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Hello, I'm Kelly Chen from UT Southwestern in Dallas, Texas, and today we'll be talking about rethinking pulmonary arterial hypertension. My disclosures are here, mostly related to research work in pulmonary hypertension, either on steering committees or clinical research that we do at our institution. Our next myth, feeling better is stable. So, this is a patient that I um also saw recently. The learning objectives here will be to determine when and how to escalate therapy in patients with PAH using risk stratification and clinical response to guideline-based treatment intensification. So another polling question. In patients with PAH who report subjective symptomatic improvement on combination therapy but remain not at low risk, which management approach is most consistent with current international guidelines? Maintain current therapy because symptomatic improvement indicates stability. B, reduce prostacyclin dose to minimize side effects. C. escalate therapy, such as increasing prostacyclin dose or adding 1/4 agent. D. Repeat risk assessment annually unless symptoms worsen, and E, transition to monotherapy to simplify the regimen. OK. So case two. So this is a woman that I saw in consultation a few years back. She was 34 years old at the time. She had a history of obesity. Her BMI was around 45, and a history of stimulant use, and none in 5 years. She presents for a second opinion. She had been diagnosed with idiopathic PAH which given the stimulant, um, use history was likely drug and toxin induced, and this has been made in, this diagnosis had been made in 2020. She was started on dual upfront therapy. She improved, but this was modest and um did not reach low-risk criteria. So after six months, subcutaneous reprostol was added and her current dose is 20 nanograms per kilogram per minute. At presentation with me, she remained improved but still symptomatic, and she had concerns about long-term prognosis, which I agree with, particularly given her young age. We need to look closely to see how overall she's doing. On exam, she's comfortable appearing, has clear lungs, no signs of right heart failure, no lower extremity edema. Her BP is 101/75 and she has a heart rate of 92. We do a non-invasive testing. She's functional class two, I think, walks 377 m and an NTR BMP is 325. So, giving her an overall risk assessment, for this case, we're gonna use the reveal light 2 risk calculator, which is appropriate for follow-up risk assessment. It is a shortened version of the longer reveal calculator. And you can do this online or there are downloadable apps that you can do to also assess risk. It has 6 measures, the same functional class, walk, and intebro PMP or BMP that's used in the ESC ERS risk calculator, and then it adds systolic BP, heart rate, and GFR. So for this patient, we go through and click on her Ntero PMP level, which was 377. Sorry, her NTRBMP level, which was 325, her walk distance, which was 377, functional class, slightly low systolic BP, so that gives her a point, and then heart rate and a GFR for an overall risk score of 6, which is in the lower end of the intermediate range. So, what does this mean for this patient, uh, prognosis-wise? That was her question coming to you. So this is a study from the, um, French registry where they looked at outcomes at follow-up by risk score. So, for a reveal light 6, this is in the intermediate range, and on the ESEERS risk, she's in the low intermediate range, which would correspond to this yellow line right here. So we've got low risk, low intermediate, the orange line is the high intermediate, and the red line is the high risk. And at 1 year, the low and the low intermediate both look pretty good, well above 95% survival there. But look what happens as you follow this out. The low intermediate, up to 40% of patients have died and the low risk is um a mortality risk of around 10% at 5 years. So this is really important to keep in mind that PAH remains a fatal condition, even those low-risk patients need to be followed closely and low intermediate is not really doing OK. So, as with the prior patient, we're gonna take a look at her heart catheterization and echocardiogram. In this case, not as alarming. Her pulmonary pressure has improved to a PAE of 45. Cardiac index is at 2.3, so slightly low, and she has a PVR of 6.3. And then these are both from her recent echocardiogram. On the four chamber view, we can see the right atrium is slightly enlarged but not very big, and the right ventricle is also mildly enlarged. When we look at the peristternal short view, you can see some septal flattening, the septal bounce that comes across here between the left ventricle and the right ventricle, and again, that mild right ventricular enlargement. So, she's coming to us in 2023 and um on the double oral combination therapy plus subcutaneous traprostinol at 20 nanograms, which is a relatively low dose. And so in this patient who had a low cardiac index, a slightly elevated intoro BMP and the echocardiogram that we just saw. We recommended going up on the subcutaneous trarosinol and actually over quite some time, but eventually over that next year, get up to 63 nanograms per kilogram per minute. You do wanna be cautious with this much of the dose increase. We tend to follow up with a catheterization to make sure that we haven't gone too far, which can be manifested both as um excessive symptoms, but also sometimes high cardiac output. So if that's starting, if the cardiac index is creeping up, then you've usually reached your limit on how much you can increase this. We also wanted to look for non-PAH contributors. She is obese. We did an overnight oximetry which we do in all of our patients. It did not show suggestions of sleep apnea. We do some basic labs to make sure nothing's going on there. And then we also refer her to, we have a weight wellness clinic. Her BMI was 45, and that's a concern both because It impacts symptoms in pulmonary hypertension, but also because if she is potentially going to need to um be evaluated for transplantation, a BMI above 30 at my center is is considered a contraindication to listing because these patients really do poorly perioperatively if they don't get their BMIs down. And she actually gets started on semaglutide and loses weight over time, which also helps with symptoms. And then finally, a referral to pulmonary rehab. So lots of things to work on that are all guideline directed recommendations. So then she comes back, it's 2024 now, and we have a follow-up risk reassessment. Also, just to refresh where we were, we um had a patient who had been on combination ERA and PDE5 therapy and then advanced to triple therapy and she is now coming back for risk reassessment on triple combination therapy. She, this time remains at intermediate low risk. So what are our options now in 2024, 2025, 2026? They've um increased now. We can add cetatercept, which is an active signaling inhibitor. We can consider a switch from a PD5 to Riosaggut, our soluble guano cyclase stimulator, or if she were not on it, we could add a prostacyclin, but of course, not an option in this patient. In her case, because her BP is low, Riosugut was not felt to be a good option. It tends to lower BP more, and so we had a discussion about citatercept. So it was shown across 3 large trials to improve 6-minute walk distance and to reduce clinical worsening in both the Zenith and Hyperion trials, which were long-term outcome trials. The main risks associated with it, it can elevate hemoglobin or cause low platelets, and so frequent monitoring is required there. It can cause bleeding, mainly as nosebleeds, some gastrointestinal bleeding, or even hemoptysis, and it can cause new telangiectasia to form. It may also cause new shunting in the lungs, which may be picked up on bubble study or pericardial effusion, but both of these have been seen only rarely and in case reports. It's recommended, as we saw in the slide before, for the low intermediate patient where there are multiple options and for the high intermediate or high-risk patient where there are fewer options for these patients. Um, and maximum medical therapy is now 4 drug therapy, including citadercept and a parenteral prostacyclin. So how did she do overall? So here I have her 2020, 2023, and 2025 follow-up catheterization and she had continued improvement in her pulmonary pressures with the addition uh or with the increase