Podcast Transcript: Genicular Artery Embolization: Current Controversies & Insights

[Dr. Venkatesh Krishnasamy]
Okay. All right. That's helpful, guys. All right. Let's go to the next topic. Embolization of any abnormal vessel versus only the painful side. Os, you have any abnormal vessel. Sid, you have only the painful side. Os, you want to start?

[Dr. Osman Ahmed]
Sure. Yes. I think there's obviously the Landers paper that suggests that the more you do, the better the patient does. If you probably survey most of "experts" in MSK field, including Okuno himself, they will basically target any vessel that shows abnormal hyperemic blush. I think probably, at least in my own practice, I have found more often than not, even if you go to the "other side", you'll see some anastomotic collateral network that then communicates to that side of the pain. Especially in the era of temporary resorbable embolics, where the embolic is more forgiving, it's probably better to commit an error of commission as opposed to omission.

[Dr. Siddharth Padia]
It's hard for me to disagree because I would argue that we don't really know yet. I'm on the fence with this one. I really am. Because, as Os mentioned, the Landers paper, so Landers did this randomized trial, which was negative and even in his own discussion said, "We didn't embolize a lot of vessels." Can you? When we did in a subgroup analysis, then we did have better results. Maybe the argument is that you need to embolize more vessels. How many do you embolize? Do you embolize six, eight? Do you start going superior patellar and recurrent ascending tibial and all the other geniculars? I don't know what the limit is.

I do agree that just doing one may be inadequate in many. I just don't know where that midpoint is as to not too many. It's like the mama bear. It's not too hot, not too cold kind of thing. I think we're going to figure this out eventually. This is going to be easier to figure out than the MRI question that you alluded to earlier. I just don't know what the right answer is. I do think embolizing more than one is probably favorable. For example, if you have medial knee pain and the descending genicular artery lighting the medial side of the knee, yes, you should embolize it, but you should at the very least examine your other medial branches.

Whether you examine your lateral ones, I tend not to. That being said, I do a cone beam CT, and if I see it wrapping around the patella, then I will. I don't know if we have a right answer here.

[Dr. Venkatesh Krishnasamy]
Okay. Let's phrase this question a little bit differently. Let's say you don't have access to resorbables, how about then?

[Dr. Siddharth Padia]
I don't have access to resorbables. Os can talk about Lipiodol, which we do have access to, but we're not using that for genicular re-embolization, we are using permanent. I think many centers, if not most, in the United States are using Permanent. We have had all of our results, including our published results, using permanent. There is a randomized trial, which has not yet been published but was presented out of Brazil, where they showed pretty much equivalent results with permanent and resorbable, maybe hedging towards permanent in terms of efficacy, but not statistically significant. That being said, I think the safety profile for resorbables is superior. I have no doubt that it is safer.

I was going to say you have to be more careful using permanent. I would argue you should be careful using both. The resorbables does give you a little bit more room for error, is the best way to put it.

[Dr. Osman Ahmed]
I certainly agree with that. I think if you are using permanent, which probably the majority in America are, definitely, and that's what I used in the first half of my GAE experience. Definitely less is more. Whether it's the amount per vessel, the number of vessels you're doing, I think you still need to be much more confident that you are selectively embolizing a vessel that you believe is a source of pain. I think the approach with a temporary, an Imipenem or a Lipiodol is much different in the sense that your threshold is reduced much lower, I think. I go into vessels and say, "Yes, it looks abnormal. I'm going to just take this out because I know that the Lipiodol is going to wash away in 10 minutes."

There's arguably very little side effects related to it. I'm with you, Sid. We don't know. There's a lot of unanswered questions. One of the unanswered, clearly, is how many do we embolize? I think the data is trending towards more is better. There is that one paper that just came out saying that even in severe OA, as long as you embolize three vessels, it seems like you're getting decent results. I have another question for you, Sid, maybe, that is on this line is let's say you did do that DGA, and you clearly see a nasty amount of communications with the inferior medial, superior medial, and you see your particles or whatever you're injecting going into those vessels, would you go into those other vessels and still embolize them?

[Dr. Siddharth Padia]
I might consider going into the other vessels and just doing a diagnostic angiogram. If there is antegrade flow and hypervascularity and neovascularity, then I would. If there isn't, I would not. In most cases, when I do see that anastomotic communication, let's say I'm in the descending after the embolization, I see that anastomosis, and then I go ahead and catheterize, let's say, the superior medial. In almost every case, what you'll see is just communication back to your descending, but not to any area of hyperemia, because that's been treated already. Then I just look and I don't embolize.

[Dr. Osman Ahmed]
Yes, I agree. That's almost to a T what I do. I guess maybe where I have an issue is, what if you can't get in the vessel, or it's a tiny vessel, it's hard to get into? Do you lower your threshold to abandon going into it?

[Dr. Siddharth Padia]
Yes, I might. I agree. I think I do lower it. That being said, this is cheating a little bit. Pretty much all of our patients are on trial, so we don't give up. I know this is not fair, but on a clinical trial, you don't want to have technical failures, right?

[Dr. Osman Ahmed]
Yes.

[Dr. Siddharth Padia]
We make sure that we are technically successful in all our targets in terms of catheterizing and doing angiography.

[Dr. Venkatesh Krishnasamy]
Okay. I like it. All right. Let's switch gears a little bit and let's stick with a permanent particle topic. Let's go with size of particles. Os, you have 250 to 300 micron. Sid, you have 100 micron. I know, Sid, you're doing more permanent embolic than temporary embolic. Os, I know you're the opposite. We're putting you in a little bit of a bind here. Os, you want to start?

[Dr. Osman Ahmed]
Sure. Yes. I think speaking on safety has been a little bit of the theme of this podcast so far. You look at the data that's out there. You have Bagla's sham data that showed that, using-- I don't think it was a sham study. It might have been another study. It was Bagla's data that showed that smaller particles in that 75-micron range did lead to plantar paresthesia. Then, you also have the van Zetelhoff data that showed two patients who had, using, again, I think, 75 or 100 micron that had ankle paresthesias that didn't resolve at four months. Then, also, one patient with a foot drop.

That makes me very nervous to use a small particle, just in the spirit of safety. I'd rather have safety than lack of efficacy in some sense. I think larger particles, if you're using permanent, probably makes more sense from a safety perspective.

[Dr. Siddharth Padia]
I agree. I think that there's probably a safe range. I wouldn't go more than 250 because then you're just going too big. If you have a small microcatheter, it's going to be messy. I wouldn't go lower than 100. I think that's a reasonable range, anywhere from 1 to 250. Of course, it depends on your brand. Some of them are more compressible, depending on the manufacturer that you use. I don't want to go into the specifics of the pros and cons of that, but that wouldn't matter as well. In other words, 100 for one brand is not necessarily the same as 100 from another manufacturer as well. I think anywhere in that range, I think it is reasonable. Just don't go too small and don't go really large. It's that sweet spot.

Going back to the resorbable, I admit that even though I don't use it, I think it's eventually going to be the future. The nice thing is there are, I don't know, maybe half a dozen companies that are studying resorbable embolics. To my knowledge, they're trying to do it the right way. They're trying to do this through PMA-level trials. Many of them randomized trials. They're trying to do really good work on getting this to market in a very fair, ethical way. This might be the future to do resorbable embolics. Clearly, the initial study, which was done with Imipenem, which is an antibiotic, but it's a crystalline Imipenem, is resorbable in one to two hours.

I don't know about you, Os, but when I read that first paper, I was like, "What? This makes no sense." It works. Something that's resorbing in two hours seems to at least permanently shut down the neovascularity, which is what is needed. It's very appealing. It's just challenging in the US when you're trying to do a study, at least today in 2025, because we don't have these resorbable embolics currently available on the market. When we're doing all our trials, we went with things that we are comfortable with, which are the permanent embolics. If we can prove that it works in those, then we can start tweaking the formula.

[Dr. Venkatesh Krishnasamy]
Okay. Then here's a question. We have a lot of permanent embolics coming onto the market, as you said. There are multiple that are in trial right now. There are multiple that are available right now, off-label, but still available. Will permanent particles still be relevant in five years in this space?

[Dr. Osman Ahmed]
I think there will always be a role for permanent, probably simply based on economics. Permanent spheres are cheap. If they work, then we're going to come back to an economics argument to use them, depending on whatever setting you're in. I think as Sid mentioned, we know it works. His data shows it works. You have many people's data shows that it works. There is some suggestion that maybe it even works potentially better in the knee. I think the question maybe probably more applies to other joints.

MSK embolization as a whole, I don't see a role for permanent embolics there. Once we and now hopefully, fingers crossed start validating things like plantar fasciitis and shoulder and elbow and wrist and all this stuff, then we're going to really probably see a renaissance or a resurgence of a resorbable or temporary agents, for that.

[Dr. Siddharth Padia]
Don't inject permanent embolics for plantar fasciitis. That's probably a bad idea.

[Dr. Venkatesh Krishnasamy]
Good point. Very good point. Okay. On that way, and Sid, the data you mentioned earlier about permanent versus resorbable, that was versus imipenem, correct?

[Dr. Siddharth Padia]
Yes, it was imipenem. I believe it was Embosphere, but I can't remember exactly. To my knowledge, I don't think it's published yet, but it was presented at Searcy. They showed better efficacy with permanent, not statistically significant, but better.

[Dr. Venkatesh Krishnasamy]
All right. Real quick, if you're using permanent spheres, what is your endographic endpoint? What is your dilution? What's your typical average volume injected?

[Dr. Siddharth Padia]
Again, it depends on which spheres you use, because they all come in different vials. One comes in a 10, one comes in 5, 7, et cetera. This is what we do. We do embosine 100 micron. It comes in a vial of 7 cc's total. We dilute it down to a total of 22 with using contrast and saline. We basically add 15, which is way more than what you're supposed to dilute it for, because we're putting it through a 1.7 French microcatheter. It's a slow infusion, perhaps not as slow as prostate embolization, but the goal is not to go to stasis or even to substasis.

The goal is to basically trim the hyperemia. The average amount we're giving into a vessel is about one CC out of that 22 cc's. The post-embolization angiogram, you want to have patency or antegrade flow of your main genicular artery, and even of the second-order branches, and then just trim that haze or that neovascularity or however you want to term it. There is a little bit of, I would argue, a learning curve, and it's a little bit almost unsatisfying when you embolize it because you're giving so little, especially compared to, let's say, a fibroid embolization. It really takes a very small amount to get the job done.

The challenge is that if you over-embolize it, you can cause complications and the most glaring ones I've seen or heard of are skin necrosis. In rare cases, we haven't had any, but I have heard of people having some really severe focal skin necrosis. That's the main thing to worry about.

[Dr. Venkatesh Krishnasamy]
Os, I know you're using resorbables, so same question for Imipenem and Lipiodol joint. Imipenem, what's your endpoint deletion volume injected? Same with Lipi joint.

[Dr. Siddharth Padia]
Yes, so for Lipi joint, basically, we've talked about this probably in multiple conferences, but it's a three-to-one emulsion of Lipiodol with Opti-Ray contrast. It basically takes 6 cc's of Lipiodol and then put it with 2 cc's of Opti-Ray. Then basically it's, and again, this is why I have liked this technique is it's much more objective and it's much more in line with what Sid was saying, like a UFE. You basically just inject it until it's completely static. If anything, you inject it until it starts refluxing down other branches and then you know you're done. When you do that, it ends up being roughly 0.5 cc's, with a 95% confidence interval between 0.3 and 1 cc. That's typically what I do. Rarely do I ever give more than three total cc's in a case.

The one thing I like about that, Os, is and I've never used it, and I'm not going to argue against you this time, it's reproducible. You can teach somebody else to do it. You can just say, go to stasis. That's it. Everybody knows what that means. This challenge of what I said is, keep the first and second order branch. Everyone interprets that a little bit differently. We all know that.

[Dr. Venkatesh Krishnasamy]
Yes, that's a challenge.

[Dr. Siddharth Padia]
It's not quantitative. We don't have a great way to quantitate angiography in terms of flow. You can't put a number on how good the flow is. People have tried. It's just always fell through. Your idea of using Lipiodol and saying, look, just go to stasis. That's it. You could tell that to 10 people and all 10 people will understand what you're talking about.

[Dr. Osman Ahmed]
That's what I found to be the most appealing about it, honestly, compared to what you said. Because I think pruning is like, A, it's incredibly subjective, and then B, it's hard to get it. You give an extra 0.2 cc's, all of a sudden, you're static. You're like, "Oh, crap." It's very counterintuitive. Like you said, it's so hard to convince your brain to say less is more, as an interventionist. Whereas Lipiodol or these temporaries like Imipenem, you can go to just stasis and just be like, "All right, I'm done."

[Dr. Venkatesh Krishnasamy]
How do you make sure Imipenem lasts?

[Dr. Osman Ahmed]
I don't use Imipenem. I know it's available and I've seen people use it. It basically comes in a powder form and you inject it. You take 10 cc's, and you inject it into the vial and basically shake it vigorously. Then you essentially drop aliquots of it, as needed. Talking to Dr. Okuno, like one of the main things he also always emphasizes, you have to constantly shake it, especially right before you give it, because it will fall out of solution very fast.

[Dr. Venkatesh Krishnasamy]
Okay, good to know. It's interesting. I think a lot of people in the US probably don't have access to it, just being a controlled antibiotic. Incidentally, I'm just putting it on formulary just to have it available for some of my patients as we get ready to start having resorables and hopefully the relatively near future. That's super helpful. Where is Imipenem going to fall into the algorithm? Let's say, the six embolics that Sid said come to market, I'm just saying six, but where's Imipenem going to fall in the algorithm? Obviously, it'll be different in the US versus worldwide. What do you think?

[Dr. Osman Ahmed]
I think US, I don't see it happening if the resorbables come to market and get approval. It's logistically hard to get. The antibiotic component of it makes no logical sense to use. You're using it for the crystalline part. If you're using it for the crystalline part, you might as well just go with an FDA-approved resorbable embolic that you're not going to have some infectious disease doctor going, "I'm sorry, you're using this Cadillac broad-spectrum antibiotic for what? I'm sorry, Dr. Ahmed, are you kidding me? I've never heard of this."

[Dr. Venkatesh Krishnasamy]
Good point.

[Dr. Osman Ahmed]
Then you have to go with an email and battle with him and email him all the papers, which he's not going to read. Then he's going to say, "No, you're still rejected for your Imipenem." I think just logistics is going to be way easier if you just get resorbables.

[Dr. Venkatesh Krishnasamy]
However, will this be the more cost-effective route for our OBL colleagues, to use resorables?

[Dr. Osman Ahmed]
That's the thing. The elephant in the room is Imipenem is dirt cheap. It is like, I think, $20 a vial. It's like the equivalent of the Nester Coil argument in embolization. It's like, you're never going to be cheaper than it. If you take it out of the argument, then everything else you can compare and say, well, this is more cost-effective, but nothing's going to ever come close to it. I think the only thing that will probably hinder its adoption in the OBL space, because it is available there, you don't have to deal with an ID doc, you can do whatever you want, obviously out there, is if there will be regulatory laws that come out and basically say, well, Imipenem is not approved because of antibiotic resistance or whatever or whatnot.

OBLs are conscious of that and say, well, I don't want to get sued or, use something off-label when I can use something off-label and not worry about lawsuits and things like that. Good points.