Common Types of Cardiac Amyloidosis
There are over 30 proteins that can cause amyloidosis. However, two of them commonly impact the heart causing amyloid heart disease.
1. AL Amyloidosis or Light Chain Amyloidosis (AL):
This is a bone marrow disease. Bone marrow has red blood cells and many types of white blood cells. White blood cells produce antibodies (proteins) to fight against infections. Light chains are pieces of antibodies produced by one type of white blood cell called plasma cells. In light chain amyloidosis, plasma cells start producing too much of abnormal light chains that do not function normally. These light chains stick together forming long fibers called amyloids. These amyloids then accumulate in different organs leading to organ failure. Any organ can be affected. However, commonly affected organs are kidneys, heart, nerves (neuropathy and carpal tunnel), stomach, and intestines.
2. ATTR Amyloidosis or Transthyretin Amyloidosis (ATTR):
The liver produces a protein called transthyretin which carries vitamin A and thyroid hormone in our body. Due to either genetic mutation or aging, this protein can become unstable and break apart losing its function. This abnormal protein then sticks together forming long threads called ATTR amyloid. ATTR is now known to be the most prevalent form of cardiac amyloidosis. Previously, ATTR was thought to be a rare disease with no specific treatment. The diagnosis was made only from a biopsy. However, with recent advances in this field, we now have a test to diagnose it without invasive biopsy and we also have a specific treatment. We now know that ATTR amyloidosis is not uncommon but is underdiagnosed.
There are two sub-types of transthyretin (ATTR) Amyloidosis:
Familial or Hereditary: This form of ATTR amyloidosis is caused by a genetic mutation. This can be passed on from one generation to another. Patients with hereditary ATTR tend to be younger at presentation. This type of amyloidosis can affect nerves, the heart, or both. There are 120 genetic mutations known to cause ATTR. Some mutations are more common in certain ethnic or racial groups like the T60A mutation in people with Irish ancestry, or the V122I mutation in people with African ancestry. If a person has the genetic mutation, there is a 50% chance of passing on the mutated gene to each of their children (autosomal dominant).
Wild-type ATTR amyloidosis: This type of ATTR affects older individuals. Due to reasons that are poorly understood, transthyretin protein breaks up and forms transthyretin amyloids. This commonly affects the heart causing congestive heart failure. It can also cause carpal tunnel (especially when both hands are involved), lower back pain (due to spinal stenosis), joint pain, atrial fibrillation, heart blockage, and aortic stenosis. This was previously called senile amyloidosis. Research studies show that 13.3% of white adults 60 years and older with increased heart wall thickness with congestive heart failure have ATTR amyloidosis. Also, 1 in 6 patients with severe narrowing of their aortic valve (aortic stenosis) undergoing replacement via TAVR (not open-heart surgery) have ATTR amyloidosis. Wild-type ATTR amyloidosis can be very challenging to diagnose. Patients with this type of cardiac amyloidosis can have carpel tunnel and spinal stenosis many years before the heart is impacted.
International experts recommend screening patients older than 65 years with increased heart wall thickness and congestive heart failure symptoms (shortness of breath, lower leg swelling, abdominal swelling) for wild-type ATTR amyloidosis. Early diagnosis and treatment initiation has proven to improve the quality of life in patients with this condition.