Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by the accumulation of misfolded transthyretin protein (TTR) in the heart tissue, leading to heart failure. It's a form of amyloidosis specifically affecting the heart and is caused by the destabilization and misfolding of the transthyretin protein, which is produced by the liver.
Causes:
Hereditary (hATTR-CM): Caused by genetic mutations in the TTR gene leading to the production of unstable TTR protein that misfolds and aggregates.
Wild-Type (wtATTR-CM): Occurs without a genetic mutation, predominantly in elderly men. The normal TTR protein becomes unstable over time and misfolds.
Symptoms:
ATTR-CM symptoms often resemble those of other forms of heart failure and may include:
Shortness of breath
Fatigue
Swelling in the legs and abdomen
Irregular heartbeat
Chest pain
Unexplained weight loss
Because the symptoms are common to other heart conditions, ATTR-CM is often underdiagnosed or misdiagnosed.
Treatment:
Treatment focuses on managing symptoms and slowing the progression of the disease. Specific approaches include:
Tafamidis: A medication that stabilizes the TTR protein and prevents it from misfolding.
Patisiran and Inotersen: RNA interference therapies that reduce the production of TTR protein by the liver.
Heart Transplant: In severe cases or younger patients with hereditary ATTR-CM.
Supportive Care: Such as diuretics for fluid overload, pacemakers for arrhythmias, and other treatments addressing heart failure symptoms.
Early diagnosis is crucial for managing ATTR-CM effectively, as treatments are more effective when started early in the disease's progression. Ongoing research continues to look for more effective treatments and potential cures for this condition.
Potential Reversibility of ATTR-CM through Anti-ATTR Amyloid Antibodies