Transthyretin amyloid cardiomyopathy (attr-cm)

• ATTR-CM is a rare heart condition caused by a mutation in a protein called transthyretin
• ATTR-CM is often linked to carpal tunnel syndrome, spinal stenosis, and biceps tendon ruptures 
• Treatment for ATTR-CM focuses on managing the symptoms while new treatment options are continuously being studied

ATTR-CM is a rare heart condition often mistaken for congestive heart failure. This condition impairs heart function as it stiffens the muscular wall of the heart, which is responsible for pumping blood to the body. Getting diagnosed correctly and starting treatment to manage this condition is essential. This guide by Ada’s medical team provides more information on ATTR-CM, its symptoms, diagnosis, and treatment options. 

ATTR-CM (Transthyretin amyloid cardiomyopathy) is a rare heart disease that needs to be managed well. The word "amyloid" simply refers to sticky protein clusters. In this condition, proteins misfold and turn into tough fibers that act like sand in the gears of the heart. This causes the muscular wall of the heart to stiffen up, which impairs its function. As the heart can’t squeeze out enough blood anymore, the condition can lead to heart failure and arrhythmias, which can become fatal. 1

There are two types of ATTR-CM, depending on whether or not other family members also suffer from the disease: 

Hereditary ATTR-CM is caused by a mutation in the transthyretin gene and can cause an amyloid buildup in the heart, nerves, kidney, and other organs

Wild-typeATTR-CM is not caused by a genetic mutation and affects the heart. It can also cause carpal tunnel syndrome, pain and numbness in the hands and feet, lumbar spinal stenosis, and biceps tendon rupture.

ATTR-CM symptoms include shortness of breath at rest, swelling of the legs or feet, and chest congestion. At a later stage, other additional symptoms can develop as well: 1

• Coughing
• Wheezing 
• Bloating 
• Confusion
• Increased heart rate
• Arrhythmias
• Numbness or tingling in the hands and feet
• Spinal stenosis
• Carpal tunnel syndrome

Because the symptoms of ATTR-CM resemble those of congestive heart failure (CHF), the disease often gets misdiagnosed. A major clue can be found by looking back at your medical history: ATTR-CM is uniquely linked to orthopedic issues like carpal tunnel syndrome, lumbar spine stenosis, and biceps tendon ruptures. Crucially, these "red flag" symptoms often appear 5 to 10 years before any heart problems actually start. Additionally, unlike regular congestive heart failure, ATTR-CM does not respond well to standard heart failure treatments.2

The cause of ATTR-CM is an instability in a protein called transthyretin. This is a protein which naturally occurs in the body and plays an important role in the transport of thyroxine and retinol. In ATTR-CM, this protein misfolds, causing it to clump together and accumulate in certain tissues. When it builds up in the heart, it causes the heart wall to get stiff, which impairs the function of the heart. This protein instability can happen in two different ways: due to a genetic variation where the protein is built differently from birth (hereditary ATTR-CM), or simply as a result of natural aging affecting a normally built protein (wild-type ATTR-CM).

Diagnosing ATTR-CM can be difficult, as the symptoms of this condition can resemble those of other heart conditions such as congestive heart failure. In order to confirm the ATTR-CM diagnosis, your healthcare provider can request some medical imaging and additional tests such as:

• An electrocardiogram
• An echocardiogram
• An MRI
• A Biopsy
• Genetic testing
  
  Recently diagnosing ATTR-CM has become much easier. While an echocardiogram or MRI may suggest the condition. The current "gold standard" for non-invasive diagnosis is Nuclear Scintigraphy (Technetium Bone Scan). In most cases, this allows doctors to diagnose ATTR-CM without a heart biopsy. Genetic testing is also performed to determine if the condition is the hereditary or wild-type form.

ATTR-CM treatment focuses on managing heart conditions like heart failure and arrhythmias, as well as alleviating symptoms in the hands and feet. Supportive therapies, such as water pills, are commonly used to reduce fluid buildup and ease breathing.

Unlike in the past, there are now specific, approved medications available called TTR stabilizers and silencers. These targeted drugs help stop the transthyretin protein from breaking apart and forming sticky deposits, which significantly slows the disease's progression.

In some cases of hereditary ATTR-CM, a liver transplant may be discussed, as the transthyretin protein is produced in the liver. For severe heart failure, a heart transplant may also be an option. However, because modern targeted medications are highly effective, organ transplants are now rarely required.3

ATTR-CM can lead to serious heart conditions if left untreated. It can lead to heart failure and arrhythmias and can be fatal. Untreated ATTR-CM also leads to a severe decrease in quality of life.

ATTR-CM (Transthyretin Amyloid Cardiomyopathy) is a serious heart condition caused by a mutation in the protein transthyretin. This can cause a buildup of this protein in certain places, such as the heart, which can impair the function of the heart and can be fatal. Treatment exists to manage the symptoms of this condition.

Q: What is transthyretin amyloid cardiomyopathy? 

A: Transthyretin amyloid cardiomyopathy, often abbreviated as ATTR-CM, is a rare heart condition which causes the muscular wall of the heart to stiffen up. This leads to heart failure and arrhythmias, which can become fatal. 

Q: What are ATTR-CM symptoms? 

A: ATTR-CM symptoms include shortness of breath at rest, swelling of the legs or feet, and chest congestion. People with ATTR-CM often also have carpal tunnel symptoms, spinal stenosis, and ruptures of the biceps tendon.

Q: How do you test for ATTR-CM? 

A: If your healthcare provider suspects ATTR-CM based on the symptoms you’re experiencing, then medical imaging such as an electrocardiogram, an echocardiogram, or an MRI can help with the diagnosis. A biopsy or genetic testing can also be used to confirm the diagnosis.
Q: What is the life expectancy of someone with ATTR-CM?
Historically, the outlook for ATTR-CM was poor because it was often diagnosed too late. However, with the arrival of modern stabilizers and silencer drugs, survival rates have improved significantly. While older data cited a 2-to-4-year window, many patients now live much longer, high-quality lives when the condition is caught early and managed with targeted therapy.