Ugochukwu Egolum, MD, Director of the Heart Failure Treatment and Recovery Center as well as the Program Director of the Cardiovascular Fellowship at Georgia Heart Institute, discusses cardiac amyloidosis diagnosis and treatment at the first inaugural Heart & Vascular Symposium hosted by Georgia Heart Institute at Chateau Elan Resort & Winery in Braselton, Georgia.
Thanks Murad for that. Very um excellent discussion about medical therapy. So my talk today, I'm gonna focus on cardiac amyloidosis. Uh this talk will predominantly be about diagnosis and treatment for the most part I really want to drive home the important fact of being able to recognize the signs and symptoms that should lead to suspicion for cardiac amyloidosis. So objectives. So we'll go over what is cardiac amyloidosis, things that should raise suspicions for it. How do we make a diagnosis and then what are the treatment options? Uh going forward. So we'll start with a patient case. So this is J. S. He's a 65 year old African American male um presented the E. M. S. After he was at the supermarket and died suddenly had bystander Cpr and and was defibrillate ID and brought in as we look through his past medical history uh he has a history of bilateral carpal tunnel syndrome perhaps five years ago. Um He had an E. K. G. As you can see an echocardiogram that showed some L. V. H. And uh strain map that showed some abnormalities there. That will go through in a second. So as we talk about cardiac amyloidosis. What exactly is cardiac amyloidosis? So keep in mind cardiac amyloidosis is a disease where proteins uh misfold behave abnormally and deposited in organs and as a result this could be a systemic disease. Now there's several proteins that are able to do this. Um refuges about 36 proteins has been identified and these can lead to uh cardiac amyloidosis in human beings. And again, as I mentioned, this is systemic illness and multiple organs can be involved. When you look at the graphic towards the right as you can see that it can be ocular involvement, cardiovascular reno you name it as these proteins deposit, they lead to different disease. Finance. Now, luckily for us in cardiology, we really only worry about two forms of proteins that can lead to cardiac amyloidosis. So that really makes it a bit simpler, at least from a cardiology perspective. So on one hand, we have immunoglobulin light chain amyloidosis. So again, that's a uh psychologic disease where the light chain of the immunoglobulin behaves abnormally and starts depositing all over the place. And then the other one we worry about is a T. Tr cardiomyopathy. Now keep in mind T Tr another name for it is pre album. And uh once this protein is made, it falls apart and leads to amyloid deposits all over. So that's that's about 95% of the proteins of the disease for cardiac amyloidosis that we worry about Most of this talk will focus on T. Tr cardio myopathy. Um L amyloidosis is really out of the realm of this discussion. But keep in mind that that's a totally different disease with a totally different prognosis. So how does a T Tr cardiomyopathy happen. So all our livers make pre album. And and some patients for whatever reason, depending on what form of it, this protein falls apart and uh and rather than having a tetra mere structure the individual pieces deposit in the heart and lead to disease It's a frequently misdiagnosed finding. Oftentimes this disease is not thought of and part of this is because of the way it presents the way it looks could be any number of diseases. And but important part to note is that once diagnosed the median survival is about 2-3.5 years. So that also underlines the importance of understanding and looking for this disease. So earlier we talked about the T. T. Are falling apart and leading to disease. There's really two subgroups. So there's a wild type where these patients don't have a genetic mutation but for whatever reason whether it's related to age or other factors that are not well understood that normal protein starts to fall apart and causes the disease. There's a territory form of the disease where it is a genetic mutation that we identify And in that case that specific gene mutation leads to a change in immuno acid sequence and then that leads to the protein being abnormal and acting as such. For example, one of the mutations we commonly identified as the v. I mutation which is oftentimes seen in African American patients. And as you can see on the graphic depending on the mutation, the patient can have variable presentation whether cardiomyopathy or a mix of cardiomyopathy and neuropathy. So what findings are things should raise your suspicion for t TR cardiomyopathy. So one of the keys is really when you have an echocardiogram and you compared to the E. K. G. The echocardiogram as LV. H. But the degree of voltage on the E. K. G. Is relatively low meaning it's a bit discrepancy what you would expect. So rather than low voltages you may just have voltages that are lower than you would think they would be. And again an echocardiogram, we may have impaired longitudinal strain as we saw earlier. Um And oftentimes the echocardiogram shows us hypertrophic phenotype that results in us having to do further evaluation. A good subgroup of patients that are often times found to have uh teach our cardiomyopathy are patients with aortic stenosis, particularly the subtype that have low grade, low s low grade low flow uh aortic stenosis, laboratory studies and other clinical phenotype Hedgpeth. There's several studies have shown upwards of 15% of patients admitted to the hospital over the age of 65 may have T tr cardiomyopathy. So good. Another subgroup of patients to look for this and additionally, when patients are placed on medical therapy for heart failure if the patient has a hyper response. So low doses of sailors in april and it becomes predominant, extremely hypertensive, you've gotta think about it in that setting. Also patients that have bilateral carpal tunnel syndrome should always always be evaluated and some discussion made about hypertrophy about T tr um cardiomyopathy. And another group of patients. uh folks that are re admitted to the hospital for unknown reasons. These are folks that come in. They get kath, we work them up and they persistently have a baseline elevated troponin that's unexplained for any other reason. Again another group to look for this and and for patients that have conduction system abnormalities needing pacemakers and there's clear evidence of L. V. H. That's another clue that make clues. And and of course any patient with any cardiomyopathy symptoms who also have neuropathy or autonomic dysfunction. Uh These are the folks to really get included on. So very important to really recognize these subgroup of patients and really commit this to memory as we go about taking care of patients um in different areas. So in summary when patients present with any of these red flag symptoms as we've outlined with the L. V. H. Clinical symptoms neuropathy e um uh profound response to medical therapy that subgroup of patients particularly from echocardiogram or some sort of image. And there's some suggestion of amyloidosis. Uh These are the subgroup of patients that we want to hone in and look for and keep in mind this is not a zebra as we're looking for it more and more. We're finding it more frequently among our patient population. So what's a good diagnostic algorithm. Right? So you've seen the patient they've got some symptoms and other findings that make you highly suspicious. So this algorithm has been fairly widely published and it's a good diagnostic algorithm to follow. And one of the things that recommend is that we when you follow this algorithm we follow it in detail without skipping steps as that can lead to issues. But the first step is again is to identify the patient have raised suspicion for possibility of the disease. Um You can use biomarkers as a way to screen pro BMPs proponents etcetera. But the first step in any work up for amyloidosis is to rule out a limited doses that has to always always happen. So the way to do this is to send laboratory studies uh for serum free light chain ratio, serum protein immune fixation and your urine protein in unification. Now, oftentimes sometimes folks are sending the aspect for those are not sensitive or specific enough to pick up these uh like chains disease. So it's important that you send a pro uh serum capital amita uh free light chain ratio and the protein in unification as an important study. Now if that's completely normal or negative and there's low suspicion for a l. Amyloidosis and you're at the center that has P. Y. P. Scan available. This is a modality to evaluate the patient further and be able to pick up the disease and it's in the correct clinical setting is highly sensitive and specific. Now if one is at the center that doesn't have access to py piece Canon then end of myocardial biopsy may be pursued on the other side of the graphic if there's evidence of monoclonal process when the l screening laboratory studies abnormal, it's very important to get an oncologist involved for further evaluation of the patient. And secondly, if the patient does have a positive P. Y. P. Scan and we make a diagnosis of T tr cardiomyopathy, we always have to obtain genetic testing to really decide for which group of the disease as a patient falling as there's implications for treatment and for family screening. So let's get back to our patient that we saw earlier. So as we mentioned, he's a 65 year old african american male. Right? So there's certain red flag things that are jumping off at us. Now he's had bilateral carpal tunnel syndrome on his echocardiogram, we clearly see that he has a thickened left ventricle. But when you look at his E. K. G. His voltages perhaps are not as elevated as you would think they would be. Um So as we mentioned earlier, our first step given the suspicions, we started with serum protein in unification urine protein unification, serum free light chains. And those were all normal upfront. Subsequent to that we obtained a P. Y. P. Scan which you can see the schematic in the middle and power phosphates. Can is a good way to look for cardiac amyloidosis as the patients that have this protein in their heart. The power phosphate sticks to it and it lights up on the on the scan images. Um and generally that's negative, it's highly unlikely that you have cardiac amyloidosis. And as we mentioned, once you've made the diagnosis, the patient always needs a genetic screen. So the gentleman had a genetic test done and he came back with a V. 1 22 I mutation. So just to summarize this case, his diagnosis was heritage story 80 tr cardiomyopathy. And with the bilateral carpal tunnel, he actually had neuropathy involvement as well. Um And based on that, we actually started them on treatment with feminists and participation. So what are these two drugs? Um and what are the treatment options for patients with this disease? So the field of cardiac amyloidosis has really expanded. And now we have multiple drug therapies to take care of these patients. So when we look at T. T. R. And the way the disease happens in terms of the cardiomyopathy, there's different drugs that can act along different pathways. So for example, patisserie in and in person are medications that act at the level of the liver and they inhibit or stop production of the protein towards by blocking M. R. N. A translation process going further up there are medications that we call stabilizers. So these are medicines you can give to hopefully keep the protein pieces together and prevent it from falling apart. And that's the group that feminist falls in along with the fluconazole and a g 10 other medications further downstream. So for the patients that already have a fair amount of deposition uh combination to prevent doxycycline of Taka can be seen to help hopefully alleviate some of the protein deposition and the problems that happen. So this gentleman, he had a predominant diagnosis of the cardiomyopathy and and neuropathy. So the feminists is currently approved for treatment of cardiomyopathy. But for patients with the neuropathy, the currently approved therapies are participant and in person and just recently voted sarin uh Sharon was just approved as well. So this gentleman was started in this therapy. We followed him closely in clinic. One of the things we tracked for disease activity or recovery is a pre albumin level. So as we talked earlier, T tr essential pre album. And and when these patients are placed in stabilizing medicines oftentimes the album and trends up. So we saw that gradually increase in him. His pro Bmp normalized. He's currently asymptomatic and he's back to his job as a police officer and living life the best he can. I just wanted to summarize our findings that T Tr cardiomyopathy is a disease that we really is not a rare entity anymore. We have lots of treatment options. I think the most important part for anyone of us who are cardiovascular specialists or whatever our roles are in a specific institutions is to really have that high index of clinical suspicion follow the diagnostic algorithm always obtain the genetic test in patients that are positive. And family screening is important as well. And now we have a plethora of treatment options that patients can partake in. I wanted to give a shout out to our Georgia heart team and and part of our and our cardiac amyloid Clinic. Um as you can see there's several of our medical assistants or nurses listed here or nurse practitioners office manager. Uh folks that do scheduling are my CO. M. D. S. In the heart failure clinic. Um I think, you know, working strongly as a team at G. H. I. We've been able to identify a lot of these patients, improve their prognosis and and get them doing better long term and do not listen on this slide. And always in my heart I want to say thanks to my wife, Toni and my my two sons for keeping me grounded. Thanks
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