Wild-type ATTR-CM: The heart condition hidden inside normal aging

Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) is a heart condition that can develop with age. It most often affects men older than 60, though it can be difficult to distinguish from normal signs of aging or other age-related heart conditions.

In recent years, researchers have discovered that wild-type ATTR-CM may be more common than previously thought. By some estimates, 20% to 25% of people in their 80s may have the condition. Growing awareness of wild-type ATTR-CM may lead to an earlier diagnosis and better treatment outcomes.

What is wild-type ATTR-CM?

In cardiac amyloidosis, misfolded proteins start forming clumps called amyloid deposits that build up in the heart. Over time, these toxic protein deposits gradually impair heart function.

ATTR-CM is one of the more common types of cardiac amyloidosis in older adults. It gets its name from the protein that forms the amyloid clumps, called transthyretin or TTR.

In wild-type or age-related ATTR-CM, the body produces TTR correctly, but the protein later becomes unstable and misfolds, leading to the formation of amyloid deposits. This is distinct from the causes of hereditary ATTR-CM, in which genetic mutations lead to the production of abnormal TTR. Scientists don’t fully understand the link between ATTR-CM and aging, or why protein misfolding occurs more often with age.

Why it’s often mistaken for normal aging

It may be difficult to identify whether wild-type ATTR-CM or normal aging is the underlying cause of certain symptoms. Early ATTR-CM symptoms are often subtle, such as mild shortness of breath. Because lung capacity decreases naturally as people get older, mild shortness of breath in wild-type ATTR-CM may be confused as a normal sign of aging.
>Other wild-type ATTR-CM symptoms that may overlap with aging signs include:

fatigue or weakness
difficulty exercising
swelling in the legs or ankles

Problems with the autonomic nervous system, which controls unconscious bodily functions such as breathing, sometimes occur in wild-type ATTR-CM and can also mimic signs of old age. Symptoms may include problems with digestion, sexual function, urination, and sweating.

Additionally, wild-type ATTR-CM symptoms can overlap with those of other age-related heart conditions, further complicating a diagnosis.

Symptoms to watch for

Older people may want to be on the lookout for possible red flag signs and symptoms that could suggest wild-type ATTR-CM, including:

carpal tunnel syndrome: numbness, tingling, pain, or weakness in the hands and forearms due to increased pressure in a nerve running through the wrist
lumbar spinal stenosis: pain and numbness in the lower back due to narrowing of the spinal canal
peripheral neuropathy: pain, tingling, or other abnormal sensations, often in the hands and feet, indicating nerve damage

These aren’t unique to wild-type ATTR-CM, but they might raise clinical suspicion, especially if other symptoms are also present.

How wild-type ATTR-CM is diagnosed

The process of diagnosing ATTR-CM is largely similar regardless of whether a person has wild-type or hereditary disease. It typically involves confirming the presence of TTR amyloid deposits in the heart, and ruling out other conditions.

After reaching an ATTR-CM diagnosis, genetic testing can determine the disease type. People with hereditary ATTR-CM have mutations in the TTR gene, while those with wild-type ATTR-CM do not.

Knowing that someone has wild-type ATTR-CM may help guide treatment decisions. It also generally means that there is no need to genetically test relatives for the condition, as would be the case with hereditary ATTR-CM, because wild-type disease isn’t passed through families.

Treatment and monitoring

In the U.S., all approved ATTR-CM medications can be used in both hereditary and wild-type forms of the disease. These fall into two categories:

TTR silencers: These drugs decrease TTR production to prevent the formation of amyloid deposits, and include Amvuttra (vutrisiran).
TTR stabilizers: These medications help hold TTR together to prevent protein misfolding and amyloid buildup, and include Attruby (acoramidis) and Vyndamax (tafamidis).

Depending on the symptoms and severity of an individual’s case, doctors may also recommend supportive therapies, including heart failure medications and lifestyle changes.

Frequent monitoring can help identify signs of disease progression, allowing treatment to be adjusted as needed. Doctors often recommend follow-up visits and monitoring tests every six to 12 months, or more frequently if the disease is more severe.

When aging symptoms deserve a closer look

Doctors can help determine whether a symptom is related to normal aging or an underlying condition such as wild-type ATTR-CM. Closer examination may be warranted if:

routine tests show abnormalities in heart function or structure
a patient responds poorly to standard heart failure medications
a patient has a history of carpal tunnel syndrome or lumbar spine stenosis
symptoms begin to worsen more quickly

One of these signs alone may not be cause for concern, but a cluster of possible red flags can trigger clinical suspicion of ATTR-CM. Individuals with doubts or questions about age-related symptoms should maintain open communication with their doctors.

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