Scott Webb (Host): Genicular artery embolization, or GAE, for osteoarthritis in our knees is a fairly recent pain management solution for folks who either aren't good candidates for a total knee replacement or aren't good candidates just yet. And I'm joined today by Drs. Chong Li and Zachary Fang, both of whom are performing this procedure with great results, for the Vascular Care Group.

Welcome to Answers in Vascular with the Vascular Care Group. I'm Scott Webb. It's nice to have you both here today. I was mentioning to you that I suffer from osteoarthritis, especially in my knees. So, I'm definitely a very interested party today. And Dr. Li, I'm going to start with you. What is genicular artery embolization? And what's the rationale or therapeutic mechanism behind its relief for arthritic knee pain?

Dr. Chong Li: Thank you, Scott. So basically, GAE, the acronym for genicular artery embolization, is a new minimally invasive technique for knee osteoarthritis, where microparticles are injected into a small artery, feeding the inflammation in the painful area of the knee. Basically, what this does is that it disrupts the cascade and the mechanism behind the pain and the tenderness from the arthritic knee pain. It was originally used to treat bloody effusions, also known as hemarthrosis of the knee, but after realizing that proliferation and the growth of a blood vessel or angiogenesis is associated with arthritic knee pain. And this technique was successfully applied to knee osteoarthritis. And, you know, we have been doing it, and our patients have been getting very good results from this.

Dr. Zachary Fang: Yeah. Just a second on what Chong was saying, GAE works very, very well for knee pain. And the mechanisms that have been proposed for how this actually relieves pain are several fold.

Actually, one of them is, like Chong was saying, you get angiogenesis and proliferation of capillary growth, as part of the overall pathophysiology of knee osteoarthritis. And we embolize these small vessels and cause them to atrophy, so they stop irritating the nerves around them. So, that's one way. And then, the other way is that, by blocking off these small vessels, we're actually preventing any inflammatory mediators from reaching their target tissues, i. e., those around the knee, thus, like Chong said, interrupting the inflammation cascade.

Host : Yeah, Dr. Fang, how or why did you all start practicing this intervention? You know, it seems so obvious, but it maybe wasn't obvious at the start. So, how, why, when did this start?

Dr. Zachary Fang: Well, it's something that, you know, was initially studied and pioneered in Japan. And prior to the pandemic, there was a lot more data coming out about its efficacy, and it was gaining some popularity. But then, the pandemic happened in 2020, of course. And so, things really were slowed down then, and afterwards, since then, it started to gain steam again as an alternative pain relief mechanism for patients who suffer from knee osteoarthritis because there's, you know, a huge population in the United States who have knee pain. And we were seeing a lot of patients in our clinics who, you know, we see folks for arterial disease all the time, as well as venous disease. And a lot of the vein patients were also saying, "Oh, yeah, you know, my knees have been hurting. I've had a knee replacement and they still hurt," or "I can't get a knee replacement yet because, you know, my orthopedic surgeon said I wasn't a candidate quite yet." And so, we started looking into it and realized that there's this other procedure that you can do that can help with patient's pain and help get them to that destination therapy, which is really a total knee replacement.

Host : Yeah. And Dr. Li, I want to dig in here, roll up our sleeves a little bit and talk about some of the data behind GAE and the outcomes.

Dr. Chong Li: So, you know, the initial evidence and research came from Japan from an interventional radiologist named Dr. Okuno. He was studying how angiogenesis or, well, you know, the proliferation of the abnormal blood vessel affected joint pain. And he eventually linked their close relationship. And, you know, there were early small cohort studies conducted by his group that really consistently demonstrated decreased pain in a pain scale for knee pain at six months, one year, and even up to two years, and as well as decreased the need for pain medications, the non-steroidal use in patients who he treated with GAE. And this was again, confirmed in larger series, and there are now randomized control trials comparing GAE to sham procedure where a catheter is inserted into a knee, but no particle was used for embolization. And the GAE arm has demonstrated superiority in pain control compared to a negative control procedure. And there are also now multiple studies from other countries, in Europe and the United States, confirming the benefit of GAE, and as well as meta-analyses, where a study pools together and sums up all the study of GAE, again, showing its benefits. So, you can really argue that there's now level 1 evidence demonstrating the benefit of GAE in pain reduction.

Host : Yeah, level 1 for sure. And Dr. Fang, wondering, maybe you could take us through the role of vascular surgeons in performing the procedure.

Dr. Zachary Fang: You know, as vascular surgeons, we do kind of the whole breadth of surgery on the blood vessels from minimally invasive surgery to kind of maximally invasive surgery. And this is definitely on the minimally invasive side of things. We perform something called endovascular therapy, which is another term for a minimally invasive surgery that we do, but we insert a catheter into an artery, either in the thigh or in the foot. And then, from there we can navigate to the blood vessels in the knee using contrast dye as well as a little bit of live x-ray called fluoroscopy to actually select these specific blood vessels and, first of all, make sure that they have capillary overgrowth, but then to treat them as well.

Dr. Chong Li: Yeah. Going off on what Zach is saying, as vascular surgeons, we basically treat most of the reasons why a patient might have leg pain, you know, whether it's arterial disease, venous disease, lymphatic, we even treat some neuropathic pain. And now, you know, having picked up this therapy for, osteoarthritis, knee pain, we really can treat a patient's pain holistically. We see a lot of patients with multiple reasons for leg pain and knee pain, foot pain. And now, we can really help them with their quality of life. We also work closely with our orthopedic surgeons and physical therapists, rehab centers to kind of tailor what's a good therapy for them. And the key to this procedure is that it's not mutually exclusive to what the orthopedics and the physical therapists do. And very frequently, probably always is that we do this on top of what the patient's already getting at the orthopedic surgeon's center and rehab. And we're just doing this on top of what they're doing at the other clinics, because whatever they're getting might not be controlling their pain enough.

Host : Yeah, I see what you mean. You know, this sort of multidisciplinary approach team, if you will. Dr. Li, who's a good candidate for GAE, and is there anyone who's just absolutely not a good candidate?

Dr. Chong Li: First of all, you know, the GAE has really just consistently demonstrated data for knee osteoarthritis. And obviously, there are other reasons to have knee pain to name a few other diagnoses like rheumatoid arthritis, psoriatic arthritis, or meniscus tears, or ligament tears, those are not good candidates. So, we first make sure that they have a diagnosis of moderate to severe osteoarthritis.

Another entity that we can use this therapy for is hemarthrosis, which, as I spoke about this before, was a bloody effusion or collection in the knee joint. GAE can also work for this. Some other reason might be that, if the patient just has mild pain or if, you know, whatever they're getting at the orthopedic surgeon, such as injection, physical therapy, pain, or non-steroidals, they're okay with their quality of life, then I usually kind of sway a patient away from this. But, you know, there's not really a contraindication besides the wrong diagnosis or having infection in the knee joint. But really, it's a benefit and risk after discussing with a patient, because it is a procedure after all, although it's minimally invasive. So, I try to select my candidates who have moderate to severe pain.

Dr. Zachary Fang: Generally, how we determine which patients are good candidates is they usually fall into three or four different categories. The first one is, you know, folks who are not good candidates for a knee placement. They've already seen an orthopedic surgeon. And they have been ruled out for a total knee for a variety of reasons. That could be, you know, they have too many comorbidities, they're overweight, they're too sick from another standpoint, you know, whichever reason they were not an ideal surgical candidate for a knee replacement, that is something where we can say, "Okay, GAE may be right for you."

The next one would be a category of patients who could be good candidates for a knee replacement, but they need to do a little optimization first. So, these are the patients who see the orthopedic surgeon and they say, "Okay, you could get the surgery, but you probably need to go lose, you know, 10 or 15 pounds." That will make surgery more likely to be successful and it'll give you a better outcome, but the patients just have too much pain to actually do the exercise to lose that weight. GAE is a good therapy for them as well, because it can give them enough functionality back in their knee through pain control that they can then use it to do the exercise and lose the weight.

And then, there's also folks who have already just had a knee replacement, but they still have residual pain afterwards. And that's one of the great things about this procedure is that you can actually do it before or after a knee replacement. And you can still get, you know, really good pain relief. We do caution patients, though, that the only thing that will definitively fix your knee pain is a total knee replacement. This is not supposed to be a replacement for that at all. This is an adjunct. It probably lives more in the realm of, say, corticosteroid injections or the hyaluronic acid injections or gel or PRP, one of those other therapies. But the difference here is that this sort of relief is shown in Japanese data to last for several years, whereas those therapies only last for several months.

Host : Yeah. And Dr. Fang, maybe you can take us through some of the procedure details, steps, and experiences, both from your perspective as a surgeon, but also the patient's perspective.

Dr. Zachary Fang: We touched on it earlier a little bit, but the way that we do these procedures is with moderate sedation or no sedation at all, depending on patient preference. And first, you know, we've already decided based on the physical exam and other patient factors of are we going to go in through artery in the foot or are we going to go in through the femoral artery in the thigh? And so then, we'll numb up the area with lidocaine over our access vessel, and we'll use ultrasound guidance to insert a needle in. And then, from there, we can insert a sheath or we can just insert our catheter over a wire. And afterwards, we'll take some pictures with the image intensifier with fluoroscopy to make sure our equipment is all in the right place and that everything looks like it should. And that will also allow us to identify the target vessels. And then, from there, it's us just working with wires and catheters to access and select each vessel, confirm that there's hypervascularity with another picture, and then very gently inject these microspheres, which are about 200 microns in diameter. And it's a very small amount that we inject into each vessel. Then, we take completion pictures, and once we're satisfied that we've gotten into usually about three or four of these genicular arteries, then that's when we usually say, "Okay, you know, we're going to remove all of our sheaths and wires and catheters" and either hold pressure or use a closure device and that's it.

From the patient's perspective, you know, this takes us somewhere between one hour, probably hour and a half has been our longest one so far. A lot of folks just have a nap, some people just chat with us while we're doing it. And then, afterwards, they hang out in the recovery area for 30 minutes to an hour. We have an ice pack on the knee, and then they get up and they can walk out. There's not really any big downtime or anything from our standpoint, and it's been very well tolerated so far.

Dr. Chong Li: Yeah. Just going off what Zach is saying, what we're looking for is an abnormal kind of blush, which is a vascular perfusion to the painful area. That's more than what's normal. And that indicates that we're at the, you know, arterioles, we selected out the right branch of the artery to inject these small microembospheres, as we call it. And we're not really cutting off any blood supply per se, but we're really just kind of eliminating the blush or the small arterial perfusion to the pain area. And that's how we eliminate the arterial blood supply to the pain and disrupt the cascade leading to the knee pain.

Host : Yeah, wondering, Dr. Li, Dr. Fang mentioned there that folks, you know, a little bit of ice and they're on their way out, walking out. But generally speaking about postoperative care and just their expectations, you know, how long until they really feel the effects, are back to their old selves or back to playing pickleball, whatever it might be?

Dr. Chong Li: Yeah. You know, so I usually tell the patients that their knee pain might sometimes get a little bit worse for a day or two before it gets better. So, you know, the effect is frequently not immediate. Some people, their first day or second day have a little more pain, because we acutely shut down some of the tiny, tiny arteries around their knee that might cause some of what we call post-embolization syndrome. That's not common, but they usually start realizing and experiencing pain relief a few days in, up to two weeks. And the patient that I've done around two weeks or three weeks when they come back, they are really happy. Most of them are very happy. They've experienced pain relief, and the benefit actually can persist, and it kind of can add on itself a few months in, up to six months. We're probably not taking away all of their pain. I would say up to, you know, 60%, 75%, 80%, it's very possible.

Immediately after the procedure, I tell them to ice their knees three times a day and not to take on strenuous weight bearing activities. I send them home with some pain medication, such as Toradol. Or in those patients that I embolize the big area of blush, I send them with a day or two of steroids called prednisone, which can temporarily, you know, further suppress some of the inflammation or post-embolization pain that they will experience. They usually also takes Tylenol for a few days as well. Overall, the patient can go back to their normal work and home life the day after the procedure. And these adjunctive medications and therapies are just there to ease the post-embolization phenomenon in some patients.

As Zach said, the catheter we use to gain entry into the femoral artery, they're very, very small. So, the bleeding risk is actually very, very small. And, you know, thankfully, I have not had anybody have any bleeding complications since the tools and the catheters are so small that that's not really a concern.

Dr. Zachary Fang: I usually tell patients that they should expect to have one to two days of possible increased knee pain. And in the past, we've actually used a lidocaine patch fairly successfully if it's particularly severe. But for the most part, everyone's just taking over-the-counter medications, Tylenol, Advil. And usually, they haven't needed, at least for our practice so far, they haven't needed any steroids or any other heavy hitters from an anti-inflammatory standpoint. We tell them that, you know, in the first week, if they're a responder, because not everyone is, about 75%, according to the data, folks have some sort of response. But for those who are in the first week, about 25% improvement in their pain is what they should be expecting. And then, that should be about a 10% increase each week. It usually tops out about at six weeks. It's interesting though, the data from Japan, you know, we have patients that we track their pain with something called WOMAC pain scale. And the data from Japan shows that that has continued to decrease over time, like Chong was saying, over months to years. So, at one month, we see them and have them fill out the pain scale again. And at six months, we'll have them fill out the pain scale again, and then again at one year and at two years. And we are expecting that we're going to continue to see a decrease in those pain scores.

Host : Yeah, it sounds like it's been an overwhelming success. Dr. Fang, I just want to finish up here. You know, maybe you can go through some of the preliminary or anecdotal outcomes for patients that have undergone GAE in our platform.

Dr. Zachary Fang: At the Wellesley office, we started doing this in February of this year, and I think we've probably done the most out of any office, but that's, you know, 25, 30 patients maybe. and At this point, everyone that we've treated so far has been a responder. So, I can't speak so far as to, you know, how much that 75% rate, if that's true or not, or if we're just getting very lucky. This is a procedure that can be repeated, but we have not had to repeat it on anyone quite yet. We have had one patient who did have recurrence of their knee pain, but they also broke their foot in between when we treated them and when we saw them back again. So, they initially had great pain relief and they were over the moon about it, but then, they broke their foot and it seemed that their gait may have changed. So, it's unclear if this was from treatment failure or if this was from re-injury or new injury to the knee itself.

Host : Sure.

Dr. Zachary Fang: But other than that, it's been very successful. People have been very, very happy. We generally are somewhat conservative about it, so we have patients come in. And if they pain in both knees or osteoarthritis in both knees, then we'll plan on doing one leg and seeing how they feel and how they respond before we go ahead and do the other one.

Host : You don't have a two-for-one special?

Dr. Zachary Fang: Usually not, but a lot of that is just for patient comfort. You know, it's a long time on the table otherwise.

Host : Right. Yeah, it does feel like once they're fully recovered and back to their old selves, as you say, if they have osteoarthritis in the other knee and this was successful and the outcomes are good, why not? But Dr. Li, I'll give last word to you. You know, just preliminary anecdotal outcomes.

Dr. Chong Li: All of the patients that I treated, they're all very happy as well. You know, I remember my first patient, she was able to kind of chase after her grandkids, which she couldn't do before, you know, because of the pain. So, that really, really echoed in my mind about-- you know, it's from one case, but looking at the data and the anecdotal initial experience that I had, that really kind of gave me confidence that this is a therapy that really works. And so far, it's been kind of stories like that, from maybe taking away a third of the pain to most of the pain.

And like you guys said, arthritis affects both knees usually. And I also see how one knee does. But frequently, you know, I would say they would like to make an appointment for their second knee to undergo the same procedure.

Host : Yeah. Go ahead and schedule it in advance, right?

Dr. Chong Li: That's right.

Host : Yeah, that's perfect. Well, it's been really educational today. Great to learn more about GAE and how it's being used, how you guys are using it. Positive patient outcomes. Brought a smile to my face. Grandmothers and grandfathers chasing their grandkids around. So, all good stuff. Thank you so much.

Dr. Zachary Fang: Thanks so much for having us.

Dr. Chong Li: Thank you, Scott. Thank you for having me on.

Host : And for more information, please visit our website at thevascularcaregroup.com. Thank you so much for listening to Answers in Vascular with the Vascular Care Group. I'm Scott Webb. Thanks for joining us.