The Relationship Between Transthyretin Amyloidosis Cardiomyopathy and Carpal Tunnel Syndrome

Being diagnosed with a heart condition, no matter how treatable, is scary. And it’s natural to think, “I wish I’d known about this sooner.”

But what if you could know sooner? For a small group of people, carpal tunnel syndrome (of all things) may provide exactly that insight into their future heart health.

Cardiologist Wai Hong Wilson Tang, MD, explains why having carpal tunnel syndrome in both wrists can help doctors determine your risk for developing a heart condition called transthyretin amyloidosis cardiomyopathy (ATTR-CM).

How is carpal tunnel related to ATTR-CM?

Carpal tunnel syndrome doesn’t cause ATTR-CM, or vice versa. But some people develop carpal tunnel syndrome because of a condition called amyloidosis. Amyloidosis is systemic, meaning it can affect many different parts of your body, including your heart. So, it’s possible this same condition that’s affecting your wrists could also affect your heart as ATTR-CM.

In order to understand why, we need to understand amyloidosis.

The role of proteins in amyloidosis

Proteins are one of the building blocks of life. There are tens of thousands of them in your body. Transthyretin (TTR) is one of those proteins. It’s produced in your liver and is supposed to carry vitamin A, hormones and more throughout your body. TTR proteins travel in your bloodstream by folding together in a very specific way. But sometimes, they don’t fold as they should.

When your body produces the TTR proteins that fold incorrectly, they can get tangled up in ill-fitting ways, turning into crystal-like deposits called “amyloid.” There are lots of different proteins that can create amyloid, but TTR is one of the amyloid deposits that can cause the condition ATTR-CM.

When TTR proteins don’t fold properly, they don’t hold together very well as they travel through your bloodstream. Dr. Tang describes them as jigsaw puzzles where the pieces don’t quite fit.

“As these proteins travel together through your body, the jigsaw puzzles — these improperly folded proteins — start falling apart,” he explains. “And when they fall apart, they get deposited as TTR fibrils.” When the buildup of TTR fibrils starts to impact an organ, nerve, muscle or tendon, you may be living with amyloidosis.

How ATTR amyloidosis affects your heart

Amyloidosis can happen in lots of different places in your body. But the TTR fibrils tend to collect in tissue that’s long-living and doesn’t regenerate. And the two tissues in the body that don’t really regenerate are the heart and the nerves.

Being diagnosed with ATTR-CM means TTR fibrils have built up in your heart specifically. And they’ve built up to the point that they’re making your heart muscle stiff and weak. In some cases, ATTR-CM leads to heart failure.

The connection to carpal tunnel

Carpal tunnel syndrome happens when something irritates the nerves running through the space between your wrist bones. A cyst, a bone spur or an injury all fit the bill. But sometimes, the thing compressing your nerves is a buildup of TTR fibrils.

“The carpal tunnel is a very narrow area. It’s kind of like the band of Velcro™ holding all your laptop cables together. Except instead of cables, it is holding the nerve supply for your hand,” Dr. Tang illustrates. “So, when these protein fibrils start building up in the carpal tunnel, they compress the nerves quickly.”

If amyloidosis caused your carpal tunnel syndrome, it could be a sign that you’ll develop ATTR-CM later in life, as those same fibrils accumulate in your heart.

“It is a progressive deterioration,” he continues. “The deposits cause symptoms first in small spaces. The heart is much bigger in terms of area and volume, so it takes longer for amyloid deposits to cause problems.”

If amyloidosis is causing your carpal tunnel, you’re likely to have issues with both of your wrists, not just one. You may also have issues with other areas of your body, including your:

• Legs
• Kidneys
• Spinal cord

Of course, there are many other reasons that you could develop carpal tunnel syndrome. It’s an extremely common condition. A lot of people get it, for example, after years and years of repetitive hand motions like typing or knitting. It can even be caused by other amyloid proteins that don’t cause ATTR-CM.

Researchers have only recently discovered the connection between carpal tunnel syndrome and ATTR amyloidosis. So, we don’t know how often (or to what extent) amyloidosis plays a role in carpal tunnel syndrome. It’s something Dr. Tang — and many others — are studying now.

When does ATTR-CM happen?

In medicine, there are exceptions to every rule. But carpal tunnel syndrome caused by ATTR amyloidosis usually occurs way before your heart gets involved. And that’s not just because it takes longer for heart complications to develop. Age is also a factor.

“We still do not know exactly why amyloid deposits over a long period of time,” Dr. Tang notes. “It is possible that when cells are younger, they are more functional and resilient. As they get older, they are less able to combat damage. It’s also possible that the body has ways of clearing abnormal proteins that are different or damaged in some people.”

Whatever the reason for the slow amyloid buildup, the result is clear: Most people don't develop ATTR-CM until they’re in their 60s or older.

But there are exceptions.

For some people, ATTR amyloidosis is caused by a genetic variation. This may increase their risk of developing ATTR-CM by up to 40%. When a person with a pathologic (illness-causing) TTR gene variation develops ATTR-CM, doctors call it “hereditary ATTR-CM.”

Not all people with a pathologic TTR variation (there are at least 120) go on to develop hereditary ATTR-CM. But those who do tend to notice symptoms earlier than usual — in their 50s or even younger.

Dr. Tang points out that research on ATTR-CM has progressed by leaps and bounds over the past 15 years. But there’s still a lot we don’t know. Not all people who develop carpal tunnel syndrome due to amyloidosis get ATTR-CM. And many people who have the genetic variations that increase ATTR-CM risk never do either. And we don’t know why.

But what doctors do know makes it much easier to assess your risk and plan accordingly.

Can you prevent ATTR-CM?

At this time, you can’t prevent ATTR-CM. But Dr. Tang says there’s hope that will change, especially when we know who’s at risk before they become symptomatic.

“That’s why we need to conduct clinical trials,” he explains. “We need to test the drugs that we think can prevent amyloid fibrils from depositing into the organs.”

You can’t prevent them. But — while they sound scary — both ATTR-CM and heart failure are treatable conditions. And the sooner you’re diagnosed, the sooner your treatment can start.

“ATTR-CM is now a treatable condition,” Dr. Tang reassures. “Ten or 15 years ago, it was different. But knowing you are vulnerable means you can prevent complications. Many people live normal lives with ATTR-CM.”

How can you determine your risk?

If you’ve been diagnosed with carpal tunnel syndrome, especially in both wrists, Dr. Tang recommends seeing a cardiologist to assess your risk for ATTR-CM — especially if you’re over 60 years old. You should also consider getting an appointment if:

• One or more members of your biological family were diagnosed with heart failure early in life
• You’ve been diagnosed with spinal stenosis that’s causing pain in your lower back (lumbar spine)
• You have unexplained muscle weakness (sarcopenia)
• You have frequent muscle or tendon injuries or a history of ruptures
• One or more people in your biological family have a history of nervous system issues like autonomic dysfunction or polyneuropathy

Your healthcare provider can run tests to see if you have TTR or other forms of amyloidosis. They’ll also test to see if you’re carrying a pathologic TTR gene variant. In some cases, they may even be able to find out if there were amyloid deposits found in the tissue specimens from the carpel tunnel surgery.

If the answer to any of those questions is “yes,” your provider will monitor you carefully as you get older. That way, if you start showing signs of heart involvement, they can start treatment immediately.

When to contact a doctor

It’s best to play it safe when it comes to your heart. Call a healthcare provider if you have the following symptoms, even if you don’t have carpal tunnel or ATTR-CM:

• Unexplained shortness of breath
• Fatigue
• Unexplained swelling or a feeling of heaviness in your legs
• Exercise intolerance
• Confusion
• Unexplained weight gain
• Eye floaters
• Irregular heart rhythm (arrhythmia) or palpitations

“When you have those concerns, you need to start seeing a cardiologist,” Dr. Tang emphasizes. “Some of these problems are very common. And there are lots of potential causes. Your provider will check to see if your heart is contributing to your symptoms and, if it is, you have ATTR-CM. If you do, they’ll see if there are ways to prevent it from getting worse.”

If any of these symptoms are sudden or severe, don’t wait for an appointment. Call emergency services.