Transthyretin cardiac amyloidosis: advances and ambiguities

Cardiac amyloidosis is a fatal disorder caused by deposition of abnormally folded protein in the interstitial space. One of the proteins most associated with the disease is transthyretin (TTR), which leads to a progressive infiltrative cardiomyopathy (CM). Previously thought to be a rare disorder, there is growing recognition of it as a common cause of heart failure in the elderly and African Americans. The application of bone scintigraphy to the diagnosis of ATTR amyloidosis now allows for accurate and non-invasive diagnosis of the disease, rather than the previously necessary tissue biopsy. Targeted pharmacotherapies have been developed in the past few years that stabilize TTR, silence genes responsible for TTR production, or remove abnormal protein deposited in tissues. As of March 2025, Vutrisiran is the latest addition to the FDA-approved medications for ATTR-CM, alongside Tafamidis and Acoramidis. Several emerging therapies, including novel drugs and promising gene editing techniques are currently under investigation. As the number of available treatments continues to grow, maintaining a high index of suspicion and timely screening for the disease using laboratory tests, electrocardiography, and imaging has become increasingly important. In addition, with advancements in artificial intelligence (AI), new methods are in development to enhance screening of patients with suspected ATTR amyloidosis. These AI-driven tools could be integrated into electronic medical record systems to flag at-risk patients and allow for more rapid diagnosis. This review provides an overview of the current landscape and future directions of the diagnosis, treatment, and screening of ATTR-CM.