Cardiac amyloidosis

Overview

Cardiac amyloidosis (am-uh-loi-DO-sis) is a serious condition that affects the heart. It happens when some proteins in the body change shape and stick together. The proteins form deposits called amyloid. When amyloid builds up in the heart, the heart walls get thick and stiff. So they can't stretch as well to fill with blood. This makes it harder for the heart to pump blood to the rest of the body.

Cardiac amyloidosis is a type of heart muscle disease called restrictive cardiomyopathy. It's called restrictive because the amyloid makes the heart less flexible. Other types of cardiomyopathy mainly make the heart weak, thick or larger than usual.

Amyloidosis can affect many other parts of the body, such as the kidneys, liver and nervous system. When it affects the heart, amyloidosis may be easy to miss at first. Shortness of breath or fast, pounding heartbeats may seem like symptoms of other health conditions. Over time, cardiac amyloidosis may lead to heart failure.

Finding cardiac amyloidosis early can help people start treatment sooner. Treatments have improved in recent years. There is no cure, but medicines can slow the disease and ease symptoms. However, the deposits and heart damage may not fully go away. Some people may need a heart transplant.

Types

There are different types of cardiac amyloidosis. Some types may run in families. That means they are inherited.

The types of amyloidosis that most commonly affect the heart are:

• Amyloid-light chain (AL) amyloidosis. This rare condition starts in the bone marrow. Some blood cells, called plasma cells, make proteins called light chains. The plasma cells make too much of one type of light chain. The light chains fold the wrong way and stick together, forming amyloid deposits. When the deposits build up in the heart, it is called AL cardiac amyloidosis. AL amyloidosis can happen with multiple myeloma or other blood conditions. It also is called immunoglobulin light chain amyloidosis.
• Amyloid transthyretin (ATTR) amyloidosis. The liver makes a protein called transthyretin (TTR). TTR helps carry thyroid hormone and vitamin A through the blood. In ATTR amyloidosis, this protein becomes unstable. It folds the wrong way and forms amyloid deposits. Healthcare experts think the condition may be more common than once thought and is often missed.

ATTR amyloidosis has two types:

• Wild-type transthyretin (ATTRwt) cardiac amyloidosis. This is the most common type of ATTR amyloidosis. It used to be called senile systemic amyloidosis. The gene for the TTR protein is not changed. Why the protein folds the wrong way is not clear. The protein may get less stable with age. The wild type mostly affects older adults.
• Hereditary transthyretin (ATTRv) cardiac amyloidosis. This type is caused by a change in the gene that makes the transthyretin protein. This gene change is called a variant. It can be passed from a parent to a child. Other names for this type are variant transthyretin amyloidosis and familial transthyretin amyloidosis.

Symptoms

Symptoms of cardiac amyloidosis happen as amyloid builds up in the heart and other parts of the body. But the symptoms can be vague. They may look like those of other heart conditions.

Cardiac amyloidosis symptoms may include:

• Chest pain, especially during activity.
• Fast, pounding or fluttering heartbeats.
• Feeling dizzy or fainting, especially after standing up.
• Feeling very tired, even after getting rest.
• Feeling weak or not able to do as much physical activity.
• Shortness of breath or trouble breathing with activity or even at rest.
• Swelling in the legs, ankles, feet or belly area.

Other symptoms can depend on the type of cardiac amyloidosis you have and what other parts of the body are affected. General symptoms may include:

• Not feeling hungry.
• Feeling full quickly after eating a small amount.
• Numbness and tingling in the hands or feet.
• Upset stomach, diarrhea or constipation.
• Easy bruising around the eyes and a swollen tongue, mainly with AL amyloidosis.
• Losing weight without trying.

Tell your healthcare team about all the symptoms you have. Your care team can help find the cause of your symptoms. Together, you can decide on the care you need.

When to seek care

Make an appointment for a health checkup if you have symptoms of cardiac amyloidosis. Also contact your healthcare professional if:

• You have cardiac amyloidosis and your symptoms are new or getting worse.
• You gain 5 pounds (2.3 kilograms) or more within a few days.

When to seek emergency care

Cardiac amyloidosis can make it hard for the heart to pump blood. Get medical help right away if you have:

• Chest pain.
• Sudden, severe shortness of breath.
• A very fast or not regular heartbeat with shortness of breath, chest pain or fainting.

These symptoms may be due to heart failure related to cardiac amyloidosis. But there are many other possible causes.

Causes

Cardiac amyloidosis is caused by certain proteins that fold the wrong way and stick together. This forms deposits called amyloid. The deposits build up in the heart, making the heart walls stiff and thick. This makes it harder for the heart to fill with blood and pump it through the body. Long ago, some people used "stiff heart syndrome" to describe how cardiac amyloidosis affected the heart.

In all types of cardiac amyloidosis, there are amyloid deposits. But the amyloid can form from different starting proteins.

Causes of AL cardiac amyloidosis

The cause of AL cardiac amyloidosis usually is a change in white blood cells in the bone marrow called plasma cells. This is called a plasma cell disorder. The changed plasma cells make too much of one type of light chain. A light chain is a type of protein. The light chains fold into the wrong shape. They stick together and form amyloid deposits in the heart.

Plasma cell disorders related to AL cardiac amyloidosis include:

• Monoclonal gammopathy of undetermined significance (MGUS). Some people have MGUS before AL cardiac amyloidosis develops.
• Multiple myeloma, a type of blood cancer. AL amyloidosis sometimes happens with this cancer. But most people with AL amyloidosis do not have multiple myeloma.

Less often, AL cardiac amyloidosis may be caused by other blood conditions that affect other cells that make antibodies. Examples are:

• Waldenstrom macroglobulinemia.
• Chronic lymphocytic leukemia.
• Some types of non-Hodgkin lymphoma.

Causes of ATTR amyloidosis

In ATTR amyloidosis, the cause is a change in a protein called transthyretin (TTR). The liver makes most of this protein. But why the TTR protein becomes less stable can vary.

• In wild-type ATTR, the TTR gene is not changed. The TTR protein gets less stable with age. The exact reason this happens is not known.
• In hereditary ATTR, a change in the TTR gene causes it to be less stable. The change in the gene can pass from a parent to a child.

Risk factors

Some things may make you more likely to get cardiac amyloidosis. Risk factors include:

• Age. Cardiac amyloidosis is more common in older adults. But the age range depends on the type of cardiac amyloidosis. Wild-type ATTR mainly affects people over age 60, often men. The age when hereditary ATTR happens can vary. It depends on the type of TTR gene change you have. AL cardiac amyloidosis is usually diagnosed around age 65.
• Genetics. Hereditary ATTR is passed down through families. That means it's inherited. A parent has a 1 in 2 chance of passing the changed TTR gene to each child. This is called an autosomal dominant inheritance pattern. However, not everyone with the gene change will develop cardiac amyloidosis.
• Ancestry. Some TTR gene changes happen more often in people whose families come from certain parts of the world. One gene change linked with hereditary ATTR cardiac amyloidosis is more common in people with West African or African Caribbean ancestry. Other TTR gene changes are more common in families from Portugal, Sweden, Japan, Ireland, Italy and Denmark.

Complications

Cardiac amyloidosis complications happen because amyloid buildup changes how the heart beats and pumps blood. The condition can lead to serious medical conditions. Possible complications include:

• Heart failure. This is a common complication of cardiac amyloidosis. In cardiac amyloidosis, the heart gets stiff. So it can't stretch as well as it should to fill with blood. As a result, the heart can't pump enough blood to meet the body's needs. Heart failure can be life-threatening.
• Irregular heartbeats, called arrhythmias. Amyloid deposits can affect the electrical signals that tell the heart to beat. The heart may beat too fast or too slow. Or the heartbeat may not follow a steady pattern. Atrial fibrillation (AFib) is one type of irregular heartbeat. It can cause blood clots that lead to stroke. AFib is more common in people with ATTR amyloidosis than in people with AL amyloidosis.
• Heart block, also called conduction block. Amyloid deposits can damage the heart's electrical pathways. This can slow or stop the signals that tell the heart to beat. Heart block may cause a slow heartbeat, fainting or dizziness. Some people need a pacemaker to help the heart beat at a safe rate.
• Sudden cardiac arrest. Rarely, a dangerous heartbeat or severe failure in how the heart beats or pumps can cause the heart to suddenly stop pumping blood. Without emergency treatment, sudden cardiac arrest can lead to sudden cardiac death.

Regular health checkups can help your care team watch for these complications. Finding and treating them early can help you feel better and protect your heart.