A Clinical Frailty Scale score ≥5 independently predicted death and heart failure hospitalization in patients with transthyretin cardiac amyloidosis (HR 2.87; 95% CI 1.11-7.41; p=0.029).
Cohort (n=107)
No
Does frailty, assessed by the Clinical Frailty Scale or hand-grip strength, predict death and heart failure hospitalization in older patients with transthyretin cardiac amyloidosis?
Frailty, assessed by the Clinical Frailty Scale, is a significant independent predictor of mortality and heart failure hospitalization in older patients with transthyretin cardiac amyloidosis.
Effect estimate: HR 2.87 (95% CI 1.11-7.41)
Absolute Event Rate: 71% vs 14%
p-value: p=0.029
Abstract Background Transthyretin cardiac amyloidosis (TTR-CA) is characterized by amyloid fibril deposition in the myocardium, leading to impaired cardiac function. Frailty is an age-related syndrome characterized by a decline in multiple physiological systems and increased vulnerability to stressors. TTR-CA patients, especially if wild-type, are usually older than patients with heart failure (HF) due to other aetiologies and are more frequently frail. Despite its recognized importance, frailty assessment in TTR-CA is poorly explored and standardized tools for its evaluation in this setting are lacking. Objectives This study aims to assess the prevalence and the prognostic value of Clinical Frailty Scale (CFS) and hand-grip strength (HGS) in patients with TTR-CA. Methods Data were collected prospectively at our Cardiac Amyloidosis Center. The study focused on patients over 65 years and with a confirmed diagnosis of TTR-CA. All patients underwent a comprehensive evaluation including echocardiography, biomarker sampling, National Amyloidosis Centre (NAC) staging and frailty assessment by HGS and CFS. Subjects with a CFS≥5 were classified as frail. HGS cut-off of 30 for males and 20 for females was used to identify frail patients Results The final study population consisted of 107 subjects. Eighty-one had wild-type TTR-CA. The median age was 80.3 years (IQR 74.6-85.3). Fifteen (14%) were categorized as frail based on CFS, with a median value of CFS of 5.5 (IQR 5.0-7.0) compared to 3.0 (IQR 2.0-3.0) in non-frail patients (p0.001). Frail patients had lower median values of HGS (17.6 (± 8.6) kg vs 28.8 (± 8.7) kg, p0.001), were older and mainly female. The median follow-up was 16 months (IQR 7-17 months), during which the composite outcome of death and HF hospitalization occurred in 23 patients (22%). The outcome occurred in 13 patients (14%) with CFS5 and in 10 (71%) with CFS≥5. At univariate analysis CFS≥5 was associated with HR of 7.2 (95% CI 3.2 to 16.7; p0.001) (Figure 1). The same outcome occurred in 6 patients (12%) with normal HGS and in 17 (31%) with low HGS. At univariate analysis low HGS was associated with HR of 3.3 (95% CI 1.3 to 8.4; p=0.012) (Figure 2). In a multivariate model including age, sex, tafamidis treatment and baseline NAC score, CFS≥5 remained an independent predictor of outcome with HR 2.87 (95% CI 1.11-7.41; p=0.029). The AUC associated to this model was 0.81. Hand-grip strength did not predict the outcome in a similar multivariate model. Conclusions Based on our findings, frailty assessed by the CFS emerged as a significant and independent risk factor for mortality and HF hospitalization in patients with TTR-CA. Our results suggest that CFS may serve as a valuable supplementary tool for prognostic assessment alongside NAC staging system in patients with TTR-CA, warranting further investigation in larger cohorts.
Passo et al. (2025) conducted a cohort in Transthyretin cardiac amyloidosis (TTR-CA) (n=107). Clinical Frailty Scale (CFS) ≥5 vs. CFS <5 was evaluated on Composite of death and heart failure hospitalization (HR 2.87, 95% CI 1.11-7.41, p=0.029). A Clinical Frailty Scale score ≥5 independently predicted death and heart failure hospitalization in patients with transthyretin cardiac amyloidosis (HR 2.87; 95% CI 1.11-7.41; p=0.029).