Learn The BasicsTransthyretin amyloid cardiomyopathy (ATTR-CM) is a rare and progressive disease affecting the heart. Misfolded transthyretin (TTR) amyloid fibers develop in the heart muscle and other body parts, causing damage.
Hereditary or familial ATTR-CM and wild-type ATTR-CM are the two types of ATTR-CM.
In hereditary ATTR-CM, a genetic mutation in the TTR gene leads to the misfolding of the TTR protein and its accumulation in the hearts and other organs. In wild-type ATTR-CM, there is no known disease-causing mutation in the TTR gene, and the misfolded protein aggregates likely form in the normal aging process.
The signs and symptoms of hereditary ATTR-CM usually appear after age 65. Patients with wild-type ATTR-CM may show no signs or symptoms.
Progressive congestive heart failure, where the heart is not able to pump blood as efficiently, is the typical presentation of ATTR-CM. The accumulation of amyloid fibrils leaves the heart muscle unable to work properly.
In addition, patients with ATTR-CM may also show signs and symptoms associated with the accumulation of amyloid fibrils in other parts of the body outside the heart.
Cardiac and respiratory symptoms
The general signs and symptoms of heart failure, which also occur in ATTR-CM, are:
- Fatigue
- Swelling in the legs, ankles, or abdomen
- Shortness of breath, especially after exertion
- A sudden drop in blood pressure upon standing
- Trouble breathing when lying down
- Feeling faint or lightheaded
- Gastrointestinal problems
- Heart arrhythmias.
Patients with ATTR-CM may experience ventricular arrhythmias. These range from ventricular premature beats and nonsustained ventricular tachycardia to sustained ventricular tachycardia and ventricular fibrillation, where the lower chambers of the heart contract in a very rapid and uncoordinated way, leading to the heart not being able to pump blood properly to the rest of the body.
Tachycardia is defined as a rate of more than 100 beats per minute when at rest. The normal heart rate ranges between 60 to 100 beats per minute.
Patients with ATTR-CM may also have other types of arrhythmias, including atrioventricular nodal block and atrial fibrillation.
The infiltration of the amyloid fibrils into the heart muscle can also affect the electrical conduction system of the heart, which is known as conduction block, and lead to arrhythmias.
Extracardiac signs and symptoms
Several extracardiac signs and symptoms should raise suspicion of ATTR-CM, including:
- Carpal tunnel syndrome, a condition characterized by numbness, tingling and pain in the wrist and first three fingers due to the compression of a nerve
- Lumbar spinal stenosis, the narrowing of the spinal canal in the lower part of the back
- Ophthalmological and neurological manifestations
- Liver and kidney disorders
- Edema
- Swelling.
These could be caused by the build-up of amyloid fibrils in the nervous system and other organs, such as the liver and the kidney, and can be a way to differentiate ATTR-CM from other forms of heart disease.
Reviewed by Kyle Habet, M.D., on November 10, 2024.