Despite recent advancements in medical therapy, heart failure continues to be associated with increased mortality and morbidity. Numerous novel technologies have been developed to help improve cardiovascular outcomes and reduce the risk of heart failure hospitalizations. In this seminar, we'll be reviewing the current state of the optimal GDMT or guideline directed medical therapies in managing patients with heart failure. We'll be also discussing some current devices that are being utilized or that are in the development process that have been proven to be clinically beneficial for our heart failure patients. We'll be highlighting the role of temporary and durable mechanical support devices while walking through a heart failure patient journey. We'll be dividing our talk today and seminar into two sessions and we'll start with session one. In our first session, we'll be discussing the indication and up titration of heart failure guideline directed medical therapy, the current ICD recommendations, the role for APP and PharmD ran clinics in helping optimize patients on GDMT. We'll also be discussing novel devices in managing patients with heart failure in addition to well known devices such as CardiMEMS. We're gonna talk about HeartLogic and Cordella as well as BareFlex activation system in addition to vagus nerve stimulation, subclanic nerve modulation and the cardiac contractility modulation optimizer device. All in all while using our patient today and his journey in his disease progression. So Mr. HF, he's a 68 year old male with history of ischemic cardiomyopathy who had an MI two months ago and he had a PCI for his LAD. He's referred to the heart failure clinic for management and evaluation. On presentation, the patient had an echocardiogram after his MI and his EF was 25%. He was on metoprosuccinate, valsartan and spironolactone. He shared with us that he was having shortness of breath with moderate exertion. And he said he was taking his medication, watching his diet and he wants to feel better and live longer as well. So here I wanna go to Sarah. Sarah, we see this patient typically in our clinic and these patients come to us on part of GDMT. So what is the best next step in managing our mutual patient? Thanks, I mean, that's a great question. You know, when you think about all of the different medications a patient can be on, if you follow the guidelines for heart failure GDMT, when I look at his particular medications, really trying to get him on the four pillars as much as we can is always crucial. And I think what's important is that trying to switch him over from valsartan to sacubitrile valsartan and also adding SGLT2s. Now, you know, it's important when you look at these studies when everything is taken in combination for the contemporary GDMT, such as ARNIs, beta blockers, MRAs, and SGLT2 inhibitors. When you compare that to traditional beta blockers and things such as ACE inhibitors or ARB regimen, it really has been shown to reduce the risk of heart failure hospitalization, cardiovascular deaths, and really all-cause mortality. When you look at the contemporary GDMT, it does estimate to prolong survival, ranging from almost six and a half years additionally for 55-year-old up to then 1.4 additional years for an 80-year-old. While this can be quite challenging, you know, when you think about all four of these classifications of drugs, sometimes these patients cannot tolerate them for quite a variety of reasons, such as really not being feasible, they have hypotension, lack of clinical stability. Some also have worsening renal function despite what our efforts, and really even a lack of medication affordability does have to weigh in on what medications we use on certain patients. That's exactly right. I mean, you know, putting patients on four different medications can be challenging, and we get a lot of questions by providers what to start first and what medication they should be starting. And usually I refer to one of nice articles that's been recently published too by Dr. Boskert, where, you know, each patient has his own or their own clinical, basically, condition that we should be addressing. For example, if somebody has history of recent myocardial infarction, they're tachycardic or have ischemia, basically we start beta-BLAFTA first. Patients who are congested, you know, we recommend starting Agil-LT2 inhibitors and MRAs because of their role in clinical decongestion. And that's an addition definitely to the diuretics. And if patients are in ANOID-SHEA class four, there's, you know, we recommend using ACE inhibitor rather than ARNI because of the current guidelines tell us to do that because ARNIs were not approved for ANOID-SHEA class four patients. Other specific phenotypes include patients with chronic kidney disease and GFR greater than 20-25. And here where the Agil-LT2 inhibitors and ARNIs are considered for early initiation because of their superior and the benefits that the patients can get to help hold the progression of their chronic kidney disease. And in this patient population with CKD, ARNIs and Agil-LT2 inhibitors have better safety profile than when compared to MRAs, for example. On the other hand, I mean, also if patient is diabetic and they're type two diabetic, not type one, Agil-LT2 inhibitors are class one indication independent of the ejection fractions. As we mentioned about some scenarios to start the medicine, there are some scenarios that we should potentially avoid medication, such as if patients are significantly bradycardic, you know, I would avoid beta blockers. If patients are hypotensive or have marginal blood pressures, I would avoid ARNIs. And my practice in this situation is that I test the patient with low dose ARB, and if they tolerated the medicine, I will switch them to an ARNI, but I would want to give them tests if they can tolerate the low dose of ARB and they don't become hypotensive. But overall, the order of initiation does not matter as long as the quadruple therapy is initiated in a timely manner. And usually we recommend that to be in four to six weeks. And speaking of the medications, adverse effect and hypertension, I want to reach and ask you, Kristen, and so what we should be looking out for when we start these medications? I mean, these are great medicines, but definitely each medicine has its potentially adverse effect. Thank you, Amin. So to start, let's talk, we'll start with our ARNIs. So first of all, we still need our 36 hour washout period with our ACE inhibitors. So it's important to tell our patients that if they are on an ACE inhibitor to make sure when they go home not to take it due to the risk of angioedema. And if the patient has had a history of angioedema, we should avoid ARNIs and start them on an ARB. Our second side effect that we are most cautious of is the risk of hypotension. So when we're initiating ARNI de novo in our patients, we should be starting them at the lowest, the low dose. And if patients do have, for our advanced heart failure patients, if they do have low blood pressure, then we can start them on a low dose ARB or ACE and then titrate up to a dose they can tolerate, just kind of to echo what Amin said. So usually when our patients' blood pressures, if they are experiencing hypotension, I try to space out the beta blocker and the ARNI just to give them a little more wiggle room and better tolerability. So I usually dose the ARNI in the morning and at night, and then the beta blocker in the afternoon. Yeah, I agree. And sometimes I use a patient's blood pressure on the lower side. I tend to, for example, use metoclosuccinate versus then carvigilol. Again, it's just where different people practice differently. So, but I always tell my patient, as you mentioned, Kristen, I stagger the medicines because that can help improve their tolerance to the medications. But, you know, what about individuals that we are considering that we want to start MRAs for these patients? I mean, we talked about ARNIs, what about MRAs? Can you share with us what kind of things we need to be concerned about? So for spironolactone and aplerinone, the most common things we need to monitor are the renal function and watch for hyperkalemia. So I still follow the RAILS trial criteria, initiating with a potassium of less than five, a serum creatinine of less than 2.5 for male and less than two for females. If their renal function is borderline, we can start them at a lower dose of 12 and a half milligrams daily compared to the full 25 milligram dose. So the guidelines do recommend on maintaining a potassium of less than 5.5. If the potassium does become elevated, we can hold the spironolactone and resume it at a lower dose to try to make sure we're really getting this pillar on the patient. Now, potassium, use of potassium binders such as lokemla and beltesla remain controversial topic and also can contribute to polypharmacy and increased costs associated with our heart failure patients. And last but not least, we have our SGLT2 inhibitors. So these medications are contraindicated in type one diabetics just because they weren't studied in the initial trials due to the higher risk of diabetic ketoacidosis. And also, as you already discussed, I mean, watching for their GFRs. So the GFR cutoff for dapagliflozin is less than 30 and for emphagliflozin, it's less than 20. And when we are initiating them, it's important to remember that they can have a dip in their GFR and that we shouldn't discontinue our SGLT2 if they do have a dip. And most importantly, we need to make sure we educate our patients on the indication of the SGLT2 inhibitor, making sure that they know it's for their heart failure in the event they are not a diabetic, making sure that they're well-educated so that if somebody does try to stop it, they can say, no, this is for my heart, not for my diabetes. You bring up a very important point, Kristen, because it happened to me on multiple instances where I started patient on SGLT2 inhibitors and they were stopped by their primary care physician or even their endocrinologist who they see for thyroid issues among others. And they were told, you're not diabetic, you shouldn't be taking these medications. So there's a lot of education that we need to do on our end as cardiologists and heart failure cardiologists to spread the knowledge that SGLT2 inhibitors now for heart failure patients are class one for reduced and class 2A for preserved ejection fraction. So a lot of good things happening in the heart failure arena and what about patients who remain symptomatic? Sarah, on the four pillars of GDMT, do they have any other options for medical management? Yeah, we've all had those patients where we've gotten to the highest doses of the four pillars that we can get, or at least on a portion of the pillars for GDMT, but we also are still having troubles. And so there may be a role for other therapeutic agents such as Virisiguat, which is an oral soluble guanylyl cyclase and stimulator. This ends up binding directly to soluble guanylyl cyclase causing stimulation, ultimately increasing CGMP production. And when it really comes down to it, the benefits from Virisiguat would be things like vasodilation, increased endothelial function and decreasing fibrosis and remodeling. So sometimes we have to think outside the box, even though we have really good pillars. Some patients just can't tolerate all four pillars and you have to think about other options that are available. Yeah, and according to the recent guidelines, this is class 2B recommendation as you alluded to currently. So the other question is that after patients are on optimal GDMT and they're taking their medications, when do we refer them for an ICD? Per the current guidelines, as you can see here, straight from the HFSA AHA guidelines for heart failure published last year, we see that patients with dilated cardiomyopathy or ischemic cardiomyopathy at least 40 days post-MI with NYHA class 2 to 3, an injection fraction less than or equal to 35, or they have EF less than 30% with NYHA class 1, have survival and with anticipated survival more than a year, these patients would benefit from an ICD as a primary prevention. And again, you can refer back to the guideline for CRTD and among others, but what about the current GDMT? I mean, now we're living in an era where we have patients on medications that can improve their survival, their quality of life, keep them out of the hospital and can reduce risk of sudden cardiac death. And the GDMT these days is totally different than the GDMT 20 or 30 years ago. Now we have the four pillars of medications. We have, as mentioned, medicines that can reduce risk of sudden cardiac death, such as the ARNIs and SGLT2 inhibitors and can help with the reverse remodeling. In addition to these two medications, we have the beta blocker. So we have published recently an article about whether we need to start reconsidering or looking into whether we need to define or when to refer patients for an ICD and how long we need to wait for these patients before we deem them that their ejection fraction has not improved or not responded to medical therapy and they need an ICD. So something to think about, and it's for the medical community to discuss in the future as well too, but we need to ensure our patients are on optimal dosages of medications before we commit them to an ICD, making sure their ejection fraction is still less than 35% as well. And there's a question sometimes for the benefits of medications. If patients cannot tolerate the highest dose of ARNI and MRAs, basically, even the modest dosages of these medications is beneficial. That's in contrast to beta blockers or ACE inhibitors. So my advice and recommendation before repeating the imaging study to assess the ejection fraction for these patients, make sure that the patients are on the maximal tolerated medical therapy and prior to referring them for ICD implantation. So, you know, we talked about medical therapy and optimal medical therapy and ensuring that these patients are on GDMT. There is always a challenge, Sarah and Kristen, that we face in the medical domain, our clinics are always full and seeing patients in short-term intervals can be challenging for the providers because there's availability of spots to be seen. Can you share with us some other measures that you guys as a PharmD or APP have taken the lead on to try to optimize the patient's medical management? Sure, I mean, thank you. So we have the CHAMP-HF registry that really shows us we're not doing a great job at optimizing our patients on their GDMT. They found that only 15% of patients on ACE, ARB, and ARMI are on target doses and only 33% of patients are on MRAs altogether. So one way we can combat this is by using advanced practitioner and pharmacist-driven outpatient clinics. So I have a little bit of experience in pharmacy GDMT clinics. I did my training at the Department of Veterans Affairs. So we have a pharmacist-driven clinic where we can initiate, optimize dosing, order labs, monitor, and follow up with the patients. So these advanced practitioner and pharmacist-led clinics can alleviate physician workload, improve initiation of GDMT, and increase patients at their target doses. The Journal of Cardiac Failure recently published a nice systematic review and meta-analysis of pharmacist and nursing-led optimization clinics in heart failure. And the study showed that pharmacist and nursing-led GDMT interventions were significantly improved RAS and beta-blocker initiation and titration to target doses. There were lower pooled rates of mortality in heart failure hospitalizations that were observed, although these effects were small and not statistically significant. Thank you so much. And then as medication experts, pharmacists can also contribute to outpatient clinics, as we said, and help patients be on medications. So Sarah, what about advanced practice providers led heart failure GDMT clinics? Can you share with us what is the current practices in some institutions? You bet. So outpatient management of medication titration really kind of varies between clinics. Some are ran by advanced practice providers, some are ran by PharmDs, and some are ran as a multidisciplinary approach. Rosner and colleagues described the benefits of utilizing advanced practice providers in the outpatient setting to be able to successfully titrate up medications for heart failure. And there is evidence from their study that this team-based approach really improves access to care. And sometimes that's really where our patients suffer the most. They also have the option of doing outpatient IV diuretic clinics that they have demonstrated when these are utilized, it does prevent readmissions for heart failure. Now in the IMPROVE-HF trial, which as a recap is a registry designed to improve outpatient implementation for evidence-based practice in heart failure management, this study demonstrated that those clinics that had more than two advanced practice providers had higher rates of heart failure education and actually higher rates of ICD implantations due to increased referrals. However, I think it is important just to note that similar HF-GDMT was practiced from a management standpoint, regardless of the number of APPs that they had in the clinic. So when you really look at the extension of healthcare, heart failure management is very beneficial to have in a multidisciplinary setting so that you can continue up titrating what you can when the patients come into clinic. That's so true. I mean, you know, always medication accessibility and being seen for the medicines has been a challenge for our patients because as we mentioned before, we ideally would like our patients to be on the quad therapy within four to six weeks. So these types of clinics can definitely help with that and you guys are doing a great job. So we talked about the medications also. I wanna touch and go back to Kristen. I mean, patients, you know, getting the medicine could be expensive and having, you know, medication accessibility is a barrier for patients to be on optimal dosages of medications. And can you please, Kristen, provide us with some tips and tricks basically for patients, how to afford the medicines, where can they find cheaper medications? What are some resources that could be beneficial for other APP or providers that see patients in heart failure clinic as well? Absolutely. One thing I encourage is for our providers to engage the pharmacist, our social worker, our case management team, or our nurse navigator to assist with medication costs and improving accessibility. Prior to, we recommend in my facility prior, 24 hours prior to discharge to send the prescriptions to determine if what the copay is and if we need to submit a prior authorization so then we can get that done and they can walk out the door with their heart failure medications. So there are manufacturer coupons available that you can get online or through your drug reps. So anytime I see my drug reps, I ask them, you need to bring me coupons anytime they come to visit. So there's two types of coupons. There's a manufacturer coupon for a free 30-day trial that anybody, regardless, if you have insurance or no insurance, you can use it, but it's only good for one lifetime. And then there's a co-pay coupon. So the co-pay coupon is for patients with commercial insurance and it can be renewed annually. The drug manufacturers for Secubitrol, Valsartan, Dapagliflozin, Empagliflozin also have patient assistance programs. Those are a little lengthier, but if you do go to the drug manufacturer website, patients can apply, provide proof of their income or proof of what they're paying out of pocket for the drugs and determine if they can qualify for that. Other sources are sometimes health systems have financial assistance programs. For example, in Miami-Dade County, we do have one, as long as you're a resident of Miami-Dade County and you provide your income, that's how it's made available to them. Also making sure if your patients are part of the VA to make sure you really use those VA benefits, especially for these expensive medications because the co-pays are much lower on them. And lastly, they can go to GoodRx and shop around at different pharmacies. Well, thank you, Kristen. That's super helpful. Going back to you, Sarah. So what happened to our patient? So that's a great question because as we see in lots of patients, we see them in the outpatient clinic and perhaps sometimes they may end up getting admitted. So four months later, Mr. HF does unfortunately get readmitted for a heart failure exacerbation, despite being on good four pillar GDMT. The symptoms that he experienced were worsening shortness of breath with exertion, orthopnea, he had two plus pitting edema in his lower extremities. And on presentation, his blood pressures were marginal, 102 over 74, heart rate was 112. Oxygen saturation was kind of on the lower end at 90%. He did describe his weight being up 14 pounds in two weeks. However, interestingly enough, his creatinine and his electrolytes were normal. We did go ahead and give him furosemide 80 milligrams IVBID for a couple of days. And thankfully his weight did actually drop eight pounds. You know, these are always the times that you want to reinforce different things that you perhaps may have reinforced in clinic. And this would include reinforcing medication compliance, reinforcing sodium and fluid restrictions, and reiterating that daily weights are very beneficial in heart failure because sometimes those are the key things that occur before patients actually feel like they're getting into trouble. So we took the opportunity of doing an echocardiogram while he was in the hospital because he was due for one. And his ejection fraction we did find was still low at 15 to 20%. And unfortunately his LVIDD was very dilated at 6.75 centimeters. So we successfully diuresed him. We were able to bring him back into the clinic. And so, you know, I mean, describe to us what you perhaps would do now that you see him in discharge post follow-up. What kind of things do you have as options for him now moving forward, knowing that we still have him on GDMT and his EF is still down? Yeah, thanks, Sarah. Definitely our patient, you know, this is his second hospitalization for heart failure technically. You know, we know that pressure, pulmonary pressure monitoring has been shown to reduce basically and detect, you know, increase in intravascular volume even before patients have symptoms and before they develop orthopnea or PND or shortness of breath. And even before having also a lower extent edema. So CardioMEMS has been developed and has been shown to be very beneficial and helpful in reduction and heart failure hospitalization in our heart failure population. So the champion trial showed that around 28% reduction in heart failure hospitalization after six months of the device implantation, which is pretty significant. I mean, most of our healthcare systems now looking for and reducing rate of heart failure hospitalizations, because also, you know, when we try to reduce that, it's not just from financial, you know, penalties that the healthcare system can get, but also from our physician standpoint, we all know that heart failure hospitalization is a sentinel event. So it's important to try to prevent the hospitalization for these patients and try to keep them out of the hospital by ensuring that they are optimized medically and clinically. And a recent data actually that came up out of from Europe in the Monitor HF trial, they found that patients who were managed by CardioMEMS had significant improvement in their quality of life. And they had 44 reduction in heart failure hospitalizations. The recent ACCHA guidelines supported consideration of an implantable pulmonary artery sensor in selected patients with heart failure. They mentioned NYHA class three and history of heart failure hospitalization in the past year, or elevated natriuretic peptides levels on maximally tolerated stable doses of GDMT to reduce the risk of heart failure hospitalization. And the level of evidence it was given was class two B. Again, CardioMEMS has shown and continues to show to be beneficial, at least for us as physicians in managing patients that keep them out of the hospital by having an extra set of eyes, seeing them while even they're not in the hospital. In addition to CardioMEMS, there are other devices that are being in the work. Currently there's a Cordella device, which is an implantable, also pulmonary pressure sensor monitor. It is implanted in the right pulmonary artery. It's currently being investigated in the proactive trial. And the primary outcome, they're looking at mortality and heart failure hospitalization in addition to safety. The other modality, it's not a pulmonary pressure sensor monitor. It is HeartLogic, which is part of Boston Scientific Device, which basically aggregates measurements from sensors and include heart sounds, thoracic impedances, respirations, and heart rates basically, and reflects the changes over time in the patient's sensor trend data from their respective baseline. So if we start seeing that the HeartLogic index is going up, it's most likely suggestive that the patients are retaining more volume and they're becoming more symptomatic from their heart failure. Again, it's usually helpful in providing additional data to be used in the context of the clinical and the regular standard of care for managing these patients. Again, it's, if you're gonna follow what the guidelines would recommend, to go back to that, for the CardioMEMS, it is, as we mentioned, class 2B evidence for patients with NYHA class 3, with heart failure hospitalization, or elevated nitriuretic peptide levels on maximal dose of GDMT. But the guidelines do not recommend for routine care use of non-invasive telemonitoring or remote monitoring of physiologic parameters, such as those used in HeartLogic, basically. And here, I just wanna ask you, Sarah, do you guys use CardioMEMS? And if so, how do you utilize it in your center to care for patients with heart failure? We do use CardioMEMS, actually, and it's been a growing thing that we've been all using, I think, across the US, definitely with new guidelines that have been coming out. So in my center, we place them as a routine part of heart failure management, obviously given the new guidelines and the recommendations. We have used this as part of our heart failure treatment, and these patients are managed mostly in the outpatient setting by the advanced practice providers within our heart failure clinic. In the hospital, though, I also wanna point out that we do have the capabilities to be able to review the CardioMEM readings to help us guide diuresis and really help further manage which direction they're going. While we talk about durable MCS later on, we have had also some clinical scenarios where CardioMEMS have shown benefits in inpatient management. And I think while CardioMEMS is becoming more of a widespread use and gaining excitement about it, I'm wondering if there's other devices, I mean, that are currently available to continue improving patient outcomes, such as a CardioMEMS. Yeah, thank you, Sarah. I mean, there are other devices that work on targeting the autonomic nervous system, which is kind of pretty cool. As we all know, the autonomic nervous system is responsible for affecting the heart rate and systemic vascular resistance, arterial blood pressure, and the cardiac afterload, basically. So when there's hyperactivity of the sympathetic nervous system, it leads to undesired outcomes. So it's definitely is going to have to be a fine balance between the sympathetic and the parasympathetic nervous system. And this is, I think, what led to the development of devices such as the VeriSTEM, which is, as you can see here, it's a device where used to modulate the autonomic nervous system. It stimulates the carotids, their receptors by electrical impulses from an implanted generator, as you can see the generator here, and the pectoral region leading to centrally mediated decrease in the sympathetic nervous system and an increase in the parasympathetic nervous system. So it's kind of like a very novel therapy and has shown actually to be beneficial. There was a clinical trial called the BEAT-HF trial, which is a multicenter randomized trial of 408 patients with heart failure with ejection fraction less than 35%, elevated antiprobian P, but yet less than 1600. And there were NYHA class three with no indication for CRT. And this trial have shown actually that the VeriSTEM have decreased the antiprobian P levels in the patients who received the device. Also, it showed that there was significant improvement in quality of life, exercise capacity, and fun proof functional status. And as I mentioned, decrease in antiprobian P, there was also a trend to decrease in heart failure hospitalization. And, but today there is no data available to fully assess mortality and heart failure hospitalization. So we can't comment on it as of yet. In 2019, it was approved for NYHA class three or class two with previous NYHA class three patients, ejection fraction less than 35% with no indication for CRT. And on the bottom right of the screen, as you can see here, what the VeriSTEM does, it decreases sympathetic tone, increase the parasympathetic and decreases the heart failure symptoms. So another device, other devices that have shown to be of promise for autonomic nervous stimulation is the vagus nerve stimulation and modulation, basically autonomic nerve modulation. With a vagus nerve stimulation, basically we all know that the vagus nerve increases parasympathetic tone. So when we stimulate that, it increased the parasympathetic activity. And what happened is there's after stimulation of the right cervical vagus nerve. And this was approved and studied actually in the NECTAR HF trial, where they randomized patients to NYHA who are EF less than 35%, NYHA class three and narrow QRS. And this study showed that there is an improvement in the quality of life, NYHA class and exercise capacity. But one thing about this study showed that there is a high implantation failure of up to 7.4%. Another modality, which is gaining a lot of press recently is the splenic nerve modulation. We all know that the splenic nerves innervate the upper abdominal viscera, which are highly connected with vascular volume management. So what happened is when patients have redistribution of blood from extra thoracic to central, basically that can lead to increased filling pressures. So we have to be very careful of that, especially in heart failure patients, when this redistribution happen of blood into the central circulation, it can lead to increased preload and that can lead to congestion as well. So the blockade of the splenic nerves decreases the splenic tone and a sympathetic tone, I'm sorry, and hence prevents the rapid blood shifts. The splenic HF1 and HF2 trials, which were single center perspective open label uncontrolled trials, they noted that there's a drop in pulmonary capillary wedge pressure and improvement with cardiac index during exercise. So there's more to come on the role of the splenic nerve modulation, but it's definitely, as we can see here, there are a lot of activity in the device arena. There are other options as well. Serum exists and some, they look at diaphragmatic stimulation, reprieve system, splenic nerve stimulation, cardiopulmonary nerve stimulation, trance catheter, renal venous congestion, the derriere catheter, which both tackle congestion in renal veins among many others. So this is pretty, a lot of options and more to come for our patients when it comes to autonomic nerve modulation. I'm actually quite impressed with how vast the device world has moved in the heart failure realm. And I remember 20 years ago, not very many of these things were even looked at for options. And so it amazes me how far this field has advanced. And I feel like we still have ways to go. Are there any other approved agents that work on different systems that have shown to improve outcomes in these heart failure patients? Yes, actually, Sarah. And we know in addition to the autonomic nervous system modulation, there are devices that target the contractility, the cardiac contractility, and they've been approved. We're gonna talk about the Optimizer device, which is, they found that patients with heart failure and reduced ejection fraction, there's an abnormal intracellular calcium handling, which can affect the mechanical and electrophysiological function of the myocyte. And this led to the CCM, which is the cardiac contractility modulation therapy, as known as the Optimizer, which delivers, as you can see here, the biphasic signal, which is around 20 millisecond. It has high voltage electrical signal to the right ventricle septum during the absolute refractory period. So it does not result in myocardial contraction. Why? Because it is in that refractory period and the muscle cannot contract. When this happens, when the signal is delivered, it leads to structural and functional changes in the myocardium, which basically include molecular changes, enhanced contractility, and decreased LV volume. And all these changes are driven by the increase in intracellular calcium. So Optimizer was approved in 2019 after the FIX-HF5C trial, and the patients studied were patients with ejection fraction between 25% to 45% EF, NYCHA Class III, and not candidates for CRT. So as we can see here, different options are available for our patients with the device therapies. And for patients, as we're going to see later, who are not potentially candidates for VAD or transplant or still want to try other options, now it's a great time to be heart failure patients because we have a lot of therapies that we can provide for them that can improve their outcomes, be it hospitalization or quality of life. And hopefully we can see more data on mortality. So I think at this time, after this overview, we're going to move on to our first discussion and question section. To start us off, please feel free to send your question in the chat box, and we're happy to answer all your questions. Hope everybody enjoyed the first part of our session today. Definitely we touched upon multiple important factors in managing patients with heart failure. We talked about the role of GDMT, role of devices, as we talked about with Sarah and Kristen, and you guys are definitely facing your clinical practice, the importance of optimizing these patients comes on the other hand of multiple other challenges, is getting these patients seen or even getting the medications. So I want to ask Sarah, before going to our audience questions, can you share with us some other challenges that we did not touch upon in our presentation? Yeah, so I think the, when I think about the clinical management of these patients, we do know that one, they're not cookie cutter, so everybody has to have their own way of managing the heart failure from a GDMT standpoint, because some don't handle certain medications and some do. I think, just like Kristen had mentioned, one of the big challenges we have for our patients is that not all the medications are either covered, you have to go through prior authorizations. I don't know how many times I've heard multiple providers across the multidimensional approach of management of having to complete a prior authorization on the medication that is approved for certain things for GDMT. And so I think that is a huge problem that we have across the nation. I'm not sure what the solution is, and I certainly would challenge everybody up here that's on the, attending today to be able to talk about what their pitfalls and their success stories are with that. And I also think another problem that we have, just at least within kind of the closest within my center, I'm sure that I'm not the only one that could say this, is that we've had problems with that ongoing follow-through, making the patients understand how important it is to follow up and to keep their appointments, take their medications like they're supposed to, because that really is what truly helps these patients improve their heart function, and sometimes be able to improve it enough where they maybe don't need a certain device. So from my perspective, those are kind of the key things that we generally consider and have to think about every single time we take care of one of these patients. Yeah, definitely. And also one of the questions that came up in the chat box is that the insurance, as you mentioned also too, I mean, they ask about the cardiomyems and whether we had some challenges. Definitely we had with some insurers, basically, and we had some successes. I can speak from my own experience, and I will ask you, Sarah, if you have anything else to add, is that I have done multiple peer-to-peer, and some even insurers say, oh, it's still not approved, and though it's part of the guidelines, and it says this is what's written in front of me, I can't change it. So we had some challenges with that, but for the most part, now most insurers are approving cardiomyems because they're seeing the value of this therapy for our patients, so they're seeing that the patients are not hospitalized for their heart failure, they're being monitored closely. And I think it's another, as I mentioned before, a set of eyes that follows these patients, even if they're not seen in clinic, these patients are cared for, and some of our patients, they can be obese, they can have other comorbidities such as COPD. It's definitely hard to assess their volume status by exam, or even just by knowing their symptoms. They say they're short of breath, and that could be from multiple reasons. And so this is where cardiomyems came in and that helped us figure it out. So insurance companies are seeing the value of it and approving it more. That's great. So one of the questions that came out from the chat box is how commonly do you see patients actually on full quad GDMT? I think at least personally early on, our goal is always to try a little bit of everything in the hospital, recognizing that it seems like at least 20, 30, 40% sometimes will be pulled off of some things because in some certain patient populations, and I'm sure we can all talk about which ones those are, there's some populations that just cannot handle all four of them. So from your perspective, I mean, how often are you seeing GDMT? Let's just say all four pillars within the first three months. I know that's the goal. Yeah. So one of the main things, as you mentioned, and Kristen can attest to that, is that starting the medications in the hospital is crucial. Multiple studies and data have shown that patients, when they have their medications started in-house, their chances of being on the medicine in the future is significantly higher. Their compliance has increased as well. So while in the hospital, we tend to put these patients after their heart failure hospitalization on the four pillars of GDMT. And definitely we consult with our case managers to make sure that these patients will be able to afford these medications in outpatient settings. And Kristen did a great job talking about some tricks how to get these medications approved for. But I can say I've had a great success personally getting all my patients on the quad therapies. And patients have really reported the improvement in their outcomes, their quality of life. And I think you see that too, Sarah. We're seeing more and more patients with improvement in their injection fractions. So that's one of the biggest benefits, as we mentioned before, improvement in EF, a reduce of sudden cardiac death. So I have most of my patients, to answer your question on GDMT, either they started in the hospital or we see them closely after discharge or when we see them in clinic. Kristen? Yeah, Kristen, from your perspective, what do you think? So when I'm managing them with my heart failure team, our goal is to get all four of them on before discharge, of course, at low doses and to follow up in the clinic. Now, when I'm managing heart failure, kind of with the general cardiology, I'm still encountering barriers of, you know, we can defer some of these meds to outpatient. Farsiga is one where I'm still having to push for that to get started inpatient versus outpatient. So at mine, it just depends on my, what team is managing them. So with our heart failure, it's a hundred percent, we're really getting our four pillars on and we're still working on it kind of with our, when we have our hospitalist managing heart failure and also our general cardiologists. Yeah, we'll get another question about REDS, which is the non-invasive lung water measurement. We don't use it in our practice. I'm not sure if you use it, Sarah, too. We haven't used it yet. So I can't speak to that. The main devices we use currently are the, for measurement and monitoring patients, our CardiMEMS. We also utilize heart logic to add as an additional modality to help us when managing these patients. We're part of the PROACTIVE trial, as I mentioned, and we use also to reduce, to improve quality of life and potentially reduce risk of hospitalizations and reduce an antiproBNP, we use Baristem as well. Yeah. So we have not used, to my knowledge, the lung water measurement device within our system. We too also are doing CardiMEMS. And then with those individuals that don't have a CardiMEMS in, or we're having struggles with trying to get things covered with insurance, then a lot of times if they've already had a device put in, as far as an ICD or CRTD, then we will try to use the CoreView or some of the OptiVol levels within their system. Although it's not completely accurate, it still gives you, from a clinical standpoint, some heads up of they're starting to retain fluid that maybe they're not having symptoms yet. So that is another option that we've used in our center as well. Well, thank you. Thank you, Sarah. Thanks, Kristen. We're going to go to the second session now. For those who are just joining us, welcome to the second session of today's seminar. And for those who attended the first session, welcome back. In our first session, we shared the story of Mr. HF, who was a 68-year-old male, referred to our clinic for heart failure management and evaluation two months after he presented with STEMI. We discussed optimizing GDMT, device therapies, including ICDs, CardiMEMS, Barostim, and cardiac contractility modulations. In this session, we will continue following our patient and his disease progression. We will be discussing the sky shock classifications, the different temporary and durable mechanical support devices, the associated adverse events, including thrombosis and bleeding. In addition, we will discuss outpatient management of patients on durable mechanical circuitry support based on the latest recommendations. Kristen, Mr. HF, who had been faring well after his ICD and subsequent CardiMEMS implant, fast forward two years, what happened to him? Here we are two years later, our patient presented with worsening shortness of breath, poor overall feeling, nausea, and worsening lower extremity edema. His blood pressure is 88 over 68, heart rate of 118, elevated respiratory rate, and oxygen saturation at 88%. On exam, he had an S3 gallop, diminished breath sounds with cool extremities and tense two plus lower, pitting lower edema. His initial blood work includes an elevated serum creatinine of 2.2 when his baseline was one, an elevated serum lactate of 3.2, elevated NT-proBNP, and his stat echo revealed severely reduced LV dysfunction with an estimated ejection fraction of 10% and a dilated right ventricle that is mildly reduced. So, Amin, the patient appears clearly in a state of cardiogenic shock. With these symptoms, what is his SCI classification? Yeah, Kristen, clearly the patient's in big trouble. But before we discuss the SCI shock classifications, I want to highlight some criteria, which is important that we use in our practice to identify patients when they progress to the end-stage heart failure. The mnemonic is I need help, as you can see in this slide. I is a meaning for inotropes, be it dobutamine or milrinone, and for neurocardioassociation class four. E if they're having worsening endorgenous functions, such as worsening renal function, hyponatremia, liver congestion. E is when their ejection fraction is less than 20%. D when they have a defibrillator and where the ICD starts shocking them. And the H in I need help is referred to their current heart failure hospitalizations. E is escalating diuretics when patients stop responding to their usual diuretic. Then we have to double the dosages or switch them to other medications within the diuretic. So, for example, if they're on furosemide, go to bumetanide or torsemide, and then we have to escalate the dosages because they develop the cardiorenal syndrome. L if they have low blood pressure and become hypotensive, and then we start taking off some medications. Take their ARB, their beta blocker, their MRAs. So, and P is when they become intolerant to GDMT, as I just mentioned. Mainly, again, their ARNI, their beta blockers, their MRAs. So, when patients develop any of these criteria, it's important to refer them to an advanced heart failure center where they're evaluated for advanced surgical options, be that or transplant, or if they don't qualify for that or transplant, refer to palliative care or even hospice if the patient also do not want to proceed with any of these surgical options. So, as we witnessed, our patient was actually doing well overall, but then he started developing worsening symptoms over the past weeks, and now he's in cardiogenic shock. So, talking about the SCI classifications, as we can see here, you know, we have the pyramid, and the pyramid consists of five different classifications, which is stage A, if patients who are at risk for developing shock and who are not experiencing the signs or symptoms of cardiogenic shock. B is the beginning of shock, mainly patients with relative hypotension or tachycardia without signs of hypoperfusion, and hypotension is defined with systolic blood pressure less than 90 or MAP less than 60. C is the classic cardiogenic shock where patients are hypotensive with hypoperfusion, requiring interventions such as inotropes or pressors, mechanical support, or even ECMO. That's beyond volume resuscitation to restore perfusion. Usually, we have laboratory abnormalities as we saw in our patient. Our patients will have impaired kidney function. The patient here, as you mentioned, is creating an increase from baseline of one to two, and also we have elevated lactic acid levels where BNP and liver enzymes also are deranged, and we go up as we progress into the pyramid to stage D. Basically, it is the deteriorating stage where patients fail to stabilize on the initial efforts like, you know, what we did when they were in stage C. They need more inotropic support. They need more, you know, pressure support or they require to be on temporary mechanical support. E is the patients where they are in extremis. The significance of this pyramid is it can help us also as a physician to risk stratify patients. As we can see here, as we go up in the pyramid, the mortality in hospital or long-term mortality is significantly increased as we can see here. So, it's important to just know the classifications, and here, Sarah, so where does our patient fall in this pyramid? Yeah, I think you've done a great overview. I mean, when you look at the vital signs of his recently presenting to the emergency room, you know, his blood pressure is 88, so clearly it's lower than where it should be. He would fall under a SCI classification of stage C or in that classic stage, and he manifested obviously hypoperfusion requiring interventions, you know, which would include inotropes, pressors, temporary mechanical support just to restore the normal perfusion. So, we had decided, you know, when you take the patient scenario, we decided to put him on milrinone infusion, place a pulmonary arterial catheter to be able to evaluate hemodynamics and watch his filling pressures, and lastly, be able to put an arterial line in because that does help us monitor closely his blood pressures. So, a couple hours later, despite being on milrinone, his hemodynamics remained compromised, and he began to become more hypotensive. So, we went ahead and started norepinephrine. At that time, his right atrial pressure was 12 with a PA pressure of 72 over 39 with a mean PA pressure of 50 and a wedge pressure of 24. His cardiac index was 1.9. So, when you look at these kind of different stages, patients can really progress very quickly from stage C to stage D, and so at that time, we went ahead and applied the multidisciplinary approach consisting of cardiac surgeons, advanced heart failure cardiologists, and then critical care specialists who really are closely following the patient in the intensive care unit. At that time, the decision was to proceed with temporary mechanical support because really the goal of early initiation of acute MCS is to mitigate the consequences that come from systemic hypoperfusion and organ dysfunction, which is what you want to try to prevent, and really our goal at the time was to stabilize him and reverse what multisystem organ failure was ensuing at the time. So, you know, I mean, can you talk us through some of those most common temporary support devices that we could have considered with him? Yeah, and as you mentioned, Sarah, that's pretty important to highlight is that some patients being an advanced heart failure cardiologist, and you work also with advanced patients who come in in cardiogenic shock, and most of the time, that's why we go out in the community and give talks for the importance of early referrals because sometimes when patients come to us, they're really too sick to do anything for them. At that time, they have developed irreversible and organ dysfunction, and they are not even candidate for advanced surgical options. So, as you beautifully mentioned, it's important to initiate support for these patients to try to prevent and to reverse whatever organ dysfunction they have developed. So, we have multiple temporary support devices that are available for us, and we contemplated the use of any of these devices in helping support our patient. We'll start with a traditional antiortic balloon pump, and it's been very well used since 1968. As we all know, balloon pump inflates during diastole and deflates during systole, and it helps improving coronary perfusion and reduce afterload. The increase in the cardiac output provided by the balloon pump is pretty modest, up to 0.5 liters per minute. So, typically, we're not using it as much as we used to in the past because we have other devices that can provide better support for our patients. So, the balloon pump, as I mentioned, can decrease the afterload and lower the LV workload. It can also decrease the blood pressure and LVDP. Usually, we would like the patients to be anticoagulated when they're on the balloon pump. The second temporary and mechanical support I want to talk about is the Impella, and Impella is very much a widely used device to support our patients in cardiogenic shock, especially heart failure patients. The Impella is a continuous flow axial flow device that basically aspirates blood from the left ventricle and injects it into the ascending aorta. There are four different types of Impella. Initially, the Impella 2.5, then Impella CP, and Impella 5.0, and Impella 5.5. You know, as mentioned, Impella 2.5 can give blood flow or cardiac output 2.5 liters per minute. The 5.5 is 5 liters per minute, and Impella 5 up to 5 liters per minute, while the CP is up to 3.5 liters per minute. The Impella 5 and 5.5 require surgical cut down. The 5.5, we're using it more in our facility, and I think other centers too, because it's more rigid and allows easy maneuverability to maneuver it basically. Also, the Impella helps with improving coronary perfusion, increases the MAP, especially they're mentioned in shock and hypotensive, and it unloads the heart and increases the cardiac output and the cardiac power. All in all, as we mentioned, since it unloads the ventricle, it reduces the LVDP, the LV wall stress, and decreases the myocardial oxygen demand. Similar to the balloon pump, the Impella needs anticoagulation as well, and patients are either on heparin or bival basically, and different institutions use different anticoagulation. So in addition to the Impella, there is TandemHeart, which is also a percutaneous temporary MCS device. It's a centrifugal pump which connects an inflow cannula, which is percutaneously inserted through the femoral vein usually, and it goes to the left atrium as we see here via septostomy, to an outflow cannula in the femoral artery. So basically, you can see here in the figure, it's a continuous device or centrifugal pump. The circuit is able to provide up to five liters per minute of cardiac output. The main effect, it unloads the heart and decreases the myocardial oxygen demand, increasing the cardiac output. Also with the TandemHeart, we need anticoagulation as well. The last temporary device we're going to talk about is the ECMO, which provides biventricular support and oxygenation, and blood is either taken from the right atrium, where the cannula is placed in the femoral or internal jugular vein, gets oxygenated, and then delivered through the systemic circulation through the outflow cannula in the femoral artery or axillary artery. The ECMO now can provide high higher cardiac outputs compared to the EMPAL or the TandemHeart, up to seven liters per minute, and it also requires definitely anticoagulation. But ECMO is usually associated with more adverse effects because, you know, we use larger cannulas, so there is an increased risk for more vascular complications and bleeding with it. Also, patients on ECMO, you know, we encounter this problem as well too, is that sometimes we have increase in the afterload, and that can cause, you know, pulmonary venous, pulmonary congestion. That's why we use venting, sometimes we use the balloon pump, or the EMPAL support to help unload the left ventricle. Of course, in extreme cases, we can use septostomy as well. So, we talked about the vascular complications because of the increase in the venous sheath or the arterial sheath as well, and in patients where we use peripheral ECMO, there is higher risk for limb ischemia. Usually, these patients, to prevent the limb ischemia, a distal perfusion, cannula is inserted through the SFA, superficial femoral artery, or through the posterior tibial artery. So, putting and weighing all the risks and benefits of all these devices, the team, the shock team came together, as Sarah mentioned, it constitutes our conventional cardiologists, our heart failure specialists, our surgeon, pulmonary critical care team, and we decided the best option for our patient is to proceed with EMPALA support, EMPALA 5-5, as I mentioned. In our center, we use it mainly compared to the EMPALA 5 or other EMPALA types, and the patient's hemodynamics have responded beautifully to the EMPALA support. His levophad infusion was weaned off, and he remained on low dose of milrinone. So, basically, he did well with that, Sarah. That's great to know. Now, I know that you had mentioned there's quite a few of these devices that obviously require anticoagulation. Kristen, can you comment about how you find a balance between the risk of bleeding and the risk of clotting? Just because I would imagine it's a little bit of a strategy with these particular devices. Anticoagulation is recommended during mechanical circulatory support to prevent device thrombosis and embolization. Heparin is the most widely used anticoagulant in the setting of mechanical circulatory support, mainly because most of the landmark trials did use those during their trials. Heparin targets antithrombin. Heparin also has a low cost and has protamine available for reversal. So, due to its complex pharmacokinetics, sometimes patients don't really respond like we think they will, which has led to bivalrutin and agatroban also being used more. These are both direct thrombin inhibitors. Bivalrutin has a half-life of 25 minutes, where agatroban has a little bit of a longer half-life of 45 minutes. Bivalrutin is also renally excreted. So, in renal impairment, we do have to lower the dose, as well as agatroban is excreted through the liver. Caution should be used, again, in hepatic dysfunction with agatroban. And direct thrombin inhibitors can be preferred due to their shorter half-life compared to heparin. And also, direct thrombin inhibitors are a drug of choice when HIT is suspected. So, the guidelines do recommend creating institution-specific protocols for anticoagulation goals and titration parameters to improve safety and minimize adverse effects with anticoagulation. Also, all staff should be educated that are involved in the care of our mechanical circulatory support patients. Amin, which anticoagulant does your institution use for mechanical circulatory support? Yeah, initially, Kristen, we used heparin a lot, but we started noticing having issues with thrombocytopenia and also having HIT. So, we switched in the past year and a half or so to Bival, and also our surgeons prevent that because we're seeing less bleeding, less thrombocytopenia, and, you know, patients are having less thrombosis on these devices. That's similar to my institution as well. So, as well as talking about anticoagulation, of course, we need to discuss bleeding. So, bleeding is a common complication associated with mechanical circulatory support, and the guidelines categorize it into early and late bleeding. Early bleeding is most commonly associated with vascular damage following insertion of the device. The guidelines do recommend compression or surgical site revision, and for any type of late bleeding or any other bleeding, they recommend discontinuing any unnecessary antithrombotic agents that are unnecessary at the time. They recommend platelets being maintained at a target of 100,000. Of course, coagulopathy also can be acquired through von Wildebrand disease, and if that is identified, the recommendation is to replace with von Wildebrand factor. After device insertion, anticoagulation monitoring is recommended based on the anticoagulation and the laboratory monitoring available at your institution. If the above recommendations are unsuccessful, they also do recommend lowering our goals of therapy for anticoagulation. For example, heparin, they do recommend lowering the ACT goal to 140 to 160 seconds, and the PTT goal of 40 to 50. And lastly, for life-threatening bleeding, all anticoagulation may need to be discontinued. Interestingly, the guidelines do recommend, they do mention from the elastography, so TEGS, which we do see in our larger institutions, they do recommend it to guide blood product and coagulation factor administration in ECMO patients. But again, our utility of TEGS is limited based on the cost and availability at your institution. Yeah, and Kristen, as you mentioned, we have the bleeding adverse effect, but also in addition to bleeding, we have the thrombotic complications. Definitely a fine balance between both two. Can you walk us with what are thrombosis management and complication that can happen on patients with temporary mechanical support? Sure. Device thrombosis is another severe complication, which it's divided into, the guidelines recommend to evaluate the patient to determine if they're hemodynamically stable or hemodynamically unstable. So for our hemodynamically stable patients, parenteral anticoagulation can be changed from if they were using heparin to agatrabin or bivalrudin. Another recommendation is to intensify the anticoagulation targets. So for APT or an ACT goal of 180 to 200 may be considered in the guidelines. They recommend against the use of thrombolytic agents due to the increased risk of bleeding and hemorrhagic stroke. And then of course, if they are hemodynamically unstable, we may need to replace the entire device. And one last complication we need to mention is our risk of HID. So if we do notice that we have a 50% drop in our platelets about five to 10 days after heparin use, we should suspect HID. They recommend calculating a 4T score, which will let us know our risk. And if they're at an intermediate risk or high risk, a PFR and serotonin release assay should be sent with all sources of heparin discontinued and switched to agatrabin or bivalrudin. Yeah, I mean, we've witnessed, as I mentioned in our facility, a lot of HID cases and that's why we switched. So thanks, Kristen. And that was very informative. Basically, our patient was unable to be weaned off mechanical support. And he was evaluated for advanced heart first surgical options by the team. And he was deemed not to be a transplant candidate because of multiple comorbidities, because of age, pulmonary hypertension, diabetes, and chronic kidney disease. He was subsequently approved for an LVAD as destination therapy. And in the past, patients on that support didn't have significant improvement in longevity, but with the advances in medical management and also with a device, especially with the HeartMate 3 now, we're seeing patients are living longer, feeling better. And I want to share here with you and the team that a recent publication, which showed and look at the five-year outcome for patients who were supported by HeartMate 3 compared to the HeartMate 2 device. And they found that the event-free survival, which is to transplant or recovery or vet support free of stroke or operation to replace the pump and overall survival was 54% in HeartMate 3 patients compared to 30% in HeartMate 2 patients at five-year, which is a significant number. And when we looked at the overall five-year survival is 58.4% for HeartMate 3 patients compared to 43% with HeartMate 2. So patients are living longer and feeling better with improvement in their neuro-heart association and quality of life. That's why it's important for the providers to still refer patients for vet support. Vet support will not go away. And it is still a very viable treatment modality to support patients who are not transplant candidates or even patients as a bridge to decision and trying to optimize them until they become better transplant candidates. So Sarah, as I mentioned, knowing that our outcomes have improved with vets, and it's not just because the device is better, but also I think we're able to manage these patients better. Can you share with us some of the standard of care management for these patients, especially in an outpatient setting? You know, I mean, I think you hit the nail on the head is the, one of the most important things about these devices for long-term support is that since patients are living longer, we need to continue medically managing them. And we've got some really good guidelines out now. One from Trachtenberg and colleagues that really assist us in guidance from a clinician standpoint to help them stay on the device longer. Core principles from this particular guideline set really focus on multidisciplinary care, guidelines of medical therapy, which I'll talk about shortly, and then device optimization and monitoring. And so one of the long-term management strategies out of all of that is really controlling the blood pressure. And as we all know, in the VAD world, longstanding hypertension has previously been shown to lead to the increased risk of stroke long-term and really decrease the effectiveness of the way that the pump functions appropriately. There's a multitude of different ways in managing blood pressure. And again, I'll talk about that here shortly with regards to heart failure, GDMT, and the MCS population, really to just help decreasing the hypertensive episodes that these patients will oftentimes have. Eisenberg and colleagues also looked at the opportunity to be able to describe the challenge of accurately treating hypertension due to the inconsistent nature of how we monitor blood pressure in these particular patients. So these are great points. And you know, there was recent publications by SHLT and also publication by HFSA at Journal of Cardiac Failure about managing patients on durable mechanical support. Can you please review the importance, as you mentioned, of initiation of GDMT? Because most of the time we forget about GDMT in VAD patients and we leave them as they are. But as you and I and Kristen believe, I mean, it's important to reinstate GDMT in these patients because heart failure has not, they still have heart failure. I mean, they still have a diagnosis. Absolutely. You know, the recent guidelines by Procter & Gamble and colleagues that I've already mentioned really recognizes the importance of GDMT post-VAD. And it's really because GDMT is designed to decrease neurohormonal activation responsible for congestion, as well as managing afterload and promoting reverse remodeling. There's been a significant number of studies demonstrating the benefits of GDMT specifically for heart failure, but there's really less studies describing the benefits of GDMT in the actual MCS population. Like you mentioned, patients still have heart failure and we have to still prevent heart failure readmissions because right now it's at astounding as high as 24%. There's still a concern for inadequate offloading with these particular pumps of the LV, which would suggest that we do need GDMT post-VAD, post-durable VAD. Intermax does show that there's increased survival benefit in durable MCS patients who were treated with at least one pillar of GDMT at the four-year survival mark. For those that were on at least one pillar, it was 56% versus 44%. Those on triple therapy, post-durable MCS, which would include beta blocker, RAS inhibition, and MRAs had the highest survival at four years of 66%. Again, it goes to show that there is definitely a role of GDMT in these patient populations. I think use of GDMT also was mentioned that it was associated with improved quality of life, as well as having this being initiated helps combat hypertension-related concerns. There's been use of hydralazine and isosorbide and other afterload-reducing agents because we do know that these patients tend to have high afterload post-VAD. I think hypertension management is really not a cookie-cutter plan, though, unfortunately. We can't just say, put them all on at the same time and let's see what happens. Really, we need to at least follow some of the guideline recommendations in helping decide what options are out there for our patients. Absolutely. As we mentioned before on the temporary support, patients on durable mechanical support still have high risk for bleeding and thrombosis as well, too. I mean, there are an anticoagulation, warfarin, and aspirin, an anti-plagued agent with aspirin to help combat death thrombosis, but definitely a risk between thrombosis and bleeding. Can you walk us through that, Sarah, please? Yes. As we all know, with any MCS device, there's a risk of pump thrombosis and subsequent risk of peripheral ischemia. We do know that current anticoagulation recommendations really include lifelong use of warfarin and anti-platelet agents, currently anyway, to minimize this thrombosis risk. At this time, warfarin is the only long-acting anticoagulant recommended for durable MCS support with an INR goal of 2 to 3. But as we also know, with a flip of a coin, there's a risk of bleeding. GI bleeding is the most common type of bleeding experienced by an MCS patient, where the upper GI tract tends to be the most common site. This is all due to arteriovenous malformations, which are commonly found in upwards of 50% of MCS patients. Strategies usually include holding anticoagulation or decreasing aspirin doses, and then resuming anticoagulation when the patient's bleeding has stabilized. It seems to be that's the most common recommended strategy. Now, octreotide has been used in VAD patients to decrease the risk of bleeding. Kristen, can you share a little bit of your knowledge with regards to octreotide use in this particular population? Octreotide is increasing in popularity, and it's the most commonly used adjunct therapy for GI bleeds in our LVAD patients. This can be due to multiple mechanisms of action for improving platelet aggregation, decreasing splenic blood flow, and inhibiting angiogenesis. Small single-center trials have evaluated use of octreotide in GI bleeds in our LVAD patients, and acutely, they have been found to decrease GI bleed-related hospitalizations, reduce transfusions, and reduce endoscopic procedures. In another study, using long-acting octreotide in the ambulatory setting as secondary prophylaxis showed a decrease in re-bleeding rate at six months. The bleeding rate was 24% for the octreotide group and 43% in the historical control group. Although generalizability is limited due to other concomitant medications used for GI bleed management and also changes in antithrombotic therapy. The third core principle of the durable mechanical circulatory support guideline is volume optimization. Amin, can you elaborate on the importance of volume optimization in this unique patient population? Yeah, thank you so much, Kristen. As you mentioned, volume overload is one of the core and standard, you know, management for patients on VAD support, and it's one of the leading causes of heart failure hospitalization in LVAD patients. It can be due to multiple factors, either inadequate unloading of the left ventricle or RV failure, or just simply that patients are not compliant with dietary and fluid restrictions and or with their medications. So it's important to re-emphasize the importance of sodium and fluid restriction, again, to them and then to take their medicines. And if we think that the VADs are not appropriately, the left ventricle are not appropriately unloaded, we need to do either a non-invasive RAM study using the acrocardiogram, or we can use the invasive method through doing a right heart cath with an echo to make sure that the VAD settings are, you know, optimized. In patients who have RV failure, you know, and who are resistant to the conservative and conventional medical management, we'll always consider initiation of onotropic support to help with increasing RV contractility and reducing RV afterload. Usually when patients require that or reach that stage, the overall prognosis and outcomes become, you know, more guarded and compromised. So it's important to try with the more conventional methods. But again, if the patients need that, we need to act on it as soon as we can to prevent further deterioration. So in addition to above, as I mentioned, it's important that we see and follow these patients closely in clinic to prevent hospital admission. And speaking of our patient here, we're using more and more cardiomems to help optimize volume status for our VAD patients. Our patient had the cardiomems implanted, and actually that was very beneficial for us to help optimize his diuretic therapy. There was recent data from Intellect2 trial, and investigators showed that patients on VAD support with cardiomems, and after unloading the ventricle and having, you know, their PADs or pulmonary arterial diastolic pressures reduced at six months, these patients have improvement in their six-minute walk compared to patients who are non-responders to LV unloading by the VAD support. This study showed that maintaining PADs less than 20 millimeter mercury is associated with lower risk for heart failure hospitalizations. So it's important again to keep monitoring these patients, re-emphasize importance of diet, medications, and close follow-up in clinic to try to prevent them from being hospitalized. That's all great. You know, I think the one last thing that we have to talk about from an adverse event standpoint is the fact that infection continues to be a bane in our existence with these patients. They account for up to 41 percent of infection rates in the MCS population, most commonly being found as bloodstream infections. It is independently related to increased mortality and risk of stroke, so those are always concerns as well, and you know, honestly gram-positive cocci, which is mostly the staph species, are related directly to the infection risk, and so recommendations for treatment really are based upon expert consensus guidelines, as we currently do not have any randomized control trials for standardized driveline management, and I can obviously understand why. Meticulous driveline care by the patient or caregiver is the most important preventative strategy, and I think if we can prevent, that's always better. Antibiotic therapy time frame really just varies, and it depends if there's biofilm that is developed, and I think that's why it's important to involve our colleagues in infectious disease to be able to help guide antibiotic therapy. Ultimately, dressing changes should be modified based upon the amount of drainage to help prevent this infection from recurring. Yeah, definitely, that's important to point out, and thank you, Sarah, for that. As we clearly saw, basically, managing that patient requires, and it takes a village, and it takes a multidisciplinary team, which includes, in addition to the heart failure physician, the APPs, the pharmacists, other subspecialties, including ID, GI, neurology, among others, and to give final updates on our patients before going into the question and answer session, our patient, his post-operative course was uneventful, and he was discharged two weeks after his VAD implant. He was followed closely in our clinic with no hospital admission in his first six months, and with this, we come to the end of our second session of today's seminar. Please type your question in the chat box, and we are more than happy to answer them. Welcome, everybody, again. We'll be looking forward for your questions, but I'm going to take an opportunity to ask Sarah and Kristen here, you know, our coordinators manage patients' INR in clinic, especially, you know, to prevent, you know, the risk of bleeding and make sure they're adequately anticoagulated. What is the strategy in your own facility for managing INR for LVAD patients? So, currently, oh, go ahead. Oh, no, you go ahead, Sarah, you go ahead. So, currently, what our practice is is that a good majority of our patients that are on LVAD support are managed with their INRs with the VAD coordinator team. We have three nurse practitioners in our INR program, and my philosophy has always been, you know, we talk to these patients very frequently, sometimes once a week, sometimes more, sometimes it's only every two weeks with their INR, but we tend to know how fast they go up, how fast they go down, you know, how much you can change their dosage or how very minimal you can change their doses, or you tell them, just go eat a salad, and then you know that they're going to be back to being in a therapeutic range. So, we have taken that practice. I know that that's a little bit different, and I know Kristen will probably speak to, you know, from an inpatient to an outpatient management side, you know, for managing warfarin in these patients, but in our center, we have it through the VAD coordinators. So, similar to Sarah, I focus more on inpatient, but I recommend consulting pharmacy always when helping manage warfarin because we're really good at managing it for the most part, but also knowing your patient, knowing how sensitive they are. Some people react very quickly to small dose changes, where other patients, it takes larger dose changes. So, just really knowing your patients and knowing when things start changing physiologically. So, if they are starting to kind of exacerbate, I can tell by kind of their INRs start rising. When I'm holding the doses, they're not changing at all if you're holding one or two doses. So, just getting really to know your patient and how they respond to their warfarin therapy. Yeah, one thing also, thanks. One thing I want to emphasize for everybody on the call today and the seminar, it's important also to talk about early referrals for advanced surgical option being transplant or VAD. One thing I noticed in my practice is that sometimes we get patients too late, as I mentioned before, to be evaluated. And that's why it's important for everybody to be an ambassador for his or her own, their own community to tell and educate providers about importance of the I need help, importance of identifying patients who require advanced surgical options or being seen by advanced heart failure cardiologists or provider. There are a lot of patients out there in the community that are managed still with maybe beta blocker or lysinopril. And then when they become significantly deteriorating, they get lifted and then be too late for them to be done anything. Somebody said before, like two years of early referral better than five years late. So, it's important again to emphasize importance of early referral. And before getting to Sarah or Kristen, you have any thoughts, there's a questions. How do you help patients and caregivers understand the progression and severity of their heart failure and particularly when they are being consulted for MCS or transplant? Sarah, you want to take that? Yeah. So, I think there's nothing more frustrating than being an advanced heart failure provider, walking into a room and the patient says, what do you mean? I don't have heart failure. So, like you said, the earliest time of referrals are always the best. I think that when a patient has the initial diagnosis of heart failure, being able to talk through the trajectory of heart failure typically, you start out with medications. If the squeeze doesn't improve, you start to think about other modalities that can help us from a monitoring standpoint. The ultimate goal is to keep you out of the hospital, but just know that when you get to a certain point where medications aren't working and the ICDs aren't working and those sorts of things is that there are options and we have much better ideas for options now with these newer devices from a long-term perspective. I think that I'm a very big proponent for anticipatory guidance. I will talk about it through and through whoever wants to talk about it with me, but I think if patients can anticipate what to expect, their anxiety level comes down, their caregivers know what to expect, and they know their trajectory of what heart failure should be. So, that's a great question. That's a great question. I think we kind of reached the end of our session today, but I encourage you guys, everybody on the call today, to reach out to any of us if you have any more questions. Our contact information is there. You can reach us through Twitter or email or through our HFSA. It was a great time having you. Thank you, Sarah. Thank you, Kristen. If you want to add anything else, and then we can close after that. Thank you to both. No, thank you both. Thank you, everyone, for joining us today. Thank you.

guideline-directed medical therapies

heart failure patients

improve outcomes

reduce hospitalizations

novel devices

medication affordability

medication accessibility

advanced practice provider

monitoring devices

vagus nerve stimulation

ventricular assist devices

LVADs