Cognitive frailty and mortality among patients on the heart transplant waiting list: A prospective cohort study

Frailty is an important prognostic factor in patients with heart failure and in transplant candidates, while cognitive impairment remains an under-recognized component that may further worsen clinical outcomes. This prospective study aimed to determine the prevalence of physical and cognitive frailty among heart transplant candidates and their association with mortality. Physical frailty was assessed using the Fried criteria; cognition was evaluated using the MoCA (cognitive screening) and WASI (general intellectual functioning); and depressive symptoms were measured using the BDI. Cognitive frailty was defined as the presence of ≥3 of 6 criteria in a modified Fried phenotype, which incorporated cognitive impairment as an additional domain. A total of 150 patients listed for heart transplantation within the previous 30 days were included at a tertiary center in Brazil. The study population was predominantly male (70%), with Chagas disease etiology (35%), and a mean age of 49.8 ± 10.4 years. Physical frailty was present in 78.7% of patients, cognitive frailty in 88.7% (MoCA) and 86.7% (WASI), and depressive symptoms in 44%, which were significantly associated with physical frailty (p = 0.021). During 1-year follow-up, 41.3% of patients died and 67.3% underwent transplantation. Physical frailty was associated with an increased risk of early mortality after listing (initial SHR = 5.47; p = 0.023), with significant attenuation of this effect over time (TVC SHR = 0.99; p = 0.008). A similar pattern was observed for cognitive frailty, measured by both MoCA (initial SHR = 1.61; p = 0.011; TVC SHR = 1.00; p = 0.011) and WASI (initial SHR = 1.57; p = 0.012; TVC SHR = 1.00; p = 0.007), indicating a reduction in its impact on mortality risk over time. However, after multivariable adjustment, neither physical nor cognitive frailty remained independently associated with overall mortality. Physical and cognitive frailty were highly prevalent among heart transplant candidates and showed a time-dependent association with early mortality risk. After adjustment for disease severity markers, this association lost significance, suggesting that frailty may, at least in part, reflect the underlying clinical status at the time of listing rather than acting as an independent prognostic factor. These findings also raise questions regarding the adequacy of the Fried phenotype as a frailty assessment tool in this specific population.