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If you or a loved one has been diagnosed with transthyretin amyloid cardiomyopathy — also called ATTR-CM — you likely have a lot of questions. How serious is this condition? Will it lead to heart failure? Are there treatments that can help?
According to Omar F. Abou Ezzeddine, M.D., M.S., a cardiologist and cardiomyopathy expert at Mayo Clinic in Rochester, Minnesota, people often feel worried or anxious after a diagnosis.
“When you search online for cardiac amyloidosis, you may come across very alarming information,” he says. “The first thing I tell people is to take a deep breath. ATTR is not the automatic death sentence it is portrayed to be online.”
ATTR-CM is often underdiagnosed, and even some healthcare professionals are not as familiar with it as they are with more common heart conditions. That’s why it’s important to work with a multidisciplinary care team that has experience treating amyloidosis, and to take time to learn about your condition. The more you understand ATTR-CM, the better prepared you’ll be to take an active role in your care.
Below, Dr. Abou Ezzeddine explains what ATTR-CM is, how it affects the body and what life can look like after a diagnosis.
What is transthyretin amyloid cardiomyopathy (ATTR-CM)?
ATTR-CM is a form of amyloidosis — a rare group of diseases that occur when certain proteins build up in organs and interfere with how they work. At the same time, ATTR-CM is also a progressive form of cardiomyopathy, meaning it directly affects the heart muscle and its ability to pump blood.
In ATTR-CM, a protein called transthyretin (TTR) plays a central role. Typically, TTR is made in the liver and helps carry vitamin A and thyroid hormone through the bloodstream. With ATTR-CM, TTR becomes unstable, breaks apart and forms tiny fibers called amyloid. These amyloid fibers clump together and collect in tissues, especially in the heart.
“When these proteins misfold, they can no longer do their normal job,” Dr. Abou Ezzeddine explains. “Instead, they form deposits that build up in the heart muscle over time.”
As amyloid builds up, the heart walls become thicker and stiffer. This makes it harder for the heart to relax and fill with blood, and eventually harder to pump blood out to the rest of the body. Over time, this can lead to life-threatening heart failure.
ATTR-CM also can affect the heart’s conduction system. The conduction system uses electrical signals in the heart to regulate the heartbeat. When amyloid disrupts these signals, the heart may beat too fast or too slow. Dr. Abou Ezzeddine explains this can lead to an irregular heart rhythm called atrial fibrillation. In some cases, it also may lead to heart block, which is an interruption of part of the heart’s electrical system that may require a pacemaker.
The two types of ATTR-CM
There are two types of ATTR-CM — wild type and hereditary.
- Wild-type ATTR-CM (wtATTR-CM). Historically referred to as “senile” ATTR-CM, this form develops when transthyretin protein becomes unstable and forms amyloid. Researchers do not fully understand why this happens, but Dr. Abou Ezzeddine says it is more common as people age. Once formed, amyloid circulates through the body and is deposited primarily in the heart muscle and, in some cases, the peripheral nerves. Wild-type ATTR-CM most commonly affects men over the age of 60, though women also can develop it. Some researchers believe women may appear less affected in part because of estrogen’s protective effects on the heart, while others note that women may be underdiagnosed because symptoms can be more subtle or appear later in life. Overall, wild-type ATTR-CM is more common than the hereditary form discussed below, especially in older adults.
- Hereditary ATTR-CM (hATTR-CM). This form is caused by a genetic change, called a mutation, in the transthyretin gene that is passed down through families. You also may hear this form called familial or variant ATTR-CM. The genetic change makes the TTR protein more likely to become unstable and form amyloid. In the United States, one of the most common genetic variants is found in about 3% to 4% of people of West African, African American and Afro-Caribbean descent. Because of this, Dr. Abou Ezzeddine notes that Black individuals may be at a higher risk of developing hATTR-CM. If hereditary ATTR-CM is suspected, your care team may recommend genetic testing. This can help guide treatment decisions and identify family members who also may be at risk.