Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

2024/12/12

What is it?

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a form of heart disease that is often undiagnosed yet can be fatal.

In ATTR-CM, a blood protein called transthyretin changes shape and misfolds into insoluble amyloid proteins. These amyloid proteins then accumulate in the heart, nerves, and other body tissues. The buildup of misfolded transthyretin amyloid proteins in the heart causes the heart muscle walls to stiffen and thicken. This stiffened heart has trouble relaxing to fill with blood and becomes less efficient at pumping blood throughout the body.

As the condition advances, the pumping function of the heart gets progressively impaired, resulting in congestive heart failure. ATTR-CM is an under-recognised condition that can severely impact heart function and lead to death if not diagnosed and treated early.

What are the symptoms?

The initial symptoms of ATTR-CM can vary depending on where the abnormal proteins accumulate in the body. In the early stages, patients may not have many symptoms. As the proteins build-up in the heart muscle, making it stiff and thick, patients may gradually develop difficulty breathing (especially with exertion or lying down), swelling in the legs or abdomen, fatigue, and reduced stamina. If the misfolded proteins accumulate in the electrical conduction system of the heart, irregular heart rhythms or an overly slow heartbeat can occur, causing dizziness, fainting, or palpitations.

Protein deposition in nerves, ligaments and tendons may lead to back pain, numbness/ tingling/ pain in the hands and legs. Some patients experience weight loss, constipation or diarrhoea. Foamy urine can happen if the proteins deposit in the kidneys.

Overall, the symptoms may be vague and similar to other conditions. This non-specific presentation has made ATTR-CM difficult to diagnose in the past.

In summary, common symptoms may include:

Shortness of breath
Fatigue
Lower limbs or abdominal swelling
Dizziness/fainting
Palpitations
Numbness of hands and feet
Pain or numbness in the lower back and legs
Foamy urine
Unintentional weight loss

What causes ATTR-CM?

ATTR-CM is caused by the build-up of misfolded proteins called transthyretin in the heart muscles. Transthyretin is normally produced by the liver to transport thyroid hormones and vitamin A in the bloodstream. But due to genetic mutations or aging, the transthyretin proteins can become misfolded. These abnormal proteins then deposit in the heart and other organs, leading to disease.

There are two types of ATTR-CM:

'Wild type' ATTR-CM

Associated with aging
Mostly affecting males over 60 years old

Hereditary ATTR-CM (hATTR-CM)

Caused by a genetic mutation in genes
Can be passed down from birth
Affects both men and women, with symptoms starting as early as 50 years old

How is it diagnosed?

Diagnosing ATTR-CM can be challenging because there is limited awareness of the condition, and its symptoms overlap with other more common conditions. If ATTR-CM is suspected, your doctor will likely order several tests, including an electrocardiogram to check heart rhythm and specialized imaging like an echocardiogram to assess heart function and thickness. Depending on the results of the initial exams and tests, further cardiac imaging may be done, such as a cardiac MRI to visualise the heart or a nuclear scan to look for abnormal proteins. Blood tests will also be run to evaluate organ function. In some cases, a small tissue sample from the heart or nerves may be needed to confirm the diagnosis. Overall, multiple tests are often required because of the non-specific symptoms and the need to rule out other potential causes.

What are the treatments?

The main goals of treatment for ATTR-CM are to alleviate symptoms and slow the progression of abnormal protein build-up in organs.

Recommended lifestyle changes may include adaptations to manage heart failure symptoms like fluid retention and shortness of breath.

Medications can help reduce fluid overload, slow heart rate, prevent irregular heart rhythms, and reduce stroke risk. Devices like pacemakers may be needed to regulate heartbeat.

New treatments are also available to reduce the toxic protein deposition in organs, and research on additional therapies is ongoing.

Though ATTR-CM is a progressive disease, with available treatments, most patients can maintain a reasonable quality of life for years. Support is available to help patients cope with an ATTR-CM diagnosis.