Getting a diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) can be scary. But understanding some of the key facts about this rare condition may help ease some of your worries.

To learn more about ATTR-CM, MyAmyloidosisTeam spoke with Dr. Ronald Witteles, a cardiologist and professor of medicine at Stanford University. Dr. Witteles specializes in the treatment of heart failure and is an amyloidosis specialist.

What Is ATTR-CM?

ATTR-CM is a type of amyloidosis, a group of diseases in which amyloid proteins become abnormally folded and are deposited in various organs and tissues in the body. There are two types of ATTR-CM. One is hereditary ATTR-CM (hATTR-CM), which is passed down in families due to a gene mutation (change). The other is wild-type ATTR-CM (wATTR-CM), which is more common and occurs with aging.

In ATTR-CM, transthyretin (TTR) protein misfolds and forms amyloid deposits in the myocardium, which is the heart muscle. This restricts heart function and can lead to heart failure, also known as cardiomyopathy, and other forms of heart disease such as arrhythmia (irregular heartbeat). Fortunately, new treatment options are improving the outlook for people with ATTR-CM.

Dr. Witteles said there are three main questions that people with ATTR-CM have. “I think one is ‘How did I get this?’” he said. “Another one is, of course, ‘What can we do about it?’” Third, people want to know what the prognosis is for ATTR-CM.

To answer these questions and others, Dr. Witteles discussed some important facts about ATTR-CM that you can talk about in more detail with your healthcare provider or cardiologist.

1. It’s Unclear Why ATTR-CM Occurs

There’s still a lot about ATTR-CM that medical professionals don’t understand, Dr. Witteles pointed out. It’s not clear why amyloid protein misfolds and is deposited in organs, such as the heart. “The short answer to that is we don’t really know,” he said. “The protein is one we all have.”

One theory is that the protein may naturally degrade. “If we all live to be 200 years old, we’d probably all develop the disease,” said Dr. Witteles. “But we don’t know why some people in a human lifespan do.”

2. Treatment Options Are Advancing for ATTR-CM

Dr. Witteles was keen to discuss the improving landscape of ATTR-CM treatment options. “Thankfully, now there are three FDA-approved treatment options for the disease,” he said, stressing that one isn’t necessarily better than the others. “There’s no right or wrong answer. They all are really good options.”

The three FDA-approved medications for treating ATTR-CM are:

• Tafamidis (Vyndamax) — Taken orally
• Acoramidis (Attruby) — Taken orally
• Vutrisiran (Amvuttra) — Taken by subcutaneous (under the skin) injection every three months

Research in treatments for ATTR-CM continues to evolve, Dr. Witteles said: “There’s of course more in clinical trials, and we will likely have even more options in the coming years.”

3. Treatments for ATTR-CM Work in Different Ways

Tafamidis and acoramidis are both classified as TTR stabilizers. “The pills work by basically stabilizing the form of the protein that circulates in the bloodstream [so it] doesn’t deposit,” Dr. Witteles said. These drugs help prevent a buildup of protein in the heart and other tissues.

“Survival, hospitalizations, how far somebody could walk, quality of life — everything was better for the people who are on [ATTR-CM] medications as opposed to placebo.”

— Dr. Ronald Witteles

Vutrisiran is classified as a synthetic, double-stranded, small interfering RNA (siRNA) drug — also known as a gene silencer. “The injection works by just knocking the liver’s production of the protein down altogether by about 80 to 85 percent,” Dr. Witteles explained. TTR protein is mostly produced in the liver.

Importantly, all three medications have proved in clinical trials to be highly effective in treating ATTR-CM. “Survival, hospitalizations, how far somebody could walk, quality of life — everything was better for the people who are on the medications as opposed to placebo,” said Dr. Witteles.

4. Treatment of ATTR-CM Slows the Progression of the Disease

Treatment of ATTR-CM can’t cure the disease or repair damage that’s already done, but it can slow disease progression. “It’s important to recognize that none of these three [medications] reverse disease. And in fact, probably none of the three truly stop any more deposition, but they greatly slow deposition,” Dr. Witteles said.

He highlighted the value of early diagnosis and treatment. “It’s really important once somebody gets the diagnosis to get started on treatments,” he said. “The sooner you start people on treatment, the better.”

5. Genetic Testing Is Important for Family Members

Along with recommending early treatment, Dr. Witteles urges people who’ve been diagnosed with ATTR-CM to have genetic testing for the TTR gene to find out if they have the inherited type. Genetic testing can help first-degree family members understand their risks.

“It’s really important once somebody gets [an ATTR-CM] diagnosis to get started on treatments. The sooner you start people on treatment, the better.”

— Dr. Ronald Witteles

“Siblings or children have a 50 percent chance of having the same mutation,” he said. “It doesn’t mean that they’re guaranteed to develop the disease, but they’re certainly at higher risk, and there’d be particular screening recommendations for them.” With proper screening, family members could potentially catch the disease in the early stages if they were to develop ATTR-CM.

“There’s simple genetic testing that can be done. Usually there’s sponsored ways to get it done so that there’s not even any cost. It’s highly accurate and very simple. It could either be from a blood test or spitting in a tube,” said Dr. Witteles.

6. With Early Treatment, Prognosis for ATTR-CM Is Improving

With better treatment options, the outlook for people with ATTR-CM is considerably better than it used to be, Dr. Witteles said. “If they’re diagnosed quite early, which now sometimes people are, then they get started on treatment. ... In all likelihood, they will ultimately die of something else, not from this.”

However, the prognosis can vary, depending on the stage of the disease. If someone is diagnosed with ATTR-CM and already has severe heart failure, the outlook may not be good, according to Dr. Witteles.

He also explained that hATTR-CM can be more aggressive and have a poorer outlook. “On average, the hereditary forms are a little worse. They tend to proceed at a faster pace,” he said. “People develop symptoms with them on average a bit earlier. And for that reason, the prognosis overall is a bit worse.”

But overall, prognosis has improved significantly for people with ATTR-CM. “It’s much, much better than it used to be,” Dr. Witteles emphasized.

7. Heart Failure Isn’t Always a Severe Condition

When people hear they have heart failure, it sounds like the heart has stopped working. But Dr. Witteles clarified that while heart failure can be a serious, life-threatening condition, it can also be mild without a lot of impact on someone’s health or quality of life. Heart failure — sometimes called congestive heart failure — is a heart condition in which the heart doesn’t pump blood normally.

Heart failure symptoms include fatigue and shortness of breath. “It’s usually exercise intolerance. You can’t go as far as you used to. You get short of breath with activity. You might start retaining fluids, [get] swollen ankles, that sort of thing,” Dr. Witteles said.

“It’s a terrible term,” Dr. Witteles said, referring to heart failure. “It’s unfortunately the term that was chosen many years ago. It’s a very big spectrum.” He went on to explain, “With heart failure, you could have very mild heart failure where you don’t even really have any symptoms, and it’s almost a nuisance in your life.”

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