my hometown. Looks a little different than when I left it several years ago, but you are also getting to experience about the 10 days a year that the sun doesn't actually shine here, so there you go. So ironically, I never actually owned an umbrella when I lived here, but I'm going to find it very ironic if I have to purchase one while I am here. So we're going to talk a little bit about today, about heart failure in general. We're going to do a little bit of a review, basically. Let's bring back some of those things out of mothballs to kind of help us talk about cardiogenic shock and heart failure therapies and where they lie. All right, so I don't actually have any conflicts to disclose. So let's talk about the basic cardiac physiology first, or as I like to say it, let's revisit those late night study sessions back in the libraries. So let's talk about the nerdy stuff. First of all, most of us have seen a picture, obviously, of something like this, about this closed loop circulatory system of ours. When I'm talking to patients or to students, you know, I'm likening it to maybe like a water pump in your car or in your home. And with this, we're going to talk about multiple different factors that affect that system so that we can kind of pull together this picture of where the drugs are working and what's appropriate at the best time. So the three parameters of the cardiovascular system that we're really going to be looking at, the three things that affect this, are going to be A, gravity, and which if you were in the late-breaking conversation here about CPR, that gravity conversation is kind of an interesting one. We're going to talk about the kinetic energy, basically, and this is the energy of the fluid actually moving through the cardiovascular system, and then ultimately the perpendicular pressure, or what we would also call potential energy, of the fluids pushing back against the wall. So who do we have to blame for this? Well, let's talk about Mr. Bernoulli here. So back in the 1700s, most of us are aware of this gentleman and his actual laws that were put forth. He won many awards in the European Congresses at that point in time. He was a physician and a mathematician who defined the properties of gases and fluids that we use in medicine today, and mainly how these move from an area of higher concentration to an area of lower pressure at that point. So the clinical practice assumptions, though, that we make, including in this, is that A, the patient is supine, so we're going to negate gravity that we just talked about, and that the patient is at rest. Our primary measure of this, though, of the cardiovascular system we're going to talk about is cardiac output, which is our general goal to increase cardiac output. So, and as we know, that's the volume of blood that is pumped from the heart in liters per minute from the left ventricle into the aorta. So as we talk about cardiac output and its friend cardiac index, what we're looking at is the stroke volume, which is the amount of blood that is, again, pumped away from the heart times the heart rate, and that's giving us an idea of how much blood is moving through the system. This can be measured a couple of different ways. There's, first of all, there's the Fick's equation. So we're used to seeing those in echo reports and cath lab reports, and we're used to seeing those in echo reports and cath lab reports, and we can also calculate this at the bedside. The problem with the Fick equation is that a lot of times it takes assumptions of various aspects of the equation that may not be particular to your patient. The other alternative to that would be thermodilution, and that's using a Swann-Ganz catheter, and so at this point we can get specific numbers for the patient. We can look at the time that it's taking blood to travel. We can look to see what the actual oxygenation is down to the molecular level this way, but there's some drawbacks to Swann-Ganz catheter. They can also worsen patient outcomes in terms of acute issues with patient harm. A lot of hospitals now limit their nurses and what they're allowed to do with Swann-Ganz catheters. Who can wedge? Who can't wedge? Are they allowed to try the thermodilution techniques? And then like everything else right now, I don't know about y'all, but ours are all on backorder, so we don't actually even have them. So they're golden when you have them. The patients that you're going to see them in are most frequently probably the patients that we work with most commonly, those coming out of cardiovascular surgery. You're going to see them in patients maybe that have a mixed picture of shock when we're not really sure what is it, what kind of shock are we dealing with? Are we dealing with cardiogenic or sepsis? You'll see them in your patients maybe that have an impella or an IABP and in your ECMO patients as well. So our cardiac index obviously though being the number that we're talking about most frequently, and that's the cardiac output that is normalized by the body surface area. So the next steps in this, if we think back to our basic Ohm's law, these were the laws that talked about how electrons move in an electrical circuit, another closed loop circuit. We modify that now and we look at that that relates to blood flow resistance and pressure. The terms that we use now in that modified Ohm's law is MAP, CVP, cardiac output, and SVR. So why SVR is so important to us is because this is an area where we can try to determine what type of shock the patient may have. So if you come into my ICU, if you are a patient of mine, you most likely have a history of pulmonary disease plus minus some pulmonary hypertension or pulmonary hypertension. You probably have CKD, maybe stage 3. You've got some element of heart failure, whether it's ischemic or non-ischemic. Right now you may have the flu or a pneumonia following flu or COVID and you're in shock and nobody knows why. So you are now on the ventilator, you have all of your sedation hanging there, we're trying to figure out what pressors to use in you. Do we actually give you diuretics? Do we not? And at that point in time I'm sure there's some antibiotics also thrown in there. So when we look at SVR and now we can actually calculate this based off of some of the information that we have. If you're lucky enough to have the machinery at bedside, you may have tools that actually calculate this for you. However though, I think a good understanding of this equation and how it works is really going to be important to understanding what type of shock you're dealing with. So in your cardiogenic shock, obviously we're talking about a low cardiac output and a high SVR. And in your shock that's more likely seeing a sepsis or some kind of anaphylactic type reaction, you're going to see the opposite. Which all of that brings us back to this lovely picture. All right, most of us right now are sitting up there in quadrant one. We are nice, we are warm, we are dry, we have a good cardiac index, good cardiac output, and we are not fluid overloaded. Most of our patients though when they come into us, they are living in that quadrant two. This is where GDMT, in the outpatient world for heart failure patients, hopes to keep patients there. The use of our beta blockers, ACE inhibitors, aldosterone antagonists, and all of those drugs. This is where we would like to see them living, if not closer to quadrant one. When you come into my ICU, you've fallen down below that line and you're in quadrants three and four. So Frank Starling's Law is something that's oftentimes thrown around. I work in a teaching institution, we have two medical residencies under our roof, and so you hear these little terms kind of thrown in there, peppered during rounds. So my ears usually perk up when I start to hear this. The full discussion of Frank Starling Law and all of the various curves is like outside the parameters of this discussion here, but basically what we know about this is this has to do with how well the heart is stretching and contracting. Is that balloon working? Is it stretching where we get the optimal preload? And then contracting again, the good old-fashioned rubber band. So the pressure, as it's stretching and increasing, the myocytes are actually stretching out where you get the actin and myosin heads. Ooh, think back to that. The actin and myosin heads where they can grab on and give you a good contraction at that point. This is intrinsic though to these myocytes. So there's no neuronal, there is no hormonal, there is no chemical regulation of this, and ultimately when we are increasing preload, we're increasing that force of contraction, and we increase cardiac output. So what does this mean in the dilated cardiomyopathy patient? These patients already have a big, baggy heart. They don't have that nice pretty V picture that you imagine of a heart, what's drawn in our textbooks. There starts to get more global and out of shape. When that occurs, the myocytes are no longer able to stretch and contract the way we would like them to do, and so now those cells actually have to try to create that contraction. So they are not able to use the fluid dynamics of Frank's Tarling Law. So they end up using more oxygen and more energy to try to create this normal stroke volume. Well, this mismatch at this point is what we define as heart failure. This is the heart unable to meet the demands of the body. So acute on chronic heart failure, or when GDMT fails. So our patients are on average of what, four to five medications? Pick a class. You got your beta blockers, your ACEs, ARBs, ARNIs now with Entresto. Diuretics, combination of lube and thiazide or thiazide-like. You may have an occasional Diamox in your pulmonary patients where we induce the contraction alkalosis they often see. You have your aldosterone receptor antagonists, your SGLT2 inhibitors, and your nitrates and hydralazine. Not to be left out, you've got Dig, Corlanor, and the nearest group, the nearest, the newest addition, Viraciquad. Most of this though is inducing this polypharmacy that you see here, or what we as pharmacists call the polypharmacy goo pile, basically. So now what do you do with these patients when they come in? What do you do with these medications? How do you address all of them? And it's not the good old-fashioned med rec where you just put a line right through all the home meds. This is where the art actually comes into play in managing heart failure patients. So let's talk about the floor patient. These beta blockers and ACE-ARB or ARNI are very likely, we may have to actually reduce the doses when they come in. We are trying not to do that because the body has auto-regulated all of its endogenous catecholamines and hormones up here. And when we start removing the drugs that are trying to modify that, you can actually worsen an exacerbation. So again, this is a real art in this. In fact, one of the things my institution has asked me to do repeatedly is look at our heart failure admission power plans. And my answer is usually the same every time. Take the drugs out. Keep all your other stuff in there, your nursing orders, your ECHO, your EKGs, but take the drugs out. Because this is not cookie-cutter medicine. You have to look at your patient, understand what's going on. What were they on at home? What were they actually taking at home? What brought them into the hospital? What are you going to do with it from there? So our diuretics, one of the funniest things I found in that power plan was Lasix 40 milligrams POQ day for an acute exacerbation. I thought that was very nice. But what we really need to be doing is more two and the two and a half times what they were or should have been taking at home. So 40 POQ day should not be in our repertoire at that point. So and at that point we're going to start to try to diurese these patients. And if we need to, these patients that are more refractory potentially for to diuresis or have your lower blood pressure, your lower cardiac output, and your increased respiratory symptoms, we can at that point start to bring in our inotropes. Well I was asked to talk about new data in inotropes. There's no new data in inotropes y'all. If somebody can get levosimendan through the FDA though, I think we would all be very happy people. But again it's just this what combination do we use it in, how do we use it, and what are the guidelines actually kind of proposing now for us. So in our floor patients we would like those inotropes maybe to be on there. You're going to talk about your lower doses, your two and a half, your five mites right in there. And at that point all we're doing is just helping to ask that heart for about 72 hours. I know you're tired baby but work a little harder for me. I just need you to work a little harder and I'm going to help you out on that on the back side. So again lower dose, usually set rate, not titratable at that point. So let's talk about those endogenous catecholamines. We have all these GDMT therapies here and what we're actually battling are those endogenous catecholamines in the system. The brain does not understand why the heart is not functioning well, so it just keeps asking it through chemicals, work harder, work harder, work harder, work harder. And so what you're getting out of this is you're getting these catecholamines that affect the alpha-1 receptors and increase your SVR. You're getting stimulation of beta-1 and beta-2 that's going to do things like increase heart rate, increase contractility. Beta-2 in the periphery is going to give you a little bit of dilatation out in the skeletal muscles. Most of us think more beta-2 having to do with bronchodilation at that aspect. And then our inotropes though are going to be added on to that to kind of help with this decompensated look. And so dopamine is going to actually be working at beta-1 and beta-2. We're going to ask it work a little harder for us, please. We're going to activate those beta-1 and beta-2 receptors. We're also going to use a phosphodiesterase inhibitor, milrinone, right? That's going to increase contractility basically through the calcium mechanisms intracellularly. It will also increase or decrease, excuse me, your systemic vascular resistance. Lastly, you might use some epinephrine or dopamine in these patients. But again, we're going to caution you to be using lower doses. We're going to actually though work to increase your myocardial contraction, your vasodilation. These agents though can be used in combination or on their own. So just a quick show of hands, how many of you will actually use dobutamine and milrinone concurrently? Okay, how many of you kind of look and your head just cocked to the right slightly when I said that? Yeah, for pharmacists, we definitely cock our head to the right and look at that. I will tell you that. However though, if you think about how they actually work, they can work together because we have such completely different mechanisms. It actually can work in some of these patients and the guidelines actually say if you need to go there, you may need to do that. But we can't tell you the specific patient to do that and actually there's not a lot of data out there to help drive that decision either. So let's get into more of the ICU patient where we all work. So these patients now have progressed. Maybe they have worsened on the floor. Maybe they just bypassed the floor altogether. Or if you're like in my institution right now, you've spent 72 hours in the ER because we didn't have a bed for you and now you're at ICU admission too. So these are your patients that may have had an acute myocardial infarction. This could also be acute on chronic ischemia that's coming into play here. This is where our inotropes and vasopressors still now start coming up more top of the list. Before we say we're going to modify your GDMT a little bit, we're going to give you a bunch of diuretic and if we need to, we'll add the the inotropes to you. Well now at this point, we need to balance asking a tired heart to work a little harder and increasing blood pressure and increasing left ventricular filling pressures so that we actually get great function out of that and a better outcome. So think about all of these agents that we're about to talk about. They actually increase myocardial oxygen consumption and they can actually increase your ventricular dysrhythmias, which is something that gives us all momentary pause when that VTAT doesn't stop after the first string across the screen. So when we try to balance this critical hypotension and these reduced LV filling pressures, you're going to have to use these agents in combination. What we're going to do though is we're going to try to use it the lowest possible doses and there are studies out there looking at the fact that you may be able to do this better than going cranking up the dose all at one and then adding a second agent and if you think about it, our sepsis guidelines tell us the same thing as well. So now this is the same screen that we looked at a few minutes ago, but now we're talking about where the inotropes and vasopressors are actually coming into play here and you'll notice though that we're going to ask now, instead of dealing with the endogenous chemicals, we're going to be giving you the chemicals in an IV bag hanging on your pole. So again, with the goal of increasing your contractility. I expect all of you to be able to see this very clearly from the back of the room where everybody's at. Everybody's in the back? Yeah, can you see it? Great. What's line three say? We all have a badge buddy or something like this that has this. I find these particularly helpful. I actually have one posted in my med room for my new nurses so that they can kind of understand when they're titrating the drugs, what might they expect out of that titration. And as a pharmacist, my job is to work closely with that bedside nurse, with the cardiologist, with the cardiac intensivist, and help with trying to figure out where's the best place to titrate up, add new drugs, and then here's the question, what do you titrate off first? And again, my favorite answer to that that most pharmacists will give you is, it depends. So it's going to depend on your patient and their responses. So out of the guidelines, what they're talking about, so the newer heart failure guidelines are really starting to get more into acutely decompensated heart failure and cardiogenic shock where they hadn't in previous years. So it's still a little scarce though, I will say that. And so when you're talking about acute cardiogenic shock or acutely decompensated heart failure, one of the things that you need to look at at that point is, where is the patient at upon presentation? So they admit to you they've had a heart attack, their LV has taken a hit, or maybe they have previous LV dysfunction. But after we go in, we cath them, our friends in the emergency department have given them lots of fluids for us. We actually see that maybe their systolic blood pressure is still right around that 70 to 100 mark. And if they're stable at that, we can talk about adding dobutamine as one of our first line agents. Now in the ICU, we're going to use it at the higher end of the scope. We're going to use more of that 7.5 or 10 mics versus the floor who's using a two and a half or a five mic dose. However though, if that patient is still in shock to the point where we're struggling with what is the heart rate looking like, say they're hypothermic or we had a patient actually the other night that was found down, had been on the sidewalk for four hours with a very high alcohol limit as well. His core temperature was 24 degrees centigrade when he came into us. So we were dealing with some cardiogenic shock, secondary hypothermia. So we were dealing with low heart rates that we needed to get up quickly. And so for some of that, what we were using then obviously would be dopamine. So using it in combination with your dobutamine, again using them at lower doses in combination together with the different mechanisms will actually help give you, the outcome is more than the sum of the two together. If you are still running low at that point and we have this mixed shock picture maybe, levophed is going to be your next friend, right? And we're usually talking at 5 to 35 months at that point. But what about epinephrine? So how many of y'all will go instead of to levophed will go right to epinephrine? Is there any takers in there? I see a few hands. Okay. The problem with that can be worsening of lactic acidosis as we know that epinephrine can do. For pharmacists such as myself, the problem with that can also be blood sugar issues, which I'm already battling otherwise. So there are concerns about epinephrine being worse in that aspect. There is also some thought that epinephrine might be pro-thrombotic as well. So that may not be the best thing for our patients at this time. So levophed has edged out epinephrine in the, which do you add next? So what about vasopressin at that point? Well, definitely vasopressin being our antidiuretic hormone. This is released primarily by the pituitary gland, can be released by the LV and also by the adrenal glands in times of shock. We like vasopressin in cardiac patients a lot of times because even though it increases our MAP, which helps us with the filling pressures, it also doesn't clamp down on the coronary arteries. So we keep perfusion to a tired and overworked coronary artery system as well. So where does this leave us all? So what I'm going to say is that a basic understanding of the hemodynamics, so stop, think, do the math, teach your team. If you're the physicians, teach your team about this. What do these numbers mean? And in the absence of something like a Swann-Ganz catheter that just pops up beautiful numbers on a screen for us to work with, how do we titrate these medications otherwise? The acute decompensation on the floor, we're going to be adjusting the GDMT that they came in on. We will be diuresing, as we call it, diuresing the snot out of them, basically. And at that point, we'll talk about do we need to add inotropic therapy again for that very short duration of time so we don't worsen a chronic heart failure picture. And then the next question is on the floor, how to restart and reintroduce or introduce new GDMT therapy to those patients. And that's something that you can definitely always come to us pharmacists. We're happy to assist you with that too. For those that are requiring ICU admission, the etiology of the exacerbation is very helpful. Is it the CKD that they're having problems with? Did they miss dialysis? Did they have coronavirus? Did they have a heart attack? Is it a COPD exacerbation? If we can help figure out that, we can utilize some of these therapies, especially the inotropic therapy to help boost up our weakened heart at that point. But we can also deal with a sepsis if we need to on that side. So this is where your choice of drugs is going to come into play. Addition of norepinephrine if you cannot control it with an inotrope such as dobutamine or dopamine for those especially of the systolic falling less than 70. And then vasopressin maybe to increase your MAP as well. So when in doubt, what I'm asking you is to think back to the nerdy stuff. Teach your team the nerdy stuff because it actually does help. What subjective and objective information do you have? Is your patient warm or cold? What does your laboratory information tell you? Frank Starling's law, swan gans, catheters, all those lovely things are great. But this has to be discussed as a team and it takes the entire team to kind of make this work as well. All right, thank you very much.

heart failure

cardiogenic shock

cardiac physiology

therapies

GDMT

hemodynamic assessments