 Welcome to Texas Heart Institute Educational Programs on Innovative Technologies and Techniques. We have a special opportunity today as a guest, Dr. Stephen R. Bailey is our guest. Welcome to Texas Heart Institute at Houston. Thank you, Dr. Grazier. You're welcome. He is a professor and chairman of Department of Internal Medicine and also professor emeritus at the University of Texas Health San Antonio. Currently he is in Shreveport and he is professor of medicine at LSU Health School. I am. So today's topic of this discussion and your presentation is related to cardiogenic shock and particularly on the updates and challenges now today in 2020. You gave an excellent presentation at our Texas Heart Institute Grand Rounds, Cardiology Grand Rounds on this particular topic. And we would greatly appreciate if you could summarize to us your current opinion and information available on the status and advances in treatment of cardiogenic shock. Thank you. Dr. Bailey, if you would be so kind, can you describe to us what is cardiogenic shock and what is the classification of shock and how do we differentiate cardiogenic shock from other shock conditions? So cardiogenic shock is one of the four types of shock. That includes distributive, which is the most frequent. It includes obstructive, the least frequent. And it is divided along with hypovolemic shock as the other of those components. The definition we use is one that's been around since 1955. It's pretty straightforward. It does a patient have a blood pressure that is less than 90, doesn't respond to fluids. It may be that they've had a drop of more than 30 millimeters from their baseline. We have to remember that. It should be defined as secondary to cardiac dysfunction, not something else. And we can characterize it more closely by evidence of lack of forward cardiac output. So it is a cardiac index less than 2.2. Or is there evidence of congestion, elevated left ventricular pressure within LVEDP that's greater than 15, making sure that the patient isn't hypovolemic? Excellent. So can you mention to us some key considerations in diagnosis and management of cardiogenic shock? Absolutely. So cardiogenic shock is something that comes up frequently. And the first question you want to make if you're deciding how to treat it is this really cardiogenic shock? One of the other forms that would be treated differently. If it is, they need to think about how severe it is. Because this is a continuum. In fact, you can have early forms that may be a little bit of a problem or you may have really severe forms that are major problems and may not, in fact, be treatable. So to define that, you want to think about what's involved. Is it the left ventricle? Is it the right ventricle? Is it both of those that are having problems? And lastly, based upon that assessment, how severe and what's involved, you can develop a treatment plan. Excellent. So tell us a little bit about the sky description of stages of cardiogenic shock. And you were the president of Sky for a certain period of time and also editor of chief of the Sky Journal. It's a journal, Kath and Cardiovascular Intervention. And you have many other accolades as well. But you also participated in this particular design of the cardiogenic shock criteria and stages. So can you tell us a little bit about it? Yeah. So as we looked at all of the different trials, everyone used a different definition and we found we couldn't really discriminate. You know, you either had shock or you didn't but we couldn't tell if you were at early stages or not and so we came up with a very simple classification. You don't have to have an app on your phone and you can figure it out. So some patients are simply at risk. They don't really have shock but you need to know they could. And some people are just starting. Some people really have the classic shock and so that we named that A, B and C. Classic for classic, B for beginning, A at at risk. And we talked about deteriorating, meaning you're treating them but they're getting worse. And lastly is are they an extremist so severe that again nothing's working. What we're hopeful is that that will allow us as we go forward with trials to more clearly identify who we're treating because we think that makes a difference and why we've had some problems showing benefit. And secondly, we want you to be able to communicate among ourselves. I want to be able to tell you I'm sending you a SkyD shock patient. You're going to know right away how sick that patient is. And it makes a difference. So there now are a number of studies that have confirmed that. Mayo Clinic has a trial that's shown here that what you can see is that those people that are in that Class A really are doing well and are going to do well. But just being from Class A to Class B is an increase of mortality at 30 days by 25%. So even though they don't really have shock, they're at that tipping point where they're going to have a much worse outcome. And of course if you're worse than that then your numbers start to look as we've seen classic shock numbers. And this is clearly shown in this graph which is quite impressive as far as the differences are concerned between A and E. Exactly. That's very dramatic. Telling you that this classification is very useful and very convincing. And in fact the Class C is right where we'd expect it to be about 50% mortality. So now we've got a way of saying what is our expected benefit and how do we treat them. Excellent. So tell us a little bit about the algorithm for shock. And what criteria do we use to make a proper diagnosis? Well I think one of the things we've learned is that we have to have a playbook. We have to understand what we do and how we do it. So here from Journal of American College of Cardiology is an approach that I think most of us adopted. So it starts with clinical assessment. How does the patient look? What's her blood pressure? Are they cold and clammy? It adds the labs that are incredibly important, lactate being one of the most important labs that we get. It tells us that we need to assess the patient very early on for right ventricular involvement. 40% of patients will have right and left ventricular involvement. I think we've ignored that and we haven't treated it. We now know we need to do that quicker. And then from there you can decide are they likely to respond to pharmacologic therapy or are they going to require something additional. Excellent. So in a few words, what are the goals of therapy for treatment of cardiogenic shock? Well there really are three things that we need to do. We need to help the patient. So we need to treat the hypoprofusion and avoid accumulation of lactic acid. We know across the spectrum that is incredibly predictive. We need to treat the ventricle. We need to help the ventricle during this acute phase so that it can improve and heal. And so that's the point where we have to decrease filling pressures towards normal if possible. We know that there's going to be remodeling events that occur. We want to limit that. We want to improve the overall prognosis by decreasing the pulmonary congestive symptoms because of its effect. And lastly, we need to provide blood flow in the ischemic state to these hearts. So is this right across the board for all the types of cardiogenic shock or is it just particularly related to ischemic myocardium in this particular image that you have shown here? No, it's across the board. Because if you think about it, even if it's non-ischemic, if you can't perfuse the myocardium because your transmocardial pressure is low, EDP is high, diastolic pressure is low, it doesn't matter if you've got coronary blockages or not. Still, they're going to have an ischemic process and a myocardial dysfunction. So let's talk a little bit about pharmacology. I mean, this has existed for a long period of time. And this was basically the mainstay of therapy for a very long period of time until the antibiotic balloon pump appeared and then many other mechanical support devices. So what has been a standard of care in the past? And do we have anything new related to pharmacology for treatment of cardiogenic shock? Well, I think we have some confirmations and that is that we really want to try to avoid arrhythmias. We want to increase the contractile function and the agent that has consistently done that for us is norepinephrine. You don't get the arrhythmias. You get a much better alpha than beta effect and that works pretty well. I think I'm excited about the use of some of the new calcium-specific agents because that's really the altered problem that we have at myocardium. And Lavaesumendrin is an agent that we're seeing increasingly used in non-eschemic but now pushing over into these acute cardiogenic shock patients. And so some of those drug substances increased the heart rate and that was certainly of concern in a lot of scenarios, particularly with ischemic myocardium. So what is your opinion on this issue? Well, clearly increasing heart rate at that cellular level and unloading can't help that. And so anything we can do to avoid that is going to give us better basal function unless myocardial oxygen consumption. So we don't want to increase the heart rate. Right. Sounds good. Well, a variety of devices have appeared in the last several decades. As I mentioned, interesting balloon pump was the first one, but there are many other ones available. And so how do they affect the cardiac function and how important are they in treatment of cardiogenic shock? Well, I think that knowing how they affect the heart is incredibly important in our decisions about how to treat and we're learning how to combine those. So if we look at pharmacotherapy or pharmacotherapy with balloon pump, we do increase the overall cardiac performance. We increase cardiac output. But we have a net negative effect on the heart looking at pressure volume areas, which is a measure of the work done. Which is nicely shown in this graph. Shown in this graph. Right. So let's talk a little bit more in detail about mechanical support. What is available? Briefly, how do they work? What is your first choice and second choice? Do you combine them sometimes? And this is nicely represented here in this image. Let's go through those quickly and get some additional information. How to use them and when to use them. So the balloon pump, I think, is the one that we've all used and I think we're most comfortable with. It's like our warm coat. But it really hasn't given us as much benefit as we need. And I think when we look particularly at cardiac shock, the amount of unloading of the ventricle versus the amount of perfusion has been limited. But it's still there. We still use it. I'm excited about the new axial flow pumps. Impala Cp in particular is the one we use percutaneously. There are other versions, like the PHP, that both all of those work to suck blood out of the LV, empty it into the aorta. So the LV volume and pressure is diminished, which decreases significantly myocardial oxygen need. Tandem heart and VA ECMO really are pumps that remove blood and then replace the blood, but they do so in a way that increases the volume and pressure that the left ventricle sees. So they are very effective at increasing cardiac output, but the increase in the amount of oxygen needed is disproportionate and can be a problem. The right side of the heart, as I mentioned, I think we neglected, but today we're excited about having axial flow devices like the Impala or VA ECMO that help with that. And of course Tandem has an RVAD form as well as Protec. So several different ways of looking at that is you ask the question, because these act differently, I think one of the opportunities we're going to have is to think about how we combine them. It's expensive in terms of thinking about technology, but if you think about the benefit and patient outcomes, saving that life, decreasing the time in the hospital, avoiding subsequent myocardial dysfunction may well be worth it. Now it's interesting as it's clearly shown here, we go from the simplest one, which is enterotic balloon pump as far as placement is concerned, and the time involved to achieve whatever goal you want to achieve to the more complicated ones with ECMO and so on, are there some newer technologies that are emerging or will be emerging probably in the next four or five years where we will have an option to use them either on a temporary basis or maybe on a little bit longer term basis for treatment of, well, cardiogenic shock but also for patients with maybe not cardiogenic shock but class 4 congestive heart failure or even class 3 congestive heart failure. We're a little bit diverging from cardiogenic shock, but I'm sure that our audience would like to know what else might be available. I know that one of them here is being actually evaluated or was designed at our institution, so-called preserion, but there are other ones like second heart assist and other companies also working on it. Do you think that this might also have an impact to a certain degree in treatment of cardiogenic shock or this is designed for other type of heart failure? So I think that we're going to see an adoption of those. I think that as we've gotten to the point where they're miniaturized but can either be temporary or permanent, I think we will get a point where we will put them in and leave them and then decide to take them out or not. That makes the most sense for patients. Then when you start to wean, you have support in case they don't wean. And I really believe that's a huge opportunity. So let's talk a little bit about models of cardiac mechanical support as far as heart function is concerned. Can you explain a little bit to what is shown in this particular slide? Well, this slide shows something that is near and dear to hemodynamicists and actually how the heart works and you see on the bottom what the pressure inside of the heart is at the end of diastole and the top straight line is what the pressure is that's developed and in between you can see how much blood gets ejected with stroke work and you can see if you look at the left-hand panel that the heart is operating at the lower end of that curve. So the end diastolic pressure is lower and there's lower volume. So it tells you there's less work. If you look on the right-hand panel, you can see that the pressures are higher there at the bottom. So it's working harder and it's having to eject against more pressure and the sizes are larger so the volume of the ventricle is larger. All of which go along with what we talked about before. Harder work being performed but more cardiac output in the ECMO. Somewhat less work but a lot less energy being expended to do it in the impella. So explain to us about device summary as far as cardiac power and myocardial protection is concerned. Looking at inotropes and all of the other mechanical assist devices. So the pressure volume loops are sort of hard to follow but this is a single chart that reduces that into telling us about all of these improve how much heart function there is. Cardiac power says here that we see the green. The myocardial protection that pressure volume area tells us how much work the heart has to do to do that. And you can see in the orange or red that most of those have a large amount of energy expended in exchange for generating more output. The impella seems to have a little bit of the best of both. So you don't work as hard and you still get an increase in cardiac output that's how we think we are going to help the hearts heal better through this process. So looking at this information obviously just looking at impella there is a big difference between 2.5 and 5. How do you decide when to use a smaller impella with less output versus bigger impella when to use tandem heart and when to use ECMO. All of those are available to you so how do you make the decision? Well actually I don't have tandem heart so one of the points that brings up is what do you have at your center and very few places have all of these. So they are contrast and compare. But this I think informs us about how we might make that choice to do that. So in our choice it really is dependent upon how profound the lack of cardiac output is. The impella 5.0 is typically a large bore either surgical or now we do it percutaneously as a clavian. But the standard is that 2.5 or 3.0 Cp so it's a moderate cardiac output. It may not be enough. And so if it's not enough then you'll think about getting the larger more capable device or combining devices. So and this graph shows actually when you have combining mechanical support so if you can explain a little bit the differences between using combined versus single device. So we addressed in the last slide the fact that ECMO gives a lot of cardiac output increase but takes a lot of work. We showed that the impella gives you a little bit of cardiac output, gives you a lot less work. And so the combination of those two therapies ECMO and impella combined to ECPElla which is what you see here compared to just ECMO alone. You can see in this small series both a short term and a long term benefit of that combined therapy. So it suggests to us a signal that these kinds of combinations to get optimal therapy adjusting the pharmacotherapy, adjusting the mechanical support may pay benefits. So it's not simply using the device but optimizing the therapy. So this is interesting and you kind of alluded to it that not all centers have all those mechanical support devices available. You might have one or two but you might not have four of them or even more. So that is an issue and a dilemma. So do you think that therefore there should be places what we call centers of excellence that can manage the most complex cardiogenic shock and that patients should have priority to be transferred to those institutions? I absolutely do. This is akin to trauma, to stroke, to any other very complicated patient group that requires not just you and I but the team we surround ourselves with. We have to have excellent heart failure doctors and surgeons and nurses and other people. So I do see the rise of that occurring and I think that we'll see truly advances in care. So what is a typical team that you assemble, that your institution to properly manage patients with cardiogenic shock? So in patients we really bring folks that represent the entire group. So we have not only interventionalists and the techs and nurses from the CAF lab but we want the heart failure individuals. We want imaging so we're going to be up front with Echo. We have nursing teams involved with our highest level of care of nurses. I bring pharmacists, respiratory therapists because of the need for rapid pharmacologic management, potential intubation and quite honestly in the most sick patients I'm looking at my palliative care team so that we can intervene early and help people have appropriate expectations. Very interesting and important thing to consider. So in the last four decades we have made tremendous strides in progress as far as cardiogenic shock is concerned where four decades ago mortality was 90% and we are now what close to around 50% or so? Yeah I think most centers through 2016 would tell us we're about 50%. So let's talk a little bit about improved outcomes and maybe you can discuss this a little bit. Where are we now? Well I think centers that have begun to develop processes like we talked about, we did the algorithm, they have put in place these other checkpoints and are active very early or beginning to show the benefits of that. And so here we can see from this slide the mortalities that we had, the survivorship and again they're in the 50% range. That's what we've seen because we just haven't been able to change that. But if you look at the denger and the NSCI initiative, the National Cardiac Stroke Initiative which has just been in place for a couple of years with Dr. O'Neill and others leading it, I think we are beginning to see if you understand the patient and you optimize the therapies, even combining therapies, all of that that we can get to 75 maybe even higher percent survival. So imagine if we flip that chart and instead of 10% survival we had 10% mortality, 90% survival and I think that's achievable. So I have no doubt that early recognition is number one priority and then proper triage and then referring the patient or sending the patient to the center of excellence to the institution that can handle the most complex scenarios. And it requires us as interventionalists to be able to take that step and say here's what's best for my patient, not necessarily how I'm most invested. So what are current recommendations as far as patient management is concerned, patients with cardiogenic shock? Well obviously we have the acute management and with all the other pharmacotherapies that would go along with acute myocardial ischemia, except for beta blockers. And so I find it, I've always found it challenging because we do have data from animals in limited studies that say that the introduction early beta blockers not just decrease arrhythmic deaths but also improve overall myocardial healing afterwards. And here's a slide that addresses that talking about the idea of we couldn't use beta blockers because patients were high-worthy hypotensive and we could make them out more. But if we could stabilize their blood pressure and then give them a heart rate specific agent, heart rate specific because that's a piece of the cardiac cycle that unloading doesn't affect, we don't decrease the work that way. So we should be able to get more benefit now that we have a stable patient that we could also add a beta block or two. Here's a very interesting animal trial in which they did just that. They used the equivalent of impella unloading and then looked at adding bradidine which is simply a heart rate lowering agent. Doesn't have any inotropic, it's purely chronotropic. And here what you can see is that there's a marked decrease in the total myocardial infarction that occurs with that combination of therapy. And I think that's an exciting opportunity for us as we go forward to think about a next step that we might pursue. Excellent. Well, Dr. Bailey, thank you very much for this very informative presentation on the cardiogenic shock 2020. Where do we stand now? And what is missing and what the future might hold? And it's a pleasure to see you again. You've been a friend for a very long period of time. I worked with you on many, many different projects. Back when we both had dark hair. Exactly. I wanted to congratulate you on all of your achievements leading Sky Society of Cardiac and Geography Intervention for a long period of time, doing an excellent job as a chief editor and scientist as well, researcher and now also in charge of a medical facility at LSU in Shreveport, Louisiana. Well, you're very kind. Thank you very much. Thank you. My pleasure to see you and be with you for this presentation. Well, thank you and I appreciate your audience as well.