- Thank you. No relevant disclosures to this presentation. The means to the end is removing Uremic toxins. That's what we want to do. That's what this is all about. We don't really know all the Uremic toxins and how they inter-relate, but there are a bunch
of compounds that have been identified. Urea obviously being one of them, although not necessarily being a particularly toxic compound. It's a small molecular weight marker of Uremia, which is convenient to use
if not clinically meaningful. We've developed, or Frank Gotch and Sargent developed this dimensionless concept of the Kt/V, an index of the body volume water space, which has been cleared fully of Urea and this index has been the standard for comparing dosing of dialysis for about 30 years now.
Since the National Cooperative Dialysis Study in the 80's. And the most recent iteration of this study has been the HEMO study in 2002, I believe this was published. Where they compared a high dose of Kt/V of 1.71 versus standard dose Kt/V of 1.3 and looked at patient outcomes and they were
concluding that the higher dose of dialysis wasn't beneficial. But this 1.3 was certainly better than we were seeing in the old days of 0.9 out of the NKDS studies, so 1.3 or that range has been accepted as the target dose
for dialysis and KDOQI guidelines now suggest that we strive to achieve a single pool Kt/V of 1.4, so we have a little cushion with a minimum delivery of 1.2, and that has been adopted now by CMS and the payers.
That's in our conditions for coverage that we achieve or we strive for a Kt/V 1.2 and now we have this quality incentive program, which might relate a little bit to the question earlier about saving access as we get penalized or incentivized
for doing certain things, and right in our penalty methodology in the top categories Kt/V, if we don't hit that target we get dinged up to 2% of the total payment for dialysis on that.
So it's something that's being identified, monitored, and if you like ... Not negatively incentivized. It's not a reward. It's a penalty for failing to achieve. And also you can go to dialysiscompare.gov now.
You login your unit. Here's my little unit in Hockessin. We got four stars. A nearby unit got three stars. They're really just as good as us, but somebody thinks those stars mean something,
and one of the components in those stars is hitting your Kt/V target, so if I want to get stars and not be seen as a poor performing unit, I need to hit these performance parameters, so that's why the Kt/V is the holy grail for Nephrologist. We need to get that number.
It's a very simple concept. Mathematically, you've got two items in the numerator and one in the denominator, and you want to maximize that parameter. Number one we can dispense with the volume of distribution
of Urea is pretty much determined by the patient. It's total body of water times the fraction. It varies a lot depending on the age, weight, gender, obesity, etc. You can put it in the calculator and same qx metal to deliver that number for you.
But we can't really change that, unless somebody has an amputation, or a large amount of weight loss or gain, then it changes. Time we have complete control over. We can dialyze theoretically as long as we want and in the U.S. we sort of like
to believe four hours has been adopted as a standard. There are some recommendations that wouldn't do that. Patient acceptance of that is variable. I can sit in front of a patient and tell them they need four and half hours, and they may look at me askance,
because they know they don't want it, and if you look at dialysis times in different countries, you can see certain countries like Germany, typically dialyzes closer to three hours. Typical dialysis time in the United States is more like... Did I say three hours?
I meant five hours. And typical dialysis time in the United States is about three and a half hours. There are also resource limitations and cost involved in that. So the third variable is the one we have
the most control over, which is the clearance of Urea. And that's depending on the dialyze of the blood, in the blood, out. the dialyze of that... capacity of that filter to remove the solute of interest, Urea in this case in a dialysate flow,
and there are specs for each kidney. Here is a Optiflux F160 at a blood flow of 300 and a dialysate flow of 500. It predicts we should get a Urea clearance of 271 mL per minute, or conversely a larger kidney, an F180 had a blood flow of 500, a dialysate flow of 800.
We should get a Urea clearance of 412. Obviously, none of these are perfect clearances. The maximum theoretical clearance would be that of the blood speed, but it's impossible to clear it 100% of the blood. So when your asked as a surgeon or a provincialist
to make a functional access what your Nephrologist is really asking for in a customer service world is give me a fistula that flows 150% higher. 150% of my intended pump speed and we're good to go. Need a little cushion on that as well.
And here's how it translates into action. Here's an example on a calculator. Here's a patient, who's a 70 kilogram female, dialysis time three and a half hours, 210 minutes. Her Kt/V calculates at 1.77. All good.
Same parameters three and a half hours, 120 kilogram, 40 year old male. His Kt/V is 0.96, clearly below the target. You're not going to get that guy's clearance with those parameters. If you goose him up to 500 mL per minute
on a minute on a bigger kidney and you achieve a clearance of 410, then the same male with the same treatment parameters will get 1.45, so you've met their target. If you want to do better than targets just put him on four hours and you only get 1.66,
so these are very easily definable, measurable, predictable quantities that you can achieve. And then you've got limiting factors. What is the pump speed? Well, hemolysis through needles is really an overstated concern.
This arterial negative pressure alarm won't let you go below 250 on this machine and if-- 300 is it Debbie? 250, 300 and at that point it will cut off, so you won't be able to drive the negative pressure that high,
and so you've got parameters for each needle, which are fairly fixed, a little latitude in it, but with 17-gauge needle you can go up to 300 and so on. With a 14-gauge needle you can go up to 500 or more, and it's a pretty si le higher flow.
And here's a case where you've got a 2 millimeter radial artery, a small fistula. The access flow measures at 450. You can dialyze at a blood speed of 300 with a 17-gauge needle and you're good to go. Where as you got a huge brachial artery here.
This access flow is greater than 2000. You can run the blood speed at whatever you want. And you can use a needle size of 14-gauge. You can put whatever needle size you want in this fistula. So the point is that one size doesn't fit all. Dialysis dose, and dialysis needles,
and dialysis fistulas need to be scaled to the size of the patient. You got a neonate. You got Shaquille O'Neal. Somewhere in between is our patient. Thank you.
- First of all I'd like to thank the organizers for inviting me to give this presentation. These are my disclosures. I'm going to divide this presentation into three main parts. I will initially make the case that at the present time we are providing relatively poor value in ESRD and Vascular Access Care.
I'll then submit to you that one way to address this issue is through Patient Centered Device Innovation and then I'll tell you a little bit about some regulatory initiatives in this area. If you define value as being outcomes over cost
then I would argue that in vascular access we actually provide very poor value in that we have pretty bad outcomes and in order to achieve these bad outcomes we actually spend a huge amount of money at about 1.5 billion dollars per year and these is no talk at all
in the construct before you about quality of life. How can we break this cycle of a lack of innovation resulting in poor quality and outcomes and a high cost burden? I would submit to you that one way that we may be able to break the cycle
is through patient centered innovations. Patient centered innovation, whether it's discovery or process of care innovation, is basically innovation that targets the issues that are important to patients, not necessarily the issues that are important to physicians,
or payors, or regulators, or to industry. The reason that this is important is that the things that are relevant and critical to patients are often very different from the things that are important to the other stakeholder groups that I mention. If you look at hemodialysis for example
the things that are important to a patient on hemodialysis are ability to travel, and dialysis free time, and not feeling washed out post dialysis. On the other hand, if you're an nephrologist as I am, the things that are important to me are survival, and hospitalization, and being a nephrologist
I completely obsess about blood pressure which is really not something that patients are that worried or bother about. The next question is, of course, how do we develop therapies that address the issues that are important to patients? I got this slide from Frank Hurst at the FDA.
It basically makes the point that we need to have patient input at every point in the product development process, from initial ideation, to clinical trial design, to patient preferences, to patient centered outcomes. The FDA actually has a number of programs
in this area, one example is their Patient Focused Drug Development Initiative which allows the FDA to speak with patients and patient groups in different therapeutic areas. Closer to home, the Medical Device Innovation Consortium is extremely interested in Patient Preferences
and in a Risk-Benefit analysis. Within the kidney health initiative, which is a public-private partnership between the American Society of Nephrology and the FDA, we are also very interested in patient preferences for renal devices, and the background for this is
that an individual patient's tolerance for risk actually varies tremendously. Patients on home hemodialysis, for example, may be happy to sacrifice some degree of safety with regard to, say, vascular access, in order for an improved
or a more independent quality of life. But if you're a regulator there needs to be a way that you can get insight in to how patients perceive the risk/benefit ratio so that it can be incorporated into the regulatory pathway, and at least at the present time
the tools for this do not exist. The Kidney Health Initiative hosted an extremely successful patient preference workshop in the Baltimore area a couple of years ago. We asked three main questions: how can patients assist in the development
of a new medical device? How can they ensure the success of future clinical trials? And how can they help with the decision to make a new device available? The proceedings of this workshop have been published, and I'm really not going to go into details there.
I'm going to share with you a video that was made to try and attract patients to this webinar, and I think it really epitomizes the importance of patient centered innovation. - Hello, I'm CeCe, a fellow kidney disease patient. For 33 years I've done dialysis, both hemo and PD.
I had a transplant for 10 years and as you can imagine too many pills, shots, and accesses to mention. As kidney patients you and I both know that a few things in life are not optional. Strength, courage,
persistence, and determination. No matter what life throws at us, we try to stay balanced, maintain our routine, and remain positive. But let's face it, we are often in a holding pattern. Kidney disease treatments have not
changed much over the years. The options for patients like us have largely remained the same for many years. You want to help change that? We need you. Each day we're asked to share our lives with our treatment. But now, let's share our voice, ideas, opinions.
From patients like us, they matter. Key people are realizing our voices matter too. Here's what I found out. The Food and Drug Administration, often known as the FDA, is looking for patients living with kidney disease like you and me, to provide input
on how potential treatments of the future could look. Picture a big table. Around it are dialysis caregivers, researchers, doctors, nurses, and companies providing new products and treatments. They want us and our families to sit beside them
and have a seat at this table. We'll work together to bring potential new treatment options, safe and effective ones, and ones that patients like you and me want and need. Imagine the future of your treatment. What does it look like?
How does it improve your day-to-day life? This future doesn't have to remain just a dream. Join me and other patients to contribute our thoughts and make our ideas a possible reality. - The driving force and also the voice behind that video was the lady on the right, Celeste Lee.
She was a dialysis patient for over 30 years, she was a member of the KHI board of directors, and Celeste died a year and a half ago, she basically withdrew from dialysis because of bone disease from the 30 years of dialysis. I really think that her death
should be a charge for all of us really to try and develop therapies that target the things that are important to patients. Thank you very much for your attention.
- Thank you, Larry and Tony, for the invitation. Larry told me I should be provocative so here we go. (chuckles) Those are my disclosures, mostly in the aortic space, although I was a PI for the Humanity Phase II trial. So this is a quote that interventional nephrologists in Arizona told me one day when we were trying
to have a educational, meaningful discussion, so we provide care that is better, faster, and cheaper than what you can provide in the hospital. And we'll address this a little later. What's the roles of the access surgeon, when it comes to advocating or educating
your dialysis patients? Well, when you google advocating for anything, you're going to find mostly political references. And I think there are a number of excellent patient related groups to advocate for policies and principles. But as the surgeon, I think we have
a couple of important roles. One, we need to create the most durable, successful access possible, and as Ted just said, that needs to be individualized for the patient. We need to try and protect and maintain the access and we also have a role in protecting the patient.
We can't underestimate or underemphasize the importance of vessel mapping, both arterial and venous. We frequently get patients referred who have already had their mapping somewhere else but as the surgeon is going to be doing the procedure, we tend to repeat that in the office,
so that we can see it ourselves, because mapping can be variable, can depend on environmental conditions, how cold the patient's room is, their hydration status, so we really try and nail that down. And frequently we find a high bifurcation
of the brachial artery, that's not noted on other mapping. And, again, I think to emphasize what Ted just said, we really need to champion communication between the patient, the nephrologist, and the surgeon, just because you don't receive communication, doesn't mean you can't be the person who provokes
and stimulates communication back to the nephrologist to try and really develop a clear plan. The timing of the hemodialysis is imperative and I think we should consider early cannulation grafts in appropriate patients. What about protecting and maintaining the access,
well these slides were provided to me by Dori Schatell, who's given this talk, you need to arm your patients with information to advocate for themselves and that's really, kind of the theme of what I want to talk about later. Give them pictures of their access,
write them very clear postop instructions, teach patients about cannulation patterns, teach them how to use topical anesthetics for cannulation. Make sure they know what to do in the case of an infiltration or prolonged bleeding, or loss of the thrill.
Make sure they have your contact information, and encourage patients to learn how to self-cannulate. What about protecting the patient? Well, I think it's our, it's the team's obligation but seems to fall on us a lot to educate the patient and their family about their right to choose.
Educate the patient and their family about available providers and facilities in their area. And educate the patient and their family about what services are available at different facilities, and nephrologists , radiologists, surgeons and anesthesiologists.
- Okay, I went to my nephrologist. He told me I needed to get this fistula put in, and then I was directed to the access center, because the way he said it, that's where I had to go to get it done, after I'd already talked to another doctor about doing it,
I was told I had to go to the access center. Okay-- - Oop, let's see. - Um, what she didn't say is that, she didn't like the center in the first place, because originally the doctor that saw her there for the fistula, didn't give us any help.
So he said, I can't do it for you, I don't know what's going to happen, and every time we would ask him, well, is there any solution for her to get a fistula, he wouldn't answer our question and he's like, well, I can't, I can't help you, I'm not going to take it.
So, when they told her told to go to that center, she had told him, can I go somewhere else, somewhere where they're a little bit more professional? And they said, no, you have to go there, they're the specialists. - So, going back to the original comment.
We provide care that is better, faster, and cheaper than what you can provide in the hospital. Well, when you're talking about better, that's really measured only by safety and durability of the interventions, not opinions. And faster, unfortunately, in our area,
some of our access centers are closed on Wednesdays, some of them are closed on Fridays and the weekend. And it's interesting, we often, the surgeons in town often get pummeled on Friday because the access center is closed. And I can tell you that my weekend on call,
I spent about half my day Saturday doing access interventions. And cheaper, cheaper's really only a function of how payers have decided to reimburse. You pay the same amount for staff, electricity, and supplies, whether you're at a hospital,
a surgery center, or an OBL. Unfortunately, some access centers frequently choose therapies that are less effective but cheaper to protect their margins. And perfect examples of these are stent grafts, and drug-coated balloons.
I think hemodialysis patients really want care that is safe, effective and durable. And really, where that's going to be best achieved will depend on what's available in a particular community or region. And most importantly, and I think,
as Ted highlighted, they're really the commitment to providing excellence in access care. And I'll finish with one more little vignette from one of my patients, and these patients, actually this was unsolicited, they just happened to be going off in the office one day
and I had gotten this assignment, I said, you mind if I video this and use it in my presentation? - Basically, in my opinion, what it is, it needs to be patient education. The ones that do talk to me, 'cause I do take control
of my treatments completely. That's why my fistula's in such good shape, 'cause I'll only run 16 gauge needles, which slows down my treatment, which keeps my heart in better shape. That's why I'm still up, walking, doing what I do.
- Thank you very much.
- Thank you Tom. Good morning ladies and gentlemen. I like to thank, too, the organizing committee and Doctor Veith for the invitation. No conflict of interest. Venous and lymphatic system are mutually dependent dual outflow system of the circulation
we all know. When one of these two mutually interdepdent should fail, it gives additional burdening to the other system. When this additional loading should exceed its limit such a condition would precipitate a fail
of other system as well resulting in total fail of these two inseparable system all together resulting in so-called phlebolymphedema. Hence phlebolymphedema represent the combined condition of chronic venous as well as a lymphatic insufficiency as the outcome of simultaneous fail
of dual outflow veno-lymphatic system. Primary phlebolymphedema represent combined condition of venous insufficiency caused by the venous malformation and they vary in severity by the lymphatic malformation simultaneously. Most common venous malformations cause
the venous insufficiency in this group is a marginal vein with a venous reflux and hypertension. Lymphatic insufficiency for this group is mostly due to primary lymphedema by truncular malformation. These two vascular malformations together to cause a primary phlebolymphedema too
as the most common vascular disorder of the Klippel-Trenaunay Syndrome you are all familiar with. Chronic venous insufficiency of secondary phlebolymphedema however, is mostly due to the sequellac of post-thrombotic syndrome following deep vein thrombosis.
The venous insufficiency of secondary phlebolymphedema is generally secondary outcome of regional lymphedema following steady progress of the local tissue damage by recurrent infection. Secondary phlebolymphedema therefore developed along the end stage of CVI caused the local condition
more complicated with local lymphedema often as a newly added condition. For the diagnosis. Assessment of the phlebolymphedema should start with proper diagnosis of etiology to differentiate two different types.
Non-invasive tests alone is generally sufficient for the basic assessment of the extent severity of the chronic venous insufficiency. However, secondary phlebolymphedema phlebography is infrequently indicated. Lymphoscintigraphy in general is essential
for the chronic lymphatic insufficiency assessment. Full investigation of the venous malformation and lymphatic malformation is mandated before proceeding to any individual assessment of venous and the lymphatic insufficiency based on the non-invasive tests.
Marginal vein assessment for the reflux to cause the venous insufficiency should be done with simultaneous deep vein assessment the for the possible coexisting venous dysplasia. Baseline therapy for the phlebolymphedema is the compression therapy reinforced
with decongestive lymphatic therapy to control venous as well as lymphatic insufficient all together. Marginal vein as the cause of venous insufficiency can be treated with resection or embolo-sclerotherapy as long as deep vein system is fully developed
to be able to handle diverted blood influx. Deep vein reconstruction to relieve venous insufficiency caused by deep vein dysplasia can be beneficial only when there is a clear evidence for the hemodynamic gain. Secondly phlebolymphedema with CVI by PTS
should be treated more aggressively to relieve the cause of obstruction with various forms of open surgical endovascular therapy. When the CVI is caused by a multilevel DVT sequellac even minimum correction is able to assist tremendous improvement efficacy.
As the conclusion, phlebolymphedema can be managed more effectively when open or endovascular therapy is added to the basic compression therapy. Primary phlebolymphedema with CVI caused by reflux of marginal vein can be treated successfully with a marginal vein resection.
And secondary phlebolymphedema with venous insufficiency caused by PTS can be further improved with correction of venous outflow obstruction with angioplasty stent. Thank you for your attention.
- So I'd like to thank Dr. Ascher, Dr. Sidawy, Dr. Veith, and the organizers for allowing us to present some data. We have no disclosures. The cephalic arch is defined as two centimeters from the confluence of the cephalic vein to either the auxiliary/subclavian vein. Stenosis in this area occurs about 39%
in brachiocephalic fistulas and about 2% in radiocephalic fistulas. Several pre-existing diseases can lead to the stenosis. High flows have been documented to lead to the stenosis. Acute angles. And also there is a valve within the area.
They're generally short, focal in nature, and they're associated with a high rate of thrombosis after intervention. They have been associated with turbulent flow. Associated with pre-existing thickening.
If you do anatomic analysis, about 20% of all the cephalic veins will have that. This tight anatomical angle linked to the muscle that surrounds it associated with this one particular peculiar valve, about three millimeters from the confluence.
And it's interesting, it's common in non-diabetics. Predictors if you are looking for it, other than ultrasound which may not find it, is calcium-phosphate product, platelet count that's high, and access flow.
If one looks at interventions that have commonly been reported, one will find that both angioplasty and stenting of this area has a relatively low primary patency with no really discrimination between using just the balloon or stent.
The cumulative patency is higher, but really again, deployment of an angioplasty balloon or deployment of a stent makes really no significant difference. This has been associated with residual stenosis
greater than 30% as one reason it fails, and also the presence of diabetes. And so there is this sort of conundrum where it's present in more non-diabetics, but yet diabetics have more of a problem. This has led to people looking to other alternatives,
including stent grafts. And in this particular paper, they did not look at primary stent grafting for a cephalic arch stenosis, but mainly treating the recurrent stenosis. And you can see clearly that the top line in the graph,
the stent graft has a superior outcome. And this is from their paper, showing as all good paper figures should show, a perfect outcome for the intervention. Another paper looked at a randomized trial in this area and also found that stent grafts,
at least in the short period of time, just given the numbers at risk in this study, which was out after months, also had a significant change in the patency. And in their own words, they changed their practice and now stent graft
rather than use either angioplasty or bare-metal stents. I will tell you that cutting balloons have been used. And I will tell you that drug-eluting balloons have been used. The data is too small and inconclusive to make a difference. We chose a different view.
We asked a simple question. Whether or not these stenoses could be best treated with angioplasty, bare-metal stenting, or two other adjuncts that are certainly related, which is either a transposition or a bypass.
And what we found is that the surgical results definitely give greater long-term patency and greater functional results. And you can see that whether you choose either a transposition or a bypass, you will get superior primary results.
And you will also get superior secondary results. And this is gladly also associated with less recurrent interventions in the ongoing period. So in conclusion, cephalic arch remains a significant cause of brachiocephalic AV malfunction.
Angioplasty, across the literature, has poor outcomes. Stent grafting offers the best outcomes rather than bare-metal stenting. We have insufficient data with other modalities, drug-eluting stents, drug-eluting balloons,
cutting balloons. In the correct patient, surgical options will offer superior long-term results and functional results. And thus, in the good, well-selected patient, surgical interventions should be considered
earlier in this treatment rather than moving ahead with angioplasty stent and then stent graft. Thank you so much.
- [C. Keith] Thank you Larry and John. I appreciate the invitation. I do have disclosure that I have consulted for Proteon Therapeutics. Also, some of the data I'm going to talk about today is unpublished and supplied by Proteon. So, Vonapanitase is a recombinant human elastase
and it cleaves elastin peptide bonds. Surgically, this can be applied to the outside of a recently created fistula and it's left on for 10 minutes. It's only active at the site of application, if it gets in the blood, it's deactivated.
Biologically, Vonapanitase may stimulate outward vascular remodeling and also inhibit intimal hyperplasia. I'm going to update you now on the Vonapanitase Fistula Trial Program. These trials have all been multicenter, randomized, double blinded, placebo controlled studies
and each includes a follow up registry. Three of these trials are already in print and one is in press. The phase two trial of which I was an investigator showed a dose dependent improvement in maturation of dialysis access fistulas at the wrist.
And thus, it moved to phase three trials. I'm an investigator in both of those and these are going to be the focus of my comments today. The patency-3 trial is fully completed. The patency-1 trial is fully completed and in press. And the patency-2 is fully enrolled.
Patency-1 enrolled about 300 patients undergoing a radiocephalic fistula and it was randomized two to one vonapanitase to placebo. Follow up was one year. The primary endpoint was primary patency and the secondary endpoint was secondary patency.
Other important endpoints were examined and also, statistically, they looked at these other endpoints beyond just the single primary patency. The primary patency was not statistically different in the trial, though there was a substantial trend. Here you see a p of 0.25 for the difference
between the vonapanitase and the placebo treated patients. However, there was a statistically significant 34% reduction in the risk of secondary patency loss and those receiving the treatment drug and this was statistically significant. It even became more statistically significant
when we discarded those that had early failure of the fistula, certainly showing a biological effect probably of this compound. And then, finally another point that we're very interested in would be actual use of the fistula for hemodialysis
and it was almost a 50% increase in use of the fistula for hemodialysis in those receiving the drug versus those getting placebo. The safety profile looked quite good for this compound and there were basically similar rates between the placebo and vonapanitase for stenosis,
thrombosis, nerve issues and post procedural pain. The patency-2 trial is almost identical but it actually began enrolling during the patency-1 trial and the analysis plan allowed for a sample size adjustment based on results of the patency-1 trial. So in negotiating with the FDA,
they agreed to the validity of reordering the endpoints to create new primary and secondary endpoints or co primary endpoints. And so, for the patency-2 trial, secondary patency and use for hemodialysis were made co primary endpoints. Also, the sample size was increased
to 600 patients to ensure adequate power. Here you're going to see some of the baseline characteristics of these patients that were enrolled in the patency-2 trial. It's a typical age and typical North American body mass index and most of the patients were male in a three to one ratio to females.
There's a nice mix of ethnicities and race. Many of the patients had been former smokers and most had diabetes and hypertension and hyperlipidemia. About half the patients were on hemodialysis at the time of randomization. And interestingly, when you look at
the anesthetic approaches, about half the cases were done under local and the others were done under nerve block or general anesthetic. The actual expose vein length was about three centimeters in this patient cohort. The vein diameters were a little over three millimeters
and the artery diameters a little under three millimeters. Most of the surgeons tended to make an arteriotomy that was about eight millimeters long. The patency-1 results have been accepted or in press in the journal of vascular surgery. The patency-1 registry data with a total of three years
of follow up will be available towards the end of this year. Patency-2 enrollment is completed, that was completed this past March and the top line data will be available in March of 2019. If the data supports these statistical significance on the co primary endpoints in this patency-2 trial,
Proteon intends to file for US approval in 2019 and EU approval shortly thereafter and they're actually planning clinical trials in Europe currently. So in summary, vonapanitase data to date in radiocephalic fistula's, certainly I think,
shows evidence of the biologic signal which I think is quite impressive in view of all the events that go into fistula maturation. The secondary analysis suggests positive impact on things that we find clinically meaningful. That is use for hemodialysis,
unassisted use for hemodialysis and secondary patency. The patency-2 trial data, the big 600 patient cohort will be available in about four months and vonapanitase certainly stands as a potentially novel adjunct to enhance AV fistula use for hemodialysis. Thank you.
- Ladies and gentlemen, I thank Frank Veith and the organizing committee for the invitation. I have no disclosures for this presentation. Dialysis is the life line of patients with end-stage renal failure. Hemodialysis can be done by constructing an A-V fistula, utilizing a graft or through a central venous catheter.
Controversy as to the location of A-V fistula, size of adequate vein and priority of A-V fistula versus A-V graft exists among different societies. Our aims were to present our single center experience with A-V fistulas and grafts. Compare their patency rates,
compare different surgical sites, and come up with preferences to allow better and longer utilization. We collected all patients who underwent A-V fistula or A-V graft between the years 2008 through 2014. We included all patients who had preoperative
duplex scanning or those deemed to have good vessels on clinical examination. Arteries larger than two point five millimeter and veins larger than three millimeter were considered fit. Dialysis was performed three times per week. Follow up included check for a thrill,
distal pulse in the arter non-increased venous pressure or visible effective dialysis and no prolonged bleeding. Any change of one of the above would led to obtaining
fistulogram resulting in either endovascular or open repair of the fistula. We started with 503 patients, 32 of which were excluded due to primary failure within 24 hours. We considered this, of course, the surgeon's blame. So we left with 471 patients with a mean age of 58 years,
51 were older than 60, there was a male predominance of 63%, and over half were diabetics. The type of fistula was 41% brachio-cephalic fistula, 30% radio-cephalic fistula, 16% A-V Graft, and 13% brachio-basilic fistula.
Overall, we had 84% fistulas and 16% grafts. The time to first dialysis and maturation of fistula was approximately six weeks. First use of grafts was after two weeks. 11 patients with A-V fistula needed early intervention prior to or after the first dialysis session.
In sharp contrast, none of the A-V grafts needed early intervention. 68 patients were operated for their first ever fistula without duplex scanning due to clinically good vessels. Their patency was comparable to those who underwent a preoperative scanning.
Looking at complications, A-V grafts needed more reintervention than fistulas. All of them were late. Infection was more prominent in the graft group and pseudoaneurysms were more prominent in the A-V fistula group, some of them occluded
or invaded the skin and resulted in bleeding. Here's a central vein occlusion and you can see this lady is after a brachio-basilic A-V shunt. You can see the swollen arm, the collaterals. Here are multiple venous aneurysms. Here's an ulcer.
When we looked at primary patency of A-V fistulas versus graft, A-V fistulas fared better than grafts for as long as five years. When you looked at 50% patency in grafts, it was approximately 18 months, in Fistula, 13. Here's an assisted primary patency by endovascular technique
and when we looked at the secondary patency for the first 24, two years, months, there was no difference between A-V fistulas and A-V grafts, but there's a large difference afterwards. Comparing radio-cephalic fistula to brachio-cephalic fistula there was really no big difference in maturation.
The time was approximately six weeks. As for primary patency there is a trend towards better patency with brachio-cephalic fistula after six months, one year, and two years, but it didn't reach statistical significance. For patients with diabetes,
differences were statistically significant. Brachio-cephalic fistula showed a trend toward shorter maturation time, needed less reintervention, and had a longer patency rate. In conclusions then, ladies and gentlemen, A-V fistula require a longer maturation time
and have higher pseudoaneurysm formation rate, but better patency rates compared to A-V grafts. A-V grafts have a faster maturation time, but more late interventions are required and infection is more common. Finally, diabetic patients have a better result
with proximal A-V fistulas. Thank you for the opportunity to present our data.
- Thank you so much. We have no disclosures. So I think everybody would agree that the transposed basilic vein fistula is one of the most important fistulas that we currently operate with. There are many technical considerations
related to the fistula. One is whether to do one or two stage. Your local criteria may define how you do this, but, and some may do it arbitrarily. But some people would suggest that anything less than 4 mm would be a two stage,
and any one greater than 4 mm may be a one stage. The option of harvesting can be open or endovascular. The option of gaining a suitable access site can be transposition or superficialization. And the final arterial anastomosis, if you're not superficializing can either be
a new arterial anastomosis or a venovenous anastomosis. For the purposes of this talk, transposition is the dissection, transection and re tunneling of the basilic vein to the superior aspect of the arm, either as a primary or staged procedure. Superficialization is the dissection and elevation
of the basilic vein to the superior aspect of the upper arm, which may be done primarily, but most commonly is done as a staged procedure. The natural history of basilic veins with regard to nontransposed veins is very successful. And this more recent article would suggest
as you can see from the upper bands in both grafts that either transposed or non-transposed is superior to grafts in current environment. When one looks at two-stage basilic veins, they appear to be more durable and cost-effective than one-stage procedures with significantly higher
patency rates and lower rates of failure along comparable risk stratified groups from an article from the Journal of Vascular Surgery. Meta-ana, there are several meta-analysis and this one shows that between one and two stages there is really no difference in the failure and the patency rates.
The second one would suggest there is no overall difference in maturation rate, or in postoperative complication rates. With the patency rates primary assisted or secondary comparable in the majority of the papers published. And the very last one, again based on the data from the first two, also suggests there is evidence
that two stage basilic vein fistulas have higher maturation rates compared to the single stage. But I think that's probably true if one really realizes that the first stage may eliminate a lot of the poor biology that may have interfered with the one stage. But what we're really talking about is superficialization
versus transposition, which is the most favorite method. Or is there a favorite method? The early data has always suggested that transposition was superior, both in primary and in secondary patency, compared to superficialization. However, the data is contrary, as one can see,
in this paper, which showed the reverse, which is that superficialization is much superior to transposition, and in the primary patency range quite significantly. This paper reverses that theme again. So for each year that you go to the Journal of Vascular Surgery,
one gets a different data set that comes out. The final paper that was published recently at the Eastern Vascular suggested strongly that the second stage does consume more resources, when one does transposition versus superficialization. But more interestingly also found that these patients
who had the transposition had a greater high-grade re-stenosis problem at the venovenous or the veno-arterial anastomosis. Another point that they did make was that superficialization appeared to lead to faster maturation, compared to the transposition and thus they favored
superficialization over transposition. If one was to do a very rough meta-analysis and take the range of primary patencies and accumulative patencies from those papers that compare the two techniques that I've just described. Superficialization at about 12 months
for its primary patency will run about 57% range, 50-60 and transposition 53%, with a range of 49-80. So in the range of transposition area, there is a lot of people that may not be a well matched population, which may make meta-analysis in this area somewhat questionable.
But, if you get good results, you get good results. The cumulative patency, however, comes out to be closer in both groups at 78% for superficialization and 80% for transposition. So basilic vein transposition is a successful configuration. One or two stage procedures appear
to carry equally successful outcomes when appropriate selection criteria are used and the one the surgeon is most favored to use and is comfortable with. Primary patency of superficialization despite some papers, if one looks across the entire literature is equivalent to transposition.
Cumulative patency of superficialization is equivalent to transposition. And there is, appears to be no apparent difference in complications, maturation, or access duration. Thank you so much.
Thanks very much, Tom. I'll be talking about thermal ablation on anticoagula is it safe and effective? I have no disclosures. As we know, extensive review of both RF and laser
ablation procedures have demonstrated excellent treatment effectiveness and durability in each modality, but there is less data regarding treatment effectiveness and durability for those procedures in patients who are also on systemic anticoagulation. As we know, there's multiple studies have been done
over the past 10 years, with which we're all most familiar showing a percent of the durable ablation, both modalities from 87% to 95% at two to five years. There's less data on those on the anticoagulation undergoing thermal ablation.
The largest study with any long-term follow up was by Sharifi in 2011, and that was 88 patients and follow-up at one year. Both RF and the EVLA had 100% durable ablation with minimal bleeding complications. The other studies were all smaller groups
or for very much shorter follow-up. In 2017, a very large study came out, looking at the EVLA and RF using 375 subjects undergoing with anticoagulation. But it was only a 30-day follow-up, but it did show a 30% durable ablation
at that short time interval. Our objective was to evaluate efficacy, durability, and safety of RF and EVLA, the GSV and the SSV to treat symptomatic reflux in patients on therapeutic anticoagulation, and this group is with warfarin.
The data was collected from NYU, single-center. Patients who had undergone RF or laser ablation between 2011 and 2013. Ninety-two vessels of patients on warfarin at the time of endothermal ablation were selected for study. That's the largest to date with some long-term follow-up.
And this group was compared to a matched group of 124 control patients. Devices used were the ClosureFast catheter and the NeverTouch kits by Angiodynamics. Technical details, standard IFU for the catheters. Tumescent anesthetic.
And fiber tips were kept about 2.5 centimeters from the SFJ or the SPJ. Vein occlusion was defined as the absence of blood flow by duplex scan along the length of the treated vein. You're all familiar with the devices, so the methods included follow-up, duplex ultrasound
at one week post-procedure, and then six months, and then also at a year. And then annually. Outcomes were analyzed with Kaplan-Meier plots and log rank tests. The results of the anticoagulation patients, 92,
control, 124, the mean follow-up was 470 days. And you can see that the demographics were rather similar between the two groups. There was some more coronary disease and hypertension in the anticoagulated groups, and that's really not much of a surprise
and some more male patients. Vessels treated, primarily GSV. A smaller amount of SSV in both the anticoagulated and the control groups. Indications for anticoagulation.
About half of the patients were in atrial fibrillation. Another 30% had a remote DVT in the contralateral limb. About 8% had mechanical valves, and 11% were for other reasons. And the results. The persistent vein ablation at 12 months,
the anticoagulation patients was 97%, and the controls was 99%. Persistent vein ablation by treated vessel, on anticoagulation. Didn't matter if it was GSV or SSV. Both had persistent ablation,
and by treatment modality, also did not matter whether it was laser or RF. Both equivalent. If there was antiplatelet therapy in addition to the anticoagulation, again if you added aspirin or Clopidogrel,
also no change. And that was at 12 months. We looked then at persistent vein ablation out at 18 months. It was still at 95% for the controls, and 91% for the anticoagulated patients. Still not statistically significantly different.
At 24 months, 89% in both groups. Although the numbers were smaller at 36 months, there was actually still no statistically significant difference. Interestingly, the anticoagulated group actually had a better persistent closure rate
than the control group. That may just be because the patients that come back at 36 months who didn't have anticoagulation may have been skewed. The ones we actually saw were ones that had a problem. It gets harder to have patients
come back at three months who haven't had an uneventful venous ablation procedure. Complication, no significant hematomas. Three patients had DVTs within 30 days. One anticoagulation patient had a popliteal DVT, and one control patient.
And one control patient had a calf vein DVT. Two EHITs. One GSV treated with laser on anticoagulation noted at six days, and one not on anticoagulation at seven days. Endovenous RF and EVLA can be safely performed
in patients undergoing long-term warfarin therapy. Our experience has demonstrated a similar short- and mid-term durability for RF ablation and laser, and platelet therapy does not appear to impact the closer rates,
which is consistent with the prior studies. And the frequency of vein recanalization following venous ablation procedures while on ACs is not worse compared to controls, and to the expected incidence as described in the literature.
This is the largest study to date with follow-up beyond 30 days with thermal ablation procedures on anticoagulation patients. We continue to look at these patients for even longer term durability. Thanks very much for your attention.
- Good morning everybody, and thank you for inviting me again for the same topic since five years now. Every time I have to rebuild my slides, and you will see why. So, you all know this story, renal denervation was almost destroyed by The Earthquake on January 9, 2014, and that was when Medtronic announced that HTN-3
did not make it to primary endpoint. What has been achieved since the earthquake? Better techniques with old devices, positive trials with old devices, new devices, and some positive trials with new devices. So, what about better technique?
More is better, that's what we learned, total number of ablation is important, circumferential ablation is important. Go distal is important in distal vessel segments, the nerves are closer to the vessel wall. We have the DENER-HTN heart trial with the old system
which was positive, and we have new devices, like the Symplicity Catheter, Spyral Catheter, the Vessix, Paradise, and Peregrine. So, what about new trials with new devices? Spyral HTN-OFF MED, HTN-ON MED, REDUCE HTN, RADIANCE HTN SOLO, RADOSOUND-HTN,
and Peregrine PMS - TARGET BP OFF-MED trial. SPYRAL HTN - OFF MED was a trial with patients without medications, or permitting discontinuing the oral drug therapy at that time, and they had to make certain values of blood pressure office and 24 hours, and you can see the results.
There was a significant effect in all parameters in systolic blood pressure ties to the blood pressure. 24-hour blood pressure and all these differences have been significant in favor of innovative denervation, so renal denervation certainly works. What about in those patients who are on meds,
and this has also been reported now. You see the patients had to have one to three anti-hypertensive medications. Again, they had to fulfill certain criteria regarding their blood pressure, and when you look at the result safety, it's very safe procedure,
no adverse events occurred, and office blood pressure changed from baseline to six months, it was a significant decrease systolic and diastolic blood pressure as well as 24-hour blood pressure, so renal denervation also works in patients
who are on anti-hypertensive medication. Reduce HTN was a trial with the Vessix system, which is not really a new system, but this is a new trial, and they used a balloon-based radiofrequency technique. They did an off-med study, the primary endpoint was reduction in 24-hour ambulatory blood pressure,
at eight weeks, which probably was too early, and the trial was stopped early due to slow enrollment and because it was determined that the trial could not achieve its primary endpoint at eight weeks, but when you look at the long-term results with this trial, there was actually a significant rate
of proportion of Vessix patients with office blood pressure below 140 versus control after six months, and this was significant and there was also over six months, systolic blood pressure continued to decrease in the Vassix group with a lesser decrease in the control group, and these differences
also have been significant to the match major part. RADIANCE HTN-SOLO trial is using the Ultrasound Based Renal Denervation using a balloon technology. You can see that these patients responded. There was a clear benefit in favor of the technique compared to a placebo group, significant difference 0.001.
Radiosound HTN was a trial, a randomized blinded trial comparing the different techniques, like ablation of the center part of the renal artery, distal part of renal artery, and ultrasound, and there was a significant benefit of ultrasound compared to the ablation of the proximal renal artery only.
Peregrine is using alcohol injected into the adventitial space, also significant effect of this technique, so now we have multiple randomized blinded renal denervation trials, OFF and ON meds, which are clearly positive. The decrease of blood pressure is, without any question,
clinically relevant, but it is smaller than expected and hoped. Everybody is asking, "Does it justify an invasive procedure? "So better not to do it?" At the same time, no major adverse events occurred, so why not to do it?
Everybody agrees that more research is needed. There are other device based approaches which are either stopped or covered by other talks in this, so I'm going to skip this. Thank you much for your attention.
- I'd like to thank Dr. Veith and the organizers for the invitation. I'm a speaker for Gore medical, and I receive grant support and speaking fees from Acelity. I'd also like to thank my former partners at UPMC for their help with this study.
So are catheters really that bad? Of course we all know the answer's yes. The risk of bacteremia is 10-fold higher than with an AV fistula, and approximately 5 1/2 septic episodes per 1,000 catheter days are seen
in dialysis patients. This is not only a costly but can be a deadly problem. This is a shot of a 23 year old patient of mine who had been maintained on catheters for a long while,
and I was treating for SBC syndrome. So why can't we place fistulas earlier and avoid catheters altogether? 80% of patients start dialysis with a catheter. This is a multifactorial problem including late referrals to nephrology,
a difficulty of nephrologist to find available surgeons. Perhaps percutaneous fistula creation which is on the cutting edge of dialysis technology might help with this problem. But right now nationwide there's a backlog
of dialysis patients needing surgeons. Compounding this problem is that many patients don't have coverage for surgery until three months of dialysis care. And the proportion of patients getting dialysis fistulas pre-dialysis may be declining
according to a recent Canadian survey. In this survey they found that even in patients who had fistulas created, 11% of those fistulas weren't usable at the time of dialysis initiation. And in patients who had had
two or more surgeries, 35% of those fistulas were not able to be used. AV grafts are associated with a faster catheter removal, but more interventions over the first year of placement than AV fistulas.
TDC removal is faster with AV grafts, but it still takes longer than we all expect. We think an AV fistula should be ready to use at six weeks when indeed the median time to use is closer to 18 weeks. AV grafts we think are ready to use at two weeks,
when the median is actually closer to 9 weeks and this data is also from UPMC. Our aim in this recent study was to compare the real world performance of standard AV grafts and immediate use AV grafts in a dialysis population looking at catheter time.
Taking results from Duke and UPMC combined, we made three groups of patients: the standard AV graft patients, immediate use AV graft patients in a conventional configuration, and immediate use grafts combined
with a HeRO catheter. The demographics across these groups were similar with the exception of HeRo patients having more central venous occlusions, and immediate use AV grafts having a lower percentage of prevalent TDCs.
This was due to a small number of patients getting immediate use AV grafts on initiation of dialysis in place of a catheter. When we looked at complications across these groups, we found that there was no significant difference
in perioperative deaths, steal or AV graft infection. However we found that AV grafts were able to be used in the immediate access group significantly more often than in the standard group.
We found no results, no significant differences in our patency results either primary or secondary between the groups. However, immediate use AV grafts matured at a significantly faster rate, they had significantly fewer catheter days,
and most importantly had fewer catheter-related complications and fewer reinterventions for prolonged patency. We also looked at other authors who had studied this problem, and found that the majority
of immediate use grafts are able to be used within 24 to 72 hours. Other facilities to or other measures to facilitate early catheter removal are to have an organized approach to dialysis access.
In my office we have a schedule and we stick to it. We schedule all appointments at the patient's original visit, and I found that this is especially important for two-stage basilic vein transpositions.
Where we schedule their pre-op, their first and second surgery, all of their post-op visits and even their catheter removal visit at the initial time. Of course these can change,
but it gives us a structure to work in. We get patients back early to clinic sort of like Dr. Shenoy was just talking about. We see patients at four weeks with a fistula, and at two weeks with a graft. And if the access is not usable at that time,
we go immediately to fistulagram. We make an appointment to return to the clinic one month after we clear fistulas for use, with the plan to remove the catheter in clinic. If the catheter is not ready to come out for any reason,
then we troubleshoot the problem to make sure we stay on track. Our goal is to get those catheters out. So in conclusion, reducing catheter days can be accomplished through several means.
I believe we can do better through early fistula placement, and insurance that the fistula is ready to use at the time that the patient is ready to start dialysis. I think we can benefit our patients by
having more practitioners place fistulas. We should consider the judicious use of immediate access grafts, and perhaps use immediate access rather than standard grafts whenever possible. And we should have protocols to facilitate
early follow-up and troubleshooting of accesses as well as being proactive in catheter removal. Thank you.
- Alright, well thank you, everybody, for having me. Thanks, Larry for inviting me to give this talk. My only disclosure is that I am the vice president of operations for (clears throat), excuse me, Azura Vascular Care and we operate 65 office based laboratories and ambulatory surgery centers. So, the undertaking to go ahead
and become a ambulatory surgery center is massive and requires a tremendous amount of pre-planning. You have to have a very sound financial model, you have to have a stable physician pool, you have to have a good patient referral base. And without lining up all those elements first,
you are sort of dead in the water. So the first thing to understand is that a physician's office and an ambulatory surgery center are separate and distinct entities. Today if you have a physician's office through an extension of your practice
you can then set up an Angio Suite, you can then perform procedures on the patients as needed. But once you're an ambulatory surgery center, you no longer have sort of the office space part. So you can't do ultrasounds, well you can do them, you just can't bill for them, right.
And so you can't concurrently run a physician's office practice out of the ambulatory surgery center, it's actually not permitted in the Medicare conditions for coverage. So that changes things for sure.
And then so if you're really based out of a physician's office and you have your Endo Suite there, you sort of have to have two offices moving forward. Anyway, you must comply with Conditions for Coverage. The ASC is now subject to State, CMS, and Accrediting bodies and they can show up at any time.
It's a major difference in the way you practice. If it's your doctor's office right now, you know, maybe there's a inspection once a year for a radiation certificate or something like that, but there's really not a whole lot of oversight. ASCs have very strict physical plant guidelines.
There are enhanced staffing requirements, circulating nurses, facility administrators, directors of nursing, all of these extra things that add a very significant amount of cost. You also have to have governance, right. So there's a governing body, a Medical Executive Committees
and requirements, right. Now they're not difficult but there's all this extra documentation that has to go along with it which is just time consuming, burdensome, task oriented. There's disclosures of ownership.
There's a quality improvement program which you have to show that you're doing and documented, and the accrediting bodies, if you don't have it right, they could cite you and it's really a lot of extra work. You need transfer agreements and patient satisfaction surveys,
all these kinds of things. Alright, other ASC fact, okay. In a typical two room facility, you can get away with essentially 35 hundred square feet versus five thousand square feet in an ASC. You would instead of typically having six employees,
you need nine employees, adding all this extra expense. The expertise of the staff is very different, alright. You actually need facility administrators, not just, you can't just pluck a nurse out of their daytime job of seeing patients on the floor and say, okay, now you're facility administrator.
They have to understand regulations, they have to understand the Medicare Conditions for Coverage, et cetera. They have also very extended timeline, which I'll show you on another slide, but the regulatory requirements from life safety,
fire safety, staffing requirements, state licensure, Medicare Deem status, accreditation, all of these things factor into the overall cost to set up an OBL, depending on how you do it, is probably about 1.5 million dollars, versus an ASC at 3.5 million dollars.
So the 800 pound gorilla in states in New York, and about 25 or 30 other states is the process of getting a certificate of need. So if you're in a certificate of need state, it's a whole thing, right. So first you have to get the CON.
The CON then allows you to get state licensure. The state licensure then allows you to apply for Medicare Deem status to an accrediting body. Once you have your Deem status, then you can submit for your PTAN, your physician transaction number, so that you can actually bill Medicare for facility fees,
and then and only then can you then initiate the entire process of getting your private payor contracts. So, all that being said, your application for a CON could be outright rejected. You could be blocked by local hospitals. You could be blocked by local politics.
There's a tremendous amount of issues. Now the one thing that's interesting, if you're in a state that doesn't have a Certificate of Need process, then one of the things that's interesting is they sort of, you sort of get tied up in the local fire marshal, the Department of Health
and this very disjointed Department of Health survey. The Certificate of Need at least, at the very least, allows you to kind of cruise through the process, so that you can, at least you understand your pathway. In states that don't even have a CON process, it can be very disjointed.
Now if you're thinking about building a new facility, well, that's about two to two and a half million dollars. If you're thinking of retrofitting, I'd go by the rule of 200 thousand. So if you need a semi-restricted corridor, and you have to move walls,
that'll cost you about 200 thousand. If you, you're going to need 20 air exchanges per hour in your procedure room, that's a hard requirement. You have to be, you have to get stuff that certifies that you are achieving that, right. That new HVAC system will cost you 200 thousand dollars.
You need three electrical panels. One to power the HVAC, one to power the electrical outlets and one to power the overhead lighting. I mean, the requirements are very, very different. Then, maybe now you're going to need a generator. Well, am I in a building where you're going to
put the generator on the roof, then the fire marshal tells me I can't store the gasoline on the roof, it has to be on the ground, and then you wind up in this big back and forth fight as to where you can put your generator.
Just for time's sake, this is a basic floor plan with semi-restricted corridors, eight foot wide hallways, enough seating for 30 people. The staffing requirements change significantly, in terms of you need a facility administrator, somebody who really knows it.
Now god forbid the facility administrator's on vacation when the state shows up or when an accrediting body shows up so you better have your DON, your director of nursing, all tuned up so that she knows how to answer the questions and knows where all of your paperwork are because otherwise you could be cited
and you could be sunk and it's very burdensome. But the difference in staff costs for typical two room facility is probably about 300 thousand dollars cumulatively. For your hours of operation, right, so now you have a business that's operating as an OBL,
now you want to convert it to an ASC, well that's great. But now you don't have your private payor contract, so what are you going to do? You going to start rejecting patients? So, no, you're not going to do that. So either you're going to lose money on those patients
or you're going to wind up having to form this hybrid operation where you flip back and forth, one day to the next day, et cetera. And the problem with doing that is each one requires its own tax ID number, its own NPI, its own billing codes. And then the staff has to be trained
that they're dedicated to one versus the other. This is your timeline to show you how everything lines up, in terms of your construction, then getting your state licensure, then getting your Medicare accreditation, and then only after you get your Medicare accreditation,
can you then submit for your PTAN, which then takes 90 days. And then only after you get your PTAN, can you being your private payor contracting. So, in conclusion, it requires more time, more staff, more oversight and regulation. The complex hours of operation ought
to maintain your existing patient base. You need a payor contracting strategy. It's probably an additional two million dollars to build out an ASC, including the working capital requirement. So for the solo practitioners that were out there thinking about it,
unless there's a very compelling financial reason to convert, it's probably best to stay an OBL at this time. Thank you.
- Good morning. It's a pleasure to be here today and I wanted to let you know that a lot of this work that was being done earlier were really driven by physician need. As you can see, the trial as well as the EXCEL registry is finally on the way, so it's very exciting.
I'm not going to spend a lot of time on this but everybody knows the primary predictor of EVAR failure is really short necks and angulated necks. The first generations have been pretty good but they were really not intended for this type of anatomy. We see a lot of patients with really distorted anatomy
but they still have a relatively lengthy or 10 mm neck. In fact, about 80% of the EVARs treated in the United States have at least a 10 mm proximal neck. They may not be of the highest quality but they're there. So, how could be achieve better results? Basically we need to use every millimeter
of this landing zone, so that we can use the 10 mm neck to its fullest advantage and I believe when you do that, the results are fairly comparable to doing any type of above renal repair, like a fenestrated or branch graft. The stabilization of the device
during delivery is absolutely crucial. So essentially what you want to do is have a device that is able to utilize every neck angle and every millimeter of that available neck. And we know that 80% of all the patients, do have that neck. So, the new conformable endovascular device
has been around for the last five years or so but recently went into trial in December of last year. It's very different proximally than the current EXCLUDER in that the fixation system is single and it has a series of nested stents very similar to a conformable C-TAC device.
As you can see, this allows the device to conform to the anatomy, but not only that you're able to adjust the device inside too and that's actually Frank Veith's terminology, is that you're able to adjust this so that you can inch it up and utilize the entire neck.
16 French, proximal fixation, trunk length's a little bit longer than the current EXCLUDER at 5.5 to 6.5. This allows further treatment in the future going forward if you need to do a fenestrated device or branch graft device above it.
This device was designed to conform up to 90 degree angles and it's designed to seal at 10 mm necks. And, the most important aspect of it is, you're able to reposition the device once you deploy it. The mechanism is really one of being able to angle the device with a steering system
before the deployment and also afterwards and also be able to restrain the device up and down. Another major difference is that it has a 30% restraining secondary sleeve just like a ZFEN device so you're able to move this device up and down the angulated neck
and I'll show that with a case. The clinical trial in the U.S. began in December of last year and so far, I'll show you the update but unfortunately the FDA disallows us to give you any data. I can give you some of the demographics but I'll show you
that the preliminary results look excellent. The goal is to implant 80 patients in the short arm which is complete and 110 patients in the high neck arm is partially complete at almost 30 patients. The trial update objective is as outlined, there are 48 U.S. sites
and the current study enrollment is 106 patients, the short neck arm again I said is complete. Primary safety endpoints, not unlike any other device. Primary effectiveness endpoints, again freedom from all of these aspects. The first device was in 2017,
this was a relatively straightforward patient. The device performed well, this is a six month follow-up. The device had no migration issues, confirmed beautifully. But this is not really what the device was designed for. So, I'm going to give you a case of a patient that was enrolled in the high risk arm.
This patient had an 8.5 cm aneurism, 82 degree angulation, 11 mm proximal neck, turned down for EVAR or fenestrated at two other institutions in the New York City area and basically came for a third opinion as most New Yorkers do.
The aneurism looks like this and it's kind of a very angulated proximal neck with extremely torturous iliacs. This is the case that we did. You can see the device being configured here with the steering wire and when you do this,
you can see the device being able to be easily moved proximally and distally and the next portion of the video shows that steering wire kind of implanting the device into the lesser curve. - [Moderator] The device is deconstrained right? - Yes.
You can restrain it and it's a combination of being able to restrain it and open it which allows you the flexibility and as you can see with this maneuver, the device looks like it's perfectly opposed but in fact, the posterior aspect did not oppose very well.
So, we adjusted it further by increasing the posterior coverage and this is the post-op and we got a seal. There was no ballooning. This device, the ballooning is optional. So, the results have been excellent so far
with the highly angulated neck arm and we'll only see, there's only 30 patients so far but the results have been excellent so far. - [Panel Member] Rob and for you and for also Mark who presented that last case last week. When you deploy this device
it seems that you have a stiff wire, you're almost fighting the very advantage you're proposing. Do you ever consider swapping out for a floppier wire so you can then really get the native anatomy configuration? Because now that fusion image is presumably the pre-op fusion without the stiff wire.
So, I just wondered whether there's any value to that. - That's a great question. In fact, if you look at this video again, not this one but, let me see, this one, there's no wire, that the tip of the Amplatz wire is right at the tip of the device.
So that device is almost unsupported at this level, so you're able to freely flex that device back and forth without the constraints of a stiff wire. - [Panel Member] Is that your personal style or is that something that's part of it. - It's actually a recommended
and the part of the deployment process is to bring the floppy wire. So, you can use like a Glidewire Advantage or an Amplatz Super Stiff or whatever wire you like to use but it has to have a very floppy unsupported section in the proximal segments
to be able to get this kind of maneuverability. - [Moderator] So for the panel who've used this device, with all this manipulation of the proximal neck and especially in a diseased neck, is there any evidence of embolization of thrombus into the renals or distally?
- [Panel Member] Of course there is the potential for that but we haven't seen it yet and I think that the FDA IDE Trial and the registry will address that. I think that you should be careful. If there is a lot of neural thrombus in that neck
then this manipulation could be a potential risk. Actually what you're doing is, it's not that easy to get it into position in just one angulation. Sometimes you have to angulate, push it a little bit, restrain it again and reposition it to come in the perfect position,
especially for high angulation. - Yes. There's definitely a learning curve here but the learning curve actually can be achieved with just a couple of cases to be able to see how the device behaves
in the human anatomy.
now let's look at non-invasive ventilation and I know about like five
percent of the patient population that you are seeing is on some form of non-invasive whether they're on by level ventilation or continuous positive airway pressures right so see if HAP using to stent the Airways open and
maintain a pro a Peyton airway and improving oxygenation but BiPAP and patients that need co2 elimination right need help with the by level support so there's a lot of questions that come up when we give
these talks I'm like how does capnography work effectively with these different technologies of non-invasive ventilation and especially because more and more of our patients are requiring these so we're gonna look at some of the
comparisons of co2 capnography data from three different sample sites and remember I showed you that picture so that picture I showed you with the patient wearing the sampling line with a nasal oral scoop and then there was the
mask sampling port and then there was the port on the ventilator circuit distally so that's what we're looking at here so the diamonds that go I wish I had a pointer I don't have a laser pointer I'm sorry but across the top the
diamonds represent our end tidal capnography values from one liter all the way up to eight liters so as the props are as the pressures go up for CPAP they were monitoring leak rates and what they found is the cat nog rafi
values across all of those were pretty accurate when we're monitoring right here the squares and the diamonds represent the mask sampling port and the the ventilator in the circuit distal to the mask and as you could see that
quality of our monitoring goes down as we progress okay to use yes but just know the limitations of your equipment right and again this is the same thing for our BiPAP Dave data are by level ventilation we're seeing again
across the top if we're sampling right at the airway we have pretty consistent readings but then they start to fall off and we look at the other devices that are further down the downstream what we're seeing here is our end tidal
measurements again with CPAP data and what we're looking at is the patient leak so there's always leaks right when we have these devices on and that's a question well sue if I have a leak how accurate am i okay so now the red is our
nasal oral scoop and if you look at the red graph all the way across depending on the leak rate pretty consistent values right the charcoal color is the mask sampling port and that's pretty consistent probably until about like 10
right until our patient like leak rate 10 liters per minute coming out of that mast and then that value starts to fall off and even more so even further distal down our circuit when we're sampling from the circuit at the past the mask
that's the cream color pretty accurate when there's a minimal leak but as the leak goes up that falls off pretty significantly and the same holds true for our by level ventilation pretty similar distribution here with the
patient leak and the sampling so when we're using non-invasive ventilation yes it's accurate and yes it's accurate we're using high flows and yes it's accurate if we have a huge leak only if we're sampling right where the patient
is exhaling so now I hope that clears that up with the patients that are getting supplemental pressure support with your sampling and you know in those just whatever it can sample from the mouth and the nose right at the source
of exhalation has proven to be the most reliable out of all of the different sampling devices so third evaluate your
- [SPEAKER] I have a disclosure, this talk is about a cannulation simulator that I've been working on for about 3 years. It's finally come to the point where we have established a company that, to further develop it and TMC is the initials of my son, whose a lawyer. I told him if you set up this company for free,
I will put your name on as the, the company. I also want to acknowledge Debbie and Janet for this. You know, as a surgeon it would be full hearty for me to sit down and invent a simulator. You need users of the device for all the in-put, so I kept going back to them, going back to the
dialysis nurses in my community, to get their input and so this is what we've come up with. I really don't need to talk about the importance or the consequences of mystics and there's a lot of literature
on that area, but what is interesting is for a surgeon to go into the nursing literature and learn about the psychological impact on patient's from mystics but also the psychological impact on the nurses and the techs. It is, it is really
it is devastating to the nurses and there are nurses that over time become less confident of their cannulation skills. There's this notion of perpetual novice, there's a lot of discussion about the culture in dialysis units that I was unfamiliar with as a surgeon and all
of these papers talk about the need for on-going education and practice. Their cannulation camps, these are expensive and they provide very little training, the simulators are un-realistic, they have high-maintenance, they don't really provide a thrill or a pulse and so most of
these nurses actually can't practice on patients. So, before we started developing this, we had a hypothesis that the perpetual novice is unable to visualize the fistula based on palpation alone and that is the fundamental problem. They have to be able to see a fistula
like this to reliably cannulate a fistula. So we went to Debbie, we went to Janet and asked, OK what is the characteristics of the ideal cannulation simulator? Would need teach the 4 core cannulation steps, we need to be affordable, low-maintenance, preferably fluid-less,
as the nurses it would be able to test those folks that are just beginning cannulation as well as more advanced nurses. It would have an alarm to prevent back-wall sticks, it would train nurses in the identification of a stenosis within in fistula. It would create a
realistic thrill and there would be no based on our initial hypothesis, this was ours. We did not want to provide any visual clues as to the location of the fistula or the depth. It would require only palpation to stick it. And this is what we came up with,
there's no up, there's no down, there's no In this, under our simulator, there are a number of fistula elements and we can turn on these individually and they are tasked to identify the fistula elements that is actually live. The skin on top of the fistulas
is silicon, it's resistant to stick, it's hard to see this cannulation needle punctures, however if those needle punctures, when they develop you can lift tops, spin it and those punctures are no longer correlated to the location of the fistulas underneath.
This is the control panel. You can control the level of the thrill, you can have different levels of the skin to make it more challenging to stick these. The wings of this needle
has been removed but the cannulator uses a standard dialysis needle for the device. When you hit the fistula it creates a light which simulates the return of blood.
So in looking at what we were able to capture all of these elements of the ideal simulator, it's affordable, it's a plug-in play where if an element breaks you can, it's modular, you can disconnect it and plug-in another one. No fluids,
it has just like the old operation games, you touch the back-wall, it alarms. We have one element that's not meant to be stuck but it creates a pulse on one side, a weak thrill on the other side to train that stenosis. We have curved fistulas.
The thrill is quite simple, we generate the thrill through the use of a cellphone motors that create the vibration. Those can be bought for less than $1 on Amazon and it provides no visual clues to the location. We've completed the development of the
device that now needs manufacture specifications, we have a manufacture initial testing has been completed by a large dialysis company and we're working through our first purchase order. We are developing a prototype that's much cheaper, must simpler sleeve that will go over a
patient's arm that overlies their existing fistula and they can self-train on cannulation and I'm working with a Ph.D. who started this project, he's applied complex sensors to the cannulation device that you saw earlier and he's received a K-1 award to study the
mechanics of cannulation and Prabir Roy-Chaudhury is his mentor for that project. Thank you.
- We are talking about the current management of bleeding hemodialysis fistulas. I have no relevant disclosures. And as we can see there with bleeding fistulas, they can occur, you can imagine that the patient is getting access three times a week so ulcerations can't develop
and if they are not checked, the scab falls out and you get subsequent bleeding that can be fatal and lead to some significant morbidity. So fatal vascular access hemorrhage. What are the causes? So number one is thinking about
the excessive anticoagulation during dialysis, specifically Heparin during the dialysis circuit as well as with cumin and Xarelto. Intentional patient manipulati we always think of that when they move,
the needles can come out and then you get subsequent bleeding. But more specifically for us, we look at more the compromising integrity of the vascular access. Looking at stenosis, thrombosis, ulceration and infection. Ellingson and others in 2012 looked at the experience
in the US specifically in Maryland. Between the years of 2000/2006, they had a total of sixteen hundred roughly dialysis death, due to fatal vascular access hemorrhage, which only accounted for about .4% of all HD or hemodialysis death but the majority did come
from AV grafts less so from central venous catheters. But interestingly that around 78% really had this hemorrhage at home so it wasn't really done or they had experienced this at the dialysis centers. At the New Zealand experience and Australia, they had over a 14 year period which
they reviewed their fatal vascular access hemorrhage and what was interesting to see that around four weeks there was an inciting infection preceding the actual event. That was more than half the patients there. There was some other patients who had decoags and revisional surgery prior to the inciting event.
So can the access be salvaged. Well, the first thing obviously is direct pressure. Try to avoid tourniquet specifically for the patients at home. If they are in the emergency department, there is obviously something that can be done.
Just to decrease the morbidity that might be associated with potential limb loss. Suture repairs is kind of the main stay when you have a patient in the emergency department. And then depending on that, you decide to go to the operating room.
Perera and others 2013 and this is an emergency department review and emergency medicine, they use cyanoacrylate to control the bleeding for very small ulcerations. They had around 10 patients and they said that they had pretty good results.
But they did not look at the long term patency of these fistulas or recurrence. An interesting way to kind of manage an ulcerated bleeding fistula is the Limberg skin flap by Pirozzi and others in 2013 where they used an adjacent skin flap, a rhomboid skin flap
and they would get that approximal distal vascular control, rotate the flap over the ulcerated lesion after excising and repairing the venotomy and doing the closure. This was limited to only ulcerations that were less than 20mm.
When you look at the results, they have around 25 AV fistulas, around 15 AV grafts. The majority of the patients were treated with percutaneous angioplasty at least within a week of surgery. Within a month, their primary patency was running 96% for those fistulas and around 80% for AV grafts.
If you look at the six months patency, 76% were still opened and the fistula group and around 40% in the AV grafts. But interesting, you would think that rotating an adjacent skin flap may lead to necrosis but they had very little necrosis
of those flaps. Inui and others at the UC San Diego looked at their experience at dialysis access hemorrhage, they had a total 26 patients, interesting the majority of those patients were AV grafts patients that had either bovine graft
or PTFE and then aneurysmal fistulas being the rest. 18 were actually seen in the ED with active bleeding and were suture control. A minor amount of patients that did require tourniquet for a shock. This is kind of the algorithm when they look at
how they approach it, you know, obviously secure your proximal di they would do a Duplex ultrasound in the OR to assess hat type of procedure
they were going to do. You know, there were inciting events were always infection so they were very concerned by that. And they would obviously excise out the skin lesion and if they needed interposition graft replacement they would use a Rifampin soak PTFE
as well as Acuseal for immediate cannulation. Irrigation of the infected site were also done and using an impregnated antibiotic Vitagel was also done for the PTFE grafts. They were really successful in salvaging these fistulas and grafts at 85% success rate with 19 interposition
a patency was around 14 months for these patients. At UCS, my kind of approach to dealing with these ulcerated fistulas. Specifically if they bleed is to use
the bovine carotid artery graft. There's a paper that'll be coming out next month in JVS, but we looked at just in general our experience with aneurysmal and primary fistula creation with an AV with the carotid graft and we tried to approach these with early access so imagine with
a bleeding patient, you try to avoid using catheter if possible and placing the Artegraft gives us an opportunity to do that and with our data, there was no significant difference in the patency between early access and the standardized view of ten days on the Artegraft.
Prevention of the Fatal Vascular Access Hemorrhages. Important physical exam on a routine basis by the dialysis centers is imperative. If there is any scabbing or frank infection they should notify the surgeon immediately. Button Hole technique should be abandoned
even though it might be easier for the patient and decreased pain, it does increase infection because of that tract The rope ladder technique is more preferred way to avoid this. In the KDOQI guidelines of how else can we prevent this,
well, we know that aneurysmal fistulas can ulcerate so we look for any skin that might be compromised, we look for any risk of rupture of these aneurysms which rarely occur but it still needs to taken care of. Pseudoaneurysms we look at the diameter if it's twice the area of the graft.
If there is any difficulty in achieving hemostasis and then any obviously spontaneous bleeding from the sites. And the endovascular approach would be to put a stent graft across the pseudoaneurysms. Shah and others in 2012 had 100% immediate technical success They were able to have immediate access to the fistula
but they did have around 18.5% failure rate due to infection and thrombosis. So in conclusion, bleeding to hemodialysis access is rarely fatal but there are various ways to salvage this and we tried to keep the access viable for these patients.
Prevention is vital and educating our patients and dialysis centers is key. Thank you.
- I will be talking about new KDOQI guidelines. I know many of you have heard about KDOQI guidelines being revised for the past maybe over a year or maybe two. Yes, it is being done, and it is going slow only because it's being done in a very different way. It's more than an update.
It's going to be more of an overhaul for the entire KDOQI guidelines. We in KDOQI have looked at access as a solitary problem like we talked about grafts, catheters, fistulas for access, but actually it sort of turns out
that access is part of a bigger problem. Fits into a big ESKD lifeline of a patient. Instated distal patients come in many varieties. It can affect any age, and they have a lot of other problems so once you have chronic renal failure, renal replacement mortality fits in
only when it becomes Stage IV or Stage V. And renal replacement mortality is not just access, it is PD access, it's hemo access, it is transplant. So these things, we need to see how they fit in in a given person. So the new KDOQI guidelines concentrates more
on individualizing care. For example, here the young Darien was an 11 year old with a prune belly syndrome. Now he has failed PD. Then there's another person here who is Lydia who is about 36 or 40 year old lady
with a insulin dependent diabetes. Already has bad vascular pedicle. Lost both legs. Needs access. Now both these patient though they need access, it's not the same.
It's different. For example, if you think of Darien, he was in PD but he has failed PD. We would love to get him transplanted. Unfortunately he's got terrible social situation so we can't get him transplanted.
So he needs hemo. Now if he needs hemo, we need to find an access that lasts for a long time because he's got many years ahead of him. On the other hand we have Lydia, who has got significant vascular disease.
With her obesity and existing infectious status, probably PD won't be a good option for her. So she needs hemo, and she's obviously not a transplant candidate. So how are we going to plan for hemo? So these are things which we are to more concentrate
and individualize when we look at patients, and the new guidelines concentrate more on these sort of aspects. Doing right access for right patient, right time, and for right reasons. And we go about planning this keeping the patient first
then a life plan ESKD lifeline for the patient, and what access we are looking at, and what are the needs of the patient? Now this is also different because it has been done more scientifically. We actually have a evidence review team.
We just poured over pretty much 1500 individual articles. Recent articles. And we have looked through about 4000 abstracts and other articles. And this data is correlated through a workgroup. There a lot of new chapters.
Chapter specific surgery like peri-operative, intra-operative, post-operative, cat issues, managing complication issues. And we started off with the coming up with the Scope of Work. The evidence review team took the Scope of Work
and tried to get all the articles and sift through the articles and came up and rated the evidence using a certain rating system which is very scientific. The workgroup then kind of evaluated the whole system, and then came up with what is clinically relevant.
It's one thing for statisticians to say how strong evidence this is, but it's another thing how it is looked upon by the clinicians. So then we kind of put this into a document. Document went through internal and external review process.
This is the process we have tried to do it. Dr. Lok has been the Chair of the group. Myself and Dr. Yevzlin are the Vice-Chairs. We have incredible workgroup which has done most of the work. And here are the workgroup members.
We comprised of nephrologist, transplant surgeons, vascular surgeons, Allied Health personnel, pediatric nephrologist so it's a multi interventional radiologist and interventional nephrologist. This is a multi disciplinary group which has gone through this process.
Timothy Wilt from Minnesota was the head of the Evidence Review Team, who has worked on the evidence building. And now for the editorial sections we have Dr. Huber, Lee, and Dr. Lok taking care of it. So where are we today?
We have pretty much gone through the first part of it. We are at the place where we are ready for the Internal Review and External Review. So many of you probably will get a chance to look through it when it comes for the External Review and would love
to have your comments on this document. Essentially, we are looking at access in the context of end stage renal disease, and that is new. And obviously we have gone through and done a very scientific review, a very scientific methodology to try
to evaluate the evidence and try to come up with guidelines. Thank you.
- Thanks very much Ken, Thanks for the in shape comment. I'm not sure that necessarily true. These are my disclosures. I think it's critical to understand that Atherosclerosis is not just the deposition of cholesterol, but it's really inflammatory cells acting
upon that environment where the cholesterol has been deposited. That ultimately leads to the inflammatory process that osis, plaque rupture, and complications related to it.
If we look specifically at our best marker of inflammation that we have, hsCRP. It's elevated with hypertension, type two diabetes, independently of LDL C.
Statins we know can lower this CRP sum, which lowers cardiovascular risks, and it does it independently of LDL C reduction. And that was shown in the Cantos trial. Cholesterol and inflammation thus equals cardiovascular disease.
And methods to reduce inflammation include: smoking cessation, regular exercise, weight loss, and actually getting adequate sleep. But the final thing, and probably in my view one of the more important things, is the diet that we take in.
You've heard recommendations through the Mediterranean, vegetarian, and low carbohydrates diet. You haven't heard recommendations to the adopt the southern diets, which is the only diet that has been proven
to increase the risk of hypertension and Atherosclerosis. And my move to South Carolina, has prompted a look at diet overall. What are anti-inflammatory diets? They're basically diets that increase the color of the foods that you eat.
Increased fruits and vegetables, minimizing trans and saturated fats, and limiting refined of processes c which are probably more important in developing inflammation than any other part of our diet.
It increases whole grains and lean protein sources. Avoiding refine sugars and spices that are anti-inflammatory can be helpful as well. Eliminating soda and all beverages that are sweetened, are particularly important. And again here you can see here that olive oil
essentially is the only oil that is actually beneficial in an anti-inflammatory diet. What to avoid: fried foods- no matter what they are fried in. Vegetable oils increase inflammation.
Anything that's a substitute for butter or milk products are problematic. And processed carbohydrates, again, are problematic along with processed meats. The benefits of an anti-inflammatory diet have been shown in a number of conditions
including cardiovascular disease. And each one of these inflammatory conditions has at least two studies that show benefits of reducing inflammatories in the diet. The association between diet and arterial stiffness and precursor turatorial disease
has been shown in this study, where these authors took almost 500 individuals, recorded their food and tonometry to assess arterial elasticity. In each situation where you increase carbohydrates versus fats or proteins,
you increase aortic pulse pressure and mean arterial pressure. And when you remove carbohydrates and replaced with protein, you reduced aortic and mean pressures. Clearly and diet affects what's happening in the arteries. This is another look at the dietary inflammatory index,
which is new categorization of diets to access their degree of inflammation. And in this study, which really looked at six different bio markers of inflammatory process in the blood stream. The authors assessed a relationship
of dietary and inflammatory index to hsCRP, and showed that if you reduce the inflammatory index, you can reduce the hsCRP. This says elevated dietary and inflammatory index cause the authors looked at index as a method to reduce overall inflammation.
But it reduces hsCRP and reduces colon risk cancer in the populations that they've studied. And in this look at metabolically obese people, whether they were metabolically unhealthy or healthy, the authors looked at over 300 individuals and recorded and their diet.
And notice that a worse inflammatory diet was associated with an increase risk for metabolic unhealthiness, And increased the risk of all these other things which elevate inflammatory markers
in the blood stream as well. In summary then, vascular disease is an inflammatory process as is obesity. And vascular specialists need to include diet recommendations into the things we use routinely
to modify lifestyles and reduce Atherosclerotic risk for our patients. Thank you.
- Thank you very much again, I greatly appreciate the honor to be able to be here and be able to present these data. These are my they're my conclusions, thank you very much. So, what I think is really very important for all of us
is to remember this Chinese Proverb, never kill a friend, never treat a stranger. And what that means is that you have to learn a lot about that patient before you just go ahead and operate on them.
Then they're not strangers anymore. And if God forbid the CT scanner is broken, you're going to have to do a history and physical. We know that chart review I hate to look at reviews of the Caprini scores going back with retrospective chart reviews,
because they're terribly flawed. We have one of the only risk assessments that looks at the history of obstetrical complications and if you look at chart review, nobody asks the questions. Six tenths of a percent,
13 percent face to face. Same thing with family history of thrombosis. Five point two percent, 17 percent live. Personal history of DVT even doubled in live versus chart review. These questions aren't asked
and of course in the National Surgical Quality Improvement Project and the American College of Surgeons. These things aren't even in there. And they have five million patients. And they talk about DVT studies, and they don't know about what's going on.
We have 39 factors in the Caprini score and that's judged to be too many. You can't have too good a history and physical. The better your history and physical, the better you can take care of the patient. So if devised in a patient friendly form,
it's in five languages. The patients fill it out ahead of time. And then, this was compared to professionals filling it out. There's excellent correlation except for a couple of problems.
And that is that the patient fills the form out, then when they come in, we reemphasize history of family history, B.M.I., obstetrical history, and then see if they have pitting edema or varicose veins.
And so that takes less than five minutes. The last thing in the world you want to do, and I would say anybody that has preoperative surgical nurses in the holding area that Caprini scores, that's flawed. Stop it.
That's no place to be doing that. Because people are worried about their surgery, are they going to get through it, are they going to find cancer, how long are they going to be out of work. You can't ask them about this at that time.
So, these are the scores that we use. Part of this is also reinforced by stuff that's been done. God bless that we would need a moment of silence for the University of Michigan. All the fabulous work that they've done there
in this regard. And we also, this is how we score these patients. Got a lot of operator error here today. Age, as you can see, and contraceptives or hormonal therapy and so forth. This, everybody needs to get this study and to read it.
This is 183000 individuals in the Scandinavian system followed for 25 years. And what they showed is, that there's an increased incidence. If you take a look at a person that's never had a clot, if they have a first degree relative with a clot,
they have an increased risk of thrombosis, slightly less for second degree relatives, slightly less for third degree relatives, and believe it or not, even slightly more compared to controls for people that are living together but of course with the person's lifestyles and so forth
so it's not totally understandable. The point of this is, the point of this is, pay attention to family history of thrombosis. Because that might uncover a whole thrombopathic family that you don't realize. And that'll be the difference in these low risk
procedures between life and death. I've seen a number of patients die with simple procedures because nobody asked about the family history. So, what we recommend is Caprini scores of one to four. You can use compression stockings when they're
if they're in the hospital if it's for ablation. You can use compression stockings according to your protocol, whatever you do. If the patient's at moderate risk, five to eight, low molecular weight heparin for seven to ten days and compression stockings.
And if they're high risk, over nine, then we also like to do a duplex scan before stopping the low molecular weight heparin. And so in conclusion, risk assessment using the score, utilize patient-friendly form,
avoid chart review, face to face critical. And remember that some of these simple procedures, these patient's are very high risk if they're thrombopathic. Provide prophylaxis for at least one week in those at risk for a score of over five.
And then extended prophylaxis for history of VTE, family history of VTE and thrombophilia. Now, I put 14 to 28 days because you have to take these situations individually. Somebody's had four family members in their past history that have had thrombosis.
That's a thrombopathic family. I would go for 30 days. If it's only one incident and one patient, then maybe two weeks. Thank you very much.
- Thank you again for the opportunity to discuss the BlueLeaf Endovenous Valve with potential benefits of on an all-autogenous solution. The last slide was a nice segue to this presentation, so the financial relationship. So we've discussed extensively at this meeting treatments for superficial venous
reflux outflow obstruction, and, really, the last sort of frontier is the deep vein reflux where invasive surgery is still the gold standard, but I basically say that the majority of us, or at least myself and many of us in our practice,
resort to what I refer to as palliative care or conservative managements in patients who have maximally been treated for their outflow obstruction and superficial venous reflux. This is sort of an outstanding review
of the current state of deep venous reconstructive surgery by Dr. Maleti, Lugli, and Tripathi who said the trap door technique as well as the neovalve and the corresponding outcomes, and I encourage all of you to look at it, are pretty reassuring even with the limitations.
The ulcer recurrence rates are in the 20-30% range and the vales remain competent in 70% of cases, and the results of the neovalve reconstruction are also reasonably promising. So how do we take these reasonably and pretty promising results and try to expand them?
Potentially, what would it look like as a percutaneous approach? And it might look something like this. And this is the BlueLeaf Endovenous Valve Formation System which uses a catheter system, a nitinol dissector, and a needle assembly,
and it's done under intravascular ultrasound guidance. This is what the procedure looks like in the basic three steps. After you've gained access with a 16 French sheath in the common femoral vein you identify the valve site,
the appropriate valve site with the IVUS, you perform, you gain sub-intimal access, and then perform the hydrodissection, and then you create your valve. And this is how it goes. So after you've gained wire access
you advance your intravascular ultrasound in order to identify the valve formation site. Right now it's quantitated at seven to 11 millimeters in diameter and at least three centimeters in length. You then inflate the balloon to appose the vein wall,
to create some tension in the vein wall, and thereafter your needle assembly can create that sub-intimal plane with the hydrodissection, and you see how the bevel tip retracts to make it less traumatic. You're checking with intravascular ultrasound.
You advance the dissector. And then under IVUS guidance you create the valve with the nitinol scoring blades on the dissector as well as the tensioner which kind of bows out towards the IVUS, and you can see it on the corresponding IVUS images.
And the very last step is to leave the blades open to open up the mouth of that percutaneous valve fully. And the advantages. You can create a monocuspid, a bicuspid valve, potentially multilevel valves as well. In this tissue demonstration
you're essentially looking from within the vein walls, so the tensioner is pointing out towards you as if you're within the lumen of the vessel, and it's just showing you how the nitinol scoring blades create the valve and then when left open for the final passage
to incise the valve mouth. And this is what the result looks like on intravascular ultrasound. It projects well the last couple seconds of the slide. So the potential advantages is that there's an increased potential for customization.
Again, monocuspid, bicuspid valve orientation, multilevel valves. (mumbles) may lead to a larger eligible patient population and expanded utilization amongst various venous practitioners. The extended feasibility study.
The trial details are currently enrolling outside of the United States. 11 patient in Australia and New Zealand. The US trial is pending IDE approval, and the inclusion criteria will be those patients with the most severe disease with C5 and C6 disease
and significant deep vein reflux. Exclusion criteria relate to inflow, outflow, and having an adequate conduit with an appropriate valve formation site. Thank you.
- Thank you to the host for inviting me to speak again this year. I don't have any disclosures other than the fact that I'm a co-author on the paper that's being presented, but got no reimbursement for that. So I flew in from Chicago on Thursday
during your first snow, for those of you who live in New York, and this was the afternoon I'd made it unscathed on my flight, everything subsequent to that from Chicago got canceled, and I got here
and it was a lot like a Chicago winter. Lots of snow, women wearing impractical shoes, but there were two things that were missing: snow plows and salt. Where's your salt game? I mean I don't understand New York,
there was nothing. So I claim that Chicago has a better snow clearing game than New York does, - [Man] And weathermen. - And weathermen, that's right.
Okay. I'm in charge with giving you some information about a publication that we did this year on the DOPPS. And for those of you who are unfamiliar with the DOPPS, just a quick background.
The DOPPS Outcomes Practical Patterns Study started in 1996, and it's resulted in a series of prospective studies from more than 20 countries around the world. It includes a cohort of Hemodialysis, CKD, and PD patients,
which now totals 70,000 patients. And its principal goal was to identify modifiable clinical practices to improve patient outcomes. And just to give you an idea of which countries are represented,
those in the blue, each wave of the DOPPS has incorporated a broader span of countries, and the most recent wave included China and many countries in the Middle East. So it's quite representative of what's going on around the world.
So we elected to look at issues related to AV fistula location and use, and compare those to countries in Japan, Europe, and New Zealand, and looked at a prospective study that spanned between 2009 and 2015.
It involved over 4,000 fistulas, about 1,000 grafts. And in order to get some trend analysis, we used DOPPS data that was collected between 1996 and 2015. And we looked at three specific outcomes:
AV fistula location, time to first use, and continued use. Some key findings here are that, for any of you who've traveled to Japan and spent time with dialysis patients, it's impressive.
This dark color represents lower arm fistulas and this lighter color represents upper arm, and you can see here that over time, as the DOPPS gone successively from the 1990s through 2015, Japan has maintained principal use
of lower-arm fistulas. When we go to Europe, what you can see is that there's been a slight decline in lower-arm fistulas from about 77% of those in the cohorts down to about 66%.
But when we get over to the U.S., we find that interestingly, there's been an inversion. Where previously, there had been lower-arm fistulas, in the 1990s, this is now switched to upper-arm fistulas,
despite the fact that the U.S. has the lowest mean age of those people that are undergoing dialysis. And interestingly, among those patients that we consider to have the lowest risk for fistula maturation failure,
namely young men, less than 50% of U.S. males less than 50 years of age, had fistulas located in the lower arm in our most recent DOPPS cohort compared to 73% in Europe and 98% in Japan. And the implications of this are two-fold.
Principally exhausting AV access sites and then complications that can be related to upper arm high-flow access. So just quickly, I want to touch on successful use, which differs internationally.
You can see here that for those patients that had continuous use for more than 30 days, Japan had 87% of its cohort who maintained this, while the United States, 64% of its cohort did. And these numbers are similar to USRDS reporting.
Japan's AV fistula use was more successful, or, I'm sorry, the AV fistula use was more successful in the upper arm versus the lower-arm fistulas in the U.S. and in Europe, but not in Japan. It didn't seem to matter
whether it was upper or lower arm, they still seemed to work equally well. Interestingly too, time differs in terms of cannulation. The mean days to AV fistula cannulation in Japan were only 10 days,
compared to nearly three months for the United States. And when they looked at median days to graft cannulation, similar pattern existed, Japan had six days to cannulation
whereas the U.S. had 30 days. So what are some possible differences for these? There're many. But Fistula First is obviously the big, the big one that comes to mind because its implementation mirrors
the timing and the trend, the shift in upper-arm fistulas in the U.S. There's also a known high AV fistula maturation rate in the United States, which may discourage surgeons
from placing lower-arm fistulas initially. There are a limited number, in my view, of experienced and skilled surgeons that have a broad fistula repertoire in the lower arm, lack of widespread pre-operative ultrasound
vessel mapping, and lack of attention to vessel preservation. So what are some possible reasons for greater time to use in the U.S.? I think that it's largely superficialization procedures that are needed
because of body habitus. There's some hesitancy around cannulation segments, maybe being limited or deep. Nephrologists really don't know how to examine and access,
and I'm one of, I'm a Nephrologist, I can say that. And then lack of cannulation expertise in a dialysis unit. So how does Japan do it? Despite an older mean age for dialysis,
there's a much lower median blood flow for dialysis. They use a 200 pump speed, whereas we use 400 to 500 millimeters per minute pump speed. And this largely achieved because they, many times, have a smaller body weight,
but they also accommodate longer treatment times and smaller gauge needles. And they limit their surgeons to those that really have experience. So for visual learners out there, this is the summary of what I've said.
The percent of fistulas in the lower arm in Japan is 95%, U.S. is 32%. The number of days to a successful fistula cannulation is significantly longer in the U.S. And some takeaways are three, then I'm done.
Patients don't necessarily require high-flow fistulas, just a modified dialysis prescription, and this can come about through an expansion of home and nocturnal dialysis.
Improvements are needed for surgical expertise and training. And, in fact, the Endo AV fistula, which you'll be hearing about later today, may, in fact, increase fistula usability and reduce time to cannulation
in certain patient populations. And because I'm the President of ASDIN, I invite all of you to come to our February meeting, escape the cold, it's in Atlanta this year. Thank you for your attention.
- Thank you (mumbles). The purpose of deep venous valve repair is to correct the reflux. And we have different type of reflux. We know we have primary, secondary, the much more frequent and the rear valve agenesia. In primary deep venous incompetence,
valves are usually present but they are malfunctioning and the internal valvuloplasty is undoubtedly the best option. If we have a valve we can repair it and the results are undoubtedly the better of all deep vein surgery reconstruction
but when we are in the congenital absence of valve which is probably the worst situation or we are in post-thrombotic syndrome where cusps are fully destroyed, the situation is totally different. In this situation, we need alternative technique
to provide a reflux correction that may be transposition, new valve or valve transplants. The mono cuspid valve is an option between those and we can obtain it by parietal dissection. We use the fibrotic tissue determined by the
sickening of the PTS event obtaining a kind of flap that we call valve but as you can realize is absolutely something different from a native valve. The morphology may change depending on the wall feature and the wall thickness
but we have to manage the failure of the mono cuspid valve which is mainly due to the readhesion of the flap which is caused by the fact that if we have only a mono cuspid valve, we need a deeper pocket to reach the contralateral wall so bicuspid valve we have
smaller cusps in mono cuspid we have a larger one. And how can we prevent readhesion? In our first moment we can apply a technical element which is to stabilize the valve in the semi-open position in order not to have the collapse of the valve with itself and then we had decide to apply an hemodynamic element.
Whenever possible, the valve is created in front of a vein confluence. In this way we can obtain a kind of competing flow, a better washout and a more mobile flap. This is undoubtedly a situation that is not present in nature but helps in providing non-collapse
and non-thrombotic events in the cusp itself. In fact, if we look at the mathematical modeling in the flow on valve you can see how it does work in a bicuspid but when we are in a mono cuspid, you see that in the bottom of the flap
we have no flow and here there is the risk of thrombosis and here there is the risk of collapse. If we go to a competing flow pattern, the flap is washed out alternatively from one side to the other side and this suggest us the idea to go through a mono cuspid
valve which is not just opens forward during but is endovascular and in fact that's what we are working on. Undoubtedly open surgery at the present is the only available solution but we realized that obviously to have the possibility
to have an endovascular approach may be totally different. As you can understand we move out from the concept to mimic nature. We are not able to provide the same anatomy, the same structure of a valve and we have to put
in the field the possibility to have no thrombosis and much more mobile flap. This is the lesson we learn from many years of surgery. The problem is the mobile flap and the thrombosis inside the flap itself. The final result of a valve reconstruction
disregarding the type of method we apply is to obtain an anti-reflux mechanism. It is not a valve, it is just an anti-reflux mechanism but it can be a great opportunity for patient presenting a deep vein reflux that strongly affected their quality of life.
- I'd like to thank Larry and John for the opportunity to speak today. This really is kind of an exciting time in Vascular Access 'cause you know this whole session's devoted to all the new tools and technologies, and they're really a lot of different options
that are available to us now to create functioning fistulas in patients. Those are my disclosures. I just want to mention one thing, when I was asked to give this talk, the name of the device was the Everlink device then,
and that was first developed by TBA Medical at Austin, Texas. Eventually the company was bought by Bard, and then Beckett Dickinson bought Bard, and then they changed the name of the device to the WaveLinq device,
just so that we're all on the same page here. The basic gyst of this system basically it's a two-catheter system, it involves punctures in the brachial artery and brachial vein above the elbow over wires, the catheters are then aligned
in the ulnar artery and ulnar vein. The venous catheter has an RF electrode on it, the arterial component has a ceramic foot plate, and there's rare earth magnets in the catheters that help them align in the artery and vein. They'll coapt, you deploy the foot plate,
and then you fire the RF energy from the RF generator, and the RF energy then creates a four millimeter hole between the artery and vein. This is just what it looks like under fluoroscopy, this is the arterial catheter going in here's the footplate here
this is the venous catheter then being directed and you can see the magnets on these they look like Lincoln Logs they'll kind of line up. You rotate the catheters 'til the foot plate aligns, you do some flyovers with the II make sure everything's lined up,
and then you create the fistula with the RF energy. Then this is just what Fistulagram looks like once the fistula's created. At the completion of that, for this device we then place coils, occluding coils, in the deep vein which was just beyond the sheath
where we accessed the brachial vein. And by putting those plugs in there, coils in there, It helps to direct the flow up to through the superficial veins which we cannulated for dialysis, and much like the other device
that Dr. Malia was talking before, this creates essentially a split vein fistula, it's going to mature both the cephalic and basilic if those veins are available through that from the perforator coming on out. This is just what it looks like you know,
this was in some early studies in the animal model, you can see that it creates exactly a four millimeter hole between the artery and vein. Eventually this will re-endothelialize they had endothelialization at 30 days. So really the nice thing about it is
it standardizes the size of the arteriotomy because it makes exactly a four millimeter fistula. Now, as I mention this is created at the level of the ulnar artery and ulnar vein, so the requirements basically to do this you need a adequate size obviously ulnar artery and vein,
but the big component is to have that adequate perforator vein that's going to help feed the superficial veins to mature that fistula. And then it's just creating a side to side fistula between the ulnar artery and vein.
This is just a composite of all the data that's been collected on the device so far so this is what the global registry looks like. The FLEX study was kind of the first studies in man. The NEAT trial was run in the Canada and the UK, that was one of the earlier trials.
Then there's a post-market registry, uh, in Europe that's being run now. The EASE trial is the trial with the Four French device and I'll share a little bit about that at one of the slides at the end. But basically pull all the data from this
there's almost 157 patients that they collected data on. And, you can see that with this the primary patency, or the primary patency's on at 75 percent, and the accumulative patency's almost 80 percent, and then the number of fistulas that were cannulated at six months successfully with two needles was 75 percent.
If you look at some of the interventions that've had to be done it really seems to be a lower number of interventions that have to be done to get a mature functioning fistula, uh, using this device. I just want to point out a couple things on this slide,
there was never any requirement for angioplasty at the uh, the ulnar artery the ulnar vein anastomosis, and there was, you know, with these embolizations that were performed, 12 of these were performed on patients prior to incorporating that into the procedure itself,
so right now in the IFU it says that the deep veins should be coiled to help direct that flow up into the superficial veins. Now as, uh, was alluded to earlier with the Ellipsys device this kind of falls somewhere between, uh, the radiocephalic fistula and a brachiocephalic fistula,
and again comparing these two devices basically you're creating, this is the Ellipsys device is radial-radial, and this device is really ulnar-ulnar, but again you're creating that split-flow fistula it's going to allow flow both up
into the basilic and cephalic veins. So, where can this be used? It can be used for primary access creation so that's the first option to provide a patient with a functioning fistula. It can be a secondary option to radiocephalic fistula,
or those that have failed the radiocephalic fistula, and it also is an alternative to surgery so there are patients that may not want to have open surgery to have a fistula created, and this obviously provides an option for those patients. In the UK now they're using it to condition veins,
so they'll create the fistula hoping to condition the cephalic and basilic veins to allow them to become usable for dialysis, and they're also using it in patients that have no superficial veins actually using it to mature the brachial vein
or the deeper veins, uh, and then superficializing the brachial vein to create a native fistula for patients who don't have adequate superficial veins. Now I mentioned the Four French device and what the Four French device allows is basically access
from a lot of different points. So now because it's a smaller device, we can place it, if the vein and artery are large enough, it can be placed at the wrists, so radial-radial fistula, so you come in from the wrist, put both catheters up, create the fistula at the radial-radial,
you can do it from the ulnar-ulnar, so it's just two catheters up from the wrist. And these cases are nice, the other option is you can come arterial from the wrist and you can come from the vein at the top, match up the catheters in a parallel
and create that fistula at the ulnar-ulnar level. And the nice thing about this is it really makes managing the puncture very easy you just put a TR band on 'em, and then you're good to go. So it really kind of opens up a lot of different options for creating fistulas.
So in summary this device seems to create a functional fistula without the need for open surgery. It has very good primary and cumulative patencies and seems to take fewer interventions to maintain and mature the functioning fistula, and this may add another tool that we have to create
functioning fistulas in patients who are on dialysis. So thank you very much.
- So my charge is to talk about using band for steal. I have no relevant disclosures. We're all familiar with steal. The upper extremity particularly is able to accommodate for the short circuit that a access is with up to a 20 fold increase in flow. The problem is that the distal bed
is not necessarily as able to accommodate for that and that's where steal comes in. 10 to 20% of patients have some degree of steal if you ask them carefully. About 4% have it bad enough to require an intervention. Dialysis associated steal syndrome
is more prevalent in diabetics, connective tissue disease patients, patients with PVD, small vessels particularly, and females seem to be predisposed to this. The distal brachial artery as the inflow source seems to be the highest risk location. You see steal more commonly early with graft placement
and later with fistulas, and finally if you get it on one side you're very likely to get it on the other side. The symptoms that we are looking for are coldness, numbness, pain, at the hand, the digital level particularly, weakness in hand claudication, digital ulceration, and then finally gangrene in advanced cases.
So when you have this kind of a picture it's not too subtle. You know what's going on. However, it is difficult sometimes to differentiate steal from neuropathy and there is some interaction between the two.
We look for a relationship to blood pressure. If people get symptomatic when their blood pressure's low or when they're on the access circuit, that is more with steal. If it's following a dermatomal pattern that may be a median neuropathy
which we find to be pretty common in these patients. Diagnostic tests, digital pressures and pulse volume recordings are probably the best we have to assess this. Unfortunately the digital pressures are not, they're very sensitive but not very specific. There are a lot of patients with low digital pressures
that have no symptoms, and we think that a pressure less than 60 is probably consistent, or a digital brachial index of somewhere between .45 and .6. But again, specificity is poor. We think the digital pulse volume recordings is probably the most useful.
As you can see in this patient there's quite a difference in digital waveforms from one side to the other, and more importantly we like to see augmentation of that waveform with fistula compression not only diagnostically but also that is predictive of the benefit you'll get with treatment.
So what are our treatment options? Well, we have ligation. We have banding. We have the distal revascularization interval ligation, or DRIL, procedure. We have RUDI, revision using distal inflow,
and we have proximalization of arterial inflow as the approaches that have been used. Ligation is a, basically it restores baseline anatomy. It's a very simple procedure, but of course it abandons the access and many of these patients don't have a lot of good alternatives.
So it's not a great choice, but sometimes a necessary choice. This picture shows banding as we perform it, usually narrowing the anastomosis near the artery. It restricts flow so you preserve the fistula but with lower flows.
It's also simple and not very morbid to do. It's got a less predictable effect. This is a dynamic process, and so knowing exactly how tightly to band this and whether that's going to be enough is not always clear. This is not a good choice for low flow fistula,
'cause again, you are restricting flow. For the same reason, it's probably not a great choice for prosthetic fistulas which require more flow. So, the DRIL procedure most people are familiar with. It involves a proximalization of your inflow to five to 10 centimeters above the fistula
and then ligation of the artery just below and this has grown in popularity certainly over the last 10 or 15 years as the go to procedure. Because there is no flow restriction with this you don't sacrifice patency of the access for it. It does add additional distal flow to the extremity.
It's definitely a more morbid procedure. It involves generally harvesting the saphenous vein from patients that may not be the best risk surgical patients, but again, it's a good choice for low flow fistula. RUDI, revision using distal inflow, is basically
a flow restrictive procedure just like banding. You're simply, it's a little bit more complicated 'cause you're usually doing a vein graft from the radial artery to the fistula. But it's less complicated than DRIL. Similar limitations to banding.
Very limited clinical data. There's really just a few series of fewer than a dozen patients each to go by. Finally, a proximalization of arterial inflow, in this case rather than ligating the brachial artery you're ligating the fistula and going to a more proximal
vessel that often will accommodate higher flow. In our hands, we were often talking about going to the infraclavicular axillary artery. So, it's definitely more morbid than a banding would be. This is a better choice though for prosthetic grafts that, where you want to preserve flow.
Again, data on this is very limited as well. The (mumbles) a couple years ago they asked the audience what they like and clearly DRIL has become the most popular choice at 60%, but about 20% of people were still going to banding, and so my charge was to say when is banding
the right way to go. Again, it's effect is less predictable than DRIL. You definitely are going to slow the flows down, but remember with DRIL you are making the limb dependent on the patency of that graft which is always something of concern in somebody
who you have caused an ischemic hand in the first place, and again, the morbidity with the DRIL certainly more so than with the band. We looked at our results a few years back and we identified 31 patients who had steal. Most of these, they all had a physiologic test
confirming the diagnosis. All had some degree of pain or numbness. Only three of these patients had gangrene or ulcers. So, a relatively small cohort of limb, of advanced steal. Most of our patients were autogenous access,
so ciminos and brachycephalic fistula, but there was a little bit of everything mixed in there. The mean age was 66. 80% were diabetic. Patients had their access in for about four and a half months on average at the time of treatment,
although about almost 40% were treated within three weeks of access placement. This is how we do the banding. We basically expose the arterial anastomosis and apply wet clips trying to get a diameter that is less than the brachial artery.
It's got to be smaller than the brachial artery to do anything, and we monitor either pulse volume recordings of the digits or doppler flow at the palm or arch and basically apply these clips along the length and restricting more and more until we get
a satisfactory signal or waveform. Once we've accomplished that, we then are satisfied with the degree of narrowing, we then put some mattress sutures in because these clips will fall off, and fix it in place.
And basically this is the result you get. You go from a fistula that has no flow restriction to one that has restriction as seen there. What were our results? Well, at follow up that was about almost 16 months we found 29 of the 31 patients had improvement,
immediate improvement. The two failures, one was ligated about 12 days later and another one underwent a DRIL a few months later. We had four occlusions in these patients over one to 18 months. Two of these were salvaged with other procedures.
We only had two late recurrences of steal in these patients and one of these was, recurred when he was sent to a radiologist and underwent a balloon angioplasty of the banding. And we had no other morbidity. So this is really a very simple procedure.
So, this is how it compares with DRIL. Most of the pooled data shows that DRIL is effective in 90 plus percent of the patients. Patency also in the 80 to 90% range. The DRIL is better for late, or more often used in late patients,
and banding used more in earlier patients. There's a bigger blood pressure change with DRIL than with banding. So you definitely get more bang for the buck with that. Just quickly going through the literature again. Ellen Dillava's group has published on this.
DRIL definitely is more accepted. These patients have very high mortality. At two years 50% are going to be dead. So you have to keep in mind that when you're deciding what to do. So, I choose banding when there's no gangrene,
when there's moderate not severe pain, and in patients with high morbidity. As promised here's an algorithm that's a little complicated looking, but that's what we go by. Again, thanks very much.
- Thank you, Larry, thank you, Tony. Nice to be known as a fixture. I have no relevant disclosures, except that I have a trophy. And that's important, but also that Prabir Roy-Chaudhury, who's in this picture, was the genesis of some of the thoughts that I'm going to deliver here about predicting renal failure,
so I do want to credit him with bringing that to the vascular access space. You know, following on Soren's talk about access guidelines, we're dealing with pretty old guidelines, but if you look at the 2006 version, you know, just the height--
The things that a surgeon might read in his office. CKD four, patients there, you want a timely referral, you want them evaluated for placement of permanent access. The term "if necessary" is included in those guidelines, that's sometimes forgotten about.
And, of course, veins should be protected. We already heard a little bit about that, and so out our hospital, with our new dialysis patients, we usually try to butcher both antecubital veins at the same time. And then, before we send them to surgery
after they've been vein-marked, we use that vein to put in their preoperative IV, so that's our vascular access management program at Christiana Care. - [Male Speaker] That's why we mark it for you, Teddy. (laughing)
- So, you know, the other guideline is patients should have a functional permanent access at the initiation of dialysis therapy, and that means we need a crystal ball. How do we know this? A fistula should be placed at least six months
before anticipated start of dialysis, or a graft three to six weeks. Anybody who tells you they actually know that is lying, you can't tell, there's no validated means of predicting this. You hear clinical judgment, you can look at
all sorts of things. You cannot really make that projection. Now there is one interesting study by Tangri, and this is what Premier brought to our attention last year at CIDA, where this Canadian researcher and his team developed a model for predicting
progression of chronic kidney disease, not specifically for access purposes, but for others. They looked at a large number of patients in Canada, followed them through chronic kidney disease to ESRD, and they came up with a model. If you look at a simple model that uses age, sex,
estimated GFR from MDRD equation and albuminuria to predict when that patient might develop end stage renal disease, and there's now nice calculators. This is a wonderful thing, I keep it on my phone, this Qx Calculate, I would recommend you do the same,
and you can put those answers to the questions, in this app, and it'll give you the answer you're looking for. So for instance, here's a case, a 75-year-old woman, CKD stage four, her creatinine's 2.7, not very impressive,
eGFR's 18. Her urine protein is 1200 milligrams per gram, that's important, this is kind of one of the major variables that impacts on this. So she's referred appropriately at that stage to a surgeon for arteriovenous access,
and he finds that she really has no veins that he feels are suitable for a fistula, so an appropriate referral was made. Now at that time, if you'd put her into this equation with those variables, 1200, female, 75-year-old, 18 GFR, at two years, her risk of ESRD is about 30%,
and at five years about 66%, 67%. So, you know, how do you use those numbers in deciding if she needs an access? Well, you might say... A rational person might say perhaps that patient should get a fistula,
or at least be put in line for it. Well, this well-intentioned surgeon providing customer service put in a graft, which then ended up with some steal requiring a DRIL, which then still had steal, required banding, and then a few months, a year later
was thrombosed and abandoned because she didn't need it. And I saw her for the first time in October 2018, at which time her creatinine is up to 3.6, her eGFR's down to 12, her protein is a little higher, 2600, so now she has a two-year risk of 62%, and a five-year risk of 95%,
considerably more than when this ill-advised craft was created. So what do you do with this patient now? I don't have the answer to that, but you can use this information at least to help flavor your thought process,
and what if you could bend the curve? What if you treated this patient appropriately with ACE inhibitors and other methods to get the protein down? Well, you can almost half her two-year risk of renal failure with medical management.
So these considerations I think are important to the team, surgeon, nurses, nephrologists, etc., who are planning that vascular access with the patient. When to do and what to do. And then, you know, it's kind of old-fashioned to look at the trajectory.
We used to look at one over creatinine, we can look at eGFR now, and she's on a trajectory that looks suspicious for progression, so you can factor that into your thought process as well. And then I think this is the other very important concept, I think I've spoken about this here before,
is that there's no absolute need for dialysis unless you do bilateral nephrectomies. Patients can be managed medically for quite a while, and the manifestations of uremia dealt with quite safely and effectively, and you can see that over the years, the number of patients
in this top brown pattern that have been started on dialysis with a GFR of greater than 15 has fallen, or at least, stopped rising because we've recognized that there's no advantage, and there may be disadvantages to starting patients too early.
So if your nephrologist is telling I've got to start this patient now because he or she needs dialysis, unless they had bilateral nephrectomies that may or may not be true. Another case,
64-year-old male, CKD stage four, creatinine about four, eGFR 15, 800 milligrams of proteinuria, referred to a vascular access surgeon for AV access. Interesting note, previous central lines, or AICD, healthy guy otherwise.
So in April 2017 he had a left wrist fistula done, I think that was a very appropriate referral and a very appropriate operation by this surgeon. At that time his two-year risk was 49, 50%, his five-year risk 88%. It's a pretty good idea, I think, to get a wrist fistula
in that patient. Once again, this is not validated for that purpose. I can't point you to a study that says by using this you can make well-informed predictions about when to do vascular access, but I do think it helps to flavor the judgment on this.
Also, I saw him for the first time last month, and his left arm is like this. Amazing, that has never had a catheter or anything, so I did his central venogram, and this is his anatomy. I could find absolutely no evidence of a connection between the left subclavian and the superior vena cava,
I couldn't cross it. Incidentally, this was done with less than 20 CCs of dye of trying to open this occlusion or find a way through, which was unsuccessful. You can see all the edema in his arm. So what do you do with this guy now?
Well, up, go back. Here's his trajectory of CKD four from the time his fistula is done to the time I'm seeing him now, he's been pretty flat. And his proteinuria's actually dropped
with medical management. He's only got 103 milligrams per gram of proteinuria now, and his two-year risk is now 23%, his five-year risk is 56%, so I said back to the surgeon we ligate this damn thing, because we can't really do much to fix it,
and we're going to wait and see when it's closer to time to needing dialysis. I'm not going to subject this guy to a right-arm fistula with that trajectory of renal disease over the past two years. So combining that trajectory with these predictive numbers,
and improved medical care for proteinuria I think is a good strategy. So what do you do, you're weighing factors for timing too early, you've got a burden of fistula failure, interventions you need to use to maintain costs, morbidity, complications,
steal, neuropathy that you could avoid versus too late and disadvantages of initiating hemodialysis without a permanent access. And lastly, I'm going to just finish with some blasphemy. I think the risk of starting dialysis with a catheter is vastly overstated.
If you look at old data and patient selection issues, and catheter maintenance issues, I think... It's not such an unreasonable thing to start a patient with a catheter. We do it all the time and they usually live.
And even CMS gives us a 90-day grace period on our QIP penalties, so... If you establish a surgeon and access plan, I think you're good to go. So who monitors access maturation? I don't know, somebody who knows what they're doing.
If you look at all the people involved, I know some of these individuals who are absolute crackerjack experts, and some are clueless. It has nothing to do with their age, their gender, their training, their field. It's just a matter of whether they understand
what makes a good fistula. You don't have to be a genius, you just can't be clueless. This is not a mature usable fistula, I know that when I see it. Thank you.
- Thank you Dr. Asher. What an honor it is to be up here with Dr. Veith and Dr. Asher towards the end. You guys are leading by example being at the end of the meetings. So, thank you for allowing me to be up and talking about something
that not a lot of vascular surgeons have experience with, including me. I have no disclosures. On your left, I have listed some of the types of diseases that we most commonly see in the vertebral artery, and there are quite a lot.
And on the right, the standard types of treatment that we pursue in vascular surgery or as a vascular specialist. And often, in the vertebral artery, if we are going to pursue treatment, it's the endovascular route.
But I'll talk a little bit about open surgery. The clinical presentation is often vague. And the things I wanted to point out here in this long list are things like alternating paresthesias, dysphagia, or perioral numbness may be something in the history to look for
that you may not be thinking about when you're thinking about vertebral basilar disease. The anatomy looks straightforward in this picture, with the four segments, as you can see. It gets a little more complicated with just the arterial system,
but then when you start looking at all these structures, that you have to get out of of the way to get to the vertebral artery, it actually can be a difficult operation, particularly even in the V1 segment. The V1 typically is atherosclerotic disease.
V2 is often compression, via osteophyte or musculo-tendon structures. And V3 and V4, at the top, are typically from a dissection injury from sort of stretch or trauma injury. The pathophysiology isn't that well understood.
You have varying anatomy. It's very difficult to access this artery. Symptoms can be difficult to read, and treatment outcomes are not as reliable. But I'm going to take you through a very quick path through history here in the description
of the V1 segment exposure by Dr. Rentschler from 1958. And I love these pictures. Here is a transverse incision over the sternocleidomastoid, just above the clavicular head on the right side. And once you get the sternoclavicular head divided, you can see the longus colli muscle there.
Anteromedial is the carotid. Of course, you surround that with a Penrose drain. And then once you do that, you can separate your longus colli, and deep to that, the vertebral artery just easily slips right up, so you can do your transposition.
It's not quite that easy. I've done one of these operations, and it was difficult finding t e. And, again, here is on the opposite side, you can see the transposition in this cartoon.
Dr. Berguer is the world's expert, and a lot of this open surgical work comes out of the University of Michigan. Here is a study looking at 369 consecutive extracranial vertebral artery reconstructions. You can see the demographics of clinical presentation.
And note that about 34% of patients are presenting with hemispheric symptoms, with 60% in the vertebral basilar distribution. 300 of these reconstructions were for atherosclerosis. And the outcomes were pretty good. Before 1991, there wasn't really a protocol in place
in assessing and doing these procedures. And you can see the stroke and death rates of 4.1 and 3.2% respectively. And then the outcomes after 1991 are considerably better with a five year patency rate of 80%. So, in summary, vertebral artery disease is,
I think if you review this, is somewhat under diagnosed. Revascularization is a viable option. Most often, it's endovascular. But if you have endo-hostility, then an open, particularly for the V1 segment, may be a better option.
And this requires people with good operative experience. Thank you very much.
- So these are my disclosures. And let's start first of all for the merit to have them, what are the potential benefits? So we'd like to get rid for permanent rigid metallic cage. We'd like to restore vasomotion, angulation, eliminate instant restenosis of metallic stents which is hard to treat.
We also have to keep the ability of late luminal enlargement, preserve the target for CABG and freedom from long-term polymer exposure, inflammation, and it is very appeal to patients and physicians not to have a permanent implant.
But with all these we have seen what is the desire. The desired is to have this absorbed treated artery looks like, very nice healing. Large lumen compared to metallic DES. Does it really happens? And the question was driven initially from data from Europe,
that look on large registries that the results of 30 days and six months with Bioresorbable Scaffolds was acceptable except for one thing, which definite, probable stent thrombosis. 1.5% and 2.1% in the coronary, it is not acceptable. This was also driven or repeated in a similar magnitude
in ABSORB II and ABSORB III which were randomized trials comparing Xience, which was the drug eluting with metallic stents to BVS or Absorb, which showed again over time higher thrombosis rate for both of those randomized trials and this was despite the patients were on DAPT.
As a matter of fact, the recommendations were extended for the Absorb now to three years, for the duration of the absorption time. So the question was whether these were two early studies without implying good technique. And then what is the good technique?
You doing pre-dilatation, you're doing post-dilatation, you're doing imaging. And that was actually implemented later on. So if we look at the latest data that was presented with the Absorb, which was ABSORB IV studies,
now the stent thrombosis are better. They're only 0.7% at one year compared to 0.3% with Xience. It still looks a little bit higher numerically, but these are within the range of what you can expect from drug eluting stent. The other thing that this study showed,
if you look on ABSORB III-like studies, your results are going to be relatively much better that what you have seen with ABSORB III. But nevertheless, this first generation stent, if you can look at the totality of the data was still higher events compared to metallic stent.
Now why did we prolong the DAPT from three years? Because we do know that the three years we still have PLLA that is still there and it could dismantle and cause scaffold thrombosis. Now Abbott pulled out the technology from the market for commercial reasons.
I think the main reason was the fear from thrombosis and patients and physician didn't want to use it. And the ESC guidance just changed their recommendations to Class IIIC, which means you should not use it unless you doing it in clinical trials. So this is really was hampering on the whole field.
And the question, can we resuscitate from this situation. First of all, we need to know how to improve it. We have to improve the technique, PSP, imaging, prolonged DAPT, and also we have to improve the technology with thinner struts, improved mechanical properties.
Are these coming along? Definitely yes. We have a array of second generation BRS with 80 micron, 99 micron, 100 micron compared to 228, 170, 150 in the first generation. So we are going to see secondary generation scaffolds
that perhaps will solve all those issues which we have seen with the thrombosis. And indeed, if it's not going to come from the U.S., probably not very soon, it's coming from China. And look at the number of programs right now. Five programs completed First In Man,
two of them in randomized clinical trials, two already completed registries. So the data from China which is randomized, will come and we'll see how that goes. This is a project that I've been working on, Magnesium just to show you,
that if you compare Magnesium to ABSORB you see no thrombosis on the porcine model shunt. And this is even better than metallic DES stent. So I think we can able to solve the thrombosis rate. If we do that, then I think we see those technology coming back again.
What about the periphery? There's was one study at ESPRIT, very small one, with actually promising result. And again, it's up to the companies to see if they're going to encroach to the SFA program. So my final thoughts are that the unmet need
for Bioresorbable scaffolds remain despite improvement of second generation DES. The first generation BRS are inferior to the best in class DES and should not suitable for routine use. We always will have to show randomized trials
that at least we have known inferiority of Bioresorbable technique to metallic DES and then with second generation BRS we have the hope to make scaffolds great again. Thank you very much.
- So first of all I want to tell everybody that you're going to have a hard time finding these tools that I'm going to show you. So before I start the talk I want to tell you how you can find these. Everybody's got phones out there that you can Google on. If you would Google "One minute access check"
it will take you to the website that is the ESRDNCC.org site, and that's where you can find the tools. The other place that these are all located is on the VASA website. If you go to the VASA website, which is
the Vascular Access Society of the Americas, which is VASAMD.org, and you go under "Vascular Access Team", all of these tools are linked. The tools that we're going to talk about were put together by the FistulaFirst and I was on the work group that created these tools,
and they're going to solve the problems that you just heard the rest of the group talk about. It talks about how to collaborate the care, how to assess the maturing and the healing access, and to level the playing field so we're all doing it the same way.
And that's basically what these tools were developed for. That's my conflict of interest. So the patient video that just showed you, the patient said patient education. This is a free, your tax-dollar money paid for this booklet. You can print these for free,
there's no copyright issues on it. This is a patient access planning booklet that explains to the patient all of their choices for renal replacement therapy, what is an access, and what's going to happen to them when they get this access.
This is a fantastic booklet and it also serves as the patient's care plan if you fill this out and use it. It can go between the dialysis facility, the surgeon, and the interventionalist. And I'm sorry it doesn't project well,
but this is just a snippet from the booklet that shows you, for the surgeons in the audience, what's going to happen at your office when the patient comes in. And it gives questions that the patient and the family should ask.
So as surgeons, if you look at this booklet, you use it with your team at your office, you'll be able to be prepared for patients coming in and you can use this tool. This is what I consider the plain ice in the sandbox tool.
This tool was created to define all of the various roles of the dialysis access care team, because we all do different parts of the process, but if we don't work together, it doesn't work. So this booklet explains what everybody's roles are, and again this is a great tool.
If you've got a nephrology practice that you're not happy with how things are coming to you with referrals, or you've an interventionalist that you're having issues with, sit down, have a team meeting, bring all the players together
and use this book to guide it. It really tells you what to do and how to do it. And this is an example of what's going to happen with the care team coming together how you go through the access planning, okay? And this is just some information of what
the surgical appointment should get. When you get the patients to show up and they come to you with no information, you don't really know much about the patient, this booklet helps to prepare the dialysis facilities so they know what to send
and they understand those records should come to you. Now, the main part of these booklets of what we're talking about today is this whole issue of what Ted's slide was about who should assess the access for maturing. Well, this answers that question.
There is a basic tool that will give you a weekly assessment of whether or not that graft or fistula is ready to go. And basically this is the care planning part of it where we make that access plan, we then find the best place to get the access,
we choose, we get the patient to the surgeon so you can place the access, patient goes for the surgery. Then we wait for it to mature, heal, we use the access, we then have to get the catheter out, and then we
have to take care of the lifeline for the rest of the patient's time on dialysis or their transition between different modalities. So, how do we do that? The tools are based, this weekly assessment tools are based on the classic one minute check.
This is actually from Dr. Bether's physical exam that's been taught to nephrologist and dialysis staff for many years. It's a simple look, listen, and feel. There's also an advanced test for the care side. This is for the patient,
and this is for the clinician side. It's the look listen and feel with the arm elevation test, and the augmentation test is also added on at the expert level. Again, all these tools are on the website for you to use. Please use them.
Once you understand the one-minute check, this is then the graft healing slides, and again it's a weekly assessment, and we called it graft healing because grafts don't mature, we just are waiting for the surgery line to heal so that
we can go ahead and cannulate it. If it's an early cannulation graft, this would be adopted for those early cannulation grafts, this is for standard graft material. So we go into week two, this tells the patient, the staff, the nephrologist, everybody on the team
what should we be looking for and what should be happening with that access and when it should be ready to cannulate. By week four, if it's not ready to cannulate, this triggers notifying the surgeon, re-engaging with the team, and figuring out
what's going on with the patient's access, okay? We cannot just let these patients sit there with accesses that are not being used for weeks and weeks and weeks. We have to have a plan. And this is what the tool does. The fistula maturation tool is the same thing.
Again it's weekly assessments, there's week one and two, week three, by week four we're looking for actual signs of change with the fistula. If it's not, we would start to already think of a plan of does this need some assisted maturation.
Week five, we're looking to see is it ready to cannulate. By week seven through ten, it certainly should be ready to go and we should be dealing with catheter freedom. There's also a catheter version, because patients with catheters still need to have their catheters
well maintained so they don't get infection. There's a patient version and a staff version. And again it's the same look listen and feel. We obviously don't listen to a catheter like we do a graft or fistula, but we listen to the patient to make sure they're not having symptoms
of infection or problems with the catheter. And we have to do that because we're all part of this interdisciplinary team. I'm a dialysis nurse, so I'm part of the dialysis team, but we have an interdisciplinary team in the dialysis unit, we have to work with the surgeons,
the interventionalists, whether you're an IN or an IR, we have to work with the patients, we have to bring the family in, it's all about this process of care, and hopefully you'll look at these tools and maybe these tools will help you
with your process of care. Thank you.
- [Evan] So today I'm going to talk about Episode Based C because a hemodialysis access measure is currently under development as we speak. This is not technically a disclosure but I do represent the SVS and serve as a co-chair for the Peripheral Vascular Disease Management Clinical subcommittee for Acumen, who's
consultants to CMS, and that will become clear in a minute. In the past, all of us had our cost accountability through the Value-based Modifiers in the old system, but going forward with MACRA, physicians have to choose to participate in an Alternative Payment Model or in a Merit-based Incentive Payment System.
Now in Alternative Payment Models, this is where, as a physician or a group, you share the risk for the possibility of higher gains, and this is exemplified by such things as Accountable Care Organizations, it requires a rather hefty investment of resources, time in order to do this, so most of us will wind up in the MIPS, the Merit-based Incentive
Payment System, and if you do wind up there, your cost accountability is going to be a composite score in these four areas: Quality, Resource Use, which is cost and that's what we're talkin actice Improvement, and Advancing Care.
So by way of background, CMS contracted with Acumen to develop episode-based cost measures. They established Clinical Disease Management Subcommittees, who received input from a Technical Expert Panel, Person-Family committee, which is patients and their families, as well as public commentary with
the goal of selecting one to two episode groups. The measures were developed in waves, which correspond to a given year, and these measures should be high impact. In other words, they should encompass a large number of Medicare beneficiaries, a large number of providers, and have a significant cost impact.
Measures are then eligible for the MIPS cost performance category in the Quality Payment Program, and the Peripheral Vascular Disease group was tasked with choosing between Limb ischemia, Aneurysms, Carotids, Filters, and Hemodialysis Access. In the first wave, which occurred in 2017, you can see there
were seven Disease Management Subcommittees. The Vascular subcommittee chose to focus on Critical Limb Ischemia, the committee had 22 members representing 19 specialty areas, and for this year, the second wave in 2018, Hemodialysis Access Creation was chosen as the measure. So what's an episode group? An episode group is
defined by an acute inpatient condition, like an MI, a chronic condition like COPD, or a procedure, Hemodialysis Access Creation. Cost Measures are Medicare payments during this entire episode and informs clinicians of the cost they're responsible for and allows for
comparison between physicians. It's calculated using Medicare claims data only, so there's no additional reporting burden. These are the basic steps in Cost Measure Development. There are some others, but we'll go through them one by one. The first is to define the episode group,
and for surgical procedures it's more or less straightforward, because you wind up with the CPT codes for the procedures that are encompassed, and you can see these are the CPT codes here that were chosen for this measure. Next, because episodes include more than just the day of
surgery, you have to establish pre- and post-trigger episode windows. These are look back and look forward periods for which related services are included. The Hemodialysis Measure actually has some variability here in that the pre-trigger window can extend as far back as
three days for things like basic labs, all the way back to 60 days for things like a cardiac echo, and the post-trigger window can go forward one day for something like anemia, but up to 180 days for a re-do procedure. Then, because these groups or the procedures tend to be somewhat heterogeneous, you have to define subgroups.
In other words, make the groups more homogeneous while maintaining enough episodes to make the measures meaningful, and in this case we have two basic subgroups: fistulas and grafts. Then you go ahead and define exclusions. So HeRO grafts really can't be compared to either these two
basic groups, so they're excluded, although any excluded procedure is eligible for use in future waves. The next steps include attributing episodes to given clinicians, so the responsibilities assigned based on either Tax Identification Number of groups or ind
e episode are assigned, these are the costs included within the episode and these are based on the role of the attributed clinician, and then risk adjusted for factors that are outside the clinician's control, such as the patient's medical status. This is kind of a schematic of the Hemodialysis episode.
Here in the big, blue triangle this is the trigger service, so is either the creation of a graft or a fistula (HeROs are lated to this can then either be assigned to the episode or not assigned to the episode, and all services that are assigned can either
be attributed to the clinician performing the procedure, or to other clinicians. For example, a balloon maturation or a de-clot done by another physician is attributed as part of the cost to the service, but not the attributed clinician. Services that are not assigned to an episode are generally
only attributable to other clinicians and providers, and the pre-trigger window as we mentioned three to 60 days, post-trigger one to 180 days. Then a score is reported, and in general before the measures go live, there's a field testing period, and this is a sample field test, it's actually
for Hip Arthroplasty, and what you see here is a couple of things: first of all, this particular group has 161 episodes, usually the minimum is somewhere between ten and 30 episodes that are required. The Risk Adjusted Expected National costs here are estimated, about $19,000, and then the actual costs for this
group were estimated here, and you see this group had a cost of $21,000, so their relative performance is 12% more expensive than the national average. There are other details in these reports that get dri n see they
break out your costs by different aspects of care. Then the next thing is what's the timeline of all of this? Here in the orange brackets you see this is the MIPS, these are the four elements for which your composite score is based, and again we're talking about cost here. So in 2019, for providers participating in the MIPS,
you are eligible either for a four percent bonus, or a four percent penalty based on this performance score. And as you march this out to 2022, that increases to plus or minus nine percent. And the APMs you see here are in a separate category. In summary, these measures are part of the MIPS cost
performance category, they are based only on claims data, the Peripheral Vascular Disease Management subcommittee was charged with measure development, the Wave One measure for chronic Critical Limb Ischemia has been proposed for use in the Quality Payment Program in 2019. Ultimately, all these measures are to align
with quality measures, but of course this depends upon either the presence or development of quality measures that are meaningful and can correlate with some of these specific episodes. I can tell you the measure development is tedious, it's complex, you go very deep in the weeds,
and a big point for CMS and for those developing has been to avoid creating unwanted incentives which result in unintended consequences, and if you'd like more information, these articles in the JVS "Under the Macroscope" can give you more detail into this and other programs. Thank you.
- Thank you for the opportunity to speak today. I have no disclosures. We've heard a lot about this, this morning, but, I'll just reiterate, for those of you who may or may not be familiar, The Fourier trial was a randomized trial of Evolocumab versus placebo in nearly 30,000 patients with atherosclerotic disease, and that the primary end point
was a composite of cardiovascular death, MI, stroke and hospital admission as well as some secondary end points as well. So what about these inhibitors in Peripheral Arterial Disease? Well, a sub analysis investigated the efficacy and safety of
Evolocumab in patients with PAD. And patients were defined as having PAD at baseline, if they had either intermittent claudication and an ankle brachial index of <0.85 or if they had a prior peripheral vascular procedure. So of the total cohort, 3,600 and some patients where 13%
had PAD based upon this definition, Evolocumab significantly reduced the primary end point consistently in patients with PAD with a hazard ratio of 0.79. What about Cardiovascular efficacy in the PAD population? Evolocumab significantly reduced both the primary end point
and the composite end point of cardiovascular death, MI or stroke very significantly and you can see in looking at this slides that the relative risk reduction was of higher magnitude in the patients with PAD than without PAD. Major advers limb events were significantly reduced in the overall population
as well as the patients with PAD and the results with regards to major amputation, I think are quiet compelling here. Again if you look at major advers limb event reduction you can see here in all patients and in patients with PAD there was a market reduction in events.
And then if we finally look at a composite outcome of MACE, and Male in patients with PAD, overall Evolocumab again reduced this composite outcome by nearly 21%, and if you look at the slide again, you can see that the magnitude of reduction, was of higher magnitude in the PAD group.
What about the safety? There were no differences in the incidents of adverse or serious events with the medication in patients with PAD. And importantly there was a consistent relationship between lower achieved LDL levels and lower risk of limb events that extended down to
very low levels of LDL cholesterol. So in summary Evolocumab significantly reduced the primary end point with patients with PAD because of their overall higher risk, patients with PAD actually had a larger absolute risk reduction for many of this end points than many patients without PAD and Evolocumab
significantly reduced major adverse limb events in all patients and in patients with PAD. What about Coronary disease as doctor Veith asked me to address? With in the of patients with prior MI, it was hypothesized that may be we could identify some that would
benefit more from this medication. So, 22,000 patients had a prior MI, and they were classified in several areas, one of them being, that based on the time of their most recent MI, 8,400 patients or 38 percent were with in two years of their most recent MI,
and this recent MI as well as other factors were independent predictors of a future cardiovascular outcome. So, if you see her in the placebo arm compared with patients with a remote MI , those with a recent MI were significantly higher risk in the placebo arm for the primary end point.
The relative risk reductions for the primary end point was greater in these high sub groups including recent MI, than for those with remote MI, and you can see this here in this slide as well. And patients with a recent MI and with remote MI and the magnitude of the reduction being much greater in the higher risk group.
So in conclusion recent MI, was felt to be a high risk condition and that these patients significantly benefit from cholesterol lowering with Evolocumab. So it's being reiterated here this morning, how low should we go, the targets are constantly changing and again changed just as recently as last week, and there
are a lot of good arguments for extensive lowering of LDL cholesterol, it's important to realize that because of the anticipated extreme reductions in LDL cholesterol regulatory agency require enhanced monitoring of adverse events. Particularly neuro-cognitive events, and in a sub study of FOURIER, there were no group differences in many of these
parameters between the placebo and medicated groups. in FOURIER the reduction in the primary and secondary composite end points was in fact linearly relate to the achieved LDL cholesterol. And in a post hoc analysis five percent of these patients achieved extraordinarely low levels.
In this group importantly, there were no associations between this achieved levels and predetermined safety event. So I tried very hard to find a slide that said when they go high we go low but unfortunately no one wanted to make that so I'll just say go low or go home.
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