Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare heart condition attributed to the buildup of transthyretin fibrils in the heart muscle (myocardium).
ATTR amyloidosis affects the heart and often leads to heart failure. Protein misfolding is a key cause of amyloidosis and may cause amyloid deposits in the organs and nervous system.
What is ATTR-CM?
Often underrecognized and underdiagnosed, transthyretin amyloid cardiomyopathy (ATTR-CM) is a disease of the heart muscle. It is a progressive, potentially fatal disease that eventually leads to heart failure.
There are two variants of ATTR-CM: wild-type ATTR-CM (wATTR-CM) which can occur with age, and hereditary (hATTR-CM) which can be inherited from family members. The experience of patients living with ATTR-CM will differ according to the type of variant and if there was any delay in diagnosis and treatment.
What is amyloidosis?
Amyloidosis refers to the buildup of an abnormal protein called an amyloid. In ATTR-CM, transthyretin amyloidosis is caused by transthyretin (TTR), a protein produced by the liver. TTR’s role is transporting the hormone thyroxine and vitamin A (retinol) in the bloodstream. If it becomes unstable due to a mutation or age, it can break apart, misfold, and then form clumps of amyloid fibrils.
These abnormal TTR proteins or fibrils accumulate in the body’s organs, nerves and heart.
The left ventricle of the heart is particularly affected, causing it to thicken and stiffen, known as cardiomyopathy (CM). This makes it difficult for the heart to pump blood around the body, leading to symptoms of congestive heart failure. These symptoms may include breathlessness, dizziness, fainting, fatigue, chest pain, heart palpitations, increased heart rate, swelling of the ankles, stomach bloating and coughing when lying down.
What is protein misfolding and how does it occur?
Protein misfolding refers to a protein that is structurally abnormal and unable to achieve its normal native state. It can occur as a result of factors such as genetic mutations, environmental stress and aging.
In wild-type ATTR-CM (wATTR-CM), protein misfolding occurs because the protein becomes structurally unstable with age and misfolds. In hereditary ATTR-CM (hATTR-CM), the protein misfolds as the result of a mutation of the transthyretin gene.
The importance of early diagnosis
ATTR-CM has often been overlooked when diagnosing heart failure, but new advances in diagnostic tools have led to earlier diagnosis and treatment. This has increased the number of patients diagnosed with AATR-CM and extended life expectancy due to early intervention and treatment.