Wild type ATTR amyloidosis

Wild type ATTR amyloidosis (formerly known as senile systemic amyloidosis ) is a slowly progressive disease. The symptoms usually start after age 65. This condition is not hereditary, and it is far more common in men than in women. No-one knows just how common symptomatic wild type ATTR amyloidosis really is but it is almost certainly underdiagnosed at present. This diagnosis may become more common in future as the population ages and diagnostic methods continue to improve.

People with this condition do not have a mutation in the TTR gene and the amyloid fibrils are made up of normal, “wild type” TTR.  These types of amyloid deposits are found at autopsy in 1 in 4 people over age 80, but in most cases they do not appear to cause any symptoms. Some patients with small ATTR amyloidosis deposits in the heart and minimal symptoms may not require any treatment.

Symptoms of wild type ATTR amyloidosis result from stiffening of the heart due to amyloid deposits (restrictive cardiomyopathy). These symptoms may include:

• shortness of breath, sometimes just after mild exertion
• palpitations and abnormal heart rhythms, most frequently atrial fibrillation or atrial flutter
• leg swelling (oedema)
• weight loss
• nausea
• fatigue
• dizziness and collapse (syncope or fainting), which may occur after exertion, or after eating
• disrupted sleep
• angina (chest pain)

Almost 50% of patients with wild type ATTR amyloidosis experience carpal tunnel syndrome – tingling and pain in the wrists, pins and needles in the hands. Carpal tunnel syndrome often appears 3-5 years before the symptoms of heart disease.

It not clear at present just how commonly the deposits actually do lead to symptomatic disease. Recent developments with diagnostic tests such as cardiac magnetic resonance (CMR) have greatly improved the detection of amyloid in the heart during life. This has led to the belief that wild type ATTR amyloidosis may be far more common than was previously thought. Cardiologists are gradually becoming more aware that wild type amyloidosis may cause otherwise unexplained heart failure and are referring these patients more frequently to the NAC.

This is demonstrated in the following NAC statistics :

• Up until 2001 wild type ATTR amyloidosis was diagnosed in just 1 out of every 200 (0.5%) of patients seen at the NAC.
• In 2016 it accounted for nearly 1 in 5 (18%) of NAC patients diagnosed with amyloidosis – a 40 fold increase!

Patients with ATTR in the heart often have fewer symptoms than those with AL amyloidosis in the heart, and wild type ATTR amyloidosis usually progresses slowly.

More on diagnosis and treatment of wild type ATTR amyloidosis.