Did you know that some people can develop amyloidosis as they age — even without inheriting a TTR gene mutation (change) from parents?

Wild-type ATTR amyloidosis typically affects people as they get older. In this condition, a protein called transthyretin (TTR) changes shape, or misfolds, and builds up mainly in the heart and sometimes other tissues.

Wild-type ATTR amyloidosis can be hard to diagnose because its symptoms often resemble those of other heart conditions, such as hypertensive heart disease or age-related heart failure. That’s why it’s important to see a specialist who is familiar with amyloidosis.

This article discusses wild-type ATTR amyloidosis, including its common symptoms, modern noninvasive diagnostic tools, available treatments, and what to expect when living with the condition.

Who Develops Wild-Type Amyloidosis?

Wild-type ATTR amyloidosis most commonly affects men 60 years of age and older, according to the Amyloid Research Consortium. Researchers estimate that at least 1 percent of males over 80 may have the condition.

However, wild-type ATTR amyloidosis may also be underdiagnosed because its symptoms overlap with those of other heart conditions. Some people with wild-type amyloidosis may never develop noticeable symptoms.

What Are the Symptoms of Wild-Type ATTR Amyloidosis?

Wild-type ATTR amyloidosis can lead to restrictive cardiomyopathy, a heart condition that makes it harder for the heart to pump blood. This happens when amyloid proteins build up in the heart, causing the heart muscle to become thick and stiff, making it harder for the heart to relax and fill with blood between beats.

Many symptoms resemble those of heart failure, such as:

• Dizziness or lightheadedness
• Fatigue (extreme tiredness that doesn’t improve with rest)
• Weight loss
• Shortness of breath
• Edema (leg swelling)
• Atrial fibrillation or other arrhythmias (abnormal heart rhythms)
• An abnormally fast or slow heartbeat

Wild-type ATTR amyloidosis can also cause symptoms outside the heart. Carpal tunnel syndrome in the wrist may be an early sign and can develop before heart symptoms.

Some people with wild-type ATTR amyloidosis also develop peripheral neuropathy, which can cause numbness, tingling, or pain in the hands and feet. A tear in the biceps tendon may also be a sign of wild-type amyloidosis.

Symptoms outside the heart, especially carpal tunnel syndrome, may show up eight to 10 years before heart-related symptoms appear.

What Causes Wild-Type ATTR Amyloidosis?

Normally, liver cells make stable TTR proteins that help transport thyroid hormone and vitamin A in the blood.

In people with amyloidosis, certain proteins don’t fold into the right shape. Instead, they misfold and stick together, forming amyloid deposits, also called amyloid fibrils. These deposits can build up in different parts of the body and interfere with how organs and tissues work.

There are several types of amyloidosis. Each type is caused by a different misfolded protein and tends to affect particular organs and tissues.

Wild-type ATTR amyloidosis is caused by TTR. As some people age, their TTR proteins can become unstable, misfold, and form amyloid deposits, most often in the heart.

Wild-Type vs. Hereditary Amyloidosis

Wild-type ATTR amyloidosis is closely related to hereditary ATTR amyloidosis. Hereditary ATTR amyloidosis (hATTR) is caused by a genetic mutation that’s passed down in families.

On the other hand, wild-type ATTR amyloidosis isn’t caused by a gene mutation and doesn’t run in families.

Both hereditary and wild-type ATTR amyloidosis can lead to protein buildup that affects the heart, but the hereditary type is more likely to cause nerve problems.

How Is Wild-Type Amyloidosis Diagnosed?

An accurate diagnosis is important because wild-type ATTR amyloidosis can resemble other heart diseases, but the treatments aren’t the same. In fact, some medications used to treat other health conditions, such as beta-blockers or calcium channel blockers, may not be well tolerated by people with wild-type amyloidosis.

Because no single test tells the whole story, doctors typically rely on a mix of methods to diagnose wild-type ATTR amyloidosis.

Physical Exam

During a physical exam, your healthcare provider will ask about your symptoms and check for signs of cardiac amyloidosis or other conditions. Be sure to share any details about new or worsening symptoms, as this information can help your care team make an accurate diagnosis.

Imaging Tests

Doctors often use imaging tests to see how well the heart is working. Imaging tests may include:

• Echocardiogram — Uses ultrasound to show how well your heart pumps blood and may reveal signs of amyloid-related heart damage
• Cardiac magnetic resonance imaging (MRI) — Produces detailed images of the heart and can help identify changes that may be caused by amyloidosis
• Cardiac pyrophosphate scan — Helps identify ATTR cardiac amyloidosis when used with blood and urine tests that may check for signs of amyloid light-chain (AL) amyloidosis

Biopsies

In the past, biopsies played a larger role in diagnosing wild-type ATTR amyloidosis. Today, doctors can often diagnose ATTR cardiac amyloidosis using noninvasive tests, but a biopsy may still be necessary in some cases.

If a biopsy is needed, your doctor may take a small tissue sample to check for amyloid deposits. The tissue can also be tested to determine which type of amyloid protein is present.

Laboratory Tests

Doctors use blood and urine tests to help determine which type of amyloidosis is present. These tests can look for abnormal light chain proteins that may indicate AL amyloidosis rather than ATTR amyloidosis.

If ATTR amyloidosis is diagnosed, genetic testing can help determine whether it’s hereditary ATTR amyloidosis or wild-type ATTR amyloidosis.

Additional blood and urine tests may be used to evaluate organ function and monitor the condition.

How Is Wild-Type ATTR Amyloidosis Treated?

Wild-type ATTR amyloidosis generally affects the heart, so most people with this condition will be treated by a cardiologist, or heart specialist. Depending on your needs, your treatment team may also include other amyloidosis specialists.

Treatments may have different goals. Some therapies help slow the progression of ATTR amyloidosis, while others help relieve symptoms and improve quality of life.

In recent years, the U.S. Food and Drug Administration (FDA) has approved several medications to treat ATTR cardiomyopathy, including cardiomyopathy caused by wild-type ATTR amyloidosis.

Some of these medications are TTR stabilizers, which help the TTR protein stay in its normal shape and reduce the formation of new amyloid deposits. FDA-approved TTR stabilizers include acoramidis (Attruby) and tafamidis (Vyndamax).

Another medication, diflunisal, is a nonsteroidal anti-inflammatory drug (NSAID) that also stabilizes TTR and may reduce amyloid formation. Although it’s not FDA-approved for amyloidosis, doctors may prescribe it off-label in some cases. However, it must be used with caution because NSAIDs can cause fluid retention and affect kidney function.

Gene-silencing therapies are another treatment option. They reduce the production of TTR protein in the liver. Vutrisiran (Amvuttra) is approved for ATTR cardiomyopathy, including cardiomyopathy caused by wild-type ATTR amyloidosis.

In severe cases with advanced heart failure, a heart transplant may be considered for select individuals.

Outlook With Wild-Type Amyloidosis

Newer treatment options can slow the progression of wild-type ATTR amyloidosis and may help some people live longer.

One study found that after nearly 5.5 years, 52.4 percent of people with wild-type ATTR amyloidosis who took tafamidis were still alive. Other studies show that nearly 80 percent of people diagnosed at 80 or older survived longer than 18 months after diagnosis.

Certain factors can affect the outlook for people with wild-type ATTR amyloidosis, including:

• Older age
• Levels of certain biomarkers related to heart function
• A person’s ability to take care of themselves and perform daily activities

Wild-type ATTR amyloidosis usually progresses slowly. Outlook can vary based on factors such as age, how advanced the condition is when it’s diagnosed, and how well treatment works.

Although wild-type ATTR amyloidosis is a serious condition, newer treatments can help slow progression and may improve quality of life and survival.