Chapters Transcript Video Understanding Group 2 Pulmonary Hypertension: Implications for Future Clinical Trials Dr. Benza discusses the pathophysiology and management principles of Group 2 pulmonary hypertension. Thank you for that wonderful introduction and it's really wonderful to meet everyone. I know this may be the first time you've seen me, but I joined the faculty back in July and, uh, really have had a fantastic experience since joining, so thank you for welcoming me to the, uh, Centaura family. Uh, today we're gonna talk a little bit about, uh, group 2 pulmonary hypertension or pulmonary hypertension related to left heart disease. We'll just skip through the disclosures. So this would be our outline for today. We're gonna talk a little bit about the prevalence and the impact of group 2 pulmonary hypertension, the classification, a little about the pathophysiology and pathology, and I want you to remember coming out of this room that this is a disease of four compartments, not just the pulmonary vas not just the pulmonary arterios, and then a management principle based on these four compartments and then finally a little bit about monitoring disease. If, uh, if any of you came to the conference this weekend, this is a little bit of review, uh, of what I mentioned during that, but, uh, I'll go into quite a bit more detail than I did, uh, on Saturday. So let's talk a little bit about the prevalence and uh and impact of this disease. As you know, pulmonary hypertension is broadly categorized into 5 distinct groups, and each one of these groups is defined by the trigger that causes the pulmonary hypertension. Now in the case of group 2 pulmonary hypertension or pulmonary hypertension due to left heart disease, the trigger is a high left atrial pressure. Whether that's from heart failure reduced ejection fraction, heart failure preserved ejection fraction, valvular heart disease, or congenital disease of the heart, it's a high left atrial pressure that is triggering this form of pulmonary hypertension. Now this form of pulmonary hypertension is very, very common, uh, and, uh, it really affects the majority of the patients that we see in heart failure and it's based on a very, very defined sequence of events that starts with a high left atrial pressure that finally translates into vascular remodeling both on the arterial and venous side, and we'll go over that uh into uh uh a little bit. Now if you look at all the patients who have pulmonary hypertension, you can see from this slide that the majority of the patients that you see and will encounter in clinic actually have this form of pH. Uh, and we'll review a little bit about the definition, uh, in a, in a future slide. Now What I tell most of my residents and uh fellows and house staff is that if you see a person with pulmonary hypertension, you have to prove it to me that this person doesn't have group 2 pulmonary hypertension before you call it anything else because 7 out of 10 people that you see in your clinic will have this form of the disease and it's really important to distinguish this. Because it's treated very differently than patients with group one disease, which gets most of the hoopla in the literature. Well, let's talk a little bit about uh the prevalence of this disease as I mentioned to you before, it's very common, and if you look at patients who have heart failure reduced ejection for action or heart failure, uh, preserved ejection for action, pulmonary hypertension is a frequent comorbidity and could be seen up from 50% to 80% of patients with these distinct forms of left heart disease. Now if you do a little mathematics and you know there are 5 million people in the United States with heart failure. And uh 60 to 50% of them have pulmonary hypertension. That's a whole lot of people walking around the United States who have this comorbidity and also knowing the fact that when you have this comorbidity associated with heart failure, its results in a much higher mortality. That's a lot of people with heart failure at risk of dying because they have pulmonary hypertension associated with its disease. Now when you look at the hemodynamics uh for pulmonary hypertension and group 2 disease, uh, it's, uh, it's very, very distinctive where this mortality, uh, pins. Initially when the disease first starts and you only have the isolated post capillary component, just a high left atrial wedge, a left atrial pressure, but no pulmoniovascular remodeling, mortality is directly dependent upon the pulmonary capa wedge pressure. It's linear, but once you develop vascular remodeling and an elevated resistance, once you pass a resistance at 2.5 wes units, the mortality steeply increases. It's like walking off a cliff. So remember in CPCPH combined pre-capillary post cap pH, once the resistance is greater than 2.5 units, these people are very, very high risk of dying. So I mentioned uh the uh the significance of this comorbidity and the setting of heart failure is pretty profound. It not only affects mortality as you can see here, but also greatly impacts uh morbidity and recurrent hospitalizations in patients with heart failure. And when present, it not only negatively affects the outcome, as I mentioned, but these patients have much more severe symptoms and much more profound exercise intolerance. Well, let's go over a little bit about the classification because this has changed recently. As you know, pulmonary hypertension is defined hemodynamically, and it's defined basically as a mean pulmonary artery pressure greater than 20 millimeters of mercury. Now in the case of group 2 disease, you have two flavors isolated post capillary pulmonary hypertension in which you have a high left atrial pressure but no change in resistance yet and you have combined pre-cala post capillary pulmonary hypertension. In which you also have an elevated left atrial pressure, but now you have an elevated resistance too, and in recent years we've kind of dropped down the PVR for this definition from 3 wood units to 2 woods units because of the mortality association I showed you earlier with that lower woods units of around 2.5. And indeed when you look at uh group 2 pulmonary hypertension, you can see that those who have isolated post-capillary pulmonary hypertension do have a worse survival uh than those patients with heart failure with no pH but look what happens when you start getting vascular remodeling. The mortality associated with CPCPH is indeed as significant as the mortality that you see with patients with idiopathic pulmonary arterial hypertension or the old PPH, and in fact 50% of our patients with CPC CPCPH will die within 5 years because of this comorbidity. And then if you add right heart failure to this mix with a high resistance as you can see on the uh the slide and the other panel, your mortality steeply steeply increases even more so this is a bad disease. Now the problem with this disease is that in many cases we see uh group tube disease in the setting of heart failure preserved ejection fraction and these people often get misclassified as idiopathic pulmonerial hypertension because they come to the calf lab and they're a little bit over diaries and they have a low wedge pressure, uh, in the calf lab and making this distinction is incredibly important because as you'll see later. The therapies for group 1 pulmonary hypertension do not work well in group 2 and in fact can exacerbate the disease and cause early demise, so it's incredibly important to be able to distinguish group 1 from group 2 disease, particularly in this setting of heart failure preserved ejection fraction. So you have to be absolutely sure it's not group two, and the best way to do this in the setting of heart failure preserved ejection fraction is to do the heart is do the HEPA score. So you have to glean from your history and physical signs and symptoms and be more reminiscent of group 2 disease like orthopnea or PND. People with group 1 disease do not have this. They do not have orthopy and PND. You look at a variety of risk factors that may predispose to group 2 disease, metabolic syndrome, prior history of coronary disease or bypass, valvulopathies, obesity, diabetes, elderly. Afib should give you a huge hint that this is not group one disease and this is group 2. The only setting in which you see afib in group 1 disease is in the setting of congenital heart disease. And if you do this, your HPE score, you wind up being very, very uh good at distinguishing these two. And if your patients have a half-E score greater than 4, make sure you're thinking that there's a group 2 and not group one. So let's talk a little bit about the pathology and pathophysiology again. I want you to remember that this is a four compartment disease. This is not a disease, just of the pulmonary arterios as it is in group one. In group 2 disease you have problems with the left ventricle, with the left atrium, with the pulmonary veins and the pulmonary arteries. And if you forget about these other compartments, that's where you run into problem when you try to cross treat these people with group 1 drugs. Now group 2 disease all starts with a passive increase in mean pulmonary artery pressure related to a high uh left atrial pressure, uh, and then this further uh progresses until you get endothelial dysfunction and this is the same sort of endothelial dysfunction you get in group one disease which is why there's always a. Uh, um, a, an urge to treat them with group one drugs, uh, because this arterial remodeling actually is similar to what we see in group one. In fact, if you look at these, uh, arteries histologically, you would not be able to distinguish the arteropathy that you see in group one from group two disease. It's distinctly the same. However, what's different is that you have equal and predominant venous remodeling. In group 2 pulmonary hypertension that you do not have in group 1 and this venous remodeling is often forgotten and is the Achilles heel of treating patients with group 2 disease or group 1 drugs because you can imagine if you dilate an artery and if you have an occluded vein, what's gonna be the consequence of that forward flow? It's gonna be pulmonary edema, so you have to be very, very careful and cognizant of this, uh, of this compartment in group 2 disease. And this is the natural sequence that you see in the evolution of group 2 disease, as I mentioned, it all starts in isolated post-capillary pulmonary hypertension in which you just have an elevated left atrial pressure and this pressure is directly transmitted back uh through the pulmonary circuit to the pulmonary arterios so there's a concordance between the pressure and the uh pressure in the left atrium. The next phase is this reactive form of combined precala post cap A PSPH. This is when the arterios and the veins are now under duress and now under stress, and in this form of the disease, you see a marked drop in pulmonary artery compliance without much change in resistance. This is still reversible when you find people in uh in this form, and you can also tell this in the cath lab by doing a nitropressite challenge. And then finally if these patients continue to bathe in these high left atrial pressure, you get permanent venous and arterial remodeling, and this is when the resistance really, really climbs out of proportion to the compliance. So within the last 5 years we've been trying to think of group 2 disease very similar to the way we think of how we categorize heart failure in general by using stages. Those patients who are at risk at risk of developing group 2 disease, those who have structural heart disease that could lead to group 2 disease, and then finally those who are symptomatic and lastly advanced with profound right heart failure. And you can see the consequences and the path of physiological changes that evolved through these various stages as I just illustrated in a more simplistic slide uh prior. And understanding these clinical stages really helps you when you start thinking about potential therapeutic targets for this disease. So this is a nice way to try to remember the evolution and how to introduce things and perhaps prevent group 2 disease before it gets out of, uh, gets out of hand. So let's switch a little bit now to the management principle, and the management of group 2 disease is based on those four compartments, trying to remodel and uh reset normality in each one of these compartments sequentially. Now what do we have in terms of what the guidelines say in terms of treatment of group 2 disease, as you can see it's not much unfortunately. It's optimized goal directive medical therapy referred to an expert center and that drugs uh for group one are not recommended in left heart disease, but I do think we can, we can go a step beyond this if we really understand how to manage it based on various principles. So in my practice, I think I found that there are 3 principles, one central and 2 adjunct principles to managing group 1 disease. The most important is keeping the left atrial pressure low. In addition, you have to manage the underlying substrate. What's wrong with the left ventricle? Is there a valve that could be fixed? And then finally, after you do these first two very central concepts, that's when you should start thinking about arterial remodeling because if you jump right to arterial remodeling again. These are all the things that can happen. You're gonna lower pulmoniovascular resistance. You're gonna increase preload to the pulmonic veins, uh, which are, uh, which are remodeled and to perhaps a non-conditioned substrate, someone who may still have an elevated left atrial pressure that's gonna worsen heart failure, further increase the left atrial pressure and result in pulmonary edema. Pulmonary edema worsens group 2 pulmonary hypertension, causes RV ischemia, which then lowers cardiac output and causes patient compromise. So remember this is a four compartment disease and you manage it by managing these four compartments. So one of the most important compartments to manage is the left atrial pressure. All the hospitalizations that we see for heart failure, uh, uh, are related to elevations of left atrial pressure and when you have combined resistance, this left atrial pressure makes the management, uh, even trickier. So understanding the left atrial pressure and also trying to understand the concept of left atrial noncompliance, which is very important and can be coexistent. With left ventricular pathology, particularly in the case of those who have undergone afib ablations, it's very, very important we can really nicely look at, um, left atrial uh compliance now, uh, using speckle tracking, which is one of my new favorite techniques. So how do we manage left atrial pressure, uh, in, uh, in the outpatient setting? Well, obviously the first thing is to, uh, uh, to control volume and reduce pressure by that by using diuretics. But the problem with using diuretics that they're often not used right. In the case of CBCPH, they really had to be protocol driven. They really need frequent rejust adjustments based on symptoms or other markers, and we'll go over those in a second what those might be. In addition, uh, you have to optimize your mineral cortico receptor uh activity because remember when you get a loop diuretic you actually increase sympathetic tone which is bad for the pulmonary arteries. So using MRIs to counter this sympathetic tone is very important. Obviously you can also use nitrates in some conditions. There are also drugs that we typically use for heart failure that are actually good against uh left atrial noncompliance because they're antifibrotic and these include the RNs and uh SGLT uh inhibitors. Another even more important reason why to use these drugs in the setting of coexisting pulmonary hypertension. And then obviously the the ultimate way to unload the left HM continuously is by using an LVAD or left atrial pump, but these need chronic and consistent unloading which is only possible with frequent speed optimization. So you just can't pop a VAD in and let them go. You gotta optimize the speed to make sure you keep the left atrial pressure low. We also have some new uh devices for managing left atrial pressure, and these are in atrial shunt devices that have now been used in a variety of clinical trials, particularly in those patients with HPE to try to reduce uh left atrial pressure. And when you look at these trials you could see that these these devices have been uh relatively well received and performed well in in terms of reducing patients' functional class, um, improving functional class, improving quality of life, and, uh, and 6 minute walk distance, but interestingly, uh, they haven't really been shown this uh uniformly to reduce the wedge pressure, which is what we really want in pulmonary hypertension in addition. By just shunting flow to the right atrium, I mean recirculating through the pulmonary arteries, doesn't make much sense that these will do a good job of reducing CBCPH. So what I think the best way to monitor these, uh, the left atrial pressures by using technology. In addition to your your exam and weights, which are often very, very late manifestations of left atrial elevations, left atrial pressure, why not try to catch the left atrial pressure when it's just rising and using these, uh, different devices, particularly these impedance devices which are readily available right now, I think it's gonna make remarkable change in the way we treat CPCPH and then these left atrial monitors and when they do become available will be equally as important. Because as you can see when you use these impedance monitors like the those that we find in our CRT devices you can see that the thoracic impedance that these devices give you are a much earlier signal for elevations of left atrial pressure than just following someone's weight. Uh, and so these are gonna be critical for you if you're managing these patients in clinic and they happen to have an impedance device, uh, already implanted, you can use this to keep the left atrial pressure low every time by monitoring this remotely. Now we have a bunch of other devices that are coming out that you can also manage uh uh thoracic impedance and might be very helpful in keeping the left atrial pressure low on patients with CPCPH or isolated post capa pulmonary hypertension. This is the device by Medtronic and many people may have used this in the past for arrhythmia management, but now the new metronic link also has a thoracic competence component to it. So not only can you detect arrhythmias, but you can also detect thoracic volume. And you can use this device again remotely to keep your left atrial pressure very low. We also have portable impedance devices that we can use in clinic, and this is an example of the RDS device, uh, and the new uh a new device by Sensodyne, and these are wearable thoracic impedance devices that a patient can either be used in clinic to look at their left atrial pressure or even you can send these patients home with these devices so you know what the left atrial pressure is every single day of the week and you can more intelligently adjust their diuretics using these devices. This is a cool little new device that's coming out, I think will be readily available for implantation in the next year. It's a, a direct lift atrial monitor um uh that is being tested in the Victorious trial. And uh as you can see here uh when you insert this into the left atrium, it gives you beautiful waveforms of the left atrial pressure and these can be transmitted uh via the Internet uh to your computer so you can watch these patients at home uh with very, very astute management of their left atrial pressure. So we talked about managing the first compartment, the left atrial pressure now managing the underlying substrate of what's going on in the left ventricle is equally important and the most important thing to do in this section is to make sure that you buff these people's heart failure medications, make sure they're on 4 pillar therapy if they have heart failure reduced ejection fraction, and 3 pillar therapy if they have heart failure, uh, preserved ejection fraction. And to make sure that you do not opt uh you don't neglect optimizing the dose of these while you're managing the left atrial pressure. You can't just throw someone on the beginning of an RE uh and expect it to work. You really have to titrate these drugs, uh, to their maximally effective doses. We can also use CRT in our patients to control, uh, mitral insufficiency, which reduces left atrial pressure. We can use hydralazine and nitrates. We also use uh a very COA when appropriate. And also there's been a lot of data now that uh GOP one receptor agonists as I'll show you in the next few slides are good here uh because these medications are not only beneficial to the left ventricle but they have shown to have uh very good benefits in remodeling the pulmonary arteries. So in addition to managing medications, you have to control exacerbating conditions like obstructive sleep apnea, and obesity, fix anatomic lesions if feasible, and according to the guidelines, we have a fantastic structural heart disease program, so patients who have aortic aortic stenosis or insufficiency or mitral stenosis or mitral insufficiency fixing these valves is critical, uh, to mitigating their pulmonary hypertension. And then obviously we have mechanical remodeling with Levants uh to uh remodel uh the left ventricle. Now as I mentioned, uh, you get a two hit, uh, double edged sword when you use uh some of these medications that we use to treat heart failure because a lot of them also have very beneficial effects on the pulmonary artery and RNs of one of these that have been shown to directly reduce PE pressure and reduce, uh, uh, adverse remodeling of the pulmonary arterios and this has actually been shown in clinical trials. In addition to this, mineral cortico receptor, uh, antagonists, uh, are very good in managing pulmonary hypertension and to directly affect the vascular remodeling of the pulmonary arterios. So there's another big bang for your buck. Similarly with S uh SGLT2 inhibitors also have direct activity on the pulmonary vasculature and can lower the PA pressures and PVR, as well as GLP-1 agonists can also be used for pulmonary hypertension. So by buffing their heart failure medications, they're not only getting improvements in the heart failure, but you're directly remodeling their pulmonary arteries using this, uh, using these drugs, so why not use them to their fullest extent. Well, now let's talk about actually how do we manage the pulmoniovascular remodeling. I told you some of the things that are critical for doing that are managing left atrial pressure and managing uh ventricular uh remodeling, but what about medications, uh, directly to affect remodeling of these arteries? As I mentioned several times in the beginning of this presentation, group one drugs have been uniformly disappointing in treating pulmonary hypertension, uh, related to left heart disease, and this is just an example, uh, of several of the trials losing. The antagonist, uh, procyclin agonist, uh, and even, uh, uh, uh, soluble guanlate cyclase, uh, agonists all have been uniformly disappointing and have had negative, uh, uh, primary endpoints. This is just a highlight of some of these, uh, this is uh the dynamic trial which used Riosequan, a drug that's very popular using group one, and as you can see here, it improved cardiac output but did absolutely nothing to change pulmonvascular resistance. Similarly, when you look at PD5 inhibitors, which really are in the water when you treat pulmonary hypertension, I've seen a lot of indiscriminate use of PD-5 inhibitors for all forms of pulmonary hypertension, most often, uh, group 2 disease, but you can see in the PASion trial, which is a very recent trial, there was actually an increase in the mortality of patients who were treated with PD 5 inhibitors who had group 2 disease. And then similarly, uh, treating patients with endothelium antagonists in group 2 disease only led to an exacerbation of edema in these patients, so these drugs have not been uniformly shown to improve. Well why not? Why, why are these drugs that we think are great for remodeling the pulmonary arteries failing in these, in these trials? It's because these trials really ignored the four compartment, uh, model. They went directly to arterial remodeling. None of these patients who were started on these medications were decongested before these medications were started. They all started off with very high wedge pressures and during the trial there was no attempt to maximize the goal directed medical therapy before even entering the trial, and there was obviously no attention to the venous component, and they really relied on conventional efficacy measurements and missed elevations and left atrial pressure very frequently. And this problem was confounded because each step required multiple touch points with the patients in order to adjust diuretics. People had to come in to be seen to get a diuretic adjustment, uh, um, uh, adjusted, and I think this is why these drugs may uh may be failing this disease, and it may be a way to repurpose this with a management schemata utilizing this for compartment syndrome that I mentioned to you earlier, and I'll show you that a little bit later. Now the one exception to this, uh, is the group one drug cetatacept. Now cetata is a brand new medication that we're using for group one disease and it's entirely different in the way it works from all the other group one drugs. It works on, uh, the active pathway and inhibits the TGF beta super pathway and in doing this markedly remodels the pulmonary arteries in group one disease. Now the cool thing about this drug is that it also remodels pulmonary veins, which none of the other group one drugs do. So this drug we might see some success in managing group 2 disease and this is now being piloted in a large phase 4 trial uh uh that is almost nearing completion. So basically this is the summary of managing group 2 disease or group 1 drugs and these are the recommendations that just came out of the guidelines and the World Meeting of pulmonary hypertension is don't do it basically. So we have another, uh, a bunch of new therapies, uh, for group 2 pulmonary hypertension that are that are on the horizon that work, uh, through a variety of different mechanisms. Uh, one that I think is very interesting, uh, is this, uh, compound, uh, uh, mirror bear. This is a beta 3, receptor agonist, uh, and it, uh, potentially can address both right ventricular dysfunction and pulmonary hypertension. Because it modulates, uh, uh, cardiac myocyte, sodium potassium ATPase, uh, and it also interestingly activates, uh, the cyclic guanoline monophosphate dependent signaling pathways. So the first pathway helps with right uh ventricular remodeling and the second pathway helps with pulmoniovascular remodeling and as you can see, uh, in this initial trial, uh there uh which was the primary change in PVR, uh. There was a 4, actually a 4% change in PVR, uh, but it didn't, uh, turn out to be a clinic uh statistically significant. The other new drug that we've been trying in group 2 disease is levocementin, and as many people know this is a calcium sensitizer and it's an odilator. Uh, and it, it increases inotropy, uh, without interfering with uh myocardial contractility, but it also activates the potassium ATPA channel which results in arterial and venous, uh, vasodilation. Now again, this was uh piloted in a small study and we didn't see any uh uh reduction in exercise wedge pressure uh in the categories, but we did see an improvement in 6 minute walk test so there's still some interest in looking at this drug. Reolazine is another drug that we've been looking at, uh, in group 2 pulmonary hypertension because it inhibits the late sodium channel and by doing so improves uh cardiac myocyte function and lucitropy, but it also acts on the pulmonary arteries to cause vasodilation. Now in this trial, which was a small trial, we saw a 30% reduction in wedge, a 4% reduction in PVR, and a 12% reduction in mean pulmonary artery pressure. And so this drug does have some hope as an additional drug that we could use to treat a group two disease. There's also a lot of interest in the compound of drugs called relaxants, and these are being trialed right now in a phase 2B trial called the refire trial. Now relaxing is a naturally occurring hormone that is recognized for its vasodilatory, anti-inflammatory and antifibrotic effects and by activating um the relaxing uh receptor, this new compound uh called AZD 3427, which is given subcutaneously uh has promise of uh inducing significant reductions in PVR and uh hopefully we'll have some answers from this trial coming pretty soon. Now as I mentioned earlier, the sympathetic nervous system is highly activated in patients with pulmonary hypertension of all forms, but in particular in group 2 disease because of the left ventricular dysfunction that we see with it. So mitigating sympathetic tone both to the heart and to the pulmonary arteries may be adequate treatment. Uh, for patients who have group 2 disease and this is being tested now, uh, in a trial using, uh, this very novel, uh, denervation catheter designed specifically for denervating the pulmonary, the pulmonary sympathetic chain in the main, uh, pulmonary arteries. And you can see there's been a number of small trials looking at pulmonary artery denervation, uh, in group 1 and group 2 disease and you can see that uniformly they've been very successful in mitigating pulmonary hypertension, uh, in this clinical scenario and there is now a, uh, a very large group 2 study, uh, looking at pulmonary artery denneration in patients with group 2 disease and we'll be participating in this trial very soon here at uh Centarum. So we talked about now how we tried to remodel the pulmonary arteries, but uh, how do we monitor it? How do we know when there are changes in this uh initially we would always have to bring people back to the cath lab to see if we were having any effect on someone's uh pulmonary vasculture and pulmonary remodeling, and, uh, we all love doing right heart catheterizations, but we recognize its shortcomings. The most important is it's really just a single time point assessment and someone in the supine condition and really an artificial environment. So now we have the advent of implantable pulmonary artery monitors that can give you real-time information about someone's pulmonary vasculature on a daily basis, and we've been using these, uh, uh, frequently in the clinical environment ready for heart failure, and many of you have used this device know that. Both of these devices will give you a good recording of the pulmonary artery systolic, mean, and diastolic pressures, but also now we've designed uh a new mathematical algorithm which is very similar to the way we define stroke volume using echocardiography. Uh, my lab was happy to participate in these studies and and develop this algorithm. So we can now very accurately determine stroke volume in addition to pressures and because we can determine stroke volume with these devices, we can now also determine in a total pulmonary resistance and track that with many of the modalities that we use. Well, is there any signal that this may be safe to use in patients with group 2 pulmonary hypertension? And the answer is yes. This is data from the MEMS heart failure trial that was conducted mostly in Germany, and that you can see when you use the cardio MMS device to manage patients with CPCPH, you got a 37% reduction in CPCDPH because you're able to manage these patients real time and a 22% reduction mean pulmonary artery pressure. So I use these very frequently when I'm managing my patients with group 2 disease in addition to group 1 disease. So I mentioned that now that we have technology to measure the left atrial pressure and the pulmonary arteries together, well, can we use them conjointly to really milk that four compartment model and possibly repurpose group 1 drugs now that we know what's going on in each compartment to treat, uh, group 2 disease. And this is an example of uh of myself managing a patient with very severe group two pulmonary hypertension related to heart failure preserved ejection fraction. This patient's baseline pulmonary hypertension had a mean pulmonary artery pressure of 50 and a total pulmonary resistance of 10, so there is severe pulmonary hypertension. And uh it you could see here this blue line I think can't see my pointer but this blue line is the pulmonary artery systolic pressure, the green is the pulmonary artery mean pressure, the red is the pulmonary diastolic pressure, the purple is the total pulmonary resistance and the orange is the cardiac output and see what happens to these when we when we milk the four compartment syndrome. So we start out putting this person on goal directed medical therapy and making sure we're paying attention not only to the types of drugs that we're starting but also the doses of the drugs and you can see just with goal directed medical therapy that we did indeed have an initial decline in this patient's pulmonary artery pressures and resistance. I then did a reds reading to make sure that I was, uh, that I had his left atrial pressure low uh and that was just uh because remember the wedge is discordant from the PA diastolic using a cardiomis in these patients so you need the reds reading to really determine the left atrial pressure when I knew I had the left atrial pressure under control, uh, for a while, I then started a group one drug, Sedenafil, and while using Sdenafil, I made sure I did frequent. Checks of the left atrial pressure to make sure it retained low as I was using this drug and by managing the left ventricle and managing the left atrial pressure. I then allowed the vascular modeling to go on without hurting this patient so much so that we're able to reduce this person's diuretics in the end, and this person has done very, very well on this therapy in the long term. We also, as you can see, got a dramatic reduction in total pulmonary resistance and an improvement in cardiac output using this modality. There's now a trial that I and Marty Gomberg at uh at Georgetown are doing utilizing this technique called the recapture trial to utilize this management schema to try to treat patients with group 2 pulmonary hypertension. So in summary, managing uh group 2 pulmonary hypertension because it is common and it is deadly really involves around looking at it from the continuing of the disease, trying to identify people very early and who are at risk of developing and mitigating those factors that may cause pulmonary hypertension to progress. Identifying people with structural heart disease that again at risk of developing disease and mitigating this by doing appropriate structural uh uh testing and corrections and also utilizing goal directive medical therapy. And then finally when you get symptomatic disease you've got to continue doing all these things, but think about some of these new clinical trials that are coming on to treat group 2 disease and this management schemata that I used, uh, utilizing high tech technology to manage this, and I think there is going to be some problems in treating this disease in the future. And with that I thank you and be happy to answer any questions you might have. Published October 2, 2025 Created by Related Presenters Raymond Benza, MD Professor and Section Head, Cardiology Eastern Virginia Medical School View full profile
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