Prognostic Value of Malnutrition, Frailty, and Physical Performance in Transthyretin Cardiac Amyloidosis: Insights From a Prospective Multicenter Cohort Study.

Abstract

Background: The prevalence of transthyretin cardiac amyloidosis among older adults (often octogenarians) is increasing. We aimed to determine whether age and geriatric syndromes bear any impact on the management and outcomes in transthyretin cardiac amyloidosis and assess the risk of ageism.

Methods: In a prospective, multicenter cohort study, 256 patients diagnosed with transthyretin cardiac amyloidosis from March 2021 to March 2024 underwent comprehensive geriatric assessment (CGA). The study evaluated the prevalence and clinical associations of CGAs across different disease stages (National Amyloidosis Centre stage). Key CGA domains included disability, malnutrition, depression, frailty, Short Physical Performance Battery, and cumulative deficits (sum of the single CGA items). Associations of these measures with disease-modifying therapy and overall mortality were analyzed.

Results: Median age was 82 years (men: n=223 [87%]; variant: n=19 [7.4%]); 129 (50.3%) patients received disease modifiers. Those ≥85 years had significantly lower odds of receiving disease-modifying therapy even after adjusting for disability, frailty, and cumulative deficits. Over 1.9 (interquartile range, 1.0-2.3) years, 45 (17.6%) patients died. After adjustment for National Amyloidosis Centre stage, diuretics and disease modifiers, CGA domains of disability, malnutrition, Short Physical Performance Battery, frailty, and number of deficits, but not age, were significantly associated with mortality. Assessment of CGA domains improved National Amyloidosis Centre prognostic accuracy.

Conclusions: In a national prospective cohort of patients with transthyretin cardiac amyloidosis, older age was associated with lower prescription of disease modifiers, even among individuals with a low burden of geriatric syndromes. However, when adjusted for geriatric domains, age was not associated with survival, indicating potential ageism. Because some geriatric syndromes may be modifiable, a CGA could enhance risk stratification, reduce age-related bias, and improve outcomes.