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9. Cardiac Amyloid part 3: Pulse check with Drs. Virginia Hahn and Joban Vaishnav


Worldwide cardiovascular disease affects the lives of hundreds of millions dedicated cardio nerds everywhere are working hard to fight this global epidemic. These are their stories they take cardio nerds Dan Parine here. Thanks for tuning in. We have such a blast recording episode seven our case discussion on cardiac amyloidosis. If you haven't already check it out it lays the groundwork for episodes eight nine on its pulse. Check in episode eight with Dr Paul Crummer at the Cleveland Clinic was riveting. Today we will continue with our third episode in the cardiac amyloid series and here from two Fabulous Hopkins Cardiologists Dr Virginia Hot and Dr Job in fashion of but before we jump in remember this podcast is not meant to be used for medical advice. The views expressed here do not necessarily reflect the opinions or policies of our employers. The goal is to simply enjoy learning more about cardiology directly from experts like our guest today. Hi Everyone Korean van here. We are so so excited to highlight one of our star co fellows and my sister from another Mista Virginia Hyphen. Dr Han is a fourth year. Cardiology fellow here at Hopkins. She went to medical school at University of Pennsylvania where she also completed her medicine residency and then moved to Hopkins for Cardiology Fellowship. After a one year hiatus as an ICU hospitalised during fellowship she completed two years on the NIH t thirty ready to training grant and one year as an absolutely fabulous chief. Fellow does fabulous. She's passionate about translational heart failure research and has really. We stood apart among her peers. With regards to what she's been able to accomplish all while mothering to young children during training. That's right Virginia. We are so excited to have you. I actually have known Virginia for many years When I was interviewing for residency spots she interviewed me at U. Penn.? And that's where we met first I but then during residency she was just a fabulous consultant and we leaned on her heavily to help us sort through cardiovascular care for our patients during residency. Eh Virginia. This is an absolute trait. Also Virginia provided us with our first flutter movement of the show definitely check it out on episode three hypertrophic cardiomyopathy. It definitely worth a listen so much. I'm so excited to talk with you today. And thanks for making me sound so good. It is easy effortless done While we're so excited to have you as you know our most recent cardio nerds. podcast episode really highlighted cardiac amyloid. And so we thought this would be a great opportunity to talk further about some of the research that you've been doing with regards to half path and deep pheno typing of half patients and particularly some of the discoveries. You've made with regards to cardiac amyloid awesome. So I I will will highlight my two mentors. So my basic science mentors David Cass. Who I've known for about a decade and my clinical heart failure mentors Beauty Sharma? Who is our section chief in heart failure here at Hopkins and they worked together to establish a clinical and research have path program About five years ago and Kavita started getting myocardial biopsies from these patients Both for clinical reasons to evaluate for AMYLOID and Also myocarditis and fibrosis inflammation and then also to use some pieces of tissue issue for research purposes so we have a variety of molecular analyses that we're working on now As part of our deep phenotype in half past project but because of the prevalence of amyloid in our half path cohort. We've actually now started looking at the overlap. Overlap in protein. KINASE G M protein quality control in amyloid So we've actually received a couple of foundation grants to further that work. We have a paper now that I've presented the abstract a couple of at a couple of meetings and we just submitted the paper. And here we really focus on the first one hundred and eight half path patients so these are patients who were deemed to have half pat based on seeing a provider in clinic who is in advanced heart failure specialists so these patients really the other causes of Disney and lower extremity Dima are excluded so these patients are all Paul referred to the Cardiac Catheterization lab for invasive human dynamics end myocardial biopsy and in the first one hundred eight fifteen of them or are fourteen percent had cardiac amyloid and the vast majority of these patients had transferred written which was in seventy three percent so out of those eleven that had translate reading cardiac amyloid seven of them were wild type in four were mutant and how many of these patients were known to have or presumed to have amyloid prior prior to biopsy yet so about half of them were suspected to have amyloid based on clinical screening or clinical just salt. None of them were known to have amyloid. We actually had to really interesting cases. One was a patient who had multiple myeloma WHO's android turned out to be wild type transpire eaten which we would have never figured out unless we had biopsies him and we had one person who actually had a negative. Give nuclear piracy scan but the person had a familial history of amyloid neuropathy and so because the suspicion Asian with high we biopsy that person and that person did turn out to have a hereditary tr so it is difficult to determine how many would be clinically clinically suspected in other settings. We are a tertiary referral center but it was about half and when we look at experts screening guidelines just under half of our patients wouldn't actually the not have been captured based on those screening guidelines. Because they would have been too young and the hypertrophy would not have been severe enough The other really really interesting thing we found. Is that strain imaging so relative atypical sparing on strain meaning that the pex contracts better than the base of the heart are is a hallmark of cardiac amyloid and actually we just in the ECHO lab. Yesterday had a case like this but it turns out that this is more often seen in patients ends with cardiac amyloid who have reduced ejection fraction. And when you actually read the papers about this data patients with half are it's known that this marker there's less sensitive when the patient has heart failure with preserved ejection fraction so we found that it was not sensitive in those patients. Because that makes sense because strain is really detecting early signs of connectivity issues. Patients have have path right so at least grossly. They don't have issues or custodian's function. So that's very interesting. Are there other markers on Echo. That are more specific to Heff path. amyloid yes so when you compare the group's non amyloid half pep versus amyloid Half Path. They did have higher. Lv Mass One of the challenges is now because our patient population have become more and more obese is just how we normalized that but the the LV mass was higher and then two two other interesting. Things that we found were that proponent and anti probey. NPR were significantly higher in the amyloid patients. If you look at the proponent particularly it was really striking the difference between the number of patients with a detectable opponent level in the amyloid versus a half and the tr- opponent in an BNP elevation is not different among different. AMYLOID subtypes you know. That's something that we didn't look at. That's a really great question. Shen the subgroups get pretty small. Al We had three patients and then we did have one patient with a amyloid so we haven't looked at that that but that's a good idea we do know that tr- opponent and be NPR predictive outcomes in Al Amyloid. Did you guys have thought since you know you had these cases out. Obviously there were. Your nuclear study was negative or patient with multiple myeloma and DDR was there any leg bought as to how to not miss those types of so we talked about creating some kind of score. was there a way where we could create an algorithm so that you wouldn't miss any of the amyloid Loyd cases and we were not able to do that because there were these outliers. I think we're limited by the small numbers so one thing that actually Jovan is working on with computers says to develop a at some kind of scoring system that would at least guide you or narrow down the patients who need screening and we do you have great noninvasive screening but from the study. We've seen that if your clinical suspicion is high in the nuclear study is negative than feel feel. You should feel comfortable going forward for viability a positive that you're done right. You have the diagnosis in nuclear scans are only for Trans tight written amyloid so so if you have somebody with Al and you're not sure if the heart is involved or not than you would need to go to buy up and the other thing to keep in mind. There was a pretty high profile paper out of the Mayo Group. That wasn't autopsy. Study that gets quoted a lot because nineteen percent of their half path. Patients had amyloid. By right you have to actually read the paper to see that. Many of the patients had mild infiltration of amyloid that would not account for clinical react namely noses and so we actually made it a criteria that you had to have at least moderate infiltration interstitial infiltration with amyloid to be diagnosed as cardiac amyloidosis now among those patients that you identified cardiac amyloid on biopsy. Can you tell us. It's a little bit about the features of those patients with regards to Saks and CO morbid conditions age. Were there any patterns patterns that you noticed yes so in all of the patients are median age with sixty six so this is actually relatively young. Compared dared to the other papers that have looked at prevalence of amyloid in half path. The median age of the non amyloid Half Path was sixty five whereas the median age of the cardiac amyloid a half path patients with seventy four. So the sex distribution was sixty percent female in the non amyloid half path in forty forty percent female in the cardiac amyloid group And remember these are all cardiac amyloid who have preserved ejection fraction of fifty percent in terms of the racial distribution distribution. So this is actually a strength of our study that we've included so many self identified black patients who are often not included in heart. Failure Research So sixty percent of our non amyloid half paths were African American self identified and forty percent of our cardiac amyloid patients were so this is actually surprising. Because the most prevalent mutation in t t are in the United States North America Archive is the failing failing to ice luchina at the one. Twenty two position and this is found in four percent of self identified African Americans yet yet. It has incomplete penetrates. We don't really understand why And it turns out that many of our African American patients here at Hopkins Have Path Jeff So we didn't see a racial difference which we were surprised by all just highlight differences so the systolic blood pressure tended to be lower in the amyloid alight patients one twenty five versus one forty one the BMI tended to be lower which was a median of twenty nine in the cardiac amyloid group versus thirty. Thirty eight in the Half Group of very interesting is as as a wade is obviously a risk factor for a path yet offer absolutely but the interesting thing is you the amyloid patients still there are many who are overweight and obese So as the demographics are changing you know just because somebody is overweight. Robie said doesn't exclude them from having amyloid and then otherwise we found more hypertension and more diabetes in the half path patients And then as I said right before the opponent and the BNP were higher in the amyloid group specifically two thirds of the amyloid patients had a proponent that was above the normal range whereas only twelve percent of the half path patients did and that makes sense because you used proponent and BNP in this state Mayo staging in for a l.. There's not as much data for using opponent and BNP as screening for tr. Anything else from your paper that you want to highlight highlight I've so we actually looked at clinical histology in non amyloid half path as well and it was. It was actually surprising that While we we found fibrosis and hypertrophy in most of the patients most time it was mild. So we're non amyloid a non on amyloid have path So part of the reason that this whole effort was started was to really understand the mechanisms of half pep in really drill drill down into the myocardial phenotype we have clinical phenotype in our heads. But we don't really know if the myocardial mechanisms are any different so this this is work that is ongoing. We did transcript. Oh Mix in a large number of these patients in that papers being prepared now. They again for everything Dan. Thanks again for your contributions to this field. which is growing? And we're learning more and more with every passing year. You are obviously a phenomenal clinician. Scientists You're just a a clinical role model for us and you basically really build both worlds that research world and the clinical world and I'm just wondering how do you juggle the two. And how do you remain so excellent at both at the same time thank you. I'll watering Cheetah boots wearing cheetah boots Sell you know. I feel the same stress that I think other people do just figuring out how to how to divide. Divide your time between these two worlds. I think it's true that you really when you're doing one thing. It means that you're not doing something else so I really try. Try to focus completely on what I'm doing at that moment in time. So when I am on the Cath rotation. I'm a hundred percent in the cath lab and I really try to tune out. All of the other distractions and you know something. My husband told me when I asked him he how he was such a great resident not just on his own service but when he rotated on other services in he just looked at me and said it's very simple just always do. What's right for the patient so I try to give it my all when I'm on these clinical rotations? And then when I'm working on my research I try to really focus on on that and be really protective of that time. I also think that it is so important and you spend a decade of your life training to be a doctor you a half to do research that leverages your clinical skills So do research that could be done by somebody who's not a physician I think that we stress a lot about not having the same time that the PhD's have but in working with several basic science pages ages and engineering they really don't have the same clinical context. We do I mean the whole purpose of research is to take better care of patients who you don't know where the holes are unless you're actually doing it and we absolutely need each other so these foundation grants to study amyloid. I basically basically worked on with a junior faculty member here named Mark Roenick And I think this is the future we will have to learn how to do team science but don't spend a decade of your life. Busting Your Butt. I mean most people listening to this are trainees who are in the trenches. You don't want this to be time time that you're not leveraging in your research so that's really important and that's one reason why when I went back to the lab. I told David I really WANNA focus on human tissue in human mechanisms. Well thank you for that. That was terrific answer in various fire and personal either great. Thank you very much votes. That's the show. Thank you so much for having me on the show such a delight. Hi Everyone Dan Corinne back here and so excited to continue tenue our discussion on cardiac amyloidosis with one of our heart failure. Colleagues here at Hopkins. Dr Jobin SCHNAPP Joe. Ben Completed Her undergraduate and medical school training at Saint Louis University. She has since been at Johns Hopkins for Residency Cardiology Fellowship and advanced heart failure fellowship. Her early research search pursuits were in heart failure with preserved ejection fraction from this and former advanced heart failure training she developed a strong clinical interest and research interest in in the early diagnosis and treatment of cardiac amyloidosis which is why she makes such a perfect person to continue our discussion on amyloid. Absolutely absolutely totally Great Jovan has been a mentor to me. She's been a year ahead of me in residency and then fellowship and has been guided me along the way we used to share clinic together and when she left to pursue her heart streams in advanced heart failure. I it was a real loss so I used to send her snap chats every clinic day which she ignored and threw it into the trash so jovan thanks so much for joining. Think for having so. We're real excited to have you. We are going to get started with in some questions that we are dying to get your take on first. We'd like to talk a little bit more about heart failure therapy in cardiac amyloid so so we wanted to get your opinion from a practical standpoint on the management of these patients in terms of medical therapy that traditional medical Michael therapy that we use for cardiomyopathy patients. What are sort of the do's and don'ts that are specific to cardiac amyloid yeah? I think that's great to discuss. fess up front with cardiac amyloidosis actually like many aspects of heart failure understanding the human dynamic. Derangement is probably the best way to understand why we do do. And why we don't treat cardiac amyloid with certain quote Unquote Standard Heart. Failure Therapies Cardiac amyloidosis as we may now as an infiltrative restrictive of cardiomyopathy the amyloid fiber deposition leads to buy ventricular hypertrophy and the LV is generally thick non dilated needed and non defensible. So this really does limit the heart's ability to various stroke volume and there is actually kind of a fixed stroke volume advanced restrictive disease so even though the major symptom manifestation of Obama light is congestion there is also this propensity for hypo dialing. HEP Of Alenia. Nia with over dire recess and importantly the hypothermia from diary says may manifest dizziness lightheadedness precinct. syncope does often to need to be distinguished from dizziness. For example from neuropathy interesting over that that can be seen in. What as one of the manifestations of amyloid correct performer apathy is mean another major manifestation of teacher Emelin so the humidity Amex are also? You know why eighth Feb is very sensitive in credit cardiac amyloid. There is a loss of atrial kick or reduction in stroke volume and this could be really consequential and then lastly there's also a heart rate dependency to to maintain your cardiac output and a need to avoid certain drugs. which will talk about a little bit like Betablockers that may lower your heart rate depending on the patient most patients chance do develop congestion though an require? Initiation of loop diuretics on which is a mainstay of therapy and often times pretty high doses are needed to achieve symptom relief. As I mentioned the caveat with diabetic titrate has just to be on the lookout for over diary system. hypoglycemia symptoms that patients will report court. If they are experiencing this are lightheadedness dizziness precinct. Piece syncope they may have an AK I in their labs or have a lower them baseline blood pressure. There is in this case. What may be tricky distinguishing the symptoms of lightheadedness and dizziness from another common carmody amyloid patients? which is autonomic neuropathy? With the which can also manifest as lightheadedness and dizziness precinct opinion syncope Visayas diabetics in particular Matola zone is sometimes needed as a booster and manifestation has is good enough renal function and especially with hypoglycemia. I do try to add ons for locked him. I think one important lesson I've learned just owing to the restrictive nature of the Aziz and one of my clinical humid enact mentors docker Wittstein. taught me early on is you may never actually normalize the JV P or you know have normal filling pressures in patients with cardiac amyloidosis patients are dependent on filling pressures to maintain their stroke volume so with diabetic tight. Ration- what I'm really assuming for is symptom relief and decongestion more than anything. That's really interesting job. What I'm hearing from you is that Dia? Radic's are really the mainstay of therapy in treating treating cardiac amyloid really to get to decrease in congestion and symptom management which is counter to what were traditionally thought with cardiomyopathy where our mainstay mainstay is really trying to get them on goal. Directed therapy are really pushing Beta blockers. Ace inhibitors year. You're really reaching for diabetics. I and so coronal acting on for example is not necessarily from the guideline directed therapy perspective. But more for to help normalize the potassium so patients don't have to take you know just like bucket. Tuck it loads of potassium. Yeah that's correct so the other standard therapies that you mention Rasa Habituation Beta blockade. That you know we are really trying to push on our dilated cardiomyopathy map. The patients have not shown similar efficacy in cardiac amyloidosis patients and again this really goes back to the underlying he amex and the concept of having a relatively fixed stroke volume so online dilated cardiomyopathy. Were you Vasil dilate in reducing increase your cardiac output. There's really but not this ability in amyloid and instead you just kinda potentiate hypertension a lot of time. Betablockers can do the same You know again related related to the negative Aina Trophy and current trophy nonetheless. There are definitely patients. Who've Kinda me on clinic there hypertensive with cardiac amyloid there on ace inhibitor? Or they're on Beta blocker because of a history of a fifth and tolerating these medications. Fine so in these cases I usually don't stop the drug but definitely regularly monitor symptoms inches. Have a low threshold to discontinue and related to this. I think one useful clinical pro to throw out there in the diagnosis of cardiac amyloidosis. Is You you know you have a heart failure patient diagnosis in the hospital. Of course everyone wants to start guideline directed medical therapy and you may not have diagnosed amyloidosis at this point will a clue that this may be. AMYLOID is patient tanks when you start. Logos Beta blocker or ace. Inhibitor on initiatives prompted. Think about if that is what's going on in the ideology aetiology so that was a great summary of traditional cardiac medications and how they defer in the in the treatment of cardiac amyloid. But what's really exciting about this particular disease entity it has been. I think the advent of novel therapies particularly for tr which is why there is now such a greater push to diagnose this disease at an earlier time now that we have a therapy. We'd love to hear more from you about the drugs that have been developed that are sort of in the pipeline Particularly the attract trial that came out at New England Journal in two thousand eighteen eighteen looking at two feminists. Yeah I think this is What's incredibly exciting about diagnosing and treating amyloid in this era? I'm there's just been a large surge of disease modifying therapy before we kind of dive into two families and attract in. I think it's important to review so what we're targeting here. which is the translate written? Protein translate written at transport. Protein is synthesized in the liver and it comes together to form a Just kind of like a four leaf clover in its natural state. So with T. T. R.. Cardiac transplant written the issue. Is it destabilizes in dissociates associates in the monomers missiles and then deposited as amyloid fibers In various organs but as we talked about particularly the heart and the peripheral nervous the system so this can happen either due to a pathogenic mutation such as in variant teacher amyloid or not do genetic mutation in its natural state which is called wild type T to our amyloid so all the different therapies that have emerged in the past few years target. Different parts of this pathogen pathway by either suppressing teacher reformation in the case of Thomas and others stabilizing the TR trimmer or by degrading the amyloid fibers that have already deposited moving onto damnedest. So it's a stabiliser and as of two thousand nineteen you know after I tracked. It was kind of fast tracked. It's the only FDA approved therapy for the treatment of cardiac amyloidosis. The attract trial was a phase three clinical trial it looked at famine EST versus placebo in both variant and and wild type teacher. Cardiac patients It's a once a day Peo- medication and mechanistically it works by binding. Tr Tetra with very high affinity and so basically inhibits a step. Where the Touch Moore dissociates into monomers which is the rate limiting step of that cascade so attract international placebo controlled like I mentioned and patients enrolled either had near accreditation class. One two three heart heart failure so the trial did exclude classes for her failure. Patients the primary endpoint was mortality credit vascular hospitalizations but he's a secondary endpoints were improvement in the KC Q.. And six minute walk test. Q- It's the Kansas City Cardi Mafi questionnaire basically focused on quality of life really commonly used in all heart failure trials. Thank you guys. Okay I was asking for the audience. It was so stupid people So commonly talked about what the ATTRAC- Trial Zero really unique statistical method for analysis. So I thought we should mention here. It's the Finkelstein show. I love this. It calculates a win ratio But really I think this method capitalizes on rare disease and a small cohort it really increase the sensitivity in power of the trial points. Eh prioritize the importance of mortality and morbidity so and you know usually composite end points you look at all of them together Finkelstein gene show and fell this hierarchical so it'll prioritize death and then then you it's like a ladder that you go up for endpoint so it allows you to sort of say say this endpoint is more important than this employment cetera crushing your stats class. No we didn't learn this incessant is that I love this method over. I'm not putting that up a real nerd so in terms of trial implants to feminist was shown to reduce mortality by thirty percents compared to placebo that generative number needed to treat of about seven point. Five just to prevent one death hospitalizations cardiovascular hospitalizations positions were reduced by thirty two percent number needed to treat correlating faddis. Four one hospitalization. I think one important lesson we can take home. I'm from attract. Is that earlier. Diagnosis in earlier. Treatment is way better. A subgroup analysis showed much more benefit in the class. One to two you near Kurt. Association patients compared to clashes three in mortality an cardiovascular hospitalizations and again class for patients weren't even enrolled and also kind of related to this notion of earlier treatment and earlier diagnosis is that It did take a little while for the benefit to be seen so the survival survival curve split at about eighteen months And in terms of hurtful layer hospitalizations occur of divergent about nine months. So you can't have a super sick a patient that you're starting on because they need to live a while to see the benefit from this drug Jovan that was a really great overview of the attract trial and it will be really exciting to see how the use of FAMAS hands out in day to day clinical practice. What has been your experience thus far with this drug? I think it's great to be able to offer therapy to my patients with chronic amyloidosis. So I'm in general very excited about it. I think besides being able to offer Therapy another major advantage is that it's really safe. And well tolerated. The trial itself had very few adverse events in clinical practice. I haven't had a patient. Don't need to come off drug. Because intolerance or side effect the big disadvantage which has been extensively discussed you know in nationwide international. Aw on an international level is the cost because amyloid was classified as a rare disease. The drug was costed as such. It can cost on average of two hundred thousand dollars per year. And it's by far the most expensive cardiovascular drug on the market. I think they're really needs to be headway. Made in this front especially if we diagnose amyloid in more and more patients as we expect to do so it will no longer be the rare disease that we have classified it as absolutely and so I know to famas sort of at this. Point is the coolest kid on the block. The one that we probably hear about the most. But tell us about the other. T. T. R. stabilisers. Yeah there are other stabilisers. That are Hopefully coming down the pipeline. Aj Ten was was recently published about in phase two clinical trial and there's an ongoing phase three clinical trial and the mechanism is interesting it mimics so mutation that has been found to be super stabiliser. Tr in the phase two clinical trial it was deemed safe and did reduce the rate of that Tetra. America Association Association. That we talked about was kind of this integral step in the cascade in both mutant. Wild type Emily so it'll be exciting to see what comes of further another trial data. It's an oral drug as well which is another advantage and I flew his. Al Is kind of the old kid on the block. I guess it's an end set in a a nonselective Stabiliser it's shown modest benefit in crop than has been shown to slow progression of neurologic impairment in those affected by neuropathy. I think they use in cardiac amyloid is a bit controversial. Because of the long term side effects events that use we tell all of our patients avoid end said all our patients with heart failure to avoid and says and has been shown with. I flew Reduction Gfr in volume retention so it has to be a select cohort that That gets this drug. That's pretty important to know so to fabulous. Aj Ten and a flu nestle as you mentioned. Our T. T. R. stabilisers Sir. But what about agents that are particularly working to suppress t t our production. Yeah this has been an exciting time for amyloid as well. There have been two drugs. Approved relatively recently for. At our peripheral neuropathy and that are actively being studied for cardiomyopathy in both aim to suppress. I teach our production. First of those participants are on Pattro and it was studied furniture up at the end. The Apollo trial the mechanism impetus rand so it is a small Paul interfering molecule in targets a sequence of the Amarna within tr and that sequences preserved in in those with the mutant and of course. It's impacting those with wild type. So in Apollo there was a significant improvement pollen or a decrease teach your levels overall improve quality of life. They did a pre specified subgroup analysis with cardiac involvement which led to the little talk about but that showed improvement in credit structure and function so decrease. I'll be wall wall thickness permanent Avi Strain and a reduction. In Mt Premium P so patients in Apollo only had hereditary eighteen tr. Apollo visa is a clinical trial that is ongoing that will look at Petit Serandon patients with cardiac amyloid both wild type. In hereditary. The main side effect in one of the things to note about participation is it is an. IV infusion into the main adverse event was infusion site reaction the other one. I'll mention that has been approved for amyloid for For at not our peripheral neuropathy is terrasson. It's an anti sense elegant nuclear tied and it binds to earn as well in leads to its degradation. This drug was studied studied in the neuro t to our trial in that trial about sixty percent of patients did have cardiac involvement but the results weren't power to measure Effects so there is also awesome ongoing trial of this crap the as well as exciting so these would be things that would really deter the whole disease like from the get-go identified ready. Terry a.d are you can identify people who had any. You know. Typical manifestations yeah. I think importantly these drugs are not getting rid of the amyloid fibers that have deposited today. That's the last step of the pathway. The drugs that degrade the amyloid fibers but they do suppress production Yet pretty exciting. The prevacid yeah. Yeah so we've talked a lot thus far about the general cardiology cardiac specific medications. And then a little bit more about the targeted therapies specifically for cardiac amyloid will be really exciting as the drugs continued to develop is hopefully improvements. It's in the early identification of the disease and initiation of therapy earlier as you mentioned in that too feminist trial really starting. The drugs earlier made a big difference. Unfortunately though some patients do end up developing and stage disease that requires transplantation. So I'd love to hear you're at your take as a transplant specialist. Sort of how you manage these patients what what goes into your thought process. When you're thinking about take transplanting cardiac amyloid patients? Are there anything. Is there anything specific that you worry about or take into consideration are there any other other organ. Transplants that you consider off the bad and you know what sort of goes into that decision making. Yeah I'll say upfront. The transplant percentage Najeh emily patients is a very small subset of patients. Who get transplanted Generoso? Our experiences. A bit limited And earlier on compared chill later Published data there were outcomes. Compared to what we're seeing now but certainly organ transplantation as something that may need to be considered in cardiac amyloidosis assists both single and multi organ. So liver transplant was kind of one of the first Considered the first liver transplant for amyloid was back in the nineteen ninety S as we have talked about since the protein is produced in the liver that thought for specifically hereditary amyloid. Is that if you replace that liver. That's producing the mutant with a brand new liver you'll remove immune tear production and decreased disease burden it is an has been accepted. Indication for hereditary attorney teacher amyloid in patients with advanced neuropathy patients who soli undergo liver transplant cannot have significant cardiac disease. That's a contra-indication occasion. They will not do well unfortunately. Cardiovascular complications are the leading cause of death post transplant in post liver transplant in in these the patients. The reason is cardiac disease can still progress. Because it's been hypothesized that while type amyloid which is still being produced by the liver can stick to the mutant the emily. That's already deposited for that reason. There is this risk of credit score disease progression with liver transplant. It's definitely been shown that certain mutations such as is be thirty m carry a much better prognosis for liver transplant. Compared to others in that should also be a factor heart liver should be considered for patients with Hereditary amyloid Loyd who have significant cardiac disease at the time of transplantation consideration earlier. The better. I think what's been shown is that there is a high weightless mortality mortality for patients with cardiac amyloidosis listed for heart transplant. And Leslie Heart. Transplant has been at therapy as well for both Newton while type eighty. TR's wells L. patients with thought behind this being teacher. AMYLOID does take a very long time to develop to lead to symptomatic disease and now especially that we have disease modifying defying therapy. If it's caught on five see we can start early treatment with al.. It's the same concept. We can suppress lights out. Production with chemotherapy and possibly stem cell transplant. Post heart transplant right. Because if you're just doing a soul heart transplant you're not. There's nothing to say that you're not GONNA get right. amyloid deposition growth as resetting the system correct. Yep you're just starting. Fresh routinely post heart transplant patients are getting into myocardial biopsies for monitoring rejection in which case we would see the amyloid deposition early Somme on Stanford had published the largest contemporary series. John Transplant outcomes in amyloid and in general these outcomes are compared to earlier series. I think this is probably just because we become better at patient selection. So you you know really eliminating patients. With other organ manifestations at our severe and from L. Ale Emily chemotherapies become much more effective and well tolerated Hala rated. Oh my Gosh Jovan. That was phenomenal. As obviously we knew it. Which is why we had you on the show Dream Team but seriously thanks for coming to the the show this is like a has been incredibly helpful for us? We obviously see that. You're very passionate about Karnik amyloid and we were just wondering. What makes your letter about Credit Galilei that made you dive into into this and take care of these patients? Yeah I kind of fell into it. I mean I think amyloid encompasses a lot of what I love about heart failure. It's challenging physiology theology. It relies on very accurate in early diagnosis with a high index of clinical suspicion. And from that standpoint. I think there's a lot of education to be done into it with our colleagues which is exciting for me and I really appreciate the multidisciplinary approach not only do you need a cardiologists circular specialists. You need oftentimes neurology and oncology a genetic counselor And so I love that team approach to treating patients he should credit gambling doses. I'm very excited to work with our faculty here on that in the next coming years and I think for everyone. This is an incredibly exciting time for amyloid. As we now have therapies that are actually treating the disease and I think in the next year is we'll just see a surge of these therapies. That will improve outcomes and quality life for our well deserving patients all that's awesome and We're excited to watch you on that journey and be one of those colleagues. They come for educational pearls like I did right before for this show. Jim Is Amazing. All right that's a wrap. Thanks guys thank you and that brings us to the end of our show. So it's time to make like an s to split. You can follow follow us on twitter at Cardiac nerds don't forget to check out the amazing illustration that Korean prepared for y'all at www dot cardi unearths dot com and please share. What made your heart clutter this week? Send us a clip. Two carts few enjoyed the show be a narrative and spread the word and now aflutter. Hey cartoon hurts. I'm David Amber a fourth year medical student at the University of Maryland passionate about all things medicine with special interests in urology. I love my brother. Dan and I've been a listener of the show. Since the onset it has has been totally awesome and taught me so much made my heart flutter recently was celebrating my match into urology medical schools along road and the pre match process is incredibly grueling. I'm thankful for my wife and kids. We're going going through the last four years and a special mentioned my brother Dan for keeping me sane during these last few weeks. I'm looking forward to celebrating with my peers. In March after general match has had to leave the Baltimore area the the real most vital organ will always be connected. I love the show and I am excited to continue being the cardio nurse biggest fan.

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