Hi, and welcome to J-Sky Conversations in Interventional Cardiology. My name is Andrew Goldswag, and I'm Director of the Cardiac Cath Lab at Baystate Medical Center in Springfield, Massachusetts, and Associate Editor of J-Sky, the Journal of the Society for Cardiovascular Angiography and Interventions. I'm honored to represent J-Sky and our Editor-in-Chief, Dr. Alexander Lansky. You can find us online at J-Sky.org, J-S-C-A-I.org, and on X, formerly Twitter, at AtMyJ-Sky, at M-Y-J-S-C-A-I. J-Sky is home to all official Sky documents. We're here today to discuss a very important official Sky position statement recently published in J-Sky entitled, Sky Position Statement on Renal Denervation for Hypertension, Patient Selection, Operator Competence, Training and Techniques, and Organizational Recommendations. I'm joined by an esteemed panel of thought leaders and international experts on this topic. First, Dr. Ajay Swaminathan, Chief of Cardiology at the Durham VA Medical Center of Duke University, and the first author of the Sky Renal Denervation document. Dr. Herbert Aronow, Director of Heart and Vascular Services at Henry Ford Health in Detroit, immediate past president of the Society for Vascular Medicine, and the senior author of the Sky Renal Denervation Statement. Dr. Debbie Cohen, Director of the Hypertension Program at the University of Pennsylvania. Dr. Tai Kobayashi, Director of the Cardiac Cath Lab at the Philadelphia VA Medical Center of the University of Pennsylvania. Dr. Eric Sikemsky, Director of Vascular Intervention and Interventional Cardiology Research at Beth Israel Deaconess Medical Center at Harvard Medical School. And Dr. David Kenzeri, Chief of Heart and Vascular Services, Director of Interventional Cardiology and Chief Scientific Officer at Piedmont Health in Atlanta. So panel, thank you so very much for joining us. We're honored to have you here. I'd like to start by directing a question to Dr. Swaminathan. First congratulations on this very important and comprehensive document. Renal denervation for hypertension is a novel and rapidly evolving technology. And selection, procedure performance are complicated issues, and they require specific expertise. So if you don't mind, could you please take us through the Sky Position Statement and your team's recommendations? Sure. Thanks, Andy. Happy to do that. And thanks for the invitation to be here with part of this group. This was really a group effort with many of us here on this panel to get this paper out. What I'll do is just give a kind of a high level overview of what's in the document and the recommendations. You know, Sky has had two publications recently focused around renal denervation. The first one was actually two years ago in 2021. It was published in conjunction with the National Kidney Foundation. And the focus of this document, it was a roundtable, so more of a conversation and topics that were discussed were, you know, the history behind hypertension control in general, the progress that's been made. A lot of the clinical trial data that has been published to that date was included in this document, as well as thoughts about patient selection considerations. And so now with the technology on the heels of potential FDA approval and getting into the hands of physicians and centers around the United States, there became a need to have a second document that focused a little bit more on the implementation strategies, kind of the nuts and bolts of how do we actually roll this out in centers. So again, we came up with this document that focused a little bit more on patient selection again, but then diving into actual procedural and technical considerations, and then talking about operator training, competency for privileging, and then institutional requirements. And so for patient selection, really, we talked about three groups of people that could benefit. So we have the resistant hypertension group, who have elevated blood pressures despite being on three medications at max tolerated doses, the uncontrolled hypertension group, and then this group, it's also those with elevated blood pressure, but perhaps more than just being on three medications and not responding to those. We talk a lot about shared decision-making here. Patients may have different reasons why they may or may not be able to take medications, access to care, side effects, things like that. And so that's another group that could potentially benefit. And then we spoke about those patients who have high cardiovascular risk, and maybe another group that could benefit. So embedded in all of this is really the foundation of shared decision-making, which is critical. We recognize that there are probably factors that can predict responders or non-responders to renal denervation, and that's something that we need to look further in through post-marketing registries and real-world data as we get more and more information about who this technology works in. We also acknowledge that patients who have low GFR, we have some limited data, also a population we need to look at, and that age is actually okay. There's efficacy across different age groups. So that was our patient considerations. In terms of procedural technical considerations, I won't go through all of that here, but things that we do discuss is the imaging requirements that need to happen around the time of renal denervation. We get into the nitty-gritty about axis size, sheet size, recommended guides and guidewires, how to take good pictures and get through the procedure, including antithrombotic and antiplatelet therapy. There are some technical considerations that are specific to each type of device, radiofrequency and ultrasound. We talk a little bit about that, and then, of course, potential complications, those are very rare, and management of those. So that's all in the document in that section. So when we got to operator training and competency, this was a topic that we discussed many, many times during the committee. What we decided was that rather than mandate certain volume requirements, we wanted to get the focus of this procedure to really be that you need to acquire certain skill sets to do it. So we wanted to focus on what those skill sets were and list those out, because we don't envision that only people with endovascular or prior renal experience would be doing this procedure. It could be open to interventional cardiologists who are doing mostly coronary work. In fact, in the clinical trials, there was a mix of operators who did this procedure, and it was still very safe, and complication rates were very, very low. So we wanted to focus on skill sets that needed to be acquired to do this, and we provided a pathway for different training modalities to obtain these skill sets. It could be through didactic modules, through simulators, and then observerships and proctorships. So you can see a list of some of the skill sets that were in the table here. You know, there was some discussions about at least suggesting or proposing some minimum volume requirements. We thought it might be helpful to hospitals and centers and local privileging boards to at least have some idea of what some minimum thresholds might look like. So what we decided to propose were just suggestions on those number requirements that we thought would be adequate or sufficient to at least obtain the skill sets that we showed on the previous slide. So if you already had experience doing renal artery interventions, you already have privileging, for example, in your hospital to do that, you wouldn't need to do any additional training. And we talked about moving on to a proctorship phase where you would do five proctored cases, and the proctorship could be with, for example, an industry representative, or it could be from an already experienced physician doing this to proctor you. So those folks would go straight to the five proctored cases. If you have not had any prior renal artery interventional experience, then we thought doing 10 interventions, at least half or five as primary, would be sufficient to gain those skill sets that were previously listed, and then you can move on to your proctored cases. So these are just suggestions. We recognize that folks have different baseline skill sets when coming into this, and so, you know, ultimately, you know, it would be up to local centers to set their own thresholds. And then finally, institutional requirements, you know, we thought it would be important for the centers to really have a dedicated hypertension program, and at the heart of that program would be a primary physician stakeholder who has had some previous training in the management of hypertension. We wanted to ensure that at least folks had access to a multidisciplinary team, and that could be a nephrologist, a hypertension specialist, having the right infrastructure for radiology services, and imaging, and folks that could be at the institution to help manage potential but rare complications. So we propose a care pathway here for the patient to go through from the beginning till the point that they get the procedure. So that's all in the document. So that's just a big overview, broad overview, and maybe I'll stop there and let the rest of the panel weigh in with your questions. Wonderful. Well, thank you so much. That's a really fantastic survey, and it's a really comprehensive document that covers a lot of different subject areas and a lot of different areas where guidance is required. Particularly, we get very siloed in our work, and if you're the renal denervation person at your institution, or in your city, or in your region, you know, without necessarily a lot of colleagues to support you there, it's great that a document like this, you know, really supported by and endorsed by a professional society and produced by a panel of experts can help guide things there. I want to direct a question to Dr. Cohen and Dr. Kobayashi, because the role of implementation of renal denervation is really still being defined, right? We're very early in the history of this field. So I want to ask you kind of practically, how do you do it, right? How does renal denervation fit into the treatment of hypertension at the University of Pennsylvania from, you know, the hypertension clinic to the cath lab, you know, beginning to end patient selection through patient treatment? Well, I can go first. So, Tan and I have been working together for a very long time, and we do have an established AHA hypertension center of excellence for more than 10 years. So, I agree with everything in the statement, and we really, I think the very important part is having two stakeholders to start with. So, you know, because we have different motivations, obviously, in doing the procedure. So that's number one. But we've been talking about this for a while. We've already come up with a, you know, protocol that we could follow for commercialization or how we would get the patients in, how we would screen them. So, things including, you know, excluding secondary hypertension and white coat hypertension, for example, and trying to really make sure we choose the appropriate patients because obviously we don't want this to be given to every single patient. So, we do have to be judicious in that. And then, you know, I think once we've done our side of the selection, really, you know, we hand it over to the interventional side where they, you know, I would leave all that up to them. But I do think what's really important as well is that after the procedure that we have standard follow-ups and measures, you know, in the real world, like how is this really going to impact hypertension? And I'll just say one last thing is that I actually recently had a meeting at the AHA hypertension meeting in Boston with other stakeholders who all have AHA certified hypertension centers. And we're actually planning to launch a registry and a protocol where everybody's followed the same in these different centers because I think that would really be helpful. Like, how often do you see them after the procedure? You know, which measures that we're going to be following and also agreeing on imaging. So, you know, this is a work in progress, but, you know, we're very excited about it. I couldn't agree more, Debbie. I think one of the great things about this particular document is that not only does it go through procedural characteristics of what we would expect our operators to get to, but it also still highlights the partnership between the interventionalist and the hypertension specialist, which may be the same person in our particular division and program. It's Debbie. So I'm just really happy to be able to rely on her for her expertise. I'll just quickly add one last thing. Sorry. Is that I do think in terms of patient selection, this is going to be highly patient driven as we've seen in all the trials. And that's a really important thing because I think we are going to be flooded by patients, you know, and they're going to be the motivator, not so much the physician, in my opinion. That's a great point. The system you've developed is clearly planned, organized, structured, and streamlined to provide seamless care for these patients. But as you point out, it's evolving. And so where we'll be in five, 10 years still remains to be seen. Along those lines, I want to ask Dr. Sikimsky and Dr. Kanzari a question. We are early in the renal denervation era and research is ongoing, or there are at least three active technologies in this space, ultrasound, radiofrequency and alcohol. Renal denervation is really a foreign language to many interventional cardiologists who are principally focused on things above the diaphragm. So I wonder if you could briefly take us through data to date and point us toward what research is ongoing, where the research is headed in this space. Sure, perhaps I'll begin. First of all, this is a welcomed opportunity to be part of this program and a contributor to this document. This document represents one of now more than 15 societal or expert consensus documents worldwide with advocacy for renal denervation. As we think about how this therapy, as you've discussed, is enveloped into clinical practice. With regard to clinical trials, to date we have nine sham-controlled randomized clinical trials examining the safety and efficacy of renal denervation therapy with fairly remarkable consistency across two very different modalities of renal denervation, radiofrequency energy delivery, as well as intravascular ultrasound. Consistently and certainly notwithstanding variance in the sham groups of these trials with regard to blood pressure reductions, the absolute magnitude of blood pressure reductions in moderate uncontrolled hypertension across these different trials and different modalities has been fairly consistent of five to 10 millimeter reductions in 24-hour ambulatory blood pressure and approximately 10 millimeter reductions in systolic blood pressure in the office setting. And we've been able to demonstrate now, given the breadth of this experience, one program, for instance, having now more than 7,000 patients treated and 12,000 patient years of follow-up that we have the opportunity to demonstrate the durability of this therapy now through three years. And in fact, some site limits, limited site reports now through durability of 10 years with renal denervation therapy. We also have some suggestions as we do with medications of the opportunity to improve clinical outcome. That certainly is not in the immediate forefront, just given the sheer size of such a required outcomes trial of more than 20,000 patients. But again, holding the standard uniquely and unprecedented to nine sham-controlled trials so far and now with a recently completed 10th sham-controlled trial in its enrollment with perivascular alcohol delivery, it's really a unique standard in cardiovascular medicine for trial design. And notwithstanding, across these studies, there's been a remarkable consistency despite variance in the technology and methods with regard to the safety. Unanticipated adverse device events related to the technology are simply not observed, at least to date. And the very few adverse events are largely related to procedural access or vascular access itself. Having said that, in terms of where we're heading with newer exploration and discovery of renal denervation, I would categorize in four elements. One is first expanding with the existing technologies that we know of radiofrequency energy delivery and intravascular ultrasound to broader, less selected patient populations with uncontrolled hypertension that were often excluded from these very restrictive criteria in the sham-controlled trials. For example, more real-world clinical experience in patients with diabetes or chronic kidney disease or isolated systolic hypertension, for example. The second category is related to what was raised in this document of this shared decision-making process or patient preference. We know from large observational studies, both in Europe and in Asia, that perhaps 30% of individuals with uncontrolled hypertension would favor a therapy like renal denervation therapy rather than an escalation in their medicines. And we more recently have performed a much more rigorous discrete choice experiment in which when we present to the patients side effects of medicines, potential risks associated with a procedure like renal denervation therapy, when we factor in issues related to durability and the blood pressure reductions that are important to our patients, anywhere from 20 to 50% of individuals may prefer a therapy such as renal denervation rather than beginning a new medicine or escalating their medication burden as well. And third, rather, is innovation. We're exploring, as I've just shared, new technologies with renal denervation with regard to perivascular drug delivery, new therapies with radiofrequency energy delivery, and beyond this, transradial access for renal denervation and further newer methods of renal denervation, for example, exploring denervation in other vascular beds that may complement the blood pressure lowering effects that we've already observed with renal denervation and other methods of renal denervation as well. And then finally is addressing this issue that's raised in the document of level setting expectations and predictors of treatment, both during the procedure, which currently has no biomarker of efficacy that we can use during renal denervation, and also before the procedure and identifying predictors or characteristics that may help inform us with regard to which patients will have a meaningful reduction in blood pressure versus perhaps those who would not. Hard to follow that, Andy. Thanks, Dave. But I just wanna highlight this one aspect of the evolving evidence is, I think most people in this space and even in interventional cardiology shut down after 2014, 15 with simplicity hypertension three. And so it's always interesting when you go back to talk about renal denervation now, and there are people who are in the know, and then there are people who are still living, you know, eight years ago, and they say, what, there's five, six trials that have come out since somebody talking about. And so, you know, I think it's really important, Dave summarizing, and honestly, there's no one in the world who can summarize this evidence better than Dave, is, you know, we have such high quality evidence with a really unique design that isn't commonplace in cardiovascular device, you know, trials as SAM control. We have data now across platforms so that we know that renal denervation, however it's delivered is effective. And then as highlighted, we have now data for a device that's been approved in Europe that now goes out for years. And so, you know, coming to the U.S. with this novel device seems like a, you know, a strange term because it's really much more mature than most novel devices we're bringing to market right now. And I think this document helps highlight really the forward thinking of how this will look in the U.S., but the wealth of data out there is gonna strongly support its adoption, and hopefully it cements its place in the role of managing select patients with resistant hypertension. Yeah. That's great. Well, it's clear that renal denervation is here to stay. You know, it's one of the most evidence-based technologies, as you both said, that we have already and data continue to accumulate. So then I think in my mind, the big question is when we look into the crystal ball, what do we see, right? You know, renal denervation is extremely promising, to treat refractory hypertension. I wanna look toward Herbera now for this. You've been at the forefront of this field for many years. What's the future? You know, currently, renal denervation is honestly only available at a select few centers. In light of your very comprehensive new Sky document, how can access to this treatment be expanded? How can we educate our colleagues, our referring providers? How can we recruit, train more operators? What can we do to make the renal denervation landscape look the way we dream it should in 10 years? Andy, thanks for the opportunity to be here and for your question. And I would say, well, it's been an honor to be at the forefront from a society standpoint, trying to create scientific documents to guide the field. There are others on this call that have really generated the evidence base that's led to documents such as ours. So I really appreciate their contributions as well. Let me take my crystal ball out here and I'll tell you exactly what's gonna happen. I wish, obviously, I knew, I think we all do. From the standpoint of rolling the technology out, it would make sense to do this in a controlled fashion, starting with centers where there is expertise and to go from there. Obviously, we're talking about a very prevalent condition. So ultimately, that small number of sites won't be able to accommodate the public health need, even if it's just a minority of patients with hypertension that ultimately need this treatment. But there are a lot of ways that I think we can get operators from point A to point B. From an educational standpoint, we've got webinars, case simulation, certainly observation and case proctoring. And I think those will all play a role. I think that the existing community of interventional cardiology providers of operators will be likely able to accommodate the need, but I don't think they're the only ones who may ultimately be qualified to do so. There may be other specialties like vascular surgery and vascular interventional radiology that may be involved as well. I think when appropriately trained, and our document speaks to what that means, I think a provider from any number of specialties could offer this therapy. I think that maybe the most important point I wanna make here from a crystal ball standpoint is that when I look ahead to what I think will happen in 10 years, I'm picturing a world where we're all doing a much better job taking care of hypertension, taking care of patients with hypertension. Because I think we've been motivated by all the exciting developments that are technological right now. And that motivation, that excitement has led us to talk more about the disease state, to organize more around the disease state, to collaborate more with other specialties and other disciplines. So I think while, again, it may be a minority of patients who ultimately need or elect to have renal degeneration, I think that the entire population of patients with hypertension may benefit because of these enhanced efforts. I'd love to open the floor to the panel and see if anybody has other thoughts. You know, I think Dr. Arenow's predictions are very, very valid. And, you know, we're all obviously all hopeful and eager to see them come true. I'm very eager to invite anybody else's thoughts about the future, about how this document will be applied and about renal degeneration in general. I'll just make one comment. I want to go back to a statement Debbie made and was followed by Ty, was, you know, now that we've kind of hit momentum here, there's so many interested parties who are coming up at meetings and asking about how to build their own RDN program, which is just fantastic. And again, so timely with this wonderful document. And I just want to mention that, you know, we'd started building our hypertension center with the idea that there was an unmet need for these hypertension patients, but also understanding the potential role of these type of technology in the future. And I think that the most important part for anybody interested in this space is to really find trustworthy and, you know, good working partners. Like this is not a one person technology. This isn't something that as an interventionist and for the SCI community can just take and start using in the lab. Like this really requires some programmatic effort and it doesn't have to be on the same scale as what is done at Penn or other institutions. But the idea that you really need a non-invasive champion to help understand the patients who really benefit from this device or technology, who may not need this now, who has other options for their blood pressure. How do we monitor post-treatment? You know, these are important things that not just one person can do. And in particular, one clinical, you know, procedurals can do. And so I just want to put that plug out there that that's what makes this document even more important. It's not about finding an operator who could put a catheter in the renal artery. It's about building a program around really a clinical need. And really this is anchored on new technology, but this need has been there for quite some time. Beautiful. Well, thank you. Oh, please. I was just going to add one quick thing, just to say that we all know the control rate of hypertension in the US is really terrible. No less than 30% are controlled in the US. So even this technology will not be applicable to most people with hypertension, but I think that the interest that's been garnered in the technology is really going to improve, hopefully, hypertension control for everybody, because, you know, people are, like, through education are becoming more aware of all these different issues. So I think, you know, this could have extended benefits. Wonderful. Okay, well, thank you very much, Dr. Swaminathan. Dr. Aronow, Dr. Cohen, Dr. Kobayashi, Dr. Zachemsky, and Dr. Kanzari, we are absolutely thrilled to include this important paper in the November 2023 issue of J-SKY, and to share this discussion with this incredible panel. Please follow J-SKY. Submit your own work to J-SKY. J-SKY is the official journal of SCI, and you can find J-SKY online at jscai.org, and on X at at myJSKY. Thank you all so much.

Renal Denervation

Hypertension

Shared Decision-Making

Multidisciplinary Approach

Efficacy

Safety

Collaboration