Clinical Phenotype and Prognostic Significance of Frailty in Transthyretin Cardiac Amyloidosis

The prevalence and clinical impact of frailty in transthyretin cardiac amyloidosis (ATTR-CA) remains poorly characterized.

This study aimed to evaluate the prevalence, clinical determinants, and prognostic significance of frailty in a large cohort of patients with ATTR-CA.

Frailty was assessed in 880 patients with ATTR-CA (median age 80 years [Q1-Q3: 75-84 years], 719 [81.7%] male) using the Clinical Frailty Scale (CFS). Frailty was analyzed as a continuous variable and categorized as CFS 1 to 3, CFS 4 or 5, CFS 6 or 7, and CFS 8 or 9.

Frailty was observed in 502 (57.1%) patients (CFS 4 or 5: 364 [41.4%]; CFS 6 or 7: 129 [14.7%]; CFS 8 or 9: 9 [1.0%]). Independent predictors of worsening frailty included older age, female sex, non-p.(V142I) hereditary ATTR-CA variants, and National Amyloidosis Centre stage 3 disease. Mortality rates increased incrementally with frailty severity (deaths per 100 person-years: 2.9 vs 11.0 vs 21.1 vs 40.9; log-rank P < 0.001). Frailty was independently associated with higher mortality risk across all age groups, genotypes, and disease stages.

Frailty is common in ATTR-CA and is independently linked to increased mortality risk. Incorporating frailty assessment alongside traditional markers enhances prognostication across genotypes and disease severities, particularly for short-term risk estimation.