Edouard Aboian
Philip P. Goodney
Presentation
A 53-year-old male with a long history of smoking presents to the vascular clinic with complaints of pain in right leg with ambulation. This pain occurs reproducibly at 50 ft and is relieved with rest. His past medical history is significant for hypertension, hypercholesterolemia, and diabetes mellitus. He is a 1 pack per day smoker.
Differential Diagnosis
Lifestyle-limiting claudication is the most common manifestation of peripheral arterial disease (PAD) and most plausible in this individual. Critical limb ischemia (CLI) is a more advanced stage of peripheral arterial occlusive disease (PAOD) than intermittent claudication (IC). It is defined as rest pain (pain in the limb while at rest, unlike claudication, which occurs with activity) or tissue loss. Venous claudicationresults from proximal venous occlusion. Patient usually has a history of venous thromboembolism. The pain develops following ambulation as veins become engorged and tense, which causes a bursting sensation or pain that is then relieved with rest or leg elevation. Diabetic neuropathy can involve the forefoot and digits and is often described as a burning pain, hyperesthesia, or a “pins and needles” sensation. A careful history should permit differentiation between ischemic rest pain and neuropathy because neuropathic pain is constant and unrelieved by dependency.
Spinal stenosis results from compression of the spinal cord or its nerve roots. Symptoms usually are not consistently associated with activity and not rapidly relieved with rest.
Detailed History and Physical Exam
This patient reports a chronic history of the predictable onset of right calf pain with ambulation, occurring reproducibly at 50 ft, that is improved with rest. He reports progressive worsening of walking distance over last 3 months and is currently unable to complete his activities of daily living because of the pain in his right leg.
He tried to quit smoking several times in his life but has been unsuccessful. He reports no prior interventions or vascular operations on his lower extremities. His diabetes is poorly controlled with an average blood glucose level in the 200 mg/dL range, with a hemoglobin A1C of 9.4. He has not seen a doctor for several months. His blood pressure is reasonably controlled, on an angiotensin converting enzyme (ACE) inhibitor and Beta Blocker. He is not taking aspirin or statin at present.
On physical examination, he is in no acute distress. He has lack of skin hair on his right leg, with slight muscle atrophy. There is no tissue loss or ulceration. His carotid upstrokes are equal bilaterally, and there are no carotid bruits. His heart is regular, and his lungs are clear. There is no pulsatile abdominal mass. There are good femoral pulses bilaterally, but there are no appreciable popliteal or pedal pulses in either extremity.
Based on the history and physical examination, the most likely diagnosis is a lifestyle-limiting claudication.
Discussion
Overall Incidence of Claudication
PAOD currently affects approximately 10 million adults in the United States, and of these, nearly 4 million have IC. This disease process therefore is common among elderly patients, and it is estimated that 13.7% of men aged 70 and older are affected. PAOD is a common manifestation of systemic atherosclerosis, and has similar risk factors to this disease, such as smoking and diabetes.
PAOD as a Marker of Overall Cardiovascular Risk
PAOD is a sensitive marker for overall cardiovascular risk. For example, patients presenting with PAOD are at significantly higher risk for premature cardiovascular events, such as myocardial infarction (MI), stroke, and sudden death. PAOD is also a very specific indicator of systemic atherosclerosis. For example, normal ankle brachial indices (whereas PAOD is defined as an ankle-brachial index [ABI] of <0.9) are almost 100% specific in identifying healthy individuals.
Types of PAOD
Patients with symptomatic PAOD are generally divided into two categories: IC and CLI. It is important to distinguish these two groups of patients because of the dramatically different natural history of each of the two different disease states. In terms of the potential for limb loss, patients with IC demonstrate a benign natural course, with amputation rates of 1% to 7% at 5 years, and a relatively low lifetime risk of clinical deterioration of the limb in 25% of cases. However, studies suggest that 40% to 60% of untreated patients with CLI will progress to amputation within 12 to 24 months. Therefore, the need for intervention in patients with IC is based upon weighing the risks of intervention against the extent of the patient’s symptoms. Those patients with “lifestyle-limiting” claudication often proceed with treatment, while those patients with more mild symptoms usually do not undergo invasive management, and are often treated with supervised exercise therapy and smoking cessation.
Presentation
The typical patient with IC presents with lower-extremity symptoms that occur in the muscles of the calf. The symptoms may range from muscle fatigue to aching while walking. The character of pain is usually burning, cramping, or aching, and these symptoms are relieved by rest. As the disease progresses, the distance to onset of claudication shortens, and symptoms become more frequent.
Location of the Disease
The affected muscle group is usually located below the level of hemodynamically significant stenosis or occlusion. Generally, the arterial tree can be divided into three levels: aortoiliac, femoropopliteal, and tibioperoneal. Stenosis or occlusion on one of these levels will typically result in IC. Occlusive lesions of infrarenal aorta or iliac vessels will result in buttock or thigh claudication, whereas superficial femoral artery disease will result in calf claudication. Patient risk factors can also be useful in identifying angiographic patterns of disease. For example, infrarenal and iliac arterial disease is associated more with cigarette smoking, whereas diabetes affects more small vessels at the tibioperoneal level.
Workup: Noninvasive Evaluation
Noninvasive studies are a useful adjunct to the history and physical exam, providing objective evidence of the extent and location of vascular disease with essentially no risk to the patient. The ABI, or ankle-brachial index, is a widely used noninvasive test to assess location and severity of the PAD. It samples blood pressure in lower extremity at different levels (thigh, calf, midfoot, and even the toes) and compares to pressure in upper extremity, often measured at the level of brachial artery. This quantitative data are supplemented with qualitative data of blood pressure wave form morphology, which informs of the level and extent of disease. Toe pressures are especially helpful in diabetic patients, as the digital arteries may not be as calcified as the tibials and provide a more accurate assessment of the extent of lower-extremity PAD. Serial ABIs are useful in measuring the progression of disease, aiding in the timing of an intervention. This test can also be an effective measure postintervention result.
While the general extent and location of disease can be addressed by ABIs and toe pressures, duplex ultrasound provides the vascular surgeon with the most detailed information available in a noninvasive armamentarium. Interrogation of the arterial system with duplex ultrasound provides information on blood flow velocities in different arterial beds. These data can then be extrapolated to determine the degree and length of stenosis, and algorithms to establish these thresholds have been derived and published widely.
Lastly, transcutaneous partial pressure of oxygen or TcPO2 is another useful adjunct in evaluating lower-extremity ischemia. While each of the tests has its limitations, when used in conjunction with a careful history and physical, it allows for quantitative assessment of the patient’s symptoms and risks from their lower-extremity PAOD.
Physical examination reveals that the patient has a palpable right femoral pulse, but an absent popliteal pulse and nonpalpable pedal pulses. Patient’s ABI is 0.65 on the right and 0.75 on the left. Duplex arteriography suggests an occlusion in the midportion of the superficial femoral artery.
Based on information provided, the importance of detailed history and physical examination is obvious, as the symptom complex (claudication) should match the anatomic findings (lack of infrainguinal pulses) and noninvasive findings (ABI of 0.65). While this patient in the stem has several risk factors, only a portion of them are modifiable. For example, smoking cessation is a modifiable risk factor. These strategies are discussed in detail in the next section.
Diagnosis and Treatment
Our working diagnosis at this point is a lifestyle-limiting IC. There are several therapeutic interventions for the vascular surgeon to consider.
Risk Factor Modification is the First Step in the Management of Claudication
Several aspects of this patient’s care need careful attention in managing his claudication. First, smoking is a modifiable risk factor. Smoking cessation has been shown to reduce the risk of MI and death in patients with PAOD and to delay progression of lower-extremity symptoms. It is also important to emphasize that after lower-extremity revascularization, the incidence of graft failure is threefold higher in smokers than in nonsmokers.
Second, diabetes is widely prevalent in patients with PAOD and it has been estimated that for each percent increase in glycosylated hemoglobin, there is a 28% increase of PAD. While some debate in this regard persists, strict glucose control reduces microvascular complications and improves outcomes with revascularization.
Third, aspirin lowers the risk of MI, stroke, and death in patients with PAOD and must be initiated in all patients after the diagnosis of PAOD has been established. It also enhances graft patency following peripheral bypass. However, there is no evidence that antiplatelet therapy directly improves symptoms of claudication, although it is widely recommended for primary prevention in patients with PAOD.
Finally, treatment of hyperlipidemia with statins is important to reduce progression of atherosclerosis. Currently, the American College of Cardiology—American Heart Association (ACC/AHA) guidelines recommend an low-density lipoprotein (LDL) cholesterol level of <100 mg/dL (2.59 mmol/L) in patients with PAOD and an even lower level (<70 mg/dL [1.8 mmol/L]) in high-risk patients with more generalized atherosclerosis.
Supervised Exercise Therapy:A Nonpharmacologic Intervention
A supervised walking program is supported by ACC/AHA guidelines and is I A recommendation. Supervised exercise should be made available as part of the initial treatment for all patients with PAD. The most effective programs employ treadmill or track walking that is of sufficient intensity to bring on claudication, followed by rest, over the course of a 30 to 60 minute session. Exercise sessions are typically conducted three times a week for 3 months, and, with persistence have shown consistently effective results. This treatment, along with a summary of medical management treatment options, is outlined in Figure 1.
FIGURE 1 • Summary of management of claudication.
Pharmacologic Management: A Noninvasive Treatment Option
Pentoxifylline was the first FDA-approved medication for the treatment of PAOD. It improved maximal walking distance by 12%. It is believed that pentoxifylline improves oxygen delivery by exerting rheolytic effect on red blood cell wall flexibility and deformability, ultimately reducing blood viscosity. Pentoxifylline is also believed to inhibit platelet aggregation. However, this finding appeared to be more statistically than clinically relevant in patients with claudication. In real-world clinical practice, some patients experience substantial long-term symptom relief with pentoxifylline, but others do not, and it is often difficult to predict patient response without a trial of the drug.
Cilostazol (Pletal) is another FDA-approved medication for treatment of PAOD. Results have shown increased maximal walking distances up to 50%, as well as significant improvements in quality-of-life (QoL) measures. There is also increasing evidence that cilostazol may modulate the synthesis of vascular endothelial growth factor, potentially stimulating angiogenesis in patients with chronic lower-extremity ischemia. However, headache, diarrhea, and gastrointestinal discomfort may develop. Cilostazol is contraindicated in patients with NY stage three to four congestive heart failure.
Revascularization Therapy: Open and Endovascular
If this patient’s symptoms remain lifestyle limiting, and no improvement was observed with initial risk factor modification strategy, initiation of medical management, and institution of a supervised exercise program, consideration must be given for intervention. Detailed discussion with the patient should precede any intervention and all risks and benefits must be explained. It is important to emphasize the relatively benign nature of IC and a low risk of limb loss.
If the decision to intervene is made, then the next step is to visualize the arterial tree and to localize an arterial lesion with imaging modality. Conventional digital subtraction arteriogram, computed tomographic angiogram (CTA), and magnetic resonance angiogram (MRA) are commonly used modalities. Conventional digital subtraction arteriogram is the most commonly used imaging modality. The advantage of conventional arteriogram is the ability to intervene in the same setting. However, it is invasive and has potential complications, such as bleeding, thrombosis, renal failure, or infection, and even has a measurable mortality risk of 0.16%. CTA and MRA, in contrast, are noninvasive imaging modalities that allow visualization of the arterial tree. However, MRA may overestimate the degree of stenosis and is not suitable for patients with metallic implants and may require sedation in patients with claustrophobia. Further, CTA may not offer adequate precision to delineate patency of the tibial or pedal vessels. Further, CTA requires large-volume intravenous contrast, which may cause or exacerbate renal failure. Additionally, in severely calcified small vessels, three-dimensional reconstruction may project occluded vessels as patent. Utility of each individual modality is summarized in Figure 2.
FIGURE 2 • Imaging modality selection.
Right lower-extremity angiography shows a segmental occlusion of the superficial femoral artery, with above-knee popliteal reconstitution, as shown in Figure 3.
FIGURE 3 • Angiogram of mid-SFA occlusion.
Endovascular Intervention: A Step-by-step Navigation
Prior to any endovascular intervention, all prior imaging of the lower-extremity arterial system should be carefully reviewed. Knowledge of previous access sites, deployed devices, and angiographic results are critical in determining both the progression of disease and the most effective intervention. Furthermore, past interventions can drastically limit current interventional options. For example, prior common iliac “kissing” stents extended into the aorta can limit a retrograde femoral approach from the contralateral groin. Review of prior procedure notes can be very helpful in planning a repeat procedure as well as avoiding previously encountered anatomic difficulties. For example, in the superficial femoral artery (SFA), there are several factors that weigh into the decision to perform angioplasty, stenting, or both. Examples of these factors are shown in Table 1.
TABLE 1. Landing Zones and the Technical Considerations to Aid in Successful SFA Interventions
Arterial access must be obtained either retrograde or antegrade common femoral artery approach. In our practice, the majority of procedures are usually performed through the retrograde femoral approach. A small diameter sheath is placed. Typically, 4 to 5 Fr sheath is sufficient for majority of diagnostic procedures and a 6 Fr sheath for most therapeutic procedures. Aortography and bilateral pelvic angiography is performed to ensure proper inflow. Selective arteriogram then is performed to define the arterial lesion and plan the intervention.
After review of the diagnostic imaging, the lesion is determined to be amenable to percutaneous intervention based on trans-atlantic classification (TASC) II classification. In general, class A and B lesions are amenable to percutaneous intervention, while class C and D lesions present more difficult technical challenges. Intervention often consists of angioplasty, and several studies demonstrate improved results when angioplasty is accompanied by stent placement, especially in the superficial femoral artery, as shown in Figure 4.
FIGURE 4 • Angiogram of stented SFA.
Preoperative Consideration in Open Revascularization
For open lower-extremity bypass, patients with active cardiac conditions should undergo preoperative evaluation. The list of conditions that require cardiac evaluation can be found in Table 2. Venous mapping must also be performed prior to intervention. Vein diameter and length are evaluated with duplex ultrasound, and patency of deep venous system is evaluated to assure adequate venous return following revascularization. Suitable vein for the bypass is ipsilateral greater saphenous vein usually 3 mm or more in diameter. The course of the saphenous vein is marked and length of suitable vein is measured to assure tension-free bypass to desired location. If no suitable veins were found in lower and upper extremities, then consideration must be given to alternative conduit, such as prosthetic material.
Infrainguinal bypass procedures need to arise from a patent and uncompromised inflow artery. If the infrainguinal bypass is constructed following an inflow procedure, anastomosis to a native artery rather than the inflow graft improves patency. Accordingly, the procedure, in a “step-by-step” navigation, is outlined below.
TABLE 2. Clinical Indications for Cardiac Evaluation Prior to Lowerextremity Revascularization
Adapted from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation. 2007;116(17):1971–1996.
The lower abdomen and the affected extremity are prepped and draped in sterile fashion. Incision is made along the previously marked saphenous vein based on preoperative venous mapping. The vein is dissected and evaluated for quality and length for bypass procedure. The saphenofemoral junction is exposed. All venous tributaries are ligated and vein is harvested by transecting vein distally and proximally. The common femoral artery enters the femoral triangle slightly medial to the midpoint of the inguinal ligament. Within the femoral triangle, the common femoral divides into deep and superficial branches. To expose the common femoral artery, a vertical incision is placed in the groin over the pulse and extended one-third above the inguinal ligament and two-thirds below. The femoral artery is identified and exposed by opening the femoral sheath. Care must be taken not to injure femoral vein that lies medial to the artery. The distal target vessel is selected to provide inline flow to the foot. For patients with claudication, commonly the popliteal artery will be sufficient to provide flow to the foot. As the infrageniculate popliteal artery is less likely to be affected by atherosclerotic process, in our practice it is used more frequently for bypass. The popliteal artery is exposed by placing incision 1 cm behind the posterior border of the tibia. If the saphenous vein has not been harvested at this point in the procedure, care must be taken not to injure it in this location. The crural fascia is incised and the gastrocnemius muscle is retracted posteriorly. The popliteal artery is identified medial to the posterior tibial nerve and the popliteal vein. The popliteal vein must be retracted to gain access to more lateral artery. Bridging veins often times have to be divided to gain access to popliteal artery. It is carefully dissected free over a distance of 4 to 5 cm.
Decisions then need to be made in terms of how to route the conduit from the inflow to outflow artery. Reversed, nonreversed, and in situ vein conduits appear to work equally well, and each strategy has distinct advantages and disadvantages. In our practice, we most commonly perform in situ technique with intraoperative angioscopy and valve lysis.
After preparation of the vein conduit and establishing a tunnel site, the patient is systemically anti-coagulated with heparin. Longitudinal arteriotomy is performed on popliteal artery and anastomosis is performed in running fashion with 6-0 prolene suture. After completion of the anastomosis, the suture line is tested for any evidence of leak or stenosis. The proximal anastomosis is then performed in similar fashion (Figure 5). If there is significant calcification at the origin of profunda femoris, an endarterectomy is performed with a patch angioplasty and bypass graft is sutured to the patch. Upon completion of the bypass, duplex ultrasound interrogation or completion arteriogram should be performed to evaluate the technical adequacy of the bypass graft.
Postoperative Management
We routinely prescribe clopidogrel for all endovascular interventions performed below the inguinal ligament. Further, recent evidence suggests that cilastozol is also a helpful adjunct in preventing restenosis. Anticoagulation with coumadin is not routinely used unless the patient took this medication prior to the procedure, or unless the bypass is “compromised” in some way, such as poor conduit or outflow. This is typically restarted on the night of the procedure. Based on findings of better primary and secondary patency with statin agents, we routinely prescribe statin agents for all those undergoing SFA and tibial interventions. Whether there is more benefit in high-dose compared with low-dose statins remains unclear, and therefore in most patients we generally treat with low-dose statins.
FIGURE 5 • A: Diagram of femoral to below the knee popliteal bypass. B: Arterial exposures for femoral to below the knee popliteal bypass.
Surveillance duplex after open bypass is performed based on the type of bypass, prior duplex US findings, and the risk of bypass graft stenosis or thrombosis. Decisions about the timing and frequency of surveillance should be tailored to individual patient characteristics. In our practice, the first duplex surveillance typically is scheduled 3 to 4 weeks following the bypass, and follow-up occurs 6 months to yearly thereafter.
TAKE HOME POINTS
· Life-limiting claudication has low risk of limb loss but is a sensitive marker of overall patient-level cardiovascular risk.
· It is important to distinguish lifestyle-limiting claudication and CLI.
· Risk factor modification and supervised exercise therapy are key elements in the initial treatment of claudication.
· Careful preoperative planning of endovascular interventions and open lower-extremity bypass procedures is vital in achieving good outcomes.
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