Good evening everyone. I think we're going to get started here so if you can please take your seats we would appreciate it. So my name is Eugene Yang. I'm a cardiologist and professor of medicine at the University of Washington and we're very grateful for your attendance tonight. So we're gonna have a really interesting session. The title of this session is called Hypertension Management the Persisting Needs and Latest Science. These are my disclosures. So I do consult for some companies that are involved in blood pressure measurement and I get research funding from Microsoft to support my research on facial video processing. So I just want to briefly talk about why we're all here. So we have a really global audience tonight and so as all of you know hypertension is a leading modifiable risk factor for disability and premature cardiovascular deaths. The global burden of hypertension is estimated to be 1.4 billion in 2010 and projected to exceed 1.6 billion by 2025. We know right now that it affects about one in three people worldwide and here in the United States only one in five people have blood pressure controlled. So let's look at this from a global lens. So if we look at cardiovascular mortality associated with high systolic blood pressure you can see that in many parts of the world where it's darker blue or purple that in European countries, African countries there's a high association between high systolic blood pressure and cardiovascular mortality and other parts of the world including the United States, Latin America, South America tend to have lower rates of cardiovascular mortality associated with high blood pressure. Let's look at from the U.S. perspective right so this paper came out about four years ago and sort of discriminated between rural and urban areas and also by region in the United States and you can see that unfortunately here in the south in rural areas you see that hypertension associated cardiovascular mortality is very high relative to other regions United States but however we look at the more urban areas you see that these numbers tend to converge. So in rural areas there's tremendous disparities in terms of hypertension related cardiovascular mortality. Let's look at the global disparities in hypertension. So this comes from the global burden of disease and what we can see is that overall you can see that blood pressure and hypertension rates are increasing worldwide over the past 20 years but there are differences in terms of cardiovascular I mean in terms of hypertension rates and control. So high-income Western countries in the top left have better control rates and then if you look at Asia-Pacific region for example in the high-income countries you see very good control relative to East and Southeast Asian countries or South Asian countries. So again we see that when we look at this from a global lens they're clearly differences with respect to hypertension control and diagnosis. Let's talk about racial and ethnic disparities in the United States. So we can see that when you disaggregate the populations based on race and look at blood pressure from three different NHANES surveys you can see that certain groups for example non-Hispanic black men tend to have much higher rates of hypertension when we look at non-Hispanic white women on the hand you see much lower rates of hypertension. So again showing that there are significant differences in disparities with respect to hypertension rates control in the United States. Then we look at this panel again coming from NHANES data we look at awareness treatment and control you can see that the non-Hispanic whites tend to have higher rates of awareness treatment and control whereas other groups including Asians have lower rates of control and treatment. So again highlighting the fact that there are significant disparities with respect to hypertension control as well as awareness. So we have a really outstanding lineup of speakers today I call it our all-star team. So the first presentation will be given by Dr. Kanzari from Piedmont Hospital. He's going to talk to us this evening about emerging technologies and new breakthroughs and we'll have three cases presented by Elliot Stein a cardiology fellow at University of Washington. We'll focus on one case with respect to disparities in hypertension management and Dr. Wang Pen from UT Southwestern will be giving a talk about this and then we'll have a second case looking at evaluation and management of patients with resistant hypertension with Dr. Anna Krajewicz coming from Beth Israel Deaconess Medical Center and then finally we're going to talk about what are the clinical indications for renal denervation and so Dr. Tai Kobayashi from University of Pennsylvania will be speaking about this. So a few final things to to do here so I think we really need to thank our sponsors and our grantors for this meeting. So I want to thank Medtronic for supporting this event tonight and the final thing is around using the audience response system so you can see the QR code so if you want to scan the code so you can open up your app that would be great. Okay so I'm going to introduce our first speaker so Dr. Kanzari is going to come give us a 20-minute talk here on new technology so thank you Dr. Kanzari. Well welcome to Atlanta my hometown and as Jean as you introduced you can understand perhaps why we're a leading center for renal denervation therapy given the sequela of hypertension in in the southeast here as well. So again a very much welcomed opportunity for me to be with you this evening and to share with you the story path the evolution of evidence for renal denervation therapy. My disclosure is related to research and grant support and perfect and and and consulting on a barrier from the interventional device industry. Approximately 15 years ago Alberto Zanchetti a very famed hypertension investigator the editor of the journal hypertension at that time stated that 20 years and 46 trials and more than 230,000 patients was probably too many to end up with the current conclusion that what really matters is lowering blood pressure whatever the agents administered and perhaps today we could expand upon that statement to say whatever agents are administered or device-based therapies that might be available. Predicated on early first in human clinical studies demonstrating reductions in blood pressure with renal denervation therapy and supported by reductions in biologic surrogates reducing the hypersympathetic signature within the body such as reductions in muscle sympathetic nerve activity or neuroepinephrine spillover led to the enthusiasm of a succession of wildly positive single-arm unblinded studies with renal denervation demonstrating quite profound reductions in blood pressure and those studies in addition to a single unblinded randomized clinical trial led to the simplicity HTN 3 study that now one decade ago reminded us that the predictable in many ways is still yet unpredicted. A study poised for for for success it seemed demonstrated the safety of radiofrequency renal denervation therapy it demonstrated the opportunity to perhaps reduce blood pressure with this therapy but not significantly so due to an unexpectedly large reduction in blood pressure in the sham control cohort. Not specific to renal denervation but Victor Zhao a former colleague of mine at Duke had stated that novel discoveries that challenge traditional thinking are often met with criticism and it's important to have objectivity belief and perseverance and to the credit of the investigators and the sponsors of this program particularly with regard to belief and perseverance it led to reexamining clinical trial conduct in device-based therapies for hypertension clinical trial endpoints revisiting the science of renal denervation therapy that arguably the enthusiasm clinically as this study as this procedure was being performed in many other geographies as part of clinical practice already had exceeded the science and revisiting the pathophysiology of the renal efferent and afferent nerves and the procedural technique itself led to a next generation of renal denervation trials perhaps in some ways of a validation however for renal denervation from that unsuccessful simplicity HTN 3 study now through three years of follow-up though as we follow those patients in the trial there is a persistent constant reduction in blood pressure among those individuals treated with renal denervation therapy without an escalation in the medication burden and in comparison there is an erosion of blood pressure control a loss of blood pressure control in the sham control group over a long term after the period of study after the period of unblinding and for many of you this may be reminiscent of the sprint trial which also in the observational period beyond the study period those individuals who had a significant reduction in blood pressure with intensification of medical therapy lost that benefit over time and more importantly forfeited the clinical benefit associated with those blood pressure reductions but more importantly aside from simplicity HTN 3 this led to the succession of a series of sham controlled randomized clinical trials with renal denervation therapy and in particular two different modalities one with radiofrequency energy delivery one with intravascular ultrasound but together demonstrating quite remarkably consistent reductions in blood pressure in these sham controlled randomized clinical trials in most instances significantly so compared with the sham control group and very importantly demonstrating not only meaningful reductions in blood pressure but blood pressure reductions in the daytime and nighttime intervals by ambulatory blood pressure assessment reductions in office systolic blood office blood pressure as well and importantly off the reductions by both systolic and diastolic criteria and in fact while there are nine studies represented in this figure by my last count there are in fact to date at least four additional sham controlled randomized clinical trials in this space holding renal denervation therapy to a standard beyond which is historically accustomed in interventional device trials these newer additional studies in newer novel device technologies in part some of which we'll soon discuss but the point being that these that these therapies have demonstrated exemplary safety and a relatively consistent message or theme of efficacy leading therefore to the approval of these two technologies intravascular ultrasound and radio frequency energy delivery in November of 2023 by the FDA with quite a broad indication for the treatment of uncontrolled hypertension when lifestyle interventions and pharmaceutical therapies have been unsuccessful the study programs today to impart because of their longevity and their duration in this space have also provided information to to inform clinical decision-making in routine clinical practice or for us to consider how this therapy might be enveloped into existing standards of care does renal denervation outstanding questions perhaps for practitioners might be that does renal denervation therapy work all the time or just during certain periods is it a durable therapy with regard to its benefit or does it wane over time my patients reduce their medications coincident with the benefits of blood pressure lowering is it a safe procedure not simply during the procedural aspect but over a long-term follow-up and ultimately are the benefits with renal denervation in reducing blood pressure translational to improving clinical outcome and finally for many is that a cost-effective therapy a remarkable consistency across the renal denervation programs today and across these two different approved modalities of ultrasound delivery as well as our radiofrequency energy delivery is what we termed from the spiral HTN omnits pilot study and always-on effect that is over a 24-hour period individuals treated with renal denervation experience a sustained persistent reduction in blood pressure at all time intervals over the 24-hour period which is quite different from the sham control groups in which there is no movement or no difference in blood pressure over the 24-hour period from baseline to follow-up and very specifically this advantage is distinctive from the limitations of pharmacokinetic profiles it is certainly limited distinctive from the limitations of drug dosing regimens clearly distinctive from patient adherence to their medic to one's medications and it may be especially relevant to those individuals whose blood pressure phenotype may convey an especially high risk for adverse events such as those with nocturnal or early morning hypertension as I've implied we've also demonstrated with renal denervation therapy not only the opportunity to reduce blood pressure blood pressure itself but also perhaps reduce the medication burden which as many recognized is an independent predictor of non-adherence specifically renal denervation therapy has the opportunity or the likelihood of about one and a half to three times greater than a sham patient in not only reducing blood pressure but perhaps reducing medications or alternatively at least after following renal denervation there may be a lesser need for Medicaid for medication intensification to achieve targeted blood pressure goals renal denervation therapy also has proven to be exceptionally safe in the sham controlled randomized clinical trials the the the incidence of major adverse events is exceptionally low less than 1% there have been no unanticipated adverse device related events in the sham controlled randomized clinical trials and moreover when adverse events occur they have been less than 1% of the time related to vascular access complications rather than to the procedure itself or to trauma to the renal arteries and in fact over a longer term follow-up equally important renal function is maintained over long-term follow-up and specifically in a meta-analysis of 52 studies of renal denervation therapy compared with control patients there is no compromise in renal function over long-term follow-up if but anything as one might expect with improvement in blood pressure there's a mitigation against the annualized decline in GFR that would be anticipated from an uncontrolled hypertensive patient population moreover with regard to renal artery stenosis put simply the incidence is almost case reportable in over 10,000 patient years of follow-up in 50 trials the occurrence the annualized occurrence of renal artery stenosis following radiofrequency or ultrasound energy delivery is about 0.2% per year which is less than that which we anticipated from a similar patient population of like or of similar atherosclerotic disease risk aside from the more formalized randomized clinical trials in part some of which I'll share with you momentarily renal denervation therapy has proven to be exceptionally durable renal efferent and afferent nerves are not myelinated structures they are non myelinated nerves and after ablation they do not regenerate in comparison to peripheral myelinated nerves and over a long-term follow-up now through 10 years both by office and ambulatory blood pressure assessment independent and sponsored clinical trials have both demonstrated a sustained reduction in blood pressure over late-term follow-up in the absence of escalating the medication drug dose or number and in fact in selected instances with significantly lower or reduced medication burden over long-term follow-up from the sham controlled randomized clinical trials to we observed in this instance through three years of follow-up in the spiral on meds pilot study a sustained if not amplified reduction in blood pressure over long term in comparison to escalating the medication drug dose or number in the sham control group and more specifically we observe at three years the sustained always-on effect with renal denervation therapy whereas in the sham control group now there is some change from baseline to three years of follow-up in an improvement over the three over the 24-hour period of blood pressure but at the cost of increasing medication burden and yet this figure also exemplifies the complementary nature of renal denervation with medications to achieve even greater absolute reductions over the 24-hour period of device and drug therapy combined that cannot be achieved with medications alone viewed in another perspective in the study roughly 85% of the patients in the study at three years achieved a systolic blood pressure of less than 140 compared with roughly half that in the sham control group today we still do not have nor are planned any direct outcome studies related to renal denervation therapy there is no reason of course to believe that the benefits of blood pressure lowering with a device based therapy would not translate into improved outcome with varied medications and recall that almost if not all of our data with regard to pharmaceuticals and the effect of improving outcome are based on large aggregate meta-analyses rather than a single anti-hypertensive therapy however to think in us as a surrogate of time spent in therapeutic range or time and target range after renal denervation therapy with the potential for an always-on effect those individuals who spend the greatest time in target range following renal denervation therapy linearly experience a significantly lower likelihood of the adverse sequela of hypertension that include myocardial infarction stroke and cardiovascular death further renal denervation therapy even in the most conservative of estimates is a very cost-effective therapy in the sham controlled placebo subtracted estimates of blood pressure reduction from these trials still and not even considering the absolute reduction from baseline to follow-up which is of course even greater renal denervation therapy is associated with an incremental cost-effectiveness ratio of approximately $16,000 that poses it as a very cost-effective high-value therapy positioning it well below referenced cost-effectiveness standards the space of renal denervation therapy also continues to expand greatly not only do we have the academic research consortium document providing guidance with regard to informing or designing clinical trial design and conduct for device based therapies but to date there are at least 18 world international societal and or consensus documents informing patient selection for renal denervation therapy addressing its its its context in in routine clinical practice and providing recommendations for treatment as well perhaps one of the most notable being this past year from the European Society of hypertension guidelines recommending renal denervation therapy for uncontrolled hypertension with a class to recommendation which is the highest standard of recommendation by the society in the absence of a dedicated outcomes trial the experience with renal denervation therapy to and recognizing from these trials when we're performing drug adherence the rates of partial or complete non-adherence that often approach if not exceed 50% raises the issues of exploring patient preference for for for therapies for hypertension acknowledging that in this country alone for instance 75% of individuals approximately do not meet their societal or targeted blood pressure goals and as an example of a patient preference study termed a discrete choice experiment arguably the most rigorous of patient preference studies in 400 US individuals with uncontrolled hypertension not part of renal denervation trials when posed different scenarios of side effects and benefits and duration of benefit of a drug or a device therapy anywhere from 20 to nearly 40% of individuals may prefer a therapy such as renal denervation compared with escalating medications the space of renal denervation therapy therefore continues to expand at great pace to date including novel methods of renal denervation therapy including new technologies for intervascular ultrasound and radiofrequency delivery and as we'll be sharing on Monday as a late-breaking clinical trial, perivascular alcohol-mediated renal denervation therapy. But beyond this, other technologies being explored for endosurgical approaches for renal denervation, and further performing denervation in other anatomic sites that may produce even greater and more consistent reductions in blood pressure than treating just the renal arteries alone. In summary, lifestyle modification and medical management remain foundational to the treatment of hypertension. But new blood pressure guidelines motivated by the benefits of the awareness of the benefits of more intensive blood pressure control are acknowledgment of abysmal levels of hypertension control. And an increasing awareness of patient non-adherence to both medications and lifestyle interventions has opened the opportunity for alternative treatment options. Renal denervation therapy, with the two approved technologies to date, result in not simply statistically significant, but quite clinically relevant reductions in blood pressure across multiple studies and more varied clinical populations. In the presence and absence of medications, demonstrating the biologic proof of principle, but also how this therapy may be considered or enveloped into routine clinical practice, and over an entire 24-hour period, and always on effect. More studies are forthcoming with regard to newer technologies and newer modalities of renal denervation, inclusion of patient-reported outcomes and measures in certain studies as well, greater understanding of the safety and effectiveness of this technology in so-termed real-world clinical trials populations of those we encountered in routine clinical practice. And with the advent of these new therapies, too, we as a medical community need to step up our attention to address what remains the global leading cause of death and disability. Thank you very much, Jean. Thank you. Thank you. Yes, thank you for that really outstanding overview, Dr. Kanzari. So I think using that as a context, I think now we're going to move into some case presentations. So our first case is going to be discussed here by Dr. Stein, if I can find it. Thank you. OK, perfect. So we'll start with a case that discusses disparities in hypertension management. I have no disclosures. So we have a 46-year-old obese black man without any regular medical care who presents to his local barbershop for a haircut. And it just so happens that there's a medical student volunteer who is going around providing blood pressure screening. And the patient's blood pressure was measured to be 156 over 86 in the right arm and 160 over 89 in the left. And so the patient's advised to seek care at a free clinic for a medical evaluation. So when he presents, he has no specific complaints. But on further questioning, he does report being sleepy during the day and falling asleep at the wheel. He wakes up often at night to urinate. And he feels winded after climbing two flights of stairs. On social history, he states he works as a public transit conductor, lives in a low-income neighborhood. He's single but has one child. He drinks six beers on the weekends, denies drug use, and he has no tobacco use, and also does not perform regular exercise. Family history, his father died of a fatal MI at age 67. And his mother's alive. She's 83 but does not seek medical care. On exam, his blood pressure elevation at the barbershop is confirmed in both arms. His heart rate's 86. His BMI is elevated at 36. His cardiovascular exam is normal, and there are no breweries. His abdominal exam is notable for central obesity. And his abdominal circumference is elevated at 115 centimeters. There are no breweries auscultated. His extremity exam is normal. His labs are notable for a creatinine of 1.43. There's no known baseline. His GFR is normal. And his fasting glucose is elevated at 118. Urine protein to creatinine ratio is normal. And his hemoglobin A1c is mildly elevated at 6.2%. TSH is normal. Lipid panel, notable for a total cholesterol of 225. LDL-C of 144. HDL is low at 35. And his triglycerides fasting are elevated at 230. So the physician seeing him uses the ACC pooled cohort equation ASCVD risk estimator and finds that his 10-year ASCVD risk is intermediate at 7.5%, with a lifetime risk of 50%. So in summary, this is a 46-year-old man with his index diagnosis of class 2 obesity, stage 2 hypertension, dyslipidemia, and metabolic syndrome. And a plan is provided that he make lifestyle and behavioral modifications to eat a healthy diet, consuming less processed foods, more fruits and vegetables. The patient states that he has limited equipment to cook with at home. And he's also recommended to initiate an exercise program using the ACC recommendation of 150 minutes per week of aerobic activity. But unfortunately, the patient reports that there are no safe places near his home to exercise and that he doesn't have time to do so. Given that his 10-year ASCVD risk is less than 10%, but that he does now have a diagnosis of stage 2 hypertension, he started on lisinopril 20 milligrams and a blood pressure goal is set of less than 130 over 80. He's also advised to purchase a home BP monitor, but unfortunately doesn't have money to purchase one. And since his 10-year ASCVD risk is intermediate, he started on statin therapy with atorvastatin. And finally, he's referred for a sleep evaluation given his diagnosis, his weight, and also his complaint that he falls asleep at the wheel. So we'll shift gears into an audience response question. And if you wanna participate, I would advise getting out your phone now because we'll have a short amount of time to answer the question. So we now have a 77-year-old black man with a history of hypertension who presents to his PCP for a routine checkup. And his blood pressure at that visit is 158 over 70. He reports he's taking all his medications as prescribed, including lisinopril 20 and amlodipine 5 daily. So here's our question. Which of the following statements regarding disparities and hypertension management is correct? A, his neighborhood walkability and distance to nearest grocery store plays a small role in explaining his uncontrolled blood pressure. B, he is likely to be salt sensitive if he increases his potassium intake in his diet. C, blood pressure control cannot be achieved with intensive titration of antihypertensive medications if he is African-American or if he has a high percentage of African genetic ancestry. And D, he's likely to use a home blood pressure monitor regularly if his PCP recommends it to him. And now we have 15 seconds to answer your question. All right, and we'll get the answer later. All right, thank you. So I'm going to introduce our next speaker, Dr. Wan-Pin Vangpananasan, coming from UT Southwestern. Thank you, Dr. Yang. So I'm going to talk about the disparity in hypertension management, and I have no conflict. So I'm going to start with the point out the racial, ethnic disparity in hypertension awareness and control. Dr. Yang already mentioned a bit about the hypertension awareness, and not only that's a racial, ethnic disparity, but also it's declining over time. This is the latest in Haines' analysis that showed a decrease in hypertension awareness, and also treatment is also declining from 77 to 71% for no good reason. At least you can see that the rate of treatment is similar between non-Hispanic black and non-Hispanic white and blue. Asian and Hispanic have lower treatment rate, but they're all going to a declining. And as such, the hypertension control rate was declining as well by more than 10%, which is very disturbing. And despite similar treatment rate between non-Hispanic white and non-Hispanic black, the non-Hispanic black have lower control rate. And the lowest control rate actually is among Asian, probably driven by decreasing lower treatment rate. But one might postulate that from that data, perhaps the African-American or non-Hispanic black population are more resistant to treatment. Dr. Amber H. Pandy of our institution actually looked at this a bit more, using a more accurate marker of genetic West African ancestry from the SPRINT trial, which you all know, a randomized patient to intensive target of less than 120 versus less than 140. And as you imagine, when you have an intensive target, you need more drugs to get it there. But in terms of what blood pressure achieved, extremely importantly, they want to show that whether or not you have the highest or lowest genetic West African ancestry, you can get the blood pressure there. You use the protocol intensively titrate to get the blood pressure there. So we shouldn't give up because of race or ethnicity, but we should use that as a marker for socioeconomic, particular social determinant of health that accompany this apparent disparity in treatment and control. This is the data from the REGARDS, which is the observational study in the South that look at cardiovascular risk factor. And you can see that the highest, the lowest socioeconomic score are the high poverty, it's associated with more uncontrolled hypertension, lack of health insurance, and also lack of physician or clinician to manage blood pressure. And overall, the social determinant of health was found to be mediate the black-white difference in uncontrolled blood pressure by at least 30%, which is large. And also, I wanted to point out there's also some evidence that there might be racial-ethnic difference in response to a DASH diet, and this is the data from a long time ago, actually, and show that the hypertensive, non-hypertensive black adults respond greater, there's a greater reduction in response to DASH compared to non-Hispanic white, thank you, to non-Hispanic white. This is shown in both systolic and diastolic blood pressure, and again, this might seem to suggest there might be a racial or ethnic difference in the diet, but actually, we should remember that nutritional survey consistently show that the African-American and non-Hispanic black have the lowest potassium consumption in this country, probably because of lack of access to nutritious food, that's what Dr. Stein has talked about. So intriguingly, we were, you know, there's many body of evidence that show perhaps increase in salt sensitivity among the black population, and when subjected to clinical trial compared to white when exposed to high versus low salt intervention, but if the study was focusing on study that look at the potassium intake greater than 87 millimoles a day, which is the USDA recommended intake, that's the black-white difference in blood pressure, salt sensitivity went away, so it's very likely that a lot of diet explain a lot of blood pressure difference, and unfortunately, we haven't done that, we haven't done it very well, there's a survey from the regards and Jackson Heart Study show that among black adult with resistant hypertension, the prescription rate for colostalidone or endopamide, which is recommended by the AHA SEC guidelines, is still less than 10%, and the use of spironolactone among uncontrolled resistant hypertension is still less than 10%, and less than 15% have ideal risk factors in terms of weight and physical activity and alcohol use. I want to shift again to disparity in treatment in older adults, this is a survey from more than 20,000 primary care visit with uncontrolled blood pressure in older adults, and they look at outcome of therapeutic inertia, meaning that lack of medication intensification when office blood pressure is greater than 140 or 90, and among the 65 to 74-year-old, the therapeutic inertia is already 75% of the visit, and as more comorbidity is increased, there's more inertia, that could be because physician might be afraid that the patient is too frail, but actually among the 75 or above, the therapeutic inertia is greater than 80% and is not explained by any comorbidity, so a lot to be done in older adults, and could be that because part of it is because physician thought that the home blood pressure of the patient might have white coat, but unfortunately home blood pressure is still not used as often as we hope for. The survey in U.S. adults, 50 to 80-year-olds show that about half of U.S. adults have home blood pressure monitor and use them regularly, about 45% either don't have them or don't use them regularly, and this study actually showed that one of the strongest factor of patient to do it is physician recommend to use it, so I think we can do a lot just at least encourage people who already have it. Also the part of the problem with disparity in home blood pressure monitoring is the Medicaid coverage for monitor and the cuff is still very low, it's only about 30-ish states that cover for that, and you may or may not know that CMS has a CPT codes for interpretation of home blood pressure and at least minimum 12 readings a month and communicate the treatment plan, but unfortunately only 18 to 20 states cover so far, and it's just a list of states that are covering for those, so it's still not an option to a lot of indigent care. We're doing clinical trial right now that at least in older adults that we are trying to use home blood pressure monitoring to facilitate blood pressure control and a prevention of cardiovascular events when in both group they get a home monitor, but the intensive arm get the, our staff help them link to blood pressure to Apple's health or Samsung health into EMR at UT Southwestern and Parkland Epic, and we have IT support to get clinical decision support to push the order for the physician to co-sign. The control group get the home monitor but do not get additional linkage to electronic medical record, and they can still communicate with the physician at each clinic visit, so we'll see if we will make improvement in cognitive function or cardiovascular events. So in conclusion, I hope to at least highlight some of the disparity in hypertension management from the perspective of patient and the represented group in older adults in terms of lack of home blood pressure monitoring, lack of access to healthy lifestyle, and also in terms of gaps of care of therapeutic inertia, which can be improved through team-based care and right preparation of medication, and like barbershop study was done by Dr. Victor, who's my mentor actually, that's a lot more implementation side that needs to be done, and Dr. Ferdinand I'm sure will have some more comment on it, and with the diverse stakeholder and equity framework, that's going to be the only way to lead to hypertension control in the community. Thank you for your attention. Okay, our second case, we'll discuss the evaluation and management of patients with resistant hypertension. We have a 63-year-old white man with type 1 diabetes for 48 years, hypertension and dyslipidemia, and he's referred for poorly controlled hypertension. He measures his blood pressures using a validated home blood pressure device. The readings at home range from 140 to 170 systolic over 80 to 90 diastolic. He denies any specific complaints. He states he's active, he exercises regularly, and he walks two miles per day. In additional history, he denies any excessive sweating, flushing, or palpitations. He doesn't use any NSAIDs, stimulants, or weight loss supplements. On exam, his blood pressure is 152 over 80 in the left arm and similar in the right arm. His heart rate's 57, BMI is 29. His exam's unremarkable. His labs are notable for a creatinine of 1.32, normal GFR. His hemoglobin A1c is elevated but within range for type 1 diabetes at 6.8%. His TSH is 1.8. His LDL-C is 58. His EKG shows sinus rhythm with left ventricular hypertrophy. His current medications include lisinopril 40 mg daily, carbidolol 25, BID, hydrochlorothiazide 50 mg daily, and amlodipine 10 mg daily. He's also on atorvastatin 20 and insulin. So does this patient have resistant hypertension? The answer is yes, and that's because he has blood pressure that's uncontrolled on three antihypertensive therapies at maximally tolerated doses, and one of which must be a diuretic. And the alternative definition for resistant hypertensive is a controlled blood pressure on four or more blood pressure medicines. So because of this diagnosis, he also undergoes secondary hypertension workup. An aldosterone re-in ratio is sent, which is less than three, and an aldosterone level is 8 nanograms per deciliter, which makes hyperaldosterone isn't very unlikely. His 24-hour urine metanephrines and cortisol level are normal. Renal duplex ultrasound shows no significant renal artery disease and normal renal parenchymal sizes. And then he's also sent for a sleep study, which does diagnose severe sleep apnea, and so he started on CPAP therapy. So in summary, we have a 63-year-old white man with type 1 diabetes, hypertension, dyslipidemia, and he has poorly controlled hypertension. And based on this evaluation, he does have a diagnosis of resistant hypertension, and the secondary workup is positive for obstructive sleep apnea, and he is recently put on treatment. So we'll have another audience response question. And so for this question, we have a 68-year-old man with longstanding hypertension who presents for management of his elevated blood pressure. He takes his blood pressure at home, and they're in the range of 140 to 150, over 80 to 90. And he's on chlorthalidone-25 daily, balsartan-320 daily, and amlodipine-10 daily. And here's our question. What are the three most common secondary causes of resistant hypertension? A, sleep apnea, renal parenchymal disease, and thyroid disease. B, sleep apnea, primary aldosteronism, and renal artery stenosis. C, renal artery stenosis, renal parenchymal disease, and thyroid disease. D, primary aldosteronism, renal parenchymal disease, and pheochromocytoma. Or E, sleep apnea, pheochromocytoma, and renal artery stenosis. So get your phones out, and here we go. All right, great. So I think we're going to move on to the next presentation. So our next speaker is Dr. Anna Krawisch, coming from the Beth Israel Deaconess Medical Center in Boston. And so she's going to talk about the evaluation and management of patients with resistant hypertension. Thank you very much. And thank you for the invitation to talk about the evaluation and management of resistant hypertension today. So I've been working for the last two years, along with my colleague, Dr. Jennifer Kluett, who is also here, to build a hypertension program at the BI that really services the most complex patients. So this is a topic I'm really passionate about. The speakers that have gone before me have really said about why this topic is important. Half of Americans above the age of 18 have hypertension, and most are not controlled. But I think it's a really exciting time in hypertension because of the new therapies, both for the promise that they bring of treatment, but also just to give us the momentum that we need to get hypertension under control in general. So I'm going to review the ACC AHA guideline approach to managing resistant hypertension and share some of the pearls from my management along the way. So first, we confirm treatment resistance. So Dr. Stein did a nice job of outlining this. What is resistant hypertension? So the guidelines tell us it's uncontrolled blood pressure while on three meds of different classes, including a diuretic, or controlled blood pressure on four or more medications. So does our patient meet these criteria? And next, you want to exclude pseudo-resistant or apparent resistant hypertension, but not really fitting the definition. So what does that mean? There are really three main things to look for here. So you want to ensure that you're getting accurate blood pressures. So there are a lot of flaws in office blood pressures, as I think people know, both as a result of not having the bandwidth to employ proper technique in the office, and also as a result of white coat effect, which is a real phenomenon and is particularly prevalent among patients with resistant hypertension. And then secondly, you want to closely evaluate medication adherence, because as others have mentioned, non-adherence is high in the resistant hypertension population. So they may not be on those medications that allow them to meet the definition in the first place. And then I mentioned this, but you want to exclude white coat effect. And so how do we do that effectively? I want to really emphasize home blood pressures are the way to go here, because you want to empower your patient to know their own blood pressures and be able to advocate for themselves. And then we know from the data that home blood pressures correlate the best with left ventricular mass on echo, and they're the most reliable. So if you're building a program, you really want to have the infrastructure in place to teach patients to do home blood pressures. And then there's ABPM, 24-hour ABPM, as well, for patients in whom you want to know their nocturnal pressures. And there are some patients who struggle with home blood pressures, but that you might need to use ABPM for. And so next, you want to identify any contributing lifestyle factors and really treat those. These do matter, and we don't have a lot of bandwidth in our clinic times to really support these efforts. So I really want to emphasize them, because they matter, and they really do reduce blood pressure. And also, in the guidelines, about 20% of patients, the guidelines really recommend that these are the only, or at least the initial therapy for that group of patients, for about a fifth of the patients. So it's really an important therapy from multiple perspectives. And I want to emphasize salt restriction in particular. You can really get the impact of a medication from salt restriction. Salt sensitivity increases with age, so you may get an even greater benefit in elderly patients. And of course, salt restriction is a core component of the DASH diet. So just to kind of exemplify this in a trial, in the SAS trial, they looked at salt substitute as compared with actual salt. And so they took patients with about a mean age of 65 years, a quarter of whom had had a prior stroke, and the rest of whom were at risk for stroke. So it's a population, a high-risk population, they were particularly looking at stroke. About 90% of those had hypertension. And they looked over a follow-up time of 4.7 years. And they found that the patients in the salt substitute group had a lower incidence of initial stroke and secondary stroke. And then they also found an association in reduction in cardiovascular events and death from any cause. So again, these lifestyle modifications really do matter. And next, you want to screen for interfering substances. So there's a long laundry list here, and I would just highlight oral contraceptives. They're just so commonly used. And so counseling patients on alternative forms of birth control, or you even get patients that are sort of still on them and may not continue to need them, which I see often enough to mention. And then non-steroidal anti-inflammatory drugs as well are really important to screen for. And so next, you really want to look into secondary causes and treat these. So in the resistant hypertension population, these are common. They're not zebras. And I want to highlight the three most common ones. So renavascular disease, primary aldosteronism, and obstructive sleep apnea are common. And really, they're contributors because you might have a patient with multiple of these. And treating them or treating multiple may take away some of the hypertension, but not all. So these are really important. So just to touch on primary aldosteronism. So again, it's probably 20% of patients with resistant hypertension have primary aldosteronism. So all patients with resistant hypertension should be screened for this. You will find it. And so you order an aldosterone, an arena, and you look at the ratio. When I look for this, I screen on all medications at any time of day to just facilitate it getting done. And then depending on the results, you can do further, more tailored screening if you get a positive test. Even if someone is on an MRI, if their renin is suppressed as opposed to above one, that can give you some information. So just from a logistical perspective, I essentially just draw this when a patient is in my office. And to kind of hammer this point home about primary aldosteronism, actually cardiovascular events occur in patients with primary aldosteronism kind of in excess of blood pressure. So what does that mean? There was a cohort study done where a group of patients on MRAs were matched with patients with essential hypertension that were age and comorbidity matched. And the patients with primary aldo were treated with MRAs. And still they had more cardiovascular events than sort of the hypertension and comorbidity matched controls. So this is really important to treat. And then just a point about renal artery stenosis. So many more patients are going to have radiographic renal artery stenosis than will actually have renal vascular hypertension. So this is really a clinical assessment in patients in whom you find this. And so when do you think about a stent? That's really in patients who are completely refractory to medication. So even if somebody has it radiographically but they're controlled on medications, that's not a patient where you would want to recommend a stent. And then somebody with rapidly progressive renal insufficiency or what they've sort of termed cardiac destabilization syndrome. So someone with recurrent flash pulmonary edema, refractory congestive heart failure, or acute coronary syndromes in the setting of sort of recurrent hypertensive episodes and also hemodynamically significant renal artery stenosis. I put an asterisk by FMD in young women because that's a population that I would screen differently of a much lower threshold to screen young women because the procedure is different. So pharmacological treatment. So critically important to have an algorithmic approach to this. And so you really want to start by maximizing dosing of first-line antihypertensive with complementary mechanisms of action. So the first-line antihypertensives, diuretics, ACEs and ARBs, and calcium channel blockers. And you really want to use them together for synergy, for their complementary mechanisms of action, and you want to use maximally tolerated doses. Then you move into the MRAs as a fourth line, the mineralocorticoid antagonists, then beta blockers, and then alpha blockers, vasodilators, you know, beyond that. And you want to use medication strategies that really promote adherence. So long-acting medications, once-a-day medications, combination tablets are really important. We know that adherence plummets with number of pills taken. And you also want to have a protocolized pathway for interval follow-up and escalation of therapy, which is one of the guideline recommendations, a class one recommendation. And so then last in the algorithm is referral to a specialist. So I'd really argue that any patient with uncontrolled blood pressure, it's reasonable to refer to a specialist, simply because they may have bandwidth for rapid medication titration and, you know, a whole set of tools that a clinician may not have. And a specialist can serve to diagnose and treat secondary causes, access multi-specialty diagnostics and therapeutics, and novel therapies. And then I always like to put up the Eisenhower matrix, because this is a framework for effectively using time and getting tasks done. And so what we sort of know from this is that tasks that are important and urgent, you know, we do those and we get those done. And those are the ones, you know, higher on the problem list. And hypertension really ends up falling here, the important, you know, but not urgent. And we know that those, that box contains things that are important for our long-term goals, but that we have to plan or they don't necessarily get done. So I also think referral to a specialist means hypertension becomes the central focus, which can just change the dynamic of treatment. And then this is a really exciting time, you know, as I mentioned at the beginning, there are lots of novel therapies available, renal denervation, new medications, and I'm hoping that this can create a lot of momentum to really control blood pressure more broadly in the U.S. Thank you very much. Thank you. All right, we have our last case. Case number three, we're going to discuss the clinical indications for renal denervation therapy. We have an 89-year-old South Asian female. She has a history of MI, HFPEF, type 2 diabetes, gout, CKD with proteinuria, Graves hyperthyroidism, which is well controlled, and she presents with resistant hypertension. She measures her blood pressures at home with a validated home blood pressure monitor, and those range from 130 to 160, over 70 to 90, and 20% of the readings are unfortunately greater than 140. She doesn't have any specific complaints, but she does have mild lower extremity edema and review of systems, and then she also states that she goes to bed often past 1 a.m. She reports minimal activity, though she does walk around her home without issue. She doesn't do any aerobic exercise. She eats a typical South Asian diet. She does not eat a lot of processed foods or snacks. On social history, she does not consume alcohol or tobacco. She's a widower with two children, and she's originally from Singapore. She's retired, and by way of family history, her mother had a heart attack and diabetes and passed away at age 84. Her father, also with MI and hypertension, passed away at age 60. Current medications include amlodipine-10, carvedilol-25 twice a day, lisinopril-40 daily, allopurinol, metformin, atorvastatin, and methimazole. And she was trialed on both spironolactone and apleronone, but unfortunately, both had to be stopped due to severe hyperkalemia, and then she was also trialed on hydrochlorothiazide, which was stopped due to volume depletion and a subacute creatinine elevation greater than two. And on her physical exam, hypertension is confirmed after five minutes of sitting with a blood pressure of 161 over 82. Her heart rate's 63, and her BMI's elevated at 30. Her JVP is normal. There are no breweries, and she has mild lower extremity edema, which is stable from a prior visit. Her sodium and potassium are normal. Her creatinine is 1.58, and GFR is 31, and her urine albumin is around 7,000 milligrams per gram. Her TSH and free T4 are normal on methimazole. She's sent to a nephrologist, given these findings and history, and is assessed to have hypertensive nephropathy, stage 3B, CKD with proteinuria, degenerative kidney disease compounded by age-related nephron loss. And a full secondary workup is performed, and it's all negative, including a sleep study. She's recommended against sodium glucose transporter 2 inhibitors due to concerns of persistent hypovolemia that was seen during her trial of hydrochlorothiazide, and she's also recommended to have a low-sodium diet. So in summary, we have an 89-year-old South Asian female with resistant hypertension and multiple comorbidities with a quite inadequately controlled systolic blood pressure. And she's, of course, unable to take MRAs or diuretics due to side effects and acute kidney injury, making this much more challenging. She does have a good quality of life. She's able to perform all ADLs, and she's compliant with medication. So we'll shift gears again into an audience response question. For this question, we have a 58-year-old man with longstanding hypertension, non-insulin-dependent diabetes, heart failure with preserved ejection fraction, obesity, and well-controlled obstructive sleep apnea on CPAP, and he presents with struggles with his blood pressure control. And he has a blood pressure of 163 over 78 in both arms, and his current medications include a baby aspirin and Pagliflozin, Carvedilol 25 twice a day, hydrochlorothiazide 25 once a day, and Lisinopril 40 once a day. So the question is, what is the next best step for management of his hypertension? A, refer for renal denervation, B, refer for sleep study, C, switch hydrochlorothiazide to chlorthalidone, D, refer for invasive renal angiography to rule out bilateral renal artery stenosis, and E, measure plasma, aldosterone, and renin levels. All right, thank you. Okay, great. So we're going to go to our final presentation. So our final speaker today is Dr. Kai Kobayashi from the University of Pennsylvania, and he's going to talk about what are the clinical indications for renal denervation. Thanks, everybody. I recognize that I'm the last one standing between you guys and getting out of here, so I'll try to make this as entertaining for you guys as possible. So my name is Kai Kobayashi. In terms of disclosures, I'm a consultant for Medtronic ReCore, but the reason why I wanted to bring in a lot more patient scenarios, and you'll see a little bit more about why, but let's go back to that original patient scenario, patient one, which is our 89-year-old South Asian female, history of myocardial infarction, HEF-PEF, type 2 diabetes, gout, chronic kidney disease, proteinuria, Graves hyperthyroidism, presents with resistant hypertension. Actually, there was a late-breaking trial about this particular person with HEF-PEF and type 2 diabetes, so perhaps we have some things that we could add here. The second patient that I wanted to bring in was a 40-year-old lady, chronically on hydrochlorothiazide, 25 milligrams for hypertension, diagnosed in her 30, her office systolic blood pressure at 145, heard about Renal Denervation on the internet, and now asking for a candidacy for the procedure, okay? So the reason why I put these together is because you have elderly patients, you have young patients, you're gonna have a spectrum of folks that are gonna be coming to you either because they're referred to you or because the patients themselves have heard about this and they're interested, and so we see this spectrum, I think, we were talking about this at our last panel, but essentially, you're gonna start seeing the spectrum once this starts getting out. You're gonna really have to know how to handle this and what the clinical indications here are. I think this is the reason why this is so pertinent to kind of cover in this talk, because the FDA approval, this is what it literally says. So I'll read it out to you for folks that are in the back there. But this device is indicated to reduce blood pressure as an adjunctive treatment in patients with hypertension in whom lifestyle modifications and antihypertensive medications do not adequately control blood pressure. There are now two devices that have literally the same wording, which means that if you interpret this the way that you do, the way that it's written, that is literally everybody, right? So what I want to impress upon you folks is that is not how we perform the studies. This is how we perform the studies for research. And so you'll see that each one of these patients prior to actually receiving renal denervation had multiple office visits for which they all went secondary hypertension workup for the most part, drug testing. We screened them with 24-hour ambulatory blood pressure monitoring to rule out white coat hypertension. They were then randomized to renal denervation versus sham. And then we were looking at whether it was ultrasound versus radiofrequency, which are the two devices that are out there right now. We were looking at either two, three, or six-month data points at that point. Now, regardless of the type of device, both technologies were performed in the same way. We had multiple office visits. We confirmed that they did not have white coat hypertension. We did mostly, we did a secondary hypertension for the majority of these folks. And then we performed renal denervation. And so when we start looking at the exclusion criteria in these research trials, this is basically what we're talking about. Not only are there anatomical considerations to exclude patient from renal denervation, including aneurysms, FMD, and renal artery stenosis, they were also excluded if they had compromised kidney function. So EGFRs of 40 to 45 is what's on label. And patients with poorly controlled diabetes, specifically those with hemoglobin A1C, I'm sorry, this should have been the opposite way, of greater than nine were excluded. Those with stable or unstable coronary syndromes, those with recent hypertension crises in the hospital, those with CHF stroke, AFib, TIA at any time were also excluded. Night shift workers were also excluded. And so you can kind of tell that the way that the FDA has written their approval, there are some holes. And so where is the mention of secondary hypertension workup? Where is the role of ABPM to rule out white coat hypertension? The highest risk patients were excluded in research. But now, with the FDA and the way that this is worded, is it okay to perform in everybody? Do we actually know the answer to that? And then the big thing here is, besides these sponsor-initiated post-market approval registries, who's watching? Who is watching all these patients? And when do we start doing these sicker patients? When is it okay for us to go beyond what we were actually studying? And so the argument would be, the reason why I put both of these patient scenarios on there is because if you look at the first patient's history, right? And she has stage three CKD. And so with a GFR of about 30, she would actually be excluded from trials. However, I don't think anybody here would argue that an elderly patient with a history of MI, HFPEF, type 2 diabetes, CKD, represents the highest risk patient. And so do we offer this patient renal denervation? And we could talk about this as a panel afterwards. But arguably, the highest risk, highest reward, right? This is that patient one scenario. And patient two, similarly, a 40-year-old woman, you know, the FDA would suggest, do you need to do anything further? If you really take the FDA's broad scope of whatever they wrote, in theory, you could just say, okay, come on in. I'll schedule you tomorrow, right? So are we okay with doing that? And so would we require a larger secondary hypertension workup? And so what do the secondary hypertension workup, specifically, I know that Ana had already kind of covered this, but one of the major things that we should be looking for in all of these patients before they show up to renal denervation, I would argue, is that we know that the efficacy works as long as you exclude other things like secondary cause of hypertension. And the biggest one that we should always be looking for, because we miss it a lot, is hyperaldosteronism. So the correct answer there was going to be renin-aldo. And so, you know, there's a lot that we need to learn in this sort of post-approval era, and really the future of renal denervation trials with post-market approvals. What we're seeing, what we should be looking for is how do we expand this into folks that are higher risk? So like, you know, what we're seeing as a general rule is as more and more renal denervation trials are starting to come, we're starting to include these sicker patients, and so one of the trials that David is actually running, Spyler Firm, originally started with patients that had more compromised GFRs. And, you know, what about diabetes? And then, you know, now we're starting to look at the secondary effects of hypertension. How does it, what does it do to AFib? Or, you know, I know that we just had, had a semiglutide just came out with HFPEF, patients with diabetes, but what about its effect on HFPEF, for example, these patients that we always see in the hospital for heart failure exacerbations that have uncontrolled hypertension? What does it do to that? What about intracranial, intracerebral hemorrhages, strokes? What do we do to that? And so what we're actually, what we need right now in general is beyond looking just at the FDA's indications and how we did the research, we need responsible operators, we need responsible people that are gonna run your hypertension clinic. We need really to start to come together and figure out who should we be treating? Are we okay just kind of willy-nilly doing whatever we want to? But the really big thing here from our perspective, and I think should be a call to arms really, is tracking for safety and efficacy in the commercial setting. And so what is the role of larger societies like ACC or NCDR? You know, we should be tracking the sort of how these patients are doing as we launch more commercially. And so that would be one of the big key takeaways that I would have as a call to arms. You know, you heard it here first. But that's really what I have from an indications perspective. I think you raised a lot of provocative questions about the role of renewable innovation. So we have a few minutes for the audience if they're interested. I think we have people who are circulating if there are questions from the audience, please come forward. I think somebody will be here. Oh yes, we have somebody in the back. So if somebody has a question, please come forward. So I'll just get started. So Dr. Kobayashi, I liked your comment about sort of the defining who would benefit. So it makes me think about when we had the original TAVR trials, right, these are patients who are not deemed to be surgical candidates. And therefore, the very high risk patients were being recruited for the initial studies and that obviously flipped over time. So in this case, you know, that it makes sense to me also that the highest risk patients who are older have those comorbidities, heart failure, coronary artery disease. So what do you think we should do? I mean, what would be the, you sort of put these two, we had these two extreme cases. So who are the patients that if you are seeing them and they've gone through the workup for secondary hypertension, who would you be thinking about what would that optimal patient look like to you? Yeah, that's a great, I think the TAVR corollary is perfect. And, you know, quite frankly, there are so many correlates to how we're launching and seeing the sort of patterns of renal denervation not only from a financial landscape that is very akin to how we were thinking about this when TAVR was initially launched. But, you know, when you start thinking about who, like exactly what you said, the patient populations that TAVR was originally studied and we're doing the exact opposite. We started with the low risk group and then we're marching forward towards intermediate and high risk, right? So it's hard to interpret that because essentially, you know, when you're talking to a patient, obviously, you want to be confident that, you know, you're going to be delivering a treatment that's proven. And what's proven is how we did the research. And so ideally, what I'd love to see is that we would be pretty clean about who we're sending forward. Now, nonetheless, arguably, and David already kind of mentioned this, is that across all platforms, what we're seeing is that those patients with the highest, you know, blood pressure to start out with get the highest benefit. And so, you know, that seems to be a recurring theme despite no matter which treatment you end up using. And so there are going to be some patients that then also carry other downstream effects of hypertension and we just didn't have this technology before they had end organ damage. But now that they do, are they not candidates? And so that's the big question I'd like to kind of throw out to the panel here. I think that this is really patient driven right now and I think that that's how it should be viewed. That, you know, it's our job to really educate and present options and I find that patients are very, very different in what they prefer in terms of the renal denervation. I have patients who hear about it. They've been hypertensive their whole lives and they want it as soon as they can get it. And I have other patients who will not go near a procedure. It is such a contrast to medications. The, you know, schedule of treatment, the reversibility, all of that, you know, it's almost opposite. So, you know, I think right now the way I think about it is really this is patient driven. So I offer it to patients, you know, that I think are appropriate, have gone through the appropriate workup and let them know and I'm really frank that we know what the average blood pressure lowering is. We don't know if they will get a great benefit, if they will not get any benefit and that they may not have perfectly fit into the trials and I think just shared decision making is key here. So David, I'm going to ask you since you've been involved in all these trials, so, you know, when you look at the data, you know, we need to find those sort of sweet spots, you know, who are the ones that are likely to get the greatest benefit and obviously, you know, it's hard to know that from, you know, these studies are small, the number of patients are small. So to try to tease some of that out is difficult but what is your sense of the patient that would likely benefit the most when we're thinking about who to refer? Maybe you can hold on. Oh, I'm there. Just as an introduction to this too, one of the rewarding aspects of the space of renal denervation is that it's moved forward. It's going in and out of the microphone. It's moved forward with support and endorsement and involvement of many different disciplines, cardiologists, general cardiologists, hypertensionalists, endocrinologists, nephrologists, interventional cardiologists and beyond. And so the recommendations really represent a multidisciplinary approach. With regard to the patient, the ideal patients, certainly we would prioritize those who have the highest outcomes risk in terms of the sequela of hypertension, end organ failure, mortality, stroke, myocardial infarction, heart failure and beyond. We do actually have evidence not as part of the formalized sham control trials but for example, we have a global simplicity registry in multiple countries worldwide of over 3,000 patients treated where the reductions in blood pressure are shared evenly across patients with declining renal function, with patients with isolated systolic hypertension, with patients of advanced age, patients with prior myocardial infarction and so on. As Ty mentioned, we started more with a moderate uncontrolled patient population and now we're considering this higher risk patient population, these higher risk patients. We did actually start with severe hypertension. That was the HTN-3 study. The challenge was just in remembering that those patients had an average of more than five antihypertensive medicines, an average systolic blood pressure of 180 or greater. And yet we realized that many of those patients were not adherent, they were confounders, there was change in the medicines. And so it really, we moved away from that largely because it was a very challenging patient to try to keep the background normalized to understand the benefit of the intervention of the experimental therapy, renal denervation. You know, when we think about, I'm coming full circle and the answer is that when we think about even modest reductions in blood pressure translate to clinically meaningful benefits, I see a wide spectrum of individuals with uncontrolled hypertension from those in the 140s and 150s to those in the higher ranges who would benefit from renal denervation therapy. As Ana mentioned too, patient preference is a fundamental part of this too, as it should be because 75, 77% of individuals in this country alone have persistent uncontrolled hypertension and there's a reason for that. You know, they're not adhering to lifestyle interventions, they can't sustain the medication burden that we're prescribing for them. And you know, in our trials, we perform adherence testing through blood and urine toxicology analyses looking for their prescribed medications. And arguably, these are the best of the best hypertension patients. They're motivated to do something about their blood pressure. They're willing to undergo a procedure where there's a 50-50 chance they may not get it and they're put to sleep and there's a catheter put in their artery, et cetera. And still, 50% of the time, they're not taking many or if not all of their antihypertensive medications. And so, there is a strong opportunity to think about an alternative option like renal denervation for a much broader patient population. The last comment I'll make is that the physicians, however, when we survey them, they reserve the thoughts of renal denervation only for those who are on multiple medicines who have very severe hypertension. And those may be very appropriate patients but there's probably a much broader range, especially younger individuals with hypertension who are asymptomatic, who don't feel a need for adherence to their medicines, you know, who are really in the long term of a great risk but could benefit from a therapy like this. Yeah, that's a great comment. I mean, I think the, in this culture, it seems like the easy way out. We can just, you know, get an injection to get our weight down, stick a catheter in to lower their blood pressure and it seems embedded in culture. And just looking at the data around the number of people who would rather undergo an invasive procedure and go through renal denervation to achieve blood pressure control versus taking more medications, I think is a striking testament to how we sort of view healthcare and how we view treatment of chronic diseases. So one pen since, you know, we have a few more minutes. So we've talked about this. I like the fact you showed cost effectiveness but let's be real, okay? We got all these fancy medicines. We got all these fancy treatments and these things are expensive and clearly are going to extend a lot of the disparity issues that we have with respect to access to treatment. Healthcare access, obviously, in health insurance is very important. So, I mean, one pen, when you think about this, how are we going to ensure there's this accessibility to communities where it may not be accessible? So I think that that's, it's always a practical issue. I think implementation studies where we can reach people in broad range, that's not an easy thing to do and I think having an innovation is great but I'm sure that that's going to be an exacerbated disparity of who's going to get this. Even now, just a simple blood pressure monitor is not covered by Medicaid and so I think that we should welcome the opportunity, anything that to do clever things in community-based studies, particularly with using a patient to help with monitoring blood pressure at home and more funded for those kind of program. And I would just say, at least for me on renal duration, I would say that I agree with the patient decision-making is very important. I think that at the very least, we should not give them unrealistic expectation. Say, you know, at least meta-analysis of clinical trial, like sham control trial right now, it's like adding one drug. So I think if they expect that if they're taking, if the blood pressure is 180 and they're going to be magically 140 with just renal duration alone, I think it's going to be very unrealistic. You're going to have so many unhappy patients but I think that we have to set realistic, at least in the short term, clinical trial, you're not going to get away more than just adding one drug. I think that even the study of sham control trial and the radiance, all the radiance and radiance too, the decrease in medication is less than one minute at about three to six months. So I think that long term, maybe as Dr. Khan has already said, but in short term, they're not going to talk to you and you're going to come back to see you in three months and six months and I don't think that we should set the expectation that they're going to give up all drugs. I think that's going to be very dangerous. Yeah, no, that's a really good comment. I mean, I think that, I think, Kai, your entire comment about the, so the need for the ACC and the society. So, you know, I chair, I came off as a chair of prevention council, but it does seem like this is an opportunity to bring in other groups within the ACC, even probably bring in others from other groups, from internal medicine, endocrinology, because I think we do need to have some guidance to clinicians, of course, the first priority is our patients who are interested in this, but then we also need to think about the healthcare economics and so, you know, until we have experts and leaders who provide that sort of guidance, I think that that's something that we really need to be thoughtful about, especially Juan Pan, your comment about unrealistic expectations. So I think without providing some framework, then I think people are just going to not really have a good sense of who those sort of patients are that may be the best fit for this specific intervention. Are there any questions from the audience? Yes. Obviously, you know, with the hypertension, for clinicians, the biggest challenge is they don't, you know, they don't have any symptoms, right? So we are trying to explain to them their future risk and all that. So in all these procedures, like renal innervation, have you noticed anything like an increased instance of orthostatic hypotension or other, you know, lifestyle-limiting symptoms? So Ty, maybe you can answer that question. The short answer is no, in terms of all of the data that we have, both radiance and for spiral, both the clinical programs have not reported an increased incidence of orthostatic hypotension. Yeah. I mean, I think it's interesting because you're not seeing that, at least from the studies. I think when we look at sort of the SPRINT trial in the SPRINT senior sort of sub-study that clearly patients were getting, especially in the older population, more orthostatic hypotension, falls, et cetera. So that is perhaps one of the reassuring things is that there doesn't seem to be this particular side effect as a result of very low blood pressure changes. So we have another question. Yes, sir. Hi. Lovely talks. I'm Dr. Shiva. In our clinical practice, especially in young women that you were referring to, there is a sizable population of non-specific aortoarthritis, which is a cause for hypotension. Yeah, so in terms of the question about young women, are you are you asking about like arterial tortuosity or okay in the setting of overall hypertensive disease and how you would manage that patient yeah I think so I think I think probably those types of patients would not have been included you know in a trial like this I'm sorry, I didn't hear your, I apologize, we could not hear the first part of your question, so I don't really understand what the question is. Is that microphone working? Right there. My question was in the whole list of the second report, is how frequently do you come across non-specific aortic arthritis or Takayasu's disease? Very infrequently, yes. So I'll screen for renal artery stenosis in a population where I can't control their blood pressure or they have systemic atherosclerosis or other things, or young women with hypertension looking for fibromuscular dysplasia. If I see signs of, if I think that their hypertension is attributable to a renal artery lesion in fibromuscular dysplasia, there's a different threshold to recommend an intervention than an older patient with atherosclerotic osteo-renal artery disease, because it would typically be a balloon angioplasty. So there's sort of a very distinct, you know, two primary populations that you're looking for in terms of renal artery stenosis. Ninety percent are that kind of atherosclerotic renal artery disease where they'd get a stent, so you have a pretty high threshold to do an intervention. And then the other population is young women. If you find fibromuscular dysplasia as the causative, what you think is sort of the causative etiology of their hypertension, then you might have, you'd have a lower threshold to offer a balloon angioplasty procedure, in addition to doing cross-sectional torso imaging and carotid imaging to sort of detect and monitor other sequelae of the disease. Okay, well, I want to thank everybody for their excellent presentations, and thank you to the audience for your participation as well.

hypertension

global burden

racial disparities

ethnic disparities

lifestyle modifications

medication adherence

access to healthcare

blood pressure control

patient education

technology utilization

social determinants of health

renal denervation