Frailty, malnutrition, and disability predicted mortality in ATTR-CA beyond age, and older patients were less likely to receive therapy despite similar geriatric profiles.
Do comprehensive geriatric assessment (CGA) metrics predict survival and the use of disease-modifying therapy better than chronological age in patients with transthyretin cardiac amyloidosis?
Geriatric syndromes, rather than chronological age, independently predict mortality in ATTR-CA, highlighting the need for comprehensive geriatric assessments to refine risk stratification and avoid age-based bias in prescribing disease-modifying therapies.
Abstract Background The prevalence of transthyretin cardiac amyloidosis (ATTR-CA) among older adults is rising. It remains unclear whether advanced age and geriatric syndromes (frailty, malnutrition, reduced physical performance, etc.) influence management decisions and outcomes in ATTR-CA. Methods In this prospective, multicenter cohort study, 291 individuals diagnosed with ATTR-CA (from 03/2021 to 07/2024) underwent a comprehensive geriatric assessment (CGA). We examined the frequency and clinical implications of CGA metrics across disease stages based on the National Amyloidosis Centre (NAC) classification. Key CGA components included evaluations of disability, malnutrition, depression, frailty, short physical performance battery (SPPB), and an overall count of deficits (sum of individual CGA items). Associations between these CGA measures, the use of disease-modifying therapy, and all-cause mortality were assessed. Results The median age was 81.6 years (male: 86.4%; variant: 18.3%). Disease-modifying treatments were prescribed to 157 (53.9%) patients. Individuals older than 85 years, even those with robust CGA profiles, were significantly less likely to receive disease-modifying therapies—an effect that persisted after adjusting for disability, frailty, and overall deficit burden. Over a median follow-up of 2.1 interquartile range 1.1–2.5 years, 49 (17.5%) patients died. When adjusted for NAC stage, diuretic use, and disease-modifying therapy, CGA parameters such as disability, malnutrition, SPPB, frailty, and the total deficit count were significantly associated with mortality—whereas chronological age itself was not. Incorporating CGA measures improved the prognostic accuracy of the NAC staging system. Conclusion In this national multicenter prospective cohort of patients with ATTR-CA, older age was linked to a lower likelihood of receiving disease-modifying therapies, even among robust individuals with minimal geriatric syndromes. However, once geriatric factors were accounted for, age alone did not predict survival, suggesting possible age-related bias. Because some geriatric syndromes may be modifiable, incorporating a CGA could refine risk stratification, help mitigate age-based discrimination, and potentially improve outcomes.
Fumagalli et al. (2025) studied this question. Frailty, malnutrition, and disability predicted mortality in ATTR-CA beyond age, and older patients were less likely to receive therapy despite similar geriatric profiles.