A rare and potentially fatal form of heart disease known as transthyretin amyloid cardiomyopathy, or ATTR-CM, is increasingly drawing clinical attention as researchers and physicians report that many patients diagnosed with heart failure may actually be living with this underdiagnosed condition. ATTR-CM is caused by the abnormal buildup of misfolded proteins called transthyretin in the heart muscle, leading to stiffening of the heart walls, progressive dysfunction, and, ultimately, heart failure if left untreated. www.heart.org

Transthyretin is a protein produced primarily in the liver that carries thyroid hormone and vitamin A through the bloodstream. In ATTR-CM, this protein becomes unstable and misfolds into amyloid fibrils that deposit into tissues, most notably in the heart. Over time, these deposits infiltrate cardiac muscle, reducing its ability to relax and contract efficiently and creating what clinicians call restrictive cardiomyopathy.

Recent epidemiological data indicate that ATTR amyloidosis, including its cardiac form, may be more common than previously recognized. A 2022 analysis of U.S. health records estimated that transthyretin amyloid cardiomyopathy occurs in roughly 12.7 people per million annually and has a prevalence of more than 40 cases per million, underscoring a rise in diagnosed cases in recent years.

The condition exists in two principal forms. Wild-type ATTR-CM generally arises with aging, typically affecting older adults without a family history of the disease. Hereditary or familial ATTR-CM is linked to mutations in the transthyretin (TTR) gene, the most common being the V122I variant found in an estimated one in 25 Black Americans. While carrying this gene variation does not guarantee the development of disease, it significantly increases risk. info.nmqf.org

Symptoms of ATTR-CM often resemble those of general heart failure, which has contributed to frequent misdiagnosis. Patients may experience shortness of breath with exertion or at rest, swelling in the legs and ankles, fatigue, irregular heart rhythms, and diminished exercise capacity. Because the early signs can be subtle, many individuals are not diagnosed until the disease is advanced.

Diagnosis is challenging and requires a high index of suspicion from clinicians. Traditional imaging like echocardiography can suggest the disease, but newer non-invasive nuclear imaging techniques, such as technetium-labeled bone scans, have improved the ability to detect amyloid deposits without risky heart biopsies. Specialists may also use cardiac MRI and genetic testing to differentiate ATTR-CM from other types of cardiomyopathy and to determine whether the condition is hereditary.

Historically, treatment options for ATTR-CM were limited to managing heart failure symptoms, but breakthroughs in recent years have expanded therapeutic approaches. Medications that stabilize transthyretin or reduce its production have shown promise in slowing disease progression. Tafamidis, one of the first drugs approved specifically for ATTR-CM, has been associated with improved survival and quality of life in clinical studies. Other agents targeting the underlying protein pathology are also in use or under investigation.

Despite these advances, significant challenges remain. A concise clinical guidance released in late 2025 emphasizes ongoing issues in the diagnosis and management of ATTR-CM, including the need for individualized care strategies and improved awareness among healthcare providers. The guidance notes that enhanced screening and diagnostic criteria are essential to ensure patients receive appropriate evaluation and treatment.

Health experts also stress the importance of considering ATTR-CM in populations at elevated risk. Black Americans carrying the V122I gene variant, for example, not only face a higher likelihood of hereditary ATTR-CM but also may encounter barriers to early diagnosis and access to specialized care. Integrating awareness of genetic and socioeconomic factors into clinical practice can help address disparities and improve outcomes for communities of color disproportionately affected by this condition.

Advocacy groups and cardiology organizations are working to increase education about ATTR-CM for both medical professionals and the public. Resources such as patient toolkits and symptom awareness campaigns aim to shorten the long delays to diagnosis that many patients currently experience. Early detection remains central to offering life-changing therapies before irreversible cardiac damage occurs.

As research continues to illuminate the true burden of ATTR-CM and new treatments emerge, clinicians and patients alike are urged to look beyond typical heart failure labels when symptoms persist. Greater recognition of this rare but serious disease could lead to faster diagnoses, tailored treatment plans, and ultimately, improved survival for thousands of patients living with transthyretin amyloid cardiomyopathy.

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Learn More: https://info.nmqf.org/attr_cm