Gilbert Tang, MD, and Sean Pinney, MD, join Randy Martin, MD for a discussion of the current thinking about the epidemiology of secondary mitral valve regurgitation and the intertwining of this condition with heart failure. Drs. Tang and Pinney highlight the importance of a team approach; including imaging specialists, heart failure experts, and surgeons/interventionalists in the diagnosis and management of patients with secondary MR and heart failure. They share current treatment options and discuss the latest on guideline directed medical management, as well as transcatheter and surgical therapies. All members of the heart team will benefit from this new information and guidance as how to diagnose and manage these patients. Hi, I'm Doctor Randy Martin. We're here at Mount Sinai where I am a clinical professor of cardiovascular surgery and I'm thrilled to be joined by two of my colleagues, uh, Doctor Gilbert T here, Gilbert is a, is a surgical director of the Structural Heart Program and is also a professor of cardiovascular surgery. And Sean Penny Shad is, uh, is the chief of the car division of cardiology at Mount Sinai Morningside. And the reason that I've got a, a heart failure cardiologist that the surgeon who deals with structural valve disease, we're gonna talk about secondary macho regurgitation, a really significant problem in which both of your professions are critical to the good outcome. So, Gilbert, you've got some stuff to show us. Yeah, I think the first point is that ma regurgitation is really a huge i, a clinical need in the United States and probably globally, you know, of over nearly 4 million patients with moderate or severe. Mr really there are very few patients 3% or so get surgery. So, so a lot of them are out there actually just being medically managed or even not being referred to a, a bowel center or high clinic? OK. So we're talking of the, how many of those patients have secondary MRI? Do we have data on that? We don't have specific data. I would say probably around 5050 split uh would be like, is that what you think? Is that what you thought? Yeah, I agree. And I think Gilbert you framed it really well, this is a big problem and it's a big problem because so many people who have heart failure have secondary Mr. And we know that there are, as you said, 55,000 people who get referred for intervention, but there are 2 million people walking around with heart failure complicated by secondary Mr. In addition to that, we know that secondary Mr is associated with bad outcomes, doubles your chance of getting hosp wise for heart failure, increases your chance of dying from cardiovascular causes or for all cause mortality in the context of those patients who have heart failure with a reduced ejection fraction. The other reason why it's a big, a big deal is because patients don't feel well, you know, and we learn that through the co op trial, the majority of those patients, they, they just don't feel good, they want to feel better. And that's one thing that I've heard from my patients, they want to feel better. And you know, it's, it's interesting because you think about the intertwining of structural and heart failure. I mean, heart failure can cause value regurgitation, mi regurge Troy cut and, and vice versa. Ma regurge can cause heart failure. So they're really intertwined, but you're right. It's really critical. Take us into the next uh next slide and show us what you Yeah, I mean, that's exactly what Sean was saying is that it's like a vicious circle. You start with the ML, then the heart basically gets stretched that because there's extra blood flow there, the colon and it is being pumped inefficiently. And so as a result that you have muscle damage and then the heart dilate and the heart function reduces. And then now the leak gets worse. So it just becomes a vicious circle. And that's how you get up in the hospital. I think that's a very important point which is that this is a positive feedback loop and the heart is damaged and becomes more damaged in the setting of mitral regurgitation. And so what that provides us then is a target, something that we can treat to prevent the heart from getting worse over time. And the atrium and the pulmonary vascular on the right side get affected in this thing too. Boy, they sure do. And you know that back pressure that's caused by severe mi regurgitation gets passed to the lungs and then from there, it gets passed to the right ventricle. And you know, if anyone's watching this video has heart failure, they know what we're talking about because their, their belly gets swollen their legs get swollen, they get really short of breath when they walk all because of that back, pressure into the lungs. Still one of the top, if not the top calls for people being hospitalized over the age of 65 for cardiovascular reasons is heart failure without a doubt, without a doubt, it's the most important. DRG, once you get over age 65 important to anyone who has heart failure. But when you look at the numbers, you know, 6.5 million people right now in the United States with heart failure, the majority of them are older than 65. All right, let's go, go, go on because there is some good news in this. A lot to complicate matters further. Actually, what we were used to seeing is, as I mentioned before, people with bad matrics, they have bad Mr and they actually got gets more and more. We now know that patients with atrial fibrillation, which is a fluttering of the, of the heart actually can stretch the heart as well. On the atrial side, the heart function itself is normal. But because of stretch, they get Mr and the A FB gets worse and natural. That's a very tough problem to treat. I think Sean is in now all these patients at the clinic, you know, this is something over the last 5 to 10 years has really risen up to our attention. We didn't really pay a lot of attention to it before. But now we understand that the left atrium begins to enlarge and those mitral valve leaflets and, and instead of being able to come together nicely, they get stretched so that the tips are barely touching. And that's what leads to the mitra regurgitation that just can't close. You've got a double door of the frame, the door frame gets too big. But, but I think that there, you know, there is the the eight year old functional mitra. You're right. We didn't, these people have characteristic large las and they made you have a normal size ventricle, but it's got significant diastolic dysfunction. Is that correct? I mean, there are certain things we see with that that can tell you, I mean, if I look at an echo or can I tell the difference in those two, I, you know, in a scheming or ventricular, is that correct? I can tell that, is that, is that the case, you can, uh obviously with the ventricular, the, the ventricle itself is a, is enlarged. And in the setting of someone who may have had an old heart attack, you can see that area of the heart is not quite ischemic, but I mean, functional the way, I mean, the atrial, the we talk about the v being more was stiff. It's really people with preserved or moderately reduced ef versus a 20% ef within a severe ischemic. That's right. You know, for so long, we, we only thought of functional mitra regurgitation or secondary mitral regurgitation in those patients who had heart failure with a reduced ejection fraction. But Randy, what you're talking about and I think it's a huge problem. Those patients have heart failure with preserved ejection fraction, stiff ventricles, maybe not that enlarged, but then the left atrium gets enlarged and either that causes the atrial fibrillation, which then causes the mitral regurgitation or the atrial fibrillation causes the left atrium to enlarge and that causes mitro gurgitation. So we've got 22 types and we don't know if you say if I said I had 100 patients with secondary Mr, do we know the distribution? We don't know that yet, do we? I mean, we start, this looks at some population studies in in this. But I think the problem is that a secondary Mr is such a more recent phenomenon that under diagnosed, I mean, look at how many patients out there. So atrial fibrillation alone without any other uh diagnosis for heart disease. So these patients are the one that are coming back with AM R and our ep colleagues actually have seen and the mechanism of the ma regurgitation is is pretty significantly different in the in the ischemic or the ventricular type versus the atrial. What Sean described the atrial, the doors don't meet basically where this one of the doors is restricted and they don't meet. Right. Yeah, the ventricular is basically the heart stretches and So the leaf is being pulled apart, right? And of course, there's some stretching in W as well. So the doors are being pulled apart and not being to meet the atrial that the shine was measuring is that the analyst is getting stretched with the atrium. So now the leaf is themselves are not really tender because the heart function is normal underneath. But now they basically flatten out and they can't touch each other. Ok. So these are two types of secondary Mr take us to the next, take us into the journey and keep going here. So I can. So how are you gonna, how, how do you, I mean, there are multiple tests you can do, there are blood tests that you can look for markers and things like that. But imaging is critical. Yeah, I think, you know, Sean and I in you as well. You know, being in this for quite some time, you know, the first thing we looked at, how do we diagnose you hear, murmur on a stethoscope, right? And then when you look at the ultrasound, the echo like, oh, well, there's still the reason for that. And I think that's the kind of the gateway is that a lot of people, you know, first I need to put a stethoscope on the chest, we will hear it. And then when they find out they need to have a low threshold to get to a cardiologist or at least to an echo to figure out why is there a murmur? What's the nature of the murmur? And you can see on this particular slide on the left side that's kind of seen while color is not good, right. No one wants to have color on the echo. And that shows the reason for that. And that's the first step in terms of making kind of an idea whether it is the the ventricle problem or atrial problem. What do you see all great points? Gilbert, I think the echo is so critically important, it gives us so much information it tells us. First of all, is there mi regurgitation? Second of all, it allows us to quantify how much mi regurgitation is there. And then the third thing, it allows us to figure out the mechanism, something we're talking about a few minutes ago, we need those three pieces of information so that we know and we are empowered to know how to act. And you're looking uh I know Gilbert, the cardiac cath is, is obviously important, especially if you're looking for ischemic, but you're working with both Mr and and echo. You're looking at things like ventricular size and at end diastole, those sort of things, your atrial sizes and all, all those factors are really important in, in helping you to know not only the etiology prognosis and how you, how you treat those folks. Now, I think the point you're right, that kind of conversation is part to work up because a patient with ischemic heart disease, especially particularly the positive history of that. And, and sometimes actually addressing that might help with the ventricular shail improvement, recruit some more myocardium and actually reduces the much regurgitation. Uh I think one thing that maybe Sean can talk about is more about other more mass imaging that we now come come to such as cardiac Mr. How does that help you in terms of your management strategy? Cardiac MRI is very helpful because it gives us an in depth look, a closer look at the, the heart muscle itself. So we can tell how big is the heart, we can tell what segments of the heart are contracting or not contracting, which areas of the heart are viable. You mentioned cardiac catheterization. If we're thinking about restoring blood flow to a particular artery and particular segment of the heart, is that heart gonna contract if it gets blood flow. And we can sometimes tease that out with an MRI. We can also quantify how much of the heart is scarred, something that has really entered our way of thinking in the last couple of years and the last year, we can find out if there are things in the heart that don't belong there, infiltrative disorders, like cardiac amyloidosis and things like that. You're a heart failure specialist and you're a surgeon and an interventionalist who's managing these patients. So you know, how do, how do we and, and what are our options in managing these patients as a team approach? It's a great team. So we talked about a lot of the the key components you have uh heart failure, cardiologist, or quite honestly, most of these patients are gonna be managed by cardiologists, not necessarily heart failure, cardiologist, but cardiologists, cardiac surgeons, interventional or structural uh interventionists, imager critically important to have a good imaging team, particularly when you start planning your interventions because they can tell you and, and let you plan, is this someone who's more appropriate for surgery? Is this more appropriate for a device? Which type of device? And how should you set up that intervention? So you gotta have all those components on your team. And I'll also shout out to my nursing colleagues uh and, and the other members of our team too, they're critical. You gotta have a team and we're gonna get a letter from an EP that says you didn't mention being electro physiologist. What's the arts? So, I mean, but what, what your point is is that you need in today's environment, you need people who are experts that can talk to each other to figure out diagnosis and management. I mean, I think it's important to have that network of support for the patient. I think, I think, you know, right, previously, historically, it has been more soiled, but now I think it's important to talk to each other particularly in semester before you know, some of these patients may need a, you know, C RT or defibrillator device, right? You know, those card device and those patient atrial are might need a frill patient to control the atrial fibrillation burden. So I think we need to have a more holistic approach and look at these patients. And I think like a systematic work up to diagnose is important and going back to uh to look back with the primary cardiologist and the internist and primary care because, you know, we work in a metropolitan area. So we kind of, you know, have all the resources at disposal. But imagine someone live very far away from a tertiary care center. They don't have access really, the primary care or internet is the gateway to getting all this access to care. And then afterwards to follow up, they don't want that we encourage, you know, medication compliance or any kind of possible intervention that are necessary. And you know, here we are talking about and obviously talking about somebody who's got much regurgitation, but it really is a complexity of dealing with ventricular, you know, valve you are and then, and then, you know, pressure changes and all that. So how do we, how do we, so if we've got an idea of what's going on, how do we treat these people? What are our options? So I think there's been some really dramatic advances there, there really have been and this, there's a beautiful slide that, that shows what we have available to us and we have to match the, the therapy to the patient. But I'm gonna start on the left hand side of the slide because I'm the, you've got heart failure doctor, I'm gonna, I'm gonna talk about the pills first because the pills work. And I'll tell you the most impressive thing to me was when II, I spoke at the mi conclave as the one cardiologist in the sea of surgeons. And uh one of the surgeons approached and said, I have a lot to learn about these medicines and what you do, you know, very humbling moment. The medicines work, they work to improve ventricular function. They work to decrease ventricular volume. They get the heart working more efficiently and they decrease the amount of mi regurgitation. So I'm I'm looking at a pile of pills. There. Are you talking about a pile of pills? Are we talking about, you know, a few pills? What tell me about that all about the challenge of polypharmacy is a real one, but it's a real, you know, but I'm gonna speak to four pillars. So there are four pillars of guideline directed medical therapy, Arnies, which are the the new ace inhibitors if you will, fantastic and improving survival and improving quality of life beta blockers, which have been around forever ever. Something called Mras. Minera corticoid receptor antagonists, which is why we call them Mras because that's too much of a mouthful. They help to prevent the heart from adversely remodeling. And then lastly the new kid on the block SGLT two inhibitors originally for diabetics. Now they're for everybody and, and they're for everyone with heart failure across the entire range of heart failure. So those are the four pillars and those are the things that all cardiologists and quite honestly, all internists do first, which is to establish those therapies for their patients with heart failure, reduced ejection fraction. You know, I I was gonna come to this later on, but the problem is compliance and people having access to it. I mean, some recent papers in the cardiology show that you looked, they looked at a large series from the VA system, like 14% of people were discharged on, on, you know, some of these, especially the SGLT, I mean, we just need to figure out a way to make them available affordable and get people to use them because they have, they really have been dramatic in their effects. They really are. And you speak to a number of barriers to getting full compliance and you know, it's not the patient's fault. Oftentimes these medicines are expensive, they create side effects. And though a lot of patients feel better on them, some patients don't. And I think that's why we're looking at interventional approaches because we know that even as good as medicines are, they can't get rid of a structural problem. And that's what we have with secondary mi regurgitation. Are they the, they're something that's essential that the patient be on and then, then we've got these other options to deal structurally with them. Is that correct? That's right. What's different about secondary mi regurgitation as opposed to primary mi regurgitation? Where in primary mi regurgitation, it's the valve, that's the source of the problem with secondary mi regurgitation. It's the ventricle, that's the problem. So we have to treat this like a ventricular disease. We have to treat maximally with medicines first. But then in that subgroup of patients who are still symptomatic, in spite of being on maximally tolerated doses of medications, we have to move forward, we can't be satisfied, we have to do more for our patients. I'll come back and ask you, is there a simplified approach that surgeons can understand with this because you're talking through things. But you're right. I mean, this has been so, so Gilbert, uh we've got, we've got a lot of other things you can do for the valve itself. And then, and then if it's, if it's needed for weapon and Turkey assist device and things like that, but take us through this, I think what I was mentioning, it's the kind of it's really the holistic approach, as I mentioned before. And so the medication is the first step. And in fact, I would say they target microscopically right in a molecular level, how the heart can increase its efficiency and function. The rest of it as as I mentioned are rhythm management, which is, you know what C RT is about to make the heart contract more efficiently by kind of rewiring some of this work in synch synchronous. Yeah. And then the rest of it is more structural uh in terms of dealing with the mechanism of the regurgitation. So you have a less invasive approach which is trans edge edge repair, which is basically uh restoring the cooptation of the two leaflets that have been either stretched or restricted to reduce the mr burden. And in fact, it allows the medication to work more efficiently because now you don't have that physiological burden. Perhaps you don't have to up titrate the medication as much. Maybe the patient can tolerate the medication regimen better. And then if your repair is not going to be a good solution to reduce the regurgitation, then perhaps a replacement. Uh meaning that you have really no regurgitation because now replacing the valve with a tissue valve. Uh most of the time that will basically solve that problem of the regurgitation. I think the most invasive approach that you see on this illustration, the alba and other patients where medication fixing the mushroom is not going to be beneficial because they're really in the advanced spectrum of the heart failure. And so really you need to either have a mechanical support to allow you to pump efficiently or you need to go on the trust and get a new heart. And Sean obviously has been the forefront of in that area. He can talk more about that. Yeah, when I look at this slide, I see many different patient stories here. You know, for those patients who are still symptomatic on maximally tolerated doses of guideline directed medical therapy. You know, mitral valve surgery does a very good job by that. I mean, once you get into thinking about interventional approaches, the the goal is to eliminate mitral regurgitation and surgery does that and it does it extremely well, not everyone's a surgical candidate. And, and for that reason, now we have these other therapies that have become open to us and things exactly the clips and, and even some of the things that are now in clinical trials, replacing the valve through a catheter based approach or TMVR, I mean, you know, we've had the, the rules and I think the thing that ideally you'd like to have no much regurgitation after your intervention because you've shown you've shown some elegant data that, that combination with, with the meds that you talked about can lead to some dramatic changes in the jerk, your size and function. So that's ideally, but there are patients, many patients and that's really work in progress. I mean, there's some exciting things being for transcatheter matra replacement versus surgical matra replacement. But there is, there is a role and we've seen that for the clips, right. For the transcatheter equipping of both the male and now the tricuspid, um, how do you select what to do? It depends upon the patient, right. It does. And my approach is treat with medicines first. If they're still symptomatic, then assess for an intervention there. And I think the MitraClip or the clip procedure we call it tier. Now, in interior mitral tier, um, is appropriate for a lot of patients who remain symptomatic in spite of those medications. And so if it's someone who has moderate to severe mitra regurgitation, whose ventricle is, is enlarged but not too enlarged and who has a lot of mitra regurgitation. The right ventricle still works, pulmonary pressures aren't too high. That tends to be the ideal candidate for a tier procedure. Yeah, you're putting in really some important caveats. I hope people are because you're exactly right. There's an interesting fact. If you go back and look at, you know, the co op data from the co op trial, that was really a very interesting trial that showed some impressive outcomes and you know, decrease in hospitalization when they looked at their five year data, there's some encouraging stuff, but there's also some discouraging data. The number of people who died or had recurrent hospitalization was substantial in, in, in defense of that data, I'm not defending it. But in the defense of that data, though a lot of that was with earlier versions of the quips, now they've improved their size and grasping. And in fact, I think somebody said recently that there were like three patients on the SGL and all. So the meds weren't there that it was there. So there's some advances this whole spectrum. Let me just finish on this and ask you about the, the, the, the va and the transplant. So VADs were, you know, have been around for a while and they've gone through and they were, you know, destination therapy and all that sounds sounds great. As long as the destination is the right destination that you're thinking about. But it are we gonna be transplants, we know work but we know that there's, you know, it's, it's a matter of supply and, and all that. What's what's about, what about that John, where are we going to be with those? I'm a big supporter of va therapy for the the right patient. What we know now with the current generation of left ventricular cyst devices, uh they're durable. They, we've got data out through five years with the survival of 58%. They improve quality of life significantly. You know, people are now able with these devices to not just walk 20 yards, but they can walk three football fields without feeling short of breath. Um The side effect profile, the adverse event profile has gotten much, much better. We call these devices more hemo compatible. It all cause the same perturbations in the blood system causing strokes and Clausing bleeding, the way that the previous generation of devices did still some challenges around in a drive line and that, that obligatory need to be hooked up to a power supply all day long. And so it requires a special patient that's willing to do that. But for the patients who go for it, I guarantee it improves quality life and it helps uh patients living and you're really looking at quality uh and longevity, but really quality while you've got longevity. That's right. That's what they're, you know, so, so we, we've got a lot of options here. We have meds which are really made a dramatic difference. I mean, I think that they really, and I think that's why I, I wasn't being facetious. I think simplifying the med, the understanding of the meds is really important because, you know, we're on calls together each week and there's this list of med and you see how many patients are taking that's a little bit overwhelming to the average patient, especially those who don't might have a difficult time with the means of access. We can make it really simple. So start an SGLT two inhibitor, start a beta blocker once you've done that, add in the Arne, the Sucu Berl Valsartan. And then after that, as long as your kidney function's OK, your potassium's OK. Add in the Mr A and you can do all of that in the course of 2 to 4 weeks and you better have a really good nurse who can help you with that. No, because patients need, need monitoring and follow up on that sort of stuff. Um ok, got some more. This is pretty good or is this, is this the end of the story here? I think, I think we got to cover a lot of grounds here. I think we have really just seen the whole spectrum from initial presentation to diagnosis to now, you know, treatment strategy, things really come a long way in terms of. And I foresee, you know, in five years that you know, a lot of these uh options will become commercial as you know, some are still investigational and most of them will become commercial. And then now we all have more tools and better tools and who knows what the next medication is going to be to treat high filler that may even opiate some of these uh more invasive options. So, Sean um we have an epidemic of comorbidities, we have obesity, we have diabetes uh related, we have an aging population so that the population that can have heart failure with or without reduced. Ef all the things we've talked about is growing, how do how do we effectively manage these patients? Because I mean, you know, you're looking across multiple ethnicities, multiple access problems. Um you're talking about a team and you know, the patients in this area are fortunate to have Mount Sinai and the and the group here to help that. But how do we, how do we deal with this? So, at the Mount Sinai Health System, we've set up uh a comprehensive approach to heart failure disease management. It starts out in the primary care practices where they have first point of contact with these patients who have heart failure and who have heart disease and all the comorbidities that you mentioned, obesity, high blood pressure, diabetes. From there, we set up clear referral guidelines. When should a primary care specialist refer to a cardiologist? When should a cardiologist refer to a heart failure doctor? And when should heart failure? Doctors refer to an advanced heart failure program? So we build that in, we provide some guidance, you know, a roadmap for providers to know how to navigate their patients. The second thing is we talked about it, it's communication, so communication between providers and patients, but also between providers. And the third thing is putting these multidisciplinary special teams together. We've got a great one around mitral valve disease. We've got one around advanced heart failure. We have one for all that. We have one for transplant. But what that allows is that specific team to develop expertise in one area. And again, we do this all our patients. So we've come really, really good, we understand where things are evolving, we communicate that back to our patients. So together in that conversation with them, we can make the right decision for them. And for their health good. So some really neat advances in this field, but it's a field that unfortunately is growing and, and the population that is affected with that. But it sounds like we're gonna make some progress here and, and being able to treat it. But it, but it is an issue. I mean, the tsunami of, of, of comorbidities is really gigantic. It is. But, you know, I remain optimistic and I'll, I'll use mitral valve as a, as an example, you know, talking about secondary mitral reunification. So 15 years ago, all I did, as I noted it in the chart, I knew it was a bad thing, but there was nothing I could do about it. 10 years ago, co A T was designed five years ago, co A T was we got the results and now we have the five year results of coop. It's interesting reflecting back on the five year outcomes is that you couldn't do co op trial nowadays because the therapies have gotten so much better. And so we're now in the next evolution of treating secondary mitral valve disease. I'm very optimistic that we're gonna help patients feel better and we're gonna help them live longer. Yeah. And I think, I think, you know, we talk about team approach but it really is a team approach in this. And I think having it's, you know, one of the things you talked about is how critical it is to have heart failure involved in these patients early and really become almost the quarterback of the team initially and with things. So I think that's, it's important. Ok. Well, I've, I've learned something. Thanks very much. I hope, I hope you certainly have learned things and uh we could all take this knowledge and know how to treat these patients better. So, thanks very much. Thank you.