Amanda Vest, MBBS MPH, Medical Director of the Cardiac Transplantation Program and Associate Professor of Medicine at Tufts Medical Center, discusses LVAD patient selection in 2022. Dr. Vest takes a deep dive into the three factors that make up LVAD patient selection – determining the right patient, the right device, and the right timing.
Okay. Okay. That's mm hmm, mm hmm. Yeah. Mhm. Yeah. Mm hmm. Mhm. Mhm. Mhm. Mhm. No. Mhm. Yeah. Okay. Okay, mm hmm. All right, Good morning everybody. Um uh it's a pleasure and a privilege to introduce our speaker for grand rounds this morning. And dr Amanda vest um as people trickle in Dr vest is a uh season leader in in in heart failure cardiology. She trained in the in the UK at Imperial College. One of my alma mater is also uh and in medicine um in advanced cardiology at the Cleveland clinic. She is uh an investigator who's focused on metabolic dysfunction in heart failure. And so as an associate professor at Tufts University um and also the medical director of cardiac transplant program. Um as you know, Tufts has been a a leading heart failure program in the nation and at the peak does over 60 Alvin's a year. We're lucky to learn from her experience in in uh in leading that program. Um and is going to talk to us today about the L. VAD patient selection in 2022. So, thank you very much doctor best and I'll pass it over to you. Thank you ever so much. Really appreciate the invitation today. Um and such a pleasure to be invited along to a surgical grand rounds as a heart failure transplant cardiologist. Really enjoyed being here today. So this is the topic of my talk. I've had patients election in 2022 and I've titled it right patient, right device, right time. Um and I think this gets to the crux of some of the challenges that we all on the heart team taking care of patients with advanced heart failure are meeting these days. And these challenges have evolved and I think are different in 2022 than they were a few years ago. So here are my disclosures. I'm psyched P. I. On a few heart failure trials funded through NIH NIH A But importantly, I must remind you that the HeartMate three is currently the only FDA approved durable left ventricular assist device. I am going to mention some of the devices that are currently in earlier stages of development, but these are all experimental and are not yet FDA approved. So, getting into our topic here, um, Elva patient selection really does remain an evolving target and I think it's a true confluence between the medical and surgical members of the team and of course the patient at the center of what we're trying to do um to figure out what is really the right patient for left ventricular assist device. What is the right device or what are we looking for in our devices? In an ideal world and that key question of right timing and converging these three factors into a successful combination. I do think it's the blueprint for an L. VAD program that really meets the needs of the patient now as a heart failure and transplant cardiologist, I do have to start with noting that I believe. And I think most of my colleagues would agree that heart transplantation remains the gold standard intervention for our patients with end stage heart failure with reduced ejection fraction and the reason for that is all in the outcomes. Um you may be familiar with graphs such as this showing a Kaplan meier across the different eras of continuous flow L. VAD generation or we start down here in yellow with the optimal medical therapy arm in rematch. One of the early studies that compared to a pulse, it'll L VAD the heart may XV. E. Which is in purple. And at the one year mark here it was a huge advancement that survival was doubled but only doubled to about 50% of patients surviving at one year. Once we got into the continuous flow era, there were additional gains with the HeartMate two. And then most recently in the Blue Kaplan meier the HeartMate three, You'll recall in the momentum three study that there was a 79% survival um as we get out here uh towards the 1 to 2 year mark, but we're still not approaching the three year heart transplant survival which in the most recent SRT our data lies around 85%. And so although it's very heartwarming to see these curves improving through the eras out to two years, we have to remember that our heart transplant curves extend out much further than that. Of course. So this I. S. H. L. T. Data internationally. And here we see the different eras of heart transplantation with the blue line being individuals transplanted back in the 19 eighties. Most of the gains have been made in the management of patients in the first Um 30 days I see you care has really evolved over that period of time and you'll see that the purple line denotes the current survival expectancy of individuals transplanted more recently. This does extend out to give us a median survival of almost 14 years in the United States. And of course it's not uncommon for our patients to survive post heart heart transplantation in the teens of years or even over 20 years. And of course this is where our survival outcomes really defer to the L. VAD recipients were very grateful and glad to have had patients survive beyond a decade of support in the destination therapy setting for an L. VAD but that is fairly rare. Um And really we're looking at implanting an L. VAD to get that medium term survival benefit in the range of 456 years. In many cases of course times are changing. And as I'm sure you've experienced also there have been some marked shifts in the patterns of L. VAD and transplantation surgeries since the adoption of the 2018 United Network for organ sharing allocation system. So to take your mind back to the earlier era you'll recall that the vast majority of patients that were going forward to transplant did so via status one A. In blue. Um and those individuals in many cases had left ventricular assist device is implanted with a complication. Many of the status one b patients in green were stable outpatients with a durable L. VAD coming on into the hospital. That was certainly the practice pattern for us up here in Boston where over 80% of our transplant recipients had a valid insight you at the time of surgery in the most recent era. How we have an early window into the post allocation change breakdown of status is now we see that the majority of our patients are either in the dark blue status one or this status to in the medium blue which really represents the bulk of our transplant candidacy at the current time. As you know, most of these individuals are supported on a temporary support device with increasingly clinicians hoping to get their patients to transplant with a single stine. Autumn E. Rather than two. And we've seen these shifts in temporary mechanical support devices as a bridge to heart transplant plantation. Um reflected in many settings. This is a paper of an early appreciation of the increase in interest bloom pumping as a bridge to heart transplantation. I think we'd see even greater shifts if we look at the impeller, continuous flow devices in our I see us as well. So in the setting of these marked changes in bridged to transplantation, there's obviously a knock on effect for our candidacy for durable L. VADs and increasingly bridge to transplantation. L. VAD implantation is an uncommon pathway. Forgetting to transplant. You can see here the 2018 allocation change in blue. We have individuals who are supported by a durable L. VOD at the time of listing for transplant and that's really dipping down through 2020. Of course we have pandemic effects here as well. But I think this is reflected in many regions of the country and it now becomes incredibly unlikely in red that a patient would receive a durable Alvan after they've been listed. If they deteriorate on the list, most would go forward to transplantation via temporary M. C. S. In 2019. There were actually a total of 3,198 continuous flow L. VADs implanted in the us which was actually the highest um in STS recorded volume. This graph only goes up to 2019. And since then there has been a subsequent overall reduction in L. VAD implantation. But it's notable that in the dark line it's the D. T. The destination therapy Vadym plants that are really starting to take off. And it's expected that this type of implant will exceed 70% of the volume in most centers and that's certainly the case in our center. And that's of course because there are so many contraindications to heart transplantation where we have to be really mindful of our stewardship role in allocating the organs and cannot accept patients with a number of these features and comorbidities in red, whereas for the vat that's off the shelf, there may be much more scope for some flexibility around these items. We were just chatting before we started about the advanced age patients. And and certainly up into the mid in some cases late seventies we've had good outcomes at our program, not so much into the eighties and I don't think there are many of those implants happening nationally, but certainly patients who are more advanced in age and have some sort of combination of these contraindications to transplantation feature very heavily in R. D. T. Valid candidates and inherently these individuals are going to have a higher surgical risk than perhaps some of our B. TT recipients in a prior era. However, being able to determine the destination therapy candidate with an acceptable combination of comorbidities and challenges that could still be compatible with great outcomes is the key to success. And so that takes me on to finding the right patient. And at least my perspective on this after several years in practice is there is no such thing as a perfect L. VAD patient. Every patient has some elements that will make them a little higher risk or they will need some extra work by the team and this is particularly important in our current era, why we need to appreciate that patients will come to us with comorbidities and in this regards the Goldilocks phenomenon is a useful framework for decision making. You may be familiar with this phrase that was coined by john Cleveland actually in regards to cardiac re synchronization but it works well for that as well. We have on the X axis increasing risk. There'll be some patients who are very low surgical risk for of AD but their trajectory would have been acceptable without mechanical support and so they're really too well to derive maximal therapeutic benefit on the Y axis. At the other end. We have too sick to benefit individuals who are in the ICU with end organ dysfunction who are also very unlikely to get therapeutic benefits because they've gone too far and are too sick to be brought back to a good quality of life by a bad and so we want the patient who's not too sick and we want the patient who's not not sick enough, but somewhere right in the middle like Goldilocks and when we're especially as advanced heart failure, cardiologists and clinic asking that question of who is the right candidate. We generally break it down into two parts and part one is who is sick enough. And this would also be a series of triggers for an advanced heart failure referral. So these are the type of elements that I encourage my colleagues in community cardiology to be looking out for when they're considering if they're patient with heart failure with reduced ejection fraction hef ref may need to seek an advanced heart failure opinion at a body transplant center. Many of these features will be very familiar to you. Um Recurrent heart failure. Hospitalizations is an important one and I'll show you one slide to support that as two is diminishing functional capacity and this really important concept of worsening renal function, worsening diuretic, refractory nous and escalation onto multiple diuretics. I think the community agrees that anybody who needs an iron A trope to maintain their end organ perfusion is inherently sick enough to be considered for an L. VAD. And we can get some useful information out of the cardiopulmonary exercise test too. We have to look out for patients with worsening type two primary hypertension and ventricular arrhythmias is sometimes the flag that the patients getting into a very adverse prognostic area. Hyponatremia is an important trigger to show us our patient is declining as to his heart failure medication intolerance. And so just to expand on a couple of those important items. I think often um when I'm speaking with our internal medicine residents, they don't realize the increased morbidity and mortality that is conferred with every successive heart failure hospitalization for a patient such that by 1/4 hospitalization. Our patients only have a 50% chance of surviving that year. And I think this is a really right opportunity, especially in our electronic medical record era for really thinking how do we flag up that patient and highlight this very adverse prognostic situation that they are now in. Similarly, there may be a role for the electronic medical record to flag up this issue, which is medication intolerance. I just had the fortune to be involved in the heart failure guidelines that came out within the last couple of weeks. And we now have quadruple therapy are four pillars of Heffron pharmacare therapy which we know save lives and improve a myriad of outcomes for our patients. But those individuals who cannot tolerate the meds who never get onto them because of low blood pressure or poor renal function or who were on a good therapy and are now having to be deescalated because of worsening hypertension or renal function are a really high risk group. With this papers showing that individuals with strong cardio renal limitations and minor tropes or just cardio renal limitations to ace ARB And no inner tropes are in much worse risk profiles than those who leave the hospital on four meds. Similarly, the G. F. R. The glamorous infiltration rate is a important window into a patient's trajectory. So typically the G. F. R. Will be worsening will be coming down in the months before we realize that the patient needs a device and then hopefully improves at least early after L. VAD implantation. But just look at the cut offs here in this worst profile group in blue where we're looking at the worst G fr and the highest. Nt pro BNP the heart failure biomarker. We're only talking about a G. F. Are below 60. And so leaving patients into a spectrum of G. F. R. S and below 30 and especially getting under 20 becomes particularly problematic and confers high risk. So picking up individuals whose end organ function is deteriorating is key. The cardiopulmonary exercise test remains a very useful tool for our ambulatory outpatients. And here we see how peak Vo two quite nicely prognosticate uh patients. And indeed it's a tool that I reach for a lot if I'm uncertain. Um and don't quite have a feel for the patients degree of acuity I often staged and with the cardiopulmonary exercise test which adds really useful information about how concerned and how fast I have to move. And all these concepts about who is sick enough are wrapped up in the pneumonic. I need help. So how patients need help if they are now needing a minor tropes have worsening functional status, high naturalistic peptides or any of these adverse risk markers that we've just talked about. And I definitely think this is a useful pneumonic that we can spread the message outside the primary implanting center about who should be referred and often cardiologists worry that they're referring a patient to soon. And certainly in our practice we like to allay those concerns would love to see a patient sooner, sooner is much better than later. And we've actually typed up these triggers onto a card that we distribute with our number for referrals. But we do have to pair that first question about who is sick enough with. The second question about is the patient's still likely to have good outcomes? Because remember that Goldilocks phenomenon, we can go far too far to the right side of the curve and have patients who sure are sick but have too much of a co morbidity burden to have a good outcome. And so these are the red flags that will be looking for um and uh and go through a few of the concepts um and the data behind these to show just how important picking up these red flags are as already mentioned renal dysfunction is a harbinger of poor prognosis in our patient with hair fraph and this um Captain Micah from the inter max cohort, which is a registry of our patients with durable calvados in the United States shows us the impact after L VAD implantation. So compared to those individuals in blue who had a good or better renal function at the time of implant, we know that even just moderate renal dysfunction which was defined here as a creatinine over two or B. U. N. Over 60 confers works outcomes. And when we get into the green line that's recipients who are on dialysis at the time of L VAD implantation are outcomes of very poor indeed. And that was highlighted by a recent publication in the Medicare population. Look at the charts on the right first. These are individuals without end stage renal disease. So not with dialysis at the time of L VAD implantation. And we see as already mentioned from the momentum data, that at one year we have about 80% of patients alive on their vat in the dark or alive with a heart transplantation. If we look though at individuals going into VAD implantation with end stage renal disease, only 25% have that good outcome at one year. And even more worrying the median time to death for individuals who had an L. VAD on dialysis was only 16 days. So the majority of these patients did not make it out of the hospital. And for that reason at least at our center, it would be very unusual for us in the modern era to place a continuous flow L VADs in a patient who either is on dialysis or is teetering near it. We also need to be mindful of liver dysfunction. And here's a recent analysis in the surgical literature on meld score pre L VAD implantation. And you'll see that even with a fairly modest cut off of 12.6 individuals with the highest meld scores do not do so well as those with better mild scores. Mhm. And a lot of these end organ manifestations are really tied in with the right ventricle and of course, as the right ventricle worsens. We see more renal failure or liver failure and we know that those individuals who are at the point where receiving a left ventricular assist device may need to be accompanied either at the time of L VAD surgery or shortly thereafter by an av add are in a particularly high risk group. And here we see only about a 50% survival in the group of patients at one year who received by ventricular support. And so particularly when we're in an era of thinking about D. T. L. Vadym plantations, we at least at our center are very cautious to avoid patients who we think have a fair chance of needing by ventricular support Because quite apart from these rather discouraging outcomes, we don't think that having to L2 devices and Salvadoran and Arvedson used off label as continuous flow devices with two sets of dr lines to worry about and two sets of controllers to manage is really the quality of life that we want to provide for a patient who's in the GT category. Mhm. It's very difficult to predict right heart failure post L VAD and there's been a lot of literature around this that I'm sure you're familiar with. The corners paper showed us that a number of features were important on the unit variant risk model with the multi variable risk model showing us vents support and the C. V. P to wedge ratio of greater than 0.63 holding true as important predictors. And I'll definitely say as a cardiologist coming to these patients, it's the human dynamics that really sway us about the likelihood of post L. VAD right heart failure above and beyond the echo which seems to not have the sensitivity nor specificity to really pick out the high risk patient. In terms of hemo dynamic parameters we favor the poppy, the primary artery positivity index has shown here and there are a number of new metrics as well that are out there in the literature that may be of use but realistically whichever predictive tool we are using there is a large limitation in terms of how accurate it is in telling us who's going to get that post covid right heart failure. And so this analysis from the pen team shows us that we don't do much better with the coin than a coin flip. With most of these tools to predict post L. VAD right heart failure risk. And really that's because I think we neither have the ideal tool to know exactly where the patient is. He made dynamically and importantly none of these tools take into account the specifics of the operation and what the patient goes through in the O. R. And early post operatively which cannot be well predicted from our pre L. VAD metrics. One recent paper from our group in the Tufts Cohort does show. I think the value of optimizing right heart failure pre-L. VAD implantation. So here we have a study of congestion that was assessed at admission. And then again preimplantation with congestion defined as an Arab pressure greater than 14. And what you'll see here is for the outcome of early right heart failure which was defined as per inter max with a composite of death within 30 days. The need for an ar VAD within 30 days or post op minor tropes for more than 14 days. The lowest risk in white was for those individuals who did not have congestion on their right heart cath either at admission or at the last right heart cath numbers before implantation. An intermediate risk was seen in individuals who came in with high are a pressures but were optimized and had better R. A pressures at the time of implants. All those individuals who developed congestion during their hospital stay with us pre implant. The worst outcomes were for individuals who had congestion that persisted at admission and implant. And so I think this tells us that optimized in a congested patient before they head to the O. R. Is important and can can yield improvements in right heart failure outcomes but also that sitting on a patient for a long time during that heart failure hospitalization. While we're all making a decision about whether or not to proceed with an L. VAD is also deleterious. And those individuals who have right heart failure creep in are in a pretty bad scenario going into their bad as well. Here we have some contemporary risk predictors for mortality in the imax cohort that's international that underscores some of the points that we've mentioned. We're gonna talk a little bit more about inter max profile and clearly the higher interfax profile patients sicker patients are at higher risk for mortality. We also see again reflected this really high risk for men or women who have dialysis pre implants. I should mention that it's increasingly reflected that patients with a small left ventricular internal dimension are at risk of having bad outcomes post L. VAD and that's predominantly right heart failure. So certainly it's our program we've become very cautious about the patient with metrics of right heart dysfunction but who also has that smaller left ventricle. They generally don't do well post op we saw that bilirubin was important that liver function metric. And interestingly in this cohort women had worse outcomes and particularly women who had a heart failure etiology that was a schematic. So that's a cohort that we have to think carefully about. I'd like to also just sneak in a couple of concepts from my research that I think are very important but aren't well captured on some of these risk scores, malnutrition is incredibly prevalent in our L. VAD recipients. And so this one assessment in a single center using the M. N. A. Which is the mini nutritional assessment. A score with a lot of parts. I know you can't see it but the screenshot here just shows you that it takes a little while to do. But it does provide useful information. Only 12% of these 101 patients had adequate nutrition by this risk tool, 66 were at risk of malnutrition and 22% were frankly malnourished and this group had the worst outcomes post LVAD implant. A similar study at another center showed that those individuals who scored as well nourished on the M. And A had a lot better outcomes over a couple of years then either those who were at risk or malnourished or having a similar level of risk. What is not known at this point is whether this is a modifiable risk factor. Can we meaningfully change patient outcomes by augmenting nutritional support in a few weeks before L. VAD implantation that's unknown a little more is now known about kiki xia and Sarka pina though, as represented by this gentleman Scaccia is a complex wasting syndrome and chronic disease characterized by unintentional adama. Free weight loss for Asarco pina related construct is actually a part of normal aging is the age related decline in skeletal muscle, skeletal muscle mass and function. And it can be best picked up with a dexter scan. Both of these related concepts do associate with worse outcomes. So we see here in the general heart failure population. A seminal study from the nineties with much more favorable survival for patients with hef ref in blue without kiki xia and only a 50% survival at 18 months for those with kiki Xia. Similarly here in the european sicker cohort. Um Those individuals who do not meet psycho pena criteria on Dexia do better with regular outpatient heart failure than those who do meet dexter criteria. And so we wanted to look into this in the heart failure cohort who are specifically going on to receive L VADs are papers just out last week in circulation heart failure. But highlights are that using the decks a screening tool, we found that over half of our L VAD population had Sarko Pioneer at the time of the LVAD implant. But Encouragingly there was a mean increase of 2.3 kg in fat free mass that predominantly is muscle mass at the three months Mark post L VAD implantation. This increase in muscle mass continued on to six months and does show us that correcting the underlying heart failure syndrome with an L VAD in this case can meaning lee reverse skeletal muscle wasting in advanced heart failure. And so here we have an individual patient participant in this study who gives his permission to show that at the time of implant he had substantial temporal wasting, loss of muscle mass, loss of subcutaneous fat across his trunk here and screened in for SArka pina on deck, sir. And you can see it six months. This manifests as a recovery of some of that muscle mass and improves subcutaneous adipose tissue with a dexter scan. Now, not meeting criteria for sarka pina. However, although the weight gain and specifically muscle mass gain in our underweight patients is beneficial. We do have to think also about our patients of a higher B. M. I. At the time of L. VAD implantation. So here in the turquoise we see the trajectory for individuals under way to tell VAD implantation Gaining weight over two years. But remember to our patients with normal weight and who already have obesity at implants do also tend to gain weight. And in fact, a recent inter max analysis told us that for patients with a baseline B. M. I. Of 35 or greater at the time of the LVAD implant, the majority of them remain either weight neutral or continue to gain weight on L VAD support with only 18% successfully losing weight. So this is very important when we're placing an L. VAD as a bridge to candidacy for transplant. That relates to an individual's ability to attain a BMI range. It's also important because obesity does associate with some increased risk of adverse L VAD outcomes. And in general multi center studies and single center reports seem to show that mortality is not affected by baseline B. M. I. But a number of other important outcomes are increased in their occurrence. Driveline exit site infections are known to be higher in individuals who have about high B. M. I. At implantation and the rates of these adverse events have all been noted to be increased for individuals with obesity. Furthermore, this analysis that we did from the advanced cohort showed us that individuals with A. B. M. I. Of greater than 35 in blue had these trends towards lower functional status. And this is incredibly important. Um We have here the Kansas City cardiomyopathy questionnaire in the six minute walk test. But if we're going to have a bad supported patients um perhaps been many years on that bad, especially if they're a duty recipient. The functional status and their quality of life are incredibly important to consider at the time of implantation. And for that reason we really espouse the idea of a multi modality weight management plan that starts right around the time of L. VAD evaluation. And to that end we have a little bit of data about um L VAD is a bridge to transplantation, including also a bariatric surgery for patients who have obesity at the time of implantation. And this 29 patients systematic review brings together a lot of the smaller case reports and in this young cohort we see very good success after the majority received a lap sleeve gastrectomy. There was a 39% Peri operative event rate around the bariatric surgery but There was good weight loss efficacy as shown here and almost half underwent heart transplantation within a 14 month average follow up period. So to wrap up my initial comments about patient selection, we must remember that only a quarter of patients going into an L. VAD with advanced renal disease will be alive at one year. So a really high risk cohort right heart failure is also a significant threat and remains somewhat difficult to predict. But especially when there is a small L. V. I. D. D. We have to be very mindful of this potential. It is however important to optimize the patient pre L VOD and getting that are a pressure down does seem to pretend better postoperative outcomes. We know that malnutrition, cake texture and Sarka pina are all risk factors for mortality in patients with heart failure. But we do see a promising recovery of skeletal muscle mass after LVAD implantation. So this is one of the ways that choosing an L. VAD for a patient with a fairly advanced heart failure syndrome may really help them to improve quality of life going forward. And then for our patients with obesity, we do need to think about weight management. From the outset of the L. VAD evaluation process. And so I'll pause here for a moment and just see if there are any questions on the first half of my talk which related to patient selection. I do see there are a few things in the chat. I don't know if any of them are addressable right now. Before I move on to other topics. It doesn't look like there are any questions in the chat. But are there any questions from the participants at this time? I have one if you don't mind. It's it's interesting the data on end stage renal disease and and that implant, I think, you know, the patient has has two guns to their head, right? One is surgery and one is no surgery. So we always have to compare the, although the outcomes are not fantastic with that, you know, the the outcomes are also not fantastic without that. Um and and so we have to always sort of think about that. And the other thing is is allowing the patient to deteriorate to the point where they enter one of these high risk categories. Absolutely. And rescuing a patient that you know, eventually is going to end up being a high risk candidate because you're sure that they need a valid at that time may not be the best strategy for the patient. The patient may be better off going in on a lower risk profile totally. And that's absolutely my interpretation of that data catching the patient before they get to those end stage end organ dysfunctions. And I think it's a programmatic choice as to whether programs do or do not implant durable L VADs, especially in the de Tierra. Um for people on dialysis, you know, our program, we have particular challenges around the fact that really none of our local HD centers will take patients on L VADs. And so we serve a very large area across New England and it's just not feasible to expect that most of our patients, especially up north of us could come down to the tough inpatient dialysis unit three times a week to get HD. And although we flirted with peritoneal dialysis in this group is still a challenge. So at least at our center we we have not really embraced that dialysis plus L. VAD combination. And excuse me, there is one question from one of our audience members says, what are the recommendations to help with treating and preventing sarka pina? Oh yeah, great, great question. So there are some things that we know from the general literature help. Um Adequacy of oral protein intake is important. Although um an area of my research interest is trying to determine whether giving additional macro nutrient supplementation in the face of the abnormal metabolic state of advanced heart failure is actually helpful in building new muscle mass and it may not be. But keeping up with protein intake as much as a patient can, especially early on in their heart failure course and importantly for the cardiologist not being overly restrictive with dietary counseling, we just have a new study out showing that sodium restriction probably doesn't help in terms of hard outcomes like mortality. Um and so not being overly restrictive in dietary counseling is very important. We do also know that light resistance exercises help maintain muscle mass. Although of course some of our heart failure patients are not functionally capable enough to really engage in that um treating the heart failure is a very important feature. We've shown that with placing an L. VAD that taking the patient out of the advanced heart failure syndrome helps them quite quickly to recover muscle mass. So doing whatever we can appropriate to the patient's degree of disease to treat their heart failure is probably also staving off that sark opinion progression dr Vaz I have a quick question first of all, I just want to say thank you for joining us today. I do wish without the covid restrictions that you could be with us in person because we could really use your expertise. So thank you. I just want to say that um comment and a question um I would echo what you've said and uh and what mike as well steve have said in the past to me that clearly with the data and evidence that you have provided for us summarize nicely is that there's a trend towards uh consideration of implanting D. T. L. VADs in patients who are less sick. I think the data is very, very convincing. And we're in the process of devaluing our program to see how we're gonna move the needle putting on the patient's hat, which is what mike was put was alluding to. Yes. It is a tough choice. I can imagine to a patient about boy the negative connotation of now I'm going to have an artificial machine attached to me. That's the end of my life as I know it. What are the mechanisms not only in terms of education but in terms of support for patients to make those difficult decisions as part of your team, not just not just social workers. I am alluding to sort of the psychotherapy side. You know a psychologist on the team. Is that a trend that the specialty is moving to? That we have psychological support as part of the heart team approach to L. VAD? Absolutely, yeah. It certainly has been in our team for a DDT recipient. There's obviously a requirement from CMS that the patient meets with palliative care. That can just be a quick check box thing or you can really embrace it and weave it into the program. And I think the palliative care team at many centers is also a great source of support that can weave through a patient's care journey. Um We obviously have um the educational pieces that you mentioned nursing social work, physicians, surgeons involved, we've found peer support to be incredibly helpful as well. And we actually have a formalized charity that some of our former patients set up called Heart Brothers that does a fantastic job in this area providing peer mentors who have been through this um to really talk with the patient early on and when they're having bumps in the road later on about their own experiences and how they dealt with them. So a combination of all of those support mechanisms were found extremely useful. Thank you. Thank you. Well, our second section is fairly short. It's right device and you may think this is a foregone conclusion because as I mentioned, the HeartMate three is the only approved durable l vod that we can implant at this time. However, I think it's worth reflecting on whether our needs are entirely met by the status quo. And you may have seen this publication just out in the last week regarding time spent interacting with the health system. So this single center study from Northwestern Looking at individuals who receive a ventricular assist device and totted up their days spent in patients or doing ambulatory visits. And rather surprisingly, they found that 23% of the days that the patients spent on their LVAD support were spent engaging with healthcare either as an inpatient or in the ambulatory setting. And when we're implanting these VADs in a large part to improve quality of life. I think we really need to take a look at and why are our patients in hospital or going to so many appointments during the L VAD support periods. And a lot of this comes down to what are now known as him a compatibility adverse events. G. I bleeding strokes mm bolic events elsewhere in the body and in that regard, I do believe that there's a lot that can still be done in evolution of the devices to improve human compatibility and reduces adverse event rates. Some of these ideas will be very familiar with here regaining some sort of arterial pulse, civility or speed modulation for example to reduce the VMS that can form in the gut and cause bleeding modulations in the surface properties that are less rumba genic to the blood that passes through them. There are modifications in terms of anti coagulation approaches and what we do with blood pressure and heart failure management that are as impactful as the mechanical device as well. But I'd like to show you a couple of the non FDA approved experimental devices coming down the pike and just reflect on how these may help our patients um and actually change the risk benefit assessment of L. VADs in the future. You may be familiar with the Everhart were participating in the current clinical trial. So we have a number of patients experimentally implanted with this device at our center and you'll see that that's in blue. This ultra thin layer of circulating sterile water which lubricates the mechanical seal interface and actually cause the area around the shaft to minimize the risk of clot formation. You've got an impeller with large flow gaps which hopefully allows for good wash out and there is also device speed modulation built into the software. So this is one approach that the investigators are looking to see whether it may reduce adverse events. Other devices under investigation include the tor vat that utilizes the Taurus, which in uh in physics is a self organizing system of energy and geometry that flows through itself constantly. So they use this Taurus within a chamber to circulate the blood. Um and then we have here the Corvin L. Vod and its selling point is that it's fully implantable and so we'll see if this makes it into trials and subsequently into clinical practice. But the cell here is a fully implantable that would perhaps reduce the risk of infections and we know infections, increased inflammation and may drive some of our symbolic and stroke events. Furthermore, we have this device that's called core wave also experimental where there's a wave membrane here at the bottom driven by an electromagnetic oscillator. And this oscillation triggers the blood flow forward in a pulse. It'll manner. The proposal here is that blood cells will travel at a physiological speed. And the hope is that there's less sharing um and less activation of abnormalities of the coagulation pathway. And lastly, we do still have um some by VADs total artificial hearts that are in generation and here we have the bible core that is ex experimental and undergoing development tested in a bovine model um that again looks at trying to reduce the trauma to blood cells and reduce the oedema compatibility events. So some good options coming down the pike and I think the really exciting thing is if we do get some advances in the technology that we have that may shift some of our comments about patient selection and timing as I'll mention in this last section. So when is the right time for L. VAD implantation? This is such a challenging question and one that comes up all the time. So there was a recent Jack Council perspectives on advanced heart failure therapies from a number of real leaders in the fields and of course they highlight that timely referral is a key to good outcomes when we're talking about either transplant or L. VAD implantation. But what is timely referral? How do we know what the right time is? And really they summarize a lot of features that I taught you about in the patient selection section about just not letting things go too far in terms of end organ dysfunction, diuretic refractory nous number of heart failure, hospitalizations and diminishing functional status. But let's think about this a little bit more globally because I think looking at single elements or one co morbidity is probably not so instructive as just thinking about the patient as a whole. And for this we of course have the inter max profiles with the definition shown here. If you're not familiar, cardiogenic shock patients are up here as interfax profile one whereas seven is the lesser end of acuity. And unfortunately we know that these inter max status what interfax profile one patients have the highest risks after L. VAD implantation. And so again with timing it's so important to try and catch the patient before they end up in the setting of needing multiple presses and I know tropes and with end organ shock. And that's underscored by this 2011 paper which was in the era when many more patients were going to L. VAD implantation from that profile one situation And we see that as compared to the profile three and 2 candidates in the upper lines. The Kaplan Meier for our profile one recipients is really quite poor. We should look though also at the lower end of the interfax profile spectrum. And so here we have our candidates at 765 and four. Now this is from the meda max registry. So these are individuals being managed on medical therapy with such inter max profiles. And we must really recognize that individuals who are in interfax profile for. So those are people who are not on an inner trope at this time but do have evidence of end organ dysfunction and who are struggling as an outpatient or having those frequent readmissions have a much worse profile of survival at one year. You can see much less than half of them will be alive at that point. And so this really is a group of patients that can be easily overlooked because they're not on inner tropes and they're not in our I. C. U. S. But as cardiologists especially in the outpatient setting we need to be picking up the roadmap trial occurred um a few years ago now and really tried to dive into these Interfax profile four through seven patients to see what was the right management strategy for them. It was non randomized. So patients were able to choose between of ads or optimal medical therapy And if you look at the outcomes as treated. So based upon whether the patient was actually supported by a VOD or on medicines during the follow up period. We see that those individuals who had an L. VAD in blue were significantly more likely to be alive and free from urgent transplants at one year. However patients were able to cross over and so if we go back to the intention to treat so what the patient had selected at the beginning of the study we actually see fairly equivalent outcomes. And this is because as people deteriorated their clinicians were able to help flip them over to an L. VAD implants strategy. And really the reason why roadmap didn't kind of take off in clinical practice and we don't see a proliferation of L. VAD implantation at the statuses for through seven of Interfax profile is because it was at the time of the heart made to pump thrombosis issues and we didn't really have the valid with a profile of safety that allowed us to confidently extend implantation into the less sick patients. But we should remember these data when we're talking to our patients in clinic who are in that interfax profile for setting and remember that the primary endpoint which was alive at 12 months on original therapy with an increase in six minute walk distance by 75 m was substantially better in the group that were assigned or self assigned I should say to an L VAD at the beginning and of course we need to bring this back to the patient and that quality of life and functional status part is so important here we have a comment from one of the quality of reviews around L VAD implantation um that I think really spoke to me when I read it about why did they take so long? Why did they let me suffer so many years and get shocked so much when I could have gotten the device when I was stronger. This harks back to our Sarka pina comments again, why did they wait until I about died before they would give me one. And this is certainly a very valid line of of thought for our patients. Of course there is the contra side here as was just mentioned with many patients being quite resistant for very good reasons to the idea of having a device. But unless we talk to our patients and offer these potential therapies and direct them towards centers that could provide an L. VAD if appropriate and desired. Then the patient won't know what options actually lie before them. And this issue of quality of life is of course so important and central to what we do and in roadmap. Ny class was recorded here in the optimal medical therapy group and then to the right in the L VAD group. These are at start of treatment assignments. And we see that it's um at 12 months um there has been um some stabilization of N. Y. H. A. Class in the study but of course these patients may have flipped over to an L. VAD. During the study process, we see a much greater reassignment of N. Y. H. A. Class in those who received an al bad. So at the time of L VAD implantation, everybody was N. Y. H. A. Three B or four. And at 12 months on L VAD support, we see that the vast majority of the cohorts are now N. Y H. A. Class one or two. And that's also reflected in these improvements in the visual analog scale for one of the quality of life metrics. With a summary comparison here between optimal medical therapy and Orange and L. Vod improvements in below. But it's still difficult to figure out what is the optimal timing. And so several of my colleagues are really working very diligently in this space and I must call out Rebecca Cogswell who's actually looking at sarka pina measurement as perhaps a useful clue towards optimal L. VAD implantation timing. She looks at the pectorals muscle mass shaded in red here on the C. T. Scan has derived a publicly accessible calculator for that. And it's really also opened our eyes to how much the renal function muscle mass interaction presents in our patients. Because of course as our patients are progressing with heart failure and losing muscle mass, that means their creatinine generation is dropping and so their serum creatinine may be lower than is really true for their degree of renal dysfunction. So she started to explore this idea of measuring for example pec muscle mass as a clue towards optimal timing. And I think this is a very instructive Kaplan meier in which she divides down her university of Minnesota and Houston. Methodist cohort into um those with different pec muscle mass groups and inter max profiles. And you see the best survival is in those who are lower risk in inter Maxa profile three and four and have the highest pectorals muscle mass. And so some key points on implantation timing. It's clear for us to see that there's a role for an L. VAD in a patient who is already in a trope dependent there'd be profile 2-3 and those patients need to be expeditiously sorted out in terms of their transplant versus vod versus palliative care strategy and I do see situations where even where we think a patient is going to proceed to an L. VADs. We delay. We try and get everything perfect or we allow the patient to go home for a period of time and still don't get it right on timing because of the risks of a line infection, worsening heart failure or VT cropping up. Meanwhile we have a lot of data suggesting that our interfax profile one patients are generally not candidates to go onto an L VAD. Although with all the temporary M. C. S. Options we have we can turn that patient maybe into a two or three profile patient and have them do quite well, optimal timing has to be individualized but clearly offering L VAD implantation around that profile for before. The adverse risk markers of renal failure, hepatic failure, right heart failure cake xIA creep in is expected to be beneficial in terms of both survival and quality of life and novel markers of disease progression. Maybe the pectorals muscle mass could really help us here and so with that I'd love to take any final questions. Um And my take home points are that L VAD recipients are increasingly going to have a co morbidity burden. We have hopefully a future where we will have ads that improve adverse event profiles in terms of better Hema compatibility. But either which way we have to find this intersection between the right patient and the right device and time it correctly. Um And there's a strong case in favor of looking at these profile for patients with a very acute eye as to their readiness for L. VAD implantation. Thank you dr vest. That was a fantastic talk. Um Thank you so much for joining us this morning. Um I want to say that probably one of the things that is the most difficult for those of us who are heart failure cardiologists who see a lot of these patients um The those who are referred on to us is um when we see them referred when we know it's too late. In other words those patients who they're generalists has held onto them so long and waited you know kind of approach it with. Well I'll wait till they get really sick. Um And then there's nothing more that we can do for these patients. Um But I really I very much appreciate you touching on this the matter of timing I wanted to ask related to that. Um You know we we do see quite often patients who we send home on mill renowned therapy um after um after they're determined to be a bad candidate. What what are you what are your thoughts on how long patients should be left to to stay on mill renowned before implant. This is such a tricky question and comes up all the time for us. I'm sure it does for you as well and really realistically we have to visualize it to the patient scenario but here are some of the things that I've really reflected on lately. After some not so good patient experiences. Um, you know, there's a lot to consider in terms of the benefits of taking a patient who has had a long heart failure, hospitalization, who's deemed themselves in a trope dependent as his diligent cardiologist. We of course try under swung guidance to wean off once, if not twice to really make that determination and we determined them to be on a trip dependent. So now there are two weeks maybe into a hospitalization. They're not so well nourished. They've been off their feet. They really want to go home and improve their quality of life. And it is in many cases very tempting and can seem medically like the best option to get them home for a while. There are also scenarios where we've had older folks who have become de conditioned and our planners, let's get them out to rehab. They'll get stronger, we'll bring them back in with an elective DT date in three weeks and that's the way we want to proceed. Sometimes it goes as well. But I would say it's about 50, 50 years of gestalt in our practice. And and increasingly I've seen so many patients get a line infection, get into worsening heart failure go out, have a have a terrible VT event and end up in our emergency room post arrest. And then you've missed your window entirely. So it's it's very difficult because in reality there are a lot of pressures on length of stay as well, right. And so often we are encouraged to sort of wrap up that hospitalization, get the patient out, make a clear plan with an elective date. But I would really encourage um clinicians to only do that if there's a very clear goal on something that is meaningful e going to get better in that home or rehab placement in salute and if you're in any doubt as to your patient's ability to stay stable through that, it's probably best just to get on with it. Right? I think the challenge a lot of times as patients go home and they're in that honeymoon period on mill run on. You know, we send them home to kind of let them get to let them get fattened up a little bit before surgery. And then you either the attending, you know, the the cardiologist will say well they're doing so well, we can wait a while or they, you know, the patient feels so well, they don't want to come in and then the next thing, you know, we're waiting months before implant. And then complications occur. I think again the scenario and of course needs a crystal ball where it may be reasonable to wait is if you're in a situation of a transplant candidate who could meaningfully get called in from home on their own a trope um and be transplanted and only take a single stone ah To me, I mean that that makes sense. And that would be very aligned with our patient's wishes but at least in the current era in our region. That's not really such a realistic approach anymore. And if we're going to leave a patient, you know, status for on a valid versus minor trips awaiting their transplant, we would usually, you know really talk about the values and getting them secure. But it's a difficult conversation in this era where we are also uncertain about when are they actually going to get that transplant if they are a transplant candidate. So I understand people's hesitancy around it. We have a question from one of our one of our panel or one of our attendees and what do you think the future is of artificial hearts? Yeah, that's a great question. Um You know, as a disclaimer, we are not a th center here where I trained in fellowship was a th center. And so we certainly appreciate um the utility of the th in certain settings, especially in perhaps HTM and amyloid um End stage heart failure. However, you know, we're more of a user of the bi ventricular central mags as a temporary support um towards transplant. Wouldn't usually be a support mechanism towards um and an L. VAD and use it in that setting when we think about th as a mechanism to replace the L. VAD. And even to go home with the patients. Although there is some experience of that with the current approved um some cardio device is very specialist at only a couple of centers. Um And and it's hard I think to see in the current era what benefits that gets a patient um As opposed to using an L. VAD if there are GT patients um or proceeding to transplant if they're eligible. I don't know what your experiences are but but it has certainly not been a direction that we've chosen to pursue at our center. I think Penn actually had the first patient was discharged on a durable th but yeah we don't I think I haven't seen one is certainly the last few years to be honest. So um there's something we've moved away from as well. Well I just want to say thank you again for a really fantastic talk. I think you hit the nail on the head with the inter max 45 population as the patient population that we need to expand on and and and potentially rescue from a higher risk of that in the future. And again we're very grateful that you spend your morning with us sharing us with us your wisdom and hopefully next time it can be in person with the with the dinner and the rest of it. But thank you very much again thanks so much for having me. It was a real pleasure. Thank you. Thank you so much. Thank you so much very much appreciate it. Thank you have a good day. Thank you
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