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The symptoms of lower extremity occlusive disease are classified into two large categories: acute limb ischemia (ALI) and chronic limb ischemia (CLI). Ninety percent of acute ischemia cases are either thrombotic or embolic. Frequently, sudden onset of limb-threatening ischemia may be the result of acute exacerbation of the pre-existing atherosclerotic disease. Chronic ischemia is largely due to atherosclerotic changes of the lower extremity that manifest from asymptomatic to limb-threatening gangrene. As the population ages, the prevalence of chronic occlusive disease of the lower extremity is increasing, and it significantly influences lifestyle, morbidity, and mortality. In addition, multiple comorbid conditions increase risks of surgical procedures. Endovascular interventions become an important alternative in treating lower extremity occlusive disease. However, despite rapidly evolving endovascular technology, lower extremity endovascular intervention continues to be one of the most controversial areas of endovascular therapy.
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In a detailed review of the literature, McDaniel and Cronenwett concluded that claudication occurred in 1.8% of patients under 60 years of age, 3.7% of patients between 60 and 70 years of age, and 5.2% of patients over 70 years of age.163 Leng and his colleagues scanned 784 subjects using ultrasound in a random sample of men and women age 56 to 77 years. Of the subjects who were scanned, 64% demonstrated atherosclerotic plaque.164 However, a large number of patients had occlusive disease without significant symptoms. In a study by Schroll and Munck, only 19% of patients with peripheral vascular disease were symptomatic.165 Using ABIs, Stoffers and colleagues scanned 3171 individuals between the ages of 45 and 75 and identified that 6.9% of patients had ABIs <0.95, only 22% of whom had symptoms.166 In addition, they demonstrated that concomitant cardiovascular and cerebrovascular diseases were three to four times higher among the group with asymptomatic peripheral vascular diseases than those without peripheral vascular disease. Furthermore, they confirmed that 68% of all peripheral arterial obstructive diseases were unknown to the primary care physician, and this group mainly represented less advanced cases of atherosclerosis. However, among patients with an ABI ratio <0.75, 42% were unknown to the primary physicians.
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Diagnostic Evaluation
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The diagnosis of lower extremity occlusive disease is often made based on a focused history and physical examination and confirmed by the imaging studies. A well-performed physical examination often reveals the site of lesions by detecting changes in pulses, temperature, and appearances. The bedside ABIs using blood pressure cuff also aid in diagnosis. Various clinical signs and symptoms are useful to differentiate conditions of viable, threatened, and irreversible limb ischemia caused by arterial insufficiency (Table 23-16).
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Noninvasive studies are important in documenting the severity of occlusive disease objectively. Ultrasound Dopplers measuring ABIs and segmental pressures are widely used in North America and Europe. Normal ABI is greater than 1.0. In patients with claudication, ABIs decrease to 0.5 to 0.9 and to even lower levels in patients with rest pain or tissue loss.167 Segmental pressures are helpful in identifying the level of involvement. Decrease in segmental pressure between two segments indicates significant disease. Ultrasound duplex scans are used to identify the site of lesion by revealing flow disturbance and velocity changes. A meta-analysis of 71 studies by Koelemay and associates confirmed that duplex scanning is accurate for assessing arterial occlusive disease in patients suffering from claudication or critical ischemia with a accumulative sensitivity of 80% and specificity of over 95%.168 Adding an ultrasound contrast agent further increases the sensitivity and specificity of ultrasound technology.169 Other noninvasive imaging technologies, such as MRA and CTA, are rapidly evolving and gaining popularity in the diagnosis of lower extremity occlusive disease (Figs. 23-59 and 23-60).
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Contrast angiography remains the gold standard imaging study. Using contrast angiography, interventionists can locate and size the anatomic significant lesions and measure the pressure gradient across the lesion, as well as plan for potential intervention. Angiography is, however, semi-invasive and should be confined to patients for whom surgical or percutaneous intervention is contemplated. Patients with borderline renal function may need to have alternate contrast agents, such as gadolinium or carbon dioxide, to avoid contrast-induced nephrotoxicity.
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Differential Diagnosis
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Arterial insufficiency frequently leads to muscle ischemic pain involving the lower extremity muscles, particularly during exercise. Intermittent claudication is pain affecting the calf and, less commonly, the thigh and buttock that is induced by exercise and relieved by rest. Symptom severity varies from mild to severe. Intermittent claudication occurs as a result of muscle ischemia during exercise caused by obstruction to arterial flow. Regarding the differential diagnosis of intermittent claudication, there are a variety of neurologic, musculoskeletal, and venous conditions that may produce symptoms of calf pain (Table 23-17). Additionally, various nonatherosclerotic conditions can also cause symptoms consistent with intermittent lower extremity claudication (Table 23-18). Nocturnal calf muscle spasms or night cramps are not indicative of arterial disease. They are common but are difficult to diagnose with certainty. Foot ulceration is not always the result of arterial insufficiency. Ischemic ulcers occur on the toes or lateral side of the foot and are painful. By comparison, venous ulcers, which are also common, occur above the medial malleolus, usually in an area with the skin changes of lipodermatosclerosis, and cause mild discomfort. Neuropathic ulcers are usually found on weight-bearing surfaces, have thick calluses, and are pain free. Ulcers may be the result of more than one etiology. Rest pain must be distinguished from peripheral neuropathy, which is prevalent in diabetic patients. Patients with diabetic neuropathy tend to have decreased vibration and position sense and decreased reflexes. Spinal stenosis causes pain that is exacerbated with standing and back extension.
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Lower Extremity Occlusive Disease Classification
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Lower extremity occlusive disease may range from exhibiting no symptoms to limb-threatening gangrene. There are two major classifications developed based on the clinical presentations.
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The Fontaine classification uses four stages: Fontaine I is the stage when patients are asymptomatic; Fontaine II is when they have mild (IIa) or severe (IIb) claudication; Fontaine III is when they have ischemic rest pain; and Fontaine IV is when patients suffer tissue loss, such as ulceration or gangrene (Table 23-19).170
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The Rutherford classification has four grades (0–III) and seven categories (0–6). Asymptomatic patients are classified into category 0; claudicants are stratified into grade I and divided into three categories based on the severity of the symptoms; patients with rest pain belong to grade II and category 4; and patients with tissue loss are classified into grade III and categories 5 and 6 based on the significance of the tissue loss.2 These clinical classifications help to establish uniform standards in evaluating and reporting the results of diagnostic measurements and therapeutic interventions (Table 23-19).
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The most clinically useful classification of lower extremity atherosclerotic disease should be based on the morphologic character of the lesions. The TASC taskforce published a guideline separating lower extremity arterial diseases into femoropopliteal and infrapopliteal lesions (Table 23-20). This guideline is particularly useful in determining intervention strategies based on the disease classifications. Based on the guideline, femoropopliteal lesions are divided into four types: A, B, C, and D. Type A lesions are single focal lesions less than 3 cm in length and do not involve the origins of the SFA or the distal popliteal artery. Type B lesions are single lesions 3 to 5 cm in length not involving the distal popliteal artery or multiple or heavily calcified lesions less than 3 cm in length. Type C lesions are multiple stenoses or occlusions greater than 15 cm in length or recurrent stenoses or occlusions that need treatment after two endovascular interventions. Type D lesions are those with complete occlusion of CFA, SFA, or popliteal artery.2
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In a similar fashion, infrapopliteal arterial diseases are classified into four types based on TASC guideline (Fig. 23-61). Type A lesions are single lesions less than 1 cm in length not involving the trifurcation. Type B lesions are multiple lesions less than 1 cm in length or single lesions shorter than 1 cm involving the trifurcation. Type C lesions are lesions that extensively involve trifurcation or 1- to 4-cm stenotic or 1- to 2-cm occlusive lesions. Type D lesions are occlusions longer than 2 cm or diffuse lesions.2
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Etiology of Acute Limb Ischemia
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ALI is defined as sudden loss of limb perfusion, and the term is applicable up to 2 weeks after an initiating event. While the instances of acute leg ischemia caused by emboli have decreased due to more effective treatment of rheumatic fever and atrial fibrillation, the incidence of thrombotic acute leg ischemia has increased. Even with the extensive use of newer endovascular techniques including thrombolysis, most published series report a 10% to 30% 30-day amputation rate.2 The short-term mortality of patients presenting with acute ischemia is 15% to 20%. The most common etiologies of ALI include embolism, native vessel thrombosis, reconstruction thrombosis, trauma, and complications of peripheral aneurysm. Most cases of lower extremity ALI are the result of thrombosis of a prosthetic conduit. This stems from increased use of prosthetic conduits to address CLI.
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Presenting symptoms in ALI are pain and loss of sensory or motor function. The abruptness and time of onset of the pain, its location and intensity, and change in severity over time should all be taken into consideration. The duration and intensity of the pain and presence of motor or sensory changes are very important in clinical decision making and urgency of revascularization. Thrombolysis may be less effective for thrombosis of ≥2 weeks in duration compared with acute thrombosis.171
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The heart is the most common source of distal emboli, which accounts for more than 90% of peripheral arterial embolic events. Atrial fibrillation is the most common source. Sudden cardioversion results in the dilated noncontractile atrial appendage regaining contractile activity, which can dislodge the contained thrombus. Other cardiac sources include mural thrombus overlying a myocardial infarction or thrombus forming within a dilated left ventricular aneurysm. Mural thrombi can also develop within a ventricle dilated by cardiomyopathy. Emboli that arise from a ventricular aneurysm or from a dilated cardiomyopathy can be very large and can lodge at the aortic bifurcation (saddle embolus), thus rendering both legs ischemic. Diseased valves are another source of distal embolization. Historically, this occurred as a result of rheumatic heart disease. Currently, subacute endocarditis and acute bacterial endocarditis are the more common causes. Infected emboli can seed the recipient vessel wall, creating mycotic aneurysms.
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An electrocardiogram (ECG) will diagnose atrial fibrillation. A transthoracic or transesophageal echocardiogram should be performed looking for a cardiac source. It is important to seek other sources of the embolus using CT scanning of the descending thoracic and abdominal aorta. More unusual sources include mural thrombus from an aortic aneurysm, and occasionally, idiopathic arterial-to-arterial thrombus occurs, usually from thrombus that has formed in an atherosclerotic aortic arch or descending thoracic aorta. The presence of mobile plaque on transesophageal echocardiography is suggestive of this source.
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Paradoxical embolus occurs when a patient has a patent foramen ovale and an embolus from a deep venous thrombosis crosses through the atrial defect into the left side of the heart and passes into the peripheral circulation. This is diagnosed using a bubble echocardiography, in which air bubbles introduced into the venous circulation can be seen traversing the septal defect.
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Thrombosis can occur in native arteries and in arterial reconstructions. Patients with thrombosed arterial segments often have an underlying atherosclerotic lesion at the site of thrombosis or aneurysmal degeneration with mural thrombosis. It is important to obtain a history, determine risk factors for atherosclerosis and hypercoagulable status, and examine the contralateral extremity for circulatory problems. Patients with thrombosis of prior arterial reconstructions have limb incisions from previous surgery, and graft occlusion can be confirmed with duplex imaging.
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Clinical Manifestations of Acute Limb Ischemia
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Acute lower extremity ischemia manifests with the “five Ps”: pain, pallor, paresthesias, paralysis, and pulselessness, to which some add a sixth “P”—poikilothermia or “perishing cold.” Pain is the usual symptom that causes a patient to present to the emergency room. The most common location for an embolus to lodge in the leg is at the common femoral bifurcation. Typically a patient will complain of foot and calf pain. Pulses are absent, and there may be diminution of sensation. Inability to move the affected muscle group is a sign of very severe ischemia and necessitates urgent revascularization. During evaluation of the affected extremity, it is important to compare findings with the contralateral limb. Clinical evaluation is extremely important in determining the etiology and location of the obstruction. One of the most important pieces of information to obtain is whether the patient has had prior vascular procedures or if there is a history of lower extremity claudication. Either of these features suggests pre-existing vascular disease, renders revascularization more complicated, and usually mandates angiography to permit surgical planning. On the contrary, in a patient with no history suggestive of prior vascular disease, the etiology is most likely embolic, and simple thrombectomy is more likely to be successful.
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Absent bilateral femoral pulses in a patient with bilateral lower extremity ischemia is most likely due to saddle embolus to the aortic bifurcation. A palpable femoral pulse and absent popliteal and distal pulses may either be due to distal common femoral embolus (the pulse being palpable above the level of occlusion) or embolus to the superficial femoral or popliteal arteries. Typically, emboli lodge at arterial bifurcations where they are trapped due to sudden reductions in arterial diameter. A popliteal trifurcation embolus will present with calf ischemia and absent pedal pulses, possibly with a popliteal pulse present. The finding of palpable contralateral pulses and the absence of ipsilateral pulses in the acutely ischemic leg are suggestive of an embolus, irrespective of presence of Doppler signals. Arteriography is not mandatory in patients without antecedent history suggestive of vascular disease; nevertheless, all patients should be positioned on the operating room table in such a way that fluoroscopic access to the entire inflow and outflow tract is possible if necessary.
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The main question to be answered by the history and physical examination is the severity of the ALI, which is the major consideration in early management decisions. Patients with ALI should be evaluated in a fashion that considers the severity and duration of ischemia at the time of presentation. Ideally, all patients with acute ischemia should be investigated with imaging, especially if there is an antecedent vascular reconstruction; however, the clinical condition and access to resources must guide further investigations.2 Unnecessary delays can result in amputation. Arteriography, if it can be performed in a timely fashion, is an excellent modality for localizing obstructions and deciding which type of intervention (endovascular, embolectomy, or bypass) patients will benefit more from. One of the goals of treatment for ALI is to prevent thrombus propagation; therefore, expedient anticoagulation with heparin is indicated as soon as the diagnosis is suspected.
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Treatment Considerations for Acute Limb Ischemia
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In the absence of any significant contraindication, the patient with an ischemic lower extremity should be immediately anticoagulated. This will prevent propagation of the clot into unaffected vascular beds. Intravenous fluid should be started and a Foley catheter inserted to monitor urine output. Baseline labs should be obtained and creatinine levels noted. A hypercoagulable workup should be performed prior to initiation of heparin if there is sufficient suspicion. According to results from randomized trials, there is no clear superiority for thrombolysis over surgery in terms of 30-day limb salvage or mortality. Access to each treatment option is a major issue in the decision-making process, as time is often critical. National registry data from the United States reveal that surgery is used three- to five-fold more frequently than thrombolysis. Three randomized studies have investigated the role of catheter-directed thrombolytic therapy in the treatment of ALI.172
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Endovascular Treatment
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The potential to reduce mortality and morbidity while achieving limb salvage is the impetus that makes thrombolysis preferable to open surgery as first-line treatment in patients with ALI (class I and IIa). Advantages of thrombolytic therapy over balloon embolectomy include the reduced endothelial trauma and potential for more gradual and complete clot lysis in branch vessels usually too small to access by embolectomy balloons. It is hoped that the more gradual clot dissolution with thrombolysis may decrease the incidence of reperfusion injury that is encountered after open surgical procedures where rapid return of blood flow may precipitate compartment syndrome. Skeletal muscle tissue appears to be most vulnerable to ischemia. Pathophysiologic studies reveal that irreversible damage to muscle tissue starts after 3 hours of ischemia and is nearly complete at 6 hours. Progressive microvascular damage appears to follow rather than precede skeletal muscle tissue damage. The more severe the cellular damage, the greater are the microvascular changes. When the musculature and microvasculature are severely damaged, amputation rather than attempts at revascularization may be the most prudent course to prevent wash-out of toxic by-product from the ischemic limb into the systemic circulation. The mortality rate associated with reperfusion syndrome is high, because of the development of concomitant adult respiratory distress syndrome, shock, disseminated intravascular coagulation, and renal failure.
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Patients with small-vessel occlusion are poor candidates for surgery because they lack distal target vessels to use for bypass. These patients should be offered a trial of thrombolysis, unless they have contraindications to thrombolysis or their ischemia is so severe that the time needed to achieve adequate lysis is considered too long. The major contraindications of thrombolysis are recent stroke, intracranial primary malignancy, brain metastases, or intracranial surgical intervention. Relative contraindications for performance of thrombolysis include renal insufficiency, allergy to contrast material, cardiac thrombus, diabetic retinopathy, coagulopathy, and recent arterial puncture or surgery (Table 23-21).
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Advances in clot removal techniques with percutaneous mechanical thrombectomy and thromboaspiration may extend the applicability of this intervention to patients with more advanced degrees of ALI (class IIb) and contraindications to thrombolysis. Several thrombectomy devices have received FDA approval for acute lower extremity arterial thrombosis. The utility of these thrombectomy devices is that they can be used as standalone therapy when there are contraindications for thrombolytic therapy. Additionally, these thrombectomy devices can be used in conjunction with thrombolytic agents, for pharmacomechanical thrombectomy, to enhance clot lysis and to limit the doses and time required for thrombolysis.173,174
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When a decision is made to proceed with open surgical intervention, the abdomen, contralateral groin, and entire lower extremity are prepped in the field. The groin is opened through a vertical incision, exposing the CFA and its bifurcation. Frequently, the location of the embolus at the femoral bifurcation is readily apparent by the presence of a palpable proximal femoral pulse, which disappears distally. The artery is clamped and opened transversely over the bifurcation. Thrombus is extracted by passing a Fogarty balloon embolectomy catheter. Good back-bleeding and antegrade bleeding suggest that the entire clot has been removed. Embolic material often forms a cast of the vessel and is sent for culture and histologic examination. Completion angiography is advisable to ascertain the adequacy of clot removal. The artery is then closed and the patient fully anticoagulated.
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When an embolus lodges in the popliteal artery, in most cases it can be extracted via a femoral incision using the techniques previously described. A femoral approach is preferred because the larger diameter of the femoral artery results in decreased likelihood of arterial compromise when the arteriotomy is closed. The disadvantage with using the femoral approach for embolectomy is the greater difficulty involved in directing the embolectomy catheter into each of the infrapopliteal arteries. Use of fluoroscopic imaging and an over-the-wire thrombectomy catheter can overcome this problem. Alternatively, use of a separate incision to expose the popliteal bifurcation may be necessary to achieve a complete thrombectomy.
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A more complex situation arises when a patient has antecedent peripheral vascular disease and in situ thrombosis develops on top of pre-existing atheroma because, frequently, embolectomy catheters will not pass through these occlusions. Similarly, when a bypass graft fails, it is usually due to progression of atheroma proximal or distal to the graft anastomoses or to intrinsic stenoses that develop within a vein graft. In these scenarios, expeditious angiography is useful to determine the extent of the occlusion, to search for inflow and distal outflow vessels, and to decide whether thrombolysis or surgery will be the better intervention. Although the surgeon’s preference tends to dictate the approach selected, the decision is based on the presence or absence of good target vessels and availability of a suitable bypass conduit. If there are good distal vessels and the saphenous vein is suitable, surgical bypass is recommended, because it is fast, durable, and reliable. In the absence of a good distal target and saphenous vein, or in a patient at high risk for surgery, lysis is recommended.
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Bypass Graft Thrombectomy
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Bypass thrombectomy is more likely to succeed with prosthetic bypasses. Bypass graft revision or replacement is more appropriate for acute vein graft failures because they are less likely to respond to thrombolysis and require some type of revision, such as valve lysis, interposition, or extension. Thrombectomy of autogenous grafts is prone to failure unless an anatomic cause for failure such as a retained valve or unligated side branch is found and corrected. The performance of a fasciotomy to circumvent reperfusion injury/compartment syndrome is an important consideration.
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Complications Related to Treatment for Acute Limb Ischemia
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Adverse events related to catheter-directed thrombolysis are primarily related to bleeding complications. The overall risk of hemorrhagic stroke from a thrombolysis procedure has been reported to be 1% to 2.3%, with 50% of hemorrhagic complications occurring during the thrombolytic procedure.175 Hematoma at the vascular puncture site has been reported in 12% to 17% of cases. Gastrointestinal bleeding is reported in 5% to 10% of cases. Hematuria following thrombolysis is uncommon and should prompt a search for urinary tumors. Hemorrhage requiring transfusion can occur in approximately 25% of patients undergoing thrombolysis.167,172 Lytic agents are absolutely contraindicated in patients with intracranial surgery, intracranial hemorrhage within the last 3 months, or any active bleeding. Most bleeding complications occur at the arterial puncture sites, but concealed retroperitoneal bleeding is possible. The most feared complication that patients can sustain is intracerebral hemorrhage. Older patients may be more susceptible to this complication, and thus many interventionalists are extremely reticent to use thrombolysis in patients older than 80 years of age.
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Patients who are treated for acute ischemia are susceptible to two major complications following revascularization: reperfusion and compartment syndromes. Other procedure-related complications include arterial rethrombosis, recurrent embolization, and arterial injuries secondary to the balloon catheter manipulations.
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Reperfusion of the ischemic limb is variable in its physiologic effects and directly relates to the severity and extent of the ischemia. Patients with a saddle embolus of the aortic bifurcation and severely ischemic limbs may develop the full-blown “reperfusion syndrome,” whereas patients with minimal muscle ischemia who are reperfused in a timely fashion essentially develop no effects. Many patients with ALI have severe underlying cardiac disease and are unable to tolerate even short ischemic periods. Complications occurring after revascularization of the lower extremity and causes of recurrent thrombosis are listed in Table 23-22.
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Compartment syndrome occurs after prolonged ischemia is followed by reperfusion. The capillaries leak fluid into the interstitial space in the muscles, which are enclosed within a nondistensible fascial envelope. When the pressure inside the compartment exceeds the capillary perfusion pressure, nutrient flow ceases and progressive ischemia occurs, even in the presence of peripheral pulses. Consequently, every patient who has sustained an ischemic event and is reperfused is monitored for compartment syndrome, which is characterized by excessive pain in the compartment, pain on passive stretching of the compartment, and sensory loss due to nerve compression of the nerves coursing though the compartment (Table 23-23 and Fig. 23-62). The most commonly affected compartment is the anterior compartment in the leg. Numbness in the web space between the first and second toes is diagnostic due to compression of the deep peroneal nerve. Compartment pressure is measured by inserting an arterial line into the compartment and recording the pressure. Although controversial, pressures greater than 20 mmHg are an indication for fasciotomy. Compartment pressures are relieved in the leg by medial and lateral incisions. Through the medial incision, long openings are then made in the fascia of the superficial and deep posterior compartments. Through the lateral incision, the anterior and peroneal compartments are opened. Both skin and fascial incisions should be of adequate length to ensure full compartment decompression. Laboratory evidence of rhabdomyolysis is seen in 20% of cases. The myoglobin from damaged muscle precipitates in kidney tubules and causes acute tubular necrosis. Alkalinization of urine increases the solubility of myoglobin, thus preventing it from crystallizing in the tubules. In addition to alkalinization, therapy consists of forced saline diuresis and removal of the source of dead muscle that is releasing the myoglobin.
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Clinical Manifestations of Chronic Limb Ischemia
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The term CLI is reserved for patients with objectively proven arterial occlusive disease and symptoms lasting for more than 2 weeks. Symptoms include rest pain and tissue loss, such as ulceration or gangrene (Table 23-24). The diagnosis should be corroborated with noninvasive diagnostic tests, such as the ABI, toe pressures, and transcutaneous oxygen measurements. Ischemic rest pain most commonly occurs below an ankle pressure of 50 mmHg or a toe pressure less than 30 mmHg.2 Ulcers are not always of an ischemic etiology (Table 23-25). In many instances, there are other etiologic factors (traumatic, venous, or neuropathic) that are contributory, but it is underlying peripheral arterial disease that may be responsible for delayed or absent healing (Fig. 23-63). Healing of ulcers requires an inflammatory response and greater perfusion than is required to support intact skin and underlying tissues. As a result, the ankle and toe pressure levels needed for healing are higher than the pressures seen with ischemic rest pain. For patients with ulcers or gangrene, the presence of CLI is suggested by an ankle pressure less than 70 mmHg or a toe systolic pressure less than 50 mmHg.2 It is important to understand that there is no definite consensus regarding the vascular hemodynamic parameters required to make the diagnosis of CLI.
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One of the most common sites for occlusive disease is in the distal SFA as it passes deep through the adductor canal. It may be that the entrapment by the adductor hiatus prevents the compensatory dilation that occurs in atherosclerotic vessels. Stenoses, which develop here, progress to occlusion of the distal third of the SFA (Fig. 23-64). When distal SFA occlusion develops slowly, it may be totally asymptomatic because of development of collaterals from the proximal SFA, or the PFA can bypass the occlusion and reconstitute the popliteal artery. Symptom development is a function of the extent of occlusion, adequacy of collaterals, and the activity level of the patients.
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Presenting symptoms of femoropopliteal occlusive disease are broadly classified into two types: limb-threatening and non–limb-threatening ischemia. Claudication is non–limb-threatening, while rest pain, ulceration, and gangrene are limb-threatening and warrant urgent intervention. Occlusive disease of the femoral artery may be isolated or occur in conjunction with multilevel disease that involves both the aortoiliac segment and the tibial vessels. Symptoms in patients with multilevel disease are more severe than in those with single-level disease. Pain from isolated SFA and popliteal occlusion typically manifests as calf claudication. Cramping pain develops in the calf on ambulation, occurs at a reproducible distance, and is relieved by rest. Activities such as climbing stairs or going uphill also exacerbate the pain. Many patients report worsening symptoms during cold weather. It is important to evaluate whether the symptoms are progressive or static. In greater than 70% of patients, the disease is stable, particularly with risk factor modification.
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Progression of the underlying atherosclerotic process is more likely to occur in patients with diabetes, those who continue to smoke, and those who fail to modify their atherosclerotic risk factors. In comparison, rest pain is constant, and usually occurs in the forefoot across the metatarsophalangeal joint. It is worse at night and requires placing the foot in a dependent position to improve symptoms. Patients may report that they either sleep in a chair or hang the foot off the side of the bed. The pain is severe and relentless, even with narcotics. Ischemic ulceration most commonly involves the toes. Any toe can be affected. Occasionally ulcers develop on the dorsum of the foot. Ulceration can occur in atypical positions in an ischemic foot from trauma such as friction from poorly fitting shoes. Injury to a foot with borderline ischemia can convert an otherwise stable situation into one that is limb-threatening. The initial development of gangrene commonly involves the digits. As with all vascular patients, it is important to evaluate their risk factors, intercurrent cardiac diseases, and any prior vascular interventions.
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Treatment Considerations for Chronic Limb Ischemia
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Patients with vascular diseases frequently have complicated medical comorbidities. Careful patient evaluation and selection should be performed for any peripheral arterial vascular procedure. The fundamental principle is to assess not only the surgical risk from the peripheral arterial system but also the global nature of the atherosclerotic process. Full cardiac evaluations are often necessary due to the high incidence of concomitant atherosclerotic coronary artery disease, resulting in a high risk for ischemic events. Hertzer and associates reviewed coronary angiographies on 1000 patients undergoing elective vascular procedure and identified 25% of concomitant correctable coronary artery disease including 21% in patients undergoing elective peripheral vascular intervention.8 Conte and associates analyzed their 20-year experience in 1642 open lower extremity reconstructive surgeries and concluded that patients requiring lower extremity reconstruction presented an increasingly complex medical and surgical challenge compared with the previous decade in a tertiary practice setting.176 With aging of the population, a growing number of vascular patients have prohibitive medical cormobidities and are deemed high-risk for open surgical repair. Endovascular intervention provides an attractive alternative.
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As for open surgical repair, the clinical indications for endovascular intervention of lower extremity peripheral arterial diseases include lifestyle-limiting claudication, ischemic rest pain, and tissue loss or gangrene. Importantly, endovascular procedures should be performed by a competent vascular interventionist who understands the vascular disease process and is familiar with a variety of endovascular techniques. In addition, certain lesions may not be amendable to endovascular treatment or may be associated with poor outcomes, such as long segment occlusion, heavily calcified lesion, orifice lesion, or lesions that cannot be traversed by a guidewire. Proper selection of patients and techniques is critical in achieving good long-term outcome.
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Endovascular intervention for lower extremity occlusive disease is continuously evolving. Success and patency rates of endovascular intervention are closely related to the anatomic and morphologic characteristics of the treated lesions. The TASC work group made recommendations on the intervention strategies of lower extremity arterial diseases based on the morphologic characteristics. Based on TASC guidelines, endovascular treatment is recommended for type A lesions, open surgery is recommended for type D lesions, and no recommendations were made for types B and C lesions. However, with rapid advancement in endovascular technologies, there are increased numbers of lesions amendable to endovascular interventions.
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There is less literature support for infrapopliteal endovascular intervention due to higher complication and lower success rates. The treatment is restricted for patients with limb-threatening ischemia who lack surgical alternatives. However, with further advancement of endovascular technology and the development of new devices, endovascular intervention is becoming an integral part of treatment (Table 23-26). By itself or combined with open technique, percutaneous intervention plays an important role in therapeutic options for lower extremity occlusive disease. As described by TASC guidelines, four criteria should be measured to evaluate the clinical success of the treatment: improvement in walking distance, symptomatic improvement, quality of life, and overall graft patency. These criteria should all be carefully weighed and evaluated for each individual prior to endovascular therapy.
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Endovascular Treatment
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Technical Considerations
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A sterile field is required in either an operating room or an angiography suite with image capability. The most common and safest access site is CFA via either a retrograde or an antegrade approach. For diagnostic angiography, arterial access should be contralateral to the symptomatic sides. For therapeutic procedures, location of the lesion and the anatomic structures of the arterial tree determine the puncture site. To avoid puncturing the iliac artery or SFA, the femoral head is located under the fluoroscopy and used as the guide for the level of needle entry. In addition, there are several useful techniques to help access a pulseless CFA including ultrasound-guided puncture, using a micropuncture kit, and targeting calcification in a calcified vessel. The antegrade approach may be challenging, particularly in obese patients. Meticulous technique is crucial in preventing complications, and a bony landmark can be used as guidance to ensure CFA puncture.
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Traversing the lesion with a wire is the most critical part of the procedure. Typically, 0.035-inch guidewires are used for femoropopliteal lesions, and 0.014- or 0.018-inch guidewires are used for infrapopliteal access. Hydrophilic-coated wires, such as Glidewires, are useful in navigating through tight stenosis or occlusion. An angled-tip wire with a torque device may be helpful in crossing an eccentric lesion, and a shaped selective catheter is frequently used in helping manipulating the wire across the lesion. The soft and floppy end of the wire is carefully advanced crossing the lesion under fluoroscopy, and gentle force is applied while manipulating the wire. Once the lesion us traversed, one needs to pay particular attention on the tip of the wire to ensure a secure wire access and avoid vessel wall perforation or dissection.
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Once the access to the diseased vessel is secured and the wire has successfully traversed the lesion, several treatment modalities can be used either alone or in conjunction with others, including angioplasty, stent or stent graft placement, and atherectomy. The available angioplasty techniques are balloon angioplasty, cryoplasty, subintimal angioplasty, and cutting balloon; the most commonly used atherectomy techniques include percutaneous atherectomy catheter and laser atherectomy device.
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Systemic anticoagulation should be maintained routinely during lower extremity arterial interventions to minimize the risk of pericatheter thrombosis. Unfractionated heparin is the most commonly used agent, administered using a weight-based formula. We typically use 80 to 100 mg/kg initial bolus for therapeutic procedure to achieve an activated clotting time above 250 seconds upon catheter insertion and administer a subsequent 1000 units for each additional hour of the procedure. Newer agents, such as low molecular weight heparin, platelet IIb/IIIa inhibitors, direct thrombin inhibitors, or recombinant hirudin, have been available and can be used either alone or in conjunction with heparin particularly in patients sensitive to unfractionated heparin. After the procedure, all patients are placed on antiplatelet therapy, such as aspirin. Additional antiplatelet agents, such as clopidogrel (Plavix), are given to selected patients with stent placement for at least 6 weeks after lower extremity interventions unless otherwise contraindicated.
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Percutaneous Transluminal Balloon Angioplasty
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After the lesion is crossed with a wire, an appropriated balloon angioplasty catheter is selected and tracked along the wire to traverse the lesion. The length of the selected catheter should be slightly longer than the lesion, and the diameter should be equal to the adjacent normal vessel. The balloon tends to be approximately 10% to 20% oversized. The radiopaque markers of the balloon catheter are placed so that they will straddle the lesion. Then, the balloon is inflated with saline and contrast mixture to allow visualization of the insufflation process under the fluoroscopy (Fig. 23-65). The patient may experience mild pain, which is not uncommon. However, severe pain can be indicative of vessel rupture, dissection, or other complications. An angiography is crucial in confirming the intraluminal location of the catheter and absence of contrast extravasation. The inflation is continued until the waist of the atherosclerotic lesion is disappeared and the balloon is at the full profile. Frequently, several inflations are required to achieve a full profile of the balloon (Fig. 23-66). Occasionally, a lower profile balloon is needed to predilate the tight stenosis so that the selected balloon catheter can cross the lesion.
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Besides length and diameter, the operators need to be familiar with several balloon characters. Noncompliant and low-compliant balloons tend to be inflated to their preset diameter and offer greater dilating force at the site of stenosis. Low-compliant balloons are the mainstay for peripheral intervention. A balloon with a low profile is used to minimize complications at the entry site and for crossing the tight lesions. Upon inflation, most balloons do not rewrap to their preinflation diameter and assume larger profiles. Furthermore, trackability, pushability, and crossability of the balloon should be considered when choosing a particular type of balloon. Lastly, shoulder length is an important characteristic when performing PTA to avoid injury to the adjacent arterial segments. After PTA, a completion angiogram is performed while the wire is still in place. Leaving the wire in place provides access for repeating the procedure if the result is unsatisfactory.
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PTA is an established and effective therapy for select patients with lower extremity occlusive diseases. Studies have shown that PTA of femoropopliteal segment achieved over 90% technical success rate and 38% to 58% 5-year primary patency rates.177,178,179 However, efficacy of PTA is highly dependent on anatomic selection and patient condition.134 PTA of lesions longer than 7 to 10 cm offers limited patency, whereas PTA of shorter lesions, such as those less than 3 cm, has fairly good results. Lofberg and associates performed 127 femoropopliteal PTA procedures and reported a primary 5-year success rate of 12% in limbs with occlusion longer than 5 cm versus 32% in limbs with occlusion less than 5 cm in length.180 Occlusive lesions have much worse initial technical success rates than stenotic lesions. Concentric lesions respond better to PTA than eccentric lesions, and heavy calcifications have a negative impact on success rates. A meta-analysis by Hunink and associates showed that adjusted 5-year primary patencies after angioplasty of femoropopliteal lesions varied from 12% to 68%, with the best results being for patients with claudication and stenotic lesions.179 Distal runoff is another powerful predictor of long-term success. Johnston analyzed 254 consecutive patients who underwent femoral and popliteal PTA and reported a 5-year patency rate of 53% for stenotic lesions and 36% for occlusive lesions in patients with good runoff versus a 5-year patency rate of 31% for stenotic lesions and 16% for occlusive lesions in patients with poor runoff.178 Literature reviews showed that 5-year patency rates varied from 27% to 67% based on runoff status.179
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Due to limited success with infrapopliteal PTA, the indication for infrapopliteal PTA is stringent and reserved for limb salvage. Current patency rates from infrapopliteal PTA can be improved further by proper patient selection, ensuring straight-line flow to the foot in at least one tibial vessel, and close patient surveillance for early reintervention. Possible future advances, including the use of drug-eluting stents, cutting balloons, and atherectomy devices, are being investigated to improve clinical outcomes following endovascular interventions on the tibial arteries. Varty and associates reported a 1-year limb salvage rate of 77% in patients with critical ischemia who underwent infrapopliteal PTA.181 In patients with favorable anatomies, the 2-year limb salvage rate after infrapopliteal PTA is expected to exceed 80%.
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Subintimal Angioplasty
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The technique of subintimal angioplasty was first described in 1987 when successful establishment of flow was made by accidental creation of a subintimal channel during treatment of a long popliteal artery occlusion. Subintimal angioplasty is recommended for chronic occlusion, long segment of lesion, and heavily calcified lesions. In addition, this technique is applicable for vessels with diffuse disease and for vessels that had previously failed an intraluminal approach, when it is difficult to negotiate the wire across the entire diseased segment without dissection.
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The principle of this technique is to bypass the occlusion by deliberately creating a subintimal dissection plan commencing proximal to the lesion and continuing in the subintimal space before break back into the true lumen distal to the lesion. The occluded lumen is recanalized through the subintimal plan. Subintimal angioplasty can be performed through either an ipsilateral antegrade or contralateral retrograde approach using the CFA approach. If selecting contralateral CFA puncture, a long guiding sheath is placed across the aortic bifurcation to provide access for the femoropopliteal and infrapopliteal vessels. The subintimal dissection is initiated at the origin of an occlusion by directing the tip of an angled guide wire, usually an angled hydrophilic wire, such as a Glidewire. A supporting catheter is used to guide the tip of the guidewire away from the important collaterals. When the wire is advanced, a loop is naturally formed at the tip of the guidewire. Once the subintimal plan is entered, the wire tends to move freely in dissection space. Subintimal location of the wire and the catheter can be confirmed by injecting a small amount of diluted contrast. At this point, the wire and the catheter are then advanced along the subintimal plan until the occlusion segment is passed. A loss of resistance is often encountered as the guidewire re-enters the true lumen distal to the occlusion. Recanalization is confirmed by advancing the catheter over the guidewire beyond the point of re-entry and obtaining an angiogram. This is followed by a balloon angioplasty. To confirm the patency following balloon dilatation, a completion angiogram is performed prior to withdrawing the catheter and wire. If flow is impaired, repeat balloon dilatation may be necessary. Frequently, a stent is required to maintain a patent lumen and treat residual stenosis if more than 30% luminal reduction is confirmed on completion angiogram.
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Multiple studies have demonstrated the efficacy of subintimal angioplasty. Bolia and colleagues reported their extensive experiences on subintimal angioplasty for treating long-segment occlusions of infrainguinal vessels.182,183 They achieved a technical success rate of over 80% for both femoropopliteal and tibial arteries. One-year patency rates varied from 53% for infrapopliteal vessels to 71% for femoropopliteal segments. Limb salvage rates reached over 80% at 12 months. They also reported that the factors influencing patency are smoking, number of runoff vessels, and occlusion length. Studies by other groups showed similar results.184,185 Treiman and colleagues treated 25 patients with 6- to 18-cm femoropopliteal occlusion and achieved a technical success rate of 92% and a 13-month primary patency rate of 92%,185 whereas Lipsitz and associates reported a technical success rate of 87% in 39 treated patients and a 12-month cumulative patency rate of 74%.184 In addition, Ingle and associates reported a technical success rate of 87% in 67 patients with femoropopliteal lesions and a 36-month limb salvage rate of 94%.186 As demonstrated herein, although technical success rates are similar in most series, the patency rates vary widely in different studies. Patient selection, anatomic character, and lesion locations may account for the wide range of outcomes.
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Although suggested by Dotter during the late 1960s, the use of an endoluminal stent was not pursued until the limitations of PTA were widely recognized. There are several situations where stent placement is appealing. The primary indication is the potential salvage of an unacceptable angioplasty result. Stent placement is typically used when residual stenosis after PTA is 30% or greater. An endoluminal stent is also used for dissection, perforation, and other PTA complications. Primary stent placement has become a viable alternative for treating ulcerative lesions that may potentially be the source for embolization. Primary stent is also used to treat occlusive lesions that have a tendency for reocclusion and distal embolization after PTA. In addition, an endoluminal stent is potentially beneficial for early restenosis after PTA. Drug-eluting stents are currently under investigation in the United States and may be promising in decreasing restenosis rates.
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Although technical success rates are high, published series on femoropopliteal artery stents show that patency rates are comparable to PTA alone, with primary patency rates varying from 18% to 72% at 3 years.134,187 Gray and associates stented 58 limbs after suboptimal PTA for long SFA lesions and demonstrated a 1-year primary patency rate of 22%.188 However, Mewissen treated 137 limbs using self-expanding SMART nitinol stents in patients with TASC A, B, and C femoropopliteal lesions and reported a 1-year primary patency of 76% and a 24-month primary patency rate of 60%.189 Appropriate patient selection and the anatomic characteristics of the lesions are crucial in the success of treatment outcomes. Additionally, stent characteristics may contribute to the patency rate.
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Several clinical studies have demonstrated the significant improvements of the new generation of nitinol stents for the SFA lesions: the German Multicenter Experience, the Mewissen trial, the BLASTER Trial, and the SIROCCO trial.190 The German Multicenter Experience was a retrospective review of 111 SFA stenting procedures and predicted that the 6-month patency rate for SMART stents was 82% versus 37% for the Wallstent. The BLASTER (Bilateral Lower Arterial Stenting Employing Reopro) Trial evaluated the feasibility of using nitinol stents with and without intravenous abciximab for the treatment of femoral artery disease, and the preliminary results showed a 1-year clinical patency rate of 83%.191
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Furthermore, the drug-eluting stent, which proved effective in decreasing restenosis in coronary intervention, may offer another promising alternative in lower extremity diseases. The drug released over a period of time interferes with smooth muscle cell proliferation, the main cellular element and source of extracellular matrix–producing restenosis. The first drug-eluting stent clinical trial used Cordis Cypher SMART stents coated with sirolimus (SIROCCO trial).192 The SIROCCO results showed binary in-lesion restenosis rates of 0% in the sirolimus-eluting group versus 23.5% in the noneluting group at 6-month follow-up angiography. The PaRADISE (Preventing Amputations Using Drug-Eluting Stents) Trial investigated the efficacy and safety of using balloon-expandable drug-eluting stents to prevent amputations in patients with below-the-knee critical limb ischemia.13 One hundred six patients (118 limbs) were treated with drug-eluting stents in this prospective, nonrandomized trial. There were 228 drug-eluting stents implanted (83% Cypher [Cordis, Johnson & Johnson, Warren, NJ], 17% Taxus [Boston Scientific, Maple Grove, MN]). The average length treated was 60 mm. The 3-year cumulative incidence of amputation was 6%, the survival rate was 71%, and the amputation-free survival rate was 68%. Only 12% of patients who died had a preceding major amputation. Rutherford category, age, creatinine level, and dialysis were predictors of death but not amputation. Target limb revascularization occurred in 15% of patients.
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The concept of endobypass using stent graft in treating atherosclerotic SFA disease has been entertained. A stent graft is placed percutaneously across a long segment or multiple segments of lesions and is used to create a femoropopliteal bypass. Theoretically, endobypass has the potential of being as successful as surgical bypass graft by relining the vessel wall in its anatomic position without the negative impact of anastomosis. Stent grafts can be divided into two categories: unsupported and fully supported. The unsupported grafts consist of segments of bypass graft, such as PTFE, with an expandable stent at one or both ends. The unsupported grafts are flexible with a low profile, but prone to external compression. The supported stent grafts consist of a metallic skeleton covered with graft fabric. The presence of a dense metal skeleton promotes an extensive inflammatory response and increases the risk of thrombosis. There is no FDA-approved stent graft for peripheral intervention. However, Viabahn (WL Gore & Associates, Flagstaff, AZ) is the most commonly used device in the United States and is composed of an ultra-thin PTFE graft externally supported by self-expanding nitinol meshwork. The Viabahn device has a specific delivery mechanism by pulling back the attached string, which results in proximal-to-distal delivery of the endoprosthesis.
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Although it is an intriguing concept, data on endobypass results are limited, and the graft thrombosis rate is high. Additionally, covering major collateral vessels can potentially jeopardize the viability of the limb if stent graft occlusion occurs. Bauermeister treated 35 patients with Hemobahn and reported a 28.6% occlusion rate at an average 7-month follow-up.193 Kedora and colleagues recently conducted a prospective, randomized study comparing covered PTFE/nitinol self-expanding stent grafts with prosthetic above-the-knee femoropopliteal bypass. Fifty limbs were randomized into each group. Primary patency at 1 year was approximately 74% for both cohorts, with a mean follow-up of 18 months. The covered nitinol/PTFE stent graft in the SFA had a 1-year patency comparable to surgical bypass, with a significantly shorter hospital stay (0.9 vs. 3.1 days).194 A recent randomized prospective study comparing the treatment of SFA occlusive disease percutaneously with an expanded PTFE (ePTFE)/nitinol self-expanding stent graft (stent graft) versus surgical femoral to above-knee popliteal artery bypass with synthetic graft material showed no difference between the two groups with respect to primary or secondary patency rates at 48 months.195 Mean total lesion length of the treated arterial segment in the stent graft group was 25.6 cm. The stent graft group demonstrated a primary patency of 72%, 63%, 63%, and 59% with a secondary patency of 83%, 74%, 74%, and 74% at 12, 24, 36, and 48 months, respectively. The surgical femoral-popliteal group demonstrated a primary patency of 76%, 63%, 63%, and 58% with a secondary patency of 86%, 76%, 76%, and 71% at 12, 24, 36, and 48 months, respectively. The authors concluded that ePTFE/nitinol self-expanding stent graft placement can be offered as an alternative to treatment of the SFA segment for revascularization when prosthetic bypass is being considered or when autologous conduit is unavailable.
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The basic principle of atherectomy is to remove the atheroma from obstructed arterial vessels. The currently available atherectomy devices can be generally categorized into directional, nondirectional, orbital, and rotational types based on their mecahnism. A few examples of FDA-approved atherectomy devices are Simpson AtheroCath (DVI, Redwood City, CA), Transluminal Extraction Catheter (Interventional Technologies, San Diego, CA), Thoratec recanalization arterial catheter (Thoratec, Pleasanton, CA), Auth Rotablator (Heart Technologies, Redmond, WA), SilverHawk system (FoxHollow Technologies, Redwood City, CA), Jetstream atherectomy system (Bayer, Indianola, PA), Diamondback 360° orbital atherectomy device (Cardiovascular Systems, Inc., St. Paul, MN), and Rotablator system (Boston Scientific Corporation, Natick, MA). These devices either cut and remove or pulverize the atheroma plaques.
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The Simpson AtheroCath has a directional cutting element that is exposed to one third of the circumference of the arterial wall. The atheroma protruding into the window is excised and pushed into the collection chamber. The Transluminal Extraction Catheter has an over-the-wire nondirectional cutter mounted on the distal end of a torque tube. The excised atheroma is simultaneously removed by aspiration through the torque tube. The Thoratec recanalization arterial catheter is a nondirectional, noncoaxial, atheroablative device. The rotating cam tip pulverizes the atheromatous lesion into minute particles. The Auth Rotablator is a nondirectional, coaxial, atheroablative device with a metal burr embedded with fine diamond chips. SilverHawk device is a monorail catheter designed to overcome the drawbacks of a directional atherectomy catheter. The working end consists of a hinged housing unit containing a carbide cutting blade. The blade is activated from the motor drive unit, and the catheter is then advanced through the length of the lesion. Once each pass is completed, the cutter then packs the tissue into the distal end of the nosecone to maximize collection capacity. The SilverHawk can then either be removed or torqued to treat a different quadrant in the same lesion or other lesions. Jetstream atherectomy system is a rotating, aspirating catheter with tip sizes of 1.6 and 1.8 mm for tibial arteries, and an expandable catheter with a tip size ranging from 2.1 to 3.4 mm for active removal of atherosclerotic debris and thrombus. The Diamondback 360° orbital atherectomy device uses a drive shaft with an eccentrically mounted, diamond-coated crown to create an orbital spin. As the speed of the crown increases from centrifugal force, it sands wider spaces, thereby providing variability in its working range. It can create a lumen that is >1.75 times the crossing profile depending on the size of the grit and the eccentricity of the offset. The greater the speed of the crown, the larger is the arc of debulking and, ultimately, the resultant lumen size. A constant flow of saline solution is delivered by a roller pump that lubricates the device and helps to flush the debris. The Rotablator system high-speed rotational device uses calcium ablation to achieve larger lumens. It has been used for more than 20 years to treat challenging, calcified coronary artery disease. The diamond-coated burr is designed to preferentially engage calcium and modify lesion compliance.