Hi, I'm Nancy Schweitzer from Washington University School of Medicine in St. Louis. I'm also the editor-in-chief of Circulation Heart Failure, and we're going to talk right now about advanced heart failure as a lead-in to upcoming talks about therapies for advanced heart failure, transplant, and mechanical circulatory support. I have no disclosures relevant to this discussion. We're really going to emphasize a few principles here. It's going to be important on the exam to recognize advanced heart failure and candidates for advanced therapy, to know the contraindications for advanced therapies, and to understand principles and roles of palliative care. From the 2022 guideline, we define advanced heart failure as marked heart failure symptoms interfering with daily life and having recurrent hospitalizations despite attempts to optimize therapies. There's also definition in the universal definition of heart failure document, which is severe symptoms and or signs of heart failure at rest, again, recurrent hospitalizations, refractory or intolerant to guideline-directed therapy, and requiring advanced therapies or palliative care. The ESC guideline document also has a definition, severe and persistent symptoms despite guidelines-directed therapy, severe cardiac dysfunction, including severe diastolic dysfunction, hospitalizations or unplanned visits, and severely impaired exercise capacity. So, like all the talks in the course, we're going to really refer to the guidelines. I'm going to just focus on one of the new recommendations for advanced heart failure at the beginning, and then at the end, we'll go through all of the recommendations for advanced heart failure. Discussion of advanced heart failure is relatively new in this guideline. It's certainly more built out than on prior guidelines. So, class of recommendation one, although level of evidence C, is to refer patients for heart failure specialty care when they exhibit advanced heart failure. So, again, you have to identify it, and then you need to refer it if you're not an advanced heart failure practitioner. This is challenging because of this well-described course of heart failure, which is this waxing and waning. Patients deteriorate, but then rapidly improve, often almost to the level of function they had previously, and then they may stabilize for some period of time. So, figuring out exactly when a patient is advanced can be incredibly challenging. It's really important to refer for advanced therapies before a patient has irreversible non-cardiac dysfunction, that's kidney or liver dysfunction, and irreversible pulmonary hypertension, because those are really contraindications to most advanced therapies. So, if you have any hint of those, you need to send the patient in. Irreversible frailty, too, can be a contraindication to advanced therapies. In many of these documents, advanced heart failure and stage D heart failure are used interchangeably, and that is true probably on the exam as well. We talked about prognostication being complex, and referral should be triggered by any suspicion that advanced heart failure is present. This is a flow diagram from the ESC guidelines, which I thought is useful. It starts really with an age less than 75, although as you all know in the U.S., sometimes we bend those age limits, but I want to draw your attention to the middle part of the screen where they talk about patients with New York Heart Association Class 2. So, they really are minimally symptomatic with their typical activities, but if they exhibit any of these characteristics, very low ejection fraction, intolerance to any of the guideline directed medications, unplanned visits to clinics or hospitals, low blood pressure, worsening organ function, arrhythmias, then that's a patient really that should be referred because they're starting to show signs of advanced heart failure, even though on a day-to-day basis they're well compensated. We don't want to lose that window when advanced therapies can be applied. Now, New York Heart Association Classes and even ACC or ACC stages and even New York Heart Association Classes are fairly crude markers when we get into the advanced heart failure stages. ACC stage C and D incorporates New York Heart Association 2 through 4, and so it's many years ago now, more than a decade ago, the Intermax profiles were developed, and the Intermax profiles really describe the advanced heart failure patient or the stage D patient with a lot more granularity, and they're shown in this slide where we have Intermax 1, which is a patient in critical cardiogenic shock, patients on inotropes in class Intermax 2 and 3, and then patients with recurrent advanced heart failure or even persistent exertional intolerance, what we call the ambulatory NYHA-4 patient, all the way to NYHA-3 patients in Intermax 6 and 7. So, it's going to be important for the exam to recognize these Intermax profiles and what's appropriate at each point. So, what's appropriate at each point? Well, Intermax 1 through 3, the patients on inotropes have very high mortality. These are three different experiences, either registry or trial experiences, in the patients on inotropes not receiving advanced therapies, and you can see that within 12 months, there's very, very high levels of death and a survival of less than 10 percent in all of these experiences. So, this is a patient in whom an advanced therapy is absolutely indicated if there are no other contraindications. But if we look at Intermax 4, 5, and 6, there's still excess mortality in these patients. Intermax 4, in particular, which is a patient with recurrent advanced heart failure therapy episodes, so someone who's having symptomatic hospitalizations more than once a year or more than once every two years even, that patient has a really high mortality over the next year of almost 60 percent, much worse than the current survival in the 80s and 90 percent that we see with VAD and transplants. So, these are definitely patients in Intermax 4 who should be considered, and these are where the vignettes you're going to see the patient with recurrent hospitalizations for heart failure despite attempts at maximal therapy should be referred for advanced therapies. There are also some other clues that things might not get better. Patients who have higher or rising biomarkers, late gadolinium enhancement to a large extent on MRI, EFs that are high but getting high at diagnosis as opposed to very low EFs, particularly the non-ischemic group, patients who've had heart failure for a long time, and patients who are ischemic generally tend to adverse remodel over time. And those are patients you might want to watch a little bit more closely. Why do you want to refer to a specialized heart center? Well, it increases access to advanced therapies such as VAD and transplant, but can also lead to more nuanced implementation of medical and device therapies, access to investigational drugs and devices, which may be the next great thing in heart failure, and may result in earlier contact with palliative care due to higher resources in these centers. It's important to recognize if you have a patient with an absolute contraindication to transplant. There aren't a lot of absolute contraindications anymore, but some of them to recognize are an active infection that's not treatable, a cancer of any organ with maybe the exception of prostate within the last five years, and some other serious organ dysfunction can be a contraindication, and it's worth a phone call to your transplant center to see if you have a question about a patient. There are a lot of relative contraindications these days to transplant. Almost nothing's an absolute contraindication anymore. We do dual organ transplants when there's severe multi-organ dysfunction, but this slide details some of the evaluation and considerations when you're dealing with a relative contraindication. And then similarly, VAD has contraindications, although they are fewer. Obviously, active infection is also a contraindication to VAD, so if you have an actively infected patient, that really needs a complete resolution prior to consideration for advanced therapies. The other issue with VAD in particular is right ventricular dysfunction. All our durable VADs are left ventricular support devices only, so looking at right ventricular function and recoverability of right ventricular function with aggressive management of the heart failure is really important. And then obviously things such as active substance abuse and very poor social network can be issues for VAD, consideration for VAD. If you look at patients who are candidates for VAD versus those who really need palliative care, we're talking about irreversible organ dysfunction, unmanageable psychiatric disease or social dysfunction, medical non-adherence, and failure to appear for appointments, and then other advanced disease that's going to limit life regardless of the heart failure. It's important to recognize that palliative care is not hospice care. Palliative care really focuses on maximizing patients' quality of life no matter what the disease state and can be really useful in patients, even if not at the end of life, who have a high symptom burden, who have behavioral or family issues that are interfering with their disease optimization, patients with limited prognostic awareness where you need some help with helping them understand how serious their disease is, and the patients with highly complex comorbidity management. Their data showing that palliative care experts can be very helpful for these patients in particular. And it's important to realize we now have literature demonstrating that palliative care principles benefit all patients with advanced heart failure. This identifies and respects patient goals of care and demonstrates congruity of therapeutic pathways with patient goals. It can improve quality and length of life regardless of the prognosis, but it doesn't make any of the hard decisions we have to make with these patients easy. It can just help with bringing more people into the communication and more empathy into the communication about the difficulty of these diseases. Patients who are not candidates for advanced therapies may well need palliation ultimately to ease death, but you should never give up the heart failure care in these patients. I think good heart failure medical therapy is part of any palliative plan. So let's turn to our guidelines. Now we already talked about the specialty referral for advanced heart failure. It's a class of recommendation one level of M and C guideline, but I think this is going to be tested. You want to recognize advanced heart failure and refer to specialty centers. A class 2b recommendation is fluid restriction is thought to be of uncertain benefit at this point. So that may well be tested as well. And then if we look at inotropic support, there's a lot of attention in the new guidelines to inotropic support. A 2a recommendation for IV inotropes as bridge therapy to other advanced therapies in patients awaiting mechanical circulatory support or transplant. Continuous inotropes in patients who are being palliated, and you clearly have advanced directives and DNR documents in place. Continuous or intermittent IV inotropes in patients for any other reason is a class 3 harmful recommendation, and that's important. They like to test class 3 recommendations. So you shouldn't be giving intermittent inotropes to a patient because it makes them feel better once a month. That's considered to be harmful or potentially harmful. When we talk about mechanical circulatory support, patients who have advanced heart failure and are dependent on inotropes, it's been well shown that durable LVAD implantation improves survival and symptoms in those patients quite markedly. That's a class of recommendation one. Patients with New York IV symptoms or advanced heart failure on GDMT not yet inotrope dependent can be considered for durable mechanical circulatory support because there's, again, clear symptomatic benefit to these devices almost universally in patients. The new guidelines have value statements. Mechanical circulatory support devices are low to intermediate economic value, but, you know, they save lives and improve quality of life. And then a 2A recommendation is temporary MCS in patients who are bridged to recovery or bridged to decision. We're all using them that way, so that's no surprise. Transplant is a class of recommendation one level of eminence. See patients with advanced heart failure have improved survival and improved quality of life with transplant, intermediate economic value for transplant. So, in summary, for your exam, I want you to recognize the vignettes of patients at Intermax 4 to 6. Intermax 1 through 3 definitely, but Intermax 4 to 6 are a little more challenging. These are the frequent flyers, the housebound, the walking wounded. These are appropriate for heart failure specialty referral for improvements in outcomes and consideration for advanced therapies, and they should be referred early. You want to recognize clear indications and contraindications for MCS and transplant. You want to refer patients before permanent contraindications develop, and you want to understand that inotropes have risks and limited usefulness in advanced heart failure for bridging your palliation. Definitely a possibility for testing. We'll stop there. Thank you very much. Well, thanks, Nancy, for an excellent introduction on the advanced heart failure phenotype, and there are a couple of questions from the audience that I thought I'd pitch to you before we move on to the next talk. The first one really speaks to eligibility criteria for transplant and how they've changed over time, and do you think in the modern era that there are absolute age cutoffs that we should employ for transplantation, particularly for the boards? And the other question was about BMI. Is there an absolute BMI cutoff we should think about? Yeah, great questions, Akshay, and welcome to everyone. It's great to see everybody's names listed here. So, you know, as outcomes have improved with transplant, we've all, I think, become a little less rigorous in our contraindications, and most things are relative rather than absolute contraindications, with a few exceptions. So, age, I think there's absolutely not an absolute age cutoff. It would probably be illegal as ageism to do that, and we are increasingly offering advanced therapies, particularly ventricular assist device therapies, to older patients who don't have a lot of other comorbidities. So, I think certainly there's opportunities to consider advanced therapies in patients who are, you know, of an age that would not have been considered several decades ago. And similarly, BMI, I think, you know, most programs use 35 as a cutoff. We do know that outcomes are worse in older patients, and outcomes are worse in more obese patients after transplant in particular, but also in VAD. So, you just have to evaluate the whole patient and take all of the contraindications and particularly the relative contraindications into consideration. One relative contraindication is different than five relative contraindications for a patient. So, I think, you know, if you're thinking about referring patients, I would you know, have a fairly low bar to refer a patient to a program as I talked about in the talk. Other things happen at the time of a referral for advanced therapies than just saying yes, no transplant. We often have experimental therapies at the transplant centers that we can offer advanced heart failure patients, research studies, and we tend to be quite aggressive with guideline-based therapy, perhaps just a little more comfortable with that aggressiveness at those centers. So, it can benefit patients even if they're not ultimately candidates for advanced therapies. Great. And on that same theme, you spoke about this in the talk a bit, but cancer, you know, many centers apply this five-year cutoff. Is it the same across malignancies or does it vary depending on the type of malignancy? Yeah. So, as we all know, cancer isn't cancer, right? Different cancers have different outcomes. Certainly, prostate cancer in particular has a quite indolent course and doesn't seem to become super aggressive with immunosuppression in some cases. So, a treated prostate cancer therapy patient who's less than five years out may be considered after a conversation, obviously, with the urologist and the oncologist and a determination of the actual prognosis, effectiveness of the therapy, etc. Similarly, things like skin cancers that have been resected, not myeloma, sorry, multiple melanoma, sorry, but squamous cell and basal cell cancers, obviously, that patient's at substantial risk for post-transplant cancer development, but it wouldn't necessarily be a contraindication with clean margins less than five years ago if the patient were otherwise really in need and a good candidate. And then the other, a lot of questions here about the eligibility criteria, but the other one that comes up commonly is substance use. So, smoking and other substances, I know marijuana is a particularly controversial one, but for the ones at least where we have evidence, what's the degree, is there a mandatory minimum degree of abstinence or duration of abstinence, or does that vary? What do we need to know to consider these folks? Right. So, I think for the boards, they're going to make questions pretty black and white, right? Somebody who was smoking last week is not a candidate, right? They're not going to give you somebody who quit five and a half months ago. Most of us use six months, but sometimes when somebody's really sick and quite young, you bend the rules. So, on the boards, it will be black and white. Programs have different thresholds and programs have different levels of absolutism. You know, some programs, six months hard and fast, no exceptions. Some programs will say, well, you know, the patient's 38 and they really did quit for four months and, you know, they're in intermax one. So, what do you do? You know, do you let them die? So, and I think the change in the allocation has affected this, right? Because now we want to take people right to transplant whenever possible, not stop at a VAD. We used to, you know, put mechanical circulatory support devices in those patients and let them get through their six months, but do that less often now. And so, I think the rules have become a little less hard and fast since the new allocation system came out. Um, do you do any routine frailty assessments or, I mean, we all know that profoundly frail patients don't do well, but is there any guidance about how to assess frailty in the transplant population or VAD population? I think not. You know, there are a number of different frailty assessment scores. None of them are actually simple to do and a lot of them are very subjective and kind of what I think about a patient's frailty. The best data actually suggests quantifying axillary skeletal muscle mass using your CT scans and looking at pectoral muscles or psoas muscles. Um, uh, but I don't think many programs are doing that routinely or making decisions. I think, um, I actually had some discussion of scoring systems in my talk in previous years and I took it out this year and now with the publication of JAMA this week showing that risk scoring systems have no bearing on outcomes use of them. Um, I'm kind of glad I took that out. I don't think you're going to get tested on risk scores, but they might throw a risk score in. So it's good to be familiar with them. Um, and, uh, because that can impact your decision-making, right? If the risk score shows you that this patient's extremely frail or, you know, a very high MELD score or some other score that tells you that the patient's extremely ill, that's going to affect their risk at the time of transplant. There's one last question here from the, uh, audience about, um, temporary or about use of inotropes. And, um, and I think you made the comment in the talk that, that these are associated with harm and shouldn't be utilized for long-term support. I think the questioner is asking the point, does this mean we shouldn't use them at all, um, uh, to support, uh, decongestion or hemodynamics or other things? And should we always be looking for an alternative? Um, I think that I guess my, maybe what's your perspective on, on how much is too much? Yeah. So I think we all use inotropes and you have to use inotropes when a patient's in shock. Um, often there's nothing else that will, um, you know, get you to the point where they're stable and you can talk about more durable therapies. I think the issue is being cautious about use of inotropes long-term outpatient in a patient, um, in whom you don't have a defined endpoint, either a bridge to transplant typically, um, or, uh, or for palliation, you know, where you acknowledge that you may be taking an increased mortality risk with this patient. Um, but, but we all use them, you know, a patient who has a cardiac index of one, um, who's well vasodilated, uh, and having end organ dysfunction needs inotropes. Even I say that. So. Then I just, and I'm loving all the questions from the audience. So please keep that up. Uh, one, uh, final one here, and then I think we can probably move on to Sean's talk, uh, is really about nutritional assessment. And, uh, I know we don't have a formalized, we generally, most of our multidisciplinary committees have a nutritionist on them, um, things we should be thinking about from a nutritional standpoint in our candidates. Yeah, I think this is a great question. And also it's important, I think, to remind people at the end of the day, we will have a more question answer time. Um, so I, I don't think that there are hard and fast rules for our, um, ancillary service evaluation, social work, uh, nutrition pharmacy. We all do those because you want to be aware if there's a problem and those, um, experts on the teams bring attention to, um, the fact that there's a problem, but I don't think there's any, you know, published guidelines that are going to be testable on the exam. Um, obviously if a patient's severely malnourished, their outcomes with transplant are going to be worse unquestionably. And so you want to be aware of that. You want to try and improve their nutrition, decreasing primarily their surgical risk and their short-term mortality risk, um, by improving nutrition and physical conditioning to the extent possible. But often, you know, these people are in the ICU and bedridden and unable to eat, and it's really hard to get their nutrition up. So looking at nutritional history, dietary patterns over long-term can just help you assess whether this is going to be, uh, you know, work long-term or not likely. Um, so I think really that's why we do those evaluations, not because there are hard stops in any of those evaluations, with the exception maybe of social work and uncovering real psychosocial disarray in a patient. All right. Well, I think that exhausts the questions we have for now. So, um, I'll hand it back to you to chair the rest of the meeting for today.

advanced heart failure

recognition

treatment

palliative care

mechanical circulatory support

heart transplantation