Transthyretin amyloidosis (ATTR-CM) occurs when your liver produces faulty transthyretin (TTR) proteins. Clumps of these abnormal proteins (called fibrils) build up in your heart’s main pumping chamber. Your left ventricle becomes stiff and weak. This cardiomyopathy makes it harder for your heart to pump blood to your body. Heart failure can occur.
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.
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
Transthyretin amyloidosis also goes by these names:
Here’s a breakdown of what the medical terms mean:
The two types of transthyretin amyloidosis (ATTR-CM) include:
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.
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.
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:
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:
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).
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:
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:
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).
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.
You should call your healthcare provider if you experience:
You may want to ask your healthcare provider:
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.
Last reviewed by a Cleveland Clinic medical professional on 05/01/2022.
Learn more about our editorial process.