Relationship of the Wound, Ischemia, and Foot Infection Stage With Frailty, Disability, and Quality of Life at Baseline, and 1-year Outcomes in All-comers With Chronic Limb-threatening Ischemia

Abstract

The wound, ischemia, and foot infection (WIfI) classification system has been widely adopted in chronic limb-threatening ischemia (CLTI) management, but validation has predominantly been among patients undergoing revascularization. This study aimed to investigate the association of WIfI stage with baseline frailty, disability, and quality of life (QoL), in addition to 1-year major amputation and survival, in all-comers with CLTI. Single-center prospective cohort study (NCT04027244) of patients aged ≥18 with CLTI, between May 2019 and March 2022. Frailty (clinical frailty scale), disability (Barthel index), and QoL (vascular QoL questionnaire; EQ-5D-5L) assessments were performed at baseline. Interim analysis of 1-year outcomes was performed in January 2023. Amputation incidence was calculated for WIfI stages, and individual WIfI score combinations with five or more patients, and presented as percentages with 95% confidence intervals (CI) (Agresti-Coull method). Associations of WIfI stage with 1-year major amputation was investigated using Fine-Gray competing risk analysis (death as competing risk), reported as subdistribution hazard ratios (HR) with 95% sCI. Associations of WIfI stage with one-year mortality was investigated using Cox regression and reported as HR with 95% CI. A total of 434 patients were included. Fifty-two patients (12.0%) classified as WIfI stage 1, 112 (25.8%) stage 2, 107 (24.7%) stage 3, 92 (21.2%) stage 4, and 71 (16.4%) had incomplete WIfI scores. Increasing WIfI stage was associated with increasing prevalence and severity of frailty (P = .002) and greater disability (P < .001). QoL scores were similar for each WIfI stage (Table I). Major amputation incidence at one-year was 2% (95% CI, 0%-11%) for WIfI stage 1, 7% (95% CI, 3%-14%) stage 2, 8% (95% CI, 4%-15%) stage 3, 21% (95% CI, 14%-30%) stage 4, and 14% (95% CI, 9%–26%) in those with incomplete WIfI scores. Amputation incidence for individual WIfI scores was largely consistent with stage classification (Table II). Increasing WIfI stage was independently associated with one-year major amputation (subdistribution HR, 2.00; 95% CI, 1.34-3.00; P = .001). Increasing WIfI stage was also associated with 1-year mortality (HR, 1.31; 95% CI, 1.02-1.68; P = .031), with frailty (clinical frailty scale score ≥5) (HR, 2.48; 95% CI, 1.33-4.61; P = .004) and nonoperative management (HR, 5.35; 95% CI, 2.98-9.59; P < .001) the strongest predictors of mortality at 1 year. WIfI classification is predictive of major amputation at one-year in patients with CLTI, but frailty status is a better predictor of mortality. Although WIfI classification is associated with both frailty and disability, it is not associated with QoL at baseline.Table IBaseline assessment scores and management strategy by WIfI stageStage 1 (n = 52)Stage 2 (n = 112)Stage 3 (n = 107)Stage 4 (n = 92)Missing (n = 71)P valueFrailty status.002 No frailty (CFS 1-3)8 (15)16 (14)10 (9)6 (7)5 (7.) Vulnerable (CFS 4)22 (42)50 (45)40 (37)20 (22)20 (28) Mild/moderate (CFS 5-6)20 (38)44 (39)52 (49)55 (60)41 (58) Severe frailty (CFS 7-9)2 (4)2 (2)5 (5)11 (12)5 (7)Barthel index20 (18-20)19 (17-20)19 (16-20)17 (15-20)18 (15-20)<.001HADS Anxiety score4.5 (2-10)7 (3-11)5 (3-9)6 (3-9)6 (3-12).414 Depression score5 (3-8)5 (3.5-9.0)5 (3-10)6 (4-10)7 (3-10).423VascuQoL score3.3 ± 1.52.8 ± 1.12.9 ± 1.13.1 ± 1.23.1 ± 1.2.143EQ-5D-5L EQ-5D value0.557 ± 0.2410.480 ± 0.2740.456 ± 0.2510.462 ± 0.2550.418 ± 0.296.237 EQ VAS55.5 ± 22.050.8 ± 23.153.6 ± 24.156.4 ± 21.847.1 ± 21.6.319Initial management<.001 Endovascular21 (40)53 (47)44 (41)40 (43)27 (38) Open/hybrid7 (13)33 (29)27 (25)15 (16)22 (31) Major amputation0 (0)0 (0)2 (2)9 (10)2 (3) Minor amputation1 (2)2 (2)3 (3)10 (11)9 (13) Nonoperative23 (44)24 (21)31 (29)18 (20)11 (15)CFS, Clinical frailty scale; HADS, Hospital Anxiety and Depression Scale; VAS, visual analogue scale; VascuQoL, Vascular Quality of Life Questionnaire.Data are presented as number (%), mean ± standard deviation, or median (interquartile range) unless otherwise stated. P values in bold are statistically significant.aData presented as. Open table in a new tab Table IIOne-year major amputation rates of individual WIfI score combinationWoundIschemia – 0Ischemia – 1Ischemia – 2Ischemia – 30––––0 (0) [0-21]–––1 (5) [0-26]–––3 (5) [1-15]–––10 (0) [0-34]–––1 (5) [0-25]2 (20) [5-52]––1 (4) [0-23]1 (14) [1-53]––1 (2) [0-13]4 (19) [7-41]––2––0 (0) [0-49]–0 (0) [0-40]0 (0) [0-32]2 (15) [3-43]–1 (17) [1-58]0 (0) [0-34]––2 (15) [3-43]4 (27) [10-52]1 (17) [1-58]–3----------------Foot infection0123012301230123Data are presented as number (%) [95% confidence interval].Color of cells denotes WIfI stage classification (estimated risk of 1-year amputation): . Amputation rates only calculated for score combinations with five or more individual patients. Open table in a new tab