CRYOPLASTY THERAPY OF SUPERFICIAL FEMORAL AND POPLITEAL ARTERY MEMORIAL HERMANN HEART AND VASCULAR INSTITUTE-SOUTHWEST HOUSTON, TX May 2, 2007

Transcription

1 CRYOPLASTY THERAPY OF SUPERFICIAL FEMORAL AND POPLITEAL ARTERY MEMORIAL HERMANN HEART AND VASCULAR INSTITUTE-SOUTHWEST HOUSTON, TX May 2, :00:09 ANNOUNCER: Over the next hour, see an innovative non-surgical treatment of peripheral arterial disease using CryoPlasty Therapy. This webcast comes to you live from Memorial Hermann Heart and Vascular Institute-Southwest. CryoPlasty therapy is an innovative new procedure that uses cooling therapy to remedy difficult-to-treat blood vessel blockage. It's a form of angioplasty that gently cools and opens arteries clogged with plaque due to peripheral arterial disease. In traditional angioplasty, scarring of the artery wall can occur that can prompt the artery to close. CryoPlasty therapy can open the artery and cause less scarring, offering hope to people with severely blocked arteries. OR-Live makes it easy for you to learn more. Just click on the "request information" button on your webcast screen and open the door to informed medical care. Now let's go live to the operating room. 00:01:05 DAVID PORTUGAL, MD: Good afternoon and welcome to our live webcast at the Heart and Vascular Institute at Memorial Hermann Hospital Southwest. Today, we're in for a real treat. We'll watch an innovative non-surgical treatment to clear blocked arteries due to peripheral arterial disease. I'm Dr. David Portugal, an interventional cardiologist here at the Heart and Vascular Institute at Memorial Hermann Southwest. I'll be your co-moderator today. I'm joined by my colleague, Dr. Ramon Ty. Hello, Ramon. 00:01:36 RAMON TY, MD: Hi, David, it's good to be here. I certainly hope our viewers will enjoy the webcast today. 00:01:41 DAVID PORTUGAL, MD: In a minute, you will meet Dr. Carlos Zorrilla and Dr. Sherman Tang. They are two of our highly skilled interventional cardiologists who practice here at the Heart and Vascular Institute at Memorial Hermann Southwest. They will be the doctors performing this innovative procedure. Before we go to the cathlab where Dr. Tang and Dr. Zorrilla are, there are just a few bookkeeping items we'd like to go over with you in regards to how to communicate via on your computer with our panel today. 00:02:09 RAMON TY, MD: During today's webcast, we'll be taking your questions via . You may send us your questions by clicking on the MDirectAccess button on your computer screen. We'll try to answer as many questions as we can during the program. You may also be able to continue to communicate with the physicians for at least four weeks after the program. And you can tell your friends and colleagues if they miss the show, they can still watch a little later. The show will be archived and available indefinitely at the following website: Innovation and quality are at the heart of our program here at Memorial Southwest in Houston. And what we want to share with you is some of the latest advancements

2 today in the treatment of peripheral vascular disease. Let's join Dr. Tang and Dr. Zorrilla in the cathlab. Sherman? 00:03:01 SHERMAN Y. TANG, MD: Hi, David, Ramon. Thank you for your introduction. It's my pleasure to be here and to demonstrate this new, innovative technology, so-called a CryoPlasty. It's new. We're treating this critical limb ischemia. We're shifting from the surgical approach to the endovascular approach. Before I start the case, I want to introduce my team. Dr. Zorrilla, standing right next to me. We have two RTs, Rovelle and Norman. And we have two nurses, Terry and Gigi. Gigi, she's sitting in the control room. And I would like to give a simple introduction about this case, his background. This patient is 60 years old. He has a history of coronary disease, diabetes, hypertension. He started having intermittent claudication less than 50 feet, which is, from ten, classification three to four. Recent diagnostic peripheral angiogram has demonstrated a severe peripheral vascular disease before -- below the inguinal ligament. I'd like to show you the diagnostic picture we just took. 00:04:20 DAVID PORTUGAL, MD: Now, Sherman, before you took this picture, so you have this gentleman here, I imagine you put a catheter, which is a small tube, and you put in the left leg. And I believe you went around across his aorta and put the catheter over to the right leg and injecting dye down his right lower extremity. And if you see on your screen, you will see the extent of the severity of the blockage that you see in this gentleman's right leg. 00:04:53 SHERMAN Y. TANG, MD: That's correct. You can see the disease started the origin right at the superficial femoral artery. And you can see, it extends all the way down to the distal portion of the SFA. The ranging of the stenosis is anywhere from 70-90% stenosis. Even below to the knee, which popped the artery below that and has a diffused disease. 00:05:18 DAVID PORTUGAL, MD: Yeah, I think those pictures are quite dramatic, and I think, you know, the technology we use at Memorial Hermann Southwest in performing these procedures, we do use subtracted images. And if you notice, in the background, a very faint background, you'll see the bony structures. You can just barely see them faintly. That's called subtracted images, where the bones don't get in the way of the actual images. And so the arteries, which are filled with dye, come across very nicely. 00:05:46 SHERMAN Y. TANG, MD: Yes. 00:05:51 RAMON TY, MD: Sherman or Carlos, could you describe how you prepped the patient? Was this done in local anesthetic? Did you give a sedation? How do you generally prepare these patients. 00:06:00 SHERMAN Y. TANG, MD: Yes, these patients go under -- called a IV conscious sedation. He has received (indistinct) and fentanyl for conscious sedation and back pain. And then we'll give a local anesthetic injection to the left. We use what's called the contralateral approach because of the problem is in the right leg but we'll start an insertion from the left side, go across the aortic bifurcation into right external iliac artery. What's the advantage of using this approach? When you finish the procedure, when you do the hemostasis, you usually use hand compression, and you have a period of time to cut off the blood flow. And in the case, we do this endovascular procedure, you want the flow -- flow will be very important. You don't want to have - - a limited flow can be a potential cost to the thrombus, even we have given

3 anticoagulation. In this case, we'll give it as intravenous Angiomax, but we still like to -- without compression the same side. Second thing is an integrate compression. Usually it's very challenging for staff, for doctors to compress in the groin because -- in that anatomic region. 00:07:15 DAVID PORTUGAL, MD: I think you see a good picture there. so this is the size of -- of the -- what we call a sheath, which is basically a tube that goes into this gentleman's groin. And through his femoral artery. And so it is quite amazing what we can do here. So this is a gentleman who is not under general anesthesia. He walked into the hospital today. That's the size of the incision, so when that tube comes out, there will be no stitches there. And within four to six hours, he'll likely be walking around in his hospital room and go home tomorrow. 00:07:54 SHERMAN Y. TANG, MD: That's correct. 00:07:56 DAVID PORTUGAL, MD: So, Sherman, this gentleman had claudication, and just to review with our -- with our audience, you know, I imagine we do have some physicians watching but a number of just patients and just general public watching this program, but Dr. Ty has a few slides I think to talk about the -- the disease that we're treating and the symptoms of -- and how it presents. 00:08:23 RAMON TY, MD: Yes. 00:08:26 DAVID PORTUGAL, MD: Ramon. 00:08:27 RAMON TY, MD: Well, in general, peripheral vascular disease is a disease of the lower extremities, but one of the take-home points I want to make today, although we are treating a leg problem, a leg blockage, you've got to remember, at the end of the day, the overall picture is the patient. The majority of these patients do not just have leg problems. At the end of the day, eventually, when they get into trouble, they eventually have heart problems. And therefore other issues that you must remember are very important to consider in total patient care is that they have to take care -- we have to take care of what they -- of what's called risk factors. They have to quit smoking, we have to take care of the blood pressure, diabetes, cholesterol problems. And taking care of the leg is a -- important, but it is a part of the total patient care. The -- in general, we think that perhaps -- in general we think it's more common in males. Of course, older people have it. And as I said, in terms of risk factors, diabetics commonly will have peripheral vascular disease. And you also have to remember, in diabetics especially, again, going back to the point of making heart disease relevant in such a case is that diabetics, 80% of diabetics eventually will have diagnosis of heart disease, without question. Smokers are going to be high-risk for this problem. High-blood-pressure people, cholesterol, fibrinogen sometimes. But the way -- 00:09:57 DAVID PORTUGAL, MD: Do you want to bring up that slide on risk factors? Okay, excellent. 00:10:06 RAMON TY, MD: Yes, Carlos, I'm sorry, you have a comment? 00:10:08 CARLOS D. ZORRILLA, MD: I just wanted to say I'm enjoying very much your comments. We're going to go ahead and proceed. You could continue giving information to the audience here, and we'll start going with the -- what we're going to do at this point is to use a wire because the obstructions that you saw in that big

4 artery that is in the thigh, the femoral -- superficial femoral artery, that artery is going to be our target. There is a, as you can -- as you saw, is diffused disease, and we're going to cross with this fine wire all the way down below the knee, and then we're going to proceed to use this technology that we've been talking about, which is CryoPlasty. So at this point, we're going to go ahead and proceed with the -- with passing the wire. 00:10:56 RAMON TY, MD: So at this time, Carlos, should I say buenos suerte? 00:10:59 CARLOS D. ZORRILLA, MD: Gracias, amigo. 00:11:09 DAVID PORTUGAL, MD: So you'll see here, that's this wire, it's inches in diameter. It has a slippery coating that gives it the ability to pass down the artery without difficulty. You see Dr. Tang passing this wire through the entry point of that tube in this gentleman's left leg. An interestingly, you see that the tube's actually in the left leg but the artery we're treating is in the right leg, and that's because that tube has gone from one side over to the left. And you can see that kind of wishboneshape appearance that the arteries in the pelvis have where the aorta branches off into two arteries into each leg. And there's that wire traversing down the distal aspect of that leg and the artery in that right lower extremity. And really that -- the wire is sort of the backbone of interventional cardiology. If we can get a wire down to that artery, then we can generally get our equipment down to that artery to treat it, so everything we use, whether it be balloons, whether it be lasers, whether it be devices that can actually shave off plaque off arteries, it has to go over that wire. So -- and Dr. Tang very skillfully passed that wire down without too much difficulty. 00:12:35 RAMON TY, MD: And I think for the medical people who have some experience or involvement in the cathlab, I think it's not just the wire that's the key, it's also very often for any intervention, balloon angioplasty procedure, we have to have good guidance support. It's meaning the catheter they slip around the aorta has to be in good position. It doesn't flip-flop out of position. 00:12:54 DAVID PORTUGAL, MD: Dr. Tang, Dr. Zorrilla, can you show the camera, before you pass that device into the body, are you able to show the camera the picture of what we're using today. 00:13:08 SHERMAN Y. TANG, MD: This is called a polar catheter made by Boston Scientific. And the material we use -- we're looking to reference size vessel. We like to choose the diameter. The balloon is just about the size of a normal vessel. And we think the five-millimeter in diameter, which is good for this vessel. And this balloon length is about 10 centimeters long. And the catheter length is about 120 centimeters. And because we use a crossover sheath on the left side, so it needs a longer catheter to get across to the proper area. 00:13:45 DAVID PORTUGAL, MD: Yeah, so in case our audience is not aware, you know, balloon angioplasty's been around really for decades. But unfortunately, even though we use it day in, day out, it does have some weaknesses. And this device that Dr. Tang and Dr. Zorrilla today -- was developed to kind of address those weaknesses of balloon angioplasty. It's really an amazing feat of engineering. It's called a polar catheter. Basically, it -- it has a balloon, which is a chamber, a plastic chamber, that fills up with nitrous oxide. And so that nitrous oxide gets passed to the cath-- distal aspect of the catheter and freezes the surrounding artery to below 10 degrees Celsius. And it is this freezing effect which, in our experience, has addressed some of

5 these weaknesses of angioplasty. You know, whenever we dilate arteries, sometimes they don't behave like we want them. You know, these arteries that we stretch open sometimes can, what we call recoil or bounce back back to the original size. And we - - we don't want that. We want that artery to stretch open, that blockage to be cleared out. This device also has the ability to perform what we call apoptosis. And that's the ability to actually freeze that artery. And you can see the catheter there. Those are the -- the catheter's being brought down to that artery, and it has markers on it. And that way our operators can see the catheter under x-ray guidance. The device Dr. Tang has and Dr. Zorrilla has, that's the catheter with -- the nitrous oxide attaches to the polar catheter. Carlos, you want to tell us what you're doing? 00:15:41 CARLOS D. ZORRILLA, MD: We're connecting the balloon polar catheter with this device that is electronic that's going to inject the nitrous oxide. 00:15:53 DAVID PORTUGAL, MD: Okay. All right. 00:15:58 CARLOS D. ZORRILLA, MD: This-- okay -- automatically is going to indicate when the device is ready for us to press the button so the nitrous oxide will go into the balloon. And the -- the inflation is going to be a gradual inflation with a maximum of 8 atmospheres of pressure for about 20 seconds. And further inflation could be maintained without the nitrous oxide for maybe one or two minutes if desired. Right now, you're going to see there that we're ready now to -- the entire catheter -- we're ready to -- 00:16:54 DAVID PORTUGAL, MD: You're ready now to deliver the therapy. 00:16:56 CARLOS D. ZORRILLA, MD: Yeah, deliver the therapy. 00:16:57 DAVID PORTUGAL, MD: So you have your -- you have your catheter in the location in the right superficial femoral artery. 00:17:02 CARLOS D. ZORRILLA, MD: We always like to start distally to proximally because that's the easiest way to achieve. 00:17:09 DAVID PORTUGAL, MD: So how long is your catheter, the balloon segment? 00:17:11 CARLOS D. ZORRILLA, MD: Now you can see the -- 00:17:12 DAVID PORTUGAL, MD: There you go. 00:17:13 CARLOS D. ZORRILLA, MD: There we go, it's inflating now. 00:17:15 DAVID PORTUGAL, MD: So we see a sort of a checkerboard appearance to this balloon catheter, and that -- those markers there are present because there's no contrast that's normally there in our balloon catheters. We usually have contrast there so we can see that under x-ray guidance, but actually inside there is nitrous oxide, so right now, that artery's being brought down to -10 degrees Celsius. That artery's being stretched open. That plaque that you saw that was restricting blood flow to that leg is now being literally squished up against the side of that wall. And hopefully improve the blood flow to this gentleman's right leg. 00:17:58 RAMON TY, MD: So, David, you might want to tell the audience, we are infusing a liquid, and what happens to it when we go -- go in there?

6 00:18:04 DAVID PORTUGAL, MD: Well, it becomes a gas, and so that liquid cools, you know, that change from liquid to gas, that's what leads to that freezing effect, so you get the -- so you get the stretching effect, you get the cryo -- the cooling effect, and -- and we hope a good angiographic result. 00:18:29 SHERMAN Y. TANG, MD: David. 00:18:30 DAVID PORTUGAL, MD: Yeah, I can hear you now, Sherman. 00:18:31 SHERMAN Y. TANG, MD: We just finished the first round balloon inflation. We're going to do a second round. Usually we'll do it twice in the same lesion. Then we're going to pull back to the proximal part. 00:18:41 RAMON TY, MD: Are you going to infuse again when you do it the second time? 00:18:44 SHERMAN Y. TANG, MD: Yes, we're going to change the concentration. This concentration lower -- 00:18:47 DAVID PORTUGAL, MD: You see Dr. Zorrilla, he's unscrewing this cartridge. Why don't you hold up that cartridge, Carlos? 00:18:52 CARLOS D. ZORRILLA, MD: Yeah, sure. This is -- 00:18:54 DAVID PORTUGAL, MD: So in that silver metallic -- 00:18:55 CARLOS D. ZORRILLA, MD: This is nitrous oxide in a liquid that, as it goes into the balloon, goes into a gaseous state, and by doing that, it causes the lowering of the temperature. 00:19:15 DAVID PORTUGAL, MD: So it's -- it really is an amazing feat of engineering. While we wait for you to get started on that second inflation, there is an question. And as you know, this is a live webcast to remind our audience that you can communicate with us. The website If you go there and a question, we'll try to get to all your questions today. The ones we can't get to today, we'll try to get to over the next several weeks. The first question says -- can you all hear me? 00:19:49 SHERMAN Y. TANG, MD: Yes. 00:19:50 DAVID PORTUGAL, MD: Okay: my mom is 87 years old with severe peripheral arterial disease and not a candidate for bypass surgery. She is having extreme uncontrollable pain and is ready to give up. Is this a procedure she could be a candidate for? What do you think, Sherman? 00:20:08 SHERMAN Y. TANG, MD: In generally speaking, yes. And as I know, elderly population, they usually have significant comorbidity, underlying medical conditions. And for this type of patient, endovascular, revascularization procedure is a less invasive compared with a surgical -- bypass surgery. So this would be the treatment of choice. Of course, not every single candidate would be eligible for this. It really depends on the anatomy. 00:20:37

7 DAVID PORTUGAL, MD: So I think the thought is that in an 87-year-old individual, she's going to be a little bit more frail, at risk of bypass surgery, exposure to the risk of general anesthesia. Most likely she has associated coronary artery disease, which raises her risk, but this is a procedure that doesn't require that. And in many places, it's done in an out-patient setting, so -- but it really would depend on what her arteries actually look like, but this procedure today could have a role to help this -- this patient's mother. 00:21:12 RAMON TY, MD: On a practical note, David, if the surgeon feels it's not operable, then perhaps the person to consider talking to is a cardiologist or an interventional radiologist to see -- essentially, the practical issue is just to get a second opinion to see if they can do something for the patient outside of surgery. That, I think, would be the more practical approach without having exact data on what the situation is. 00:21:36 DAVID PORTUGAL, MD: Yeah, I think that's an excellent comment, Ramon. I mean, the general principle of whenever one physician tells you something can't be done -- and really, in any situation that involves, you know, risky procedures -- you always want to get a second opinion. But I think the paradigm has shifted really, at least in the interventional aspect of lower-extremity disease, that traditionally, open surgical procedures have been the mainstay, and they have had very good results, but it exposes the patients to higher risks. So if we can do it with an endovascular approach with small tubes and wires and without general anesthesia, go home the next day, they're walking within four to six hours, then we really think we've done a patient a service. 00:22:24 RAMON TY, MD: Also, for the knowledge of our viewing public, in general, in appropriately selected patients, the procedural success rate could be generally 85 to about 90%, meaning there's a 90% chance we might get an artery open. But our current dilemma is not just getting it open but the dilemma is how to keep it open. And this is where a lot of companies or technological-device companies are trying to compete for a technology that can keep the artery open longer. And certainly CryoPlasty's one of the new advances that people are trying to work with to see if actually that is indeed good for the patient long-term. And -- and that's also a problem with surgery. Surgery doesn't last long, forever. And that's why we're trying different options. 00:23:12 DAVID PORTUGAL, MD: So explain to us, Dr. Tang and Dr. Zorrilla, where do we stand? 00:23:19 SHERMAN Y. TANG, MD: We're doing the first inflation right now. You can see the screen, the balloon just inflated. While the balloon's inflating, the nitrous oxide gas is filling into the balloon and it cools down the temperature, just like you just stated. It will drop the temperature below the 10 degrees Celsius. And -- 00:23:42 DAVID PORTUGAL, MD: So this portion of the artery is upstream from the portion that you already treated, correct? 00:23:47 SHERMAN Y. TANG, MD: Right, exactly. We are sort of like the middle right now because this lesion is fairly long. Just looking at our dye map, we still have another segment needs to be treated. So this is sort of like the middle. 00:24:00 DAVID PORTUGAL, MD: How long is that catheter you're using? Or, the balloon aspect?

8 00:24:04 SHERMAN Y. TANG, MD: The balloon is five by ten centimeters. 00:24:08 DAVID PORTUGAL, MD: So five -- 00:24:10 SHERMAN Y. TANG, MD: This is the longest balloon they have. 00:24:19 RAMON TY, MD: The -- 00:24:20 CARLOS D. ZORRILLA, MD: I'd just like to make a comment. You know, as you mentioned, David, balloon angioplasty is an old procedure, really, because we've been doing this for a long time. And one, of course, disadvantages of balloon angioplasty was first of all, the problem with re-stenosis that was happening up to 60, even 70% in only a year or two years. So we're really excited about this new technology because the initial reports indicate that the patency rate is rather high. In a year, in one year, could be as high as 80%, in two years, 70%, so that's -- we're really very excited. So that's why we're trying to do this and seeing -- you know, many of the long-term results will be when most people are doing this procedure and they're having the personal experience if it truly is going to hold up. The other thing is, you know, the problems with your ballooning lesions, as we all know, is the problem of splitting of the wall of the artery, what we call dissection. You know, it's just because the pressure of the -- of the balloon exerting on the wall of the vessels can cause this particular problem. And CryoPlasty has a tendency to diminish the frequency of this dissection, you know, which is a splitting of the wall of the artery. And the reasons are because the low temperatures causes micro-crystals in the plaque, causing little micro-fractures, making easier the expansion and dilation. And so -- so far our experience in that regard is very favorable. You know, I've been very impressed about the fact that they don't easily -- the arteries dissect following this particular intervention. So we just have to wait and see. You just never know. 00:26:33 DAVID PORTUGAL, MD: Yeah, as you know, this is still a relatively -- it is a new technology, so there's -- the word is out somewhat, whether this therapy will hold up. But certainly in preliminary trials, there's been some very, very promising data. We have another question. This gentleman states: are the performing surgeons exposed to any significant amount of radiation from the fluoroscopy machine or whatever it's called, the continuous x-ray? Ramon, what do you think? 00:27:09 RAMON TY, MD: Now, obviously, there are two sort of parts of a procedure. When we take an x-ray called fluoroscopy, there's less radiation. When we recorded it on cine, we are more exposed to radiation. So in general, you're absolutely right. We are -- we are exposed to radiation, and therefore we do take some precautions. We have lead shields on, we have shields to cover our thyroid. And some people also use goggles to protect our eyes from radiation. And unfortunately, it is a hazard that the cardiologists and the x-ray technicians, the nurses do take. It is an occupational hazard, radiation. 00:27:49 DAVID PORTUGAL, MD: Yeah, but if it's -- we wear our radiation badges, and it actually measures the amount of radiation one is exposed to over a month's period, and so there's acceptable levels, you know, that are well-published, so, you know, it is a small risk. These procedures can take longer than, for example, some typical procedures we do on the heart, but in the end, we really feel it's worth it. And the relative risk to the physician and his staff is small. 00:28:19

9 RAMON TY, MD: Maybe let me clarify some of the statements I made, but the immediate radiation risk to the patient is really trivial. The patient exposure for that one case, in contrast to the physicians and the nurses and techs, they're there day in and day out, so they get more exposed to radiation. But for -- on a per-patient case, I think the radiation is quite acceptable, quite minimal 00:28:39 DAVID PORTUGAL, MD: Okay, Dr. Tang, Dr. Zorrilla, where -- where are we? 00:28:43 SHERMAN Y. TANG, MD: We are doing the second segment, another balloon inflation again. And -- go ahead. 00:28:52 RAMON TY, MD: This is the second cartridge? 00:28:54 CARLOS D. ZORRILLA, MD: This is the second, right? 00:28:55 SHERMAN Y. TANG, MD: This is a second cartridge, yes. Looks like we're going to do another round, more proximal. That will be the final. I think we've reached the origin SFA. And, you know, do this type of procedure compare with the intravascular stent? One of the -- unique to this procedure is you don't have to put a stent. You can imagine, this is almost somewhere around centimeters in length, you have to put a module stent. As you know, the more stents you put in, the higher likelihood you deal with stent thrombosis or instant re-stenosis, particularly there have been recognized that they can cause the stent fracture for some reason, even if you put it in a non-venting area, it does happen with a stent fracture, which is associated with a high instant re-stenosis, so one unique to this procedure, you have good results with no dissection, there's good flow. You don't have to put in a stent. And they have changed the concept. Used to, when we're dealing with SFA lesions, we try to put a stent to get optimal results, angiography looks very good. but in the long run, after three years, the patency rate has dropped substantially. 00:30:23 DAVID PORTUGAL, MD: Yeah, I think the -- the you know, the excitement of this procedure is that -- I mean, we -- we insert coronary stents -- I mean, peripheral stents, you know, stents are, you know, a scaffolding device, right? They're -- they're metal tubes that we place down the artery, and they are also a very important part of our armamentarium in treating peripheral arterial disease, but the advantage of this procedure is that you don't -- in many instances, don't have to use a stent, so you don't burn any bridges, so to speak. So you have the possibility of getting -- at least the hope of a stent-like result without -- without deploying a stent. 00:31:06 RAMON TY, MD: In this particular procedure, we are not leaving a stent behind. We are just ballooning it using the cryo-balloon, using change in temperature, freezing temperature, to open the artery. A stent, the metal device is not left behind. That's the big difference between that and a stent. 00:31:24 DAVID PORTUGAL, MD: I think we have a slide here of what an artery -- kind of a cartoon of what an artery -- blocked artery may look like before and after a CryoPlasty procedure. I don't know if we can bring that up. 00:31:39 RAMON TY, MD: While we're looking at this also, I was wondering if the team down there could comment on the cost. You've used two cartridges, and the cartridges are relatively cheap, right, David? 00:31:48

10 DAVID PORTUGAL, MD: Yeah, in fact, we have a question from Josh in Connecticut about that nitrous oxide cartridge. Those cartridges are actually just a few dollars, so that's actually the least expensive aspect of this procedure. And the question from Josh is: is there any danger from that nitrous oxide? And there's not, there's absolutely not any danger at all. And once it's infused into the balloon and that cartridge is emptied, so it's a very controlled delivery of this cryotherapy. And you know, cryotherapy's been available in medicine for a number of years. It's been used in other fields; urology, for example. But this is the first instance that we know of to be able to use in interventional cardiology. 00:32:36 RAMON TY, MD: Carlos, did you say somebody on the floor had a comment from the vendors? 00:32:42 CARLOS D. ZORRILLA, MD: Ramon and David, the -- the cost of each of these nitrous oxide cartridges is only like $50, so actually turns out to be very inexpensive when you're dealing with very long lesions and you use the same balloon because, believe me, when we're dealing with these lesions are very long, I have to use two, three long stents, we're talking about maybe even $10,000 or something versus the cost of these, which will be like in the order of maybe $2,500 or something like that. 00:33:19 RAMON TY, MD: Because the balloon is more expensive. 00:33:21 CARLOS D. ZORRILLA, MD: Right. And the nitrous oxide is only $50. You can use the same balloon for that lesion, you know. It does work -- that's exactly what we're doing right now. 00:33:31 DAVID PORTUGAL, MD: Yeah, I think, you know, in today's environment, you know, we always do what's best for the patient, so in general, you know, we don't look at cost when it comes to treating an individual patient, but -- but we do need to be somewhat aware, you know, of the environment. Unfortunately, health care and hospitals particularly and reimbursement, unfortunately, is generally drifting down, and so we have to be somewhat cognizant of the costs of the devices that we bring into the lab. And so far, this seems to be, you know, reasonably -- reasonably priced. So we're now up to that very beginning portion of that narrowing in that artery. So we're just about -- should be just about at the end of our therapy. Is this the first treatment of this part of the artery, Sherman? 00:34:27 SHERMAN Y. TANG, MD: Yes. This is a first treatment. 00:34:29 DAVID PORTUGAL, MD: Okay, so we have one more treatment in that segment, and then we'll take a picture, I would imagine. 00:34:32 SHERMAN Y. TANG, MD: Yes. 00:34:33 RAMON TY, MD: The other advantage -- you know, not -- in relation to cost that we don't talk about is how many days is a patient going to stay in the hospital? This patient, if -- if we just finish the procedure, in about four or five hours, he could be up and around. And there are times when they are discharged the same day. After a local anesthetic, minimal sedation procedure, they could go home the same day. In contrast, the surgical patients have to stay much, much more than that -- two, three, four days sometimes in the absence of complication. And if you get an infection in surgery, of course you're going to stay much longer. And the risk of local infection in such a procedure is also very low, and that's why often they're very

11 discharged certainly very often within a 24-hour period. And often much less than that. 00:35:21 SHERMAN Y. TANG, MD: Yes, I agree with you. And when you're dealing with a critical limb ischemia, and when you do the surgical approach, those incision wounds are going to be a problem. And sometimes they get a wound infection and they have a problem to heal. So with this type of procedure, less invasive, and you don't have involvement in any surgical incisions. 00:35:43 DAVID PORTUGAL, MD: Yeah, so that actually speaks to another . It says: after surgery, does the patient feel pain or a freezing feeling? And then what is the rehabilitation period for this individual? 00:36:00 SHERMAN Y. TANG, MD: This type of procedure is pretty comfortable. And as we're doing so far, even patient being sedated, that he does not have that much pain. He's just having the pains from the back pain, not from the balloon inflation side. I don't think they have like a chilly feeling along the balloon inflation side. 00:36:22 DAVID PORTUGAL, MD: But sometimes they'll get a little bit of stretches, just feels like maybe a little bit of a cramp there in the leg, like a little charley horse they may get for a few seconds while these balloons are inflated, but other than that, patients tolerate it very well. And in terms of the rehab period, you know, it -- of course, it speaks to what this patient was like before he had this procedure done, but in general, like Dr. Ty said and we mentioned before, these patients can be up and around very soon and back to work within hours, full activity. 00:36:58 RAMON TY, MD: We generally don't tell them to run a marathon in 24 hours, but they're up and around pretty much in about three, four days, we would probably not limit a patient anymore, and to go back to what they were doing. 00:37:10 DAVID PORTUGAL, MD: Of course, these patients will need to be on a blood thinner. The patient's receiving a blood thinner currently. He'll need to be on a blood thinner after the procedure, but in most instances, aspirin would be adequate to treat it. Some -- some physicians in some instances may prescribe a medicine called Plavix, which is a little bit stronger blood thinner. It really depends on what the procedure was done and what -- what other medical illnesses this patient may have. 00:37:38 RAMON TY, MD: If we were to put a stent in, generally we -- most physicians would feel more strongly about using aspirin and Plavix together for the stent, would you say so? 00:37:47 DAVID PORTUGAL, MD: Yes. Exactly. How are we doing there, Sherman? 00:37:53 SHERMAN Y. TANG, MD: Yeah, we just finished the final round, so all we're waiting is for the thing to finished and deflate the balloon, remove the catheter, and we'll take a picture, see how look like. 00:38:04 DAVID PORTUGAL, MD: Yeah. So I think in this instance, you know, not all instances are like this, but this was a very long segment, so multiple inflations are used. Many times, just one long balloon may cover it, but every -- every individual is different, so this is a fairly complex case with the long areas of narrowing, so -- but Dr. Tang and Dr. Zorrilla are being very diligent and very meticulous, and -- and we're anxiously awaiting what the angiograph result will be after -- after this device.

12 00:38:37 CARLOS D. ZORRILLA, MD: David, in relation to -- you were just talking about a question about the surgery versus this procedure. You know, as you know, there was a recent study made in which they compared both, surgery versus angioplasty for limb -- to solve legs for severe ischemia. So it has been already proved that there is no difference, you know, with just plain balloon angioplasty between surgery and angioplasty as far as salvaging the limb. The -- the difference, the main difference, as Ramon mentioned, is the fact that with this procedure, the morbidity was cut down significantly. The patient can -- can return home sooner, so -- and that's only taking into consideration only balloon angioplasty, but not considering CryoPlasty. Maybe with CryoPlasty, things might change even more favorably to percutaneous intervention. 00:39:40 DAVID PORTUGAL, MD: I've got a question here. It must be from a physician. It says: what is the anticoagulation strategy during and after the procedure, and is there a risk of perforation? Let's -- let's watch this angiogram, and then we'll get to this gentleman's question. 00:40:01 SHERMAN Y. TANG, MD: You ready? 00:40:04 DAVID PORTUGAL, MD: So what you'll see is dye traveling down the artery. And this is after the multiple inflations of the cryotherapy device. And it looks... looks quite good. 00:40:29 CARLOS D. ZORRILLA, MD: Looks rather good. 00:40:30 DAVID PORTUGAL, MD: Looks very nice. 00:40:33 CARLOS D. ZORRILLA, MD: Good flow distally all the way to the... 00:40:37 DAVID PORTUGAL, MD: I think I see flow going down. One or two dissections, but they're very small. 00:40:44 RAMON TY, MD: They're not flow-limiting. 00:40:46 DAVID PORTUGAL, MD: Not flow-limiting. Got a very brisk flow. I think in this anticoagulation, what are you all using to thin this gentleman's blood for the procedure? Are you using heparin or are you using Angiomax? 00:40:56 SHERMAN Y. TANG, MD: We use Angiomax. We feel like Angiomax has the data treating with coronary intervention, has a lower bleeding risk and a short half-life, so when we stop the Angiomax, in approximately two hours, you can remove the sheath compared with heparin, you might have to wait four to six hours. And I just looked -- take the picture one more time. We're all looking at the angiogram right now, as I say, as you guys mentioned, it has some dissection, but not flow-limiting. 00:41:27 DAVID PORTUGAL, MD: I think it looks very nice. 00:41:29 SHERMAN Y. TANG, MD: Yeah, we probably don't need -- 00:41:30 DAVID PORTUGAL, MD: Is it possible to bring up -- you want to bring up the before and an after? I think that way, you know, it's -- it was a long treatment of the

13 segment, and individuals may have forgotten actually how -- how severely narrow this artery was. 00:41:43 SHERMAN Y. TANG, MD: What we'll do is, can we take one more picture on the digital imaging? This is jus a regular x-ray imaging. So I want to see how it look like, and then we'll do the digital imaging. Okay, let's hook it up. 00:41:58 RAMON TY, MD: Sherman, in response to the question about anticoagulation, I think in my -- in terms of my practice, I think it depends on where I'm doing the intervention. If I'm doing an iliac stent, I feel that it's going to be a quicker procedure, I can probably get away with a few thousand units of heparin and be done with. I may not use Angiomax as an infusion. In this case, certainly, with doing the legs, I may be certainly more biased towards using it because it may take a little longer and it's a smaller vessel. David, do you have a... 00:42:29 DAVID PORTUGAL, MD: Yeah, I think that that's a good point. I was reading one of the s. It says: if the arteries in that same area become blocked again, how many times can a patient have this procedure? Well, it -- given the nature of it, given that nothing was left behind, this patient would be a candidate to have this procedure again, you know, within a few months. I think -- so of course, we always hope that patients will not need another procedure done. We do know that, based on the trials so far, only about 10 or 15% of patients will need another procedure done at the end of one year, so 80-90% of patients are -- are cured of their symptoms after this -- after this procedure. 00:43:20 RAMON TY, MD: Also, in terms of location, if we do an intervention just above the groin in the iliac artery, generally they do better. The bigger the arteries, stay open a lot longer. Their patency rate is superior. The problem is, as we go further down the leg, to the thigh and then below the knee level, our results -- whatever we do, whether it's surgery, balloon angioplasty, atherectomy, or CryoPlasty -- may be more limited. The arteries for some reason don't stay open as well as a larger artery in general. 00:43:55 SHERMAN Y. TANG, MD: Can you hear me? 00:43:56 DAVID PORTUGAL, MD: Yeah. 00:43:57 CARLOS D. ZORRILLA, MD: You're right. Below the knee, you know, many times we do interventions to -- even we know that the artery's going to close eventually, just to give him enough blood to heal, for example, an infection or heal an ulcer, you know? And after -- after, for example, you know, if he's patent for three, four months, it's enough to heal that, and that would be, you know, a success. Now you're seeing -- as you can see here, you're seeing the results, the end results, of this intervention. And actually, you heard the claps, we're actually very satisfied with the results if you compare the before and after. And there is evidence, as we expect, there's some dissection, it's a not flow-limited dissection. Of course, the wire is there, too. 00:44:48 DAVID PORTUGAL, MD: So just to educate our audience, you know, dissection, we throw that term in and we're so used to using it. It sounds like an intimidating term, but it is a -- a tiny split in that plaque, that cholesterol plaque that was blocking up that artery. But it is also an important part of the angioplasty process to help, you know, open up that plaque, clear that artery, and so -- so this is actually not an

14 injury to the artery, per se. I mean, this man's leg is not in jeopardy. This is an expected part of the procedure, so... 00:42:57 SHERMAN Y. TANG, MD: Hey, David? 00:42:58 DAVID PORTUGAL, MD: Yes. 00:45:29 SHERMAN Y. TANG, MD: I think that you said a dissection might be from the guide wire, so what I'd like to do -- looks pretty good in the distal flow, and so what I want to do is take the wire out and repeat the angiogram to see this area. 00:45:43 RAMON TY, MD: Yeah, that's a very valid point. Dr. Tang is saying that the wire may create the illusion of a tear when it's present when we'll take the picture. 00:45:54 CARLOS D. ZORRILLA, MD: Also, you will know, it could be the other way around. The wire could be keeping the artery open, so that's very important to -- to recheck. Be sure that those dissections are not -- not will cause obstructions. 00:46:08 DAVID PORTUGAL, MD: One point of confusion, you know, to clear up. You know, this is, you know, peripheral arterial disease. I mean, this gentleman presented with claudication. And again, claudication is basically a cramping of the leg when this gentleman walks. That cramping occurs because that muscle and that leg is not getting enough oxygen in the blood supply. So that is a common symptom of peripheral arterial disease, but it has no relation to things like varicose veins, for instance. So varicose veins are -- are a cosmetic problem and no relation to peripheral arterial disease. 00:46:50 SHERMAN Y. TANG, MD: David, there was a question about perforation? 00:46:53 DAVID PORTUGAL, MD: Yeah, the question was: is this gentleman at risk of a perforation with this procedure? 00:46:57 SHERMAN Y. TANG, MD: If you choose the balloon size larger than your reference size, you run the risk of perforation. So this type of procedure, we choose the ratio of 1:1 to your reference-size vessel. We don't want to oversize. 00:47:16 CARLOS D. ZORRILLA, MD: Absolutely right. The risk is about the same with plain balloon angioplasty. You know, risk related to the size of the balloon, risk related to the use of wire that can go through the wall, so this procedure doesn't increase the risk more than just plain balloon angioplasty. And if you take all the precautions as we usually do, probably that should be a very -- a very rare event. 00:47:41 RAMON TY, MD: Also, you need to understand, in small arteries like these, if you have a perforation, they usually could close on -- by themselves. In a larger artery, let's say inside the body, you might not be able to stop the bleeding. But sometimes in the legs, even if you perforate a little bit, especially if it's a perforation from a small wire, a very tiny, slim wire, these perforations may just seal on their own. Has that been your experience, David? 00:48:07 DAVID PORTUGAL, MD: Yeah. Yeah. I mean, the risk of perforation is, you know, is less than 1%, so it's a -- it's a very rare complication. It's a very serious complication when it occurs, but -- so we don't -- but it is very uncommon. And we always have devices that -- these devices that are called covered stents. These are

15 metal tubes that have a lining on it that one can insert into the artery and plug the hole, so to speak, if that were to occur. But again, that's a very rare -- rare complication, so... 00:48:42 SHERMAN Y. TANG, MD: Dave and Ramon, did you see the second picture without wire? 00:48:47 RAMON TY, MD: Without the wire. DAVID PORTUGAL, MD: Yes. 00:48:48 SHERMAN Y. TANG, MD: You see, this is a dissection which is described as a linear dissection. Again, as you can see, right after the bifurcation, there's the Profundus artery, and if you go a little bit further down, has some dissection. And some residual stenosis distal, but if you look in the whole run-off, I'm pleased with this. It's a good distal run-off. I mean, usually the turn... I mean, they don't usually flow in the legs for some reason, but I see the distal flow very brisk. So this is not a flow-limiting dissection. So I tend to stop here instead of putting in another stent. 00:49:29 RAMON TY, MD: So basically, if you think that the flow might be compromised, you would go in and put a stent in. 00:49:34 SHERMAN Y. TANG, MD: Yes. If you had suboptimal results, you definitely will. But be careful. You put it in this area which is right at the groin area, it's a bending point, and you try to avoid that area unless you have to. 00:49:49 DAVID PORTUGAL, MD: Yeah, I think, you know, one of the principles of interventional cardiology in the use of stents is that, you know, stents can block up just like the artery can block up down the road. You know, what happens is that there's a scar-tissue formation. You know, whenever an artery is stretched, scar tissue can form just like -- and block the artery just like it was when the cholesterol blockage was there prior to the procedure, so -- and the more stent you put in, this increases the likelihood of that scar-tissue formation. So we use it when we have to, and -- but we're trusting the results of this cryotherapy to help us limit the amount of stent that we may have to use. So Dr. Tang so far is very pleased with the blood flow -- the rate of that dye going down that leg is very brisk compared to what it was prior to the procedure. 00:50:47 CARLOS D. ZORRILLA, MD: The other thing is, surprisingly, when you go to see later on those dissections, when they heal, it looks extraordinarily very good. And they even get better when they heal, you know, so that's another thing I wanted to mention. 00:51:01 DAVID PORTUGAL, MD: There's a few questions here about, you know, treatment of peripheral arterial disease and what we can do about peripheral arterial disease. 00:51:08 SHERMAN Y. TANG, MD: David. 00:51:10 DAVID PORTUGAL, MD: Yes, Sherman. 00:51:11 SHERMAN Y. TANG, MD: I'm going to turn the program to you. I'm going to wrap around here. So you can answer the rest of the questions from the audience. 00:51:19 RAMON TY, MD: Are you finished, doctor, is that what you're saying?

16 00:51:22 SHERMAN Y. TANG, MD: Yes. And you can see the picture on the screen right now -- I don't know if you can see that. One is a before, the other one's after. And we call this a success. That means he had a procedural stenosis of less than 30%. And then you have non-flow-limiting dissection, so I'm going to call -- call on this case. I'm going to wrap it around. Thank you. 00:51:48 DAVID PORTUGAL, MD: All right, excellent. 00:51:51 RAMON TY, MD: David, you want to comment? Or guys, do you want to comment on how do we follow-up on these patients? After they get discharged, what do we do with them? What do you do? 00:51:57 DAVID PORTUGAL, MD: Well, there's a couple different aspects. Again, you know, when -- you know, these patients -- and like Dr. Ty alluded to at the beginning of the program, arterial sclerosis is -- is a diffuse body disease, and so this -- the peripheral arterial disease is one aspect of it. We know from studies that a third of these patients or more are going to have significant coronary artery disease, they're going to have -- which is blockage of the arteries that supply their heart -- they're going to have cerebral vascular disease, which is blockage of the arteries that supply the brain. So these individuals are at risk of strokes, they're at risk of heart attacks, and they're at risk of further blockage in their lower extremities, in their legs. So what are the things we can do to prevent that or certainly address the problem they currently have? Well, certainly lifestyle changes. So these are the th-- these are the aspects that fall on the responsibility of the patient. They need to lower the fat in their diet, they need to learn to exercise, they need to see their doctor regularly, and they need to take certain medications that we know lower the risk of strokes and heart attacks and blocked arteries. And what are those medications? Well, they're cholesterol-lowering medications. And we're very fortunate to live in a period where we have very strong, very potent cholesterol-lowering medications that can drop their risk of heart attacks in half, lower their risk of strokes by one-third, and lower their risk of blocked arteries by one-third to one-half. There's blood thinners, like aspirin and Plavix, that we mentioned earlier. These are medications that -- that thin the blood, so to speak, knock out their platelets. And there's controlling their blood pressure. And those are the tried and true methods that we know to treat this -- this rampant disease. 00:53:53 RAMON TY, MD: And in terms of a follow-up, I think on the -- for the legs specifically, for instance, in three months, six months, or nine months depending on whether the patient is very symptomatic or not, we have the option of following these patients with an ultrasound, with duplex studies, their ultrasound pictures of the legs. And by evaluating the velocities inside an artery, we can sort of make some kind of conclusion as to whether the blockages have come back. And obviously, some clinical common sense is going to be important. If a patient says, "I'm hurting all over again," that's a sign something's probably wrong. And currently, also, we don't always have to use invasive procedures all the time to assess the blockage as a screening process. We have other modalities; outside of ultrasound, we can do MRAs, that's an MRI of an artery, of the MRA angiography of the legs. We can use CT angio, one of the latest, you know, pieces of technology we have here at Memorial Southwest. CT angiography could help define whether the blockage has come back or not. The major limitation with that technology is with the patient. 00:55:04