CRITICAL LIMB ISCHEMIA

Limb-threatening ischemia or newly defined critical limb ischemia (CLI) occurs when arterial blood flow is insufficient to meet the metabolic demands of resting muscle or tissue. It has been estimated that limb-threatening ischemia occurs in 1 to 2% of patients with PAD who are 50 years of age or older (2, 3).

According to the 2007 TASC II guidelines and those of the ACC/AHA published in 2006, a sudden decrease in limb perfusion that causes a potential threat to limb viability (manifested by ischemic rest pain, ischemic ulcers, and/or gangrene) in patients who present within two weeks of the acute event is definined as an acute limb ischemia (2, 3). Patients with similar manifestations who present later than two weeks are considered to have critical limb ischemia, which is by definition chronic.

The natural history of CLI usually involves inexorable progression to amputation unless there is an intervention that results in the improvement of arterial perfusion. This is in contrast to the often benign natural history of mild and moderate claudication.

Critical limb ischemia is defined as limb pain that occurs at rest or impending limb loss that is caused by severe compromise of blood flow to the affected extremity. The term “critical limb ischemia”

should be used for all patients with chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease.

Unlike individuals with claudication, patients with CLI have resting perfusion that is inadequate to sustain viability in the distal tissue bed. Although it may be challenging at times to ascertain the limb prognosis in patients presenting with lower extremity ischemic rest pain, ulceration, or gangrene, CLI is defined de facto by most vascular clinicians as that pathology in which the untreated natural history would lead to major limb amputation within 6 months.

Critical limb ischemia is usually caused by obstructive atherosclerotic arterial disease; however, it can also be caused by atheroembolic or thromboembolic disease, vasculitis, in situ thrombosis related to hypercoagulable states, thromboangiitis obliterans, cystic adventitial disease, popliteal entrapment, or trauma.

Factors that can contribute to the development or exacerbation of CLI include syndromes that are known to reduce blood flow to the microvascular bed, such as diabetes, severe low cardiac output

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states, severe renal failure and, rarely, vasospastic diseases (e.g., Raynaud’s phenomenon, cold exposure). Other conditions that accelerate or compound CLI include those in which demand for blood and nutrient supply is increased markedly, such as infection, skin breakdown, or traumatic injury (2)

Atherosclerotic arterial occlusive disease that precipitates CLI is most often diffuse or

multisegmental, involving more than one arterial anatomic “level.” Frequently, because of the systemic nature of the atherosclerotic process and a predilection for symmetrical disease, the contralateral limb may also be affected by ischemic symptoms and may also demonstrate objective signs of ischemia on examination.

Patients with CLI present with a spectrum of clinical manifestations, depending on the degree of ischemia and the time course of its development. The Rutherford or the Fontaine clinical categories (described previously) are used to classify the degree of ischemia and salvageability of the limb.

Critical limb ischemia is associated with a very high mid-term morbidity and mortality. Patients with lower extremity PAD have a 3 to 5 times overall greater risk of cardiovascular mortality than those without this disease. Those with more advanced lower extremity PAD, as manifested by CLI, have even greater risk of experiencing cardiovascular ischemic events (15, 47, 256). Thus, care strategies for individuals with CLI must recognize the cardiovascular ischemic burden. Ideal care strategies for individuals with CLI will therefore include recognition of the possibility of severe coronary artery disease, cerebral vascular disease, or aortic aneurysmal disease and include the impact of these illnesses on patient outcomes with or without specific CLI interventions.

In addition, such long-term integrated care plans will offer risk factor modification for secondary prevention of cardiovascular ischemic events, to maximize the possibility of achieving an improved long-term morbidity and mortality (62).

6.0.1 Predictors of developing CLI

In addition to the classical cardiovascular risk factors, several other clinical predictors should be considered by evaluating the risk of developing a CLI. The severity of the PAD, in terms of decreased ABI, as well as the age of the patient are important co-factors by determinating the risk of a future CLI.

However, the most powerfull predictor of developing of a CLI remains the presence of diabetes, and especially that insulin-dependent (Figure 42).

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Figure 42: magnitude of the effect of risk factors on the development of CLI [reproduced from the TASC II Guidelines (2)]

6.0.2 Prognosis of the Limb

The prognosis of the limb is determined by the extent of arterial disease, the acuity of limb ischemia, and the feasibility and rapidity of restoring arterial circulation to the foot. For the patient with chronic arterial occlusive disease and continued progression of symptoms to CLI (e.g., development of new wounds, rest pain, or gangrene), the prognosis is very poor unless revascularization can be established.

Few studies of the natural history of PAD have been performed to objectively quantify disease progression. Claudication symptoms usually remain stable and do not worsen or improve at rapid rates (56). The temporal progression of symptoms across arterial beds in patients with known atherosclerotic disease has also been studied on a limited basis (57).

According to the initial clinical findings, as well as the degree of the arterial compromise only 50% of the patients presenting with a CLI undergo a revascularization attempt (either percutaneous or

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surgical). Indeed, due to the associated co-morbidities and the extent of the arterial disease 25% of these patients are managed with a conservative attitude, which propose a medical treatment only, while the remaining 25% of the patients are managed with a primary amputation approach without any revascularization attempt (Figure 43).

In this CLI patients group, the one year outcomes are characterized by the occurrence of an up to 25% of mortality, mostly secondary to cardiovascular events. Thirty percent of these patients had undergo different degree of amputation, ranging from the minor ones (i.e. toes and for-foot

amputations) to the major ones (including below and above the knee amputations). Finally, the remaining 45% pf the patients are further divided into those in whom the CLI has resolved (25%) and those still presenting a persistent CLI (i.e. non-healing ulcer) (Figure 43).

Figure 43: Fate of the patients presenting with chronic CLI [reproduced from the TASC II Guidelines (2)]

6.0.3 Lower Limb Amputations

Once the patient undergoes a major amputation, he/she remains at increased risk of different cardiovascular events. Accordingly, the peri-operative mortality rate may be as high as up to 10%, and this is probably related to the fact that >50% of the performed amputations occur in the elderly (i.e.>

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80 years old). Once over-pass the peri-operative phase, patients may present a sufficient wound healing process in up to 75% of the cases (i.e. 60% primary healing, 15% secondary healing), while the remaing 15% of the amputated patients, do not present a satisfactory cicatrization of the wound and thus they have to undergo several additional interventions (i.e. above the knee amputation) (Figure 44).

At two years, outcomes are even worse, if one considers that up to 1/3 of the patients died and that only 40% of these amputated patients regain a full mobility.

Figure 44: fate of the patients with a below the knee amputation [reproduced from the TASC II Guidelines (2)]

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