Acquired ATTR Amyloidosis

Acquired ATTR amyloidosis, also known as wild-type ATTR, is a protein disorder that develops with age and affects the heart and nervous system. Unlike hereditary forms, it is not passed down through families but occurs when normal transthyretin proteins produced by the liver become unstable, misfold, and form harmful deposits in the body’s organs.

Table of contents

• What Is Acquired ATTR Amyloidosis?
• What Causes This Condition?
• Who Is Most Likely to Be Affected?
• Signs and Symptoms
• How It Is Diagnosed
• Treatment Options

Wild-type ATTR amyloidosis, ATTRwt, Wild-type ATTR-CM, Senile cardiac amyloidosis, TTR amyloidosis

What Is Acquired ATTR Amyloidosis?

Acquired ATTR amyloidosis is a disease where a protein called transthyretin (TTR) becomes misshapen and forms abnormal clumps called amyloid fibrils. These protein deposits build up in the body’s organs and tissues, most commonly affecting the heart and nervous system^[1][2].

Transthyretin is a protein made mostly in the liver. Its job is to carry vitamin A and a thyroid hormone called thyroxine throughout the body^[1][5]. In acquired ATTR amyloidosis, this normal protein breaks apart, folds up incorrectly, and forms clumps that get carried through the bloodstream and deposited in various organs. Over time, these deposits cause the organs to thicken and stiffen, preventing them from working properly^[2].

When these protein deposits build up in the heart’s main pumping chamber (the left ventricle), it becomes stiff and weak. This is called cardiomyopathy, which makes it harder for the heart to pump blood to the rest of the body. This can lead to heart failure^[2][5].

What Causes This Condition?

Unlike hereditary ATTR amyloidosis, which is caused by a genetic mutation passed down through families, acquired ATTR amyloidosis occurs for no known reason. It develops with age and is not inherited^[1][2].

Medical experts are not entirely sure why some people develop this condition. The fact that it most commonly occurs in older adults suggests that age may be an important risk factor. Sex also appears to play a role, as the condition is more common in men^[2][5].

In this condition, the body produces normal transthyretin proteins, but over time these proteins become unstable. They break apart, misfold, and form clumps of amyloid fibrils that get deposited in the heart, nerves, and other organs^[2][5].

Who Is Most Likely to Be Affected?

Acquired ATTR amyloidosis most commonly affects males over the age of 65^[2][5]. Medical experts believe the disease is probably more common than currently recognized, as it is thought to be underdiagnosed^[2][5].

Recent improvements in imaging techniques have helped doctors recognize that some patients previously thought to have other heart conditions may actually have cardiac amyloidosis^[8]. This means many people with the condition may have gone undiagnosed in the past.

Signs and Symptoms

You may not experience symptoms of acquired ATTR amyloidosis until later in the course of the disease. The symptoms can vary depending on which organs are affected and how much damage the amyloid deposits have caused^[2][4].

When the heart is affected, common symptoms include^[2][4]:

• Shortness of breath, especially during physical activity
• Palpitations (feeling your heartbeat) and abnormal heart rhythm
• Swelling in the ankles and legs
• Serious fatigue and weakness
• Chest pain
• Dizziness and low blood pressure
• Fainting

Earlier in the disease, people may experience primarily heart rhythm problems. For example, they may have atrial fibrillation, an irregular heart rhythm that may bring them to see their doctor or visit the emergency room^[2]. Later, the most common symptom is difficult or labored breathing, especially with physical effort. In more severe cases, you might even have trouble breathing while resting^[10].

When the nervous system is affected, symptoms may include^[1]:

• Numbness, tingling, or pain in the hands or feet
• Difficulty walking
• Limb weakness and pain

Additional symptoms can include^[4]:

• Diarrhea, possibly with blood
• Constipation
• Nausea and loss of appetite

You might also notice fluid buildup in your abdomen or legs^[10].

• Heart (left ventricle)
• Nervous system
• Liver
• Kidneys
• Gastrointestinal tract

How It Is Diagnosed

If ATTR amyloidosis is suspected, doctors carry out a number of tests. These tests help confirm the presence of amyloid deposits and determine which organs have been affected^[1][7].

Common diagnostic tests include^[1][7]:

• An abdominal fat pad biopsy to confirm the presence of amyloid deposits
• Blood tests to check organ function
• Nerve and muscle tests
• Echocardiogram (ultrasound of the heart)
• MRI and other types of scans

In some cases, organ biopsies may also be needed to determine which organs are involved. Some scans can help identify the type of amyloidosis and distinguish ATTR from another type called AL amyloidosis. Doctors also use special tests, called immunohistochemistry and mass spectrometry, to tell the difference between ATTR and AL amyloidosis^[1][7].

A blood test showing no genetic mutation in the TTR gene helps confirm wild-type (acquired) ATTR amyloidosis rather than the hereditary form^[1][7].

Treatment Options

There is no cure for acquired ATTR amyloidosis, but treatments are available to help manage symptoms and slow the progression of the disease^[10]. The treatment approach focuses on preventing and slowing the generation and deposition of amyloid fibrils, as well as providing supportive care for complications^[8].

Several medications have been approved for treating ATTR amyloidosis affecting the heart^[6]. These include:

• Tafamidis (Vyndamax) – a medication that stabilizes the transthyretin protein, preventing it from breaking apart and forming amyloid deposits
• Acoramidis (Attruby) – another transthyretin stabilizer
• Vutrisiran (Amvuttra) – approved under an expanded indication for ATTR heart disease

Continuing follow-up over many years suggests that long-term treatment with tafamidis may provide a survival benefit^[6].

In the past, liver transplantation was the main treatment option. However, with the introduction of disease-modifying medications in recent years, the number of liver transplant cases for ATTR has declined significantly^[6].

Supportive care is also important and involves managing heart failure, heart rhythm problems, conduction disturbances, blood clots, and other complications^[6][8]. Your doctor might prescribe a diuretic to help reduce fluid buildup and swelling. They may also recommend reducing your intake of high-sodium foods and monitoring how much water you drink^[10].

Because amyloidosis can affect many parts of the body, you may need to see several specialists. If you have unexplained back pain, pain or numbness in your arms or hands, or stomach problems like diarrhea or weight loss, be sure to tell your care team. They can refer you to other specialists if needed^[12].

As with any heart condition, it is important to make heart-healthy choices, work to lower stress, and get quality sleep. Talking with other people who have the condition may also help^[12].