Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

ATTR-CM: The Basics

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare heart condition in which fibers of amyloid protein build up in the bottom left portion of the heart muscle (the walls of the left ventricle). As a result, the left ventriclethe heart's primary pumping chamberstiffens and becomes unable to relax sufficiently to fill with blood and/or squeeze enough blood out of the heart to meet the body's needs.

"These proteins that are sitting there do not allow the heart muscle to function as it was designed to function," says New York cardiologist Dr. Philip Weintraub. "And in fact, they can cause scar tissue that can limit the pump function of the heart."

“These proteins that are sitting there do not allow the heart muscles to function as it was designed to function” – Dr. Philip Weintraub

He adds that the amyloid fibers can also become arrhythmogenic, meaning they can lead to various heart rhythm disturbances called arrhythmias. For some people with arrhythmias due to ATTR-CM, an implantable defibrillator is necessary to avoid cardiac arrest or other severe complications.

Because ATTR-CM is a rare condition and not especially well understood by many physicians, the actual prevalence of the disease isn't clear. A 2021 study of heart failure patients suggests that 10.1 percent of men and 2.2 percent of women had ATTR-CM. The findings suggest that screening individuals with heart failure, especially older male adults, could identify more people with ATTR-CM who could benefit from proper treatment.

Dr. Aeshita Dwivedi, a cardiologist at Lenox Hill Hospital/Northwell Health, explains what ATTR-CM is.

What Causes ATTR-CM?

The amyloid protein in the heart is made of transthyretin, which is known as a "transport protein," as it carries substances such as thyroid hormone and vitamin A throughout the body.

"Sometimes what happens is that this protein becomes unstable or misshaped in your body," explains Dr. Aeshita Dwivedi, a cardiologist at Lenox Hill Hospital/Northwell Health. "And when this happens, it can deposit in multiple organs of your body, like your heart, leading to the condition known as transthyretin cardiomyopathy."

There are two types of ATTR-CM:

• Hereditary ATTR-CM involves a mutation of the transthyretin gene, which leads to amyloid deposits in the heart and elsewhere in the body. It tends to run in families and may cause symptoms to appear starting at age 20 or much later in life.
• Wild-type ATTR-CM doesn't involve a gene mutation and typically starts to cause symptoms when someone is in their 60s or older. The origins of wild-type ATTR-CM aren't well understood, and this could mean that the condition is underdiagnosed. An individual with wild-type ATTR-CM may have no symptoms or mild symptoms for a long time, while someone else with the condition may go on to develop severe heart failure.

Males are at higher risk than females for both types of ATTR-CM. And while hereditary ATTR-CM may present with symptoms at a young age, older adults are generally at higher risk for both types.

Symptoms

Because ATTR-CM is directly related to the heart's ability to effectively pump blood throughout the body, some of the more common symptoms may include those associated with heart failure, including:

• Decreased exercise endurance
• Fluid retention and swelling
• Lightheadedness and fainting
• Shortness of breath

"You could have lightheadedness," Dr. Weintraub adds. "You could have fatigue, but a lot of that is based upon the fact that without the necessary oxygen that needs to be in your bloodstream, it'll compromise the body's ability to function properly. The heart works best when it's enriched with oxygen and nutrients, and to deprive the heart of that leads to a compromised lifestyle."

“A lot of [the symptoms are] based upon the fact that without the necessary oxygen that needs to be in your bloodstream, it’ll compromise the body’s ability to function properly”
– Dr. Philip Weintraub

ATTR-CM also tends to bring on problems such as an enlarged heart and arrhythmia, such as atrial fibrillation. ATTR-CM is an unusual heart condition in that some common symptoms appear to have little to do with the heart and circulation. For example, carpal tunnel syndrome is present in about half of people with ATTR-CM, according to a 2019 study in the Journal of the American College of Cardiology.

"When the protein deposits in your nervous system, patients may develop condition called neuropathy, commonly this presents with carpal tunnel syndrome or spinal stenosis," Dr. Dwivedi says. "A lot of patients may also find that their blood pressure becomes variable."

And because ATTR-CM can involve other organs and the nervous system, it's not unusual to experience other symptoms, such as:

• Abdominal pain
• Balance problems
• Constipation
• Muscle impairment
• Vision problems