Dr. Andrey Espinoza sat down with distinguished vascular surgeon and deep venous authority, Jose Almeida, to meticulously discuss all things venous stenting.
Dr. Andrey Espinoza: Dr. Almeida, I had the pleasure of interacting with you on a professional level some time ago. You took care of a patient I sent down from New Jersey who had an extremely complex inferior vena cava (IVC) filter and iliocaval occlusion that was chronic. You did a very complex intervention on him. The patient had been suffering for years, and reading your operative note, it sounded like it took about 12 hours to complete the procedure. Thank you for that ridiculously impressive intervention; he is still doing remarkably well three or four years later.
Dr. Jose Almeida: Great, great.
Dr. Andrey Espinoza: You've grown through this field as it's emerged. You've been involved pretty much since day one. You can speak to everything from the Z-stent and Wallstent days all the way to today. Can you give us an idea of the historical journey of venous intervention?
Dr. Jose Almeida: I'm a fellowship trained vascular surgeon. I did my general surgery down here at University of Miami at Jackson, and I went to Mizzou, University of Missouri, for my fellowship from '96 to '98. During my second clinical year, one of the responsibilities of the clinical fellow was to welcome one of the grand round speakers who, in this case, was Bob Kistner. He is a true gentleman and is very well- known in our space for the Kistner valvuloplasty or deep vein valve repair; that put him on the map and made him the venous guru of his day. We all go into vascular fellowship to do aortas and thoracoabdominal aneurysms and all this sexy stuff. No one wants to bother with veins. After preparing for a talk on venous disease that I had to give in front of the whole department, including the guest speaker, Bob Kistner, I saw these great venous procedures and that kind of initiated things for me.
Then I came back to Miami. There were no vascular groups. I was the vascular guy in a general surgery group, but I didn't want to do general surgery, so I went solo. I was doing solo vascular for the first five years out, covering eight hospitals by myself, 24/7, 365, and obviously, after about five years, I just got burned out and became that typical irritable vascular surgeon. I needed to figure out how to make some changes. That's when office-based venous surgery became attractive to me. It started with in-office vein stripping. In '99, radiofrequency ablation came out. I did one case, and that was it. I knew that was where I was going, and so I weaned off of arterial. I did my last aortic aneurysm in '03.
The start of the endovenous revolution, I would say, was around 1999 with endovenous thermal ablation for superficial venous disease, and it started carrying over to the deep space with Drs. Seshadri Raju and Peter Neglén doing iliocaval stenting, probably around 2000–2001. Then I went out to visit Drs. Raju and Neglén in Mississippi in about '08, '09, and that's when I started endovascular stenting in the hospital and now in my office. That's how it all started. Now, obviously, you see the stent evolution and acute thrombus evolution with the new devices, moving away from lytics to thrombectomy catheters.
Venous open surgery is really relegated for when you can't do anything else. With vena cava work, open surgery now is really only for malignant disease, and venous bypasses have gone by the wayside.
Maybe the endovenectomy in the groin would still be open, but it's pretty much all endo at this point. We pushed the envelope with tough cases to try and help develop the deep venous space further.
Dr. Andrey Espinoza: Listening to someone who has grown up in the field is really exciting. Let's talk about those early days. What balloons were available? What was your early experience with the Wallstent and the Z-stent like?
Dr. Jose Almeida: I did an open surgery fellowship, and when I came back to Miami, I was in a unique situation. I'm sure you've heard of the interventional radiologist Barry Katzen. I was on his team, and that's when endovascular on the arterial side was developing. These were endovascular repair (EVAR) with homemade devices, so we were doing things homemade at Miami Cardiac and Vascular Institute around 1998, and then at the University of Miami-Jackson Memorial Hospital. I was also on staff there, and we were doing homemade endografts. For example, one thoracic abdominal aneurysm we did years ago was using an open technique in the infrarenal aorta and then a metal urologic tube going up the thoracic aorta. We sewed Z-stents under the ends of Dacron grafts that were crimped into this metal tube and then deployed in the thoracic aorta.
That's the kind of stuff we were doing. I got familiarized with tinkering and doing things on the back table off- label. When it came time to put an off-label Wallstent in an iliac vein, that was standard-of-care for me.
So as far as iliac vein stenting, it was the off-label Wallstent, of course popularized by Raju and Neglén. But this has limitations. A braided Elgiloy stent, in that the radial force is not strong at the end, so they kind of taper down. For that reason, we had to push it into the vena cava, and then we saw that about 10 to 20% of cases five to 10 years out started to get some contralateral jailing and other problems. Then came the Z-stent composite graft, where you push a Z-stent more into the infrarenal cava, because the large strut interstices are better set up for contralateral flow. You do that in composite with a Wallstent. You solve the end radial force problem of the Wallstent by buttressing it with a Z-stent. Of course, now we have laser-cut nitinol, which has good, chronic outward force at the ends and throughout the stent length. Then we come to the issues of flexibility versus stiffness. Thus there was a trade-off in engineering. You trade one for the other, open-cell versus closed-cell, and now we have the four approved stents on the market, of which two are in recall.
Dr. Andrey Espinoza: Before we move into the specifics of the stent, can you give the
audience an idea of what the Almeida algorithm of patient selection is? I would suggest that patient selection drives everything. Select the appropriate patients, and the patients do well. Select poorly, and the patients do poorly.
Dr. Jose Almeida: I'm glad you used that word, appropriate, because appropriateness, as you know, is a hot issue in the field. For me, we use ultrasound above the inguinal ligament and below. We've had a good collaboration with a well-known registered vascular technologist (RVT) named Jan Sloves in New York, and he's really taken it upon himself to take this to the next level. He's been down here several times and trained my techs to the point where we now feel very comfortable looking at the retroperitoneum of a trans-abdominal ultrasound and getting a good look at the vena cava and iliac veins, measuring them with ultrasound calipers and getting our waveforms with pulse doppler. We have eliminated cross-sectional imaging from the algorithm unless it's something extraordinary.
I always emphasize, look at the leg. This is the type of patient that goes on the table. It's not a normal leg. Not a 40-year-old with spider veins.
I don't care what the ultrasound shows. If she's got a normal leg with spider veins, she doesn't belong on the OR table, period. I don't care if the iliac vein is two millimeters. It's a symptom- driven algorithm, buttressed by imaging.
Non-thrombotics I tend to do in the office. It's very predictable. It's going to take me 30 minutes or so under a local anesthesia and conscious sedation. I pretty much know it's going to be a common iliac lesion. It's going to be a 16 x 120mm laser-cut nitinol stent, more or less. Maybe a 14 in a smaller person, but the 16 x 120 is my workhorse. I’m going to give a little heparin and anti-platelet therapy afterwards. Non-thrombotics are very predictable.
Post-thrombotics are a different animal. I do these on Fridays at the university hospital. I pick one case and plan on spending the entire day there. For example, the patient that you send down. Most of these are complex vena cava iliac vein chronic occlusions. It could be from an occluded vena cava filter. A lot of them have previously placed stents elsewhere that other people have tried to open unsuccessfully, and they come to me to reopen these things. They're more difficult. I don't know how long it's going to take me. Under general anesthesia with a foley catheter, and I've got all the toys on the shelf, and I start pulling all kinds of wires, balloons, stents, Colapinto needles for sharper re-cannalization. I have a cone-beam CT, so if I need an on-table CAT scan, I'll do that.
It's a different animal, and of course, those are all going to be anti-coagulated for life afterward. We've gone to Lovenox for one-month post-procedure to transition to a direct-acting oral anticoagulant (DOAC). I like Eliquis because of the BID dosing. That's pretty much the algorithm, but it's definitely symptom-driven, and then non-thrombotic versus post- thrombotic will kind of dictate the complexity of the disease and the site of service.
Dr. Andrey Espinoza: Let's talk a little bit about the stents. We've moved from commercially available Z-stents to Wallstents to these laser-cut designs that you can deploy more elegantly and exactly. Talk a little bit about the differences, if any, between the types of stents you select for a post-thrombotic patient versus a non-thrombotic vein lesion (NIVL). How do you select a device in the 21st century with all these options available to you now?
Dr. Jose Almeida: I don't have all the answers there, because there is no long-term follow-up data. We're just getting a feel for the nuances of each stent.
In general, I've moved toward laser-cut nitinol. Now that Venovo and VICI are on pause, the Abre and the Cook are the ones that are available.
I like the Abre in the sense that there are more sizes and lengths available. A patient's going to need an 18 every now and then, and I like the long lengths, especially for post-thrombotic disease. One of the limitations with the Wallstent was the 90cm length, and in non-thrombotics and post-thrombotics, if you start placing these, you'll realize that the end of a 90mm stent lands at the sacroiliac (SI) joint. The significance of the SI is that's where the pelvis turns, and if we're in the sitting position, that stent is going to be at 90-degree angle at the SI joint. With the Wallstent, you'd have to put another stent, and the overlap site always seemed to be right at the SI joint, and you get shelving of the stent and in-stent restenosis, and five, 10 years out, we start seeing the problems.
Then, if you only leave a 90 there, now you've got this migration issue that we've heard about with the laser-cut nitinols. It's stiffness; it's poor sizing. My sense is that it's operator dependent and poor sizing, but that's the way I feel about it.
The braided Elgiloy Wallstent—even though you traditionally would put in an 18 doesn't mean that it expands to 18 when it's placed. It conforms to the vessel wall, so when you look with intravascular ultrasound (IVUS) afterward or do your measurements, you
can have an 18mm Wallstent that only gets you 180mm2 area, so clearly, it's not fully expanded to 18mm, whereas a laser-cut nitinol is one-to-one.
If you put a 16, it's going to be 16. Now, if you're going to place a 14, it's going to be 14 on your post-IVUS and diameter measurements. For that reason, you don't need to oversize much with laser-cut nitinol, but you do need to make sure that it's going to oppose the vein wall so it doesn't migrate. One of the things is diameter, and the other one is length, so I really like the 120 for non-thrombotic, or even longer if need be for post-thrombotic, because it goes all the way through the SI joint, and you've got a lot of stent material interacting with the vein wall for incorporation later, and that's not going to migrate.
In contrast to arterial disease, we're always tempted to translate arterial concepts to venous. It doesn't really apply well. In venous disease, you need to cover the disease with metal, unlike arterial disease. If you're leaving disease behind, compressed areas or post-thrombotic areas are probably not going to do well. As you alluded to, in post-thrombotic disease, the stent patency—I don't think it's the stent. It’s related more to the inflow or the outflow and the underlying disease.
For me, I like laser-cut nitinol. That's my go-to right now. Venovo and Abre have the widest selection of sizes. They're both open cell. I don't know what open-cell versus closed-cell really means clinically right now, except that closed is probably a little stiffer and maybe doesn't conform to the vessel as well. The Cook is a little soft, and it only goes up to a 16mm diameter, same as the VICI, which, there's some limitations in length, but they're okay also.
Z-stents I will use in the vena cava still, especially when we remove filters, and we have to cover a renal or hepatic vein. I prefer a Z-stent with the bigger interstices. Of course, they come in 25mm, which most vena cavas need, and most of our iliac stents don't get up to 25, so I like it for that.
Having said that, in a completely occluded vena cava chronically, those hepatic and renal inflow vessels are occluded, and the patient's already developed collaterals to drain the viscera, so you can cover that with Wallstents. Raju showed this in a paper, Stenting atria to caval confluence, that you don't get hepatic or renal ischemia afterwards, because they've already got built-in collaterals to those organs, and the primary drainage is not the occluded vena cava.
Wallstents are still okay in that situation. I just tend to feel better if I see a renal vein lighting up on venogram. I want to preserve it and cross it with a Z-stent instead of a Wallstent.
Dr. Andrey Espinoza: You mentioned a little bit about your go-to laser-cut now, with the 16mm being the default. Again, a little bit different from what you’ve done in the past, and there are some discrepancies in sizing and cross-sectional area. Can you comment a little bit on that with regards to the cross-sectional area? With the 16mm, you're probably not going to get a 200mm2 result, is that true? How do you apply the aspect ratios?
Dr. Jose Almeida: Actually, the 16 millimeter does get you to 200mm2. What's interesting is, when we do our post-IVUS on the 16s, we're always over 200 now. When we're putting in 18mm Wallstents, we're barely reaching 200 often. So I like those novel numbers that Raju put out. A 16mm common iliac translates into 200mm2. A 14mm external iliac translates into 150mm2, and a 12mm common femoral vein translates into 125mm2. I use that as my reference vessel, instead of using adjacent vein or normal adjacent vein, which, of course, on post- thrombotic disease, the adjacent vein can be small, and in non-thrombotic disease, you can have a pre- stenotic dilatation and the adjacent vein's aneurysmal. I like the numbers that Raju put out there. That's kind of what I go to. If I have a 60mm2 stenosis of the common iliac vein, I'm going to put that against 200mm2 to calculate the percent stenosis.
Now, again, it's not so much the number. I would feel really uncomfortable putting a stent in something that's less than 50% stenosis, but even at 50%, I get a little squirrely. Knowing that, I make sure that the legs on the table have advanced disease. I'm there to do an intervention, and if it's 50%, a stent's going in. If it's an abnormal ankle, and if I've got a number of 50% or above, they're getting a stent. I think they'll benefit. Their venous hypertension will improve. But if it were 30, 40%, I'm not going to stent it, no matter what the leg looks like. That's just my own little guideline.
Dr. Andrey Espinoza: That makes a lot of sense. You'd mentioned the closed-cell and open-cell designs. That's the end-all debate in just about every vascular territory. We've always found that it probably means absolutely nothing at the end of the day. It's the technique and the way you deploy the stent that really matters. To that point, does oval versus ellipse matter? That's what these new stents are designed for, to give you that benefit.
Dr. Jose Almeida: In theory, hemodynamically, with f luid physics, an aspect ratio of one, meaning a perfect circle, has a better f low characteristic than an ellipse. That's the idea between chronic outward force, radial force and crush resistance on the new stents.
In non-thrombotic, we're more interested in crush- resistance for the two compression points—artery and the lumbar spine. We want crush-resistance, whereas in a post-thrombotic, we want chronic outward force to expand against the circumferential fibrotic disease in a post-thrombotic vein. Even these nitinol stents that are purported to have four times more chronic outward force than a braided Elgiloy, when we place them underneath a tight iliac lesion or a May-Thurner lesion underneath the artery, we don't get a perfect circle. It's close to a circle, but it's not.
Does it mean anything? I don't know. Probably not. They seem to stay patent, but the aspect ratio issue, that's going to continue to evolve as to whether the ellipse or the perfect circle is best.
Now, we know that veins are capacitance vessels, and when they're empty, they're dumbbell-shaped.
A dumbbell-shaped configuration has a higher resistance, and as we fill our venous volume, the vein takes on a more circular pattern. This is called the tube law, where the pressure really starts to build after the perfect circle is formed, with filling the vein called the “bending regimen” of the tube law.
The point is that many of our veins are collapsible vessels, and it's about the boundary conditions. For example, the vena cava is in the belly, and it's in a chamber. It travels in a chamber, which acts like strong resistor. Raju's written about this, and when you look with IVUS, the vena cava is not a perfect circle. It's an ellipse, and you can see it with respiration going in and out.
If you're going to say that's compressed, you're going to be mistreating a lot of patients. That's just the way the vena cava is. The muscular layer of veins decreases, so our leg veins are much more muscular and round than our more central veins.
The iliac veins are unique in that they're a cylindrical muscle but they're non-valved, except 24% of iliac veins will have one valve, and they don't reflux. They're round on IVUS unless they're compressed. There's a lot of really unique features about the vascular tree, the hemodynamics and the boundary conditions and the shape that we don't understand, and we're kind of grossly putting in this metal device that increases the stress on the wall to open this thing and hoping that it's non-thrombogenic and decreases peripheral venous resistance and that it benefits the patients. We all know. We've all seen that 30% of asymptomatic people have compressed iliac veins.
I personally also have May-Thurner syndrome (MTS) on the left. I saw it on cross-sectional imaging when I blew a lumbar disc. I've managed with a stocking. I don't want a stent unless I need one.
You'll see on ultrasounds veins that are two millimeters by Duplex imaging, and the patient has a normal leg. Then you've got somebody else with their leg blown up, clearly asymmetric from the other side, and the common iliac vein is 12, 13mm. Their collateral, their ability to compensate, is decreased, and that's the other variable that we don't understand. Limited outflow resistance. Andrew Nicholaides has shown this with air plethysmography (APG) of increased outflow resistance. How does that correlate with IVUS in quantifiable numbers?
At the end of the day, we go back to the same thing. It's clinical symptoms, so some people who develop adequate collaterals around a lesion do not need a stent. They will not benefit from a stent, even though the iliac vein is tight, even though, knowing that in order to replicate the flow in a 16mm common iliac vein, you would need about 16 saphenous veins or 256 four millimeter collaterals, so the conductance on fluid physics doesn't always jive with what you see clinically. That's the part of the art of medicine or just learning to individualize the patients because nothing's ever cut in stone in medicine, as we all know.
Dr. Andrey Espinoza: You're going to inspire a lot of people to go back and remind themselves about the importance of understanding the basic fundamentals of hemodynamics and how the body works, understanding why we do what we do, and appreciating the fact that most people's issues are not resolved in a procedural or operating room. Most can be managed clinically, but there are clearly people that need help.
To your point: the IVC. I've seen a lot of operators, when they start doing intravascular ultrasound, struggle with the level of temptation to do something about the compressed inferior vena cava, not appreciating respiratory variation, volume status, things of this nature.
That's where this sort of education becomes so widely important, because they need to hear that. Most IVCs do not need a stent, but some people are very tempted, because they think it's compressed when in reality it's just physiology.
Talk to us a little bit about two specific things. One—medical management for the patient post-intervention. You had alluded to the use of low molecular weight heparin followed by the DOAC, which, I think in the past, you had used rivaroxaban. Now it sounds like you've morphed into apixaban. Also, how do you follow these people surveillance-wise, looking to maintain patency? What are your thresholds of re-intervention? Are they clinical driven or are they ultrasound driven?
Dr. Jose Almeida: For non-thrombotics, baby aspirin should be adequate. Post-thrombotics are going to get a lifelong DOAC—as you said, apixaban. If it's a difficult re-cannalization, and we cause a lot of balloon trauma and inflammation, we all think that enoxaparin has an anti- inflammatory effect, that it blocks more factors than a specific factor-10 blocker, so I think a lot of us have gone towards this bridge of enoxaparin after a difficult post-thrombotic re-cannalization for a month or so, to let the body adapt to the new stent and “endothelialize” it, if that's the right word. Whatever the body does to reline it, whether it's fibrin or something else. Allow that process, that thrombogenic period. Patients will do better with enoxaparin, we're seeing, and then bridging to a DOAC. I like apixaban better than rivaroxaban for stent management.
Dr. Andrey Espinoza: Is that lifelong?
Dr. Jose Almeida: Yes, lifelong. Now, the one thing I'll say is that maybe if somebody's done well after a couple of years, I'll do the half-dose. I'll go for five milligrams BID to 2.5 BID, but whenever I take them off completely, I just regret it. So they always know that going in.
When you see somebody initially, you'll see some of these post-thrombotic patients and their iliac vein is occluded, and their leg looks fine, and part of the conversation is, "How miserable are you?" That's my bottom line—the misery index, I call it. "On a scale of one to 10, how miserable are you?” If it's a nine, we'll do something. If it's a three, you're in stockings. Just note that, if we put a stent in you, it's lifelong anticoagulation. That's in the algorithm. If you had your DVT 10 years ago, and your vein has been occluded for years, and you've been off anti-coagulation, and you're doing okay, and you're here because of possible intervention, just know, lifelong anti-coagulation and bleeding risk. Non-negotiable. So they know that upfront.
So that's really it. Non-thrombotic is aspirin; post-thrombotic is a DOAC. I hate Coumadin. There are good data out there that 30% of the time, Coumadin therapy is not therapeutic, so the patient is always bouncing around. And then the leafy vegetable Vit K problem and the lab draw, and we all know Coumadin is not a good alternative with the modern choices.
Dr. Andrey Espinoza: And your Duplex surveillance post-intervention?
Dr. Jose Almeida: As far as surveillance, I like to do it. We always put a stitch in the wound in the access site. We don't use any of these closure devices. I put in a stitch and a compression wrap. We like to bring them back in a day or two to get the stitch out and do the Duplex. If they're open in one or two days, then they're likely going to do well. These stents either run or they don't.
Then, more for our own data and for Vascular Quality Initiative (VQI) data, we like the one-month, six-month, and annual follow-up. Then, yeah, we'll see a lot of in- stent restenosis, and I think a lot of that was just the size mismatch problem, where the body just accommodates or remodels to a normal flow channel with a transition from smaller to larger going centrally, and just all the stent step-offs that occur during an implant.
We'll see in-stent restenosis (ISR), and then it's about symptoms. We can see a lot of ISR in Duplex. If you're asymptomatic, we'll just continue to follow that. Again, they've compensated for it, and they're doing okay. We're not going to kick a winning horse. But if they're starting to swell up again and are having symptoms, we tend to do these in the office and put an IVUS catheter up and measure and offer hyperinflation balloon treatment, then just squeeze what ISR we can, get more luminal gain, and usually, that's okay.
The ISR people that get ballooned are the ones that seem to need to get re-ballooned in the future. The ones that never get ballooned are the ones that never need ISR in the future. So they seem to fall into one of those two camps, the aggressive and non-aggressive ISR.
It doesn't seem to be related (or not yet anyway) to the stent, open-cell versus closed-cell or braided. I haven't really parceled that out yet. It's just, some people form it and others don't.
Dr. Andrey Espinoza: Looking forward to the future, pie in the sky, what's missing
technologically? Where is the clinical research going? How do we manage a stent that then develops a chronic total occlusion, as those become really challenging cases? What tools do we have or not have right now? In your perfect world, if you could script the next five or 10 years, what would that look like?
Dr. Jose Almeida: This new iteration of stents is a plus compared to what we had, because again, the radial force at the ends, the lack of foreshortening on deployment, some more predictable proximal or distal landing, the chronic outward force.
So I think the stents have made a leap forward already from where we were to where we are. Where we're really lacking are two places, in my view. One is thrombus age. We can't really predict thrombus age well, so, as we all know, all of these new thrombectomy-type thrombus-management devices all pretty much do well if thrombus age is less than two weeks, and they all start to fail if thrombus age is older than two weeks.
It's always hard to predict. When the patient comes in, we have this little adage—just feel free to add a week of thrombus age to what the patient tells you. They tell you, "Yeah, my leg started swelling a week ago,” and they showed up in the ER four days ago. Well, you think, "Okay, four-day-old DVT. No, that's probably a 14-day old DVT." Steve Black in the UK has done some work on MRI imaging of thrombus age. There are other people working on this too.
That certainly will help the thrombus-management space, and then just the biology of venous disease and hemodynamics. Part of the endovascular revolution has been, up until now, just rapid device development and enthusiasm for new devices, so the clinical trials tend to be industry-sponsored safety and efficacy trials to get their device approved by the FDA. Our literature is laden with these industry trials. What about the biology of the disease? That's what's gotten lost.
We've actually got a book coming out. It should be out by the first quarter of 2022. Dr. Raju called a few of us to do this thing. It's called Hemodynamics for Surgeons, originally written by Dave Sumner and Gene Strandness. It's this hemodynamics book that all of us boomers and older generation docs refer to, and it hasn't had a second edition since '75. We're doing this venous edition of Hemodynamics, myself, Ghassan Kassab, a biomedical engineer in California, and Fedor Lurie. We are the three editors, and Dr. Raju has helped oversee everything. We've got the book pretty much in the final stages. We'll be doing some videos to help educate on hemodynamics. It's really cool stuff. I mean, it's next-level, and to help us all understand some of these things we've been discussing this morning.
Back to your point—the biology of venous disease, fluid dynamics, the interaction of biomaterials with biologic tissues like stent on stent wall, thrombogenicity, wall stress, circumferential stress, axial stress. All these things that we don't know, here, really have an effect. All the cytokines and biologic markers that go into effect with inflammation, how to mitigate them, and where to mitigate them with new drugs and biologics. All of that stuff is just wide open for the future, so we're early, an early stage in that sense.
Dr. Andrey Espinoza: Bravo. It's amazing what we've been able to get away with doing without understanding all of that. Fantastic. Well, I'm going to stop there, out of respect for your time. I could spend another hour picking your brain, but I am sure you have work to do. Again, I’m humbled, Dr. Almeida, to have a few minutes of your time. Thank you for sharing such insight into this evolving space.
Dr. Jose Almeida: All right, my pleasure. I enjoyed meeting you.
Dr. Jose Almeida is chair of the International Vein Congress being held in Miami May 16–20, 2022 (https://ivcmiami.com). He is also co-chair of the venous program of VEITHsymposium being held in Orlando November 16–20, 2021 (https://www.veithsymposium.org)