Transthyretin Amyloid Cardiomyopathy

TTR amyloid cardiomyopathy (ATTR-CM) occurs when the heart is predominantly affected. In this disease, which is also known as familial amyloid cardiomyopathy (FAC), TTR amyloid is deposited in the heart and causes heart failure. One common mutation, V122I (substitution of isoleucine for valine at position 122), occurs with high frequency (prevalence of approximately 3.5%) in African-Americans.

A mutation in transthyretin is not a pre-requisite for developing ATTR-CM. In the elderly, wild-type or normal transthyretin may become unstable resulting in the development of abnormally folded TTR individual protein units that ultimately form amyloid. The disease, also known as senile systemic amyloidosis (SSA) primarily affects the elderly, with approximately 16-25% of individuals >80 years old have TTR amyloid deposition in heart tissue by autopsy studies.

Patients typically develop symptoms after the age of 60. Although the heart is the primary organ involved, many patients (>40%) may complain first of symptoms of carpal tunnel syndrome (numbness and tingling in the hands, wrist pain) due to local deposition of TTR amyloid in that area. Heart symptoms can include shortness of breath, fainting, generalized fatigue and ankle swelling.

The only currently available treatments for ATTR-CM are aimed at relief of symptoms, such as diuretics (water pills) to treat the swelling of the ankles.