Chapters Transcript Video Amyloid Everywhere Dr. Tushak describes the screening protocol and treatment for Amyloid. this morning. It's my pleasure to introduce uh dr zack to shock. Uh Zack recently joined us from uh completing his heart failure training at UPMC in Pittsburgh. Prior to that, he had undergone uh general cardiology training at VCU and his internal medicine training at the University of Connecticut will be involved in all aspects of advanced heart failure, but he has a particular interest in both cardio oncology and infiltrated heart disease fact. Thank you, john thank you for the warm welcome. Um It's my pleasure to be here and thank you for attending. So my my talk is entitled Amyloid everywhere. I have no disclosures. So, to set the agenda first, talk about the kind of the preamble to talk about what it is, why it's important, a screen protocol, a briefcase review and then treatments. So as part of the preamble, um here's where I ask for some participation in the crowd here gathered. Uh so who's comfortable diagnosing? Who's comfortable with screen patient populations and deciding who to evaluate a show of hands, please. About 50%. Who's comfortable with ruling out al amyloid by ordering the specialized labs and interpreting those labs. So about 1 6 and who's comfortable with sending specialized skins, whether it be ordering fries or skins about three quarters and who's comfortable with sending genetic testing In about 1 6 here. Clearly there's some work that we can be, can be done here. Um and who is comfortable with treating ordering the various disease modifying treatments about 16 and who knows what medications can be harmful to the stations In about 16. And so you know the supreme is kind of gonna cover what we're gonna talk about today. Um And then look at this. You know, these are three patients with P. I. P. Scans who thinks that patient A. Most likely has cardiac Emily doses based on the P. I. P. Scan and show of hands probably. Uh yes there's some grumbling in the crowd. Maybe a third think that this patient has cardiac amyloidosis. How about patient B. Another third and have a patient C. I have zero. So who here thinks that patient A. Has the genetic predisposition for arteriosclerosis. Have it be? Uh huh. Or even see people are not quite sure about this. So what is it? So there are two types really three of correct employee involvement. There's the LM Lloyd and there's a T. T. Are employed. T. T. R. Itself is just a touch more synthesized by the liver. Uh And it's used to bind and transport the hormone rock scene and retinol binding protein with systemic circulation. The teacher employees is a systemic disease caused by the one destabilization of the humor into too unstable monomers that then three misfold and then four aggregate as insoluble Emily fiber ALs. That which then deposits five in tissue. There are two types of T. Tr. Kartik Emily doses and there's a wild type formerly called the sea now in the hereditary formerly called the familial the wild type is the un mutated form. It's connected to advanced aging. It's probably more common than the hereditary variant. Uh In one study that possibly up to 24% of all patients might have underlying underlying um wild type Emily doses. And then on autopsy one in five octogenarians actually have noted cardiac involvement. The hereditary version is a familiar version. It's also more dominant. The mutation can result in a syndrome of the heart and Euro system. There's the predominant cardiac phenotype, the predominant neuropathic phenotype called the familial Emily poly neuropathy. And there's oftentimes a kind of a combined phenotype and this stems from over 100 potential mutations in the CFTR gene. The most common variant involves the substitution of veiling for I solution in that position 1 to 22. Historically, this is called V 1 22 I, but the nomenclature changed recently and now we call it V 1 42 I. And of note three or 4% of all African Americans are gino positive for the mutation. That's one that's one version of the hereditary T Tr cardiac amyloidosis. But there are a number of other variants that have produced positions so early V. 50 met predominantly affects uh younger female patients of Portuguese and japanese descent and the symptoms are primarily neuropathic in an ideology or nature. The late onset v. 50 met is primarily middle aged men of Swedish descent and it's primarily cardiac symptoms. We see The V142 I that we just talked about is primarily men above the age 60 affects African Americans and has combined symptoms. Uh 39 80. Allen een uh is another variant of the affects middle aged irish and english uh patients of irish and english descent has combined symptoms. And then the wild type variant affects patients above the age 70 is male predominant, can affect any ethnicity or nationality and has combined symptoms. So, you know, while while employee has kind of been on the uh on the talk recently, we always think of it being a primarily african american disease process. Clearly there are other variants affect other nationalities and ethnicities. So next we'll talk about manifestation. So it's a systemic condition and results in the results in the deposition in affected organs that can include the heart, kidney and nervous system. Cardiac manifestations can include myocardial dysfunction with diastolic dysfunction, restrictive restrictive physiology and eventual systolic heart failure. It can cause conduction disease such as brady arrhythmias, heart blocks and other arrhythmias including atrial fibrillation and had it can cause vascular disease the classic being a calcified aortic stenosis. Um there are two subtypes of neurologic manifestations. That's the peripheral neuropathy. Uh here you see paras these ideas and weakness starting as symmetric like length dependent loss due to small fiber destruction, including the media neuropathy. The classic, we see bilateral carpal tunnel. We see single cranial nerve neuropathy and plex are these like spouse or step educate and then there's the autonomic dysfunction here we see Ortho static hypertension we see. Oftentimes these patients are intolerant to traditional hypertensive medicines or even G. D. M. T. We see postprandial diarrhea alternating with constipation. You may see gastro paris's urinary retention with incontinence or even erectile dysfunction. And then there's all the other manifestations. Um You see bicep tendon rupture primarily with the wild type. We see early hip and knee arthropod. These. You may see a real function out of proportion to the compared age. You may see hypnotic abnormalities including transit and hypoglycemia. So why is it important? So there's a macro implications to this. Uh the population of the United States is about 328 million people if one in five patients over the age of 40 developed heart failure. Uh and about one half of those uh I'm sorry if one in five patients above the over the age of 40 develop heart failure. That equates to about 6.5 million people. If one half of that 6.5 million people of all the heart failures have passed like waste to about three and a quarter million patients. And based on that that study from Dr Redfield in Mayo, they found that 24% of patients with actually had underlying Wild type cardiac amyloidosis. So 24% of that could lead to about 800,000 patients in the United States. Further one study out of Columbia found that 16% of patients referred for severe stenosis undergoing tavern uh actually had underlying uh wild type cardiac amyloidosis as well. Uh And then uh you know three or 4% of african american in the United States are positive for the V. 1 42. I um so the african american population is about 42 million. If you take 3 to 4% of those people being at least you know positive. That equates to about 1.5 million patients. So really there's there's there's quite a lot of patients out there that could be experiencing correct Emily doses up to 800,000 for the wild type and up to 1.5 million patients Arduino positive for the hereditary variant at least one variant of that. Taking into context in our area, the population of the Hampton roads is about 1.7 million people. So up to 400,000 patients could be affected with the disease. And clearly we did not see this this number in our clinics. So now that we know what it is and why it's important. Let's talk about the screen profiles. So first we'll do a detailed history here, we'll ask about heart failure symptoms, neuropathic symptoms, any family history of neuropathy heart failure or sudden cardiac death. Next we'll get an E. K. G. Which may show low voltage or a pseudo infarction pattern will get lab tests. Troponin nt pro BnP renal function and liver function. And next we'll be we'll get an echo. Some findings may see what cards. Amyloidosis can be. An increased the thickness of one of the 1.4 cm. You may see a loss of uh global internal strain with a pickle sparing that so called bullseye or cherry on top. You may see low tissue velocities and you may see a pericardial effusion here. We see a an echo. Uh We see a patient clearly has L. V. H. When I measured it was approximately 1.71 point six centimeters. Uh So we C. L. V. H. With a normal systolic function And we see a pericardial effusion here with the red arrow. These all can indicate underlying character amyloidosis. Here we see G. L. S. With a typical sparing. You see that the higher negative G. L. S. Pattern pattern in the apex with lower values um You know as we get more towards the base. And so at this point I think we have enough evidence were not enough data to try to determine what could be the underlying cause of the patient's symptom. Um You know, we always have to have a differential diagnosis and so we should ask ourselves could it be something else? Could it be february? Could it be HCM Could it be just constrictive pericarditis or could it be hypertensive heart disease. If you think it could be something else or as possible as something else. The next step would be to get a cardiac MRI um with the cardiac M. R. I. You know we can see some findings that could be indicative of underlying cardiac amyloid and that includes elevated T. One values. You may see increased extra cellular volume fractions. You may see late galilean enhancement in a pattern of diffuse 70 cardio or trans mural distributions. And you may see abnormal galilean kinetics when they do the T. One. Scouting here we see uh some late gadolinium enhancement in the sub and cardio regions indicated by the right chevron eros. And we see that's pretty diffuse. Uh You see that the normal my card is pretty dark and the L. G. The lake got enhancement. Is is that kind of the lighter areas. Here's another picture that I found on the internet that I thought was you know especially um interesting because it really diffuse and in multiple patterns we see both trans neural distribution as well as some cardio distribution that affects both the L. V. The RV and the atrium. Then that same patient in the short access really diffused. And then looking at T. I. Scout imaging. Um A. T. I. Scout just entails um the inversion time. And what they do is they pulse the photons and they do a very very quick turnover. And ordinarily the blood pool will become black or null before the my cardi. Um Here we see a normal T. I. Scout, we see going from time from left to right and they pulse the mic, the pulses of the heart. And we see that on the second image from the left, you see that the blood pool turns black before the my cardi. Um However, in in cardiac amyloidosis because there's a higher exercise of the volume, the mic Rd um I will actually null at the same time or before the blood pool itself. So here going from left to right. We see that the my cardi um uh null at the same time as the as the blood pool. Here we see a scene uh the red circle is um Icardi um The white circle is the blood pool. And here uh we keep a keen eye. We see that the the my card is actually turning black before before the blood pool. Mhm. So, we have our card M. R. I. Um If it could be something else. If it's not if it couldn't be something else, we think for sure, this is probably the underlying amyloidosis. The next step is the screen L. For uh L. Amyloid. And with this we'll get the Syrian free light light chain assay in the serum and urine immune fixation. Now, often times, you know, we get these um uh you Pep and S. Peps of unclear significance and it can be confounded for many reasons, primarily, you know, the primary cause is underlying renal disease. But the unification I think is kind of the key and kind of the gold standard at this point. So if it's positive if you see a monoclonal game apathy, this is really a human logic emergency. The patient should be referred to our colleagues and he monk as the um the mortality rate is about 50% of six months. If it's negative then we go down our passive confirming T tr amyloidosis. So with that we ordered a technician power phosphates can. So uh Farrah Fawcett scan is a bone integrity scan. Uh in the United States we use technetium 99 but in europe and other other areas they use different agents. Um the sensitivities about 99% with the specificity of 86%. Now that's you know, somewhat skewed because clearly the patients are being very thoroughly screened prior to this test but it's a fairly accurate test but it should be noted there are false positives with al amyloid. Hence the reason why we need to roll that out first. And when you order your technician para you should always order respect imaging. If you don't wear respect imaging. It's not always done. It can lead to confounding patients or false positive. We actually had two patients that we saw that had false positive technician pyro phosphates cans because it wasn't order respect imaging and they were diagnosed with T tr amyloidosis and started on treatment but they actually didn't have it. They had underlying HCM and so and so you know there's different medications and actually exclude certain medications if you have chronic amyloidosis. So it's very important. The order with spect imaging uh Para para faucets can itself uses technology um as a tracer it's administered and then um if patients have underlying Kartik amyloidosis, the fibers themselves take up the technology um and they measured at certain intervals and they do a visual uptake score. So how much did the myocardial absorb the Tekken Easy. Um uh And that's rated on a scale of 0 to 30 being no uptake, one being democratic uptake but less than the rib. Uh to being Kartik uptake that equals the rib and three being Kartik uptake greater than the rib or no rib scene. And so essentially if the patient doesn't have cardiac amyloidosis is the bones glow very white. Uh you know, very bright white. If they do have cardiac amyloidosis, the uptake up taken by the cardiac Emily fiber als and it glows white on the left. We see a visual take score of zero. So the maximum is not taking up any technology. Um On the right we see a visual take score of three we see that the heart is very white and very bright. And we see no other bones. To this point if you're uh Prp scans positive. If it has a visual take score of two or three as positive for for underlying t tr amyloidosis at this point we have to determine if it's hereditary or if it is the wild type and that is where we do the genetic testing. If it's negative then we need to reassess by possibly a cardiac MRI. We're considering a biopsy. Now there's a screen caveat um 30-40% of of elderly patients with wild type ATT are actually have a monoclonal game apathy of unclear significance. Or in that situation there is a famous Hartzler cardiologist named Dan judge. He says he stands for must go under skin. So we need to confirm to the biopsy at this point. So at this point we talked about why it's important what it is and how to screen for patients. We're gonna apply that to a series of patients. Mr. C. Mr. L. And MS. T. So Mr C. is a 62 year old African American male. He was referred for evaluation of heart failure after repeated treatments. Insurance Abreast. He has a history of bilateral carpal tunnel syndrome, spinal stenosis with lower extremity neuropathy and hypertension Reports Disney after one flight of stairs lower extremity edema. In Orthodontia. Mr L. is a 68 year old African American male who was referred for dismissal with exertion. He has a history of hypertension carpal tunnel syndrome and spouse stenosis. He reported occasional dysthymia but denied limitation activity And finally misty she's a 64 year old African American female who was referred for evaluation of dis Mia. She has a history of diabetes mellitus hypertension carpal tunnel syndrome in renal cell carcinoma. And she staff posting affecting me. She reported mild exertion but denied limitation activity. So MR. C. We classify him as having N. Y. J. Three symptoms. MR L. Has class 1 to 2 and misty has class 1 to 2. Uh We obtain labs on these patients. So MR C. Has abnormal cardiac biomarkers, an abnormal pre albumin but normal renal function. Mr El misti both have normal cardiac renal and liver by biomarkers. On E. K. G. MR C. Had a low voltage had an infarction pattern. MR L. Had L. V. H. And MS T. Had a normal E. K. G. On T. T. E. MR C. Has severe diastolic dysfunction with a simple wall thickness of 2.1 centimeters and A. G. L. S. Of negative five low Mr L. Had my mild diastolic dysfunction has set the wall thickness to 1.4 centimeters and normal G. L. S. M. S. T. Had a normal diastolic dysfunction had uh normal set the wall thickness to 1.0 centimeters and normal G. L. S. So Mr C underwent a cardiac MRI uh at the top panel on the left. We see a. T. I. Scout imaging. We see that going from left to right. The myocardial is knowing at the same time as the blood pool. This is abnormal on the bottom panel we see late gadolinium enhancement of the cardio region. So this is abnormal and can be both. These together are indicative of cardiac amyloidosis. So he underwent confirmatory P. I. P scanning to the right and we see he has a visual take a score of three which is consistent with correct Emily doses. Mr. L. Had a card memory. On the top panel we see T. I. Scott imaging. And we see that the uh the myocardial is knowing after the blood pool. But on the imaging the LG imaging on the bottom panel we see that he actually does have some subtle LG in the southern Ontario region. And then he underwent TCP scan into the right. We see that his key piece can was actually was positive and you can write this between two and three. So this would be indicative of underlying cardiac amyloidosis. And then finally misty she had a normal critic M. R. I. With a normal P. I. Scott imaging no L. G. And R. P. I. P. Scan was zero on the right. You see that the sternum uh feeling very bright white and we see no uptake in the mind of cardi. Um at this point MR C. Has abnormal cardiac M. R. I. M. P. I. P. MR. L. Has an abnormal cardiac M. R. I. M. P. I. P. And he has a normal cardiac M. R. I. M. P. I. P. And so the next step on our algorithm is to undergo genetic testing. So very interestingly. Mr C. Was home as a guest for V. 1 42. I Mr L. Was hetero saga for V. 1 42. I and misty was actually headed home as a guest for V. 1 42. I. So all three of these patients had the genetic mutation for correct Emily dosa. And what's more interesting is is actually two brothers and a sister. And so we went ahead and wrote this up as a specific spectrum of transferring incorrect doses in a family. And so there is variation based on sex and genetics. Homosexual men tend to have symptoms 10 years prior to his men and their symptoms tend to be more severe. Women tend to have less symptoms or no symptoms with a less disease burden regardless of of inheritance patterns. Even if their homes august they may not they may never exhibit any actual fanatic uh symptoms of the disease itself. But it's very important because this is also dominant disease. So it's important for family screening in planning. You know if misty would have uh you know boys they have quite an increased risk of also having karl amyloidosis. The next let's shift to the treatment. So patients are often intolerant of traditional G. D. M. T. And diaries is and this is primarily due to restricted physiology with a fixed stroke volume and also autonomic dysfunction. In addition re control medications can cause bradycardia especially in the al amyloid patients. Um you know these re control medications can actually bind to the amyloid fiber ALs and cause dysfunction. And further the AL amyloid fibers themselves can be cardio toxic itself themselves. And then further there are no evidence for I. C. D. S in this population studied considering atrial fibrillation patients are often intolerant of a fib due to the six stroke volume instructor physiology. So it's better to get them out of a fib and keep them out of a fib. The chat vast scoring system was never applied to the patient population. They should always inter coagulate. And there are no studies to date comparing warfarin versus no a cardiac. In addition um you know, possibly with these patients you should always get e regardless. To rule out left atrial appendage. There was a study that was done out of mayo that found that 33% of patients referred uh for a. T. Cardioversion had underlying cardiac amyloidosis actually had left a clot. And 46% of those patients had confirmed therapeutic doses of any calculation or they had confirmed onset of fibrillation less than 48 hours prior to the T. Or part of the tv cardioversion. So with that should be ready for complications if they undergo cardioversion, there's a much higher risk of VT VF. There's a higher risk of brady arrhythmias requiring pacing and there's a higher risk of stroke by 14%. So the final part of our talk will be talking about disease modifying treatments. So again we see the instagram of deliver producing um the uh T TR that becomes pathologic when it breaks down into monomers and becomes these disjointed uh five rolls and aggregate. So the first class of medications are called T tR silencers. That includes uh patterson patterson participant and Patrice sarin. So T tR silencers uh include the antisense nucleotides and they're designed to bind to messenger RNA to prevent translation and protein synthesis. And that includes the Paterson and next generation Peterson formerly called a K. C. A. T. T. R. L. R. X. Uh And this utilizes a ligand to conjugate uh in a sense the chemistry to increase potency and lower the dose improving safety profile. Uh The other class of these medications are small interfering RNA molecules are also called short interfering RNA or or silencing RNA. And there are non coding, non coding double stranded RNA molecule that activates and binds to the M. RNA. That also kind of prevent translation and protein synthesis and that includes the first generation patisserie in in the next generation of Lutheran and overall the T TR silencers. Uh repeated studies have reduced the circulating T Tr by by about 82% up to 97%. Depending on which study you you you investigate. So the sound sir will go and block the production of of T.T. on average 85%. The next class of medications are T TR stabilizers and that includes all day feminist and informative. Definitely. Diesel is a derivative of the feminist is a non inside derivative and a Communist is a actually made by using a special molecule in a chemistry library. So the stabilizers will go and prevent the tetra from breaking down and becoming a pathological uh summer. And the last class of medications are T TR disruptors. So this includes doxycycline and bile acid derivatives, um E C G G C G, which is just high dose green tea. And then the new, the newest medication is PR 004, which is a monoclonal antibody. These disruptors are thought to disrupt the labral themselves or even possibly act um by breaking them down. I tried a little aggie. But uh so these medications have all been studied for T. Tr Emily doses, but as mentioned before, there are several types of T Tr Emily doses. That includes the primary cardiomyopathy version of it and the neuropathic version F. A. P. And then there's the gray area where patients have both. So, for the cardiac involvement, the current treatments that are approved are just disseminate for the F. A. P variant. There are three medications you notice in participant antisemitic, the feminist or the brand name of vita max is a uh derivative Non NSAID medication that first developed in the 19 nineties. It's an oral pill is initially studied in F. A. P. And but they had an open label extension for the cardiac uh you know, genotype And they eventually did a phase three trial called a T. TR ACT trial, which should benefit in patients with N. Y. H. A. Two and three symptoms. And it was subsequently the first medication approved in 2019. However, there are a couple of medications that we use as kind of off label use and that includes all cycling and these bile acid derivatives and high out dose of green tea. So if patients are improved for feminist, sometimes you can start medications on these off label use medications. So that's one result or diluted. Is it N said derivative is also an oral pill is initially studied in patients with F. A. P. And um with a single center study uh with 23 patients with wild type and hereditary A. T. T. R. And they found that the patients tolerated. So the current statement is that this may be a reasonable medication. If the patient does not have any other therapeutic option, it has preserved renal function and compensated heart failure. But there was some hesitancy given that it's a derivative. And then further uh you know, when they started doing additional studies in patients with F. A. P, they started including patients with F. A. P. With some cardiac involvement. And so they kind of skirted the uh you know, doing cardiac only testing. And by adding on the subset of population that had cardiac involvement as well as a way to, you know, prove safety to prove the safety profile to you know, possibly extend into other trials. And so another Sin or Tech city. The first generation A. S. O. Is injected once weekly. It's approved for F. A. P. Based on the neuro T. TR study. And in that study itself it had actually had 63% of the patients had cardiac involvement. And uh they had ny say one and two symptoms that they excluded patients with a three in four symptoms. Currently there's no trial for cardiac involvement but there is an open label extension or N. Y. J. One through three symptomatic patients. And then participants were on petro is a first generation small interfering RNA is infused every three weeks. In the initial study, the Apollo trial was for F. A. P. But 56% of the patients had cardiac involvement. And so they designed a new trial that should be wrapping up shortly. The Apollo B trial which was for the 80 tr subtype and include patients with NY one and two. And they did this caveat where they included Ny che three unless they were high risk. And they also excluded watch a four and the results that are currently pending. And then the next medication uh patterson, there are two pending trials, the cardiac T tR and the euro T TR trials. So patterson is the next generation A. So it has a special login that and it's also injected once weekly um T TR neuro transform was for F. A. P. And the cardio cardio transform was for the cardiomyopathy version of it. And these this included patients with N. Y. H. A. 123 symptoms and excluded patients with N. Y. H. A. Class four symptoms and then the mattress or in their ongoing helios A. And B. Trial helios A. Actually um just wrapped up for F. A. P. But this is a next generation small interfering RNA. It's injected subcutaneous every three months. It's approved for F. A. P. Based on the helios a trial and they have an ongoing trial he'll be. But again they excluded patients with a class three with high risk symptoms and class four symptoms. And then the last medication is a core medicine. So there's the ongoing attribute CM. And attribute PN trial for the A. T. T. R. And F. A. P. Uh variance respectively. So Corman, it was actually designed using this chemical library and it mimics stabilized mutation and it prevents the testament from from dissociating. And the attribute PN trial had also included patients with cardiac symptoms. Um They included patients with nyC A Class one and two symptoms that excluded N. Y. J. Three and four and the attribute cm, which is ongoing um included patients with a class one through three symptoms. And then finally uh there's a newer medication that's kind of on the horizon. It's called Pyrex 004 is A. I. V. Administered monoclonal antibody that was actually developed to selectively target T. TR crowd hopes that are only expressed on the monomer or non native confirmation. So it does not bind, it does not affect normal T. T. Are circulating in the bloodstream. It only affects pathologic T. Tr um It was developed and a trial was actually recruiting at the onset of the pandemic. But with the onset of the pandemic, this trial was actually temporarily shelved. But on recent evaluation they restarted the trial. And so it could be very exciting because an initial in vitro studies, they showed that this medication has a high affinity binding and actually may suppress fiber production and aggregation. It may actually break down the fibers themselves. So all the other medications that we talked about either uh silence or stabilize the T. Tr the pathologic T. Tr this medication can actually break down the fibrous possibly. And so uh you know, we talked about how all the other trials included anywhere from N. Y. H. A. 12 up to three. Um They prevented any kind of um worsening disease process but did not reverse the underlying disease process. So this medication may be a game changer in that it can uh potentially break down the fibers themselves and actually reverse the damage that's been done. So looking at a timeline before 2018 there was zero treatments in 2019 to feminists came out. And there was one treatment now there's potentially six or even more on the horizon for cardiac amyloidosis and then further um there was a recent article in august of 2021 talking about the use of CRISPR to do gene editing and T. Tr Emily doses. And very interestingly I remember reading this article about a year ago. Um and there's a lot of controversy uh in recent news about the use of CRISPR and gene modification. But actually saw my patient about about a week ago. And the first thing she asked about was when can I get CRISPR to modify my genes to make the cTR go away. So with that I'd like to leave you with a few pearls. Um you know have a high level of clinical suspicion if the patient has L. V. H. Neuropathic symptoms should be noted that patients actually develop cardiac symptoms about 10 years after neuropathic symptoms. So don't wait for those. Those cardiac symptoms don't wait for dysthymia or any any symptoms. Screen is important and can be stored in your office but we're happy to help at any point always order your P. I. P. Respect to prevent any kind of false positives. Traditional volume management strategies and G. D. M. T. Can be harmful in these patients. That restricted physiology and that thick stroke volume be mindful of fibrillation and know that there's a higher risk of complications and have left atrial. So potentially always get a. T. E. With your cardioversion. And there are treatments now which can slow the progression of disease with many addition on the horizon. But early referral is key because you know the way the disease or the way that the medications work is that currently there's no reversal medications approved by the FDA. So with that I thank you for your time. I'll open open up for any questions and I'll leave my contact information here and feel free to email with any questions or any patients of interest. Published January 23, 2023 Created by Related Presenters Zackary Tushak, D.O. Sentara Advanced Heart Failure Center View full profile
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