 Hello everyone, my name is Priyanka Sen, I'm one of the new staff members here at Texas Heart Institute. I work in the divisions of clinical and interventional cardiology, as well as advanced heart failure and transplant. And today I'd like to give you a talk about extra corporeal life support, specifically discussing VA ECMO support. So to start off with regarding the epidemiology of cardiogenic shock. So there's the hallmarks of the syndrome itself, and that includes acute myocardial contractile dysfunction with resultant hyperperfusion. There are various definitions that might have different blood pressure cutoffs or map cutoffs, depending on the paper that you look at. But typically they say if the systolic blood pressure is less than 90 for greater than 30 minutes in somebody who normally does not live with that blood pressure. They're requiring the use of inotropes or vasoconstrictors to maintain that blood pressure, in addition to the evidence of end organ hyperperfusion. Because cardiogenic shock as a syndrome is not just the heart not functioning well as a pump, but also what are the downstream effects of that. So things like an elevated lactate might support that diagnosis. It is still despite years and years of this diagnosis having been in existence still associated unfortunately with significant morbidity and mortality, approaching anywhere from 25 to 50% in majority of those cases but can be even more depending on how recalcitrant the disease ends up being to medical management. And above all else, it is a very time sensitive diagnosis. The idea being that if any intervention is to be done, it has to be done before this becomes before this goes from a cardiac to a cardiometabolic process, at which point, all the damage is kind of done. Now looking at the causes of cardiogenic shock, the vast majority are still related to ACS which is in that purplish color in the pie chart. And this is followed by acute on chronic heart failure on down the list. Now Sky is one of the interventional cardiology organizations in America and they about two to three years ago they came up with this kind of structure hierarchy about thinking how to risk stratify a patient whom you see in the hospital. And it was defined by five stages, stage A through E, A starting as those people who are at risk. Those are people who for instance have had a heart attack in the past prior infarction acute or chronic or acute on chronic heart failure, those being the risk factors for development of cardiogenic shock and future. This stands for beginning. And that's people who have clinical evidence of relative hypertension so those patients who might be just starting to have blood pressures less than 90, or tachycardia without hyper perfusion. Sometimes the earliest things that we can see clinically is a diminished pulse pressure and tachycardia to go along with it before the patient begins to feel cold and clammy. This is classic. These are the patients who, without a doubt are in cardiac shock. They are hyper perfused, however, they are not yet to a point that they cannot be revived. These are people who might still be going through some resuscitation, resuscitative process, whether they're on inotropes or they've already started to be on mechanical patients. This already includes those people who could be on ECMO but are not deteriorating on it. And that defines stage D. There are of course, fallacies in my opinion with this, this way of classifying patients because it also the distinction between C and D also has to do with did you provide enough support to begin with. You're deteriorating on the support that's been provided and he is extremists. So that is the crashing and burning patient of Intermax one. And of course, as would be expected, the sick or somebody is the higher the stage there and the higher likelihood of mortality or bad outcomes. So again, becomes an inflammatory process. It elicits and inflammatory cascade, which initially is supposed to be compensatory, but eventually these compensatory mechanisms actually need to more harm, leading to more things like ischemia, more myocardial dysfunction and just leading to progressive myocardial dysfunction. Many inflammatory markers can be elevated. These are a lot of things that are currently being studied right now to see if they can function as prognostic markers in future, but those are still kind of in the works of researchers. And again, once the cardiometabolic process has started here we're just focusing on lactates. And this is one paper that looked at that. They marked a cutoff value of 3.1 of lactate, and especially if it persisted even eight hours after presentation, the risk of mortality was substantially lower. So just another example that after you've let the pump fail, and it has already exhibited its consequences on the rest of the body here by with elevation of the lactate which is a marker of anaerobic respiration. It just shows that the spiral has started and is not patient is not doing well. Again, how do we solve the hemodynamic support equation. If we look at it that way there are three approaches to it, and it's a team effort that involves cardiologists, sometimes surgeons and definitely perfusionists. It's a three pronged approach both to increase the circulatory support. Second is provide ventricular support, and three is to provide a timely coronary perfusion because ultimately time is muscle, and we need to revascularize as soon as possible if that was the inciting factor. In terms of providing circulatory support our goal is to increase the mean arterial pressure, because that ultimately is going to what is going to help us perfuse the rest of vital organs. And again, clinically at bedside we can assess that with increases in urine output or improvements in mentation, if that was a problem before, and certainly by markers like serum lactate. So serum is another good marker of course because 20% of the cardiac output is supplied to the kidneys. So it becomes a quick measure of how the body overall is doing. And ultimately we also want to reduce the inter cardiac filling pressure such as the LV, EDP and the wedge. Initially when somebody comes in shock. I think most people would be jumping towards mechanical circulatory support we like to use and to some extent exhaust some of the medical management first, but there are limitations with that, as would be expected, the more number of vasoconstrictors or inotopes that are being used, and that not only marks the fact that a patient is needing more support and therefore are sicker and therefore are more likely to have bad outcomes. But the chemicals that we are using to artificially improve the perfusion or the blood pressure have harmful effects on the heart. And that can not only increase arrhythmias, especially if you're using beta agonistic medications, but also the severe vasoconstriction peripherally can lead to all the ischemic digits and just worsening of your lactate. So the use of the endostatic tractomyalysis all of these problems which only make it harder for the heart. And analogy that I've often heard is, it's like flogging an old horse, flogging with all of these chemicals in the situation. So the goals of using acute percutaneous MCS then is to target these following things. One is to decrease the left ventricular endostatic filling pressures. That will also help in turn leave some of the congestion that's occurring behind the left side of the heart, which is the lungs. We want to augment cardiac output to improve forward flow. We want to increase reliance on vasoconstrictors and inotropes. So sometimes by providing a timely percutaneous MCS device, we can actually start coming down on some of the very astronomically high doses of pressures, which have their own harmful effects. And ultimately, all of this is to increase organ perfusion, especially to the kidneys and the brain. So with real MCS, of course, you know, there are many choices when we see a patient, and I don't think there's necessarily one perfect one it really depends on the situation. Something as simple as a balloon pump might be just what somebody needs for severe MR, which is mitral regurgitation, but somebody with full blown myocarditis might need something much more aggressive for biventricular support like a VA FMO. So it really depends on the clinical situation, but before embarking on implanting any of these devices, we should always consider that this should be a bridge to either recovery or a bridge to a decision. Hopefully something that will lead to either a completely either a heart transplant or a durable mechanical circulatory support device, such as an LVAD. So for patients when we're choosing MCS, of course, vascular access matters, because these devices are going into the arterial system, the artery size matters because it must be able to accommodate the cannulas that we will be putting in. And that also will affect whether we have any kind of ischemic problems distal to where we've placed the cannula. There are also hemocompatibility issues that need to be taken into account, many of which have improved over time because the materials being used in the cannulas are probably not as thrombogenic as they once used to be. And regardless, because there is that interaction and because in some of these pumps the blood is being taken extra corporeally or outside of the body. It becomes very important for us to keep such patients on anticoagulation at all times. And then of course looking at the hemodynamics and the pump position matters to once it's in, whether it's balloon pump whether it's ECMO whether it's tandem or impella imaging can be very vital in our daily sort of assessment of the patient to determine that at least our positioning of the device is optimal. So when it comes down to it of our percutaneous MCS options. There are a few that I'd like to mention, but really our focus is going to be on VA ECMO. The ones that we use at this hospital is the balloon pump intra aortic balloon pump which uses a counter pulsation method to essentially decrease the afterload and improve coronary perfusion. And of the content and that's a pulsatile pump where basically it inflates in diastole and then decompresses in system. Of our continuous pump pumps, we've got the axial flow pumps which impella CP is the one that we're using in the medical center here. And basically by saying that it's axial flow means that the blood that is being moved through the pump is in the same direction of flow as the native blood. And then centrifugal pump is the extracorporeal ones, the tandem heart as well as the VA ECMO extracorporeal meaning that the blood is taken out of the body goes to a pump that sits out of the body. And when we compare inter corporeal pumps to extracorporeal pumps which I know you all are probably a much more expert in this is that inter corporeal pump, because it's sitting out of the body, it can be a bigger pump, and that allows it to spin much faster to achieve the same flow that a VA ECMO might be able to achieve versus an impella CP which is sitting in the body. The impella CP has just been significantly faster. And therefore, it would be more prone if we're trying to achieve the same flow for more hemolysis than what a bigger pump that's sitting outside of the body. And what's also important in making the decision is what is the level of circulatory support that each of these devices can provide balloon pump and at least the two point five, even the CP they do not provide necessarily full support. CP can take you to about three three five or so. But definitely much more flow can be achieved with a VA ECMO or tandem and impella FIVO is also another option but here I think we'll stick to those that are purely percutaneous because FIVO requires the help of a surgeon to place an axillary graph. Now going again into this this is an example of some of the things that would go into place if somebody were to use a shock protocol or the decision making. Once of course the diagnosis of cardiogenic shock has been achieved, or made, then you try with medications to improve the hemodynamics, and you're looking for things like evidence of serves the pulmonary congestion that spiral of things that ultimately can lead to death has already started. So at the intervenable portion once you've assessed the hemodynamics, if you have a little bit of luxury of time a right hard cat definitely goes a long way. Sometimes unfortunately, especially in emergent situations of somebody's crashing before you, you might not have that that time to be able to do it. But if you're able to do a right and left hard cat that really helps determine whether you're dealing with a univentricular process. Versus the biventricular process which might need more than let's say a balloon or an impella. And so in that there are various hemodynamic kind of parameters that we can use such as PAPI such as CPI, but essentially all to help us determine whether we need more support to provide for both ventricles or just one. The US has been evaluated in many cardiac shock trials over the years starting from 2012 actually even before that, initially with balloon pump then gradually tandem heart came up in later on, and then in the impressed shock trial impella was evaluated. So you can see regardless of the trial the mortality has been quite significant and shocking, even despite the advent of more progressive kind of machines. And so we're ranging still 30 to 50% on a lot of these trials. And of course now there are a lot more trials that are kind of still ongoing. I think historically it's been difficult to do sort of randomized trials for for cardiogenic shock, because it's hard to randomize somebody who's crashing before you to say we're only going to do medical treatment, or something that you feel is an inferior choice versus go for VAC mongol the whole nine yards. So I think that has been a big barrier to doing randomized control trials. And now kind of getting to VAC mo which was to be the heart of this talk peripheral VAC mo is a right atrial to femoral circulatory support, which to which we add an oxygenator. It does provide by ventricular support, because it directly siphons blood out of the right from the right atrium. The equipment required typically is going to be a 17 to 19 but in rare circumstances we can also go up to a 21 front arterial cannula. All depends on how big the femoral artery is to see how much we can accommodate. But it's important to remember that our flow is is directly related to our cross sectional area of that cannula times the velocity of the flow going through velocity of the blood going through it. So essentially, if we have a fixed velocity, a cross sectional area is going to matter a lot. So in a person who really needs it, the support if they have small vessels, it's not really doing them a big service if we're going to be in ending up putting a 15 French cannula because we'll never be able to generate the flow that they require. And then of the Venus cannulas is 21 to 25 French. So common VAC mo indications, of course refractory cardiogenic shock in the setting of acute coronary syndrome acute heart failure post cardio cardiotomy is another instance. Those patients are already on cardiopulmonary bypass in the OR, but sometimes they cannot be weaned off in which case they're either transition to a central VAC mo and then later to peripheral VAC mo depending on how long they need the support for myocarditis of course these both post cardiotomy and myocarditis tend to be by ventricular processes hence they need VAC mo support if refractory to medications primary graft failure after heart transplantation refractory ventricular arrhythmias and in severe cases of infection drug intoxication and severe hypothermia. There are some of course contrary indications to that are worth mentioning, you know if somebody's life expectancy is not long because of other comorbid conditions, then VAC mo is not a good idea specifically a disseminated malignancy. If it was an unwitness cardiac arrest. Typically this would not be offered just because the likelihood of them coming out of it prolonged being down the neurologic consequences of that many of which cannot be directly assessed right when they hit the door with EMS would make them definitely a poor candidate and definitely severe aortic insufficiency is really a contraindication for many of these devices which are going to be increasing after load. So many of these devices that are going to give you retrograde blood flow. It's not going to be a good idea, because it's just going to worsen your aortic regurgitation. Of course if they have severe peripheral arterial disease, it just cannot accommodate the size of these cannulas relative contraindications of course are advanced age and bleeding diathesis because they are going to end up needing a lot of anticoagulation because of the probability issues with the pumps. And then outcomes of VAC mo's again. If you look at this. This was a compilation of many papers that are out there in Jack Hart failure. And basically it's looking at what were the outcomes of VAC mo whether it was done for post cardiotomy versus post transplantation versus just cardiogenic shock myocarditis or cardiac arrest. It is a wide mortality range, but in a lot of them the mortality average is still very high on the order of 50 to 60% partly you can say also because if somebody ventured to put in a VAC mo it was probably definitely because this patient was just that sick. And then distinguish are there are there scores out there that can sort of help us restratify and see does this patient even have a shot is it worth pursuing. And there are some out there. Some that are mentioned also registry for example this one is the save score, and it takes into account a lot of things, one of them being diagnosis, what initially led to the shock in the first place. Carditis fares a lot better than for example congenital heart disease which would generate negative five points age of course the older somebody is the worse off they are so it helps to be younger, as would be expected, kind of being mid range with weight is better than being on either end of the spectrum. And of course if somebody has other comorbid features they already have shock liver they already have renal failure these do not bode well. So take all of these into account, in addition to how much how long they've been intubated etc. We can generate a safe score, and just in general the higher the score the more positive the score, the higher the chances of survival and probably more justification for proceeding with something Now, in general if we're talking about using this in refractory cardiogenic shock. Obviously, then we would say that the VA acro does have some beneficial aspects to the heart. And those include things like increasing the central aortic pressure. It is delivering the blood through the femoral arterial cannula the outflow graft essentially in a retrograde fashion. And so that is helping us increase the central aortic pressure, thereby helping us perfuse the rest of the body. So it does help with coronary perfusion to some extent by doing so. And then it would help with normalization of the blood oxygen content, and hence improve myocardial oxygen delivery, because it's got the oxygenator there. And finally by us being able to manipulate things like the sweep. It helps us normalize the acid base and other metabolic abnormalities such as the lactate just by helping us perfuse better. And of course as you know we can also dialyze through the circuit. But there's a price to pay for just trying to achieve a higher systemic perfusion. And here we can see in just a sort of pressure volume loop. You can see that the total work that is being done by the heart is linearly correlated with the pressure volume area. And that comprises of the stroke work that is in the blue area, plus the potential energy. And there is a flow dependent increase in end diastolic pressure as you can see in the graph to the right, where we can see at baseline is the blue circle baseline cardiogenic shock. And as you go up with the ECMO flow, yes you are achieving higher blood pressures as you can see the peak pressures are getting higher. But at the cost of it, your diastolic performance is getting worse and your EDP which is your end diastolic pressure inside the left ventricles getting worse. And it's getting worse also by the fact that as you go up higher and higher on the pressures on the flows from the ECMO which is going retrograde against an alterative weak heart, it can lead to a point where your aortic valve is no longer opening so you've lost a lot of energy. And that combination of things, the increased effective arterial elastins as well as just the backflow against a weak heart, making it harder for the heart to pump against, eventually leads to higher intracardiac filling pressures, and also decrease stroke volume. The stroke volume here you can see is the difference between the furthest out point, the right most line of each of these PV loops minus the left most line. So that is your stroke volume. It's the EDB or end diastolic volume minus your end systolic volume. So then the question becomes do you unload or not. And this is something that is being studied more and I think it's sort of become common practice at a lot of places where if somebody had a weak heart going into this, and they've gotten via ECMO and they're needing a lot of flows and they've become non pulsatile that you just from the get go you put in an LV vent. When we're doing everything percutaneously, we would use something like an impella for this and impella CP. As you can see in the picture to the right. But of course if this is a central via ECMO. Then it's usually done already where there's a direct LV vent, or something that's going in from say the right upper pulmonary vein which is essentially achieving the same thing. And the benefits of LV unloading again going to these PV loops which you've studied, you can see the differences when you take the normal physiology looking at the left of the screen which is the circle in the red. Then we have a right word, a shift of the curve with decrease in our stroke volume when you have systolic left heart failure. When you add a VA ECMO to that you have improvements in the blood pressure as we expect but you have a decrement in the stroke volume, and you have more actually cardiac work being done. And this can be mitigated. If you look to the right with use of a left ventricular venting, where you can really start shifting that curve back to the left, closer towards normalcy. And most of those is achieved with use of an impella. And I wanted to make a distinction here between cardiopulmonary bypass which you all do probably even more than you help with the pulmonary, sorry with the peripheral via ECMO cannulations. The idea is very similar. However, there are a couple differences with the cardiopulmonary bypass machine, there is a venous reservoir. The big chunk of the blood is actually sitting outside of the body, and that predictably would create more hematocompatibility issues potentially need for a lot more anticoagulation. And in general those patients are already under hypothermia, which is not a requirement for peripheral via ECMO. And in peripheral via ECMO we do not have a reservoir outside of the body where the blood is sitting. Furthermore, if you keep comparing the two cardiopulmonary bypass hopefully is not required for any longer than a few hours peripheral via ECMO is kept for days, hopefully not for weeks but it has been used that long. The advantage of cardiopulmonary bypass or central via ECMO is that you can use much larger cannulas. So, going back to the idea that cross sectional area matters and how much flow you can generate. It helps to be able to use bigger cannulas, which we are limited peripherally because we can only as interventionals can only access the femoral artery. And here's the central via ECMO another very big distinction between cardiopulmonary bypass and I will lump that with central via ECMO versus the peripheral via ECMO which we would do is that the directionality of the flow is different. The outflow graph that comes out of a central via ECMO is going to shoot blood in the native or integrate fashion so it's not competing with the heart's own flow. This is very different from peripheral via ECMO where a femoral cannula is shooting blood against the heart, increasing the afterload for the heart to work against. So here we discuss this, of course with central via ECMO the big disadvantage is that it must be surgically placed with the sternotomy and therefore it cannot be done emergently outside of the or. The situation in which this happens is when the patient is already in the OR and some something has happened. So now going back to it, what are the hemodynamic pitfalls of peripheral via ECMO. We discussed several of these but a big one also has to do with the fact that the directionality of the flow is different from how the body normally behaves. The LV is also not totally unloaded, even though we are trying to unload the right side of the heart and therefore that's unloading the rest of the heart. It's not taking out all of the blood because the left side still gets blood directly from pulmonary and bronchial circulation. The retrograde flow again increases afterload to the LV. This may lead to LV distention increasing the wall stress further increasing the LV EDP, further reducing the coronary flow, which is the difference between your diastolic systemic pressure minus your LV EDP. And therefore worsening your pulmonary edema and hypoxemia because everything is just backing up. This leads to LV distention and these are the major issues. So one issue that is very unique for those of you who might not deal with the peripheral via ECMOs as much as you do the central ones. This one is unique to peripheral. This is called North-South syndrome or Harlequin syndrome and it's named so because it causes differential hypoxemia. So it's as if the right arm for instance which would get blood flow from the aorta earlier than the left side would be a different color almost that would be blue or cyanotic compared to the left side of the body which would be more responsive and more receptive to the blood coming directly post-oxygenator from the via ECMO circuit. And that's why it's called Harlequin syndrome because of the outfits that the Harlequins used to wear. In this picture you can see that where the white contrasted blood is only coming to a point in the aortic arch and so it's possible that the right carotid is not getting the fully oxygenated blood from the oxygenator. It's instead seeing the blood more directly from the heart which is ejecting partially deoxygenated blood because the lungs are wet so they're not able to do the appropriate gas exchanges. And this is the reason why post peripheral via ECMO we usually put a right-sided radial arterial line and that's where we get all of our ABGs for monitoring from because it's a surrogate for what essentially the brain is seeing. And the solutions of course if we're having terrible north-south syndrome is to increase the pump flow so the oxygenated cloud or the mixing cloud is pushed closer and closer to the aortic root. So all of the carotids and great vessels get the super oxygenated blood. We can also diaries, improve the vent settings to improve the lung mechanics so that what little blood is ejected by the heart is has improved oxygenation. And when all of these things fail, there are other things we can do with the circuitry by being able to add certain limbs by making it a venial arterial venous system, where the arterial or outflow cannula is why connected to another return venous cannula to improve more oxygenated blood returning to the venous system itself pre-lung. So after discussion of that of course, you know, we discussed that we want to evaluate a patient with their hemodynamics as best as we can to determine if they need biventricular support before venturing onto something like via ECMO. But there are situations again where we are seeing a crashing patient and we do not have the luxury of time to do that. And a classic example of that is ECPR where essentially this via ECMO is being placed in a patient who is actively coding. That of course you can imagine increases the risks associated with cannulation significantly. But there are other places not so much in our med center necessarily but there are other countries for example that do quite a bit of ECPR. But here again timing is key. Here is if somebody is beyond 20 minutes of refractory arrest the chance of survival with just standard CPR becomes less than 5%. So these are the patients that we're talking about and it's, it's tricky doing ECPR because you don't want to intervene and place the pump in too early, because if you do it too early without giving them about, you know, 1015 minutes of good CPR. It might be that Ross could have been achieved with CCPR alone, in which case you've subjected them to the morbidity associated with cannulation without necessarily a need for it, or it could be too late. If you're deliberating and deliberating and haven't made the decision because you didn't have all the information available to you by the time you decide to put it in 3045 minutes later. So that's time that the brain was under perfused, and you might have irreversible organ damage. So when we're talking about the bridge to a decision or bridge to recovery, that opportunity is lost. So, you know, in general, examples of inclusion criteria for ECPR would be age less than 70 a witness arrest, presumably would have started the CPR process almost immediately so would have better chance. So ECPR should be less than five minutes initial cardiac rhythms of either VT VF or PEA, and some sign of life would of course be a positive predictor. If you saw the patient grimace or something like that. Those would be supportive. Again, quick cannulation, it can be unilateral or bilateral a lot of times we're doing these at bedside. So, rather than deliberating on which side, of course, if you have more operators than it would be faster to get access on both and go from there. At no point should a CLS be interrupted, while the cannulation is being done, if possible. Ideally, you would want to use fluoro but of course if you're doing it at bedside that is not something that we have access to ultrasound would be a good second. If just to see the wire since all of these things are being done over stiff wires. And then of course when you're about to turn on the pump that's when even if a CLS calls for it at that point you might want to hold the epinephrine push, because as soon as you turn on the ECMO, the blood pressure is going to go quite high. And then of course you want to gradually increase the flow to about three to four liters over 20 second period and stop CPR once you're over three liters because you've already provided decent profusion at that point. With peripheral VA ECMOs situation that we deal with more than with central is mitigation of limb ischemia, because these cannulas can be 17 to 21 French. French is third of a millimeter so if you multiply that out, we're talking pretty large cannula is going in, and they can be obstructive to the leg beyond one thing that we try to do to mitigate this is we put a distal infusion catheter, and that would be maybe a seven or eight French sheet that we put into the ipsilateral SFA, which we then connect to the side port of the outflow cannula of the VA ECMO, so that at least some of that blood will make it down the leg. But this is a common problem, it can affect even up to 30% of patients who end up being on VA ECMO. And here are some other other complications that are noted bleeding is of course the most common even up to 30%. Just because they're on blood thinners, many of them by that point are coagulopathic thromboembolic complications are also there, though with the use of more biocompatible materials and use of anti coagulation can mitigate that somehow somewhat. But when we do see clots more often micro thromboemboli that we see in the oxygenator, and sometimes it gets to a point where that has to be changed. Fundamentally, we want to achieve a balance of course between hemostasis and thrombosis to avoid the neurological complications that can occur as well as bleeding. And finally there's a risk of infection and vascular complications which we discussed. Coming to the end, of course, we don't intend to keep any of these devices in forever. We always want to give a shot to a patient on a daily trial to see how much they can mean what is their dependence. We don't just want to cruise control and leave them on three and a half liters for 10 days and not have tried to see if they're recovering at all. There are both hemodynamic parameters if you have a swan in place that we can assess with, as well as echocardiographic parameters, realizing that we can never fully assess the RV dependence or lack of dependence on the vehicle till it's completely clamped, because even at a flow of 0.5 it's still siphoning some blood out of that RA, and therefore providing some RV support. But essentially once we do that, once the decision has been made, and you've tried maybe even with a momentary clamp that this patient should tolerate it, you will want to increase the flow back up to two and keep them there till they go to the OR for decannuation. And usually if they had a vent in place such as an impella, we will keep the impella for a couple more days to provide some ongoing support, even cranking that up a little bit higher while the VA ECMO is removed. And finally, when we're talking about this, especially for a lot of these patients who are coming in, they have a history of heart failure, they have had recurrent decompensations and they never really quite recover from any of those back to their baseline. Here we can see we're talking about advanced heart failure patients. These are the patients who ultimately are never going to have enough cardiac recovery. And we're talking about these percutaneous MCS as being bridges to something more definitive, such as a heart transplant, such as a left ventricular assist device, which is a durable mechanical circulatory support device which is surgically implanted, or we're talking about palliative care. And just the final slide here is with all of these percutaneous MCS really taking hold in a lot of hospital, large hospital systems, which use more of a hub and spoke model essentially to use their satellite hospitals to send them hopefully in a timely fashion, the patients who are still salvageable. A lot of places are instituting shock teams. In Baylor College of Medicine, Texas Heart have also done the same since January. So hopefully to facilitate this if you see somebody who needs help that would involve the heart failure person on call and interventionalist on call, as well as the pulmonary critical care doctor and of course you. So thank you very much for your attention. If you have any questions, please go ahead and ask. And I hope to be working with all of you at some point. Thank you.