Prevalence of frailty in cardiac transthyretin amyloidosis: A systematic review and meta-analysis

Background: Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure. Frailty is common among older adults and strongly associated with adverse outcomes. However, its prevalence and clinical relevance in the context of CA have not been systematically examined. This review aimed to assess the prevalence of frailty in CA and qualitatively synthesize the evidence on its association with clinical outcomes. Methods: A systematic review and meta-analysis of observational studies was conducted to assess frailty prevalence in CA. Databases searched included Embase, PubMed, CINAHL, Cochrane Library, and Google Scholar up to April 15, 2025. Studies reporting frailty prevalence in CA patients were included. Six assessors independently screened the articles, extracted data, and resolved conflicts by consensus. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Results: Out of 565 articles identified, six studies met inclusion criteria, including a total of 1422 participants with cardiac transthyretin amyloidosis (ATTR-CA). Reported frailty prevalence ranged from 14.5 % to 75 %, depending on the assessment method. A meta-analysis restricted to studies using the Clinical Frailty Scale (N = 1164) yielded a pooled frailty prevalence of 66 % (95 % CI, 57–74 %), with substantial heterogeneity (I² = 89.1 %). Frailty was consistently associated with higher mortality and poorer quality of life. Conclusions: Frailty is highly prevalent in individuals with ATTR-CA and is independently associated with adverse clinical outcomes. These findings support the routine evaluation of frailty in the management of individuals with CA. PROSPERO registration (CRD42024607807).