In this virtual lecture, Cardiac Surgeon Dr. Michael Ibrahim discusses three points: 1) normal valve function is sophisticated and depends on a sophisticated living structure which is active and adaptive, 2) living valves give rise to important clinical properties we care about, and 3) using standard techniques, we can restore or replace living valve structure and function. He also highlights the reemergence of the Ross Procedure.
Mitral Regurgitation | Penn Medicine Grand Rounds Update in Antithrombotic Therapy – COVID-19 and NOACS | Penn Medicine Twitter @PennMDForum Dr. Ibrahim’s physician profile Okay. Are we live, Linda? I was muted yet for life. All right. Good morning, everyone. I see. Um um, folks are beginning to log in, so I want to say thank you for joining us this morning. My name is Wilson Zito. I'm wanted to cardiac surgeons here at Penn Presbyterian. Uh, this is our monthly cardiovascular surgery. Grand rounds, Um, here for the month of December Again, I want to thank everybody for sharing with us their time. I know everyone's busy. Uh, just a quick introduction, and we'll get right to it. Um, were it is a pleasure and a privilege for us today. Toe. Have Dr Michael Abraham speak to us. Um, as many of you may or may not know, um, Dr Abraham will be joining us on staff here in July of 21 2021 as a faculty cardiac surgeon based at Presbyterian. We're excited. Toe have them. Um, I like to think that I'm sure he will bring a very fresh and unique and new perspective to cardiac surgery being in the generation that he's training in, which is a lot of innovation. A lot of forward thinking today. Um, Mike will be speaking to us regarding his perspective on the future of valve surgery, specifically valvular repair. His focus obviously will be working on mitral valve surgery, building on the platform that Clark has done so well for us over the last two decades, really leveraging that platform and expanding it. So I love to hear Mike's perspective about the future of microsurgery, but also he's gonna talk about aortic valve surgery, aortic valve repair. He's gonna touch a little bit for us today on this emerging sort of re emerging excitement about the Ross procedure. Most of you know about the Ross procedure. Um, there now appears to be a resurgence in his interests, and I think that's exactly very appropriate Giving all the new technology and what how to manage young patients with valvular aortic disease. So without any further ado, I'm gonna introduce Mike here just for housekeeping sake for everyone on the call. Couple of things, please. Mute Um, when, um e think Linda will meet everybody? There is a chat box. Please feel free to ask questions through their We'll have a Q and A at Session A. D N. And the C M code which is obviously very important. The Event Co. For this session is 66873 again. 66873 So, Mike, thank you. And please take it away. Okay. Good morning, everybody. And thank you. Got zero for your introduction and the opportunity to talk to you all this morning. Um, I I'm gonna be talking to you about the living valve repair replacement options for long term durability, survival and quality of life. Andi, I have no financial disclosures, but I do disclose my bias, which is I was introduced to protect surveyed by sending the active one of the world's great art surgeons who there's a pioneer of reconstructive valve surgery in the yogic position on the mitral position and also a major pioneer of the Ross operation on an advocate for it. And I think we've seen the the re emergence as Dr Rosita was saying of the Ross procedure all over the world, partly due to his influence. And so I do disclose my bias and as a bias, I hope that you will share by the end of this talk. I have three points, Really, That I want to talk about this morning. The first is that normal Val function is sophisticated on git depends on a sophisticated living structure which is active and adapted these air not just passive structures that open in response to trans valuable ingredients. The second point is that the living valves give rise to important clinical properties. That we care about when we're managing patients on the third point is that using standardized techniques, we can restore or replace living valve structure and function on, hopefully achieve superior clinical outcomes. By doing so, eso That's what I'm going to talk to you about, and we'll start with the aortic valve. Attn least in terms of its its anatomy. This is a study from Stanford, where they used radio pick markers at every level throughout the aortic valve complex and the silent triple junction, and analysts and the valve leaflets on the Sinus segment itself. And there are two really striking things about this slide. The first is that the root complex undergoes very sophisticated movements. The valves are not just opening passively. Their torch inal changes in the route in the analysts and the Sinus segment, the shortening of the Sinus segment throughout different elements of the cardiac cycle. Andi. The other really striking thing is that the valve opens prior to the development off a trans valuable ingredients. So this this valve is a sort of active structure. The valve leaflets themselves are also highly active and adaptive. This is a study from Dr Jacobs Group looking at the effect on stiffness of aortic valve human aortic valve cusp sis in response to various Veysel active substances. And you can see that the very radioactive substances do change the the stiffness of aortic valve custom. You can imagine a situation, for example, in severe hypertension, where there is elevated expression of vase of active substances that the valve leaflets may stiffen as a means to cope with that extra human dynamic load a missile arise because the valve leaflets themselves are a multi cellular complex off sophisticated cell types. There are my oh fiberglass, fiberglass and smooth muscle cells capable of contract. I'll function. There is an indoor fetal layer on college. Um, there are also these neuro filaments throughout the the aortic valve Onda mitral valve leaflets. The exact sort of function of these has yet to be determined, but again it points to the fact that these are not purely passive structures and are highly active and adaptive. This is a study of the micro analyst, and we won't belabor the point in going through every detail here. But what is important is that again, every aspect of the valve complex varies in its size and shape during the cardiac cycle, and this is specifically altered in, uh, both primary and secondary M R and different ways. And this was recently put together by the Yell Group in what they call a mathematical blueprint of a mitral valve on. What you can see is that throughout the cardiac cycle, the annual IHS undergoes again not just a diminishment of its size but changes in its shape. Throughout the cardiac cycle. The papillary muscles undergo translational movements, um, rotational movements on the annual and the leaflets themselves also open prior to development, the trans valve, the radiant and they open in a very sophisticated way. Ensuring laminar flow on this living structure translates to complex function the end of helium. By its ability, Thio Mount Inflammatory Response provides resistance to infection by its capacity for the production of nitric oxide. It provides resistance to Trumbo embolism on. Do you know these leaflets are exposed to massive stresses and strains for a normal human lifetime on they have a capacity for road repair and regeneration, which allows them to deal with that. The leaflet viscosity is equal to blood. On dis is part of the way in which they're able Thio, you know, with very little energy expenditure, uh, produce their sophisticated pre emptive pre pressure movements on the living valve. Complex results in minimal ventricular work laminar flow, an interaction with the tethered chambers, dynamic annual emotion in both the mitral and annual position and really perfect human dynamics. And this is important for us because this translates to survival. It translates to durable freedom from valve related complications, and it translates to quality of life. So what are we talking about when we say, you know, living valves? What do we mean clinically? Well, for A S and I were talking about valve repair, which I'm not going to talk about a whole lot this morning on really living valve replacement in the Ross for micro repair. We're talking about, you know, eso micro station. We're talking about micro repair techniques and That's really what we're gonna focus on this morning on the focus of the talk is ready for non elderly adults. I think when we see patients in their twenties, thirties, forties, you know, we think that they have a long life to live on bond. Sometimes when we see patients in the sixties and seventies, yeah, we forget that a patient who's 60 has a 20 year conditional life expectancy. A patient who's 65 has a 15 year conditional life expectancy, and these are really stretching the limits of our the duration of the bio prosthetic valves and also prospective house in general that we have to offer. Non elderly adults are characterized by certain unique features that have high physical activity. They have a longer exposure to valve related mobility, which may occur a low rate per year. But when added up over 20 years, becomes very significant for biological values. Talking about from the embolism, structural valve deterioration, patient prosthesis, mismatch, mechanical vows, we're talking about bleeding and threatened from the embolism. These patients suffer from the inferior human dynamics of these prosthetic valves. And there, you know, they demand a high quality of life and there is an impact on that. So let's get straight to it. Um, I think several groups have shown similar data. This is a large perspective multi center international registry from six Reference Micro Centers around the world. On what you can see here is the mitral repair. A living mitral valve produces superior survival Thio, mitral replacement. And they really went to great lengths to try and match their patient cohorts. Um on do you could see that in both the propensity matched analysis on din the, uh, invest probability waiting analysis both show that might to repair his superior in terms of survival on. That's a really sort of hard end point that there's really not open Thio any interpretation. At 20 years there is a There is a survival advantage, and they looked at various sub sections of their population in the population that less than 65 years of age again in the overall population and both the inverse and propensity match populations, there is a survival advantage that extends out the 20 years for Mitt to repair over mitral replacement. It's also true for older patients. They looked at patients over 75. Um, Michael repair had a superior survival in both matched on non match populations over mitral replacement against the living valve structure appears toe portend a survival advantage. This is a really impressive slides me because across age groups across from abilities like hypertension, um, diabetes, poor ventricular function, regardless of yh a Stasis there really was not a group that did better with mitral replacement. Um, it is important to remember that this is referring to degenerative mitral disease and not to secondary M r, which is a different disease, but certainly in the generative mitral repair regurgitation. You know, we must focus on producing a repaired valve whenever possible. Um, one of the sort of concerns is in durability, and we often think of prosthetic valves being more durable. But I think that the capacity of the valve to repair itself and to withstand the strain of a normal psychotic cycle is telling. In this slide, you can see the freedom from the operation. Um is fact, frankly, identical between repair and replacement groups out of 15 years, and it also confers freedom from valve related complications. You can see that, uh, the repair group is superior in terms of its freedom from Val related complications. Such a stronger embolism sentence, a stroke and bleeding, and so on and again durable out to 15 years. These findings have been confirmed by many other groups. This is Dr David's 20 year outcomes of his micro repair on you can see out 20 years, you know, a very good good survival again, Um, that there is a price to pay in terms of yh a status won't talk about that in a second, but excellent outcomes for producing a living mitral valve. Dr. Adams has really been a pioneer of the concept of reference centers on duh you know, showing what is achievable in near 100% repair rate for degenerative M. R. I think what is very impressive about this is that it does not come at the expense of durability. Uh, in this paper, he is describing, um, 91% freedom from to plus Omar at seven years, which is which is pretty good. Um, this is an analysis of the UK minimum invasive micro experience could have shown you many similar studies, but essentially what it shows is that that sonata me and minimal access surgery produce similar survival. This is a matched population. I think that's important because, you know, we do have to be selective Bond. That is not a criticism of invasive surgery. I think the point is that with patient selection, not despite it but with patient selection we can produce equivalent, um, outcomes. It's one of the controversies you know is always went to intervene on. Duh. This is analysis from the same international registry looking at you outcomes based on the primary initial sort of tragedy adopted. So, you know, we see these patients in clinic. They have m r. And based on a spectrum of factors. Sometimes we up for early surgery, and sometimes we watch up for a wait. Wait for watchful waiting sort of strategy. And what you can see is that there is a survival disadvantage to the initial strategy off medical management compared to early surgery, I think this is also true in a match population of patients where they tried thio as as much as possible. Match patients, apart from the initial strategy, adopted um, so that's important also seems to portend a a freedom from congestive heart failure. You can see that the medical Management Group. You have a much higher risk of developing heart failure over over 20 years than the cohort that went within a early surgery strategy. And again, this was, you know, found to be the case. Also in the propensity matched cohorts. This is another way of really looking at the same question of when to intervene. Um, this is from Dr Szasz Group. Basically, he looked at outcomes based on the indication. So, um, you know, for patients we see in in clinic, we describe them, an indication that's either a class one indication class to with based on complications such as a defibrillation, Palmer, hypertension or, you know, early class to indications. And what he showed is that there is a survival disadvantage to waiting for Class one indications. So the patients who operated on because of Class one indications the most severe did worse than those who operate who operated on because, of course, to complications based on sorry. But class to indications based on complications on those potions did worse than the patients who were operated on the software class. Two indications. So you know, he describes what he thinks is an outcome penalty linked Thio. Strict adherence. The guideline based indications for microsurgery. Well, Michael, the trans cancer therapy has arrived for for mitral insufficiency. This is the five year results of the Everest to randomized trial. Onda uh, you know, I think it's important. Sort of. Look what the this in its context. So they describe micro clippers, a procedure modeled after surgical theory double orifice technique of micro repair, which has been shown to have durable results when performed in conjunction with an annual capacity ring for the generative Emma. I think it's important to remember that the ring is also always part of the Alfieri because these are the results off on Alfieri without annual capacity ring, which are pretty terrible at 12 years, 43% freedom from three or four plus m. R. So, you know, that's sort of what we're looking at in terms of a pure Alfieri approach. Nevertheless, these were their five year outcomes, and the primary outcome was freedom from death, mitral operation or or three or four plus m. R on. Do you know they were not people Thio to meet the sort of standard of surgery primarily based not on survival but on ah, high rate of mitral re operation within the first 6 to 12 months and also ah, high rate of three or four plus m r at, uh, primarily within the first six months on. I think there are a few important elements that are worth just taking a minute to think about when we talk about pocketing is mitral therapy, but also, you know, aortic therapy. The first is that the study populations should be should not be heterogeneous, and part the problem with Everest to is that included both patients with structural on degenerative, um, are inclusion criteria should mirror current guidelines and practice. Another challenge with Everest to was that you know, not all the patients really met the indication for facility that we would apply and, you know, operating on patients because, you know, 5% of them have multi moderate M. R ah, third of patients who failed micro therapy did not go on to have surgery, which implies that it didn't really have a surgical indication on. Do you know we also recruited patients with three plus M R. High quality repair centers are important when we're comparing these groups. Um, the average number of repairs I believe in Everest to was 2.5% on. We know that patients that tended to do poorly and have complications were operated on in centers that less than 15 microns per year. Patient compliance in terms of follow up, has to be a major focus of these studies. Unfortunately, the surgical group in Everest to I believe that 70% of patients reached, you know, we're sort of lost. Sorry, 30% were lost to follow up in the surgical arm and another very important consideration. When we're looking at young and low risk patients, we really have to exclude them from any trial that includes irreversible devices. And I think it's an open question, really. Whether the micro clip, um, limits your your chances of repair, certainly in Everest to there was a signal that it may, because 21% of patients who were randomized thio to Metro Clip underwent surgery. And half of those patients got a replacement on bats that you're talking about 10% of patients getting a replacement, which is far in excess of any published syriza's of mitral repair. And so, um, you know, we have to be careful that to do these trials in a way that protects patients, given the survival advantage of a living mitral repaired valve, then points have to be clinically relevant, you know is a big sort of concern. An area of controversy about the M points in Everest to the FDA preferred a two plus m are sort of standard, and the trial is went with a three plus m r standard. And so you know that that is gonna be important. Designing future trials It's important that the inclusion criteria should, uh, include plan surgical repair of the valve and Everest to included patients who, um, we're recruited based on an intention to replace the mitral valve that some of these elements have been ironed out in the repair, um, our study, which is currently recruiting. But we'll have to wait and see how that pans out. There also some challenges with that style, but in any case, just some things to think about. Both entrance catheter mitra. But also many of these things apply to the aortic spaces as well. I think we're all happy that micro repair is really the standard on. There are many ways to do it Transfer after therapy is being evaluated, then we'll see where that lands. And so I'm gonna move on now to talk about the chaotic space and they're awesome. I think it's worth beginning by, uh, mentioning, you know, the prosthetic. KBR has several advancers. It is standardized. It is relatively safe. It is widely available on. We have known long term outcome, certainly in elderly patients. And I think we have this general consensus that general feeling that if you have a s or a and you undergo on a VR, you know you're not, you're you're basically cured and your survival should be normalized. And I'm gonna ask whether that's true. So this is the everybody who has heart surgery in many European countries, including Sweden, is including a national registry, and this is their observed to expected survival after aortic valve replacement on what you can see in the the White Group is essentially the survival of patients undergoing aortic valve replacement. Um, and this is the survival oven age and sex matched population that is matched this cohort of patients and what you can see, there is excess mortality. So, um, so that's the other way around, but the same same point that there is an excess mortality between that observed after the aortic valve replacement compared Thio that observed after in age and sex matched population they dug a little deeper on. Looked at this in different age strata. What they found was that if you're elderly and you undergo aortic valve replacement, your observed to expected survival is equivalent to the normal population. In fact, some Siri's aortic valve replacement is actually protected because there's a selection bias towards operating on healthier elderly patients and so seem to be protected. But in any case, there is no major survival disadvantage by undergoing a VR. But as you get younger, the observed to expected survival becomes, you know, pretty bad 4.5 times the risk of death over the time course of this study. This has been found in many other groups, so you know, mechanically, we always think off the standard in any younger patients. And this is from the Montreal Group. Um, and what you can see is that patients on to go isolated mechanical a VR on this study really did try to remove any confounded. So no patients with endocarditis. No patients with significant current disease, no emergency operations. These were just really straight isolated mechanical A V R s, and compared to a normal age and sex matched Quebec population thesis vie vel over. You know, 10 to 14 years was significantly worse. You could see it 10 years. Patients who had a mechanical area had an 87% survival compared to the peers who had a 94% survival Mechanical Wave ers put in the low risk of re operation. So this is primarily driven by death and not by not by re operation. So not as rosy as as we think. And this is analysis of young patients 52 16, 9 years old and the New York Registry and they found that they did not compare it. Thio normal agent sex match population in this study. But what is, I think? Important toe think about here is the influence of mechanical a VR on bleeding, um, in in young patients so you can see in the mechanical a VR group. At 15 years there is a 13% risk of major bleeding on. I think you know, we think about that. It's sobering Thio Thio Think about 15% immortality within 30 days of admission for major bleeding. That was the finding of this from the New York registry. So this is not cutting your finger and having to hold pressure for for 10 or 15 minutes. This is a major event that we need to think about. You know, these these low rate of events when we think about young patients who are having these valves for 20 or 30 years are important. There's been a move Thio more and more biological Avie, ours and young, younger patients on disses from the Cleveland Clinic. You know, analysis off several 1000 patients, 3 3000 patients with a tissue by prosthetic a VR. And you know, they say, Although older age was a risk factor for death, elderly patients had survival comparable to their age. Race and sex matched cohorts, as we found in the previous study, whereas younger patients had the worse than expected, survival was further diminished with the insertion of a small prosthesis. So there's a warning signal there that that you know this is far from curative on, but we are exposing patients to excess mortality. This is another study from the French registry of a V R, showing that very long term outcomes at the 25 years and initially doesn't look bad. This is this is actually a structural valid deterioration 50% at 17 years. That looks pretty good until you look at the survival curve on. Do you realize that you know 60% are dead at that time point, and so they're competing risk between structural valve deterioration and death. And so if you're dead, you can't be re operated infrastructural valve deterioration. So it's always important to look at these nuances and young patients. Really, it's not a very good option again. They looked at what they felt was the expected popular survival of a match population of French patients and in young patients who had age, age of surgery in the 50 to sixties, you can see there is a very large discrepancy between their observed and expected survival after tissue. A VR on this diminishes over time. So if you're having surgery in your 70 years seventies, you know that that that discrepancy is small. We all know this paper well from former Karez and Andrew Goldstone in the new England. And he they looked at, you know, 10,000 patients undergoing aortic called micro replacement with tissue and mechanical vows and their major finding was that mechanical valve seem toe producing enhanced survival that they did not compare it to an age and sex matched population. But I think it's it's actually sobering when you look at these results because this is simply death, which is, you know, hard end point. Um, not very good. 15 years. Either of these prosthesis air producing one and 4 to 1 and three patients between the ages of 45 54 55 64 who were dead. Um, at 15 years on, Do you know that that's not really good enough? Tavern in low risk patients has arrived. As we all know, the this is the updated outcomes of the partner. 32 year results in you know, Year one. There was a significant advantage of Taba for death and disabling stroke, and these curves look really the same for either of those things presented separately. But two years that Tava group has has done considerably worse. Where's the social group has done, um, has done better, but I've just spent the last 10 minutes telling you that surgically of your itself is not very good. So, um, you know, this is tavern is not a magic bullet in these patients. We have concerns about valve durability in Taveras, certainly in low risk patients for more active, we can see there is some evidence that there is an increase in valve radio between year one and two that we're not seeing in the surgical group that we have long term data on. So, you know, we just have toe worry about valve durability, and this is just a reminder of the average age of the patients in Partner. Three were in their seventies on DSO. You know, low risk does not equal low age on. Do you know this is not young patients that we're talking about here who are likely toe go through these valves even faster? This is just came out this week from again. Another former, uh, colleague at Penn. Um, doctor for a cow is now at Michigan, and he looked at the national STS outcomes of surgically ex planted tava vows, which may become more and more common if these vows, you know, implanted in younger and younger patients on go quite sobering results of patients who mortality of 13.9% for patients who underwent isolated surgical area after a tava on up to 23% for patients required concomitant procedures off the Taber. As you can see the rate off, you know, total cases of tab or ex plant um, is rising significantly. So a via on the young, I would argue, far from curative valve related mobility's occurs a significant rate, which is even more important in patients who have a long life expectancy. This excess mortality occurs in young patients up to the age of 16 will continue to rise. His life expectancy rises, limited your ability. So do living balance produce better outcomes. This is the original description of the Ross operation in 1967. It is, I'm sure he knows is it involves removal of the pulmonary valve on insertion in the aortic position. It was widely used and sort of fell out of favor and is undergoing a renaissance, as Dr Zito was mentioning. This is the late results of the pioneer Siris of Donald Ross. Is actual operations from the Royal Brompton in London. I'm not gonna go through the although my new shite, but I think this is an important slide. This is a valve that was removed 26 years after it was implanted for a good for regurgitation. And, um, what he says is that the tissue architectures well preserved, except for some fibrosis and thickening of the admin Tisha Nuclear President, all layers and in a separate stain, the proliferated market proliferating cell nuclear antigen was positive in the Maya fibroids, confirming viability so that the pulmonary autograph, when placed in the Arctic position, is a living valve with a full cohort off alot multi cellular components that we described in the beginning of this discussion. Andi e think that's worth mentioned. I could have shown you many other ex planted valves that have similar findings, but what we care about is really data. So let's move on to that. The general sentiment of that the Ross has not being very good. People describe it as a as a converting in one valve disease to a two valve disease has high complexity and higher than standard avian mortality on higher rates of re operation. Some of these things are true to a greater or lesser extent. And we're going to talk about these things and and really think about whether the more nuanced discussion is required. Um, when it comes to the Ross, this is Tyrone Davis. Analysis outcomes of 20 years of the Ross operation On what you can see again, the the curve up top is, um, age and sex matched population. Um, Canadian population on black is the outcomes off his his roster patients out for 20 years. And what you can see is the survival. And this is again just survival, not survival free from the operation, nothing else. Just survival, which is probably the most important thing, is absolutely equivalent between these two groups. Um, but it is. It's just a operation that's that's great in the hands of a few people. Well, this is analysis of the German Ross Registry, which consists of 16 centers Onda, about 25 heart surgeons and a total of almost 2000 patients. And again, what they found just survival is that survival was absolutely equivalent to a general population out to 15 onda longer years. This is an analysis, uh, in Children and young adults up to the age of 50 from the UK registry, and it compared in a propensity match way, um, by a prosthetic a VRS, which you can see event free Survival was pretty poor of 15 years compared to mechanical valves and then ultimately compared to the Ross operation, which outperformed both of those valve confidence. This is analysis of the Canadian Ross Registry again using propensity matching to compare patients undergoing mechanical a VR, which we think of as the standard in younger patients compared to the Ross operation on What you can see is that the freedom from cardiac involved related mortality was significantly higher, um, in the Ross Group than in the um in the mechanical of your group. P value was positive. Freedom from major bleeding and stroke was was also significantly higher. This is another analysis of mechanical A VR versus Ross in in, uh, Adults Andan analysis of almost 2000 patients in the Aviall Group on 400 patients in the Ross Group. Over time, this is from Peter Skeleton, Clinton's group in in Australia, and what he found was that again, the rock's had a survival advantage. After 20 years in match mechanical valve patients and I could show you a love these studies. But you know, at a glance, this is a low published Siri's over 3600 patients. Andi, here's the 15 year survival. 95% 90% 93.6%. And wherever you see two Asterix, that means that that survivors being compared to a match population of age and sex matched, uh, patients without able to disease. And it has been found to be equivalent. Well, you know, we hear the accusation that this is all just patient selection. Somehow, despite all the matching despite all the Siri's, despite all the different surgeons doing these operations, the some level off, off patient selection. And so um, there was a trial from our group in in the UK of the long term outcomes after the autograph, the Ross versus Hama graph root replacement, which at the time was a was the standard and also, you know, is the root for a root replacement. And so a fair comparison group. And, uh, you know, when we were thinking about patient selection, let's just look at who these patients were, their patients who you know up to the age of 60 10% of them almost were over 60. Andi. Almost 30% were over 50 thes patients had a high rate of endocarditis. Almost, uh, 8% had active. And the Politis in both groups on We're talking about patient selection. I think this is the most important thing. These patients were really quite sick. We're talking about patients who 30% of them had previous Hama graft operations. 12% of them had previous mechanical valves on 40% of them had a had a radio operator had a read operation as their Ross eso these air not patients that were destined for greatness. You know, these air fairly sick, non selected patients, I would argue. What did you find? Well, uh, in in black, you can see the match population of the UK Age and sex matched cohort of Ross off normal patients. On green is the Ross patients. And you can see that the Ross achieves a survival that is absolutely equivalent out to 12 years off. Uh, compared to the the home, a graph group which did significantly worse. But really, the Haman rock group is not the important comparison. I think The point here is that this is a randomized trial which you can't accuse too heavily of of severe patient selection. Given what we've seen about who the patients were, um, that were randomly assigned the Ross on, do you know they seem to do pretty well on? We've confirmed that finding of valve related off equivalent survival tone or normal population freedom from a root replacement significantly higher in the Ross Group compared to the home a graph route at 12 or 13 years? Um, which, you know, I, I believe, arises through the valves capacity for repair and regeneration giving its living structure. Um, and this is the song that that that that we presented on Val function in autographs for just looking at patients who reached 15 years or greater. Follow up on. What you can see is that red is severe. Ai Andi Purple is moderate ai and really out 12 to 15 years. The vast majority of patients are free from, you know, moderate or severe ai. And in terms of the valve, Grady INTs. One of the most impressive things about the Ross operation is its capacity for for producing ultra low of Al Gore agents that are durable, um in green. Here is the valve grades of Ross patients over 13 years, and as you can see, it's well below 10 and single digits versus the holograph group that you know undergoes structural valve deterioration. The other important benefits of Ross operation in young patients is it's human dynamic properties. This is a comparison between patients who had normal valves, normally aortic valves. That's the white circles, Ross operations in the closed circles squares or the stent lis by prosthetic valves, things like freestyles and hama. Graphs on these air are centered valves. So you know the values that we put in every every day, Uh, in the magnet valves and spirits, valves and other valves, although obviously in spirits files were not part of this particular trouble. In any case, extended tissue valves and what you see is a rest. You know, these Ross valves perform very well. They perform in a manner that is very similar to patients with completely normal. I'll take vows, but also, um, or impressive is that at exercise, they perform again in a very similar way, too normal, living chaotic, bounds on. And I think this is really important when we're thinking about young patients who have high demands of their quality of life, high demands for survival. This is just a video that was shared with me from my friend is melanomas. Use the Mount Sinai now. It was one of the world's great Ross Surgeon has a series of over 600. Here's trimming the Pommery autographed Uh, this is a new, important concept because I think it's on. The early failures that were observed in the Ross operation really were technical. So this is an aortic valve root complex, and what you can see is that there's a fibrous analyst that the aortic valve sits in in the Pommery side. This is not the case that the primary valve does not have a true fibrous Anya's inserts into muscle. And that is really important because what you have to do when you're doing a rocks is to insert it in a really deep down into the analysts and and make sure that it's supported by the old aortic annual ists. And you can see that, um, here I put this video plays yeah on so you can see that you know the stitches have to come out fairly deep in the l Vot Onda, right at the cusp insertion line in the primary autographed Andi that ensures that the valve is supported by the the, uh, old idiotic analysts. And the other important concept is the sutra lightning. The pulmonary autographed is used to pressures of 30 40 50 and is not used to pressures of, uh on the systemic side. And so it's important that the distal sexual is performed as close as possible to the commercial rural insertion line of the leaflets on DSO you trim the autographed after sowing s owning it in to just above the common shores, leaving enough space to connect that you can see that this operation has been combined where they on a sending aortic replacing you can see some Dacron that comes into view here on day. That's also an important concept that if these patients have aortic aneurysms or any element of disloyal to disease, that that should be fixed a swell. What about patients over 50? Well, this was analysis just looking at the Canadian West registry of patients, um, undergoing Ross survey who are less than 50 years old and over 50 years old, you can see that they really have equivalent outcomes, both based on re intervention on on survival. So, you know, we recently put this together myself, Doctor. Very indulgent humanity for nature of use and way believe that the biological living valve has these properties that are off benefit to younger patients. And I think what we have are basically to think about them on a spectrum of age and co mobility's on what their goals are. Are we really looking at younger patients who we should focus on these long term goals of survival durability, In which case the Ross really has something to offer that cannot be matched by what we have available and in older patients, we're focusing on short term objectives such as relief of symptoms, avoidance of surgeon rapid recovery and in that setting, you know, trance cast the valves surgical by a prosthetic valves on dso on can can produce a good result. So who is a good Ross? Can I think? Ideally, patients less than 65 probably a better way of saying that is patients with an anticipated life expectancy of greater than 15 years really patients with limited capabilities limited selected concomitant procedures are acceptable. Re operation is okay, but not ideal. A maximum of moderately reduced LV functioning. Doctor Jacoby always used to make the point that the best thing you can do for a sick LV is to give it the lowest Val Grady. Impossible. And you know, E didn't belabor the point. But a lot of those patients in the trial had diminished Shelby function. And so the Ross, you know, produces valuations in single digits that they're really cannot be matched by other valves. And so it's an especially attractive option and patients less than 60 who are active women who wish to have Children. People have a contra indication toe and take anti calculation on a small aortic root. Because the pulmonary and aortic roots are almost always identical in AI, they can be a little discrepancy, but in generally are fairly similar, and you, you know you produce zero patient processes. Mismatch with the with the Ross contraindications, you know, severe and the kuraitis very disruptive. Palmer aortic analysts and longstanding AI. It can be done, but it does require complemented procedures of annual stabilization, limited long term life expectancies, severely dysfunctional lvs, extensive car energies and mitral replacement on this again, you know, looking at the patient's specifically over 50 you know, we were found that there is not really a significant disadvantage. So we're now at a point where, you know, really, there's a call to action from around the world is a risk and avoiding risk for younger patients or the values is by opting for a operation that seems safer, you know, Are we Are we really exposing our patients to a longer term risk of death that comes from a sub optimal valve conduct under use of the Ross operation? A lost opportunity Autologous is the best from Hans Evers in Germany and really, you know, I think everybody would pay attention to what? Dr David? As the saying, he put it very, uh, forthright. Lien said the Ross operation is the best operation to treat aortic stenosis and younger middle age adults. And I have to say that I share that view and you know, this is the start of the rocks program. Is Mohammed Aziz experience in Montreal before he moved on? You know, he was doing very, very few of these in 29 2010. I think he did actually a three in In in the group that has the arrow and over time, you know, I think with Aziz. His group of cardiologists, Andi referring physician, saw the really exceptional outcomes with long term freedom from complications. And, uh, and you know, these exceptionally low Val grade in the program has really grown on. Now he's actually out to almost 500 patients in his Ross Siri's. So again, I think we have to think about patients on a spectrum of age and comb abilities. Younger patients with physical abilities who have a longer life expectancy, high physical performance and human dynamic demands. They experience a higher rate of structural valid deterioration on. They have a longer exposure to valve related complications on more bicuspid valves. These patients, both in they all began mitral positions. They require long term valve your ability, which is excellent. They require normalized or near normalized human now performance. They require excellent quality of life, and we should be aiming to normalize long term survival on for these patients. We really must opt for a reconstructive biological approach consisting the aortic valve repair when possible, there are operation when that is not possible on micro repair wherever possible. Onda We have to accept that there are some trade offs and some upfront, measurable mortality, which is really limited. I could have showed you many Siri's that compare Ross 30 day mortality compared to a VR mortality and match patients. And it's very equivalent, UM, does require, perhaps travel to a center of excellence like pen a recovery period and follow up for older patients with a high burden mortality of capabilities. They have a shorter life expectancy. They have limited human Amick demands. They have a lower rate of structural value, degeneration and higher burden of capabilities. These patients is appropriate to focus on short term goals, relief from symptoms, avoiding tsunami and ONDA a rapid recovery. And for these transcript, the therapies are gonna be really important. But we do have to accept the trade offs of that unknown durability. Higher parabolic hired patient, uh, hire permanent pacemaker implantation on unstable post op radiance perhaps, and in the middle there is a population who benefit from prosthetic heart valves. But really, I hope to have shown you that that that there is a survival advantage from from that. And these patients, of course, exist on a spectrum. So we we, you know, lucky to be in the really reference center for valve surgery. I think our aim together is is to have an informed patient on. You know, we have incredible cardiologist leading translate. The therapies such as Dr Chang and others way have the latest and best money. Invasive options. Robotic and port access might draw appear on so on. We have access the latest trans catheter trials. We have incredible Codec anesthesia with which is incredibly adept and comfortable with advanced imaging on hopefully we have surgeons with advanced reconstructive valve Syrian just to give a little insight. I've been lucky to benefit from this opportunity for advanced reconstructive valve traveling fellowship focusing aortic valve repair with Doctor A very Dr Zito and Doctor decide for several months on advanced micro repair from Dr Hargrove, one of the world's truly master micro surgeons. I'm only invasive, uh, cardiac surgeons as well, and also some time with Rob Smith in Texas working on trans catheter therapy and some dedicated time with Doctor Humam Z, whose work you've seen throughout this presentation on the rescue operation and so just thio end up, finish up. I I want to emphasize the mitral Aortic valves have complex functions, and these functions that are derived from a highly sophisticated living structure and treatment modalities that we use must respect that sophistication wherever possible, because this appears to drive improved clinical outcomes. And our aim together should be a collaborative heart team approach which matches patient goals determined by their age and capabilities, with all available options in the setting of truly informed patient consent. So with that, I thank you very much for your attention, and I look forward to a robust discussion. Mike, that was fantastic. Very much enjoy that. I think we have some questions from the audience. I'll start, Um, I comment and a question. I would agree with you, I think, um, a Zai. I've learned from my cardiology colleagues over my career. Uh, it's about patient selection in finding the right procedure, whether it's open or trans catheter for the right patient. I don't think there's one perfect procedure fit that fits every patient, and I think your talk really, um, make a very strong point for that. So I'm glad you were able to be that important nuance in such early part of your career. My question. Um, you talked a lot about the Ross procedure three. I think the data is certainly becoming more and more supportive, even though it had a very negative perception, You know, during my error training. And it comes from a couple of things, obviously askew striked on. Um, but I have a question on baby, You can comment on this. You talked a lot about the autograph. What about the home? A graph that is implanted implementing position. Um, the perception is that that is the Achilles heel number one, number two. If indeed that is true. Which I don't think so. Um, with trans catheter therapy now for the right side of heart, do you think there is data? And also, do you think perception will change regarding that particular I would say criticism to be fair of the Ross procedure. Not the autograph, but the home. A graph in the harmonic position. Yeah, That's an excellent question. I think part of the early work to do with the sizing Onda. What we've learned from all the Siri's is that you must oversize the pulmonary Hama graft as much as possible. The other thing is that they oughta. Comma graphs were used in the permanent position, which we know do not survive. Well on now we've realized the importance of using pulmonary Hama graphs in that position. Peter's Killington just published his specific outcomes of primary autographed in the annals a few months ago, and over 20 years his survival, his freedom from the operation of Harmony Side was 85 to 90%. Um, and so I think, with the correct approach, it's actually not that big a problem. Of course, the primary side is exposed to much less him Islamic strain. But as you rightly points out, we now have valve conduits that are trans catheter that can be used on the primary side on those air. Absolutely, you know, appropriate to use for a low pressure system like the primary system in a patient who is 15 or 20 years out from the Ross and his and is suffering from Paul Marie degeneration. Okay, Thank you. And I have a couple of questions here. I want to try to get to all of them. Um, I'm I'm reading a chat from Dr Williams. Um, could you comment on the database results of the Ross operation in need for volume to build a center of excellence? Yeah, this is an important point. You know, I think that there are two. There are 2 to 3 really important things when you're thinking about Ross Program. One is that it has to exist within the context of a complex aortic root program that is comfortable with stainless tissue routes that does stainless tissue routes frequently, like we do with free styling, holograph valves. The second thing is that you know, you do need, I think, advanced training to do this and specialist training like I am getting the doctor. Hm. Um Z with the rial Ross expert, you know, supported what with that. And the third thing is, I do think, you know, although the first few years will obviously be a matter of cultivating this, you know, ultimately, you know, I think it needs to be done within the context of a sentence tissue program at least 15 to 20 a year. I would say it's probably a reasonable number, including stent list. Issue out. Not my opinion. That's the opinion of people like Dr Yeah, Cuban Doctor Alhamzi. Who do you think? I mean, it's ultimate. It's a valve. Replacement is not a complex valve repair, its ultimate valve replacement. And so sitting within the context of a, um, of a senseless tissue experience, I think it's very reasonable to do it. Agree, Um, question from Dr Steve Weiss. Um, how do you think a Ross in a 50 year old patient? Well, compared to biologic a VR in the valve and valve TVR air. I know you talked a little bit about that, but can you expand on that question? Yeah, I think that's really excellent question. And I think if that try a lot of trouble being done today, we would be comparing the Ross to A to A by prosthetic valve. The criticism then would be that you're doing a route compared to a a v. R. So that's why I think the root to root comparison waas was good. Um, and you know, I think to get answer this question for me, you know, I think there is compelling evidence that that putting a biological valve in a 50 year old patient has a survival disadvantage on bond. Um, that is the bottom line and and really, that the Ross is the only operation for your exterminators that has achieved equivalent survival to a normal population. And so I would expect that it would outperform that in the match analysis that I showed you from the UK It did outperform both biological and mechanical A VR. Um, but, you know, we don't with this is all that data. We don't have that specific data point in a randomized trial, but all the data suggests that it would be superior. The valve valve data, I think has not matured yet. And we don't know. We're really When we're talking about this long exposure to evaporate complications and 50 year olds, we have to be cautious. Next question is from Dr Rich Wise. Um, what is that? I think he means what? What is the typical pump run for Ross procedure? Yeah, Well, how long is the operation? Yeah, it is obviously longer than a stand in the Dave er, that is for sure. Um, the the typical pump run is about two hours. I would say in general, Whereas you would say that probably in a VR is about an hour. Um, to give you some real life context, you know, I mhm Esma will do two or three of these in a day and he'll be done, you know, at 66 o'clock, isn't it? Is not, you know, a a very complex. It is a slightly more complex operation. And but I really would not put it any more than that. And a question from anonymous attendee I apologize. I can't tell who asked that question. But the question is a good one. Should we be doing a Ross procedure for young patients needing a thoracic aortic repair and a VR you had showed a video demonstrating that Yeah, that is an excellent question, Theo. Answer is absolutely yes. This has been published separately again. If the limits of time. I didn't show you that data, but it's actually incredibly important that you have Ah, you know, inappropriate and low threshold for replacing descending aorta if it is delayed because what? That's one of the things that was learned from the early failures. People being reluctant to replace to replace the A Sunday Also, when you know when it when it is abnormally enlarged. Great. I think we're coming up on the hour. We have one more question here from me and Javi. Thank you. A great question here. I'll read it to you, Mike. When the pulmonary valve is exposed to room air during surgery, do cells die prior to re implantation? I think he's alluding to Does the autograph somehow, you know, sustaining the scheme IQ, um, injury during the harvesting. Yeah, it's a good question. You know, that the autographed undergoes absolutely no preservation. It's removed, it's trimmed and it's immediately implanted. Um, the only evidence that I have on it's all about data. Is that the long term results? As I showed you that that slide of a patient from a valve 26 years old with complete viability in all layers of the valve. So the evidence is No, it doesn't. I mean, maybe undergo some insult or something, but certainly seems to produce a living valve. And I think, um, the clinical results, to my mind, speak to the durability of that. That living vow now on that note talking about the autograph, Um, is there a subset of patients, Uh, in this alludes to preoperative evaluation. Um, is there a subset of patients where you know, prior to surgery. Hopefully that the autograph. It's not the appropriate anatomical criteria for re implantation. Meaning the harmonic valve doesn't fit the aortic Angeles. What is the preoperative evaluation? Is it a C T. Is it a t e? What does the surgeon have toe look for before he commits to a Ross and then realizes that he can't do it? Yeah, this is an incredibly important question. And it's one of the nuances of the Ross. You know, I think if you have a longstanding ai, uh, the pulmonary valve is generally smaller than the aortic analysts. And so you can do a Ross, and this has been published again, presented for limits of time. But you must also then support the aortic annuals. Um, uh, if it is very dilated, which I would say it's more than five millimeters discrepancy. I would not do a Ross in that situation on that is from C T or T measurement e eso all your patients will get So for my for all cardiology colleagues here, um, we don't typically obviously performed t e and someone with aortic stenosis. Eso eso their consideration for Ross you would recommend a transit service to echo for someone with aortic stenosis. Well, it could be done in the but generally is now has done it in the oh, you take the patient to the O. R. And you say my I'm trying to do a Ross and I will measure your primary valve and compare it to the aortic valve. If it is equivalent, we will do a Ross. If not, we will do whatever else is the second option. Um, but yeah, the other other cohort of patients, which is very important radiation because we know that that radiation does damage the primary autographed on dso. That is a you know, it. There are some published reports by except welcome. But really, I would be wary of that. We have a question from Dr Reardon. Uh, colleague bars from mercy fits. Good question. Um, Mike Status post a Ross procedure. Does diploma Neri route ever dilate in the aortic position? Especially in the subset with a baseline or underlying aortic aneurysm? Yeah, So a very good question. Um, it does in some situations. And so two things to say. First of all, it's all technical if you implant the valve in the chaotic analyst in the proper way, the risk of debilitation is far diminished. Um, the second thing is you must, as I said, support the analysts. If there are significant AI and preoperative debilitation of the animals, and you must have a low threshold to replace the also if there's an indication to replace it, which adds very little time. Uh, the other thing is that although there is evidence of probably autograph dilation, some Siri's, um, this generally has not been associated with clinical problems, so dilates in a slightly different way. It's almost a remodeling than than than a true aortic dilation. It doesn't generally result in a I. It does not generally result in dissection risk on so on and so forth. So it's a little bit different. But in general, if you do a good operation, you should have durable freedom from from civilization. Well, fantastic. I think that's all the questions. Thank you for everyone's engagement. We're right at the hour. Mike, that was fantastic. I think this is a great beginning to a fantastic career. I'm excited that you will be joining us. I'm really looking forward to July 2021 for many reasons. Um, And to the group. Just one other housekeeping again to everybody I think you've seen in the chat. Um, the event code for this event is 66873 Um, and you can see here Mike's email and cell phone. I'm sure he would be happy to speak with anybody further if there are any other questions, either by email or phone. Absolutely. Thank you, everybody. Everyone have a good day. Thank you for joining us. Thank you. Thanks. So, yeah.