 Texas Heart Institute educational programs on innovative technologies and techniques. We're talking about breaking the barriers in endovascular interventions. I'm your host. My name is Von Rueckrazier. I'm an interventional cardiologist at Texas Heart Institute and Baylor CHI Medical Center. Special guest today is Dr. Maddy Rizavi and he's an interventionist and also electrophysiologist at Texas Heart Institute and Baylor College of Medicine and it's a very exciting time to have Dr. Rizavi here on this occasion because he's not only an interventionist and electrophysiologist but innovator in the field of vascular and cardiovascular medicine. Thank you for joining us for this special event. Thank you for having me. So the topic is the latest advances in diagnosis and prevention of vascular complications. This is a serious problem. Technology however continues to drive towards less invasive solutions and also payers and hospitals demand better resource utilization and also demand to find a way to reduce the cost of the procedure. As far as transfemoral access site complications are concerned one of the most common one is hematoma and it varies tremendously depending on the patient's anatomy and also on the operator experience but it ranges somewhere between 1 to 10 percent of the diagnostic and interventional procedures. So the aneurysm is another relatively common complication that occurs between 1 to 6 percent of patients and this certainly can carry significant consequences and occasionally requires surgical intervention. Intimal dissection is another complication that occurs with aggressive manipulation of caters and wires in the arterial system. Access site closure or thrombosis is relatively rare occurrence but it occurs in less than 1 percent of cases. There also is an AV fistula that occurs occasionally with less than optimal access to the arterial anatomy and circulation and of course one of the most dramatic and concerning complication is vessel laceration or evulsion that is relatively rare but it can lead to catastrophic events. Retropartial hemorrhage related to perforation or laceration or evulsion is a very serious complication that frequently will require surgical intervention. There's also risk of nerve damage, embolization to the lower extremity, risk of infection particularly the access site and venous thrombosis. Now we know the challenging anatomy increases the risk of access site complications. One of the most common challenges as far as the access site is concerned is severe calcification of the common femoral artery which can present itself with either minor calcification or major anterior wall calcification or circumferential calcification. Another scenario that adds to the risk of complication is iliac artery complication and iliac artery tortuosity that is shown here on this slide. Morbid obesity is a problem for a great majority of interventions because of the distance that occurs between the skin and the femoral artery like in this particular scenario is over 11 centimeters and most of the devices that we have available for access are difficult to deploy in this particular scenario. One of the great concerns with less than optimal access or so-called blind access without using intravascular ultrasound or paying attention to anatomy is access that's above the inguinal ligament that can lead to retropertoneal bleeding and severe consequences. Sheath manipulation in a narrow or diseased or tortuous vessel can also cause vessel laceration and evulsion as it is seen here on the right hand side with so-called iliac on a stick type of a finding. They should be avoided by all means because this usually leads to catastrophic retropertoneal bleeding and the need for emergent surgical treatment. Now we all know from experiences and the literature that significant delay in diagnosis of bleeding can cause serious complications. Current protocols unfortunately still rely on symptomatology for detection which can take hours to develop and add to significant complications and consequences that we have to deal with later. There is a report from a single center where incidents of after catheterization retropertoneal bleeding occurs in 40 percent of patients and leads to hemorrhagic complications and hemorrhagic shock. This type of occurrence usually is very insidious and it happens really slowly in a lot of instances particularly if the perforation or laceration is relatively small and typically will be manifested sometimes 15 or 30 minutes after the intervention is completed. So it is very important to address this type of a problem related to bleeding and complication as early as possible and identify it before it becomes a serious problem. Now Dr. Rosave, how big is this problem in your particular experience as far as bleeding is concerned and what is the impact on the cost of the procedure related to this type of complication? Thank you Dr. Crazier. Bleeding it's a big problem, it's a major problem, it's a problem that affects not only the patient's short-term outcome but their long-term outcome. If you bleed your chances of a delayed recovery from a procedure increase the chances of you dying in the hospital increase and certainly the cost to the hospitalization increases significantly. Here you can see that bleeding complications rate associated with large bore arterial procedures are as high as 18 percent across the board and when they happen you have a double the risk of death and you have increased the cost of hot the health care cost to the system by about 60 percent and why do we have a need for early detection again as I said it's frequent it's expensive and it occurs in one in five patients and when it happens you can die you know almost double the increase risk of death and so something has to be done about it. How expensive is this problem? It's very expensive. In the United States if you look at a across a data set of patients who were entered into the Medicare system the CMS system and analysis of CMS system showed that the cost is upwards of $1.5 billion with an 18 percent complication rate and 450,000 procedures that were analyzed. From the average it was an $18,000 average additional cost of a bleeding complication when it happened. So this is a very serious problem. So that is interesting and surprising to a certain degree. So what can be done to prevent vascular access site complications? Well it's a canary in the coal mine right? Early detection is absolutely critical to managing these patients. These bleeds are not you know they're not bleeders it's not as if a surgeon has sliced through a large artery. They are leaks but the problem is that the leaks are not detected frequently enough and early enough so that the physician does not have an opportunity to intervene. The early bleed monitoring system is a system that can be used that can detect the onset and progression of bleeding during procedures not only during procedures as they're happening but immediately after procedures too. If I may interrupt you're an inventor and can you tell me a little bit you actually participate in invention of this device this is the early bird system as you can see it and you can also see it on the screen and as you can see here it has markers that tell you about severity of bleeding so if you don't mind can you tell me a little bit how did it evolve what was your process of thinking and how it works. And so you're hearing these audible tones these audible tones are giving the kind of signaling the progression of a bleed from the onset of the bleed as it progresses and whether or not it progresses or not based on what the physician has done to intervene. So not only is it onset but is the physician's maneuvering or the physician's intervention at that point affecting the progression of the bleed and this will be the third and final beep as it marks the progression process. The way I initially came up with this concept was we had just finished a procedure and after the procedure the patient had had a significant drop in their blood pressure by then I was you know as it happens often you're traveling between hospitals and I was in the middle of traffic and they called me and they said your patient's blood pressure has dropped what to do and I thought to myself I wish there was a way that I could actually find out right now if the bleeding is ongoing or not and I I did so by you know right at that moment I thought to myself well you know there's certain variables that we look for in the field of electrocardiac electrophysiology and one of these field one of these variables is resistance of tissue that's something that's commonly analyzed when we do our work and so my thought was I wonder if blood in that field would change the resistance of the tissue and it turns out you know one thing led to another and it does and it does so very very precisely and very very reproducibly. This is very visionary I'm well thank you so resistance plays a significant role and impedance to the blood flow and so tell me a little bit about how was this catheter designed to address this issue there are few components there that need to be explained to our audience how this system works you already showed that we have alarm system which is visual and also audible but also there are sensors there that play a significant role so if you don't mind mentioning that part again. So that the the meat of the matter actually in fact are those sensors that you see those you see those four ring electrodes in pairs too closer to the end at the tip and then too closer to the area in the hub and what we call the proximal aspect and what's happening is soon as you insert that sheet otherwise except for what you see with that is connected to the actual sheet itself which is the the processing information in the software and the hardware of the devices is housed in what we call the hub or in the flushing port of the of the catheter itself and so what happens is soon as the device is inserted in a standard way without any difference from what you do in a normal standard cell dinger technique be it with vascular ultrasound guidance or not or micro puncture needle or not once the sheet is placed in the electrodes do two things a pair of electrodes emit a very high frequency and very low intensity electrical stimulus this intensity is much much lower than anything required to for example capture or irritate the nerves or the muscle so there's no twitching or anything like that the other pair of electrodes are measuring the resistance to the current that was just applied and as we all know you know electricity really likes to conduct through saltwater and blood after all is a glorified form of saltwater and so as blood is being introduced into that space because of this slow leak you see that the level of resistance what we call the bio impedance just a fancy way of discussing that resistance to electrical current starts decreasing because the blood is enabling that current to move faster and more easily and so with the onset of a bleed you start noticing on the right side figure you can see that there is a there's a beginning of a drop in the impedance and as the bleeding progresses that drop goes on and on that's how we enable the onset and tracking of the extent of bleeding now if you were to do an intervention and you would see that the onset of the bleeding has happened and you know you would use whatever technique the clinician or the operator may want to use to abort that bleeding you would see that that level would taper off that drop would taper off and you would say okay whatever I've done I have now been successful there's no more bleeding and so the device tells you not only when it happens but also when it stops this is very ingenious I mean really to use the impedance to figure out how much of blood loss occurs and to quantify it that's truly ingenious stuff of approach and not only that you can do this intra-procedure but also post-procedure yep and another great advantage is that there are two devices or two sheets or systems that are available one is six French and the other one is eight French so they're really small in size and typically I have been one of the investigators in the clinical trial that was carried on you typically place it adjacent to the Fremel artery access site so you can read any problems related to the large bore sheets that occurs in proximity to that particular catheter and we use it on numerous occasions at our institution we have found that it was very sensitive to an identifying bleeding even minor degree of degree of bleeding which was absolutely fascinating now if you don't mind tell us a little bit about validation of this technology how did you actually get to the point to say well this is a reliable means of assessing bleeding sure so we did a series of first of all we met with the FDA and sought guidance from them the FDA thought that this could be done and the clearance could be achieved in a series of preclinical studies without having to resort to clinical cases and so we followed suit there was 40 sample sizes samples experiments with the groins on either side and what we would see is kind of what's depicted here that there was a correlation not only with the onset of introduction of fresh blood into that site but with the progression we controlled the onset and the progression of bleeding by introducing fresh blood and we would see that the device would track the onset and it would track the propagation of the bleeding very very accurately and the amount and the amount correct and that correlated with the amount as we can see here from level one to level three yes which again even a minute changes in the amount of bleeding was detected with this particular correct and this shows you are this bleeding signature if you want to explain yes so you can see in the beginning we'll start on the on the x-axis if you will the unit is time and you don't need to right now worry about those precise numbers and the y-axis the unit is the resistance and and you know at the bottom where it says 20 the resistance is low and all the way up at the highest box around 60 or so or even higher you I'm sorry 40 or so you're even higher you can see the higher resistance so at the beginning we start the procedure at time zero and then what we do is you can see as we're moving right word in time we introduce the bleeding and you see that there's a downward obvious downward drift of that impedance and again as blood is being introduced resistance decreases and therefore that on that x-axis as time is going on you see it that downward drift on the on the y-axis and as it's going lower and lower the device triggers it says that okay now the bleeding is ongoing and then as it progresses the device keeps up and and does so in a very sensitive and specific way and what do I mean by sensitive and specific sensitivity means that how good are you at picking up a an event specific means how reliable are you and picking up an event in other words if you are sensitive your you don't miss any events from happening if you're specific if you say it and you that means that if you declare an event has happened an event has happened there's no false alarms if you will so the device not only can pick up everything it doesn't even give you any false alarms when it goes off that means that the real deal is happening so that that's very very powerful this is really impressive I I don't recall any study where we had a hundred percent sensitivity and hundred percent specificity that's in most scenarios wishful thinking but so tell me what was the next step after the animal study and talk a little bit about again you mentioned it before biopedic response and blood loss as far as quantifying the amount of blood loss yes so you know as you know this is a somewhat of an arbitrary but we think a clinically valid number that if 500 mls of bleed is currently probably around what you've done when you start by the time you start having symptoms such as a drop in blood pressure or pain in the flank or things of that nature and we wanted to correlate our level of detection with what is right now clinically the threshold and as you can see here by the time you get to that 500 ml bleed you've already had a significant 30% drop in the resistance of that omega sign stands for ohms which is a unit for resistance you've had a 30% drop in the resistance of conduction and we have detected we detected the onset well well before you see the third line is around where it would have been and we have detected it well to the left much earlier before you know what clinically would have been detected so the early bird would start beeping yes and you will go to the third marker if this happens yes which is very reliable and very important and meaningful information so obviously the next step was a clinical trial that is exactly and tell tell us a little bit about the clinical trials so that a clinical trial was a multi-center study in a I believe the exact number escapes me I think it was yeah there was five clinical sites across the country different operators in each site and we were one of the center you were kind enough yes you were one of the centers and and the endpoint was assessing whether or not the use of this sheath would detect the bleeding and what the correlation was between the devices triggering and the actual events so what happened is you would do the procedure as per normal we would get a CAT scan a CT scan after the procedure and you would we would correlate the number of lights that have gone off if any with the extent of bleed if any found on the CT scan so now you have a correlation between my a set number of lights have gone off now let's see how much bleeding was detected and now you could compare apples to apples if you will these were done in a variety of high-risk arterial large bore procedures and that is here you know shown on the diagram here tavern was the most common ever was stranger correct and but other interventions were done as well as PCI the use of an impeller device for hemodynamic support to balloon vavoplasty mitral clip and evar as well so we really tested this device in all kind of scenarios in the variety of the procedures now the procedural characteristics are included here and we can see that the great majority of patients actually underwent procedures with the use of large bore sheets which is 12 French or higher all the way up to 24 French for Evar Tivar and Tavern like procedure so variety of procedures were performed with different size of sheet sizes and this is very important because we wanted to know if this device is sensitive for all sheet sizes not just for small ones but also for large ones as well and a large variety of closure devices was also used as we can see proglide was the most common closure device used in 82% of cases this is a very popular large bore closure device followed by pro star Excel and you see there were also patients with manual compression and crossover balloon and and so on but the important thing is that a lot of closure devices were used in this particular study so tell us about early bird results now this is probably the essence of that's right how close is it to the animal study and whether we can use this in everyday clinical applications I think that the short answer is that it's it's close we saw that here's kind of a rundown and about a about a third of the cases there was no bleed detected and about a third of the cases there was a level one that triggered and then about a third of the cases there was either a level two or a level three that's that's concerning because this is like a 32% of patients one almost had had more than mild amount of bleeding which is really bothersome and it tells us if we don't have means of assessing it we can get ourselves in the patient in trouble absolutely I do want to quantity or kind of qualify one thing it my feeling on this is that probably a level two or three is where it's going to become a problem somewhere in that zone maybe that a level two if you've stopped the bleeding by then you're going to be okay probably but if it hits a level three that you're probably gonna you know that there's things are getting worse and you need to take more aggressive and drastic action so maybe you can share with us some of the information when did that bleeding occur or alarm occurred as far as something bad is happening sure how often was it inter procedure and how often was it post procedure and the answer is it was usually post procedure and is that surprising actually probably not it was surprising to me I thought that you know when you're in the in the lab itself when you're still doing the procedure everyone is paying attention everyone is focused on the patient they're being monitored it I thought that after the procedure when now kind of the attention level may be a little bit less intense that they're perhaps in the holding area and and things may not be as closely monitored that you would have you would run into trouble and so one way or another about 70% were post procedural amazing this is absolutely amazing the bottom line is how reliable how sensitive it is of course the gold standard at the present time to identify significant amount of bleeding with large ball sheets is CT scan assessing retropertoneal bleed so maybe you can mention this and what was found so we found that you know there was in about a little less than a little you know less than 10% of cases there was absolutely no changes and the vast majority and about 60% there was what we would call infiltration or what the radiologist would call infiltration and I would say that that is where you that you need to know that it's happening but you don't if you can control it there probably isn't going to be any long-term sequelae and then another third had a what we could call a hematoma which can depending on its size can have effects that this is pretty generous what we can see in this particular example that's right so that patient usually has symptoms related yes and then we did not find any retropertoneal bleeds which is to be expected given the reported incidents which is you know quite you know in the 1% range or so so we did not find there were no retropertoneal bleeds and this is partially I believe true because I'm truly experts were involved in yes that is absolutely we pay attention to the details so but it happens it happens it can happen to anybody so that is something that would have to be evaluated further in some other type of a trial but so tell us a little bit more about primary end point and accuracy as far as level one level two and level three is concerned and tell us about what is coins capital not all of us are familiar with it so what it what it is doing is that there is it's talking about the correlation between your findings and a combination of the what I was saying earlier at the sensitivity and the specificity the pause what we call the positive predictive value and the specificity which is if you say the incidence of false alarms or the reverse of the incidence of false alarms so if your specificity is 100% that means you had no false alarms essentially and you can see that you know these numbers are quite you know robust if it said that you don't have a bleed or if you have a minimal bleed you did not have a bleed if it alerted something was going on and then you see that at the level two the specificity was a little bit lower that is to say that it may have a slightly over called some stuff not in terms of saying the onset of a bleed but the progression to a level two bleed and that kind of makes sense because when you're in a level two on one bit on one your neighbor on one end is very low or no bleeding your neighbor on the other end is extensive bleeding so becomes a little bit more grayish in terms of differentiating so that probably is you know to be expected and gives us the slightly lower specificity and again the specificity for one for the highest level of bleeders 100% as was the sense level three is the most important that's that's right and you know I give presentations on this topic and frequently I'm asked questions what about this level two why you know the specificity is not as high and I always answer and maybe it's incorrect there is also a human human component added to it depends who reads the cat scan that's right and how aggressive or less aggressive they are interpreting the findings because there is no standardization as far as reading the CT and amount of bleeding is concerned it's to a certain degree subjective yes don't you think that that plays a role absolutely okay so very interesting so what are the clinical actions that were taken during the study based on the information that was provided to the internationalist sure so and about you know a majority vast majority of cases about 75% of cases the physician was no when they were notified they and said okay let's just continue observation and that's all they did because again think about the times that you had a level one or level two did not that did not progress about a third of the times they would and and I just want to make a point that that you see that the numbers are adding up over a hundred percent because they could have done a number of different things or multiple interventions at the same time so about a fifth of the time they just did the manual compression 15% of the time they did the crossover balloon technique obviously that is still while they're doing the procedure because you know once the patient is on the holding area you can't you after the procedure you can't do that about 13 percent of the patients required a transfusion and then to 5% required the fem stop and and one patient had their anti-coagulation reversed so this is very interesting because when we look at the need for transfusion it's it's pretty high considering what is the current status as far as the large bullsheets and transfusion it has dropped tremendously obviously related to expertise paying attention using newer generation closure devices so it's somewhere in the range of about 7% so it means that the the physicians were alerted relatively early and they checked hemoglobin and hematocid and found it was very low and therefore found a reason to give a blood transfusion but there was a significant number of interventions actually perform on the basis of this information so that is very important and very very meaningful information so so how does a early bird system compared to existing options what we've been doing until now well unfortunately up to now there really has not been much that has been done other than waiting for the clinical presentation intra procedurally especially we're quite limited because doing any kind of real-time imaging intra procedurally it's already such a crowded field that it's just not feasible to be doing you know CT scans or ultrasounds the vascular access ultrasounds that we often use are too under power to penetrate deeper into the tissue to give us good imaging of potential deeper retro perineal bleeds and the like the CT scan obviously it's not really feasible and so really what you have is the standard sheath and the clinical clinical presentation and so there is also the cost issue and time issue sure yeah that plays a significant role so I see major advantages of using this particular system when it tells you that there is a problem you don't have to transfer a patient to the radiology suite particularly the patient is the hemodynamically unstable or the ultrasound equipment might not be available or is suboptimally identifying the problem so those are very important things I would add one point also and that's the specificity if you have a patient who's critically L who's in the ICU who has multiple lines and devices and you get a report that they're hypotensive and the sheath has not detected a drop in impedance you are virtually assured that bleeding is not the problem and you don't have to then take the time and the effort and you know transporting these patients can be very very challenging and you can really start focusing quickly on other causes of the drop in blood pressure as opposed to bleeding in the access site. So what does the future hold for early birth as far as there's always a first generation second generation and third generation of course there are needs there are unmet needs I mean I'm interventional cardiologist or interventionalist and not only that I would like to know if the patient is bleeding I would like to know where the patient is bleeding is it just at the access site or is it in the retroperitoneum whether it's in the pelvis or it's higher up and all of those things that would be very useful and meaningful in preventing further complications so do you envision any progress another thing is could we have a one two three and four yes or would be big bleeding big retroperitoneal bleeding that we didn't see in this particular scenario of course we get more alerted and worried if there is a major major retroperitoneal bleeding occurring so if you don't mind to answer this yes so that is exactly what you have read our minds and the thought is you know is there a way by either you know do we is it requiring more electrodes is it requiring a longer sheath is it requiring fine-tuning of the algorithm but indeed the first question can we help in any way to localize the event and that's that is you know something that we are very focused on at this time and then I think in kind of a converse of that is to say okay let's kind of see whether or not we can make this more applicable to the general population patients who have central lines in the ICU patients who are going p undergoing PCIs but not necessarily with the largest bore sheets patients who are doing electrophysiology ablations such as what I do for a living will this become a standard of care in the ICUs and the CCUs for monitoring and so as we are trying to make it more specific to give the operator and the interventionist more specific data where is the bleed we also want to see if we can take this to a broader patient population outside of the realm of interventions very very interesting well dr. Rizavi thank you very much for sharing with us this very important and valuable information and this truly belongs in breaking the barriers and endovascular interventions and I believe personally this is going to simplify and make our procedure better and safer for our patients so thank you very much. Thank you very much. Appreciate it. Thank you very much.