Transthyretin Amyloidosis (ATTR-CM)
What is transthyretin (TTR) amyloidosis (ATTR-CM)?
Transthyretin amyloidosis (am-uh-loy-DOH-sis) is a protein disorder. In this condition, clumps of irregular proteins called fibrils build up in your heart. These protein deposits stiffen your left ventricle, your heart’s main pumping chamber, making it harder for your heart to pump blood to your body.
What are other names for transthyretin amyloidosis?
Transthyretin amyloidosis also goes by these names:
- Cardiac amyloidosis.
- Amyloidosis ATTR.
- Transthyretin amyloid cardiomyopathy (ATTR-CM).
- Transthyretin cardiac amyloidosis (ATTR-CM).
- TTR amyloidosis.
What does transthyretin (TTR) amyloidosis or ATTR-CM mean?
Here’s a breakdown of what the medical terms mean:
- Transthyretin (TTR) is a protein found in cells that circulate in your blood. Your liver makes TTR. This protein carries vitamin A (retinol) and a thyroid hormone called thyroxine to different parts of your body.
- Amyloidosis occurs when abnormal proteins build up in organs. Cardiac amyloidosis affects your heart. Clumps of malformed proteins (fibrils) cause your heart to thicken and become stiff. The weakened organ can’t function as it should. Another protein called light chain causes amyloid light chain (AL) amyloidosis, a different type of cardiac amyloidosis.
- Cardiomyopathy (CM) is a disease of your heart muscle (myocardium). TTR deposits in your heart muscle, leading to thickening and stiffening of your heart. As a result, your heart struggles to pump enough blood to the rest of your body. This often leads to heart failure.
What are the types of transthyretin amyloidosis (ATTR-CM)?
The two types of transthyretin amyloidosis (ATTR-CM) include:
- Familial (hereditary) ATTR-CM: An inherited change (mutation) in the TTR gene causes amyloids to build up in your heart, nervous system or both. It can also affect your kidneys. Different TTR mutations cause ATTR-CM in various races and ethnicities around the world. In the United States, people who are Black are more likely to develop familial transthyretin amyloidosis.
- Wild-type ATTR-CM: This type occurs for no known reason. It most commonly affects your heart and nervous system.
How common is transthyretin amyloidosis (ATTR-CM)?
Medical experts aren’t sure how many people have transthyretin amyloidosis (ATTR-CM). But the disease is probably more common than we think. Experts believe it’s currently underdiagnosed.
Black people are most likely to develop the familial type. An estimated 1 in 25 Black people have a changed TTR gene. But not everyone who has this gene mutation develops transthyretin amyloidosis.
Symptoms and Causes
What causes transthyretin amyloidosis (ATTR-CM)?
A change to the TTR gene causes familial (hereditary) ATTR-CM. In rare instances, this gene change arises in a person without a family history (a de novo mutation). Black people who were assigned male at birth are more likely to develop familial ATTR-CM.
Experts aren’t sure why some people develop wild-type ATTR-CM. This type most commonly occurs in males over 65, which suggests age and sex may be risk factors.
Regardless of the underlying cause, your body starts to produce faulty TTR proteins. These abnormal proteins break apart, fold up on themselves (misfold) and form clumps of amyloid fibrils. Your blood carries these fibril clumps throughout your body, depositing them in nerves or organs like your heart. Over time, organ or nerve damage occurs.
What are the symptoms of transthyretin amyloidosis (ATTR-CM)?
Symptoms of transthyretin amyloidosis (ATTR-CM) vary depending on the type. People with wild-type ATTR-CM may not have any symptoms. If symptoms occur, they often appear after the age of 65.
Familial ATTR-CM symptoms most commonly occur for the first time in people over 50. However, symptoms can occur as early as your 20s or as late as your 80s.
Symptoms of transthyretin amyloidosis (ATTR-CM) are similar to heart failure symptoms, which include:
- Shortness of breath (especially when lying down or doing minimal physical activity).
- Bloated stomach.
- Confusion or difficulty thinking.
- Coughing or wheezing (especially when lying down).
- Edema (fluid retention in your legs, ankles and feet).
- Arrhythmia (irregular or fast heart rate), especially atrial fibrillation.
- Heart palpitations.
- Dizziness or passing out.
What are the complications of transthyretin amyloidosis (ATTR-CM)?
Transthyretin amyloidosis (ATTR-CM) can lead to heart failure and atrial fibrillation (Afib), a type of arrhythmia.
Amyloid deposits that build up in the nervous system can cause:
- Carpal tunnel syndrome, often in both wrists.
- Eye floaters.
- Peripheral neuropathy.
Deposits may also affect the spine, leading to spinal stenosis. Deposits in tissues can cause tendon ruptures.
Amyloidosis is also often seen with a condition called aortic stenosis (narrowing of the aortic valve, which connects the main pumping chamber of your heart to your aorta). If you have aortic stenosis, your healthcare provider may consider testing you for amyloidosis (especially if you have other signs of the disease, such as abnormal heart rhythms or carpal tunnel syndrome).
Diagnosis and Tests
How is transthyretin amyloidosis (ATTR-CM) diagnosed?
Transthyretin amyloidosis (ATTR-CM) can be challenging to diagnose correctly. The familial type can mimic heart (cardiovascular) disease caused by high blood pressure. Some people get an incorrect diagnosis at first.
The wild type doesn’t always cause symptoms. That version of the disease can go undetected until severe problems like heart failure occur.
Tests to diagnose transthyretin amyloidosis include:
- Electrocardiogram (ECG).
- Cardiac imaging like echocardiograms, MRIs and positron emission tomography (PET) scans.
- Bone scan (bone scintigraphy) to check for amyloid deposits.
- Heart biopsy.
- Blood tests to look for changes to the TTR gene.
Management and Treatment
How is transthyretin amyloidosis (ATTR-CM) treated?
There isn’t a cure for transthyretin amyloidosis (ATTR-CM). And there’s no way to rid the body of existing amyloid deposits. But medications can halt disease progression by slowing or stopping the buildup of protein deposits. You may also receive treatments to ease symptoms caused by other problems like heart failure, arrhythmias and neuropathy.
Certain medications for familial ATTR-CM bind to the TTR protein. These medicines stabilize the condition and stop proteins from misfolding. These drugs include tafamidis (Vyndaqel®, Vyndamax®) and diflunisal (Dolobid®), a nonsteroidal anti-inflammatory drug (NSAID) that providers may use as an off-label treatment. Off-label means the U.S. Food and Drug Administration (FDA) hasn’t approved the drug to treat that specific condition. But the drug is FDA-approved to treat other conditions.
Other medications like inotersen (Tegsedi®) and patisiran (Onpattro®) slow the liver’s production of faulty amyloid proteins.
In rare instances, you may need a:
Can you prevent transthyretin amyloidosis (ATTR-CM)?
If you have the TTR gene mutation that causes familial ATTR-CM, there’s a 50% chance of passing it to each of your children. Not every child who inherits this gene mutation develops ATTR-CM.
Before having children, you may want to meet with a genetic counselor. This specialist can discuss options like preimplantation genetic diagnosis (PGD). This technique may lower the risk of passing the changed gene to your child. With PGD, healthcare providers select embryos that don’t have the faulty gene. They then implant these embryos into your uterus using in vitro fertilization (IVF).
Outlook / Prognosis
What is the outlook for people with transthyretin amyloidosis (ATTR-CM)?
Transthyretin amyloidosis is a progressive disease that eventually causes serious complications. But with newer drugs like tafamidis, and new treatments under development in clinical trials, the outlook is improving. One study showed a 13% increase in the survival rate among people who took tafamidis for 30 months. It's very important to see a heart doctor regularly to make sure you're on the appropriate medications to treat your heart.
When should I call the doctor?
You should call your healthcare provider if you experience:
- Confusion or memory problems.
- Eye floaters.
- Irregular heartbeat or heart palpitations.
- Shortness of breath.
- Unexplained swelling (edema) and weight gain.
What should I ask my provider?
You may want to ask your healthcare provider:
- What type of transthyretin amyloidosis do I have?
- What caused the transthyretin amyloidosis?
- Do I have a mutated TTR gene?
- What treatments do you suggest?
- What are the medication's side effects?
- Will I need an organ transplant?
- Should I look out for signs of complications?
A note from Cleveland Clinic
A buildup of faulty proteins called fibrils causes transthyretin amyloidosis (ATTR-CM). These protein deposits stiffen and weaken your heart chambers, leading to cardiomyopathy. Black people are most likely to inherit a gene change that causes familial transthyretin amyloidosis (ATTR-CM). Some people develop the disease for no known reason. This is wild-type ATTR-CM. Medications can slow the buildup of faulty proteins, helping to prevent heart failure. In rare instances, you may need an organ transplant.
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy