 Okay, good afternoon. I want to thank the ACC Arizona for letting us do this joint session. I'll introduce our panelists and then our moderator. To the left is Dr. Julie Rosenthal, Mayo Clinic Arizona, Director of the Emily Dosis Clinic. And next is Dr. Nishanshah, the Director of Nuclear Cardiology at Lifespan in Providence, Rhode Island, and Governor-elect of the Rhode Island Chapter of the ACC. Next is Sharon Dickinson, who's a position assistant in the West Valley at Heart One. Next is Dr. Amber Andrade, who's a Director of Cardiomopathy and Recovery at Banner Phoenix. And next is Andrew Boshara, Director of Mechanical Circulatory Support at St. Joseph's Dignity. I'm Sunday Shtave. I'm a Cardiologist at Southern Arizona VA and at ASU. And our moderator today and speaker will be Michael Polinario, who is a Cardiology Fellow at Mayo Clinic Arizona. Michael, it's very nice to meet all of you. There's a few familiar faces out there, so nice to see some familiar faces when you're talking to a crowd, of course. So we're going through a case presentation of a little bit of an atypical way to uncover some amyloidosis, cardiac amyloidosis. So let's begin. And I only have Dr. Dev, Dr. Rosenthal's names up there, but also thank you to every panelist here for helping. It starts off 76-year-old Caucasian male. He presents to our emergency department. This is our first time meeting. Symptoms of chest pain for one hour. He has a history of hypertension, albeit long standing, poorly controlled hypertension according to his wife. Hyperlipidemia, a chronic right bundle. His medications at the time was Aspirin-81, Recivastatin-40, and Balsatin-160 daily. Other risk factors. He has a very remote history of tobacco use. He's a non-drinker. He has no family history of cardiovascular disease that we're aware of. So he was shopping at Costco, and then he quickly began experiencing some chest pain. He was pumping gas. He had an 8 out of 10. In nature, it was aching. It was across his chest, down his bilateral biceps, but he didn't have any other symptoms, no nausea, no vomiting, no diaphresis, nothing else on top of that. He reports somewhat similar symptoms, but much, much less severe prior for the two to three months prior. He's an avid road cyclist here in the valley. He's a part of a group that rides about 10s of miles a day without any issues. So he had a similar, but very, very minimal symptoms prior to this. So his wife, who I always say married men live longer, decided he ought to come to the emergency department immediately after that. So on presentation, he was a-febrile. His pressures were no more intensive. Harry was 71, and he was not to kip-nick. He was sitting at 64% on room air. On physical examination was relatively benign. Normal body habitus, he was well groomed. He appeared uncomfortable, but not in acute distress. He had a normal heart rate, as we see up there. He had a regular rhythm, no additional murmurs, rubs, or gallops. His lungs were clear. He had no issues with breathing, and no lower extremity of demon presentation. Some of his labs prior to what we're going to talk about is a hemoglobin of 14, platelet of 196, white kind of 11.6, so mildly elevated. Gratin was normal without any electrolyte abnormalities. His lipid panel, total cholesterol is 206, LDL is 127, high-density lipid was 39, and triglycerides are 223. His initial troponin was 2,721, just x-areas normal, and then our ECG is the next slide here. So I'm going to pause here. It's going to be a little difficult, so I apologize, but we'll have a discussion on what our thoughts of this ECG is. So we love any audience participation. Please ask or comment. Give your thoughts on this ECG. We do not have a priori PHG to compare, because this is the first time coming in for us. But maybe a few things that we were discussing since there's the, this is a major secret that this is an amyloid discussion, but he doesn't really meet criteria here for low voltage, because there's less than five millimeters in the limb leads. So we'll do that discussion. So I guess with the ST elevation, chest pain, elevated troponin, you have to respect all of these at a 10-foot view. So what would you like to do for this gentleman? I think everyone would have the same exact thoughts. He went to the cath lab. He had 100% occlusion of his proximal RCA. He also had a few disease processes, stenosis in his OM1 and in his LAD. We ended up fixing that 60% OM1 because the following day he was planned to have a stage PCI overnight. He had evolution of chest pain that was not treated with medications and he ended up going for a semi-emergent cath lab over in the middle of the night. So RCA was fixed and that OM1 was fixed. Here is an EKG. We're sorry, here's an echocardiogram. Let me play these again for us. So I'll turn to our panelists or the group. Any initial thoughts of this echocardiogram? So just looking here, well, they're not really playing. Okay, there we go. So reasonably preserved LV function, but the wall is probably mild to moderately thickened. The aortic valve has some thickening as well. The mitral valve over there on the apical view has some thickening as well. We can't really tell the images here whether or not there's really that left atrial dilatation that we talked about on the EKG, but certainly some concerning findings for amyloid, but nothing really definitive, at least on these images as he presented them. Although not the view to really assess RV wall thickening, you do see some hints of that here as well. A few other notable things here since it's an amyloid discussion is that there's no pericardial effusion that's noted on the echocardiogram. Ejection fraction, I'll just go to this, was 49%. They called a mild moderate left ventricular hypertrophy. Wall thickness was increased in the septum to a greater degree in the posterior wall, but otherwise the no real significant valvular heart disease and again no pericardial effusion. The bottom right shows the regional wall motion abnormalities as you just mentioned. This is the actual read? Correct. Okay, so just because I think Dr. Alberta Warner, who spoke this morning in our amyloid session, made I think some really important points about how we can use the ECHO lab to really kind of drive downstream testing for amyloid. There's a few things that I've started doing in my reporting that aren't on here that I wanted to kind of bring up. One is that the wall thickness, calling it mild to moderate is okay and buried somewhere in the report I'm sure is the actual measurements, but I've moved those now up into the final impression to say here's what the average wall thickness was at least between the septum and the posterior wall. The other thing that Dr. Warner talked about this morning was incorporating relative wall thickness measurements and I don't know if those are included on your reports, but having bumping those things up into sort of the conclusion can really help people at least key in on those things. As you know in an ECHO report, there's a bazillion different numbers that you get and so bringing those up and if you have any concern about those is something really important I think. Absolutely. So in our reports we can look at the EDA measurements. A lot of the times if there's no abnormalities, number three says we typically will write normal left ventricular feeling pressures on top of that, but I agree those ought to be highlighted. We have to take a step back and say that this is really at the time we had no idea that there's going to be amyloidosis on the horizon for this gentleman and this was in the acute setting of an MI. So I think a lot of the question or focus would have been for ejection fraction and regional malmotion abnormalities too. These are actually the left ventricular measurements so the thickness was at 13 of the ventricular septum and then the posterior wall was at 10, but albeit this is again done in a hospital bed without an ECHO table where we don't have that nice drop down area, perhaps the patient is only laying on his back etc. So not the most ideal situation to perform an echocardiogram. Yes. So all wonderful comments which we will circle back on. So ultimately he was all of the symptoms had resolved after PCI again was to the RCA and the OM1. He was discharged at Aspirin, Brilenta, and Metropole of 25 milligrams twice daily. So I was seeing him as a three month follow-up and during our three month follow-ups after MI we typically get basic lab CBC, BMP, and echocardiogram and anti-pro BMP. So those are all things that were nicely completed prior to our visit. When I saw him he was feeling well, he was feeling great. He doesn't actually complain too much. The only thing he really complained about was that he wasn't back to his baseline and part of that was probably his hesitation to exercise again but also his he doesn't feel like his physical prowess was really quite up to date. He completed cardiac rehab and he was able to walk several miles and he worked out in a stationary bike for 30 minutes to 45 minutes at a time. Never got back on the road quite yet but he just didn't feel like his self was the big thing that he kept kind of bringing up with us and his wife kept agreeing that he was just not as energetic and when he wanted to exercise he felt like he was quitting a lot earlier than she expected. Medications at the time was ongoing DAP therapy. He was the only in Metropole 25 milligrams BID that's tartrate and resuva statin and then his physical examination he did not look like he was in any decompensated heart failure, no lower extremia edema his lungs sounded clear there was nothing of concern on physical exam. When he initially presented I think you said he was on Valsartan was that switched out for the metoprolol? So during his hospital stay he was hypotensive on the on discharge actually I oddly enough so that's a really important piece right and and being on metoprol instead of the Valsartan is a clue particularly for amyloid we talked in our other session that sort of intolerance to you know blood pressure lowering medications is is potentially at least a sign of amyloid so just highlighting for folks that there was this switch between Valsartan and metoprolol and and knowing that he was hypotensive going out the door from the hospital is a key piece. I will just dovetail on that with amyloid patients thinking about starting a beta blocker and someone perhaps a fixed stroke volume and then further limiting it maybe that could also raise a red flag or question my patients now on some form of guideline directed medical therapy feeling a little bit more fatigued not having that same pep in their step should certainly make you ask the question could something else be going on. Absolutely very astute a very astute finding there so here again was his labs that were completed prior to our visit renal function looked to be stable without any electrolyte abnormalities his creatinine was around 1.1 to 1.2 during his hospital stay so no major changes the the thing that sparked me the most was his anti probe BMP was 1707 all in the setting of someone who does not look like they're in any acute decompensated heart failure no renal dysfunction so it's really something out of out of context or out of proportion to the gentleman presenting in front of me that seems to be a little bit more than what I expect that gfr is in fact low and for a guy that's otherwise sort of healthy right that raises a flag for me too so I wouldn't call that normal sure absolutely absolutely and did you say you do you don't get a follow up troponin we so we typically don't for for in this scenario it's really just cbc bmp and anti probe bmp ekg but Sharon to your point with regard to follow up cardiac biomarkers or just looking at your patients when you order cardiac biomarkers if the biomarkers are out of proportion to what you see clinically that is raising the question of some sort of myocardial injury process happening so once again ask yourself with this I mean with this bmp specifically you got to keep in mind you do have other reasons right the renal failure the age so a lot of other things also factor in obviously not to this degree of raising the bmp but just to keep in mind for other scenarios as well I think just the fact that you did a bmp should be congratulated because uh I don't know that that's standard practice for a lot of people so you weren't you know in fact why did you order a bmp um to be I would love to take all of the credit here but a lot of it is a a panel that we typically get um so it was kind of a silver lining that it was lucky for this gentleman to allow me to pick up a stootlee on something that is not easily seen by the naked eye so you got lucky well I just wanted to point out the the the natural peptides are indeed really promoted right now in the current our field of guidelines so we do want to promote them so thank you absolutely so along with this was an was an echocardiogram so I'll start off um within three months there's pretty dramatic changes the lv thickening is pretty profound um in that parasternal long axis view I'm also concerned about the patient being more brita cardiac um than he previously was um there may be some signal that there's some by atrium enlargement happening and then the important distinguishing factor is remember we pick our words pretty pretty carefully in emilydosis when we're describing the left ventricular thickening we don't call it lv hypertrophy so I'd be interested in seeing what the ekg looks like right now too as well as a chest x-ray any other thoughts on the echo I agree with the lv wall thickening especially if he's only on metoprolol 25 which is a pretty weak anti-hypertensive and he was hypotensive like you said and the only other thing I'll say is compared to the last one this kind of increase in the wall thickness over that short a period of time to me at least from what I've seen in my career not not a long career yet but um that's to me al amyloidosis until you prove otherwise because there's almost nothing that makes you not hypertrophy but I'll say thicken as as quickly as that yeah and if we knew nothing about the case you know our differential diagnosis would be hypertensive heart disease and end stage renal disease patient would want more views of the aortic valve is this a aortic stenosis case those sorts of things would come to mind absolutely curious did they do strain imaging on this study or no they did they did do stream imaging and this kind of helps to highlight the quality the quality and difference of an echocardiogram performed in the hospital in a bed versus an outpatient echocardiogram where you have optimal settings and you have all the time in the world for a sonographer to be able to get the correct images and and get the correct angles so absolutely I wish I had the EKG with on on here but I believe me there was no change in the echocardiogram or the ECG sorry yes the STs STs were no longer present yes so here is our strain image from this echo yeah so here you can see a very nicely delineated apical sparing pattern and a markedly reduced average global longitudinal strain which is consistent with possible amyloidosis made the point earlier in our other room for those that didn't hear it there's a paper that just came out last week there's a multicenter consortium that looks specifically at this pattern and while we at least thought that this was fairly pathodemonic for amyloid it's actually not and there are a number of other conditions that have the exact same pattern so while it's suggestive of amyloid it's not diagnostic and so we made that point in the other room but this for this audience here does the audience know what this is called and to Nishan's point also from European data as well they found that looking at LVEF to GLS ratios are actually have a high sensitivity and specificity for this condition as well so odds ratio for that marker as opposed to just cherry on top pattern alone is drastically better perfect so so echoing Dr. Shaw here and the color doesn't help but as soon as you see you want to immediately think cherry on top this is amyloidosis but again this is a gentleman's long-standing history of hypertension poorly controlled according to the significant other also in the setting of someone who had a RCA infarct and an OM infarct so kind of the abnormal strain patterns might also be secondarily explained by those items I have a hard time reconciling the uncontrolled hypertension with someone who came in on a single antihypertensive that wasn't at max dose correct it sounds like historically his blood pressures are typically in the 130s to 140s for an unknown amount of years but his wife just said that he typically doesn't check his blood pressures before us us finally meeting him so we just had to take her word for it so with those thoughts in my mind I didn't want to jump to conclusions let me also add they had a recent MI so the strain pattern is going to be abnormal absolutely so in the inferior portion and the anterolata portion those could be explained by this possible RCA infarct and his OM infarct at the same time so this is the final overall read of the echocardiogram so a moderate concentric left ventricular hypertrophy with apical sparing pattern on the strain imaging consider evaluation for infiltrative cardiomyopathy if clinically indicated ejection fraction I went from 49 percent to 40 percent his global longitudinal strain is negative 11 so normal is greater than or more negative than negative 18 get a 1 out of 3 left ventricular diastolic dysfunction get a mildly reduced right ventricular systolic function with FAC of 30 percent and then again no pericardial effusion seen on it just one comment to add to what I said earlier in this particular case like I said the the change in the the wall thickness is extremely important so writing that again here either either up where you're talking about the moderate concentric hypertrophy or adding a statement at the bottom compared to the prior study you know there is a market increase in in wall thickness etc I think those kinds of things again clue people into to sort of the acuity from reading just this yeah there's a lot of concerning stuff but it's not clear that there was an acute change from the prior study absolutely and then here are alve dimensions and alve measurements where the ventricular septum was measured at 13 before and the posterior wall I believe was 10 so slight increase there you know yet while there's significant lbh I'm not seeing that the relative wall thickness is greater than 0.57 so this is not screaming amelie to me yet so what would what would you guys like to do next before as the next step of evaluation the shunt as a board of governors of the asnc what would you like to do next I'd love to do cardiac bone centicrophy with pypr hdp um and at the same time I would like to get serum and urine labs to assess for al amelie doses and just to clarify does everybody know what these labs that we're talking about are somebody else yeah right so the three labs that you want to obtain to rule out al amelie dosis which is the equivalent of your st elevation mi there are three so that includes your serum and urine immunification alongside a serum-free light chain so immunification of the serum and the urine and a serum-free light chain the other thing I'll say is that I don't know if we're going to get this imaging or not but with my clinical suspicion now with the increase in the wall thickness so so if you're thinking amelie dosis you need to also think about the different types here I'm specifically thinking al amelie dosis because of the time frame um even though I'm asking for a cardiac bone centigrafy study in most cases not all in most cases that study will be negative um and so that's I'm I'm really trying to rule potentially in something by being negative as opposed to looking for something that'll be positive just to compliment that I don't know about each of your centers but if you order let's say a cardiac MRI or a pyp scan usually those they book out right how many can get a pyp or an MRI within a week raise of hands within a week nobody how many usually like month three months okay maybe your centers get them faster than me but again imaging is a great tool but once again you do not want to miss al amelie dosis so it's really quick and cheap to order these three labs so that as long as they're negative that's fine we can wait all the time in the world for an MRI or a pyp but again um wanting check those check that box make sure you're not missing something I just remembered we didn't really take that good of a history so what um or now that we're thinking about amelie so what what are the history elements that um we would we would want to look for so anyone from the audience or the panel please yeah so carpal tunnel spinal stenosis what else tendon rupture so how would you assess for that by the way I think that's a really good question we usually start pretty broadly you know I want to know about family history as a patient losing weight like just a full review of systems but you're correct you know typically when we're thinking about a ttr amelie dosis you worry more about the neurological manifestations but you know this is after an mi I wanted to ask you what was your conversation like with the patient when you're potentially working through this diagnosis in your mind but um before we get to that did you guys have anything else to add about your review of systems when you're trying to differentiate al versus ttr amelie I think there is a lot of overlap but I can say for my al ameloids probably the two things I see more common al than ttr would be the macroglossia when you have them look inside the mouth and you see the tooth indentations I have seen that in ttr but more rarely that's more classic for al ameloid there is overlap in the carpal tunnel but I would say the sort of non-traumatic bicep tendon rupture this is going to be more patho-nemonic or the nephrodic syndrome and asking about that foamy bubbly urine that's more classic al so there are classics so I think the key is just doing a head to toe and that might raise some red flags and one of the red flags we've already heard a little bit from Dr. Apollonero that I think is making him scratch his head because this is his case and he actually did this all on his own um was the question of just still not feeling better not having that same pep in the step on very minimal beta blocker therapy so I think that was a cardinal or heralding sign in this case the only other thing I'll say because we're talking a little bit about PYP, HDP imaging we made this point in the other room but I'll make it for this audience that you can have a false positive result at the time or around the time of an MI you're three months out I think you're okay the inflammation and what not has subsided but the idea being that a recent MI or active myocarditis will give you potentially a false positive and I'm sorry this is a way we used to diagnose like 50 years ago I'm exaggerating MI was using bone scientific rate this is an old MI scan which I'm not an imager so yeah no absolutely so we we don't want to image too early in this case I think you're you're fine at the time frame that you're at now but if they had chosen to do that within the hospital there could have been some issues with interpretation at that time given that you're so close to an MI would you have opted for a cardiac MRI if you were more in that time frame versus of going with the PYP so my personal opinion is is that you know a cardiac MRI so the cardiac MRI doesn't fall out sort of in the diagnostic pathway it's suggestive but it doesn't actually establish the diagnosis so for for the time being I would not have selected that as the first test but certainly there are things that you can see on an MRI that are suggestive of amyloidosis but but there's nothing definitive in the same way that you can get a non-invasive definitive diagnosis how would you assess for biceps tendon rupture so I think I just want to mention sometimes patients don't even know they have a ruptured biceps and so you actually have to actually do that as part of your cardiovascular exam so you'd be surprised how many patients you actually make the diagnosis it's very interesting and then what other musculoskeletal aspects anything else carpal tunnel spinal stenosis biceps tendon rupture what else sorry skin changes okay any other musculoskeletal manifestations sorry osteoarthritis right that's a good point so hip and knee replacement and then rotator cuff injury so this point about the avid cyclist so our colleague over at Cedars has written this up but you will find a lot of amyloids and athletes they run in the same circles but I would say if your patients even if they don't have carpal tunnel or biceps tendon rupture ask them about trigger fingers you're going to see recurrent trigger fingers definitely needing a lot of releases and all the joint replacements and multiple kind of also goes with being the athlete but the trigger finger I think is another classic telltale sign I think the story is going to evolve so you'll soon find out so so to answer an earlier question so this gentleman and his wife we're sitting in in clinic and reviewing all of this data going forward I asked him all of these questions whether he has any sign symptoms of amyloid deposition in his musculoskeletal system with formal urine etc and everything was time again negative negative negative so we're having a gentleman with a recent pretty significant mi anti-propene p that is elevated to out of the expectation of his of his physical examination an echocardiogram that shows abnormal strain pattern but also something that can be uh consequently uh described by his is mi in hypertension so I didn't have a very strong inclining in either way to be quite honest so um I casted my nets out a little bit wider than doing the al amyloid evaluation right away with s pep u pep in a in a possible p y p and actually went to a cardiac MRI instead to see if there's any information about deposition anywhere else whether there's an infiltrate of cardiomyopathy or as can be completely so here's an image of of the cardiac MRI this is kind of a kin to our picture of a paraceral short almost mid ventricular view um if there's any images that would like to make any comments uh it's familiar with cardiac MRI so I'll just I'll say you know obviously it was on the prior slide but um there's a significant amount of lge sort of in a sub endocardial pattern that um you know uh is suggestive potentially of amyloid but I'll say that there's a lot of that that's missing on here you know so I know on the prior slide it said something about the t1 time being a little bit long so we would like to see those numbers but the other thing that we talked about again in the other room earlier today in my talk was um that there's a on the inversion scout images there's usually a reverse nulling pattern so I'd like to see if that was true in this particular case um what I mean by that is is that usually the blood pool nulls first meaning that it turns black and then um and then the myocardium null second um in a normal patient because of amyloid deposition um on cardiac MRI you will see nulling of the myocardium first and then the blood pool later so essentially a reverse nulling pattern um so it would have been nice to see something like that in addition again the the point with with cardiac mrs is that while you see an lge pattern that's suggestive it's only suggestive there is nothing definitive about what we're we're seeing here and it's also quite difficult to in the context of somebody who's had recent in this case mi's times two to sort of understand what you're seeing relative to to the mi's and and calling amyloid on top of that is a little bit difficult again it's suggestive but but not definitive absolutely so kind of going through these these images the the red lines um at the bottom of the image is is inferior infarct so that's uh get lge of basically the seven undercard it's sub endocardium all the way to the epicardium and you can see that again kind of at the two o'clock of the the third and fourth image so those are the red lines that's showing the schemic disease what's circled in the first two images is this area of where there's lake anilium enhancement that doesn't involve the endocardium which wouldn't be explained by an infarct though it is close to the area to where the infarct actually is in the yellow arrows within the blue circles kind of showing that the end the sub endocardium is not having any lge there the green arrows seen in the second third and fourth image is showing lge in the septum that's more towards the right ventricle and then the yellow stars is is indicating that the the i might butcher this a little bit but the the blood pool is supposed to be whiter than it actually should so what happens is that patients with um amyloid deposition the amyloid ends up pulling some of the uh gadolinium from the blood into the myocardium making the blood a little bit less bright is my understanding so again these are all things that are suggestive that there's uh an infiltrated cardiomyopathy with amyloid but not definitive so these are kind of the uh what we discussed here um I'm sure it's hard for you guys to read these little small text so I apologize um so and this is the the t1 mapping that dr. Shah was talking about if you have any comments on this no just that it prolongs as the disease sort of you know progresses I don't know that they're definitive cutoff values um we just know that as the disease progresses the the t1 time tends to prolong what would you guys like to do next so all this is not definitive but it is subjective suggestive so when we had our discussion again we we um I gave him a call I gave him and his wife a call we had a discussion on his MRI findings all things we were saying we're starting to lead to Rome so we we said we decided to do the appropriate evaluation for amyloid so we ended up ordering a SPAP UPAP and figure out if these are positive and net or negative just to clarify serum immunofixation and urine immunofixation electric race it's not SPAP and UPAP yes sorry I apologize yes sorry about that um and then our plan was if these were negative to go to a PYP scan so so here is our serum immunofixation along with that I did get a biologic marker so I grabbed the troponin at the time um and probably this is four to four to five months out now maybe four months out so his troponin was elevated and then his serum immunofixation findings are listed below so here we see a positive serum immunofixation so a monoclonal protein is present now there are two other studies to look at to see if monoclonal protein is present but this is one of the three labs and the other thing I think just to highlight here now is troponin that was I believe over a thousand it's come down but it's still abnormal I should raise a question what's going on a chronic low level troponin is one of the red flag signs for amyloidosis so be interesting to note if there were any troponin levels drawn at any point in the past I know you said you said he's new to your system but you know for someone that's not looking back and chronic low level troponins are in my practice at least a really strong clue one of the stronger clues for amyloidosis. Cool questions for the audience how many of you have never ordered an outpatient troponin everyone's ordered outpatient troponins a couple hands never ordered has anyone experienced a difficulty ordering them or a concern can you comment on that Dr. Warner what percentage of patients with ATTR have an m-guss or monoclonal protein anyone want to take a guess sorry yeah I think that's right so this could be either AL or ATTR or some other form do we have any other proteins to look at so here you can see that there's a discrepancy between your kappa light chains and your lambda where you have a disproportionately elevated kappa to lambda and when we're thinking about AL amyloidosis we want to see one sort of of these light chains out of proportion to the other so this is still concerning with an monoclonal protein in the kappa and once again we have this serum immunofixate or the urine immunofixation is positive for the monoclonal kappa that we saw not only in the serum but in the serum free light chains so overall we have a positive monoclonal protein so I'll ask my colleagues in the room now what is our next step call you where do you all want to go we've got bone marrow we've got fat must go under skin so that's sort of my mantra anytime you see a monoclonal protein m-guss must go under skin okay so we'll see what Dr. Apollin arratures to do like in terms of yield of fat pad biopsies availability of general surgeons to do them any luck um we ordered one and this patient we actually talked to you about I think and IR did it at our center so I can say at my center it's actually our hematology nurses the nurses just do the fat pad in the clinic I don't know what happens at first centers our nurses definitely that's pretty cool though um no I think uh for the most part it's it's either heme I don't think we've had IR do one but certainly heme or the general surgeons in our institution yeah usually they're low yield not super helpful and then we're looking for other tissue for this one I would have gone for the bone marrow so let's have all of our panelists take a vote I want to know what what is your biopsy of choice on this patient so Dr. Boshara let's say bone marrow here bone marrow same I'm gonna stay quiet okay I'm gonna say go for the heart the only thing I'll say that I learned this morning actually is is that if if right now the only thing that we're thinking that we know is an organ involvement that we really know of is cardiac so you know it might be worth an end of my cardio biopsy here as as opposed to a bone marrow which you know I learned this morning can be potentially negative and still doesn't rule out the fact that you've got ale and I just want to point out the guidelines the the heart failure guidelines actually do point towards the cardiac biopsy in the heart so and I realize there's definitely vigorous discussion but that's sort of how it reads right now so I yeah I don't disagree with you but I think a lot of hematologists would see this and say this doesn't look like myeloma and they might not be interested in doing a bone marrow biopsy I will be the first to admit and humble enough to say that I was maybe a seven month into my cardiology fellowship and writhing and perseverating every single night on what I should do next and a gentleman who's you know four months outside of a major MI on DAP therapy and thinking about what type of tissue to go through after a few days of a few probably a day or two or three of perseverating then I was fortunate to have Dr. Rosenthal walk in the same pod as me and I said Dr. Rosenthal I'd like to run a patient with you and she always has all the time in the world to talk with us and fellow so we're all grateful to have her and so I went through this case with Dr. Rosenthal at the time and she said and I asked her would a fat pad biopsy and a bone marrow biopsy be something appropriate and Dr. Rosenthal agreed with that and helped to coordinate those two next steps so that's what we're going to go through so here's our fat pad biopsy done by hematology nurses so the it was negative for amyloid they use congo red stain that was not seen on the fat pad aspirate and then going forward with the bone marrow biopsy so the bone marrow biopsy the ultimate read was a plasma cell neoplasm monotypic kappa hyper diploid with nine percent plasma cells and a normal cellular bone marrow no morphologic evidence of amyloidosis with congo red staining so dr. houses go to the heart any other thoughts what would you do next cardiac biopsy okay so there was a slight deviation here this is a gentleman again on dap therapy he's still under six months and we'd have to hold dap for cardiac biopsy there's shared decision making to try to go for another fat pad biopsy to see if that would yield any since um that would be kind of a a lower risk procedure so we ended up doing a second fat pad biopsy and there was rare minute foci of congo phyllo material suspicious or focal amyloid deposition so when they tried to do a further evaluation on it with mass spec there was not enough tissue or not enough sample there for evaluations here so my general surgeons probably wouldn't have gone back in they would have laughed at me you know this week knowing that we also scheduled the cardiac biopsy at the same time and i don't know if anyone in the room does cardiac biopsy or not but i think knowing use on dulanthi platelet and risk of perforation is not a benign thing which is kind of contemplating is there a non-invasive way to do that right a lot of our amyloid patients or just cardiac patients in general aren't anticoagulation so stopping anticoagulation for um cardiac biopsy need to do like he was not but he was on dap so just trying to be thoughtful here also the cadence of this case we're now several months in typically al amyloid patients are more rapid progression while there was changes on the echo clinically he wasn't really progressing so it also made me take pause is this al or is this ttr something to think about now i have seen smoldering al cases but typically probably the ones that present to my advanced heart failure colleagues that i share the stage with usually they're no longer smoldering they're rip roaring but i think for a lot of us in the community who are seeing there are some al that are kind of just kind of slowly moving but most of the al particular within a few months they're really going to start to be falling off the cliff at this point so i was questioning those things you can have al amyloid and not have a very large free light chain difference with just this showman's was i think 10 or 11 so it wasn't like high but still there and sometimes those concern me as well could you just stop here like you have a negative fat pad a negative bone marrow um are you done can you treat for a ttr what do you need another biopsy yeah no yeah you don't need a diagnosis you don't have anything definitive that tells you that you have ttr there's nothing positive towards that diagnosis okay so basically if you have an m gus you need you need tissue to definitely make the diagnosis um yeah i wanted to talk about right heart cath and biopsy so in our practice for our heart transplant patients they might be on dapped and we don't interrupt we'll go ahead and do the biopsy with potential amyloid cases and native hearts i like to take appropriate precautions so i would have had issues biopsying this patient on dapped as well do you guys agree yeah just make sure you have the cardiac surgeon on standby or your interventional colleague and be careful you know i'm sure we've all seen myocardial perforations and the amyloid patients so it's not something that we take lightly that's why i wanted the bone marrow biopsy first yeah just a dr warner's point so i think aspirin monotherapy you're okay with biopsying but that burlinta really really adds a risk factor there so um if the patient's otherwise stable with newer stents transitioning to monotherapy and and then doing the biopsy definitely an option in this case okay so with this uh we'll move on to cardiac biopsy sorry so this these were provided by dr but one of our pathologists at at Mayo Clinic here um so this is an h&e stand at high power uh the blue is pointing out the amyloid fibrils that's deposited in the myocardium here so and then this is a a stain that we use along with congo red called sulfated calcium blue stain um this stain and and congo redder are uh ethnomonic staining for amyloid so common question what did you do uh to mitigate the dapped scenario i don't actually know if dr apollinario knows do you know what we did for this patient i didn't actually don't so i we had him hold for five days that the um i think he was on tecagular so we did the biopsy on just monotherapy and then had him resume following um and what i can say here is this is a really nice slide of amyloid but i need you all to know that all amyloid looks exactly the same so this could be one of many different types of amyloid so i think we need to learn more i agree did you get any any additional information so what is what are people's experience with ordering a biopsy how has been your experience in in getting the results and and sending sending them to someone any comments i'll be honest um we're not in a specialty center we're a physician-owned practice so we would have been working with hematology who would have and uh advanced center to do the biopsy show us the mass spect so here here is the biopsy uh results here so but it was kind of the speed of the case made me question too but did you send genetic testing we did so genetic testing was negative for for auditory TTR very interesting case it yeah you don't you don't typically see TTR progress this fast so it's interesting um but uh yeah so so in this particular case um a PYP if it had lit up would have changed my thinking as well um but i want to make the point that you can have PYP or HDP uptake um either with AL or TTR so it doesn't really rule in or rule out either diagnosis in the absence of the AL labs um but it certainly does increase your suspicion potentially for for TTR so you do PYP they have current yes have this gamut does your work up and there or would you still no so there are definitely patients that have TTR and AL and so you have to finish the AL work up in addition to potentially giving them a diagnosis of TTR but again just like in this case you you need tissue to figure out what's going on i i think that's the one scenario where where biopsy so if you have a discordant PYP and you have abnormal light chains in that scenario i'm going for tissue every every single time and that's consistent with aznec guidelines as well as our amyloid guidelines um that were published what in the last year or two so really there should be no role of PYP in this case because you had a positive monoclonal protein and you should have gone but in case you weren't thinking that if you just do the PYP you still could have missed let's say the mass spec came back for AL amyloid then you would feel terrible because now you're like six months into missing time to treat light chains and put out the fire so genetic testing was negative for our TTR chemotherapy diagnosed with wild type TTR is ultimately was is continuing to follow with Dr. Rosenthal in clinic he's being treated with tifamidus at this moment beta blockers were titrated off and he seemed to maybe get a little bit better physical physical function i think another thing that we wanted to highlight too is that this gentleman came in with a STEMI so CAD management is still very very important the tifamidus is the medication that that happens to have caused statin sensitivities to go up because of the serum concentration of statins end up being higher so let me just pause there because i don't know how many people in the room have seen this so this gentleman's feeling fine he was on resuva statin i think 10 or he was on 40 he's on 40 of resuva statin and feeling fine he's not having any aches or myalgias you've now started tifamidus this is the only FDA approved therapy for TTR cardiomyopathy patients and about two weeks after starting your tifamidus he comes and sees you in complaints of diffuse body aches so what are you thinking why is he suddenly having myalgias particularly in the thighs and in the calf muscles and it's at rest um and with exertion he's he's um symptomatic so what would you all be thinking you'd be thinking about statin rhabdo but why now it hasn't gone on for six months so the thing to know about yes tifamidus and i i'm sure i can pass this to my colleagues so i don't steal the microphone but tifamidus and certain statins do not mix well together so if you read your package insert of Pfizer there are a few drug-drug interactions for the most part tifamidus is very well tolerated you saw that there was equal amount of adverse events in the ATTR trial that led to approval but there are a couple drug interactions that you should be aware of when thinking about it i've probably seen five cases of this in the last few years so anyone familiar so the brcp substrate is inhibited so the breast cancer receptor protein is inhibited and this specifically will lead to elevated concentration particularly in resuvastatin of all your statins so something to think about um if suddenly your patients are complaining of myalgias and you're thinking statin intolerance when for several months they've been on a statin and it's a little unusual to say now so um it's something to think about and that happened in this gentleman just one other question about treatment um you know so that the ef was 49 percent on the last echo that we have right 40 40 40 percent yeah so you know clearly things you know aces arbis arnees etc are going to be the same as sort of the beta blocker issue but that doesn't have a terrible blood pressure um and he's also not on jarion so i just wanted to kind of bring up that question you know is that something you i thought about is that something that that we should put them on i'll ask my colleagues here how many of you are using sglt twos and your amyloid patients yes you know i mean these patients weren't included in the trials right so it's very difficult to make the case one way or another um if a patient and and with heffpeff specifically a lot of the current thought has moved to phenotyping so congestive phenotypes versus non congestive phenotypes so if i've a patient that's coming in with um attr amyloid has a congestive phenotype it might be something that i consider but again keep in mind that that data we don't have that data currently so um i want all the panelists to kind of come up with one recommendation from this case and i'm going to have dr rosenthal start and then we'll move into the cocktail reception i think the one comment i would make in this case is bravo to my fellow and our fellows right because we have the opportunity to teach them i think when most of us in the room we're learning about amyloid there was no hope like why did we care about making the diagnosis there was nothing we could do for these patients but times have certainly changed particularly since 2018 so i think it starts by asking each of us in this room and my fellow was doing that you know what's going on it's not enough to just start as dr warner said i think she stepped out but this morning she referenced guideline directed medical therapy or gdmt is what goddamn medical therapy right it's not enough about adding four pillars and i think this year if you have not read the new heart failure with preserved ef guidelines by dr kittleson and colleagues you know hefpef is sort of a diagnosis of exclusion so you need to exclude why are they have heart failure with preserved x-meg is it amyloid is it fabry's like what what is going on here is it a valvular disease those diagnoses alone are not hefpef they're their own entity particularly thinking about hypertrophic cardiomyopathy we now have disease target treatment for hypertrophic cardiomyopathy so i really ask each of you to ask the question why is this patient struggling and that's what dr pollinario did so my takeaway from this case is that as we all up here on the stage know and hopefully all of you now appreciate amyloid is really tough and you need to follow the algorithms that have been set out in the guidelines and really understand the nuances along the way so that you come up with the right diagnosis if you skip any of the steps along the way you can easily make the wrong diagnosis and put the patient on the wrong treatment which can be in some cases very very expensive so just to say follow the the guidelines and and you know think critically as as this wonderful fellow did along the way i think yeah i think you just demonstrated in this case just the threshold just looking for the wise and as for me involving your colleagues because i don't have the resources to do it but i know people very well who do and so just maintain that level of suspicion ask the questions and if you're in a center of excellence or use your colleagues to make the right diagnosis i think my take home message is have a high index of suspicion when you're treating patients with cardiovascular diseases look at your own primary data i tell our cardiology cardiology fellows this all the time look at your own ekgs echoes etc i can't tell you how many times patients come to my cardiomyopathy clinic with the diagnosis of ttr amyloidosis and the work up hasn't been done so follow the algorithms the guidelines that are out there and we all are in a small community ask each other for help yeah i'll just ditto what a lot of people have have been saying so far so um if you're if you're in a situation where you don't have the support staff available to you make sure that you're leveraging your community around you and so there may be there may come a time where you develop those initiatives at your own hospital but your patient's not going to wait for you to do that so i think i think involving your community early on is the best way to go and it's a learning process you're going to learn from them as much as they're going to learn from you so keep that in mind depending on your practice you're going to see 20 of your suspected amyloid patients will have an m gust so you're going to be facing this type of case a lot and i think you have a choice of fat pad biopsy and bone marrow or you can go directly to endomyocardial biopsy unless you have a strong suspicion for lichen amyloidosis i think it's reasonable to start with endomyocardial biopsy because most of the patients in my practice have a ttr and so you're going to get an answer al or a ttr at that point with endomyocardial biopsy so if you have a solid interventional cardiologist or other person who can perform the biopsy it's completely appropriate to send directly for endomyocardial biopsy directly but i want to thank our panelists and really most importantly our moderator so thank you michael of course of course