ATTR-CM (Transthyretin Amyloid Cardiomyopathy)

ATTR-CM, or transthyretin amyloid cardiomyopathy, happens when clumps of irregular proteins build up in your heart muscle. They replace healthy heart cells. These protein deposits (amyloid fibrils) stiffen your whole heart, making it harder for your heart to pump blood throughout your body. ATTR-CM can lead to life-threatening complications like heart failure and arrhythmias.

ATTR-CM is a complication of transthyretin amyloidosis (ATTR). ATTR can affect several other parts of your body — not just your heart — like your limb nerves, ligaments and tendons.

Types

There are two types of ATTR-CM:

• Hereditary ATTR-CM (hATTR-CM): A genetic change causes this type. It can run in biological families. Symptoms can start as early as your 30s. But they often show up in your 50s or later.
• Wild-type ATTR-CM (wATTR-CM): This type doesn’t run in families. It develops due to aging-related changes. It most commonly affects males over the age of 65. This is the most common type of ATTR-CM.

Symptoms of ATTR-CM

Symptoms are similar to those of heart failure, which include shortness of breath, especially when lying down, and swelling in your legs, ankles and feet (edema). Other symptoms include:

• Bloated stomach
• Confusion or difficulty thinking
• Dizziness or passing out
• Coughing or wheezing, especially when lying down
• Fatigue
• Heart palpitations
• Irregular or fast heart rate (arrhythmia), especially atrial fibrillation

ATTR-CM develops from transthyretin amyloidosis (ATTR). So, you may have other symptoms of ATTR, like carpal tunnel syndrome or lumbar spinal stenosis (chronic lower back pain).

ATTR-CM causes

ATTR-CM happens when transthyretin (TTR) proteins build up in your heart muscle. The proteins break apart and fold up on themselves. They then form clumps of amyloid fibrils. Your blood carries these fibril clumps throughout your body. When the clumps build up in your heart muscle, they cause damage (cardiomyopathy).

A change to the TTR gene causes hereditary ATTR-CM. Your body makes faulty TTR proteins.

Wild-type ATTR-CM is an aging-related disease. Normal TTR proteins become structurally unstable and build up in your heart.

Who is at risk for developing this condition?

Hereditary ATTR-CM is most likely to affect Black males in the United States. The most common gene variant in the U.S. that causes it occurs in 3% to 4% of all Black people. It’s also more common in parts of Portugal, Brazil, Sweden and Japan.

Wild-type ATTR-CM is most likely to affect males over the age of 65.

What are the complications?

Without treatment, ATTR-CM can cause worsening complications, like:

• Heart failure
• Arrhythmias
• Conduction system diseases, like heart block

These conditions can cause sudden cardiac death or a stroke.

How doctors diagnose this condition

Tests to help diagnose ATTR-CM include:

• Electrocardiogram (EKG)
• Heart imaging like echocardiograms and cardiac MRIs
• A cardiac PYP scan to check for TTR amyloid deposits in your heart
• Heart biopsy
• Genetic testing

ATTR-CM can be challenging to diagnose correctly. The hereditary type can mimic heart disease caused by chronic high blood pressure or hypertrophic cardiomyopathy. You may get an incorrect diagnosis at first.

The wild type doesn’t always cause symptoms. That version of the condition can go undetected until severe problems like heart failure occur.

How is ATTR-CM treated?

There isn’t a cure for ATTR-CM. Treatment for it may involve:

• Medications to slow or stop the production or buildup of amyloid deposits
• Managing complications like heart failure and arrhythmias
• Organ transplantation

Medications for ATTR-CM

A medication called tafamidis (Vyndamax® and Vyndaqel®) can slow or stop the buildup of amyloid deposits in hereditary ATTR-CM. These medications have the most benefit if you’re able to start them early in the development of the condition.

Another medication, acroamidis (Atrruby^TM), is a TTR stabilizer that can help with both types of ATTR-CM.

The latest medication approved for the treatment of ATTR-CM is vutrisiran (Amvuttra®). It can also treat hereditary TTR polyneuropathy. Vutrisiran is a shot you get every three months. It can decrease the production of TTR proteins altogether, decreasing buildups in your heart.

Researchers are currently studying other medications that target the underlying cause of this condition. Ask your healthcare provider if you can join a clinical trial.

Managing complications

Therapies that may help manage heart failure and arrhythmias related to ATTR-CM include:

• Anticoagulants
• Antiarrhythmic medications like amiodarone
• Cardiac ablation
• Compression therapy
• Diuretics
• Limiting salt in your diet
• Pacemaker

Organ transplantation

In cases of advanced heart failure, a heart transplant may be an option. Your liver makes the abnormal transthyretin protein in ATTR-CM. So, some people may get both a heart and liver transplant. Healthcare providers haven’t recommended this option as much in recent years because of the newer therapies available.

Overall, organ transplantation is a rare treatment for ATTR-CM. But it’s highly effective when needed.

When should I see my healthcare provider?

ATTR-CM is a progressive disease, which means it gets worse over time. You’ll need to see your cardiologist regularly to make sure your treatment is working. It may help to ask your provider the following questions:

• What type of ATTR-CM do I have?
• What treatments do you suggest?
• What are the benefits and risks of my treatment options?
• Should I look out for signs of complications?
• Should my family members get testing for the condition?

What is the outlook for someone with ATTR-CM?

ATTR-CM is a progressive disease that eventually causes serious complications. Early diagnosis and treatment are key to a better outlook (prognosis). Living with ATTR-CM is easier than it used to be thanks to advancements in diagnostic tests and medications (like tafamidis, acoramidis and vutrisiran).