Dr. Paul Grayburn of Baylor Heart and Vascular Institute presents at Penn Cardiology’s Grand Rounds. He elaborates on the concept and research surrounding disproportionate mitral regurgitation.
Related Links: Twitter @PennMDForum Deconstructing the Mitral Valve - Penn Medicine Incorporating SGLT2 Inhibitors into Heart Failure Management Treatment for Inherited Cardiac Disease - Podcast with Drs. Sharlene Day and Anjali Tiku
Yeah, yeah, yeah! Mhm. All right. Good morning, folks. I'll give everyone another minute here, um, to log in. In the meantime, the CMI code for today is 70670 And we'll be sure to place that in the chat box as well. And I'll read it at the end of the talk again. All right, why don't we get started here? It's my great pleasure and honor to introduce Dr Paul Gray burn today for our pen cardiology grand rounds. Dr. Grey Burn graduated from Texas A and M University. Then he went on to UT Texas School of Medicine and then to the University of Kentucky, where he did his cardiology training. Dr. Grey Burn has been his offered contributions in so many different areas of cardiology that we're truly indebted to him. Early in his career, he was very involved with the Timmy trials. After that, he was involved with contrast echocardiography the stitch trial and then more recently, with valvular heart disease. Paul was an interventional cardiologist and they just learned, uh, stopped working in the cath lab, but is still involved with TV and image guidance for valvular heart disease and his contributions. The mitral try custody. Aortic valve disease are second to none. And anybody in the field of cardiology. So we truly are all indebted to him. I'm very excited to have him speak to us today about the concept of disproportionate mitral regurgitation. This is something we've been hearing a lot more about, and always one of the the pioneers and leaders in this field. So with that, I'm going to turn it over to Paul one more time. The CMI code today is 706 70 And as a quick plug in, we are trying to focus the next month here on mitral valve disease. And so there will be some additional evening sessions. Um, that are mitral valve team is going to be putting on. And this is going to deal with degenerative mitral regurgitation, functional mitral regurgitation, and in some cases, so Linda Lafferty and the mitral valve team will be in touch, and they will forward and invite for some of these evening sessions as we try to dive deeper into the mitral valve. With that, I think Paul, we welcome you virtually. I have to give Paul a lot of credit. He's braved the ice storms and freezing temperatures. Loss of power down in Texas. I was worried that we may not be able to pull this off, but truly impressed with possibility to, um to find not only electricity, but also Internet access and be able to join us here. So we we truly do appreciate the effort that you took Welcome virtually to Penn cardiology grand rounds, and I will turn over the computer to you now. All right, get my screen up here. All right. Thank you. Samira. I sure appreciate that. I kind of lucked out. My daughter lives next to a fire station, and they So she's on a portion of the grid where they they keep the electricity running. So, um, let me just see if I can get this slide show up. We're gonna talk about this idea of this concept of disproportionate FMR today, and I was glad to see on your slide uh, there, Samir, that you're you also use the term FMR. I like that term. I'll show you why in a minute. These are my disclosures. Most of these are related to structural hard interventional programs with various companies. Uh, what's in a name. There are tons of things that we call mitral regurgitation. Primary, secondary, organic. You know, you've heard all of these names. I personally hate the term secondary. Um, are And the reason is that all of them are is secondary to something. So it seems to me silly that m are secondary to a flail leaflet is primary and that m are secondary to a tethered leaflet is secondary that, um, are secondary to acute papillary rupture in a, uh in an inferior M. I is the primary cause of him a dynamic collapse. But we call that secondary m r. So I'm going to use the term functional today. As it looks like you guys use, uh, there at Penn. What do we know about functional M R? Well, it's classically a disease of the left ventricle, and that's what we're going to talk about today. But you at Penn introduced the world to the concept of atrial functional m r. And we've learned a lot more about that. We know FMR is associated with LV remodeling, heart failure and death. We know that therapy that improves they'll be function can improve fmr. We've seen that with medical therapy, CRT and revascularization in select cases. So our ability is to predict which patients will, will or will not improve is not very good. And so, uh, for years there was no evidence that surgery improved outcomes. Part of the reason for that is there's never been a trial of randomized trial of surgery against medical therapy with enough power to look at things like mortality. And then we know more recently that micro clip, improved outcome and Coop, but not far. And that last bullet point is the focus of today's talk. So these two trials came out. You have one very, very positive one very, very negative. And it really set the world, uh, kind of on its year back in 2018. And so at that time, many experts were calling for a third tiebreaker trial. And it turns out that if that had been the response to the medical community, we would not have approval of Micro Clip today for FMR. So what was needed back then was some kind of rational explanation of these trial differences, and the way this actually happened is I was talking to my colleague and friend Milton Packer and I said Milton, you were not involved with either of these. You need to, You know, you're an expert in heart failure trials. Why don't you explain this and write a paper? And he said, Well, I won't do it unless you're unless you write it with me. Since you're you know Mm, our experts. So we put this paper together and we were kind of thinking about all these different things that Mitra fr had larger lvs compared to co apt. You can see the numbers there. They had less, um, are severe. M. R was defined by the EU criteria. They did not require integration of multiple parameters, whereas in co apt, everybody had had an integrated approach. You've seen this tiered algorithm that was done in co apt where everybody was felt to have three or four plus m r Importantly, micro fr did not exclude severe RV dysfunction tr pulmonary hypertension, whereas coop did. And then in my tree, fr you could get into the trial before your medical therapy was optimized. So that could be that could be done along the way. And in co apt. You had to have failed optimization of medical therapy. So these are very different patient populations here. And so we wrote this editorial to kind of conceptualize that and Greg Stone and I presented this to the FDA in very great detail. We were there for a long time and convince them that they should approve this device and functional M r for patients who had a co apt, like profile or would have been eligible for the coop trial. And so when we did this, we we did put a plot of er away. We also did one of regurgitate volume. But I'm just showing er oa here against in diastolic volume with with a very important point. And that is that this plot is derived from the Gorlin equation from for patients with an E f of 30% and a regurgitate fraction of 50%. Why those numbers? Well, co AP, the EF was 31 my true fr it was 33. So in terms of group data for two trials, the ES were about 30% in both, and everybody agrees and has long agreed in the guidelines that are regurgitate fraction of 50% represents severe, um are certainly possible that an FMR a lower regurgitate fraction represents severe. Um, are But this is very specific and everybody agrees with it. And so what we're showing here is the smaller ventricles and larger degrees of M R and Co apt as reported, you know, put them in this what we call disproportionately severe m r. Whereas Mitra fr is over here and the difference here is that in this sort of orange area here, M R dominates the picture. If you fix the m r, the patients likely to get better, whereas if you're down here, you don't have severe, um, are the LV dominates the picture, and in the middle you have sort of a co dominant picture, which we termed proportionately severe. Um, are now, while this explains the trial differences, there are many issues that remain. Uh, and one of that is I'm going to show you this is that the slope of the e r o L ve TV relationship varies with a lot of different variables. Uh, and it's therefore hard to apply this to individual individual patients. It applies pretty well to these two trials because, you know, the group differences average out all these individual differences. And there are other trial differences, some of which I've shown you like the RV dysfunction that may be important and then measured values of er, oo and l ve TV that we do typically in an echo lab. But we can do it with CMR other techniques. Cat. They're not the same as theoretical values. So the values that I'm showing you our theoretical or ideal values derived from the Gorlin equation, with the assumption then that these are the accurate and perfectly measured values. And we know that's not true with things that we do clinically. And it's certainly also possible that rig urgent volume or regurgitate fraction, if accurate, would be a better parameter than er o a. We don't really know that, but again, FMR is a disease of the left ventricle. You have normal here on the left and on the right. You have this, you know, dilated ventricle. Where the this wall is pushed out. It displaces the papillary muscle, a prickly and outwardly and one gets a mitral regurgitation. You don't get my little laser pointer up there, that's better. And so this is a slider that I put together for brunch walls textbook on valve disease A while back, these are actually core lab images from a study to we did with cardio band and over on the far right. You have an EF of 60 in diastolic volume of 1 40. Not that dilated in normal global strain. Uh, this is a patient that has functional m. R. Was treated with cardio band on the far left. You have a very large globular ventricle. You know, this virus city index is abnormal. E f is 22 in diastolic volume 3 10 and strained minus seven. And I would argue that this patient in our correction is going to still leave them with a very bad ventricle. Hi, Wall stress. One should at least consider l VAD transplant plant, maybe even hospice care. If you fix the m r in this patient, they're still going to have a terrible ventricle. Whereas on the right, even though this is functional m r, it behaves like primary m R in that the heart failure is unlikely due to LV dysfunction and correction of the m R is going to leave this person with the ventricle. It'll be nearly normal this is an example of what we call disproportionate M. R. That from a patient about a month ago that we saw. And if you look at this CMR image, you can see that the septum anterior wall and the you know most of the apex and the rest of the heart looked pretty normal. The shape of the ventricle is normal, but there's this a kinetic segment at the posterior base here that's tethering the posterior leaflet and causing M. R. This is again a patient where the LV geometry is preserved. The EF is preserved. The poster relief that is tethered by this little infra basil aneurysm and medical therapy isn't going to make this better. So this is a patient that has functional M R. But really, M R is the issue. Uh, now there's a problem with this philosophy that we put forward, and we recognize this, and that is one might look at this concept of proportionality and think that the bigger the LV gets, the more the M R. That is the larger the LV, the more M R you get. That's actually not true because we all have seen patients with 400 cc lvs and heart failure clinic that don't have any, um, are at all. So So There are many reasons for that. So just because the L V gets big doesn't mean you get em, are you? May not. There may be a balanced reduction of closing forces and increased tethering forces. There is natural variation in the length and area of mitral leaflets. Bob Levin has shown that anterior leaflet augments in sheep models and in humans with functional M R. So that if the leaflet gets bigger over time, it can compensate for the L V and annular dilation and result in less m r or no m r at all. Uh, and in fact, he has a very nice paper showing this in core bovine um, due to chronic A A are where the ventricles are huge and there's rarely any EMR. It's because the anterior leaflet augments over time him on dynamics volume, status, dynamic in Mark and I'll play a role. And then, of course, you can have a focal wall motion abnormality like I just showed you and that CMR where there's severe tethering and severe m. R. So the guidelines have had these sort of different definitions, which creates a lot of angst among people. This is the American guidelines here where the ER over a is 0.4 reversion of volume 60 regurgitate Fraction 50 and then the European guidelines for functional M R E R O of 0.2 centimeters squared and regurgitate volume of 30 MLS and these are different now in the European guidelines. This is based on the fact that these numbers shown here in red are associated with an adverse prognosis. Now I'm going to get to that in a minute because it's very important. But where do these numbers come from? Well, it comes from an old paper from the Mayo Clinic from 1997 and I was a review of this paper, and it had a lot of weaknesses. But what they basically did is they compared to Echo, er oh, and regurgitate volume against an geographic grade. Using you know, in Rick Nishimura is lab high quality by playing sini angiograms. You know, that's what they did. And when you look at this, the statisticians came up with these numbers. The best separation of an geographic grade was at an e. R. O of 40 uh, 30 and 20 and a resurgent volume of 60 45 30. But when you look at the data, you see tremendous overlap here, just absolutely tremendous overlap so that there are patients here. You have an geographic four plus m r. But havi roos less than 40. And conversely, you know, you know, there are patients, uh, you know, and not many, but a few that have large bros despite less and geographic m r. Unfortunately, this data which I think is at the time, was the first validation of eco er oh is not great. And yet it's made its way into the guidelines, and we'll come back to that a little bit. But let's think for a minute of two different lvs, both of whom have this European number 20.2 for e. R O A. And regurgitate volume of 30. So by European standards or by the micro fr trial, these this would be severe. FMR Patient one has an in diastolic volume of 1 50 an EF of 40. That's a total stroke volume of 60 so notice they couldn't possibly have a rig. Urgent volume of 60. That would be all of their cardiac output going backwards if they if they have a resurgent volume of 30. Their forward stroke volume is 30 which is low, and the rig urgent Infraction is 50%. It's easy to say this person has severe uh, FMR, and this person would be kind of typical, if you will, somebody in co app. Over here you have an in diastolic volume of 400 e. F A 30. That's a total stroke volume of 1 20 forward stroke volume of 90 and regurgitate fraction of 25 in Europe. This would be severe FMR, and this patient would be entered into my true fr. But we would probably look at that patient at Plano, where I work, or U Penn where you guys are and say that's not severe and more so. There's some real issues here about grading, Um, are and let's talk a little bit about some of this concept. So on a sunny know who's you know, been my fellow for a while and is now on her own, published this meta analysis literally 53 studies and 46,000 patients looking at prognosis of FMR, and so I go back to my sixth grade math class and say, if a equals B and B equals C, then a equals C. So let's apply that to secondary. Um, are if mild m r equals a poor prognosis. And this is what the European guidelines say, what many people here say and it does So here's from that meta analysis. 41% Odds ratio 141 Increase in mortality If you have mild FMR compared to know FMR and poor prognosis equals severe FMR again, the guidelines say that then that means mild, um are equal severe m r. And I think all of us would say No, that's that's ridiculous. So the problem is this idea that a poor prognosis equals severe Amar is a false idea, and we've known this in medicine for many, many years, And that that is that an association in this case, the Association of FMR and Prognosis does not mean causation, and it does not mean treatment, and there are many trials that have looked at this back in the day when when I was a fellow and a resident, six PVCs in our post him I on a Holter monitor increased your mortality and people were aggressively treating PVCs. We did the cast trial and show that didn't work. The treatment increased mortality. Same for the promised trial, oral mill reknown and heart failure. It increased mortality even though it made patients have better thermodynamics. Anna Swan Ganz catheter. Same with classic. One on another oral, uh, China Tropic Agent. Same with Tor SEPTA crib and LDL HDL cholesterol. And I would argue that micro fr is an important trial because it tested the hypothesis that these lower values that are prognostic Lee important, um, you know, needed to be treated, and they found that they do not. So I think there are lots and lots of trials, almost five of them here. There are dozens and dozens of them that show that just because there's an association with prognosis doesn't mean that treatment changes that prognosis. All right, so let's go back then and say that the guideline definition is just too simplistic, as our guidelines would say, regardless of diet in diastolic volume and er oh of 0.2 or less as miles and point in the 0.0.3 range is moderate and above 0.4 is severe, and that is really not the case. As you see the white line here, the regurgitate volume goes up with the R O depending on your end diastolic volume. So that brings up the point. Why, to quantitative measures of em are severity not include LV size and function when LV size and function are the main driver of functional m R. So if you look at the Gorlin equation, they garlands. Both started with area equals flow divided by velocity, uh, in echo or by the Gorlin equation in the cath lab. That basically means the E. R. O is equal to the resurgent volume divided by the velocity time integral. And we measure that with Doppler in the Echo lab and in the cath lab, with the square root of the mean pressure gradient a constant and the time over which flow occurs. But basically because regurgitate volume is the end diastolic volume times the F times really urgent Infraction E. R. O is actually dependent on the size and function of the ventricle that are given our F and VT, and that's where we really came up with. This concept is from that simple equation you know, published this back in 2014 before CO apt and and before my true fr Just really trying to point out that a given value for er o or regurgitate fraction depends on the size and function of the L V. And again, we wrote this in this recent paper. I've shown you this slide already, but just to point out again that there is this relationship. But unfortunately that relationship depends on a lot of things. So if you look at it here we take this patient. They have an e r o point to an L V end diastolic volume of 1 40 they fall in this range. This green area here, where the EF is 30 r f is 50% so that would be severe m R. Even though the Eero is only 0.2, here's another one falls in the same range. The fs 30 RFs 50 er oh is 0.3 and in diastolic volume here is about to 20 that is typical of most of the big heart failure clinical trials. This patient who falls over here either has an r f that's way below 50 or an L V E f way below 30. The LV is the dominant lesion. This is not severe M. R. Even though the hero is 0.2 and this patient there are the rig. Urgent fraction is way above 50 and or the EF way above 30. And this patient M R is the dominant lesion. So these slopes vary. And I just showed this very quickly to show you that the slope of this curve varies with the F Here's 2030 40 and 50. And, um, and and that's at a rig. Urgent fraction of 50. And if you have a rig, urgent fraction of 50 and you plot regurgitate volume again. It varies with the F, so every individual patient falls on a different line or a different slope, so you can't use the slope we published to pick out individual patients. People are trying to do that in the literature, and I want to just point out why you can't do that. Nevertheless, there is some evidence from group data that this works. Milton Packer put this together. Different trials the two in Red Sea TSN trial here and Mitra fr were negative and they fall kind of on the lower end of this curve where the more positive trials co apt beta blockers, mitral valve replacement and acorn and the CRT trials fall above it. So there is some evidence supporting this. Uh, this is Joanne Linden Fells subgroup of CO Apt. Where the group on the right are more my tra fr like that is they have a I mean sorry. The group on the left is more micro fr they have a er oh, less than 0.3 and a larger integral. And there was no difference in the outcome in those patients. This is combined hospitalization and heart of heart failure and mortality. But the other patients had a big difference. So there is some evidence supporting this. This is a paper from Bartko in Vienna looking at medically treated patients. The ones with disproportionate mar have the worst prognosis treated medically. There are also some studies that are coming out now that don't support this as well. And these come largely from my tree clip retrospective registries. And so here is co ap Dmytro fr And what you have is my true fr is here where blue is medical therapy. And I'm sorry. Blue is my true clip and gold is medical therapy, and then over here is co apt. Well, there's a big European trial call you, um Euro SMR. Your house lighters is published. That falls. It's only my triplet. There's no medical arm, but it falls right here, right next to co opt. It's almost identical to co app, and when they broke out subgroups into turtles, it didn't really matter what turtle you were in. The mortality at two years was the same. So they they conclude that the E r o L ve TV ratio doesn't really matter. And, uh, and certainly when you break out the coop subgroups, they also fall along. This and there are some other trials that are coming out not yet published, that follow the same line, so there's no difference in mortality with my tree clip. According to the e r O L VE TV ratio. You can interpret that, if you will, as being evidence that it's a useless ratio. However, if you take the medical therapy arms, they fall along a very different curve, and so it actually does support the ratio, which is that if you're down here in the metro fr like patients with huge ventricles and not much. Um, our medical therapy and mitral clip are sort of similar, whereas the further you get up here with smaller ventricles are more M R. Medical therapy is a terrible option and has a very high mortality. So there is a difference. So again, this kind of highlights the idea that trial can be positive or negative, depending on which patients you decide to put in it. Bill Gash has done a similar thing. Reviewing the literature and showing that in primary m R, that's the open circles. There's a high risk, urgent volume to end diastolic volume ratio, typically around 0.3. But in functional M R, it's typically 0.1 point 15 meaning that there's not that much regurgitation relative to the size of the L. V. So all of these foregoing slides to talk about this in theory are based on assumed values are basically garland values measured values are often incorrect, and measurement errors further complicate the situation that I've already kind of explained, Kelvin said. If you can't measure it, your knowledge is of a meager and unsatisfactory kind. It may be the beginning of knowledge, but you have scarcely advanced to the state of science, Whatever the matter, maybe including micro regurgitation. So we know this is a meta analysis that two D echo dramatically underestimates LV volumes compared to CMR. And really, if you look at this little red not down here at the bottom, it underestimates by more than 40 ccs. That's a lot. And, uh, and so it underestimates LV in diastolic volume and LV in systolic volume. But those under estimations are balanced so that the EF comes out roughly the same, but with a wide confidence interval. Uh, and so Pisa is the same way. This is a paper, Davidson wrote back in 1988 Pisa, the Leaning Tower. You know, it's hard to see the orifice. Any error in the Radius is squared. It's not always a hemisphere you have to angle correct which nobody ever does. It has constraining wall effects, and very importantly, it only measures a single frame insistently. So here's just an example of radius squared. This is the same picture measured twice by my one of my sin Agua furs. They just measured it here and got a radius of seven millimeters in here. Eight and the differences, uh, you know, really large and, er oh 8.16 versus 0.26 Original volume of 30 versus 42. So tiny measurement errors make a big, big difference. The other thing important there is that you can stick a number two pencil in an orifice that's 20.38 Or, let's say, 0.4 so severe. M. R is a hole that a number two pencil goes in and mild M. R is a whole that an oral thermometer goes in. So we're trying to tell the difference between these holes and say, That's the difference between severe and mild m. R. I actually think that's ludicrous. So the other thing that's really important is this by physical marching. Judy Hung at Mass. General first reported this in 1998 in a jack paper, and this is commonly seen in the Echo lab. So in early sisterly, there's a huge Pisa right here, a big Imar jet and in mid sisterly it's almost gone. And then it comes back a little bit in late, sisterly. And on CW Doppler, you see a signal here the thing goes away and mid system early and comes back in late. Sisterly. The Ecotech has traced this like this. They made it up because there's no m r right here. But that's the way they trace it, because that's the way it's supposed to look. Um, it turns out by physical Mars really common. And if you go back and read garlands 1952 paper about using his formula to calculate mitral regurgitation, it says the formula only works if there is a fixed orifice, as in rheumatic mitral regurgitation, the orifice is not fixed in functional M r. As shown here and really even in ordinary, functional M r with the whole systolic jet, the orifice is not fixed. We measure the largest Pisa at any point of time. Garland is measuring the whole orifice over the entire duration of flow. Big difference. So I'm gonna conclude so we can have some discussion. FMR is a disease of the L V. Do not forget the LV and quantitative and evaluating the patient treat the LV dysfunction first, with appropriate titillation of medicines known to improve survival and Hef ref. And as you saw from the Champ HF trial a couple of years ago, only 1% of Americans with FR fr treated with appropriate doses of these medications. Consider MV mitral valve intervention when severe, um are persists after appropriate medical therapy, which should be considered to include c R T M P C I. These are the co op like patients in patients in whom M. R is disproportionately severe relative to LV dilation, maybe the ones that derive the greatest benefit of mitral valve intervention in terms of reduced mortality and heart failure. Hospitalization. I would say, though, that evidence is accumulating that they may have symptomatic benefit. Thank you very much. Alright, Paul. Thank you. Fantastic talk. Um, let me I'll let you have your screen back. Perfect. Thank you. All right, let's start with some questions and I have a few here that I'll start with. In the meantime, if anyone has any questions comments, please feel free to leave it in the chat box or in the Q and A tabs. And before we get started one last time. The CMI code for today is 70670 Alright, Paul, I'm gonna start with one question here, and it has to do with patient selection cause you stress. That's really a key in determining who benefits from therapy. Can you talk a little bit about trying to identify the right patient, either By caf, LV, Graham Echo MRI. You showed images of all three modalities. And what's your approach to determining which patients derive the greatest benefit? I think that echo still remains kind of the screening tool for finding these patients. And I think oftentimes it is good enough to tell you that this is clearly mild m r. This is clearly severe. Um, are But there's a big gray zone there where you're not sure. And this we see this all the time in our mitral valve clinic where you know this is this may be moderate or it may be severe. Let's get further information. We'll often, you know, do a right and left heart, Cath with quantitative in, uh, including a ventricular graham. As old fashioned as that is, uh, and we'll often get a CMR uh, as we're moving more toward trans catheter. Mitral valve replacements were using, you know, M D. C. T to measure LV volumes. And and that helps us as well. So there there still is a grey zone. But I think Echo still plays the dominant role in picking these these patients out, and I didn't really go into this. But there are also, of course, clinical factors that come into play just like they do in Taber Clinic, where if you see somebody with advanced Alzheimer's disease or you know some other severe medical condition that limits their their long term outlook, that may tell you that it's not worth pursuing an intervention on those patients. Do you feel that three D echo volumes and ejection fractions are better than two D measurements? I'm a bit skeptical of it. The data looks good. In fact, that meta analysis I showed you the the limits of agreement for three D echo were better than for two D. But remember, when you go to three D, you lose that axial resolution of echo that is sub millimeters. So sometimes the three D images give you great spatial orientation. But the resolution is a little bit imperfect, and so sometimes, and I didn't go into this either. But sometimes when you do, say, a three d Vienna contractor area and you get something like a e r O of one that's really almost impossible to have. If you had an e r O of one point. Oh, and a VT. 1 50 had ever read urgent volume of 1 50. I mean, how can you have that? You have to have a 600 cc ventricle in a normally f you know. So I think sometimes we get numbers that actually don't make any sense building on that. What about stress echocardiogram to assess? Yeah, I think that's I think that's very helpful. And degenerative m R. Where you'll often see somebody who you know, the M R doesn't look that bad, but they're left. Atrium is quite dilated and they're in Sinus rhythm and, you know, and you don't think it's diastolic dysfunction to some young person with, say, mitral, annular disjunction. And oftentimes you put them on a treadmill. Their P a pressure goes up, they get symptomatic, and the M R goes from late to stop late, systolic and mild to hola, systolic and severe. So we use it a lot. We use it more for mitral stenosis and degenerative M r than we do for functional M. R. Oh, I think when collapsed in my Tra fart came out and, you know, I remember at T C. T. When Greg Stone gave the presentation to the packed audience shortly thereafter, people wanted to like a lot of things in the news pin the two studies against each other. Um, I think in a lot of ways they were actually very important and complementary to our understanding of mitral valve disease. And they showed the same thing. Maybe we wouldn't have this deep of an understanding. Do you agree with that? Or can you? Yeah, I completely agree with you. I I think you you hit the nail on the head. That's exactly right. And and in fact, I was a little irritated with the any J. M and the reviewers for on my tray fr for allowing them to call that a severe Imar trial. I think if they had, they written the introduction slightly differently and just said there's been a discrepancy between the U. S. And European guidelines. We tested the hypothesis that these European guideline numbers known to be associated with prognosis are, you know, uh, improve outcomes when treated with micro clip. And if they would have said that there wouldn't have been this disagreement, they would have said, uh, you know, the that. Those prognostic numbers don't pan out, But the co app does, because there, you know, smaller ventricles and, uh and you know more M r. I think that that could have been done better. But there were multiple editorials, not just ours, but multiple other excellent editorialists that all pointed that out. So I think you're exactly right. What do you think explains the difference in functional mar between surgery and micro clip? In terms of outcomes? You know, it's it's interesting that it's, I think, I think if I were one of the heart surgeons and I worked very closely with him, I want to I want to do a trial, you know, to literally compare them. And no one ever did that trial. You know, no one ever took patients and randomized into guideline directed medical therapy versus, you know, surgery. And the CTS in trial was never powered to look at a mortality difference between, say, annual plasticky and mitral valve replacement. So the big difficulty of doing that trial with surgery is one. It's always hard to do to get patients to agree to randomize to medical therapy versus surgery. That's hard to do. We did that in, uh, you know, stitch, for example. And it was tough. Uh, and second of all, you know, see, TSN has got the surgeons now trying to figure out Should we replace this valve or should we do an undersized ring? There's advantages and disadvantages to both, so it would be a little tough to do, but I think you could do it against Micro Clip. Do you think that will happen? I don't know. If it happens, I think it might be through CTS n. I'm not sure that that Abbott you know, that makes Micro Clip or Edwards that makes Pascal has any incentive to spend millions of dollars funding a trial that could hurt them if surgery came out looking good? No, absolutely. So we know the mitral valve is a complex structure, and the mitral clip is one piece of that, but it also has to do with the ambulance with the cords. Where do you see the future of per cutaneous mitral valve therapy? Well, I think I think one of the interesting things that your question brings up is that when we look at differences between Mitra Fr and Co. After patients who succeeded and didn't succeed, you know, we talk about LV size M R Severity all these things. There's really not been strong data about which an an atomic features predicts success or which technical procedures, you know. I mean, when you go in and do a micro clip, if you pin wheel a little bit, you know you can get more m r S M R Reduction. There's a couple of recent papers that are either out or in press or one that I know that's probably going to be published, that are looking at annular dilation and showing that the really large analysts, uh, has a more likelihood of initial failure and late failure with micro clip than smaller annual asses. And in some of those papers compare leaflet length to Angeles area or leaflet area to Angeles area as well. So I think we need to learn more about which patients are, um, you know, likely to have a good clip result versus which don't and to a certain extent, there's some luck involved. I think there's some unpredictability involved, but we need to know more about that so that we can help target. Hey, this patient is going to do fine with a edge to edge repair. And this patient is going to need an annual plastic or replacement. We're not there yet. I know in cardiology, we've always been very LV centric, and we kind of think of the atrium and the right ventricle, a second area or past structure. Yet there is this idea of of atrial, functional M r. I know you briefly mentioned it. You don't really spend much time. Can you comment a little bit about that? And your thoughts on that? Yeah. So what? What, what? We're seeing a lot of it and you guys first reported it. So you know, it's basically pure annular debilitation from a dilated atrium. Usually that is chronic A fib. It can be LV, diastolic dysfunction or an infiltrated cardiomyopathy. And because it's pure annular dilatation, one would think that an annual plastic would be the the right procedure, with or without a ablation for a fib, depending on Cronus City in size and all those things. But I think that's an important entity, and the thing that really distinguishes it is the LV function is normal and there's no tethering of the leaflets. The leaflets aren't pulled down into the ventricle, but they're up in their normal place. I do think that's a very important entity. We're seeing a lot of it, and I think that's going to end up being an area where although we've had success with my triplets, I think at least mechanistic Lee an annual plasticky or replacement makes sense there. Paul, can you comment about how to own a Baylor? You guys run your mitral valve multidisciplinary clinic. How are patients evaluated? Who's involved with the decision making and and just operationally, how does that work? So we have a We have an unusual setting, and, uh, I don't think many people do it this way, but we have a clinic. On Tuesday afternoon, I go Zui Wang, one of our other interventional echo people Go Rob Smith and Tim George, who are micro valve surgeons. Go uh, Molly's Europe zur Lip and Kareem Al Azizi. Interventional lists go. We see the patients together, and it's really helped us to have the surgical perspective on anatomy, and but they see things in three D space that we don't see and it really is useful. They've taught us a lot. We've taught them a lot, and so we kind of make a combined decision. And we do see the patients together. No, that's fantastic. And I think that Trueheart team approach for some of these patients is is really important and kind of working together to figure out the right treatment strategy rather than trying to compete between the two. Um, all right, there's some questions coming in here through the chat that I'm going to ask. It seems that linear dimension for measuring LV or flawed thoughts about index values and ratio based on index values How would you index for PSA or height? Yeah, that's a great question. I don't know the answer. I wish I did. But because I've thought about that a lot, and I think it's, uh, it's true that everything we measure has potential flaws. As I showed you the the meta analysis comparing LV volumes by Echo to CMR shows that we really underestimate a lot, and, uh, and yet the linear dimensions have the problem of, you know it can be completely normal, and the whole apex blown out so the linear dimensions can really under represent LV size. They work better and there are lots of papers. I'm sure the question is referring to, uh, we're indexing for, you know, indexing a linear dimension for body ah, surface area results in prognostic value in m R and A R and in other conditions. And I think that there is some value to that and notice that the FDA approval for my truck clips says the in systolic diameter has to be less than 70. That's just taken right out of the co apt protocol. That's not, you know has not been compared to body surface area. So I think we you know, we're still struggling a little bit with, uh, you know, with the limitations of the methodology next question through the chat, how do you feel about late systolic M r. And how do you assess that? Yeah, so, um, with with functional m r, which is what we're really focusing on today, we don't see that very often. That's, uh, with functional m r. We see early systolic, especially if there's dissing Quran e. You may have an early burst of them are that goes away And you see that by physic m. R, where it's worse early, goes away in mid sisterly and comes back. But the late systolic tomorrow we see often with prolapse, and that's a situation where Pisa er oh, greatly overestimate. And I've had patients come to me in tears. You know, 26 year old women who run five miles every day and or asymptomatic they're left. Atrial size is normal, and somebody told them, You have to have your micro valve replaced based on late systolic m. R. So we have to pay attention to that because it will lead us astray. I think that's where exercise testing can can help in a lot of ways. You know, you put that patient on a treadmill on a Bruce Protocol, and they go 20 minutes and nothing happens. It reassures the patient. It reassures the doctor, and you know you can tell them. Don't don't go see a surgeon. What would your advice be in general, to a patient with severe functional M R. That is asymptomatic with normal LVF, but dilated LV or poor LV geometry? Yeah, it's We don't see that very often, either. Most people with functional M R have symptoms, and and the dilemma for us is, are the symptoms due to LV dysfunction or M R or both? And that is the real critical question because, as you know, we have patients come in with the F so 30 ischemic cardiomyopathy and heart failure symptoms who have no m r whatsoever. So the real challenge is to figure out is the, um are playing a role in the symptoms? Do I need to treat the mar? Can I leave it alone? And usually, you know when patients are asymptomatic, if you take a careful history or put them on a treadmill, you'll you'll figure out that they maybe they have more symptoms than they think. Sometimes I'll ask the patient or the family. What what was the most vigorous thing you did five years ago? What's the most vigorous thing you do now? And you'll figure out that, yeah, they used to, you know, they used to run or play golf and carry their clubs, and now the they don't get out of the couch because there they really are symptomatic. How do you think co apt impacts evolution of other trans catheter mitral valve therapies, especially as mitral clip experience and technology continues to evolve. It impacts it a lot. I I think now that you have a trial that shows a strongly positive reduction in heart failure, hospitalization and mortality that becomes the standard to which new devices have to compare. And and you know, I'm involved with some of these protocol development teams of these companies, and you've seen an evolution towards that way of thinking. You see that, for example, with the tendon trial where they're now looking at needing to compare to micro clip. And you're seeing that with the repair trial, which is a degenerative M r trial Now that's going to be looking at surgical repair versus micro clip in intermediate risk patients sort of following the tavern paradigm. So I think as time goes on, you're going to see more and more studies where new devices are compared to Micro clip. Do you try to average er away through Sicily? No, I would like to, but I would be at the hospital 26 hours a day. Uh, it is a great idea, It really is. And I think if if there was some way to do that in an automated fashion that was accurate and reproducible, that would be very helpful, because I do think that when we're picking out the largest er oh, what we're measuring is peak. Er Oh, not Garland Er Oh, and this is why you'll see people criticize co apt because they'll say their e r o is too big, you know, they're they're regurgitate. Volume was 60 but the total stroke volume was 60. Will remember that LV end diastolic volume is overestimated by 40 ccs by echo, so that solves that problem. But it also creates a problem for micro fr because it makes it look like they treated a bunch of mild, um, are which they probably did. All right, um, I feel like I'm rapid firing at you. I appreciate you taking all the questions. How do you reconcile the differences between severity of em Are by cardiac m r and echo. Seems that CMR accounts for variability during sisterly. Unlike pizza, that's correct. CMR gives you the you know it's a volumetric technique. So you're calculating the er Oh, uh, you know, over all of time. So So the numbers come out lower, and in some ways the numbers make more physiologic sense. However, I've seen some CMR papers that that also missed the whole point of this talk today, which is that, you know, you can't say Oh, the the you know, regurgitate volume is 32. It must not be severe. Remember if that could be a rig. Urgent infraction of 50%. So I'm trying to in this concept of disproportionate m r. I'm trying to get people not to get stuck on a number because that number depends on the size and function of the L V. That's the message. All right, well, I think we got through all the questions. Um, thank you again very much for taking the time to join us here for grand rounds, Berg for making it work somehow, through the power outages and the ice storms and everything else on top of your busy schedule. We really appreciate it. This was This was fantastic. So thanks for inviting me now. Sure appreciate it. Take care. Right. I think we got through all the questions. Take care, Stay safe down there and hope to see you soon. All right. Bye, everybody
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