Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

What is transthyretin amyloid cardiomyopathy?

Transthyretin (trans-thy-re-tin) amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed and potentially fatal disease of the heart muscle. In ATTR-CM, a protein called transthyretin that normally circulates in the bloodstream becomes misshapen and builds up in the heart, nerves and other organs. 

When these amyloid deposits build up in the heart, the walls can become stiff, making the left ventricle unable to properly relax and fill with blood – called cardiomyopathy. As the condition progresses, the heart can become unable to adequately squeeze to pump blood out of the heart, ultimately leading to heart failure.

Hereditary ATTR-CM

There are two types of ATTR-CM. In hereditary ATTR-CM (hATTR-CM), which can run in families, there’s a variant in the transthyretin gene, which results in amyloid deposits in the heart, nerves and sometimes the kidneys and other organs. Symptoms may start as early as age 20 and as late as 80. 

Hereditary ATTR-CM is more common in localized parts of Portugal, Sweden and Japan; however, there are a number of variants in different parts of the world. Some variants are more common in people of Irish ancestry while others are common among people of African descent. 

Different variants may progress in a different way and involve different organs. The most common variant in the United States occurs in 1 in 25 of all African Americans and in older patients who may be misdiagnosed with high blood pressure-related heart disease.

Genetic testing may provide important information to developing a treatment plan. 

Wild-type ATTR-CM

The second type is wild-type ATTR-CM (wATTR-CM), in which there is no variant in the transthyretin gene. Wild-type ATTR-CM doesn’t run in families. It most commonly affects the heart and can also cause carpal tunnel syndrome and pain and numbness in the hands and feet, called peripheral neuropathy. Symptoms usually start after age 65. 

What are the risk factors?

Risk factors for hereditary ATTR-CM include:

• A family member with ATTR-CM or heart failure
• Age 50 and older (although symptoms can begin anywhere from age 20 to 80)
• Gender (patients are primarily male)
• Race – African American

Risk factors for wild-type ATTR-CM include:

• Age 65 and older
• Gender (patients are primarily male)

What are the symptoms?

Symptoms of ATTR-CM can vary or be subtle, and the condition is often misdiagnosed. In its early stages, it may mimic the symptoms of other conditions, such as heart failure related to high blood pressure, or hypertension, and enlargement and thickening of the heart, or hypertrophic cardiomyopathy. Some patients may have no symptoms, while others may progress to end-stage heart failure. The symptoms of wild-type ATTR-CM may be mild and remain undiagnosed.

ATTR-CM symptoms are like those associated with heart failure.

Shortness of breath is the most common, especially with minimal exertion and when lying down.

Other symptoms usually occur after the shortness of breath is already there, including:

• Coughing or wheezing, especially when lying down.
• Swelling in the feet, ankles and legs
• Bloating in the abdomen
• Confusion or trouble thinking
• Increased heart rate
• Palpitations or abnormal heart rhythms

Additional symptoms for ATTR-CM may include:

• Numbness or tingling in the hands and feet (hATTR-CM)
• Carpal tunnel syndrome (wATTR-CM)

How is it diagnosed?

ATTR-CM may be suspected because of typical symptoms and the results of a routine cardiac test — an electrocardiogram or echocardiogram. Once suspected, more specialized tests are needed to confirm the diagnosis. These could include:

• Imaging studies of the heart, most commonly a cardiac MRI and/or a nuclear medicine scan of the heart
• A tissue biopsy of an affected organ
• Genetic testing 

How can ATTR-CM be treated?

There are several promising new therapies for ATTR-CM on the horizon or available, so it is important to talk to your health care professionals about treatment options. 

With ATTR-CM, health care professionals focus on easing the heart failure symptoms and slowing or stopping the amyloid deposits. Medications are approved for hereditary transthyretin amyloidosis affecting the nerves, causing a condition called neuropathy.

In cases of advanced heart failure, heart transplantation may be an option. Because the abnormal transthyretin protein is produced by the liver, some patients may require both heart and liver transplantation.  

Talk with your health care professionals

Awareness of ATTR-CM among health care teams is low. In fact, it’s often misdiagnosed as hypertensive heart failure or hypertrophic cardiomyopathy and may already be advanced by the time the patient receives a diagnosis. 

If you are living with heart failure and have additional unresolved or seemingly unrelated symptoms, speak to your health care professional about your symptoms and treatment options. Starting that conversation could be a lifesaver. 

Tell your doctor about any shortness of breath and ask for a diagnostic testing and treatment plan. If the diagnostic tests don’t provide an answer, or if the treatment fails to improve your symptoms, talk with your health care professional about next steps. It’s important not to give up until the tests reveal a diagnosis and the treatment relieves your symptoms. 

If you do have ATTR-CM, genetic testing may offer important information to your health care professional to develop a treatment plan. 

Get support

Getting support for you and your caregivers is important to your health. Research shows that going it alone and not seeking support during a heart diagnosis can reduce your ability to make the lasting changes you need to live a longer, healthier life. 

Learn more about ATTR-CM and connect with others impacted by this form of cardiomyopathy on the American Heart Association’s Support Network. There, you will find a community triumphing over their health obstacles each day. 

You can share your experience to help others and get support from others who have been there. Connect for free today at heart.org/SupportNetwork.