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: 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 (KM) 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, IQR 62-77). CL-CLTI developed in 36.4% of patients at a median of 24 months (IQR 10, 55). Univariate analysis revealed significant associations between CL-CLTI and Black race (p=0.037), diabetes (p<0.001), neuropathy (p<0.001), retinopathy (p=0.002), chronic kidney disease (p<0.001), end-stage renal disease (ESRD) (p<0.001), history of coronary artery bypass grafting (p=0.01), and lower baseline contralateral leg toe-brachial index (TBI) (p<0.001). Multivariable Cox regression identified low baseline contralateral TBI (HR 0.18; 95% CI 0.07-0.43, p<0.001) and ESRD (HR 1.95; 95% CI 1.26-2.99, p=0.003) 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=0.003) compared to unilateral patients. During follow-up CL-CLTI patients experienced significantly higher rates of major amputations in both the index leg (43.3% vs. 12.0%, p<0.001) and the contralateral leg (22.0%). KM analysis showed significantly reduced amputation-free survival (AFS) in patients with CL-CLTI (70.9 months, 95% CI 58.9-82.8) compared to those with unilateral disease (85.3 months, 95% CI 76.8-93.9, p<0.001). 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 CLTI patients develop CL-CLTI, which is associated with worse outcomes. Patients with end-stage renal disease and low initial contralateral TBI are at particularly high risk for contralateral disease progression. These findings help to define appropriate monitoring intervals for CL-CLTI patients and identify those at highest risk of disease progression.