Steve Elias: Welcome, everybody. We are going to be speaking about the Holy Grail of venous disease that is somehow gaining a functioning valve in the deep venous system. All of you have been intimately involved with venous disease and certainly deep venous disease for a long time. Some of you have been involved with industry and some of you have been involved as physicians, trying to get a functioning valve into the deep venous system.

Why do we need this nowadays? Can’t we take care of 98 percent of the vein problems with what we have now and do we need a functioning valve, considering the path of physiology of most venous disease in 2017?

Thomas O’Donnell:From a historical perspective we followed the principles of Linton and Cockett for patients with advanced chronic venous insufficiency, so that in C5/6 patients we treated the superficial venous system through various operations. These procedures were intended to reduce superficial venous hypertension-ligation & stripping and/or interruption of incompetent perforating veins.

Although our current techniques are less invasive (thermal and non-thermal ablation of the saphenous or perforating veins), the concept is the same. A certain group of patients, who were referred for this treatment—those patients with deep venous disease did not fare well and the venous ulcers never healed or quickly recurred.

The large ESCHAR trial of C5 and C6 patients provides the proportion of patients with deep venous insufficiency and their response to surgery on the superficial venous system exclusive of the perforating veins. The investigators were careful to term the deep system involvement as reflux.

Indeed one of their exclusion criteria was “presence of deep venous occlusive disease or other conditions precluding superficial venous intervention (at the discretion of the local research team).” This would most likely rule out patients with post-thrombotic deep venous involvement.

Nearly 40 percent had “mixed” superficial and deep involvement, with 25 percent segmental deep venous distribution and 13 percent total deep venous involvement. With recurrence of ulcers as the outcome measure, patients with total involvement of their deep venous system failed to respond to treating the superficial venous system alone, with ulcer recurrence rates similar to the compression group, while the patients with segmental deep venous involvement had a higher ulcer recurrence rate than those with isolated superficial venous reflux, but less than the compression group.

This study clearly identifies a percentage of patients who won’t respond to the “traditional” reduction of superficial venous hypertension, so that we need to correct the deep venous disease. Moreover, the extent and the type of deep venous involvement, post-thrombotic or non-thrombotic, influence the choice of intervention.

Steve: Do we feel that there were more people than we would appreciate back in the late 1970s or early 1980s who really had disease above the inguinal ligament that we either didn’t appreciate or we said we can’t do anything about so let’s deal with the problem from the groin down?

Fedor Lurie: Steve, I think you’re right. In the 1970s and 1980s we grossly underestimated the influence of iliac obstruction and didn’t know the prevalence of that condition. However if you look at the pathology in CVI patients, it’s not always obstruction; it’s either a combination of obstruction and reflux or just reflux alone.

This is especially true for severe disease. Some patients with combined reflux and obstruction disease are improved after treating iliac obstruction, but will the remaining reflux cause problems? I believe the answer is yes, and the longer follow-up should clarify this.

Steve: Nicos, if you had to either fix somebody’s obstruction or fix somebody’s insufficiency from a hemodynamic viewpoint, which one do you think would give you the biggest bang for your buck?

Nicos Labropoulos: Obstruction in the iliofemoral veins is most important. However, in many patients you need to address also the reflux. In superficial veins it is easy, but in femoropopliteal veins it’s very challenging. To add to what Tom said earlier, if you look at some of the data and the reviews done on this, about 20 to 70 percent of people with ulceration have post-thrombotic changes.

The mean value is about one third of these patients, so one in every three people with an ulcer is going to have some obvious post-thrombotic disease, most of which is actually in the femoropopliteal veins. There is an enormous need to solve this issue.

It has not been addressed because currently we do not have the means to an easy and durable treatment. If we develop them, I think it will be of great service to the community.

Thomas: Steve, to answer your question directly, regarding whether you treat obstruction or reflux, Raju has done a study that shows just correcting obstruction, even in the face of reflux, helps remedy the situation with ulcer healing, at least in the small number of patients they followed up with.

Nicos: This is true for the iliac veins, not the femoropopliteal segment.

Thomas: I totally agree with Nicos. The principal problem is reflux.

Steve: Frans on your side of the Atlantic, what is the current thinking regarding the search for a functioning deep venous valve?

Frans Moll:There’s great interest in this pathology in Europe. Our own group is looking for it as well. We started in the late 1980s and 1990s. In Europe, we often have to prove evidence. As soon as you go in the direction of evidence-based, we realize that our current status of experiments and studies is still too early to start RCT’s.

However, we have enough proof from our animal studies, and preliminary clinical studies, that going in the direction of “flow regulation” applied in a percutaneous implantable way, might be ultimately beneficial for patients with severe deep venous insufficiency. There is great interest in Europe. The patient population with severe post-thrombotic deep venous valve insufficiency is huge and trashes the health care budget.

Steve: Bob, talk to me first about what your thoughts are when thinking back on your pioneering work doing valvoplasties. What patients do you think really had suprainguinal disease that wasn’t appreciated at the time because none of us were thinking about it?

Bob Kistner: We were doing venography on all the patients, so we knew whether there was obstuction above the inguinal ligament. When they had post-thrombotic disease above the inguinal ligament in the post-thrombotic, we approached that either simultaneously or primarily, fixing the obstructed flow first.

Steve: And then you went to taking care of the persisting insufficiency symptoms?

Bob: Yes. Some of those were iliofemoral which we would repair with a combined procedure, clean out the system above and put a stent in. We were stenting in the 1990s and to establish an outflow above and then working on the valve below.

Steve: Fletcher, what do you think of some of the challenges that face the inventor or industry when they’re trying to consider developing a system or a valve that’s going to work in the deep venous system? Just give me a few and then we’ll go to some others.

“We have the imaging modalities to determine the size of the vein and the post-thrombotic damage. If I had to bet where to put the first valve, if one valve is enough, it would be on the lower third of the vein or in the popliteal.”

Fletcher Wilson: From an industry perspective, there are a lot of different obstacles to consider. Some of them are technical and clinical and others have to do with fundraising and market uncertainty, but I’ll focus on the technical and clinical, for now.

Vein valve failure is a very difficult problem to solve, and many people have been trying to do this for a long time. One of the biggest issues is a lack of a really good venous model. The animal vein is far too compliant to mimic human veins, which is critical in testing our concept of autogenous valve formation.

You can use cadaveric tissue, but that has obvious shortcomings in terms of determining what the biologicial response will be to therapy. So we end up using a variety of different models to answer specific sub-questions. The problem is, we can iterate in our lab and develop different ideas, but it is hard to know how something will behave in clinical use based on these disparate testing set ups.

One of the other biggest hurdles is being able to raise enough money to do all the product development and testing required to persuade an ethics committee that a product is appropriate for limited clinical trial use. Given the difficulty of the technical problem, and the issues with testing models, it took us about five years to get to our first clinical case. It costs a lot of money to survive that long, and so you need committed and patient investors.

Steve: Marc Glickman, talk to me a little bit about some of the inherent anatomic issue in developing deep venous valves in terms of the vein size, location or placement, and how you approached the venal valve.

Marc Glickman: I think one of the biggest issues is patient selection. You want enough flow to the femoral vein, more axial flow through the femoral vein than through the collaterals because with any type of model, if you don’t have enough flow through the femoral vein then any type of device you put in probably will fail.

We’re working with an eight to 10 millimeter diameter for the femoral or popliteal vein. I’ve gone down the surgical intervention route as opposed to percutaneous, just being a student of history, knowing that most things start with surgical intervention and migrate to endovascular.

It is essential to have adequate flow within the femoral vein or a popliteal vein. Vein size and the characteristics of the vein are secondary but also very important. A sclerotic, obstructing vein is not going to be helpful for any type of surgical intervention or for valvoplasty.

Steve: Nicos, how can we determine location or placement of valves from an anatomic viewpoint and what are the things we can use to help us put a valve in the best place?

“It’ll be interesting to observe how the artificial valves fare, and whether they will be affected by the inflammatory process that occurs in the post-thrombotic state.”

Nicos: There are typically about three valves in the femoral vein–one proximal, one mid and one distal. Hemodynamically, it makes more sense to put the valve in the distal place. The vein can be evaluated with regular ultrasound because the imaging in most patients is great, but if you want to enhance the imaging, use venography, or better yet, IVUS.

We have the imaging modalities to determine the size of the vein and the post-thrombotic damage. If I had to bet where to put the first valve, if one valve is enough, it would be on the lower third of the vein or in the popliteal.

Steve: Okay, then you both must be right. Frans, say you have a system that’s insufficient from external iliac down to the popliteal. First of all, what are you going to use as your way of determining what size you’re going to put in and where you think it’s the most ideal way and place to put it?

Frans: Sizing is a big issue for me, because the concern is if we have to oversize by about 20 percent, how do we measure the “true” diameter? How long should the patient stand up in order to measure the diameter of the target vein? At this moment, we focus on patients with the post-thrombotic syndrome.

Recanalization of the superficial femoral vein has occurred and consequently the diameter of the vein is less variable. The vein wall is more rigid. The diameter does not change as much as in veins that have never been through a thrombotic process.

The design of any kind of “valve” has to be able to deal with variable diameters. In my experience with the percutaneous implantable VenPro valve, we had to select patients with a congenital anomaly, no valves in the deep vein system, a very rare pathology.

It was not unusual that we oversized a little bit more, because that vein didn’t go through a thrombosis history. But I think such a population is too small to develop a percutaneous implantable valve only for this very selective group of patients.

My aim at the moment is to treat patients with a post-thrombotic syndrome. For the percutaneous technology, I prefer a modification of a Valve concept and we prefer to call it a venous “flow regulator.” I worked with the valve concepts for many years, starting with a monocusp implantation at the origin of the superficial femoral vein at VenPro.

This didn’t work at the midterm follow-up. We had initial success with the percutaneous implantable tricusp bioprosthesis. Even did a very successful live case from the Jobst Medical Center Ohio, which was broadcast at a Dietrich meeting in Phoenix early 2000, but as just explained, this was indicated only for patients with congenital valve agenesis.

We left that project, the implantable tricusp valve became a model for the current TAVI and we went into the development of a novel concept, the flow regulating Sail Valve.

Steve: I want to get some semi-consensus here for our listeners and readers. If everything is equal, and I know that’s hard to say, where is the best place to put a functioning valve? We’re talking about common, proximal femoral vein, mid-femoral vein, distal femoral vein or popliteal.

Fedor: First of all, when we talk about reflux as the main contributor to the disease, we mean veins below common femoral vein; the veins above that level rarely have valves. There are three possible scenarios. One is the axial reflux through the incompetent femoral vein, into incompetent popliteal vein, and into the calf veins.

Another is the axial reflux through incompetent profunda into incompetent popliteal vein, and into the calf veins. And the third is the combination of the two.The best place to put a competent valve depends on which scenario is present in a diseased extremity.

Either incompetent profunda or incompetent femoral veins should be the target in one of the first two scenarios. If both profunda and femoral veins are incompetent, then the popliteal vein will be the best as Tom O’Donnell showed early on.

Thomas: Right Fedor, we decided to place the competent valve in the popliteal vein segment, because in that anatomic site it sits over the calf muscle pump and a non-functioning popliteal valve has been associated with venous ulcers.

Therefore, we felt that a venous valve in that location would be extremely advantageous hemodynamically and the diameter match of the axillary vein segment would better match that of the popliteal vein. I would re-emphasize the distinction between post-thrombotic and primary valvular incompetence, because post-thrombotic disease is totally different. Besides destruction of the valve, the entire vein segment is damaged with thickened and stiff walls and the lumen may contain several channels.

Moreover, the post-thrombotic state continues as an inflammatory disease and if you employ local autogenous tissue, you may be doomed to destruction of your valve reconstruction by the persistent inflammatory process. If “clean” tissue, uninvolved by the post-thrombotic process, is “transplanted” into the popliteal area, it may fare better.

It’ll be interesting to observe how the artificial valves fare, and whether they will be affected by the inflammatory process that occurs in the post-thrombotic state.

“I was looking for another concept and came up with the idea of a flow regulator, just as a Spinnaker on a sail boat. It catches the wind in one direction and is a floppy piece of tissue in the other direction.”

Steve: Bob, give me your thoughts about placing a valve in a fairly post-thrombotic system because that’s going to be more of the basis of primary insufficiency.

Bob: We have always put the valves has been in the femoral vein down to the popliteal vein, or as an interposition valve at the profunda vein. If you have leakage in both the profunda and the femoral vein, then the popliteal vein is the only place to put a single valve, or if you’re going to put a double valve in some way, you can repair or interpose a valve in both the profunda and the femoral veins.

I don’t think it makes any difference regarding the level in the femoral vein, whether it’s at the upper end or at the adductor canal.

Steve: I tend to agree with you. When I spent my time with Syde Taheri in Buffalo as a surgical resident, we started putting them lower and lower down and wound up in the proximal popliteal vein as well. When you’re creating this, Marc, where are you planning on having the VenoValve being placed? Would you have it placed somewhere in the femoral vein?

Marc: Proximal femoral vein or in the popliteal vein, depending on the type of reflux. If they have a profunda valve insufficiency, you’re going to need one in the popliteal vein to really accommodate these patients.

Steve:All right, let’s go to the actual construction of the valve itself. Some of the valves are monocuspid and some are bicuspid. We always try and recreate nature when we’re thinking of making something prosthetic but maybe that’s not always the best way of doing it.

In terms of the valves, what is the reason why some of the valves are monocuspid and some of them are bicuspid? Frans, do you have any thoughts about bicuspid versus monocuspid?

Frans: When I joined VenPro in early 2000, the surgically implantable monocusp was still in their portfolio, but success was marginal. The company agreed upon the development of a tricusp implantable device, framed into a nitinol ring to accommodate the changes in diameter in order to have ultimate reduction of leakage/reversed flow. Theoretically, a tricusp is able to do this much better than a bicusp valve. I think that most of us know that the tricusp concept was used later on for the TAVI.

But having said this, I was looking for another concept and came up with the idea of a flow regulator, just as a Spinnaker on a sail boat. It catches the wind in one direction and is a floppy piece of tissue in the other direction.

As soon as you stand up, vertical position, the Sail Valve captures the reversed flow and when you are in a horizontal position the flow commutes up and down on the respiratory rhythm and muscle contractions without any restriction and no blood left in the notches of some kind of valve concept increasing the risk for thrombosis at longer follow-up.

Sail Valve is a different concept. It averts any problem of thrombosis inside the cusps at the long-term follow-up. So that was the whole idea behind the development of such a Sail Valve. I still try to avoid the word “valve,” because it isn’t a valve, it is actually a flow regulator.

Steve: Fletcher, your Blueleaf device has a way of creating both monocusp and a bicuspid. What is your preference when you’re doing this?

Fletcher: The goal of the procedure is to limit flow in the backwards direction, and I think our procedure allows for real-time decision-making based on that vein and its specific hemodynamic condition. The physician would create a monocuspid valve and then check for competency. If it seems that there’s still too much reflux, the physician can then form another leaflet on the other side creating a bicuspid valve.

For us, we found that with smaller veins, a monocuspid valve tends to do the trick, whereas on bigger veins, bicuspid valves seem to be better. For us it’s really a clinical risk-benefit assessment made by the physician. Bicuspid valves cause a little bit more damage to the vein wall but may act as better flow restrictors for a given vein, so the physician can start with monocuspid, assess, and determine if bicuspid is necessary in real time.

And another important thing specific to our procedure, the goal isn’t necessarily for every valve to be 100 percent competent. Because we have an intravenous delivery system, we can place valves at multiple levels, and in specific locations, such that the cumulative effect of the treatment can have a clinical benefit, even if each valve isn’t perfect.

Ours is really a more customizable procedure based on venous flow patterns, where collaterals are coming in, and the health of the vein wall. This allows the physician to make appropriate decisions as he/she goes.

“Some degree of clinical improvement can be provided by any valve that reduces the degree of reflux. The question remains—will that be enough and how long is it going to function?”

Steve: That’s good. Marc, the VenoValve, it’s really a monocusp valve.

Marc: That’s correct. When Dr. Maleti did his procedure, it was a monocusp. I think we don’t need to have perfection here. We need to have improvement and if you can reduce the reflux and prevent a lot of regurgitation, you’re going to get an improvement in a patient’s symptom. You don’t need to be 100 percent, you just have to be 80 percent to get good results.

We’ve seen with our hemodynamic models that we have very limited reflux with our monocusp. We have a little less tissue than a bicuspid venue and I believe that in a monocusp we can provide marked improvement to patients without going through more complicated issues with a bicuspid valve.

Steve: Fedor, you’ve discussed this and you’ve studied the valve in humans. What are your thoughts about a monocusp or a flow regulator versus something that exactly mimics the human valve in terms of what we’re trying to accomplish?

Fedor: I agree that some degree of help can be provided by a monocusp valve or Sail Valve. The real question is how much improvement will it get and more importantly, how long is it going to function? There is a growing body of evidence that a bicuspid valve provides the optimal flow in the vein.

This geometry is more optimized than tricuspid or monocuspid structures. That’s obviously an evolutionary development in low velocity vasculature. There are also studies that show that mechanical forces applied to the leaflets itself by the blood flow, are optimized in bicuspid configuration, not in a tricuspid or monocuspid valve.

Some degree of clinical improvement can be provided by any valve that reduces the degree of reflux. The question remains—will that be enough and how long is it going to function?

Thomas: I think it’s interesting when you have “the ideal valve,” a human venous valve taken from somewhere else in the body, such as the axillary segment, and then place the valve in the popliteal vein and examine the long-term post-transplant clinical and hemodynamic outcomes. We had the opportunity in our vein valve transplant series to examine clinical outcomes and hemodynamics (APG) values in these patients post-op, and then at a mean of 5.3 years.

Of these, 87 percent returned to work and had an average cumulative ulcer free state of four years by life table analysis. What was interesting was that venous filling index (VFI), a measure of global reflux in the limb, returned to the normal range in only a few patients.

The mean post-op value was improved, however, to 6.3 ml/sec, which was similar to the findings of Marston and his vein valve transplant group with this hemodynamic value. Moreover, none of our patients had deterioration of this parameter in sequential follow-up.

Residual volume fraction (RVF), which correlates with ambulatory venous pressure, was reduced to a mean of 31 percent, where normal is less than 35 percent. Most importantly, when RVF was correlated with VFI in a sector analysis, as popularized by Christopoulos, all but one patient were in the sector with less than a 30 percent probability of ulcer recurrence.

Basically, what this data demonstrates is that I agree with other discussants, you may only have to improve hemodynamics, but not normalize these values.

Steve: Yeah and I agree. We all have spoken about this hypertensive threshold, this certain level that you need to get the venous pressure below in order to get improvement in healing and/or symptoms and you don’t have to be perfect. Nicos, have you ever studied the flow patterns in the monocusp situations versus bicuspid by ultrasound? Does it really matter from a flow viewpoint whether it’s bicuspid or monocuspid?

“I think the advent of IVUS is a key tool for us in selecting the right vein segment and patient, but I think the two non-obvious reasons percutaneous is important outside of morbidity and the ability to treat less severe patients would be the ability to treat in multiple locations in the same procedure and multiple orientations as well.”

Nicos: I think hemodynamically and evolutionarily the bicuspid valve is more secure because it prevents almost any leakage. I went to see Dr. Maletti operate and I discussed with him this matter several times.

He told me that the monocusp valve does the job but five years later over 50 percent of them are going to fail. Which of the valves that is going to fail from the get-go is not known, but 50 percent are going to fail at five years.

Marc: I still think the quality of life for these patients, even satisfaction for five years, is certainly better than what the alternative is for many of these patients. We want improvement in their quality of life and that really has to be very important when we evaluate outcomes. Not only are we looking at APGs and everything else but we have to be looking at quality of life and how people are responding to therapies.

Steve: Right, and again, that’s what we’re all talking about when we’re managing vein disease in general. It’s not about limb salvage; it really is about quality of life no matter what interventions we’re doing on vein patients.
I want to switch a little bit to some of the ideas that we’ll be talking about.

I wanted to talk a little bit about the concept of an open insertion versus a percutaneous insertion and what are the positive and negatives of each. There are technologies out there now that involve some open and some percutaneous. Let’s see, Bob Kistner. Talk to me a little bit about open insertion versus a percutaneous insertion and does it matter?

Bob: I hate to talk about things that I don’t know anything about.

Steve: That’s usually the best way to talk about things. Then you’re not biased by anything.

Bob: Well, I think there’s great precision to an open procedure but it is an open procedure and I think it would carry some additional risk of thrombosis, perhaps. But I’m not sure that that’s really true. It might be the same. Probably the effect is how well you can seat the valve, whatever the dimension, and have it remain in the place where you want it and where it gives ideal function.

But, to me, if we’re going to have a valve that we can put in through a catheter, and put it in various places, that would be ideal it can be shown to work for the long term. I think that percutaneous, if it’s nearly equivalent, would be the way to pursue it.

Steve: Frans, a lot of the VenPro valve was percutaneous and the problem with it was never delivery of the valve, it was really thrombosis that developed later on or some other issue. But do we think that the percutaneous way was a negative thing and if that valve or other valves were put in open it might have been more advantageous?

Frans: Percutaneous is not the cause for a negative outcome. The live case with the VenPro Valve, broadcasted from the Jobst Medical Center in Ohio, showed a perfect and accurate placement at the target location. The indication was rare, valve agenesis. But there was an additional reason why we stopped.

The safety and efficacy trial, which was started, six patients had already a successful percutaneous implantation, was never actually finished. Strategically, it was preferred to go into the direction of the development of an implantable valve in the heart.

Steve: Marc, talk to me a little about open insertion and some of the positives about open insertion.

Marc: I think that the major issue with percutaneous is can you get the right size and make sure that the valve opens up? First, I’m going with a surgical approach so I can make certain that I have a good-quality vein. Second, I’m going to control the size of the vein so I know my monocusp will have a nice wall to oppose to.

If I have direct inspection, security and placement of the valve, then I know it’s not going to be angled and it’s not going to be five, 10 or 20 degrees off where I can’t control it, just like Dr. Kistner said. Once we have proof of concept and also that it works, then someone can take it to percutaneous.

But we don’t have proof of concept and I think that’s really going to be imperative to do it surgically just like we did with open aortic aneurysm repairs, before EVAR evolved.

Steve: Fletcher, just to give you your say here. Obviously the proof of concept’s kind of been done already with the Maleti valve in an open viewpoint and now you’re creating a similar type of valve in a percutaneous viewpoint. Do you have any ideas? Do you think you are better served percutaneously than open?

“…having a valve in the deep system that works could be a paradigm shift regarding how we approach these patients and although we’ve talked about doing the ablations, et cetera, if we do have a valve that functions, that does well, it could be a paradigm shift in the treatment modalities.”

Fletcher: Yeah, I think obviously technical complexity goes up when you go percutaneous. I think the advent of IVUS is a key tool for us in selecting the right vein segment and patient, but I think the two non-obvious reasons percutaneous is important outside of morbidity and the ability to treat less severe patients would be the ability to treat in multiple locations in the same procedure and multiple orientations as well.

An elephant in the room would also be how interventional radiology is a growing faction in this field. So many of those doctors are stenting patients and I think being able to include that group in the long term, in addition to vascular surgery, is really important in terms of the future of venous disease treatment.

Hopefully no one on this call starts throwing tomatoes at me for saying that. It’ll be important because there’s a lot of different types of physicians treating venous patients now, so those are two non-obvious reasons percutaneous is important but the technical hurdle is certainly higher than when you’re in there with your bare hands and able to get a more precise procedure done.

Fedor: Let me bring up one more issue that was not touched upon when you discussed open procedures. They are not just more invasive. They can be technically challenging, time consuming, and expensive. Anyone who has operated on post-thrombotic veins knows that sometimes it’s not easy at all, even for the femoral segment.

Dissecting chronically inflamed and organized tissue surrounding the postthrombotic vein sometimes is a struggle, as well as time consuming. It is also unclear how the manipulation with the vessel at those conditions affects the outcomes. Endovascular approach has clear advantages.

However, a selective group of people who understands the pathology, know how to use that device or devices, and can convert to an open procedure if it becomes necessary are a much better fit to secure successful development during initial adaptation of new techniques.

Bob: Well first of all, when you deal with these veins your preoperative impression before you’re going to open them up is right about 80 to 90 percent of the time and wrong about 10 to 20 percent of the time. You sometimes find pathology that you didn’t anticipate before and if you’re at an open procedure you can often find a way around that, whereas I don’t know what you could do with a percutaneous procedure.

But I have real concerns about having people be able to just drop a valve in the veins without a lot of knowledge about the natural history of the problem and what this thrombosis might do. These post-thrombotic veins are not simple and they have all kinds of problems up and down the vein that weigh into the flow characteristics and the longevity of any valve that we place.

My concern is if you make it too easy it’s going to be mal-used—it’s likely to be overused and abused and inappropriately placed.

Steve: Nicos, what percentage of people, primary insufficiency versus post-thrombotic, are going to have enough of either ulcers or significant symptoms that are going to need these valves placed? Can you give us any idea about that?

Nicos: I will tell you. At least in the patients I have seen over the years, by far more than 95 percent are post-thrombotic limbs. Primary sufficiency on the deep veins is a very rare thing.

Steve: Right. That’s great. I think that points out what we’ve seen—these are not your slam dunk, easy, pristine veins that have not had post-thrombotic changes that you can just shove your valve into. These are the more difficult veins to get access to, the more difficult veins to work on, and that it’s open or close, so it’s not for the person who just has good catheter skills.

It’s really for the person who understands the complete pathology and how they’re managing the entire patient and not just putting a valve in. I’m glad to see all of us shaking our heads, “yes, yes and yes.” That’s not to put down other people but it’s really to say that the initial people putting these in are those who have really thought about the underlying problems and pathology with the patients.

We’re kind of getting down to the end here in time. Does anybody want to bring up something that hasn’t been brought up?

Marc: I would like to just say that having a valve in the deep system that works could be a paradigm shift regarding how we approach these patients and although we’ve talked about doing the ablations, et cetera, if we do have a valve that functions, that does well, it could be a paradigm shift in the treatment modalities. We’ve talked about this before—that we treat it with ablations and foam and other ways, but if we have something that really treats a disease, it could change the way we approach these patients.

“I have real concerns about having people be able to just drop a valve in the veins without a lot of knowledge about the natural history of the problem and what this thrombosis might do.”

Steve: Do the other guys agree with that? Obviously people who have developed valves may be thinking that but let’s ask some of us, do we think this is going to be the first or second thing you go through or the fifth or sixth thing you go through if you have a durable functioning valve?

Bob: I can give you a different approach. I grew up in veins by trying to construct deep veins and we did a lot of that for a long time. People kept telling me, “well, you don’t have to do that much if you just fix the surface veins.” In maturity I found out that they’re right and if you fix the surface veins, the majority of the people are adequately served.

I don’t think we know the true natural history of deep vein reflux but many people tolerate it for many years, and yet it may be the source of recurrent disease and ultimate failure of the system in the later years of life. I think we have so much to learn that it’s rather dangerous to encourage insertion of valves in too many veins.

Thomas: I would echo that, Bob. We went through stages in our interventions for advanced venous disease. I was influenced by my work with Professor Norman Browse and then fellow research colleague, Kevin Burnand, at St Thomas’s Hospital in London, where we showed poor clinical and hemodynamic results with treatment of superficial disease alone for venous ulcers in the face of concomitant deep venous involvement.

As a result in the 1980s and in the early 1990s we performed a number of deep venous reconstructions—vein valve transplants, valvuloplasties, both open and angioscopic. Our experience is nothing like Bob’s volume, but certainly in the 30 to 50 procedures range. When we then returned to aggressive treatment of superficial venous disease with SEPS, the need for treating patients with venous ulcers by intervention on deep venous reflux dropped dramatically in our vein center.

Like atherosclerosis in peripheral arterial disease, we do not cure venous disease; we only delay its re-emergence. Now the patients with deep venous disease, who have failed that superficial treatment return with recurrent ulcers. They become the candidates who will require deep venous reconstruction, which I think is the next great frontier for venous surgery, if not vascular surgery.

Steve: I think we’ve begun to scratch the surface. We’re in a very exciting time, we have a significant number of technologies available coming out hopefully that are going to work and we’ll have choices for our patients. Thank you all for your thoughts.