Cardiac Amyloidosis

What is cardiac amyloidosis?

Cardiac amyloidosis is a heart condition where misshapen proteins get stuck in and around different parts of your heart. As these proteins build up, your heart struggles to pump blood so it tries to pump harder. Ultimately, the extra effort weakens and damages your heart, causing it to fail.

There are many possible causes of cardiac amyloidosis. Some people inherit it from their parents. Others can develop this condition on their own, or it can happen because of other diseases like cancer. While amyloidosis isn’t curable, some types are treatable.

What are the different types of amyloidosis?

Proteins are long molecules that stretch out like chains. Your body uses them for energy, internal chemical reactions, sending messages between different body systems and more. But there’s a catch: Your cells can only use these chains if they have the right shape. Protein misfolding disorders like amyloidosis distort and twist proteins so they won’t work properly.

When this happens to enough proteins, they can tangle together and your body can’t use them. With nowhere to go, the tangled proteins bunch up, stick together and then get stuck in different places throughout your body.

Amyloidosis can affect many systems throughout your body, especially your heart. There are three main types of amyloidosis that affect your heart (other types can also affect your heart, but that only happens in rare instances).

AL (light chain)

Your body uses light chains as part of your immune system, which defends against germs like viruses and bacteria. AL amyloidosis happens when cells in your bone marrow malfunction and make too many light chains. This can happen on its own or because of certain types of blood or immune system cancers. Diagnosis of this type of amyloidosis typically happens after age 50.

ATTR

Transthyretin (often abbreviated TTR) is a protein that helps carry certain chemicals throughout your body. It gets its name from how it transports thyroid hormone and retinol (also known as vitamin A). An older name for this protein that’s no longer in use is thyroxine-binding prealbumin (TBPA).

Amyloid TTR (ATTR) can have a wide range of symptoms, and it can appear as early as age 20 or as late as age 70. It has two main sub-types:

• Hereditary. This sub-type of ATTR is genetic, meaning you inherit it from one or both of your biological parents.
• Wild-type. This happens when TTR begins misfolding on its own without any genetic mutation. This is usually something that happens when you are over the age of 60. This condition was once known as senile systemic amyloidosis or senile cardiac amyloidosis, but these names are no longer commonly used.

Dialysis-related amyloidosis

People who are on dialysis for several years have a higher risk of developing amyloidosis. That’s because dialysis typically doesn’t filter out β2 (beta-2) microglobulin proteins. These proteins, often abbreviated β2Ms, build up in your heart and other areas of your body.

Rare types of cardiac amyloidosis

There are several other subtypes of cardiac amyloidosis, but overall they are very rare. They include:

Who does it affect?

The factors most likely to influence who has this condition include:

• Age. Some people may develop amyloidosis in their 20s, but overall the condition is rare in people under the age of 40. Diagnosis usually happens after age 50, especially with wild-type ATTR amyloidosis.
• Sex. Cardiac amyloidosis is more common in men than in women. This is especially true with wild-type ATTR amyloidosis, with 25 to 50 cases in men for every case in women.
• The country where you were born. A genetic mutation that causes familial ATTR amyloidosis is much more common in some countries. These include Portugal, Japan, Sweden and Finland, as well as several other European countries.
• Race. Another mutation that causes familial ATTR amyloidosis happens in approximately 4% of Black people of West African descent. This includes African Americans and Black people from Latin America and the Caribbean.
• Regular dialysis for several years. Symptoms of this condition are more and more likely to develop the longer you’ve been on dialysis.

How common is this condition?

Overall, amyloidosis is rare, but certain types of amyloidosis are more common than others.

• AL amyloidosis: Doctors in the United States diagnose about 4,000 new cases of AL amyloidosis each year. That’s approximately 1 case for every 64,500 adults.
• Hereditary ATTR amyloidosis: This condition may happen in up to 4% of Black people of West African descent. In people of European descent, this condition happens in 1 out of every 100,000 people. That rate is higher in the aforementioned countries. An example of this is Portugal, where it happens in about 1 of every 538 people.
• Wild-type ATTR amyloidosis: Experts believe that wild-type ATTR amyloidosis is an underdiagnosed condition, and it may happen in as many as 20% of men over age 80.
• Dialysis-related amyloidosis. About 20% of those on dialysis for two to four years have this condition, and virtually everyone on dialysis for 13 years or more has it.

How does this condition affect my body?

Cardiac amyloidosis is a disease that changes the structure of your heart and interferes with the heart’s ability to pump. It does that in the following ways:

• Thickening of heart walls. As amyloid proteins build up in your heart muscle, the walls of your heart thicken and your heart enlarges. As that happens, your heart has to work harder to pump enough blood through your body. Your heart’s extra effort ultimately leads to heart failure.
• Disruptions in your heart’s electrical system. Cardiac amyloidosis can cause irregular heart rhythms (arrhythmias), or weaken your heart’s electrical current. A type of arrhythmia that’s common with amyloidosis is atrial fibrillation.
• Amyloid buildup. Amyloid proteins are waxy, stick together easily and form large clusters. If those clusters get stuck in a heart valve, they can partially block the valve and limit blood flow.

What are the symptoms of this condition?

Not everyone who has a genetic mutation that can cause amyloidosis will develop this condition. Some won’t ever develop it. Others may have a case that isn’t severe.

Symptoms of cardiac amyloidosis typically involve your heart, plus other vital organs like your liver and kidneys. In the end stages of cardiac amyloidosis, the severe symptoms of heart failure (listed immediately below) are likely.

Possible symptoms include, but aren’t limited to, the following:

• Shortness of breath. This can happen when you're active or lying down.
• Swelling from fluid accumulation. This is usually affects your feet, ankles, legs and abdomen.
• Fatigue. This is feeling very tired or exhausted for an extended period, usually days or more.
• Heart palpitations. This is the unpleasant ability to feel your heartbeat without trying.
• Enlarged neck veins. These happen with heart failure because your heart is struggling to pump hard enough. The extra effort puts too much pressure on the veins in your neck, causing them to get bigger.
• Swollen liver (hepatomegaly). This also happens with heart failure, and for the same reason as enlargement in your neck veins. The extra pressure from your heart puts too much pressure on the blood vessels in your liver, making that organ swell up.
• Kidney problems. This includes inflammation in your kidneys or changes in how effectively your kidneys are operating.

Symptoms that may also be signs of cardiac amyloidosis, but that don’t involve your heart, liver or kidneys, include:

• Unusual bruising.
• Swelling in your tongue.
• Carpal tunnel syndrome (this can be an early warning sign years before this condition otherwise becomes apparent).
• Lumbar spinal stenosis (narrowing in the space around your lower spine).
• Eye problems.
• Hearing problems and deafness.
• Numbness or tingling in your arms or legs.

What causes cardiac amyloidosis?

Different types of amyloidosis happen for different reasons, but most of them involve your DNA.

DNA is much like a family cookbook, containing instructions for your cells on how to work and make certain proteins. Passing DNA from parents to children is like if your parents worked together to make your very own handwritten copy of that cookbook.

Genetic mutations are just typos in your DNA cookbook, and a big enough typo can ruin a recipe. That’s exactly what happens with diseases like amyloidosis. Your cells are doing their best, but they only know how to follow the recipe. These typos can happen to you in two different ways.

Inherited

Cardiac amyloidosis is often familial, meaning you inherited it. This happens when one or both of your parents’ DNA has a mutation and that error in their version of the “cookbook” gets copied over to yours.

Acquired

Acquired conditions are ones that you don’t inherit, meaning you develop them at some point in your life. Wild-type ATTR amyloidosis and dialysis-related amyloidosis are both examples of acquired conditions, but neither of them involves mutations in your DNA.

• Wild-type ATTR amyloidosis happens because your body makes the proteins correctly, but the proteins become unstable over time (which is why this condition is so heavily tied to your age). Eventually, the protein misfolds on its own.
• Dialysis-related amyloidosis happens because your body has too much of a normal protein that dialysis — unlike your kidneys — can’t filter out. Over time, that protein accumulates to the point where it starts to cause problems.

Is it contagious?

Amyloidosis is not contagious in any form.

How is it diagnosed?

A doctor will first suspect cardiac amyloidosis based on a combination of factors, including your symptoms, a physical examination of your body (where the doctor looks, feels and listens for signs of a condition) and your family history. They’ll then use diagnostic tests, imaging and lab tests to confirm or rule out cardiac amyloidosis.

If you have a family history of a familial type of amyloidosis, you may not need to undergo certain tests, or you may need to undergo other tests. Genetic testing is also possible to see if you have any of the genetic mutations that can cause any form of cardiac amyloidosis.

What tests will be done to diagnose this condition?

If your healthcare provider suspects you have cardiac amyloidosis, they may order one or more of the tests listed below.

Lab testing

These tests involve samples of tissue, blood or other bodily fluids. Many of these tests use Congo red, a specific type of dye, which will make amyloid glow green under certain types of lighting.

• Tissue biopsy: This is where medical providers take a small sample of tissue, such as from your heart muscle, for lab testing. This can involve tissue samples from other places, but a positive result from a non-heart sample will need confirmation using imaging tests.
• Blood testing: Certain types of cardiac amyloidosis involve amyloid proteins circulating in your blood. Lab tests can detect those circulating proteins.
• Urine testing. Certain conditions can lead to amyloid proteins in your urine (pee). Testing your urine for those proteins can help diagnose this condition.

Imaging

Because cardiac amyloidosis can cause your heart to enlarge and change shape, imaging tests can often help with diagnosing this condition. Possible tests include:

• Echocardiogram. This test uses ultra-high-frequency sound waves like a bat uses sonar. By holding a sound-emitting device against the skin of your chest, medical providers can "see" your heart because of the way sound waves bounce and reflect off different structures inside your body. This test is especially useful in showing when certain parts of your heart are unusually thick, which is a key symptom of this condition.
• Scintigraphy. For this test, medical providers will inject a tracer, a substance that is slightly radioactive (but not harmful), into your blood. Areas with accumulations of amyloid proteins will also accumulate that tracer, making those spots extremely easy to see on an imaging test called single-photon emission computed tomography (SPECT) scan.
• Magnetic resonance imaging (MRI). This test uses an extremely powerful magnet and computer processing to generate an image of your heart. MRI is extremely detailed, which also allows healthcare providers to see thickening or other relevant changes in your heart’s structure.

Electrocardiogram (ECG or EKG)

An EKG uses several sensors (usually 12) that stick to the skin of your chest. Those sensors detect the electricity traveling through your heart and display the strength of that electrical current as a wave on a paper printout or a screen display. Trained experts, including doctors, can analyze that wave for any unusual changes in how certain parts of your heart conduct electricity.

Genetic tests

Depending on the results of other tests, your healthcare provider may want to run genetic tests. Those tests can identify mutations in your DNA that might be the cause of your amyloidosis.

Is there a cure or treatment for amyloidosis?

Most forms of cardiac amyloidosis are treatable, but curing this condition isn’t always possible. The treatment also varies depending on the type of amyloidosis. In general, early detection is extremely important. Catching amyloidosis early can help long-term limit heart damage. Without early detection and treatment, permanent damage is possible. The only way to fix permanent heart damage is a heart transplant.

AL amyloidosis

AL amyloidosis treatment is similar to many common treatments for treating cancer. These include:

• Chemotherapy. Similar to its use in cancer, chemotherapy can destroy the malfunctioning plasma cells.
• Stem cell transplant. This treatment usually happens along with chemotherapy and replaces the malfunctioning plasma cells. The stem cells are usually autologous, meaning they come from you. Because they’re yours, your body already recognizes them and won’t reject or negatively react to them.
• Immunotherapy. Your immune system can ordinarily recognize malfunctioning cells as hostile and destroy them. With diseases like cancer or AL amyloidosis, your immune system doesn’t recognize that those cells are faulty. Immunotherapy teaches your immune system to see the malfunctioning cells and destroy them.

ATTR amyloidosis

This type of amyloidosis happens because your liver is making proteins that break apart too easily. Treating this problem always involves putting a stop to that. The following list includes some methods that have government approval and some that are still experimental.

• Liver transplant. In years past, the only way to stop your liver from making faulty proteins was a liver transplant. While this is no longer the only option, it’s still a helpful and effective one.
• Genetic silencers. ATTR amyloidosis happens because of a genetic mutation in your DNA, much like a typo in a cookbook recipe. Genetic silencers are drugs that act as a temporary recipe card. Instead of your cells following the recipe with a typo, this medication gives them new instructions so they can make the protein correctly.
• Stabilizers. These medications keep TTR molecules from misfolding or breaking apart.
• Fibril inhibitors. When amyloid proteins start to clump together, they form fiber-like structures called fibrils. These medications stop fibrils from forming.

Dialysis-related amyloidosis

This type of amyloidosis happens because people who need dialysis have a buildup of β2M proteins. Normally, your kidneys filter out those proteins, but standard dialysis can’t do that. That’s why it takes years for people on dialysis to develop this condition. Currently, there are two ways to treat this:

• Kidney transplant. A healthy kidney means you don’t need dialysis anymore, and a transplanted kidney can filter out excess β2M proteins. While a kidney transplant will stop dialysis-related amyloidosis from getting worse, there’s disagreement among researchers on whether or not it also reverses amyloid protein buildup in your body.
• Special filters. While standard dialysis filters can’t remove β2M proteins, there are specialized filters that can at least partially remove them. Unfortunately, these filters are costly, and they don't filter out all of the proteins. That means that years of dialysis will eventually lead to dialysis-related amyloidosis even with preventive measures.

Non-specific treatments

There’s a wide range of other treatments and medications that can help people with cardiac amyloidosis. These typically treat symptoms of this condition and usually involve the following:

• Heart transplant. For people whose hearts have too much damage because of cardiac amyloidosis, a heart transplant is sometimes necessary. This procedure often happens after resolving or treating the underlying cause of the amyloidosis.
• Anti-arrhythmia medications. These medications help prevent irregular heart rhythms, some of which can be dangerous.
• Implantable devices. These devices include pacemakers and implantable cardioverter defibrillators (ICDs). They deliver electrical shocks to manage your heart rhythm and prevent dangerous arrhythmias.
• Diuretic medications. These medications are especially helpful with fluid buildup, a common symptom of heart failure, by improving your kidney function. However, these medications aren’t an option if you have conditions like severe kidney disease.
• Doxycycline. AL amyloidosis light chains also are toxic to your heart cells. For reasons experts still don’t fully understand, the antibiotic doxycycline can counter the toxic effects.

Complications/side effects of the treatment

The possible complications and side effects of this condition vary widely. Below are some of the general possibilities. However, your healthcare provider can better explain complications, side effects and other risks. That's because they are the ones who know your case directly and can tailor their information and explanations to your specific situation.

Medications

Allergic reactions and adverse effects are possible with all medications regardless of what they treat. In the case of immunotherapy or other highly specialized medications (genetic silencers, stabilizers and fibril inhibitors), the possible side effects or complications are very specific to the medication(s) you take. Talking to your healthcare provider is the best way to learn the likely or possible side effects of any medication, especially those that treat specific symptoms or problems.

Chemotherapy medications

These medications damage cells that reproduce quickly. This includes cells that are cancerous and malfunctioning (which may also cause amyloidosis). However, they also damage normal cells that behave similarly, such as your hair follicles (causing your hair to fall out), your gastrointestinal tract (causing vomiting and diarrhea) and more.

Organ transplants

Replacing a damaged or faulty organ with a donor organ is a complicated process that has risks. These include:

• Rejection. This is when your body sees the new organ and mistakes it for a threat, much like an infection. Your immune system then attacks the new organ, which can cause complications that are dangerous or even deadly.
• Immune system suppression. Preventing rejection involves medications that intentionally weaken your immune system. Unfortunately, that also means your immune system is less effective at stopping actual infections, whether they are viral or bacterial.

Implanted devices

Pacemakers and ICDs require surgery to be placed and maintained. Those surgeries have their own potential risks and complications, including bleeding, infection, or negative reactions to anesthesia. The devices themselves can sometimes cause heart rhythm problems, or part of the device may move out of place and cause complications.

How soon after treatment will I feel better?

Treatment of cardiac amyloidosis usually manages your symptoms only. Some of these treatments can provide some relief, but the effects are only temporary. In some cases, the treatment will cause side effects that might make you feel worse for a while, but your healthcare provider can also provide medication and guidance to help reduce the severity of those side effects.

Chemotherapy effects

If you take chemotherapy for this condition, your healthcare provider can best explain to you what you will likely experience. Chemotherapy medications can cause a wide range of side effects, including weight loss, nausea and vomiting, loss of hair and more. However, the effects are temporary, and your healthcare provider can help with treatments for the symptoms of side effects.

Dialysis filtering changes

If you have dialysis-related cardiac amyloidosis, you should start to feel better as special filtering methods pull the problem proteins out of your body. However, it may take multiple treatments before you feel better.

Transplants

If you undergo any kind of transplant, this is major surgery, and it will take you time to recover from the procedure itself. Your healthcare provider will be the best person to explain what you can expect, especially the timing of your recovery and when you should notice improvements in your symptoms.

If you have a liver or kidney transplant, you should start to feel improvement in your cardiac amyloidosis symptoms within the weeks that follow the procedure. However, some symptoms may linger because of damage or changes to your heart from this condition.

If you have a heart transplant, you should start to feel some relief from your symptoms within the weeks that follow this surgery. A heart transplant is usually only possible after treating or curing your amyloidosis. Controlling the amount of amyloid produced in your body or curing the amyloidosis altogether are essential to preventing the condition from damaging your new heart.

How can I prevent this or reduce my risk of developing it?

Unfortunately, it's not possible to prevent amyloidosis (with one exception, see below). The cause of non-inherited amyloidosis is unknown, so there's no way to prevent it. Inherited amyloidosis is also not preventable because it's carried in your DNA, which you inherited from your parents.

The only exception to this is dialysis-related cardiac amyloidosis. Preventing this condition may be possible if you are not on dialysis for an extended period or with the use of special filters to keep β2M proteins from accumulating. However, the filters usually can’t stop the accumulation entirely, meaning this is often only a way to delay this condition from developing.

What is the outlook for this condition?

Cardiac amyloidosis is a condition that gets progressively worse, with heart failure symptoms that become more and more severe. Ultimately, this condition causes your heart to weaken to the point where you can’t survive. If it isn’t treated, the outlook is especially bad.

Without treatment, the typical survival time with AL amyloidosis is less than eight months. For those with especially severe cases, it’s three to six months. With ATTR amyloidosis, the typical survival time without treatment is two to five years. People with untreated familial ATTR amyloidosis tend to do worse, with an average survival time of two to three years.

While dialysis-related amyloidosis does often affect your heart, other effects in your body — especially on your joints and bones — are more severe. Research and data on long-term heart effects from dialysis-related amyloidosis are also limited because the condition is less common, thanks to improved filters and methods.

How long does cardiac amyloidosis last?

Cardiac amyloidosis is usually life-long. Once you develop this condition, the only way to keep it from being permanent is with a heart transplant. However, if you still have an underlying cause for your amyloidosis, the condition can return after a heart transplant.

What is the prognosis with treatment?

The prognosis for cardiac amyloidosis strongly depends on two factors: What type of amyloidosis you have and the severity of your case. That’s why early detection can make a big difference. People who undergo successful transplants of their heart, kidneys or liver typically do better, but the majority of people who need a transplant either aren’t eligible or have to wait a very long time to receive one (which can affect how long they survive).

The typical survival times for AL and ATTR amyloidosis (there's limited data on dialysis-related amyloidosis survival) are as follows:

• AL amyloidosis: In the earliest stages, just under 70% of people survive five years or more. In later stages, that falls to 14%.
• ATTR amyloidosis. In the earliest stages, the median (similar to the average, but without distortion from unusually high or low numbers) survival was more than seven years. In the latest stages, the median survival was between 18 months and two years.

How to take care of myself or manage my symptoms?

Unfortunately, there’s not much you can do to directly help amyloidosis once you have it. If you have a family history of this condition, you should talk to your provider about genetic testing. While not everyone who has a mutation related to cardiac amyloidosis will develop this condition, it’s important to know if you can develop it. That way, you can watch for symptoms and start treatment quickly.

If you do have cardiac amyloidosis, it's important to follow your healthcare provider's guidance when it comes to medications and treatments. Many of these medications work in very specific ways, and for them to work properly, it's essential that you take them as your provider instructs.

When should I see my healthcare provider or when should I seek care?

Your healthcare provider will schedule regular follow-up visits after diagnosing you with cardiac amyloidosis. Depending on the severity of your case, you may need more frequent visits with your provider.

Your healthcare provider will also be able to tell you the symptoms that need medical attention. However, in general, you should contact your provider if you have any of the following symptoms:

• Dizziness or fainting when you sit or stand up. Known as orthostatic hypotension, this happens because low blood pressure decreases the blood flow to your brain when you get up too quickly.
• Swelling in your limbs or abdomen. This usually happens because of fluid buildup in your body.
• Sudden, noticeable weight loss. This is an important symptom, especially if you aren’t trying to lose weight.

When should I go to ER?

Because cardiac amyloidosis can severely disrupt your heart function, some of the symptoms are signs that you need immediate medical care. Some of those include:

• Heart palpitations.
• Unusually fast, slow or irregular heart rhythms.
• Struggling to breathe for any reason.

A note from Cleveland Clinic

Cardiac amyloidosis is one of the most common conditions that happen with any of the specific amyloidosis disorders. While this condition is progressive, can cause severe symptoms and is ultimately deadly, early detection can improve your outlook. In some cases, it’s possible to cure this condition with organ transplants. There are also new medications and treatments, which mean that many people with this condition can manage their symptoms and survive for several years after they develop the condition.