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Preventing Sudden Cardiac Death in Heart Failure
HF with Recovered EF (>45%) (Presenter: Jane E. Wi ...
HF with Recovered EF (>45%) (Presenter: Jane E. Wilcox, MD)
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Video Transcription
All right, so we'll be talking about preventing sudden cardiac death in heart failure with recovered ejection friction. And again, I'm from Chicago, not Australia. So this will be sort of our roadmap of our learning objectives. I think it's really important as we talk about sudden death in this new phenotype or new population that we review some current definitions of recovered EF, because it's definitely a moving target. We'll talk about remission and recovery as it relates to sudden death. Some of this is sort of my opinion based on the data, obviously, but there's not much of that, and we'll go over it. And then we'll talk about some modalities to risk stratify your patients who have experienced an improvement in their ejection fraction to prevent sudden death. And then finally, I'll talk about the utility of genetic testing in patients who've recovered EF. So this is sort of what we had previously been taught about the natural history of heart failure, that it's this sort of progressive downward spiral with acute decompensations and periods of stabilization. But we all know that this is in fact not true. And this natural history of heart failure perhaps should look something like this. And this is work that Dr. Stevenson published a couple of years ago that's really fantastic. And this really summarizes the early era of heart failure where we sort of had this stepwise progression, everyone stage B, then stage C. And then finally, this is my wheelhouse of patients with stage D or refractory heart failure. And in the middle here, everyone can experience sudden death. And in fact, patients, that risk of sudden death really doesn't go away. But we do have patients that do experience improvement in their ejection fraction. So if this is heart failure with better EF or cardiomyopathy, improved EF, recovered EF, whatever nomenclature we want to call this, these patients are definitely different than these patients, both in terms of their risk for pump failure and perhaps in sudden cardiac death as well. So indeed, a new phenotype has emerged. And for the purpose of this talk, I'll call this recovered EF. But there are, again, various terminologies out there. And we see this in our clinical practice all the time. This is work that we did from the Improve HF Registry several years ago now that was a performance improvement initiative to get people on guideline-directed medical therapy. And what we saw was, in fact, over a third of patients had durable improvement in their ejection fraction that was clinically meaningful. It started with 24% and went to 46%. And this is associated with improved survival as well. This is data from the Penn Heart Failure Study that shows that you've got patients here with heart failure with recovered EF as opposed to half-PEF and half-REF and their risk for mortality. And this is a period of time over eight years. So these patients do have improved survival. But then we're sort of troubled with, obviously, what we'll talk about is sudden cardiac death. And just before we do that, though, I think it's important to talk about definitions. And this slide is not, you know, B33 bingo. But what it's meant to do is really look at, this is the middle. This is heart failure with recovered EF. And these are the different studies that are out there defining these populations. And the important part here is that the definitions vary. And so you have people, is it EF 40 to 50? Is it EF greater than 50 that was previously lower? And so I think the, and then who sort of improves? And what is the percentage of people? And across all of these studies, what I'll draw your attention to is that about anywhere between 10% and 20% do have recovered or improved ejection fraction. And most patients, I think it's easier to sort of define what recovery is not as opposed to what recovery is. I think recovery is not mid-range EF. We have to keep in mind the idea of trajectory. So patients who improve their EF that's not accompanied by positive remodeling or an improvement in volumes, that is also not recovery. And anything that's sort of within standard error of an ejection fraction on your echocardiogram where one sonographer or one reader may call it 41 and another calls it 35, that is not also recovery as well or recovered EF. So now that we have sort of these definitions in place, I think if you have a patient who has greater than 10% absolute improvement of their ejection fraction to an absolute, to a number of greater than 50% with their final EF, those are patients that we're starting to think about in the recovered EF population. So how do we risk stratify this recovered EF patient for sudden cardiac death, aka I'll call this the generator change, because this is the clinical question that we're faced with is this patient had an ICD, they were started on GDMT, and their EF is now 45, and it's time for the generator change. You know, what do we do? And so this is some data from Circarrhythmia EP from a couple years ago now. And I'll just walk you through it. This is a retrospective look at two large academic centers. So it was Mayo and BI over 10 years. And they had 1,700 generator changes. They excluded patients who had secondary prevention. And this is a primary prevention population. And they also excluded patients who had prior appropriate ICD therapy. So obviously, if you've received a shock for VT or VF, go ahead and they thought it was, there was no equipoise, you know, to patients, they excluded them. And this was purely a primary prevention look. And so we had 253 patients. And what they saw is, so here's the patients, this is sort of the table one. These are the characteristics. And I'll draw your attention to, these are mostly men, they're mostly white men, older, and they're mostly ischemic cardiomyopathy. And what they saw is, here are the Kaplan-Meier curves, and these are the patients who had persistently reduced EF as opposed to patients who had recovered EF. And while there was a reduced risk of appropriate ICD therapy, there was a 10% of patients who received a shock at two years. So sort of a persistent risk of sudden death, or at least appropriate ICD therapy. And when we look at predictors of future shock or therapy, any heart failure doc can look at these and say, well, this makes sense. Serum sodium tracks with overall mortality and heart failure, as well does a drop in EF. And so there was a hazard ratio of 1.9 for a drop in EF and 4.3 for serum sodium. So this, what about data from a clinical trial? And so this is data from, it's a post-doc analysis of the SCUDHEF trial, Sudden Cardiac Death in Heart Failure trial. And what we see here is that patients who had an improvement in EF to greater than 35% during the follow-up period accrued a similar mortality benefit with an ICD as those whose EF remained less than 35%. And importantly, there was no interaction between ICD and repeated EF for predicting mortality. So for the gen change question takeaway, I think, importantly, we can just recognize that this is an important clinical question. Over a quarter of patients without prior appropriate therapy will have an EF greater than 35% at the time of generator change. That was from the paper that I first presented. So this is going to come up a fair amount in our clinical practice. And what we can say is that patients with an EF greater than 35% continue to receive appropriate ICD therapy, albeit lower than persistent reduced EF. It's 5% per year, but probably should be doing generator changes, at least in this population. Again, limited by, this is a retrospective analysis, but mostly ischemic cardiomyopathy older white men that they would accrue a similar mortality benefit. What about the idea of remission versus recovery in sudden cardiac death? And this is a little sort of out there, but maybe we can get some answers from the MADE AT CRT trial. And what this is is, again, a post-hoc analysis of MADE AT CRT where they looked at patients who did, in fact, they're sort of super responders. They responded very well to CRT pacing, and their EF got greater than 50%. And when we look at the overall risk of VTAs, which is a VT, an arrhythmic event during the three-year follow-up period, patients who had reduced EF are here, mid-range EF are here, and then these sort of super responders with the EF greater than 50%, there were only 6% among this normalized or recovered EF population that had a VTA, and there were actually no shocks and no deaths in patients who had an EF greater than 50%. Now importantly here, if you look at, this is, the follow-up period is about two, two and a half years on average. So this is a short follow-up period, but maybe these super responders, their risk for sudden death is, in fact, close to zero. So how else can we risk stratify our recovered EF patients for sudden cardiac death? And I'll just take a little bit into looking at imaging characteristics, and then this is my friend and former fellow, Monica Aurora, who is very good at talking to patients. And so family history is very important, and then some imaging characteristics, and then finally genetics. And so what we see here, this is a picture of, this is a cardiac MRI, and mid-wall fibrosis is definitely a predictor of sudden death, and we see this in dilated cardiomyopathy patients who are undergoing CRT, where they, in fact, had a very, very low risk of cardiovascular mortality in patients who did not have fibrosis. So imaging characteristics can help risk stratify our patients as well. Family questions, I think it's really important as we're talking about patients who have this recovered EF, who have, these are for our sort of non-ischemic cardiomyopathy patients. You really have to ask in a way that patients understand, not necessarily, you know, did someone have an arrhythmic death, it's did they die suddenly, were they in the motor vehicle accident, fainting, that sort of thing, and obviously remembering muscular dystrophies that can associate with arrhythmic deaths and also cardiomyopathy. So this is a question that I think comes up a lot in clinic as well. So you have a patient who has a recovered EF, but they were not a traditional candidate for ICD or CRTD. So the patient presumably was started on guideline-directed medical therapy for heart failure, and they improved their ejection fraction to above 35 percent within that three-month period of time, maybe after their de novo diagnosis of heart failure. What about those patients? Are they at persistent risk for sudden cardiac death? And this is where I'll make the argument that we should be thinking about cascade, about genetic testing in this population. Clearly asking a family history of any arrhythmias or associated dilated cardiomyopathies will be important, but I think it's also important to look at these patients because their risk of arrhythmia or sudden death may still be there, may still be persistent, despite normalization of their, or close to normalization of their ejection fraction. And these are some genes that are really important that you may recognize here, PKP2, filament C, SCN5A in the EP audience. And because there are genotype-specific responses to both guideline-directed medical therapy, but also for persistent sudden cardiac death, despite normalization or even a normal EF. And so one cardiomyopathy that I think we should all be aware of is Lamin, Lamin A cardiomyopathy. It's almost 10 percent of all dilated cardiomyopathy. It's autosomal dominant, usually presents with more arrhythmic-type features early on, and systolic dysfunction is late. And these patients are at high risk for sudden death, and an ICD is recommended, even with normalization of EF. Again, a highly morbid form of dilated cardiomyopathy, and this is where genetics and a careful family history can really guide our shared decision-making with patients. So our take-home points here, I think recovered EF is a moving target in terms of definitions, but really what we're looking at is positive remodeling to guideline-directed medical therapy, and even pacing therapy for super responders. In EF of greater than 50 percent, and they have to have this absolute improvement of greater than 10 percent. We've seen from some post-hoc analyses that patients do get benefit from ICD-Gen change, albeit at a lower absolute percentage than patients with persistent EF, but we probably should be doing that generator change, or we don't have data to suggest otherwise in the current era. The CRT super responders, if you do have someone who has normalization, you image them, they have no fibrosis, those patients may not need CRTD. I think the jury is still out there. And finally, for risk stratification of sudden death, using MRI to look at fibrosis, family history, and considering genetic testing in our patients. I'll just make a plug for our recovery clinic here, where we're really focusing on recovering patients using fibrosis imaging characteristics, genetics, to inform durability, and also their risk for sudden death. So thank you, and I'll take questions. This is a beautiful and very thoughtful analysis, Jane, I think, and getting right at the questions that we need to answer even before we have data. Very nice. One of the things that I've been humbled by is that whenever I talk about, you know, the people never recovering, except for, of course, the peripartums. And now what we know about Titan suggests that even in the peripartums who recover, that many of them may have a Titan genetic mutation, such that maybe they're not normal. So we're learning an amazing amount to show that we weren't right before. Question? So patients with PVC-induced cardiomyopathy or tachycardia-mediated cardiomyopathy that receive ablation, and their EF recovers, would you stop their guideline-directed medical therapy or not? I love this question, because it's a two-parter for me. We struggle. I'm a neurophysiologist. That's my disclosure. So first of all, I'll push back a little bit and say that how do you know it's tachy-mediated and how do you know it's PVC? I think we throw around these terms, but we have no idea. And those patients might have a lamin mutation. They may have a Titan mutation that, you know, which comes first, the chicken or the egg, we don't necessarily know. But I think we do ourselves a disservice when we try to label them as these types of cardiomyopathies, and we haven't really understood the myocardial substrate. So that's the first thing. The second thing is I would never stop their medical therapy after they've recovered, and we have some data to support that from the TREAD-HF trial. So it's a small trial, 50 patients, half were randomized to withdrawal of medical therapy, and within three or four months, they had recrudescent heart failure. So I don't think at this point, at this juncture, we have enough data to stop GDMT. And then the second point is, you know, I would look further into what's going on with this tachymediated and try to really get away from, you know, labeling people when we don't understand the substrate. So how would you explain, then, the improvement in EF after the procedure? Yeah. So we see that. I mean, clinically, we see that. Even if they have lamin? Yeah. No. Yeah. We see that all the time. I think AFib is bad. We can all agree that AFib and PVCs are bad. But doing something to modify the substrate, getting them back in normal sinus rhythm always is good. You know, clinically, patients like that. For our lamin patients who present more with arrhythmias first, if we can get them out of AFib, it's like whack-a-mole, if we can modify the substrate, their EF does improve. But we have to figure out what's going on, like what caused it, not just, you know, make it go away and then, you know, hope for the best. Thank you. That's great. Thanks. Back microphone. Hi. Jason Davis from Halifax in Canada. Thank you for the presentation. With the patients who are medical therapy, they've been on optimal medical therapy for three months, these are patients that, in electrophysiology, we don't normally see because they never get referred for consideration of an ICD. Who are you doing the genetics on to screen? Are you screening everyone or? I'm having trouble hearing. I think your question was in these patients who have recovered their EF within three months, three to six months of GDMT, would you still do genetic screening on them? So that's a great question. I think if you have, I think we have to have a clear trigger for what happened to them. So if you did a biopsy and they had myocarditis and they recovered, I mean, that's one thing. But if you have a patient who, you know, a peripartum, for example, and I actually pulled this up. If you have a patient who is peripartum or a patient who maybe was alcohol induced or you don't have a great reason why they developed heart failure in the first place, I will take off. What I'll end up doing is take a really detailed family history with those questions that I put up and 90% of the time I'll find somewhere in three generations that someone else had an arrhythmic event, sudden death, heart failure that comes out in an autosomal dominant pattern and I end up doing genetic testing and we find something. So I'm not saying that we should, you know, blanket do genetic testing, but we really need to be, I guess, more thoughtful and put it on our radar. Thank you. I think since you come from a place other than the U.S. that part of the point of your question is probably the cost, effectiveness of genetic testing. I think certainly many of us towards the front of the room would like to do genetic testing on all these patients and do when we get the chance. On the other hand, from a governmental standpoint who has to control resources, I think currently we would feel that those people with the strongest family history and the clinical phenotype of an inherited disease are those in whom we would focus first. Absolutely. And younger patients as well. So, you know, if you have a patient who's 60 and presents with heart failure, that's a different story than a 35-year-old, I think. Jane, very nice talk. Thank you. It seems like today we've seen so far as well as the more recent data on kind of the dynamic nature of EF really highlights what a poor marker it is of sudden death and of potential benefit. So my question is, are we ever going to get totally away from that? And how do you guys, you or the panelists, see us re-stratifying these patients better? Because EF of 30 to 36, EF that changes, I mean, they might, whether a patient gets a primary prevention device, sometimes just depends on when they happen to get their echo, it seems. And so how are we ever going to get away from that? I'm interested what you think as well. But what I try to do is use multi-modalities, you know, using echo with contrast, using strain imaging, using MRI for fibrosis. I mean, if someone has a ton of fibrosis and their EF is 35% or 34%, you know, I think they're probably at higher, I know they're at higher risk. But I have to get that paid for. You have to get that paid for? Well, that's... So as the electrophysiologist here, I'm going to ask both of you to tell us what to do. Because typically, you're absolutely right. We use an echocardiogram. And if we don't like that, we'll use a nuclear medicine study, and then that's it. But I think we need some direction how to better look at these patients. Is that kind of... Yeah, right. And then we have to fight with somebody to get it paid for when the EF is 36. Well, I think in terms of asking what we can do better, you have to recognize that we're looking at most a few events a year in terms of sudden death in these patients. So it's going to be very hard to come up with a test that's really accurately going to predict it because it's going to be multifactorial. It's going to be the substrate plus a trigger, probably plus some other permissive event. So we're never going to be able to predict them with much accuracy, no matter how good our test is. So I would start with that. You know, we can't predict the rare event well. I think that we do look at a combination of things, not only the EF, but the ventricular size. And certainly I think MRI fibrosis is increasingly going to be something we're going to be looking at as soon as we can do it more commonly in people who already have hardware. But the question is, if you have an EF of 36, you repeat it until you get 34. If you have some reason to be really concerned because they have frequent non-sustained VT or there's a questionable family history. The other thing I think in terms of the guidelines, if you find a family history that you think is suggestive of a sudden death phenotype, you can put a defibrillator in for any evidence of cardiac disease. It does not have to be an EF of 35. And I use that frequently in this population. Thank you. Thanks. That was great. All right, thank you.
Video Summary
The video discusses the prevention of sudden cardiac death in heart failure patients with recovered ejection fraction. The speaker reviews the definitions and characteristics of recovered EF and highlights the importance of risk stratification for sudden death in these patients. The video emphasizes the need for guidelines on generator changes for patients with recovered EF, as well as the potential benefits and limitations of genetic testing in these patients. The speaker also discusses the role of imaging characteristics, such as fibrosis detected by cardiac MRI, in risk stratification. Overall, the video highlights the emerging understanding of recovered EF as a distinct phenotype with its own associated risks for sudden cardiac death.
Meta Tag
Lecture ID
5016
Location
Room 152
Presenter
Jane E. Wilcox, MD
Role
Invited Speaker
Session Date and Time
May 09, 2019 4:30 PM - 6:00 PM
Session Number
S-046
Keywords
prevention
sudden cardiac death
recovered ejection fraction
risk stratification
genetic testing
fibrosis
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