Hereditary Transthyretin Amyloid Cardiomyopathy | Cardiology | JAMA Cardiology | JAMA Network
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JAMA Cardiology Patient Page
December 22, 2021

Hereditary Transthyretin Amyloid Cardiomyopathy

Author Affiliations
  • 1Northwestern University, Chicago, Illinois
JAMA Cardiol. Published online December 22, 2021. doi:10.1001/jamacardio.2021.5006

Amyloidogenic transthyretin (ATTR) amyloid is a disease in which a protein called transthyretin (TTR) builds up in the organs.

ATTR protein buildup leads to heart muscle thickening and stiffening and causes a type of heart disease, ATTR cardiomyopathy. This impairs the ability of the heart to pump effectively and can result in heart failure where fluid builds up in the body and causes shortness of breath and swelling in the legs. Patients with ATTR cardiomyopathy can also have arrhythmias (abnormal heart rhythms) that can lead to stroke or death.

Transthyretin, or prealbumin, is a protein made in the liver and functions to transport substances, such as thyroid hormone and vitamin A, throughout the body. ATTR amyloid occurs when this protein does not form correctly, causing it to accumulate in tissues such as the heart, nerves, and other organs. There are 2 types of ATTR cardiomyopathy. The most common type happens spontaneously in a person and is not passed down in a family through genes. The other type is inherited and caused by a change in the TTR gene. It is important to note that not everyone who inherits the genetic change or variant that causes ATTR will develop the disease.

Amyloid buildup in the heart can cause symptoms of heart failure, including shortness of breath, fatigue, and swelling of the feet, legs, or abdomen. Amyloid buildup in the heart can also cause heart rate problems (eg, palpitations, lightheadedness, stroke, and even sudden death). Your physician may use medications to treat the heart rate issues; however, an implantable pacemaker or defibrillator may be needed. ATTR can affect tissues outside the heart and cause problems such as carpal tunnel syndrome; kidney issues; digestive problems; numbness, tingling, and weakness in the hands or feet; and narrowing of the spinal canal in the lower back (termed lumbar spinal stenosis) due to the TTR protein accumulation.

ATTR cardiomyopathy may be suspected in a patient who has signs and symptoms of heart failure, and the walls of the heart are very thickened. First, a comprehensive history and physical examination should be performed, including a discussion of family history of heart disease. Unfortunately, routine heart testing is unlikely to identify ATTR cardiomyopathy. If a clinician suspects ATTR cardiomyopathy, specialized testing is often needed to make the diagnosis, such as a nuclear scan to look for TTR deposits in the heart. In addition, blood tests to rule out other forms of amyloidosis should be done. Sometimes, a biopsy of the heart muscle is needed for the diagnosis, which can be done through a vein in the neck and with minimal discomfort.

Blood or saliva tests can look for some of the many genetic variants responsible for the misfolded TTR protein. This can sometimes be helpful, but it is not accurate enough to be used as a screening test. Only a physician can confirm the diagnosis.

ATTR cardiomyopathy can cause progressive heart failure and even be fatal. However, several new treatments are now available or in randomized clinical trials to help with symptoms and even improve survival. Available medications work in different ways, ranging from binding to and stabilizing the misfolded protein to preventing the production of the protein. Potential medications include tafamidis, patisiran, and inotersen. Other possible treatments that may be needed focus on controlling symptoms of heart failure, which include diuretic medications, and rhythm abnormalities, which may include a pacemaker. In severe cases, transplant of the heart and, in some cases, the liver where the abnormal TTR protein is made, may be considered.

Section Editor: Mintu Turakhia, MD, MAS.
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Article Information

Published Online: December 22, 2021. doi:10.1001/jamacardio.2021.5006

Conflict of Interest Disclosures: Dr Shah reported grants from Pfizer and consulting fees from Pfizer, Ionis Pharmaceuticals, Eidos, Prothena, and Regeneron outside the submitted work. Dr Khan reported grants from the American Heart Association and the National Institutes of Health outside the submitted work. No other disclosures were reported.

Sources: American Heart Association. Restrictive cardiomyopathy. Accessed November 1, 2021.

Amyloidosis Foundation. Accessed November 1, 2021.

Amyloidosis Research Consortium. Accessed November 1, 2021.

Amyloidosis Support Group. Accessed November 1, 2021.

MedlinePlus. Cardiac amyloidosis. Accessed November 1, 2021.

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