So, thanks everybody for coming to our controversies in the management of central sleep apnea. It's listed as a pro-con debate. There's going to be some pro-con, a little bit of panel discussion, but we're going to try and talk about some of the real-world dilemmas that we face when we see patients with central sleep apnea. Before we get started, I would like to introduce the panel. We have Dr. Tim Morgenthaler, who is from Mayo Clinic. And we have Dr. Michelle Kao, who's from Stanford. And then we have Dr. Joyce Lee Iannotti. And I would like to point out that she is a neurologist. So I feel very, very lucky to have her here today at a pulmonary conference. So thank you all for coming, especially Joyce. It's torture to be in Honolulu. I know. I really had to beg her to come here. All right. So like I said, we're going to just discuss, I'm going to present a few cases that highlight some of the challenges and dilemmas that we face when managing this patient population. And what I'm hoping is that all of you can take a little bit of knowledge with you back and think about these discussions as you're treating some of your more challenging cases of central sleep apnea. All right. Those are presenters again. Thank you to them. Okay. So case number one. A 65-year-old man with a BMI of 23 has hypertension, hyperlipidemia, and coronary artery disease. He presents to sleep clinic. He had a recent MI, and his EF is now 50%. Since the MI, he has been experiencing daytime sleepiness and repeated awakenings at night. When asked if he snores, his wife says that he's quiet when he sleeps, and sometimes she has to reach over and poke him to make sure that he's still breathing. He had a polysomnogram, and he was found to have severe central sleep apnea with an AHI of 56. He commences treatment with adaptive cerebral ventilation, ASV, and his symptoms improve, and he tolerates the therapy really well. He returns to clinic two years later, and he's still enjoying a very good sleep quality. He has no daytime sleepiness with the use of his beloved ASV, and he calls it his little buddy, and he loves the ASV. His download shows no significant residual disordered breathing, and a recent oximetry is normal with well-supported oxygen saturation and no oscillatory variability of oxygen tracing. So he is your dream patient. He loves the ASV. He's responded so well. You've done a great job. Success. But then he informs you that he had another MI a couple of months ago, and his echocardiogram which he just had yesterday shows that his ejection fraction is still reduced at 30%. He's already on the appropriate medical management for his CAD and heart failure. You know, he's not in fluid overload. He's well-optimized. But what do you do now? Do you take his ASV away from him, or do you allow him to continue the therapy? Hey, Cara, actually, if you don't mind, back up to the case. Yeah. I think there's a good, you know, point of discussion there as well. And I don't know if maybe some of the rest of you saw this, you know, but so this gentleman apparently developed his symptoms after his MI, and his EF is 50%, and yet he has central sleep apnea. And I don't know if that kind of maybe surprised some people, but, you know, I think it does highlight, at least I think this is a controversy in terms of my own experience and the literature. In the literature, it certainly talks about diastolic heart failure or diastolic dysfunction also being a risk factor for central sleep apnea. I have to say, I'm not sure I see as many of those people. I see a lot of people walk into my clinic with diastolic, you know, badness on their echoes, and they carry the diagnosis of heart failure. But it seems to me that most often those are obstructive, although I would say more commonly those are the people that have treatment emergent central sleep apnea. That's just my, but I don't know what my colleagues think about that. Yeah, I was just asking Tim that as well when you were talking, that I have never seen an EF this high with central sleep apnea unless it's treatment emergent, or they have AFib, or they're on opiates for whatever reason. He's a special guy. So let's go to your, we didn't step by your question successfully? So no, you guys are not getting out of this one. We tried. We tried. I don't know if the audience also has seen, you know, these rare cases. Yeah. I mean, I totally agree with you guys. I feel like I have seen central sleep apnea with a little bit higher ejection fraction in the past, but I do agree that it's less common. And there are some people that I meet, I had a guy recently who had central sleep apnea, and he actually had central sleep apnea, you know, kind of like as he was falling asleep too, and really didn't have any reason for it. He had grade two diastolic dysfunction on his echo. And I kind of wondered, is this one of these rare people who have CSA from their diastolic dysfunction? But it's, you know, it's so hard to prove that. So I guess the question that you're throwing in front of us, and it's one that I know all of us have dealt with, is we have somebody who, on the one hand, ASV seems a very reasonable treatment because it's effective. We're seeing good control of kind of the breathing parameters. And by the way, they're adherent to therapy. And by the way- They love it. He feels better. But now we've got this blasted 30%. So I'm just going to take a troll down memory lane for a second. You know, 2005, you remember, was the CANPAP study, which was a multicenter prospective study that really was trying to look at whether or not CPAP, now that was untitrated or relatively untitrated CPAP, would decrease or improve transplant-free survival. And you'll remember that the study was terminated before total enrollment because what they learned is that they're never going to get to their end point because the control patients weren't dying fast enough. Basically there was no difference between the two lines in the control versus the CPAP study. Now the really juicy stuff happened in a post hoc analysis that was performed by Dr. Artst. In that, what they found was that the patients who actually had control of their central sleep apnea did have an improved transplant-free survival. And so that sort of fueled the flames of the believers, shall we say, that said, yeah, we should really control central sleep apnea. We know that it's associated with a bad outcome, and doesn't this suggest that maybe we should try to treat central sleep apnea for the sole purpose of improving transplant-free survival? And as it so happens, about that time, initially the ResMed ASV came online, FDA-approved, for that indication in the United States. It had already been used in Europe. And so that was the genesis of the CERV-HF trial. And the CERV-HF trial, you know, everybody was very excited about until the abrupt halt of the CERV-HF trial in 2015 came out. And lo and behold, there was an absolute increase in cardiovascular mortality of about 2.5 percent, 2.8 percent, I think. And so you'll remember that that created a lot of furor. That study actually was published very shortly before a sleep meeting, and I had the unpleasant circumstance of being the president at that meeting, and so we had to scurry to create a special session. It was the largest group of people I've ever addressed, apart from a big meeting in China. And people were very upset about the results. And you'll remember it created a lot of confusion, because, you know, like, why would this be the result? And, you know, but I think the answer, I'm going to just be provocative, the answer here is if you want to follow the current guidelines, you would have to say, oh, we need a different treatment for you. And that's as far as I'm going to go, but I'll bet some of my panelists have some thoughts on that. Go ahead, Michelle. You go first. Well, so, for those of you who've been to the recent sleep meeting in June, there was a discussion on the ADVENT trial versus the CERV-HF, and then the data was also presented, I think, at the European cardiology meeting. So the abstract is there, but it hasn't been published yet. So you know, I agree. I think right now, like, what do we do with this patient, right? We have to tell the patient to stop ASV. But let's talk about the ADVENT, at least what we know so far of the results that were presented. So, first of all, the two algorithms for the ASV for ResMed and the Auto-SV are different. One targets minute ventilation, the other one targets peak flow. And in the study itself, the minute ventilation ASV did not titrate for obstructive apneas or it just kept EPAP constant and also used higher pressure support, whereas for the ADVENT, they used auto-titrating EPAP and they used much lower pressure support starting at zero to three. So there's some differences there. The preliminary data showed that the compliance to the device was much higher, believe it or not, than the CERV-HF and all the other studies that have studied, you know, just compliance on CPAP, which is, you know, not sure why, maybe because the ASV was more comfortable. And also, they did monitor patients every six months, so then they found that the first month, patients who were compliant the first month tend to be more compliant 12 months later. So that's one result. The other result was that the AHI was much better controlled down to five or less on the ADVENT compared to the ASV for the CERV-HF. And so, all-cause mortality, cardiovascular mortality, there was no differences. However, there was no increase in mortality. So, sorry, the CERV-HF had increased mortality, but the ADVENT did not have an increase in mortality. Right. But, so, you know, I had a chance to talk with some of the authors, and also I think Doug Bradley shared at that meeting, and I don't, is he here at this meeting? He's not here at this meeting. So, you know, the upcoming trial that I think we're all waiting for with the ADVENT, it hit a perfect storm, because in the middle of enrollment, we had this little thing called a COVID pandemic. The CERV data also then, you know, kind of created some additional doubt, and basically the European centers were told they could no longer enroll or continue the therapy. And so, between all that, they basically did not recruit the total in that they were looking for, and they didn't have complete follow-up on all of the patients. My understanding, pardon me? And then the, yes. Oh, yes. The Philips recall killed it. Oh, that. The other perfect part of the storm was the Philips recall, so all total, they have about a, this is rough, because it's from memory, but they have about 100 patients in the obstructive group, and they have about 100 patients in the central sleep apnea, because they took all kinds of sleep apnea, and in the central sleep apnea group, you know, they don't, Doug Bradley's words were very careful. He said, what this shows is that a peak flow ASV can be safely used in this patient population. It did not show a mortality benefit, nor an increased mortality. So this has really fueled the fire now to say, okay, could we please do the trial and complete enrolling people? And so I would not be surprised to see an additional trial, you know, with either device that continues hopefully to the power that we need, you know, to enroll enough people. But I want to share another part of that, that's still part of this question. So you've got this patient who's on the ASV. We all know about the warning that said, you know, oh, you shouldn't use this in people with a reduced ejection fraction because of this concern. But I'm going to tell you an experience that we had at Mayo Clinic that was only published in abstract form, but that has been published now by German authors, very same experience. We recalled all of our patients that were on the ResMed ASV. And we had a discussion with all of our patients to say, you know, sorry about this, but here's this report and, you know, we need to advise you of this and you may, you know, you should probably stop using this and we'll have to work to find an alternative. And what we found was that actually 65% of the patients that we recalled said, no, thank you. I'm happy with my treatment. It's working well. It improves my quality of life. And of course, many of these patients have other chronic illnesses and they were like 2.8% increase in mortality, what, that means nothing to me. I got other things that are trying to kill me. I'd like to be sleeping well, thank you very much. And so they did not recall. And so we just made a very careful documentation of this is an informed decision, just like any other, you know, surgical procedure we're going to undergo or something where you accept a certain amount of risk and we continued to follow them. Two weekends ago, or was it last weekend, I was meeting with some colleagues from Germany and they had the, they published their exact same experience where they called in all of their patients and they had the same kind of discussion. They had a bigger recall than we did. And they found that the majority elected to continue therapy. So I say that because in this particular case, what I would probably do is have that discussion and I would say, okay, so, you know, these are the data, so forth and so on. And then I would, you know, try to let the patient make an informed decision about should we stop therapy or should we, you know, seek, you know, just continue the therapy or seek an alternative. I don't know. What do you guys think? Yeah. So I had a similar experience and Tim, I was at Mayo Clinic in Scottsdale at the time. So we sent out all these letters based on this study. A lot of people were upset because they didn't want to let go of their little buddies, their ASV machines. And similarly, we had to consent them to sign away to say that they wanted to continue therapy. I want to stop back and talk about how this study was fraught. It was not a beautiful study. And a lot of people in this room know that. So one, they were first generation ASV devices and they didn't titrate the EPAP accordingly. Secondly, they didn't even have EF on like over 200 of the patients, both controls and in the experimental arm. Thirdly, a lot of the patients were non-compliant with therapy. So we were making this really big generalization and then for medical legal reasons, let's be honest, we were taking them off of their little buddies. What we found was that a lot of patients wanted to stay on ASV. And this is how our field has evolved as well. So I think this is a lot with editorials and commentaries, but a lot of sleep physicians in general, multidisciplinary, are getting more comfortable at saying, you know what? There's newer literature showing that ASV is actually superior to CPAP and bilevel PAP. We know that bilevel PAP, and this is ST mode, so backup rate, is actually intended for patients with neuromuscular disease. And so that's central sleep apnea with hypoventilation, right? Hyperventilation, like our CHF patients. There is a new study, and then CPAP as well. So there was a study that came out that showed that ASV compared to CPAP was superior. So it dropped the overall HI by 20 points compared to CPAP, and it increased remodeling. So the EF actually increased 7% more on ASV. There is a new study, and I'm interested to hear who has preliminary data on this. But the FACE study, which is out of France, and it's similarly looking at ASV therapy in CHF patients with central sleep apnea with more patients than ADVENT-HF. Do you know preliminary results from that? I have not heard any preliminary results. I did see a retrospective study, again, out of the German groups, you know, again, looking at this that did not show a benefit. But maybe I can ask, can I ask the audience a question? By all means. So we've got this patient. We've kind of discussed the controversial, you know, not as solid data as we would like. But let me just ask this. If you had the discussion with your patient, and you advised them about the pros and cons, such as you've heard them, how many of you, if the patient said, I'd like to continue therapy, would continue ASV therapy? Just show of hands. Okay. So it looks to me like this is a controversy in that we would all like better answers, but in terms of a practical solution to this kind of thing, it sounds like we're not that controversial. Most of us treat patients and not studies. I mean, I hope I'm not oversimplifying here. Oh, I think that that's an excellent point. And, you know, I chose this case. This was actually a patient that I saw. And we did have that conversation. And he did choose to continue his ASV therapy. With his little buddy. Yeah, with his little buddy, because he was so happy. And, you know, he'd had some hospitalizations and other medical problems going on. And he was just like, I really don't need, like, you know, this other issue coming back into my life while I've got all these other things going on. So, you know, I think, yeah, maybe it is an easier decision than it is on the surface. But it still makes, I don't know, it makes me feel a little weird that we don't have this data that really tells us it's a, you know, great choice. I had the same experience. Most people do not want to talk. But I had one patient who asked me an interesting question. He said, so if people die from the CERB-HP study, does that happen when they're awake or when they're asleep? So I actually did ask the authors. And they said, it doesn't look like they die during their sleep. It looks like death during their sleep. Yeah, so most of the deaths were arrhythmic deaths. They did not seem to happen, particularly during sleep hours, is my understanding as well. And then, you know, there are so many difficulties with that study. And again, it's no criticism. It's very hard to do these studies. So when we hear these criticisms, I don't think we should think, you know, oh, they were not thoughtful. But there was an unusual preponderance of patients on antiarrhythmics in the group that died, you know, proportionally. Babak. So there were two follow-up studies from CERB-HF. One was, and this was a difficult analysis to do, was looking at usage. Because think about it, if you're having a follow-up for a year and a half, you could be on ASD for six months, give it up for two months, go back on it, on and off, right? So they did on-treatment analysis to see how much people actually used it. And the people who used it the most died. And another analysis that they published was, I'm sure you're aware, the ejection fracture, right? If you're below 35, you had a higher chance. So... Lower was worse. More was worse. Lower EF was worse. So as long as the patient is informed, and you're right, it happens at any time of the day, you know. So there could be shopping and they dropped dead, or there could be sleep. There was no preponderance of any time of the day. So you're right, I mean, it could be 2%, 3%. But in a subgroup like him, who's a high user, an ejection fracture of 30, he may not be 2%, 3%, he may be higher. Yeah, I brought that up. As long as he's informed, and he's informed, then it is what it is. Yeah, and a patient with an ejection fraction of 40% and a patient with an ejection fraction of 15% are usually gonna be very different patients, so. I have a very simple clinician-oriented question. When they say they were sleeping more, the simple thing that comes to my mind is, were they sick because they were sleeping more, or they were sleeping more because they wanted to sleep more? Because a lot of patients who are ill with multiple comorbidities, COPD, I'm talking about CODF, Parkinson's, you know, the list goes on and on. Most of those people are not very active. They can sit in front of the TV, they will be sleeping. So when they calculated the sleepiness, was it with sleep, and during daytime, or was it just that they were sleepy and they calculated that I sleep nine plus hours a day, you know? So the question, the answer is, are we comparing apples to apples, or apples to oranges, you know? So let me see if I understand your question. Your question is related to the readings of sleepiness, which in the survey chat, there was a lot of disappointments there. One of which was, hey, not only did it seem like there was some increased mortality, but it didn't seem like there was much benefits in what subjective data they collected. Is that your concern, or are you talking about the time on machine? The time on the machine was that the people who were sleeping more died more. Yeah, or at least the people who were using the machine more, which I don't know that I would say is always sleeping more. Because we have, you know, obviously, we see patients every day who are not using their PAP devices who are sleeping. So they're different. Yeah. I mean, there is that U-shaped mortality curve, you know, where if you're sleeping more, you have an increased mortality, and sleeping less. So yeah, I think that's a good thing to wonder about, but probably we don't have the hard facts on that issue. And you bring up a good topic in terms of sleep duration versus quality. So we all hope for better quality sleep, not necessarily duration. But that sweet spot for all of us and all of our patients is seven to nine hours. So people who sleep less and more have higher mortality. I just wanted to add a comment to Favik's comment about the highest mortality rates based on CIRV-HF being in those less, with an EF of less than 30%, and then more than 20% of chainstokes breathing. So I wonder, with all of us and everybody in the audience, do you think it should be modified, then, in terms of the criteria of who should come on and off ASV? Well, I wish I had the answer. But what I've done in my practice is, if it's below that threshold of, again, these are all post-hoc analysis, there's always problems with that. Correct. And as a historical perspective, a post-hoc analysis got us into this problem. Yeah. Because a CAMPAP trial, they did a post-hoc analysis, and then that justified ASV. Here we are. So we have to be careful with post-hocs. But yeah, if a patient has less than 30%, 35%, I try to make sure, at least with my heart failure docs, we're doing everything. Many of these patients are on maximum therapy. But one would argue, for example, does this patient have an ICD? Because if they don't have an ICD, a defibrillator, that's much more benefit than giving them ASV, in my opinion. And the data is very clear on that. And many times, these patients don't have an ICD, and they have very low ejection fraction. But I tend to use that data, and again, but I don't feel strongly about it. I think we need more data, but I don't know if another study's going to ever get done. Yeah. I wonder if any of you try to switch patients out to oxygen or adrenocine stimulation? I was just going to ask a leading question about that. What if this guy comes in, and he says, I hate my pep therapy, and I'm not continuing any of this C-crap? You know, again, we have a lot of unanswered questions. And you have a patient sitting in front of you who is pretty sick. I give him very few things that are helping him feel better. I tend to, I give him the data, but I tend to really concentrate on the quality of life, right? Because that's really the only thing we have in patients at this time. And if they're worried about the data, then I'm happy to take them off your right. A lot of patients hate the C-crap, and they can definitely come off of it. But we've all seen the patients who felt so good on it, right? And I think those are the ones who are hesitant to stop on the basis of these data. And I think the quality of life is an acceptable outcome as compared to 2% increase with mortality, right? And so, of course, it's joint decision-making. But in these patients, I really tend to emphasize the quality of life and what they're getting. So, Kara, you asked about what then. And we have started, what if they are done with C-crap? It's no longer his buddy. It's now his blasphemy or something. Yeah, and I don't want to talk about medications, because that's the next question. Well, so you're obviously leaning into, is this a candidate for a phrenic nerve stimulation? And I think that this might be a good candidate for phrenic. I'd have to kind of look more carefully, but it might be a very good candidate for phrenic nerve stimulation. Phrenic nerve stimulation now actually has a good amount of longitudinal data showing efficacy, improved quality of life, certainly improved parameters of central sleep apnea. It's been pretty well tolerated. In our center, we've done four. We're about to do another three. So it's something that we're doing more. We don't have wealth of experience. But so far, the experience has been good. So, I mean, yes, I think that's a coming therapy that you'd have to really look into. And I want to make the, and stress the caveat that these are for CPAP non-compliant and ASV non-compliant patients. This is not necessarily first line therapy. And there's a lot of data, Costanzo wrote it up in like 2016, and it showed that the HI went from 25 to two, which is normal. The patient satisfaction was like 95%, the ESS dropped to normal. All the data looks great, but it is MRI conditional. So I'm a neurologist. You take my MRI away from me of my brains and I have nothing left, right? Other than my exam. But the new one, you can't use MRIs. With the phrenic or with the hypodermic? Yeah, with the phrenic. Oh, I didn't realize that. Yeah, as long as you have the right testes, yeah. I think they just announced that, like very, very recently. And again, you know, and I agree. I mean, if you have a, you know, somebody who doesn't have a reduced ejection fraction and they're doing just lovely with their positive airway pressure and so forth, you know, I don't think this is a discussion we need to have, but you know, this is this, this is the, in my view, this, you know, the modification of this that you've given us where we have a reduced ejection fraction, very symptomatic patient, and they're no longer interested in ASV for whatever reason, that might be the perfect candidate for phrenic nerve stimulation. I don't know, I disagree. I think if I have an EF, a patient with EF of 20%, and I would have a discussion and try to switch them out. I'm a little worried about that data. From what to what? Just because of the data that Bobak was saying, you know, they're more severe from ASV. No, but he's already, I'm saying the patient who's already done with PAP, they're not going to do that. Oh yeah, that's different. Like the patients who don't want to use PAP therapy, this is a great excuse, right, not to use it. But Michelle brings up a good point. But the patients who are, like this one, who loves his ASV, and let's say his EF is 15% or 20%, I would be a little hesitant to say it's okay to use ASV. I would do my best to try to get him on oxygen or phrenic nerve stimulation, and if it's not an option, then I think it's... And a simple solution is the ASV machine can be switched to CPAP. So you can put him on CPAP and... But now it's asking if they need to do a titration to make sure it's okay. Yeah, yeah. And as a result... But that's a good point too, and that's going back to like these subgroups of patients to, you know, if you have a patient with an ejection fraction that's really, really low and they're on an antiarrhythmic, you know, maybe you would want to think twice about leaving them on ASV. So I'm going to move on to the next question, because we're... Oh yeah, go ahead, sorry. I'll give you props for being in front of that crowd a few years ago, because that was an angry crowd. I was there. I was probably one of the people there. I was somewhere in line. Maybe I didn't even get to the front, because there were like 50 people waiting at the microphone. But what I recall about CERV-HF at that particular talk was they were standing up saying it was well done, people were well controlled, they were doing great on therapy, they had appropriate implant therapy, and so it's interesting that so much has come out, perhaps afterwards, that that maybe wasn't the case at the time. I mean, I think a lot of us felt that it was ResMed throwing ASV under the bus, because they weren't going to benefit from it any longer. That was, I don't know, grumblings in the hallway. But if there is something published somewhere or where there are, like perhaps an editorial about all the different critiques of CERV-HF, if you could direct me there, I would love to read it. Yeah, no, there is, where did it, it was Java, Harry, and Ken, was it in CHEST? It was in CHEST. It was in CHEST, and it's a very detailed, you know, like 12 points to know why the CERV-HF should be really a question. But if you want to see for yourself, this is, for me, this is the most concerning part of the CERV-HF. You know, the front material is all about central sleep apnea and ASV not doing well and so forth. Take a trip into the supplemental files and look for yourself what the residual apnea hypopnea indexes, and in particular, the obstructive apnea indexes were on their populations. And I think you will be very much concerned that the patients that were being treated were not being treated the way that we would treat a patient now, because they had very high residual, they were not treated, let me just say that. There was a very high proportion of patients that were not treated, and one of the reasons why I think we are not gonna see that safety signal from the ADVENT is that they had an autotitrating and expiratory pressure, and that's why the AHI came down so well, because a lot, you know, as you know, most patients don't come out of the box and say, hi, I'm pure central sleep apnea. They usually have obstructive for part of the night or times and so forth, and so having that autotitrating capability, I think makes a difference. And if Dr. Jabahari were here, I know he would say that. He actually was among the crew that was gonna be here, but he was not able to come, so. Yeah, I know him well. The other thing I would add is that this is a patient that we, so we're one of the bigger remedy implant programs. We've done over 50 of them, and these are the people we're routinely implanting right now, or people coming in with reduced ejection fractions. Many of them are on ASV, and a lot of them, actually, the DMEs in our area will no longer fill prescriptions for people like, if it's, they don't care if we're documenting informed consent. If somebody's got a reduced ejection fraction, they've been told by their superiors to simply cut off support, which is kind of crazy, right? But I will tell you that we've had a high level of success with implanting frantic nerve stimulators in people who meet this exact criteria, so. Great. Well, thank you, everybody, for the, oh, okay, one more question. Yeah. You know, there was a really, at least I thought it was a very informative article published, and I think it was in JCSM, in fact, I'm pretty sure it was in JCSM. One of the authors is Adam Bengefeld, I think Atul Mahotra is on that article, and it actually looked at a big data approach to the ASV, and I wrote an editorial on that, because what they looked at was, what was the effect of differing PS minimum, PS maximum on AHI, and so forth and so on, and actually, there was very little association with that PS min, and that's a big population, I don't remember how big, it was quite large. What was much more important was leak, and they found that actually, by my clinical standards, it was a lot more attention to the leak than I normally pay, and so in my own use of ASV, and I've been using a lot of resident ASV over the years, I've actually more and more been just letting that PS minimum go to zero, because I'm just not convinced that it really makes a difference. Now, if the patient's complaining, and then it becomes almost like tweaking the trigger sensitivity or things on non-invasive ventilation, I mean, you're just trying to make them more comfortable, but that's just my opinion, and I think the data, at least not individualized, but just on that population, really, I'm not sure that we need that initial PS minimum. That's just my opinion. All right, this has been an amazing discussion. I didn't know that it was gonna take so much time, but I'm glad that it did, because it seems like people wanted to talk about it, so that's wonderful. All right, so we're gonna move on to the second case. So this is another interesting situation with a lot of rich discussion points, hopefully. So a 56-year-old woman with hypertension, hyperlipidemia, diabetes, and coronary artery disease with one stent presents to sleep clinic. She lives in Minnesota most of the year, but she also has a home in Aspen at 8,000 feet. She states that when she's at her home in Aspen, her sleep quality is awful, and it's impacting her ability to ski and participate in social events, because she's so sleepy. When she is at her home in Minnesota, her sleep is fine. She went to a doctor in Colorado, and an overnight oximetry was performed and showed a baseline oxygen saturation of 89% and significant oscillatory waveform variability with an oxygen desaturation index of 34. Polysomnogram confirms the presence of severe central sleep apnea with an obstructive apnea index of less than five, so mostly central. You are seeing her in Minnesota, and you perform another overnight oximetry at near sea level, and it shows a well-maintained baseline oxygen saturation of 95% and very little oscillatory waveform variability. She wants to know if there are treatments that might help her while she is in Aspen, and what are her options? I think we need to first know if there's anybody here that practices in Aspen, Colorado. All right, get on up here. No. No. By the way, I'm the director of the sleep lab in Aspen Park, the highest sleep lab in Colorado. Yeah, 7,200 feet. Oh, cool. If she had a PSG, she was probably in my lab. Although, there is this little kind of like trailer thing that they sometimes do. I think it's in Carbondale, so a few, but they don't score well. They don't score central hypopnea, so screw it. Oh. No, I just was curious. Yeah. No, I was just curious, you know. We see this all the time. This is like, you know, treatment-inversion central apnea, like, you know, you have many people who have well-controlled sleep apnea on CPAP at sea level, the Midwest, wherever they come out to Colorado, even on their CPAPs, and they'll have AHIs in the 50s and 60s. Sometimes it's transient for a few days, and other times it's not, and it'll keep going on and on. So a lot of these people end up on ASV with a diagnosis of complex sleep apnea, but is that really what it is is the question. So this patient, though, apparently only has central sleep apnea at altitude and nothing at her, in Minnesota. Oh, yeah, I've got my guy who's got an HI of, a central HI of four and a half in St. Louis, 30 in Fort Collins at 5,000 feet, and 120 at 7,200 feet, and that's his park. So, yeah, we see that. So what do you guys think? What are you gonna do with this lady? So we see similar phenomena, not to your degree of height. So I'm in Phoenix, we're at like 800 feet above sea level, but we have a lot of Sedona people and Flagstaff people, and they're at like 8,000 feet. And what happens is they're well-controlled in Phoenix, they vacation up there, and their obstructive sleep apnea worsens, they develop central sleep apnea, and then, like you said, worsening of TEXA. So she has vascular risk factors. We need to treat her somehow. And so one of the big questions is, with central sleep apnea at high altitude, with periodic breathing, do we even have to treat these patients? And she's a special situation where she's only there for like a couple months. And I would argue yes, because it's still hypoxia, she's a vascular patient, we need to treat her. And Kara's gonna go on, because the story unfolds and it gets a lot more complicated. But just at this point, I would offer her supplemental oxygen and azetazolamide, starting at like 125 milligrams, kind of low dose, and watch the body carb. But I would use that combination therapy based on her pulse oximetry. You know, I think it's interesting that you brought up her vascular history, because some years ago, probably it was in the setting of, you know, I had to give a case conference at our institution and I kind of had a high altitude. But, and somebody here probably knows this data better than I can recall it. But I was just looking at, apart from sleep apnea, you know, we see patients all the time who have cardiovascular or cardiopulmonary disease, and they're gonna go to, you know, snow mass. And what do we advise them? You know, I mean, are they safe? I get that. I see some shaking heads. And of course, with the patient with COPD, there's always, you know, do I do a simulated, you know, altitude test and so forth. But even apart from those people, there's pretty good data that show that people like me, well, I don't have any cardiovascular disease, but guys die during physical activity. You know, they hit the slopes and they're doing the physical activity. And if you have predisposing cardiovascular disease, it's during the strong activity that the deaths tend to occur. And so, you know, this case in one way is related because what you're balancing is, okay, she has cardiovascular diseases, and having central sleep apnea is a challenge. I mean, there's a lot of increased sympathetic tone. The studies that have been done looking at healthy people, and you take them from C-level and you go to 8,500 or higher, and you just measure their sympathetic tone, it goes up, and it's particularly related to the frequency of sleep disordered breathing. So there are also, I think there've been some studies, again, kind of more researchy studies rather than clinical studies, showing that there are increases in nocturnal blood pressure. They kind of lose the dipping at night and so forth with the central sleep apnea. So there is, it is a cardiac stress test to have this, whether or not you have symptoms. Yes, okay. So that's interesting. But you would, how would you do her right now with nothing else? You would? So if she doesn't have coexisting obstructive sleep apnea, I'd give her supplemental oxygen and azetazolamide combination therapy. So just a question though, just practically, you know, how are you gonna qualify her for oxygen? Which is the problem I have whenever these patients come to, you know, yeah. She needs a diagnosis, right? We can have an oximetry, but she needs a diagnosis. So we do. We can ask questions. Yes. So. Well, I will. So I. That's exactly what happens with my patients. There's no pay. You can, you can. So, and that's something good, a practical, I'll give you a practical and then a kind of almost wildly not practical. But, you know, in these towns, you can just go pay for oxygen. They have like oxygen rental things. And I have had patients do that, you know. I think the most extreme form of that, I had a patient who was building a beautiful estate up in Snowmass or something. It was a little higher altitude. And he had this problem with, you know, not feeling well. And apparently, now maybe you can, the gentleman in the back may know about this. Apparently they're selling, like some of the builders, upscale builders are selling like a, almost like a shower nozzle that fits over the bed that will kind of spray oxygen over the pillow. And I was just like, man, I hope you don't smoke. Please don't. I don't want you to be. Oh, God. Do you know something about the shower nozzle? Is that your business? Oh, no. There's, there's, yeah, the oxygen tent. But they actually, some, I have a guy who's super rich and he actually, his entire house is hyperbaric pressurized. Like I've seen this. He lives in Evergreen at about 6,700 feet or so. But, so there is, yes, you can rent a supplemental oxygen for fee for service, you know. You can order it online before you get there. They'll deliver it to your hotel. The biggest downsides of oxygen I see are loss of altitude acclimatization. So I've seen, seen people get themselves in trouble. For one thing, their athletic performance falls off. Like this person who cares about skiing will not like this, most likely. So when I do use supplemental oxygen, I'll usually recommend they get some sort of pull sock so they continue. And I'll say, use the minimum amount of oxygen that your desaturation index is just like, you know, less than 10. And don't, you know, you don't want to drive your oxygen level too high. So, so that's one trick of kind of optimizing things. But they don't like the fact that they can't ski as hard. And I do think you see more cases of high altitude pulmonary edema. Hey, we've seen a few cases where people are using oxygen at night at high amounts and they're going killing it up at, you know, Bracken Ridge, you know, at the top of the mountain and getting themselves in trouble because they never acclimatize. But you said the key thing, which is setazolamide along with it, because that'll actually speed acclimatization. So yeah, we do that all the time. So usually setazolamide for two to three days beforehand. The whole time you're there, don't, you could stop it, but you probably shouldn't. You won't enjoy the beer, sorry. I actually saw a one case that was a fatality of HACE, which is the high altitude cerebral edema. It was awful. It was in a 20 year old. I've had HAPE and HACE personally. I'm a mountain climber too in a former life. Sucks. But we've had luck. I will tell you, and it may be state by state, but just by getting an overnight pulse oximeter, we usually go through the DME and documenting that five minutes of less than 88. We've had success in getting patients oxygen. Just with the diagnosis of sleep related hypoxemia. I've heard tales of that, but. I usually try to find something like coronary artery disease and low oxygen or something like that. Right. They receive that thing after three years of treatment. That's right, yes. That's another problem. Yeah. It's a problem in Cusco and Peru, where you can pay for a hotel that needs oxygen and those people don't activate as quickly. Mm, that's really good, that's really good info. Do you know this person that's flying around and spending a lot of time on the skin, can't they just buy their concentrator? They can. And they're back. Possibly. That's what Michelle said. Yeah, yeah, yeah. Now, do you ever use any medications other than acetazolamide for treatment of central sleep apnea? I have not. And again, I'm a neurologist. We use a lot of Diamox for things like benign hydrocephalus, so BPH. So it's a comfort level that I have in using it. But there are other medications. So theophylline is one, I'm interested to hear stories. And the other one is Boost Bar, or Boost Barone. And I think Atul and others have published that it helps both central and obstructive sleep apnea. And it's a 5-HT1 agonist. So I'm interested to hear, have you guys experimented? I haven't with that. I mean, in this case, I'm relatively unsophisticated. I tend to just use acetazolamide, or if they're willing to get the oxygen at altitude. And I like the tip about the oximeter. Now, in non-high altitude, like idiopathic central sleep, I have used Zolpidem. I have used theophylline. I'm old enough to have used theophylline for a lot of different purposes. And it's not fun. But I would say that I've had sporadic success with that. With the theophylline, I like to stop it as soon as possible because it's just got such a doggone narrow therapeutic window, and so many drugs can pop it up. And then, I just, it's like one of these drugs that I don't know that we need anymore. Right, and if you have a cardiovascular comorbidity. No, it's just very, you know, it's so funny. It's always made me nervous. We used to just use water in all of our COPD patients, and then it was evil, and then it was good again, and then it was evil again. And now it's just like, I don't think I need it. Yeah, well, we have like one more minute. I, you know, the rest of this case, you have a thorough discussion with her regarding pap therapy and medications, but she's claustrophobic, she can't tolerate a mask, she's worried about medication side effects. She's just not gonna do anything. I think we kind of already addressed, you know, this part about should we treat her or not, but the curveball I was gonna throw at you guys was that, okay, now she has OSA, and her AHI's 25 at C-level, and she uses CPAP. But then she goes to altitude, she's got symptoms on her CPAP. And we talked about this a little bit, but I think, you know, if you guys wanted to offer some clarity on what exact advice you would give her, or anyone who has OSA at C-level, and they ascend to altitude and get more symptoms. I had a dead space mask. The Swiss, the Swiss is just retargeted, so it's just, I don't wanna see that. Yeah, yeah. Would it randomize patients with obstructive sleep apnea to acetazolamide versus placebo? This was a paper in JAMA. While continuing CPAP. While continuing CPAP, and they demonstrated that the central apnea index went down. Yep. And their obstructive AHI, while on CPAP, remained low. Mm-hmm. The placebo went up. They didn't do any oxygen. They just said, continue your CPAP. And, you know, of course, if they stay there for a long time, usually central apneas go away. Mm-hmm. But most people just go there for vacationing, and they feel bad. Right. So, I think Dymart is a good choice. But in this case, I mean, we don't know why her symptoms are worse. I mean, we assume it's central sleep apnea. Yeah. Yeah, I mean, there's literature to suggest that it's really a mixed bag. You know, you can get worsening of obstructive apnea. You can get worsening of central apnea. You can get replacement of obstructive apnea by central apnea. So, sometimes it's a little bit challenging to know. And I actually wanted to ask you, too, you know, there is conflicting literature about use of ASV in patients with high-altitude periodic breathing. Some of it says that it works, and some of it says that it doesn't. You know, what is your clinical experience? So, it usually works. So, I have people where, there's different patterns. There's people where it's bad for like a night or two, maybe to have them take acetazolamide for the few days before they show up back in Estes Park. That usually works. They don't need to continue it. Then there's some people where it lasts for like several days, where I might continue the acetazolamide a little bit longer. But there are people out there who absolutely, I have this one guy, he's an emeritus professor from Texas who spends half the year down in Texas and comes to Altawk, and his HI goes from two or three on ASV or at C-level, because he had a complex sleep apnea diagnosis there. And in Estes Park, it's usually in the 30s and 40s. And so, we've tried acetazolamide. It really didn't work that well. So, with him, we've added just enough oxygen to just keep his HI's on the downloaded data on his ASV machine, kind of in the, seems like in the 10 to 15 range, he doesn't notice the loss of altitude acclimatization. He can still go hiking in the park. So, adding just enough oxygen to get you where you need to be is kind of the key there for a lot of those people. But I do have other guys who are, they're on CPAP and they have the same thing where they have transient bumps in HI, all central for like a week after it'll taper down. And that's not a problem, except for like some people like to travel a lot. So, if every time they're coming back to high altitude, they have to deal with this again, they'd rather not take acetazolamide. So, I've switched some of those people to ASV. I will specifically do the in-lab titration study the day they get back from Florida and they qualify. And it works great in many of them. Although, we've had a few people where we have had to add a little oxygen into ASV therapy like that professor I was trying. So, it doesn't always quite get you there. Yeah. What does the dialogues show you? 250. 250. I was gonna say for the patients who have, you know, they spend like half a year in their second home, they would go to a sleep lab up there and get their central diagnosed and get ASV. Then when they go back to their, you know, wherever they're at, then they can go just switch to CPAP because the ASV can do CPAP as well. Right, a lot of them actually. So, I have several patients like that, that I just have. They can switch to CPAP in Florida when their ASV is in Estes Park. It works great. Yeah, and I think that the data that's published on ASV altitude question, you know, it kind of comes out on the side of saying, well, you know, people who are long dwellers, you know, probably ASV is an effective modality for those who have, you know, long dwelling persistent central sleep apnea. On the short stayer, the one week and so forth, you know, I think the data are controversial in terms of how well it works, where it seems to be at. And it actually doesn't work too badly to just say, yeah, continue to use your CPAP, and take, you know, acetazolamide for a couple of days before you get there and while you're there. And I don't know, I have some patients that really, you know, find it objectionable, but I don't have a lot of them who've complained that much about acetazolamide. I always feel like I'm poisoning the waters by telling them that they might experience the metallic taste and so forth, but. It's not like Paxilovit, it's not that bad. No, but it makes your beer taste flat, and we have a good beer in Colorado, so that's kind of a bummer. And kidney stones, I mean, that's the major concern, is acetamol, solomide has a high incidence of kidney stones. So hydration, watching their bite bar to prevent the metabolic alkalosis. And how about paresthesia, do you get a lot? A lot of paresthesia, you're right, but like Topamax, it usually goes away. It does, okay. Mm-hmm. Not to complicate things, but I have a couple of patients who are also at least with cardiovascular issues, and they have severe concentrical heart and also hypodendritory, in terms of obesity, hyperinflation, what do you do with those patients? That's a good one. I should have thought of that. Right in front of you, for OHS. Yeah. Popek, what do you do? Yeah, I do. I said this actually at the sleep conference when the ASV thing came out. I have a mentor that I still very much cherish, Dr. Jay Roo, he might be at the conference, and he has the perfect answer for you. Tough case, no data, good luck. Yes, you know, I don't know what else you're gonna do. Yeah. I mean, you're gonna have to just kind of, that's a one-off. I'm sorry, that's too many comoridities. It's harsh. Yeah. Yeah. I'm on that. No, I think you're going to, you're basically gonna have to adjust your therapy, but I don't think there's a predictive way to do that. I might be wrong, maybe there's somebody brilliant. You're gonna have to do an adjustment in that patient's therapy and figure out what's gonna work for them at altitude, you know, and. ASV with a pressure support of eight to 15. I don't know. Well, I would expect that they wouldn't have sensuals when they're at altitude. If they really are hypercapnic, I'm not sure they would. Have you seen that? Well, but if they're acclimated at whatever their CO2 set point is, now you make them more hypoxic. Yeah, they're the opposite. It's just like the person who you, yeah. They have to kind of find their new set point. So yeah, tough, tough problem. No data. Good luck. I do want to ask though, are people using VAPS therapy for sensual sleep apnea? Not necessarily high altitude. No. There was a paper that came out by Moncy Diaz from University of Maryland that showed it could be superior to CPAP and ASV. What kind of sensuals though? Yeah, they're mostly hyperventilation, so neuromuscular vision. Yeah, I mean, should use a VAPS or VAPS therapy for hypocapnic sensual sleep apnea. Yeah, I agree. True. Same way you should not use DSV. For hyperventilation? Yeah. Exactly. Yeah. Good.

central sleep apnea

ASV therapy

reduced ejection fraction

treatment options

supplemental oxygen

acetazolamide

theophylline

boostbar

obstructive sleep apnea