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Worldwide, more than 200 million people are affected by peripheral artery disease (PAD). The definition of PAD is variable, but in general consists of a disease state characterized by compromised arterial perfusion to meet the oxygen and metabolic needs of organs. PAD overwhelmingly involves the lower extremities and to a much less extent upper extremities. Approximately 5% to 10% of patients with PAD of the lower extremities will progress to develop critical limb ischemia (CLI) over a 5-year period characterized by rest pain and/or the presence of nonhealing wounds or gangrene.1 If left untreated, rates of limb loss are nearly 40% over the first year.2 Despite a variety of available limb sparing open and minimally invasive surgical options, amputation rates among patients who are not candidates for treatment are as high as approximately 70%.3 Furthermore, it is reported that patients presenting with CLI have as high as 20% mortality rate in the first year after presentation.4 Risk factors for progression to CLI include advanced age, smoking, diabetes, hypertension, age, renal disease, and hypercholesterolemia.4 Due to increased prevalence of uncontrolled tobacco use and diabetes, the number of people affected is only expected to increase. In addition, nearly 90% of patients with CLI also have concomitant coronary artery disease of which two-thirds require treatment.5 Therefore, the clinical knowledge required for appropriate prevention, diagnosis, and treatment are critical to allow for concise evaluation, workup, and treatment.


CLI typically occurs in the lower extremities with the most distal foot being the most symptomatic. However, it is a systemic disease, and atherosclerosis is common in other arterial beds. Most commonly, the disease process is secondary to atherosclerotic changes that affect arteries from the aortoiliac region to the terminal lower extremity vessels. Regardless of the etiology, the resulting disease process is caused by a mismatch of arterial perfusion to tissue dependent oxygen and nutrient requirements resulting in ischemia, vasodilation, inflammation, and angiogenesis.6 Early symptoms of PAD consist of calf, gluteal, thigh, or foot pain, discomfort, or fatigue induced with activity that ultimately subsides with rest, commonly referred to as claudication. Progression of the disease to CLI as opposed to an acute process must have been present for greater than 2 weeks, and pain is experienced at rest with limb elevation or dependent positioning.7 Classically, patients will complain of waking up at night with foot pain relieved by hanging their feet over the edge of the bed, and hyperemic-dependent rubror. Physical exam findings consistent with CLI include diminished or absent palpable distal pulses, elevation pallor or dependent rubror, thin and shiny skin, absence of hair, and increased capillary refill time.8 Chronic ulceration, typically seen as well-demarcated punched-out lesions involving the lower extremity, can also be pathognomonic of the disease process and should heighten suspicion for ongoing vascular compromise.9 Progression to gangrene indicates an advanced stage. ...

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