Condition can lead to heart failure

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Today I'll be talking about a cardiac condition that can lead to heart failure, but could be treatable if diagnosed early, with cardiologist Cynthia Taub. Dr. Taub is professor and chair of medicine at Upstate, and her specialty is echocardiography and cardiac imaging with a special interest in cardiac amyloidosis. Welcome to "The Informed Patient," Dr. Taub.

[00:00:37] Cynthia Taub, MD: Thank you, Amber. I'm delighted to join you today, and I'm excited to talk about cardiac amyloidosis.

[00:00:45] Host Amber Smith: Well, let's start with a description of what cardiac amyloidosis is.

[00:00:50] Cynthia Taub, MD: Well, first off, let's talk about amyloidosis. It is a systemic disease affecting many organs in the body, such as the heart, kidney, lungs, joints, and the brain. Talking a little bit about the history, I found this really fascinating. Dr. Rudolph Virchow, in 1854 -- so that's about 170 years ago -- introduced a term, amyloid, to describe a peculiar staining on brain tissue. He believed that what he saw must be starch. As it turned out it was not starch. It was misfolded protein.

So what does it mean, by misfolded protein? Think about a Swiss army knife. When it is nicely folded, it's harmless. However, when it is misfolded, some sharp edges are sticking out. When depositing in tissues in the body, misfolded Swiss army knife becomes toxic and damaging to the entire system.

So I just first talk about the amyloid, per se, but let's focus on cardiac amyloidosis.

[00:02:06] Host Amber Smith: Well, let me ask you: You use the term misfolded. What causes the proteins to be misfolded?

[00:02:13] Cynthia Taub, MD: There are many reasons. It depends on the reasons for amyloidosis. That goes back to describing different forms of amyloidosis.

One is a misfolded protein, transthyretin amyloidosis. People call it ATTR amyloidosis. And the protein is made from liver. And the connection between these protein units can become unstable. Therefore they can be misfolded. And another form is from plasma cell, which makes immunoglobulin light chain amyloid. We call it AL amyloidosis. And that immunoglobulin can clump together, leading to the misfolding.

So these are the two bigger picture of precursor proteins, but among the transthyretin protein misfolding, there are two other reasons, to answer your question. One is because of aging. When we age, these protein can become more prone to misfolding. Another is hereditary, familial TTR of protein misfolding. We can talk a little more on that later.

[00:03:37] Host Amber Smith: So this is an inheritable disease, or does it ever just develop on its own without a past history in the family?

[00:03:46] Cynthia Taub, MD: Oh, there are wild- type, meaning without family history. As you age, you might develop misfolding of the protein. But, a number of mutations can be transmitted through family tree and causing these hereditary misfolding of the protein. And so far more than 140 genetic mutations have been identified that may contribute to the misfolding of the protein. In the genetic mutations, I think it's important to mention thatone of the mutations -- V 122 I, you don't have to know exactly what it means -- but there is a substitution of valine by isoleucine. These forms of mutation were found in 4% of African-American population in the US. So we need to identify these mutations and make early diagnosis of vulnerable population that may develop cardiac amyloidosis.

[00:04:50] Host Amber Smith: How common is cardiac amyloidosis compared with other heart diseases?

[00:04:55] Cynthia Taub, MD: Yeah, that is a intriguing question. Twenty years ago I became aware of cardiac amyloidosis, and it was called a "zebra." You know, it was considered very uncommon. And now when you look around, they're "horses" -- if you see them. You know, you have to be aware that they exist.

So, let me give you some numbers. So the ATTR cardiac amyloidosis was found in up to 16% of patients who need aortic valve surgery for aortic stenosis. And these patients are from 80 to 84 years of age. So as you age, as you survive to your golden age, there are a lot of patients who might be affected by cardiac amyloidosis.

And in addition, you know, heart failure is a huge problem in the US health system, affects many, many, patients. And in older patients, older than 82 years of age, 13% of these individuals who suffer from heart failure with normal ejection fraction are found to have cardiac amyloidosis. And what does it mean? A heart failure with normal ejection fraction? The hearts squeeze well, you know, normal ejection, normal squeeze. But they can't relax, because the amyloid fibers deposit in the heart, making the environment too crowded to relax.

So when patients have symptoms of heart failure, and when you take an echocardiogram, your doctor says, "OK, the heart squeezes. Wow." But what's the reason to cause heart failure? Consider cardiac amyloidosis. Before, in the past, we didn't really have the awareness, so we didn't do the screening.

Another evidence I can tell you, Amber, in several postmortem studies, patient died and their heart were looked at. It was noted that 25% of these older individuals have amyloid buildup in their heart. So all these data suggest in the aging population, in the current era, we are dealing with patients who might be affected by cardiac amyloidosis. We just need to have awareness. We need to diagnose them and hopefully treat them early before they go down to end stage heart failure realm.

[00:07:28] Host Amber Smith: Other than age, are there factors that would increase someone's risk for developing this? Well, age and genetics?

[00:07:36] Cynthia Taub, MD: Right? Correct. So it's aging and your genetics that are two major risk factors. Of course, there are malignant hematologic light chain amyloidosis that patients usually develop these malignant disease early on at a younger age. And this needs to be treated also early on by the oncologist and hematologist.

[00:08:02] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host Amber Smith, talking with Dr. Cynthia Taub. She's a cardiologist and professor and chair of medicine at Upstate, and we're talking about cardiac amyloidosis.

Let's talk about how this is usually detected. You described, it sounds like some people have this but don't know it, and it's just discovered incidentally when they have other medical procedures. Are there symptoms that someone might have that would bring them to the doctor, and this would be discovered that way?

[00:08:37] Cynthia Taub, MD: These patients with amyloidosis tend to have very non-specific symptoms. They might have fatigue, weakness, shortness of breath. Who doesn't have fatigue, right? And they used to have a high blood pressure, and later on they notice they don't need to take blood pressure medications. And they might develop orthopedic problems, bilateral carpel tunnel syndrome, spinal stenosis, numbness, pins and needles (feeling in) their foot and fingers, sensation, those polyneuropathy that we described. These patients tend to see at least five specialists, trying to figure out the mystery. And then once you see the right doctor who has the awareness that they were able to put together the diagnosis. And the delay of diagnosis can be very long, five to 10 years. Again, awareness is important, and the symptoms can be quite nonspecific.

[00:09:39] Host Amber Smith: So do physicians, primary care doctors, do they refer patients to Upstate's cardiac amyloidosis clinic to get diagnosed, or do they get diagnosed and then they get sent to the clinic?

[00:09:52] Cynthia Taub, MD: I have to say when I first arrived here, I noticed that there was really no good pathways for physicians to refer patients to make diagnosis. And thanks to Dr. Mary McGrath from the nuclear medicine department who spearheaded the PYP (pyrophosphate) scan -- that's a nuclear scan that can pick up signals in the heart that's been infiltrated by amyloid fibers. And this service is the first for the city of Syracuse. And patient doesn't have to travel, uh, to Rochester to get the diagnostic testings done. So this is progress I envision in the next few years: Upstate will become a center of excellence for the diagnosis and treatment of cardiac amyloidosis.

Currently, it takes astute primary care physician, orthopedic surgeons and hematologists to refer patients to cardiologist for the diagnosis and potentially treatment of cardiac amyloidosis. We're far from perfect. We're still trying to make sure our pathway is being worked out. The goal is to provide the best patient care possible for early diagnosis.

[00:11:12] Host Amber Smith: Well, let's talk about treatments. What treatments are available?

[00:11:17] Cynthia Taub, MD: The No. 1 thing is treatment of heart failure. That's very important,- heart failure management -- decongestion by diuretics, beta blocker, ACE inhibitor, SGLT2 inhibitor, people have heard of some new kids on the block -- Jardiance, (empagliflozin) -- and manage atrial fibrillation by blood thinners, by beta blocker, by ablation sometimes. And the new medication that employ advanced biotechtechnology are transthyretin (TTR) stabilizers. An example is a tafamidis. That medication can reduce patient's heart failure hospitalization, and improve survival.

And there are other medications such as silencers, a (a genome editing tool,) CRISPR technology- facilitated medication that can help our familial amyloidosis patients to manage their neuropathy. So these are all exciting new medications on the horizon that we look forward to prescribing them to our patients and help their symptoms.

[00:12:29] Host Amber Smith: Do any of these new treatments or medications, do they work on the protein that is misfolded, that is at kind of the root of all of this? Are there any treatments that can reverse the damage?

[00:12:43] Cynthia Taub, MD: Very good question. Right now these medications are used to slow the progression of disease. We don't really have enough data to say that we can reverse disease. Of course, if you make the diagnosis early, you are hoping that the damage is not done yet; we can reverse disease.

You know, this is something that I would love to think about. I was at Dartmouth, and we had a very thoughtful hand surgeon who performed carpel tunnel release surgery. And we formed a team, a multidisciplinary team, where every time he had a suspicion of amyloidosis where patients have bilateral carpel tunnel syndrome, spinal stenosis, men older than 50, women, older than 60, and they come to his operating room, and he would take a little biopsy. And if there is amyloid deposition on the biopsy, he would refer these patients to me.

OK, so 25% of these biopsies were found to have positive amyloid deposition. And several of these patients don't even have cardiac involvement. So most of these patients, when they get referred to me, they already have evidence of cardiac involvement, but some of them did not have cardiac involvement.

What does it mean? We are capturing these patients early. They have amyloid deposition in their tendon, in their bones, but they haven't reached a point it will affect the heart. So can we use our treatment early to stop the deposition of these amyloid fibrils to the heart? Can we do that? Right now, FDA (Food and Drug Administration) has not approved this indication, but we're hopeful with clinical trials, with research, we're able to answer your question, Amber.

[00:14:47] Host Amber Smith: Well with the treatments that are available now, if you're able to slow the progression for someone, have you seen that help people? Do their symptoms get better?

[00:14:56] Cynthia Taub, MD: Oh, absolutely. That's why FDA approved the medication tafamidis. They've tested this medication in patients with symptoms. You have to have symptom before you can start the medication. And after six months, these patients feel much better, and there's fewer hospitalizations for heart failure, and these patients live longer.

You know, years ago when I learned about cardiac amyloidosis, once you have the diagnosis, your survival, it is six months, and now you know, people live five years after diagnosis, or even longer.

[00:15:34] Host Amber Smith: Let's talk about the overall outlook for people with this condition. What is daily life like for them, or how might it be interrupted?

[00:15:45] Cynthia Taub, MD: Well, like everything else, you can have heart failure symptoms. Your activities are going to be somewhat limited. You might experience exercise intolerance. When you climb up a flight of stairs, you might get winded easily. And some of the patients will develop atrial fibrillation. When they walk, they might feel a little palpitations. So these are the symptoms related to heart failure.

And despite the fact they have symptoms of heart failure, they need to take their medications, and they need to exercise. It doesn't mean that you should just sit around on the couch. You need to walk. You need to go outside, and pay attention to your nutrition, not to consume too much salt in your diet. And, just a heart healthy diet as per Heart Failure Society (of America)'s guidelines, in the management of patients with these symptoms.

And, in particular for cardiac amyloidosis, drinking green tea in clinical trials might help. and like many other reasons for heart failure management, emotional, psychological, spiritual support is equally important.

[00:17:06] Host Amber Smith: Well, we talked a little about some of the therapies. Are there others on the horizon that you know about that are showing promise, that are in development, maybe in the lab, still?

[00:17:17] Cynthia Taub, MD: Yeah. So, medications to stabilize these misfolded proteins, medications to silence these misfolded proteins.

And, there's one medication, diflunisal, that has been utilized for neuropathy, for numbness, tingling of the fingers and toes. So research is quite intensive in this area. This is a rare disease research that the government is supporting, and yet -- you know, from zebra to horse -- and actually these research are helping many, many patients.

[00:17:54] Host Amber Smith: Well, I appreciate you making time to tell us about it, Dr. Taub.

[00:17:58] Cynthia Taub, MD: Oh, it's my pleasure. There's so much I would like to share with you. This is such an exciting field for cardiology. And many, many othersubspecialists are joining forces, and we're excited.

In the spring, we're hoping to have a multidisciplinary amyloidosis symposium to describe the science, describe our trials, and hopefully the community will join us.

We also welcome patients to be part of the exciting endeavor.

[00:18:29] Host Amber Smith: My guest has been cardiologist, Cynthia Taub. She's a professor and chair of medicine at Upstate where she leads the cardiac amyloidosis clinic. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at glenviewelectric.com/informed. If you enjoyed this episode, please tell a friend to listen too. And you can rate and review "The Informed Patient" podcast on Spotify, Apple, YouTube, or wherever you tune in. This is your host, Amber Smith, thanking you for listening.