During the past half century, vascular specialists have made major progress in treating vascular diseases with chronic ischemia of the lower extremities. Peripheral arterial occlusive disease (PAOD) presents a clinical spectrum from asymptomatic, intermittent claudication, or critical ischemic change.

The TransAtlantic Inter-Society Consensus (TASC) conference defined critical limb ischemia (CLI) as persistent recurring ischemic rest pain requiring opiate analgesia for at least 2 weeks, ulceration or gangrene of the foot or toes, and ankle systolic pressure <50 mm Hg or toe systolic pressure <30 mm Hg (or absences of pedal pulses in patients with diabetes).

Most patients with rest pain or tissue necrosis have limb loss. Small ulcers may heal with aggressive local management and intermittent rest pain or night pain may improve with the development of collaterals or improvement of cardiac hemodynamics. The mortality rate associated with patients who have claudication is 50% at 5 years, and for patients with CLI, the rate is 70%. This high mortality rate is most commonly associated with cardiac disease, and is generally unrecognized by clinicians. Consequently, the opportunity for risk factors or cardiac intervention maybe overlooked.¹

Atherosclerosis is a systemic disease that is most frequently associated with fatal and nonfatal myocardial infarction (MI), stroke and disease of the aorta, and lower extremities. Peripheral arterial disease (PAD), atherosclerosis in the arteries of the lower extremities; whether it is asymptomatic or symptomatic is a common disorder in the general population. The prevalence of PAD increases with age and presence of vascular risk factors. The estimated overall prevalence of PAD among people of 55 years of age or older varies between 9% and 23%.² The incidence of PAD measured in an open population is 9.9 per 1000 people per year.³ Because of aging population in Western societies, the prevalence of PAD will rise and the medical treatment will become increasingly important.

The majority of patients with PAD is asymptomatic or has leg symptoms other than classic intermittent claudication, which is defined as leg pain usually involving one or both calves that arises by walking and is relieved by rest only. It is estimated that only 22% of patients with PAD have these symptoms.⁴ Elderly male patients with diabetes are especially more likely to have asymptomatic PAD.⁵ The overall annual incidence of symptomatic PAD, with typical intermittent claudication is 1.5 to 2.6 per 1000 men and 1.2 to 3.6 per 1000 women.⁶

Of the patients with asymptomatic PAD, only 5% to 10% will develop symptomatic PAD in a period of over 5 years.⁷ The majority of patients with intermittent claudication as the clinical symptoms of PAD can remain stable over many years. Approximately 15% of these patients develop critical leg ischemia (with ulceration and rest pain) and a high risk for amputation. The annual incidence of CLI is estimated to be 0.25 to 0.45 per 1000 persons.^8,9 Of the patients with CLI, between approximately 20% and 45% will require an amputation of the leg.¹⁰

Approximately 30% of the symptomatic patients will die within 5 years because of vascular diseases and 5% to 10% because of a nonvascular cause.^11,12,13 There is even a trend toward an increased total as well as cardiovascular mortality in patients with asymptomatic PAD.^7,14,15

Risk Factor Modification

Smoking Cessation

Smoking behavior is associated with a considerably increased risk of symptomatic PAD.¹⁶ Symptoms of PAD arise approximately a decade earlier in smokers than in nonsmokers, whereas smokers with PAD have amputation rates twice as high as those who have never smoked.¹⁰ There are suggestions that smoking cessation will decrease the risk for critical leg ischemia and reduce the mortality in patients with PAD.^17,18 Smoking cessation is considered to be critical step in the risk factor management. Although smoking cessation probably reduces the severity of claudication, a meta-analysis concluded that it did not significantly improve the walking distance or walking capacity.¹⁹ There are several possible strategies to support the cessation of smoking, including nicotine replacement,^{20,21,22,23,24} and bupropion, an antidepressant drug.^{25,26,27,28,29} A combination of pharmacology and counseling achieves the highest rate of smoking cessation,²⁹ although there are other modalities including hypnotherapy, acupuncture, aversive smoking.^20,30,31,32

Hypertension

It is recommended that patients with PAD acquire a blood pressure of <130/85 mm Hg,^33,34 although there is no data available to suggest that hypertension treatment alters the arising of intermittent claudication or progression of the disease in the peripheral circulation.

ACE inhibitors showed significantly greater hemodynamic improvement in the extremity in which baseline blood flow is decreased by limb arterial atherosclerosis compared with either or beta-blockers,^35,36 although there is no evidence that beta-blockers are particularly culpable as has been suggested previously.^37,38

Diabetes Mellitus

Diabetes mellitus is highly associated with PAD and its progression.^39,40

Hyperlipidemia

Lipid modification is associated with stabilization and even regression of femoral atherosclerosis.^41,42,43,44 Although diet and exercise have been found to alter the lipid profile toward a less atherogenic type, many patients require lipid-lowering medications. Statins are effective at reducing low-density lipoprotein (LDL)-cholesterol levels, causing a significant reduction in all-cause mortality from 14.7% to 12.9% with the use of simvastatin compared to placebo. For the first occurrence of a major vascular event, a relative reduction of 24% (in absolute terms from 25.2% to 19.8%) was found in the Heart Protection Study.⁴⁵

Lowering the total cholesterol and LDL by 25% with a statin reduces cardiovascular mortality and morbidity in patients with PAD by approximately 25% (relative), irrespective of age, sex, or baseline cholesterol concentration.⁴⁵ In one study,⁴⁶ simvastatin significantly reduces the incidence of new intermittent claudication by 38% compared with placebo (in absolute terms from 3.6% to 2.3%) over 6 years in patients with hypercholesterolemia and coronary heart disease. Both simvastatin and atorvastatin significantly increased the pain-free walking distance after 1 year of treatment with 63%, compared with placebo.^47,48 This effect is most likely to be independent of the effects of serum lipid measurements because of statin use.^47,48

Other lipid-lowering agents including bezafibrate, nicotinic acid, and cilostazol, which have proved to be beneficial in lowering nonfatal coronary events or cardiovascular morbidity and mortality and decreasing plasma triglycerides.^{49,50,51,52,53}

Hyperhomocyteinemia

This condition has a strong association between the increases in plasma homocysteine concentration and PAD.^54,55 There is no current trial available on the treatment of hyperhomocyteinemia in patients with PAD.⁵⁶ An increased level of homocysteine is associated with an increased risk of death from cardiovascular causes.⁵⁵

Antiplatelet Therapy

Antiplatelet therapy with aspirin in patients with PAD showed a significant reduction of 23% (in absolute from 7.1% to 5.8% over an unspecified period) in subsequent serious cardiovascular events, with similar benefit among patients with intermittent claudication.^57,58

Aspirin. Antiplatelet therapy is to be considered in the management of PAD. There is strong evidence that antiplatelet agents reduce major cardiovascular events over an average of 2 years compared with controlled treatment.^57,58 Based on the available evidence, the first line of antiplatelet therapy should be aspirin or clopidogrel.⁵⁹

Clopidogrel. Clopidogrel is a thienopyridyne antiplatelet and associated with less gastrointestinal hemorrhage and upper gastrointestinal upset compared with aspirin.⁶⁰ Although there is little evidence, a combination of antiplatelet therapy with aspirin and clopidogrel could be initiated if a patient experiences a second vascular event while receiving monotherapy.^59,61 However, potential risk of a prolonged bleeding time during this combination of antiplatelet therapy is a concern.⁶²

Dipyridamole. There is no evidence that dipyridamole, as monotherapy or combined with other antiplatelet agents, reduces the risk of vascular death, although it may reduce the risk of further vascular event.⁶³

Anticoagulant Therapy

There is no evidence to support the routine use of warfarin in patients with intermittent claudication who show regular sinus rhythm.⁶⁴

Management of PAD

Exercise. Exercise for the treatment of PAD is highly effective.⁶⁵ With exercise therapy, there is an overall improvement of maximum walking distance of approximately 150% (ranges from 68% to 230%).⁶⁵ Supervised exercise therapy program has significant effect in prolonged maximum walking distance of approximately 300 m after 6 months.^66,67

Pentoxifylline. Pentoxifylline has a small effect on walking ability, although the available data are insufficient to support its widespread use.^19,68,69,70 Several reports were not able to reveal consistent benefit of pentoxifylline versus placebo.^71,72,73,74

Cilostazol. The treatment with drug has shown an increase of the maximum walking distance of approximately 28% to 100%.^{74,75,76,77,78,79} The use of cilostazol was also associated with improvements in physical performance and functional status.^76,77 Cilostazol treatment for up to 12 weeks maybe needed before improvements are experienced, but a favorable response maybe seen as early as 2 to 4 weeks after initiating the therapy.⁷⁹ Cilostazol is contraindicated if symptoms of heart failure are present.

Naftidrofuryl. Several studies with this drug revealed greater efficacy in improving walking distances compared with pentoxifylline and buflomedil by approximately 50% to 80%,^80,81,82 although another study showed no significant difference.⁸³ In other studies, this drug also improved the quality of life of the patient with intermittent claudication.⁸⁴ However, in our routine practice, this drug has not been used as a routine drug.

Other Agents. Both statins and ACE inhibitors are associated with the pain-free walking distance.^{36,85,86,87,88} Several meta-analyses of studies evaluating the Ginkgo biloba special extract, EGb 761, showed a clinically relevant benefit for the treatment of patients with PAD, with significant increase of the pain-free walking distance compared with placebo.^89,90,91 There is insufficient evidence of effective of treatment of propionyl l-carnitine, ozonated autohemotherapy, and chelation therapy in patients with intermittent claudication to recommend its use.^92,93,94 In addition, buflomedil, beraprost, ketanserin, nifedipine, fish oil supplementation, vasodilators, calcium channel antagonists, and alpha-adrenergic blocking agents have shown to be ineffective in the treatment of intermittent claudication.⁹⁵

Prostanoids. This may have beneficial effects on wound healing, limb loss, and survival in patients with CLI.¹⁰ The currently available data support the use of iloprost in patients who are unsuitable for any procedure or in whom revascularization attempts have failed.¹⁰

Antiplatelets and Anticoagulants. Long-term treatment with aspirin and ticlopidine has been shown to reduce the progression of femoral atherosclerosis.⁹⁶ Anticoagulant treatment with low-molecular-weight heparin showed positive results with a decrease in rest pain and an improvement in healing of ulcers previously resistant to treatment.⁹⁷ No clinical trials have been published on the use of unfractionated heparin for critical limb loss or CLI.

Gene-Based Therapy. Therapeutic angiogenesis is suggested to be effective in the treatment of CLI, improving collateral vessel development with subsequent significant improvement in tissue loss, resolution of rest pain, and lowering the level of amputation.^98,99,100 The efficacy was associated with the clinical objective findings of an improved ankle-brachial index (ABI) with a difference of approximately 0.14,¹⁰⁰ a significant increase in pain-free walking time (from 2.5 to 3.8 min) at an average of 13 weeks after gene therapy (p = 0.043), and blood flow on magnetic resonance angiography.^98,100

Vascular endothelial growth factor (VEGF)-induced angiogenic gene therapy in patients with PAD showed clinical efficacy including resolution of resting pain, and healing of ischemic ulcers, associated with objective findings of improved ABI, and blood flow on angiography, on phase I study with intramuscular VEGF gene transfer in their study.¹⁰¹

There is a large volume of literature available on the use of the VEGF gene in ischemic animal limb models. The first group to describe this technique was Takeshita et al.^102,103 who administered plasmids coding for VEGF by the intra-arterial route after ligation of the femoral artery in rabbits and documented an augmentation in collateral circulation through angiography and an increase in capillary density through histology. Using the same model, the authors¹⁰⁴ obtained similar results with an intramuscular injection plasmids coding VEGF 165 (500 μg).

In a recent phase I trial involving treatment of 20 patients (7 with stage IV PAD and 10 with stage III PAD) with 4000 μg of plasmids coding for VEGF, after a 6-month follow-up period, the investigators noted a nonsignificant increase in systolic pressure index with healing of trophic lesions. Angiomagnetic resonance imaging demonstrated increased collateral circulation in all cases. Limb salvage was achieved in three patients. After amputation in one patient, immunohistochemical examination of the ischemic muscle showed intense proliferation of endothelial cells. No systemic complications were observed. The only side effect was treatable lower extremity edema secondary to the increased capillary patency induced by VEGF.¹⁰⁵ Another report showed similar results on the feasibility, efficacy, and safety of VEGF plasmid therapy.¹⁰⁶

Experimental data reported by Ohara et al.¹⁰⁷ showed that the angiographic criteria and capillary density were significantly higher in the treatment group than the control group after adenovirus-mediated transfer of fibroblast growth factor (FGF) via the intra-arterial route in rabbit ischemic hind limb model. This study suggests that transinfection had a beneficial effect.

There are two studies now underway to evaluate the use of FGF for treatment of patients with occlusive arterial disease. One uses a plasmid coding FGF-1 and the other an adenovirus coding for FGF-4, result of which has not been published.¹⁰⁸

Another alternative for using therapeutic angiogenesis is bone marrow mononuclear cell therapy. The bone marrow cells have a natural ability to supply endothelial progenitor cells and to secrete various angiogenic factors or cytokines. In a small randomized trial, the ABI significantly improved with a difference of 0.09 (95% CI: 0.06–0.11), the transcutaneous oxygen pressure increased from 28.8 to 46.3, and pain-free walking distance significantly improved by approximately 3.5 min 24 weeks after injection with bone marrow mononuclear cells. Besides these ischemic status, improvements also rest pain was resolved in 16 out of 20 treated patients, which all was maintained during 24 weeks follow-up.⁹⁹

Pain Relief. A recent meta-analysis about spinal cord stimulation showed that the additional use of spinal cord stimulation to the standard conservative treatment is better than the standard conservative treatment alone.¹⁰⁹ Pooled data showed a significant beneficial effect in terms of limb salvage with a relative risk of 0.71 (95% CI: 0.56–0.90) after 12 months of treatment. Beside pain relief and ulcer healing it may also improve walking ability, and also enhance local circulation.

Thrombolysis. In acute limb ischemia, an acute onset because of an embolic or thrombotic occlusion, thrombolysis is indicated. Two meta-analysis in patients with acute limb ischemia concluded that there is an equal mortality (RR 1.24; 95% CI: 0.80–1.90) and amputation rate (RR 0.89; 95% CI: 0.58–1.38) between patients treated with thrombolysis or surgery. The need for open major surgical procedures on the contrary is reduced after thrombolysis, although with a higher rate of bleeding (RR 2.9; 95% CI: 1.1–7.9) and distal embolization (OR 8.4; 95% CI: 4.5–15.6).^110,111 Urokinase and recombinant tissue-type plasminogen activator are most widely used agents. Both agents reported a similar efficacy and safety level in the STILE study,¹¹² although thrombolysis using low doses of tissue plasminogen activator has a shorter duration and therefore provides a significant overall cost reduction.¹¹³

Additional Agents. The combination of eptifibatide and tenecteplase showed to be a viable option in the treatment of acute limb ischemia. In a study, a high immediate clinical and technical success was demonstrated, as well as an acceptable 3-month clinical outcome, without any case of death, intracranial hemorrhage, or remote-site bleeding.¹¹⁴

Another adjunctive therapy using abciximab, which prevents the binding of fibrinogen, and by this means inhibiting platelet aggregation.¹¹⁵ This treatment was associated with a reduced need for hospitalization, interventions, and amputations and also markedly shortened the duration of clot lysis in comparison with aspirin.¹¹⁶ It is reported that thrombolysis occurred faster using a combination of urokinase and abciximab compared with urokinase alone, although with a higher rate of nonfatal major bleeding.¹¹⁷

In conclusion, all patients with PAD should be treated with the best possible medical modality and risk reduction. When the best medical management and risk reduction management fails to control the problem, the next management plan should be in place including interventional procedure or surgical revascularization. Medical, cardiac, renal, and endocrine optimization of the PAD patient will lead to a successful vascular intervention and surgical revascularization.

Endovascular Procedures

Aortoiliac Occlusive Disease

In 2000 and again in 2007, the release of the TASC statement on treatment of peripheral vascular disease gave stratification by length and morphology of lesions and reinforced the concept of treating short, focal stenoses through endovascular techniques. Long-segment occlusions have been treated using surgical revascularization.

TASC-B lesions include unilateral common iliac artery occlusions only. TASC-C iliac lesions include unilateral external iliac occlusions that do not extend into the common femoral artery, or bilateral common iliac occlusions. TASC-D lesions are bilateral external iliac occlusions, ipsilateral common and external iliac artery occlusions, or diffuse disease of the aorta and both iliac arteries. Endovascular procedures are thought to be the treatment of choice for type A lesions (stenoses <3 cm only), and open surgical therapy is thought to be the procedure of choice for type D lesions. According to the TASC statement, more evidence is needed for type B and C lesions, with a preference for endovascular methods for the former and surgical methods for the latter.¹¹⁸

Several studies have documented the outcomes in the treatment of more complex iliac occlusions of the TASC-C and TASC-D lesions. Review of the data published since 1995 reveals that primary patency ranges from 69% to 76% at 2 years, with a secondary patency rate of 85% to 95% at 2 years.^{119,120,121,122} Furthermore, overall complication rates were lower in recent series (1.4% to 4.8%), likely because of improvements in technique and device technology. In a series of 212 patients with chronic iliac occlusions, successful recanalization was accomplished in nearly 90% of patients, with marked clinical improvement in the vast majority of patients.¹²³ The primary patency at 4 years was 75% in that series.

In the Cleveland Clinic, a total of 89 patients underwent 92 procedures for symptomatic iliac occlusions using endovascular techniques. Recanalization and percutaneous transluminal angioplasty (PTA)-stenting was successful in 82 (91%) of 89 patients, with success rate of 95% and 94% in patients with TASC-B and -C lesions, respectively, as opposed to 86% in TASC-D lesions (not significant).

The inability to completely cross the occluded segment or reenter the distal native artery safely, led to the technical failures. The mean ABI increased from 0.45 to 0.83 after successful treatment.¹²⁴ In their series, intraoperative complications included flow-limiting dissection (n = 5), which was resolved with prolonged balloon angioplasty and stent placement in all cases. Extravasation was seen in two patients and was also treated with prolonged balloon inflation and additional stent placement. Postoperative complications included pseudoaneurysm formation at the access site in two patients treated successfully with thrombin injection. Two patients had distal embolization during the recanalization procedure. One patient required a below-knee amputation and eventually died. The additional patient had embolization that required a minor toe amputation. An additional two perioperative deaths occurred (total n = 3; 3.4%) from cardiac arrest and respiratory arrest.

The primary patency for the complete cohort was 76% at 36 months. Primary patency did not vary significantly (p = 0.99) with TASC stratification and ranged from 73% to 80%. The secondary patency rate for all patients was 90% at 3 years. Patients with TASC-B and TASC-C lesions had secondary patency rates of 95% and 93%, respectively, whereas TASC-D patients had a secondary rate of 83%. However, this difference was not statistically significant (p = 0.86) (Figures 37-1 and 37-2).

Femoral and Distal Arterial Occlusive Disease

PTA is increasingly replacing bypass surgery in the treatment of chronic limb ischemia without compromising patient survival or limb salvage rate. In a study of 57 patients who previously untreated with 71 limbs having chronic arteriosclerotic superficial femoral artery (SFA) occlusion with suprageniculate reconstitution and patent tibial runoff, with critical ischemia (Society for Vascular Surgery category, 4–6), showed 1- and 3-year patency rates of 54.6% ± 6.3% and 29.9% ± 6.6% in primary patency; assisted primary 72.3% ± 5.6% and 59.0% ± 6.8%; and secondary, 81.6% ± 4.8% and 68.3% ± 6.5%. Three-year secondary patency when preprocedural thrombolysis was required was 35.7% ± 12.5% compared with 70.6% ± 7.4% for limbs not requiring periprocedural thrombolysis (p = 0.02); the differences in occlusion length and severity of ischemia were not significant between these two groups. In that study group, length of occlusion was 14.4 ± 9.9 cm, with the mean length of stented artery was 24.3 ± 11.1 cm (mean ± SD). ABIs increased from 0.59 ± 0.14 to 0.86 ± 0.16. PTA and stenting yielded higher patency rates than historical controls undergoing PTA alone. When periprocedural thrombolysis is required, subsequent patency appeared to be significantly worse.¹²⁵

The patencies observed in this study do suggest better results, more comparable to those achieved with bypass, may eventually be achievable with devices such as coated stents^{126,127,128,129,130} or possibly with addition of adjunctive brachytherapy.^131,132 Ultimately, as endovascular devices and methods improve and mature, good prospective trials comparing conservative, endovascular, and surgical therapy will be needed to understand the optimum roles of each of these management technologies. PTA is increasing replacing bypass surgery in the treatment of chronic limb ischemia, without compromising patient survival or limb salvage rate¹¹³ (Figure 37-3).

A large perspective cohort study of patients, confirm the poor progress of chronic limb ischemia. The overall mortality rate at 12 months was 19.1%, indicating that the prognosis is similar to that of MI and stroke. The suitability and practicability of revacularization profoundly affected the prognosis of the patients. Compared with patients for whom revascularization was deemed unnecessary, the risk of dying within 6 or 12 months was double among patients considered unsuitable for intervention.¹³⁴

In a randomized study of 104 patients comparing primary stent implantation or angioplasty had severe claudication or chronic limb ischemia because of stenosis or occlusion of the SFA, the intermediate term, treatment of SFA disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting.¹³⁵

There was a multicenter and randomized controlled trial on bypass versus angioplasty in severe ischemia of the leg (BASIL). The randomized 452 patients who presented to 27 UK hospitals, with severe limb ischemia caused by infrainguinal disease, were to receive a surgery-first (n = 228) or an angioplasty-first (n = 224) strategy. The primary endpoint was amputation (of trial leg) free survival. Analysis was by intention to treat. The BASIL trial is registered with National Research Registrar (NRR) and is an International Standard Randomized Controlled Trial, number ISRCTN45398889.

The trial ran for 5.5 years, and follow-up finished when the patients reached an endpoint (amputation of trial leg above the ankle or death). In their findings, after 6 months, the two strategies did not differ significantly in amputation-free survival (48 vs. 60 patients; unadjusted hazard ratio 1.07, 95% CI: 0.72–1.6; adjusted hazard ratio 0.73, 0.49–1.07). There was no difference in health-related quality of life between the two strategies, but for the first year, the hospital costs associated with a surgery-first strategy were approximately one-third higher than those with an angioplasty-first strategy¹³⁶ (Figure 37-4).

They have summarized their trial as follows; severe limb ischemia imposes a very high human cost as well as a major economic burden on health and social care, not only in developed countries, but also increasingly in developing countries. It is their hope that BASIL trial data will help the clinician advise, and obtain fully informed consent from, their patients in the knowledge that the decision-making process is based on level 1 evidence regarding the relative risks and benefits of strategies of bypass surgery first and balloon angioplasty first. The medium-term result of the BASIL trial indicates that patients presenting with severe limb ischemia caused by infrainguinal atherosclerosis and who seem technically suitable for both treatments can reasonably be treated with either method in the first instance, depending on individual characteristics and local expertise. However, notwithstanding the high failure and reintervention rate associated angioplasty, patients who are expect to live less than 1 to 2 years and have significant comorbidity should probably, when possible, be offered angioplasty first. Thus, even if the procedure fails, the patient may not be disadvantaged in the short term and can go on to have surgery if regarded as appropriate. Angioplasty also seems to be a much less expensive option than surgery, at least in the short term. By contrast, in patients expected to live more than 2 years and who are relatively fit, the apparent durability and reduced reintervention rate of surgery could outweigh the short-term considerations of increased morbidity and cost. Long-term follow-up and a detailed analysis of the BASIL trial dataset will probably allow these provisional recommendations to be refined in the future.¹³⁶

The number of diseased vessels in the treated limb was found to predict long-term limb salvage according to multivariate analysis: limbs with one to five diseased vessels diagnosed on preoperative angiography had a better prognosis than limbs with six or more diseased vessels. Factors that have previously been associated with limb salvage according to multivariate analyses are the number of diseased vessels, the number of treated lesions, the type of treated lesions, the state postprocedural peripheral runoff,¹³⁷ renal insufficiency, and lack of angiographic improvement achieved by PTA at the site of most severe ischemia.¹³⁸ The limb salvage rates were worse at all time periods when surgical revascularizations were included. More than half the limbs that required repeat surgical operations had already undergone repeat endovascular operations. Therefore, profound ischemia and the presence of severe trophic lesions may have affected these findings.

The survival rate of cases in one study showed 72%, 26%, and 14% at 1, 5, and 10 years.¹³⁹ The similar findings were reported in other series.¹⁴⁰ Therefore, chronic limb ischemia is a serious threat to patient’s lives and limbs.¹⁴¹ Despite the progression of PAD to the end stage in these patients, aggressive systemic risk factor modification is still warranted to decrease morbidity and mortality in patients with chronic limb ischemia.¹⁴² In a population of patients with unrevascularized chronic limb ischemia, only 28% were alive without amputation of their affected limb at 1 year¹⁴³ compared with 53%.¹³⁹ Further randomized studies maybe necessary to compare crucial and final outcome of PTA with other surgical revascularizations.

Open Surgical Management

Aortoiliac Arterial Occlusive Disease

Aortofemoral Bypass. When patients present with ischemia requiring revascularization, caused by occlusive disease limited to the aortoiliac segment, the vascular surgeon has only to deal various surgical options available for the treatment of aortoiliac occlusive disease and need not be concerned about the treatment of infrainguinal occlusive disease.

There are three types of lesions:

1. 
   

   Type I, or truly segmental aortoiliac disease, occurs in only in 5% to 10% of the patients. These patients are commonly younger and smokers. Half are women, and they frequently have elevated blood lipids. With localized bifurcation disease, they characteristically have symptoms of thigh or buttock claudication. Impotence is common in male (Leriche’s syndrome).

   
   
2. 
   

   Type 2, with atherosclerotic involvement of the distal aorta and iliac arteries, comprises an additional group of approximately 25% of the patients. Involvement is still confined to the abdomen without significant distal disease. As a result of collateral circulation in the pelvis, claudication is most common presenting symptom in such patients and advanced distal ischemia is unusual.

   
   
3. 
   

   Type 3, with diffuse, multilevel disease, comprises 65% to 75% of the patients. It involves the infrainguinal arterial tree as well as the aortoiliac system. Associated occlusive disease in these patients most commonly involves the SFA, popliteal or runoff vessels, and/or the profunda origin. There is clearly male predominance (7 to 1) in this group. Many of the patients have diabetes and hypertension as well as other sites of atherosclerotic involvement such as in the carotid and coronary vessels. Symptoms of more advanced ischemia, including rest pain and tissue necrosis, often are the presenting complaints in this category.¹⁴⁴

Aortofemoral Dacron reconstruction for aortoiliac occlusive disease was instituted over 40 years ago. Following the original publications, its efficacy was soon recognized and it became probably the most widely employed arterial reconstruction.^{145,146,147,148,149,150,151,152}

One large series of aortobifemoral bypass graft procedures had late patency rate of 74% and 70% after 10 and 15 years, respectively.¹⁵³ Operative mortality rates of 2%, 2.9%, and 4.5% have been reported.^153,154,155

One study showed that aortobifemoral bypass is the preferred operation for extensive iliac artery occlusive disease that is hemodynamically significant only on the symptomatic side unless specifically contraindicated by prohibitive risk or abdominal disease. This is particularly true in the face of SFA occlusion.¹⁵⁶

Transabdominal Approach. This approach is most commonly used for the aortofemoral bypass procedure in our practice, as well as many other surgeons. A midline incision is made, extending from the xiphoid process down to the pubic bone, removing the umbilicus, at the time of midline incision, in order to eliminate a potential source of contamination from the umbilicus. Dissection is carried out with sharp dissection at the midline. Following abdominal exploration, the transverse colon and small intestines are eviscerated onto the right side of the abdominal wall or within the right side of the abdominal cavity using self-retaining retractor devices. The retroperitoneal space is entered. The abdominal aorta proximal to the disease and slightly below the renal artery is routinely used for proximal anastomosis. In the event the proximal aorta has extensive disease and/or juxtarenal aortic occlusive process, temporary aortic clamping is done above the renal artery origin for infrarenal aortic endarterectomy. Following the infrarenal or juxtarenal endarterectomy, aortic clamps are then safely moved on the infrarenal aorta for the proximal anastomosis. It is the author’s practice to do proximal anastomosis at the most proximal end at the infrarenal portion of the proximal aorta.

In most cases, particularly with extensive proximal disease, the proximal aorta is transected for true end-to-end anastomosis. However, if there are good segments of proximal aorta in a young male patient, the author prefers to do end-to-side proximal anastomosis.

The distal anastomoses are chosen, most of the time, on the femoral arteries. At the time of femoral artery anastomosis, if the patient has occlusive or stenotic disease at the profunda femoral artery with an occluded SFA system, the author’s preferred choice would be profundaplasty at the time of distal anastomosis with or without endarterectomy. At the time of endarterectomy, we use liberal dissection into the distal profunda femoral artery beyond the disease point to insure that proper reconstruction is accomplished.

In most cases, double velour Dacron Y graft, No. 18, is used. In the small aorta, particularly in female patients, No. 16 polytetrafluroethylene Y graft has been utilized. The prosthesis is completely covered using vascularized pedicle of omentum¹⁵⁷ (Figure 37-5).

Retroperitoneal Approach. Retroperitoneal aortic reconstruction has been performed successfully since the report by Rob¹⁵⁸ on 500 aortic reconstructions performed through the retroperitoneal approach in 1962. They listed benefits to be less ileus, less atelectasis and pain, reduced incidence of wound dehiscence, easier anesthesia, a shorter stay in bed and in the hospital, and faster return to work.

Certain pitfalls of retroperitoneal aortic reconstruction deserve comment. These include injury to the vena cava, which is very difficult to manage through the retroperitoneal approach. Vigorous retraction in the upper aspect of the operative field may lead to unrecognized splenic trauma. This should be minimized using self-retaining retractors. The lumbar branch of the left renal vein must be identified not only because it serves as a marker to the left renal artery, but to avoid injuring it as well.

Similarly, although rarely, a retroaortic left renal vein or circumaortic left renal vein may cause problems, if not recognized. During mobilization of the retroperitoneum, it is important to identify the left gonadal vein so that, during the course of sweeping the retroperitoneum anteriorly, the gonadal vein is not avulsed from the left renal vein. A left pneumothorax may occur and be unrecognized, particularly if the left 11th intercostal space incision is not made carefully. Both the inferior mesenteric artery and the left renal artery are swept anteriorly when retrorenal dissection is performed and must be identified to prevent injury.

Proper positioning of the patient is important. The left thorax is elevated 45 to 60 degrees, while the hips should lie as flat as possible to allow access to the right groin should that become necessary. The patient’s position is secured by placement on a vacuum Styrofoam been bag. The midpoint between the patient’s left costal margin and iliac crest is centered over the table flexion point, so that flexing the operating table causes the incision to spiral open. Wound closure is facilitated by flatting the operating table. The surgeon stands to the left of the patient. Rotation of the table away from the surgeon facilitates retroperitoneal dissection, while rotation toward the surgeon facilitates groin dissection.

An oblique left flank incision is used starting midway between the umbilicus and symphysis pubis and extending from the lateral margin of the left rectus sheath into the 11th intercostal space for 8 to 10 cm. The abdominal wall and intercostal muscles are divided in the line of the incision, taking care not to injure the 11th and 12th dorsal neurovascular bundles. Damage to these nerves denervates the abdominal wall, leading to muscle weakness, manifest as an asymmetric abdominal contour with unsightly bulging.

The retroperitoneal space is entered at the tip of the 12th rib, and with blunt dissection, the anterior peritoneum is dissected away from the transversalis fascia as far as the rectus sheath. Dissection medial to the rectus is not necessary for exposure. Also, this prevents tearing the peritoneum where it is firmly attached at the lateral border of the rectus.

Posterior laterally, the plan of the flank musculature, psoas, and diaphragm are followed as the peritoneal sac and its contents are dissected and retracted anteromedially. This plane is developed along the lumbodorsal fascia behind the left kidney and ureter anteriorly. Alternatively, dissection can be performed anterior to the left kidney and ureter, but an advantage of the retroperitoneal approach is lost, since the left renal vein obscured the juxtarenal aorta. However, dissection anterior to the kidney is useful when exposure of the superior mesenteric artery beyond its origin is required for endarterectomy or when endarterectomy of the pararenal aorta is anticipated.

The aorta is easily exposed from above the renal artery to the aortic bifurcation. To prevent injury to the left renal artery, its identification is important. The artery can usually be identified behind the lumbar branch of the left renal vein, which is a fairly constant structure. Ligation of this lumbar branch, which crosses over the aorta, provides good exposure of the aorta and origin of the left renal artery.

Lymphatics and fat overlying the aorta are ligated to minimized lymphorrhea. Blunt dissection of the aorta, anteriorly and posteriorly, either above or below the renal artery, is performed to allow placement of the proximal clamp. Circumferential aortic dissection is not required as long as the tip of the clamp can reach beyond the aortic wall. Inferior vena cava injury is not a concern, as it is not immediately adjacent to the aorta at this level.

If suprarenal aortic control is required, dissection is carried out cephalad, with longitudinal division of the diaphragmatic crus. Suture ligation of the areolar tissue surrounding the origin of the superior mesenteric artery minimizes potential lymphatic leaks. With the need for supraceliac exposure, dissection proceeds further cephalad. Investing fascia around the aorta is incised and blunt dissection anteriorly and posteriorly creates tunnels to accommodate the jaws of an aortic clamp. Supraceliac control is often easier to obtain the juxtarenal control because of the relative paucity of lymphatics and fat at the para celiac level. If juxtarenal or supraceliac aortic clamping is anticipated preoperatively, a ninth or tenth intercostal space incision is recommended.

Distal exposure of the iliac arteries is accomplished by blunt dissection of the peritoneal sac out of the iliac fossa. The left iliac artery can be exposed easily over its entire length. Exposure of the right iliac artery is more challenging. Minimal dissection of the distal aorta is required when managing occlusive disease and the inferior mesenteric artery is preserved.

Anastomoses to the right distal common iliac or external iliac arteries are difficult through the left retroperitoneal approach. Some authors have advocated extending the abdominal incision across the midline into the right lower quadrant to facilitate right iliac arterial exposure. A right lower quadrant counterincision a few centimeters above the inguinal ligament with extraperitoneal dissection of the iliac vessels provides excellent exposure for right external iliac artery anastomoses. This avoids groin dissection with its small but real risk of infection even though one should not hesitate to make a groin incision if necessary.^{155,156,157,158,159}

A meta-analysis published in 1997 on 23 studies that met the inclusion criteria. The aggregated operative mortality risk in the older studies (started before 1975) was 4.6%, as compared with 3.3% in the more recent groups (p = 0.01).

This study was based on a MEDLINE^® search based on the literature published between 1970 and 1996. Studies were included if (1) they reported patency rates based on life tables and the number at risk was provided at yearly intervals and (2) patients and study characteristics were reported in sufficient detail. Mortality and morbidity risks were reported using a fixed-effects model. The patency data were combined using a technique that enables adjustment for differences across studies in patient characteristics or reporting methods. In the current analysis, they corrected for the symptomatic status of the patients at the time of surgery (claudication vs. ischemia) and the unit of observation used in the report the patency (limb vs. patient).

The aggregated systemic morbidity risk was 13.1% in the older studies and 8.3% in the more recent studies (p < 0.001). Limb-based patency rates for patients with claudication or 91% and 86.8% at 5 and 10 years, respectively, as compared with 87.5% and 81.8% for patients with ischemia. Patency rates reported in the older studies were markedly similar to those of more recent studies (p = 0.58). The conclusion of this meta-analysis is that the studies suggest the mortality and systemic morbidity rates of aortic bifurcation graft procedures have dropped since 1975, whereas patency rates seem to be fairly constant over the years.¹⁶⁰ Type III pattern is the most common form of occlusive disease, ranging 50% to 75% of the time in the literature, as far as our experience.^{161,162,163,164,165} In this group of patients, proximal reconstruction may fail to achieve satisfactory relief of ischemic symptoms in up to one-third.^{163,166,167,168,169,170,171,172,173,174} Careful preoperative assessment using hemodynamic studies and clinical evaluation including ischemic pattern of distal portion of the limb may predict a need of a simultaneous distal bypass or revascularization to achieve a successful outcome of a combined procedure.

Associated Visceral or Renal Artery Lesions. The dilemma of whether or not to attempt simultaneous correction of both abdominal aortic and visceral lesions is frequently encountered and difficult to resolve.^175,176 In our practice, preoperative evaluation is given to those incidental findings and an individual decision is made including preoperative angioplasty of the distal vessels or renal artery lesions, if so indicated with a careful assessment. In rare incidences, and on an individual basis, it is necessary to combine the procedure at the time of aortic surgery.

In carefully selected patients, combined reconstruction of associated renal artery disease can give a reasonable outcome.^{177,178,179,180,181} Simultaneous aortic operation and renal artery revascularization has increased morbidity and mortality^177,178 (Figure 37-6).

Complications

Early Complications

Hemorrhage: With the current reliable prosthetic graft and suture material, early postoperative bleeding is unusual (1% to 2%). The most common cause of postoperative bleeding is technical error or abnormality of the coagulation mechanism.¹⁸² Meticulous techniques and proper hydration and limiting blood loss are essential keys to prevent these complications.

Limb Ischemia: This is caused by thrombosis of the graft or more commonly distal embolization.¹⁸² Besides technique, careful layout of the graft is essential to prevent this complication. Acute thrombosis of an aortofemoral bypass graft limb is extremely rare, ranging 1% to 3% in practice and/or literature.¹⁸³

Intestinal Ischemia: This complication occurs in 1% to 2% of the cases.^184,185,186 Most common site of ischemia is the rectosigmoid colon. The cause of these complications is multifactorial including critical loss of blood flow to the involved intestinal segment or thromboembolic complications during the manipulation of blood vessels during surgery.

Postoperatively, high index suspicion is the key for early diagnosis. If clinical suspicion of intestinal ischemia exists, prompt sigmoidoscopy or colonoscopy is indicated. Initial management should be supported care with gastrointestinal tract decompression and intravenous antibiotics. However, if the patient develops any clinical deterioration indicating the need for prompt operative intervention, there should be no waste of time for best protection and lifesaving. During the reexploration, care should be taken to avoid graft exposure. This event of complication has significant mortality ranging from 50% to 75% in many series.^182,185

Acute Renal Failure: Acute renal failure is a rare complication ranging from 1% to 8% with overall mortality of 40%. However, if emergency aortic surgery is indicated, the incidence of acute renal failure is higher with 50% to 90% mortality.¹⁸⁷ To prevent or minimize this complication, careful monitoring intraoperatively to minimize risk of hypovolemia or decrease in cardiac output, particularly during the declamping procedure. The incidence of declamping complications is less in aortic occlusive disease than aortic aneurysm, because the aorta has been chronically occluded, giving less of a hemodynamic impact in cross-clamping. During the cross-clamping for juxtarenal aortic renal occlusion, it is safer to cross-clamp at supraceliac rather suprarenal in some cases, in order to avoid atheroembolic insult to renal arteries.

Late Complications

Graft Occlusion: Five to ten percent of patients within the first 5 years after operation and in 15% to 30% of patients in 10 years or more postoperatively,^188,189,190 the most common occlusion affects one limb of the graft with a patent contralateral graft limb. Depending upon the situation and individual basis, there are a variety of techniques including extra-anatomic bypass, thoracic aortofemoral bypass, femoral–femoral bypass, or other intervention.

Anastomotic False Aneurysm: With excellent suture material and grafts, this complication is extremely rare, ranging from 1% to 5%.¹⁶⁴ Recognition of femoral anastomotic aneurysm is usually simple. Detection of retroperitoneal or at the aortic anastomosis maybe difficult unless graft surveillance is available or CT scan is done. Management is individualized depending upon the location.

Once the anastomotic false aneurysm is diagnosed, it is advisable to correct the aneurysm to prevent thromboembolic complications or rupture. This fearful complication is extremely rare with modern graft and suture material and techniques as well as prophylactic antibiotics. However, this incidence is reported to be approximately 1% or less in many series.^{181,182,191,192}

Infection: Graft excision is usually required, and revacularization via remote uncontaminated routes or use of autogenous methods of anatomic revascularization is often necessary to maintain limb viability.^{193,194,195,196,197,198} If the patient’s condition is stable and diagnosis of graft infection is established, extra-anatomic revascularization preceding graft excision appears to give a better outcome.^199,200

Another approach to the treatment of entirely infected aortofemoral grafts consist of graft excision and in situ graft replacement, sometimes with “neoaortoiliac systems” constructed from autogenous superficial femoral veins.²⁰¹ This rare and formidable complication is best treated with early diagnosis with a high index of suspicion. When the patient has episode of gastrointestinal hemorrhage with a history of aortic graft in place, high index suspicion should prompt the diagnosis using upper gastrointestinal radiographic evaluation or endoscopic examination.

Aortoenteric Fistula: An acceptable method of treatment for aortoenteric fistula generally requires removal of all prosthetic material, closure of the infrarenal abdominal aorta, repair of the gastrointestinal tract, and revascularization by means by an extra-anatomic bypass graft.^{202,203,204,205}

Symptomatic atherosclerosis in young adults has been reported in the literature as a poor prognostic finding because of multiple vascular bed involvement and accelerated nature of the disease process.^{206,207,208,209} Some reports indicated that younger patients have more localized aortic atherosclerosis.²¹⁰ In a study which directly compared 45 patients of less than 50 years of age with groups from 50 to 59 years of age (n = 93) and of more than 60 years of age (n = 146) and found that younger patients had significantly inferior patency rate, with a 66% 5-year cumulative patency rate compared with 96% in the older age group (p < 0.05).²¹¹ In that study, the age and aortic size were important predictors for graft failure. There were a no appreciable differences in patency when looking at construction of the proximal anastomosis or gender.