Ibrahim Sultan, MD, and Dustin Kliner, MD, discuss improving patient outcomes by developing a lifetime management strategy for patients with aortic stenosis with real-world expectations.
Hello. My name is Dustin Kleiner. One of the cardiologists at the UPMC heart and vascular institute and today myself and dr. Ibrahim Sultan, my partner from cardiothoracic surgery are going to talk about the revolution and management of aortic stenosis. I'm an assistant professor of medicine at the Heart and vascular institute and involved with the Taber program. I'm the director of the cardiac cath lab at UPMC shady side. I have no financial disclosures related to this talk. I am a co investigator for both prior and ongoing trials using all commercially available Taber products including the medtronic low risk trial Sir Tavi and optimized pro as well as Edward life sciences trials. The objectives for today's talk, we're going to review the indications for aortic valve replacement. I want to talk about the respective roles for surgical versus trans catheter valve replacement. Will highlight additional considerations for deciding between these two approaches for patients. And I'm going to introduce the concept of a multidisciplinary center for heart valve disease and the appropriate timing of referral to us. The ideology of aortic stenosis. As we know in patients who are younger. The ideology is most frequently bicuspid aortic valve disease. Approximately 50 Post inflammatory rheumatic makes up about 25% in the United States degenerative 18 and then some other ideologies are a minority of valvular disease. However, in patients who are elderly degenerative. Aortic stenosis is the most common pathology followed by bicuspid and then post inflammatory or post dramatic state diagnosis of aortic stenosis is certainly made. Most importantly by a history and physical examination with the history of congestive heart failure signs or symptoms and a characteristic murmur. On examination. However, the trans thoracic echocardiogram provides significant information with respect to the severity of the disease process. I want to point out here that the diagnosis of aortic stenosis and severity of aortic stenosis should be judged by multiple parameters on the echocardiogram. And before you we see valve area calculations, we see mean gradient numbers, peak velocities and index two valve areas. And it's very important to look at this and include most of these factors because a lot of the Taber trials that have been done have included a valve area within the severe range, but also a mean gradient that is significantly elevated or augments with stress maneuvers such as the debut to mean stress echo, or debuted. I mean, at the time of invasive thermodynamics during catheterization. So it's very important to think not only about the aortic valve area, but also the mean gradient and the peak velocity. When we look at the guidelines for aortic valve replacement. If we look at patients who have severe symptomatic aortic stenosis on the left hand side of the screen, severe aortic stenosis with symptoms, the classic elevated peak velocity and mean gradient stage D. One is a class one indication for an aortic valve replacement as opposed to continued observation and we see that now that is included both surgical and trans catheter aortic valve replacement as possible options. I'll come back to that in a moment when somebody has a peak velocity less than four an aortic valve area less than one and a low ejection fraction to be too mean stress echocardiography has indicated to determine whether this is true severe aortic stenosis or pseudo stenosis related to low flow and low cardiac output. On the right hand side of the screen, we see folks with no symptoms related to the aortic stenosis and on the left hand side, there are two Class one indications if somebody has severe aortic stenosis with the peak velocity greater than four and a low ejection fraction, or they're undergoing an additional cardiac surgery such as coronary artery, bypass grafting or mitral valve repair. They have a Class one indication for aortic valve replacement. And then you see Class two indications such as ability to perform on an exercise tolerance test, peak velocity is greater than five, so on and so forth. When we talk about the history of Tavern and the intervention itself, This was initially based on the observation that a balloon inflation performed within the aortic valve would open the aortic valve in a circular fashion, tearing the calcified valve or native valve along the commissioners. However, restenosis occurred soon after this. The next step was to place stents in the aortic valve and animals to see if we could stent open the aortic valve and because the animal with the stent in their aortic position had no competent aortic valve. They were met with rapid demise and autopsy studies showed continued expansion of these extents within the aortic valve analysts. A small startup company in New Jersey began working on a stent with valve leaflets inside of it. And the first human implant was April 16 in 2002. In France, which was certainly not a stereotypical aortic stenosis patient. By 2021 standards, this was a 57 year old male with cardiogenic shock who was inoperable ejection fraction of 12. The operation went well. However, the patient had progressive multi organ system failure and did not survive the hospitalization. And in 2004, this small startup company was acquired by Edward's Life Sciences. So when we talk about risk for operations, which is something that's very important to determining who should receive. A surgical valve versus a trans catheter valve. What do we mean by low risk intermediate risk or high risk? The sts or society of thoracic surgeons calculator is used to look at the national database for all cardiac operations that are done all aortic valve replacement operations that are done and generate a risk of mortality intra operative or within 30 days. And you can see the cut offs here low risk less than 3%. Intermediate risk, 3- 8%. High risk, greater than 8%. An extreme risk or an sts risk which is normally above 15% would be considered inoperable. The partner trial is the first randomized trial of Tavern and this goes back to what I had mentioned earlier about that small startup that was acquired by Edward's life sciences. That particular valve that was used as a first and man became the first generation of the Edwards valve. So this was in 2000 and 10 published in the new England Journal 358 patients and 17 centers with an aortic valve area of less than 0.8, which was the severe definition at the time and an aortic valve, peak velocity or mean gradient in the severe range divided into two cohorts. Cohorts A were considered to be operable despite a high risk and cohort B Were inoperable because they're predicted 30 day mortality was 50% or greater folks that were excluded were patients with bicuspid valves, acute myocardial infarction C. A. D. Requiring revascularization, ejection fraction less than 20 severe concomitant disease of the mitral valve or severe aortic insufficiency. Recent stroke, end stage renal disease and those that were randomized to Tavern were treated with the Edwards SAPIEN valve. I point out the exclusion criteria and these randomized trials because there are multiple patients that we see clinically that were asked to provide Tavern for these particular ideologies, bicuspid valve low ejection fraction and stage renal disease. And it's important to know that the randomized data does not include these patient. The Cohort B results which were the first that were published at one year. The mortality was 30.7% in patients that received a valve replacement as compared to 50.7% in patients with quote medical therapy. And I put that in quotes because there is really no significant medical therapy for Aortic stenosis. And in fact, 84% of these patients received balloon aortic valvular plastic and were included in the medical therapy arm. The composite endpoint of death and recent hospitalization was lower with tabby than it was with Um expectant management including balloon Bavel a plastic. However, at 30 days, Tabby was associated with a higher rate of stroke and major vascular complication. This makes sense the delivery systems were quite large at that time, 24 and 26 French and the tortuous anatomy of the Aorta with this large delivery system was difficult in increasing the risk of stroke. So these were the initial red flags that came out of the very early delivery systems and devices. The choice of intervention based on the 2014 valvular heart disease guidelines. These were the original guidelines to include Trans Catheter Valve replacement as a potential option. As you see at the top surgical aortic valve replacement was a class one indication for patients at lower intermediate surgical risk. Tavern makes an impression on the third line, 2nd and 3rd line down for patients in whom tava or surgical a VR is being considered heart team should convene, including both cardiologists and cardiac surgeons to determine the optimal strategy for valve replacement. Tavern was recommended for patients who have an indication for aortic stenosis and have a prohibitive surgical risk With expected life of greater than 12 months. So prohibitive surgical risk, 12 months of life expectancy. First time that tavern made it into the valvular heart disease guidelines. However, if you see at the bottom class three, no benefit not recommended for patients in whom their existing comorbidities would preclude an expected benefit from correction of the aortic stenosis. So If somebody is prohibitive for surgery but expected to live a year, it's appropriate to consider tabby. As per the 2014 guidelines, I noted that that's a moving target because these trials continued to happen in the data continue to roll in. In 2011, the second partner trial to cohort, a study which was the symptomatic patients that were randomized to trans catheter valve replacement or surgical aortic valve replacement was published. The mortality at 30 days was no different between the two groups, however, trended towards an improvement with tabby with a 3.4% mortality as opposed to 6.5% mortality in the surgical group one year, there was no different. There was an elevated risk of stroke in the Tavern group 3.8% as compared to 2.1% at 30 days and at one year 5% vs 2.4%. However, neither of these were statistically significant. This was published in 2011. The core valve or medtronic trans catheter valve product was also studied in high risk patients. And at that time, high risk was defined as a 30 day mortality of greater than 15% as determined by cardiothoracic surgeons. Two of those and one interventional cardiologist. Again, as I pointed out, 0.8 centimeters squared was the cut off for severe valvular stenosis. At that time that's been liberalized to one centimeter. And also the inclusion criteria mandated a peak velocity of greater than four or mean gradient of greater than 40 millimeters of mercury. This was done at 45 United States sites. We were one of the large n rollers in this trial and the primary endpoint was death have any cause at one year significantly lower in the Tavern group than in the surgical group. And this is the first trial to show superiority rather than non inferiority of a trans catheter valve technology as compared to surgical aortic valve replacement. Again published in New England Journal 2000 and 14 let's move to intermediate risk. So again, sts score of 3 to 8% for intra operative or 30 day mortality. This is the SAPIEN three intermediate risk trial which is partner, another partner cohort. 2000 patients, 57 centers randomized to surgery or trans catheter vow. They were also split into groups based on whether trans femoral or trans thoracic meaning trans a pickle or direct aortic access were used. The rates of death or disabling stroke were similar amongst the two groups. However, at two years, Tavern in the trans femoral cohort resulted in a lower rate of death and disabling stroke. With the confidence interval touching one Taber. Also resulted resulted in larger aortic valve areas, lower rates of acute kidney injury, severe bleeding and knew a fib while surgery resulted in fewer vascular complications and less aortic regurgitation. So there's less para valvular regurgitation when the surgeon so's the valve into place. There's also less vascular complications during the surgery because we're not using large bore access to place the valve. These criteria and risks and benefits for surgery and trans catheter valve tend to hold true for the remainder of the trials that we show with respect to lower risks of bleeding, atrial fibrillation and A. K. I. And the Tavern group. Higher risk of vascular complication and aortic insufficiency in the surgical groups. And we'll come back to those and you'll see those frequently. The search to be trial was the Medtronic version of the intermediate risk trial 87 centers 1700 patients. We were again a large N roller in this trial severe symptomatic aortic stenosis and intermediate surgical risk. You can see it two years. The composite endpoint of mortality or disabling stroke was 12.6% for tavern and 14% for surgery, which was non inferior. Again surgery having higher risk of acute kidney injury, transfusion and atrial fibrillation. Tavern having higher rates of residual aortic insufficiency and also permanent pacemaker implantation, which is traditionally higher with self expanding valves such as the medtronic valve. As compared to the balloon expandable valve. There was no difference in structural valve deterioration between the surgical and trans catheter valve groups at two years. However, the pacemaker rate was not trivial. Here, we're talking about 25% of these intermediate risk patients requiring a pacemaker as compared to 6.6% with surgery. And again, there's a lot of innovation that's gone into not only the valve technologies, but how should we properly implant these things to avoid pacemakers from occurring. And these numbers have come down substantially since then. But as of 2000 and 17, when this was published, these are the numbers that we were looking at in intermediate risk patients based on these intermediate and high risk trials. There was a 2000 and 17 focused update to the valvular heart disease guidelines and the valvular heart disease guidelines were not something that had moved this rapidly prior to a lot of the trans catheter technologies that have come about. But in looking at patients with severe aortic stenosis who were symptomatic and stage D that we showed you on the left side of the earlier graph. Low surgical risk remained a surgical A VR. Class one indication. Intermediate surgical risk added Tavern as a Class two, a indication based on the S. Three I And Sir tabby trials for the Edwards and Medtronic Products, respectively? High surgical risk was felt to be a Class one indication for Taverner or surgical aortic valve replacement based on partner A. And core valve pivotal and prohibitive surgical risk based on partner B. Gave a class one indication for Taverns. So these are the updates. As of 2000 and 17. The final risk strata to be studied was the low risk patient strata. And these data were published in 2019. Again in New England Journal of 1000 patients mean sts score of 1.9. So well within that low risk surgical range of 0 to 3 composite endpoint of death stroke and rehospitalization with one year follow up. So the plan originally for these trials and the long term plan is 10 year follow up. But the data that have been published and changes made based upon this, our one year follow up for the SAPIEN valve or Edwards product and a two year follow up for the Medtronic product. They looked at both non inferiority and superiority. The primary endpoint occurred in 8.5% of tavern patients as opposed to 15.1% of severe patients. Both P values were statistically significant. The 30 day stroke rates were lower with Tavern as were death or stroke New A fib and they noted a shorter hospital stay. So this is a change from prior. Remember when I showed you the original partner cohort a The risk of stroke were higher, not statistically significant, but certainly higher with trans catheter valve replacements than they were with surgical aortic valve replacements. And now with multiple iterations and innovations in the technology, Tavern seems to have caught up with respect to stroke rates. There were no differences in the rates of moderate or severe P VL and the new pacemaker rates were similar between the two groups. So this is really the first time that we've seen surgery and trans catheter valve. Again, a balloon expandable trans catheter valve, I'll show you pictures of these later have similar rates of pacemakers with respect to surgery. The medtronic low risk trial. Again, we tend to participate more actively in the Medtronic trials and we were a largely enrolling site for this 1400 patients mean age of 74. As I said, death or disabling stroke at 24 months, the primary endpoint was happening did occur in five point 3% of tavern patients as opposed to 6.7% of surgery patients, Which was non inferior. The stroke rates were lower bleeding rates were lower, kidney injury rates were lower and atrial fibrillation rates were lower. With tavern. The rates of moderate to severe aortic insufficiency and pacemakers were higher with tavern than they were with surgery. And again, nontrivial pacemaker rates 17% as compared to 6%. At 12 months. The tavern patients had a lower mean gradient and a larger effective orifice area of their valve 2.3 versus 2.0 cm squared. Based on these data. Another update to the valvular heart disease guidelines. And now we have not only taken into account the patient risk, but we've also taken into account as you can see in the top box on the left, the life expectancy of the patients. So if we have symptomatic Patients with severe aortic stenosis and an indication for aortic valve replacement, if they're less than the age of 65 and projected life expectancy of greater than 20 years is present, surgical aortic valve is recommended patients who are 65 to 80. If there's a contra indication to trans femoral Tavern, we can consider surgery or trans femoral tabby. If there's shared decision making between the patients, I'm sorry. No, no. An atomic contra indication to trans femoral tavern, then this can be considered as well as surgical aortic valve replacement. One of the things that comes up here is the need for concomitant coronary revascularization, track husband valve repair mitral valve repair, maze procedures. Is there something else that we can offer for symptomatic patients who are greater than the age of 80 there is a class one level of evidence. A recommendation for trans catheter valve replacement. If trans femoral tabby is recommended. So this is what we're seeing here with moving targets depending on life expectancy and patients who are now not only looking at a long life expectancy, also on the right hand side of the screen if a bio prosthetic valve is preferred, but vascular or other factors are not suitable for trans femoral tabby sava is recommended. And also the the need or the possibility of receiving a mechanical valve for these young patients as a one and done intervention has crept into the decision making process as well. So the updated guidelines certainly relate more to age than they do to risk status, but are also taking both approaches into account. So who can we treat with Tavern after all of this? And all the research and all the studies who can we treat with Taverns? So remember the inclusion criteria And this is what I stressed on the second slide that I showed we need to have an aortic valve area that's in the severe range, which is now less than one centimeter. We also like to see a peak velocity greater than four and a mean gradient greater than 40. If we have a normal ejection fraction, if we have a low ejection fraction, we want them to augment to a mean gradient greater than 40 or a peak velocity greater than four. On the W two mean study while maintaining an aortic valve area of less than one centimeter squared patients that have bicuspid aortic valve disease ejection fraction less than 20. End stage renal disease and severe disease of another valve, including severe mitral or severe trauma hospital vegetation have not been studied in a randomized fashion and these are not uncommon co morbid conditions. When we're talking about elderly patients with severe calcification, arctic stenosis, moderate to severe coronary artery disease has also been excluded from trials. So looking at syntax scores greater than 22 in the low and intermediate risk trial from the original partner trials, N. E. C. A. D. That required revascularization was an exclusion criteria. So we have to remember these things as well. Randomized data for young patients with unprotected left main disease and critical aortic stenosis is just not present. So how do we look at coronary disease? This seems to be something we worry a lot about in this patient population when it comes to valve choice longevity of the intervention. Do they require concomitant surgical revascularization? I mentioned already that in the initial high risk trials, patients were excluded for untreated clinically significant coronary disease. They required a PCI within 30 days if they were randomized to tavern? Thus, there was no randomized data of tavern patients with severe CKD. So if we look at the guideline recommendations, what are we supposed to do and what do we fix? So this came out in 2016 and this is an expert consensus opinion statement looking at coronary angiography. Prior to tavern patients that have no significant C. A. D. On the right are very easy proceed with tavern patients on the left that have significant C. A. D. Again with no randomized data. These consensus statements came out saying if there's proximal endo cardio vessel or left main stenosis that is amenable to PC. I. We can choose to PC. I. Those patients and consider it to be done at the time of Tavern, which again has been debunked. And I'm going to show you that in a moment if there's not any evidence of disease, there's non proximate or branch vessel stenosis, we only would have fixed that based on this consensus statement. If we thought that it was contributing to the patient's symptoms, is their dismay on exertion related to their aortic valve. Are there symptoms out of proportion to their aortic valve disease? And could this potentially be an and general equivalent? If so we considered PCI. Prior to Tavern. If not, we proceeded directly with Tavern and then reassessed after the valve procedure to see under the appropriate use criteria if they had symptomatic coronary artery disease. There was a meta analysis published in 2017 looking at this 3800 patients in nine studies with coronary disease and a lesion from 50% to 90% undergoing Tavern, 25% of them received revascularization prior to Tavern and there was no difference noted in 30 day cardiovascular death AM I. Or stroke between those groups. There was, however an increase in 30 day all cause mortality in the PC. I. Group which was related to an increase in bleeding and major vascular complications. When patients did then undergo a tabby. So a red flag here for patients treated with P. C. I. That there's not only no benefit but there may be a harmful outcome if treating these patients with stenting. Prior to having a tavern. We finally have randomized data as of 2020. So the activation trial looking at a relatively small number 300 patients Greater than 50% left main disease or staff in this vein graft disease greater than 70% proximal epic, cardinal native coronary artery. 1 to 1 randomization between PC. I prior to taverna or no PC. I. There was no difference in death or rehospitalization at one year between the groups. There was however again now randomized data showing a higher risk of bleeding in the PCI group before and after the tabby procedure if they were treated with stenting prior. So based on this we've gotten away from routine PC. I unless we feel that the patient's symptoms are related to angina, in which case we may proceed with PC. I see them back in the valve clinic and reassess symptoms. However, if we're concerned and convinced that they have severe symptomatic aortic stenosis. There's no randomized data that treating them with a PC. I prior to their tavern procedure has any impact at all other than to increase bleeding. So extreme high risk patients if we're talking about who can we treat with the tavern. We want the extreme extreme risk and high risk patients. We we prefer Tavern to Sabourin. These folks obviously assuming that their life expectancy is greater than a year. If we have somebody with a life expectancy of less than a year and they're very limited based on congestive heart failure symptoms, we will consider a palliative balloon aortic valvular plasticky, but they're not a candidate for trans catheter valve replacement. We also want to make sure that they're going to have symptomatic benefit at their current functional status. So if I see somebody who's extreme risk who's got severe aortic stenosis, but they're limited by an orthopedic injury or otherwise limited. Such that there, you know, bound to a wheelchair or they live in a nursing home, were not convinced that they're going to have significant benefit with their activity tolerance based on going through the operation. We would not offer that. We want to make sure that it's anatomically feasible and preferably in this patient cohort, especially from a trans femoral access perspective, which certainly lowers the risk of the intervention itself. And we want to know that there's no other dominant cardiovascular condition that would warrant surgical correction that maybe alternatively responsible for their symptoms. Do they have severe mitral valve disease or a revascularization, severe coronary artery disease that we would not be able to address. If we thought the symptoms were consistent with Angela in intermediate risk patients, both approaches may be appropriate. And there are multiple things that we take into consideration. As I already showed you, the age of the patient is a big player in this. If we're looking at patients greater than the age of 80 we favor trans catheter valve replacement based on the 2020 focused update of valvular heart disease guidelines. If the patient is between 65 79 we consider both approaches and we have a heart team discussion, we lean more towards surgery. If there is presence of coronary artery disease that requires revascularization. If we do not have really ephemeral access for Tavern were less likely to offer Tavern. We look at the size of the aortic annual lists and the annular anatomy relative to the favorability of trans catheter valve replacement. Is there heavy calcification that would benefit from being surgically removed as opposed to being left in place? Or is the patient going to be at higher risk of an annular injury or para valvular regurgitation? If we don't do an annular debridement patient preference always is taken into account once these other factors are adjusted and we feel that both approaches are safe and that's when we sit down with cardiology and cardiac surgery and our multidisciplinary clinic, we both discussed the risks and benefits of each approach if we feel that both are reasonable. We allow the patient to choose and this is how we make the decision in these intermediate risk folks, low risk patients. Again, Life expectancy, major thing that we want to talk about. Also remember the first slide that I showed you the ideology of aortic stenosis in patients less than the age of 70 is frequently bicuspid. We don't have randomized data and bicuspid aortic valve patients for trans catheter valve replacement. We also are concerned about the presence or absence of an aortic empathy. Not only is this something that is often needing to be addressed in the setting of bicuspid aortic valve disease surgically, it also increases the risk of an aortic injury during a trans catheter valve replacement procedure. So certainly if we feel that the aorta empathy is present and will require intervention at some point during the patient's lifetime. We feel that a one stop shop with a surgical aortic valve replacement. In ascending aortic repair. Maybe the appropriate pathway, the presence or absence of concomitant conditions. As I talked about earlier, severe coronary disease, severe disease of another valve and the one that we often forget is need for a rhythm control procedures such as a maze procedure with the left atrial appendage ligation for a low risk patient who has persistent symptomatic or chronic atrial fibrillation. Also patient preference comes into account when all things are considered to be equal here based on life expectancy and also the age of the patient. We certainly consider them for a mechanical surgical valve when possible. As a reminder, there are no commercially available or currently being researched trialed mechanical trans catheter aortic valve replacement. So I want to introduce the concept of a lifetime plan. This is something that I talked to most of the low risk patients about when we see them in the multidisciplinary heart center like congenital heart surgeons were discussing retaliation and one or two steps ahead rather than just discussing what may be appropriate for the patient right now because we're seeing younger and younger patients with aortic valve disease. As these interventions make it into the lay press. If we have a 70 year old who's still working, is it appropriate to do a trans catheter valve? Now let them finish their work without having a three or six month delay for recovery from a surgical valve replacement and consider them from an open replacement six or eight or 10 years down the line when the valve fails, depending on how good of shape they're in. If there's a 70 year old with a large annual list, large sinuses, high coronary artery takeoffs, can we consider a trans catheter valve now and a trans catheter valve inside of a trans catheter valve later. If we have a 70 year old, should we do a tissue surgical valve now and a trans catheter valve inside of that surgical valve later. And as I ask patients all the time, if we know that you're going to likely need an open heart surgery based on your anatomy at some point in your life. Would you rather do that when you're 70 or when you're 80 and I think that's an important consideration for the patients to have. How long is this thing going to last anyway? So we're currently in planting valves that were FADA approved in 2015 and 2017. They've had some subtle tweaks since 2019. So there's not a lot of long term data about the valves that we're currently putting in the prior iterations and generations of these valves were implanted in extreme risk patients in the late two thousands to early 2000 and ten's and a lot of these patients were 90 years old at the time of their implants. So we don't have a lot of long term 8 to 10 year follow up on these patients simply because they passed away at 95 years old, not necessarily from valvular disease, but mainly because of their age. So we don't have a lot of long term follow up information about these valves. Thus we don't have a great answer on the longevity of currently available trans catheter valves. So why don't we just put one inside the one that's failed? If we can do so through a catheter, why don't we just keep layering them on top of each other. So this was a study in 2000 and 19 by Gilbert Tang who's a cardiac surgeon who's very actively involved in trans catheter interventions at Mount Sinai in new york. He looked at a retrospective review of post deployment angiograms in 550 SAPIEN three patients, the most recent iteration of the SAPIEN at two centers. He looked at the feasibility of future left main coronary artery access and classified the aortic root anatomy as to what the likelihood of re accessing the left main coronary artery would be if the patient then had a second trans catheter valve placed inside the current iteration of trans catheter valve. And interestingly, I'll show you the pictures of this in a moment. This was felt to not be feasible in 20% of patients overall and in 55% of patients with what he referred to as a Type three route. And you can see on the top in column a type one, Type two and type three the yellow boxes a trans catheter valve that's been implanted in the aortic cannula. You see the sinuses of al salva and you see the left main takeoff. And what you're seeing is the trans catheter valve distance or distance from the sinus of val salva to the top of the frame of the trans catheter valve as well as the distance from the top of the trans catheter valve to the sinus of el salva with respect to height. Then you see both of those measurements made all the way to the left. Not only do you have adequate sinus surrounding the valve but you also have adequate sinus of val salva above the valve. So this would be easy to sneak a catheter in on top of the trans catheter aortic valve and to get into the left main coronary artery for coronary re access on the right side is the type three route and you can see in the bottom, right hand corner, the valve to sinus distance is almost negligible. You have a valve that is touching the sinus of val salva. If I were to put another layer of trans catheter valve inside of that, of note, there's no way for me to control where the metal struts and cells are lined up when I put this valve in. So if I put another layer of struts or another chain link fence, as I refer to patients when I'm talking about this In front of their left main coronary artery inside a valve that is already covering their left main coronary artery. My ability to get through that with Catheters is going to be much less. And as you can see, 55% of patients did not have feasible left main coronary artery access or theoretical feasible left main coronary artery access. If this were the case. And you can see that on the top, the n 30% of patients had this particular aortic root anatomy. So trans catheter valve inside trans catheter valve that has failed is not something that's been studied in a randomized fashion. And there have been some red flags raised about the potential for that moving forward. So something to keep in mind when we're talking to patients about options. The limitations of Tavern. As I've said, the valve durability and longevity is completely unknown. We do not know the strategy for a failed trans catheter valve. Do we need to respect this and place uh an aortic root replacement inside the patient because there's often significant adherence to the aortic root which may involve re implantation of coronaries and dr Sultan can talk more about that. Do we simply put a valve inside the valve? I just showed you that. That may not always be possible. Again, a permanent pacemaker may not be an issue when you're 85 years old. But if you're 60 in a low risk patient, the low risk trial, 17% of patients required a pacemaker. We've adjusted this based on currently available implantation techniques and a technology known as the cusp overlap technique. However, the numbers are still not trivial when we're talking about pacemaker implantation and the inability to treat severe concomitant conditions such as coronary artery disease, a sending aortic disease or concomitant disease of other valves. Yeah, the currently available platforms include the Medtronic platform and this is what the Medtronic eh veloute pro platform looks like you see that this is a night nol frame valve that's approximately 4 to 5 centimeters tall. They have open cells that are made of Knighton Hall That are approximately 10 French in size or will accommodate a 10 French catheter for re access to the coronary arteries moving forward. This is referred to as a supra annular valve, which means the valve leaflets are anchored at approximately the mid portion of this frame above the aortic cannula, which allows for a lower trans valvular gradients After implantation. You also see at the bottom, there's a ceiling skirt on the bottom two diamond shaped cells and that decreases the rate of para valvular regurgitation. Once these valves are implanted, this is a self expanding valve platform and it comes in four different sizes. The delivery system is advanced over a stiff wire across the native aortic analysts. There's a capsule that is covering the valve that is slowly retracted, allowing the valve to flower into place and this is the final result that you have the valve springs into place. The delivery system is removed and the trans catheter valve is left behind. So that's the medtronic valve self expanding valve design the Edwards SAPIEN. This was the valve that I talked about studied in the partner trials. There have been four different iterations and these are those four SAPIEN SAPIEN XT SAPIEN three and SAPIEN three Ultra with SAPIEN three Ultra being the one on the right side of the screen, the most commonly used. Now this valve is made of a cobalt alloy metal. It has bovine, pericardial leaflets and a ceiling skirt around the bottom that is made of cloth. You can see the ceiling skirt is higher than it was on the prior iteration of the valve. This is to limit para valvular regurgitation. This is a balloon expandable valve which means the valve is mounted on a val Villa plastic type balloon. It is placed across the aortic cannula stand positioned appropriately. The balloon is blown up, leaving the valve behind and then the delivery system is removed. The newest kid on the block is the portico valve, which is made by Abbott vascular. And this was FDA approved very recently for high risk patients and is currently being studied for intermediate and low risk patients. The portico is again a self expanding valve platform. The difference between this and the medtronic valve are that in the current iteration, there's no ceiling skirt available, although this is being added in the next iteration. It also has larger open cell designed to facilitate easier coronary artery access and this valve is an annular valve so the leaflets of the valve are anchored lower within the frame and to be positioned within the aortic annual list as opposed to the super annular design of the medtronic valve. The hemo dynamic effect is likely to be slightly higher mean gradients after these are implanted given the annular as opposed to super annular design, but also to allow for easier coronary access with lower valve leaflets. So these have not been compared head to head and again, the low and intermediate risk trials Are currently ongoing as of November 2021. This is the delivery system which is the flex nav delivery system. Again, it's a capsule that is wrapped around the valve. The capsule is retracted using this dial that is outside the body, the valve flowers into place and the delivery system is removed in total. So who do I think should still have a sovereign 2021. I'm the interventional cardiologist on the team. It's often difficult to talk about who should have surgery or recommend surgery. I think this is one of the advantages to the relationship that we have between our cardiologists and cardiac surgeons in the multidisciplinary Center for heart valve diseases that I am often very aggressive and pushing patients who are of young age and would otherwise do well with a mechanical valve towards the surgeons. The surgeons are often aggressive because they do both surgery and trans catheter valve replacement and saying we feel that because of some other um risk factor that is not involved in the sts calculator, that this patient would be higher risk for open and we feel that trans catheter valve disease is more appropriate. So I think the collaborative effort is very important from my standpoint as a cardiologist low and maybe intermediate risk patients with severe symptomatic aortic stenosis and coronary artery disease, especially of the left main or left anterior descending. I strongly believe that a lima to LAPD will outperform a drug eluting stent if done by a surgeon with excellent technique and if done in the current generation Patients less than 65 and maybe less than 70 with a normal life expectancy greater than 20 years, especially if they're willing to take uh an anti coagulant for a mechanical valve. I think that's a one and done and we don't commit them to a second operation by the strategy that we pick at the first operation. I think that's very important patients who are lower intermediate risk with bicuspid aortic valve disease and concomitant aorta apathy or coronary artery disease. The one and done surgical approach to the aorta and the bicuspid aortic valve I feel are the most appropriate based on the surgical risks and the the abilities and skills of our aortic surgeons do a great job with these cases. Our multidisciplinary heart valve center. I've alluded to this multiple times. This is a combined patient evaluation with both interventional cardiologists skilled in tavern and high risk PC. I. As well as cardiac surgeons who performed both of these operations. In addition to mitral and try cuspide valve and heart rhythm procedures. We have an in person explanation of all options and risks and benefits with all patients that are coming to see us. We participate in shared decision making. I talked to them about the PC. I. And the tava risks cardiac surgeons. Talk to them about the open risks and we sit down and we make a shared decision with the patient about what is best at this time and what may be best in the long term. The information is presented in an unbiased fashion because we're both there at the same time. We're all part of the same program. We're all going to be involved in these things on both sides of the surgical and trans catheter valve approaches. And we discuss all of these options simultaneously. We feel that this is important to not have a patient referred to us with a preconceived notion of being sent by a cardiologist for a tavern or being sent to a surgeon for surgical aortic valve replacement. But being sent to this clinic where they can truly be evaluated by both of us can commonly and come up with the best approach for the patient. We feel that that eliminates a lot of the bias that we deal with at this time. I'll turn it over to my colleague, Dr Sultan, who will discuss the surgical approaches and the surgical techniques available for aortic valve disease. Thank you. I want to thank DR Kleiner for his talk. I will continue on and focus on the surgical management and focus on bicuspid aortic valves. In my talk and my name is Ibrahim Sultan. I am uh belt cardiac surgeon with the UPMC heart and vascular institute and the surgical director for the structure of heart and heart valve center. I have no personal disclosure but we do receive institutional research support as listed here. So there really has been a revolution in the management of aortic stenosis really throughout the world. This gives you a snapshot of what that looks like in the United States. Early in 2016. Uh Tavis d or tab are really outperformed as far as quantity and numbers surgical, isolated surgical A VR. Uh and in 2019 really surgically VR for all forms. And now tower continues to be the dominant way aortic stenosis is treated really in the US and throughout the world. And so it's been almost two decades since. Alan Carpentier performed the first trans catheter aortic valve replacement. And what have we learned from the past two decades. Number one, as I mentioned, Taber truly has been a revolutionary technology in patients with aortic stenosis. Tavern will likely continue to be the dominant mode of treatment for patients. We degenerative aortic stenosis and most importantly a true multidisciplinary evaluation and a heart valve clinic is likely to provide the most thoughtful and comprehensive treatment plan for patients with heart valve disease and in this case the aortic stenosis. This means that surgeons who participate in the heart valve clinic have expertise in both trans catheter and open heart surgery and cardiology interventional cardiologists or structure heart cardiologists have experienced with complex P. Ci apart from structure heart intervention. So this is the term that is quite popular and and being thrown around a lot which which is what is truly the lifetime management of the aortic stenosis patients, the natural history of patients with aortic stenosis. This was over a decade ago. Was was the fact that if patients lived more than five years, they're likely to drive a significant benefit from aortic valve replacement. Now for those patients who survived past six months, their life expectancy generally matched that of age matched controls. The life expectancy back then. If a 65 year old was 18 years of age. Now, that has changed over time. Now, women who are at the age of 65 now yearly have 20 years of life expectancy compared to what it was back then. And so and so our patients continue to live longer and grow older. And this is important for us to take into account. So what is the young patient who comes into the office or here? And this is a combination of what's available on the internet and what they may hear from uh their, their physicians And friends. So go ahead and get your first procedure as a surgical aortic valve replacement when you're young. Because of all the newer by prostheses that are available, valve durability is likely will be almost 20 years. And your second procedure will be when you're close to 80 years old, which will be a tavern and a savage or tavern sap. This is the north therapy that's relatively well established and the valve durability will likely last the remainder of your life. The reality is really far from this. And what that young patient should really know is that the first by prosthetic valve that That they're about to get when they're in their 60's or fifties, The time to first failure, depending on if you look at the valve and valve registries really around 7-8 years. So, what this means is your second intervention or the valve in valve tabby, based on that paradigm would really be between 65 to 70 years of age. Now, what we don't know is what the time to failure is from this. The reality is that this is really unknown. And so what happens after that? The third intervention? Would this be a valve in valve in valve or would it be open surgery again, at that age? The goal that we always try to tell patients is It is critical that they have less invasive therapy. However, would you rather have open heart surgery when you're in your 60s or would you rather have open heart surgery when you're well into your 80's or worse, what is being recommended by some folks now, which is first Just undergo a tavern when you're in your 50s or 60s. But again, the reality is that the kind of failure is unknown. The second therapy would then potentially be a valve in valve tabby. And again, the time to failure from this is also unknown and as dr kleiner pointed out that the feasibility of tabs and tab is really unknown and majority of patients are likely not going to qualify for this based on anatomical constraints. And so what would be your third intervention, valve and valve and valve? So there's a Russian doll effect that occurs with this uh with time and patients continue to have significant patient prosthesis, mismatch, increased gradients and quite frankly at this point, they may be committed for life long anti coagulation, which is what they wanted to avoid in the first place by avoiding a mechanical valve. What is also important to recognize is that the exploitation of the tabby bath is just not the same as a standard reduced surgical A VR. These are data from the surgical x plant registry from 42 centers, just over 250 patients. And as you can see that in hospital mortality was nearly 12 And then hospital stroke rate was almost 6%. Several of these were done urgently. Nearly half of them for endocarditis or other reasons. And despite that, uh majority of these patients did have a redo aortic replacement. However, a small percentage needed to undergo a root replacement. And so the survival after this operation is quite poor when you compare to regular reducers, believe you are and I think it's important to consider this and keep this in mind. The valve in valve strategy also is highly dependent for surgeons and interventional ists who are are talking to patients about this to consider now, valve in valve strategy is really is an outstanding strategy for high risk patients with structure, valve degeneration. But again, it all depends on what the first about the patient had. The reality is that the most common bio prosthetic surgical valve implanted in the United States. It's a 21 millimeter valve, which then limits the number of interventions or the quality or the durability of the valve and valve intervention that the patient has to occur. This example on the right is a patient with who had an annular enlargement to up size the aortic root by multiple sizes. Now, again, the perception by majority of patients is that most surgical valves have planted are good enough for valve and valve strategy. The reality is development valve registry actually demonstrates that 70% of the patients had either intermediate or small valves. Right. And so based on the definition that large valves or any thing over 25 mm in size intermediate. We're about 21-23 and small, less than 21 and so angular. And the large one is truly key in these pages as the smaller the value you start off with this will limit the number of valve and valve interventions and the outcomes from that. Now, structure valve degeneration is obviously very unique to buy a prosthetic valve. Uh, the time. The first durability can really range anywhere from 7 to 13 years. The original thought process was that all these valves would last approximately on average, 13 to 15 years. However, this was pre valve and valve era. A lot of these patients were sent home for with palliative care or hospice or we're not intervened on Now with the availability of velvet valve, this is likely going to change and the modern data will most likely show that the time to first failure is significantly shorter than the 13 years that has been historically advertised. The longevity of bio prosthetic valve is also comes into question when only a very small percentage of the population is actually followed up to about 20 years. So even though the mean time for structural degeneration was approximately 13 years, there was a significant standard deviation from this. As the risk of re operation by 20 years is nearly 50% for young patients. And so her 55 year old, the risk of re operation or re intervention is 10 times higher than patients who had mechanical vowels. So there's a significant survival benefit and patients receiving mechanical valves in the aortic positions in the young population. And despite quote newer bio prostheses that are being developed with claims of Increased durability, there truly are zero long term data to support this. This includes all sorts of tissue valve treatments, polymer or stateless vows or Zakia PR strategy. So how about patients with bicuspid aortic valve and this is a topic that is very near and dear to our hearts. This is an example of a patient who has a bicuspid aortic mouth heavily calcified as you can tell. Has a Raphael on the inter cusp. Um and a poster cups, cups that is not fused. Clearly very different pathology that patients would try custody aortic valve. It's important to recognize that bicuspid aortic valve is truly a syndrome and not just an isolated valve pathology. It is very common. Approximately 2% of the population does have this and valvular dysfunction is really the most common complication that is seen from patients bicuspid aortic valve. It's associated with a nationwide network aneurysm co optation and endocarditis. Now the typical normal aortic anatomy Really is three customer 3 leaflets behavior bicuspid aortic valve patients have to unequal sized cuts with the fusion of two costs. Raffaele's president as is highlighted right here at the fusion of the conjuring customs and the right and left. Fusion is more common. Historically, deceivers classification was the most common and acceptable uh definition or classification for patients with bicuspid aortic valves as an example of a type zero seaver's patient with really no raph, a type one patient with one graph or a type two patients with two Raffaele's or what many refer to as a unit cost. Bell, There's been more recent changes in classification known as the international BV classification that is generally more targeted towards interventional approaches with transplanted A heart valve. So why is this important patients with bicuspid aortic valve were excluded from pivotal tower trials. If you look at the retrospective data, there's an increase in incidents and bicuspid aortic valve. Tower patients right this and this includes a higher risk of stroke, higher risk of coronary obstruction, higher risk of para valvular league and a higher risk of annular rupture. And the difference is really to do with anatomical constraints. And it's important because when you're extending this lowest population, Almost 50% of patients, less than 70 year olds are bicuspid and bicuspid aortic mouth pathology and the autopsy is truly real. We know this because nearly half the number of patients who have elected based and aortic replacement have bicuspid aortic valves. This has been shown in multiple series from multiple institutions. Our own institution shows that nearly 46% of the patients having an ascending elective aortic replacement had bicuspid aortic valve now is the bicuspid aortic valve or the navy or the really different than Tv or that the answer to that is yes. The pictures and the two images in the left demonstrate pictures of images of bicuspid aortic valve aorta, which is very different characteristics than try custom valve aorta, the shape of the face and neurotic aneurysm is different. This may be a root phenotype. This may be an ace and a neurologic phenotype and rarely in arch phenotype, we also know that by the time we see patients, the BfV auras are much larger than try custard valve aortas and they're more likely to grow much faster than patients who have Tv orders, which means surveillance is extremely important to these patients and treating them competently at the time of surgery is also very important and this is unlikely to change if the patient's aortic stenosis is corrected because there are no data again to support that, that that's not process. Now. While the incidence of aneurysm or the growth is not as aggressive as patients with Marfan syndrome or louis cesar earlier stand loads. It is still significantly higher than the control or the trick hospital aortic valve patients. So in general, Tavern can be performed safely and selected by christmas. Aortic valve patients. The rate of stroke need for pacemaker rate of para behaviorally and coronary obstruction is significantly higher. And unfortunately there's been no prospective randomized studies performed for being patient and the growth and the goal really of the aortic replacement in these patient populations is to prevent any acute aortic dissection or any or transfer. So when is Sabra the preferred strategy. So in patients with isolated aortic stenosis with life expectancy of greater than 15 to 20 years, which is less than 75 years of patience And it's important to recognize 90% of these patients should not require astronomy. This can be done with less invasive strategies such as a right thoracotomy approach complete sternal sparing or partial astronomy approach. Intermediate risk patients who have been common in diseases such as coronary artery disease, specifically when it's left main proximity and healthy vessel atrial fibrillation. Or can accommodate or Carpathian, the customer group and non high risk patients with bicuspid aortic valve stenosis. No, if patients do have isolated aortic valve stenosis again are preferred. Strategy is to use external sparing, minimally invasive approach, right thoracotomy approach. And this can be done safely with no change in outcomes and significantly faster recovery and back to work for these patients. It's important to recognize again that other procedures such as root enlargement can be done through this with some experience. So what is the tower sour strategy? So this is highly, highly patient specific and patients truly are the center of our heart. But in general, this is the algorithm that we typically follow. So if a patient is high risk, we know that the savage versus tavern outcomes that approximately five years are relatively the same. Despite this, we prefer Tavern in this patient population because of their limited life expectancy in the intermediate risk group, this is highly patient dependent and concomitant disease specific. Even though Sabra versus tavern outcomes are generally the same at approximately five years based on the basis of partner data, sovereign will be preferred if patients have concomitant diseases such as corner disease, fibrillation, incompetent or telepathy or multi valve disease. Otherwise, Tavern is strongly considered patients who are otherwise low risk with very limited long term data, minimally invasive surgical aortic valve replacement is to prefer strategy unless there's something to tell us that the life expectancy is rather limited. These patients, patients with uncommon and left main or proximity disease sovereign with cabbage neuropathy including aortic surgery, prior prior bio prosthesis. Unless patients are truly high risk reduce search play VR is preferred or patients, patients do have large bio prosthesis in place. Tavern can certainly be utilized if somebody has a life expectancy of less than five years. Taverna is certainly the preferred strategy. Now again, this is a rough algorithm and and these thoughts are usually discussed with patients and all of these are very highly patient specific. So going back to you PMCS volume and outcomes we know based on data that's published from the TVT registry, that there is a very strong correlation between annualized hospital procedure, volume and a relative reduction in mortality. Now, the UPMC is the system we performed Somewhere approximately 12- 1300 tabbies a year. As you can see from this graph, very small number of hospitals perform More than 300 to 400 towers every year. And this is important to recognize because with increasing volume, there is a clear relative reduction in risk adjusted mortality. Again, Our mortality rates and our outcomes are something that were exceedingly proud of. This includes a less than 1% mortality, 30 day mortality after tavern UPMC, a one day, medium length of stay and most patients who are able to be discharged home with appropriate rehab. The most important reason, quite frankly is that patients get a comprehensive treatment plan for their heart valve disease. Whether it's medical management, catheter based therapies or surgery, it's important again to have surgeons who are well versed with trans catheter, heart valve replacement with minimal invasive heart surgery, advanced coronary disease with complex P. C. I. With respect to interventional cardiology expertise and outcomes that are really significantly better. As mentioned by it appear institution, there's a significant role for innovative cutting edge I. D. Premarket post market and pivotal trial access that benefit patients and do benefit the field. And most importantly we have a large network of nearly 40 hospitals that allows for continuity of care throughout their lifetime as opposed to a visitor or concierge medicine where patients may only be seen by us once or twice.
