Infrainguinal Occlusive Disease

Etiology

The most common risk factor of arterial occlusive diseases is atherosclerosis. This condition may result from increasing age, smoking, diabetes mellitus, hypercholesterolemia, hypertension.

Other causes include increased C-reactive protein levels, homocysteinemia, thrombophilia, inflammation, and trauma.

Having more than one risk factor increases the degree of occlusion and severity.

Epidemiology

An estimated 20% of adults above the age of 55 years present with the disease.[3]

The disease affects almost 5 million people in the United States. Ethnicity and gender play a significant role; the condition is common in African Americans and people of Hispanic origin.[4]

Smoking is one of the main modifiable risk factors and increases the risk of developing the disease fourfold.[5]

Pathophysiology

Atherosclerosis causes occlusion of the arteries. Depending on the site of occlusion and involvement of the artery, collateral pathways can form. However, over time, the oxygen demand during exercise increases, which is insufficiently compensated, leading to intermittent claudication, i.e., calf pain and fatigue on walking or activity. As the severity of occlusion increases, the symptoms may present even at rest, leading to ischemic rest pain, minor and significant tissue loss, which includes ulcers and gangrene.

Acute occlusion is common in the infra-inguinal arteries. This condition leads to the atherosclerotic phenomenon of thrombosis and embolus. Thrombus is a localized clot that leads to impaired circulation. Emboli may travel to bifurcations and cause occlusion and present more acutely with no collaterals. The most common site of embolus is the distal common femoral artery and popliteal arteries. The level of impalpable pulses helps locate the site of occlusion.

The six P's characteristic of arterial occlusion includes pain, pallor (color change), poikilothermia (coldness), pulselessness, paresthesia, and paralysis.

Histopathology

The most frequent histopathological findings are thickening of intima, fibroatheroma, fibro-calcification. Atheromatous plaques are composed of collagen and calcification.

Luminal occlusion is also observed in chronic limb ischemia, without significant atherosclerosis, potentially due to the athero-thrombo-embolic phenomenon.[6]

History and Physical

The disease is more common in males. The patient is usually above the age of 50 years; if younger, other differentials may be explored, such as Buerger disease and autoimmune conditions such as vasculitis.

The central aspect of the history would be the complaints to progressive difficulty walking and pain—intermittent claudication, which is a pain in the calf precipitated by walking and relieved by rest. Rest pain is characteristically worse at night and is aggravated by lying supine and elevating the foot and is relieved by hanging the foot off the bed and sleeping in a chair.

Ulcers most commonly present on digits, as well as gangrene.

The severity requires evaluation, and the site of pain to help determine the location of the occlusion. The most common sites to ask about are mainly buttocks, knees, calves, and digits. Complaints of impotence also merit attention and abdominal pain after eating to rule in or out mesenteric ischemia. The previous history of stroke and transient ischemic attack is essential.

The examiner should query risk factors, such as the previous history of diabetes, hypertension, hyperlipidemia, and, if present, medication dosage, and compliance require assessment.

On examination, the main points are the built and general appearance of the patient to look for cachexia and muscle wasting, eyes for pallor (anemia) or jaundice, palpate all pulses including femoral, popliteal, posterior tibial, dorsalis pedis artery. Examine the abdomen for abdominal aortic aneurysm and auscultate for bruits. Asses the gait, and do special tests to determine the severity, Buerger's test to determine the angle, check for dependent erythema, ulcers, skin texture, loss of hair, pigmentation, dependent rubor, amputated digits. Check for sensation and numbness. 

One of the most crucial parts of the examination and assessment is the ankle-brachial pressure index (ABPI). The normal values are 1 to 1.3. A value of less than 0.9 suggests intermittent claudication, less than 0.5 is associated with rest pain, and less than 0.3 is critical limb ischemia. The ABPI is a highly sensitive test and is essential to form a diagnosis and assess disease severity.

The ABPI may show a value of more than 1.3 in patients with diabetes due to calcification of the vessels. In that case, a segmental waveform analysis or toe-brachial index is an alternative.

Evaluation

Laboratory investigations: Complete blood count, fasting blood sugar, lipid profile, serum creatinine, serum electrolytes, electrocardiogram (EKG), 

Radiological investigation: The most appropriate initial investigation is an ultrasound plus doppler, which is a duplex scan to determine the blood flow and localize the clot. It also serves to determine the ankle-brachial pressure index, as described above.

Angiography: Computerized tomography (CT angio)/magnetic resonance angiography (MRA).

Treatment / Management

Conservative management: Lifestyle modification is the most effective, which includes weight loss, exercising, modifying dietary habits, foot care.

Medical management: Low dose aspirin, a statin, cilostazol (vasodilator for intermittent claudication), along with strict control of comorbid illnesses through antihypertensives and anti-hyperglycemic medications, with regimen compliance. Note: beta-blockers may exacerbate claudication.

Endovascular: Involves percutaneous transluminal angioplasty and stenting. Hybrid procedures are being performed by vascular surgeons to improve outcomes and decrease mortality.[7](B2)

Surgical management: This includes bypass and endarterectomy. Amputation may be necessary in cases of unsalvageable tissues.

• Bypass, according to the site of obstruction - Superficial femoral artery occlusion - femoropopliteal (above the knee). Five-year patency is fifty to seventy-five percent. A bypass is more effective in proximal major arteries compared to distal. 
• Infrapopliteal - Femoro-distal (below the knee). Five-year patency is fifty to sixty percent.

Great saphenous vein graft is most patent and has a low rate of infections. If the vein is unavailable, then prosthetic grafts such as ePTFE are used.

In other diseases such as Buerger disease (thromboangiitis obliterans), the first step in management is always smoking cessation.

Differential Diagnosis

• Leriche syndrome: Aortoiliac occlusive disease, which presents as a triad of buttock claudication, impotence, lower limb extremity wasting.
• Buerger disease: most common in young male smokers, may present with gangrenous digits, pain, and impalpable pulses.
• Vasculitis
• Deep venous thrombosis: can present with calf pain and swelling. Risk factors may be present.
• Osteoarthritis
• Popliteal compartment syndrome
• Neurogenic claudication: Lumbar stenosis, herniated disc; this can be differentiated as it may not be reproducible with exertion and may not be present at all times.  Examination findings such as skin temperature, delayed capillary refill, and absence of pulses will be absent.

Toxicity and Adverse Effect Management

Clinicians should ask patients taking aspirin about any previous history of gastric or duodenal ulcers and, if present, should receive prophylactic proton pump inhibitors to prevent gastrointestinal bleeding and gastric erosions.

Staging

The disease is classified using various established classifications, which include Fontaine, Rutherford, Wagner, UT, PEDIS, SVS WIfI, TASC.[2]

The Rutherford classification is as follows :

• 0- Asymptomatic,
• 1- Mild claudication (pain on walking at a certain distance known as the claudication distance),
• 2- Moderate,
• 3- Severe,
• 4- Rest pain,
• 5- Ischemic ulcers on digits - minor tissue loss,
• 6- Gangrene or ulcers - significant tissue loss.

TASC classification of femoropopliteal arterial occlusive disease :

• Type A single lesions: endovascular treatment
• Type B multiple lesions: endovascular treatment
• Type C multiple or recurrent stenoses: open revascularization
• Type D chronic total occlusion: surgical treatment

Prognosis

Infrainguinal occlusive diseases may lead to limb-threatening ischemia in 5 to 10% of patients. 

Management of the disease is mostly by medical treatment with positive outcomes.

Patency of the endovascular approach is less compared to surgical treatment.[8] 

The survival rate is 50% for ten years but significantly drops to five years for patients requiring surgical treatment.

Complications

The commonest complication is critical limb ischemia and limb-threatening stenosis, often leading to amputation and increased mortality.

The surgical approach leads to postoperative complications, including infections, bleeding, cardiac, renal, pseudoaneurysm formation, graft rejection, and thromboembolic complications.

There is also an increased probability of 30-day readmission and in-hospital complications and mortality.[9]

Restenosis is the most common late-onset complication.