This Keynote address by Dr. Rick Nishimura looks at conventional framework for treating valve disease and new paradigm for future techniques for valvular heart disease management.
Thanks, Steve Pack. It's, it's um it's really great to see your little babies grow up and they're such great people. So, uh th this is good. Um Don't, don't worry too much. I'll only be asking one or two things and we'll, we'll keep going. Anyway, I have no disclosures. And what we're going to talk about is valve disease and you know, Eric, I noticed you kind of alluded to tricuspid regurgitation and mitri regurgitation with atrial fib and II, I really think that with our electro fiddlers, there's going to be a new wave of people with both electrical and valve disease um that we're going to have to address. So here we've got a case pay attention. 58 year old attorney. Now, when an attorney comes, that's always a bad sign, but we'll, we'll get over that. He's asymptomatic bikes, jogs, no limitation, healthy, no medical problems. Went to his primary care physician. A murmur was heard an echocardiogram was done. They had the diagnosis of severe aortic stenosis and he comes to you. Now for your advice, what are you gonna do? The smartest person there? Yell out what you're gonna do and we'll see if D PAC has properly trained. You. Thank you so good. I'm gonna offer intervention. You what I'll offer him. Intervention, intervention. Oh, deep. Ok, guys, first of all, you have to examine the patient. Now, iii I know it sounds old fashioned. But if you just go on the basis of an echo report in our practice, you're going to be wrong 20 to 30% of the time and you'll have no idea what the patient wants. Ok. So you've got to sit down, you've got to talk to the patient, shake his or her hand and examine them. Now, on examination here, you have findings consistent with, OK. Now, what do we have findings consistent with second, smartest person delay, crowded up stroke, late peaking murmur, second single heart sound. What's aortic stenosis? How severe can you tell just by palpating the corot? Yeah, of course, you can, I'm assuming if you have enough experience, it's severe. And, and it's important because many of the times an echocardiogram might say it's severe when it's only mild on examination or the echocardiogram might say it's mild when it's really severe on examination. In that case, you have to go further before you start sticking catheters in these patients. Ok. So now you have the diagnosis of severe aortic stenosis based on your examination and you get your echocardiogram and there's left ventricular hypertrophy. The aortic valve is calcified, the mean gradient is 42 and that means that there is indeed severe aortic stenosis with a bic cuspid aortic valve. And you always have to look at the ascending aorta because there's an aortopathy associated with a bic cuspid valve. And if there's a dilated aorta, that's going to completely change your management. Ok. So now you've examined the patient, you've done the echocardiogram, you've got the diagnosis of severe aortic stenosis, but it's completely asymptomatic. Now, I'm gonna ask audience response, what are you going to do with this patient? Asymptomatic attorney, severe aortic stenosis comes to you because he wants the best thing done. What are you gonna do? Watchful waiting surgical A VR tabby, so on and so forth. A lot of tabbies. OK. Are you, are you guys gonna be taking your board soon? Because if you're gonna be taking your board soon, uh A lot of you are gonna flunk? OK. So this is where we are. It's kind of a mixed group. Everybody is saying something different, which is good because that means that there's a learning opportunity here. Now, let's go back to the slides. I got a patient with severe aortic stenosis. When you give a talk, we're supposed to tell you what we're going to tell you, then we need to tell you and then we're going to tell you what we told you. So, what I'm going to tell you is this is number one, I'm going to describe the conventional framework for the management of patients with valve, your heart is I'm going to use aortic stenosis as an example here. And for the fellows, the conventional framework are what the guidelines say and that's what you need to answer on your boards. OK. So, so take the first part of it and remember that, but then we need to go into a new paradigm and the new paradigm for management of these patients are lower thresholds for intervention. I have to tell you why we're going to go with a lower threshold and less invasive intervention and then say a few words about the future management of these patients with valvular heart disease. We just had a discussion with your it people. Um And I think it and A I is going to play a great role here. So let's describe the conventional framework for the management of patients with, let's say aortic stenosis. Now, if you look in the textbooks and you actually do, do you know what a textbook is? Have you ever been to a library? Ok. So before your boards, you really ought to go to a library and get a textbook and read it or look at the board review tapes because you'll find that the conventional wisdom for aortic stenosis is that they're going to do very, very, very, very well for a long period of time and then boom, once they get symptomatic, they're either gonna die or go into heart failure. Ok. That's the conventional wisdom. And in the past, the only thing that we could do was a surgical aortic valve replacement, which at the time we wrote our initial guidelines centuries ago. And Eric you your comment about now, you know why it takes so long to write guidelines is very true. Everybody has to agree to something. All experts have to agree. But back when we first wrote the guidelines, the operative risk for an aortic valve replacement was 8 to 10%. At that time, we had terrible valves. You know, you remember the valves, the Star Edwards and the Bjork Shiley, which would take inrs of 4.0 they would bleed like stink and the tissue valves would go ahead and degenerate. So the risk of the operation, the consequence of the operative intervention had to be weighed against the risk of observation. And we then said, and this is still true for class one indication for aortic stenosis. It's either symptoms or when the ejection fraction drops less than 50% which means the afterload is overwhelming, the left ventricle. Ok. Those are the only two class one indications for your boards. Remember that. Now, if you think about it though, as we started to look at more patients with aortic stenosis, because we actually had echocardiography that could give us a good baseline and follow up patients with asymptomatic aortic stenosis. We found out that that five years, three out of four patients would either develop heart failure or die. So it wasn't this thing where they go, go, go, go and then they, boom, there's something else going on here that gradually makes them worse and worse and worse. And that's why I want to present to you a new paradigm for thinking about the natural history of aortic stenosis, how it's going to cause us to intervene earlier and earlier. And they say few words about Matt and Daks uh change here where you can do a percutaneous procedure. Now, the new paradigm for aortic stenosis should be more of a gradual decrease in outcome of these patients. So you start out with mild to moderate stenosis, you go to severe stenosis, you get compensatory hypertrophy. You remember it's that increase in wall thickness that normalizes wall stress. At the very end, you drop your ejection fraction and then you have symptoms. But the thing we never understood before is that there is this period of time here where there is going to be progressive myocardial damage, damage to the heart muscle itself from the pressure overload, that's gonna gradually cause the outlook of these patients to become poorer and poorer. Now that myocardial damage is probably due to changes in the extra cellular matri reactive fibrosis, they get scarring in there, but there's progressive damage that occurs as you have. These patients continue with their severe aortic stenosis which we're now seeing on MRI scan with gallium enhancement defects so on and so forth. Now, the other thing for the fellows and the residents is it's very useful to categorize the patient. And uh and you know, for the A PPAS uh nppas that work in cardiology in your summary, put down what stage you think these patients are? So stage B are patients who have only mild to moderate stenosis that's going to progress. Stage C one are patients who have severe stenosis but are asymptomatic. Stage. C two are patients who started to drop their ejection fraction. And stage D are finally patients who are symptomatic and it's very easy then because right now in stage B, we're going to follow them and once they reach stage C two or D, we're going to replace their aortic valve, either with a surgical valve or a tavy. Ok. That's why it's very important to put them into these categories. You'll sound really smart when it comes out on your summary too and it'll tell you exactly what you're thinking of. Now, the problem though, as I alluded to is what about that stage? C one that's that lawyer who's come to you, that you've properly examined and found to have severe stenosis, but is asymptomatic. When should we intervene? Because you can never make a person who's asymptomatic feel better with an intervention. But are you going to be preventing problems in the long term? Now, coupled with the fact that we now know we should probably be intervening before the onset of irreversible left ventricular dysfunction. We've got a much lower operative risk. It's not that 8 to 10%. It's now less than 1%. And with our surgical valves, they are much, much better. Um, you know, some of our valves we can do with INR is between 1.5 and two and the tissue valves last 15, 20 years now in our older patients. So the stage c one, we're going to start looking for patients who are at higher risk. You don't want to plop a valve in everybody. But if you know that they're not going to do well in the future, you're going to start thinking about it. And there's stuff like how severe is that stenosis, you know, we said gradients greater than 40 is severe, but then there's really severe of 50 then there's really, really severe of 60. And on the left, you can see that the more severe, the poorer the outcome. The other thing is you can look at biomarkers such as B MP, which BNP is telling you that that wall stress is overcoming the left ventricle. You got an elevated biomarker, the higher the BNP, the worse the prognosis. So that is why when we look at stage C one severe asymptomatic preserved ejection fraction, we should start looking at those predictors that are going to say they're not going to do as well without an intervention. So the things we use are a drop in blood pressure on treadmill. Very severe A s let's say your gradient 60 you're more apt to intervene rather than if your gradients 40 your B and P is elevated. We used to say that the ejection fraction is less than 50% we should intervene. But boy, if it starts out at 78 and then goes to 72 and then goes to 60 then goes to 58 that's progressive drop. And then we should intervene and rapid progression of the A S if the progression is greater than 0.3 m per second. And we're getting data now on myocardial strain, gadolinium enhancement defects, a whole lot of other things. And the guidelines, I can tell you we're trying to get together so that it can be more updated. And I think there's enough evidence that some of this other stuff may come out to tell us. Yeah, it's OK in the asymptomatic patient to intervene. Now, not only do we now have an incentive for intervening earlier, but we've got this type of a thing with Matt and D Pack heading that you all know, I mean, this was just tremendous. First time I saw this, I just went wild in the Cath lab. You, you now have the ability to take a catheter, put it across a valve, blow up a balloon and boom, you've got a new aortic valve and it's a dramatic relief of obstruction within seconds. Now, DP A was in our lab. When we did this old fashioned balloon valvuloplasty. And I don't know if you remember, but boy, it was terrible. I mean, you, you open these valves just a little tiny bit and you say it was success and they bleed out from their 12 French catheters and, you know, it would be horrible. But now we've got these very safe transcatheter aortic valve implantation. We've decided to call it A TV, because it's actually an implant rather than TVER, which is a replacement. Now, randomized trials, we all need the trials for all of the companies did very well in setting up randomized trials and found out that first the inoperable patients tay was better than medical and high-risk patients ta I was as good as surgical. So the guidelines changed uh in 2017 to go down the intermediate risk patients ta I was uh comparable to surgical. And then in 2020 guidelines, even more data came out to say that even in low risk patients TA I was comparable to sr in select patients. So you can see how over the years, you know this new procedure came out. But because we now have randomized data, we have very adequate information to back us up to go ahead with this. But in all of these trials, we have to remember that the patient population was the older patient. Now, doctor warns and I don't say elderly if it's greater than 65 anymore, but it's uh older patients, they were all over 65 years old and they all had the class one recommendations, um which meant either symptoms or the ejection fraction was down. It didn't apply to those other patients. So we really don't know what to do about ta I in younger patients. That lawyer, for instance, because we don't really know the long term outcome. 8, 10, 12 years in a younger patient or what happens to our uh protocol of valve and valve and valve and valve. If things start to go haywire, we don't know about tavy and B cuspid valves. Yet, we don't know about the tavy or savvy in asymptomatic patients. We're even starting to figure out that patients with moderate, what we define as moderate aortic stenosis have a bad outcome and perhaps we should be intervening in moderate aortic stenosis, not just Tavy. So I'm really looking forward to this afternoon and D pack. I think you've set up a wonderful little um uh a session here where you're gonna hear from these people about what they think about where TV versus SR is today and the future of what TV is. I've just kind of giving the basis the foundation on how we've dramatically changed our thinking. I would warn the fellows again when you take your boards just do that class one recommendation, but you'll find out when you graduate and actually become real doctors that you're going to have to be able to make these clinical decisions based upon new data and what the patient wants. You're going to have to do this shared decision making so on and so forth. So I, I think it's important for the fellows and residents to understand that there's got classic recommendations, but we have to start making changes. And Eric, I don't know if, if we're ever going to get to the point where every three months we can make changes in the guidelines. But we're, we're, we're trying to get to that place and stuff and it's going to take a bunch of experts to sit down and tell us whether or not these are going to be appropriate. Now that was passed. This is present, let's say a little word about the future, the future of valve disease. And, and the reason I'm saying this is because even in the United States, about 40% of patients with severe aortic stenosis who should be undergoing a full evaluation to determine whether or not they would be candidates for sr or tay are not sent. I don't, we, we don't know why we're trying to explore why, but they're out there and they're not being recognized and they're not being sent to this group who might be able to do life saving technology. So the future is number one earlier diagnosis. Number two, as I said, lower threshold for intervention, we'll talk a little bit about how that's going to change. And then the latest invasive intervention which is developing and developing now out there in primary care, when you don't have access to echocardiograms for every patient to come in. It really takes something simple like a stethoscope. I'll, I'll show you what a stethoscope is. Next, next time we talk. But you got to use a stethoscope. You've got to look at the electrocardiogram. You've got to look at the chest X ray and a master clinician like Doctor Warrens could tell you right away whether or not this patient has severe aortic stenosis. Without an echocardiogram, she could even tell you what the uh ejection fraction is. She can tell you how big the aorta is. She could tell you what the filling pressure is. She could tell you all of this from these simple 25 buck tests rather than the, how much does your echo cost now? 506 $100 or $600 for an echo? Now, we don't have master clinicians like this guy. Tell Raja nationwide though. So we're not going to be able to identify all of these patients who require further intervention. So what, what, what can we do now that we have this brand new technology? Now, if you think about it, all of this information is digital information. You know, it's all kind of 1010 some way and where, where is your it guy that I met? Where is it? Yeah. So, so you know, there's a huge a mountain of information in just a 12 liter electrocardiogram. And, and I can tell you that we've got, I mean, I I know you've got smart electrophysiologists, but we've got this guy named Sam er Vam, who's the smartest guy. I know and he can look an electrocardiogram and he can tell me, oh, this person has uh aortic stenosis. The gradient is 30 the chances of him developing atrial fibrillation are 30% in one year. And the chances of him dying from his aortic stenosis are 50% in two years. He can do that from a 12 liter electrocardiogram. So he's seen things that mere mortals like myself cannot see, but perhaps the data can do that. So they've actually done this. They've taken these 12 lead electrocardiograms and use machine learning to diagnose significant valve disease. We started out saying, yeah, we can diagnose left ventricular dysfunction. We know if a patient's got an ejection fraction of less than 30% based on only the electrocardiogram. We know hypertrophic cardiomyopathy, we can diagnose hypertrophic cardiomyopathy with a 90% accuracy. Now, we've even looked at valve disease. We've looked at aortic stenosis. Now, this little chart here on the left is what um we report out at mail. So we get a 12 lit electrocardiogram and then we hit, well, let's look at the A I of the 12 liter electrocardiogram and this is the probability of aortic stenosis. And this is a uh uh uh a gentleman who had been followed in our primary care clinics for year decades and um nothing was ever done. And when I saw him last year, he was in critical aortic stenosis and heart failure pretty much too late. I mean, we, we, we were able to make him better, but it really was too early to be able to intervene. But if you take a look at this probability of aortic stenosis on the, on the y axis and the years are on the X axis there. When he was first seen, he had this electrocardiogram, probably not much there. Um A number of years later he had this electric car. I don't see a difference but the computer did and said he's starting to develop aortic stenosis, which is significant. A few years later, I don't see a difference. Sam Eer Botham could have seen a difference, but I don't see a difference. And the same boy, that chance of aortic stenosis significant aortic stenosis is markedly increased. And then finally, when I saw him, he had hit the roof, but it just shows that there's digital information out there isn't something as simple as a 12 lead electrocardiogram that's gonna help us identify these patients. So you can send them to Matt and D pack for their evaluation and figure out what they need. And it's interesting that even those with nowhere mild or minimal aortic stenosis to start with that 12 liter. There's something in that electrocardiogram that tells you this person's gonna progress. So um if they have a positive electrocardiogram, their chances of developing severe aortic stenosis are twice as much over 15 years, that if they did not have a positive electrocardiogram, kind of interesting kind of out of this world, but it's here and it's here for us to see. So the future of valvular heart disease is to take this digital information and put it through a convolutional network artificial intelligence. Now that will help us with earlier diagnosis. And I think that's important because those patients can then be identified and sent to this gang here to take care of. But it also is going to help us with the lower threshold because you probably sensed when I was talking to you about when we're going to intervene today in 2023 on the patient with asymptomatic severe aortic stenosis. I was kind of hedging saying, well, you could think about this or you could think about that because all we actually had was the ejection fraction symptoms and the gradient and valve area. But there's a whole lot of other things that are starting to arise. I showed you some of them. But if you think about it, we've got diastolic function, we've got stroke volume, we've got this thing called torsion. Torsion is you know how much this heart twists and untwists and how, how, how that myocardium works. You can do it at strain. You can look at biomarkers, you look at gadolinium enhancement defects. And there's been groups that have developed a network tomography for understanding these patients with aortic stenosis and have combined all of the information. That's why I'm glad you've got this. You, you know, uh uh huge EMR in your system now because you can take all this data in and, and you can try to develop because there's going to be data there that we don't even realize is going to be important. And it can all go through a machine learning process to provide a precise phenotypic risk of assessment for an individual patient. Right now, we've got these big groups and these groups are based on these large trials. But what you want is an end of one and to derive all of this information from your E hr and your echocardiograms and so on and your electrocardiograms to be able to say, hey you Mr Jones at 58 years old, even though you are an attorney, I can tell you that you've got this risk of developing severe problems and we should probably intervene sooner rather than later. The other future is, you know, this group is very, very aggressive, very cutting edge, very on top of things. Right now, we've got Tabby, we've got MitraClip, but there's this whole bunch of percutaneous valves in the future that are coming in that are going to be better and better and better. I see the surgeons going out of business soon because they can do so much as the technology increases and increases and increases. And that will again lower our threshold for intervention knowing that the risk is going to be markedly decreased. So I was supposed to tell you what I was gonna tell you. I think I told you. But what I told you is this is number one for the fellows, the conventional framework aortic stenosis operate at symptoms or a drop in ejection fraction. Number two, though, understand the new paradigm that we've got to have a lower threshold for intervention because of the progressive myocardial dysfunction that develops from long-standing pressure overload. And the same applies for mice regurgitation and tricuspid regurgitation and aortic regurgitation with volume overload. They're developing better and better, less invasive interventions. And we are going to be using machine learning artificial intelligence to tell us how to manage properly an individual patient in the future. Thank you very much for your attention.
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