's after shockwave, after trans-cable, then it's trans-carotid. So people have to have gone through four rejections before they get to trans-carotid. And another reason that this is less and less needed alter the access is because the profile of the devices have decreased. And I expect them to get better, don't you? Right, absolutely. So there is less and less need for alter the access. I agree, 100% agree. Okay, so let's talk about differences as far as the growth is concerned between TAVR and SAVR. You are a cardiothoracic surgeon. So you started with SAVR first and now you're embracing more and more TAVR. But what is happening? What are the trends? Yeah, so I think you're right. This week for me is a mix of both, right? I did five TAVRs today. I've done three aortic valves since Wednesday, right? So in two days, it's been a total of eight of ways of eight valve patients, aortic valve patients. Three have been open, five have been trans-catheter. So I've embraced both of those equally. But what we'll see in the country is the black line represents TAVR. You can see the exponential growth of it. Number one represents the intermediate risk patients. Number two represents the low risk patients. So you can see the escalations in late 25 and the escalations in 2019 from those two components. And the very top line, which is all SAVR, that includes AVR cabbage, AVR mitral valve, bental procedures, root replacements. As you can see, that's now for the first time it's starting to decrease from 64,000 to 57,000. The blue line is isolated SAVR only. And you can see that line is slowly decreasing, I think since 2016. So overall now, there are more TAVRs implanted than all surgical valves. But you must also acknowledge that we are now treating more patients of the aortic stenosis as a whole. So if you look at 2012, the number of weird patients we were treating was only about 66,000. Now you look at it and it's over 130,000, 40,000. So the overall number of patients we're helping is more, and I think TAVR is leading the charge of helping those patients. Very interesting. Now, one of the hottest issues is valve valve procedures. And what is your personal point of view and then what did the literature show as far as the trends are concerned? Yeah, so of course, we're only going to talk about TBT tonight for this session. We're only talking about TBT, so we're showing trends. We do a lot of valve and valves. Now, lately, quite honestly, we've been doing some TAVR and TAVRs. That's a whole new ball wax. This doesn't really include that part of it. This is more of TAVR and SAVR. I think that these are something that we're seeing more and more of. I get very upset when I see 19 valves and 21 valves from surgeons because they've become a bigger problem for you and I when we do a valve and valve TAVR because the gradients remain high. And so that becomes a problem. Look at this. You're starting to finally see an increase. This is the orange, the red lines, or the actual elective planned TAVR and SAVR. And so this is escalating from 1,300 patients to 4,500 patients. I think this will increase more and more because more and more surgeons are putting in tissue valves. The number of mechanical valve implantations has gone down dramatically in the United States over the last decade. You can see immediately and during TAVR, that's a complication. That's an intraprocedural complication that is going down. And so the need for a implantation of, let's say, one valve and then right away you had a periodic leak or you had embolization and you have a second valve, that complication is going down. But the overall elective cases for TAVR and SAVR are going up. It's nice to see this, but I don't think we've cracked this nut yet. I think there's a lot of issues with gradients and thrombus that we still have to work on for this patient population. Now we need to discuss a little bit of the issues that are still persisting or the unmet needs as far as TAVR is concerned and what is coming in the future or what are we doing at the present time to overcome those unmet needs? Yeah, I think that stroke has always been there for us. And I would say that the best data is the 30-day data in hospital data. The CMS link data is not a complete data set because it's in older patients. But we have not made a significant dent. We've gone from 2.8 to 2.4. Remember, I showed you the mortality slides that has declined in mortality over this time period. We've seen decline in the length of stay, decline in the age, everything. We haven't seen a huge decrease. We're still seeing a 2%, just north of 2% stroke rate. Even when treatment protection was added in 2018, we're still seeing a 2.4. Let's see what happens with 2020. We did see a small decrease as you see in the in hospital because I have that data for 2020 Q1. It went from 1.6 to 1.4. So this is adjudicated through the TVT through DCRI. So this is the one of the endpoints that we do adjudicate through the TVT database. So I think the data is good. I think that we need to find better ways to decrease the stroke rate. So how does this compare with the cyber? So it depends. So I actually published a paper on animals of thoracic surgery. It depends dramatically on the risk of patients. And I think that we need to dissect this out in the risk categories of patients. In low-risk patients, the stroke rate was very low, similar to this. But in high-risk patients, it was higher. So it'll be interesting. I think that overall what we originally saw from Part 1, we had a much higher stroke rate in TAVR. I think that right now we're probably seeing a lower stroke rate in TAVR than we are in surgery. Yeah, so there is an issue whether cerebral protection devices significantly improve or reduce the risk of symbolic events. And what we have seen here is there's no dramatic drop. And this is understandable because any manipulation with catheters or wires across the aortic arch that has a lot of ethnometer changes can contribute, including placement of the cerebral protection devices. When you use a transcranial Doppler, and you start at the very beginning, you can see that any manipulation of any devices contributes to those hits or micro-embolytes. Now you're absolutely right. I think our experience, the positive thing, even though with issues that we still have to deal with is that those strokes are really minor. There are cognitive changes to a certain degree or minimal changes and very, very few patients need a major rehabilitation. Is that your experience as well? Yeah, I 100% agree with you. I think that the amount of stroke burden is less with transcatheter valve than it is with surgery. I do believe that. Commonly with the surgery ones, it's a large particulate matter that I think causes a very heavy or debilitating disease process. You're right. So pacemaker rate originally was about the 9% to 10% range. When we introduced self-expanding into the market, there was an increase in pacemaker rate. It has come down to about 7.8 to 10.6%. I think this is somewhere that we need to be better at. I think 11% rate maybe in a high-risk patient's okay and maybe not so good in a low-risk patient. And these are across the board higher than surgery when we look at these patients. So I think this is something that we're either gonna be setting ourselves up with a lot of tricuspid regurgitation down the road, but I think that we need to get better. The devices need to get better to decrease the amount of pacemaker rate. I'm not okay with 11% low-risk pacemaker rate personally. Right. Well, we have seen now numerous publications from different centers, talking about special techniques, so-called CUSP over lab technique to reduce the pacemaker rate all the way down to somewhere in the range of no more than 3% to 5%. And that's what I have. Last year I looked at my data for 2020, our data at Piedmont Heart Institute and ours was less than 5%. And so I think it does make a difference. Okay, so let's mention about some newer technologies and techniques that are available or that are on the horizon. And we already did discuss a little bit about cerebral protection devices. Yeah, I just wanted to give you a glimpse of what are the... People ask me, is what percent of the device in the United States are using Sentinel? So when it was introduced in 2018, 7%, right? Right. It went up to 11% in 2019 and 2020 we're sitting at in the United States, 13% of all TAVRs done are using the Sentinel device. So everybody, I do them in valve and valves, I do them by cuspids, I do them in certain scenarios, those with previous strokes, those with heavy calcium burden, but not at every patient. That's probably represented. This is why we do about 15% of our patients are have a Sentinel device. And that's what the country's showing right now from our database. And there are some other devices on horizon that might be... That's right. That will cover all major cranial vessels and hopefully that will... Right, including the vertebrals and everything. Right. Yeah, so this just gives you an overall look at the adjuvant technologies that are being captured in a TBT registry. One is a Sentinel device, which is prevention of embolic strokes. As you can see the total number from 2018 to 2019 were over 11,000 native TAVR patients and 960 of the valve and valves. There's fracturing of the surgical valve rings, which is reduction of post prosthetic PPM, the patient prosthesis mismatch and valve. You can see there are over 300 of those put in. And there's the basilica procedure at the prevention of coronary obstruction, post a TAVR, so in a valve and valve case or others. And you can see here that we're starting to just getting close to maybe 200 patients for these. So we're starting to increase overall these unique techniques that are being done in the country. And it says no one site is doing too many. This will... The TBT database allows us to aggregate those in a much larger population. Very good. So let's summarize, if you don't mind, all the achievements that have been made in the last decade for treatment of patients with aortic stenosis and using TAVR approach. Well, I'll summarize in the TBT and I'm honored that the STS and ACC have allowed me to be on the executives for the registry. And what we've learned a lot from the United States database is that the procedure is now approved for high intermediate and low risk symptomatic patients. Mortality over the last five years, six years has significantly lowered. And I'm very happy and glad to see that. Bascular complications have significantly improved over this time period. The length of stay has been rapidly improving such that most patients are going home at one to two days. Femoral access has gone from in the 60 to 70% to all 96% now. And I think that's been a huge reason for the improvement in all of our outcomes. I think that the postoperative pacemaker implantation and also the stroke rates have decreased, but at moderate rates. And I think that's still what we, you and I and others need to really work on to provide better care for those, for our patients in that regard. And I think that, well, and I mentioned this earlier for us to really adopt this in all low risk patients, we need a longer follow up. And that's something that we're working on not only the TBT database, but also in the randomized trials. So it looks like the future is bright as far as stamina is concerned. Absolutely. And maybe the last comment that I wanted to ask you to give us is what do you see in the future as far as improvements in TAVR are concerned? What are the potentials? What's coming as the new technology and what will make TAVR even better? Yeah, I think that, you know, we'll start, we've been working with alloys that are a little bit antiquated night and all and also Chromium cobalt. I think that we'll start to see a development of more better alloys that'll allow us to get down to maybe 10 French instead of 14 and 16 French. And that'll give us a lot more capability of doing procedures. I think we'll streamline them so that we can better predict by computer simulations. We can decide this valve is better for this valve for this patient scenario. I think computer simulations, I know we're working with some guys at Georgia Tech on this that's gonna, I think, improve which valve is the best, which valve has the least amount of thrombosis, which has the best amount of coronary access. So I think that computer simulation is gonna become important. I think that having a technology that allows us to have better federal access to 99.9% and allows us to get to 10 or 12 French sheets will become really important adjuncts to improve this procedure. And of course, that will somehow will need to work on computer simulations also for pacemaker implantation, where to put it, where not to put it and decreasing stroke rates. So I think we have major areas of improvement. I think the next five years is gonna be an absolutely exciting time for patients to have this new technology. Very good. Vinod, I greatly appreciate your participation and to give us the opportunity to join this Texas Art Institute educational programs. I think you are one of the shining stars as far as staff are concerned and promoter of this technology. And we are all indebted to you and appreciate all of achievements that you have made in this field. Thank you very much for your participation. Thank you. I'm very honored that you asked for me to participate. Thank you very much. Thank you.