There are two types of transthyretin amyloid cardiomyopathy (ATTR-CM): wild-type ATTR-CM (wATTR-CM), which is associated with aging, and hereditary ATTR-CM (hATTR-CM), which is inherited.
While both variants of ATTR-CM are often diagnosed later in life, symptoms and survival rates can differ considerably between the types.
What is ATTR-CM?
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare form of heart disease that leads to congestive heart failure. It occurs as a result of an accumulation of faulty transthyretin proteins (fibrils) in the left ventricle of the heart, its main pumping chamber. These proteins, produced by the liver, lead to a thickening and stiffening of the left ventricle, which makes it more difficult for the heart to pump blood around the body.
A number of tests are involved in diagnosing ATTR-CM, including blood, nerve and muscle tests, echocardiograms, magnetic resonance imaging (MRI), organ biopsies and in some cases, immunohistochemistry and mass spectrometry.
A blood test is used to screen for genetic mutations that cause hATTR-CM. If these genetic mutations are not found, wATTR-CM is confirmed.
Wild-type ATTR-CM
The wATTR-CM subtype is known as an aging disease. It occurs most often in men 70-80 years old. It is thought that the TTR proteins become structurally unstable with age, causing them to misfold and form amyloid deposits in the heart.
When this occurs, the heart finds it difficult to pump blood to the body, leading to symptoms such as fatigue, shortness of breath, bloating or swelling of legs, ankles or stomach, confusion, irregular heart rate, coughing or wheezing, dizziness and heart palpitations.
Treatments for wATTR-CM slow disease progression by stabilizing the TTR protein, stopping the TTR protein from being produced and removing the amyloid deposits in the heart.
This subtype has the worse survival rate of the two variants, of around 3.5 years following diagnosis. However, early diagnosis and treatment may extend life expectancy to 5.5 years.
Hereditary ATTR-CM
The hATTR-CM subtype is caused by a genetic mutation in the transthyretin (TTR) gene and is often diagnosed earlier than wATTR-CM, with most patients diagnosed at 30 to 60 years old.
There are over 120 different gene mutations, with the most common being ATTR V30M, ATTR V1221 and ATTRT60A. Symptoms vary according to the gene mutation and the organs affected. They can range from shortness of breath, palpitations, fainting, fatigue, swelling of the ankles and chest pain to numbness in the legs and feet, limb weakness, dizziness, bladder or bowel problems and gastrointestinal issues.
Until recently, the only treatment available for hATTR-CM was a liver transplant to reduce the production of the TTR protein. However, similar to wATTR-CM treatment, recent therapeutic developments target the TTR protein, aiming to stabilize and stop production.
Removing amyloid deposits is also an option. Average survival rates for this type are around seven to 12 years following diagnosis.
