Infrainguinal Occlusive Disease Treatment & Management

Guidelines for management of infrainguinal occlusive disease have been formulated by the Society for Vascular Surgery (SVS), ^[39]  as well as by the European Society for Cardiology (ESC) in collaboration with the European Society for Vascular Surgery (ESVS). ^[40]  (See Guidelines.) Guidelines for management of chronic limb-threatening ischemia (CLTI; a term increasingly favored over chronic limb ischemia [CLI]) have been formulated by the SVS, the ESVS, and the World Federation of Vascular Societies (WFVS). ^[6]

Indications for lower-extremity revascularization include the following:

• Gangrene
• Pain at rest
• Nonhealing arterial ulcer
• Disabling claudication

In nonambulatory patients with ischemic pain at rest, gangrene, or extensive nonhealing wounds, primary lower-extremity amputation may be a better choice than vascular bypass surgery.

Technological enhancements and wider availability of existing technology should continue to improve the safety and efficacy of endovascular and vascular surgical techniques. ^{[41, 42]}

Imaging technology continues to be refined. ^[43]  Three-dimensional (3D) ultrasonographic (US) visualization can help better detect early plaque formation to allow for even more timely correction of vein graft stenoses. Gadolinium-enhanced 3D magnetic resonance angiography (MRA) images can provide highly detailed views of the arterial system. The applications of MRA, including guidance of endovascular interventions, ^[44]  will expand with continuing improvements in hardware, software, and nonnephrotoxic contrast agents.

Endovascular procedures continue to benefit from improved technology both in imaging modalities and instrumentation. ^[45]  In the performance of an in-situ bypass, endovascular technology allows valvulotomy and coil occlusion of side branches by direct angioscopic visualization.

As in other surgical fields, endoscopy may have a greater role in infrainguinal vascular surgery. For example, endoscopic harvesting of the saphenous vein limits the extent of the dissection required for bypass procedures. ^[46]

Studies have suggested that in patients with limb-threatening ischemia but inoperably diseased distal arteries, arterialization of the distal venous bed may be of benefit. ^{[15, 47]}

Gene therapy holds promise for inhibiting vascular restenosis after endovascular procedures or bypass surgery. Rat and rabbit models suggest that neointimal hyperplasia after arterial injury is inhibited by overexpression of the GAX gene and that adenovirus-mediated delivery of the GAX gene diminishes proliferation of intimal cells in animal models. Gene therapy may be suitable for vein grafts prior to implantation.

Some research is underway on inhibitors of smooth-muscle proliferation, such as drugs that block E2F transcription factors. ^{[2, 48]}  A multicenter, randomized, double-blinded study of 1404 patients revealed no benefit from the use of edifoligide, an E2F inhibitor. ^{[49, 50]}

Low-dose intravascular beta-irradiation may inhibit restenosis by blocking early medial and adventitial cell proliferation. ^[51]

Various endovascular devices have been developed for lower-extremity revascularization, including the following ^{[52, 53]} :

• Catheters to cross chronic total occlusions ^[54]
• Reentry device
• Stent graft
• Debulking devices (excisional atherectomy, rotational atherectomy, laser)
• Cryoplasty
• Embolic protection device
• Cutting balloon

Development of new technologies and refinement of existing devices will improve the armamentarium of endovascular therapy. The long-term outcome of endovascular treatment compared with open surgical bypass has not yet been sufficiently well studied, and further research is warranted. ^{[55, 56]}

Most patients with atherosclerotic lower-extremity disease do not undergo surgical treatment. In fact, only 25% of patients presenting with intermittent claudication eventually require invasive treatment of limb-threatening ischemia or intractable symptoms, and only 5-10% do so within 5 years of the onset of claudication.

The cornerstones of medical management of intermittent claudication are walking and elimination or control of medical risk factors. ^{[57, 58]} (See also Noncoronary Atherosclerosis and Coronary Artery Atherosclerosis.)

Walking

Encourage walking. ^[59] Regular walking of approximately 1 hour per day usually results in a significant increase in walking distance over time. This increase in walking distance has been noted to range from 80% to more than 200%. Improvement results from improved flow in collateral pathways.

Risk factor management

A major factor contributing to progressive and intractable atherosclerotic disease is cigarette smoking. One study noted an 85% chance of improvement if smoking is stopped versus only a 20% chance of improvement if the patient continues smoking.

Other medical risk factors that must be assessed and controlled are obesity, hypertension, hyperlipidemia, and diabetes. ^[60]

Because an ischemic foot is at risk for developing limb-threatening ulceration from even minor trauma, good foot hygiene and appropriately fitting shoes are important. This is even more vital for patients with diabetes, who are also at risk for neuropathic foot ulcers.

Pharmacotherapy

Currently available drugs that may benefit patients with mild or moderate claudication include pentoxifylline and cilostazol. ^{[61, 62]} Controlled studies suggest that each of these drugs improves walking distance by approximately 20% more than placebo, cilostazol perhaps slightly more than pentoxifylline.

Cilostazol, administered at 100 mg orally twice daily, has demonstrated some benefit for claudication symptoms. ^[63] Cilostazol is contraindicated in patients with congestive heart failure, ^[64] as noted in the product's black box warning.

Pentoxifylline, 400 mg orally three times per day taken with meals, has been available for many years. After 2-3 months of use, 25-60% of patients demonstrate some improvement in walking distance. However, much of this improvement may be attributable to exercise and to modification of the risk factors mentioned above. The major adverse effects of this medication are gastrointestinal in nature.

Antiplatelet agents (eg, aspirin, clopidogrel), angiotensin-converting enzyme (ACE) inhibitors, and statins should also be considered.

Caveats regarding pharmacotherapy are that vasodilators and chelation therapy have no demonstrated benefit in the treatment of claudication. Beta-blocking agents may worsen claudication and must be discontinued, if medically feasible.

Surgical or endovascular intervention is indicated for intractable and disabling claudication, for ischemic pain at rest, and for ischemic necrosis. Surgery also may be useful for nonhealing ischemic ulceration.

Before considering surgical intervention, the clinician must address the possibility of coexisting atherosclerotic heart and cerebrovascular disease, which are extremely common in patients with atherosclerotic peripheral arterial disease (PAD). One study found that only 14% of patients with PAD had normal coronary arteries, whereas 15% had severe coronary artery disease (CAD) that required surgical correction. (See Atherosclerosis for the cardiologic workup.)

Patients with a prior ipsilateral peripheral endovascular intervention have been found to have a higher likelihood of a poor outcome when undergoing lower-extremity bypass for CLTI. ^[65] Reported 1-year amputation and graft occlusion rates have been higher in these patients than those who have not undergone prior revascularization procedures (eg, prior ipsilateral bypass). These factors can help determine revascularization options in patients with CLTI. ^[65]

However, Uhl et al carried out a retrospective analysis comparing patients who had undergone tibial or peroneal bypass surgery for CLTI after prior endovascular interventions with patients who had received a tibial or peroneal bypass as a primary revascularization procedure because primary endovascular therapy had been considered unfeasible. ^[66] They found that prior endovascular intervention in femorotibial vessels did not negatively affect the outcome of subsequent tibial or peroneal bypass surgery.

A British study reports that the major amputation rate after femorodistal bypass remains high, with adverse events occurring after approximately 38% of femoropopliteal procedures and nearly 50% of femorodistal bypasses. The main predictors of a poor outcome reportedly were diabetes and chronic renal failure. ^[20]

Obtain appropriate imaging studies. Before surgical intervention, the exact extent of the atherosclerotic disease is mapped by using high-quality contrast angiography (see Imaging Studies).

In recognition of the importance of the pathologic anatomy in decision making, the Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) published a set of guidelines for treatment of lower-extremity PAD (see Table 2 below). ^[67]

Table 2. TASC Classification for Femoral Popliteal Lesions (Open Table in a new window)

The general recommendations are endovascular intervention for TASC type A lesions and open surgery for TASC type D lesions. Insufficient data are available on type B and C lesions; however, type B lesions are probably best treated endovascularly and type C lesions best treated with open surgery.

Preparation for surgery

Prior to vascular surgery, a routine laboratory workup is performed, including complete blood count, biochemical profile, clotting studies, urinalysis, chest radiography, and electrocardiography (ECG). Abnormalities are addressed.

Although some suggest discontinuing clopidogrel preoperatively to minimize intraoperative bleeding risks, one analysis suggests that this is not necessary and that clopidogrel therapy can be safely continued. ^[68]

Radiographic contrast

If an endovascular procedure is to be performed, iodinated contrast material is required, and hence, one must check for renal insufficiency, a history of contrast allergy, and the use of metformin (see Imaging Studies).

Infection prevention

Take appropriate measures to prevent vascular graft infection. For routine prophylaxis in bypass surgery, a broad-spectrum antibiotic (eg, a broad-spectrum cephalosporin, a penicillin/beta-lactamase inhibitor, or an aminoglycoside) is administered just before surgery and postoperatively for one to three doses. If there is known colonization with or local prevalence of methicillin-resistant Staphylococcus aureus (MRSA), consider vancomycin or teicoplanin. ^[69]

Consider a preoperative antiseptic shower or scrub.

Patients harboring a potential infection (eg, foot ulcer or gangrene) may fare better having the infected tissue excised, even with limited amputations, prior to vascular intervention in order to avoid graft or wound infections.

Urgent intervention

If urgent intervention is required, the workup may have to be truncated. In the case of acute arterial occlusion, the workup may have to be minimal because prompt thrombectomy is often required for limb salvage. Preoperative angiography may still be warranted, especially if evidence of underlying atherosclerotic disease is present.

Operative details

Although PAD is a diffuse process, the preponderance of findings can often be attributed to a particular segment of the arterial tree. Angiographic findings combined with knowledge of the patient's symptoms, physical findings, and noninvasive laboratory results leads the vascular specialist to determine which artery or arteries are best treated by invasive means. ^[70]

This determination is not an exact science, and it is not unusual for the vascular specialist to correct a single lesion and then discover that the recurring symptoms dictate another procedure at a later date. Nonetheless, attempting to correct all diseased segments at once usually confers too high an operative risk.

Disease of iliac artery

Hemodynamically significant disease involving the iliac arteries, particularly short-segment stenotic and even occlusive disease, can usually be successfully treated with percutaneous angioplasty, percutaneous insertion of an arterial stent, or both. ^{[71, 72]}

If endovascular reconstruction is not possible, femorofemoral crossover bypass is usually the best choice for unilateral iliac artery occlusion, and aortobifemoral bypass is usually the best choice for bilateral or diffuse aortoiliac disease. ^[73]

Axillofemoral bypass is an alternative in high-risk patients who cannot tolerate an intra-abdominal or retroperitoneal operation (see Aortoiliac Occlusive Disease).

Disease involving femoral artery

Hemodynamically significant disease involving the femoral artery is usually the result of relatively long-segment occlusion of the distal superficial femoral artery in the adductor canal.

Endovascular approaches to infrainguinal disease have become increasingly successful. Secondary interventions are often required, but assisted patency rates are reported as over 90% in appropriately selected patients.

Correction of this type of disease often requires bypass from a pulsatile distal common femoral artery to the pulseless popliteal artery. Such a bypass is best performed by using the ipsilateral great (long) saphenous vein (GSV). If this vein is not suitable or has been used previously, alternative conduits for above-the-knee bypasses include expanded polytetrafluoroethylene (ePTFE) prosthetic graft, Dacron graft, tanned bovine umbilical vein graft, and glutaraldehyde-tanned human umbilical vein. ^[74]

Because of inferior patency rates with prosthetic grafts extending below the knee, the vascular surgeon usually tries to locate a usable autologous vein from the contralateral lower extremity by combining available short segments from both sides, upper-extremity veins, or even composite grafts (in which a prosthetic graft extends to the knee and a piece of autologous vein is attached distally or when a vein patch is used to attach the prosthetic graft to the distal artery).

In a study of diabetic patients with CLTI, autologous saphenous vein operations for below-the-knee bypasses were superior to ePTFE grafts in terms of primary patency. However, secondary patency rates were not statistically different between the two procedures, and limb salvage rates were comparable. ^[75]

Angioplasty with or without stenting may be appropriate for short-segment superficial femoral artery occlusive disease.

Disease involving infrapopliteal arterial tree

Extensive disease involving the infrapopliteal segments is best managed by means of autologous vein grafting. Arguably, the best technique is the use of the ipsilateral saphenous vein in situ.

This is a somewhat tedious procedure in which the saphenous vein is first disconnected from the femoral vein in the groin and anastomosed to the common femoral artery. The vein is then transected distally, and a valvulotome is inserted retrograde and withdrawn so as to destroy the valves that would have prevented arterial flow from the groin to the leg in the vein.

Next, an anastomosis is created between the distal end of the vein and a usable small artery, even as far distally as the dorsalis pedis at the ankle or foot. Finally, the vein branches are ligated to stop arteriovenous flow.

Patients must be selected carefully for this technique. The vein must be patent and of adequate length and caliber, and a usable, soft distal artery must be available. Preoperative vein mapping using duplex scanning is sometimes helpful.

Endovascular procedures

Percutaneous transluminal angioplasty is often appropriate for strictures or short-segment occlusions of the superficial femoral, popliteal, and, occasionally, infrapopliteal arteries. ^{[76, 3, 77]}  Angioplasty is performed by passing a guide wire through the lumen of the strictured artery and then advancing a balloon angioplasty catheter over the guide wire. The balloon is inflated to several atmospheres of pressure under angiographic visualization. This effectively disrupts the plaque and provides a wider, patent lumen.

Although angioplasty has been used increasingly for claudication, whether the risks justify the benefits for many patients in this group is a serious question. ^[78]  In a randomized controlled trial, Bradbury et al found that angioplasty has a high failure rate (~25%) in patients with severe limb ischemia from infrainguinal occlusive disease and that patients who underwent bypass after failed angioplasty fared significantly worse than those who underwent surgery as their first procedure. ^[79]

Nevertheless, Bradbury et al suggested that in patients with severe limb ischemia whose life expectancy is less than 2 years, balloon angioplasty should usually be offered before bypass surgery, in that it is associated with less morbidity and cost, and such patients are unlikely to enjoy the longer-term benefits of surgery. ^[79]

In patients who are expected to live beyond 2 years, bypass surgery should usually be offered first, especially where a vein is available as a conduit. However, patients who cannot undergo a vein bypass may often be better served by a first attempt at balloon angioplasty than prosthetic bypass.

Somewhat surprisingly, even if the guide wire cannot negotiate the lumen of a stricture and instead passes through the subintimal plane, subintimal (extraluminal) angioplasty may succeed. ^[80]  This method seems to create a new channel in a virgin plane. Low echogenicity at the distal end of the plaque, as measured by duplex ultrasound–derived gray-scale median, seems to increase the chance of successful subintimal angoplasy. ^[81]

Chronic total occlusions of infrainguinal vessels may be resistant to conventional guide-wire techniques. In the PATRIOT trial, which included 85 patients with a previous or concurrent failed attempt to cross such an occlusion with a standard guide-wire approach, Laird et al found that the Crosser chronic total occlusion recanalization system facilitated the crossing of chronic infrainguinal occlusions that were resistant to guide-wire crossing, while posing only a minimal risk of clinically significant vessel perforation. ^[54]

Angioplasty approaches making use of drug-coated balloons (DCBs) have been described. A systematic review and meta-analysis of industry-sponsored trials by Caradu et al found that DCB angioplasty was associated with high procedural success in the treatment of femoropopliteal disease and that it consistently reduced late lumen loss, binary restenosis, and target lesion revascularization as compared with plain balloon angioplasty. ^[82]  The authors noted the need for further independent, non-industry-sponsored RCTs to better delineate the role of DCBs in this setting.

Angioplasty may be combined with percutaneous stenting. Self-expanding nickel-titanium alloy (nitinol) stents have demonstrated a 2-year primary patency rate of 47% and a limb salvage rate of 66% when used to treat limb ischemia. ^[83]

Despite the success of drug-eluting stents in the coronary circulation, initial reports using drug-eluting stents in the peripheral circulation were disappointing. However, European investigators documented success with a slow-release everolimus stent to prevent restenosis following peripheral arterial intervention.

The first-in-human Superficial Femoral Artery Treatment with Drug-Eluting Stents (STRIDES) trial showed primary patency (freedom from ≥50% in-stent restenosis) rates of 94 ± 2.3% and 68 ± 4.6% at 6 and 12 months, respectively, for the treatment of symptomatic superficial femoral and proximal popliteal arterial occlusive disease. ^[84]

In addition to intra-procedure anticoagulation, patients are typically treated with an antiplatelet agent, such as clopidogrel, both before and for a month or more postprocedure. ^[83]

Percutaneous endovascular removal of atherosclerotic plaque (ie, atherectomy) seemed promising in the early 1990s, but it was abandoned because of very poor long-term success rates. Subsequently, however, it garnered some renewed interest in research settings. ^{[85, 86, 87, 88, 89, 90]}

Endarterectomy

Removal of atherosclerotic plaque and underlying diseased arterial intima (endarterectomy) at anastomotic sites is sometimes necessary as an adjunct to bypass surgery but is indicated only rarely as the sole management for lower-extremity arterial occlusive disease.

One exception is endarterectomy of the deep femoral (profunda femoris) artery (profundoplasty), which may be useful in the rare case of severe limb-threatening stenosis of the origin of the deep femoral artery associated with a superficial femoral artery occlusion that cannot be bypassed for technical reasons.

Another indication for endarterectomy is to remove localized embolizing ulcerated plaque.

Management of acute arterial occlusion

The usual immediate management of acute arterial occlusion consists of immediate heparin anticoagulation and rapid surgical thromboembolectomy. If time allows, especially if atherosclerotic thrombosis is suggested, preoperative angiography is often wise. It may provide information vital to performing bypass surgery should thrombectomy disclose severe underlying atherosclerotic disease.

In some cases, particularly very high-risk patients, thrombolytic therapy by selective intra-arterial infusion (if available) is a reasonable alternative to emergency surgery. For infrainguinal acute occlusions, a medial approach to the distal popliteal artery trifurcation is usually the best method to allow complete evaluation and clearance of all outflow vessels.

After relief of an acute arterial occlusion, one must be alert to the possibility of reperfusion complications such as compartment syndrome or myopathic-metabolic-nephrotic syndrome. Compartment syndrome is characterized by tense edema of the leg, which raises interstitial tissue pressures and impedes arterial inflow. Emergency four-compartment fasciotomy can save limbs.

Myopathic-metabolic-nephrotic syndrome is the result of reperfusion of essentially irreversibly ischemic muscle. It is characterized by metabolic acidosis, dark urine, and renal failure. Emergency limb amputation may be required to save the patient's life.

After emergency treatment to salvage the ischemic limb, the clinician must determine the etiology of the acute occlusion. If it was thrombotic, the underlying atherosclerotic disease may require correction. If it was embolic, the source must be sought.

Ninety percent of arterial emboli originate in the heart. The remaining emboli originate in the aorta (see DDx) or from venous thrombi that pass into the arterial circulation via a right-to-left intracardiac shunt (paradoxic embolism). Sometimes, the source can be treated, but usually, long-term anticoagulation is required.

Aneurysm resection is indicated for symptomatic, expanding, or sizable popliteal artery aneurysms. A vein graft is usually used to replace the resected or excluded popliteal artery segment. (See Thoracic Aortic Aneurysm.)

Postoperative care after vascular surgery requires in-hospital observation in order to expeditiously detect and treat complications. ^[91]

Occlusion

The most frequent complication of endovascular and vascular surgical procedures is occlusion. Some authorities recommend the use of antiplatelet therapy (eg, aspirin or clopidogrel) starting before angioplasty or bypass surgery and continuing indefinitely. For grafts considered to be at high risk for thrombosis, such as those with poor runoff, with a previous occlusion, with a prosthetic graft, or in a hypercoagulable state, heparin may be given perioperatively, and warfarin may be administered for long-term prophylaxis.

Acute postoperative thrombosis

Any change in circulatory status beyond the bypass graft warrants a rapid evaluation. If thrombosis has occurred, rapid return to the operating room for thrombectomy and repair is required. In such cases, a technical problem (eg, intimal flap) must be sought.

Normal postoperative recovery

Ambulation with the assistance of a physical therapist usually starts gradually on postoperative day 1 or 2. The timing of hospital discharge varies with the extent of the procedure and the patient's general condition. If bypass surgery has been performed in conjunction with significant distal amputations, recovery in a skilled nursing facility or rehabilitation center may be beneficial.

Management following percutaneous procedures

After percutaneous procedures, the patient is observed from 4 hours to overnight to ensure absolute bed rest and detect possible complications of the puncture and intervention. Antiplatelet therapy is usually prescribed. For patients with renal compromise and those on metformin, check serum creatinine values 1-2 days after the procedure.

Important complications of vascular surgery include early postoperative occlusion, hemorrhagic problems, graft infection, cardiac morbidity, and restenosis.

Early postoperative occlusion

Early postoperative arterial or graft occlusion usually occurs as a result of technical factors such as an intimal flap or the use of a suboptimal conduit. ^[92] Early reocclusion warrants a quick return to the operating room for thrombectomy and repair of any potential technical defect. Unfortunately, the long-term prognosis after a take-back procedure for early graft occlusion is poor, with only approximately one quarter of such grafts still functional 5 years later.

Hemorrhagic problems

Hemorrhage and pseudoaneurysm formation may occur at the arterial puncture site or, less commonly, at a graft suture line. Management of the latter usually requires a return to the operating room for surgical repair; however, endovascular puncture site pseudoaneurysms can sometimes be treated with US-guided compression repair. ^[93]

In this technique, guided by continuous duplex scanning, the pseudoaneurysm is compressed just enough to stop flow outside the lumen of the involved artery but still preserve distal arterial flow. This compression continues for approximately 45 minutes, until the pseudoaneurysm thromboses. Arteriovenous fistulas have also been treated using this technique.

US-guided percutaneous thrombin injection has also been shown to be quite effective and more expeditious. ^[94]

Graft infection

Prosthetic graft infections are rare but serious and may require removal of the bypass graft and even amputation of the limb. They occur in approximately 1% of prosthetic graft bypasses. Currently, methicillin-resistant S aureus is the preponderant pathogen.

Treatment usually requires complete removal of the graft and, if possible, reconstruction using a new graft via an extra-anatomic pathway, such as an iliopopliteal bypass from the iliac artery via the obturator foramen to the popliteal artery beyond the infected graft's distal anastomosis. ^{[95, 96]}

Cardiac morbidity

Plaque in the superficial femoral artery tends to be a late development in patients with generalized atherosclerotic disease. Therefore, the presence of superficial femoral artery plaque conveys a very high likelihood of coexisting cardiac or carotid atherosclerosis. ^[97]

Because of this association of atherosclerotic CAD with PAD, postoperative myocardial events such as cardiac death, nonfatal myocardial infarction, unstable angina, ventricular tachycardia, and congestive heart failure may occur following infrainguinal bypass operations.

Although most studies suggest an overall cardiac complication rate of approximately 5%, one study found that such myocardial events occurred at an alarming rate of 24% in 87 patients undergoing infrainguinal reconstruction.

Restenosis

The most common late complication of both endovascular and vascular reconstructive procedures is restenosis resulting from a proliferation of smooth-muscle cells causing an excessively thickened neointima, which can lead to late arterial or graft reocclusion. This is best prevented by routine postoperative graft surveillance and managed by endovascular repair, patch grafting, of bypass revision before occlusion occurs (see Long-Term Monitoring). Postoperative statin use may decrease restenosis rates. ^[98]

A routine postoperative follow-up assessment is essential, for two reasons.

First, medical management of the underlying atherosclerotic disease must continue.

Second, bypass graft surveillance using noninvasive vascular laboratory testing may help detect problems that can threaten graft patency, such as progressive atherosclerotic disease of inflow or outflow vessels or buildup of scar tissue (neointimal fibrous hyperplasia) at the anastomotic sites. If these problems can be detected before they lead to graft thrombosis, they may be corrected by endovascular means (ie, angioplasty or stenting). Open surgical revision for restenosis of vein grafts, however, carries a higher long-term success rate than percutaneous intervention. ^{[99, 100]}

A typical schedule for outpatient follow-up after peripheral arterial intervention is at 2 weeks, 1 month, 3 months, 6 months, and every 6 months thereafter.