What Is Transthyretin Cardiac Amyloidosis (ATTR-CM)?
Published on September 16, 2025
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Transthyretin cardiac amyloidosis (ATTR-CM), also known as transthyretin amyloid cardiomyopathy, is a rare and serious heart condition that occurs when your liver produces misshapen transthyretin proteins that accumulate in the heart muscle. These abnormal protein deposits, called amyloids, cause the walls of heart muscle to stiffen, reducing its ability to pump blood. The initial symptoms are similar to those of heart failure.
ATTR-CM is a progressive, incurable, and life-threatening condition that can strike at random or run in families. In the United States, it is most common among Black men. Fortunately, new diagnostic tools and promising treatments are improving outcomes and extending lifespans.
Types of ATTR-CM
There are two distinct forms of ATTR-CM. One is caused by a genetic component, and the other is associated with aging.
- Hereditary ATTR-CM runs in families and is caused by inherited mutations in the transthyretin (TTR) gene. More than 130 genetic variants have been identified, but not all people with a genetic mutation will develop the condition. Hereditary ATTR-CM causes amyloid deposits in the heart, nerves, and sometimes other organs like the kidneys.
- Wild-type ATTR-CM occurs without a genetic mutation, meaning it doesn’t run in families, and it typically impacts older men. The average age of diagnosis is 75, and it’s related to TTR protein accumulation. Wild-type ATTR-CM mostly affects the heart, though it can also cause musculoskeletal issues like carpal tunnel syndrome and spinal problems.
Signs and Symptoms of ATTR-CM
Initially, ATTR-CM symptoms mimic those of heart failure, the most common being shortness of breath while resting or with little activity. Additional heart-related symptoms include:
- Fatigue
- Swelling in the legs or abdomen
- Chest congestion
- Coughing or wheezing, especially when lying down
- Confusion
- Heart palpitations and abnormal heart rhythms (arrhythmia)
- Atrial fibrillation (rapid, irregular heartbeat), which nearly all people with ATTR-CM eventually develop
- Dizziness
The condition can also cause a variety of symptoms outside the heart, some of which may be more common in one type or another, and some of which appear before any cardiac symptoms. They include:
- Gastrointestinal issues like diarrhea, constipation, nausea, bloating, and feeling full quickly
- Carpal tunnel syndrome (wild-type ATTR-CM)
- Spinal stenosis, causing pain or numbness in the lower backs and legs (hereditary ATTR-CM)
- Tendon ruptures in the biceps (wild-type ATTR-CM)
- Ocular issues like glaucoma, dry eye, and dark floaters (hereditary ATTR-CM)
- Kidney impairment
- Peripheral neuropathy, causing tingling or numbness in the hands and feet (hereditary ATTR-CM)
- Erectile dysfunction
Causes and Risk Factors of ATTR-CM
ATTR-CM is ultimately the result of destabilized transthyretin (TTR) proteins. Produced by the liver, TRR circulates in the bloodstream to transport vitamin A and thyroid hormones throughout the body. Structural changes in the protein can cause it to misfold and lose its normal shape, forming amyloids, which are fibrous deposits in the heart and other organs that disrupt normal function.
With hereditary ATTR-CM, inherited genetic mutations in the TRR gene cause structural changes in transthyretin protein to develop. In the United States, the condition is usually associated with a few different genetic variants — the most common is V122I, which primarily affects African Americans. The second most common variant in the country (and the most common in the United Kingdom) is T60A, which primarily affects people of Irish descent.
For wild-type ATTR-CM, age-related protein misfolding is responsible for the condition, rather than genetics. But why this occurs is not completely understood.
Risk factors for ATTR-CM include:
- Older age
- Male sex
- Black race (hereditary form)
How Is ATTR-CM Diagnosed?
Because it mimics other heart conditions and not everyone will experience symptoms, ATTR-CM is often misdiagnosed or only caught after it’s reached an advanced stage.
Diagnosis starts with your healthcare provider discussing your symptoms and family history. They will then use various diagnostic tools to determine if you have ATTR-CM:
- Blood tests, used to detect cardiac biomarkers in your blood that suggest heart disease
- Echocardiogram, also known as an echo, is an ultrasound to look for amyloid deposits in the heart and increased wall thickness of the left ventricle
- Magnetic resonance imaging (MRI), which is useful for creating images of heart changes when EEG results are inconclusive. But echo and MRI cannot differentiate thickening caused by ATTR-CM from other forms of heart disease.
- Biopsy, the removal and examination of small heart tissue samples, which remains the gold standard for diagnosing ATTR-CM.
- Nuclear scintigraphy, a noninvasive imaging technique that uses tiny amounts of radioactive substances like technetium pyrophosphate that bind to amyloid in the heart. This is the only imaging technique that can diagnose ATTR-CM without a biopsy.
Once diagnosed, genetic testing can differentiate if you have hereditary or wild-type ATTR-CM.
Treatment and Medication Options for ATTR-CM
There is no cure for ATTR-CM, and in the past, treatment focused on supportive care to help improve quality of life and control symptoms. But newer, targeted therapies can help slow or halt the progression of the disease.
Targeted Therapies
A class of drugs called TTR stabilizers can help slow ATTR-CM progression by binding to the TTR protein to help maintain its stability and shape, reducing new amyloid deposits. There are two TRR stabilizers approved by the U.S. Food and Drug Administration (FDA) for ATTR-CM:
- Tafamidis (Vyndaqel/Vyndamax)
- Acoramidis (Attruby)
Both tafamidis and acoramidis stabilize 96 percent of TTR proteins, and have been proven to significantly reduce the risk of early death of users.
A second class of drugs called TTR silencers are similarly effective. These drugs slow ATTR-CM by suppressing the production of new TTR proteins. Vutrisiran (Amvuttra) is currently the only TTR silencer to receive FDA approval for ATTR-CM, though other silencers like patisiran and inotersen are approved to treat ATTR-polyneuropathy, which occurs when amyloid accumulates in the peripheral nervous system.
If you are treated with a TTR silencer, you will need to take daily vitamin A supplementation to avoid deficiency.
Diflunisal, a type of nonsteroidal anti-inflammatory drug (NSAID), has also shown promising TRR stabilizing properties, but it is not yet FDA approved for ATTR-CM. Some doctors may prescribe this drug off-label for certain patients.
Supportive Therapies
Supportive care seeks to help manage ATTR-CM symptoms and complications, such as heart failure and arrhythmias, using medications such as:
- Diuretics and dietary sodium restrictions to treat heart failure
- Anti-arrhythmic medications like amiodarone to regulate abnormal heart rates
- Anticoagulants for blood clots in the heart
- Catheter ablation, a minimally invasive procedure to treat atrial fibrillation
Liver transplants were once used to treat tATTR-CM, but they’re rarely performed now that TRR-specific therapies are available. Heart transplants are rarely performed given the advanced age of most ATTR-CM patients.
Prevention of ATTR-CM
ATTR-CM currently cannot be prevented, given that it's caused by age- or genetics-related changes.
If you have hereditary ATTR-CM, it’s important to encourage your family to pursue genetic testing. Hereditary ATTR-CM is autosomal dominant, meaning that first-degree relatives of someone with the condition have a 50 percent chance of inheriting the gene variant and passing it on to their children. Genetic counseling can help you and your family members understand the testing, results, and risks of having ATTR-CM. If you want to have children, genetic counselors can also discuss options to lower the chances of passing the impacted gene to your child.
If genetic testing shows you carry a TTR mutation, regular cardiac monitoring can help you catch and treat ATTR-CM early, before it does significant damage.
Researchers are investigating whether treatment with acoramidis in asymptomatic people with a TTR variant can delay or prevent hereditary ATTR-CM.
Lifestyle Changes for ATTR-CM
Behaviors that support heart health can also improve the quality of life for those who have ATTR-CM.
- Reduce or limit dietary sodium, especially if you experience swelling.
- Maintain a heart-healthy diet that limits fats, sugar, and processed foods.
- Stay hydrated, but monitor your fluids if you experience leg swelling.
- Raise your legs on pillows or an ottoman if they swell.
- Maintain physical fitness with gentle movements like walking and swimming.
ATTR-CM Prognosis
ATTR-CM is incurable and it can be fatal. The median survival rate for hereditary and wild-type ATTR after diagnosis is 2.5 years and 3.6 years, respectively.
That statistic, however, doesn’t take into account the newest treatment advancements: TTR stabilizers and silencers can significantly improve longevity. Research suggests, for instance, that vutrisiran treatment reduces the risk of death within 42 months by 36 percent.
It’s important to recognize that every case is different, and statistics can’t predict how long you’ll live.
Complications of ATTR-CM
When left undiagnosed or untreated, ATTR-CM can result in these serious illnesses:
- Progressive, worsening heart failure and arrhythmias, which may cause sudden cardiac death
- Atrial fibrillation
- Stroke
- Neuropathy (nerve damage)
How Many People Have ATTR-CM?
Roughly 5,000 to 7,000 people are diagnosed with ATTR-CM in the United States each year.
But experts believe ATTR-CM is significantly underdiagnosed, with possibly only less than 2 percent of cases being identified. Roughly 3 to 4 percent of Black Americans carry the V122I mutation, making them more prone to ATTR-CM.
Black Americans and ATTR-CM
ATTR-CM is more likely to be diagnosed in Black Americans, particularly those of West African descent. The genetic mutation responsible — V122I — is the most common cause of late-onset ATTR-CM in the country.
Research also suggests that Black Americans with ATTR-CM experience worse outcomes, such as heart failure–related hospitalization and death, than other populations. This is partly because V122I causes a more aggressive form of hereditary ATTR-CM. Additionally, Black patients diagnosed with ATTR-CM are more likely than white patients to experience lower socioeconomic status, a factor linked to delayed diagnosis and reduced access to quality medical care.
Related Conditions
There are dozens of different types of amyloidosis, and they can be localized to another organ rather than the heart.
- Light-chain (AL) amyloidosis makes up nearly 80 percent of all new amyloidosis cases. The condition stems from a bone marrow disorder, and about two-thirds of the patients are male.
- AA amyloidosis happens as a reaction to another illness, such as inflammation or an untreated infection. It is linked to rheumatologic diseases like rheumatoid arthritis and ulcerative colitis.
- LECT-2 amyloidosis is associated with kidney failure
Support for People With ATTR-CM
This site is a resource center for all things amyloidosis, including regional support groups, a treatment center location finder, a patient registry, and information about clinical trials. It also has a list of amyloidosis-related blogs written by people who’ve been impacted by the disease.
Amyloidosis Research Consortium
With a mission to raise awareness for scientific research and treatment of amyloid disease, this nonprofit offers resources for those who are newly diagnosed, a one-to-one peer support program for patients and caregivers, and other patient resources.
The Takeaway
- ATTR-CM is a rare, progressive disease that’s caused by protein deposits in the muscles of the heart. This leads to stiffer heart walls that don’t pump blood as efficiently, and the outcome can be critical or fatal.
- There are two main types: hereditary ATTR-CM, which is caused by genetic mutations, and wild-type ATTR-CM, which mostly occurs in older men.
- There is currently no cure, but recent advances in treatment, including medications such as TRR stabilizers and TRR silencers, are improving patient outcomes, slowing disease progression, and extending life expectancy.
Common Questions & Answers
If I have the genetic mutation for hereditary ATTR-CM, will I definitely develop the disease?
Not necessarily. The genetic mutation increases your chances of getting ATTR-CM, but it doesn’t guarantee you’ll develop symptoms.
What’s the difference between hereditary and wild-type ATTR-CM?
The hereditary form is caused by a genetic mutation that is passed down in families, while wild-type occurs without mutation in older people, particularly men.
Are there treatments that can reverse ATTR-CM?
No. Current treatments slow progression and improve survival, but they do not reverse existing amyloid deposits. Treatments to reverse ATTR-CM by destroying existing amyloid deposits are undergoing clinical trials.
Should relatives of someone with ATTR-CM get tested?
Yes, especially if their family members have the hereditary form. Genetic testing can identify their risk and guide early diagnosis and care.
Does ATTR-CM affect only the heart?
No, both the hATTR-CM and wATTR-CM can cause symptoms in other areas of the body, including the wrists, spine, gastrointestinal system, and eyes.
Resources We Trust
- Cleveland Clinic: Transthyretin Amyloidosis (ATTR-CM)
- Mayo Clinic: Genetic Testing
- Amyloidosis Foundation: Patient Resources
- American Heart Association: What Is Heart Failure?
- Mass General Brigham: Genetic Heart Conditions
EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
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Chung Yoon, MD
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Chung Yoon, MD, is a noninvasive cardiologist with a passion for diagnosis, prevention, intervention, and treatment of a wide range of heart and cardiovascular disorders. He enjoys clinical decision-making and providing patient care in both hospital and outpatient settings. He excels at analytical and decision-making skills and building connection and trust with patients and their families.
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