Key Takeaways
- Hereditary ATTR-CM is a genetic condition in which abnormal transthyretin protein builds up in the body, including the heart, where it can stiffen the ventricles and affect blood pumping efficiency.
- The condition is inherited, with a 50% chance of passing the gene variant from an affected parent. Symptoms may begin as early as age 30 but typically appear later in life.
- While there is no cure, early diagnosis can help guide treatment. Disease-specific therapies may slow progression and support quality of life.
Hereditary (familial) transthyretin amyloid cardiomyopathy (ATTR-CM) is a protein disorder that you may also see referred to as:
- hereditary transthyretin amyloid cardiomyopathy (hATTR-CM)
- transthyretin cardiac amyloidosis (ATTR-CM)
- amyloidosis ATTR
- cardiac amyloidosis
The condition involves the abnormal formation of the protein transthyretin (TTR). The protein can misfold, bundle together, and form clumps, known as fibrils, in tissues, nerves, and organs.
When TTR builds up in the heart, it can stiffen the left ventricle. This stiffness makes it harder for the heart to pump blood throughout the body, a condition known as cardiomyopathy, which can lead to heart failure.
ATTR-CM can be difficult to diagnose and is often underdiagnosed. If you have a family history of this condition, it’s crucial to talk with a doctor or another healthcare professional about evaluation and early testing.
Knowing about the condition, its symptoms, and warning signs is essential to ensuring timely management.
Hereditary ATTR-CM runs in families, which is why healthcare professionals may also refer to it as familial. You may notice symptoms starting in your 30s, but they more commonly appear later in life.
Immediate family members, such as parents and siblings, may share genetic variants that cause ATTR-CM. You only need one copy of the mutated gene to develop the condition. This means that if one of your parents has an ATTR-CM diagnosis, you have a
Mutations in the gene that produces TTR can cause the protein to misfold and form amyloid. These amyloid deposits can build up and form bundles in the:
- heart
- eyes
- nerves
- kidneys
- other organs
More than 120 types of ATTR have been identified, and each may progress differently and affect various organs.
In the United States, the most common variant is ATTR V122I. This variant is more common in people of African descent, including between 3% and 4% of those individuals living in the United States.
Symptoms of hereditary ATTR-CM aren’t always obvious and can vary from person to person. They
- shortness of breath
- chest congestion or tightness
- swelling in the lower limbs
- Irregular heart rhythm
- numbness or tingling in the hands and feet
Some people may also experience neurologic or musculoskeletal symptoms, which can be important for diagnosing the condition. These may include:
- carpal tunnel syndrome
- spinal stenosis
- tendon rupture or unexplained tendon problems
Other symptoms may include digestive issues, such as diarrhea or nausea, as well as frequent urinary tract infections (UTIs).
An early diagnosis can help ensure you receive the right treatment to maintain your quality of life and may even slow disease progression.
If you’re experiencing cardiac symptoms, the diagnostic process for ATTR-CM usually begins with a medical history and physical exam, followed by heart-focused testing.
Your healthcare team may start with tests such as:
- electrocardiogram (EKG)
- heart ultrasound (echocardiogram or echo)
- blood and urine tests, which can help rule out other forms of amyloidosis
- technetium pyrophosphate (Tc-PYP) scan
A Tc-PYP scan is one of the most commonly used tests to help identify ATTR-CM. During the scan, a small amount of radioactive tracer is injected or swallowed. Cameras then rotate around the body to capture images of the heart. While the overall appointment time may take longer because of waiting periods, the actual imaging time is usually less than 1 hour.
In some cases, additional testing, such as a cardiac MRI, may be used. A heart biopsy is less common but may be recommended if the results are unclear.
Once ATTR-CM has been confirmed, genetic testing may be used to determine whether the condition is hereditary or wild type. Genetic testing involves a blood draw, saliva sample, or cheek swab.
If someone in your immediate family has ATTR-CM, talk with your healthcare team about whether genetic testing is appropriate for you. If you’re experiencing symptoms but aren’t sure whether you carry a gene variant, it’s still important to discuss your symptoms with a doctor or another healthcare professional so they can guide next steps and testing.
There’s currently no cure for ATTR-CM. Once TTR protein deposits form, they can’t be reversed.
However, several treatments are available that work by stabilizing or reducing transthyretin. These disease-modifying therapies may slow disease progression, support heart function, and improve quality of life.
Tafamidis (Vyndamax)
The Food and Drug Administration (FDA) approved Tafamidis to treat ATTR-CM. It works by binding to transthyretin and stabilizing the protein, which helps prevent harmful amyloid deposits from forming in the heart.
Tafamidis is taken once daily, which may make it easier to manage as part of long-term treatment.
Acoramidis (Attruby)
Acoramidis is another FDA-approved treatment for ATTR-CM. Like tafamidis, it works by stabilizing transthyretin to help reduce amyloid formation and slow disease progression.
Acoramidis is taken by mouth, making it another oral treatment option for managing ATTR-CM.
Vutrisiran (Amvuttra)
Vutrisiran is an FDA-approved therapy for ATTR-CM that works by reducing the production of transthyretin in the liver. By lowering the amount of abnormal protein in circulation, it may help limit further amyloid buildup.
Vutrisiran is given as an injection, rather than as a daily pill.
Other medications
In addition to disease-specific treatments, your healthcare team may also prescribe medication to help manage related conditions. These may include treatments for heart failure, abnormal heart rhythms, or nerve-related symptoms, depending on your needs.
There are
- hereditary ATTR-CM (hATTR-CM)
- wild-type ATTR-CM (wtATTR-CM)
Let’s look at the differences between them.
| Hereditary ATTR-CM (hATTR-CM) | Wild-type ATTR-CM (wtATTR-CM) | |
|---|---|---|
| Onset age | varies by mutation type but may begin between ages 30 and 80 years | often age 60 years and over, with an average diagnosis age of about 75 years |
| Cause | TTR gene mutation leads to irregular, unstable TTR proteins | proteins become unstable with age |
| Genetics | genetic mutation passed down through families | no genetic mutation; nonhereditary |
| Who is more susceptible? | varies by geographical location and variant type; the most common mutation in the U.S. is v122l, seen in 3% to 4% of African Americans | more commonly affects males |
Treatments are the same for each type of ATTR-CM.
The outlook for people with hereditary ATTR-CM can vary based on the specific gene variant involved and other health considerations.
ATTR-CM is a serious and progressive condition. If left untreated, life expectancy can range from 2 to 5 years. However, early diagnosis and treatment may help slow disease progression and improve outcomes.
If you have a family history of heart failure or any symptoms of cardiac amyloidosis, a cardiologist can evaluate and determine whether testing for amyloidosis is needed. Receiving a diagnosis early can allow you to begin treatment before heart failure develops.
Hereditary ATTR-CM runs in families and involves a mutation in the gene responsible for making the TTR protein.
Because early diagnosis is important, knowing your family health history can help you and your healthcare team plan for appropriate testing and care.