Transthyretin amyloid cardiomyopathy (ATTR-CM) is approaching a turning point in its classification as a rare disease, according to an editorial published recently in Expert Review of Cardiovascular Therapy.
It was once considered an uncommon condition, but growing awareness, advances in diagnostic tools and improved screening methods have revealed that the disease is more prevalent than initially believed.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
The shift in classification may help more patients receive an accurate diagnosis and timely treatment, but it also presents challenges in ensuring proper care, reducing misdiagnosis and addressing health care disparities.
Read more about ATTR-CM testing and diagnosis
“The increasing recognition of ATTR-CM, particularly the wild-type form, raises an important question: what is the significance of ATTR-CM no longer being classified as a rare disease?” the editorial’s authors said. “While the growing awareness of the condition and broader understanding among specialists are undoubtedly positive developments, they also introduce new challenges. One key concern is the need to streamline care for ATTR-CM to avoid diagnostic errors and inappropriate treatment strategies.”
ATTR-CM is a progressive heart condition caused by misfolded transthyretin proteins that form amyloid deposits in the heart. It was historically considered a rare disorder, often overlooked in favor of more commonly known causes of heart failure.
But research over the past decade has demonstrated that the wild-type form of ATTR-CM is far more common than previously thought. Studies have found its prevalence may be as high as one in 220 in older populations — well above the threshold for rare disease classification in both the United States and Europe.
This growing recognition has been driven by increased scientific interest, with the number of published studies on cardiac amyloidosis rising from 279 in 2015 to 902 in 2022.
Increased screening has revealed ATTR-CM in many different patient groups, including those with severe aortic valve stenosis, heart failure with preserved ejection fraction and pacemakers and even individuals with noncardiac conditions such as carpal tunnel syndrome and spinal stenosis. Studies showed prevalence rates in these populations ranging from 3% to 25%.
ATTR-CM can sometimes present as an isolated heart condition, but it is more often part of a broader disorder affecting multiple organ systems. The findings suggested that the disease has been significantly underdiagnosed in the past.
Although the wild-type form of ATTR-CM is no longer as rare as once thought, the hereditary or variant form remains uncommon, with prevalence varying by region. Some genetic variants, such as Val50Met, are more frequent in Portugal, Spain and Japan; others, such as Val142Ile, affect 3% to 4% of African Americans and 8.5% of Afro Caribbean individuals.
The question of when to start treatment for patients with genetic mutations, particularly before heart symptoms develop, is a growing area of research. Ongoing clinical trials are exploring whether early intervention with disease-modifying therapies could slow or prevent progression of disease.
Despite the progress in recognizing ATTR-CM, significant challenges remain. Many cases go undiagnosed because of the condition’s nonspecific symptoms and their similarity to those of other heart conditions. African Americans, in particular, are often diagnosed at later disease stages when fewer treatment options are available, leading to worse outcomes.
There is an urgent need for improved diagnostic protocols, broader physician awareness and health care policies that ensure all patients receive timely and equitable treatment, the editorial’s authors said.
Looking ahead, ATTR-CM is likely to be increasingly recognized as a common, treatable heart disease rather than a rare disorder. This shift brings hope for earlier diagnosis and better treatment access, but it also underscores the importance of developing standardized care pathways to ensure high-quality management for all patients, regardless of where they live or their genetic background, the editorial said.
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