Thanks so much for that introduction. So I'm going to start off, and some of this is going to be a little bit duplicative of what you saw earlier, but maybe from a slightly different perspective. So I'm going to start off initially with a case, and I also zoomed back a little bit, and I'm going to talk a little bit about heart disease in general on sepsis, and not specifically cardiomyopathy as caused by sepsis, partially because we have so little data in that population. So I'm going to talk a little bit more about general approach to these patients. So this is a patient. I'm on service right now. I actually just rounded this morning. And so some of these are, like, right from the headlines kind of cases. So this is a patient with urosepsis and reduced ejection fraction heart failure. We have, as you can see here, a picture of the heart on the left side of the screen, and those of you who took the ultrasound course in the last couple days could tell us about the very poor systolic function in this patient. This patient has rapidly escalating vasopressors, vasopressin are up and going up. Despite that, the lactate's increasing, the patient's oxygen needs are increasing. The urine output is going down, and the patient now has nausea and abdominal pain with tenderness. So we'll talk some more about this, then we'll come back to this, and I have some other illustrative cases at the end that we'll work through. So again, thinking about this, so many of our patients now have preexisting cardiovascular disease, and there's a lot of great data from the cardiology literature and from the critical care literature about how common heart disease is in our ICUs, and I think we all have this personal experience of taking care of a lot of folks with a lot more heart disease. So I was kind of thinking about this, I was putting together this talk, I was trying to think about this in kind of two different ways. Patients without preexisting cardiovascular disease, or maybe we talk about the, I think pretty much everybody has something, so maybe not clinically relevant or significant preexisting cardiovascular disease, who get infection, and then they get a variety of cardiac pathologies, like Dr. Parker talked about earlier, and a lot of these, it's, you know, there's probably a little bit of overlap, presumably, to a lot of these, since we don't have clear mechanistic pathways that cause, for example, sepsis-induced myocardial dysfunction. So I thought about some other things on here that we commonly see in our ICUs that occur in patients with infections, such as Takotsubo, which was already discussed, pulmonary embolism, new structural heart disease, a common cause of infection that we see, and I'm sure a lot of other folks do, is endocarditis, which causes, of course, severe valvular disease in addition to other problems, myocarditis, and arrhythmia, extremely common in our septic patients. I also thought about this from patients who have preexisting cardiovascular disease, then get an infection, and then what happens to these folks? So long list of things on the left side, most of which, if you walk around the ICU that I work in right now, you'll find at least one of all of these, and then infections that happen, they're unrelated to their heart disease, so like the case I just showed you where a patient gets urosepsis, or infections that are a consequence or related to their underlying heart diseases and infection of implants. I brought in a patient with severe aortic insufficiency from endocarditis and pacemaker lead infection just in the last 12 hours of our ICU. Super common stuff, immunocompromised patients, and then post-op patients and the infections that they get, and many of us in critical care specialize in the care of post-op cardiac surgery patients, so this is a common problem. As has already been discussed, the prevalence estimates of cardiomyopathy, and this goes back specifically to septic cardiomyopathy, and I grabbed a screenshot, I don't normally do this, but I thought that picture was illustrative of the large number of studies, and it's already been discussed how the criteria for classifying septic cardiomyopathy vary by study, so there's a tremendous range. In this review, seven to 70% of patients in an ICU had some sort of septic-induced cardiomyopathy. Various factors, as mentioned, again, from this specific review, were male sex, younger age, higher lactate admission, and pre-existing heart failure, which makes me wonder if a lot of these patients actually had heart failure before they got septics. Maybe it's not a septic cardiomyopathy, but in fact, heart failure in the setting of sepsis. This again is one of the figures from Dr. Parker's seminal study, and I bring this up to illustrate the consequences of septic, and I'm going to try and separate these things out a little bit when I talk about them, but septic cardiomyopathy, in particular, there doesn't seem to be, or there's no consistent worse survival decrease in patients with septic cardiomyopathy, so in this initial trial, the occurrence of septic cardiomyopathy did not change the ultimate survival in these patients compared to patients who didn't have septic cardiomyopathy, and again, if I have anything wrong, I'll ask for a correction later. Septic cardiomyopathy, this is another more recent review, and in this, these are contemporary cohorts, and again, lots of challenges with putting these studies together because they frequently are so different, but in this more recent review, in-house mortality did not change in patients with septic cardiomyopathy. Now in the same review, the same meta-analysis, in patients after discharge, there was an increased mortality in the patients with septic cardiomyopathy. Again, I think really hard to tease out if that's a result of sepsis causing a heart problem or if these patients had underlying heart disease that was unrecognized previously. You can hypothesize a lot of ways that you could come up with this result. Takotsubo, interestingly, this is a paper from the Mayo Clinic, and Takotsubo, they show the prevalence of Takotsubo was increasing over time, however, Takotsubo in this trial, this study was also associated with lower mortality than sepsis without Takotsubo cardiomyopathy. So unclear how that affects sepsis outcomes. Shifting just a little bit, and again, shifting from the cardiomyopathy induced by sepsis to patients with heart failure and heart disease who get sepsis, we know that sepsis is a common cause of mortality in patients with heart failure. You can see here sudden cardiac death, just below that is sepsis. So in this large data set, sepsis was one of the more common causes of death in heart failure patients, suggesting that this is a population we need to pay special attention to and think carefully about the physiology and treatment when we approach them. This is data from the Critical Care Cardiology Trial Network, which is a large network of cardiac intensive care units. And you can see here, again, that so this is specifically cardiac ICUs, and occasionally in these ICUs there are MICU overflows in this data set, however, a large percent of these patients are classified as mixed shock, meaning they didn't just have cardiogenic shock, they had something else, typically infection, and that a small proportion of these patients, 70 percent, are purely distributive shock, implying that they may not have had an underlying cardiac disease. So about 30 percent of these patients in this data set in our modern CICUs with mixed shock. We look at the outcomes in this population, and we can see that the long-term outcomes of mixed shock in hospital mortality is higher, and it's higher than not statistically significantly, but it's higher in patients with mixed shock than it is for patients with AMI cardiogenic shock or cardiogenic shock without AMI. The CICU mortality is a little bit lower, but the ultimate mortality is higher. So we know that getting, if I can go as far as to suggest these patients had sepsis on top of their underlying cardiac disease, we know that combination is bad, and it's worse than having cardiac disease alone in this sample. This is data from Jake Jenser at the Mayo Clinic, and what he showed here that's interesting and valuable is that this is patients who had sepsis who were in the CICU, so presumably some amount of heart disease, but didn't present predominantly with shock from heart disease. The patients who presented primarily with a septic shock picture, their outcomes were similar to those who, in the very sick patients on the far right of the figure, the patients were, the cardiogenic shock, severe cardiogenic shock outcomes were about the same for the patients with severe sepsis when the sky shock classification was used to grade the severity of shock. You can see on the left-hand side of the figure, in patients with less severe shock as classified by the sky shock system, the sepsis patients, the patients with sepsis shock did better, or pure septic shock did better. So it tells us something about the difference between these patients. And again, RV function, if you have RV dysfunction and you get septic, your survival is worse. Not a huge surprise. I think all of us have had experience with these patients, and they do extremely poorly. Also, this has become, as the shock literature has evolved in the cardiac ICU, we've learned much more about these phenotypes of shock. And this is a recent paper from the Cardiogenic Shock Working Group. And I think it's also really relevant to these patients, especially as we think about how we're going to manage them, which we'll discuss in a minute, that the patients with this cardiometabolic phenotype, and the cardiometabolic phenotype is patients who have elevated lactate and other end organ dysfunction other than the renal dysfunction. Those patients have the highest mortality. So I think it's, and there's, what we've hypothesized is that if we can prevent patients from progressing to that cardiometabolic phenotype, or if we can reverse it, and we don't really have a lot of data for this, that those patients are going to do better. So guidance for vasoactive agents in these patients. And this is the SCCM guide. So you can see there's relatively little. I think this is great. It's an easy slide to present. Because it pretty much says, use dobutamine if you think it might help. So I'm going to tell you, which is, I love starting in a place with no data, because then I can just tell you what I think. So I didn't go through, there's a lot of small trials looking at vasopressors and inotropes and things in septic shock. And I think most of the folks in this audience are very familiar with that data. So I didn't review any of it. And I think we're, it's widely recognized that none of those agents have been definitively shown to give you any beneficial outcomes. So I just looked at some limited data that's available, looking at how we treat patients who have heart disease with sepsis. So this is one large, relatively recent trial. And they simply looked at the amount of volume given to heart patients who had sepsis and also had reduced ejection fraction. We can see that the lower the EF, the less flu is administered. I don't think that's terribly surprising. I think it just informs us that we're already thinking about this. And we're already thinking about, is it the right thing to do to give fluid to these patients? And I had, whoops, we'll go back here. So and actually, there's two more slides, I think, that are relevant to that, that hopefully are still in the slide deck. So optimal treatment for cardiogenic shock, again, I think that we need to tailor the therapy for the individual patient, optimize cardiac filling pressures, the PA catheters is useful again, we'll talk about that briefly, decongest the end organs and perfuse the end organs. Briefly, this is data from cardiogenic shock and PA catheters. And I put this out there, there's a number of these studies suggesting that PA catheters are useful in cardiogenic shock, given our current approaches to management. So I would encourage folks to consider PA catheter use. Some of the MCS devices we have, again, this is data from C3TN, showing that in some of these distributive and mixed shock patients who did get device treatments, the device treatments were beneficial. So worthwhile thinking about a device treatment in these very sick patients. And then tailoring therapies for what we have. So if a patient has reduced ejection fraction heart failure, which patients with cardiomyopathy induced biceps do, we want to think about optimizing our filling pressures, reducing our afterload, maintaining coronary perfusion, and maintaining adequate systemic blood pressure. Coronary disease, maintaining coronary perfusion, HFPF, avoiding volume depletion, and PHRV failure, avoiding volume overload, and avoiding pulmonary vasoconstrictors. I'm going to look at some of the agents we have, and then I'll show you a couple of cases on how we might put these together. Norepinephrine, it's a positive inotrope. It does increase afterload quite a bit, and it can increase arrhythmias because of the beta agonism. Vasopressin, it's a pure afterload agent. It's thought not to increase RV afterload, which is a useful characteristic. Phenylephrine, little use in many patients with heart failure, because it's a pure afterload increasing agent. Might be less arrhythmogenic, though, which can sometimes be useful. Dobutamine and milrinone, both positive inotropes. Dobutamine, thought to increase myocardial oxygen demand, perhaps more than milrinone. Milrinone worses hypotension, especially in renal dysfunction. The DO-RE-MI trial showed, as recently, there was no difference in these drugs in cardiomyopathy. Whether that's true in other settings in our ICUs, I think, is a little hard to know, and we have to think about these specific characteristics. So thinking about the underlying pathophysiology and how these drugs affect that physiology, we can come back to this case. So in this case, PA catheter placed. We measure an index of 1.6. We add dobutamine to achieve an index of 2.2. Our blood pressure gets better. We change our systolic blood pressure target to 90, because someone with a ventricle like this does not need a systolic of 120. And my practice is to look at the MAPs and systolics, because sometimes when the MAP is 65, the systolic is 140, especially in some of our older patients with vascular disease. And then signs of hypoperfusion resolved. Our next patient, severed C. diff in a PAH patient. I rounded on this patient this morning. Terribly difficult to manage. PA catheter and judicious fluid resuscitation, because volume loading a sick RV will make the worsened RV dysfunction, tricuspid regurgitation, and compress the LV further. Continue PAH therapies. Oftentimes these are decreased, because there's a worry they're contributing to hypotension, but they're really RV support. Dobutamine and nitric oxide were added for additional RV support. The systolic blood pressure was raised above the PA systolic blood pressure, which is a good reason to have the SWAN in place. We think that's necessary to have adequate coronary perfusion to this severely abnormal RV. And then primarily using vasopressin as a first line vasopressor, because we think that that causes less pulmonary vasoconstriction. Another example here, a patient with MSSA bacteremia. This is probably the patient I admitted overnight, my team admitted overnight. So you can see here on the bottom picture that that patient has severe wide open aortic insufficiency. In this case, norepinephrine was administered, rapidly titrated to try to maintain a MAP over 65. However, in some of these patients, because we're increasing the afterload so much, we actually worsen the aortic insufficiency, decrease the cardiac output, and further worsen the blood pressure. So what we might do instead is titrate the norepinephrine for systolic, as low as systolic as the patient can tolerate, while maintaining adequate perfusion. We can also add dobutamine to lower the LVEDP and improve the injection from the left ventricle. And then, of course, we need emergency aortic valve surgery, because these medicines aren't going to fix this valve problem. And one last one, a Takotsubo patient. These are great. These are super fun patients. Again, a PE catheter placed, the cardiac index was low, so we added dobutamine and cranked that up, because we wanted a higher cardiac output. What we found instead is the cardiac output dropped, and the blood pressure got worse. And that's because in these patients, dobutamine can induce a left ventricular outflow tract obstruction. Because the base of the ventricle is working, dobutamine forces that base to contract harder, and that base obstructs blood flow out of the ventricle when it pumps harder. So dobutamine was reduced, norepinephrine and vasopressin, drugs that don't increase inotropy, titrated carefully to achieve adequate perfusion, oftentimes still with a low index. And we have to work with that. This is a setting where mechanical support, again, may be very useful if this patient is septic, but their cardiac output is low, and we can't increase it adequately to resolve end-organ hypoperfusion. Mechanical support may be a useful and helpful thing to do. All right, that's the last one.

sepsis

heart disease

cardiac pathologies

septic cardiomyopathy

treatment