Martha Grogan, M.D., Cardiovascular Medicine, Mayo Clinic: Hi, I'm Dr. Martha Grogan, and I'm a cardiologist at the Mayo Clinic, and today I would like to discuss with you some information concerning a condition called cardiac amyloidosis. And if you're watching this, it's probably because either you or someone close to you has been diagnosed with cardiac amyloidosis. And this is a very scary thing, but you really cannot beat any disease until you understand it. So my goal today is to review what every patient needs to know about cardiac amyloidosis. So first of all, what is amyloid? How does it affect your heart? I'll explain the tests that you need to evaluate your heart--basically, what do all those numbers mean? And what are your treatment options if you have cardiac amyloidosis?

Well, amyloid is a disease of what we call protein misfolding. So there are normally soluble proteins in your bloodstream that for a variety of reasons become insoluble, and they deposit abnormally in the tissues and organs throughout your body. They can deposit in the kidney, the intestinal tract, the carpal tunnel ligaments, and the heart and other structures.

So why does that happen? Well, there are three main kinds of amyloid that actually can affect the heart, and there are over 20 proteins that can form amyloid, but only really three that affect the heart. So first we'll talk about those. The first type is called AL amyloid, and the A stands for amyloid and L stands for light chain type. And this is an immunoglobulin, a protein that is normally made to fight infection. But you have abnormal cells in your bone marrow that are making too much of these light chains, and they form to then form amyloid protein that deposits in the organ and tissues of your body. So in this case, the main problem are the cells in the bone marrow that are making too many light chains. And the AL type of amyloid often affects multiple organs. It can affect the heart, the kidneys, the gastrointestinal tract, and the nervous system.

The other main type of amyloid that can deposit in the heart is what's called transthyretin amyloid, and it's named because the protein that we all actually have in our body. It transports thyroid hormone and retinol, which is vitamin A. So the letters TTR are for transports, thyroid hormone and retinol. So we abbreviate that as TTR. And there are two types of TTR amyloid that can affect your heart. The first type is what's called hereditary or sometimes called familial amyloid, and in that type, an individual has a mutation which makes the protein abnormal. So the TTR protein has a different structure that makes it unstable, and it tends to form this amyloid fibral that then gets deposited throughout your body. The hereditary form of TTR amyloid most commonly affects the nerves and can cause neuropathy, or it affects the heart or sometimes both. The other type of TTR amyloid is called wild type. It previously was also called senile, but a lot of our patients are a little bit happier to be called the wild type rather than senile. Another name for it is age-related TTR amyloid. And this is really a mysterious situation in which the protein is actually normal. It's normal protein that we all have. There is no mutation or abnormal molecular structure that we can find, but for reasons that are mysterious, this protein becomes misfolded and forms the amyloid substance that deposits in the heart. And in this type of amyloid, usually only the heart and ligaments of the carpal tunnel are involved, and it almost exclusively affects men usually over the age of 60. So what happens when the heart is involved with amyloid is really the same in all three of these types, whether it's AL amyloid or whether it's the hereditary TTR or if it's the wild type TTR. But the diseases themselves have different building blocks of the protein, and they actually behave very differently.

So now I'll show you some images about how does this actually affect your heart? What those amyloid do and how does it affect your heart function? So your heart is about the size of your fist, and it's in the left side of your chest, and it's divided into upper and lower chambers. So you have two upper chambers. Here's the right atrium and the left atrium, and these are called atria. They're primarily collecting chambers. They don't really do too much pumping. And the lower chambers of your heart are called the ventricles, and they're the ones that really pump the blood around your body. So the right ventricle pumps blood to the lungs, where it gets oxygen, and the left ventricle is the main pumping chamber of your heart that pumps blood to the rest of your body. So when blood comes back from your lungs after it's gotten oxygen, it comes into this upper chamber on the left side, the left atrium. Then it goes through a valve. And you have four valves in your heart. They just open and close to make the blood continue to flow in the right direction. Then blood goes into the left ventricle, and when the left ventricle squeezes, it then sends blood out through this aortic valve and into the aorta, which is the main blood vessel of your body, so that blood can travel up here to your brain and then on down to the rest of your body, to your kidneys, your legs, and all of the various organs to deliver oxygen, the fuel that we all need.

So what happens in amyloid heart disease is that the walls of the heart, particularly the lower chambers, have become much thicker than they should be. So here we see that both the walls of the right ventricle and of the left ventricle are much thicker, and that's due to the process of amyloidosis. But why does that really happen? It's really very interesting. It's not that you have more muscle in your heart, it's that you have this substance called amyloidosis. So if we were able to look at heart muscle under the microscope, if we took some normal heart muscle and looked at it under a microscope, we would see that there are nice individual heart muscle cells, and they're arranged in an orderly fashion, and they're packed pretty tightly together. And interestingly, each one of these cells actually contracts, and then as they shorten, that makes the heart squeeze and pump blood around your body. But in amyloid, the walls of the heart are thicker than they should be. But you can see it's not because there's more muscle cells. And in fact, the muscle cells are disrupted, and that's because of the abnormal protein from amyloidosis that deposits in between the heart muscle cells. So here we see what we call the amyloid fibrals that form from abnormal misfolded proteins, and then they get in between the heart cells and cause dysfunction. So your heart should normally be quite elastic. It should be flexible. And when the heart relaxes, your heart stretches out, and then it squeezes and contracts. But when the heart is infiltrated with amyloidosis, it's much stiffer than normal. So the main problem for most patients with cardiac amyloidosis is not necessarily that their heart is weak, it's that the walls of the heart are too thick and they're too inflexible. So it's hard for the heart to fill with blood, and when you can't get as much blood into your heart, then you don't have as much blood that you can send around to your body. So that leads to a condition called heart failure, when there's not enough blood to meet the demands of your body and when pressure, then, can build up into your heart and cause a syndrome caused congestive heart failure. So, again, we see here's what it would look like with normal heart, and this is the heart muscle that's been infiltrated by amyloid.

So I hope that these pictures have been of some use for you, explaining a little bit about cardiac amyloidosis and how it happens. And in another segment, we'll talk about what are the tests that we use to diagnose cardiac amyloidosis and what are the treatment options?

Sept. 27, 2024