Podcast transcript
Can we talk first about what critical limb ischemia is, what the factors are that contribute to its development and what population is typically affected by this condition?
Critical limb ischemia is at the end of a spectrum of a disease called peripheral arterial disease or PAD. Peripheral arterial disease is basically when there's plaque buildup within the arteries outside of the heart, in your arms, in your legs, even in your neck, and that causes significant narrowing. When we talk about PAD in general, most people are talking about your lower extremities or your legs. PAD itself can be presenting sometimes with no symptoms or many patients that we see have problems walking.
And when you get to critical limb ischemia, or it's also referred to more commonly nowadays as CLTI (chronic limb-threatening ischemia), what that means is, to me, the end stage of PAD. And what that means is that you have pain when you're just sitting around at rest. Or you may have ulcers in your feet and parts of your legs that won't heal because of a lack of blood flow. And that's because the blood vessels are either so narrowed or blocked or they've changed so much over time due to underlying disease factors that they no longer supply the amount of blood flow needed to either relieve your pain at rest or to heal a wound, which could then result in major amputation. Most of the patients with PAD and CLI, CLTI have diabetes, they have a history of smoking, they have kidney failure, sometimes genetics, high cholesterol and blood pressure. It can be any or all of these together, which cause patients to have PAD and then sometimes progress to CLI, CLTI.
Limb preservation is a passion of yours, but really the chief problem with amputation and avoiding it starts with several lifestyle factors. Can you elaborate on what some of those precursors are to developing peripheral arterial disease in the first place?
PAD and CLI, like we briefly mentioned, has to do typically with diabetes, kidney failure, high cholesterol, hypertension. These are all chronic diseases that affect many parts of the body for patients. The saddest part about PAD and CLI is that this is kind of a late-stage manifestation of all this. If we did a better job with preventative medicine, which is very difficult to do with our patients in our population and in America. It's very hard to get them on the right track early on. If you look at our obesity epidemic, our lifestyles, the health habits and the diets of everybody, I think it's really hard. So we're playing this catch-up game at the end trying to prevent them from dying.
The stats are pretty bad. If you look at it worldwide alone, PAD affects about 200 million patients. In the U.S. alone, it's estimated somewhere around 10 to 12 to 15 million patients. It's a significant cost. Somewhere between $80 and $300 billion is the cost of the U.S. healthcare system. Diabetic foot ulcers actually is the single highest cost of the entire medical system. If you think about it from a numbers’ perspective statistics, it's about 50 percent of the major amputations that occur every year, and that is about 100,000 major amputations a year. A major amputation means anything above the ankle. So when they say a BKA or AKA, that's considered major amputation. The patient can no longer walk on their own. Because they can't walk on their own, several other comorbidities kick in. They become more sedentary because of things they have to deal with, prosthesis issues and things like that. So, 50 percent of the major amputations are related to diabetes and PAD. And a really sad fact is that less than 50 percent of the major amputations have had a proper angiogram or workup by a proper specialist.
The risk factors that would've helped us prevent getting here would've been improving diabetic management, preventing diabetes. It's sad. I had an 18-year-old patient about last year who had diabetes and CLI, which is something we should not be seeing. Typically, PAD and CLI are stuff that we see in patients well over 50 years old, in that 60-to-80-year range is when we're seeing most of these patients. But we're starting to see younger and younger patients. I had to do a complex procedure on a 38-year-old male to save his leg, and that's not something we should be seeing. So it's lifestyle modification, smoking cessation, cholesterol management, high blood pressure management. These are all things that are chronic diseases that all of us in medicine need to help our primary care doctors and our patient population do a better job of preventing them from getting to these stages of PAD.
One thing I thought that was particularly interesting in your work is the angle that you've taken to think of peripheral arterial disease as the same way that we think of cancer.
I've been saying that for a while in many different formats and platforms because I think the only way to make things stick in physicians’ and even the patient population's mind is when you use words that raise an alarm or flag in their head. And cancer, I think in the medical community and in society, is the biggest fear for everybody. There are so many different societies and marketing and education platforms that use the different cancers that have done such a wonderful job. I'm not trying to belittle cancer by making this term arterial cancer, but I'm trying to use it to raise the awareness because it kills more people than most of all the cancers in which we are well-versed in the community and the healthcare system.
CLI has a mortality rate, without amputation, of about 50 to 60 percent at five years. Now, that's higher than pretty much every single cancer that we all hear about other than maybe lung and pancreatic. But it's higher than breast cancer, colon cancer and several other cancers. And again, that's not to belittle it, but that's the reality of statistics. Yet most of us in hospitals and clinics and society don't put that much emphasis on doing things to prevent getting there, and also to prevent patients who have options for revascularization or surgery or something else to save their legs. That's kind of why I use that terminology to try to get awareness.
I think it does have more impact when I tell a patient in clinic, "This is how I think about, and that CLI, CLTI is kind of the terminal stages of cancer that we want to get you back into remission somehow." It really puts something into their head, to the patient and their families and also several other clinicians that I talked to. I think it's just a way of trying to get people to understand the gravity of it.
You’re sort of reformatting the problem in a way that makes sense on a different level.
Giving people statistics and terms and lectures doesn't stick as well. When you tell them impactful with numbers, pictures and terms that stick with them, I think that's the only way we get awareness to really start becoming viral.
Revascularization is a way that you can help patients avoid amputation. Can you give some historical perspective on how this approach has altered the way clinicians treat peripheral arterial disease?
A patient with peripheral arterial disease that progresses to a point where they need some type of intervention, whether it's surgical with a bypass or with endovascular, meaning from within the vessel, which is what our specialty and several others focus on, primarily it's avoiding an open surgery if possible. When you get to that stage, revascularization used to be, decades ago, just bypasses. And then in the '60s, Dr. Dotter, who's one of the godfathers of IR (interventional radiology), did an endovascular procedure to open and fix the narrowing of the artery in the thigh, the SFA. That was the first ever intervention done for limb preservation. The first CLI patient that was treated with it actually did save that foot.
Since then, over the last 10, 15 years, we've seen kind of a spiraling, exponential growth of revascularization strategies, techniques, approaches, whether it’s more advanced bypasses if you have a good vein in your body, if you have sometimes prosthetics. But it’s more on the endovascular side, which is what we specialize in, going further and further down the leg to open arteries that have never been able to be opened before. That involves techniques and newer tools and approaches that we never did before, such as, up until about 10 years ago, nobody was sticking the foot in the artery to come back up the artery that couldn't be passed before. That's called a safari or retrograde access, pedal access. That was never done until 10, 15 years ago. And since then, it's become much more used and applied to patients that were previously told, "You can't do anything here." Some surgeons are doing farther and farther bypasses in a small select number of patients.
So revascularization has changed from going from just the aorta iliacs to below the groin up to the knee, and then from the knee to the ankle. Nowadays, half my procedures are spending time below the ankle and doing things to open arteries that are down to 1 millimeter or 2 millimeters. And by doing these things, sometimes we can save a patient from a major amputation. We can keep them at a toe amp, a TMA, and some other operations that keep their ankle joint to keep them walking. And if we can do that, that's a success. It's not going to be for every patient, but it's definitely changed the game of preventing major amputations when appropriate.
Can you go into some more detail about how you use revascularization with CLTI specifically?
Most of the patients with CLTI, CLI have tibial disease. The majority of them will have issues with the three arteries below the knee, and then often the arteries in the foot. So, the goal of CLTI — primarily when I'm talking about wound-healing to prevent a major amputation — is we try to get as much blood flow to that wound, whether it's on your toe, on the top of your foot or your heel. Most patients, including many of my patients, have none of those tibial vessels intact. So quite often I have to spend time going from above and from the foot trying to tunnel through blocked arteries and use balloons and atherectomy devices and whatever I have to do to restore direct inline flow so that at the end of the procedure, hopefully, they have blood coming from their heart all the way to their toes or wherever their wound is.
Now, some patients with diabetes and renal failure, some of their arteries in their foot no longer look like normal arteries. They become microvascular disease. They become little tiny wisps of vessels. The problem with that is you have no surgical options to bypass because you need a target. And even from an endovascular approach, you may not be able to target anything because those normal arteries are gone completely. So the success of an endovascular surgical bypass requires that you have some target in the foot to connect to. In these patients now, we've innovated and adapted techniques of connecting arteries to veins called deep vein arterialization. That has been a little bit of a game changer, that's still not offered in many places around the country, as a true last option procedure for patients that had no options before. And in recent years, I've been able to save several legs on patients that were sent as second and third opinions, and that's part of the point of arterial cancer saying second and third opinion.
We've tried to become a second, third opinion center just like cancer is where if someone tells you somewhere there's no options, there are still options such as a DVA, deep vein arterialization, that myself and some of my partners here perform. And we're one of the only centers that does them and have a high success rate of them. It's a growing procedure that does not have a lot of long-term evidence, but this is something for patients where the other option is losing their leg. So far, none of the patients that I've treated have said, "I'd rather lose my leg." So we're pushing the boundaries, we're adapting new techniques. We're coming up with new ways to treat these patients. And we're sharing it globally so that we can all do a better job because we're doing a very dismal job so far.
Below-ankle recanalization interventions have become more critical to durable limb salvage success. What are some of the reasons why outflow can be a challenge for patients with PAD or CLTI and what have you learned?
The biggest problem with outflow is that as you come down the leg, the arteries get smaller and smaller. And when there's calcium buildup like in diabetes, kidney failure or some other diseases that cause it, if you have a big blood flow vessel coming down into nothing or into narrow point, you get kind of a waste. You get a stopgap. It's like you have pipes in your house and you fix one part of the pipe, but there's still nothing coming out of the faucet. It really does nothing to clean out everything until you open it all the way to your faucet. So the faucet won't run full blow until you clear out the whole pipe.
It’s the same thing here. If you fix the arteries in the thigh and even the tibials, but then your pedal circulation, meaning the arteries of your foot below the ankle, then really that blood hits basically a water hammer. It has nowhere to go below the ankle. And all that's going to happen is that blow flow is never going to really reach the foot. That artery is going to thrombose and it's not going to really have any durable effect.
In order to have a successful revascularization, you need to ensure that either the patient already has open or patent outflow in the below-the-ankle vessels or that you find a way to create an outflow. Otherwise, none of that blood flow has anywhere to really go. So that's why it's critically important. We've gone through ways of creating the pedal loop to create an outflow from finding other vessels to target for the blood to go through to kind of divert it, the deep vein arterialization, which provides a completely different system for the outflow. So all these pathways, because the critical importance in that is you need the blood to go somewhere, effectively and continue circulating through that system.
What are some of the ways that you're tackling those challenges with the blood pooling down in the feet?
Number one, if there's some form of a distal artery in the foot such as a dorsalis pedis or a plantar artery, we will stick whatever artery we have to, if it's even slightly visible under ultrasound or fluoroscopy, to reconnect the tibial vessel to that area. Sometimes we've actually stuck the arteries between the first and second toe web space — the first dorsal metatarsal artery — just to find a pathway. That's something that was revolutionized, and it's kind of started in Italy, by Dr. Manzi, a famous IR physician out there. And doing that, doing a pedal loop where we get a wire to go all the way from the plantar and dorsalis pedal circulation to create a multi-channel outflow, we've used atherectomy devices through the pedal loop in the foot with caution because things can happen, like aggressive ballooning. We've done the deep vein arterialization where the artery connects to the vein. And then that requires sometimes some touch-ups and some other procedures that we're learning as we go.
These are all off-the-shelf techniques that have been developed and utilized, and we're trying to use that to spread the knowledge at our meetings and multidisciplinary things that myself and others are part of to try to make others aware that, "Hey, you can push the boundaries here and learn some new things when the other option is not good." There are no stents for below the ankle. So really it's just balloons and atherectomy devices that really we have right now. But in order to use any of that, you have to successfully cross one of these occlusions and connect it to something. The biggest problem we see in the community, and even in-house or elsewhere, is that several people can't get to certain limits of those places and they say there's nothing left to do without offering a second opinion or seeking help. That's why several of these complex patients come to me from outside areas, even out of state, just because they know or they're aware that there's another option that may be available for patients.
You said that RUSH is sort of a second and third opinion center for a lot of these cases. Is there any advice or guidance that you would offer referring providers, or providers in the community, to have them look at CLTI or peripheral arterial disease in a different way, or earlier on, that would help with getting patients treated more quickly?
I think the biggest thing is that it's too much of a burden to ask every physician, especially who's not in the vascular space to say, "Is everything being done? Is this right?" But the question is, I think physicians should always say when they have a patient with PAD or especially CLI or they recognize it as saying, "What are the options for this patient? Are there any other options? What kind of second opinion can we have?" I think there's a little bit of fear to ask questions or ask for, "Are there some other ideas or other thoughts or other people to ask about this?" I think that should be an open policy. We should all be able to have frank discussions and say, "Why is there no other option? Tell me what other options are."
So if someone tells you that this patient has nothing left, unless it's a threatened limb, meaning that the limb is threatening that patient's life, there are still potentially options. I tell physicians and patients that they should always be asking, "What else? Why not? Is there a chance for venous arterialization in this patient? Is there an option for something in the foot? Is there an option for some extreme bypass?" Asking those questions starts creating dialogue and it starts spreading amongst each other. And I think it's not fair to tell the primary care or the endocrinologist or the infectious disease specialist, "Hey, did you consider this?” It should be more, “What other options are there and why not?"
What do you see as the evolution, or the next step or next steps, in CLTI or PAD treatment?
I honestly hope the next steps are that we reduce the number of patients with PAD and reduce the number that have PAD that progress to critical limb ischemia, CLTI. I think we all know that one of the issues with patients with PAD is that a lot of them, in the early stages, get maybe unnecessary surgeries or procedures that may progress them into CLI. So, I think education, prevention and some better guidelines in CMS governance as to how to protect patients and how to prevent them from getting these stages are going to be kind of the first step.
The second step is going to be opening the discussion channels and multidisciplinary approaches for each patient with CLI. And I think we need to do a better job as physicians talking and working together to make sure that each patient is getting the best care and outcomes. I think there's a global push for people to talk and work together, because working in a vacuum only harms the patient. And if we can get rid of some of the political, financial and other personal issues—and I think working together—we can open up all these procedures and ideas and techniques that, honestly, we learn every day, like some new approach or some new idea.
I think the evolution for CLI is not going to be tons of new techniques or innovations. It's going to be working together and early detection, early treatment and early appropriate intervention for these patients so that they don't ever get to the stage of, "Why did this one little toe wound turn into an entire gangrenous black foot?" I think that's going to be where the evolution's going to be. Tools and techniques, because of vessels are so small on the foot, I think getting new tools may be a little bit limited, but adaptation of the techniques that we're doing like we've done before may be the only other thing where it becomes more universal.
