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Peripheral Arterial Disease: Impact on Wound Healing and Limb Salvage

It is suggested that PAD is a devastating, underdiagnosed and undertreated cardiovascular disease, which is an important marker for more widespread atheromatous disease and is associated with a three to six-fold increase in the risk of cardiovascular events and mortality. The authors argue that PAD is a global problem, with three out of four patients residing in lower-income countries. It is suggested that the disease prevalence is likely to increase in the future due to greater life expectancy and a rising incidence of diabetes. This opening section ends with an outline of the clinical staging of PAD, which is used to classify a patient based on the presence and severity of their disease and helps determine treatment strategy. This section provides a good initial overview of the issues involved with PAD and does well to set the scene in terms of the severity of the disease and its likely effects on individuals’ health. The comment regarding the global nature of PAD and its likely increase in prevalence is particularly interesting and highlights how the disease may place an increasing burden on healthcare resources in the future. Importantly, the section finishes by highlighting the clinical staging of PAD, a concept that recurs throughout the article and is fundamental in determining the severity of disease and likely prognosis of the patient.

Overview of Peripheral Arterial Disease (PAD)

The section begins with a concise but thorough examination of the pathology of peripheral arterial disease (PAD). The authors explore the different ways in which PAD is classified and then go on to explain its prevalence and natural history. Importantly, the natural history discussed here is related to wound development and limb loss rather than the more general symptoms which PAD patients may present with. Epidemiological studies are cited to demonstrate the increased risk of death and cardiovascular events compared with those without PAD. This contrast is highlighted as those with PAD generally die from cardiovascular events rather than directly from limb amputation. These points help to underline just how serious PAD can be and how it can substantially lower life expectancy. One of the most important parts of this section is its examination of the pathophysiology of PAD and how it relates to its symptoms. Critical limb ischemia is defined as chronic ischemic rest pain, ulcers or gangrene attributable to objectively proven arterial occlusive disease which the author describes as the worst manifestation of PAD. This is important since CLI is synonymous with limb loss and the development of non-healing ulcers and serves to list the possible consequences without treatment to patients with PAD. This provides a natural linkage to the next section of the essay.

Importance of Wound Healing and Limb Salvage in PAD

The substantial consequences and elevated risk of mortality associated with chronic wounds and limb loss make limb salvage a critically important goal in caring for patients with PAD. Maintenance of functional mobility and prevention of further disability are also key considerations. An additional aspect is the economic cost of chronic wounds and amputation, which is large and growing, given aging populations in many countries. A multinational study found that the average 2-year health care costs for a patient with critical limb ischemia are significantly higher for those who undergo major limb amputation compared to those who have successful limb salvage. These various factors point to a major public health issue and a significant challenge in caring for the large and increasing number of patients with severe PAD, especially those with limb-threatening ischemic conditions.

An Australian study demonstrated that such patients have a 1-year limb loss or amputation-free survival rate of only 46%, and the 1-year mortality rate is as high as 25%. The mortality rate is even higher for patients with critical limb ischemia who have undergone major limb amputation, reported to be 25-35% at 1 year and 50% at 4 years in various studies. This shows that limb loss in the context of chronic wounds or ischemic tissue damage is a strong marker for poor patient outcome with high risk of death.

Patients with chronic wounds and limb gangrene due to advanced PAD suffer substantial morbidity because of pain, limited mobility, and the potential for limb loss. Jan Ahrén describes the experience of such patients as that of living with a “death sentence amputation” (referring to eventual limb loss), thereby highlighting the very serious nature of wounds and ischemic tissue damage in patients with PAD. While there is a spectrum of severity of chronic wounds in PAD, patients with limb-threatening ischemic ulcers, especially those who experience sudden clinical deterioration such as ulcer infection or development of frank gangrene, have a high likelihood of limb loss unless appropriate medical or surgical intervention is undertaken.

Factors Affecting Wound Healing in PAD

Angiogenesis, the growth of new blood vessels from pre-existing vessels, has been suggested as a potential therapy to help stimulate wound healing in PAD patients. By directly intervening in the root cause of the healing impairment and providing the alternative supply route needed to bypass or supplement the damaged peripheral vessels. However, as yet no therapy involving angiogenesis has been brought into widespread clinical practice and there remain concerns regarding the safety of such treatment in cancer patients due to its potential to stimulate tumor growth.

The pace at which a wound heals is a good measure of the extent of the healing process taking place within the body. Wound healing can be divided into several separate but overlapping processes: the inflammatory phase; re-epithelialization; and the formation of granulation tissue and new blood vessels which is necessary to provide oxygen and nutrients to the growing tissue. It is during this final phase in particular that the microvascular damage resulting from PAD has been shown to have a significant impact. This is often reflected in the failure of chronic wounds to progress beyond the inflammatory phase, becoming ‘stuck’ in this phase due to a lack of available growth factors and nutrients.

Reduced Blood Flow and Oxygenation

When compared with individuals who have normal peripheral blood flow, ulcers in individuals with PAD demonstrate unimpaired perfusion, even in the face of critically ischemic limb threat or following minor amputation. This suggests that the underlying problem in such ulcers is the inability to increase blood flow to meet the metabolic demands of healing and references the concept of ‘effective macrocirculation’. On a systems and organ level, deep soft tissue and bone perfusion relative to that required for the metabolic processes of inflammation, proliferation, and remodeling. Given that effective macrocirculation is ultimately derived from microcirculatory events, the latter the act of ulcers in PAD and their response to therapy must be rooted in a clear understanding of the pathophysiological effects of ischemia on the microcirculation. This cannot be easily assessed at the clinical level, particularly with respect to quantification of the ischemic burden in individual patients, and as a result, there has been relatively little improvement in predicting the outcome of ulcers in PAD or for the selection of interventions which might optimize the healing event. Profiling of the ischemic ulcer has been facilitated by the application of simple non-invasive tests of microcirculatory function (Laser Doppler Fluximetry and transcutaneous oximetry) both in experimental work and in clinical studies. These tests provide information on flux (the movement of red blood cells in the capillaries per unit time) and oxygen tension at various points around the wound and can be used to categorize ulcers according to their potential for healing and response to specific interventions. Although there is little doubt that impaired blood flow and oxygenation are detrimental to all phases of wound healing, a detailed knowledge of how these factors impact on specific ulceration responses can provide signposts to therapy and, importantly, can result in detaching the study of ulceration from the intangible concept of ‘attempting to improve clinical outcome’ and allow work with more robust endpoints.

Impaired Nutrient Delivery

There is also evidence to show how effective revascularization is in improving nutritional status. Recent studies have identified a group of patients with peripheral artery disease (PAD) with chronic critical limb ischemia (CLI) who are at considerable risk for amputation and at an especially high risk for death, despite treatment. These patients have a consistently elevated erythrocyte sedimentation rate and fibrinogen level, and attenuation of inflammation or normalization of those acute phase reactants is a significant prognostic factor for survival. This information gives the assumption that an increased rate of inflammation is associated with decreased survival and that nutritional repletion with the aim of inflammation reduction may improve the prognosis. The Nutrition as a therapeutic approach in patients with peripheral arterial disease and intermittent claudication trial by Chrysohoou et al found that nutrient supplementation can have a positive effect on inflammatory markers and walking ability.

This broad subject includes the chemical and hormonal changes that occur with aging that may impair digestion, absorption, and metabolism, and/or increase nutrient losses. Polypharmacy increases the potential for nutrient-drug interactions (negative or positive) and for adverse effects of drugs that can mimic specific nutrient deficiencies. The intake of drugs is said to inhibit nutrient absorption in several ways. For example, cholestyramine, a drug used to lower cholesterol levels, interferes with fat absorption and also decreases absorption of fat-soluble vitamins. Alcohol is a known inhibitor of nutrient absorption and metabolism, creating a state of malnutrition even with sufficient caloric intake. It is also mentioned that some over-the-counter medications act as appetite suppressants, further lowering food intake and nutrient absorption.

Increased Infection Risk

Simulation of an infected wound in the ischemic or neuroischemic setting results in far from favorable outcome.

Early events in the natural history of infected wounds in normal individuals involve inflammatory and immune responses that limit the extent and duration of the infection. This is achieved through increased blood flow, delivering oxygen and nutrients requisite for white cell bacteriocidal activities, and a white cell exudate, which serves to wall off and destroy invading microorganisms. These mechanisms are, however, highly dependent on adequate tissue perfusion and effective immune and inflammatory responses.

An open wound provides a direct port of entry for infectious microorganisms, and the inimical microenvironment resulting from immune dysfunction and bacterial colonization of the skin in PAD serves to further increase the risk of wound infection. Infection has many and varied detrimental effects on wound healing, and can often result in the failure of the wound to heal, with resultant chronicity.

Delayed Inflammatory Response

In the process of normal wound healing, macrophages, which are white cells that are part of the immune system, work to remove any foreign materials and bacteria from the wound, which helps to prevent infection. After this, they work to stimulate the growth of new blood vessels and skin cells. With the increased blood vessel growth seen due to an increased level of VEGF, wounds with normal healing show high levels of macrophage content between days 4-14. However, in chronic wounds, macrophage cells are present in excessive levels, yet do not function correctly to promote healing. The cause of this is unknown. This has been seen in a study where wounds were made in diabetic animals and those with normal blood sugar levels. The wounds in the diabetic animals showed a prolonged macrophage cell presence.

Effects of Diabetes and Other Comorbidities

The consequences of impaired peripheral arterial perfusion have been the subject of a number of reviews. Whereas CLI has been shown to be associated with a high chance of amputation and poor survival, it is also recognized as an independent marker of increased mortality in patients with or without a history of cardiovascular disease. It is said to be related to the fact that critical limb ischemia occurs more frequently in patients with widespread atherosclerosis and carries a high risk of cardiovascular events, making it an important systemic manifestation of atherothrombosis. This could have unfavorable ramifications for patients with PAD and CLI and associated cardiovascular disease, as these are all potential confounders that might prevent the ischemic wound of a PAD patient from healing.

Diabetes has long been associated with poor wound healing and increased wound complications. The combination of neuropathy and macrovascular and microvascular disease in diabetic patients increases the risk of an inability to feel an injury or wound, thus allowing it to go unnoticed and untreated until it becomes a more serious health problem. Neuropathy, which results in the loss of protective sensation, can lead to a number of unfavorable outcomes for the patient, such as undetected trauma, unrecognized foreign bodies in the foot, walking barefoot at home or outside, and poor nail care. All of these behaviors increase the risk of foot injury.

Strategies for Enhancing Wound Healing in PAD

The poor prognosis for healing chronic wounds in the setting of PAD led to the development of revascularization techniques for the direct purpose of wound healing. Revascularization is the only intervention that has been proven to enhance wound healing by increasing blood flow to the ischemic limb. However, it should be undertaken only after careful consideration of functional status, co-morbid conditions, and life expectancy, since the benefit of revascularization on a limb without tissue loss is equivocal compared to medical therapy and the risks of the procedure may outweigh the benefits in a patient with severe co-morbid disease. The different revascularization techniques have varying efficacy for wound healing. Bypass surgery has consistently been shown to be more effective than angioplasty or endovascular stenting. In particular, bypass using autologous vein confers the best chance of wound healing. Data from a recent trial comparing surgical bypass and endovascular revascularization demonstrated significantly better clinical outcomes including wound healing with surgical bypass. Therefore, for a patient who is a suitable surgical candidate, bypass using autologous vein is the recommended method of revascularization for the specific purpose of wound healing. If the bypass is intended to promote wound healing rather than relieve severe ischemic symptoms, a less invasive below-knee surgical approach is often sufficient. This method is associated with lower peri-operative morbidity and is a good option for patients with limited life expectancy or co-morbid disease.

Revascularization Procedures

Endovascular revascularization techniques in general are minimally invasive and result in short hospital stays and fast recovery. CCWs heal faster with endovascular therapy, and adjuvant wound care is optional. Other factors that favor revascularization include status of limb ischemia less severe than major amputation, limited life expectancy due to co-existent medical conditions, and situations where the patient and family have made a firm decision that they want limb salvage. In patients who are reasonable surgical candidates, the decision on which method of revascularization is best achieved through a multidisciplinary approach involving internists, cardiologists, and vascular surgeons. Unfortunately, there are many patients who are not candidates for revascularization given a poor risk-benefit ratio based on their coexistent medical conditions. Given that PAD patients have a high cardiovascular and cerebrovascular event rate, their survival can still be improved with a history of revascularization. This is important in the context of the current increase in amputation rates in CCWs, and an obvious decrease in limb loss compared with the pre-revascularization era is seen in contemporary clinical practice.

A reduction in amputations in the highest amputation rate states could have a substantial public health impact. This study analyzed Medicare fee-for-service beneficiaries who had a dysvascular amputation using the 5% nationwide sample of Medicare claims data from December 2015 to March 2016 linked with the 2010 US Census data for block group socioeconomic data. There were 6296 individuals who had a dysvascular amputation in 49 states and the District of Columbia and were matched to a same-state general population comparison cohort (n = 314,790). The overall age- and sex-standardized amputation rate was 89 per 100,000 persons and was higher than the Healthy People 2020 target rate of 29 per 100,000, and the unadjusted highest amputation rate was 166 per 100,000 in Mississippi. After conducting a multilevel analysis, the strongest predictors of a state’s amputation rate were the percentage of black individuals and those living in low SES block groups, and states in the stroke belt had significantly higher amputation rates even after adjusting for individual characteristics. Of the patient-level SES factors, Medicaid insurance status had the strongest association with amputation.

Wound Care Techniques

There are a variety of ways to enhance healing in the patient with chronic wounds and critical ischemia, beginning with local wound care. Patients should be advised to keep the wound clean and dress it with dry bandages daily. For wounds with necrotic tissue, long-term treatment with enzymatic debridement, autolytic debridement, biological debridement, or, in the most severe cases, surgical debridement may be necessary. Care should be taken to avoid desiccation of the wound and surrounding tissue. This will help to achieve moist wound healing, which is the most effective way to stimulate healing in a chronic wound. Using the moist wound healing concept as a temporizing measure, various types of occlusive dressings, hydrocolloids, hydrogels, alginates, or other specialty dressings are useful. Granulation tissue formation can often be stimulated by applying topical growth factors, which will be discussed in further detail in the pharmacological interventions section. Hyperbaric oxygen therapy can also be useful in enhancing wound healing, particularly in diabetic patients, although it does not consistently increase the incidence of limb salvage in patients with severe PAD.

Pharmacological Interventions

Cilostazol is a phosphodiesterase inhibitor, which has both antiplatelet and vasodilating effects. It inhibits the breakdown of cyclic AMP and potentiates prostacyclin. At a dosage of 100mg bd, it has been shown to significantly improve intermittent claudication and quality of life. Cilostazol has been shown to be a drug that benefits most, if not all, the phases of wound healing. A recent trial has evaluated the efficacy of adding cilostazol to the treatment of CLI with endovascular revascularization. This was a small prospective study including 11 of the 3 phases of wound healing. Cilostazol has also been shown to improve microcirculation and oxygen supply to tissues, which would then prevent and treat ischemic ulcers.

Pharmacological agents are aimed at influencing various aspects of the wound healing process. There are specific classes of agents designed to enhance the phases of wound healing. These agents are aimed at correcting systemic and local abnormalities that impair wound healing in patients with PAD. These agents include antiplatelet agents, anticoagulants, vasodilating agents, and antibiotics. Platelets play a vital role in hemostasis and the inflammatory phase of wound healing. Antiplatelet therapy has been shown to be effective in preventing the progression of PAD and in preventing the development of new cardiovascular events and in reducing the risk of amputation. Aspirin is one of the most widely used antiplatelet agents and has been used extensively in patients with PAD.

Physical Therapy and Rehabilitation

One common recommendation for peripheral arterial patients has been to exercise to a point of moderate to severe claudication pain with the goal of increasing the time to onset of pain. However, the safety of this advice has been questioned. In the past, it was thought that exercise did not increase the risk for patients with PAD, but recent information indicates that patients with PAD have a high risk for adverse outcomes with functional decline. A recent analysis involving patients at risk for PAD has also suggested that antiplatelet therapy and possibly statins can reduce the impact of exercise as a precipitating factor for worsening symptoms or limb complications. This information is relevant not only to patients who are encouraged to exercise for claudication but also to those with more severe symptoms and those who will undergo revascularization. New information on the effects of various medications with exercise for patients with PAD would be helpful in recommending whether to continue currently prescribed medications during an exercise program.

Exercise therapy has long been considered a low-cost and low-risk intervention to improve both cardiovascular and limb-specific function in patients with PAD. More specifically, supervised treadmill exercise has been shown to improve walking distance in patients with claudication and has been recommended as initial therapy for this symptom. This class of patients has been the major emphasis for exercise interventions. It is also known that various modes of exercise can be beneficial for patients with intermittent claudication, and there is emerging evidence that exercise training may also improve the quality of life for patients with critical limb ischemia.

Recently, a study has tried to identify patients with critical limb ischemia who benefit most from revascularization compared to exercise therapy. Their analysis concluded that revascularization was superior in patients with limited lower extremity functioning and those with limb-threatening ischemia. This information is useful to help direct patients toward the most appropriate therapy for their condition. However, the decision for revascularization in some patients may be based on procedural risks based on their comorbidities and projected quality of life benefit. In these patients, a better understanding of the potential effects of exercise therapy would also be beneficial.

When patients with PAD present with significant symptoms or limb-threatening ischemia, revascularization is often considered. In high-risk patients or those without specific indications (rest pain, ulcers, gangrene) for revascularization, it is not clear whether revascularization is superior to medical therapy. Furthermore, medical management may be more cost-effective and less likely to result in complications. The decision for revascularization should be undertaken with consideration of overall patient health and the function of the affected limb.

Patient Education and Lifestyle Modifications

Patients with PAD must be counseled about the severity of their disease process so that they can make necessary lifestyle changes to hinder disease progression. Often patients are unaware of the significance of PAD and its association with systemic atherosclerosis. Risk factor modification is an essential part of the treatment plan for the patient with PAD. Smoking cessation is perhaps the single most important lifestyle change a patient can make to improve claudication and to stop or reverse atherosclerotic disease. If the patient is a smoker, the goal is complete cessation. Patients who stop smoking decrease their risk of heart attack, stroke, amputation, and death from cardiovascular disease, and those with intermittent claudication will usually note less leg pain within 3 months of quitting. Regular walking and leg exercises help to improve the distance the patient can walk without pain. A structured home-based exercise program has been found to increase walking distance and improve the speed at which patients with claudication can walk. Supervised exercise programs are also effective and are especially useful for patients who have difficulty adhering to an independent exercise regimen. A formal program of treadmill exercise can also improve exercise performance. High intensity interval training (HIIT) seems to be very effective. Although the effect was not sustained, more than 90% of patients were satisfied with their training and would recommend it to a friend. The training seems also to be safe and has a low risk of adverse events. Patients with leg ischemia should avoid regular heavy weight lifting and isometric leg exercises by working through pain, because these activities may be harmful. The most important aspect of an exercise program is long-term adherence with the goal of incorporating exercise into daily life. Patients with PAD should also be counseled to minimize time spent sitting and to increase the frequency of standing or engage in light activity while standing. An increase in time spent sitting is associated with a higher risk of developing PAD and worsening symptoms in patients with PAD. The benefits of exercise and other lifestyle changes for patients with PAD can be maximized when combined with proper patient education and counseling. This will help increase patients’ awareness and knowledge of their overall disease process. A study in 273 patients with PAD found that a nurse-managed educational intervention improved patient walking ability, functioning, and total QOL at 3 and 6 months. These findings were independent of age, sex, and comorbidity, showing that it is possible for patients with PAD to improve their QOL and walking ability with proper education and counseling. The information patients should receive on exercise and other lifestyle changes should be very detailed and specific. This can be facilitated by interaction with a multidisciplinary team of health care professionals who can provide counseling based on individual patient needs and preferences. The best knowledge transfer occurs by a combination of methods that are easy to understand and tailored to individual patients. Functional and health literacy may be poor in some patients, so knowledge must be delivered in an understandable format. Videos, audio, phone applications, and online resources may help enhance learning, but these methods must still be combined with regular verbal or written communication between patients and health care professionals.

Limb Salvage Approaches in PAD

Lifestyle changes need to be a part of all the above forms of therapy. The optimal choice in a given patient is based primarily on the expected relief of claudication, the potential for limb salvage, and relief of ischemic pain. There is no one right answer, and patients with advanced peripheral arterial disease can be reassured that contemporary technology provides several different options for relief of their ischemic symptoms. In the absence of specific comparative data, the choice of revascularization method often reflects the best judgment of a physician based on the individual patient’s medical and anatomic considerations.

Surgical therapy is considered the best option for most patients with arterial occlusive disease who are candidates for revascularization. Bypass operations using the patient’s saphenous vein are the procedures of choice, particularly for those with critical ischemia and the likelihood of a long or short occlusion in the above knee or below knee popliteal artery. For those with a short occlusion in the iliac and/or common femoral artery, angioplasty with or without stenting is a reasonable alternative to surgery. However, the long-term patency of iliac stents is still unknown. As a general rule, the presence of gangrene, rest pain or nonhealing ulcers, along with the potential limb threat, tilts the decision in favor of a surgical revascularization. Numerous investigators have documented the superiority of limb salvage rates at 1 and 3 years with bypass surgery versus angioplasty or medical therapy.

Surgical Interventions

Surgical interventions are often sought out by patients suffering from advanced PAD, yet due to the systemic nature of the disease, these procedures do not always provide effective revascularization and can result in poor wound healing due to recurrence of the ischemic state. However, when performed properly and in combination with medical therapies, surgical revascularization can be incredibly effective in healing ischemic wounds and preventing amputation. There are several general factors to consider when determining whether a surgical or endovascular intervention is appropriate for a patient. These include the location, extent and character of the arterial lesions, the presence of runoff vessels, the status of the arterial wall and the presence and severity of limb-threatening ischemia. The primary goal of surgical intervention is to bypass as many arterial segments as necessary in order to provide a direct route from a healthy artery to a diseased artery, allowing blood flow to the ischemic area. This can be accomplished in several ways, some of the more traditional methods have involved using a synthetic graft to create the bypass, while others utilize a vein from another part of the body, grafting it from the healthy artery to the diseased artery. More recently, the greater utilization of microsurgical techniques has led to the development of minimally invasive methods such as percutaneous transluminal angioplasty, which is an alternative to the more invasive surgical bypass.

Endovascular Treatments

Thrombolysis is useful when there is a recent change in the intensity of limb ischemia. It is not recommended for patients with existing ulcers as it does not help ulcer healing. The top four factors limiting success in angioplasty and endovascular therapy are the diffuse nature of the disease, heavy calcification of lesions, presence of total occlusions, and lesions at arterial branch points. Comparing all forms of angioplasty with bypass surgery in intermittent claudication, there is no difference in short and long-term relief of symptoms.

Endovascular therapy includes angioplasty, stenting, atherectomy, and thrombolysis. Angioplasty dilates the lumen of the artery by means of a balloon and may involve selective or high-velocity injection. Frequently, small vessels may obstruct blood flow to the extent that critical limb ischemia ensues. These lesions frequently do not respond well to balloon angioplasty but may respond well to atherectomy. Atherectomy is the removal of atherosclerotic plaque and can be done mechanically or via laser. Laser atherectomy uses thermal energy to vaporize or melt plaque. However, the cost and the lack of data regarding its long-term benefits limit its utility.

Amputation Considerations

Regrettably, the high mortality and morbidity associated with major amputation often make it a self-fulfilling prophecy, and what was intended to salvage life results in its premature termination. This must stress the importance of attempting limb salvage to the very last in order to prevent amputation. However, if it cannot be prevented, then the most suitable level of amputation must be determined. This dictates the rehabilitative outcome for the patient and therefore their future quality of life. High levels of amputation are associated with increased mortality and a poorer functional outcome.

In the USA, 82% of all lower extremity amputations are performed in diabetics or patients over the age of 60, most of whom have PAD. This is a striking figure as it draws a comparison with the older population of PAD sufferers who are more often than not the same people. Unfortunately, these amputees are often left wheelchair-bound and have a one-year mortality rate of 24%, rising to 70% in 5 years compared to a 5% mortality rate in all amputees. These figures reflect the fact that major amputation is often performed as a salvage procedure in those who are already very debilitated, with the hope that removal of a non-healing wound or gangrenous digits will prevent further sepsis and death.

Amputation is a life-changing event for any person, and for many PAD sufferers, it is the failure of previous attempts at revascularization which leads to amputation. Patient selection is therefore of paramount importance, as those unsuitable for revascularization will have a higher chance of success from a primary amputation, provided this is at an appropriate level.

Rehabilitation and Prosthetic Solutions

Amputation of a limb leads to an immediate loss of function and a radical change in lifestyle. The amputee must essentially relearn even the most basic activities of daily living and maintaining independence can be a challenge. Fortunately, advances in prosthetic technology have greatly improved patient outcomes following limb loss. Modern lower-extremity prosthetics are designed with a focus on replicating normal biomechanics during walking in an attempt to reduce energy expenditure and joint forces on the intact limb. This is accomplished with the use of dynamic elastic response feet with a smooth “toe-heel” transition during gait and knees which are able to mimic the stance and swing phase movements of the normal knee. The outcome of prosthetic use on bilateral amputees has a demonstrated effect on overall quality of life as well as reduced cardiovascular mortality compared to age matched unilateral amputees.

The concept of limb salvage maintains an important focus in the management of PAD. Amputation poses a significant risk to the older, poorer surgical candidate and is significantly more common in patients of advanced age and who are diabetic. 15 Over the past several decades, the shift has been towards a more aggressive approach to distal revascularization in an attempt to prevent amputation. However, in cases where limb ischemia has resulted in profound tissue loss, ischemic gangrene, or unmanageable pain, amputation may be the only viable option. This is particularly true in patients where attempts at open or endovascular revascularization have failed. Comparatively, the rise of amputation rates in ESRD patients with PAD (where attempts at revascularization may be less viable) has led to efforts to improve the rate of successful prosthetic rehabilitation.

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