 Good evening, everyone. I'd like to thank you for coming to the first ever cardiac amyloid research seminar series I'm Sandesh Dave at Arizona State University. I Want to thank our sponsors the Arizona Biomedical Research Center Which is a funding from the state of Arizona to bring together National and local experts to engage Arizona researchers and clinical professionals on emerging topics for the research community The goal here is to foster collaboration among researchers and clinicians and to encourage networking So I'm really excited about this event How did we get here? we had our first ever CME event in January of this year and We had a really good turnout for what you know We knew was a relatively new emerging topic and we're really excited by all of the enthusiasm and engagement of people here in The Valley and in Arizona and even audience and you know nationally So I wanted to thank April Johnson who's my colleague and project coordinator for amazing eye-to-detail and organization and planning this event so You know this is an exciting time in amyloid we have new therapies we have drug approvals We have clinical trials in development We have improvements in imaging We have a focus on health equity and we have concerns about health care value. So I think this is a really Great opportunity to dive into some of this And I think that the transformation with this this new innovation will require really a village approach in the medical community And so that's necessary to change practices and beliefs And so we think this debate is going to be a great opportunity to engage a variety of stakeholders from cardiology primary care and geriatrics So I wanted to introduce the debaters today So We have our We have our pro team That yes amyloid screening should happen for all Adults older than 65 with heart failure. So we have dr. Suzanne Soroff She is a she graduated from medical school from Baylor College of Medicine She did a year of research in congestive heart failure. She did her cardiology fellowship at Metro health hospital She's been practicing in Arizona since 2007 and She was the president of the American Heart Association Local chapter and has been on the ACC board of directors She's also faculty at Creighton University with interest in pulmonary hypertension cardiology and women's health and I have to say I learned that she's been to more states during her training than I have so that's major honor and then to her left is Dr. Michael Castro Who's a founder of arrowhead internal medicine board certified in internal medicine? Associate program director of the internal medicine residency at a brazzo health network Assistant professor at Creighton School of Medicine He's also professor at at least three or four other medical schools He's chief of staff at a brazzo arrowhead campus in a brazzo Arizona heart hospital Until August 2020 And he graduated from University of Puerto Rico medical science campus in 1994 Into the internal medicine residency of Maricopa Medical Center and like me. He's a fan of Lin-Manuel Miranda And to my left the the naysayers We have dr. Nimeth Agrawal director of division of geriatric medicine program director of the geriatric medicine fellowship clinical associate professor in internal medicine at u of a college of medicine phoenix and President of the Arizona geriatric society in his free time he developed smart protocols and technologies to innovate and care around delirium And he helped banner become a geriatric emergency department and age-friendly health system And to his left is dr. M bar andrade a direct for cardiomyopathy and recovery at Banner University Medical Center Associate clinical professor at University Arizona She's an advanced heart failure cardiologists with a focus on recovery She trained at Northwestern Memorial, Texas Heart Washington University and Most recently she was at Advocate Christ in Illinois and she has survived two summers in Arizona and looking forward to more Right, and so your your host for this evening are Dr. Chris Vijay Who's been instrumental in helping to plan some of these events? He's a heart failure cardiologist With one of the few cardiorenal metabolic specialists in the United States he's a member the Arizona Heart Foundation executive board and cardiology medical director of school of ultrasound and he has numerous passions including helping the underserved He's very active in the field of preventive medicine With a non-profit and he's also a published author of a book Invoking your inner therapist in heart failure Thank You dr. Vijay and his co-moderator and judge is dr. Lexis Koskan She has a PhD from University of South Carolina, Columbia and postdoctoral fellow at Moffat Cancer Center and a lot of her work has been around HP V and Public Health and we're happy to get her involved in Trying to find solutions for amyloidosis So I'll turn it over to you too Okay, so we are Going to be debating the question of whether or not you should screen all adults with heart failure over age 65 So we've got our two teams in front of us We've got our yeas, and we've got our nays and the format for tonight is that each group will spend 15 minutes Presenting their case in which then after they each present their side. They'll both have time to have a rebuttal Using the evidence that was presented by the other team We do have criteria and how we're scoring everyone tonight Not necessarily in a competitive manner, but just to score the debate to make it a little more fun Which includes content delivery delivery the quality of slides analytical thinking rebuttal and defense and also audience voting So everyone gets to participate including those who are online in helping to provide some criteria for How this this? Discussion is reviewed. So with no further Waiting time sorry words are escaping me at the moment Exactly We will introduce the first team to come up and present their case for screening all adults over age 65 Who are living with heart failure? for this discussion Everybody can you guys hear me? So when I was I was sort of thinking how do I do this? You know, I think Dr. Vijay Dr. Dev said hey just just have this debate about pros and cons and you know How do we approach this disease as far as like do we really need to screen this disease? This is rare disease. I Was like man, I don't want to break the bank. I'm in primary care You know, I'm here like every single insurance company. You have to be frugal. You can be spending money You need to you know, really best value for the patient All those lines that we hear from the private sector is that if I if we screen all this population where you're going to break the bank So I think Why do I want to screen? Who do I want to screen size that I just have to screen just People that meet my criteria formulae doses. So I'm thinking I want to screen people that are African-American Western descent Caribbean Hispanics people that come to see me with bilateral carpal tunnel syndrome people that have spinal synosis people that have heft peps the phenotypic heft peps and And then I also want to screen people that could have the wild variant too, you know, so I Just going around the room today. I found out that a few people here Yeah, I know this person died of amyloidosis at age 48 So I want to talk to Susan and say the doctor sort of said, yeah, Michael this is there's a genetic variant You know, it's autosomal dominant and and these people could come earlier than you know So I was just thinking wow that's just a wild type then so I even get confused in the primary care, you know arena Do you have to? Kind of organize your thought process when you're trying to see, you know Who do you really screen for for these DCs? I think with the therapies that are available now. It probably easier to To just justify, you know, just screen for amyloidosis because it really does make a difference You know by the time you're diagnosing somebody with amyloidosis They could have like 2.5 years so live by the time they bounce between doctors. It could be over a year So the diagnosis is rich Definitely not a diagnosis that it's hard to to make if you're thinking about it if you're aware of it and And you know, we have non-invasive testing It's not that we're just gonna put a patient through like a colonoscopy that has to get prepped something that is invasive or anything like that As far as like who to screen I sort of touch about this a little bit male patient of age of 165 would have pep especially Western African descent black Caribbean Hispanics and then I also think so Let me just organize so if a patient comes to see me and I think the patient has cardiac amyloidosis So I think 90% of the time with the diagnosis with the history that I'm taking I should be able to make the diagnosis So patient has like I'm short of breath. I'm fatigued. My legs are swollen I mean, I'm struggling with my ADLs. I can really complete them any more, you know Get a really good history see whether they have any orthostatic symptoms see whether they have, you know Conceptions where they have impotence where they have diarrhea, etc Their family history of course and just some simple Examination findings like I've been saying the carpal tunnel the spinal synosis the Pope I sign they also could have arthritis of the shoulders hips and knees and and Also when you look at the EKG the usual suit in for a pattern Although they could have a lot of other things from, you know first-degree AB blocks to low voltage to a fifth of integral arrhythmias So, you know as far as like screening for for the disease It would just use tools like the EKG and the echo and but a phosphate scanning a free light chain essay It's probably not expensive. So it's probably worthwhile just going ahead and and you know using those Affordable, you know diagnostic testing to be able to Reach a diagnosis and finally, you know pull the trigger. So let me just make sure this is about ALDCs versus, you know Cardiac amyloid doses either wild type or You know ATTR I touch on this And I think this is just a really good point on why should we be very methodic when we are just trying to Select those people that we would just screen, you know Just get a very good history on physical examination get over their family history past medical history check their blood work Check their cardiac enzymes So I forgot the drop-on in there definitely check the immunofixational atrophoresis free light chain essay 12-lead EKG echo with strain PYP scan and of course at this Stage if the free light chain essay, it's positive Then you're kind of sending over to him along because it really is an emergency These are some of the things that I would look, you know When I'm examining the patient with they have bycipital tendon dislocation or rupture and that's a part of phosphate scan to the right You know, that's a positive part of phosphate scan the heart optic. It's just similar to the rib optic that makes it positive And this is just a macroblows. Yeah, and this is AL amyloid doses and This is the patients with the pre-orbital propa in amyloid doses So this is how I would screen for the disease, you know, it's not that I'm going to just be like Throwing a part of phosphate scan it everybody that walks into my office with distant exertion of heart fate or preserved rejection fraction This is who the patients that I would definitely Consider for screening. That's it. Thank you. So as a cardiologist We often see patients with constellations of symptoms and sometimes you have to put things together And it's not so obvious That hey, maybe I'm dealing with this problem. So I kind of put this slide deck together as to How I work up patients when I think that I might have a patient with amyloid So I'm gonna start with a case because I think we all remember the very visual learners And this is actually a patient that I had a 73 year old African-American male who had progressive heart failure symptoms over five years But really for me as an interventional cardiologist every time that I would check his labs his troponin was positive So he actually did have a number of hospitalizations Three of them he kept coming in his echo kept showing thickened wall And they kept calling it severe LVH But however when you see the EKG it was low voltage. And so why would you have severe LVH? You should have type ginormous Voltage on your EKG's again. He was high output He had JVD up to the angle of the jaw and when we went and took him to the right to do a right heart His cardiac index was really low. So he was in surely was in heart failure His BMP was elevated and the troponin that I put in red were always positive So again, he had hypertension and he did have chronic kidney disease He had a carpal tunnel release that was one of the things that I put together and then of course he had some spine surgery So when we start thinking about this, I started putting together This had to be something that was going on with something that was depositing in all of these areas He did have a cath. We when I did the cath. He did have some mild disease 60% we would not fix we usually do 70 and above his EF was 30 40 percent It was globally down but again it was first moderate and then he became severe in LVH and although his Wedge pressure everything kept going up and he was diagnosed all along with ischemic cardiomyopathy So he was put on heart failure meds But of course those medicines do not do anything for this problem Once he started getting the spinal stenosis and the carpal tunnel I said we need to start figuring out what's going on and then we actually did an s-pep and a u-pep And he got he got diagnosed with ATTR amyloid it was not ever considered and then we did the endomyocardial biopsy and Certainly we did genetic testing and he did have a genetic variant for this type of Amyloid so Basically one of the things that I've read about is that a lot of patients in the United States that are under diagnosed There's probably 44 million people in the United sense and the prevalence of this disease is about 3.5 percent We think that there's a lot of carriers. We think that over age 65 There's probably around 200,000 people that have been diagnosed and this is just from census from research from different papers and I have all my My sources here, but males again 70 percent compared to females. It's genetic It's an autosomal dominant pattern and there's lots of genes now that they're identified usually chromosome 18 There's going to be some diagnoses of that So there are two main types of amyloid that affect the heart There's the AL and then there's the ATTR The ATTR is what we're really going to focus on because we have actually treatment and it actually changes lives The AL is going to be in the hematology realm because that's a very poor prognosis It comes from the bone marrow comes from plasma cells and it's isolated It is also hereditary But it's going to be the light chain amyloidosis and those actually don't have a very good prognosis at all But if you actually have the ATTR either the wild type or the hereditary We have lots of treatment options and so you don't want to make you don't want to miss this diagnosis It's just like thinking do I have a pulmonary embolism if you do think it you start them on blood thinners until you prove That they don't have it so you got to think about these diagnosis in these patients So what actually happens so there is a protein called trans theretan it is they transport protein of thyroxine and retinol It's a binding protein It has four identical monomers and it used to be called pre albumin and you could still see it in the lab but it is a abnormal tetramer that forms and the the protein actually folds on itself and when it folds on itself it makes amyloid Fibrils it could it can be deposited in any of the tissues So we have the wild type and the variant type the wild type is not hereditary Median age is 74 25 percent of patients will have this on on autopsy So again, we're diagnosing that this is a very under diagnosed problem The variant or the genetic is hereditary. It's autosomal dominant and it's more of a late onset so again, we have a We have a Continuum when you first see this patients may be asymptomatic The septum starts growing large and then it's going to go bigger and bigger and bigger and once you start having more problems You're going to see atrial fibrillation Conduction disease problems and these are all the people that walk into my clinic on a daily basis Complaining a shortness of breath. We're seeing a ton of a fib and over the course of the years Then we're missing at the end. It's this full-blown ATT our cardiomyopathy So this is what a heart looks like with amyloid when you actually have the infiltration You can see the infiltrated heart with the amyloid fibrils and what happens is it impairs contraction? And so you actually don't you get heart failure even though you have a big thick heart. It can't pump. It does not work well So what are some of the signs again? Chest pain shortness of breath edema, especially in the lower legs We see this all the time as cardiologists Exercise intolerance a fib aortic stenosis. These are people that should be screened for sure for this Now if they add other symptoms eye floaters spinal stenosis carpal tunnel syndrome bilaterally ascites All of these add as Mike said to the diagnosis that they should these patients should be screened So if somebody over age 65 starts coming in with these symptoms, of course, we want to do a GI complaints I'm just gonna keep going so here's the EKG because it's gonna be a very thick wall But you can see very low voltage all of these are less than one box So it's a low voltage for the opposite of what you're gonna see when you're actually looking at the heart and Here's what LVH looks like up on top and this is what amyloid looks like so it's a much different EKG So you could see a paracetamol long axis of my EK echo of the amyloid This is an amyloid heart and I'm gonna show you at you could see that it's hardly pumping although the walls are really thick you have by atrial enlargement These are some of the signs and then of course a restrictive filling pattern, so they have diastolic heart failure They have a non-compliant So some of the issues are that there's a lot of things that are mimics This is the PYPP scan when you actually want to make the diagnosis We have something called the Perugini score and you're gonna compare it to the uptake in the ribs if it's equal to the rib It's likely positive, but if it's greater than the rib, this is the heart you have a positive scan So I just want to show you one last thing Heart failure and amyloid can coexist Hypertension and amyloid can coexist you want to think of all of these diagnoses. This is hypertrophic cardiomyopathy Right on this side. This is amyloid heart and it looks very similar You have a hypertension heart with someone with renal failure and this is somebody with lysosomal storage disease So although we're seeing all these patients come in it's very similar presentations on echo And so you want to have the ability to test these patients So again, why should we screen because it's life-threatening. It's progressive. It's infiltrative early diagnosis is key We have treatment. We have treatment options It's easy to misdiagnose, but if you put it all together you can make this treatment and make their lives much better Again, a lot of the routine medicines for heart failure do not work in these patients And so you since there were drugs that are gonna thwart the progression my my thing would be we're Screening for so many other things. I think that we should just go ahead screen patients You have to have a gestalt that you think this is going on and their findings, but you really want to actually make the diagnosis You don't want to miss it