In this presentation, Cardiologist Dr. Joyce Wald kicks off with an introduction to a larger cardiogenic series. She specifically talks about the shift toward personalized therapy and the larger trends emerging. Examples are perfusions vs. pressure and macro vs. micro-circulation.
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I'm the first talk of a series of talks that are discussing cardiogenic shock, um E C O and other devices. And I think we have a wonderful lineup. My talk is kind of going to be the big overview and then to follow. As you see, we have multiple wonderful discussions from Eddie Rame, Christian, Bermudez, Marisa Savas and Demitrius Yiannopoulos. And then after that, we will have some cases to present. So I want to thank everybody for coming. We also have Kevin Mitchell here who is one of our patients who is here and uh benefited from one of the devices. So let's go ahead and get started. OK. So when we look at the current era of cardiogenic shock, I think we're seeing now a couple of big shifts. One is is that it's going to be the era of personalized therapy in cardiogenic shock. It's about perfusion, not pressure, it's about mi macro microcirculation, not necessarily just macro circulation and what's new in cardiogenic shock. You can see here that about AAA large number of results when you Google it and the overall themes when you look at when you type that into your Google search are what's new in the lingo, what's new in drips in terms of medical therapy, do invasive human dynamics matter, new devices, um targeted temperature management and cardiogenic shock teams. So first the lingo, so most of you guys in the audience already know this, I put this up there. But we have multiple definitions that en encompass both the clinical criteria that a patient is hypotensive or persistently hypotensive or requiring medications, pressors to maintain pain, their blood pressure. And you can see the major criteria there. We also have invasive hemodynamic criteria of a card index less than 2.2 and an elevated wedge. And especially if you need IOP pressures to achieve those um hemodynamics. The different types of cardiogenic shock that we're seeing is expanding. We have obstructive cardiogenic shock. We talked about a little bit the last time, pe pulmonary hypertension, deno valvular lesions, we'll talk a little bit about V T storm, acute M I cardiogenic shock, which used to be the mainstay. And now the majority of cases are acute to compensated heart failure, cardiogenic shock. And we know that it becomes a vicious cycle of decreased cardiac perfusion leading to tissue hypoperfusion and end organ and cell death. And so how can we stop this cycle and or reverse it? So first, the lingo we you traditionally spoke about shock patients as in the inter max criteria. So the inter max profiles you see here with profile 56 and seven being those that are short of breath profile, four are like the pre inotrope, walking wounded. Folks. Three are those that are inotrope dependent but are stabilized. Two progressive decline on inotrope support and then one are the crash and burns. And then of course, Dave Baron and others came out with a sky classification for cardiogenic shock. So that when we are talking about our patients as a community that we are talking the same lingo about how we are um presenting them in which phase of shock that they are in. And you can see that here that stage A or those that are at risk, they might have coronary disease, but they're not yet showing any signs of hypotension or hypoperfusion B is the beginning where there's either their blood pressure is a little lower, you're having to pull back on some of their meds or that they're starting to be tacho car suggesting that their stroke volume is down. C is a classic cardiogenic shock where they're hypoperfused and they need end organ, they need inotropes and or IOS to achieve end organ perfusion. And then those that are deteriorating despite your best efforts, which are stage D and then e or those that are an extremist. And you can see here that we can look at them also in terms of biochemical markers in that middle column and as well as the hemodynamics that you see there. But the bottom line is, is to make sure that as we move forward in our clinical research, that we're categorizing our patients the same way so that we can understand if and what interventions we should be using. This is the proportion of patients um that you can see there on the left in the red and the associated hospital mortality. So of patients presenting in cardiogenic shock, 46% are stage A are classification A and they have a 3% mortality, 30% B 7% mortality, 15% C with a 12% mortality, 7% are d with a 40% mortality. And then you see those patients who are in extremists, which are what we are talking a lot about today. And those are the patients who have the highest mortality of over 50%. This is a little bit of a tickler tickler because Audrey speld is going to discuss this on session four when we talk about the micro circulation and this is big, big, big and coming up that we know that we can maintain a blood pressure, but with some of the agents that we use and Esther VVI is also going to talk about that in a later session. What meds are the best meds to use when somebody is hypoperfused, you can increase the macro circulation. But what's happening at the microcirculation because there can be a heterogeneity in terms of the auto regulation and the response to medical therapies. So more to come from Audrey on that. But when we look at a preamble to Esther's discussion on what medications we have out there to treat. Um cardiogenic shock. It's about pressure. When you look at the current guidelines and really not about perfusion or what's happening at the end organ function. And when you look at the A H A guidelines, no epinephrine is first and then dopamine and then an inotropic agent. And so we're really with this statement and guidelines, prioritizing pressure over end organ perfusion. And you can see here that in the gray, let me see that the classic pathophysiology of cardiogenic shock is a low cardiac output at a compensatory mechanism to vasoconstrict. So if we're saying that we're going to vasoconstrict, what's going to happen when you look up here at this table that the normal heart, if you raise the blood pressure or I'll argue it's not about pressure, it's about vascular resistance that your overall stroke volume is going down and then take into account somebody who has a poor ventricle and that even worsens the ability to fuse. We know that maybe late once you have tissue death cell death, that you start to get an inflammatory response and you may have a mixed low cardiac output and low S V R state. But our traditional early on are the low cardiac output, high S V R. And I'm arguing that you really should not be using vasopressors. This is just a graph looking at that are in the red our organs such as our heart and our brain can auto regulate flow against um perfusion against flow. Whereas in the blue, some of our other organs, kidney and liver have uh more limited auto regulatory capabilities. And so we see that when we physically exam somebody right, that somebody who is in cardiogenic shock, they're peripherally getting cold and modeled because they're shunting, trying to shunt blood to the brain and to other organs. So when you look at this um study which was a cochran uh systemic review, and you look at the current scientific guidelines as we showed that there really isn't sufficient evidence to say one pressor or one inotrope should really be is superior than others in terms of mortality in this group of patients. So really, it needs to be up to us, the physicians to personalize that therapy depending on what phase of shock they're in and what phase their tissue injury is in. So, through this review, these guidelines suggest that if you're hypotensive and you don't have a P A catheter in dwelling that your first drug in the calf lab will be no epinephrine. But if they continue to be hypotensive and not perfusing their end organs, then reach for dobutamine. Um for somebody who's hypoperfused versus considering something like Lebo sin that we have not used a lot of here in patients who have been given beta blockers as a calcium sensitizer to increase inotropy and you can see the doses there, there's a current trial that is about to start called the Levo heart shock trial that is looking at levosimendan in cardiogenic shock. So about P A catheters are P A catheters good or bad. And Doctor Rame is gonna be speaking coming up about the hemodynamics and what you're going to look at. But as a general overview, what gave us a bad name was the escape trial. So in the early two thousands, this study was close to 500 patients at 26 sites. They took patients who walked into the hospital with acute dec compensated heart failure but did not obviously need inotropic or pressure therapy. But it wouldn't be a crime to put a P A catheter in, but they didn't absolutely need a P A catheter. And so with those patients, what they found was that at six months, the patients who are alive and out of the hospital, there was no significant difference in the patients treated using a P A catheter versus not. And all that did was give P A catheters a bad name, but it was the wrong population of patients to um study. So when you look at the cardiogenic shock working group that you see here of um a consortium of multiple different centers and look at our P A catheters good or bad. And you can see here that the um outcomes are dose dependent on the amount of humans that you are working with. So in the um the blue are patients who are, who presented to their uh centers in cardiogenic shock, but there was no P A catheter capability in the red are those that you maybe they followed A CV P, maybe they followed A P A pressure but they had incomplete hemodynamics. And then in the black are the patients who had a full set of hemodynamics CV B P A pressure wedge, cardiac output index S V 02. And you can see that the overall mortality was improved in the Black Bar in those patients in whom we had a full cohort of human dynamics and especially in those who are sky. E so even the especially I should say the most sick, you should have P A catheter guided therapy more to come tomorrow when we talk about shock teams. And then here's another teaser for Doctor Marisa Savas and Chris Ramirez who are both gonna talk specifically about devices in cardiogenic shock. So I'm not gonna spend a lot of time on this because there's gonna be dedicated um lectures, but we have balloon pumps that can go femorally, axillary ECMO that we spent the morning talking about tandem heart impella devices, including femoral and axial cannulation and a lot about right sided support. And we know we have a lot of devices at our fingertips as an overview with our full support devices shown in blue, we know that ECMO increases afterload and we have our rights sided support shown there that folks are going to be talking about in detail. But when we look historically at some of our reviews and this is a great paper, it shows that the overall outcomes in cardiogenic shock, looking at balloon pump versus impella C P impella 25 and then the impella 50 that the outcomes really did not benefit. I think we're in a different era now. So this is we have better pumps now we have better pumps coming. So um we'll talk more about that in the ensuing lectures. But when we talk about what do we need, when we're looking at temporary mechanical support, we need to make sure we're perfusing the end organs, we want to achieve full flow. So full support, at least more than three liter of flow. The ease of placement should our ca um attendants be able to put it as opposed to having to call C T surgery? But what about our smaller stature patients in whom we can't pass these large bore catheters? And we want the patients to be ambulatory. We also want to make sure that we decrease complications, hemolysis, vascular access issues. And I said emulate them and should cost be a consideration when we are considering bridging a patient. Should we care about the cost of the device? This is just some data that shows hemolysis and you can see here that our smaller devices lead to more hemolysis on the bench. Whereas the 55 is our newest impella device that gives full support, that really has a low risk of um hemolysis. So you can see why here, although it's a larger motor 19 French versus 13 French, you can see that to achieve um six liters of flow, you're running running at 33,000 R P MS. Whereas with, with the C P on the bottom left at P eight, to achieve three liters of flow, you're going at 46,000 R P MS. So when we look at our outcomes with the newer uh percutaneous devices and this is a database uh registry that looked at number one. If you're using impel devices in a cardiogenic shock patient, they should have a P A catheter in you can improve their outcomes. And that if the more you use these devices, the better the outcomes because you learn which patient is suitable, you also learn um how to decrease your complication rate. And this is by Dave Ramsey. The 1st 200 patients um supported with cardiogenic shock with the impella 55, the new, the newest version and this was at 42 US centers. And what was found was that the predominant profile of the patients with cardiogenic shock were acute accumulated heart failure, cardiogenic shock. So we were shifting away from um acute M I to heart failure and that there was a 90% use of P A catheters and most were placed in the right axillary. And that the overall survival was 74% with the range of support being from um 1 to 64 days. Even. This is the FDA approved for 14 days when you look at advances in heart failure and the conceptual considerations for what other devices might be out there. These are a group of devices that are um being looked at and trialed in patients with acute to compensated heart failure. With the next group that it will be studied in will be cardiogenic shock as well as pulmonary hypertension. With the targets being, if you think about the physiology, what should we target? It should improve central hemodynamics, increase renal perfusion, remove salt and water and decongest, right. So the pneumatic for it is dripped. So the D stands for dilators, R for removers, I for inotropes, interstitial P for pushers and pullers and then s selective. And you can see the me mechanism shown here, the drug examples that we we have and then the devices that we are now trialing out in the community to achieve what some of these medications might have failed at in acute comps, heart failure. And then in the future in cardiogenic shock with spla denervation, it's a catheter based procedure where you can decrease the wedge, increase the cardiac index, isotonic fluid removal using Aquarius, the alpha pump reprieve cardiac plexus nerve stimulation instead of inotropes which increase the risk of um ventricular arrhythmias. And you see the different uh devices that you can see here with stimulation of nerves in the R P A or the bra of veins. And then lymphatic duct decompression as well as counterpulsation devices to increase uh renal arterial pressure and then reducing afterload with other counterpulsation pulsation devices and then some renal um intrarenal artery dilators with uh feno pam and papaverine. So, animal studies are underway and there's a 78% relative reduction of contrast induced neuropathy in patients with renal disease. So more to come on that we know that in the era of cardiogenic shock that there has been an increased utilization of temporary M CS. And a lot of the reason for that is we have better devices but also the changing listing crit changing in the cardiac listing criteria that came out in October of 2018. The bottom line is is that the patients who are status ones and twos who are the predominant patients who are getting transplanted, are those with temporary mechanical support. And further that if you transplant them as an inter max two, they far way better than if you're transplanting them as inter max one. Do you really want to get them before they slide in terms of temperature targeted management? There's one study, major study out there that now has changed the landscape that we know that um heading for our blood pressure of 33 Celsius no longer is necessary. And that we're aiming for 37.5 um degrees Celsius. There's gonna be a lot more on cardiogenic shock teams tomorrow. And so just a quick, I'll go into this in more detail tomorrow. But you can see that overall P A catheter use is higher in centers with a shop team in dark blue. The overall temporary M CS use is lower in centers with a shock team. But that when they are used that there is traditionally more advanced M CS and that the overall cardiac ic U mortality is benefited. They also got their P A catheter sooner, less inotrope use, less likely to require me mechanical ventilation and less likely to need renal replace. We're targeting the patient personalized medicine. So not throwing um everything or the kitchen sink at the patient. So in conclusion, we reviewed the lingo, um we know that the drips drips need to be tailored to what phase of cardiogenic shock the patient is in and that we will talk more uh with invasive human dynamics. We know that they are now beneficial. So we should be placing P A catheters in these patients and that we'll hear more about temporary devices and that shock teams improve outcome.
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