Progression of the contralateral limb in chronic limb-threatening ischemia

Abstract

Objective

For patients initially presenting with unilateral chronic limb-threatening ischemia (CLTI), the progression and natural history of the contralateral limb (CL) remain underexplored, and current guidelines provide insufficient guidance for monitoring progression and managing contralateral disease. This study aims to evaluate the prevalence, risk factors, and outcomes associated with the development of contralateral CLTI (CL-CLTI) in patients initially diagnosed with unilateral CLTI.

Methods

This was a single-center, retrospective cohort study including patients with unilateral CLTI. Data on comorbidities, Wound, Ischemia, and Foot Infection (WIfI) grades/clinical stages, and outcomes were collected. Statistical analyses included univariate and Cox regression, as well as Kaplan-Meier survival estimates where appropriate.

Results

Over a 9-year period, 439 patients with unilateral CLTI were included in the analysis (63.1% male; median age, 69 years; interquartile range, 62-77 years). CL-CLTI developed in 36.4% of patients at a median of 24 months (interquartile range, 10-55 months). Univariate analysis revealed significant associations between CL-CLTI and Black race (P = .037), diabetes (P < .001), neuropathy (P < .001), retinopathy (P = .002), chronic kidney disease (P < .001), end-stage renal disease (ESRD) (P < .001), history of coronary artery bypass grafting (P = .01), and lower baseline contralateral leg toe-brachial index (TBI) (P < .001). Multivariable Cox regression identified low baseline contralateral TBI (hazard ratio, 0.18; 95% confidence interval [CI], 0.07-0.43; P < .001) and ESRD (hazard ratio, 1.95; 95% CI, 1.26-2.99; P = .003) as independent risk factors for CL-CLTI development. Patients with CL-CLTI exhibited more severe tissue loss in the index leg, higher wound scores (WIfI-W2), and more advanced disease stages (WIfI-Stage 4, 52.9% vs 37.9%; P = .003) compared with unilateral patients. During follow-up, patients with CL-CLTI experienced significantly higher rates of major amputations in both the index leg (43.3% vs 12.0%; P < .001) and the contralateral leg (22.0%). Kaplan-Meier analysis showed significantly reduced amputation-free survival in patients with CL-CLTI (70.9 months; 95% CI, 58.9-82.8 months) compared with those with unilateral disease (85.3 months; 95% CI, 76.8-93.9 months; P < .001). Mortality rates were similar between groups (unilateral: 16.0%, contralateral: 20.7%; P = .21).

Conclusions

Within a median of 24 months of initial presentation, over one-third of patients with CLTI develop CL-CLTI, which is associated with worse outcomes. Patients with ESRD and low initial contralateral TBI are at particularly high risk for contralateral disease progression. These findings help to define appropriate monitoring intervals for patients with CL-CLTI and identify those at highest risk of disease progression.