Progression of the contralateral limb in chronic limb-threatening ischemia
Cuneyt Koksoy1, Ilse Torres Ruiz1, Zachary S Pallister1
1Division of Vascular Surgery and Endovascular Therapy, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX.
Insights
Over one-third of patients with chronic limb-threatening ischemia (CLTI) develop contralateral CLTI within two years, facing worse outcomes. End-stage renal disease (ESRD) and low toe-brachial index (TBI) predict this progression, aiding risk stratification.
Area of Science:
- Vascular Surgery
- Cardiology
- Nephrology
Background:
- Unilateral chronic limb-threatening ischemia (CLTI) management often overlooks contralateral limb progression.
- Current guidelines lack specific monitoring and treatment strategies for contralateral disease in CLTI patients.
Purpose of the Study:
- To determine the prevalence, risk factors, and outcomes of contralateral CLTI (CL-CLTI) development in patients initially presenting with unilateral CLTI.
Main Methods:
- Retrospective cohort study of 439 unilateral CLTI patients over 9 years.
- Data collection included comorbidities, Wound, Ischemia, and Foot Infection (WIfI) staging, and outcomes.
- Statistical analysis involved univariate and Cox regression, and Kaplan-Meier survival estimates.
Main Results:
- CL-CLTI developed in 36.4% of patients within a median of 24 months.
- Independent risk factors for CL-CLTI included low contralateral toe-brachial index (TBI) and end-stage renal disease (ESRD).
- CL-CLTI patients had more severe index leg disease, higher amputation rates (43.3% index, 22.0% contralateral), and reduced amputation-free survival.
Conclusions:
- Over one-third of unilateral CLTI patients develop CL-CLTI, associated with significantly worse outcomes.
- ESRD and low initial contralateral TBI are key risk factors for CL-CLTI.
- Findings inform monitoring intervals and high-risk patient identification for CLTI management.
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.
