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Updated: Mar 26, 2026
Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia
Published on: September 22, 2020
Predictors of major amputation despite patent bypass grafts
Ann D Smith1, Alexander T Hawkins1, Maria J Schaumeier1
1Center for Surgery and Public Health, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Insights
Despite patent lower extremity bypass (LEB) grafts, critical limb ischemia (CLI) patients may still face major amputation. Preoperative gangrene, diabetes, race, and poor kidney function are key predictors of amputation risk, even with a functioning bypass.
Area of Science:
- Vascular Surgery
- Critical Limb Ischemia Research
- Graft Patency Analysis
Background:
- Major amputation remains a risk for patients with critical limb ischemia (CLI) despite patent lower extremity bypass (LEB) grafts.
- Identifying factors predicting amputation in the presence of a patent LEB graft is crucial for improving limb salvage rates.
Purpose of the Study:
- To analyze predictive factors associated with major amputation in patients with critical limb ischemia (CLI) who have patent lower extremity bypass (LEB) grafts.
- To differentiate predictors of amputation with patent grafts from those with occluded grafts.
Main Methods:
- Analysis of data from the prospective randomized PREVENT III trial (1404 patients) undergoing LEB for CLI.
- Primary outcome: major amputation with patent LEB. Cox proportional hazard model used to identify independent predictors.
- Exclusion of patients who underwent amputation due to occluded grafts.
Main Results:
- 11.5% of LEB patients underwent major amputation (6.3% with patent grafts).
- Predictive patient factors for amputation with patent grafts included preoperative gangrene, diabetes, Black race, low creatinine clearance, prior coronary artery bypass grafting, and lower quality of life scores.
- Postoperative factors like wound necrosis, infection, and recurrent CLI symptoms also significantly predicted amputation.
Conclusions:
- While graft patency is vital, other factors significantly influence limb salvage in CLI patients.
- Early surgical intervention before gangrene or severe activity limitation, alongside optimized patient conditions (nutrition, diabetes, cardiac health), is essential.
- Absence of identifiable graft lesions for revision and severe adverse events can lead to amputation despite a patent graft, highlighting the need to mitigate non-graft-related complications.
Objective:
Despite patent vein bypass grafts, some patients with critical limb ischemia (CLI) receive major amputations. We analyzed the predictive factors leading to major amputation in the presence of patent lower extremity bypass (LEB) grafts.
Methods:
Data from the Project of Ex-Vivo vein graft Engineering via Transfection III (PREVENT III), a large prospective randomized trial of 1404 patients who underwent LEB with vein graft for CLI, were queried for outcomes. The primary outcome was major amputation with patent (PMA) LEB compared with patients with patent LEB who achieved limb salvage (PLS). The population excluded those who received amputation for occluded grafts. A Cox proportional hazard model identified independent predictors.
Results:
Of 1404 LEB patients, 162 (11.5%) had major amputation: 89 (6.3%) with patent and 73 (5.2%) with occluded LEB. For PMA, 21 of 89 (23.6%) developed critical stenosis and 11 of 21 (52.4%) were revised. For PLS, 460 of 1242 (37.0%) developed critical stenosis and 351 of 460 (76.3%) were revised. Predictive patient factors included having preoperative gangrene (vs rest pain; hazard ratio [HR], 3.504; 95% confidence interval [CI], 1.533-8.007; P = .0029), diabetes (HR, 1.800; 95% CI, 1.006-3.219; P = .0477), black (vs white) race (HR, 1.779; 95% CI, 1.051-3.011; P = .0321), baseline creatinine clearance <25 mL/min (vs >65 mL/min; HR, 1.759; 95% CI, 1.016-3.048; P = .0439), prior history of coronary artery bypass grafting (HR, 1.702; 95% CI, 1.080-2.683; P = .0221), and lower baseline activity quality of life score (HR, 1.401; 95% CI, 1.105-1.778; P = .0054). Postoperative wound factors included gangrenous changes (HR, 5.830; 95% CI, 1.647-20.635; P = .0063), surgical wound necrosis (HR, 5.319; 95% CI, 1.478-19.146; P = .0105), deep (vs superficial) wound infection (HR, 3.815; 95% CI, 1.220-11.927; P = .0213), and wound healing abnormally (HR, 3.754; 95% CI, 1.061-13.278; P = .0402). Associated postoperative consequences leading to PMA included having recurrent CLI symptoms (HR, 2.915; 95% CI, 1.816-4.681; P < .0001), a severe (vs mild) adverse event (HR, 2.751; 95% CI, 1.391-5.443; P = .0036), fewer percutaneous revisions (HR, 2.425; 95% CI, 1.573-3.740; P < .0001), discharge on low-molecular-weight heparin (HR, 2.087; 95% CI, 1.309-3.326; P = .0020), and decreasing days to critical stenosis/occlusion/revision/amputation (HR, 1.010; 95% CI, 1.007-1.012; P < .0001).
Conclusions:
Whereas a patent vein graft is important to all vascular surgeons, additional factors should be considered in trying to attain limb salvage for patients with CLI. These factors include intervening surgically before CLI has progressed to a state of gangrene or limited activity and optimizing nutrition, diabetes control, cardiac conditions, and activity level. Revision offers hope for clinical improvement but may be delayed when there is no graft lesion identified. The absence of a graft lesion to revise may also portend amputation despite a patent graft because of nongraft-related factors such as infection. Finally, the experience of a severe (vs mild) adverse event may also result in limb loss despite a patent graft. Systematic efforts to reduce severe adverse events among patients may also lead to increased limb salvage.
