Cardiac Amyloidosis in Older Adults With a Focus on Frailty

Amyloidosis, which is caused by misfolded proteins that form amyloid fibrils, is predominantly diagnosed in older adults. Although previously considered a rare disease, increased awareness and noninvasive diagnostic methods have resulted in a rise in diagnoses. As a multisystem disease that affects multiple organ systems (cardiac, gastrointestinal, renal, and neurological), there is significant overlap with both geriatric conditions and common conditions in heart failure. Frailty is recognized as a distinct biological syndrome of declines across multiple physiological systems, which prevents maintenance of homeostasis and limits the ability to respond to stressors. Frailty was initially characterized as physical frailty alone; however, it is increasingly recognized that it is multidimensional with components including nutrition, cognitive, psychological, and social. Frailty in cardiovascular disease has become an important risk factor, indicator for disease severity, and can help guide decisions around intervention. In certain patients, frailty may be reversible. Given the lack of consensus definitions, tools, and implementation of frailty in both clinical and research settings in the field of amyloidosis, we convened a group of experts from cardiology, geriatric cardiology, geriatrics, hematology, and allied health to form this state-of-the-art review. There are many points of intersectionality between amyloidosis, aging, and frailty which herald a need for multidisciplinary care. This review document aims to provide guidance in how to understand and address frailty in older patients with a specific focus on cardiac amyloidosis. (JACC Adv. 2025;4:101784) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).