The evaluation of a patient with PAD begins with a detailed history and careful physical examination. Although patients with PAD may report limitations in exercise performance and walking ability, the 2005 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on PAD suggest that only 10–35 % of patients present with classic claudication symptoms (Fig. 7.1) [2]. Less than 3 % of patients present with symptoms of CLI. Instead, the majority of patients with PAD are either asymptomatic or complain of atypical leg pain at initial clinical presentation. An estimated 5–10 % of patients with asymptomatic PAD or claudication will progress to CLI within 5 years.

Identification of risk factors for PAD can aid in distinguishing symptoms of PAD from other less common causes of lower extremity ischemia such as radiation fibrosis, fibromuscular dysplasia, popliteal entrapment, vasculitis, and adventitial cystic disease. Non-arterial and nonvascular pathologies should also be considered in the differential diagnosis of lower extremity discomfort, including deep venous thrombosis, peripheral neuropathy, spinal stenosis, and musculoskeletal disorders. Because atherosclerosis is a systemic disease, the risk factors for PAD mirror those of coronary artery disease. In patients with a history of hypertension, tobacco use, diabetes mellitus, chronic renal failure, and dyslipidemia, PAD is more likely to be the underlying cause of their lower extremity complaints [6–9]. The 2005 ACC/AHA guidelines also identified the following groups to be at increased risk for lower extremity PAD: age ≥70 years, age 50–69 years with a history of smoking or diabetes, and age 40–49 with diabetes and at least one additional risk factor for atherosclerosis, leg symptoms suggestive of claudication with exertion or ischemic pain at rest, abnormal lower extremity pulse examination, and those patients with known atherosclerosis at other anatomic sites (e.g., coronary, carotid, or renal artery disease) [2].

Clinical findings consistent with PAD include cool temperature of the leg, absent or diminished pulses in the legs or feet, thin or shiny appearance of the skin, hair loss, nonhealing wounds or gangrene, pallor with elevation of the extremity, dependent rubor (foot redness with dependent position), and hypertrophic changes of the toenails. Patients may also demonstrate restricted mobility as a result of numbness, weakness, or heaviness in the muscles of the leg. Examination in patients with suspected lower extremity arterial disease should include a thorough search for the presence and strength of all lower extremity pulses, as well as evaluation for cardiac murmurs, bruits, and aneurysms. Pulses should be assessed on both legs at all levels and any abnormalities correlated with lower extremity symptoms to determine lateralization of occlusive disease. A diminished or absent femoral pulse suggests inflow disease due to aortoiliac occlusive lesions. A normal femoral but absent distal pulse suggests preserved inflow but impaired infrainguinal outflow to the leg.

Despite the utility of the pulse examination, physical exam of the femoral artery pulse has been shown to be little better than relying on subjective symptoms of claudication to diagnose large-vessel PAD. Moreover, the absence of pedal pulses tends to overdiagnose PAD as evidenced by the fact that only 18 % of patients with abnormal posterior tibial pulses have additional objective evidence of PAD [10]. The diagnosis of PAD in suspected patients must therefore be confirmed using noninvasive screening tests and, if needed, other hemodynamic or imaging studies.

The resting ankle-brachial systolic pressure index (ABI) should be performed in all patients with a clinical history and/or physical exam suggestive of PAD. This chapter describes the technique for measuring an ABI.

The normal reference range for ABI is 0.90–1.2. A decreased ABI in symptomatic patients confirms the presence of hemodynamically significant peripheral arterial occlusive disease between the heart and ankle, with a lower ABI correlating with more severe occlusive disease. An ABI of less than 0.90 is 95 % sensitive in identifying angiographically confirmed PAD [1, 11]. Patients with claudication generally have an ABI in the range of 0.40–0.90, whereas those with rest pain or tissue loss have an ABI in the range of 0.20–0.50 and zero to 0.40, respectively. It is important to note, however, that over 50 % of patients with an abnormal ABI will fail to demonstrate typical symptoms of claudication or CLI due to the presence of other major comorbidities [1]. In addition to its ability to detect PAD, the ABI may also function as a marker for systemic atherosclerotic disease. Several studies have noted a strong correlation between ABI and mortality [12–14], with one report even noting a near linear relationship between ABI and fatal and nonfatal cardiovascular events [13].

Significant arterial calcification causes blood vessel incompressibility which will falsely elevate the ABI. In such cases, a toe-brachial index may be used to diagnose PAD as digital vessels are often spared from calcification. The toe-brachial index is calculated by dividing the toe systolic pressure by the highest brachial systolic pressure and can be measured by a noninvasive vascular lab using small blood pressure cuffs. A normal toe-brachial index is greater than 0.70. Most cases of CLI are associated with ankle systolic blood pressures less than 50 mmHg or toe systolic blood pressures less than 30 mmHg. Foot lesions usually heal when toe pressure exceeds 30–40 mmHg (or slightly higher in diabetic patients).

To evaluate PAD in more detail, the noninvasive vascular lab can perform segmental limb systolic pressures, plethysmography, Doppler waveform analysis, and exercise testing. More details of these exams can be found in this chapter.

Duplex ultrasound provides a reliable and inexpensive imaging option to evaluate arterial occlusive disease and other vascular pathologies. Capabilities of duplex ultrasonography include the ability to differentiate stenoses from occlusions, characterize the occlusive nature of specific arterial segments, evaluate for arterial trauma, assess adequacy of surgical intervention, and provide surveillance for bypass grafts. Duplex ultrasound scanning usually proceeds from proximal to distal, recording artery diameter, presence and character of atherosclerosis, and velocity spectral waveform. In stenotic lesions that significantly reduce the vessel diameter, arterial flow becomes turbulent with increased systolic and diastolic velocities. Velocity criteria can classify the severity of the lesion with greater than 80 % accuracy depending on the arterial segment scanned.

Although the exam quality depends on the technical skill of the sonographer, duplex ultrasound has proven to be a sensitive and specific test for arterial occlusive disease. A meta-analysis of 14 studies demonstrated the sensitivity and specificity of duplex scanning for ≥50 % stenosis or occlusion to be 86 and 97 % for aortoiliac disease and 80 and 98 % for femoropopliteal disease [15]. In a recent prospective, blinded study, Eiberg et al. [16] compared duplex ultrasound scans to the angiographic findings in 42 patients with claudication and 127 patients with CLI. The interobserver agreement between duplex ultrasound and angiography was generally good with both techniques independent of the severity of PAD. Duplex ultrasound was noted to perform better in the supragenicular arteries than in the infragenicular arteries but still compared favorably with angiography down to the level of the tibial vessels. Several additional studies reported a similar correlation between these two imaging studies [17–19]. Such findings support duplex ultrasound as a useful noninvasive alternative to conventional contrast angiography, particularly among those patients with renal failure and contrast allergies.

Multidetector computed tomographic angiography (CTA) allows for the rapid acquisition of high-resolution, contrast-enhanced arterial images. The CTA images can then be reviewed in multiple projections and reconstructions to illustrate artertial anatomy, localize occlusive disease, and detect vessel wall calcification. The abundance of information gained from CTA has made it a widely used exam for treatment planning. A meta-analysis of 12 studies evaluating 9,541 arterial segments in 436 patients showed that multidetector CTA detected greater than 50 % segmental stenosis with a pooled sensitivity and specificity of 92 and 93 %, respectively [20]. The diagnostic performance of CTA was noted to be lower in the infrapopliteal arteries but not significantly different from that observed in the aortoiliac or femoropopliteal arterial systems. More recently, a meta-analysis published in 2009 of 20 studies similarly compared the diagnostic performance of CTA to the reference standard contrast angiography for the evaluation of 19,092 lower extremity arterial segments in 957 symptomatic patients [21]. The overall sensitivity and specificity of CTA in that analysis was 95 and 96 %, respectively.

The drawbacks of CTA include its high cost and the associated exposure to both ionizing radiation and intravenous nephrotoxic contrast agents. CTA requires an intravenous bolus of more than 100 mL of iodinated contrast in the average adult, making it less desirable for patients with chronic renal insufficiency (estimated glomerular filtration rate (eGFR) <60 ml/kg/min). An imaging pitfall specific to CTA involves the use of narrow window settings to optimize image quality in the presence of arterial wall calcifications or previously placed stents. These imaging settings may overestimate the degree of stenosis or suggest a spurious arterial occlusion. In patients with diabetes or ESRD, extensive atherosclerotic calcification within small crural or pedal arteries may make it impossible to detect a patent vessel lumen regardless of the window/level selection. Fortunately, most of these artifacts are easily identified by examining additional views, complementary imaging modalities, or source images [22].

Three-dimensional gadolinium-enhanced magnetic resonance angiography (MRA) offers an increasingly common noninvasive option to assess the peripheral vasculature without the need for sedation, catheterization, ionizing radiation, or iodinated contrast agents. The sensitivity and specificity for the detection of greater than 50 % arterial stenoses or occlusions using this modality exceed 90 % [23–25]. Owen and colleagues [26] conducted a prospective comparative study of 30 patients who underwent both MRA and contrast angiography. Evaluation of 390 arterial segments in these patients demonstrated a higher sensitivity in distal segments (92–96 %) compared with more proximal segments (69–79 %). Specificity was similar in both distal (90–91 %) and proximal segments (86–96 %).

Magnetic resonance angiography generates a three-dimensional data set that can be reformatted to reproduce digital subtraction angiography-like vascular images that feature details pertinent to prognosis and treatment planning, including those related to the thrombus characteristics, plaque composition, presence of dissection, or extent of arterial wall inflammation. An MRA’s ability to image arteries and the surrounding musculoskeletal structures also makes it ideal for evaluating patients with popliteal artery entrapment syndrome.

There is increasing evidence to suggest that some patients with renal failure who are exposed to gadolinium-based magnetic resonance imaging contrast agents may develop a rare but serious fibrosing disorder referred to as nephrogenic systemic fibrosis (NSF). This disorder is characterized by hardening of the skin and development of fibrotic nodules and plaques. In its most severe form, NSF may result in systemic fibrosis affecting solid organs such as the lungs, heart, and liver [27, 28]. Current clinical guidelines advise against the use of gadolinium in patients with an eGFR less than 30 ml/kg/min. An MRA is also not appropriate for claustrophobic patients or patients with pacemakers or metallic implants.

Digital subtraction angiography (DSA) remains the gold standard imaging modality in peripheral vascular surgery. Angiography should usually be reserved for patients who are expected to undergo attempted revascularization. The exam begins with percutaneous needle access to the common femoral artery in the contralateral limb to allow complete imaging of the inflow, diseased segment, and outflow vessels. DSA involves the generation of fluoroscopic images by subtracting a pre-contrast image from images taken after the administration of an intra-arterial contrast medium, thereby producing a net image showing only contrast-filled blood vessels. The combination of excellent spatial and temporal resolution and a large field of view allows for rapid imaging of the entire peripheral arterial tree. A complete evaluation of the aorta, iliac, femoral, popliteal, and tibioperoneal vessels may be performed simultaneously or, more commonly, sequentially with overlapping runs. In addition, the presence and extent of collateral blood flow can be readily evaluated with this form of imaging. In some cases, measuring the pressure gradients across an arterial lesion (usually in the aortoiliac segment) can increase the arteriogram’s sensitivity and gauge the response to intervention. Hemodynamically significant lesions have a resting systolic pressure gradient which exceeds 20 mmHg.

The clinical utility of angiography must be balanced against the fact that it represents an invasive form of imaging. Angiography requires arterial access, ionizing radiation, and nephrotoxic contrast exposure. Potential complications of angiography include distal atheroembolization, arterial dissection, and access site complications (e.g., pseudoaneurysm, hematoma, thrombosis, arteriovenous fistula). DSA imaging requires a stationary target, and any patient movement will produce significant artifact. Optimizing technical factors such as frame rate, contrast injection volume, and C-arm projection angle will also produce the highest-quality images.

Severe aortoiliac occlusive disease has been traditionally treated using a variety of open surgical approaches, including aortobifemoral bypass, aortoiliac endarterectomy, iliofemoral bypass, and extra-anatomic bypass. Of these, aortobifemoral bypass has long been considered to be the gold standard treatment for hemodynamically significant aorto-bi-iliac disease in low-risk patients given its safety and efficacy (mortality rate less than 5 %; 5-year patency rates greater than 80 %) [38–41]. The bifurcated bypass graft in this procedure originates from the infrarenal abdominal aorta and routes one limb to each femoral artery via either a transperitoneal or retroperitoneal approach. A preoperative CTA is essential to assess the calcium and thrombus content of the proximal aorta. An aorta with thrombus and plaque extending to the level of renal arteries requires a proximal thromboendarterectomy with a suprarenal aortic clamp in place and the renal arteries controlled with clamps or vessel loops. Once the proximal aortic cuff has been cleared, the clamp can be moved to an infrarenal position and the proximal anastomosis can be performed in an end-to-end or end-to-side fashion. An end-to-end configuration is favored when the aorta is completely occluded to the level of the renal arteries or when severe aortic calcification precludes safe placement of a side-biting clamp. Aortic occlusive disease associated with aneurysmal dilatation also requires an end-to-end reconstruction. An end-to-side configuration has the advantage of maintaining pelvic perfusion in patients with occluded or diseased bilateral external iliac arteries. Preserving distal aortic flow may also be important in patients with a large patent inferior mesenteric artery or accessory renal arteries arising from the infrarenal aorta. The presence of femoral artery occlusive disease requires the addition of a common femoral endarterectomy and profundoplasty. Late complications include graft thrombosis (5–30 %), graft infection (0.5–3.0 %), aortoenteric fistula (<3 %), and anastomotic pseudoaneurysm (1–5 %), which is more common in patients with an end-to-side anastomosis.

More recently, a laparoscopic aortobifemoral bypass has been described as a less invasive alternative to open surgery. Tiek et al. [42] conducted a multicenter randomized controlled trial of 28 patients with TASC C or D aortoiliac occlusive lesions who underwent either open or laparoscopic aortobifemoral bypass. The laparoscopic group had a shorter mean hospital length of stay (5.5 vs. 13.0 days), earlier return to normal daily activities, and fewer postoperative complications compared to the open group. While early studies confirmed the safety of the laparoscopic aortobifemoral bypass, it has not been widely performed and the long-term patency of this approach remains unclear. Future studies may help determine whether laparoscopic aortic surgery is appropriate for a subset of patients with aortoiliac occlusive disease.

Prior to the availability of prosthetic graft material in the 1970s, aortoiliac endarterectomy served as the standard procedure for the treatment of aortoiliac occlusive disease. In a large single-center series of patients who survived over a decade after undergoing either aortoiliac endarterectomy (n = 39) or aortobifemoral bypass (n = 166), 10-year primary patency rates were 89 % for aortoiliac endarterectomy and 78 % for aortobifemoral bypass [43]. Graft infection or aneurysmal formation occurred in 5 % of aortobifemoral bypass cases. Aortoiliac endarterectomy has the advantage of potentially avoiding the need for prosthetic material; however, external iliac arteries often prove difficult to endarterectomize. Investigators therefore concluded that aortoiliac endarterectomy is preferable to aortobifemoral bypass in the following circumstances: (1) patients whose aortoiliac occlusive disease does not involve the external iliac arteries; (2) male patients with aortoiliac occlusive disease who, in addition to claudication, have erectile dysfunction and stenotic internal iliac origins; (3) patients with aortoiliac disease including the external iliac arteries who are not candidates for aortobifemoral bypass because of infection risk or small vessels; (4) patients with localized aortoiliac disease; and (5) patients after removal of an infected aortobifemoral bypass graft (with or without an enteric fistula) that had initially been placed end to side for aortoiliac occlusive disease.

Iliofemoral bypass and femorofemoral crossover bypass are additional open surgical options in patients with aortoiliac occlusive disease and are typically indicated in patients with unilateral iliac disease or in patients deemed not suitable for aortobifemoral bypass. In cases of bilateral iliac disease, a femorofemoral bypass may also be constructed as an adjunct to aortoiliac endarterectomy, iliofemoral bypass, or successful unilateral iliac angioplasty and stenting. Iliofemoral bypass appears to be a safe, effective, and durable bypass. Carsten and colleagues [44] reported a 10-year experience comprising 40 patients who underwent iliofemoral bypass grafting for unilateral aortoiliac disease, 58 % of whom had CLI. There were no perioperative deaths in their series, and limb salvage rates in patients with CLI were 85 and 79 % at 1 and 5 years. In addition, a multicenter randomized trial involving 143 patients with TASC type C or D aortoiliac lesions found that late patency was higher after direct iliofemoral bypass compared to femorofemoral crossover bypass in good-risk patients with unilateral iliac occlusive disease not amenable to angioplasty (93 % vs. 73 %). This study underscores the effectiveness of iliofemoral bypass, and the authors concluded that crossover bypass grafting should be reserved for high-risk patients with unilateral iliac occlusion not amenable to percutaneous intervention.