Comprehensive geriatric assessment and frailty in transthyretin amyloid cardiomyopathy: toward more individualized and appropriate care

Abstract Transthyretin amyloid cardiomyopathy (ATTR-CM), once considered a rare disease, is now an increasingly recognized cause of heart failure. This rise in diagnoses is driven by increased awareness, the availability of non-invasive diagnostics, and the introduction of disease-modifying therapies (DMTs) in an aging population. Available DMTs are costly and may require 12 to 18 months before clinical benefit becomes apparent, making careful assessment of expected treatment benefit essential. Because ATTR-CM predominantly affects older adults, frailty, multimorbidity, and competing health risks are common. Frailty is associated with poorer outcomes and reduced quality of life, yet is not captured by current prognostic staging systems, which primarily reflect cardiac disease severity. Frailty assessment may complement cardiac evaluation by supporting personalized DMT decision-making and identifying modifiable vulnerabilities for targeted interventions. This narrative review integrates cardiology and geriatric perspectives to examine the role of Comprehensive Geriatric Assessment, including frailty assessment, in ATTR-CM. Evidence on frailty prevalence, prognostic significance, and the concept of a disease-specific frailty phenotype is summarized. The role and key components of the CGA are outlined. Additionally, a multidisciplinary care pathway incorporating CGA into clinical practice is proposed to support personalized DMT decisions and targeted interventions.