Dr. Baran is the System Director for Advanced Heart Failure and Transplant at Sentara. He has co-authored many publications about cardiogenic shock. In this presentation, he discusses the history and early management of cardiogenic shock and discusses the most recent data for the SCAI Shock Classification. He concludes with data behind the devices used for early revascularization in acute myocardial infarction complicated by cardiogenic shock.
Thank you, john thank you everyone. Uh, you know, basically this has made the sport so you can see the team. My disclosures are worked with a variety of that. The companies and the circulatory support arena, uh, but on some steering committees and so forth. So in outline, we're gonna talk about cardiogenic shock and really some of the, some of the beginnings of where this was recognized and history talk about new data and then about this, that's the data behind the various devices. One of the things that always comes up is the idea that this device or that device is superior. Uh, and so I hope to give you some actual data to consider Next time you're in the cap club was a patient and shop. I talked a bit about the scott shock classification, which I co chaired. There's action update coming out and really been in very interesting project, uh, work on. And does anything work in 2021. And so how we imagine the future? You know, we imagine oh is that someday in the future? It seems to be so much different and remarkable and and uh you know, childhood grew up in the seventies and eighties. And you always think that you know about the year 2020 wow, when we would have. Um but unfortunately often times what happens as time goes on and instead of uh our high fire and things, we have uh small drones and instead of light sabers, this unfortunately is all we have. We have capitals that really seem meek in comparison. So long, long time ago, galaxy far away in 1967. It was actually newsworthy when you developed a coronary experience. This is actually developed, this is killed uh publication from Kilburn kimball back in new york. And uh this is publishing A. J. C. In 67 a two year experience with 250 patients. Imagine now you couldn't even get an abstract at a minor meeting with such a thing. But this was a big deal at the time. The idea that you had to specialize to use with the defibrillator of each bedside. That the nurses actually were trained to take care of these conversations. They even went ahead and did courses with the faculty to be able to staff this unit. And it was a big deal if they could do a cardioversion. This is a new york Cornell and killed classification school mentioned today was one of the things we thought about when we developed the sky classification. Uh It was an idea of uh portraying severity of heart failure from a of no heart failure to be having heart failure. See frank former demon. Andy was cardiogenic shock. And you notice that the definition was Interesting one. Hypertension, lots of blood pressure, 90 with personal days of construction from Liguria, cyanosis, dia freezes, um very straight cord And you think, well, 32 years later, certainly we would have expanded and gone beyond. But actually circa 1999, this is dr judy Hoffman's landmark shop trial in New England Journal. Uh And this trial actually trial day, my shock. And it really answered the question for the first time whether it was the role of emergency revascularization versus initial medical stabilization, the first one to actually do a trial and this compromised population patients in shock. And these are patients who are defined by having the same things cool Germany's or urine output Blood pressure less than 90 court. Again, it's less than 2.2 with support with the adequate filling pressures Really no different actually than what you had in the 60s. And We must have something more today at 2021. Well, we're still stuck with yield two blocks of shock. Uh We of course have drugs. Everybody throughout the ages has always been interested in drugs. Right? So melanin on um you know a drug that could be used p. d3 inhibitor. A variety of other drugs are available, including some outside the us. But largely people have felt that drugs are a mistake to use in cardiogenic shock. Mm Probably largely because of a push by companies that make devices. And it's often times quoted this famous paper and trump's kill lose samuels at all. And I thought it's always interesting to go back to the actual data Before we just blindly accept the file of the slide that's shown to you. Look at the actual file. So this is back in 99 dR samuels. Very excellent cardiac surgeon published pharmacologic criteria for that insertion following postcard Iata me appearance with the Obama DVs. Probably most of you have never seen one of these. But I did I was in training at the time. The BBS. Is this large half refrigerator device? Pneumatic? The bed itself is right here uh bedside. And God forbid that the thing actually would fall down because of a fell down, that it wouldn't pump anymore. Worked on gravity. And in that study, they showed that the mortality was based on the immediate postoperative china trip requirement. And if patients needed a high dose side of tropes, they had a very high mortality. And you could see a linear advanced Okay. But this is very, very old data. This 3462 general cardiac surgical patients, very much akin to saying that knowing about cars is known about a model T. This is old data doesn't really apply, was only in postcard anatomy and therefore china tropes have a role. They have a risk just like anything else. But certainly the data does not guarantee that just use the vagina tropes alone without thought is causing patients to die. What about the next thing? Well, so bloom pumps pretty common. You know, they're Condra gentler way to step up and round trip alone. You can't beat them in terms of costs. The cheapest Implantable device, five or 800 bucks a catheter is almost universally available, invented in the late 60s, has a great track record. And there's only one thing we have this great inexpensive, cheap thing. This In 2012, the whole Garfield uh, colleague of mine, you know, was in Germany publishes very nice paper of the I be shocked to trial Uh, and single handedly based on this one large well done trial uh, signalled almost the death knell of balloons. But is that really warranted? It's based on this finding that the mortality was identical. And as you look at these figures noticed that they all end up about 40-50% and one month. And that's really important because we're going to keep trying and trying and trying to crack that Nut to reduce the mortality from about 40 to 50% of the patients dead in one month. And the balloon pump didn't do that. However, um, nothing is ever as clear as it may seem. This trial only included acute shock. Most of the balloon pumps were placed after the intervention was complete. It didn't look at non ischemic or heart failure shock. It only included patients of course, like any trial where there was equal poise. So if you're willing to randomize, you could not be, you would be in this trial if you're not willing to randomize who are not. One of the most brilliant things that Dr Hochman didn't her is that she had a registry. So patients that either were not willing to sign consent or the investigator felt they had already made a decision about what the patient neither were in a registry and really gave invaluable data. But that's not available in the I'd be shocked to trial. And so the bottom line is if you could flip a coin and you already did the intervention and it didn't matter to you as the investigator whether they got a blue pump or not. Well, are we anybody surprised that that therapy didn't work because clinical judgments usually pretty good. What else? More data? Not everybody responds the same. So when I was in my previous position I had a lot of interest in looking at the human dynamics of bloom pumps, particularly 50 cc larger bloom pumps, and published this back in 2018, and some of the figures from that paper showed that in fact, our clinical judgment is correct that some patients respond much better than others. We've all had patients where you put a balloon pump in and the remarkably surprised how much better they get and others where you're very disappointed. And the point being that if you categorize patients to respond er, a non responder based on balloon pump, human dynamics, Those who have any improvement at all tend to increase by 1.6 L per minute, with a wide confidence intervals shown here, and those who didn't respond actually get worse. And the problem is that the next some of the two is an overall increase of about 20.5 liters. So you often times will hear people say, well bloom, probably give you half a liter when that's really dissonant with the fact that some patients do really respond. Looking at the bottom, you can see that if the baseline cardiac output in the non responders didn't get much better, but these are Kordic outputs that are quite good, whereas the responders did increase And particularly we did Multivariate analysis and that paper, looking at the best predictors of response on the scatter plot, you can see if you're on the top left quadrant. If you're on the left side of the curve that you're Kordic index is below 2.2, most of those patients tended to respond. So in fact, if you measure with human dynamics patient has a preserved cardiac output, perhaps the hypertensive for something else, but the cardiac output is preserved, it's unlikely that a balloon pump may make a big difference. But in fact, the Kartik indexes reduced you oftentimes we'll see a significant benefit. But we're not satisfied with balloon. The you know, everybody likes the news bite bloom pump. Bad. Okay. So of course we need a bigger catheter because we have this figured out it's just like heart failure. When we used to think that all of heart failure was just human enamel. If human annex were enough china troops would have been the cure for heart failure. But that's not the case. So how about the impeller? Very nice catheter. Re leaders of flow and the ct version more is better. You're my only hope. Well, there's a whole family. They proliferated and this has been up. I need to update this with the 55 lost. The Pigtail gained a few $1000 lost a French size. Um But let's see what is the data. So the strongest data is actually this interesting trial called the press T. T. It should have been a no brainer in Pella, C. T. Vs. Balloon sort of a rigged match. Don't you think this is published in Jack in 2017? And this was looking at the balloon pump versus a paella And am I shocked? Um should have been straight forward. They were only able to randomize 48 patients. It was multi center open label. Um They actually took all really sick patients. All of them were stemming a media pc Cardiogenic shock by the usual definition of the last 40 years of low blood pressure and adequate profusion. But interestingly in this trial, all patients done Germany were ventilator dependent to be enrolled. If you could agree to the trial you could not be in. So these really all actually talk to the investigators not picking up. That should really be a great trial for a patient, good device. And in fact, you can see little picture on the right of the patients. Both groups balloon and a paella were really inflamed. These were super sick people. When you delve into that paper, the systolic blood pressure was in the eighties, almost all of them and had a cardiac arrest With a long time to Ross. This is not like a simple little shock in the holding area. The average time to Roscoe was more than 20 minutes. Lac tapes were really, really high. The majority had LV dysfunction. If you got an echo, the majority of these people end up going on therapeutic hypothermia. If there was any opportunity to show that more flow saved lives, it would be here. But I sadly give you this, you might as well take this figure and apply to almost every device because it's always the same. The lines converge. The survival is about 50%. And you can see that the majority of the hazard as it occurs and shocked In the 1st 30 days. These patients are irreparably damaged. Unfortunately, this did not help. And the editorial with this paper also by feel and Partner Ritzheimer suggested that perhaps this trial did not work because the patients were not in cardiogenic shock. I'm not quite sure how this got passed the editor, but if these patients are not in shock and I'm not sure who is. But what about some more current data published in circulation? Looking in a paella comparing appellate patients to uh matched pair of those in the Aib shock to trial. Uh and this is very interesting that 237 patients with am I shocked treated with um Paella, they match them uh by a variety of characteristics of patients in the I'd be shocked to trial. And you could see the same finding on the figures. The survival is literally almost identical. So at some .1 has to start questioning whether it makes sense. Certainly our hypothesis has some fault in it. When we think that yeah, there's no doubt that the larger catheters do produce better flow, but somehow it's not translating to any effect. Well, we will just go at and with techno, the ultimate support, you know, when we hear somebody is critically ill and we think these other sentence, they don't have ECMO. Your lack of ECMO support is disturbing. Well, ECMO support is full cardiopulmonary support works in the operating room quite well, places the after load, but it's relatively easy to do. This must be the answer. And in fact, there's an entire organization set up to monitor ECMO, which is extracorporeal membrane oxygenation, essentially a portable heart lung machine worldwide. There's so much interest in doing extraterritorial life support that there's a whole organization. But this is nice because you actually have current data. So this is the report from Elsa From April 2021 and there's different flavors of ECMO will concentrate today on the one that's cardiac acma, taking venous blood oxygenating and putting it back. But there's also one for lung failure, such as our covid patients. And if you focus on the middle, you can see that the survival of the ECMO is about 59% of their welcome. Okay, that's a little bit better than the 50%. But in fact, survival to discharge a cancer about 44%. Even with the most potent support, we have still not really doing much better than the original therapies we talked about. Okay, well, if two therapies don't work, we'll combine them because that must be better Eskimo and impel uh Yeah. Well, people have done this before and that's fine. This is from Pappalardo and europe, published in Your Dream Journal of Heart failure. They took 157 non randomized patients. They combined ethno within paella, Combine the two together to see what would happen. Uh And what happens is somewhat predictable. You can see back here. Well, this is the first the population of patients, middle aged patients, lot of them with pc very elevated last tape. Um Most of these are comparable. This slide is shown that the population of the two is relatively comparable. But unfortunately so is the uh survival. Survival is 48% of the 21 patients who had ECMO and um paella, but mortality at 74% with extra alone because these are very selected patients. So those that you chose to put. And the idea was, well the survival is a bit better if you had the impeller onto the but everything comes with a cost. Look at the bottom and you see the amount of Hamal Asus quite large. Once you add a device onto these critical people and in particular bleeding because there's no free lunch every castle that you add to six patients because bleeding will cause complications. And what about the idea that you study this to see if you can place the um paella and and drain the left ventricle because when you use ECMO, you raise after load. And therefore another very recent study just published of a Shagan Westerman looking at the idea of combining the two. Uh and this one actually showed that if you combine an impeller with ECMO, you could actually reduce mortality. And this is a multi center international study and look how impressive this is. It matches to be AP value of .03. So Akmola ECMO and um paella Slightly better by 30 days. You look and say, Okay, maybe we finally succeeded. We have 686 patients in this registry study. Perhaps it's a little bit better that if you need ECMO for the same, by the way, 50% survival at 30 days, maybe we should add another device to it But look a little deeper under the hood. If you look at 30 day mortality, these trends mostly cross one. So this trend towards favoring the use of impeller along with AO, but none of these are startling. And what is in fact impressive is the increase in severe bleeding. And with 686 patients, a variety of experience, European centers is not that we don't know how to do large for access. It's not that, you know, we don't know how to manage these is the reality is that the risk is high no matter whose hands it in. Whether it's italian investigators, european investigators with those in America sick patients putting large devices in, there's always a price to pay for a very modest if any non randomized mortality benefit. Well maybe we're looking at the whole problem wrong and this is actually this kind of thing. That's exactly what God is thinking about uh generating a language for cardiogenic shock. You know, with heart failure, we have your card association class not great, but at least, you know, somebody refers to a patient and they described the class, you have some idea of what they're talking about, but apples and oranges with heart failure and different than shock, there was no common language. So if you look on the left of the figure person clearly can look and see uh four bars without a doubt and then on the right from their point of view, it's clearly only three. And this idea about four years ago was that it was something wrong in the field that we had no actual common language recorded in shock and that you needed to actually prepare many times. All of us had the same experience that call and tell you how this guy is really sick. You know, I don't know he's not going to survive. You have your surgeon sitting there waiting for the patient to land patiently and they come in and you elect really that's all they needed. A little bit of fluid bullets or other times when I tell these guys a little bit sick and it comes in and looking disastrously ill. And so it was really important, developed that common language question is which droid are you looking for? You really need a common way of describing them? Saw his privileged co chair this which was published in 2019, I must say is actually Garnered more success than we could have ever hoped for, really has been adopted as the standard language of cardiogenic shock. Now, coming up on 20 independent manuscript, published looking and validated examining this uh, classification. And essentially you can think of it like this and the scent of a pyramid, the sky stages with the base of the pyramid has the majority of patients who are uh, stage a at risk then followed by beginning shock. And I'm going to go over these and some of the tail classic cardiogenic shock to cheering and the tip extremists because we all knew that there were different kinds of patients in shock. But this is a way of actually looking and really classifying and in the manuscript and actually describes the table including physical exam, biochemical markers and human dynamics. And the idea is that at the end of today's lecture, if you have a basic sense, you can use the information on hands, the class of agitation, the recognition that not every patient will have a swan, so may not have last tape. Some may not have a physical exam that covered by a cath lab sheet. If you have the gestalt, you can actually make assessments and will show whether that actually produced anything. So patients stage A. Is that who is not currently experiencing cardiogenic shock but is at risk. So these are patients that typically look completely normal. The labs are fine. If you measured human dynamics, you would not find anything. But these include patients with non stem e chronic heart failure. To me, those who may not have anything at the moment but have the substrate that places them at grave risk of developing shock at some point, if something were to go wrong versus a patient with beginning cordage and shock beat, This is defined by patients who have either tactic, cardia or hypertension or both, but still have preserved profusion in a sense, this is what has been called pre shock in the past. Uh, so these patients look perfectly well perf used their lactate and so forth, is okay. But either a heart rate above 100 or blood pressure below 100. Uh, and these patients that that theoretically in the past have not been considered cardiogenic shock. Classic cordage in a shock. So the nice thing here is that one doesn't necessarily need to have a swan to recognize. You know if you ask any ICU nurse they can tell you which patient looks sick. Manufacturing pre hospital providers are very familiar with seeing a patient that looks terribly ill, diaphragmatic what not. And so classic cardiogenic shock can be defined even if you don't have access to all the sophisticated things or a bedside last tape monitor. And if you do do the human dynamics you find the typical human dynamics of cardiogenic shock with an index below 2.2 inadequate filling pressures. But we basically in this classification divorced the need for high tech from the ability to take care of the patient so you can diagnose these stages without the advanced moderate if you have a great. The key other concept is that we define stage D. As the patient is deteriorating the bedside recognition. That whatever you try first, if the patient doesn't get better, they're fundamentally on a different trajectory there, hanging out with the wrong crowd, something bad is going to happen to them. Uh And as I'll show you later, this actually does this possible. It actually works if whatever you tried first, whether that drips in the ambulance drugs in the Cath lab, if that doesn't work, the patient is security and they would be considered di di And then the tip of the pyramid. The patient you really don't want to have get to that point is the patient extremists. The one where you walk into the ICU, everybody's running in and out of one room and literally all hands on deck to try and keep somebody alive with cardiovascular collapse, we define a single modifier in that system that of a for cardiac arrest. And so the idea being that if you have a cardiac arrest is another modifier that you're on a different trajectory. Uh And that's oftentimes the case that in various clinical trials you see patient may recover heart function, but according arrest has a lot of longstanding sequentially oftentimes including neurologic sequelae. So three snippets of cases case number one is this shock. 48 year old man was a dilated cardiomyopathy. We've all had such patients clinic I suspect stopped taking Lasix because the prescription was 30 days. And he comes to you on the 35th day. He notices for some reason he's not been able to breathing too well, but it's better in his lazy boy uh in the clinic. He's hypertensive, little bit tackle. Kartik examine the lungs is not very impressive but he has some Madama but he's not called meditating perfectly fine. In fact he has his bag of Doritos. He picked up from the vending machine on the way into the clinic and he offered you some because it looks like you've had a hard day. Is that shock? Well that would be considered sky. Be shocked because that patient is hypertensive tachycardic but still adequately profusely. Is this one shocked 62 year old man seen in the E. R. Uh with chest pain and anti R. Stem. Me quite hypertensive and tachycardic looks like crude his extremities. So we can say that they're intact after signs. Taking them upstairs to have a P. C. I. So you don't have the swan. You don't have the lactate. You don't have the labs. Everything is door to balloon boom. You got to go. But you don't need anything more. You know this guy is when skies see shock for this one. The 78 year old man brought in by M. S. After collapsing at the home depot. Initial rhythm was Bs got a above 200 Joules Instrument runs of v. p. during the transport. But when the M. S. Workers come and hand you the patient, they tell you he's stable, stable on wide open fluids, 30 of dopamine. We've all been there. Why could they not have warned you? What was coming with the blood pressure of 80 heart rate of 1 30 crackles everywhere E. K. G. This is not the same. This is Skye D. With an a. My dream is that someday just like you have your E. M. S. Providers telling you and standing over to medical control the E. K. G. That you would have shock centers and that the VMS workers and ambulance folks pre hospital providers could actually use the classification to tell you, Hey got a sky deer. I gotta go sky E and divert those patients to where they might actually be able to get help. The sky stage predict outcome. All of this sounds very nice and dancing and it's nice to have a manuscript. But does it actually work with the darn well. So my colleague Jake Genser uh, published along with myself, is really nice analysis from Mayo Clinic. Whereas the first analysis published shortly after we published the manuscript looking at this in a very large population, we had 12,000, 904 patients in the Mayo clinic, ICU. After some exclusions for readmissions and so forth. We end up with a roughly 10,000. And in this figure it shows you the majority of patients turned out to be in Ska and then some lesson B and so forth. And the tip of the pyramid. Indeed is those patients and extremists. Uh and we made definitions before starting the analysis to try and retrospectively assigned sky stages. This methodology is held up the patients who are either neither hypertensive nor tachycardic, but um it is the view patients and be who were hypertension, hypertension according or so forth. Uh And in the paper, we actually define the different levels that allow you to use a medical record. E. M. R. Can actually make these A through E assignments. And if you look on the right, the observed mortality is exactly, you could imagine both. I see you and the hospital mortality directly correlate with the sky staging. So this methodology invented by a bunch of us actually worked Then validated. It works. It ought to be validated by multiple groups Shriek. And Westerman actually published this in 2020 where they looked at patients uh in their unit about 1000. And you can see interestingly the exact same finding of very significant correlation. If you knew what the sky stage of the patients that based on, you could predict what line the patient well beyond A. B. C. C. Or unfortunately eat. And notice that in the beginning all of the mortality is right in the beginning its life. So essential to classify them. If you have any hope of getting out, you have to try and get them off the line and on the right, you can see the odds ratio is very good if you're stable and you can say, well, okay, that's that's pretty obvious. But this is a bit more we actually, since we helped develop this um kelly, Um It and I worked on this along with one of our medical residents to prospectively validate this because we have a shock team here at some terrible and actually in every case we would prospectively assign a sky stage. So the previous studies that showed you a retrospective assignments of sky stage. But this is that time zero from the medical record. And we took 168 patients over about the first year of the shop team. Um And the analysis showed the breakdown was very similar. We didn't really get called for any sky. A patient's obviously otherwise the denominator would be larger but B. C. D. Any and on the right you can see that is very good. If you have relatively beginning shocked most of those patients did very very well and survived without particular trouble. Whereas progressive drop in the value was highly significant. Although if you know this you could say well C. D. And E. Dave are pretty well closer together. In fact the interesting thing by assigning things prospective, we were able to generate these really interesting observations regardless of your initial sky stage at our hospital. If you improved by any sky stage, you're on a different trajectory. So now we're getting into the idea where you can actually predict who's going to get better. So if in fact you started to see and he became a. B. Or you were A. D. And you're stabilized to a C. Um you actually had a remarkably different clinical trajectory. And interestingly if your sky stage was unchanged at 24 hours or it got worse, you had equivalently poor outcome. So now that gives us a goal post something to try to fix At first golden 24 hours as we try to improve cardiogenic shock because it makes a difference. In fact, it's a dose dependent effect. You can see on this slide that in fact if you improved 3-4 sky stages, you're gonna be just fine. And in fact at each level, depending on how much you improve even one sky stage, it's on a completely different trajectory. The relevance of this as well. And one of the reasons I think they published it is that if you're in the outside hospital and you don't have all the toys And at 24 hours your patients not getting better. This graph says you should try your best to move them if they are movable. If there's somebody that somebody would be able to intervene on. Because if you don't, the outcome is clear putting it together. It is the tool, not the tool rather is the team. We have all these fancy devices and veering costs, sizes, morbidity burdens. None of that has actually made a difference. It is actually the team of colleagues working together all the disciplines. That actually makes a big difference here at centaur, you can actually call the shock team and the easiest way nails to call the operator 12 and ask for a shock alert or Muller. And this can be done at any time. And what happens then that gathers colleagues from interventional cardiology, advanced heart failure, pulmonary critical care, drastic surgery, a shot coordinator kelly and then a profusion, putting all of ourselves together. So here's the Oda, do or do not. There is not try. The point is that we will try our best to help that patient to put all of our heads together and make a good judgment. That doesn't mean that we're going to render futile care to somebody, but that we really give them their best shot of looking all the angles. And you can imagine for those of you in the Cath lab, if you're doing an intervention, you really focus on opening an artery dealing with christ. Is it not better to invite the fire squad in? Let us help assist. We don't do the intervention. We don't take over the patient. But having somebody that can be objective and level headed can actually be very, very helpful in helping you manage. And if it's a patient coming from outside, at least it renders a team with all the available expertise to rapidly make a decision about what is it If anything, that can be done to help the patient. So this is a snippet from the paper now back at Philip in 1967 at that time, he bemoaned the fact that the failure of intensive care to improve the mortality rate from shock represents a continuing challenge. The current therapy or concept, What was true in 1967 is still true in 2021. In many ways, it's not different than steps. We don't truly understand what happens in the spiral. Once the cornucopia drops, how is the patient injured in such a way that even if we restore flow, if we put them on the heart, lung machine and restore heart and lung circulation, it still doesn't matter. Sometimes patients will still die. We've all been in the circumstance where you try your best, we are still not able to save them and I submit to you. That is because we still don't truly understand all the path of physiology is of what happens. You know, when you go to house, if the house is burned down, it doesn't much matter how it starts. It's just that there's no house left and that's really the continuing challenge of the next 20 years is to understand. And I suspect that whatever will work, receptive shock, not found yet. No, in fact work except for cardiogenic shock. Some conclusion. Perhaps we need the force Uh cardi Jack Marshak mortality has not changed since Judith Hoffman's seminal observations in 1999, devices are increasingly more capable and we keep having better and better devices Developed by industry partners, but we have not cracked 50% death 30 days. One thing that can be helpless to categorize patients by sky stage at least, let's you know what you're dealing with. That's helpful in terms of communication. That's helpful if you're not the mothership to be able to decide where the patient is best to go. Not unusual today, if the patient has a semi, you wouldn't go to a non stem the hospital and has published two years ago by the H. A. Perhaps someday we'll have shock centers where patients with significant cardiogenic shock go to the highest level centers, patients with more modest degrees of shock go to one of the other outlying hospitals in the hub and spoke model. Certainly my plug after utilize the shock team. You're critically ill patients and to at last to leave you with the right device, the right patient the right time. I thank you all for your attention today. Mhm.
