Causes wild-type ATTR amyloidosis
The cause is unknown –we do not know why ‘wild-type’ TTR, which is a normal blood protein, forms amyloid deposits in some people and not in others although advancing age is undoubtedly a risk factor. People with this condition do not have a mutation in the TTR gene, and the condition is not hereditary.
Who gets wild-type ATTR amyloidosis?
This condition may affect people from any ethnic background. Symptoms usually start over age 65 and the disease usually progresses slowly. The condition is far more common in men than in women. In a recent study of patients diagnosed with wild-type ATTR amyloidosis at the British National Amyloidosis Centre, nearly 90% were men. This condition is not hereditary.
Symptoms of wild-type ATTR amyloidosis
The symptoms result from stiffening of the heart due to amyloid deposits (restrictive cardiomyopathy). They may include:
- Shortness of breath, sometimes just after mild exertion
- Palpitations and abnormal heart rhythms, most frequently atrial fibrillation/ flutter
- Ankle swelling (edema)
- Fatigue
- Dizziness or fainting, which may occur after exertion, or after eating
- Angina (chest pain)
- Weight loss
- Nausea
- Disrupted sleep
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.
Diagnosis of wild-type ATTR amyloidosis
Doctors may suspect ATTR amyloidosis based on patients' symptoms, findings on physical examination and sometimes family history. The diagnosis can be confirmed (or eliminated) by tests including:
The ‘gold standard’ test (the best available method) for diagnosis is a combination of detection of ATTR amyloid on heart biopsy together with genetic testing showing that there is no TTR gene mutation. Biopsies from other parts of the body, such as abdominal fat or the rectum are often used to diagnose other types of amyloidosis. In wild-type ATTR amyloidosis, these tests can be useful if they do show amyloid. But in many patients with this condition these tests are negative despite the presence of amyloid in the heart. Recently nuclear imaging using PYP tracer has become the diagnostic test of choice replacing the need for a cardiac biopsy.
How common is wild-type ATTR amyloidosis?
We do not know how common symptomatic wild type ATTR amyloidosis really is. It has long been known that wild-type TTR commonly forms microscopic amyloid deposits in elderly people. These types of amyloid deposits are found at autopsy in 1 in 4 people over age 80. Clinical disease caused by this type of amyloid was very rarely diagnosed. Some patients with small wild type ATTR amyloidosis deposits in the heart and minimal symptoms may not require any treatment.
It is believed to be underdiagnosed at present. Progress in new imaging techniques such as cardiac magnetic resonance (CMR), now available at ANAC, 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.
This diagnosis may become more common in future as the population ages and diagnostic methods continue to improve.
Treatment of wild ATTR amyloidosis
Treatment of all types of amyloidosis is currently based on the following principles:
- Reducing the supply of amyloid forming precursor proteins.
- Supporting the function of organs containing amyloid.
In addition, avoiding fluid balance problems is extremely important for all amyloidosis patients. Check the section supporting the function of organs containing amyloids and how to avoid fluid balance for more information about treatment.
Click here for specific frequently asked questions on ATTR amyloidosis
