Fumagalli Carlo, Ioannou Adam, Cappelli Francesco, Maurer Mathew S, Razvi Yousuf, Porcari Aldostefano, Zampieri Mattia, Perfetto Federico, Rauf Muhammad U, Martinez-Naharro Ana, Venneri Lucia, Petrie Aviva, Whelan Carol, Wechalekar Ashutosh, Lachmann Helen, Hawkins Philip N, Olivotto Iacopo, Marfella Raffaele, Ungar Andrea, Marchionni Niccolò, Gillmore Julian D, Fontana Marianna
National Amyloidosis Centre, University College London, London, United Kingdom; Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy; Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.
National Amyloidosis Centre, University College London, London, United Kingdom.
JACC CardioOncol. 2025 Apr;7(3):268-278. doi: 10.1016/j.jaccao.2025.01.018. Epub 2025 Mar 12.
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.
转甲状腺素蛋白心脏淀粉样变（ATTR-CA）中衰弱的患病率及其临床影响仍未得到充分描述。
本研究旨在评估一大群ATTR-CA患者中衰弱的患病率、临床决定因素及预后意义。
使用临床衰弱量表（CFS）对880例ATTR-CA患者（中位年龄80岁[四分位间距：75 - 84岁]，719例[81.7%]为男性）进行衰弱评估。将衰弱作为连续变量进行分析，并分为CFS 1至3级、CFS 4或5级、CFS 6或7级以及CFS 8或9级。
502例（57.1%）患者存在衰弱（CFS 4或5级：364例[41.4%]；CFS 6或7级：129例[14.7%]；CFS 8或9级：9例[1.0%]）。衰弱加重的独立预测因素包括年龄较大、女性、非p.(V142I)遗传性ATTR-CA变异以及国家淀粉样变中心3期疾病。死亡率随衰弱严重程度逐渐增加（每100人年死亡数：2.9 vs 11.0 vs 21.1 vs 40.9；对数秩检验P < 0.001）。在所有年龄组、基因型和疾病阶段，衰弱均与较高的死亡风险独立相关。
衰弱在ATTR-CA中很常见，且与死亡风险增加独立相关。将衰弱评估与传统标志物相结合可改善对各基因型和疾病严重程度的预后判断，特别是对于短期风险估计。
