Nolan Alexander (Host): Meaningful Medicine is a Novant Health podcast, bringing you access to leading doctors who answer questions they wish you would ask. From routine care to rare conditions, our physicians offer tips to navigate medical decisions and build a healthier future. I'm Nolan Alexander. And today, we're speaking with Dr. Zachary Garrett, a cardiologist, and Tucker Johnson, a nurse practitioner, to discuss rare heart diseases. First, though, gentlemen, how are you today?

Zachary Garrett, MD: Doing great, Nolan. Thanks so much for having us on.

Tucker Jonhson, FNP: Yeah. Nolan, it's a balmy 95 degrees here in Wilmington. So, it's good to be inside doing this.

Host: Don't worry, this podcast will stay inside the entire time. Hopefully, you don't break a sweat. Dr. Garrett, many listeners, they're familiar with some of the more common heart concerns, right? Like blocked arteries or rhythm problems such as AFib. I understand, though, you focus on rare diseases. What are some of those issues that you treat?

Zachary Garrett, MD: So, there's two issues we predominantly focus on. The first of which is called cardiac amyloidosis, and the second is something called hypertrophic cardiomyopathy. We could spend hours talking about both of these, but kind of giving an overview of these with cardiac amyloidosis, this is a problem in which our body creates these abnormal proteins. Our body creates all kinds of proteins naturally, but what can happen is that that process can go awry and you get these proteins that are mismade and they can stick to one another. And then when they do that, they can start to build up in our body where the body can't break them back down. They can start to build up in the heart, the nerves, joints, and different locations. And so, that's where it can really start to cause problems and heart-related issues. The second of which we manage is something called hypertrophic cardiomyopathy. This is something that tends to be genetic and causes the heart to become thickened and can start to cause issues with the heart because of this thickening and everything.

And so, even though we call these rare, they're more or less uncommon than what we really thought they were. And so, they're just not something that we typically see on a day-to-day basis within your normal clinic or normal cardiology clinic. And so, what we really did is about three to four years ago, Tucker and I created this rare disease clinic, and then added a third physician assistant, Carolyn Crocker, last year. But we created this clinic to really help streamline the identification, the diagnosis of patients with these more uncommon issues, and also help improve the quality in which they're treated and then managed. And a lot of these patients that, you know, beforehand probably would've been referred elsewhere to specialists that they would have traveled long distances to see and had the complications of having to travel and to be able to see specialists, get the treatments and everything else. And so, it's really been helpful to be able to focus these patients and see these people with these more rare conditions and everything.

So, a couple of things that we do within this clinic as well, is provide a lot of education to our partners and help them identify these patients that need further testing and further screening, and also helping them to understand what new treatments are available and what's out there for these patients and really kind of what we can offer and everything to improve their quality of life.

Host: So, what I'm understanding there, local access, more screening, more knowledge of treatment options?

Zachary Garrett, MD: Absolutely. Especially over time, as we've really learned more and more about these conditions, particularly something like cardiac amyloid. This was something that we 10, 15 years ago did not know very much about. And you see the amount of research and the amount that we've actually learned and the knowledge that we have of this has really exploded within the past several years. Previously, over the past five to 10 years, we've had one treatment for this. Now, we have three FDA-approved treatments with more that are probably, hopefully, on the horizon within these next couple of years.

Hypertrophic cardiomyopathy itself has also had significant advancements in treatment to where before really we had to focus on surgical interventions for a lot of these patients in order to improve quality, and now we have new medicines and everything too. And so, there's really been a lot of expansion of knowledge and everything within these conditions. And when we have this type of a clinic that specializes and focuses on these things, allows us to really take that time, spend the time educating patients, take the time for them to make sure they understand what we're looking for, and then if we found it, how we're treating this and what things look like going forward for them. And then, providing them access to treatments that they otherwise would not been able to get; working, you know, within our clinic, working specifically with our pharmacists in kind of really a multidisciplinary fashion to get these patients treated.

Host: So Tucker, tell me a little bit more about what Dr. Garrett just said there. What are some of the treatment options that are available?

Tucker Jonhson, FNP: Treatment options are very disease specific. So within our cardiac amyloidosis space, it really depends on the type of cardiac amyloidosis the patient has will determine their treatment path. So, our job in this clinic is to identify what type of cardiac amyloidosis we believe the patient has, nail the diagnosis, and then get them on the appropriate therapy.

So, a lot of the current therapies, at least the mainstay of cardiac amyloidosis treatment, is a drug called tafamidis, was FDA approved in 2018. And this drug in particular was aimed at, you know, stabilizing these proteins. What happens, as Zach alluded to earlier, is this TTR is a protein your liver makes. Everyone's liver makes this protein. It's a carrier protein. What happens in the disease state is it becomes unstable, breaks down, and then stacks up in an unusual form. And so this drug was aimed at keeping that protein stable. It's an oral drug. You take it once a day. Because it's so disease specific, there's essentially no drug-drug interactions and very few if no side effects. And it really helped improve quality of life and longevity for patients.

So, following tafamidis in 2018, another stabilizer was given FDA approval in 2024, a drug called acoramidis, also oral. You take it twice a day. Very similar, treatment response, very similar sort of pharmaceutical profile as far as its mechanism of action. And then, there kind of is another sort of mechanism of action in what we would call gene silencers. So, cardiac amyloidosis, once diagnosed, if you have true TTR, which is these abnormal proteins coming from the liver, there is what we call silencers. So, it helps to tell the liver, "Hey, let's just not make this protein."

And so, what happens is, you know, for folks that have either a hereditary type cardiac amyloidosis because there is a sort of hereditary expressive phenotype, for folks that have that, this drug was already available, if you have that and what we call polyneuropathy, which is a kind of a secondary expression of amyloidosis. These are injections that people get. Depending on the formulary, there's now two different drugs sort of in this space that sort of treat down this similar pathway. One is an infusion every three weeks.

So, a lot of options in the amyloidosis sort of space, specifically with TTR, which is great. And a lot of new exciting things coming down the pipeline. Current therapies really target disease stabilization, and kind of just holding folks where they're at, which is great, because before there was nothing.

But coming down the pipeline, there's some kind of cool potential options that are sort of getting fast-tracked from the FDA as far as research goes. Outside of amyloidosis, if we think about hypertrophic cardiomyopathy, like Zach alluded to, typically, we would sort of borrow from the heart failure space and some of those meds that we would use to manage, really mostly targeting that lowering heart rate and helping to reduce the heart's contractility, because the symptoms from hypertrophic cardiomyopathy usually come from the sort of hyperdynamic state, and just the disruption of hemodynamic flow from the heart's pumping function out to the body.

And so, now we have some medications that do a much better job at that. And so, that's pretty exciting for patients that aren't good surgical candidates, for folks that wouldn't tolerate open heart surgery well, because, you know, that was essentially the gold standard for these folks. But now, there's medication options so people can kind of get that care local. They don't need to travel to academic centers or out of state to sort of see these, you know, specialists. Some of them still do, and some are still appropriate for that, but we're able to take care of them locally, which is really cool.

Host: What else is important with how you work in the clinic to support patients in these rare issues besides the treatment options that you just laid out?

Tucker Jonhson, FNP: Yeah, really, you know, that's a good question, Nolan. Thanks. I think what's probably most important is the education piece, you know, helping them to understand the disease state, things that they can do from a lifestyle perspective that can help modify the disease state. And then, also just longitudinal care, kind of tracking them through the disease state. So, I think that's really beneficial, having those patients sort of siloed under our care. We're able sort of to kind of see some of these other things that are pretty common with these disease states and kind of help catch them early and get them in front of the right subspecialists, you know.

I think specifically with our amyloid patients, high risk for conduction disease, needing pacemakers, high risk for arrhythmias like atrial fibrillation, and they tend to have more issues with those other problems, meaning more symptoms, higher risk for stroke with AFib. So, kind of by us knowing them, identifying them, we're tracking these things and kind of addressing those other issues a bit, more urgently as they come up.

Zachary Garrett, MD: I think the other thing too is that, a lot of these conditions we kind of talked about, both of these do have some degree of inheritability within families, particularly with, something called TTR amyloidosis, which can be hereditary. One form of it can just happen just because in older age, usually beyond the sixth decade of life.

But there are people that can have hereditary variations of this. And then, also with hypertrophic cardiomyopathy, it does tend to be genetic and run in families. Within this clinic, we do offer genetic testing, and we're able to help identify gene mutations that may cause these issues to where we can help family members get screened. And that way, we're not just taking care of the patient themselves, but we're taking care of families and helping identify these patients and help them find family members that may have the potential to develop this and get them identified much sooner in that way that we're able to get them on appropriate treatments and everything and watch for the things that we need to be doing before they even may develop full, complete, you know, clinical development of the disease. That's another big part of, I think, what we do is the genetic testing is a big help.

Host: So building off of that, Dr. Garrett, what are some other risk factors and even prevention methods that are available for some of these uncommon diseases that you see?

Zachary Garrett, MD: Unfortunately, there's not really much that can be done to prevent any of these diseases. As of right now, there's not a lot from an environmental perspective or something extrinsic to what someone can do or something that they do that will cause these type of things. At this point, most of them can be genetic or inheritable. Some of them just happened for unknown reasons at this point. We've not identified things within that would increase the risk of it developing in someone.

Now, certainly living a healthy lifestyle, making sure that, you know, someone is maintaining a good diet, regular exercise, healthy weight, and all these type of things are helpful and beneficial just in general, but would not necessarily prevent from one of these things from happening or one of these conditions. Really, the focus is that if someone were to develop symptoms and things that would go along with these, cardiac amyloidoses, the problem with cardiac amyloidosis is that it tends to cause a multitude of different symptoms that are pretty common, especially when we're talking about people that are in their 60s to 80s, things like carpal tunnel syndrome, back disease like lumbar stenosis, neuropathy, heart failure, atrial fibrillation. These are pretty common things to happen as we advance in age. But it's really all these things get tied together, and it's not really until you kind of take ten steps back and look at everything as a whole that you say, "Maybe amyloid actually links all these things together."

Whereas with hypertrophic cardiomyopathy, it can present at many different times of life. It can present very early in life, it can present very late in life. And it also can create different spectrum of symptoms. And so, there are people that are very young, 15 to 20 range, that have the development of hypertrophic cardiomyopathy and be very symptomatic. Shortness of breath, dizziness, abnormal heart rhythms or it may be something that we find incidentally in somebody that's 80 years old and never had a problem with this.

And so, it can be a very wide spectrum than what you see under a thing. But ultimately, what it comes down to is there's not a lot that people can do to really prevent it or anything. But if they were to have such type of symptoms, seeing your provider, making sure that they're, you know, being assessed for things and particularly if having some of these things that kind of go along with this is having that high suspicion and proceeding with appropriate testing.

Host: So speaking of that, you know, we've been educated for heart attack symptoms for years, but what are the symptoms of one of these more rare heart diseases?

Zachary Garrett, MD: Yeah. So with hypertrophic cardiomyopathy, there are a couple different things that can happen and cause symptoms. The predominant symptom is typically shortness of breath. The heart becomes so thick that it actually can either cause the heart to become very stiff, or it can actually obstruct the blood flow out of the heart.

And by doing so, it can cause exertional symptoms, shortness of breath, dizziness. Sometimes it doesn't really cause so much shortness of breath, but sometimes it can cause abnormal heart rhythms or arrhythmias, which is really one of the more concerning things that can happen with hypertrophic cardiomyopathy.

Now, a lot of times with those symptoms, it will tend to drive somebody to seek assessment for those type of things. And with testing like ultrasounds of the heart, where we take pictures of the heart, look at the heart, it allows us to see this thickening and make a diagnosis of hypertrophic cardiomyopathy.

Whereas amyloid, as kind of we've mentioned, amyloid's a little more non-specific. Amyloid, because it affects so many different parts of the body and so many different organs, affecting joints, the nerves, the heart, it's really hard to have one specific type of symptom that goes along with this. When it affects the heart, it can cause things like heart failure, abnormal heart rhythms, atrial fibrillation. Sometimes it can cause problems with slowing of the heart rhythm, where it can cause things like heart block and the need for a pacemaker. When it affects the joints, it can cause things like arthritis, can cause carpal tunnel syndrome, can involve the back and cause narrowing of the back and lumbar stenosis. A lot of times the more musculoskeletal type things that go along with this, the arthritis, the back, the carpal tunnel, these things tend to kind of predate a lot of the heart-related symptoms, usually about six to seven years or so beforehand. And then, you really kind of start to see more of the heart-related manifestations with these.

Host: Well, you're both so passionate about the topic today, and I can tell this means something to you. So as we prepare to close, I'm curious, how did this specialty become a passion of yours? Starting with you, Dr. Garrett.

Zachary Garrett, MD: When, I was in training, again, there really wasn't a ton known about this, and there wasn't a lot of great treatments for a lot of these conditions. And so, throughout that time, as things started to come in online where we started having more treatment options and things to help people live better and live longer, that's where it really started to become interesting to where we were able to take something that before we had pretty limited options in really both of these. Either limited options that just we didn't have anything to help treat with or the treatments just were very invasive and, you know, were things that patients had to really go through a big process in order to treat.

And so now, with having treatments and everything else, and being able to diagnose and with our learning of how to find these things and how to treat these things, it's really where it became an interest of mine of, being able to help these people and help patients that really before did not have much in the way of options to where now we're able to really help with their quality of life and really make an impact.

Tucker Jonhson, FNP: For me, early in my career as a nurse practitioner, I realized I love solving clinical puzzles, and amyloidosis in particular is a clinical puzzle. And so, kind of being able to find what we would coin unifying diagnosis to kind of help tie together a bunch of different clinical symptoms and different disease states is really satisfying because then patients really feel like, "Ah, it was that all along."

And so, I think being able to offer those answers to patients is really fulfilling and being able to give someone a meaningful extension of their quality of life and quantity of life through, "Hey, take this pill once a day, and you will actually live longer and feel better," I think that's incredibly satisfying as a clinician. So, that's sort of what drew me into it, I guess, is the mystery of the disease state, identifying the disease state, and then helping people get on the right treatment.

Host: Well, I loved hearing your stories, and we learned so much today. Gentlemen, thank you very much for your time and insight.

Zachary Garrett, MD: Thanks, Nolan.

Tucker Jonhson, FNP: Yeah. Thanks for having us, Nolan

Host: That was Dr. Zachary Garrett and nurse practitioner Tucker Johnson. To find a physician, visit novanthealth.org. For more health and wellness information from our experts, visit healthyheadlines.org.