Heart failure can have many causes, but for some patients, the diagnosis may not tell the whole story. A condition called transthyretin amyloid cardiomyopathy, or ATTR-CM, is increasingly being recognized as an underlying cause of heart failure, yet it can be difficult to identify because many of its symptoms look like other heart conditions.

That diagnostic challenge is receiving new attention in 2026. In May, the American Heart Association announced a multicenter study examining whether a structured education program for health care providers could improve detection of ATTR-CM among patients hospitalized with heart failure. The effort comes as the AHA’s 2026 Heart Disease and Stroke Statistics Update estimates that up to 13% of older adults hospitalized with heart failure with preserved ejection fraction, or HFpEF, may have ATTR-CM. That figure does not mean 13% of all people with heart failure have the disease, but it highlights why researchers and clinicians are looking more closely at patients who may otherwise go undiagnosed.

ATTR-CM develops when transthyretin, a protein produced in the body, becomes unstable and forms abnormal deposits called amyloid. When those deposits build up in the heart, the heart muscle can become stiff, making it harder for the heart to relax and fill properly. Over time, the condition can progress to heart failure. The disease can occur in a hereditary form, known as variant or hereditary ATTR-CM, or a non-hereditary form known as wild-type ATTR-CM, which is more closely associated with aging. The symptoms can make ATTR-CM particularly difficult to recognize. People may experience shortness of breath, fatigue, swelling in the legs or feet, chest congestion, an increased heart rate or irregular heartbeat. Those symptoms can occur with many forms of heart disease, so they do not by themselves point to ATTR-CM. The American Heart Association notes that ATTR-CM may initially resemble other causes of heart failure or conditions involving a thickened heart muscle. What can make the condition especially important to consider are symptoms that occur outside the heart. Depending on the type of ATTR-CM, people may have numbness or tingling in the hands and feet, carpal tunnel syndrome, spinal stenosis or a history of tendon problems such as biceps tendon rupture. Some of these problems can occur before noticeable heart symptoms.

For patients, that does not mean that carpal tunnel syndrome or back problems automatically indicate ATTR-CM. These conditions are common and have many possible causes. But when certain symptoms occur alongside unexplained heart failure, particularly in an older adult, the combination may provide information worth discussing with a health care professional.

Why ATTR-CM Can Be Missed

Awareness also matters because hereditary ATTR-CM can involve genetic variants that are more common in certain populations. The American Heart Association reports that the most common hereditary variant in the United States occurs in approximately 3% to 4% of Black people. Carrying a transthyretin gene variant does not mean that a person will necessarily develop ATTR-CM, but knowing about a family history of the disease or a known genetic variant can help inform conversations about evaluation and testing.

One variant that has received particular attention is V122I, a change in the transthyretin gene associated with hereditary ATTR-CM. NMQF’s ATTR-CM education materials emphasize the importance of recognizing this hereditary risk while also noting that ATTR-CM can occur in people of different backgrounds and that wild-type ATTR-CM is associated with aging rather than an inherited gene change. The distinction is important for health access. Genetic risk is not the same thing as disease, and race alone cannot determine whether someone has ATTR-CM. At the same time, communities with higher prevalence of certain hereditary variants may face consequences when a condition is unfamiliar or its symptoms are attributed to more common diagnoses. NMQF launched its AskAboutATTR.org campaign to provide culturally relevant information and encourage people, particularly in Black and underserved communities, to recognize potential symptoms and have informed conversations with health care professionals.

Diagnosing ATTR-CM requires more than recognizing a symptom. A health care professional may begin with routine heart testing, including an electrocardiogram or echocardiogram, and then use additional testing when ATTR-CM is suspected. Depending on the situation, evaluation can include cardiac magnetic resonance imaging, a nuclear medicine scan, blood and urine testing to distinguish ATTR-CM from other forms of amyloidosis, and genetic testing when hereditary disease is suspected. The growing focus on detection is occurring alongside changes in treatment. The FDA has approved therapies for adults with ATTR-CM, including acoramidis for wild-type or hereditary transthyretin-mediated cardiomyopathy and vutrisiran for the cardiomyopathy associated with both wild-type and hereditary transthyretin-mediated amyloidosis. Treatment decisions depend on the individual diagnosis and should be made with a qualified health care professional.

For someone already living with heart failure, persistent or unexplained symptoms deserve attention, particularly when there is a history of carpal tunnel syndrome, spinal stenosis, certain tendon problems, nerve symptoms or a family history of heart disease or ATTR-CM. Those clues do not establish a diagnosis, but they can provide a reason to ask whether another underlying cause should be considered.

ATTR-CM remains a serious and often underrecognized condition, but the growing focus on earlier detection reflects a broader effort to understand why some patients develop heart failure and how those causes can be identified. For patients and families, knowing that heart failure can have different underlying causes may be an important starting point. NMQF’s “Know Your Heart” message encourages people who have been diagnosed with heart failure and have additional symptoms to talk with their health care provider about ATTR-CM. Learn more and explore resources at AskAboutATTR.org.