Frailty as a Predictor of Mortality in Patients With Interstitial Lung Disease Referred for Lung Transplantation.

BACKGROUND: Frailty is a clinically recognized syndrome of decreased physiological reserve and a key contributor to suboptimal clinical outcomes in various lung disease groups. Interstitial lung disease (ILD) is fast approaching chronic obstructive pulmonary disease as the number one indication for lung transplantation worldwide. Our aim was to assess whether frailty is a predictor of mortality in patients with ILD referred for lung transplantation in an Australian cohort. METHODS: Consecutive patients with ILD referred or on the waiting list for lung transplantation from May 2013 to December 2017 underwent frailty assessment using the modified Fried's frailty phenotype. Frailty was defined as a positive response to ≥3 of the following 5 components: weak grip strength, slowed walking speed, poor appetite, physical inactivity, and exhaustion. RESULTS: One hundred patients (82 male:18 female; age, 59 ± 7 y; range, 30-70) underwent frailty assessment. Twenty-four of 100 (24%) were assessed as frail. Frailty was associated with anemia, hypoalbuminemia, low creatinine, and the use of supplemental oxygen (all P < 0.05). Frailty was independent of age, gender, measures of pulmonary dysfunction (PaO2, forced vital capacity percentage predicted, total lung capacity, total lung capacity percentage predicted, DLCO, or DLCO percentage predicted), cognitive impairment, or depression. Frailty and DLCO % predicted were independent predictors of increased all-cause mortality: 1-year actuarial survival was 86 ± 4% in the nonfrail group compared with 58 ± 10% for the frail group (P = 0.002). CONCLUSIONS: Frailty is common among patients referred for lung transplant with a diagnosis of ILD and is associated with a marked increase in mortality.

Reversibility of Frailty After Bridge-to-Transplant Ventricular Assist Device Implantation or Heart Transplantation.

BACKGROUND: We recently reported that frailty is independently predictive of increased mortality in patients with advanced heart failure referred for heart transplantation (HTx). The aim of this study was to assess the impact of frailty on short-term outcomes after bridge-to-transplant ventricular assist device (BTT-VAD) implantation and/or HTx and to determine if frailty is reversible after these procedures. METHODS: Between August 2013 and August 2016, 100 of 126 consecutive patients underwent frailty assessment using Fried's Frailty Phenotype before surgical intervention: 40 (21 nonfrail, 19 frail) BTT-VAD and 77 (60 nonfrail, 17 frail) HTx-including 17 of the 40 BTT-VAD supported patients. Postprocedural survival, intubation time, intensive care unit, and hospital length of stay were compared between frail and nonfrail groups. Twenty-six frail patients were reassessed at 2 months or longer postintervention. RESULTS: Frail patients had lower survival (63 ± 10% vs 94 ± 3% at 1 year, P = 0.012) and experienced significantly longer intensive care unit (11 vs 5 days, P = 0.002) and hospital (49 vs 25 days, P = 0.003) length of stay after surgical intervention compared with nonfrail patients. Twelve of 13 frail patients improved their frailty score after VAD (4.0 ± 0.8 to 1.4 ± 1.1, P < 0.001) and 12 of 13 frail patients improved their frailty score after HTx (3.2 ± 0.4 to 0.9 ± 0.9, P < 0.001). Handgrip strength and depression improved postintervention. Only a slight improvement in cognitive function was seen postintervention. CONCLUSIONS: Frail patients with advanced heart failure experience increased mortality and morbidity after surgical intervention with BTT-VAD or HTx. Among those who survive frailty is partly or completely reversible underscoring the importance of considering this factor as a dynamic not fixed entity.

Cognitive impairment improves the predictive validity of physical frailty for mortality in patients with advanced heart failure referred for heart transplantation.

BACKGROUND: The aim of this study was to identify whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty provides better outcome prediction in patients with advanced heart failure referred for heart transplantation (HT). METHODS: Beginning in March 2013, all patients with advanced heart failure referred to our Transplant Unit have undergone a physical frailty assessment using the Fried frailty phenotype. Cognition was assessed with the Montreal Cognitive Assessment and depression with the Depression in Medical Illness questionnaire. We assessed the value of 4 composite frailty measures: physical frailty (PF ≥ 3 of 5 = frailty), "cognitive frailty" (CogF ≥ 3 of 6 = frail), "depressive frailty" (DepF ≥ 3 of 6 = frail), and "cognitive-depressive frailty" (ComF ≥ 3 of 7 = frail) in predicting outcomes. RESULTS: Frailty was assessed in 156 patients (109 men, 47 women), aged 53 ± 13 years, and with a left ventricular ejection fraction of 27% ± 14%. Inclusion of cognitive impairment or depression in the definition of frailty increased the proportion classified as frail from 33% using PF to 42% using ComF. During follow-up, 28 patients died before ventricular assist device implantation or HT. Frailty was associated with significantly lower ventricular assist device- and HT-free survival, with CogF best capturing early mortality: 12-month survival for non-frail and frail cohorts was 81% ± 5% vs 58% ± 10% (p < 0.02) using PF and 85% ± 5% vs 56% ± 9% (p < 0.002) using CogF. Combining the Depression in Medical Illness score with PF or CogF did not strengthen the relationship between frailty and mortality. CONCLUSIONS: The addition of cognitive impairment to the assessment of PF strengthened its capacity to identify advanced heart failure patients referred for HT who are at high risk of early death.

The Prevalence and Prognostic Significance of Frailty in Patients With Advanced Heart Failure Referred for Heart Transplantation.

BACKGROUND: Frailty is a clinically recognized syndrome of decreased physiological reserve. The heightened state of vulnerability in these patients confers a greater risk of adverse outcomes after even minor stressors. Our aim was to assess the prevalence and prognostic significance of the frailty phenotype in patients referred for heart transplantation. METHODS: Consecutive patients referred or on the waiting list for heart transplantation from March 2013 underwent frailty assessment. Frailty was defined as a positive response to 3 or more of the following 5 components: weak grip strength, slowed walking speed, poor appetite, physical inactivity, and exhaustion. In addition, markers of disease severity were obtained, and all patients underwent cognitive (Montreal Cognitive Assessment) and depression (Depression in Medical Illness-10) screening. RESULTS: One hundred twenty patients (83 men:37 women; age, 53 ± 12 years, range, 16-73 years; left ventricular ejection fraction, 27 ± 14%) underwent frailty assessment. Thirty-nine of 120 patients (33%) were assessed as frail. Frailty was associated with New York Heart Association class IV heart failure, lower body mass index, elevated intracardiac filling pressures, lower cardiac index, anemia, hypoalbuminemia, hyperbilirubinemia, cognitive impairment, and depression (all ρ < 0.05). Frailty was independent of age, sex, heart failure duration, left ventricular ejection fraction, or renal function. Frailty was an independent predictor of increased all-cause mortality: 1 year actuarial survival was 79 ± 5% in the nonfrail group compared with only 54 ± 9% for the frail group (P < 0.005). CONCLUSIONS: Frailty is prevalent among patients with advanced symptomatic heart failure referred for heart transplantation and is associated with increased mortality.