Hi, Nancy Schweitzer again from Washington University School of Medicine in St. Louis and circulation heart failure. We're going to turn now to cardiogenic shock. I have no disclosures relevant to this talk. We're gonna, this is a talk in which we're going to talk about definitions of shock, the physiology of shock and spend most of our time on evaluation and management. The guidelines have not dealt with shock prior to this iteration. And now we have some recommendations for shock and we'll go over these in detail during the talk but really, as you can see on the left, the guidelines focus on when to use inotropic support, temporary MCS, multidisciplinary team management, invasive hemodynamics, and then triage. And I've put a flow diagram on the right where I think the logical order of these inotropes are a level of evidence B, but class one recommendation. Invasive hemodynamics, a 2B recommendation. Although I think most of us in shock would say they should be used. Multidisciplinary teams are a 2A and a temporary MCS, a 2A recommendation. So what is cardiogenic shock? Well, shock is hypotension resulting in organ hypoperfusion and cardiogenic shock is a low cardiac output with inadequate or end organ perfusion or tissue hypoperfusion that's secondary to cardiac damage. So the shock state results from cardiac injury. The physiology of cardiogenic shock is a primary insult leading to reduction in myocardial contractility typically or reduced cardiac performance, low cardiac output, hypotension, systemic vasoconstriction and response, and then cardiac ischemia. And we'll talk more about that. If untreated, even in a patient who was initially physiologically normal, filling pressures will begin to rise because of the impaired stroke volume. It's important to recognize that in patients with chronic heart failure in particular who present in shock, the primary derangement may be cardiac output, but it may be excessive vasoconstriction, which results in low cardiac output in these highly afterload sensitive hearts. We'll talk more about that. Trial definitions of shock are sort of all over the place, but there's usually some requirement for hypotension and or tachycardia as well as a requirement for hypoperfusion. The severity and duration of hypoperfusion in particular and the oxygen depth that results determine severity of multi-organ system dysfunction and ultimate outcomes in shock. And so hypoperfusion is a really important and critical piece of the shock definition in cardiogenic shock in particular because we all know patients, particularly chronic heart failure patients on aggressive therapy who are persistently hypotensive, but not in shock. So you really need the evidence of hypoperfusion impacting organ function. There are multiple types of shock shown in this slide, and it's important to recognize that while they're typically isolated pictures of shock, there is a significant overlap. And you'll need to understand the physiology of the different types of shock, which are shown in this slide, but I think it's really most easy to think of it in our classic heart failure two by two diagram, wet, dry, warm, cold. So classic cardiogenic shock patients are cold and wet, low cardiac output, high SVR, high wedge pressure. They're cold and clammy at the bedside. They have mottled extremities and they're volume overloaded if not initially, eventually, typically. There is in the top right-hand corner euvolemic cardiogenic shock in which the filling pressures have not yet risen or for some reason, because they're also simultaneously hemorrhaging, they're not wet, but this is much less common. And then in the lower left-hand corner, vasodilatory cardiogenic shock or mixed shock, where in fact the SVR is not elevated and the patient is not as cold perhaps as they otherwise would be. But filling pressures are clearly elevated and cardiac index is low. Often we see this in patients with sepsis who are having myocardial depression as a result of a SERS-like syndrome. And then pure vasodilatory shock, not cardiogenic shock, those are warm and dry patients. So it's gonna be important to identify what kind of shock you're dealing with. How can you do that at the bedside quickly? Well, one of the most helpful signs, if you see it, it's not very sensitive, but it's very specific, is a low proportional pulse pressure. That is a systolic and diastolic blood pressure that are very close together. Blood pressure like 108 over 100. If you measure a blood pressure like that, or you see it on an arterial line tracing, what that tells you is the patient's very constricted to defend their pressure. Their diastolic pressure is elevated and the performance of the heart is leading to very little change in blood pressure, a very bad situation where the heart isn't contributing very much to blood pressure. When this ratio is less than 0.2, it's a very specific sign for cardiogenic shock and low cardiac output and index, and should be recognized and taken very seriously. Similarly, resting tachycardia, pulses alternans where every other peripheral pulse is stronger or weaker than the other, or you see it on an A-line monitor. Those signs are signs of a very advanced heart disease typically seen in very advanced cardiomyopathy patients. Obviously patients who are cool, who can't finish a sentence because their perfusion is so poor. These are just things at the bedside that can help you identify that you have a patient in trouble. The escape trial looked at a number of findings and how well they predicted low cardiac index of less than 2.3. And this proportional pulse pressure was a very potent predictor of low cardiac index, although while highly specific, not sensitive, seen in only 10% of the patients with low cardiac index. Low blood pressure can be helpful, but again, not particularly sensitive. Interestingly, cold profile, which was just the doctor saying my patient is cold, was highly predictive of low cardiac index. So if you feel at the bedside, like you have a patient who's cold, touch your patient, they're cold, that's a patient in whom you want to rapidly escalate therapies. We all know about acute MI and decompensated or advanced heart failure as causes of cardiogenic shock. But of course, anything that impairs cardiac function and performance can lead to cardiogenic shock. And it's important to run through your differential. We don't have a lot of randomized control clinical trial data in shock. There are three trials, all in acute MI shock. The shock trial showing that rapidly going to the cath lab and opening arteries in acute MI improved outcomes in shock. IABP shock showing that routine placement of intra-aortic balloon pumps did not improve outcomes in shock. And culprit shock demonstrating that culprit vessel intervention as opposed to complete revascularization was a superior strategy with fewer complications. I put the National Cardiogenic Shock Initiative on here. There are not yet reported randomized trials from this, but we're getting a lot of interesting registry data that's informing shock management. Sorry. Sky in the mid 2010s or 20-teens published a shock classification going from stage A at risk for shock to stage E extremis with the idea that this is a progressive condition that if you recognize it early and reverse it early, you will prevent progression to advanced stages where it is much, much harder to reverse a patient. And so you should understand the sky classifications. And this shows the sky classifications in a physiologic spiral where patients have, for example, here in acute myocardial infarction with cardiac dysfunction leading to low cardiac output, hypotension, and decreased coronary perfusion. Even in the absence of critical coronary stenosis, this can lead to cardiac ischemia and progressive cardiac dysfunction, as can the resulting pulmonary edema when the stroke volume is no longer moving forward, it's moving backward, leading to progressive hypoxia, which contributes to the ischemia and progressive dysfunction. And in addition, over on the left here, you have a SIRS pathway with inflammatory markers and vasodilatory or vasoplegic state that can result, again, contributing to progressive cardiac dysfunction and death. So it's important to understand these primary pathways and how they contribute to the shock spiral. So when a patient presents with shock, initially we want to stabilize and resuscitate that patient. And this is universally done through fluid resuscitation, oxygenation and ventilation, and vasoconstrictor support. But of course, fluid resuscitation and vasoconstrictors are not particularly helpful in the cardiogenic shock state, necessary for stabilization, but it's important then to turn your attention to how to reverse the shock state. These are the vasoactive medications used in a table for you to review. Norepinephrine is typically the most commonly used initial drug as there are controlled trial data showing superiority to both epinephrine and dopamine for norepinephrine in cardiogenic shock. And then dobutamine and milrinone are inodilators, and we're going to focus a lot on the inotropes. The pharmacology of these medications is largely an adrenergic spectrum of pharmacology with vasopressin and PDE inhibition as mechanisms for some of the drugs. And of course, you'll need to know this. After initial fluid resuscitation, often even simultaneous with it, we get the ultrasound machines to the patient to evaluate the level of LV systolic performance abnormality, RV systolic performance abnormality, find things like tamponade or volume issues that we didn't suspect, valvular pathology is often detected by echo, so an essential tool in early evaluation. And then when reversible causes are identified, those must be immediately treated, and we do that with PCI and type 1MI. We tap effusions if we detect them, and then there are certain lesions, typically valve lesions or mechanical complications of myocardial infarction that need operative evaluation, although temporary support devices have given us a little more time for this decision-making, which is often complicated in these very sick patients. So if we go back to our guidelines, we're using inotropes, invasive hemodynamics, multidisciplinary team decision, and mechanical circulatory support in these patients. Let's talk about the inotrope. The DO-RE-MI trial was published last year in the New England Journal and shows the results of a trial where patients were randomized to milrinone or dobutamine as the initial inotrope in a cardiogenic shock presentation and demonstrating no difference between milrinone or dobutamine as the primary therapeutic choice useful in these days of dobutamine shortage. It's important to recognize because vasoconstrictors are universally used nearly in initial treatment of cardiogenic shock that we're dealing with failing hearts, which are extremely afterload sensitive, shown in this slide. So as mean blood pressure as a surrogate for afterload rises, you see rapid fall off of stroke volume in patients with severe myocardial dysfunction. So these are patients who tolerate vasoconstrictors very, very poorly compared to normal hearts. And you can get a patient into trouble through over aggressive use of vasoconstrictors. Similarly shown in the red lines on this graph is the cardiac power output. If we look at the solid red line, the normal heart, cardiac power output continually goes up as blood pressure goes up until quite high levels. But if you look at the large dash line on the bottom, you see that in the failing heart, the optimal mean blood pressure is substantially lower than in patients with normal hearts, normal myocardium. So in a patient with a failing heart, you wanna target very low mean blood pressures to reduce the amount of vasoconstriction and afterload faced by that dysfunctional myocardium. That's a really important concept. So how do you figure out when medical therapy is not enough for these patients and you need to advance therapy? There's a number of scoring systems with variable performance, none of them super excellent, but the most useful things are serial testing. When a patient's going in the right direction versus the wrong direction, you wanna detect that quickly and start acting if things are going in the wrong direction and invasive hemodynamics, which can be really, really helpful in figuring that out quickly that things are going in the wrong direction and instituting appropriate therapies to reverse the shock state before it's too late. So let's talk about hemodynamic management and shock. This is really the bailiwick of the heart failure cardiologist and how we have transformed shock management because initial blood pressure stabilization is typically achieved with vasoconstrictor medications, but it's really important very rapidly after that to turn to improvement of cardiac performance and organ perfusion in these patients. And that typically requires reduction in vasoconstrictor medications. And this often needs to be done in a patient who's still marginally or even truly hypotensive. So often you need to place a PA line to figure out what's the SVR, what's the level of organ perfusion I'm achieving with my current therapy and can I optimize that further? The optimal map differs from patient to patient and it's important to refine your map targets, particularly in advanced patients, to lower targets if you can using markers of perfusion. If mixed venous saturation is not falling at lower maps, you can target lower maps. If lactate isn't rising at lower maps, you can target lower maps. And it's very important in these patients sometimes to do so. And targeting SVR and management of cardiogenic shock can be really helpful. You want an SVR in the 800 to 1000 range to optimize forward stroke volume and cardiac performance in these patients and start to improve organ perfusion. And often in patients who come up to the CVICU on many vasoconstrictors, the SVR is much, much higher than this and it's actually hurting the situation rather than helping. You also want to start reducing filling pressures to near normal. And this figure shows what's happening often. You have a volume overloaded high wall stress situation with high afterload in the systemic circulation and the blood isn't going forward as stroke volume, it's going backwards as mitral regurgitation. And I like to say these patients are arterially hypovolemic and venously hypervolemic. And when we give fluid and vasoconstrictors, we worsen that situation. We worsen the venous hypervolemia and we worsen the arterial hypovolemia by dropping stroke volume. So you really want to start targeting the heart, the problem at the level of the heart and how you can reverse that. And if you can't reverse it and it's not targetable, then you need to think about advanced therapies. The response to lowering SVR often helps determine the need for mechanical circulatory support. And with a PA line in place, you can do this really quickly with IV vasoactive medications. If a patient's vasoconstricted, you can try some vasodilator. And if cardiac output and index improve and forward flow improves and organ perfusion improves, you may not need advanced therapies in that patient. You might be able to transition them to guideline-directed therapy. But if they're well vasodilated and the output and index remain critically low, then you're going to need inotropes and MCS for palliation or of palliation in that patient. And knowing that early and making those decisions quickly can be life-saving for a patient. In the guidelines, the heart failure guidelines talk about invasive hemodynamic monitoring, not in the context of shock, but rather in the context of heart failure. But if you read these, they're really describing a shock state. You have a patient with impaired perfusion as a class one guideline, that's shock. And in class 2A guidelines, uncertain perfusion status, uncertain SVR, persistent low BP, worsening organ function, need for IV vasoactive medications. We're describing shock patients here. So indications for invasive hemodynamic monitoring and heart failure include patients in shock. It's important to do this quickly and early because as you apply vasoconstrictors and raise mean arterial pressure, you might look like things are going okay, but you may in fact be having persistent hypoperfusion with end organ injury, progressing to multi-organ dysfunction. And if you don't improve forward flow and perfusion in these patients, you start to develop systemic inflammatory response syndromes with vasoplegic or vasodilatory states, acidosis and irreversible organ dysfunction, and nothing can help. So there's a golden period here where mechanical circulatory support institution is beneficial and you need to act quickly and identify that quickly. Many people are finding the cardiac power output equation useful. It's mean arterial pressure times cardiac output divided by 451, pretty easy to remember, can be useful. These are data from the National Cardiogenic Shock Initiative that show when cardiac power output is above 0.6, which is the magic number for that equation, and lactate is less than four, patients have really good 12 to 24 hour survival, as opposed to patients who have a lactate of greater than four and a cardiac power output less than or equal to six, very poor survival in the initial 12 to 24 hours. So if you identify a patient here, you have to work to rapidly reverse the situation. If it's not reversing, you've got a very poor prognosis and it's important to share that with families. This is a really nice decision algorithm for cardiogenic shock that goes through once you've identified it, what should you do? And it includes all of the things in the guidelines. Here are your inotropes, here's your PA catheter, here's your heart team management, here's your assist device implantation. They talk, this is a really nice diagram because they talk about the different levels of support for the different assist devices from a balloon pump, which is pretty minimal support. Impella 5.0 and 5.5 provide quite robust support for our patients. If you're unable to provide those support, those levels of support, you need to think about transitioning a patient to a level one shock center where all of the different temporary circulatory support device options are available and the patient can receive the support they need for the best outcome. RV failure can cause shock as well. And this flow diagram just shows how to, you know, identify, medically treat, identify persistent right ventricular shock and deploy right ventricular support devices as needed. And it all holds there. We are getting better at this. This is historic reports of mortality from cardiogenic shock. And on the right in the green bar is the National Cardiogenic Shock Initiative showing with that algorithm that we just went through that mortality has dropped to 28% in this registry, vastly improved over prior historical data. And there are accumulating reports, again, non-randomized data showing that PA catheter placement shown in the dashed line here in cardiogenic shock patients does in fact in recent years improve outcomes. And I think it's partly because this is a tool and we're getting better at using the tool because the tool is very important when you're deploying circulatory support devices and we're pretty routinely using it there now. So consider PA catheters early to help optimize outcomes for patients. In your slide deck, I have a number of situations where you have a hypotensive patient in shock with various hemodynamics and you need to identify what type of shock you have. There's also an answer key present. And so I'll leave you with the new shock guidelines. Inotropes as a level of evidence one or class of recommendation one, invasive hemodynamics strongly recommended in shock patients, multidisciplinary team management and use of temporary mechanical circulatory support where needed. And I'll finish there. Thank you very much. Thank you. Well, thanks Nancy for a fantastic survey of shock. I think we have a few questions that'll be coming in from the audience, but as we do that, I thought a great place to start would be with your pre-test question. And I was looking at the polling results and many of the scenarios were straightforward for the audience, but not all. So the ones that tripped the most people up were the first scenario, which was a patient who had high felling pressures. And I can just tell you the numbers. The blood pressure was 84 over 48. The CVP was 22. The PA pressure 52 over 34. Wedge was 28, index was two and SVR was 1200. So maybe start with that case and then I can give you the other one. Sure. So this is an example of a patient, I would say these are the hemodynamics of a well-treated chronic heart failure patient who shows up in cardiogenic shock. This is clearly cardiogenic, low cardiac output, high felling pressures, but SVR is normal. It's not low like you'd see in distributive shock where there's a vasodilatory state. The patient has a normal SVR and that's often the case in well-treated heart failure patients. So this is a patient who needs inotropes because the primary problem is the low cardiac output. You can't afterload reduce that patient more. You'll probably make them more hypotensive. And so the correct answer is this is pure cardiogenic, not a mixed shock picture because of the SVR being normal. Great. And then the other case that was complex for folks was case six, which was again, a low blood pressure patient with a CVP of 24, a PA pressure of 52 over 34, a wedge of 10, the cardiac index of two and an SVR of 2000. Comments about that case? Yeah, so this is a tricky one, but this is RV failure, right? So the wedge is normal, but the right side is clearly failing. And the key is that the SVR is very, very high. So that tells you cardiac output is low. The patient is vasoconstricting in response to the low cardiac output, but the low cardiac output is because of failure of the right side, not the left side. The left side is actually, you know, probably a little underfilled because of failure to move blood forward to the left side from the right. But this patient's gonna be cold, modeled with elevated CVP, but not elevated wedge. Hard to treat, obviously, this patient, but probably most of us would start with some inotropes to support that failing right side, potentially move to right-sided mechanical circulatory support if the patient's otherwise salvageable. Perfect. Well, thanks for that. I think the other ones were relatively straightforward for the audience. More than 90% got the other ones correct, so we won't focus on those. As we're waiting for questions from the audience, I think people are slowly filtering in and getting geared up for the day. I had one that I posted to the chat. One was, which is really, you know, you gave us a nice array of options for management of pressors and shock. How do you start and how do you select pressors for shock? And are there any to avoid in cardiogenic shock? Yeah, you know, there are some data, and I think for purposes of the boards, you're really gonna be tested on the data. So there's one small randomized controlled trial comparing norepinephrine versus dopamine as initial choice. And the norepinephrine arm had improved outcomes in that trial. So between those two agents, you wanna choose norepinephrine. And then there's another larger trial actually comparing norepi to epi. And again, norepinephrine had better outcomes than patients randomized to norepinephrine. So I think for purposes of the boards, if you're choosing an initial vasoconstrictor in a shock patient, norepinephrine is the correct choice. Now, I think a lot of people clinically like to use epinephrine, right? Because you might get some inotropy with your vasoconstriction with epi. But you have to remember anytime you're using an inotropic drug that it's energetically unfavorable for the heart. The heart has to use more ATP, and you may worsen sort of lactate production and things like that that are markers of poor outcome in shock. So the data for those drugs suggests that they tend to be harmful. And so the randomized control data we have suggests norepi has fewer adverse outcomes than epi. And that would be the right choice for the boards. Although clinically, we've all seen all of these drugs used. And as I mentioned in the talk, the important thing really is once you've stabilized the patient attending to the problem at the level of the heart, because ultimately vasoconstrictors and fluids, which may be necessary for stabilization are going to not be viable long-term if the problem is truly cardiogenic. You need to get that patient on therapy that improves cardiac output. And those two agents typically don't do that. And is there, there are a couple of questions that have now come in. Any change in your answer for patients with dominant RV failure, for example, in the setting of mechanical circulatory support? Yeah, so RV failure, as we all know, is incredibly difficult clinically to manage. And there are no randomized controlled trial data. I think most of us do use inotropes. In every large study that's done, there's a group of what they call HEF-PEF patients, or heart failure with normal EF, who are put on inotropes. And everybody says, why would you do that? And the reason is the RV. Those are RV failure patients. And just trying to get that RV to pump forward to the LV often requires inotropes, particularly if the patient's massively volume overloaded. To get that volume off in a reasonable time period, you have to get it over to the kidneys. So I think most of us would use inotropes. Milrinone has better pulmonary vasodilation than dobutamine. And so if the patient has systemic blood pressure that will tolerate milrinone, it's probably a better choice in RV failure. Right now, there is no dobutamine. So we're all using milrinone in patients. We wouldn't use it in any way. But sometimes patients just don't tolerate milrinone because of the systemic hypotension. You might counter that with norepi or tridobutamine in an RV failure patient. But it's really empiric, and ultimately placing RV support devices to get a patient through who's otherwise got endpoints and isn't a palliative patient. That's great. Yeah, we've occasionally used inhaled lipoprostanol as another. Right, yeah. Pure pulmonary vasodilators, if you have them available, might help, especially if the LV is really normal, right? You've got to make sure the LV is really normal in those patients. One additional question that came in through the chat before we move on to another topic is about phenylephrine. Any role in, where would you consider it, particularly in patients with cardiogenic shock? Yeah, I mean, people use phenylephrine. There are no randomized controlled trial data to guide its use. And so I think, again, for the boards, norepi is the right answer. Phenylephrine is typically added to norepi when things are really bad. And we know that days and minutes and dose over time of vasoconstrictors is a strong predictor of failure to recover and organ damage. So if you're reaching for multiple vasoconstrictors in a true cardiogenic shock patient, you're probably contributing to peripheral hypoperfusion, and you really need to think about what you can do at the level of the heart to provide perfusion to the rest of the body. And often, if you're reaching for phenyl or multiple vasoconstrictors in a cardiogenic shock patient, pure cardiogenic shock, you probably need to talk to your heart team about mechanical circulatory support. Now, in mixed shock, it may be different. If they've got a diffuse vasoplegic or vasodilated state, you may need multiple vasoconstrictors just to get SVR up to normal and start restoring organ perfusion and do things like correct acidosis, which may be damaging cardiac function. These are really complicated shock patients, and I don't think this is gonna be tested. You're gonna have pretty straightforward shock scenarios on the board. And then two quick questions, well, they're not that quick, but in order to get a few more in, one is really briefly your thoughts on when to use hemodynamic monitoring in shock, and then the second question was about steroids. Yeah, so I think increasingly in the, particularly in the heart failure world, we believe that hemodynamic monitoring is very helpful in intelligent use of vasoactive medications in the shock patient so that you're not harming the patient in terms of impairing peripheral perfusion. And you can really, if you understand the medications and how to use the hemodynamic monitoring, you can tailor the IV vasoactive medications to try and optimize the hemodynamics, and you can do it relatively quickly if you've got a PA line in place and all your IV vasoactive medications to be used. You wanna try and get that patient to the closest as possible to normal hemodynamics. So if the patient's extremely vasoconstricted or extremely vasodilated, use your medications to get that SVR into the normal range. And inotropes, once your SVR is normal, to get cardiac output up if it's not responded to optimization of vascular tone. So I think that's really, you know, intelligent use of a PA catheter, as I tried to show at the end of the talk, can really improve outcomes in these patients, I believe. And when you don't know what's going on or the patient's going downhill, get that PA catheter in, it would be my advice. And then I think the last one was really any role for steroids. I know mostly in the, but I guess specifically here, we're talking about cardiogenic shock or- Right, not in cardiogenic shock. There's no data to show that steroids will improve outcomes. Of course, if you have a mixed shock patient in whom there's an inflammatory syndrome that might respond to steroids, otherwise, you know, I would talk to your critical care colleagues or if you're critical care trained, great. And use steroids as appropriate for that shock state, but not for cardiogenic shock, no.

cardiogenic shock

evaluation

invasive hemodynamics

inotropic support

organ perfusion

temporary mechanical circulatory support

management