Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious heart condition caused by the abnormal buildup of proteins in the heart muscle. These protein deposits, known as amyloid fibrils, stiffen the heart walls and impair its ability to pump blood effectively. This can lead to progressive heart failure. Recognizing ATTR-CM is increasingly important due to advancements in diagnosis and treatment.
What is ATTR Amyloidosis?
Amyloidosis is a group of diseases characterized by the accumulation of abnormal protein deposits, called amyloid, in various organs and tissues. In ATTR amyloidosis, the specific protein involved is transthyretin (TTR).
Transthyretin is a protein primarily produced by the liver, transporting thyroid hormone and vitamin A. Under certain circumstances, the TTR protein can become unstable, misfold from its typical structure, and then aggregate into insoluble amyloid fibrils. These misfolded protein clumps then deposit in various tissues.
When amyloid deposits accumulate in the heart muscle, they cause the heart walls to thicken and stiffen. This stiffening prevents the heart’s main pumping chambers, particularly the left ventricle, from relaxing and filling properly. As a result, the heart struggles to pump enough blood, leading to cardiomyopathy and eventually heart failure.
Forms of ATTR Cardiomyopathy
ATTR cardiomyopathy presents in two primary forms: wild-type and hereditary.
Wild-type ATTR cardiomyopathy (ATTRwt-CM) typically develops spontaneously as part of the aging process and is not caused by a genetic mutation. It is more commonly observed in men over the age of 60, with the average age of diagnosis being around 75. This form results from the misfolding of normal, non-mutated transthyretin protein.
Hereditary ATTR cardiomyopathy (hATTR-CM), also known as familial amyloid cardiomyopathy, arises from a specific genetic mutation in the TTR gene. This mutated gene is passed down through families, leading to the production of an unstable TTR protein that is prone to forming amyloid deposits. Symptoms of hereditary ATTR-CM can appear earlier in life, sometimes as early as 30, but more often in later adulthood, and can vary depending on the specific genetic alteration.
Common Symptoms
Symptoms of ATTR cardiomyopathy often resemble other heart conditions, making early diagnosis challenging. They largely stem from the heart’s impaired pumping ability due to amyloid deposits.
Common heart-related symptoms include shortness of breath, particularly with exertion or when lying flat. Individuals may also experience fatigue, swelling in the legs and ankles (edema), and irregular heartbeats or palpitations. Lightheadedness or fainting spells can occur.
Beyond the heart, ATTR amyloidosis can affect other parts of the body, and these non-cardiac symptoms might appear years before heart-related issues. These can include carpal tunnel syndrome, often affecting both wrists, and spinal stenosis, which is a narrowing of the spinal canal. Some individuals may also experience peripheral neuropathy, characterized by numbness, tingling, or pain in the hands and feet, or gastrointestinal issues like nausea or changes in bowel habits.
How It’s Diagnosed and Treated
Diagnosing ATTR cardiomyopathy involves clinical evaluation and specialized tests to confirm amyloid presence and type. Initial suspicion often arises from symptoms and routine cardiac tests.
Echocardiograms can show thickening of the heart walls, a common feature in ATTR-CM. Cardiac MRI provides detailed images of the heart, helping to identify amyloid deposits. A highly specific non-invasive test for ATTR amyloidosis is nuclear scintigraphy, which uses a special tracer that binds to TTR amyloid in the heart. If these imaging tests are conclusive and other types of amyloidosis are ruled out, a heart tissue biopsy may not be necessary for diagnosis. Genetic testing is also performed to differentiate between hereditary and wild-type forms of the disease.
Treatment approaches for ATTR cardiomyopathy focus on managing symptoms and slowing the progression of the disease. Supportive care includes medications like diuretics to manage fluid retention and reduce swelling. Medications or pacemakers may be used to address irregular heart rhythms.
Disease-modifying therapies specifically target the TTR protein to halt or slow amyloid progression. Transthyretin stabilizers, such as tafamidis, work by preventing the TTR protein from misfolding. Gene silencers, like patisiran or inotersen, reduce the production of the TTR protein by the liver. Early diagnosis and initiation of these treatments can substantially improve outcomes and quality of life for individuals with ATTR cardiomyopathy. Managing this complex condition often involves a multidisciplinary team of specialists, including cardiologists, neurologists, and genetic counselors.