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Preventing Sudden Cardiac Death in Heart Failure
Heart Failure with Preserved Ejection Fraction (HF ...
Heart Failure with Preserved Ejection Fraction (HFpEF >50%) (Presenter: Nancy K Sweitzer, MD, PhD)
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Video Transcription
So thank you very much for including me as part of this session. I'm going to summarize the data that exists on sudden cardiac death in the population with heart failure and preserved ejection fraction. And this is the title I was given, so we're really going to talk about sudden death, which is different than sudden cardiac death or even sudden arrhythmic death, clearly. And we'll talk about what's known. So this is a somewhat complicated slide, but what it gets at is the growing problem of heart failure with preserved ejection fraction, particularly as we age, relevant to Dr. Steinberg's presentation. So this is a collection of about nine epidemiologic studies, arranged in order of the mean age in the study, from age 58 to age 80. And then looking at the prevalence of heart failure in the green bar, which gets as high as 8% in the elderly groups, and which proportion of that is due to heart failure with preserved ejection fraction in the orange here. And so the absolute prevalence of HFPEF is about 3% to 5% when you look in the very older groups. And the percentage of patients with HFPEF of all the patients with heart failure is well above 50 in most of these studies. And that's clearly true as patients age. More women are older. Women are predisposed to HFPEF. So I think all the points that Dr. Steinberg just talked about are inflated by orders of magnitude in this population. The other thing that's very clear is that HFPEF is probably not a single disease. It's a collection of diseases. Maybe you need two or three of these hits to actually manifest the clinical disease, but it's a combination on the left here of physiologic and anatomic abnormalities combined with comorbidities, many of which can be very important and contribute to risk of sudden death, as we'll see. If we look at modes of death in heart failure and heart failure with reduced ejection fraction, it's pretty easy. They die of worsening heart failure or sudden cardiac death, and the sudden cardiac deaths are overwhelmingly tachyarrhythmic in nature. And other cardiovascular or non-cardiovascular causes are quite rare in this population. It makes discussions about death with patients actually quite straightforward. In HFPEF, it's much less straightforward. They have multiple modes of cardiovascular death. It's an elderly, often hypertensive population, so they have a lot of cerebrovascular deaths along with MIs and other vascular causes of death. Sudden death can be bradyarrhythmic events as well as tachyarrhythmic events or non-arrhythmic sudden death. And there are many non-cardiovascular causes of death, and we'll look at the epidemiology of this, but in some cohorts, non-cardiovascular death is a very, very considerable competing cause. The best adjudicated data we have about mode of death, and particularly sudden death in HFPEF, is from the TopCat trial, and this is an analysis we published looking at the American cohort or the Americas cohort, excluding the Eastern European cohort. And they had a very well-thought-out a priori definition of sudden death for this trial. It was pre-specified as an endpoint in the TopCat trial because it had been seen in previous HFPEF trials at a fairly high rate. So it had to be a witnessed or presumed unexpected death or an aborted cardiac arrest to be counted in this analysis. And in the analysis, what we found was that about 19% of total deaths met this definition of sudden death and 32% of cardiovascular deaths in the Americas, which, if you're not familiar, was probably a more pure HFPEF cohort than the entire trial. However, if we look across all randomized trials of HFPEF where they've looked at sudden death, which includes the iPreserve trial, the CHARM-Preserve trial, and the TopCat trial, you can see that in these clinical trials, the majority of deaths are cardiac. So the numbers of cardiac deaths are on the top, non-cardiac deaths on the bottom for each of these trials. And all of these trials showed a predominance of cardiac death in these populations. So if we look at, for example, in the iPreserve trial, there were 231 sudden deaths, 43% of the cardiovascular deaths, and 26% of the total deaths were sudden death. In CHARM, these were the numbers, and in TopCat, these were the numbers. And this is in the whole TopCat cohort, so a little bit different. But if you look at these, about a quarter of the total deaths across the board were sudden deaths in all three of these trials, which is relatively impressive. If we look at epidemiologic trials, not randomized clinical trials, the data are a little bit different, and it's incredibly variable. So if we just look at these two trials that reported non-cardiovascular deaths, there's a Japanese registry called J-Care Card. In that registry, 28% of the deaths were non-cardiovascular, as opposed to Olmstead County, where 49% of the HFPEF deaths were non-cardiovascular, so very widely variant there. But if we look at sudden death, and we look at it the same way, they're very small numbers in these three trials, less than 20 in all three of these epidemiologic trials, but very consistently 10% to 20% of total deaths. So I think when we move from the randomized trial population to the epidemiologic population, we have to realize that we're generally going to an older, highly comorbid population, and sudden death is going to be a much smaller percentage of total death in those studies. When population studies are done comparing HFREF and HFPEF, it's actually quite consistent across trials that rates of sudden death are about half of what is seen in HFREF. So it's not as prevalent a cause of death in this population, while heart failure death rates are quite comparable in these studies. So can we predict who's at risk for sudden death in the HFPEF population? Well, I preserved in an analysis, and they came up with six predictors of sudden death. And if you look at these predictors of sudden death, they're really largely coronary disease markers, male sex, age, diabetes, prior MI, and left bundle branch block. So it looks like it's the people with potentially at least ischemic substrate, and then high BMP. In the Japan registry, interestingly, they saw that lowered GFR was actually the strongest predictor. And that's a population nobody likes to put devices in. And then in TopCat, there's a mixture. Low GFR did come up in TopCat as a predictor of sudden death, but also markers of ischemic disease and smoking came out in TopCat. So I think that looking at the ischemic population may be interesting, and this is a registry from France where they took patients with heart failure and stratified them by coronary disease and cause of death. And whereas in HFREF, both sudden and heart failure related death are more common in the coronary disease population, but not all that different for sudden death. In HFPEF, there was a quite distinct difference. Heart failure death was more common in the no coronary disease patients, but coronary disease patients had a much higher risk of sudden death. I think that cardiac imaging might help us in this population. These are T1-weighted cardiac scans looking at a normal heart here on the left, and you can see that there's about 20% extracellular volume in this normal myocardium, whereas on the right, a HFPEF patient has more like 40% to 50% extracellular volume in many areas of the myocardium. And so these don't show up as gadolinium. They're not confluence scars, but it's extracellular matrix growth or expansion in these patients. And there are a few studies now showing that this pattern seems to be more associated with sudden death risk in this population. This was an interesting recent paper showing two phenotypes of HFPEF patients by T1 imaging and then looking at differences between whether there's a primary myocardial problem with very high myocardial stiffness or more of an arterial problem with hypertension and arterial stiffness and a hypertensive response to exercise. So I think we're going to get smarter about this and maybe figure it out. To target sudden cardiac death, particularly with ICDs, we have to know that tachyarrhythmic death occurs in the population at a significant rate and then find those populations. And this is difficult. All of these studies I've showed you show sudden death, not sudden cardiac death or arrhythmic death. And all of this really, really important information is unknown in most of these studies. We don't know what was happening to the patient when they died. And so, of course, sudden death can be due to non-cardiac events, cardiac events that really aren't arrhythmic or arrhythmic events, and device therapy is only going to help a percentage of this. So we have to get a little bit more educated about what's happening in these patients when they die suddenly. And there is some hope. There's a trial called VIPHF, which has completed enrollment, which put implantable loop recorders in HFPEF patients. So presumably we'll learn something from that about what's happening when these patients die. The MAIDET-SICD trial is putting subcutaneous primary prevention ICDs in patients with intermediate EFs, and you're going to hear about mid-range EF in a minute, but that might give us some clues to what might be important in the preserved EF population. And then I think because diabetes does repeatedly come up as a risk factor in this population, we're going to learn some things from the SGLT2 inhibitor trials that are happening in HFPEF about whether sudden death risk is reduced by these drug therapies. And I'll stop there and take questions. Thank you very much. This was a wonderful analysis, Nancy. I have a question, and this is particularly relevant to the MAIDET-SICD. Do you suppose that some of these deaths are, in fact, bradycardic or in some way reflex-mediated, such that what we need to do is to be pacing them, not defibrillating them? Yes. So, you know, that's a really intriguing thought. I think, as we all know, there are two questions there, right? Are they bradyarrhythmic deaths, which I think certainly probably many of them are, just based on the age of the population alone? And then the second question is, are they preventable bradycardic deaths, right? So would pacing actually change the natural history of that terminal arrhythmic event? And many of these patients, with the risk factors, diabetes, worse renal function, are going to have metabolic abnormalities that make them less responsive to pacing as a rescue therapy. So I think we have so much to learn about how we're going to prevent death, and we don't, I mean, we have nothing that prevents death in this population yet, so maybe devices will be better than what we have. I just worry if the sub-QICD trial is negative, we wouldn't necessarily know that an implantable device would be negative because it provides pacing. Absolutely. I think that my hope for the sub-QICD trial is that we learn something about the patients who respond and don't respond. Even if it's negative, we might get a signal that can help guide us as we look to device therapies in subsets of these. I don't think we're ever going to do this in HFPEF across the board, right? We're going to pick HFPEF patients we think are going to benefit. It seems that the earlier you get to them, the better, and that you almost have to have a differential diagnosis of the HFPEF population because they're not all the same. But it does beg the question about whether, in the future, wearables that not only tell you about heart rates but tell you about other things might really be very helpful in this population. I do think we're about to enter an age where things change in this disease. One of the things that's going to change it is that we now have an effective therapy for amyloid. So patients with HFPEF or LVH are going to start getting referred in, and maybe we'll start diagnosing this disease earlier in the non-amyloid patients. And then, absolutely, the wearables are going to give us a lot of information about what's going on with patients, sleep apnea, heart rates, activity levels, all kinds of things that will be really informative, I think. Thank you. This was a wonderful presentation. Do you see any role of strain imaging in risk stratification of these patients with HFPEF? So, great question. Strain imaging, clearly, I mean, some of the work I've done shows that strain is not normal in these patients, and particularly with exercise. So they don't increase strain with exercise like normal patients do at all. In fact, most of them have no change with exercise. So there's impaired recruitable contractility in these patients. The problem is that, as with everything with these patients, often at rest it's not that different from normal. It's really exercise that brings out the abnormal phenotype by imaging in these patients, and that's made it much harder clinically, right, because they don't like to exercise, and exercise imaging is just more difficult. So I do hope that we can, as we get better at strain, that we'll pick up subtle abnormalities at rest, but there will still be a population of these patients who are stone-cold normal at rest and really only abnormal with exercise, and that's challenging clinically. Thanks. Thank you for the presentation. Is there any relations of sudden cardiac death and atrial fibrillation in these patients? Great question. So atrial fibrillation is quite common in this population. Estimates range from 25% to 40% of them having atrial fibrillation. And is there any relationship between atrial fibrillation and sudden cardiac death? Yes. Not that I have seen, but I've not seen an analysis that broke it down by atrial fibrillation. So the question, I guess, would be, is atrial fibrillation a marker of fibrosis, which may also predispose to ventricular arrhythmia? I've not seen that. It's a really intriguing analysis that could probably be done quickly. Thank you.
Video Summary
In this video, Dr. Nancy Moss discusses sudden cardiac death in patients with heart failure with preserved ejection fraction (HFPEF). She presents data showing the prevalence of HFPEF in the elderly population and highlights that HFPEF is not a single disease but a collection of diseases. Dr. Moss explains that the modes of death in HFPEF are more complex compared to heart failure with reduced ejection fraction (HFREF), with multiple modes of cardiovascular and non-cardiovascular deaths. The data also suggest that sudden death is less prevalent in HFPEF compared to HFREF. The video discusses predictors of sudden death in HFPEF, including coronary disease markers, male sex, age, diabetes, prior myocardial infarction, and left bundle branch block. Dr. Moss also introduces the use of cardiac imaging and wearable devices to aid in risk stratification and potential prevention of sudden cardiac death in HFPEF patients.
Meta Tag
Lecture ID
15771
Location
Room 152
Presenter
Nancy K Sweitzer, MD, PhD
Role
Invited Speaker
Session Date and Time
May 09, 2019 4:30 PM - 6:00 PM
Session Number
S-046
Keywords
sudden cardiac death
heart failure with preserved ejection fraction
HFPEF
modes of death
predictors of sudden death
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