Understanding the early signs of cardiac amyloidosis

Early signs and symptoms of ATTR-CM

ATTR-CM can be difficult to diagnose because its symptoms often resemble those of more common conditions like heart failure. However, there are several early signs and symptoms that may point to ATTR-CM:

General symptoms

• Fatigue or shortness of breath during everyday activities
• Swelling in the legs, ankles, or feet
• Bloating in the abdomen

Neurological symptoms

• Numbness or tingling in the hands and feet (peripheral neuropathy)
• Carpal tunnel syndrome
• Dizziness or fainting

Gastrointestinal symptoms

• Diarrhea or constipation
• Unexplained weight loss
• Feeling full quickly
• Nausea

Cardiac symptoms

• Irregular heartbeat or palpitations
• Chest discomfort
• Signs of heart failure (fluid retention, fatigue, breathlessness)

Other physical signs

• Biceps tendon rupture
• Difficulty climbing stairs or walking long distances

You can take a free ATTR-CM Assessment to understand the risk factors and help guide your conversation with a doctor. If you're looking for a specialist, the Doctor Finder tool can help.

Wild-type ATTR-CM (wtATTR)

Wild-type ATTR (wild-type transthyretin amyloidosis) develops with age is more common in older adults, especially men 60+. “Wild-type” refers to the fact that as people grow older, TTR proteins with a normal (non-mutated) genetic sequence can become unstable and misfold. When that happens, the misfolded proteins build up in different organs and tissues as amyloid.

While the heart is the main organ affected, amyloid deposits can also accumulate in other tissues, causing non-heart symptoms like carpal tunnel syndrome or lumbar spinal stenosis that often precede heart symptoms by several years.

Because symptoms can be vague, progress slowly, and often occur alongside other age-related heart conditions, wtATTR is often misdiagnosed as general aging or other heart-related issues.

wtATTR is more common than hATTR (hereditary transthyretin amyloidosis).

Hereditary ATTR (hATTR)

Hereditary ATTR (hereditary transthyretin amyloidosis) is caused by a mutation in the gene responsible for producing the transthyretin (TTR) protein. When that gene is altered, it can cause the TTR protein to fold incorrectly.

The main types of hATTR are generally categorized by the main organ system affected. hATTR-CM (cardiomyopathy) mainly affects the heart, while hATTR-PN (polyneuropathy) primarily affects the peripheral and autonomic nervous systems.

hATTR is more common in certain ethnic groups, such as Black, African American, and Afro-Caribbean communities, amongst others. More than 100 different TTR mutations have been identified, and the age at which symptoms appear can vary depending on the specific mutation. In the United States, the most common mutation is Val122Ile, which is found in approximately 3–4% of African Americans, although being a carrier does not mean you will develop the disease.

Other types of amyloidosis

Beyond wtATTR and hATTR, there are several other forms of amyloidosis, each with its own set of symptoms and causes. These include:

• AL amyloidosis is caused by abnormal light chains produced by plasma cells. It can lead to bruising around the eyes (periorbital purpura), an enlarged tongue (macroglossia), nerve pain, heart problems, and kidney dysfunction.
• AA amyloidosis is typically linked to chronic inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease. It often affects the kidneys and gastrointestinal tract.
• Dialysis-related amyloidosis can occur in people who have been on long-term dialysis. It often affects the bones and joints, causing pain and stiffness.

Each type of amyloidosis presents differently, but all involve the buildup of amyloid proteins that disrupt normal organ function.

ATTR-CM can be tricky to diagnose

ATTR-CM is often underdiagnosed because its symptoms can mimic other conditions. But early recognition can lead to better outcomes. If you or someone you care about is experiencing unexplained symptoms such as fatigue, swelling, nerve pain, or digestive issues, it’s important to speak with a healthcare provider.

Who is more likely to develop ATTR-CM?

ATTR-CM is more frequently seen in certain populations. wtATTR-CM is most common in older adults and tends to affect men ages 60+ more than women. People with a family history of amyloidosis may be at higher risk for hATTR, while wtATTR can occur without any genetic link.

Individuals of African American descent may also be at increased risk for specific hereditary mutations associated with hATTR. Recognizing these patterns can help guide conversations with healthcare providers, especially when symptoms are present but unexplained.