Dr. Rajeev C. Mohan discusses the World Health Organization (WHO) classifications for pulmonary hypertension and appropriate diagnostic and treatment strategies for each group.
Back to Symposium Page » So our next lecture again. One of my esteemed colleagues, Dr Mohan, who was one of our fellows here and then went to Cedars Sinai and were able to lure him back. He's going to talk to us about a very common clinical problem that's often overlooked. And that's, uh, elevated P A pressures. I think there's a lot of confusion about this, but again, this is an area that's rapidly changing and something that we could do a lot about. So I'm very anxious to hear what he has to say. And I think this will be very helpful in your practices again. So take it away, Raj. All right, great. Thanks. Dr. Heywood. We'll be talking about, as you said, treating elevated pulmonary pressures, and there's sort of a broad spectrum of what can cause elevated pulmonary pressures on dso. We're gonna kind of covers much of this, Aziz, We Azzawi can eso with that. I'm just gonna There we go. Here are my disclosures. So the diagnosis of palma hypertension. You know, this is often made when we're doing an evaluation for shortness of breath. Um, and the key part of the diagnosis for Pullman hypertension and the key part of the work up for shortness of breath should always include an echocardiogram. Provides a lot of information about the overall function of the right and left ventricle. Provides an evaluation for any structural and or valvular heart disease. But the key part of it is that it provides an estimation of the pressures in the heart. And this is a key component of what we call cardiac Disney. Um, so one of the things that we're looking for on echo when we're doing an evaluation for shortness of breath. So wall motion abnormalities Certainly ischemia can present a shortness of breath. Um, ejection fraction or evidence of cardiomyopathy. Low cardiac output. Of course, patients can have low cardiac output, and that may manifest is shortness of breath valvular heart disease. So things like aortic stenosis, my short vegetation, those were all gonna affect the filling pressures within the heart, and that can cause patients to become district. But really, what we're looking at more when we're doing an echo for patients who are short of breath is we want to know what the filling pressures are. That's the key component when we're looking at echoes. Andi In fact, we'll often do bedside that goes with our many echo machine to do an assessment of pulmonary pressures specifically to see if they're elevated. So this is a key kind of component. This doctor Heywood just mentioned. You know what? We're doing these evaluations and it's really the pulmonary artery pressure that we're worried about. In any pulmonary artery, pressure higher than 40 really deserves. Ah, further investigation, Andi, even in patients who really aren't that symptomatic or for getting an echo for one reason other, and there they're pressures. Air elevated certainly requires some some further evaluation to ensure that there isn't something else going on. So I like this quote of cardiac this, Nina, You know what? What causes? Shortness of breath and patients with cardiac disease. And this is actually taken directly from chapter in Harrison's internal medicine textbook, written by Eugene Braunwald. So I read the quote quickly because I think it's really important. Thio kind of understand where what causes shortness of breath, and they put it very succinctly here. So it's the elevation of hydrostatic pressure in the pulmonary vascular bed, which results in the translation of liquid into the interstitial space reducing the compliance of the lungs. The competition for space among vessels, airways and increased fluid within the interstitial space comprises the compromises the Lumina of the small airways and increases the airways resistance, dimunition and compliance. And an increase in airway resistance increases the work of breathing. And this is really that increase. That feeling of increased work of breathing is really what people describe a shortness of breath. But of course there's a whole host, different reasons that could cause him. We're going to spend most of our time here today talking about two broad categories of of elevated palming pressures or pulmonary hypertension. And that's probably arterial hypertension or what we call pre capita hypertension or pulmonary venous hypertension, what we call post capital hypertension and again, looking at the echocardiogram, this slide, you know, kind of highlights all of the specific things that we're looking for on echoes to help us differentiate between Palma arterial versus Pullman Venus Hypertension. Um, so you can see here, um, right ventricular size uh, typically with pull material hypertension. It's enlarged with Pullman Venus hypertension and may become enlarged over time as the left ventricle causes some amount of right ventricular dysfunction. The left atrial size is a key, uh, component of what we look for. So and probably arterial hypertension is typically small, Uh, whereas with Palmeri Venus hypertension, we often see unlock urged left atrium. Because, of course, the elevated left atrial pressure is really what's driving the Palmeri Venus hypertension. Um, the ratio of the right toe left atrium can be abnormal in pulmonary arterial hypertension. It's typically increased because we're seeing higher. Ah, bigger right atrium. In those patients theater atrial septum can bow from one side to the other. If the right atrial pressure is higher, it's gonna bow towards the left. The left nature pressure is higher. It's gonna bow towards the right. Some some more kind of specific findings we see on echoes, our bot notching. So this is looking at blood flow through the right ventricular outflow track. Um, sometimes we see this notching pattern in in patients with pulmonary arterial. Hypertension is blood is flowing out of the right ventricle. You can see that's highlighted. Here. You can see this little notching, uh, of that signal, the eat a ratio. So this is something that we look at when we're doing a Nev valuation of diastolic Gee, what's the diastolic function of the heart? Andi? Typically in patients with pulmonary venous hypertension that eat a ratio is going to be higher. The next two are sort of components again of diastolic function. But really, when it comes down to it, it's this moment capitally wedge pressure on. We have some ways to estimate that by echocardiogram, uh, eso for estimating that the pressure is elevated higher than 15 than that's more consistent with Palmer Venus. Hypertension on diff It's less than 15 that that's more consistent with pulmonary arterial hypertension. So we're going to kind of go into that in great detail. Um, but really what? It comes down Thio. You know, if we suspect that somebody may have Pullman hypertension by echo, it's really, um, you know, we're not sure 100% what could be causing it. It comes down to doing a right heart. Cath, we really need to do a right heart Cath to help identify whether or not this is arterial versus Venus and one of the things that we're looking for. So the Swan Ganz Katherine, of course, is gonna be measuring the right atrial uh, right ventricular Pullman artery pressures. But of course, we get the Pullman capitally wedge pressure, which is a nest emit of what the left atrial pressure is like. So not only do we get an assessment of the right pressures, the right side of pressures we get an assessment of the left atrial pressure, but also the pulmonary vascular resistance, or PVR. That's a key component also in helping us make the diagnosis of whether this is arterial hypertension, what we call pre cap Ilary. Then you can see here kind of why we call this pre capita hypertension. Because, of course, the pressures air elevated before, um in the vessels before the pulmonary capillaries, as opposed to pull Marie Venus hypertension here on the right side of the screen, where the vessels of the Pullman pressures air sort of elevated throughout the circuit but caused primarily by issues in the post capillary part of the system, the left side of the heart. So here is sort of our sort of diagnostic algorithm. In a sense, you know, if we the definition of Palma hypertension, number one is pressure's elevated beyond a mean pressure of 20 s O. That defines Palmer hypertension. Then it really comes down to the wedge pressure. If the wedge pressure is elevated greater than 15, then that's considered pulmonary venous hypertension. Everything that's in red here on the right side of the screen. Um, that is what's called W H O Group, too. So World Health Organization group to Palmer Hypertension will go through kind of specifics of that here in a bit, and that could be due again to a number of different things related to the heart. But we kind of break that down into whether they have reduced ejection. Fraction of preserved ejection fraction. On the other hand, everything over here on on the left in blue. If the wedge pressure is elevated beyond 15, I'm sorry if the wedge pressure is lower than 15, then that's consistent with pulmonary arterial hypertension, and that is part of either Group one Group three or group for hypertension. And there's a whole different variety of things that need to be evaluated to ascertain whether it's which one of those groups it is because the treatment of that is much different. So we talked earlier about the pulmonary vascular resistance that is defined as the mean pulmonary artery pressure minus the wedge pressure. So the differential pressure within the pulmonary circuit divided by the cardiac output. So in those patients with Anel avai did, uh, mean print pressure with normal wedge pressure, you could see that difference across the circuit. Something called the trans pulmonary Grady, Um, that's gonna be elevated. And so we divide that by the cardiac output, we're going to get a higher number. So anything beyond three Woods units is considered, um, high A supposed to patients with an elevated mean artery pressure but an elevated wedge pressure than that transform ingredient. The top number. The numerator is gonna be lower on DSO the woods units are going to be lower less than or equal to three. There are many instances where we see that patients can have sort of mixed disease where that PVR sort of in the 3 to 6 range where their P a pressures air elevated and their wedge pressures air elevated. But the pressures may be elevated beyond what we would expect with the degree of elevation of the wedge pressure. So these patients may have some component of what we call combined pre and post cap Hillary Palmer hypertension. Sometimes we see that in patients with significant mitral valve disease who have had longstanding micro vegetation, where over time there's some development of pulmonary vascular issues where they're they're the Palme vascular resistance starts to go up those patients sometimes a little bit trickier to treat. So let's quickly go through the W H O classifications here of Palma Hypertension Group one is due to actual Palma vascular disease. Typically, we see this in patients with connective tissue diseases. Such a scleroderma crest, Lupus, sometimes mixed connective tissue disease. Often we see this in patients with liver disease, part of pulmonary hypertension. Um, toxins such as methamphetamine or fen phen. Uh, HIV can cause this drugs certain drugs, chemotherapeutic drugs are known to cause palma hypertension, and it could be idiopathic or heritable. Aziz Well, and so we see sort of idiopathic palma hypertension on. This is classified as a group one. Group two, of course, as I said earlier, is due specifically toe left sided heart disease, and this could be related to reduce DF heart failure or preserve the of heart failure on been preservative heart failure. We think of it as diastolic dysfunction. But we also don't that it's not just the left ventricular diastolic dysfunction that can be, uh, bad, but also left atrial dysfunction can play a role in the development of palming hypertension, pulmonary venous, hypertension, things that we see the commonly mawr commonly now the specific types of restrictive cardiomyopathy, things like amyloid heart disease or valvular heart disease. Um, Group three is related to lung disease, so things like COPD, sleep apnea, interstitial lung disease, uh, in pulmonary fibrosis. These are things that are affecting their lung parang comma but can ultimately lead to chronic hypoxia mia and vessel constriction leading to pulmonary arterial hypertension. And lastly, Group four Eyes related thio chronic from bomb bolic disease. So patients with chronic PES can, over time, develop Palmer hypertension as well. There's a summary slide of the different groups, but again, 13 and four being Mawr lung related. Pre capital area hypertension group to being more heart related post capital of hypertension. There is a Group five, which is sort of a multifactorial disease. Um, certain human logic disorders and sometimes are quite can cause it as well. Eso the key part of, you know, on that sort of bottom left side of that slide that we looked at before with pulmonary pressures on the wedge pressure. So if we've made the diagnosis of pulmonary arterial hypertension, it's key that we differentiate whether this Group one versus Group three versus Group For because the treatment strategies are much different. Eso How do we do this? Ah, lot of it has to do with the patient's history. Certainly, if they've got a history of connective tissue disease or liver disease or history methamphetamine abuse, then that kind of drives us. It kind of gives us clues that it may be one type of one group versus the other pft s uh uh, overnight sleep Study High red CT looking for fibrosis on the C T angiogram, or sometimes more commonly for suspecting Group four will do a V Q scan looking for small vessel disease, a chronic PES on that's helpful to kind of help differentiate between these groups. The key part of what we're what we're interested in here when we're seeing these patients is saving the right ventricle. We really want to get treatment started, whether it's Paul Martel, hypertension or Palmer Venus hypertension, the key here is Thio. Prevent right ventricular failure. This is sort of a classic slide, looking at the progression of different human dynamic parameters and cardiac output as well as mortality as time goes on. So what you can see here is that the cardiac output starts decline over time is the pulmonary pressures get worse. The palming artery pressure starts to increase and then eventually starts to decrease again as the right ventricle starts to fail and as the right ventricle starting to fill, you see this bottom line, the right atrial pressure starts low and then starts to increase. So once we see patients with elevated right, ventricular uh, sorry, right. Atrial pressures. That's when we get really concerned that we need to be more aggressive in treating these patients because, um, again, we want to save the right ventricle because these patients develop right ventricular failure. Um, end stage right ventricular failure than they develop, uh, Paddick, congestion, renal disease. And then those patients, the mortality rates and those patients is much, much higher. Yeah, so we'll talk here. Next about treatment of Palma. Hypertension will first focus on the left side here, which is a Pullman arterial group. Typically, what we do is that right? Heart catheterization? Once we've confirmed that it's arterial in nature, with lower wedge pressure, we often in the Catholic. When we're doing that, we do a baser reactivity tests with inhaled nitric oxide. That's the help. See if they may be candidates for treatment with calcium channel blockers. It's very low yield test did not. Very many patients are truly reactive, but we do this test to see if they may be candidates for this, because this is an easy treatment to start with. Otherwise, if they're non reactive and we've confirmed that their Group one Palma hypertension, is part of our work up, then we'll start therapy, which is directed at dilating the blood vessels within the pulmonary vasculature. Certain high risk features highlighted over there on the right that may, uh, make us do combination therapy or even I v therapy for this are things like sink api significantly decreased six minute walk test evidence of RV failure Already, you know, are a pressure being elevated, cardiac output being low pericardial effusions or, if they're biomarkers, air significantly elevated, we may get more aggressive, so treatment for this is very specific. This deals with treating the pulmonary vasculature. There's three pathways that we look at and to feel in pathway in the on the left, that nitric oxide pathway in the middle and the process cycling pathway on the right. Basically, all of these pathways promote visibility ation and prevent vessel constriction. But in patients with all my heart pretension, the balance between vase debilitation vessel constriction has been misaligned, so there's more of a drive towards phase of construction. So what we're trying to do is promote these intrinsic pathways that are involved with visibility ation. So on the end of feeling pathway we have in the field and receptor antagonists this help increase visibility ation, nitric oxide pathway. We can either give exogenous nitric oxide or we have the faucet dia straits type five inhibitors, um, that help change signaling pathways that promote visibility ation and then, in the process cycling pathway. We have actual process cycling derivatives that we can give in various forms that again also help visibility ation, um, and improvement in the reduction of the Pullman basket resistance and improvement in the pressures. So these are some examples of the medicines that we give. There's a whole host of different medicines Um uh, in each of these different pathways. But now, uh, several new medicines, particularly the process cycling pathway available where we actually have aural agents available in this category previously was predominantly ivy therapy for these patients if they needed process cycling pathway. But now we have inhaled subcutaneous as well as Orel options. For this group, we have again a low threshold for the addition of the second or even the third agent, particularly if they're not symptomatically improved. And again, the goal is thio prevent art, right ventricular failure which can lead thio lead to cirrhosis and, you know failure Group three You know, this is specifically lung disease things like COPD, sleep apnea, palmeri fibrosis. So there's really no strong evidence for using any of those medicines that we talked about before. For Group three, the underlying the bottom line is to treat the underlying lung diseases aggressively as possible. So CPAP for those with sleep apnea, um, the inhaled medicines for those with COPD. So we work very closely with our pulmonary pulmonologist colleagues in these patients for group for, um, anti coagulation, of course, is key because we think it's chronic pulmonary embolisms that are causing this recycle. What is one of the medicines and the nitric oxide pathway, which can promote base facilitation? This has been studied in combination with an end of feeling receptor antagonist for patients with group for So sometimes we get these patients on that therapy. Um, and there's actually surgical treatment for this where the surgical team could go in and extract these small vessel clots on DSO. There are on occasion patients that we will send for surgical evaluation for for treatment of this group of Pullman hypertension as well. Um, rare instances where if there have significant RV dysfunction, they may be considered for a step tosta me to bring down pressures. This is only is either retaliation or is a bridge to lung transplant. Andi, also the use of right ventricular mechanical circulatory support things like ECMO or isolated right side of ventricular assist devices which there are a couple that we can use, um, in rare instances as well. So key points must establish the W H O group specifically because the medicines that we used primarily for Group One, we typically avoid using those Palmer antihypertensive in group to an early aggressive treatment with frequent surveillance. Eyes key again to avoid right ventricular failure. So now we'll talk predominantly now about the group, too. So left sided heart disease have half and half in half, ref, which can also cause Paul my hypertension. Eso again. A vast majority of patients that we see with elevated Pullman pressures are actually group to a related to either reduce DF for preserved e f heart failure. So again, this has to do with elevated left sided pressure, so either left ventricular dysfunction left atrial dysfunction. So I really like this slide, um, which is relatively new in a paper that came out recently. It's kind of hard to see on on the slide here, but we'll get that out to you guys. But it really kind of goes through the pathology of both preserved and reduced F heart failure. And what are the sort of what are the specific triggers that could cause it and one of the human dynamic changes that occur? But ultimately you can see here in the small boxes there are some pressure volume loops, but ultimately what happens is the left side of filling pressures increase whether that's again related toe left ventricular pathology or left a trail pathology. The left side of pressures increase the left atrial pressure increases. And ultimately, that leads to primary pulmonary uh, Pullman pulmonary pressure increase in shortness of breath. So we have, of course, very specific therapy that Dr Heywood reviewed very nicely for Loewy of heart failure. We have, you know, four kind of pillars now with treatment for reduced. You have heart failure, beta blockers, Arnie SGL t two inhibitors and spinal black toner. Uh, memories. But of course, we've got defibrillators in CRT therapy on and advanced therapies like Elba and Transplant. For those who are candidates for preservative heart failure, the guidelines are limited. There's not a lot of data, unfortunately, with the same medicines that we use with preservative reducing of heart failure in this preservative group. So the recommendations here from the A. J A. C C. Are Class one diuretics to control the volume and filling pressures control blood pressure, revascularization If we think ischemia is causing issues on sign the restoration of science that we think that a fib is making the patients worse. So really not a ton of data that we have in terms of the medicines being helpful. The S E L T two inhibitors are being studied now in the preservative groups specifically, so we'll see what that data shows. What we do have data on for treating patients with elevated filling pressures is a cardio memes devices Dr Heywood already described. We have a number of patients, so we find that those patients with preserved, if actually do quite well when we're trying to balance there. They're fluid levels and renal dysfunction and symptoms. Cardio manage devices quite helpful on dso What you can see here. This is ah, sub study analysis from the champion Pivotal trial that looked at preserved CF patients versus reduced CF patients on on the right. You can see that those patients that had preserved the F compared to preserve the F in the treatment group they actually fared better than the reduced DF group. There, there, there they met their primary. They were able to, you know, avoid the primary outcome. And so we we again, in our program, have a lot of cardio memes patients. But we do have many patients that have health. Pef, where we found it very beneficial. Here's a quick case of ah, 71 year old with hyper lymphedema sleep apnea who has exertion, all dystonia. And there's her echo there, you know, some very basic Oh, are sort of first level evaluation of her. Was that her life? Metro volume with relatively normal. Her pay pressure was relatively normal. Her right atrial pressure was normal and she had a full work up, including an echo nuclear profusion scan and a coronary angiogram. All of that was normal, including arresting right heart Cath Onda. She was being sent to us for evaluation, shortness of breath. And she had a pretty profound shortness of breath at this stage. So what we did was a neck, sir size right heart, cath, to evaluate her human dynamics not at rest, but with exercise. And this is what we found. So on the left side of the screen here, you can see our baseline Human dynamics all very normal pressures. Um, you know, wedge pressure of 11 N p. A pressure of 24/12, a normal cardiac output. But with exercise, this is what happened. Her peer pressure's went up to 60/27 with a mean of 38 in a wedge pressure of 42. Andi, she essentially had findings of what we call stiff left atrial syndrome. So her left atrium was very stiff. It was It was almost enlarged on the resting echo. But they're the catheter Findings, you know, showed us these very tall V waves where the left atrium wasn't capable of accommodating All this extra blood returned during exercise, which led to an elevation pressure. Very significant elevation and pressure here. Um, so there is data to suggest that these people actually do worse if they had. This was a rest prospective trial of of about 355 patients that had exercise right hard cats, Aziz, part of an evaluation for dispute, and those patients where the wedge pressure went up with exercise. If you focus in kind of on the red solid line and the red dash line, you can see this is wedge pressure. If it went up beyond 12 here, the red dash line, their outcomes, their mortality was actually higher. And this was a long term study looking out over 10, 12 years. But you can see that a pretty significant increase in mortality. A za time went on compared to those patients who did not have an increase in wedge pressure with exercise. So those patients with actual cardiac ischemia with exercise induced elevation pressures are significantly symptomatic. And also there's data to suggest that their mortality is worse. So what can we do about these patients? So it's diastolic dysfunction of the left ventricle, or abnormal function of the left atrium that ultimately leads to elevated left atrial pressures, pulmonary congestion and dispute with exertion. But what if we can reduce the left atrial pressure directly? Eso. That's what we're studying now with these what are called intra atrial shunt devices. So these air small devices that are in study currently that air where the interventional cardiologists puts thes within the international septum. So you can see here this picture on the bottom, right? Um, it's basically creating a small ASD in order to allow blood to flow from the left atrium to the right atrium to decompress the left atrium. And they're sort of flow dependent. So at normal resting flow, there's not much. Uh, there's not much shunting going on from the left to the right, But his patients increased cardiac output, increased their exercise. Then there's gonna be more flow from the left to the right. Eso Here's data. You know, preliminary data on this. You can see here that pressures on the left side of the screen or overall decreased a 20 weeks. But more importantly, on the right side, you can see in the top the color coded graph here that the New York Heart Association functional class had significant improvements in these patients in their six month follow up after they got the device. Um, this is the same cohort of patients, uh, in the one year follow up, eso that improvement in the New York Heart Association class maintained from six months to 12 months. So there was. There was more patients in class one and class two, as opposed to Class three and class four, where they started off most of class three where they started off. And also quality of life scores were improved and sustained as well. So this was studied in the reduce left atrial pressure. Heart failure study, multi center international study. We just completed enrollment of this study and scripts, was fifth in the world for enrollment in that study. We're very proud of that. So were, you know, continuing to collect data on these patients and hopefully within the next year and a half or so, we'll have results of this trial. We do have another study that's ongoing. It's a different, uh, company. A different shunt. Same concept s Oh, this is called the Relieve Heart Failure Study. We're currently enrolling in this study. Same concept, multi center, randomized controlled trial. This the previous study was for preserved. You have heart failure alone. This one is for reduced and preserved. You have heart failure. Onda primary outcome is a composite of death. Need for heart failure, hospitalization, transplant held that in six minute walk. So we're current currently currently started enrolling in that study, and we're looking forward to the results of that. So right on time here, 9. 30. There's a lot of information to get through on Pullman hypertension covering sort of pulmonary arterial hypertension, pre capita Larry issues and how to treat and then post capillary specifically as it relates to have path. Eso. With that, I'll, uh, you'll back to Dr Haywood. I think we're going into cases next. Thank you so much. Uh, can we bring up our first case? There were a couple of questions. Meanwhile, go through that case and stuff. I think the first question was for you. Uh, it was How do you approach prescribing SGST too, inhibitors. Do you? When do you send you an endocrinologist? When do you do it? Um, so if they're being seen by an endocrinologist or something or primary care doctor, that's managing it. We we alert them that we're going to do this, but I don't. I used to send them, but that would take months of delay to get an appointment or whatever. So we just we just prescribed them and let them know that we're doing this. And as I said, the rates of hypoglycemia are very rare, and it's not really seen in patients who don't have diabetes. So we think the benefits are so huge that delaying eyes a problem, so we just go ahead and prescribe it. Obviously, there was some. You have to get over the hump on that Teoh, you know, to feel like we're comfortable doing that. But once you've done it a few times, it's just like any other medicine. These drugs should have been invented as a cardiovascular drug with diabetes side effects because they're much more important for their cardiovascular effects than their diabetes effects. Thank you. I'll take the next question. Will a patient in evolving heart failure show mental state changes in line with other declining lab Marko's and vital signs as cardiac function declines? So I like this question a lot for a couple of reasons. A good friend of mine who I went to fellowship with, he is the director off Geriatrics, Cardiology Attn. Y you and he's a practicing geriatric cardiologists. And I think this field is going to evolve mawr because I think majority of patients and heart failure are in the elderly age groups. And right now I think in some ways we approach our heart failure treatment at the one size fits all. But there are certain issues inherent to the elderly population. You know, whether it's subclinical, declining cognition, depression, Um, you know, and especially are now being locked up for a year without having to get out and do much like the isolation. And, you know, as these age related factors creep in and now you compound that with heart failure and reduced cardiac output? How do you differentiate between the two? We've certainly seen patients with reduced cardiac output and, well, this is well established that they will develop radius cardiac output manifestations just like cardiac xia. They also have a more rapid decline in cognition and depression and dementia escapes. We've seen some number of patients where you treat their heart failure, and this gets better X amount. We don't have a perfect tool to differentiate how much of it is age related with his heart failure related, we do recognize that low cardiac output worsens it, and we do everything we can to treat them from a heart failure viewpoint. I've seen a couple of patients where there by Mocha score is one example. You can assess significant improvements in their cognition aan den once you've done as best as you can in optimizing their heart failure, and they still have residual effects either at that time, you can refer them if there is do a mental health or a neuroscience specialist, or you could get them involved early on because I think it's complimentary and not sort of mutually exclusive. Treating them. Uh, the mocha score is useful and some use sort of like even the quality of life measures or the five D to assess those air useful as well. There is not one test that supersedes the other. The second question was the third question. If there is no treatment possible for heart failure and cardiogenic shock is present and its multi organ failure, what are the steps to palley eight symptoms for patient comfort? So usually in our advanced heart failure and especially the shark patients, uh, anyone who's getting mechanical support, or even otherwise, if we think they're not a candidate for mechanical support, we almost routinely get palliative care involved to help guide us in a bringing more clarity to the patient and be what we offer to Palley eight from a symptom viewpoint, whether it's anxiety medicine, Spain Medicines, diuretic management. We partner with hospice. We have patients on China troops who are at home hospice patients with not a 90 tropes on home hospice. What do you to explain Mexican get at home? Um, just get palliative care involved up front. It is not necessarily even hospice, but partnering with valuation and sort of helping patients understand to multiple visits. Now some patients are resistant and will not see palliative care and hospice. And in those cases, it's just our job to sort of try with every visit, to get them to understand goals of care. But if and when there's an opportunity, we just try to get palliative care involved. Early on in the shop patients, yeah.