Educational disclaimer. This article is for clinician and student education. It is not medical advice, does not establish a clinician–patient relationship, and does not replace individualized assessment by a licensed vascular surgeon, interventional cardiologist, or multidisciplinary limb-salvage team. Treatment thresholds, device choices, and antithrombotic regimens evolve; consult the current versions of the Global Vascular Guidelines, the 2024 ACC/AHA Lower Extremity PAD Guideline, the ESVS guidelines, and the IWGDF guidelines before clinical decision-making.
Chronic Limb-Threatening Ischemia
Introduction
The first reversed autogenous femoropopliteal vein graft was performed by Jean Kunlin in 1949, and direct arterial reconstruction has since become the cornerstone of lower-extremity revascularization. In the decades that followed, the field was transformed by endovascular techniques, drug-eluting and drug-coated devices, refined patient selection, and the emergence of best medical therapy that reduces both limb and cardiovascular events.
The condition previously labeled “critical ischaemia” or “critical limb ischemia” is now called chronic limb-threatening ischemia (CLTI) in the Global Vascular Guidelines (Conte et al., 2019) and the 2024 ACC/AHA Lower Extremity Peripheral Artery Disease Guideline (Gornik et al., 2024). CLTI is defined as ischemic rest pain lasting at least two weeks or tissue loss (ulcer or gangrene) attributable to objectively documented arterial occlusive disease. CLTI is staged with the Society for Vascular Surgery WIfI (Wound, Ischemia, foot Infection) limb-threat classification (Mills et al., J Vasc Surg) and the Global Limb Anatomic Staging System (GLASS) (Conte et al., GLASS).
This article presents a historical case of severe lower-extremity ischemia treated with reversed saphenous vein femoro-tibial bypass, and uses it as a starting point to discuss the contemporary diagnosis and management of CLTI.
Case report
The case below is historical. Its modern equivalent follows.
This 72 year-old gentleman, G.G., presented with a four-month history of pain in the left leg. The pain was initially intermittent, precipitated by walking, but subsequently became constant and worst at night. He also claimed that his left foot felt cold. He had essential hypertension and ischaemic heart disease and was maintained on antihypertensive and anti-cardiac-failure therapy.
On physical examination he had an irregular pulse of 80/min and a blood pressure of 140/70 mmHg. His heart sounds, chest and abdomen were normal. His left lower limb felt cool below the knee and his left leg had a 5 cm diameter arterial gangrenous patch (Fig 1) over its lower half. His left femoral pulse was palpable but his left popliteal and ankle pulses were not. All right lower limb pulses were palpable although his right foot felt cool.
Fig 1: Arterial leg ulcer
His investigations were:
| Test | Result | Unit | Test | Result | Unit | |
|---|---|---|---|---|---|---|
| Hb | 12.3 | gm/dL | WBC | 7.0×10⁹ | /L | |
| Na | 139 | mmol/L | K | 4.2 | mmol/L | |
| Cl | 104 | mmol/L | HCO3 | 23 | mmol/L | |
| Urea | 10.0 | mmol/L | Creat | 160 | μmol/L | |
| Gluc | 6.9 | mmol/L |
| Test | Result | Control | Unit |
|---|---|---|---|
| PT | 13.7 | 13.7 | sec) |
| PTT | 24.7 | 34.0 | sec) |
Platelet count was normal. Chest radiograph showed an enlarged heart while electrocardiogram showed changes of left ventricular strain and a healed anterior infarction. Arteriogram revealed a left femoral artery with irregular atheromatous areas, occlusion at mid thigh and reconstitution distally. The popliteal artery and its branches had atheromatous changes. Preoperative ankle-brachial pressure index was 0.6.
The patient was on digoxin, benzdrofluazide and potassium supplements. He was given prophylactic antibiotics and had an autogenous reversed saphenous vein femoro-tibial by-pass. Immediately postoperatively, he was bleeding from the incision and was returned to the operating room where an untied saphenous vein tributary was sutured. He had prophylactic heparin and developed a 4 cm diameter wound haematoma which was managed expectantly. His ankle-brachial pressure index was 0.92 and he was walking with assistance when discharged on postoperative day 15. At home his drug compliance was poor and consequently he developed cardiac failure. Nevertheless, his ischaemic leg ulcer healed. Eight months postoperatively, he was treated for heart failure but when seen one year and four months after surgery, he had no complaint.
Modern equivalent
A patient presenting today with rest pain, a 5 cm gangrenous lower-leg patch, absent popliteal/ankle pulses, ABI 0.6, and ischemic heart disease and hypertension would be admitted for urgent multidisciplinary CLTI care. Initial workup would include ABI plus toe-brachial index (or toe pressure / TcPO₂ in calcified vessels), duplex ultrasound followed by CT angiography or MR angiography of the entire inflow-to-outflow tree, and structured WIfI staging at the bedside (in this case, broadly W2–3 / I2 / fI dependent on infection) (Conte et al. 2019; 2024 ACC/AHA PAD Guideline; Endovascular Today, 2025).
Revascularization choice is informed by GLASS anatomy and conduit availability. If a suitable single-segment great saphenous vein (≥3 mm) is present, surgical bypass is preferred for most CLTI patients with infrapopliteal disease based on BEST-CLI cohort 1 (Farber et al., NEJM 2022). If no suitable vein is available, endovascular-first is reasonable based on BEST-CLI cohort 2 and BASIL-2 (Bradbury et al., Lancet 2023; ACC review of BEST-CLI and BASIL-2, 2024).
Best medical therapy starts on day one and continues lifelong: high-intensity statin, aspirin 81 mg daily plus rivaroxaban 2.5 mg twice daily after revascularization (VOYAGER PAD), BP control 25% in WIfI Stage 4** (Mills et al., WIfI).
– In BEST-CLI cohort 1 (patients with adequate single-segment great saphenous vein), surgical bypass achieved an approximately 71% amputation-free survival at 2 years, superior to best endovascular therapy in the same cohort (Farber et al., NEJM 2022).
– Primary major amputation remains appropriate for non-ambulatory patients with non-healable wounds, end-stage comorbidities, or anatomy that cannot be revascularized; thoughtful counseling about quality of life and prosthetic rehabilitation is essential.
Cost-effectiveness analyses of contemporary CLTI care consistently favor revascularization plus best medical therapy over primary amputation when revascularization is technically feasible (Conte et al. 2019).
3. Investigation
Workup is risk-stratified and non-invasive when possible.
Bedside hemodynamics
- Ankle-brachial index (ABI) is the first-line screening test; an ABI ≤0.90 is diagnostic of PAD. In CLTI, ABI is often <0.4 or unmeasurable.
- Toe-brachial index (TBI) or toe pressure is required when ABI is non-compressible (commonly in diabetes mellitus or chronic kidney disease). Toe pressure <30 mmHg or TcPO₂ <30 mmHg supports CLTI (Conte et al. 2019).
- Transcutaneous oxygen pressure (TcPO₂) and skin perfusion pressure are useful where available, particularly for wound healing prognosis.
Anatomic imaging
- Duplex ultrasound is the first-line anatomic test; it can map the entire arterial tree including pedal vessels in experienced labs.
- CT angiography is widely used for whole-tree mapping; in patients with renal disease, MR angiography (or non-contrast techniques) is an alternative.
- Diagnostic catheter-based digital subtraction angiography is reserved for cases in which non-invasive imaging is non-diagnostic or as the first step of an intended endovascular procedure (2024 ACC/AHA PAD Guideline; Endovascular Today, 2025).
4. Best medical therapy
Best medical therapy is the foundation that supports any revascularization strategy and continues lifelong. For all patients with CLTI (2024 ACC/AHA PAD Guideline):
- Statin: high-intensity statin (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) for LDL-C lowering; consider adding ezetimibe or PCSK9 inhibitor to achieve LDL-C goals.
- Antiplatelet therapy: single antiplatelet therapy with aspirin 81 mg daily for symptomatic PAD; clopidogrel 75 mg daily is a reasonable alternative and is often preferred after prosthetic infrainguinal bypass.
- Rivaroxaban 2.5 mg twice daily plus aspirin 81 mg after lower-extremity revascularization for PAD reduces major adverse limb and cardiovascular events versus aspirin alone, with a modest increase in bleeding (Bonaca et al., VOYAGER PAD, NEJM 2020; VOYAGER 2025 net outcomes update).
- Blood pressure control to 2.0–3.5 depending on lab criteria) defining hemodynamically significant stenosis. Pre-emptive treatment with vein patch angioplasty, segmental vein revision, or endovascular angioplasty/stenting preserves assisted-primary patency in approximately 60–80% at 5 years and reduces the risk of graft thrombosis and limb loss (Conte et al. 2019; 2024 ACC/AHA PAD Guideline).
Graft failure
Early graft failure (<30 days) is most often technical (anastomotic stenosis, kinks, retained valve cusps, thrombus, intimal flap) or systemic (low cardiac output, hypercoagulability, inadequate anticoagulation). Late failure is most often hemodynamic, from neointimal hyperplasia, progression of inflow or outflow disease, or graft degeneration. Immediate exploration is indicated for an acutely failed graft when limb viability is threatened.
Conclusion
The patient with chronic limb-threatening ischemia today benefits from a multidisciplinary, risk-stratified pathway that combines aggressive best medical therapy with the appropriate revascularization strategy: surgical bypass when single-segment great saphenous vein is available, endovascular-first when it is not, and team-based judgment guided by BEST-CLI, BASIL-2, and the Global Vascular Guidelines. Lifelong surveillance and risk factor control preserve the limb and reduce cardiovascular events well after the operation is over.
References
American College of Cardiology. "Lessons Learned From the BEST-CLI and BASIL-2 Trials." ACC.org, March 26, 2024. Link: https://www.acc.org/latest-in-cardiology/articles/2024/03/26/11/50/lessons-learned-from-the-best-cli-and-basil-2-trials.
American College of Cardiology. "2024 ACC/AHA/Multisociety Guideline for Lower Extremity Peripheral Artery Disease: Ten Points to Remember." ACC.org, May 14, 2024. Link: https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2024/05/09/15/00/2024-guideline-for-lower-extremity-pad.
Armstrong, Ehrin J., et al. "A Modern Day Perspective on Smoking in Peripheral Artery Disease." PMC, 2023. Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC10175606/.
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Bradbury, Andrew W., Catherine A. Moakes, Matthew Popplewell, et al. "A Vein Bypass First Versus a Best Endovascular Treatment First Revascularisation Strategy for Patients with Chronic Limb Threatening Ischaemia Who Required an Infra-popliteal, with or without an Additional More Proximal Infra-inguinal Revascularisation Procedure to Restore Limb Perfusion (BASIL-2)." The Lancet 401, no. 10390 (2023): 1798–1809. Link: https://pubmed.ncbi.nlm.nih.gov/37778500/.
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Endovascular Today. "CLTI Imaging: What's New and What's Next?" Endovascular Today, May 2025. Link: https://evtoday.com/articles/2025-may/clti-imaging-whats-new-and-whats-next.
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