 to Texas Heart Institute educational programs on innovative technologies and techniques. The purpose of these presentations is to inform and educate physicians, allied medical personnel, and general public on the latest advances in cardiovascular medicine. I'm your host. My name is Van Ver Krazier. I'm an international cardiologist at Texas Heart Institute. Our special guest today is Dr. Brianna Costello. She's an international fellow at Texas Heart Institute in Baylor. And Dr. Costello, welcome to this program. Thank you, Dr. Krazier, for having me. It's a pleasure to be here. I look forward to our talk today. The topic is May Turner syndrome or Iliac vein compression syndrome. Dr. Krazier, to start, can you briefly describe the anatomy and the natural history of this syndrome? Well, as we mentioned, this is commonly known as May Turner syndrome. But also it is known as Crockett syndrome and also Iliocable compression syndrome. This syndrome was first described by a German pathologist, Rudolf Ludwig Karl Werho, in 1851. He was a well-known pathologist that identified this particular problem to exist on his evaluation of patients after tragic events. Interesting. So can you describe a little bit more about how he found this syndrome or how this was identified? Was this all post-mortem on autopsy? Right, this was a post-mortem analysis. And really, it didn't become well-known for almost a century after that. Interesting. So in October of 1957, two individuals, again, pathologist May and Turner, described in the Journal of Angiology this particular condition, again repeating the same description that was described by Werho. And they call it Iliac vein compression syndrome. And they identified that the problem occurred because the Iliac artery compressed the Iliac vein. And namely, they described that the right Iliac artery was crossing over the left Iliac vein and causing this compression syndrome, which is described here and shown clearly in their pathological analysis. Dr. Kreiser, it's pretty here just with illustration. You can understand why the left is often more involved compared to the right side. But I know that you've mentioned in the past that the right side can also be involved, the right Iliac vein. Have you seen that frequently or is it pretty uncommon? Of course, the most common scenario is the left Iliac vein compression by the right common Iliac artery. But there are many other scenarios. And actually, May Turner or May and Turner described this clearly. And they found it on 430 cadavers that it occurs somewhere between 22% to 32% of cases. So it's a very, very common occurrence. Not only that it causes compression, but it can also produce a lot of other complex and problematic scenarios, such as thrombosis of the Iliac vein and also a lot of fibrotic changes in scarring and spurring, as is shown here after the thrombosis disappears. So obviously, this is a very, very common problem that is present in a huge number of individuals in the United States as if it occurs in 30% of female population or about 20% of male population, you can imagine that millions of people have this type of a problem. And the consequence is related to this particular problem. So we just touched on this a little bit. The incidence is 20% to 30%. And do you think that we under-diagnose this because not many people are looking for it? Yes, this syndrome is obviously grossly under-diagnosed because the great majority of patients do not have symptoms or they do not have symptoms in their early stages of May Turner syndrome. And the only time when it's really typically diagnosed is when the problems happen, such as thrombosis or a DVT of the lower extremity or problems related to chronic venous inefficiency, which this leads to. So I would say probably no more than maybe 5% of patients with May Turner syndrome develop symptoms at one stage of their life, but when it happens, it could have serious consequences. And obviously, it is very important to identify it early to prevent problems that could happen later. This is particularly of importance in patients that have a hypercoagulable syndrome because they are at higher risk. Also females during pregnancy or individuals that undergo various type of surgeries, particularly abdominal surgery or even lower extremity surgery, they are at significant risk of thrombosis and problems related to DVT and also chronic venous inefficiency. So touching a little bit more on this in pregnancy, in women that are pregnant, do the symptoms usually arise during pregnancy or is it after pregnancy or is it mostly just clot related? For example, do they have significant left lower extremity edema out of proportion to the right when they're pregnant if they have this disorder or is it just post delivery? They have more of the issues. Well, as I mentioned, this compression occurs in more than 25% of health individuals. As I mentioned, it's more common in female population and male population. And this obviously has to do something with anatomy. There is a much steeper angle between the lumbar spine and pelvis or coccyx in female population. And of course, it also is related to pregnancy and compression that occurs in addition to compression that is present from the right common iliac artery on the left iliac vein. So this obviously plays a significant role during pregnancy. So a lot of individuals during pregnancy will have findings and classical symptoms of leg edema, more pronounced in the left lower extremity, and evidence of venous insufficiency. But also it presents itself with thrombosis. And that is a challenging situation because any intervention in this type of scenario has potential complications and consequences. Absolutely. All right, so Dr. Acasio, we talked a lot about the right common iliac artery on the left vein. What about other places that can be compressed in this syndrome? What other areas of the venous system? Here we have listed all the possible scenarios. Of course, the most common one is proximal left common iliac vein. But as we can see in this schematic drawing, the iliac arteries can compress iliac veins either on one side or the other side or both sides at any location. Of course, that certainly has more serious consequences when we have several areas that could be compressed from that particular anatomic variation. All right, so now that we kind of know what this syndrome is, what are the tests that are used to diagnose it or to evaluate the problem? Typically, obviously, the most important part is to talk to the patient, evaluate patient symptoms, evaluate the patient's findings. And once you see problems related to pronounced, unexplained left leg edema, evidence of varicose veins, or even telangiectasis, you have to suspect a possibility of may turn a syndrome. So of course, we start first with very simple, non-invasive readily available tests such as duplex ultrasound evaluation. Of course, one has to have expertise in this because it is not easy to diagnose and establish proper diagnosis unless you have a significant experience in evaluating those patients with may turn a syndrome. There are scenarios where this is more challenging, such as in patients that did not have adequate preparation for the ultrasound and also morbidly obese patients as well. But duplex ultrasound, as we will see, is a very reliable and useful tool in doing a non-invasive evaluation prior to proceeding with more invasive or more costly type of procedures, such as contrast vinaigrafy, CTA of the abdomen and pelvis, magnetic venous resins evaluation, and then finally, intravascular ultrasound that we typically use during the intervention. Very good. So what would be your initial approach for any patient that you suspect has a iliac vein compression? Do you automatically do a Doppler or are there patients that come into the office and have a clear cut story that you're convinced is may turn or you'd go right to the MRV or the CT? I always proceed with non-invasive evaluation using Doppler and one has to pay attention and recognize what are the normal values and what are the abnormal values? For instance, we know that the inferior vina cava is typically more than two centimeters in diameter and common iliac vein should be at least one centimeter in diameter or larger, as we can see here. We can see normal findings as far as the ultrasound image is concerned but also as far as Doppler images are concerned. Another thing that we use very frequently is phasic flow because if you have no compression, you will have a normal phasic flow during inspiration, expiration and unsolvable maneuver and that is very important step in evaluation of patients with this condition. Then as we move forward with additional information from the duplex ultrasound, we can look at other parameters such as extrinsic compression which is seen here on the left upper corner image and this is with color Doppler as we can see here. There's a significant compression of the common iliac vein and so what are the normal values? Obviously more than 50% diameter reduction is considered significant. Also changes in velocities are more than 2.5 to one ratio between a normal segment and a normal segment and turbulent flow with mosaic as we can see on the right-hand side is another important parameter to take into consideration. We also measure the velocities approximately and decently so that is very, very useful as is seen here on the bottom image and of course we can do plymetry which is very important as far as identifying the severity of stenosis. You have to measure it in the segment that's narrowed as well as approximately and decently as well. Then there are several other what we call indirect criteria for detecting iliac vein obstruction using duplex ultrasound. There is so-called non-phasic or asymmetric flow in a proximal, common, formal vein. There is also non-phasic low or no flow on augmentation with ulcalva. It means that obstruction is so severe that ulcalva cannot augment the flow. There might be also a reversed flow in the ipsilateral iliac vein and the difficulty in compressing common formal vein because of such high venous pressures as we can see here. All of those parameters are very important. And then we have also additional indirect criteria that we could use, presence of collateral veins that are easily identifiable on the duplex ultrasound as well as on angiography, as we can see here. There is a cephalod flow in the inferior pigastric vein, which normally is in the opposite direction. So that has to be evaluated as well. And then there is a reverse flow in the deep external pudendal vein, which is again very unusual and abnormal observation. Very interesting. So we talked a little bit about the ultrasound in the duplex studies. When are MRV and CT indicated for this diagnosis? Or what do we find usually in patients with Materna when we have these studies? So we use MRV very frequently. We less frequently use CTA, particularly female population in childbearing age because it adds extra radiation. And MRV obviously doesn't have that risk. And here we can see two images. One in a view where we can see clearly the compression on the left-hand side from the MRV of the iliac vein. And the other one also, we can see the anatomical finding where the right common iliac artery is totally compressing left common iliac vein. And actually there is an obstruction, there is no flow. This vein is completely thrombosed. And we can see extensive collateral here that are connected as we can see to the flow up higher, which is actually in this particular scenario, the ovarian vein. So both CTA and MRV are very, very useful and meaningful tools in further evaluation. We can see furthermore as far as CTA is concerned on the left upper panel mild compression from the iliac artery. And on the bottom panel, more significant compression of the iliac vein from the iliac artery. And then on the right-hand side, the lateral view where we can see again, significant compression of the iliac vein from overlying iliac artery. Another image here, we can see again compression that causes dilatation of the iliac vein due to that compression of so-called pancaking. And on the right-hand side, actually when we remove the overlying iliac artery, we can see indentation in the left common iliac vein. So all those tools are extremely important in evaluating patients with this particular condition. All right, so that's very interesting. Now tell me more about when we're in the procedure or when you're in the procedure, how do you use intravascular ultrasound to guide you in your intervention and tell us the steps that you take for pre- and post-intervention? So I was, in my opinion, is extremely important tool. It's almost mandatory tool during the intervention because it will give you a detailed information on the location of the compression, the extent of the compression and the presence of collateral as well. And also it will guide you as far as selection of interventional tools, such as stents, what size stents should be used and also on the outcomes after the stenting is performed. As I mentioned, stents are routinely used for this type of condition because plain or balloon angioplasty is inadequate and you will not achieve satisfactory results with balloon angioplasty alone. Very good, so a little bit more on the stenting. So there are a couple of venous stents now on the market. Can you tell us a little bit about those and what sizes we might have for those or maybe the difference in the, you know, build the makeup of those stents if you choose one over the other for May Turner in particular. And then what generally do you send people home on in regards to any medication-wise anti-platelets or anti-coagulation? If you could just briefly summarize, I know it's a lot to talk about there. Well, a little bit about the history of stenting of the iliac veins, particularly related to the May Turner syndrome. This started in the early 90s and at that time we only had one large stent available for this particular application, it was wall stent. And it comes in various sizes from very small, let's say eight millimeter diameter to 24 millimeter in diameter. So larger wall stents have been or have been used for that particular scenario. For the last four or five years, particularly abroad in Europe and now more in the United States for the last several months, we have dedicated stents that were specifically designed for this particular use, their self-expanding stents. And there are precise as far as placement is concerned, which is advantageous in comparison with the wall stent, which sometimes gives us challenges in placing exactly where we have to. For instance, wall stent typically is placed protruding into the inferior vena cava, just to make sure that we do not have a difficulty in assessing where the main compression is. While newer stents, and there are two of them available on the market in the United States, they can be precisely placed in the location where the compression is. Of course, the guidance is with the ultrasound and also determining the location and the outcomes is using the ultrasound. Let me give you a few examples and we will show this in one particular image, but our optimal goal in stenting iliac vein is to achieve a round type of end result rather than an oval end result. There is now evidence with recent publications that round type of an expansion of the stent is preferential as far as preventing restenosis or thrombosis. So the diameter by itself is not a good indicator. Actually, proper expansion is more important and that is achieved with newer generation of stents that have a significantly higher radial force. Very good, very good. So now that we talked about the stenting and what we have available to do that, what is the follow-up of these patients after you stent them? Are you repeating duplexes, six months, one month, three months to check on the patency of the stent or just going by symptoms? The classic treatment that I think is the most appropriate for the great majority of patients unless there are contraindications is we use antiplatelet agents for at least two or three months but we also use anticoagulants more frequently recently, NOAAX, but before warfarin. However, when there are contraindications to anticoagulants such as pregnancy or whatever, we will only use antiplatelet agents. Typically, anticoagulants are used for at least three months, maybe six months, particularly in patients that had thrombotic event and or complications related to that. So I think that's a probably standard of care for a great majority of interventionists as far as may turn a syndrome is concerned. Very good. We touched earlier on contrast vinaigrafy. In your use of IVAS now that IVAS is pretty mainstream for treating these lesions, what can you say about your experience in the past just by doing procedures with vinaigrafy alone versus now doing it with IVAS? Vinaigrafy is obviously a suboptimal test as far as assessment of severity of obstruction in May Turner and also as far as management of patients during the intervention. As we can see here on this particular image, we can see that there is probably suspicion of compression but we cannot assess the severity of obstruction. This is particularly true in antroposterior type of imaging but if we do it in oblique or lateral projection, there are certain scenarios where this might be more visible. Of course the gradients are not important as well because venous pressures are very low so that's not very meaningful. Frequently see so-called pancaking as we have seen on the previous one or flattening of the vein. There might be some stagnation of flow. There is a contralateral cross-filling and preferential collateral flow as we can see here through the pervertibular vessels and stenosis and presence of thrombus. All of those things are useful but they are not extremely beneficial in guiding us as far as size of the stents or location of the stents and all of those things that are very important in treatment of patients with early vein compression syndrome. Just interrupt for a second. The significant collaterals that a lot of these patients develop over the years because they most likely had this syndrome since they were born. After you stent them and fix the obstruction, do those collaterals go away? They're not used anymore and then is there any implication for those shutting down? I have seen scenarios where a collaterals vessel disappear instantaneously after appropriate stenting of the iliac vein so yes, they can disappear. Some of them will disappear a little bit slower and particularly if there are also other comorbid conditions or associated conditions present such as ovarian vein insufficiency or the nutcracker syndrome and compression in other areas that could be playing a role. Very interesting. So we talked a little bit about IVIS and I think these pictures are pretty telling at what you were saying about the ovaloid shape versus the circular shape and after you put the stent in, this one here on the right seems to be the more optimal round shape stent. Right, so here we have two perfect examples of on the left-hand side suboptimal expansion with a stent on the right-hand side optimal expansion and that should be done routinely with the IVIS at the end of the procedure. Obviously different stents offer different type of results. On the right-hand side, we can see a very good result with the later generation stents and suboptimal result in a patient that had practically total occlusion of the iliac vein and suboptimal expansion. So that is very important as far as long-term outcomes are concerned. Certainly. Can you summarize now after we touched on all the imaging modalities and therapeutic options the role for in the future after these patients leave the CAF lab? If you use this, you know, vinaigrafy or CT or MRV or an ultrasound or if you have them follow-up at all or if the symptoms just dictate what you do. So typically what we'll do, we will see the patient at one month follow-up and we will obtain a duplex ultrasound. We will compare the findings with the previous one that was performed prior to the intramational procedure. This particular tool is extremely practical. It's inexpensive, has no side effects and is easily repeated. So I will do this on a routine basis. What we didn't mention before and it's important to mention, in every patient with iliac vein compression, we will also look for any finding of venous insufficiency or regurgitant valves or venous incompetence in the lower extremity. We will assess this pre-procedure and also after the procedure. Occasionally, we will see almost complete resolution of venous insufficiency if the valves are not grossly deformed and distorted after adequate expansion of the iliac vein with stenting. Now some of the patients will continue to have chronic venous insufficiency and symptoms related to it because the veins have been stretched to the point of no return. So, again, duplex ultrasound is extremely important. Now as I mentioned, IVAS is the gold standard for measurements as far as location is concerned, diameter, length, stead selection and assessing the results during the procedure. Other imaging modalities that we mentioned such as CT and MRV are also very useful, but obviously we cannot use them during the intervention so IVAS would be the most appropriate one for that particular purpose. All right, so the bottom line is who, at least in your mind, actually needs the intervention, the stenting of the iliac vein. Are there clear-cut guidelines or is it, you know, I know it's a gray area for those patients who maybe have symptoms but have never had a thrombotic event. What do you generally do for practice? So this is a very kind of debatable type of a situation. There are no clear-cut guidelines. I think that most of the experienced operators would agree that only patients that have symptoms should be treated. So it's not for cosmetic reasons or not even for anatomical reasons because there is compression of the iliac vein. Typically, the patients will be referred to us because they develop thrombosis, either during pregnancy, after pregnancy, with trauma or with surgery. That's the great majority of patients. The second subset of patients that are referred to us are patients that have chronic venous insufficiency and symptoms related to it. And we see it in a lot of families. We have seen that where every single member of the family has findings of chronic venous insufficiency of the left lower extremity with a diagnosis of May Turner syndrome. And then the question is, who should be treated? Again, only those that have symptoms. First, we'll try medical therapy, exercises, weight reduction, elastic stockings, but in patients that have a severe stenosis and persistent symptoms, we will resort to stenting. And then, if needed, treatment of chronic venous insufficiency, which is easily treated on our patient basis on the local anesthesia without any surgery or incisions. Very good. All right, so can you give us a recap of everything we kind of talked about, from who gets it, who needs workup, and then ultimately, who needs to be referred as an outpatient provider? Who do you need to think of to send to a cardiologist or interventionalist to help your patients? Well, as I mentioned previously, only a small number of patients with complications related to May Turner syndrome will require treatment. Iliac vein stenting is essential to achieve good long-term results. And now we have dedicated Iliac vein stents, and I think that the treatment for this particular condition is better, will be better than it has been in the past. So I'm quite optimistic that we will be able to treat those patients in the best possible way. Yeah, stent technology seems to really be improving, especially in the venous side, which we didn't have options for before, which is great. Well, Dr. Costello, thank you very much for participating in this program. It was a pleasure to have you here. Pleasure to be here, thank you for having me.