Prevalence and prognostic implications of frailty and other geriatric conditions in patients with transthyretin amyloid cardiomyopathy. The AMYLO-FRAIL study.
M Antunez-Ballesteros, I De-Rosende-Celeiro, E Barge-Caballero, G Barge-Caballero, D Enriquez-Vazquez, D Couto-Mallon, M J Paniagua-Martin, M Padilla-Bautista, Z Grille-Cancela, P Blanco-Canosa, C Vera-Paredes, B Facal-Martinez, C Riveiro-Rodriguez, J M Vazquez-Rodriguez, M G Crespo-LeiroAbstract
Background
Transthyretin cardiomyopathy (ATTR-CM) is a recognized cause of heart failure (HF) in the elderly, but frailty (FR) -a key factor in this population- remains poorly characterized.
Purpose
to determine the prevalence of FR and other geriatric conditions (OGC), their relationship with cardiac disease severity, and their prognostic implications in ATTR-CM patients.
Methods
single-centre, observational, prospective study. ATTR-CM patients underwent comprehensive geriatric assessment (CGA) since October 1st, 2024, to April 30th, 2025. Frailty was defined according to four different scales [Clinical Frailty Scale (CFS) >4, Tilburg Frailty Indicator (TFI) >4, Frailty Instrument for Primary Care of the Survey of Health (SHARE-FI)>2 and Short Physical Performance Battery (SPPB)<10]. National Amyloidosis Centre (NAC) score was used to assess cardiac disease severity, Six-Minute Walk test (6MWT) to determine functional capacity and Kansas City Cardiomyopathy Questionnaire (KCQ12) for Quality of life. Follow-up was extended to December 20th, 2025. Endpoints: all-cause mortality and the combined all-cause mortality or worsening of HF (outpatient HF requiring iv diuretics/HF admission). Survival analyses were performed using the Kaplan–Meier and Cox proportional hazards regression.
Results
110 patients were enrolled (median age 85 years, 78.2% males, 95% wild type ATTR-CM). Estimated prevalence of FR varied significantly depending on its definition, with a range from 32.7% (95% Confidence Interval (CI) 24.0-41.5%) according to a CFS >4, up to 62.7% (95% CI 53.7-71.8%) according to a SPPB <10 (Figure 1.A). Prevalence of OGC is shown in Figure 1.B. The mean (SD) 6MWT was 287(135)m and the mean KCCQ12 was 81.5(SD14.2). Frail patients walked less and showed poorer quality of life than non-frail patients, whatever criteria was considered to define frailty (p<0.001). Patients were followed over a median time of 352 days (IQR 295 to 393). Figure 2 shows the Kaplan-Meier cumulative estimates of overall survival (2.A) and survival free of worsening HF (2.B) in frail vs. non-frail patients. Cognitive impairment, dependence for basic activities, nutritional risk and depressive symptoms were also associated with reduced survival and reduced survival free of worsening HF. In univariate analysis, FR was independently associated with higher risk of mortality and the combined endpoint whatever definition was used. After adjusting for age, NAC stage and Tafamidis, these associations remained significant for FR by CFS>4 [HR (95% CI) 9.4 (1.9-47) and 4.8(2.1-11.0) for all cause death and combined endpoint respectively)] and for FR by SHARE-FI>2 [HR (95% CI) 6.8 (1.4-32.8) and 3.4 (1.6-7.5).
Conclusion
FR is common and related with worse outcomes in ATTR-CM in terms of cardiac disease severity, worsening HF and survival. Future studies should explore the utility of CGA in selecting candidates for disease-modifying treatments.Prevalence of frailty and OGCFor image description, please refer to the figure legend and surrounding text.Survival analysis according to FR statusFor image description, please refer to the figure legend and surrounding text.