Who should be tested for cardiac amyloidosis? In this episode, Andrew Perry, MD, talks with Daniel Lenihan, MD, an expert in cardiac amyloidosis at Washington University in St. Louis. They review the exciting advances in the field of cardiac amyloidosis from epidemiology to treatments.
You might be surprised to hear how common this condition is. Links to articles referenced:
A transcript of the podcast follows:
Perry: Hi, everyone. It’s Andrew here. I’m really excited about today’s episode on cardiac amyloidosis. Dr. Lenihan is a leading expert and master clinician when it comes to cardiac amyloidosis. He was recruited here to WashU recently to head up their Center of Excellence of Cardio-Oncology. He had a lot of interesting data to share about cardiac amyloidosis, and our discussion has already shaped my approach to patients with heart failure with preserved ejection fraction, and you’ll soon learn why. I think you’ll really enjoy this episode, and there’s a lot to learn and to take away from this.
… Thank you for meeting with me today, Dr. Lenihan. Can I have you first introduce yourself, your name and your title for our audience?
Perry: The reason why I’m meeting with you today is that recently you gave us a grand rounds, particularly on amyloidosis, and you spoke specifically about cardiac amyloidosis. There’s been a lot of exciting developments in that field recently, particularly in terms of therapeutics that are now able to be offered. To kind of start just briefly for people who are listening, amyloidosis is characterized by deposition of protein within various body tissues. It can be caused by many different subsets which we won’t necessarily get into talking today about those specifics. A question for you, Dr. Lenihan is how often in people with amyloidosis, in general, how often does the deposition occur in the myocardium within the heart?
Lenihan: It actually probably occurs more frequently than we know, especially because in order for somebody to have a proven diagnosis of amyloidosis, you have to be suspicious of it and then you have to do a number of detailed tests in order to prove that. So in the situation where we are convinced that a person has amyloidosis, most of the time they have cardiac involvement, but not always. Probably 75% of the time if somebody has established amyloidosis, they will have cardiac involvement if you look hard enough.
Perry: You’re saying if you look hard enough … so they probably have cardiac involvement, but it may not be clinically obvious at the time of their diagnosis of their amyloidosis. Is that kind of what you’re saying?
Lenihan: Yes, and also, it’s a very common condition that people would come into the hospital or to an office visit with symptoms of heart failure. And if you do an echocardiogram, for example, and their heart function is normal, you attribute this to some non-descriptive cause such as high blood pressure or excessive sodium intake or some sort of common thing. But in the instances where something made you suspicious and you pursued it further, it’s usually non-specific symptoms that ultimately are the presentation for amyloidosis. People have fatigue and shortness of breath and maybe some unexplained weight loss or weight gain. Those symptoms don’t always lead towards the pursuit of amyloidosis, rather they’re attributed to something else more common. I think that it really does matter how aggressively you look for it, because the more aggressively you look for it, the more likely you will find it.
In those patients in which we’re convinced that they have amyloidosis by whatever tests, the likelihood that it ultimately is going to have cardiac involvement is pretty high.
Perry: Since you bring that up, let’s go there now. Thinking about patients who get admitted to the hospital and we just generically label them as HFpEF, heart failure with preserved ejection fraction. What are the maybe extra triggers that you should think, “I should test this person for amyloidosis?” Because I think I remember correctly from your talk in saying that within that population of hospitalized patients with HFpEF, there’s a relatively high prevalence of cardiac amyloidosis.
Lenihan: Yeah. This is just now kind of being sorted out in different places. But, for example, the one recent study looked at patients that were admitted for heart failure who had a normal EF, and when they pursued the diagnosis of amyloidosis, they came up with that diagnosis in 13%. So there’s a lot of patients admitted to the hospital with HFpEF, about 500,000 per year in the United States. If you took 13% of 500,000, that’s a lot of patients.
Perry: That is a lot of patients.
Lenihan: That’s a lot bigger number than what we would have proposed as the incidence of amyloidosis. Yeah, I think it’s a whole order of magnitude higher than what we are previously thinking of.
Lenihan: Then if you do autopsies on people that die and you look at their cardiac tissue, staining appropriately for amyloidosis, as you age, if you do autopsies on people that die when they’re 80 or 90, basically 100% will have evidence of amyloidosis in their heart. Again, if you look for it, you will find it. The question is we don’t want to wait until it’s so obvious where some image or EKG findings or MRI or whatever other tests that you’re doing is so abnormal that you say, “Yeah, for sure this is amyloidosis.” Unfortunately, that’s way too late, so we have to learn how to … perhaps, we have to learn how to read the tea leaves a little bit better, the little signs, the little symptoms that tip you off that something is not right.
Perry: Gotcha. That’s interesting. You’ve stated that basically as people age, the prevalence of amyloidosis being found in them increases almost to like 100%. It’s almost like you cannot avoid getting amyloid deposits as you age.
Lenihan: Yeah. One of the more common questions is when they talk about Alzheimer‘s and dementia and they say they’re amyloid deposits. People then go, “Are those the same amyloid deposits?” I honestly still don’t know the answer to that question, but it’s quite possible in that the signs of early aging in your brain are amyloid deposits. That may be, for lack of better description, a sign of aging in your heart or other tissues, the amyloidosis deposition.
Lenihan: It’s one of those things that our standard clinical tests that suddenly say, “It’s very obvious that there’s cardiac involvement.” If we wait for that, then a long time has passed and the disease has deposited extensively. Just like if it was a cancer, for example, you don’t want to wait until it’s stage VI cancer. You want to get it at its earliest place where an intervention is going to have the most likelihood of success.
Perry: Sure. When we’re talking about these elderly patients who develop amyloidosis, is that what we call this senile or wild-type amyloidosis, because there’s multiple subtypes within amyloidosis depending on their configuration of their light chains.
Lenihan: Again, you probably could find parallels in our definition of myocardial infarction. Back in the day when I was in training, we called it Q wave or non-Q wave infarction. Then a few years later, we started calling it ST elevation or non-ST elevation. The terminology has changed when we’ve defined it differently. That happens in many things, but certainly in cardiology issues. Historically, senile amyloidosis was detected in older people and so that’s how it got its name. Now that we’re in a different age, we now are defining amyloidosis by the type. TTR amyloidosis is a type, and we know that some people have a mutation, so we refer to that as mutational-TTR amyloidosis. Those that don’t have an identifying mutation, we call it wild-type.
Perry: Is that mutational the same thing as the familial amyloidosis?
Lenihan: Yes. So familial amyloidosis is an older name, just like senile amyloidosis is an older name. Now that as we’ve hopefully defined it better to a particular type, so yes, the senile amyloidosis, for the most part, is what we refer to as wild-type TTR amyloidosis now. But honestly, senile amyloidosis 10 or 15 or 20 years ago encompassed familial, also, because we didn’t know about all the mutations.
Perry: I see.
Lenihan: Now we know about more mutations. There was a subset of those that were considered senile amyloidosis that probably had mutational TTR, but we just didn’t know it.
Lenihan: I think that as we’ve been more discerning in defining the type and identifying mutations that now we can be more specific.
Perry: Sure. No, that makes sense. As our knowledge increases, we can be more specific in our diagnoses. But of these types or these subtypes within amyloidosis, are there types that are more prone to cardiac involvement than others?
Lenihan: Yes, that’s a good question and we’re constantly learning more details, and so whatever we thought 10 years ago we may think differently now. But, for example, familial amyloidosis, if you lived in Portugal, for example, is associated with a particular mutation because it was carried down in generations from royalty, really, but the mutation carried down in all the generations. It’s basically an autosomal-dominant transmission that those patients in Portugal or Brazil are more likely to have nerve involvement than cardiac, whereas the patients in the U.S. that may have come from Africa or Jamaica, some other South America source of mutation, that they may have predominantly more cardiac involvement.
Then there are different mutations where it’s in between. I showed one figure where it kind of highlights that. The V30M mutation is predominantly neuropathy, and that’s the one that’s in Portugal or it came from the Portuguese and Spanish royalty, whereas V122I, it’s in 3% to 4% [of] African Americans in the United States, and in particular, in the St. Louis area, there may be a little bit higher prevalence of that mutation because that’s where those families have settled, whereas when I was in Tennessee, there was an Appalachian variant that was more likely to be encountered, and that’s this T60A. It does matter what region of the country or world that you’re in as to how the amyloidosis may manifest. It usually is a combination, at least TTR is a combination of neurologic and cardiac disease predominantly.
Lenihan: That’s a good question, but we don’t think that it is in the same … I mean sickle cell is an autosomal recessive condition, so in order to have true sickle cell disease, you have to have both genes. Or I see a S-C trait, so you can be a carrier and you may ultimately transmit that to your children, but you’d have to be married to a similar carrier for a child to have sickle cell. In the case of most or all of the TTR genes that are felt to be autosomal dominant, so if you get the gene, then you have it. It doesn’t matter whether you have both genes or one gene. You have enough, but the complex issue there is penetrance. You have the gene. It doesn’t necessarily mean you’re going to have the disease.
We’re still trying to learn what brings disease on, and I’ve had families of people that had disease. They were all the same sex, for example, similar age within a couple of years, and two of them had the mutation and one of them didn’t. One person had tremendous disease manifestations, another one who had the mutation had no disease manifestation, and then the person who didn’t have the mutation was otherwise fine. You can have a wide variability of how the disease manifests in any individual patient. You can have the mutation and not necessarily have the disease.
Perry: No, it’s very similar I think to hypertrophic cardiomyopathy. I was talking with Dr. Bach about this. There’s a lot of genes in there that can confer that disease, but it’s a greater issue of their penetrance, just having the gene itself …
Lenihan: Yeah. The other thing about hypertrophic cardiomyopathy that’s both similar and different is that there’s a certain number of genes that are clearly associated with hypertrophic cardiomyopathy, and there’s certain genes of those that are very high risk, so they’ve matched those to some sort of familial condition and it’s high risk. There’s a whole other set of genes, so if you say, “We’ve got these 10.” Let’s just put a number on it, 10 high-risk genes. There’s fully another 40 or 50 that aren’t necessarily high-risk genes, but they’re abnormal. There’s something not right about them, so they refer to those as variants of unknown significance. They recognize that it’s not “normal,” but it may not confer disease and it also may not confirm high-risk disease. There’s a lot, in the case of hypertrophic cardiomyopathy, there are a lot of possible disease mutations, and we don’t know whether they really mean anything or not. To say that process is similar for TTR is partly true.
There are a number of genes that we know are highly associated with disease. I think that there are probably a number of other genes that are kind of like the hypertrophic thing where there’s variants of unknown significance. It’s going to take a lot of careful research to, say, graduate one gene from a variant of unknown significance to one of disease manifestation. I think this is something we’re learning about all the time. Right now, there’s a certain set of genes that are known to be associated with TTR and that’s what we screen for.
Perry: Gotcha. Okay, very interesting. So when we’re talking about, then, screening for genetic mutations, I want to circle back again to this issue of are inpatients in that relatively high prevalence on amyloidosis within HFpEF patients like that, 13%. As you’d mentioned, there’s this end-stage presentation of amyloidosis that’s catching it too late. The conduction abnormalities, the thickened myocardium, clinical heart failure with congestion, shortness of breath. I suspect that there’s probably some thoughts or some people who’d argue for just universal screening of all inpatients with HFpEF to screen for amyloidosis. What might be other clinical suspicions or other laboratory evidence anyhow on your initial evaluation that may suspect you to lead and thereby enrich your population even more for who you’re testing?
Lenihan: That’s a really good question and I would say we’re already screening for it. We just don’t realize it. We don’t recognize it. If you have a person that’s admitted for HFpEF to the hospital, what percentage of those patients get an echo?
Perry: I mean, there’s a lot. I’m in the renal consult service right now and I just went and saw somebody admitted with HFpEF, and they had an echo just a couple days ago.
Lenihan: What would be your estimate for the number of people that get an echo, first-time admission for HFpEF?
Perry: I’m going to say it’s probably not 100%, but it’s easily over 50%. Probably 70% or 80%.
Lenihan: I mean, of course, I’m a cardiologist. I see cardiology patients, so they’re probably not even going to call me until they get an echo, but the likelihood, and actually if you just look at indicators for people who are admitted for heart failure in the country, what is one of their indicators? The first indicator that they ever even put out for CMS [Centers for Medicare and Medicaid] to determine readmission rate was EF. You have to do an EF assessment, one form or another, most people are going to do an echo. Yes, basically 100% of people will get an echo or should at some point during a hospitalization. You’re already screening for that. Then, also, what percentage do you think get an EKG who are admitted for heart failure?
Perry: 100%, easily.
Lenihan: So 100%. How many of those people admitted for heart failure do you think you do a troponin?
Perry: Again, it’s everyone.
Lenihan: It’s 100%. You’re already screening for it 100% of the time. The question is whether you’re putting those three things together to tell you that I need to be suspicious of something else. That’s the real question. If you do an echo and the EF is normal and they have mild LVH [left ventricular hypertrophy] and their troponin is 0.04, just barely abnormal, and you look at their EKG and it doesn’t have any LVH signs. Let’s just say that. Minor, non-specific ST Q wave changes. That person right there easily could be somebody whose first presentation for heart failure was from amyloidosis. I’m not saying every one of them would be. But you’ve already screened for conditions, and if you have LVH on echo, even mild LVH on an echo, and you don’t have any LVH findings on an EKG and you have troponin abnormalities, those are all pointing in one direction or they should. That doesn’t mean you go and do a myocardial biopsy on every person that comes into the hospital with HFpEF that has a little bit of LVH and a little bit of troponin and all that, but I would at least run it across your mind.
Perry: But you might try to then get an SPEP, a serum protein electrophoresis, or a serum free light chain and immunofixation.
Lenihan: Exactly, you might do those other tests or if you see kind of a large mismatch between the LVH and the voltages, for example, making you a little more suspicious of amyloidosis and you want to …
Perry: That’s what you’re referring to when you see the LVH on the echo, but you’re not seeing the corresponding EKG criteria of LVH on their EKG. That’s the kind of mismatch you were talking about.
Lenihan: Yeah, absolutely. That’s a very typical presentation, and then you might decide to do some other tests to look at the cause of cardiomyopathy. If you have mild LVH on an echo, what are you attributing that to? Since you’re on nephrology, you might attribute that to hypertension.
Lenihan: You might just say, “This person, they’ve been struggling with high blood pressure for 5 years. That explains it.” I mean that may be true, but that same thing happens in the neuropathy space where a diabetic who suddenly has neuropathy, maybe it’s even fairly prominent. They’re really bothered by it. You’re going to attribute that to diabetes. But if you had some of these other parameters that we’re saying, “That may not explain everything,” that you may investigate that neuropathy as not being from their diabetes, but from some other condition. I think common things are common, of course. High blood pressure resulting in HFpEF admission to the hospital is certainly a common thing. I’m not saying that all of those equal amyloidosis, but I am saying that maybe 10%, maybe 13% do.
Perry: That’s, I think, maybe what I was wondering about earlier when I asked about screening. Do we get an SPEP on all these people when they come through, a screening to that level, checking for different amyloids?
Lenihan: Yeah, I think that if their EKG and echo make you a little suspicious and let’s say they have a couple of troponins that are just a little bit abnormal, then yeah, I would say you might want to do one other test or two, whether you do serum free light chains to look for AL amyloidosis or whether you do a TTR scan looking for TTR amyloidosis or whether you do an MRI to look for any evidence of amyloidosis. An MRI is a good test to point you in that direction, but it doesn’t tell you the type. Serum free light chains is pointing you towards a type. The TTR scan is pointing you towards a type. The MRI is just presence or not.
Perry: The TTR scan, if I remember right, that’s a nuclear scan, right? A tagged nuclear scan and then you can see that uptake where the TTR protein is deposited. That kind of leads into this next topic about additional diagnostic measures like the nuclear scans, MRIs. It’s my understanding that to fully 100% make the diagnosis of cardiac amyloidosis you need the endomyocardial biopsy. Are there situations in which these other testings could be positive or conclusive enough that you could say, “Maybe we don’t need the biopsy for it?”
Lenihan: That would also depend on the region of country that you’re in and what your practice patterns are. There would be a difference, for example, somebody who’s used to seeing a lot of TTR amyloidosis and they do TTR scans all the time and their nuclear medicine department is highly attuned to how to do the study properly, etc. Then their testing characteristics may be better than somebody who does one a year.
Even though the published reports suggest that TTR scanning is very sensitive and specific, I have not found that to be the case. I think it’s a useful test, but it’s not a definitive test. There are some people that would say if you have an identified mutation and you have a TTR scan that is definitely positive that you don’t need to do a biopsy. I have a number of individual examples of where things are more complex than that. I tend to go towards a biopsy, whether it’s a cardiac biopsy or some other tissue depending on which organ is most affected, then a kidney biopsy can be a really diagnostic test, for sure. It’s just I’m not a nephrologist, so I don’t do kidney biopsies, but if I was a nephrologist, I would probably be saying, “A kidney biopsy is a really good test.” It proves not only the extent of involvement from the kidney point of view, but it also will frequently give you the type just by the way that they do the sampling. I think a kidney biopsy is a very important test, but I don’t order those and I don’t do them, so the nephrology team has to come up with that. But if I’m involved in a patient and there’s a suspicion of cardiac involvement, I’m inclined to do a biopsy because we’re comfortable with that.
Perry: This is a center that does a lot of biopsies here. I assume probably the same thing there. From an endomyocardial biopsy, you can determine the type of amyloidosis from there.
Perry: Maybe just to kind of recap what I’m hearing to diagnose that there are extra imaging modalities. This TTR scan. That’s pretty specific for type, but your echo, your EKG, your MRI can show you that there’s amyloid there, but to then find out what type is going to require tissue or some kind of mutation, like genetic screening would be my suspicion. Is that correct?
Lenihan: That’s generally correct. Yes. The standard clinical tests that we do all the time can point us in the right direction if you put the pieces together, but frequently we don’t put those pieces together. I mean the collective we, everybody. Again, the example being a long-standing diabetic who has a neuropathy symptom. For the most part, unless you have some reason to be suspicious, you’re going to attribute that to their diabetes. It’s only when you start pursuing it that you find that it may be due to something else. Just like HFpEF admitted to the hospital, if you attribute all of that or the 98% of it due to hypertension poorly controlled or dietary indiscretion, the other common things — that may be true. That may be the case in 90% of patients, but there’s 10% of patients that that’s probably not the right assumption. Can we be more discerning about who those 10% are?
Perry: Sure. I’ve got a comment on that. I’ve heard someone else describe this population of patients with HFpEF as that diagnosis of just kind of saying, “You have cancer,” and leaving it at that. Whereas really, HFpEF is probably going to encompass many different diseases and diagnoses within that that have yet to be fully delineated. One of these that we’re learning about currently or recently is amyloidosis probably making up a big chunk of these patients.
Lenihan: Yeah, I mean I think that’s a good analogy. I would say it’s a lot like that. If somebody is admitted to the hospital for heart failure, that’s a serious diagnosis. We know that anybody who’s admitted for heart failure to the hospital that they have about a 50% 5-year survival rate. That’s worse than most cancers except for, perhaps, untreated lung cancer or pancreatic cancer. Is it acceptable to say to a patient admitted to the hospital for heart failure that you have cancer of an unknown type? If you’re going to follow through on your analogy, no, you wouldn’t do that. You would say, “You have cancer. We’re not sure which type. We’ve got to do other tests to figure that out.” If you have HFpEF and you’re admitted to the hospital, it could be or it most likely is this, but we need to make sure it’s not something else. That’s probably how we should think about it.
Perry: I think part of what drives that attitude, as well, is that a lot of the trials for HFpEF have been largely negative. I’m speaking in terms of ACE inhibitors, ARBs, spironolactone +/-. But when you’re talking about amyloidosis, that space has already changed recently as well, so it’s not just the case of if you have amyloidosis, “We can’t really do anything for your cardiac amyloidosis.” That space has also changed dramatically in the last couple years.
Lenihan: Yeah, and there was a paper about a year ago published and it showed people with HFpEF that were admitted to the hospital, and this was a big database study, like 70,000 patients or something. The ones that had a low blood pressure had the worst prognosis. It was significant. If you came to the hospital and you had HFpEF, if your blood pressure was low, then you had a far worse outcome than if you had a normal or a high blood pressure. You think, “Okay, I guess that makes sense.” Does that make sense to you, in general?
Lenihan: These are all people with normal EF.
Perry: That’s true, but I think EF also can be a misrepresentation of their cardiac function.
Lenihan: Of course.
Perry: Have a reduced stroke volume or maybe they have reduced strain as another marker.
Lenihan: Exactly, so if you said, “What if those patients that present to the hospital with HFpEF that had a low blood pressure actually had amyloidosis, and that explained why their prognosis was so poor compared to the other population?” I mean, wouldn’t you find that to be rather amazing? I mean you’d go, “Wait a minute. Maybe a low blood pressure with HFpEF is an indicator that I need to look for something else.” That’s exactly what I would say. You are screening already. Most people are already screening with an echo, an EKG, a troponin, and a blood pressure. If their blood pressure is low when they present with HFpEF, yes, you should think of another condition.
Lenihan: All those screening tests are done. They already are done, but whether we’re putting them together is the real question.
Perry: A collective “we.” We’re doing all the screen tests already, but the collective “we” aren’t thinking of it in that regard.
Lenihan: Right, and I just think that it would be really interesting, for example, to go back at that study that I was referring to and really look at that population that had a low blood pressure. Are there ways in which we could tell that amyloidosis was an important consideration in those patients? I mean I think that’s quite possible, because I mean if you have diastolic heart failure and you get admitted to the hospital, what is overwhelmingly the cause of that, usually?
Perry: I mean usually we’d say hypertension, diabetes?
Perry: Interesting. No, super interesting. Let’s transition a bit to talk about therapeutics, maybe in our last kind of topic here, therapeutics for cardiac amyloidosis. As far as I know, there’s been three new drugs recently. I think it was the last couple years when they’ve come out.
Lenihan: This year.
Perry: All of them this year.
Lenihan: All of them this year.
Perry: Prior to that, treatments for amyloidosis had been stem-cell transplants and chemotherapies that were primarily brought from oncology. What can you tell us about these newer medications? This is tafamidis, patisiran [Onpattro], and inotersen [Tegsedi].
Lenihan: Yes, that’s correct. Those are all since April of this year, those all three have been published in the New England Journal [of Medicine], so those are exciting drugs to consider. Patisiran and inotersen are approved by the FDA for peripheral neuropathy, not cardiac, but for peripheral neuropathy.
Perry: Like carpal tunnel peripheral neuropathy?
Lenihan: That is one manifestation of peripheral neuropathy, but the specific FDA recommendations are polyneuropathy. Usually that involves autonomic dysfunction or peripheral neuropathy predominantly in your legs.
Perry: Gotcha, okay.
Lenihan: Those two drugs are FDA approved. They are very expensive. Patisiran is given IV. The other one is given sub-Q. They can be very effective at treating the peripheral neuropathy. Whether they are effective at treating cardiac disease is not as well established. There’s a suspicion that they may be effective, but the length of time that those studies were done is probably not enough time to see a difference. That brings us to tafamidis, which was recently published. They looked at 36 months, whereas the other two drugs were 18 months. If you look at the survival curves with tafamidis, they don’t separate until after 18 months, so it takes a while of treatment to really have an impact on the cardiac structure, but in the case of tafamidis, it was a very powerful effect. When it started to occur, when it became apparent, it was very substantial.
Perry: Interesting. My understanding of these at a mechanistic level is that tafamidis primarily stabilizes the protein and doesn’t allow more deposition of the protein. Whereas these other two, patisiran and inotersen, they can actually remove the protein from where it’s been deposited.
Lenihan: No, they can’t actually remove it. They suppress the production. They primarily act on the liver and suppress the production of TTR, which is a normally-produced transport protein in your body. The patisiran and inotersen are broadly categorized as RNA-silencer type medications. They shut down the production at the liver.
Perry: I see.
Lenihan: Tafamidis is more about stabilizing the protein so that it doesn’t deposit in tissues. We are hopeful that there are new drugs being developed that are probably going to be monoclonal antibody based that may leach protein out of the tissues, but those to date have not been proven, but we’re hopeful.
Perry: Gotcha. Very interesting. Thank you. Are there any other medications that are specific towards cardiac amyloidosis other than tafamidis, I guess?
Lenihan: Not really. Diflunisal [Dolobid] is a non-steroidal agent that functions somewhat like tafamidis. It’s just not as potent. In people that can tolerate that, we generally would use it. In the case of AL amyloidosis, doxycycline also functions similar to tafamidis in the way that it stabilizes the protein so that it won’t deposit, but again, that’s both diflunisal and doxycycline. Their positive effect is more modest as opposed to tafamidis, which is quite pronounced. The benefit of diflunisal and doxycycline is that they’re available, so we can get them and we can prescribe them, and patients may be able to tolerate them.
Perry: Very interesting. Very cool. A lot of interesting developments in the amyloidosis space.
Lenihan: Definitely, and I mean we’re really excited about the new drugs that are being developed. Each one has a potential important mechanism. Ideally, I would hope that for amyloidosis, whether it be from AL or TTR or some other version, that we have multiple avenues to treat those patients. We’re not there yet, but I think it’s not hard to see that might be the way to go to treat with an RNA silencer, for example, plus tafamidis and ideally then a monoclonal antibody, so you get at the condition in all three ways. That would be, at least conceptually, that would be really great.
I think if you think about heart failure, for example, if you just say systolic heart failure, we started out with ACE inhibitors. We added beta-blockers and made a huge difference adding it to and then adding spironolactone on top of that added another chunk. It was really triple therapy in that setting that made the biggest difference. One drug is good. Two drugs is better. Then three drugs is much better. In the case of systolic heart failure, we have other options, too, but that’s just the summary of what happened in that space. If you apply that summary to amyloidosis, you might be able to see the same thing. One therapy works. Two therapies work even better. Possibly, three therapies would be the best. I don’t know. That’s a little ways off, for sure.
Perry: We’ll see if we end up in that area with multitargeted therapy.
Lenihan: I think that it’s good that people are thinking about it and companies are investing in trying to develop new therapies. It’s an exciting time.
Perry: Thank you for letting me visit with you about amyloidosis.
Lenihan: Super. Thank you very much.
Perry: To review, the most useful clinical pearl I gleaned from this discussion was how to use the information I already have with my patients admitted for heart failure to screen them for amyloidosis. Remember, look at their echo, their EKG for discordance in LVH. The other pearl is that if you have a HFpEF patient admitted with a low blood pressure, probably your suspicion for amyloidosis would also be increased. Thanks again for listening.