Understanding Cardiac Amyloidosis: Evaluation and Diagnosis

On episode 46 of Inside the Studio, Dr. Joseph G. Rogers sits down with Dr. Mathew S. Maurer to explore cardiac amyloidosis, highlighting the importance of patient evaluation and diagnostic algorithms. They discuss the necessity of thorough diagnostic processes, including biopsies, and the significance of genotyping. 

Further in the discussion, they cover:

• The practical approach to diagnosing cardiac amyloidosis from initial patient presentation.
• The critical steps in differentiating AL and TTR amyloidosis.
• The role of genotyping in determining prognosis and guiding treatment decisions.
• The importance of endomyocardial biopsies, particularly when monoclonal proteins are identified.
• Insights into the natural history of wild-type TTR amyloidosis and the factors influencing its development in older adults.
• The latest therapeutic strategies and the necessity of multidisciplinary collaboration, particularly with hematology-oncology.

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Transcript

0:04

[Music] hi I'm Dr Joe Rogers and I'm the director of the Texas Heart Institute at Baylor College of Medicine and I'm joined in the studio today by Matt Mau who just gave a wonderful talk on on amalo dois and cardiac osis in particular and sort of walked us through um your not only your approach which I think is I think the world is following but really a very forward-looking view into some of the therapies so out we're just and so happy that you took the time to join us here at Texas heart great to be here and uh we're old friends so I really appreciate the invite it's great to see old people and really a fantastic place you've uh created here keep sheering forward so thank you so the purpose of this is just to sort of take what we discussed in the last hour and make it very practical uh and so there were some things that really struck me that I wanted to just explore further from your talk yeah and and I guess what I'd like to do is start with this idea of of an evaluation of a patient who comes to you with a presumptive diagnosis of ameloid and and would you just I mean you probably have one of the largest experiences in the world and but you have a very methodical way of thinking through the diagnostic algorithm so could you just walk through that patient from the like when the when you first walk in the room what are the things you're asking what are the things you're looking for and what are the tests that you're doing to make sure that you've got the diagnosis right yeah well I think one of the main things I was trying to communicate is the perceptions this is a you know very rare condition and um for those who don't know the fastest growing segment in the US and worldwide population or people believe it or not over the age 75 who are you know disproportionately afflicted by this so I think everyone's um going to experience this in clinical Cardiology and general medicine um the sinanan is usually patients have um an increased wall thickness on their Echo card or some Imaging that prompts people to think of this particular condition so are the lot are the people that you're seeing often times being sent because they have unexplained or unexplainable left ventricular hypertrophy not anymore for us I mean we used to see a lot of those patients and back to the diagnostic algorithm it would be that you know someone thought of the condition or they had certain subtle symptoms and um you know again increased wall thickness maybe many of the orthopedic manifestations I mentioned previously carpal tunnel lumbar spinal stenosis biceps tendon rupture um often they had biomarkers that were out of proportion to their clinical syndrome so they'd have a you know anran P that was way higher than you would expected Andor they had a troponin leak for years went to when a bunch of cardiac cations that didn't show carne disease those are some of the clues in some regard and once you raise a suspicion of the diagnosis the algorithm is is really um very simple it's a exclude light chain amalo dosis that is still a ultra rare dis disease I mean literally there are like 4,000 patients diagnosed in the US every year and so even if you know people live you know 10 15 years there there's not a lot of people with that condition but you must exclude it because it's so malignant and it's excluded with essentially three blood test uh serum free light chain assay not a total light chain assay but a Kappa Lambda free light chain assay which has a very high sensitivity like 92% for diagnosing the substrate for aloid and then a serum imuno fixation electroforesis and a urine spot amuno fixation the key here is not to order an spep but rather what we call an spy ask the lab to look for small monoclonal proteins and the combination of those three tests has like a 99% sensitivity for basically saying does this patient have the substrate for aloid if they don't then they can't have aloid then you basically do pyp scan and if it's positive it's 100% specific for TTR and then you genotype them if they have monoclonal proteins then the pyp skin is not 100% specific and in those circumstances you have to kind of see who you're talking about if you have a 100-year old patient in front of you to be honest you know they may be a little reluctant appropriately to have a biopsy the chances are they still have age related wild type with a monoclonal gammopathy of unknown significance not aloid yeah and so to be honest you're 95% certain you're not 100% specific and you have a conversation but in some patients who really do need you know a younger individual who could be at risk for Al looks much sicker than you really do need to go on to tissue biopsy and are you working then closely with with hematology or Hematology Oncology for those sort of patients that are that overlap and absolutely I mean I have a I didn't show it today but I have a slide of all the you know um chemotherapeutic agents and oncologists get a new drug approved like every week you know like it seems um and so um you know you need an expert individual not just a Myoma doctor but someone who takes care of light chain amalo does to guide therapy there are a whole host of antiplasma cell therapies I slides tittled something like don't do this alone you know you really need to get a colleague but they're wonderful and really helpful does Echo fit into that algorithm yeah I mean Echo is one of the things that raises the suspicion of the diagnosis but not necessarily I guess it is a critical component probably it's a critical but it's not going to tell you like someone was asking today well how do you distinguish Al or TTR it's still back to the monocon proteins yeah tissue analysis or the craphy neither echo or MRI is going to tell you which type you have but they rais the suspicion quite a bit and you know MRI in particular I think people have uh cardiopathies that have been undefined for years and someone finally disorders an MRI and the conclusion basically says you know High ecv a lot of delayed enhancement think amalo yeah usually the providers kind of I call a peak and squeak test they peek at it and they squeak because they feel like oh my God I missed the diagnosis and they refer the patient in for further evaluation now you you made the other point you've made a couple of other points in the diagnostic algorithm that I'd love to just explore a little bit more you talk about doing genotyping yeah how do you use the genotyping clinically or prognostically great question so patients who have variant disease or you know have a a genetic cause they do have a worse prognosis it's pretty clear and the disease progresses at a faster rate they usually have uh they're usually manifest at a a younger age about five or 10 years younger so genotyping right now is important for that prognosticating it's also important right today may not be a month or so if vuser approved but right now it's essential to get access to silencer based therapy so stabilizers teamus acarus were approved for cardiopathy um but not um and neuropathy but silencers right now today are only approved for patients who have variant disease they have to have a genetic variation and a neuropathy they can have a cardiopathy but if they don't have the first two variant and neuropathy they're not eligible and and you you made the point uh at the end of your talk about family screening when you identify a genetic abnormality you sort of said well I'd be much more worried about the cibs than it would be about the kids yeah because this is a disease that has what's called an age dependent penetrance so you're born with the gene but there's no one at the age of three four and five or even 20 or 30 who has you know TTR amalo we'll get um an example we'll get someone calling us and saying you know there's a young kid he has a thick weld heart he had renal transplant he's been on cyclos Bor and his heart's thick and he's 25 and the answer is he he just carries a gene that's not causing his phenotype it doesn't happen at that age right he we used to say to people it was a disease that penetrated after the age of 60 and Men 70 and women we're probably a little wrong it may show up a little bit earlier so the point here is if you have a patient who is affected they're very worried about their kids which I understand and we try to explain to them you can be but the real people they should be worried about are their siblings who are the same age were marked increased risk for having disease now the other thing that you had in your diagnostic algorithm was biopsy yeah how does biopsy fit into this larger sort of ecosystem of tests that you're doing to either rule in or rule out it's still very important I tried to make the point like uh you know surrogate biopsies fap pad or other things are reasonable but you can't stop the workup with those if you still have a high clinical suspicion because they're not very sensitive yeah and you know people need to be able to call on a center like this to be able to get an endom myoc cardiio Vibe still has a important role to play especially in someone who has monoclonal proteins and you suspect light chain amid then the only way to definitively separate out the two you're not going to use a scintigraphy you're not going to use an echo or an MRI is to look at the tissue and actually do what they call Mass spectrometry which is to kind of identify what the precursor protein is and as I highlight it's still you know it varies but 10 15 20% of our patients still need an endomyocardial biopsy um and they need the expertise of a center that does enough of them so that um there's no trouble when they're doing that I always was struck by um our colleagues who've said well I think this person might have amalo it looks like it might be amalo in the heart I'm not entirely sure so let's do a fat biopsy fat pad B I thought it's sort of like Willie Sutton yeah exct you know the bank robber like why do you rob a bank because that's where the money is I hard yeah I that's what I do I you know our hematologist will do fat pad biopsies and it's great if they're positive but if they're Negative they often will call us and ask for and then and again an endom cardio Vibes that you and I know is is really not that big a deal my point was an amalo with a thick Wild Heart you'd have to really work hard at causing a big problem you know like it's not something I've ever seen there was one other question that was asked uh online uh at the end of your talk and we didn't have a chance to get to it but I'd love to get your understanding and it has to do with the natural history of amid somebody asked a question like why do people get wild type amid later in life like what why does the tetramer begin unfolding or breaking into into you know smaller fragments as we get older yeah so um it's a great question and to be honest the biology of wild type TTR is not entirely clear I mean we published data which surprises people um in that Jeff Kelly who invented tfam an asset a measure of stability um TTR stability in older adults is no different in those who have disease than those who don't hate to be alarmist but everyone's TTR is falling apart so it's probably something to do with the body's ability to handle misfolded proteins in these particular C circumstances um we have a a grant we'll see if it gets funded but um there's a phenomenon called loss of Y so as men me you everyone ages we lose our Y chromosome and loss of Y is disproportionately higher we found in patients with wild type TTR and it could be that there's genes on the Y chromosome that handle misfolded proteins and so we've been all very TTR focused but I was trying to make the point that for those getting into the field we would love to have a bedside blood test that could tell us who handling proteins well and who isn't we don't have that yet listen again I just want to thank you pleasure this a great great chance to just sit down and explore a couple of other issues and and thanks again for coming to to Houston today and shape journey home yeah great[Music]