Cardiovascular Medicine

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?

Martha Grogan, M.D., Cardiovascular Medicine, Mayo Clinic: Hi. I'm Doctor Martha Grogan. I'm a cardiologist at the Mayo Clinic, and I'd like to discuss with you the treatment options for patients who have cardiac amyloidosis. In previous segments, we talked about the diagnosis and what amyloid really is, and now we'll talk about the treatment options.

So the most important thing for you to know is really pretty simple. The treatment for cardiac amyloidosis depends completely on which type you have, and in order to establish a diagnosis of amyloid you must first have what we call a tissue biopsy. So, some part of your body has been sampled and found to have amyloid deposits. That can either be from the fat or the bone marrow, the kidney or the heart, or other parts of your body. And once that's been stained and found to have amyloid, then we need to know particularly what type is it? What type of protein is making up the abnormal amyloid deposits? Pathologists use a technique called mass spectrometry to determine the type of amyloid that you have, and it's very important to make sure that your specimen has been examined by someone who's very expert in this technique.

We unfortunately don't have a specific treatment for cardiac amyloidosis, so we don't have a medication that will take the amyloid out of the heart. The most important part of treatment is to treat the underlying protein problem, so we want to either stop the abnormal protein from being produced, or stabilize the protein so that it doesn't do that misfolding that we talked about and deposit within the various organs, particularly the heart.

So for the AL type of amyloid — remember, that one is called light chain, or immunoglobulin-associated amyloidosis — the hematologist is going to be certainly the complete key to your treatment, and a hematologist who's an expert in this area will tell you whether or not you're a candidate for chemotherapy, whether or not you might have a procedure called autologous stem cell transplantation, or whether there are new or experimental medications that might be used to treat the AL type of amyloid. And that's the best way to try to stabilize the heart function.

For the TTR — that’s the transthyretin type of amyloid — if you have the hereditary form, then the problem is that your liver is making an abnormal protein. And liver transplant is an option for some patients with hereditary amyloidosis, and there are soon going to be a variety of different, new medications that will help try to stabilize that protein or even prevent it from being formed.

Now the wild type, or previously called senile type of amyloidosis, we don't have specific treatment for that just yet, but the same type of medications that are being used for familial amyloidosis to stabilize the protein are hopefully going to be available very soon as part of clinical trials to try to stop the process of amyloid deposition in patients with this wild type.

Now for any type of amyloid, one of our mainstays of treatment from a cardiology perspective is to try to get rid of excess fluid. When your heart is stiff because of amyloidosis, it’s hard for your heart to fill and pressure builds up in your heart. And eventually that pressure and fluid leaks out into your lungs, and then into your leg, sometimes into your abdomen. So diuretics are an important treatment option and we need to find out the best diuretic for you and the right dose for you.

There are certain medications that we use for other types of heart failure that we have to avoid, particularly in the AL type of amyloid. And heart transplant, you might wonder about, well could I just get a new heart? It's occasionally done in some very selected patients. Usually patients who don't have a lot of problems with amyloid deposits elsewhere in their body. So in the AL type of amyloid, it has to be primarily localized to the heart, and it has to be a young patient who's otherwise doing well, and the patient will still need to get treatment for the underlying disorder. For the other types of amyloid, the familial and the wild type or senile amyloid, heart transplant is a potential option, particularly if the patient is identified at an age when transplantation still might be an option.

We also have something called a ventricular assist device so we have artificial heart pumps that can support the heart, and those can be used whether a person is waiting for a heart transplant but now we even use them for patients who aren't ever even going to have a heart transplant. So, they are a controversial option, and it depends on the patient, but occasionally we are able to use these pumps, and they are improving and we probably will have better options over time.

The other question that, of course, patients and their family really want to know about is what's the prognosis? What's my outlook with this condition of cardiac amyloidosis? Well again, just as the treatment depends completely on the type, the prognosis depends completely on which type of amyloid you have.

Patients who have the AL type of amyloid affecting the heart do have the worst prognosis, and in fact, for those patients, if they start to get heart failure symptoms, severe shortness of breath and fluid building up, a person generally will deteriorate quite rapidly unless they receive effective treatment. So the prognosis is quite poor unless the treatment can stop the process.

For the TTR types of amyloid, whether it's for the TTR types of amyloid, whether it's the hereditary or the wild type, the progression there is much more slow. So the amyloid deposits build up much more slowly, and that allows the heart and the body to adapt to some degree. So they're very different, and if you have familial TTR, the hereditary type, your clinical course, or how you will do, often depends on what mutation you have.

For the senile type of amyloid, or again, the wild type, patients may have this condition for many, many years. And so it's very important for you to realize that, if you have the TTR type of amyloid, particularly if you have that wild type or senile, really you shouldn't read about the AL type of amyloid, because it's truly a different disease, and vice versa. So that's important to recognize. And because this is still a rare disease, unfortunately, a lot of doctors don't know too much about it, because they just haven't seen patients with this condition. It’s important for you to make sure that you are seen by individuals who really understand amyloid.

So in summary, amyloid is a disease of abnormal proteins that deposit in your organs and cause dysfunction. The heart is very commonly involved. It becomes very stiff from amyloid deposition, but the treatment is to treat the underlying problem. And there are three main types of amyloid that affect your heart, and the type that you have completely determines what kind of treatment options you have and what your outlook might be. And although this is a very serious and frustrating disease, treatment options are really rapidly expanding, and there are now treatments being developed for all different types of amyloid that affect the heart. So I hope this information is of some use to you. If you're interested in more information or obtaining an appointment, that could be found at mayoclinic.org.