Clinical Assessment
Peripheral artery disease (PAD) is caused by a number of pathologies affecting the arteries of the lower extremities. The most common cause in industrialized countries is atherosclerosis, but the interventionalist needs to be aware of other pathologies that may be best treated by noninterventional approaches. The history and physical exam can distinguish most causes of peripheral artery disease and determine the need for further testing and urgency of interventional therapy.
Causes of Peripheral Artery Disease
Atherosclerosis is the most common cause of peripheral artery disease, principally related to the conventional risk factors of age, cigarette smoking, elevated cholesterol, hypertension, diabetes mellitus, and associated inactivity and obesity. Other causes of large artery arterial disease include aneurysms, dissections, emboli, compression syndromes, and vasculitis.
About 50% to 90% of patients with atherosclerotic peripheral artery disease are asymptomatic. The diagnosis is made by clinical exam or other tests that are clinically indicated or ordered for other reasons. Asymptomatic disease is a marker of elevated risk of cardiovascular events. Thus, the interventionalist shares responsibility with the referring doctor in initiating risk factor modification by encouraging smoking cessation, initiating treatment for hyperlipidemia and hypertension, and promoting physical activity.
The symptoms of peripheral artery disease help distinguish acute from chronic presentations and often give an indication of the location of disease. The temporal relationship of disease onset is particularly important in determining the urgency of treatment.
Acute Limb Ischemia
Acute limb ischemia is a sudden decrease in perfusion (defined as within 14 days) that threatens the viability of the limb. Rapid assessment and treatment are needed to salvage the limb, although a high mortality often relates to coexisting comorbidities. Acute limb ischemia is due to embolization most commonly from the heart, in situ thrombosis related to atherosclerosis ( Figure 18-1 ), or increasingly, graft thrombosis or stent thrombosis.
Emboli may occur in patients without symptoms or signs of preceding peripheral artery disease. In situ thrombosis is often accompanied by signs of atherosclerosis in both limbs, but it can occur from impaired flow in a graft or stent (e.g., restenosis or graft hyperplasia), thrombosis of a popliteal aneurysm, hypercoagulable states, or dissection.
The classic symptoms and signs of acute limb ischemia are known as the six P’s . These are pain, pallor, pulseless, poikilothermia (a cold limb), paresthesia, and paralysis. The order of these symptoms and signs also relates to the viability of the limb and whether revascularization will salvage it. As sensory and motor function is lost progressively from the distal to proximal limb, a simple test of intact motor function is dorsiflexion of the big toe to resistance. Table 18-1 shows the Rutherford classification of acute limb ischemia and the management suggested by Inter-Society Consensus for the Management of Peripheral Arterial Disease. Patients with Rutherford class I and IIa may be able to tolerate an overnight infusion of catheter-based thrombolysis. Patients with class IIb ischemia require more immediate revascularization by endovascular aspiration or mechanical thrombectomy in conjunction with thrombolysis or classically by surgical embolectomy or bypass grafting. Typically, surgical treatment is employed if fasciotomy is required to prevent or treat a compartment syndrome associated with reperfusion injury and edema of the revascularized limb.
| RUTHERFORD CLASS | PROGNOSIS | SENSORY EXAM | MOTOR EXAM | ARTERIAL DOPPLER SIGNAL | VENOUS DOPPLER SIGNAL | SKIN EXAM | INITIAL THERAPY | DEFINITIVE THERAPY |
|---|---|---|---|---|---|---|---|---|
| Class I Viable, Not Threatened | Not immediately threatened | Normal | Normal | Audible | Audible | Normal capillary return | Anti-coagulation | Imaging and revascularization |
| Class IIa: Marginally Threatened | Salvageable with prompt therapy | Minimal loss | Normal | Often inaudible | Audible | Decreased capillary return | Anti-coagulation | Imaging and revascularization |
| Class IIb: Immediately Threatened | Salvageable if treated immediately | Mild sensory loss and rest pain | Mildly to moderately abnormal | Usually inaudible | Audible | Pallor | Anti-coagulation | +/− Imaging and revascularization |
| Class III: Irreversible | Irreversible tissue and nerve damage | Profound loss | Paralysis and rigor | Inaudible | Inaudible | No capillary return and marbling | Anti-coagulation | Amputation |
Chronic Limb Ischemia
Chronic limb ischemia has an indolent presentation and is far more common than acute limb ischemia. The two classifications of chronic limb ischemia are the Rutherford scale commonly used in the United States and the Fontaine scale commonly used in Europe ( Table 18-2 ). Both scales distinguish the two main clinical presentations of intermittent claudication and critical limb ischemia.
| PAD CLASSIFICATION | CLINICAL SYMPTOM | RUTHERFORD | FONTAINE |
|---|---|---|---|
| Asymptomatic | Asymptomatic | 0 | I |
| Intermittent claudication | Mild claudication | 1 | IIa |
| Moderate claudication | 2 | IIb | |
| Severe claudication | 3 | IIb | |
| Critical limb ischemia | Ischemic rest pain | 4 | III |
| Minor tissue loss | 5 | IV | |
| Ulceration or gangrene | 6 | IV |
Intermittent claudication is classically described as a cramping, aching discomfort or pain with exercise that is relieved by rest. Claudication results from muscle ischemia due to an inability to augment blood flow to a leg muscle related to a stenosis or occlusion of the large and/or small arteries. However, up to half of symptomatic patients describe atypical symptoms with exercise, including fatigue, slow walking speed, and gait disturbance. Claudication has major effects on quality of life by impairing function and activity. It also relates to a high risk of cardiovascular events over the subsequent years. The risk of limb loss is usually low, so that it is perfectly safe and appropriate to attempt medical therapies (e.g., exercise programs and/or cilostazol) for several months before considering revascularization. In many cases, medical therapy resolves symptoms and improves quality of life and function to a level where revascularization is unlikely to offer extra benefits.
Critical limb ischemia occurs when blood flow at rest is inadequate to meet metabolic demands. Symptoms include pain at rest usually in the lower leg and often with a sensation of coldness or numbness in the limb. Symptoms are exacerbated by cold and leg elevation and relieved by leg dependency (e.g., hanging the leg over the edge of the bed) to improve blood flow to the foot by gravity. Ischemia can progress to infarction with gangrene and ulceration. Patients with critical limb ischemia are at high risk of major amputation (amputation above the ankle) and myocardial infarction and stroke. Thus the goals of therapy are to improve blood flow through revascularization and ensure adequate treatment of risk factors for atherosclerosis.
Physical Exam
The exam should include a complete check of the skin, heart, lungs, abdomen, and upper and lower limbs to look for systemic disease and causes of lower limb ischemia. Blood pressure should be measured in both arms, with a difference of more than 15 mm Hg to 20 mm Hg indicating significant unilateral upper extremity disease. All peripheral pulses are palpated and coded as absent (0), diminished (1), or normal (2). Expansile or hyperdynamic pulses may indicate aneurysms (e.g., of the abdominal aorta or popliteal artery). Ausculation of bruits indicates disturbed or turbulent flow and may indicate a stenosis. Shoes and socks should be removed to look for ulceration or gangrene, which may be missed by the patient with neuropathy. Arterial ulcers often have a dry base or an overlying eschar, in contrast to venous ulcers, which tend to be more beefy and moist. More severe forms of ischemia lead to pallor and coolness of the limb, particularly on elevation, and in critical limb ischemia, lowering the limb will reveal a dependent rubor due to hyperemia related to arteriolar and venule dilation and improved flow with gravity.
Physiological Tests
The ankle brachial index (ABI) is a simple office-based method to identify PAD. A handheld 5-MHz to 10-MHz Doppler device is used in conjunction with a conventional blood pressure cuff to measure the systolic pressure at both brachial arteries and the pedal arteries in both feet. Recent guidelines recommend recording the ABI for each limb as the highest pedal pressure in that limb over the highest brachial artery pressure. A normal ABI is greater than 1.0 up to about 1.4. Higher ABIs often indicate calcification of the tibial arteries, in which case the ABI is unreliable for identifying obstructive disease. An ABI of 0.9 to 1.0 is borderline, and an ABI of less than 0.9 is abnormal and a sensitive and specific indicator of obstructive PAD as well as elevated risk of cardiovascular events.
Vascular laboratories are able to provide additional physiological data beyond the ABI. These include segmental leg pressures that help to localize disease by using blood pressure cuffs at different locations to identify marked drops in systolic pressure between cuffs. Pulse volume recordings use blood pressure cuffs expanded to low pressure and identify the subtle expansion of the limb with each systole. These are particularly useful when calcified arteries prevent accurate measurements of ABI. Treadmill testing using standardized walking protocols can quantify the walking times or distances and identify a fall in ankle pressure with exercise in patients with PAD who have borderline results at rest.
Arterial Imaging
Duplex ultrasound uses a combination of B-mode two-dimensional grayscale imaging with color-encoded Doppler imaging and pulsed-Doppler velocity analysis. Grayscale imaging and color Doppler can identify the artery and direction of blood flow, but they are not reliable at grading the degree of stenosis. Stenoses are identified by turbulent flow with varying velocities and graded by pulsed-Doppler comparing velocities in the stenosed segment to a proximal reference segment. Greater stenosis relates to increasing peak and subsequently diastolic flow velocities.
Magnetic resonance angiography uses two techniques to identify arteries by coding blood flow white ( Figure 18-2 ). These include time-of-flight techniques and contrast-enhanced imaging. Time-of-flight relies on laminar blood flow. It tends to overestimate stenosis severity compared to conventional angiography, particularly in regions of disturbed blood flow (e.g., at bifurcations) and regions with reversal of flow. Contrast-enhanced techniques use one of several contrast agents such as gadolinium. Contrast increases the accuracy of the imaging and is better able to define smaller distal arteries. Three-dimensional rendering can allow the reader to rotate the image to help identify eccentric stenoses. A disadvantage of gadolinium is the small risk of disabling nephrogenic systemic sclerosis, which is related to renal function and a particular concern in patients with end-stage renal disease on dialysis. For this reason, gadolinium is usually avoided in patients with severe renal dysfunction.
Computed tomographic angiography uses high-resolution x-ray scanners and iodinated contrast to image the arteries. Volume and three-dimensional rendering can strip surrounding tissue away from the artery images and provide images similar to conventional angiography or magnetic resonance imaging. High-resolution multidetector computed tomography is generally faster than magnetic resonance angiography, but it is sometimes difficult to assess stenosis severity in heavily calcified arteries due to the blooming effect around calcium. Most techniques require 100 mL or more of iodinated contrast, which limits its use in patients with renal dysfunction at risk of contrast nephropathy.
Invasive conventional angiography is still considered the gold standard for arterial imaging. Digital imaging equipment is now capable of conventional “cine” imaging as well as digital subtraction angiography, which removes nonarterial structures to better view the artery ( Figure 18-2 ). Noninvasive angiography has largely superseded the need for conventional angiography in the diagnosis and location of disease, but invasive angiography can provide additional physiological assessment of specific lesions using pressure gradients at rest and with vasodilators. Generally a 10-mm Hg gradient at rest or a 15-mm Hg to 20-mm Hg gradient with vasodilators (e.g., nitroglycerin) is considered significant. However, even a 4 Fr catheter placed through a lesion can falsely increase the gradient. Measuring gradients by pullback from proximal to distal or using 0.014-inch pressure wires helps avoid this error.
Percutaneous Revascularization Tools
Approach and Access
The four major access sites for a lower limb artery are retrograde access from the contralateral femoral artery, antegrade access via the ipsilateral femoral artery, an upper extremity limb traversing the aorta, and retrograde access via an ipsilateral distal artery such as the popliteal or tibial arteries ( Figure 18-3 ). Each access has its advantages and disadvantages.
Retrograde access of the contralateral femoral artery is familiar to many interventional cardiologists and sheath removal at the end of the case is facilitated by a number of closure devices ( Figure 18-4A-C ). Catheters and sheaths are directed over the aorto-iliac bifurcation into the contralateral leg. This provides easy access to the iliac, common femoral, and proximal superficial femoral arteries but is often used to treat more distal disease. The advantages of this approach are the ability to quickly balloon occlude the distal aorta or proximal contralateral iliac artery in the event of perforation of a more distal artery and the ability to treat the contralateral common femoral and proximal superficial femoral arteries. The disadvantages are that it may be difficult to negotiate a tortuous or calcified iliac artery system, and it may offer less support to push through extensive disease in the distal arteries (popliteal or tibial arteries).
An upper limb artery (typically the brachial artery) can provide access to the lower limbs, but due to distance, most equipment can only treat the distal aorta and iliac arteries ( Figure 18-5 ). This technique is useful when a femoral artery approach is not possible due to disease or chronic occlusion of the iliac arteries. Although radial artery access is appealing, it is generally too far from the lower extremities for most interventional equipment.
Antegrade access of an ipsilateral femoral artery is useful for providing greater support for popliteal and tibial interventions ( Figure 18-4D ). It requires skin entry well above the common femoral artery and is therefore more difficult and often not feasible in overweight or obese patients. Since the subcutaneous path to the femoral artery is usually longer than with retrograde femoral artery access, closure devices are more difficult to use and tend to have a higher failure rate.
Retrograde access from a more distal artery is useful when antegrade access is unsuccessful (typically in crossing a chronic total occlusion) ( Figure 18-6 ). Manual compression is required to control hemostasis after the case, as the arteries are smaller. The key disadvantage of this approach is the potential to create an ischemic ulcer at the access site if revascularization is unsuccessful. Thus it is generally used as an approach of “last resort.”
Guides and Sheaths
A variety of guides and sheaths are used for lower limb diagnostic cases and interventions. Both are measured in French size (1 French = 0.33 mm), but sheath French size refers to the inner diameter and guide French size refers to the outer diameter. Thus sheaths have a larger external diameter than the same French guides.
Typical sheaths for the contralateral femoral artery access include the Balkin and Ansel sheaths, which have preformed curves but can be shaped further if required. Conventional short and long sheaths can be used for antegrade femoral artery access, including sheaths with radio-opaque tips that show where the tip of the sheath is in relation to the segment being treated.
If access is from the contralateral or ipsilateral femoral artery, a multipurpose guide can be directed into the distal superficial femoral or popliteal arteries for interventions below the knee ( Figure 18-7 ) ( ). This can provide greater support than a femoral sheath and also reduce the amount of contrast required for an intervention. Conventional 0.014-inch coronary balloons or specific peripheral balloons can be used through a 5 Fr or 6 Fr multipurpose guide in this manner.
Wires
A multitude of wires are available to help navigate tortuous stenoses or long chronic total occlusions. These include 0.014-inch wires used for coronary artery interventions, which come in a range of tip stiffness and hydrophilic wires. Balloons designed for 0.018-inch wires usually have a low enough profile to be used with 0.014-inch wires, but 0.035-inch balloons have such a mismatch between the balloon nose and wire that they often do not track well on a 0.014-inch wire. Regular and hydrophilic 0.018-inch wires provide greater support than 0.014-inch wires but are often less torquable than the 0.014-inch wires.
Conventional and stiff 0.035-inch wires (e.g., Amplatz and Rosen wires) provide increased support for directing catheters and guides (e.g., from the contralateral femoral artery). The Wholey wire has a soft tip on a stiff shaft but is often less torquable than a hydrophilic wire. Angled hydrophilic wires can help select arteries for catheters and can be exchanged for stiffer J-wires to direct sheaths into position. Angled hydrophilic wires can be used to cross lesions but can perforate the artery quite easily, so confirmation of location by angiography from multiple views or other methods should be attempted prior to balloon angioplasty.
Anticoagulation
All interventions and often prolonged diagnostic cases require anticoagulation to prevent thrombus forming on wires and other equipment. Unfractionated heparin is often used at a lower activated clotting time (e.g., 220-250 seconds) compared to coronary interventions. Heparin is usually the anticoagulant of choice when treating long total occlusions due to the high incidence of wire perforation and the risk of larger perforations that may require immediate reversal of anticoagulation with protamine.
Perforation of the iliac arteries can be catastrophic due to the high volume of blood flow (approximately 200 mL/min at rest) and requires early identification and treatment. Although the recommended dose of protamine is approximately 10 mg per 1000 U of heparin used (and up to a maximum of 50 mg), often lower doses are successful in stopping bleeding, particularly when used with low-pressure balloon tamponade near the site of perforation. If unsuccessful, covered stents can be used to treat perforation (see below).
Newer anticoagulants such as bivalirudin and potent antiplatelet agents may offer better anticoagulation based on their experience in coronary interventions, but there are no direct comparisons of their safety and efficacy compared to heparin in lower extremity interventions.
Reentry Devices
Reentry devices are designed to locate the distal true lumen after dissecting through a chronic total occlusion. All of these devices work on a principle that if a guidewire dissects down the side of a plaque into a plane beyond the distal cap, the reentry catheter will direct a guidewire into the true lumen. After accessing the distal artery lumen, the reentry device is removed and followed by conventional angioplasty and/or stenting. These devices await formal testing against standard interventional techniques to cross occlusions.
The Pioneer Plus catheter (Volcano Corp. San Diego, California) has a multiple array intravascular ultrasound at the end of the catheter. This is connected to a Volcano intravascular ultrasound system and used to image the true lumen. The catheter is rotated until the distal true lumen appears at the 12 o’clock position of the ultrasound image, which corresponds to the direction the curved needle at the tip of the device will deploy ( Figure 18-8 ). Once the needle is in the true lumen, a 0.014-inch wire can be advanced through the needle into the true lumen.
