with the Heart Failure Society of America for our special seminar on heart failure and sleep apnea, focus on sleep, failure to sleep. This is a topic that I think is fascinating because there are so many, so much overlap between sleep disorders and heart failure, and many of us who are clinicians deal with this on a daily basis, and so we're very excited to bring to you today this special seminar. First, I'd like to thank our supporters. Both Zoll and Inspire Medical Systems have provided us with educational grants today to provide this information. This program today will be recorded and be available through our learning center as well for those of you who want to share this with your colleagues. And to claim credit, learners are required to complete a course evaluation, and the evaluation will be available in the Heart Failure Learning Center at the conclusion of the event. So first to introduce our program planners. I'm Jennifer Cook. I'm from the University of Cincinnati, where I serve as a heart failure cardiologist. We have with us today Ann Laramie. She is from the University of Vermont Medical Center, where she is an advanced practice practitioner in heart failure, and also Erica Schoenborn, who's from Eastern Carolina University, where she is a heart failure PharmD. And so both of them are volunteers and work really hard with the Heart Failure Society of America, and we're really glad to have them volunteering their time to put on this program today. Thank you and welcome to both of you. Our faculty include Dr. Gregory Jackson from the Medical University of South Carolina. He is a heart failure faculty there who has an interest in sleep apnea and is always looking for sleep apnea and how to treat sleep apnea in his patient population. Second, we have Dr. Sogal Jabahari, who's at Harvard Medical School, who has an interest in, who is a sleep medicine physician who has an interest in cardiology as well and is participating in research where the two fields combine. And then we have the distinguished Dr. Atul Mahutra, who is here from UC San Diego, who is well known in the field of sleep apnea, who has both served as an editor, a publisher, and also educator in the field. So we're very glad to have this panel of speakers who are going to allow us to explore over the next time period sleep apnea and heart failure. So we're going to actually begin and end today with case discussions. And so what we've done is prepared some cases that are very common presentations that we see in our clinic that I personally often struggle with. So I've come with some questions myself of how to solve some of these problems. Then we're going to have a pathophysiology lecture, followed by some descriptions of both central and obstructive sleep apnea, followed by a deeper dive into cardiology and sleep disorder breathing, and like I mentioned before, a follow-up with a case discussion on diagnosis and treatment. And so without any further ado, we're going to get started with our first case presentation, which is going to be presented to us by Erika Schonborn. Erika. Thank you, Dr. Cook. Yes, I'll be presenting our first case today. So we have a 58-year-old female with recently diagnosed non-ischemic cardiomyopathy with HF-REF. Her ejection fraction is 30% with NYHA class 2. She's being seen in your heart failure clinic. She complains that she can't sleep since starting her new medications. Her vital signs are fairly unremarkable, aside from a BMI that places her in the obese category. She appears euvolemic on exam. Her labs are relatively normal and at baseline. Her current medications, which were started at the most recent hospitalization prior to this clinic visit, include bumetanide, carvedilol, impagliflozin, sacubitrildalsartan, and spironolactam. The patient remembers being told in the clinic or in the hospital that her medications would likely be increased in clinic, but she declines any medication changes at all. But she declines any medication changes at this time and reports fear of her sleep getting worse. She asks if any medications can be stopped or changed. How would you approach this patient? I think this is such a great case because as a heart failure physician, we always ask about sleeping, you know, curious about orthopnea and PND, but what we end up hearing is complaints of insomnia, which I am not prepared at all to deal with. So how do we start with this? So how do we start to assess a patient who is complaining of insomnia? So I can start. My voice isn't great today, but I'll try. You know, insomnia is tricky because it falls into different categories. There's trouble falling asleep, trouble staying asleep, and early morning wakening. When somebody says they can't sleep, you really want to dig into the history of what they mean by that. Some people say they can't sleep because they wake up short of breath and some of them have sleep apnea or something. Some people can't sleep because they have restless legs or aching pain in their legs and that's bothering them. Other people with heart failure or on diuretics or whatnot can't sleep because they have nocturia and they get up to pee and that kind of thing. So you really want to dig into what do they mean by I can't sleep. It's true that Jardians and some of these medications have insomnia as a side effect, particularly in older women, but I'd like to know more in terms of what do they mean by I can't sleep. Piggybacking. Oh, go ahead. No, yeah, go ahead. Just piggybacking on what Dr. Malhortra said, there's a high prevalence of what we call co-mysa, comorbid sleep apnea and insomnia. And so it's really important to rule out other sleep disorders, like Dr. Malhortra said, like the restless legs or sleep apnea in patients who present with insomnia symptoms, because especially with central sleep apnea, you can present with insomnia symptoms. But additionally, you can have both conditions and they both need to be addressed. And with the insomnia, you'll often have patients tell you that they have racing thoughts or it's difficult for them to turn their mind off, which can make it difficult for them to fall asleep. Or if they wake up in the middle of the night and have these racing thoughts, it can make it difficult for them to go back to sleep. So that's one thing you could also consider asking. Do you have racing thoughts that make it difficult to turn your mind off when you go to bed at night? This is the first that I've heard that Jardiance causes insomnia. This is not good news for me. Is this anything that anyone's come up with in their practice yet or has it affected their practice? So it's just the tip of the iceberg, I imagine, as we're using so much SGLT2 inhibitors. Erica, do you have any advice for us as far as pharmacotherapy for insomnia? Is it something that heart failure doctors should feel comfortable doing or is this something that we should defer to more expert opinion, expert providers? Yeah, that's a great question. I do feel like, you know, the further assessment and sleep studies are recommended, especially if we look at our guideline recommendations, that's what they're going to recommend. But truly just looking at insomnia, if you can pinpoint that it's insomnia, it is something that we can assess. And so, like you mentioned, SGLT2 inhibitors may increase the risk of insomnia. Beta blockers can actually block the body's natural ability to create melatonin, so that can also cause some insomnia. So sometimes it's looking at do we try trial different types of our GDMT? Do we trial when they take the GDMT? And certainly that's something that our heart failure providers could look at. Another thing to think about, especially, you know, kind of purported in the literature, is assessing a patient's depression and anxiety because this may be contributing to their insomnia, which is, of course, something that we want to do based off of the guidelines. And so maybe thinking about starting an anxiolytic or an antidepressant may be helpful to treat the patient's anxiety and depression, which would also then help with the insomnia. And I'm not sure how often you all see that in your practice where you really need to treat the underlying thing, which may be depression or anxiety. Insomnia and depression, anxiety are very interrelated. They're distinct, but overlapping entities. And they are, I think, two independent conditions that should be treated concurrently. You're absolutely right. Treating the anxiety or the depression can improve the insomnia. But if you don't also address the insomnia, they may have more likely to relapse into depression and anxiety. So it's very important to target both conditions if and whenever possible. And I think she clearly has a new diagnosis of heart failure, and she's probably scared about that and that may be contributing to some of that. And I think that warrants some counseling. But I think importantly is she's saying that she doesn't want to make any adjustments with her medications. And we know that we want to try to optimize and titrate GDMT to get them on target doses with the best chance of recovering her ejection fraction. And so we really need to get to the bottom of why she's having insomnia, why she's not sleeping, try to get her comfortable with that, and be more comfortable making medication adjustments. I would also ask, you know, she's taking diuretics twice a day. What time is she taking them? Is she taking them and she's up, you know, urinating all night? Can we make adjustments with the timing of that? Yeah, if I may, I'd just like to echo what's already been said. And I think the rookie mistake is just give them Ambien or something saying, you know, this isn't my problem. But I think there's several things that have already been pointed out. Some of the pharmacotherapy could be contributing, but also some of the underlying heart failure pathophysiology may be contributing to disrupted sleep. So for example, there are good data that optimizing medical therapy for heart failure can help alleviate chain stokes and other kind of funny breathing patterns. And so aggressively treating the heart failure can actually improve the underlying sleep problem. And you might say, well, this is a goofy problem. I don't care. But, you know, in the era of patient report outcomes, these are sometimes the things that matter most to patients. And in some cases targeting those can help the rest of your treatments. And so patients are more likely to take their medications if they know that they're not contributing to their sleep difficulty and they're sleeping better than they feel better and they become more adherent with other treatments. And so it really can be part of the overall sort of holistic care of that patient. So I agree with Greg and Eric and Sogel in that context. And to that end, you mentioned Erica, the beta blockers. So the more lipophilic, the beta blocker, the more likely it is to cross the blood brain barrier and the less lipophilic it is, the less likely it is. So sometimes it's also a matter if in fact, the beta blocker is triggering insomnia symptoms, or I've had patients say that it disturbs their sleep or affects their dreaming. You could consider switching to one of the less lipophilic beta blockers, such as a TENOLOL, which don't cross the blood brain barrier as much. Yeah, we had a little randomized trial a few years ago to mitigate the sleep effects of beta blockers. We gave melatonin or placebo and there was quite a decent effect. It was about an hour of improvement in sleep. It was a pretty big effect. You don't think of beta blockers as being that big a culprit, but it is amazing, particularly lipophilic ones, as Sogel mentioned, can be problematic. And we don't normally think of beta blockers in that context, but I work in the ICUs as well. And you get beta blockers all the time. You don't think of the systemic effects in time. I just wanted to invite the participants also to place any questions that you might have in the chat. I have it open and available. And so if you have any questions of our speakers, either now or as we continue, please add them there and we will make sure that we address any questions that you have. Any final thoughts on this case and in the heart failure patient who complains of insomnia? I have a quick question for everyone, just really quick, just a quick question, just especially for the audience. So how often do you recommend or recommend against melatonin? You mentioned it. And so I know we see it in a lot of our patients, especially on the inpatient side, it's given out like candy. So is it something we should be recommending to patients on the outpatient side? In general, no, we did a very specific trial because the beta, as you mentioned, Erica, the beta blockers attenuate the melatonin. So we're just trying the pharmacology to see if we could mitigate the beta blocker side effects of melatonin. In general, melatonin is not a very good hypnotic. It's good for shifting body clocks and for jet lag and for certain circadian problems. But in general, it's not a good hypnotic. And as Greg and others pointed out, treating the underlying cause and optimizing heart failure therapy is by far and away, the more important priority. The other point to make, which might've been implied, but not stated is that the pretest probability for this particular patient with FRF to have some sleep apnea or sleep disorder, breathing problem is, you know, 70 or 80%. So getting a sleep test or sleep study might well be fruitful as well. Completely agree with Atul. And I'll add that the FDA did a screen of melatonin and looked at 17 different brands and found other ingredients like diphenhydramine and Viagra in the formulations. So we have to be careful sometimes with supplements and what else they could have in them. So along those lines, I agree with using melatonin very specifically in the important populations that we know it has an effect in. Okay. And one final question we have from Carol, which guideline directed beta blockers for HFRF are lipophilic? Absolutely. So your metoprolol, go ahead. If you want to answer, go ahead. I was just saying your metoprolol is probably one of the ones that I'm aware of. That's the most lipophilic, one of the most lipophilics. And then, so then you have curvatalol is probably a better option. Yeah. And I believe propranolol is as well. And there was mention of switching over to a less lipophilic agent like atenolol. I think when we think of HFRF patients like this and guideline directed beta blockers, we're really looking at curvatalol, metoprolol, succinate and bisoprolol are the three beta blockers that have been shown to have mortality benefit in HFRF patients specifically. So I think we want to try to focus on one of those three agents. That's great. That's great to end on. And so we're going to move on. And of course, this isn't the last opportunity to ask questions. And so we will have more discussion as the seminar continues, but we're going to move along and actually have some questions, some audience response questions that have been prepared prior to our next, to our first didactic session. And so if we could please show the questions and get, have the audience be prepared to vote for their answers. So which of the following is true regarding positive airway pressure and heart failure? Second question is which of the following is true regarding ASV and congestive heart failure? All right. We'll be coming back to those questions after the presentation. And so we'll have Dr. Mahutra go ahead with your presentation, the first presentation of the evening. You see my slides in my mouse? Yes, we sure can. Okay. So thank you so much to the organizers for having me here. I apologize for my voice. If you think I was yelling at the Pittsburgh Steelers on Sunday, it's true, but my voice was bad before that. The Heart Failure Society was very astute to get this topic on the docket because it is a very important one. I'm going to talk about the pathophysiology and I'm honored to share the podium with such distinguished speakers today. I'm at the University of California, San Diego. I do have some relevant disclosures that are listed at the bottom. The first point I'd like to make is just pre-test probability. As I mentioned in the discussion just now, if you take 100 heart failure patients with half-ref, reduced ejection fraction, roughly a third have chained-stokes respiration, roughly a third are obstructive sleep apnea, roughly a third are normal. That's a fairly consistent finding across lots of different studies, whether they're beta-blocked or not, whether they're well-diarrheased or not. It's about a third, a third, a third. That means if you see three heart failure patients this afternoon, roughly two of them will have sleep-disordered breathing, whether you recognize it or not. There are different forms of sleep-disordered breathing. Dr. Javahari is gonna talk more about this. This is a form of central apnea known as chained-stokes respiration. There's cessations of airflow. There's a thermostat in the abdomen. So the thermostat has no airflow at the mouth and nose, suggesting a cessation of airflow without respiratory effort. There's a form of central apnea in contra distinction to obstructive apnea, where there's ongoing respiratory effort during a cessation of airflow. There are three things to point out in association with this breathing pattern in terms of pathophysiology. The first is that every time there's an apnea, there's a desaturation. There's a time delay from the apnea to the desaturation because of the circulatory delay that's common in congestive heart failure. There's also reoxygenation. Hypoxia with reoxygenation can contribute to oxidative stress and progression of cardiovascular disease. The third thing, or the second thing to point out is with the hyperpnea, when the person's breathing a lot, they wake up from sleep. It's hard to see on this timescale, but the EEG shows some alpha activity suggesting arousal from sleep. The reason that's important is that paroxysmal nocturnal dyspnea, a classic symptom of congestive heart failure, is almost always related to this breathing pattern. When people are breathing a lot, they wake up from sleep, and it's that respiratory disturbance that drives the PNT. So if you see a patient with paroxysmal nocturnal dyspnea, more often than not, they have an underlying symptom. More often than not, they have an underlying sleep disorder. The third thing to point out is a burst attack of cardiac in the EKG here. There's surges in catecholamines that happen here. And the reason cardiologists are giving beta blockers in heart failure is they know catecholamines are not our friends. They contribute to the neuroendocrine activation and progression and deterioration of cardiac function, dysfunction over time, suggesting the catecholamines may be driven by this sleep disorder breathing pattern. So three things to emphasize, cessations of airflow without respiratory effort, associated intermittent hypoxia with reoxygenation, leading to oxidative stress, recurrent arousals from sleep leading to paroxysmal nocturnal dyspnea, and recurrent surges in catecholamines contributing to neuroendocrine activation and deterioration in cardiac function. We're doing some studies in Africa as well, and even in Maputo, Mozambique. Irina Mbanzi is a cardiologist there who published this in the journal Clinical Sleep Medicine recently. You can see these sorts of breathing patterns, even in teenagers and young adults who have a heart failure from congenital or valvular disease there. And so even in very skinny people, you see these abnormalities, and so you don't have to be fat to have sleep apnea. You can have sleep disorder breathing even in very lean people in Africa. And it was roughly 80% had abnormalities in this context as well. You might say, who cares? But Dr. Javahari, a different Javahari, the father of our panelist here, published in the American Journal of Respiratory and Critical Care Medicine, this observational thing from the Medicare registry. On the Y-axis here is the percent of cohort alive. X-axis here is time. If you're diagnosed and treated for sleep disorder breathing with heart failure, your survival looked pretty good. If you weren't tested and weren't diagnosed and weren't treated, your survival looked pretty bad. Clear separation here suggesting this and don't ask, don't tell approach does not work. And being diagnosed and treated is associated with a much better outcome. I'll emphasize this is not a randomized trial, and so it doesn't prove that treating sleep apnea will improve survival, but certainly the association is quite strong. There's a lot of focus these days on readmissions, and it's important here as well. So on the X-axis here is the number of readmissions. Y-axis here is the percentage. If you don't have sleep disorder breathing, you're overrepresented in this group without readmissions. But if you do have central sleep apnea, you're overrepresented in the group with one, two, or three readmissions. So again, these are associations, not proof of causation, but the association suggests that central sleep apnea may contribute to cardiac readmissions. One of the questions in the preamble was about adaptive or autoservo ventilation. It's a form of positive airway pressure that gives support depending on the person's breathing pattern. If they're breathing a lot, they don't get support. If they're not breathing, they do get support. And so it's sort of the opposite what the patient's asking for. It doesn't hyperventilate if the patient's already ventilating, but it does help the patient who's having apnea. And this sort of approach may be helpful in stabilizing breathing. So we're initially excited about this. We published this study in CHEST some years ago, and the X-axis here is the apnea hypopnea index, which is the cessations plus reductions in breathing per hour of sleep. You can see on a forest plot here, very consistent improvement in the apnea hypopnea index with adaptive or autoservo ventilation. This is a smart ventilator that tries to breathe for the patient. You can see improvements in the sleep disorder breathing index. Concomitantly, you also see improvements in left ventricular ejection fraction. So this favors adaptive or autoservo ventilation. You can see the LVEF improving in lots of different studies suggesting you've done something good with this intervention. Why is that? Well, this is a New England Journal CPC some years ago. The bottom line is a positive airway pressure will reduce both preload and left ventricular afterload. This is based on Laplace's law and based on changes in venous return that happened based on the Guyton model of blood flow. So you get reductions in preload, reductions in afterload. Those may both be beneficial in the context of positive airway pressure. The problem is when you put theory into practice, it doesn't always pan out. And so this was the adaptive servo ventilation for central sleep apnea published in New England Journal in 2015. There was a field safety notice issued suggesting concern for toxicity and adaptive or autoservo ventilation in patients with HEF-REF, heart failure reduced ejection fraction, and central apnea. The signal was stronger in HEF-REF. The ones with preserved ejection fraction were not in this particular study, but subsequent studies have suggested it may actually be beneficial or certainly not harmful in that context. So I'll show you some data here. On the y-axis here is the cumulative probability of an event. An event was deterioration, cardiac function, or death. It was over-representing the ASV group versus control, suggesting concern for toxicity. Has a ratio of 1.13. And based on this, there was a black box warning on adaptive autoservo ventilation, suggesting it may be problematic in those patients with reduced ejection fraction. This is one study, not multiple studies. And so it's worthwhile seeing if this gets corroborated in subsequent studies, which we'll talk about. So people asked why. Why is there toxicity in this ASV? And the answer is we don't know. It could be spurious. It was a surprise finding, so it needs to be reproduced. There may be direct cardiovascular effects of the adaptive or autoservo ventilation. So perhaps reducing preload and afterload may be problematic in patients who have been aggressively diuresed. Perhaps you could compromise cardiac output if you drop preload in somebody who's been aggressively diuresed, for example. There may be indirect effects of the ASV. In some cases, patients feel so much better they stop taking their pills, including their beta blockers, and that could obviously be problematic. The bottom line is we don't know why there's toxicity in that particular study. The day the CERV-HF study was stopped, they also stopped the CAT-HF study because there was concern that this technology may be problematic. And so this was published in Jack in 2017. And the interesting part here is the HEF-PAF patients actually did better. The study was stopped prematurely because of a different study. But in that context, they did see some improvements in outcomes with HEF-PAF in patients with acute congestive heart failure. So I'll show you some data here. There are 126 patients randomized. It was stopped prematurely because of the other study, the CERV-HF, but 24 of them had HEF-PAF. This is a pre-specified subgroup. And in fact, those patients did do better in this particular study, suggesting maybe HEF-PAF is the group that does better than HEF-REF, who did poorly in the CERV-HF study. So what's the bottom line here? An acute congestive heart failure may be quite different from chronic in the standpoint of positive airway pressure. They're not aggressively diuresed yet, and so perhaps there's more room for positive airway pressure. The HEF-PAF group was pre-specified, but the group was small. So again, we need corroboration and replication. For now, CPAP, continuous positive airway pressure for acute heart failure is reasonable, but need to consider ASV or adaptive cerebral violation for heart failure preserved ejection fraction. We have some studies as well we've been doing with the MedEx Cloud. The MedEx Cloud is an academic industry partnership. Fatima Surge is shown here. This was just published in Jaha. Look at the association between adherence to positive airway pressure and healthcare resource utilization in patients with sleep apnea and heart failure with reduced ejection fraction as well as preserved ejection fraction. This is a look at U.S. administrative claims dated from over 100 health plans. We have about 3,100 HEF-REF patients, about 4,200 HEF-PAF patients. If you look at baseline, the groups look quite similar. The standardized mean differences are very similar between groups before positive airway pressure, meaning they're balanced here based on propensity matching. One year after positive airway pressure, you do see some improvements in the adherent patients versus the non-adherent. In terms of ER visits, there are fewer. Hospitalizations are also fewer, though not statistically significant. So these data in HEF-REF are consistent with the notion that treating positive airway pressure, adherent patients do better than non-adherent. Of course, that's problematic because of the so-called healthy user effect. People that take their placebo have better outcomes than people that don't, so maybe adherence is the marker. We've done a variety of different analyses to try and account for the healthy user effect, as I'll show you. We don't think it's just based on the healthy user effect, but that's certainly a possibility until we have robust randomized trials suggesting or corroborating these findings or refuting them. If you look in HEF-PAF, Heart Failure Preserved Adrection Fraction, Kimberly Sterling is the lead on this, also published in JAHA recently. Okay, adherent versus non-adherent using propensity matching. At baseline, they look very similar, just like in HEF-REF. Here in HEF-PAF, they look similar at baseline. One year after positive airway pressure, the adherent looked much better than the non-adherent for the composite endpoint. ER visits look better in the adherent patients. Hospitalizations also look better in the adherent patients, again, suggesting positive airway pressure in heart failure with preserved adjection fraction may be a good idea. However, we need randomized trials. We've looked at these analyses various different ways. I won't get deep into the stats here, but we did this inverse probability of treatment weighting. There's different ways to look at adherent, non-adherent, intermediate adherence. We're seeing improvements here suggesting that no matter how we slice and dice the data, we are seeing improvements with the adherence to positive airway pressure therapy. Christian Mickels in my lab, my lab was closed during the pandemic because of the lockdown. And so we ended up doing these systematic reviews and meta-analyses because the lab was closed. And so Chris did some work with acetazolamide or Diamox and looking at obstructive sleep apnea, central sleep apnea with heart failure, central sleep apnea with high altitude or central sleep apnea idiopathic. Seeing very consistent improvements here with central sleep apnea and congestive heart failure as well, suggesting acetazolamide or Diamox may be a helpful thing to do for sleep disordered breathing. There was a New England Journal paper recently as well, looking at acetazolamide in heart failure, suggesting you could diurese people adequately and safely in that context. Let's say a little bit about neurostimulation as well in central sleep apnea. You can see more than 50% reduction in the apnea hypopnea index in this Lancet paper using phrenic nerve stimulation for central sleep apnea. When you look at the central apnea index, that's markedly improved for the treatment with phrenic nerve stimulation and emerging data are looking at cardiac function in this context as well. The bottom line is if you look at from the top here, people on treatment, the bottom here, people on control, there's a lot more people in the treatment group getting decreases in their apnea hypopnea index or severity of sleep disordered breathing with phrenic nerve stimulation compared to controls where there's a lot that are getting worse, not better. And then I'll close with two other studies before I summarize. One is the ADVENT-HF study. This paper is currently in peer review, but not yet published. It was terminated by Phillips Respironics, which had a recall on equipment. It's this adaptive rotoservo ventilation effect on survival. It's the so-called ADVENT-HF study that Doug Bradley was doing up in Toronto, a multinational study. The ADVENT-HF results were presented at the European Society of Cardiology at the sleep meetings this year. They're not yet published, but results are known. The study is negative for any primary outcome, but they're reporting some trends and some symptoms are improving, but it's an unblinded study, so it's hard to make much of that. There's a lot of emphasis on people comparing various devices from various companies. In my view, that's not helpful. None of the devices is currently available. This one was recalled. The other one has been updated, and so I don't think the device matters as much. Suffice it to say that SRV-HF that showed harm, at least this is showing no benefit, but at least not harm with ASV in heart failure with reduced ejection fraction. There was also some talk about giving oxygen for chain stokes, breathing. That study was also terminated because of the pandemic. This was a study that Shirok Chabahari and Susan Redline were involved in. They enrolled 98 patients. It was terminated by the NIH due to enrollment issues during the pandemic, and so unfortunately, we're not going to have a result on that one either. So I'll summarize by saying we need more data, which is always a cheap way to summarize, but in this case, it's true. CPAP, continuous positive airway pressure is the first-line treatment for obstructive sleep apnea and congestive heart failure. It's been shown to improve ejection fraction. We don't have a mortality signal, but certainly some associations suggest benefits. ASV-adaptive road with severe ventilation may have a role in HF-PF, particularly in the acute setting based on that CAD-HF study I showed you. Acetazolamide needs more data in terms of heart outcomes, but certainly breathing patterns can improve. Chronic nerve stimulation may have a role. I showed you improvements in sleep-disordered breathing, although again, heart outcomes we don't know. And then optimizing underlying medical therapy is always good. That's kind of a motherhood and apple pie statement, which shouldn't be ignored. So I'll stop there. I'd like to thank you all for your attention. Again, it's been my pleasure to be here today. Thank you so much for that presentation. What I'd like to do next is to revisit the polling questions that we had prior to your presentation and then we can discuss them and see if there are any additional points that we wanna make. So the first question is, which of the following is true regarding positive pressure and heart failure? And it raises afterload, it raises preload, it lowers preload and afterload. This is a great physiology question and one that that is really interesting to revisit. I don't know, we had 100% until some outliers. Yeah, so what are your thoughts? Do these results surprise you? No, I think lowering preload and lowering afterload is probably the best answer. It lowers preload, there's a gradient for venous return from the mean systemic pressure to the right atrium. If you raise right atrial pressure, you'll get a higher gradient against venous return or a lower preload. The afterload goes down because of the law of Laplace based on wall pressure, wall tension, or wall stress is a function of the transmittal pressure across the ventricle, the radius of curvature of the ventricle and the thickness and so forth. If you make the ventricle smaller and you make the pressure inside minus the pressure outside smaller, then the wall tension or wall stress will go down or lower afterload. There's different ways to think about that, but it's the same with PEEP on a ventilator or CPAP from a positive airway pressure, they'll both lower afterloads. Lowering preload and lowering afterload, I think is the best answer. You'll see in textbooks that it falsely elevates the right atrial pressure, the CPAP or something that's simply not correct. It's not a false elevation, it's a real elevation. And so this lowering preload and afterload, do you think this is what contributes to the increased ejection fraction that's been seen in some studies? Yeah. Some people say, why can't you get there with diuretics or just diurese people that can lower preload that way? The issue with diuretics is they don't particularly lower afterloads, and so my view, positive airway pressure has the dual benefits that you improve forward flow through reducing afterload in patients with HFREF in particular. It's also helpful, though, to attend to those catecholamine surges we talked about. So people have high levels of catechols that are contributing to neuroendocrine activation, deterioration, cardiac function. That also probably helps over time. It's not just a mechanical effect of the positive airway pressure. The other thing that this brings up for me is thinking about my patients who have acute heart failure and who are in the hospital and typically have their CPAP machines be at home. Do you think that it's really important for the heart failure physicians to get patients back on their therapy, especially when they're acutely decompensated? Yeah, even the ones that aren't previously using it, that Andrew Bernstein had a New England Journal paper some years ago looking at giving CPAP, positive airway pressure to acute congestive heart failure, and that could prevent intubations and stuff by doing that. So it is a really helpful therapy. Bill Abraham, some of you guys know, is a heart failure cardiologist in Ohio, and he's also shown improvements in LVEF and stuff in the inpatient side. So I think that is a good thing to be aware of. Okay, terrific. Let's move on to the next question. Which of the following is true regarding ASV and congestive heart failure? Deliberately made this a bit nuanced. I won't forgive people that don't get it right, but I just wanted to dig into it a little bit. And you'll hear people trying to trot out their hobby or just to push their ideas, but try to be objective in my response here. Yeah, I think that this is such an important question because having lived through the trials being published and understanding what our thoughts were about sleep apnea and ASV prior to CERV-HF and then afterwards, and then how that has alienated many heart failure physicians from the world of sleep apnea, I think it's really important to dig deep in this and to really understand what the clinical trials show. So we have- I just want to emphasize the two devices that were studied in both CERV-HF and ADVENTER both discontinued. So they're both kind of antiquated in the sense of guiding therapy today. So in my view, the best answer here is that no consistent proven benefit in congestive heart failure. As proven mortality benefit is not correct. I don't know any study that showed mortality benefit with ASV. It raises mortality in multiple randomized trials I think is not correct. The CERV-HF showed a harm signal based on a composite endpoint of survival plus cardiac deterioration, whatnot. So arguably in that study, mortality was a problem, but that was just the one study that showed that. So multiple randomized trials I think is not correct. It's particularly problematic in HEF-PEF is not correct. I showed you it's potentially beneficial in HEF-PEF based on that CAT-HF study. It has no consistent proven benefit in congestive heart failure I think is probably the best answer. That ADVENT-HF study, which is reported but not yet published as a negative result although some improvements in symptoms and stuff. So I think no consistent proven benefit is probably the best response here, recognizing that people will want to debate the nuances of that. Yeah. It doesn't surprise me that the audience is mixed on this because there is so much confusion about the literature and understanding both diagnosis and treatment of sleep apnea and heart failure. But I'm wondering if I have a patient who's in the clinic who has really bad HEF-PEF and is not responding to my medical therapy and has multiple admissions to the hospital, should we consider ASV for them? Yeah, it sort of depends what's wrong with them. If they have obstructive or central apnea and treat the underlying cause, optimize their heart failure management. If they do have sleep disordered breathing then I would consider it. The CAT-HF was more in the acute setting than in the chronic setting. If they do fine with CPAP, I would leave them on CPAP because at least we have observational data which can reduce ER visits and hospitalizations. If CPAP doesn't get the job done, then I think ASV is a consideration. The contraindication is with HEF-REF with very low ejection fractions. And HEF-PEF appears to be safe and perhaps effective, I don't know. Very good. Okay. Well, thank you so much for these questions and thank you for the conversation about them. Really appreciate you joining us today. We're gonna move on to our next set of polling questions. So the pre-poll questions for Dr. Javahari today. So the first question here is asking which of the following is correct? A, randomized controlled trials show treatment of central sleep apnea and heart failure with oxygen improves survival. B, randomized controlled trials show that treatment of OSA, obstructive sleep apnea and heart failure with CPAP improves survival. C, randomized controlled trials showing treatment of central sleep apnea and heart failure with ASV does not improve survival. Or D, randomized controlled trials shows treatment of obstructive sleep apnea with ASV improves survival. So a little overlap there with... Okay. We can move on to the next question. Which of the following is true? A, in heart failure, sleep apnea is under-diagnosed because patients are not typically asleepy or may not exhibit typical symptoms. B, HST or home sleep test is the preferred diagnostic test for central sleep apnea. C, randomized controlled trial with phrenic nerve stimulation shows improved survival. Or D, atrial fibrillation is not associated with central sleep apnea in heart failure patients. All right, well the final votes seem to be in and so we'll revisit these after your presentation. Great, thank you. I'm just gonna share my screen. All right, can everyone see this? Yes, we can. Okay, perfect. So I'm going to talk about obstructive and central sleep apnea as well and these are my disclosures. So as Dr. Malhotra already described, an obstructive apnea is cessation of breathing despite a normal respiratory effort. So you can see in the respiratory bands here in the ribcage and abdomen, there is increasing effort for diaphragmatic contraction but no airflow due to a mechanical obstruction. And in contrast, in a central apnea, there is flat lines along airflow, ribcage, and abdomen because there is no mechanical obstruction and no respiratory effort. So there's some interruption from the signal of the brain to the diaphragm telling the diaphragm to contract here. And as Dr. Malhotra also said, it's often in heart failure associated with chainstokes respiration, this crescendo de pattern of breathing punctuated by these central apneas. So there is a high prevalence of both obstructive and central sleep apnea in all spectrum of heart failure patients. They frequently coexist together, the OSA and CSA, but one variant generally predominates. And the OSA prevalence in the heart failure population is generally quoted to be between 20 to up to 55%. And the central sleep apnea prevalence in the heart failure population is generally quoted to be between 10 to up to 40%. Risk factors for obstructive sleep apnea include male sex, menopause in women, increasing age, obesity, craniofacial abnormalities, such as enlarged tonsils, retronathia, smaller receding chin or jaw, increased neck circumference. And in contrast, in central sleep apnea, while it does share the risk factors of increased age and male sex, we see less regarding body habitus and upper airway tissues, atrial fibrillation, higher NYHA functional class, lower ejection fraction, higher BNP all have been associated with it. And in fact, male sex and atrial fibrillation are independent risk factors of central sleep apnea in the heart failure population. Symptoms are sometimes difficult to determine causes of in this population. So as we already discussed with the insomnia case, sometimes there's a lot of overlap and we don't know what's being caused by the heart failure and what's potentially being caused by the sleep disorder. With obstructive sleep apnea, traditionally you see loud disruptive storing. You may see excessive daytime sleepiness, but you may not in the heart failure population. Patients may wake up choking or gasping for air or a bed partner may comment that they hear pauses in breathing. Nocturia can be a common symptom, but again, that can also occur with diuretic use and patients may also complain of morning headaches. With central sleep apnea, we see less sleepiness and more fatigue. Typically in this population, we may also see insomnia, difficulty falling or staying asleep and frequent nocturnal awakenings. Again, nocturia can be a confusing symptom, so it can sometimes be hard to say when or when not to screen these patients. The diagnosis is typically done with a home sleep test, but the gold standard is an in-lab polysomnogram. And the home sleep test is 80% sensitive in the general population and was previously not recommended for central sleep apnea, more for obstructive sleep apnea because the in-lab test is much more sensitive at detecting central sleep apnea than the home test. Although recently, the Journal of Clinical Sleep Medicine did have a publication showing that the home sleep test was actually pretty good for both obstructive and central sleep apnea in the heart failure population specifically. So, this may be increasing in popularity, but for those severe heart failure patients, NYHA class three or four, I would still recommend getting an in-lab sleep study to diagnose what type of sleep apnea they might have. For treatment, CPAP has typically been the first thing we've reached for for obstructive sleep apnea. Side effects of using a CPAP machine may include nasal congestion, dry mouth, sometimes sleep disruption from mask leak or discomfort from using the device. But in symptomatic patients, it can be really effective in improving quality of life, daytime sleepiness, and other symptoms. What we know about CPAP use and obstructive sleep apnea in the heart failure population. So, first of all, there are no randomized controlled trials looking at survival specifically in the heart failure population with CPAP and OSA. In small randomized trials, it does lower heart rate and blood pressure, and it does improve left ventricular ejection fraction. And in large prospective trials, it has reduced rehospitalization and mortality in Medicare beneficiaries. So, there may be a role for CPAP here in the heart failure population despite some of these other trials. And it should be carefully monitored once started, making sure it's working effectively, the patient is tolerating it well. For central sleep apnea treatment, as Dr. Malhotra already told us, you want to optimize heart failure treatment. Treating their heart failure better can reduce their central sleep apnea and chain stokes respiration. CPAP, I think there are responders and non-responders. And again, that's why it's important. If you start a patient on CPAP, it's ideal if they can follow with a sleep doctor to download the data from their machine and see how is their AHI doing on the machine or not, how do they have leak, and how are they subjectively really feeling. Dr. Malhotra presented a lot of data on ASV and potential excess cardiovascular mortality in patients with reduced ejection fraction, though there's possible improvement in patients with preserved ejection fraction, as he discussed in the CATHF trial. He also mentioned phrenic nerve stimulation and medications like acetazolamide for treatment of central sleep apnea, and that with oxygen, which can stabilize breathing and reduce central sleep apnea, small randomized control trials are supportive of this, but we don't have any large randomized control trials to demonstrate efficacy and safety in this specific population. So CANPAP was a trial that showed CPAP had no effect on heart transplant-free survival in the original study, which looked at 258 patients with heart failure and central sleep apnea who were randomized to CPAP or no CPAP and followed for an average of two years. CPAP did result in long-term reductions in the AHI, shown in panel A, and in increases in mean nocturnal oxygen saturation, shown in panel B, some improvement in LVEF in panel C, and minimum nocturnal oxygen saturation later was also improved in the CPAP arm in panel D, but when they did a post-hoc analysis where they divided patients by their efficacy of the CPAP, meaning did the treatment reduce their AHI to less than 15 or not. So they divided the patients into effectively a CPAP, central sleep apnea suppressed group, where treatment reduced the AHI significantly below 15 versus those who are unsuppressed. The CPAP did not reduce it. So about 43 patients in unsuppressed group and 57 patients in the CSA suppressed group, they compared them to control, and now there was an improvement, a statistically significant improvement in heart transplant-free survival in the central sleep apnea suppressed CPAP arm compared to control, whereas there wasn't in the CPAP and central sleep apnea unsuppressed arm. I'm not going to get into the CERV-HF trial too much. Dr. Malhotra really talked about that, I think, but basically in about 1,300 patients randomized to ASV or control, they found this 2.5% absolute increased risk of annual cardiovascular mortality. What I'm going to get into more is these challenges in conducting these randomized control trials and why we may be seeing these negative trials despite all this prospective data that's so promising with CPAP and treatment of sleep apnea in general in the heart failure and general cardiovascular population. So it's difficult to blind or find appropriate control conditions with CPAP since it is non-pharmacologic. There's a lot of randomization concerns, the ethics of not treating sleepy or hypoxic patients. So even though the patients who are hypoxic are the most likely to benefit and the most likely to have improved cardiovascular outcomes since hypoxia may be a better predictor of adverse cardiovascular sequelae, these patients are excluded. The same thing with the sleepiness. Often we exclude excessively sleepy patients due to lack of equipoise, but again, the sleepier patients are more likely to have adverse cardiovascular sequelae and may benefit the most. Adherence has been notoriously low in our trials. I think even in CERV-HF, the mean adherence was three hours, which is very low, and we generally have very small sample sizes. The cardiovascular trials have thousands of patients and ours are often less than 2,000 patients, unfortunately. I'm not going to get too much into phrenic nerve stimulation because again, Dr. Malhotra really addressed that, I think, but it is a physiologic treatment of central sleep apnea that can improve quality of life and daytime sleepiness. It has been shown to improve the AHI, and the most common side effect reported has been therapy-related discomfort that can sometimes be addressed. So to conclude, there's a very high prevalence of both obstructive and central sleep apnea in the heart failure population. With absence of the typical clinical symptoms compared to the general population, it can be a diagnostic challenge. The in-lab polysomnogram is more sensitive, but recent data has shown that the home sleep test is acceptable in the heart failure population. That said, I may still get the in-lab study, especially in patients with advanced heart failure. Treatment remains a challenge. If you start a CPAP in a patient with central sleep apnea, I would follow up to assess their CPAP response to see if it's working effectively or not. You could consider ASV in a person with heart failure with preserved ejection fraction and can consider phrenic nerve stimulation or alternate treatments like acetazolamide if PAP is not effective or is intolerable. Thank you very much. And I'd also like to say Atul said he was honored to be here, but really the honor is mine. He was actually one of the attendings that mentored me when I was a fellow at the Brigham and Women's Hospital. So it's my honor to be here with him and with all the speakers. Thank you so much for that. Let's go ahead and revisit your questions and see if we can drive some of these points home. So we have the poll up. Do we also have the PowerPoint we can add? So this first question really is driving home the fact of the randomized control trials, right? Yes, and we almost had 100% correct here. The correct answer is C, that randomized control trials do not show that treatment of central sleep apnea and heart failure with ASV improves survival. So we don't have any data that it improves survival. There is post hoc analysis from CANPAP shows that CPAP can improve heart transplant-free survival in CPAP responders. So that's in CPAP, but not ASV. And also that was a post hoc analysis, not the original trial design. But there's no data on oxygen yet, and we don't have any evidence that ASV improves survival either. Okay, very good. Let's go on to the next one. All right, so this is, do you think it's safe to? Yeah, I think so. Let's go ahead and chat about it. All right, so answer C is correct here. I'm sorry, answer C is not correct. Answer A is correct here. Answer A is correct here. In heart failure, sleep apnea is underdiagnosed because patients are not typically as sleepy or may not exhibit the typical symptoms. So C was very popular, that randomized controlled trial of phrenic nerve stimulation shows improved survival. So it shows reduction in AHI, it shows improvement in quality of life, reduction in sleepiness, but it hasn't been tested in survival. We actually don't have a trial looking at that outcome as of yet. And then choice D, atrial fibrillation is actually associated with central sleep apnea in heart failure patients, actually an independent predictor of having central sleep apnea in heart failure patients. I think that this question is really interesting, especially because of the fact that the heart failure population of patients may not have the characteristic sleepiness. They have a lot of sleep disorder and sleep complaints often, but as far as the classic falling asleep at the wheel, we're not typically seeing in the heart failure population. That's right. Yeah. So just because they're not sleepy doesn't mean they don't have sleep apnea. Some would argue that they should all, because of that, get a sleep test if they have any sleep complaint at all. Yeah. And then what can you say about the relationship between sleep medicine physicians and heart failure physicians? What type of collaborations are ideal and how can we work with our sleep partners to make sure our patients are getting the best treatment? I invite Dr. Jackson and Dr. Malhotra to contribute here as well if they'd like, but I think it's really important to have a patient-centered approach with open communication. I do like to talk to the heart failure physicians, especially if the patient isn't tolerating the PAP device, about alternate approaches. For example, I share a mutual patient with one of our heart failure doctors at the Brigham. The patient has a lot of fatigue and the heart failure doctor felt that this was not related to his... It could be related to his cardiovascular injury, but everything had been optimized as much as it could. So he really wanted to push treatment of the central sleep apnea. And now we're having the patient actually go to BI to get workup for phrenic nerve stimulation because we exhausted some of the other options. That was a decision we came to together, trying to make sure the heart failure was optimized as much as possible and that going for something more invasive was the right step. So I think communication, maybe deciding the best beta blocker for the patient, deciding things like that, depending on what their complaint is in the patients who aren't doing as well is really important. I think that's very... I completely agree with you. And I think also having heart failure physicians that are invested in sleep disorder breathing and treatment of sleep disorder breathing, I think really helps the patients as well because we have... All the time are in the process of trying to talk to our patients about how important guideline-directed medical therapy is. And when they hear that the evaluation of their sleep disorder breathing and treatment of their sleep disorder breathing is important as well, I think that really helps with adherence. I agree. So a team-based approach is really important. Maybe if sleep doctors can give talks to their cardiology counterparts at different institutions to raise awareness or things like that, that might help. But definitely the team-based approach can really benefit patients, especially the ones who aren't straightforward or who have more complex complaints. We have a couple of questions in the chat that I'm actually going to save for our question and answer session at the end. And because of interest of time, we'll go ahead and move on to the next pre-polling questions with Dr. Jackson. Thank you so much, Dr. Jabahari. Thank you. So our first question is, what percentage of patients with decompensated heart failure also have sleep disorder breathing? Is it 20%, 45%, 60%, or 75%? Okay, let's go ahead and move on to the next question. So we have the question up. We're just waiting for the poll. Here's the poll. All right. Which of the following conditions is the leading cause of resistant hypertension? Primary aldosteronism, renal artery stenosis, obstructive sleep apnea, or primary hypertension? Okay, terrific. Well, let's go ahead and move on. We will be revisiting these after the didactic discussion. Sorry about that. Well, thank you. My name is Greg Jackson. I'm at the Medical University of South Carolina in Charleston, South Carolina. Proud to be here as one of the few, one of the presenting cardiologists in the group. And I think based on one of our questions, we have a little bit of teaching to do and the other one looks like folks did pretty well with. So today I'll be talking about sleep disordered breathing and cardiology. When I first started here after fellowship, one of the sleep medicine docs approached me and said, you know, we really wanna cross the aisle to the point of how do we improve our outcomes and how do we improve communication between our cardiology colleagues and our sleep medicine colleagues. He reached out to me and said, we really need to form a collaborative approach and set up a network between our divisions to really optimize the care of our patients since a lot of cardiac patients have unrecognized and undertreated sleep apnea. So here are my disclosures, prior honorarium with Respicardia. And I hope at the end of the talk today, you'll be able to appreciate the relationship of comorbid sleep disordered breathing in cardiovascular disease and understand the pathways for the screening and diagnosis of sleep disordered breathing in heart failure patients. So why is this important? There's a lot on this list of things that we try to take care of in our patients every day. And we're not focused on sleep apnea. We're focused on treating their stroke, trying to manage their hypertension, managing their atrial or ventricular arrhythmias, working on coronary disease and MIs, right heart failure, pulmonary hypertension, left heart failure, and the risk of sudden cardiac death. But we're left not often treating their sleep apnea as a group of cardiologists. So we'll go through a few of those comorbidities. This here, you can see on the left, that obstructive sleep apnea accounts for about two-thirds of cases of treatment-resistant hypertension. So we're looking for zebras like renal artery stenosis and thyroid disease or aldosteronism, but two-thirds of the cases really are from obstructive sleep apnea. And on the right, you can see that over time, over a follow-up period of 15 years, patients who had either mild, moderate, or severe obstructive sleep apnea had a much higher cumulative incidence of hypertension than patients without obstructive sleep apnea. Having a little glitch with my slides. And here you can see on the right, with hypertension and obstructive sleep apnea, actually treatment with CPAP, this was a small study of only 11 patients, but treatment with CPAP for two months reduced systolic blood pressure over a 24-hour period of time by 11 millimeters of mercury and had a more significant effect with nocturnal systolic blood pressure dropping by an average of 14 millimeters of mercury. And the recurrence of atrial fibrillation after cardioversion and ablation is also strongly associated with the presence of sleep apnea. So on the left, you can see that after cardioversion, there's about a two-fold higher recurrence of atrial fibrillation after cardioversion than patients who have treated sleep apnea or the control group. And this may even be underestimated as the control group was just said to not have a history of sleep apnea, but did not actually have formal testing. So this may actually be even a little bit of an underestimation. And the same is true after pulmonary vein isolation for atrial fibrillation. You can see the group with untreated sleep apnea has about a two-fold increased recurrence of atrial fibrillation compared to those with treated sleep apnea and a hazard ratio of about 2.8. This is a nice study that enrolled about 190 patients, consecutive patients that were being referred for atrial fibrillation ablation. And they did a stop bang questionnaire, which is one of the questionnaires for assessing for sleep apnea. And they also did concurrent home sleep tests or HSTs in patients that were gonna undergo atrial fibrillation ablation. About 80% of them had a positive sleep study. About 80% of those had obstructive sleep apnea and they got patients started on treatment. I think what it's important to realize here is that 90% of patients were compliant at one year. And I think that's in part because they associated their atrial fibrillation and their atrial fibrillation ablation with their history of sleep disorder breathing and linking the two together improved compliance. And as we've seen also reduces the risk of recurrence. There's also an increased risk of ventricular arrhythmias, the following, go ahead one slide please. There's also an increased risk of ventricular arrhythmias in both patients with central sleep apnea and obstructive sleep apnea. And this is due to elevated blood pressures, activation of the renin-angiotensin-aldosterone system, increased vasoconstrictors and increased myocardial turnover and fibrogenesis. And if we can go back one slide. Thank you. And there's also a significant association of sleep apnea in patients that we are referring for coronary artery bypass surgery. About 50% of patients that we refer for CABG have obstructive sleep apnea. It's strongly associated with increased risk of repeat revascularization, typical anginal symptoms, atrial fibrillation and there's a prolonged length of stay. And there's also an independent association with perioperative MI in off-pump CABG, as you can see on the right here in a study published a couple of years ago. And this is an interesting study, which was a retrospective cohort looking at the UK Biobank of a little over 400,000 patients. And it really highlights an important point, which is if people have healthy sleep habits, perhaps heart failure and the sequelae of heart failure are somewhat preventable. They looked at things like, are you a morning person? Do you get seven or eight hours of sleep? Do you have symptoms of insomnia? Is there snoring or excessive daytime sleepiness? And you can see in patients who have all five of those healthy sleep habits, there's about a 60% reduction in the development of heart failure. And each individual component also has a reduction and cumulatively has a significant, statistically significant reduction in the incidence of heart failure. And it doesn't go away after we treat patients with a heart transplant. You can see on the left here, Dr. Javahari and colleagues looked at a little under 60 patients in the VA population and about 36% of those patients had significant sleep apnea characterized by an AHI greater than 15 per hour. And some work that we've done here, looking at patients post LVAD, interestingly enough with central sleep apnea and chain Stokes respirations, it nearly is abolished after the placement of a left ventricular assist device, which I think highlights the mechanism of delayed chemosensitivity and low cardiac output in some of these patients. So as we've talked about, this has a lot of consequences, hypertension, MIs, arrhythmias, heart failure, sudden cardiac death. It may even have intellectual and personality changes, depression, worsening ADHD, headaches and stroke. And so I think it's really important that we try to screen these patients appropriately and make the diagnosis and get them treatment so that we can try to improve outcomes. You can see here about 75% of patients with heart failure are known to have sleep apnea. Worldwide, about 50%, whether it's HFREF or HFPEF have heart failure and obstructive sleep apnea accounts for about a quarter of those in reduced ejection fraction as well as preserved ejection fraction. You've seen this slide on the right here that there's a significant difference in mortality in a large Medicare cohort of patients and there was improved survival in those that were tested, diagnosed and treated for heart failure. And you can see on the bar graph on the left here in those with acute decompensated heart failure, about 78% of patients have an AHI of greater than 15. So a significant percent of patients that we're seeing in the hospital have some form of sleep apnea, about 50% are obstructive and about a third are central. So we talked a little bit about outpatient sleep studies. Some of the issues that we've had at our center was there's delays and referrals to the time of testing. There were then further delays from the time of test completion to getting started on therapy. We've heard a lot about compliance issues and adequate follow-up. You can see a few pictures of patients that undergo outpatient sleep studies. I always talk to my fellows and some of my patients and say, I'm not sure I could undergo a test having all these wires and gadgets attached to me. So there is the option to look at home sleep studies which we've talked a little bit about or perform inpatient sleep studies on patients who are hospitalized with heart failure. A couple of the devices we've used at our center are shown here and they have about a 90% or 95% correlation to a formal sleep study. Some of this has been shown over the years where you can see here, there was no absolute change in ejection fraction if you look at the intention to treat analysis, but in an exploratory analysis, looking at patients who are compliant with positive airway pressure devices for three or more hours, there was a slight improvement in ejection fraction. This study looked at patients in only a three-day window of their hospitalization for heart failure and using CPAP. So in such a short period of time of three days, we could see an improvement in ejection fraction on the order of about five to 7%. And this also held true in the reduction of six-month readmissions for patients who are compliant for three or four hours per night, there was about a 60% reduction in heart failure readmissions at six months. And similar findings are seen in central sleep apnea. So we can see in table one here, there's a significant increase in readmissions in patients with central sleep apnea compared to those with no sleep disordered breathing at both three and six months. And there's also a significantly higher cumulative cost of those readmissions per patient of both three and six months in those with central sleep apnea compared to no sleep disordered breathing. So some of the work we tried to do as we formed our sort of hybrid sleep and cardiology collaborative at our center was to start doing inpatient tests on patients. And we did a six-month retrospective review. And although the numbers are small, we only had 28 truly adherent patients, which we defined as greater than four hours a night and greater than 70% of the nights of the week compared to 61 patients who were ultimately our control group. You can see there's a reduction in the number of readmissions, repeat readmissions, and there's a reduction in death. And when we look at those patients who are truly adherent for greater than four hours a night, greater than 70% of the nights, there's a statistically significant reduction in readmissions, and there's a signal of a reduction in death. We also found that compliance was poor, only about a quarter of patients were truly compliant despite worse findings such as AHI and worse metrics of obstructive sleep apnea. Those in the CPAP group and the truly adherent groups had improved outcomes. And this supports some of the prior evidence that there's an association between greater use and improved outcomes. So inpatient sleep studies and certainly home sleep studies may expedite receiving therapies and therefore improving outcomes. And we've talked a bit about some of the treatment modalities. This is from a review article that we recently published on the management of sleep apnea in patients with heart failure. And the way that I always think about it and talk to our fellows and my colleagues is, you know, we're managing again all of the cardiac comorbidities, but we're leaving a lot of under-recognized, under-diagnosed and under-treated sleep apnea, and it's just the tip of the iceberg and it's worsening all of our outcomes. Thank you so much, Dr. Jackson. Let's go ahead and revisit the polling questions again before we leave this cardiology issue. So our first question was, what percentage of patients with decompensated heart failure also have sleep disordered breathing? And so I guess the important part of this, Dr. Jackson, is the decompensated heart failure, right? Dr. Jackson is the decompensated heart failure, right? Exactly. So this is acute decompensated heart failure patients. So patients coming into the hospital with decompensated heart failure. I think most of folks are getting this right here. So a significant number of our patients that are right in front of us, you know, we've talked about not paying much attention to sleep apnea when we're treating them. We're diuresing them. We're optimizing their GDMT. We're sending them for heart caths. We're sending them to our electrophysiology colleagues. We're doing all kinds of other work focused on the cardiac side of things. And we often don't focus on the sleep disordered breathing part. And one of my respiratory therapists that I work with always said, you know, it's really important for you as the physicians and the healthcare team on rounds to talk to the patients about it. It doesn't carry the same weight coming from the sleep technician or the respiratory therapist. It really carries a lot more weight when we discuss it with the patient from the medical team. Well, I think this is a really good reminder that that really the majority of our patients are suffering from this. Let's let's go on to the next question. Oh yeah, this is a good one. So which of the following conditions is the leading cause of resistant hypertension? So I think that you showed this nicely in your slides. Yeah, so it looks like most folks got this one. So about two thirds of patients obstructive sleep apnea accounts for their treatment resistant hypertension. We often go looking for all these kind of zebras and rare things and rarely find them and we don't go for the the easy fish so to speak. Okay, well this has been terrific. Thank you so much for joining us and and being brave to speak with these sleep physicians about sleep apnea. So really great to have you. So let's go ahead and move on to our last case presentation and then we'll have a discussion with all of our speakers. Well this has been great. I've had all my questions answered already. The second case here is a real case. A 54 year old man with diabetes, hypertension, obesity admitted to the inpatient service for acutely decompensated heart failure. Symptoms were fatigue, disbanded exertion and leg swelling. He was hypertensive and a little bit faster heart rate. His O2 sat at room air during the day was fine but his nurse astutely noticed that he was desatting at night and snoring very loudly. His jugular penis pressure was not able to be determined because of his body habitus. I did have some edema. Labs somewhat abnormal, a little bit lower GFR as BMP was elevated. The house staff decided to do some screening for sleep apnea so they did the stop bang which was seven points and the Epworth sleepiness scale was just 10 points. His echocardiogram showed EF of 50 to 55 percent, had moderate LVH and pulmonary systolic pressures were mildly increased in a range of 45 to 50. His current medications, well he had stopped taking his medications a couple of years ago. So looking forward to hearing the the presenters comments on what would be the next steps. We can all come on video now. And so for the heart failure physicians and practitioners in the audience, can somebody speak to the stop bang and the Epworth sleepiness scale? What are these ranges and is this a sleepy patient or a non-sleepy patient? Dr. Chaudhary, do you use the word sleepiness? Dr. Chaudhary, do you use the stop bang and the Epworth sleepiness scale when you're evaluating patients in the clinic? I definitely use the Epworth sleepiness scale. We use the stop bang more for research personally but some clinical centers do use a stop bang to evaluate patients as well. At the Atrial Fibrillation Center of Excellence Clinic in the Brigham, they actually use a stop bang to screen for sleep apnea in the AFib population there. So it kind of depends on what you're looking at. But it can be useful. I would call this patient sleepy to be sure because their Epworth sleepiness scale is 10 and 10 and above is considered excessively sleepy. And particularly what we talked about how sleepiness is typically not a major component in heart failure patients or may not be. I think that's particularly telling in this case. And so this patient, would we guess that they have obstructive sleep apnea or central sleep apnea? So they may have both especially because if they have decompensated heart failure, they may have some element of both. And it's also possible that with treating the heart failure, it could largely resolve. But this symptomatology is more consistent with obstructive sleep apnea because of the sleepiness I would say. Hmm. There's a question from the chat from earlier. This is really for anyone. I don't know the answer to this question. Is there a genetic component to developing central sleep apnea? No, there may be a genetic component to the cardiovascular conditions that could predispose them to the central sleep apnea. But central sleep apnea in contrast to obstructive sleep apnea isn't known to have a genetic component to my knowledge. So Dr. Jackson, the case that Ann presented, is this pretty classic of what you're seeing in the hospital with heart failure? It is, although we're not there at night to directly observe it, at least on the attending level. But I think the desaturation at night is a really important part. That in and of itself is a feature of obstructive sleep apnea and in some ways can lead to at least a suggestion of a diagnosis. It's not a formalized sleep study, but there's some evidence that just nocturnal hypoxia is strongly associated with obstructive sleep apnea. Would it be your recommendation then that this patient get a sleep study at discharge? Absolutely. I think it sounds like they're quite decompensated and they're going to be in the hospital for a bit of time. So they should absolutely be diaresed first. I guess it would not be unreasonable if they're going to be there long enough to try to do it in the hospital if there's the ability and that the equipment and staff to do that. But certainly they should be referred in the outpatient setting. In our center, we had a sort of a sleep navigator working with us on rounds, seeing patients, and he would help collaborate those referrals to the sleep medicine department and make sure they were getting set up for testing upon discharge. Is it irresponsible of me as a heart failure physician to put this patient on CPAP without a sleep study? I had similar thoughts. I almost said we should diarese them and put them on CPAP. What do the sleep doctors think? The insurance won't cover it unless you have a sleep study anyway. So unless you have another reason to put them on CPAP outside of sleep apnea, their insurance probably wouldn't cover it unless you were just doing it in the hospital during the hospital stay. But if you want them to go home with the CPAP, I don't know any vendors that or insurance that accept without the objective documentation. That's what I mean, though, is in the hospital because I have CPAP machines. Yeah. Atul, go ahead. Yeah, just I agree with what has been said. So that Andrew Bernstein paper in the journal that I mentioned, he gave CPAP, continuous positive airway pressure for acute congestive heart failure and showed reductions in intubations and whatnot. That wasn't based on sleep studies. It was just based on buzzer pressure, reducing preload and after that. So Jen, your approach, I think, is reasonable not to treat a sleep disorder, but just to treat the heart-lung interactions and improve preload and after that and all that. There's sort of debate about this about, you know, is the acute setting the time to do that? On the one hand, if you can prevent intubation, that's great. On the other hand, you know, if the patient's a moving target, you're about to diurese them and their physiology is going to change, then maybe doing a sleep straight today might not tell you much about tomorrow. You know, Abraham, as I mentioned, had that paper in CHESS looking at improvements in LVF acutely with congestive heart failure. There's the CATHF thing I mentioned that showed some improvements in outcome with ASV as well. So even within our group, we debate this back and forth. Some people say wait until their chronic stable outpatients and then intervene. Other people, including me, suggest what you're saying, Jen, makes sense. And the acute congestive heart failure, putting them on positive memory pressure in the short term is a good idea. What you do with them longer term, then maybe guided by a sleep study or their overall clinical status. I think one thing about these patients who are in the hospital is they're a captive audience. And a question from Diane is, are there tips on how to get patients to agree to be tested and also to be managed with their sleep apnea? And so many of them are not willing to wear a mask. Any thoughts on that? Yeah, I can respond. I get that a lot from cardiology colleagues of mine saying, you know, patients refuse the test. And I always ask them, when was the last time somebody refused a cardiac cath and they say, oh, they never do. And I was like, would you rather have a needle in your femoral artery or a sticker on your head in terms of a diagnostic test? Like, well, obviously, cath is important. It's like, well, if you sell the cath is important, then of course, patients will agree to do that. So it doesn't matter just how the cardiologist says it. You know, this is going to help your quality of life. This could improve your LVF. This could improve your catecholamine levels and all that. Showing patients recurrent desaturations can be an eye opener. Showing them all the PVCs and stuff that go away with treatment can be an eye opener as well. So I don't have patients refuse it by the time they get to me. And after I talked to cardiologists, and I think if they frame it the right way, most people don't refuse a diagnostic test, particularly knowing now that there's home testing that Sogel mentioned as well. Some people think it's as cumbersome in lab test, which it is, but the home tests are much more accessible. And then regarding therapy, it's true that not everybody is amenable to CPAP therapy, but the most recent data we published on that suggested the cloud-based analysis, about 87% of patients were meeting Medicare criteria for adherence using modern technology. And so the vast majority of people will tolerate that. And it blows away most other chronic medical therapies. You look at inhaler use and asthma or anticonvulsant use and epilepsy, CPAP actually blows those things away. Again, that's partly an education thing. If you explain to patients that there's different masks, there's a nasal pill, it looks like a nasal cannula that patients tolerate well. They think of the Darth Vader thing and get scared off, but I think a back and forth education thing can be quite helpful in terms of having people tolerate it. And then some people feel so much better after they try it that they don't care what it looks like. Yeah. There was also a mention in one of the further questions is in those who cannot wear CPAP because of claustrophobia, what do we do? And we didn't really talk about it a lot, but there are hypoglossal nerve stimulators, which are sort of like pacemaker generators in the pectoral area and then have electrical lead in that stimulates the hypoglossal nerve when folks are sleeping to try to keep the tongue out of the airway. And I think that's certainly another alternative for patients or potentially if there's an airway obstruction, they need to see ENT for potential surgical interventions. I think that really just highlights the importance of us sitting down and talking with our patients about their sleep and their sleep disorder, breathing, and really engaging them both in the diagnosis and the treatment options that are available. And through that partnership, especially with the support of our sleep medicine physicians, being able to make a difference in that way. There was an additional question that kind of revisits the physiology. So what do we know about neurohormonal stimulation during sleep and patients with sleep disorder breathing? Is there a surge of norepinephrine during sleep? Yeah. So I showed that in one of the recordings, the sort of bursts of tachycardia. So there's certainly catecholamine surges that occur. And then if you treat people's sleep disorder breathing, you can see suppression of catecholamines. Matt and I showed that back in the 1990s. There's some controversy about what exactly drives the catechol excess in heart failure. Some people will say it's underlying heart failure. Some people say that sleep disorder breathing. And it's one of those things that's so interwoven, it's hard to separate. Certainly some data suggests that treating the sleep disorder breathing will suppress the catecholamines. That's likely to be from relief of hypoxia and recurrent arousals that are alleviated by the sleep. We also know that some of that is what contributes to the ventricular arrhythmias and sudden cardiac death at night. There's a huge surge in catecholamines. And then immediately following those apneic spells is when patients have these ventricular arrhythmias and sudden cardiac death. I was just going to add that sleep is usually a time of cardiac rest for the most part in most stages of sleep. And the sleep apnea really deprives the heart of that adequate rest that sleep normally offers with decreased sympathetic nervous system activity, increased parasympathetic nervous activity, reduced blood pressure, which the dipping pattern you see in the blood pressure and things like that. Also, Anna, when you presented a thickness patient had some AFib as well, if I recall. Is that correct? You're muted. Sorry, he was in regular rhythm. Was there some history of AFib or something? Or did I misread that? I don't recall that, but he certainly is at risk. Yeah, so the swings in the interthoracic pressure, surges in catecholamines, surges in catecholamines, inflammation, all those things can contribute to AFib as well. And some data suggests that, at least by association, that treating sleep apnea can improve risk of recurrence of AFib. And then, you know, as Greg points out, and so we'll mention as well, several studies have shown if you give people CPAP, PBCs, and these things are suppressed by doing that. In fact, Chirouk, Javari, and Clodorin, Chirouk had a paper circulation on that some years ago, and then Clodorin had one in the thorax where you can see the PBCs and these things improving on CPAP therapy. Well, I cannot believe it, but we're at the end of our hour here, and this has been such a great discussion. I am so pleased that each of you joined us today, and that we've been able to have this conversation about sleep disorder, breathing, and cardiology, and heart failure. On behalf of the Heart Failure Society of America, I say thanks to all of our speakers and all of our participants today. Thank you for the great questions in the chat, and as a reminder, to claim your CME, you'll need to go to the Learning Center, and there's a link to the Learning Center in the chat, and this material will be available for future viewing. If you have any friends or trainees or colleagues that would like to watch this, it'll also be available in the Learning Center. Thank you all so much. Thank you. Thank you, Jen.

sleep apnea

heart failure

risk factors

diagnosis

treatment options

obstructive sleep apnea

central sleep apnea

home sleep tests

CPAP

ASV

acetazolamide

collaboration