A. Rutherford classification

The Rutherford classification is commonly used and incorporates all these clinical forms of PAD into six categories: 0 = asymptomatic; 1–3 = claudication; 4–6 = critical limb ischemia, with 4 = rest pain; 5 = minor tissue loss/skin loss at the digits; 6 = major tissue loss with gangrene.

B. Critical limb ischemia (CLI)

CLI is defined as one of the following (in order of increasing severity): ischemic rest pain, non-healing ulcer, or extensive ulceration with gangrene. CLI is a chronic process that progresses over weeks or months and should be distinguished from acute limb ischemia (Table 19.2). Traditionally, CLI occurs in patients with ABI ≤ 0.4, ankle pressure <50 mmHg, or toe pressure <30 mmHg. However, multiple studies have shown that up to 30% of patients with CLI have normal ABI, 15% of them have elevated ABI, and most have ABI in the mild-to-moderate rather than severe range.16 ABI commonly underestimates the severity of PAD in CLI patients with predominantly infrapopliteal disease. This is related to the fact that tibial arteries are partially non-compressible (creating a falsely normal or elevated tibial pressure), but also to the fact that a substantial proportion of CLI patients have significant pedal/below-ankle disease, sometimes with a “desert” foot (narrow or occluded plantar and metatarsal arteries). Toe-brachial index (TBI) is more reliable than ABI in CLI patients and should be systematically measured in this context. The clinical features of the wound and the low TBI suggest the need for angiography in patients with normal ABI.

Ischemic rest pain is typically a nocturnal pain that forces the patient to wake up and dangle his legs. On physical exam, CLI is characterized by a cool, dry, and fissured skin, lack of hair, dystrophic thick toenails, lack of superficial veins (flat skin), calf atrophy, and dependent rubor cyanosis. Ulcers often occur distally at the toe level and at pressure and friction points (between toes), or at the lateral malleolus level (Table 19.3). An ulcer occurring at another location for another reason may not heal if ischemia is present (mixed ulcer). Dependent rubor is an important marker of rest ischemia. To test for dependent rubor, raise the leg for 30–60 seconds, observe for pallor, then let it down and see how it slowly fills with a dusky red color suggestive of CLI, rather than quickly fills with a normal pink color.

CLI is associated with a 25% mortality risk at 1 year and a 25% amputation rate, with only 50% amputation-free survival at 1 year. Amputation is required in patients who cannot be revascularized or who present at a stage of deep necrosis. Amputation is associated with the highest mortality (40% at 2 years).

C. Acute limb ischemia (ALI) and acute compartment syndrome

Acute limb ischemia is rest ischemia that develops over hours, sometimes days (occasionally weeks, generally <14 days), and is usually due to: (i) acute embolization from a cardiac or aortic origin (30% of cases), (ii) acute thrombosis of an underlying atherosclerotic stenosis or popliteal aneurysm (60% of cases), (iii) thrombosis in situ from a hypercoagulable state or traumatic injury/dissection, or (iv) graft thrombosis, which mainly occurs when there is obstructive disease at the inflow or outflow of the graft (e.g., disease progression in the common femoral or profunda past an aortofemoral graft; early or late anastomotic stenosis). Regardless of the underlying process, multiple distal emboli are characteristic of ALI. Acute thrombosis generally manifests less severely and less abruptly than acute embolization (days or weeks), as it occurs on top of chronic disease and pre-existing collaterals.

As opposed to ALI, CLI and non-healing ulcers are due to severe progressive atherosclerosis, frequently with some amount of thrombus, and develop over weeks or months (Table 19.2). CLI generally requires revascularization soon (days or 1 week), but not emergently. In ALI, the abrupt occlusion does not allow for the development of robust collaterals, which explains how ALI can lead to limb loss within a few hours (6 hours), dictating emergent reperfusion. In addition, distal embolization is universal in ALI and further accelerates tissue loss. Distal pulses are usually audible on Doppler exam in CLI, but often not in ALI.

CLI progresses at a much slower rate than ALI yet provokes tissue loss and ischemic ulcers at a relatively earlier stage. ALI has the following progression:

• Stage 1. Rest pain with audible, monophasic distal pulses by Doppler.
  
• Stage 2. Very distal sensory loss with inaudible distal pulses by Doppler (“limb threatened”). The skin is initially “marble” white, then becomes dark purple and mottled as it fills with deoxygenated, stagnant blood.
  
• Stage 3. Sensory loss beyond toe level or moderate motor loss (“limb immediately threatened”).
  
• Stage 4. Profound paralysis and/or major tissue loss (irreversible necrosis of muscles and skin).

Stage 1 dictates urgent revascularization, while stages 2 and 3 dictate emergent revascularization. Stage 4 requires early amputation, followed by revascularization to allow healing of the wound and the remaining viable tissue, limiting the need for a more extensive amputation in the future.

In ALI, stages 1 and 2 may be treated with a local thrombolytic infusion (12–48 hours) delivered through an endovascular approach. After the extensive thrombus burden and emboli are attenuated with thrombolysis, attention is turned towards the endovascular or surgical therapy of underlying/residual stenoses. For stage 3 ALI (motor loss or extensive sensory loss), ischemia needs to be emergently improved and one cannot wait 12–24 hours for thrombolysis to be effective. Surgical revascularization, if feasible, may need to be emergently performed at stage 3; moreover, at this stage, patients have a high risk of reperfusion injury and compartment syndrome and often need prophylactic fasciotomy during surgical revascularization.

D. Atheroembolization

Atheroembolization is embolization of atheromatous cholesterol debris rather than thrombi, and is therefore different from ALI. It typically occurs after angiography or aortic surgery that sloughs off aortic atherosclerotic debris and leads to cholesterol embolization in the small vessels of the kidneys, dermis, lower extremities, and gastrointestinal tract. Yet, ~50% of the cases are spontaneous. Atheroembolism often induces progressive renal failure that develops a week or more after the procedure and is frequently irreversible. It leads to livedo reticularis, “blue toes,” and distal cyanosis or gangrene despite preserved distal pulses, as the ischemia is due to small vessel occlusion. Obstructive PAD may, however, be present and may reduce distal pulses, yet the ischemic findings are generally disproportionate to PAD and ABI. No specific therapy is provided; limb ischemia often improves spontaneously in patients without a severely obstructive underlying PAD. Revascularization may be required in patients with severe PAD to allow healing, but invasive manipulations are better avoided in patients with only mild PAD, as these manipulations may induce further embolization. The role of anticoagulation is unclear (some data suggest benefit while other data suggest harm).

A. Ankle–brachial index (ABI)

ABI has two purposes: (i) diagnosis of obstructive PAD and its severity; (ii) cardiovascular prognosis (the risk of death/MI of patients with a low ABI approximates or exceeds the risk of patients with CAD) (Table 19.4). If PAD is suspected in a symptomatic patient with an abnormal pulse exam, ABI is first performed, followed by a lower extremity arterial Doppler study if revascularization is considered.

Asymptomatic patients at a high risk of PAD need to be screened with ABI only, particularly if the pulse exam is abnormal (age >65, age 50–70 with diabetes or smoking). A low ABI correlates with increased mortality and dictates more aggressive medical therapy, but not further workup and revascularization, per se.

To calculate ABI, posterior tibial (PT) and anterior tibial (AT) pressures are measured using a well-sized BP cuff and a Doppler stethoscope, then the highest of these pressures is divided by the highest arm pressure.¹ ABI testing is ~85% sensitive and 100% specific for angiographically confirmed PAD.¹ ABI has the following three pitfalls: (i) ABI may be normal or falsely elevated in calcified, poorly compressible vessels; these vessels are not compressible even if the pressure and flow inside them are low (elderly, longstanding diabetes, or CKD); (ii) ABI may be normal at rest if sufficient collaterals are present; (iii) ABI may also be normal at rest in symptomatic patients with moderate aortoiliac stenoses.

Thus, when ABI is normal at rest but pitfall (ii) or (iii) is suspected, exercise ABI or an arterial Doppler study should be obtained. During exercise, peripheral vasodilatation occurs; a flow-limiting stenosis prevents blood flow from increasing enough to fill the dilated distal vascular space, and thus the distal pressure paradoxically decreases. This process translates into a low exertional ABI (ABI drops ≥ 20%, or >0.2) and explains how DP and PT pulses that are weak but palpable before exercise may become non-palpable after exercise. In fact, post-exertional pulse exam is valuable in the assessment of the PAD patient with only mild pulse abnormality.

B. Ultrasound and Doppler study

A Doppler study is over 95% sensitive and specific for the diagnosis of obstructive stenoses. It is only indicated in patients with severe symptoms who qualify for angiography and revascularization (class I indication). It allows localization of the disease and planning for a potential peripheral intervention. A stenosis is characterized by a focal increase in velocity (>250 cm/s, or >2.5:1 in comparison to the proximal segment), and by a monophasic flow distal to the stenosis (Figure 19.1).

D. CT angiography (CTA)

CTA is particularly helpful when aortoiliac disease is suspected with absent femoral pulses, in which case CTA delineates the disease and allows the planning of a peripheral intervention. CTA has several pitfalls: (i) it may not properly delineate infrapopliteal disease; (ii) heavy calcifications may preclude accurate assessment of the severity of disease; (iii) additional radiation and contrast is used before the eventual angiography or intervention. While a Doppler study has a class I indication before performing angiography, CTA has a class IIb indication.

E. Peripheral angiography is only performed when revascularization is indicated.