 All right, can you hear me? Okay. All right. Thank you again to the organizers and to dr. Dev for including me in this opportunity to join you guys for this meeting So these are my disclosures And this is my other disclosure why I'm with a cane And that was on January 8th, so I'm happy to be here now with just a cane so My objectives today is just to briefly review and get my goals are going to be to talk about when to suspect amyloid and Then the keys to diagnosing light chain and TTR amyloid Again, I had this slide forever and I've been doing amyloid talks since for 2014 But I love a job of the hut because Virchow described this is what the iodinated staining looks like in 1884 Amyloid means starch in Greek in which and he called it lardaceous and amorphous deposits in the heart and Again, these are protein misfolding disorders and there's numerous causes of amyloid doses But we're going to be focusing on the two most common and again It's these when a protein dissociates and these fibrils become insoluble and deposit in the tissues Again, what every practitioner really needs to be aware is in 95% Vamalloy the effects of heart and again is dr. Davos Dave was talking about this is a systemic disease But I find that it's cardiologists that are often reaching out to neurology hematology and we're the ones that are One's recognizing this what everybody knows the two of the most common that we're going to be talking about is light chain Which which I can see if I can get my pointer to work I'm not sure if I can well anyway Anyway, the things that look like Look like olives or plasma cells And this is a plasma cell dyscrasia where a clone of plasma cells in the bone marrow are producing these cardiotoxic proteins or light chains and that is although not as common as TTR is very important to diagnose Transthraetan is liver is the production and a lot of people don't know it We'll talk about this TTR can either be wild type Which means there's no mutation in the gene or hereditary where there's a variant that causes this protein to misfold And again, I'm I think my colleagues are me talking about this I've always had this slide to emphasize to my primary care and to my cardiologists that how critical it is for them to make sure that they follow these algorithms that we're going to be reviewing and because of especially in the nature of Al which is really what got me passionate about this in 2012 when I had a young 42 year old Dying of light chain and trying to navigate getting him the care He needed and because we have new chemotherapies and stem cell What's really important that we reach out and get this diagnosed early? My one of our colleagues is gonna be talking about Amgus But I always needed something to dumb it down for me because I'm often actually arguing with my hematologists that I want the heart biopsy Because they often just want to stop at a bone marrow biopsy and again Because they often mislabel my patients is M. Goss when they really have light chain amyloid So it'll be important to as a cardiologist. Sometimes you have to go to bat So transthraetan amyloid TTR transports thyroxin retinol TTR The amazing thing is we don't really have to depend on it And only 10% of our thyroid Transportation is from thyroxin Vitamin a because it's so fat-bound we can actually as we'll be talking about in treatments We can get by without TTR I also remind people that it's pre albumin the reason it is is on old days when we used to do something called electrophoresis It's the protein just before albumin, but it's amazing that we never knew but we could actually measure TTR Stabilized levels in our routine pre albumin thing So as we're going to talk about I can't quite see my slides We're going to talk about the pathology and again This is a nice cartoon from the guidelines that talks about how this tetramer of Thyrox of TTR can dissociate and that's what forms these Vibrals that start accumulating these insoluble fibrils in the tissues that leads to the pathology This is an old slide happen I think it's important to think about the phenotype and this gets a little bit into how to apply the guidelines That you have to decide what about my patient am I going to do the rule-out light chain? We're going to go through that algorithm that is everybody should be aware of I'm at the VA my biggest population as I deal with about 40% African-American So I see a lot of hereditary TTR, which is common because of this mutation present in 3.5% of blacks Don't haven't seen as many other variants But it's very aware and again the common thing we're gonna see is older men And this is that wild type phenotype This is from the new guidelines, which really the emphasis it to our colleagues. Let me see if I can get my pointer Anyway Anyway, the main thing is to make sure that people are aware as a cardiologist I'm the one making the referrals to neurology and hematology Is that the extra cardiac manifestations and those are the clues to suspecting? Ameloidosis we're familiar with the cardiac manifestations, but often we miss the carpal tunnel When we did our assay even though I found that probably most my patients if I had questioned them They had carpal tunnels and symptoms, but they hadn't been diagnosed the spinal stenosis is due to TTR in this case because it deposits in the ligament and phylovum that causes spinal stenosis we see the neuropathy and Autonomic dysfunctions often written off as just do Orthostasis due to medications, but the intolerance of cardiac medications is really a clue or the hypotension And I do orthostatics as part of my routine physical on every patient What I want to make sure people were aware of this slide is that we are talking about Systemic I'm talking about ameloidosis and protein urea. It's very important to pay attention So I often order spot urine with everybody to look for Nefrotic range because that's really a big concern for light chain And again, this is something that I think's already been underscored And we're hoping when these gatherings with this interest that we're getting people to not do this where we have patients going To three different doctors and the diagnosis for one or two years when they really could have been on treatment much earlier So what are the keys to diagnosis? Step one suspect it step two. We're going to screen for light chain step three We're going to do centigraphy for TTR. Those are the things you're going to go home with today This is the new algorithm, which I will say the graphics are not as good as the old algorithm But I feel figured I better bring the 2023 guidelines. We're going to start with step one. What are the clues and Again, this really hasn't changed, but this is from the current guidelines And again, I want to underscore on the right all the extra cardiac manifestations the carpal tunnel the spinal stenosis Hip or knee surgery. How many people do we know with that? Again, not specific but again clues the Neuropathy a lot of people aren't aware especially in the autonomic how GI symptoms either do either gastroparesis or often misdiagnosed or ignored And urinary symptoms on the cardiac one thing I did add that they didn't put in the guidelines This is aortic stenosis, which I'm going to discuss that we see this low flow severe aortic stenosis Then what I'm going to be going through is the EKG and echo criteria to have what for that step number one is suspicion suspicion suspicion So One of the things this we were talking about a lot of people say well if the heart if the EF is reduced It can't be amyloid. That's not true So it's just important to heartfelt and the reason is a lot of times my patients may Manifest when they develop new a fib or heart block and the EFs are often reduced in that setting So I try to say don't worry about the EF focus on the other issues The other clinical things is often a fit may not be fast despite them being on no rate control drugs Why would a 70 year old have a heart rate of 70 or 60 in a fib? It should be higher tells you there's AV nodal disease They're not tolerating their heart failure medicines Of course, you'll hear me talk about GDMT because I find my provide my colleagues are all just focused on GDMT, but they never ask why does this patient? So I call it goddamn medical therapy Because they're not doing the diagnosis and they're going like oh well Let's just let's just take the corvaital off and put them on my topical So we can try the intresto again, and and then you know it's like no the blood pressure 75 Let's think about why the blood pressure 75 rather than keep messing around so GDMT think about maybe it's amyloid and why this is why the patient's not tolerating it Again, this is from the unveil trial that I added the notation think about aortic stenosis, especially low flow severe AS Doesn't mean don't do the taver, but it's important to think about it in this one study with Matt Maurin colleagues They looked at the prevalence by Centigraphy of TTR amyloid and patients undergoing taver and it was 16% of the population had at least Level one two or three of TTR evidence and they're on that scan So I personally wonder if we shouldn't be scanning everybody with it going for a taver Especially if they're out wall thickness is above 1.2 My last one I add here is not in the guidelines But this is my little pet peeve is I've had a couple patients present with stroke that later came out to be amyloid and Often if I have a patient with the L a thrombus, especially if they've been on anicoagulation Think of amyloid because it's a pro thrombotic state both light chain and TTR So what are the clues on EKG and then most you guys are already Eligicated enough I grew up in the era where they said you had to have low voltage Bottom line TTR only 10% have a low voltage maybe 30% of light chain It's the absence of LVH or the absence of high voltage and somebody with a thick heart The other thing is the pseudo-infarct pattern You'll see what looks like an inferior am I into your lateral interoceptal Again in the absence of wall motion abnormality or evidence of scar think amyloid Why is there a pseudo-infarct pattern? conduction problems AV nodal bundle This is one of my patients who again very typical doesn't have high voltage, but his wall thickness is 1.6 So why does he have this pattern? There's no perfusion abnormality says normal coronaries But what is he out who had inferior q-waves and interolateral q-waves and in the absence of LVH So echo this is my pet peeve So the criteria are very the bar to suspect is very low thickness of 1.2 Normal is 711 7 millimeters to 11 You should be thinking and this is a big deal because I grew up in error where we ignored Everybody until the wall thickness got to 1.6 No more everybody was written off as hypertensive heart disease So you what we're going to talk about is whether you're a cardiologist or not reading the report Don't trust your readers and sometimes I don't trust my sonographers. I probably re-measure the heart 40% of the time Look at the measurements. I'm going to show you how to look at a report If your lab isn't reporting relative wall thickness Start doing it and have it auto-calculate it and we're going to talk about the role of this getting this relative wall Thickness score and show you how we calculate that By atrial dilation not specific It helps me if I have somebody who's got a thick heart in the L left atrium is normal They don't have diastolic dysfunction. I go like maybe it's something else But most these people are gonna have left atrial enlargement diastolic dysfunction And then we're gonna talk a little bit of tissue Doppler I call it the 5 5 5 rule and I'll just show you a picture of that again how to look at the report And again because I'm an echo person. I always look at my own images I can tell what first thing I ask is who read it never mind. I'll read it myself We all have that bias and then we'll talk about strain imaging Okay, so I don't know if my pointer is gonna work For the non echo people the heart should shorten Insistently so it was about 20% shortening between if you take two spots. The normal is that red red bullseye Is working This is one of my amyloid patients where we can see the strain is completely abnormal in the base and the midwall But the apex is preserving I've gone to where you can almost see it when you look at the echo The apex is contracting and the base is not This is one of my patients who just recently had an echo very typical of the very thick notice How it's not necessarily thick everywhere the septum often is more thick He has grade 3 diastolic dysfunction in this for the non echo people This is the tissue Doppler signal and one of my clues is what's called the S prime What it is is insistently the at the annulus should be pulling down to the apex should be at least a 10 cent I mean 10 millimeter displacement, so I look at my report So if somebody's got a normal EF and the S prime is down, there's this is discordant There's something wrong and then finally this is our strain imaging which it should be But minus 20 minus 18 So one of the things we report routinely is the global longitudinal strain and our guidelines if it's less than minus 15 We should be suspecting amyloid So look at your report. I actually look at the report before I read the echo and It's one of the new habits. I've developed And notice this patient 1.66 he'd been written off as you know hypertrophic or hypertensive heart disease This is the relative wall thickness point seven six normal is less than point four two So we have it in all of our reports and try to get my trying to train my my readers to Bring that out and down here is the tissue Doppler and you'll see that the S prime is only four point nine Clues so I always start by reading the numbers and then I look at the images and I make sure my numbers are accurate And this is just a typical patient that you shouldn't even have to like look at the echo Because there's a gentleman that probably had so many echoes before he was diagnosed 74 black black gentleman. He'd been labeled as n-stemmy. He even had a fib He was in having hypotension. He was needing my to drain. He had carpal tunnel. He had spinal stenosis I mean other than having you know, TTR, you know tattooed on his forehead He had just about everything and again his echo showed a high thickness and again bottom line He actually ended up needing a biopsy because he had MGUS and we confirmed TTR So for my sonographers, I always say make sure your measurements are accurate for my readers Report the wall thickness look at it and make a conscious effort should be as important as the ejection fraction and For my ordering providers read the report look at the numbers Don't rely on your interpreter to tell you to what to suspect our job is to suspect And this is from the European guidelines They say if you have a septal thickness of 1.2 and any of these things Suspect it and these are people to think about screening. So and Then this is the Davies score that I was talking about from the Mayo Clinic from Margaret Redfield and Martha Grogan's team Where they came this score which helps a clinical score to help us suspect And again, this is especially powerful for wild type amyloid. We're aging just being old is a risk factor And it's something that Sandesh was talking about do we screen all 90 year olds? So the lab clues oops, I missed that sorry about that, but but the base thing of what we wanted to score I don't know how to go back here. We go is To look for the light it's for troponins Still even a month ago. I had one of a new amyloid patient They'd labeled him as n-stemmy took him for a cath and again. He had persistent troponins We order outpatient troponins make sure your lab can enable that and then I also have in our lab and anti-pro BMP It's disproportionately higher in amyloid patients in the ratio instead of being 4 to 1 is often 10 or 20 to 1 be might be NP and So now step 2 Look for light chain amyloid now We're going to talk about this but the bottom line is you should order this lab and if your lab We have a whole amyloid order set Make sure your lab has a clear order set and again. It has to be immunofixation My the VA it says s-pep But everyone goes to Tucson all of our lab samples go to Tucson where they do immunofixation of the urine and the protein The reason is is s-pep is not sensitive enough. You have to do immunofixation And then you need to do quantitative cap and lambda light chain. So all three must be ordered and done And then what you're trying to do is find out is there a monoclonal gamma But the if there is then you have to work with your hematologist to figure out what it is and Then if any of these three are you have to work with your hematologists Like I said, sometimes I have to tell my hematologists. I want the cardiac biopsy Because they often would say no, no, no, it's fine. The bone marrow is fine You cannot diagnose tissue from the bone marrow necessarily. Okay, so this is what we're gonna be talking about the work Up of the monoclonal gamopathy and another talk coming up here But now the next thing is step three. So number one suspect number two screen for light chain number three suspect for Centigraphy and I put I keep emphasizing spec but my colleague dr. Shaw's gonna be talking a lot about that importance So you need to see grade two or three uptake. I Tend to follow the older algorithm So I'm being gotten nice and I brought up the 2023 guidelines I tend to order depending my phenotype both the centigraphy and the light chains because if I've got a 85 year old Caucasian veteran with heart failure. I'm Exelecting TTR it takes sometimes a week to get the the light chain stuff. So I order both at the same time and This is where they have this little Michelle Kittles and where they say It's okay to do both at the same time But if I had a 45 year old female with new heart failure and a thick heart, I'm gonna start with the light chains So this is the centigraphy which Nishan's gonna talk more about about how we learned that the these phosphonate Tracers bind to the heart with bind to TTR more commonly and this was the pair of the paper that kind of led to us identifying what became the non biopsy diagnosis and Nishan's gonna talk more about these things So in summary, you should order the centigraphy and anybody you suspect again I order simultaneously or you can order it after you've done your light chain So again and again the final thing is when you need biopsy and we're going to talk about that in another talk but if you have positive Gamopathy or At all you're in the need of biopsy So I'm not going to talk about genetic testing But once you confirm TTR by biopsy or non biopsy then we'll do the genetic testing So in summary, these are the remember the clinical do clues to this Don't forget about the echo clues and again the the biomarkers and again the first thing is to always suspect and Make sure you do the step 1 2 3 suspect screen for al and do centigraphy and Thank you for your for your attention