Learn The BasicsTransthyretin amyloid cardiomyopathy (ATTR-CM) is a rare heart disease caused by the buildup of a misshaped protein called transthyretin (TTR) in the heart, nerves and other organs.
A brief history of ATTR-CM
Cardiac amyloidosis was first described in two patients by Isidor Soyka in 1876. Amyloidosis is a general term for the buildup of amyloid, a protein, in bodily organs.
In 1934, John W. Budd described a case of cardiac amyloidosis in one patient and illustrated atrial nodules as a characteristic feature of the disease for the first time.
Other reported cases included three patients from Scandinavia reported in 1946 and 12 patients from the United States in 1948 and 1957.
The first cases of hereditary or familial ATTR were described in 1929 and 1952, though these predominantly affected peripheral nerves.
How common is ATTR-CM?
It is not known exactly how common ATTR-CM is. Some researchers think it may be much more common than initially thought and that a lot of patients go undiagnosed.
The familial form of the disease affects African Americans more than Caucasians, with one in 25 African Americans carrying an altered form of the TTR gene. Not everyone with abnormalities in this gene will develop ATTR-CM.
What are the different types of ATTR-CM?
There are two types of ATTR-CM: familial or hereditary ATTR-CM and wild-type ATTR-CM.
Hereditary ATTR-CM results from a mutation in the TTR gene, which codes for the TTR protein. Different types of mutations can affect this gene and cause ATTR-CM.
Wild-type ATTR-CM develops sporadically with no known cause but usually occurs in men over age 65, suggesting that male sex and age may be risk factors.
What causes ATTR-CM?
ATTR-CM is caused by the accumulation of misfolded TTR protein in the heart tissue. These misfolded proteins are called amyloid fibrils.
Over time, the accumulation of these amyloid fibrils in the heart causes cardiomyopathy or heart muscle disease.
What are the symptoms of ATTR-CM?
The symptoms of ATTR-CM include the following.
- Swelling in the ankles, legs or abdomen.
- Coughing or wheezing.
- Trouble breathing when lying down.
- Confusion.
- Irregular heartbeat.
- Numbness or tingling in the hands and feet.
How do doctors diagnose ATTR-CM?
An electrocardiogram or echocardiogram may lead to doctors suspecting ATTR-CM.
Other tests are needed to reach a final diagnosis. These include the following.
- Imaging studies such as magnetic resonance imaging (MRI) or a positron emission tomography (PET) scan of the heart.
- A heart biopsy.
- Genetic testing to see if there is a mutation in the TTR gene known to be associated with ATTR-CM.
How do clinicians treat ATTR-CM?
Some health care providers may treat ATTR-CM with nonsteroidal anti-inflammatory drugs such as diflunisal. Research has shown that diflunisal can bind to and stabilize common familial TTR variants against the formation of amyloid fibrils.
Tafamidis is a TTR protein stabilizer that can be used to treat ATTR-CM. Research has shown it slows the progression of the disease and significantly reduces mortality.
Acoramidis, another TTR protein stabilizer, has also been found to significantly reduce mortality, as well as hospitalizations.
Vutrisiran is a small interfering RNA therapy. Studies have found that it also reduces mortality in patients with ATTR-CM, as well as heart problems.
Other drugs can be used to slow the production of faulty TTR proteins by the liver. These include inotersen, eplontersen and patisiran.
In severe cases, patients with ATTR-CM may need a liver transplant, kidney transplant or heart transplant.
Reviewed by Kyle Habet, MD, on Nov. 14, 2024. Updated March 24, 2025.