Critical limb ischemia
Limb ischemia can be classified as acute and chronic. The diagnostic work-up in acute ischemia must be performed promptly, and most cases require immediate revascularization. Chronic critical limb ischemia is the most severe type of peripheral arterial disease (PAD). It is characterized by rest pain and necrosis or gangrene.
Acute limb ischemia ("ALI") refers to acute limb perfusion with acute onset and not older than 2 weeks. It is usually caused by embolization or local thrombosis secondary to preexisting pathology such as PAD.
Chronic limb ischemia ("CLI") refers to rest pain or ischemic skin lesions such as ulcers or gangrene (Fontaine stages III and IV and Rutherford categories 4-6). It is closely associated with cerebrovascular and cardiovascular events. Chronicity is defined as symptoms persisting for more than 2 weeks.
TASC II criteria
The TASC II (Transatlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease) consensus document addresses aspects of revascularization in PAD [1]. The TASC criteria recommend therapeutic treatment options depending on the length of the local occlusion/stenosis. The length of the stenosis and its regional location determine the treatment: endovascular or open vascular surgery.
TASC II classification of aortoiliac lesions:
Type | Morphology | Procedure |
A | Unilateral or bilateral stenosis of CIA; unilateral or bilateral single short (<3 cm) stenosis of EIA | Endovascular |
B | Short (≤3 cm) stenosis of infrarenal aorta; unilateral CIA occlusion; single or multiple stenosis totalling 3–10 cm involving the EIA, not extending into the CFA; unilateral EIA occlusion not involving the origins of IIA or CFA | Endovascular |
C | Bilateral CIA occlusion; bilateral stenoses 3–10 cm long, not extending into CFA; unilateral EIA stenosis extending into the CFA; unilateral EIA occlusion involving the origins of IIA and/or CFA; heavily calcified unilateral EIA occlusion with/without involvement of origins of IIA and/or CFA | Open revascularization |
D | Infrarenal aortoiliac occlusion; diffuse disease involving the aorta and both iliac arteries requiring treatment; diffuse multiple stenoses involving the unilateral CIA, EIA, and CFA; unilateral occlusions of both CIA and EIA; bilateral occlusions of EIA; iliac stenoses in patients with AAA requiring treatment and not amenable to endograft placement; or other lesions requiring open aortic or iliac surgery | Open revascularization |
There are no recommended morphologic characterizations of the infrapopliteal segments.
Guidelines
The S3 guideline of the German Society of Angiology/Society of Vascular Medicine on the diagnosis, treatment, and follow-up of PAD includes the following remarks on CLI [2]:
- Paramount in CLI is rapid and adequate revascularization regardless of the treatment modalities employed.
- In multilevel lesions, elimination of run-in obstructions takes priority over treatment of run-off lesions.
- In CLI, run-in, and subsequent run-off, lesions should be treated by intervention whenever possible.
- A combination of open surgical procedures and intraoperative endovascular treatment is useful in the presence of simultaneous high-grade stenoses or occlusions of the common femoral artery, deep femoral artery, and lesions in the aortoiliac inflow axis and/or the femoropopliteal run-off (hybrid procedure).
- Preference should be given to endovascular treatment if the angiomorphologic findings suggest that a technical outcome comparable to that of open surgery can be achieved.
- If the comparable surgical procedure poses a higher surgical risk because of comorbidity, preference should be given to endovascular intervention.
- The primary technique in the treatment of femoropopliteal lesions should be endovascular. In TASC II D settings with no increased risk of surgery, no significantly limited life expectancy, and available autologous vein, preference should be given to bypass procedures.
- Popliteal artery lesions should primarily undergo balloon angioplasty.
- In patients with critical ischemia, infrapopliteal vascular lesions should primarily undergo endovascular treatment. Vascular surgical procedures may be considered if the surgical risk is acceptable and autologous vein is available.
For patients with CI and CLI, the recommendations of the European Society of Cardiology (ESC) in collaboration with the European Society for Vascular Surgery (ESVS) include [3]:
1. Revascularization in aortoiliac occlusion
- In short lesions (<5 cm), the recommended initial strategy is endovascular.
- In aortoiliac occlusion, aorto-(bi)-femoral bypass should be considered if patients are fit enough for surgery.
- In patients with severe comorbidity and extended and/or bilateral occlusions, endovascular management should be considered.
- In aortoiliac lesions, the initial measure can be endovascular if expertise is available and provided that this does not compromise subsequent open surgery options.
- In aortic occlusion extending to the renal arteries, open surgery should be considered if the patient is fit enough.
- Iliofemoral occlusions may warrant consideration for a hybrid procedure – iliac stenting plus femoral endarterectomy or bypass.
- In the absence of alternatives to revascularization, extraanatomic bypass may be an option.
- Primary stenting should be considered a temporary rather than final measure.
2. Revascularization in femoropopliteal occlusion
- Primary endovascular revascularization is recommended in short (<25 cm) occlusions.
- Primary stenting and drug-eluting balloons may be an option in short lesions (<25 cm).
- Drug-eluting balloons may be considered for the treatment of in-stent restenosis.
- Bypass surgery is indicated in long (≥ 25 cm) lesions of the superficial femoral artery, provided that patients are not at high risk for surgery, autologous vein is available, and life expectancy is greater than 2 years. For patients not fit enough for surgery, endovascular treatment may be an option.
- Autologous saphenous vein is the bypass material of choice in femoropopliteal bypass.
Below are some of the recommendations issued by the American College of Cardiology (ACC) and the American Heart Association/AHA) for CLI patients [4]:
- In patients with CLI revascularization should be performed whenever possible to minimize tissue loss.
- An assessment of revascularization options should be performed by an interdisciplinary care team before amputation in the patient with CLI.
1. Endovascular revascularization
- Endovascular interventions are recommended to restore perfusion to the foot in patients with nonhealing wounds or gangrene. A staged approach to endovascular procedures is recommended in ischemic rest pain.
- Angiosome-guided endovascular treatment may be an option in patients with CLI and nonhealing wounds or gangrene.
2. Surgical revascularization
- A planned bypass to the popliteal or infrapopliteal arteries should be performed with an autologous vein.
- Surgical procedures are recommended to restore perfusion to the foot in patients with nonhealing wounds or gangrene.
- If endovascular treatment fails and no suitable autologous vein is available, a synthetic graft may be employed.
- A staged approach to open surgical procedures is recommended in ischemic rest pain.
Outcomes
1. Percutaneous intervention vs bypass surgery in CLI
The largest meta-analysis to date on this topic includes over 45 studies totaling nearly 21,000 patients and dates from 2018 [5]. Comparison of endovascular revascularization (ER) with open bypass surgery (OR) revealed:
- ER reduced the risk of 30-day mortality, major adverse cardio-/cerebrovascular events, and wound infections, but increased the risk of long-term mortality and failure of primary patency.
- Compared with autologous bypass, ER also performed worse in secondary patency and was more likely in the long run to result in amputations.
The authors of this meta-analysis concluded that OR was the better choice for patients in good general health and with rather long life expectancy, in particular when autologous bypass material was employed.
A 2017 Cochrane Review compared the efficacy of bypass surgery in chronic ischemia with other interventions (PTA; endarterectomy; thromboendarterectomy; thrombolysis; exercise; and spinal cord stimulation) [6]:
- The bypass vs. PTA comparison revealed that bypasses suffered more frequently from nonthrombotic complications, but were associated with higher technical success rates.
- One year post intervention, primary patency was higher in the bypass group than after PTA; four years later, no difference was seen.
- The bypass and PTA groups did not differ in terms of mortality; clinical improvement; amputation rate; and revision/reintervention rate.
The authors concluded that high-quality evidence regarding the efficacy of bypass surgery compared with other treatment modalities was limited.
2. Sex-specific differences in lower limb revascularization outcomes
A systematic review with meta-analysis studied the impact of sex on lower limb revascularization outcome [7]. Forty studies were included; 15 studies reported outcomes following OR, 19 following ER, and the remainder included hybrid procedures:
- Women had significantly higher 30-day rates for mortality; amputation; early graft thrombosis; embolization; access site complications; and general complications (cardiopulmonary, cerebral) compared with men.
- No differences were found with respect to reinterventions and renal complications.
- On analyzing the OR and ER outcomes, the increased risk of postoperative mortality and complications in women remained. However, no significant differences were found between men and women in long-term outcomes.
Among the reasons for the less favorable outcomes in women, the authors attributed patient age (women were older than men at intervention) and undertreatment of women with antiplatelets, statins, and cardiovascular medications compared with men.
3. Angiosome-guided revascularization in CLI
An angiosome is an area of skin and underlying tissues vascularized by a source artery. There are 6 such arteries in the human foot (medial and lateral plantar arteries; calcaneal branch of posterior tibial artery; lateral and medial branches of fibular artery; dorsal artery of foot). It is thought that the rate of wound healing can be improved by direct revascularization, i.e., by placing a bypass on a segment directly supplying the angiosome.
There is one systematic review with meta-analysis on angiosome-guided revascularization in CLI from 2017 that includes nearly 4000 patients [8]. Compared with indirect revascularization (IR), direct revascularization (DR) significantly improved wound healing, major amputation rate, and amputation-free survival. However, in a sensitivity analysis, the significance for the major-amputation rate in bypass surgery was lost, and IR and DR did not differ with respect to overall survival.
The authors concluded that their analysis supported the angiosome concept, at least in endovascular treatment. Once collateral vessels were present, the outcomes of ER versus IR were similar, suggesting that patients without collaterals were most likely to benefit from DR, thus making the angiosome concept less useful in bypass surgery.