CHAPTER 63
Peripheral Arterial Disease
OUTLINE
Epidemiology and Demographics
Patient Presentations and Natural History
Pathophysiology and Anatomy
Evaluation of the Patient With Peripheral Artery Disease
Medical Management
Key Management Concepts: WIfI, GLASS, TAP and PLAN
Peripheral artery disease (PAD) is the most common condition
requiring treatment by vascular surgeons and vascular specialists.
Over the last decade, the global prevalence of PAD has continued
to rise, and it is a major contributor to rising healthcare resource
consumption.1,2 An estimated 8 to 12 million individuals in
the United States are afflicted with PAD, and at least 202 million
people suffer from PAD across the globe.3 A recent metaanalysis of
more than 34 studies showed a 23.5% increase in the prevalence
of PAD during the first decade of the twenty-first century.4 The
primary drivers of this dramatic rise in PAD prevalence are the
underlying increases in the major risk factors for the development
of PAD around the world. These risk factors include population
aging (i.e., increased longevity); the global epidemic of diabetes,
hypertension, and obesity; and the persistence of tobacco smoking
in many parts of the world (Fig. 63.1). An increased PAD prev-
alence has been noted in both high- and low-income countries
(Fig. 63.2), although the rise has been more dramatic in low- and
middle-income countries (28.7% increase) than in high-income
countries (13.1% increase).3
The economic impact of PAD has been growing in parallel
with its increased prevalence, especially in the United States and in
many industrialized countries. In 2001, PAD-related treatments
comprised approximately 13% of all Medicare Part A and B ex-
penditures and contributed to an estimated economic burden of
over $4.3 billion. By 2004, according to a detailed analysis of the
Reduction of Atherothrombosis for Continued Health (REACH)
Registry, the total estimated costs of vascular-related hospitaliza-
tions in the United States was $21 billion.3,5 The main contribu-
tor to these costs was revascularization procedures, particularly
rises in the use of endovascular therapy (EVT).
The chapter which follows will review the pathophysiology,
anatomy, patient presentations, natural history, diagnosis, and
management of lower extremity PAD. While there have been
many advances in therapy over the last decade, there is still a
striking relative lack of high-level evidence for many of the treat-
ments in common use. The condition is underdiagnosed, medical
Joseph L. Mills Sr., Zachary S. Pallister
Endovascular Versus Open Surgical Therapy
Endovascular Therapy
Open Surgical Therapy
Surveillance
Endovascular Therapy Surveillance
Open Surgical Bypass Graft Surveillance
Assessment of Outcomes
management is underutilized and often not maximized, and there
are wide regional differences and disparities in the application of
revascularization procedures and strategies.
EPIDEMIOLOGY AND DEMOGRAPHICS
Aging is a major risk factor for the development of PAD. Lower
extremity PAD most commonly presents in patients more than 50
years of age and increases markedly with each decade beginning
at 60 years of age. The prevalence of PAD has been estimated at
14.5% in patients more than 69 years of age and as high as 20%
in patients 80 years of age and older.3 Cigarette smoking and its
intensity is also strongly associated with PAD with one study es-
timating its population attributable fraction at 44%.6 In the last
20 years, it has become evident that diabetes has become one of
the most prominent risk factors for the development of PAD.7
There is an ongoing global epidemic of diabetes and currently over
383 million people are affected; this number is expected to almost
double in the next 15 to 20 years. Diabetes is strongly associated
with PAD; population-based studies have reported odds ratios of
1.9 to 4 (Fig. 63.1).3 Patients with diabetes are more likely to de-
velop a foot ulcer and to present with chronic limb-threatening
ischemia (CLTI). Hypertension and hyperlipidemia are the other
major risk factors associated with the development of PAD.!
PATIENT PRESENTATIONS AND NATURAL HISTORY
Patients may have detectable PAD and yet be completely asymp-
tomatic; this situation is not uncommon in the aging popula-
tion as other factors may limit activity levels while PAD lurks in
the background. Individuals may also present with atypical leg
symptoms that result from other conditions such as lumbar spine
disease, neuropathy, degenerative joint disease, and myopathy.
Typical symptoms of PAD include vasculogenic claudication and
CLTI. The latter category includes ischemic rest pain, ischemic
ulcer, and gangrene.
1767
1768 SECTION XII Vascular

Renal insufficiency

Black race

Hyperhomocysteinemia

Hyperlipidemia

Risk factors Hypertension

Smoking

Diabetes

Age

Male gender

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5

Odds ratio

FIG. 63.1 The approximate odds ratios (ORs) for risk factors associated with the development of peripheral
arterial disease (PAD). (Adapted from Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the
Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5–67.)

History of CVD

CRP (per 1 mg/dL)

High HDL cholesterol

High cholesterol

Smoking (past)

Smoking (current)

Diabetes

Hypertension

BMI (per 1 kg/m2)

Male sex OR (LMIC)

OR (HIC)
Age (per 10 yrs) OR (Global)

0.5 1 1.5 2 2.5 3

FIG. 63.2 Odds ratios (ORs) for peripheral artery disease (PAD) in high-income countries (HICs) and low- and
middle-income countries (LMICs). (From Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ
Res. 2015; 116:1509–1526.) BMI, Body mass index; CRP, C-reactive protein; CVD, cardiovascular disease; HDL,
high-density lipoprotein.

Symptoms typical of vasculogenic claudication are character-
ized by cramping or aching discomfort in the buttock, thigh, or
calf muscles that is induced by walking and relieved by rest. The
location of muscular symptoms often correlates with the anatomic
site of disease, such that aortoiliac disease produces buttock and
thigh claudication, while femoropopliteal occlusive disease results
in calf claudication. Such complaints are usually reproducible in
onset but may arise sooner by walking at a faster pace or uphill.
Vasculogenic claudication typically resolves with a short period of
rest (which reduces the muscular metabolic requirement), and in
contrast to neurogenic claudication, is neither variable in onset
nor does it require a change in position for symptom resolution.
Symptoms related to nerve root compression are often variable
in onset, can take a long time for recovery, may arise from stand-
ing alone (without walking), and are often relieved by changes in
spine position (such as spine flexion or sitting down). These two
conditions may coexist, and a good history and physical examina-
tion will often help the clinician differentiate them.
Complementing the history, qualitative components of a physi-
cal examination form the cornerstone of PAD diagnosis. These
components include pulse examination (brachial, radial, femoral,
popliteal, posterior tibial, and dorsalis pedis), observation for lack
of distal hair growth on the involved extremity and dry skin which
may result from apocrine gland dysfunction. The measurement of
ankle-brachial index (ABI) forms the objective, quantitative basis of
PAD assessment. An ABI of less than 0.9 has a sensitivity of 79%
 CHAPTER 63 Peripheral Arterial Disease
to 95% and a specificity exceeding 95% to establish the diagnosis
of PAD in patients in whom it is suspected.2,3 In some individuals,
particularly those with diabetes or the aged, medial calcinosis will re-
sult in falsely elevated ABIs. Because the toe arteries are often spared
calcification, a toe-brachial index may be measured to quantitate
PAD in individuals found to have noncompressible ankle arteries.
A toe-brachial index less than or equal to 0.7 is abnormal and indi-
cates hemodynamically significant PAD.3 If the diagnosis of PAD is
still in doubt, particularly when compelling symptoms are present
in the setting of palpable pulses, an ABI test with exercise can be
helpful. This test and other useful studies will be subsequently dis-
cussed in more detail under “Evaluation of the Patient with PAD.”
Ischemic rest pain has long been recognized as a classic symptom
of advanced PAD and is one manifestation of CLTI. It is more com-
mon in smokers than patients with diabetes mellitus, likely masked
in the latter by peripheral sensory neuropathy related to underlying
diabetes. It occurs in the forefoot and is typically described as hav-
ing its onset with leg elevation or recumbency (i.e., when going to
bed at night) and is relieved by dependency (i.e., dangling the foot
off the bed at night). The increase in pedal blood pressure related to
gravity is sufficient to relieve the pain. Affected patients lack pedal
pulses and usually suffer from distal hair loss in the affected extrem-
ity. Pallor on elevation and dependent rubor are common physical
findings. The diagnosis is confirmed by one or more of several he-
modynamic parameters, including an ABI less than 0.4, an ankle
systolic pressure less than 50 mm Hg, a systolic toe pressure less than
30 mm Hg, a transcutaneous partial pressure of oxygen (TcPO2)
less than 30 mm Hg, and flat or minimally pulsatile pulse volume
recording waveforms in the forefoot.8 It is simple and important
to objectively confirm the diagnosis with hemodynamic testing, as
other conditions such as diabetic neuropathy, night cramps, degen-
erative joint disease, and gout may be confused with rest pain.
Tissue loss (lower leg or foot ulcer) and gangrene can be obvi-
ous manifestations of CLTI. The strict definition of CLTI-related
tissue loss requires that it be present for at least two weeks (to ex-
clude minor traumatic lesions that heal spontaneously) and that it
be accompanied by objective evidence of PAD of sufficient sever-
ity to impede wound healing. This topic will be addressed in more
detail below when the wound, ischemia, and foot infection (WIfI)
classification9 of CLTI is reviewed as one of the key management
concepts recently recommended by the Global Guidelines Com-
mittee on CLTI.8!
PATHOPHYSIOLOGY AND ANATOMY
This chapter focuses on PAD due to atherosclerotic occlusive dis-
ease. Other uncommon arteriopathies and vasculitides that may
produce peripheral ischemia are beyond its scope. These non-
atherosclerotic conditions include giant cell arteritis, Takayasu
arteritis, polyarteritis nodosa, Wegener granulomatosis, thrombo-
angiitis obliterans (Buerger disease), Behcet disease, pseudoxan-
thoma elasticum, iliac artery endofibrosis, popliteal entrapment
syndrome, and cystic adventitial disease.
Arteries are generally grouped into three types: elastic, muscu-
lar, and arterioles. The elastic arteries are the aorta and the pulmo-
nary arteries. They need to be elastic because they receive blood
directly from the heart and are relatively thin compared to their
diameters. With each contraction of the heart, blood is forcibly
ejected into the elastic arteries, whose walls must stretch to ac-
commodate this systolic force. During diastole, their elastic walls
recoil, thus continuing to propel blood forward while the heart
refills. The muscular arteries are distributive in nature and include
1769
the coronary and peripheral arteries. These arteries are thicker
relative to their diameters than the elastic arteries, with reduced
sheets of elastin and characteristically well-defined longitudinal
and circular smooth muscle layers. Contraction and relaxation of
the muscular arteries alter the amount of blood flow delivered de-
pending on local requirements (e.g., increased peripheral arterial
flow is induced by exercise). Arterioles are the vessels of blood
delivery to the capillary bed. Arterioles are characterized by con-
centric rings of smooth muscle whose contraction and dilation
control blood flow into the capillary bed; they are generally less
than 300 microns in diameter.
Arteries consist of three layers: the endothelium, media, and
adventitia (with vasa vasorum). These layers vary in composition
and thickness depending on location and health/disease state. The
endothelium is considered an organ. As such, it has autocrine,
paracrine, and endocrine functions that regulate blood flow and
thrombogenicity. The endothelium is remarkable in that it synthe-
sizes multiple compounds that regulate vascular tone and provide
vascular homeostasis. Dysfunction of the endothelium is the earli-
est hallmark of vessel injury (Ross hypothesis of atherosclerosis)
and it can be detected before histologic changes associated with
atherosclerosis are evident. The injury response is currently thought
to be similar in many ways to a chronic inflammatory response.
After initial epithelial dysfunction, changes in the arterial wall per-
meability occur and in response to a multitude of growth factors,
stimulatory factors, and interactions between smooth muscle cells
(SMCs), monocytes, lymphocytes and platelets, a fibroprolifera-
tive response takes place that results in plaque deposition. There
are three stages of plaque, with the earliest stage termed the fatty
streak. Fatty streaks are focal, yellow, usually linear streaks that can
be seen on the luminal surface of arteries and are evident in most
individuals after three years of age. These streaks are microscopi-
cally macrophages (foam cells) full of lipid that accumulate in the
intima. They often occur at branch points. Atherosclerotic plaque
also tends to develop at branch points. The intermediate stage is a
fibrofatty lesion characterized by increased deposition of layers of
matrix around layered macrophages, T lymphocytes, and SMCs.
The most advanced stage is the complicated or fibrous plaque.
Such plaques have begun to compromise the arterial lumen and
protrude into it. On their surface is a fibrous cap beneath which
lie dense layers of connective tissue and SMCs with a core con-
taining lipid and necrotic debris. Rupture of the cap characterizes
an unstable plaque, which exposes the vessel lumen to lipid and
cellular debris, leading to the thrombotic complications associated
with atherosclerotic plaque (Fig. 63.3).
Atherosclerotic disease is a chronic, degenerative, inflamma-
tory process to which the body attempts to adapt to maintain both
the structure and underlying function of the arterial circulation.
Although systemic in nature, atherosclerosis tends to develop at
specific, anatomic locations within the arterial tree. Adaptive re-
sponses include compensatory changes in wall thickness and lu-
minal diameter, which are thought to result from changes in shear
stress. Glagov and associates were among the first to note that as
atherosclerotic plaques enlarge, the lumen enlarges to compensate
and maintain similar flow rates.10 This process has been shown to
occur in the coronary, carotid, and superficial femoral arteries as
well as the aorta. Such compensatory enlargement may serve to
prevent flow-limiting luminal stenosis until the plaque area reaches
approximately 40% of the cross-sectional area of the affected lu-
men. While coronary, carotid, and aortoiliac lesions tend to occur
at branch points, obstructive superficial femoral artery plaque tends
to develop in the distal portion of the vessel, which is generally
1770 SECTION XII Vascular
Leukocyte
adhesion
Endothelial
adhesion
Endothelial
permeability
Leukocyte
migration
Fibrous cap
formation
Macrophage
accumulation
Formation of
necrotic core
FIG. 63.3 Initiation and progression of atherosclerotic plaque. Cardio-
vascular risk factors, hemodynamic forces, toxins, and infectious agents
interact with the vessel at the level of the endothelium to produce injury,
resulting in decreased nitric oxide production and increased permeability.
Once injured, the endothelium increases the expression of leukocyte ad-
hesion molecules such as vascular cell adhesion molecule-1, intracellular
adhesion molecule-1, and P- and E-selectin, which increases the adher-
ence of macrophages and other leukocytes. Permeability of the endothe-
lium also increases and permits entry of leukocytes and lipoproteins into
the subendothelial space. Chemokines and cytokines such as monocyte
chemotactic protein-1 and interleukin-8 further enhance the recruitment
of leukocytes and smooth muscle cells (SMCs) into the subendothelial
space. Lipoproteins retained in the subendothelial space are biochemi-
cally modified such that they can be taken up by macrophages and SMCs
to form foam cells. Foam cells at the central-most position of the develop-
ing atheroma become necrotic and form the central lipid core, whereas
the shoulder regions contain SMCs, macrophages, and other leukocytes.
Platelet-derived growth factor and transforming growth factor-β stimulate
SMC migration and collagen formation in the subendothelial space, as
well as formation of the fibrous cap. (From Owens CD, Ho KJ. Athero-
sclerosis. In: Sidawy AN, Perler BA, eds. Rutherford’s vascular surgery
and endovascular therapy. 9th ed. Philadelphia, PA: Elsevier; 2019:44–53.)
straight, with few branches. This predilection for PAD to occur in
the superficial femoral artery at the adductor hiatus has been attrib-
uted to the anatomic compression by the adductor tendons, which
limits compensatory arterial dilation to growing plaque.
In general, patients with claudication will be found to have
single level disease, frequently involving either the aortoiliac seg-
ment or the femoropopliteal segment, with relative sparing of the
distal extremity arteries. These patterns of disease are common in
cigarette smokers. Patients with CLTI more often have multilevel
disease. Patients with PAD associated with diabetes tend to have
patterns of more distal occlusive disease and more frequently have
involvement of the deep femoral (profunda) artery and the in-
frapopliteal arteries.11 CLTI patients often have femoropopliteal
artery stenosis or occlusion along with tibial occlusive disease,
but especially in diabetes, they may be found to have isolated
infrapopliteal occlusive disease. The pedal arteries are often spared,
with more than 85% of patients having a patent pedal vessel,12
although severe pedal occlusive disease seems to be increasing in
frequency, especially among patients with end-stage renal disease.
For reasons that remain yet unexplained, the anterior tibial and
posterior tibial arteries are most frequently involved, with rela-
tive sparing of the peroneal artery. These patterns of disease are
important to recognize as they have significant implications for
management (Fig. 63.4).!
EVALUATION OF THE PATIENT WITH PERIPHERAL
ARTERY DISEASE
A detailed history and thorough physical examination should be
performed in every patient suspected of having PAD. It should in-
clude elucidation of pertinent symptoms and the degree of disabil-
ity associated with them; past medical history (particularly prior
surgical operations or revascularization procedures); assessment of
all major cardiovascular risk factors (smoking, diabetes, hyperten-
sion, hyperlipidemia, obesity, and sedentary lifestyle); palpation
of all accessible peripheral pulses (carotid, brachial, radial, ulnar,
femoral popliteal, posterior tibial, and dorsal pedal); auscultation
of the neck, abdomen and groin for bruits; auscultation of the
heart and lungs; and palpation of the abdomen, femoral, and pop-
liteal regions for aneurysm. The extremities should be inspected
for temperature changes, color (elevation pallor or dependent ru-
bor), signs of muscle atrophy, distal hair loss, and ulcers of the
leg and foot, especially examining all surfaces of the foot and be-
tween the toes in patients with diabetes. An adequate extremity
examination requires removal of the socks and shoes bilaterally,
even if there are only complaints in one limb. The shoes them-
selves should also be closely examined for signs of uneven wear
and foreign bodies within them or stuck in the soles (nails, tacks,
screws, etc.). Patients with diabetic neuropathy will not feel these
items. All patients with foot ulcers should be tested for neuropa-
thy to detect loss of protective sensation (the Semmes-Weinstein
monofilament test is the simplest) and probe-to-bone test should
be performed in any patient with a foot ulcer.7!
MEDICAL MANAGEMENT
PAD is a localized manifestation of systemic atherosclerosis. PAD
is associated with high cardiovascular morbidity and mortality
from myocardial infarction and stroke. These risks are particularly
high among CLTI patients. Major risk factors for the develop-
ment of PAD include age, sex, hypertension, hyperlipidemia,
diabetes mellitus, smoking status, and sedentary lifestyle. Major
cardiovascular risk factors should be evaluated in all patients with
PAD. Medical management of patients with PAD includes modi-
fication of these medical comorbidities when feasible to reduce
lower cardiac morbidity and mortality. The Society for Vascular
Surgery Global Vascular Guidelines were used as a framework on
which the following recommendations were based.3,8
Antithrombotic therapy is strongly recommended for all patients
with PAD to reduce major adverse cardiac events (MACEs), defined
as a composite of nonfatal stroke, nonfatal myocardial infarction,
and cardiovascular death. The mainstay of this therapy is low-dose as-
pirin. Recent data suggests that further benefit might result from the
use of alternative antiplatelets agents such as clopidogrel or ticlopi-
dine. The benefit achieved in these patients is a lowering of MACEs.
A metaanalysis performed comparing single-agent antithrombotic
use in PAD patients suggested that clopidogrel monotherapy was
 CHAPTER 63 Peripheral Arterial Disease 1771

Age Male Diabetes Hypertension Hyper- Current

gender mellitus cholesterolemia smoking

Iliac

Femoro-
popliteal

Crural

FIG. 63.4 Association of risk factors with the level of atherosclerotic target lesions. The red overlay on the ana-
tomic cartoon illustrates the association of risk factor with patterns of atherosclerotic disease. (From Diehm N,
Shang A, Silvestro A, et al. Association of cardiovascular risk factors with pattern of lower limb atherosclerosis
in 2659 patients undergoing angioplasty. Eur J Vasc Endovasc Surg. 2006;31:59–63.)

most effective for lowering MACEs. Currently, there is no clear ben-
efit for dual antiplatelet therapy (DAPT) or systemic anticoagula-
tion in patients with PAD to lower MACEs, though there are several
ongoing clinical trials to evaluate this issue further.
Lipid-lowering therapy is essential in patients with PAD and
has been demonstrated to decrease MACEs. Additionally, there
appears to be a direct antiinflammatory effect in PAD patients,
which has been postulated to lead to atherosclerotic plaque stabil-
ity and reduce vascular events. It has been well established that
high-intensity statin therapy decreases MACEs in patients with
PAD. Specifically, this includes high intensity rosuvastatin (20–40
mg/day) or simvastatin (40–80 mg/day).
Control of hypertension has been shown to decrease MACEs
in patients with PAD. Data suggests that targeting systolic blood
pressure (SBP) less than 140 mm Hg and diastolic blood pressure
(DBP) less than 90 mm achieves optimal reduction in MACEs in
patients with PAD. Specific categories of antihypertensives have
not clearly been demonstrated to be optimal in PAD patients,
with angiotensin-converting enzyme (ACE) inhibitors, calcium
channel blockers, beta blockers, and diuretics all being effective
to lower MACEs.
Diabetes mellitus is a significant risk factor and contributor
to the development of atherosclerosis and PAD. The extent and
severity of disease correlates with blood glucose control. Therefore,
glycemic control should be a focus of care in patients with PAD.
The specific goal is for patients is to maintain a Hemoglobin A1c
level of less than 7%. There has been a noted advantage for using
metformin as the primary hypoglycemic agent for patients with
Type II diabetes and CLTI. Adjunctive medications as well as in-
sulin should be considered to achieve this A1c target.
Tobacco abuse is a frequent comorbid condition for patients
with PAD and specifically those with CLTI. The extent of ciga-
rette smoking has been shown to correlate with PAD severity. To-
bacco abuse leads to higher MACEs in patients with PAD and also
contributes to PAD disease progression. Patients should be asked
about the status of their tobacco use at every visit. Clinical sup-
port, adjunctive medications, and counseling should be offered to
all active smokers with PAD.
Exercise has been shown to have clear benefits for patients with
PAD and intermittent claudication and should be the attempted
prior to revascularization in these patients. This is especially true
for patients with stable symptoms that are not lifestyle limiting.
Specifically, patients should be referred for a supervised exercise
therapy program with an exercise physiologist if possible. There is
greater established benefit for supervised compared to nonsuper-
vised programs, but home-based plans have also shown benefit.
Exercise has been shown to improve walking distances in claudi-
cants by increasing calf blood flow, improving endothelial func-
tion, reducing local inflammation, and inducing angiogenesis.
The general recommendations are for these patients to perform
a minimum of 45 to 60 minutes of exercise, 3 times per week for
12 weeks, typically walking on a treadmill. The exercise should be
sufficiently intense to elicit claudication. No specific randomized
controlled trial has been used to evaluate this benefit in CLTI pa-
tient symptoms, although the benefit from reduced MACEs asso-
ciated with cardiac rehabilitation regimens has been demonstrated.!
KEY MANAGEMENT CONCEPTS: WIfI, GLASS, TAP
AND PLAN
Perhaps the most significant recent change in the diagnosis and
management of PAD relates to concepts concerning CLTI. These
changes were driven in large part by the global epidemic of diabe-
tes. Diabetes currently affects nearly 400 million people around
the world and its prevalence is increasing in virtually every country
for which data are available. Due to neuropathy and PAD, about
one in four patients with diabetes will develop a foot ulcer during
their lifetime; 80% of diabetes-related amputations are preceded
1772 SECTION XII Vascular

TABLE 63.1 SVS WIfI clinical limb stage based on estimated risk of amputation at one year.
ISCHEMIA - 0 ISCHEMIA - 1 ISCHEMIA - 2 ISCHEMIA - 3

W-0 1 1 2 3 1 2 3 4 2 2 3 4 2 3 3 4
W-1 1 1 2 3 1 2 3 4 2 3 4 4 3 3 4 4

W-2 2 2 3 4 3 3 4 4 3 4 4 4 4 4 4 4
W-3 3 3 4 4 4 4 4 4 4 4 4 4 4 4 4 4
fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3

Key:fI, foot infection; W, wound.

Clinical Stage 1 or very low risk

Clinical Stage 2 or low risk

Clinical Stage 3 or moderate risk

Clinical Stage 4 or high risk

Clinical Stage 5 = unsalvageable limb

Adapted from Mills JL, Sr., Conte MS, Armstrong DG, et al. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification
System: Risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg. 2014;59:220–234 e221–222.
IDSA, Infectious Diseases Society of America; PAD, peripheral artery disease; PEDIS, perfusion, extent/size, depth/tissue loss, infection,
sensation; WIfI, wound, ischemia, and foot infection.
Premises:
a.Increase in wound class increases risk of amputation (based on WIfI, PEDIS, University of Texas, and other wound classifications systems).
b.PAD and infection are synergistic (Eurodiale); infected wound + Pad increases likelihood revascularization will be needed to heal wound.
c.Infection 3 category (systemic/metabolic instability): moderate to high-risk of amputation regardless of other factors (validated IDSA infection
guidelines).

by a diabetic foot ulcer (DFU).7,9 A significant fraction (49%–
66%) of people with DFUs have detectable underlying PAD.9,13
Even in many, modern, complex healthcare systems, patients with
DFU are not routinely evaluated for PAD and the opportunity for
diagnosis and revascularization is missed. All too often, DFUs are
managed with wound care alone or even amputation (both major
and minor) without any evaluation for correctable PAD, despite
the well-known association of PAD with delayed wound healing
and amputation in such patients.13 It became apparent that the
dated concept of “critical limb ischemia”14 first proposed in 1982,
as well as the most common classification systems used for decades
by vascular surgeons (Fontaine15 and Rutherford16), failed to ad-
dress numerous issues related to management of DFU. In fact,
the authors of the original consensus statement on critical limb
ischemia specifically stated that patients with diabetes were to be
excluded from the definition as wounds in such patients were often
complicated by neuropathy and infection, and the perfusion re-
quirements to achieve healing in patients with diabetes were likely
greater than in patients with foot ulcers and gangrene occurring
in the setting of pure chronic ischemia from PAD seen in ciga-
rette smokers without diabetes.14 The hemodynamic parameters
for “critical” limb ischemia proposed in the existing classifications
were likely too rigid, and both the Fontaine and Rutherford sys-
tems lacked sufficient detail about wound characteristics and failed
to consider the presence and severity of infection. Both of these
factors influence care and outcomes of care, especially in patients
with DFU. With these considerations in mind, the Society for
Vascular Surgery created and published a new classification system
intended to stratify amputation risk and impact clinical manage-
ment. This classification is applicable to patients with and without
diabetes and is based on three major factors: wound, ischemia, and
foot infection (WIfI).9 Since its publication in 2014, the WIfI con-
cept has achieved broad acceptance and has been adopted and rec-
ommended by many societies across the globe including, among
others, the Society for Vascular Surgery, the European Society of
Vascular and Endovascular Surgery, the European Society of Car-
diology, the International Working Group on the Diabetic Foot
(IWGDF), the American Podiatric Medical Association, and the
very recently published Global Vascular Guidelines Committee.8
WIfI is a limb staging system. The underlying principle of
WIfI is that the limb must be staged at presentation, prior to
planning treatment, and in that way, it is analogous to the tumor,
node, metastasis (TNM) system for cancer staging. Each of the
three factors is graded on an objective scale from 0 to 4, a pro-
cess which therefore yields 64 potential combinations of WIfI.
By Delphi consensus, these combinations were grouped into one
of four clinical stages (I–IV), each associated with progressively
increasing risk of amputation at one year (Tables 63.1 and 63.2).
Although initially based on a consensus approach, when subse-
quently applied in clinical practice, WIfI has been shown to have
considerable prognostic value in predicting amputation risk. A re-
cent metaanalysis17 of 12 studies comprising 2669 patients with
CLTI demonstrated that the likelihood of amputation at 1 year
increased progressively with increasing WIfI stage, 0%, 8% (95%
confidence interval [CI] 3%–21%), 11% (95% CI 6%–18%)
and 38% (95% CI 21%–58%), for WIfI stages I–IV, respectively.
Other analyses have yielded similar findings.18 WIfI may also be
used to predict the likelihood of benefit of revascularization, al-
though the data supporting this particular utility of WIfI are less
robust.19,20
 TABLE 63.2 Society for Vascular Surgery Lower Extremity Threatened Limb (SVS WIfI)
classification system.
I. Wound
II. Ischemia
III. Foot Infection
W I fI score
W: Wound/clinical category
SVS grades for rest pain and wounds/tissue loss (ulcers and gangrene):
0 (ischemic rest pain, ischemia grade 3; no ulcer), 1 (mild), 2 (moderate), 3 (severe).
GRADE ULCER GANGRENE
0 No ulcer No gangrene
Clinical description: ischemic rest pain (requires typical symptoms + ischemia grade 3); no wound.
1 Small, shallow ulcer(s) on distal leg or foot; no exposed bone, unless limited to distal No gangrene
phalanx
Clinical description: minor tissue loss. Salvageable with simple digital amputation (1 or 2 digits) or skin coverage.
2 Deeper ulcer with exposed bone, joint, or tendon; generally not involving the heel; Gangrenous changes limited to digits
shallow heel ulcer, without calcaneal involvement
Clinical description: major tissue loss salvageable with multiple (≥3) digital amputations or standard TMA ± skin coverage.
3 Extensive, deep ulcer involving forefoot and/or midfoot; deep, full thickness heel ulcer Extensive gangrene involving forefoot and/or midfoot; full thickness
± calcaneal involvement heel necrosis ± calcaneal involvement
Clinical description: extensive tissue loss salvageable only with a complex foot reconstruction or nontraditional TMA (Chopart or Lisfranc); flap coverage or complex
wound management needed for large soft tissue defect.
TMA, Transmetatarsal amputation.
I: Ischemia
Hemodynamics/perfusion: Measure TP or TcPO2 if ABI incompressible (>1.3)
SVS grades 0 (none), 1 (mild), 2 (moderate), and 3 (severe).
GRADE ABI ANKLE SYSTOLIC PRESSURE TP, TcPO2
0 ≥0.80 >100 mm Hg ≥60 mm Hg
1 0.6–0.79 70–100 mm Hg 40–59 mm Hg
2 0.4–0.59 50–70 mm Hg 30–39 mm Hg
3 ≤0.39 <50 mm Hg <30 mm Hg
ABI, Ankle-brachial index; PVR, pulse volume recording; SPP, skin perfusion pressure; TP, toe pressure; TcPO2, transcutaneous oximetry.
Patients with diabetes should have TP measurements. If arterial calcification precludes reliable ABI or TP measurements, ischemia should be documented by TcPO2,
SPP, or PVR. If TP and ABI measurements result in different grades, TP will be the primary determinant of ischemia grade.
Flat or minimally pulsatile forefoot PVR = grade 3.
fI: foot Infection:
SVS grades 0 (none), 1 (mild), 2 (moderate), and 3 (severe: limb and/or life-threatening)
SVS adaptation of Infectious Diseases Society of America (IDSA) and International Working Group on the Diabetic Foot (IWGDF) perfusion, extent/size, depth/tissue
loss, infection, sensation (PEDIS) classifications of diabetic foot infection.
IDSA/PEDIS
CLINICAL MANIFESTATION OF INFECTION SVS INFECTION SEVERITY
No symptoms or signs of infection 0 Uninfected
Infection present, as defined by the presence of at least two of the following items:
• Local swelling or induration
• Erythema >0.5 to ≤2 cm around the ulcer
• Local tenderness or pain
• Local warmth
• Purulent discharge (thick, opaque to white, or sanguineous secretion)
Local infection involving only the skin and the subcutaneous tissue (without involvement of deeper tissues and without 1 Mild
systemic signs as described below).
Exclude other causes of an inflammatory response of the skin (e.g., trauma, gout, acute Charcot neuroosteoarthropathy,
fracture, thrombosis, venous stasis)
Local infection (as described above) with erythema >2 cm, or involving structures deeper than skin and subcutaneous tissues 2 Moderate
(e.g., abscess, osteomyelitis, septic arthritis, fasciitis), and No systemic inflammatory response signs (as described below)
Local infection (as described above) with the signs of SIRS, as manifested by two or more of the following: 3 Severe*
• Temperature >38°C or <36°C
• Heart rate >90 beats/min
• Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg
• White blood cell count >12,000 or <4000 cu/mm or 10% immature (band) forms

From Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and
treatment of diabetic foot infections. Clin Infect Dis. 2012;54:e132–173.
PACO2, Partial pressure of arterial carbon dioxide; SIRS, systemic inflammatory response syndrome.
*Ischemia may complicate and increase the severity of any infection. Systemic infection may sometimes manifest with other clinical findings, such
as hypotension, confusion, vomiting, or evidence of metabolic disturbances, such as acidosis, severe hyperglycemia, new-onset azotemia.
1774 SECTION XII Vascular
The limb itself, however, is only one issue to be considered in
the treatment of patients with CLTI. Patient risk factors, life ex-
pectancy, and the underlying vascular anatomy in patients felt to
benefit from revascularization also constitute integral components
of the decision-making process. The Global Vascular Guidelines
on CLTI were recently published in an effort to initiate evidence-
based guidelines for the diagnosis, evaluation, and management
of such patients. The guidelines include an expanded and more
modern definition of CLTI, are based upon a three-step process
that includes limb staging with WIfI, and introduce three other
new concepts: patient, limb, anatomy (PLAN), target artery path
(TAP), and Global Limb Anatomic Staging System (GLASS).8
These guidelines are succinctly summarized below as they repre-
sent an important advance in CLTI care.
The Global Vascular Guideline begins by establishing impor-
tant definitions and nomenclature. The Global Vascular Guide-
lines suggest abandoning the outdated term “critical limb isch-
emia”14 as it fails to encompass the complete spectrum of patients
in modern day practice who are evaluated and treated to prevent
limb amputation. Instead, the term CLTI is now proposed so as to
include a much broader spectrum of patients with varying degrees
of ischemia sufficient to contribute to the development of foot
and leg ulcers, delay healing, and increase amputation risk. CLTI
includes only patients with chronic atherosclerotic disease and is
not intended to be applied to patients with acute thrombotic or
embolic leg ischemia, trauma, pure venous disease, or nonathero-
sclerotic conditions such as the vasculitides and Buerger disease.
The target population therefore includes any adult with CLTI, de-
fined as a patient with objectively documented PAD and any of
the following clinical presentations: ischemic rest pain with con-
firmatory hemodynamic measurements; DFU or any lower limb
ulcer present for at least two weeks; and gangrene involving any
part of the lower limb or foot. CLTI is thus a more inclusive and
well-defined term that can be more appropriately applied to the
spectrum of patients presenting with limb threat than the dated
or imprecise terms, critical limb ischemia or severe limb ischemia.
Given a patient presenting with any of the above manifesta-
tions of CLTI, the next step is to stage the limb with the WIfI
classification system, which provides an evidence-based estimation
of the degree of limb threat and helps focus limb salvage efforts.
PLAN includes a focus on the patient and his/her estimated risk
for intervention, in particular estimates of short- and long-term mor-
tality. In contrast to patients with CLTI, patients with claudication
are generally at lower risk, with a predicted 75% to 80% 5-year life
expectancy and a 5-year risk of amputation of only 5%.3 Interven-
tions should only be undertaken in claudicants after failure of exercise
and medical therapy, when anatomic factors are favorable for inter-
vention, and prolonged patency and symptom relief is likely. In con-
trast, CLTI patients overall have a 50% 5-year mortality,21 but also a
much higher amputation risk, based primarily on the limb stage at
presentation. Simons and associates22 suggested that CLTI patients
could be grouped into three risk groups for mortality based on a
combination of factors including age older than 80 years, oxygen-
dependent chronic obstructive lung disease, stage 5 chronic kidney
disease, and bedbound status. Using a predictive model based on
these factors from a large cohort of over 38,000 patients derived from
the Vascular Quality Initiative, patients were defined as low-risk (30-
day survival >97% and 2-year survival >70%), medium-risk (30-day
survival 95%–97% or 2-year survival 50%–70%), or high-risk (30-
day survival <95% or 2-year survival <50%).22 These data and those
from the BASIL trial23 were considered in the Global Guidelines and
it was recommended that CLTI patients be grouped into average
(anticipated periprocedural mortality <5% and estimated 2-year sur-
vival >50%) and high-risk groups (anticipated periprocedural mortal-
ity ≥5% and estimated 2-year survival ≤50%). One of the reasons for
this adjustment was because the BASIL trial had shown that EVT for
severe limb ischemia patients had similar outcomes compared to open
surgical bypass for patients living less than two years from their ini-
tial revascularization attempt, whereas patients living longer than two
years appeared to benefit from bypass surgery.24,25 Other factors have
also been examined including functional status and frailty,26–33 but
the data in CLTI patients in predicting perioperative and long-term
survival is not yet well defined. The final component of PLAN, after
assessing individual patient risk and WIfI limb stage, is to evaluate
the arterial anatomy in those patients in need of revascularization and
who would be candidates for revascularization. These three pieces are
then considered to formulate a revascularization strategy (Fig. 63.5).
To define the arterial anatomy, many groups start with duplex
imaging because it can be done in the office, is relatively inexpensive,
and requires neither an intravenous catheter nor contrast administra-
tion. Computed tomography angiography and magnetic resonance
angiography can be considered, especially when inflow disease (aor-
toiliac disease) is suspected. Most commonly, patients are evaluated
with catheter-based digital subtraction angiography because it is the
most direct method and offers the best views of the foot (Fig. 63.6).
Studies which do not include the foot in CLTI patients are inad-
equate.7,8 Contrast can be diluted in patients with kidney disease
and CO2 arteriography offers excellent views of the proximal vessels
down the popliteal level and is therefore often used to limit contrast
in patients with significant baseline renal impairment.
Any inflow disease, if present, must be corrected, most commonly
with angioplasty with or without stenting. The entire affected limb is
evaluated angiographically and classified using the GLASS. GLASS
classifies the limb disease burden from the groin to the foot, with
the underlying assumption that inflow disease is not present or has
already been corrected. GLASS was designed to address inconsisten-
cies and the overall lack of utility of the older, TransAtlantic Inter-
Society Consensus (TASC) I and II anatomic classification systems,
which were lesion and arterial segment based and did not correlate
with expected patency rates and outcomes of therapy.8 There are sev-
eral underlying key assumptions and principles defined by GLASS.
The first is that in-line flow to the ankle and the foot is a primary
goal of therapy, and to accomplish that, one must select a TAP. The
TAP is selected by the operator and is a continuous route of in-
line flow from groin to foot. Assessment of patency is limb based,
not lesion or segment based. The femoropopliteal and infrapopliteal
segments are each graded in severity on a scale from 0 to 4 based
on length and other important characteristics of the stenosis or oc-
clusion, such as whether or not the origin of the vessel is involved
and whether or not significant calcification is present (Figs. 63.7 and
63.8). Pedal anatomy is used as a modifier/descriptor (Fig. 63.9).
CLTI is most often a multilevel disease, so GLASS combines the
grades of the infrainguinal segments to create an arterial anatomic
stage, analogous to the way in which the WIfI system is used to
stage the limb itself. Stages range in progressive severity from I to III,
based on consensus estimates of the estimated technical failure rates
and 1-year limb-based patency (Table 63.3). The system is geared to-
ward an endovascular approach but should allow meaningful com-
parison with open bypass surgery for comparable WIfI limb stage
and GLASS arterial anatomic stages. Although based on current
best evidence and expert consensus, the GLASS classification has
not yet been validated. However, neither were the TASC systems it
is intended to replace and GLASS makes more clinical sense because
the entire limb is staged from an arterial anatomic standpoint and it
 CHAPTER 63 Peripheral Arterial Disease 1775

Clinical suspicion of
CLTI
Rest pain – tissue loss

Complete physical No Search for alternative

exam suggestive of
diagnosis
PAD

Yes
ABI >1.40 or
Measure ankle
Normal ABI discordant ankle
pressure, ABI, and
(0.90 – 1.40) pressure, ABI, and/or
doppler waveforms
doppler waveforms

Abnormal ABI <0.90

Yes Measure toe pressure,

Tissue loss or
TBI, and doppler
gangrene
waveforms

No

Search for alternate Stage limb severity

cause of rest pain (WlfI)

Obtain vascular
imaging if patient is a
candidate for
revascularization

FIG. 63.5 Flow diagram for the investigation of patients presenting with suspected chronic limb-threatening
ischemia (CLTI). (From Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management
of chronic limb-threatening ischemia. J Vasc Surg. 2019;69:3S–125S e140.) ABI, Ankle-brachial index; PAD,
peripheral artery disease; TBI, toe-brachial index; WIfI, wound, ischemia, and foot infection.

considers that more than one level of disease may have to be treated
to obtain in-line flow to heal the foot (Fig. 63.10). Going forward, it
is anticipated that the combination of patient risk, WIfI limb stage,
and GLASS anatomic stage can be put together to predict the ben-
efit of revascularization and the best means of accomplishing it (i.e.,
EVT vs. bypass, see Figs. 63.11 and 63.12)!
ENDOVASCULAR VERSUS OPEN SURGICAL
THERAPY
The emergence of EVT for the treatment of PAD has created the
dilemma of which revascularization option to select for any given
patient. Once the determination has been made that an indica-
tion for revascularization exists, vascular surgeons are charged
with determining the appropriate avenue of intervention. EVT
has advanced to such an extent that it is often the first option
selected for patients undergoing infrainguinal revascularization in
contemporary practice.
A paucity of Level 1 data exists to direct the decision-making
for choosing endovascular versus open surgical intervention. In
fact, the sole completed randomized, controlled, prospective,
multicenter trial comparing angioplasty to open surgery therapy is
the BASIL Study from the United Kingdom.24,25 While this trial
demonstrated no significant differences between the open bypass
first group versus the balloon angioplasty group at six months, a
trend toward improved amputation-free survival was noted at two
years in the group initially undergoing open surgical bypass.
Anatomic considerations previously deemed to necessitate
open surgical therapy have become less stringent in parallel with
these endovascular advancements. The now dated TASC 2007
guidelines suggest that bypass is still preferable in TASC D (long
segment, extensive) aortoiliac and femoropopliteal lesions. Ad-
ditionally, extensive literature suggests that patients with limited
tibial runoff should be considered for open revascularization to
avoid further damage to the remaining runoff vessels.34 It is im-
portant to note that despite these recommendations, all lesions
are considered by some to be appropriate for either open or EVT
based solely on anatomic considerations.
The underlying indication is important to consider at the time
of operative planning. Expected long-term patency rates should be
considered prior to selecting a treatment plan. Patients with clau-
dication or ischemic rest pain treated with EVT will often have
1776 SECTION XII Vascular
Image arterial
anatomy
Duplex ultrasound
CTA
(not recommended
for detailed Diagnostic catheter
infrapopliteal angiography
visualization)
No
Adequate imaging
No
Yes
Define preferred
target arterial
pathway
FIG. 63.6 Suggested algorithm for anatomic imaging in patients with chronic limb-threatening ischemia (CLTI)
who are candidates for revascularization. In some cases, it may be appropriate to proceed directly to angiograph-
ic imaging (computed tomography angiography [CTA], magnetic resonance angiography [MRA], or catheter)
rather than to duplex ultrasound (DUS) imaging. (From Conte MS, Bradbury AW, Kolh P, et al. Global vascular
guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg. 2019;69:3S–125S e140.)
recurrence of symptoms when the intervention fails. Conversely,
patients with tissue loss can often heal their wounds or amputation
incisions in the period of EVT patency and may not require further
intervention if the index wound(s) have healed, despite recurrence
of the underlying arterial lesions. Restenosis is extremely common
after EVT, especially for complex and more calcified lesions. Pa-
tients with CLTI often have long segment and multilevel disease
which has inferior patency rates after endovascular intervention.35
Medical comorbidities should also be considered when
determining the type of intervention. EVT can often be per-
formed under local anesthesia with monitored conscious seda-
tion (avoiding general anesthesia), with minimal blood loss and
reduced physiologic stress to the patient. These considerations
may lead to the selection of an EVT approach in patients with
severe medical comorbidities, including advanced coronary ar-
tery disease or chronic obstructive pulmonary disease. However,
some patients with severe medical comorbidities can be medical-
ly optimized and may then tolerate open intervention. Finally, as
demonstrated in the BASIL trial, one must consider patient life
expectancy. A significant benefit for open surgical bypass over
angioplasty was not evident until two years following interven-
tion. Therefore, angioplasty should be strongly considered as the
primary therapy for patients with shorter life expectancies to
avoid prolonged hospitalization or morbidity, as these consid-
erations likely outweigh issues of patency and durability of the
revascularization.
The BASIL trial also demonstrated a very high level of treat-
ment crossover. Specifically, patients undergoing EVT first had a
MRA
(depending on
availability and
expertise)
No Adequate imaging of
Detailed foot MRA
tibial and foot
(if available)
vessels
Adequate imaging of
tibial and foot vessels Yes
Yes
high rate of subsequent open bypass and those treated first with
open bypass frequently required subsequent endovascular inter-
vention to maintain patency. This finding suggests that the two
forms of intervention are complementary and reinforces the need
to have both options available when treating patients with PAD.35
Of note, due to the lack of level 1 data to guide this decision-
making process, two additional randomized controlled trials are
currently ongoing. The BASIL 2 trial (United Kingdom) and the
BEST-CLI (primarily United States and Canada) trial seek to fur-
ther inform surgeons and patients determining appropriate treat-
ment courses.
Endovascular Therapy
EVT has exploded due to rapid evolution of devices and techniques
over the last two decades such that it has now become the first op-
tion for intervention in many patients with clinical manifestations
of PAD. While initially limited to focal lesions in larger diameter
vessels, it currently is used even to treat long segment lesions in the
tibial and pedal vessels. Historically, this same evolution of treat-
ment from proximal to distal vessel occurred with open surgical
therapy. Although in many cases EVT patency rates remain inferior
to those of open surgical bypass, with appropriate patient and le-
sion selection and with the use of advanced, meticulous techniques,
favorable patient-centered outcomes can be achieved.
General Considerations
There are certain aspects of technique applicable to all forms of
EVT and these include gaining arterial access and sheath, catheter,
 CHAPTER 63 Peripheral Arterial Disease 1777

0 • Mild or no significant (<50%) disease

1 • Total length SFA

disease <1/3 (<10 cm) CFA DFA
• May include single focal
CTO (<5 cm) as long as SFA
not flush occlusion
• Popliteal artery with mild
or no significant disease
Pop

2 • Total length SFA

disease 1/3-2/3
(10-20 cm)
• May include CTO
totaling <1/3 (10 cm)
but not flush occlusion
• Focal popliteal artery
stenosis <2 cm, not
involving trifurcation

3 • Total length SFA CFA

disease >2/3 (>20 cm) DFA
length
• May include any flush SFA
occlusion <20 cm or
non-flush CTO 10-20 cm
long
• Short popliteal stenosis
2-5 cm, not involving Pop
trifurcation

4 • Total length SFA CFA

occlusion >20 cm DFA
• Popliteal disease
>5 cm or extending
SFA
into trifurcation
• Any popliteal CTO
Pop

FIG. 63.7 Femoropopliteal (FP) disease grading in Global Limb Anatomic Staging System (GLASS). Trifurca-
tion is defined as the termination of the popliteal artery at the confluence of the anterior tibial (AT) artery and
tibioperoneal trunk. (From Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management
of chronic limb-threatening ischemia. J Vasc Surg. 2019;69:3S–125S e140.) CFA, Common femoral artery; CTO,
chronic total occlusion; DFA, deep femoral artery; Pop, popliteal; SFA, superficial femoral artery.

and wire selection. Choice and technique of arterial access are of
fundamental importance to the success of endovascular thera-
pies and careful attention to access reduces complications. Access
should be obtained in every case using a combination of anatomic
landmarks (based on palpable bony or fluoroscopic landmarks),
pulse palpation (if present), and ultrasound guidance. Most op-
erators routinely employ ultrasound guidance to optimize ves-
sel access and subsequent access site closure. The most common
complications of EVT are related to the access site; they can be
minimized by careful site selection and meticulous technique. In
general, retrograde common femoral artery access is most com-
monly used for aortic and common iliac artery interventions, with
up and over retrograde common femoral artery access for contra-
lateral external iliac and superficial femoral/above-knee popliteal
interventions. Antegrade common or proximal superficial femoral
artery accesses are preferred by many when treating infrageniculate
disease, and because of the characteristics of proximal and distal
caps for longer or calcified occlusive lesions, retrograde access of a
tibial or pedal vessel is often used either alone or in combination
with antegrade access in treating more complex CLTI cases. All
1778 SECTION XII Vascular

0 • Mild or no significant disease in the primary target artery path

1 • Focal stenosis of
tibial artery <3 cm

Focal stenosis

Anterior
tibial
artery
target

2 • Stenosis involving
1/3 total vessel length
• May include focal
CTO (<3 cm)
• Not including TP trunk
or tibial vessel origin Stenosis
of 1/3 total Focal CTO <3 cm
vessel
length
Posterior Anterior
tibial tibial
target target

3 • Disease up to
2/3 vessel length
• CTO up to 1/3 length
(may include tibial vessel
origin but not tibio-
CTO up to
peroneal trunk)
1/3 vessel
Disease length
up to 2/3
vessel
Anterior length Anterior
tibial tibial
target target

4 • Diffuse stenosis
>2/3 total vessel length
• CTO >1/3 vessel length
(may include vessel CTO of
origin) TP trunk
• Any CTO of tibioperoneal
trunk if AT is not the Diffuse
target artery stenosis CTO
Anterior >2/3 of Posterior >1/3
Peroneal
tibial vessel tibial of vessel
artery
artery length artery length
target
target target

FIG. 63.8 Infrapopliteal (IP) disease grading in Global Limb Anatomic Staging System (GLASS). (From Conte
MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening isch-
emia. J Vasc Surg. 2019;69:3S–125S e140.) AT, Anterior tibial; CTO, chronic total occlusion; TP, tibioperoneal.
 CHAPTER 63 Peripheral Arterial Disease 1779

Inframalleolar/pedal descriptor

P0 Target artery crosses ankle into foot, with intact pedal arch

P1 Target artery crosses ankle into foot; absent or severely diseased pedal arch

P2 No target artery crossing ankle into foot

P0 P1 P2
FIG. 63.9 Inframalleolar (IM)/pedal disease descriptor in Global Limb Anatomic Staging System (GLASS). Rep-
resentative angiograms of P0 (left), P1 (middle), and P2 (right) patterns of disease. (From Conte MS, Bradbury
AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc
Surg. 2019;69:3S–125S e140.)

TABLE 63.3 Assignment of Global Limb Anatomic Staging System (GLASS) stage.
INFRAINGUINAL GLASS STAGE (I–III)
4 III III III III III
3 II II II III III
2 I II II II III
FP Grade 1 I I II II III
0 NA I I II III
0 1 2 3 4
IP Grade
From Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg.
2019;69:3S–125S e140.
After selection of the target arterial path (TAP), the segmental femoropopliteal (FP) and infrapopliteal (IP) grades are determined from high-quality
angiographic images. Using the table, the combination of FP and IP grades is assigned to GLASS stages I to III, which correlate with technical
complexity (low, intermediate, and high) of revascularization.NA, Not applicable.

of these approaches are facilitated by a thorough understanding
of bony, skin, and fluoroscopic landmarks as well as facility with
ultrasound guidance. After access is obtained, diagnostic angiog-
raphy is usually performed to confirm lesions suspected on preop-
erative assessment. Once the lesion(s) are identified, they must be
crossed with a suitable wire to allow treatment.
Wires come in a variety of lengths, diameters, weights and rela-
tive stiffnesses. Wires 0.035 inch in diameter are used for most
aortoiliac and femoral interventions, while 0.014 and 0.018 are
most often used for tibial interventions (and renal and carotid
arteries). Wire tips vary but are generally floppier than the rest
of the wire and may be preshaped or be shaped by the operator
depending on preference. Some wires are hydrophilic and must be
kept moistened/wet or they will become sticky and not function
properly. A torque device may be attached to the wire to make
it more steerable. For nearly all stenoses, and many occlusions,
the goal is to maintain the wire in the true lumen of the artery,
cross the lesion, and then treat it with either angioplasty, atherec-
tomy, or primary stenting depending upon the type and length
of the lesion. If difficulty crossing a particular lesion occurs, the
use of additional catheters for support, which can be telescoped
through a long access sheath, may help, as well as using a stiffer or
heavier wire. More recently, several devices have become available
to facilitate crossing of difficult/resistant lesions and true lumen
reentry, including plaque microdissection (Frontrunner XP CTO
Catheter; Cordis, Bridgewater, NJ), fast and bidirectional cath-
eter spinning (CrossBoss CTO Catheter; BridgePoint Medical,
Plymouth, MN), and catheter tip deflection capability with spi-
ral wedges to facilitate advancement (Wildcat Catheter; Avinger,
Redwood City, CA).36
A useful alternative to difficult transluminal lesion cross-
ing is intentional subintimal angioplasty, a technique initially
1780 SECTION XII Vascular
Patient with CLTl, candidate for
revascularization
Obtain high-quality
angiographic imaging including
ankle and foot
Define the target artery path
(TAP)
Grade the femoropoliteal (FP)
segment (Fig. 5.2)
Grade the infrapopliteal (IP)
segment (Fig. 5.3)
Look up the overall GLASS
stage (Table 5.3)
Define the preferred
revascularization strategy by
integrating patient risk, limb
severity (Wlfl) and anatomy
(GLASS) according to the
PLAN concept (Section 6)
FIG. 63.10 Flow chart illustrating application of Global Limb Anatomic
Staging System (GLASS) to stage infrainguinal disease pattern in chronic
limb-threatening ischemia (CLTI). (From Conte MS, Bradbury AW, Kolh
P, et al. Global vascular guidelines on the management of chronic limb-
threatening ischemia. J Vasc Surg. 2019;69:3S–125S e140.) FP, Femo-
ropopliteal; IP, infrapopliteal; PLAN, patient risk estimation, limb staging,
anatomic pattern of disease; TAP, target arterial path; WIfI, wound, isch-
emia, and foot infection.
described 30 years ago by Bolia and colleagues.37 A wire, typical-
ly with a short J-shaped tip is formed and directed via the cath-
eter against the arterial wall just proximal to the occlusion and
used to initiate a subintimal dissection plane. The wire formed
in this fashion is then intentionally advanced in this subintimal
plane until the lesion is crossed, and then attempts are made to
reenter the true lumen with catheter support. True lumen reen-
try is confirmed by return of blood through the catheter and easy
advancement of the wire without resistance. If there is minimal
disease in the reentry zone, this step is not difficult and often
occurs spontaneously. If true lumen reentry is difficult, there are
reentry devices available or, in complex cases, one may combine
with retrograde access.36
Once the culprit arterial lesion has been successfully crossed,
balloon angioplasty can be performed. Balloon angioplasty frac-
tures the plaque and may cause focal dissection, so appropriate
sizing is important. Many operators use IVUS (intravascular ul-
trasound) to size balloons and stents and to assess results after
angioplasty or stent deployment. Balloons come in a wide vari-
ety of lengths and sizes and may be compliant or noncompliant.
There are also scoring and cutting balloons, which are used to
treat fibrotic and resistant lesions such as those due to intimal
hyperplasia. Cutting balloons have three or four microtomes ori-
ented longitudinally around the balloon that create controlled
cuts in the fibrotic lesion and then allow standard angioplasty
with a larger balloon to enlarge the stenotic lumen. There are
also drug-coated balloons available analogous to the coronary
circulation but their use has become controversial due to con-
cerns about potential increased mortality risk when used in the
periphery.38
In general, angioplasty results with respect to primary patency
are better in larger, more proximal arteries and for shorter lesions.
However, the rapid evolution of smaller profile systems with lon-
ger balloons has facilitated the treatment of disease in the smaller
arteries, including tibial and even pedal arteries. Although not
comparable to the results of open bypass with vein conduit, distal
lower extremity angioplasty results are improving and with careful
patient selection, patency of distal angioplasty may be sufficient to
heal wounds and prevent amputation. Recently compiled results
for infrapopliteal angioplasty are presented in Table 63.4. Endo-
vascular techniques have improved such that even long segment
disease in CLTI patients can successfully be treated endoluminally,
an important option to have available for higher risk patients or
those with no suitable autogenous conduit (Fig. 63.13).
Stents are reserved by some for residual stenosis, dissection
or other complications of plain balloon angioplasty. However,
for iliac lesions, data would suggest that primary stenting is su-
perior to angioplasty (percutaneous transluminal angioplasty)
alone (Table 63.5) with primary patency rates at four years bet-
ter in both in claudicants (77% stenting vs. 68% percutaneous
transluminal angioplasty) and those presenting with CLTI (67%
vs. 55%).39 Stents may be balloon expandable or self-expanding,
covered or uncovered, drug-coated, or bare. Balloon expandable
stents are often used when precise deployment and landing are
critical. Covered stents may be used for a variety of indications,
such as to treat embolic lesions or to prevent or treat vessel rup-
ture (e.g., “pave and crack” technique for iliac lesions). Stenting
in the femoral-popliteal segment is widely used. Stent selection is
beyond the scope of this book, but good discussions are available
elsewhere.36,39
Atherectomy devices (orbital and laser) are widely used, but
high-level data supporting their use compared to numerous alter-
natives are still lacking. One possible advantage is that debulking
the lesion may allow treatment with angioplasty alone, avoiding
the expense and potential long-term sequelae of long-term stent
implantation.
The results of EVT depend on a multitude of factors, es-
pecially the following: procedure indication (claudication vs.
CLTI); lesion length; vessel calcification; poor runoff status;
and specific comorbidities such as diabetes and end-stage renal
disease.36,39 Despite current limitations, EVT is widely used;
short-term results have improved over the last decade and EVT
would currently appear to be the better choice in older, higher
risk patients with shorter life expectancies who would not ben-
efit from the long-term patency afforded by bypass surgery and
would be at increased risk for open surgery. Application of the
WIfI, PLAN and GLASS approach to therapy of CLTI should
help define the role of EVT versus bypass in the future, as well
as the awaited publication of trial results from BEST-CLI and
BASIL 2 and 3.!
 CHAPTER 63 Peripheral Arterial Disease 1781

Patient with CLTl

Low limb risk

(Wlfl stage 1)
Wound care,
Stage severity of limb
surveillance for
threat (Wlfl)
deterioration

Intermediate or higher
limb threat (WlfI stage ≥2)
Primary amputation

No Candidate for
limb salvage?

Palliation/wound care Yes

Estimate procedural
risk/2-yr survival

No option for
revascularization
Consider need for No or unclear need
revascularization

Yes

Anatomic staging of disease

(GLASS)

Revascularization
feasible
High-risk patient Standard-risk patient

Perform endovascular Determine vein

intervention if possible conduit status
(e.g., ultrasound mapping)

Revascularize using
preferred strategy
(endo or open)

FIG. 63.11 The patient, limb, anatomy (PLAN) framework of clinical decision-making in chronic limb-threaten-
ing ischemia (CLTI); infrainguinal disease. Refer to Fig. 63.12 for preferred revascularization strategy in standard-
risk patients with available vein conduit, based on limb stage at presentation and anatomic complexity. Ap-
proaches for patients lacking suitable vein are reviewed in the text. (From Conte MS, Bradbury AW, Kolh P, et al.
Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg. 2019;69:3S–
125S e140.) GLASS, Global Limb Anatomic Staging System; WIfI, Wound, ischemia, and foot infection.

Open Surgical Therapy
Despite the rapid evolution and utilization of EVT in the treat-
ment of patients with lower extremity PAD, open surgical therapy
is still a viable and often preferable option for these patients. The
hallmark of open lower extremity revascularization remains arte-
rial bypass, including aortofemoral bypass and infrainguinal by-
pass. There are extraanatomic reconstructions available to bypass
to the lower extremity in the presence of aortoiliac occlusive dis-
ease, including axillofemoral bypass, femoral-femoral bypass, and
thoracofemoral bypass. However, a discussion of these is beyond
the scope of this chapter, as these procedures are typically only
performed to address complications of previous aortofemoral re-
vascularization or other endovascular aortoiliac reconstructions.
Aortofemoral bypass most often utilizes prosthetic bifurcated con-
duits to bypass from the aorta to the common femoral, profunda
femoris, or superficial femoral arteries. Infrainguinal bypass is de-
fined as any major arterial reconstruction using a bypass conduit,
either autogenous or prosthetic, that originates below the inguinal
ligament.
Indications
The two primary indications for infrainguinal bypass are claudi-
cation and CLTI. Nonoperative management is appropriate, and
initially preferable, for most patients presenting with claudication.
However, following an exercise program, smoking cessation, and
optimization of medical therapy, patients significantly disabled by
1782 SECTION XII Vascular
Anatomic complexity
Open bypass
III
(GLASS stage)
Indeterminate
Endovascular
II
No revascularization
I plex ultrasonography can also be successfully used for preoperative
1 2 3 4
Limb severity (Wlfl stage)
FIG. 63.12 Preferred initial revascularization strategy for infrainguinal
disease in average-risk patients with suitable autologous vein conduit
available for bypass. Revascularization is considered rarely indicated in
limbs at low risk (wound, ischemia, and foot infection [WIfI] stage 1).
Anatomic stage (y-axis) is determined by the Global Limb Anatomic Stag-
ing System (GLASS); limb risk (x-axis) is determined by WIfI staging. The
dark gray shading indicates scenarios with least consensus (assumptions
inflow disease either is not significant or is corrected; absence of severe
pedal disease (i.e., no GLASS P2 modifier). (From Conte MS, Bradbury
AW, Kolh P, et al. Global vascular guidelines on the management of chron-
ic limb-threatening ischemia. J Vasc Surg. 2019;69:3S–125S e140.)
claudication should be considered for operative treatment. This
includes patients unable to perform their primary occupation or
who cannot carry out the activities of daily living. The primary
indication for performing infrainguinal bypass in selected clau-
dicants is to improve quality of life, not to prevent limb loss. The
risk of limb loss with claudication is quite low (<1%/yr), with
major amputation occurring in only 5% during a 3- to 5-year
period.3 In contrast, the majority of patients with CLTI (rest pain,
ischemic ulcer, gangrene) require intervention to decrease the risk
of limb loss or significant clinical deterioration. As previously
mentioned, the Society for Vascular Surgery Lower Extremity
Guidelines Committee created a consensus stratification system
for threatened limbs based on the WIfI objective grading system.9
This system stratifies the limb in patients with CLTI with respect
to amputation risk into four clinical stages and has been validated
to predict 1-year major limb amputation risk. This system addi-
tionally identifies patients who would benefit from revasculariza-
tion to decrease their risk of major amputation. Patients meet-
ing these two indications should be considered for open bypass if
functional, of suitable risk, and if adequate vein conduit is present.
Prior to intervention, it is imperative to assess the medical
comorbidities of potential open surgical candidates. There is a
high rate of concordant chronic obstructive pulmonary disease,
diabetes mellitus, renal insufficiency, and coronary artery disease.
The patients should have optimized control of blood pressure,
diabetes, congestive heart failure, and angina prior to interven-
tion. Postponement of intervention should only routinely occur
for patients with unstable angina, recent myocardial infarction or
uncontrolled congestive heart failure.!
Preoperative Planning
A successful bypass has several prerequisites to support long-term
patency. Adequate inflow and outflow must exist. Additionally,
the conduit used must be optimized to ensure long-term patency.
In the case of lower extremity revascularization in patients with
CLTI, it is also important to determine the best outflow target
vessel to provide “in-line flow” to the foot.
As with all surgical bypasses, it is imperative to obtain adequate
preoperative imaging to evaluate for each of these criteria. The tra-
ditional route to obtain this necessary anatomic information is by
performing standard angiography of the lower extremity. This will
often be available at the time of planning if the patient underwent
previous unsuccessful endovascular intervention. CT angiography
can be considered for assessment of inflow disease, although its
use in the lower extremity vessels, especially in the CLTI cohort,
is limited by the frequency of small, long segment calcified vessels
in patients with CLTI.40 Magnetic resonance angiography and du-
planning.41,42 Particularly with angiography, the operator can de-
termine the appropriate vessel from which to originate the bypass
and determine the optimal outflow target vessel. When properly
performed, the vast majority of patients with an indication for
revascularization have an adequate target artery.43 Target artery se-
lection requires views of the foot (a minimum of anteroposterior
and lateral) in patients presenting with CLTI. The lateral foot view
is extremely important (Fig. 63.14).
Assessment of the inflow must be performed prior to perform-
ing a bypass. In patients with a normal palpable ipsilateral femoral
pulse and triphasic common femoral Doppler arterial waveforms,
intervention on the inflow is unlikely to be required. In patients
without a palpable femoral pulse or an abnormal femoral Dop-
pler waveform (especially when bilateral), additional preoperative
imaging should be considered. If disease exists in the ipsilateral
aortoiliac segment or common femoral artery, these should be
treated either concurrently or prior to performing the infraingui-
nal bypass. Both endovascular and open surgical options exist to
optimize inflow, including aortofemoral bypass, iliac balloon an-
gioplasty with or without stenting, and common femoral endar-
terectomy with or without profundaplasty. Once completed, the
bypass will have optimal inflow to support graft patency.
Similarly, detailed assessment must be performed to identify
the most suitable distal target artery. We are proponents of con-
ventional digital subtraction arteriography to identify the ideal
distal target. This can be performed prior to the operation or
at the time of the operation. Interventions can be performed
to improve the distal target artery as well, though this is rarely
needed, as a relatively spared segment of artery is almost always
available. The general principle in selecting a distal target ves-
sel is to choose the most proximal vessel distal to hemodynami-
cally significant disease that has continuous runoff to the foot
through at least one tibial vessel. Patients with claudication typi-
cally require a popliteal distal target. CLTI patients often require
a more distal target to a tibial, peroneal, dorsalis pedis or plantar
artery (Fig. 63.15).
Conduit selection is perhaps the most critical factor under-
lying successful infrainguinal bypass. Autologous vein conduits
include ipsilateral and contralateral great saphenous vein (GSV),
short saphenous vein (SSV), femoral vein, arm (basilic and ce-
phalic) vein, endarterectomized superficial femoral artery, cryo-
preserved vein, and radial artery. Preoperative imaging, typically
with duplex ultrasound, is adequate to determine the presence,
caliber, and quality of adequate autologous veins. Prosthetic
conduits include Dacron, heparin-bonded Dacron, human um-
bilical vein, polytetrafluoroethylene (PTFE) with and without
covalently bonded heparin, and expanded PTFE bonded with
heparin.
Autologous vein outperforms all other conduits for infraingui-
nal bypass, including above knee popliteal bypasses. A single seg-
ment of autologous vein is superior to spliced segments. GSV and
SSV are superior to arm veins. Autologous vein should be used
for infrainguinal bypass whenever feasible. Prosthetic conduits for
infrainguinal bypass should only be considered when autologous
conduits are truly not available. Dacron has recently been shown
to outperform expanded PTFE in above knee popliteal bypasses.44
 CHAPTER 63 Peripheral Arterial Disease 1783

TABLE 63.4 Results of infrapopliteal angioplasty, stenting, and atherectomy.

NUMBER MEAN LESION TECHNICAL PRIMARY LIMB SALVAGE
AUTHOR YEAR TREATED CLI LENGTH FAILURES PATENCY RATE
Angioplasty
Giles and colleagues 2008 176 100% NR 7% 53%, 1 year 84%, 3 years
51%, 2 years
Conrad and colleagues 2009 155 86% NR 5% 71%, 2 years 86%, 3.3 years
62%, 3.3 years
Sadek and colleagues (single vs. 2009 89 77% NR 9% 34%, 1 year 67% 1.5 years
multilevel PTA)
Single level Single level
58%, 1 year 63%, 1.5 years
Multilevel Multilevel
Peregrin and colleagues 2010 1445 100% NR 11% NR 76%, 1 year
Schmidt and colleagues 2010 62 100% 18.3 cm 5% 50%, 3 months 100%, 15 months

Subintimal Angioplasty
Ingle and colleagues 2002 70 91% NR 14% NR 94%, 3 years
Vraux and Bertoncello 2006 50 100% 78% 18% 46%, 1 year 87%, 1 year
>10 cm
42%, 2 years 87%, 2 years
Tartari and colleagues (SFA only in 2007 109 100% 59% 17% NR 87%, 1 year
27 limbs) ≥10 cm 85%, 2 years

Cutting-Balloon Angioplasty
Engelike and colleagues 2002 16 31% NR 6% 67%, 1 year 93%, 10 months
Ansel and colleagues 2004 73 71% 2.7 cm 0% NR 89%, 1 year
Vikram and colleagues 2007 11 NR NR 18% 50%, 1 year NR

Drug-Coated Balloona
Tepe and colleagues 2008 48 15% 7.5 cm 2% all cases 80%, 6 months 96%, 6 months

Stenting
Feiring and colleagues 2004 92 68% NR 7% NR 87%, 1 year
Bosiers and colleagues 2006 300 100% NR NR 76%, 1 year 99%, 1 year
Donas and colleagues 2009 34 100% 6.5 cm stenosis; 3% 91%, 10 months 100%, 10 months
7.5 cm occlusion
Randon and colleagues 2010 16 100% 38% 13% 56%, 1 year 92%, 1 year
≥10 cm

Drug-Eluting Stent
Scheinert and colleagues 2006 30 63% NR 0% 100%, 6 months 100%, 9 months
Fering and colleagues 2010 130 100% NR 9% NR 88%, 3 years
Karnabatidis and colleagues 2011 51 100% 7.7 cm 0% 30%, 3 years NR
Rastan and colleagues 2011 82 51% 3.0 cm 0% 81%, 1 year 98%, 1 year

Atherectomy
Zeller and colleagues 2007 36 53% 4.6 cm 2% 67%, 1 year 100%, 2 years
60%, 2 years
Safian and colleagues 2009 124 32% 3.0 cm 2.5% NR 100%, 6 months
From Montero-Baker M, Mills JL. Endovascular repair of infrapopliteal arterial occlusive disease. In: Moore WS, Lawrence PF, Oderich GS, eds.
Moore’s Vascular and endovascular surgery: A comprehensive review. 9th ed. Philadelphia, PA: Elsevier; 2019:460–468.
CLI, Critical limb ischemia; NR, not reported; PTA, percutaneous transluminal angioplasty; SFA, superficial femoral artery.

Our group generally does not perform infrainguinal bypass with
prosthetic conduit solely for the indication of claudication, since
graft failure frequently converts a patient with stable claudication
to one with acute limb-threatening ischemia, and may thus actu-
ally increase amputation risk.!
Aortofemoral Bypass Techniques
Aortofemoral bypass should be considered when hemodynamically
significant aortic and iliac stenosis leads to the aforementioned indi-
cations. The typical reconstruction performed is an aortobifemoral
bypass with the outflow target either the common femoral arteries
1784 SECTION XII Vascular

A B

C D E
FIG. 63.13 A 77-year-old high-risk patient with diabetes and great toe gangrene. (A) Critical limb ischemia with
ankle-brachial index (ABI) of 0.39. (B) Three-vessel long-segment (>25 cm) tibial artery occlusions with (C) distal
anterior tibial artery reconstitution. (D) Subintimal angioplasty of long-segment occlusion. (E) Anterior tibial artery
after long-segment subintimal angioplasty with ABI improved to 0.81. Toe amputation healed and the vessel
remains patent 6 months after intervention. (From Montero-Baker M, Mills JL. Endovascular repair of infrapopli-
teal arterial occlusive disease. In: Moore WS, Lawrence PF, Oderich GS, ed. Moore’s Vascular and endovascular
surgery: A comprehensive review. 9th ed. Philadelphia, PA: Elsevier; 2019:460–468.)

or the profunda femoris arteries bilaterally. With respect to the sur- when the indication is infection of a previously placed prosthetic
gical reconstruction of aortoiliac occlusive disease, the optimal in- conduit, in which case, after excision of the infected prosthetic, the
flow site is almost always just inferior to the renal arteries. Prosthetic choice of replacement conduit may be the femoral vein(s) to create
conduits (Dacron or expanded PTFE) are generally used except a neo-aortoiliac system (NAIS) or cryopreserved arteries and veins.
 CHAPTER 63 Peripheral Arterial Disease 1785

TABLE 63.5 Review of outcomes in interventional treatment of aortoiliac occlusive disease.

NUMBER OF PRIMARY PATENCY
SERIES YEAR PATIENTS INDICATION TYPE OF INTERVENTION (%)
Parsons et al 1998 45 PTA 74 (5 year)
Klein 2006 279 Primary stenting versus selective stenting 83 (5 year)
Bosch and Hunink 1997 1300 Claudication vs. CLI Selective stenting versus primary stenting 70 (5 year)
(metaanalysis) 1997 1300 Primary stenting 77 (4 year)
67 (4 year)
Murphy (metaanalysis) 1998 2058 Primary stenting 73 (5 year)
Schurmann et al 2002 110 93% claudication Primary stenting 66 (5 year)
Galaria and Davies 2005 276 TASC A and B Primary stenting 71 (10 year)
Leville et al 2006 92 TASC C and D Primary stenting 76 (3 year)
Rzucidlo et al 2005 34 TASC B, C, and D Stent grafting 80 (5 year)
Chang et al 2008 171 TASC B, C, and D Stent graft 41%, bare metal sent 59% 60 (5 year)
Mwipatayi 2011 40 TASC C and D Stent graft 95 (18 month)
24 Bare metal sent 50 (18 month)
Psacharopulo 2015 11 TASC D Stent graft 91 (2 year)

From Powell RJ, Rzucidlo EM. Aortoiliac disease: Endovascular treatment. In: Sidawy AN, Perler BA, eds. Rutherford’s vascular surgery and
endovascular therapy. 9th ed. Philadelphia, PA: Elsevier; 2019:1423–1437.
CLI, Critical limb ischemia; PTA, percutaneous transluminal angioplasty; TASC, TransAtlantic Inter-Society Consensus.

hemodynamically superior. There are certain settings, however, in

FIG. 63.14 Lateral foot view obtained by distal selective superficial
femoral arterial catheter injection identifies excellent collaterals from the
distal peroneal artery to both the dorsal pedal and posterior tibial circula-
tions. (From Mills JL. Infrainguinal disease: Surgical treatment. In: Sidawy
AN, Perler BA, ed. Rutherford’s vascular surgery and endovascular thera-
py. 9th ed. Philadelphia, PA: Elsevier; 2019:1438–1462.)
Rifampin-bonded Dacron grafts are also occasionally used, both for
primary reconstructions, as well as in the replacement of infected
grafts in the setting of low virulence organisms. The preferred proxi-
mal aortic anastomosis by many vascular surgeons is end-to-end,
as it is thus easier to cover/protect the prosthetic from the adjacent
duodenum and although unproven, it has been felt by some to be
which an end-to-side proximal anastomosis may be considered or
even be mandatory. These circumstances include the presence of a
large, patent inferior mesenteric artery and in anatomic situations
in which an end-to-end aortic anastomosis would eliminate flow,
even retrograde, to the hypogastric arteries. For example, if the com-
mon iliac and external iliac arteries are both occluded on one side,
and the common iliac and internal iliac arteries are patent on the
contralateral side with contralateral external iliac artery occlusion,
creation of a proximal aortic end-to-side anastomosis would pre-
serve perfusion to one hypogastric artery. In contrast, an end-to-end
aortic anastomosis would eliminate pulsatile flow to the pelvis, in-
creasing the risk of colonic and pelvic ischemia (including buttock
necrosis or so called “trash can,” a disastrous complication). If the
surgeon elects to perform the proximal anastomosis end-to-end in
the former circumstance, the inferior mesenteric artery should be
reimplanted into the body of the aortofemoral graft (Fig. 63.16).
When faced with anatomy such as that described in the second cir-
cumstance, the distal limb on the ipsilateral side is brought down to
the common femoral artery while the contralateral limb is sewn to
the distal common iliac artery or proximal patent hypogastric artery
An additional graft limb is then sewn to the hood of the contralat-
eral limb and brought down to that common femoral artery (Fig.
63.17). This approach preserves hypogastric flow and simplifies the
pelvic anastomoses, as the deeper anastomosis to the iliac artery is
performed first, and the more superficial anastomosis to the limb
that will be extended to the common femoral artery is relatively
easily performed.
Clamp application and release are important maneuvers. The
clamp should be applied to a normal arterial segment whenever
possible. This can be assured by thorough preoperative prepara-
tion and review of all pertinent images (duplex ultrasound, CT
or conventional angiography, depending on which are available).
Intraoperative arterial palpation with a right angle behind the ar-
tery can also be used to identify significant posterior plaque. If
clamp application to normal or near normal artery is not possible,
particularly when posterior plaque is present, one should consider
a clamp that compresses the artery from front to back rather than
from side to side. If anastomosis to a very diseased vessel is needed,
1786 SECTION XII Vascular

A B
FIG. 63.15 Detailed diagnostic arteriography with fixed imaging, proper timing, and appropriate catheter
placement almost always identifies suitable target arteries. Each of the patients depicted had popliteal artery
occlusion and extensive trifurcation and long-segment tibial disease, but diagnostic studies identified suitable
target arteries in the foot. (A) Completion arteriogram after inframalleolar posterior tibial bypass in a patient
with diabetes and forefoot gangrene. Despite a small-caliber outflow vessel, the bypass remains patent, and
the ischemic foot ulcers healed and have not recurred at two years. (B) Completion arteriogram after bypass
to a diseased dorsal pedal artery. Despite poor outflow and diseased arch and pedal vessels, the graft remains
patent at one year. This patient with diabetes healed and ambulates with a transmetatarsal amputation. (From
Mills JL. Infrainguinal disease: Surgical treatment. In: Sidawy AN, Perler BA, ed. Rutherford’s vascular surgery
and endovascular therapy. 9th ed. Philadelphia, PA: Elsevier; 2019:1438–1462.)

one can consider proximal balloon control rather than ill-advised

clamping of a diseased segment. Following creation of an arteriot-
omy of appropriate length, and matching that to the graftotomy,
the needle is generally directed from outside the graft to inside the
graft and from inside the artery to out when performing arterial
anastomoses, especially in the presence of arterial wall thicken-
ing from occlusive disease. These clamping and sewing techniques
reduce the chance of lifting up native arterial intima and creating
an intimal flap. This sewing technique also encourages eversion
of the graft and native artery, making the anastomosis creation
simpler and faster. If the artery is thickened and resists eversion,
medial and lateral mid-arteriotomy stay sutures can be used to fa-
cilitate the anastomosis and reduce the need for repeatedly grasp-
ing a diseased artery with forceps. A properly created end-to-side
anastomosis is everted and has a small cobra-head appearance (Fig.
63.15).
Aortofemoral bypass is an operation of considerable physiolog-
ic magnitude and is associated with several major complications.
Immediate complications include hemorrhage, intestinal isch-
emia, buttock and pelvic necrosis, acute renal failure, myocardial
infarction, pulmonary complications, and death. Late complica-
tions include limb thrombosis, aortoenteric fistula, graft infection,
and anastomotic pseudoaneurysm.!

Infrainguinal Bypass Techniques

There are multiple variations available for performing infrain-
FIG. 63.16 Inferior mesenteric artery reimplantation into body of bifur- guinal bypass, including reversed vein, nonreversed vein, in-situ
cated aortic graft sewn end-to-end proximally. vein, spliced veins, and prosthetic bypass. When available, in-situ
 CHAPTER 63 Peripheral Arterial Disease
FIG. 63.17 Inferior mesenteric artery reimplantation into aortic graft
body, right limb sewn to sole patent hypogastric artery with jump graft
to the right common femoral artery to preserve pelvic and colonic flow.
GSV can be used by mobilizing the proximal GSV to the in-
flow artery, performing valve lysis and subsequently mobilizing
the distal segment of the GSV and anastomosing it to the target
artery. This technique has the advantage of avoiding full length
GSV harvesting and matches vein conduit vein to native artery
diameter for both the inflow artery and the target vessel. Nonre-
versed vein bypass also allows for easier matching of vein to artery
diameters. However, using the nonreversed vein requires full vein
harvesting, tunneling of the graft and valve lysis. Reversing the
vein avoids the need for valve lysis but does require full harvest
and potentially creates the issue of vein bypass to artery size mis-
match. Despite the theoretical size mismatch with reversed vein,
no data suggest that reversed vein conduits are inferior to tech-
niques requiring valve lysis, and reversing the vein obviates prob-
lems with incomplete valve lysis and allows significant latitude
in tunnelling the bypass. All grafts can be tunnelled either ana-
tomically along the vessel which is being bypassed or subcutane-
ously. Subcutaneous bypasses require a longer vein conduit than
anatomic bypasses but are often very useful in reoperative cases
to avoid scarring from previous operations. Many of these issues
are avoided with the use of prosthetic bypass, especially harvest
time, conduit length issues, and dealing with vein valves. Avoid-
ing vein harvest also decreases the operative time and decreases
the incisional lengths, potentially avoiding morbidity. However,
the inferior patency rates and increased risk of infection asso-
ciated with prosthetic bypasses greatly outweigh these potential
benefits for most patients.
Inflow for infrainguinal bypasses can arise from the common
femoral artery, the profunda femoris artery, the superficial femoral
artery and the popliteal artery, and less commonly, even a tibial
artery. The profunda femoris artery is often an excellent option
1787
when previous common femoral artery procedures have been
performed, as this artery can be exposed from a lateral approach,
thereby avoiding dense scarring from previous operative site in the
femoral triangle. Additionally, when an adjunctive inflow proce-
dure has been performed, the bypass can originate from the hood
of the proximal bypass, from an arterial patch, or even from the
native artery beneath the inflow graft-artery anastomosis. Bypass
graft origins distal to the common femoral artery are especially use-
ful in reoperative cases and when available vein length is limited.
Distal origin grafts do not compromise long-term graft patency
when vein conduit is utilized and if there are no hemodynamically
significant lesions proximal to the graft origin. A metaanalysis of
popliteal origin grafts, which are especially applicable to patients
with CLTI and diabetes, reported nearly 80% 2-year patency with
this configuration.8
Completion studies following bypass should be considered
to avoid potentially early graft thrombosis or hemorrhage and
subsequent “take back” operations. Options include distal pulse
palpation and Doppler flow assessment with and without graft
compression, completion arteriography, intraoperative duplex
scanning and angioscopy. Not all bypasses require completion im-
aging and unfortunately clear consensus on when to use these ad-
juncts currently does not exist. However, one should note that the
best opportunity to salvage a potential problem is at the time of
the original operation. We therefore remain advocates of comple-
tion angiography, especially in an era when open surgical bypass
operations are being performed with diminishing frequency.
Complications. Major complications following infrainguinal
bypass include wound problems, graft occlusion, graft infection,
bleeding, and death. The PREVENT III trial demonstrated the fol-
lowing complication rates associated with infrainguinal vein bypass
procedures: death (2.7%), myocardial infraction (4.7%), major
amputation (1.8%), graft occlusion (5.2%), major wound compli-
cation (4.8%), and graft hemorrhage (0.4%).26 Late complications
include lymphedema, infection, graft aneurysm, and graft stenosis
or occlusion. Early graft occlusion is typically associated with tech-
nical or judgment error and should be remedied as soon as possible.
If an underlying cause for graft failure is not identified, long-term
patency is poor. Intermediate and late graft occlusion occurs due to
a number of underlying causes, including intimal hyperplasia (with
a peak incidence in the first 18 postoperative months), anastomot-
ic aneurysm, and recurrent atherosclerotic disease. These should
generally only be treated for high-grade restenosis or whenever the
patient has return of symptoms or a nonhealing wound. For vein
grafts, structured serial duplex graft surveillance has been shown to
reduce intermediate and late bypass graft occlusion.!
SURVEILLANCE
Surveillance is a fundamental aspect of longitudinal PAD manage-
ment and is an important component of providing comprehen-
sive care to maximize patient outcomes. The mode and frequency
of surveillance depend on the patient, the specific intervention,
and the anticipated time frame and modes of failure of the inter-
vention performed. Structured follow-up is intended to identify
threatened interventions prior to actual failure and to guide ap-
propriate and timely reintervention. Concurrent clinical evalua-
tion is paramount to add adjunctive information with respect to
recurrent symptoms and wound status. The Society for Vascular
Surgery published a guideline in 2018 regarding surveillance fol-
lowing lower extremity arterial procedures, which will serve as a
reference for our recommendations.45
1788 SECTION XII Vascular

Endovascular Therapy Surveillance

There has not been an established interval or optimal algorithm
for following lower extremity endovascular interventions. How-
ever, it is clear that longitudinal follow-up to ensure adequate
medical management of comorbid conditions is essential and
may improve patency as well as amputation-free survival after
endovascular intervention.46 Follow-up requires full history and
physical examination to assess new medical conditions, wounds,
symptoms, and measurement of ankle-brachial indices. Addition-
ally, a baseline duplex ultrasound surveillance (DUS) within the
first month after EVT is recommended. Following EVT, arterial
restenosis frequently occurs through several mechanisms includ-
ing neointimal hyperplasia, constrictive arterial remodeling, and
recurrent atherosclerotic disease. Routine imaging with DUS or
contrast imaging beyond the first month following the procedure A
has not produced clear benefit with respect to limb salvage. Part of
the reason for this lack of benefit is difficulty establishing velocity
thresholds and criteria predictive of progression that are sufficient-
ly accurate to recommend reintervention following angioplasty,
atherectomy, and stenting. Further imaging and subsequent rein-
tervention are generally only required if the patient has developed
recurrent symptoms or has failed to heal existing wounds. The
Society for Vascular Surgery guideline suggests continued clinical
follow up at 3 months and then subsequently at 6-month inter-
vals. However, routine DUS is currently not recommended be-
yond 1 month in the absence of recurrent symptoms or without
the presence of nonhealing or recurrent wounds. For patients with
recurrent symptoms or unresolved CLTI, duplex imaging may
help identify an area of restenosis (peak systolic velocity [PSV]
greater than 300 cm/sec, velocity ratio [Vr] greater than 3.5).45
Such restenosis merit reintervention in patients with unresolved B
or recurrent symptoms and in very selected patients who are as- FIG. 63.18 Duplex surveillance identified a critical vein graft stenosis in
ymptomatic after catheter-based intervention.! the proximal aspect of a femoropopliteal vein graft. (A) Marked spectral
broadening and pronounced elevation of both the peak systolic and end-
Open Surgical Bypass Graft Surveillance diastolic velocities are diagnostic of a high-grade vein graft stenosis. (B) A
As opposed to the unestablished surveillance recommendations focal, severe proximal graft stenosis (arrow) was confirmed by arteriog-
after lower extremity EVT, open surgical therapy has clearer raphy and treated with a short interposition vein graft harvested from the
guidelines for clinical and imaging surveillance. These surveil- upper extremity. (From Mills JL. Infrainguinal disease: Surgical treatment.
lance mechanisms include clinical monitoring, ABI assessment, In: Sidawy AN, Perler BA, ed. Rutherford’s vascular surgery and endovas-
cular therapy. 9th ed. Philadelphia, PA: Elsevier; 2019:1438–1462.)
and DUS. A general guideline following open surgical revascular-
ization includes early postoperative assessment within 4 weeks of
intervention and then at 3-, 6, and 12-month intervals following the culprit lesion to prevent graft thrombosis (Fig. 63.18). Pri-
the operation. Thereafter, surveillance can be continued every 6 to mary patency is the term applied to a bypass graft when patency
12 months.45,47 DUS criteria have been established to define re- is maintained over a specified time interval without reintervention
current stenosis and vein bypass graft-threatening stenoses. These on the graft itself or its anastomoses. Successful reintervention on
criteria are based on duplex-derived PSV and Vr at the site of the a patent, but restenotic graft, is termed assisted-primary patency.
stenosis. Resurrection of an occluded bypass results in loss of primary pa-
Surveillance has been especially well established for autologous tency, but if successful, is termed secondary patency. The purpose
vein grafts, for which identification and treatment of restenosis has of vein graft surveillance is to prevent loss of primary patency, as
clear benefit to prolonging graft patency and avoiding thrombosis reintervention for “failed (occluded) vein grafts is not as durable
of valuable vein conduit.45,47–50 DUS has added utility over ABI as reintervention for patent, but “failing” grafts. Vein graft surveil-
assessment alone. A full evaluation of the bypass is performed, lance is generally recommended every 3 to 6 months for the first
including the native inflow and outflow, proximal and distal anas- 2 years, and then annually thereafter. The most common cause
tomoses, and at multiple intervals along the entire length of the of vein graft failure (75%–80%) in the first 3 to 8 postoperative
graft. Criteria have been established based on PSV, Vr, low flow months is an intrinsic vein graft stenosis due to intimal hyperpla-
velocity, and changes in ABI to stratify the risk of thrombosis of sia. Such lesions are readily detectable and can be monitored for
infrainguinal vein grafts. Grafts are at high risk for thrombosis progression by serial duplex surveillance. After 18 to 24 months,
when any of the following are identified: PSV greater than 300 the de-novo vein graft stenosis rate falls off markedly, so in the
cm/s and/or the Vr greater than 3.5 at the site of a stenosis; global- absence of recurrent symptoms, annual surveillance is sufficient.50
ly low peak systolic graft flow velocity less than 45 cm/s; or a drop Following prosthetic lower extremity bypass, surveillance does
in ABI greater than 0.15.49,50 Any of these findings should prompt not clearly predict graft failure, and specific DUS criteria have
consideration for diagnostic angiography and reintervention on not been established to accurately identify threatened prosthetic
 CHAPTER 63 Peripheral Arterial Disease
grafts. Early baseline ABI should be established and repeated at 6
and 12 months. Subsequently, clinical evaluation and ABI assess-
ment should occur at yearly intervals or with changes in patient
clinical condition. If the ABIs are suprasystolic due to medial cal-
cinosis, as is common in patients with CLTI, diabetes or renal
failure, toe systolic pressure, and waveforms can be very useful to
monitor hemodynamics.!
ASSESSMENT OF OUTCOMES
Longitudinal assessment of vascular interventions, particularly
those performed for lower extremity PAD, have long focused
on endpoints such as patency (primary, assisted primary, and
secondary), hemodynamic success (based on ABI or toe pres-
sure), limb salvage (lack of major amputation), and mortality.
However, quality evidence to support indications and type of re-
vascularization is generally of poor quality and quite weak when
compared to that available for pharmacologic risk reduction and
interventions for coronary artery disease and stroke. Many de-
vice trials have used anatomic or surrogate markers such as the
presence or absence of restenosis, target lesion revascularization,
and target vessel revascularization to define treatment success.
None of these markers, however, are highly meaningful limb or
patient outcome measurements. In an effort to address this issue,
suggested objective performance goals were published in 2009
for evaluating catheter-based treatment of CLTI and to per-
mit suitable comparison with surgical bypass.51 This document
suggested the following endpoints as safety and efficacy mea-
sures: major adverse limb event; MACE; major limb (proximal
to ankle) amputation; amputation-free survival; and DEATH.
Reinterventions were grouped into major and minor categories.
Major reinterventions include the creation of a new bypass graft,
graft thrombectomy or thrombolysis for graft occlusion, or a
major surgical revision such as a jump or interposition graft. Mi-
nor reinterventions include primarily simpler reinterventions for
patent reconstructions with restenosis, both endovascular (an-
gioplasty, atherectomy, or stenting) and minor open procedures
such as focal patch angioplasty. The objective performance goals
set targets for EVT for CLTI based on the datasets from three
large trials, which had a surgical control group.
Important patient outcomes of revascularization for CLTI
include freedom from death, relief of ischemic pain, complete
healing of any index wounds, freedom from major amputa-
tion, relative freedom from reinterventions, resumption or
maintenance of ambulation; and independent living status.
Numerous studies have shown more sanguine results of lower
extremity bypass when all of the latter endpoints are evaluated
in the CLTI subpopulation. As one example, a study from the
Oregon group evaluated 112 consecutive patients 5 to 7 years
after infrainguinal bypass. While only 26% of these patients
lost their limb during this extended follow-up period, the
authors reported that less than 20% of patients had an ide-
al outcome as defined by the presence of all of the following
criteria: patent graft, healed wound, no need for reoperation,
continued ambulation, and independent living status.27 This
report and other studies clearly demonstrate that longitudi-
nal follow-up and care are clearly necessary for PAD patients,
particularly those with CLTI, and that ongoing efforts are
required to maintain limb salvage and preserve ambulatory
and functional status.31-33 From this longitudinal perspective,
while timely and appropriate revascularization for CLTI can
undoubtedly offer clinically important and often prolonged
1789
palliation, it does not cure and rarely yields what would be
viewed by most patients and objective surgeons as ideal pa-
tient-centered, functional outcomes.
SELECTED REFERENCES:
Bradbury AW, Adam DJ, Bell J, et al. Bypass versus angioplasty
in severe ischaemia of the leg (BASIL) trial: Analysis of ampu-
tation free and overall survival by treatment received. J Vasc
Surg. 2010;51:18S–31S.
Remains the only randomized prospective trial of angio-
plasty versus bypass for severe limb ischemia. Patients
surviving more than two years are likely to benefit from
bypass first.
Conte MS, Bradbury AW, Kolh P, et al. Global vascular guide-
lines on the management of chronic limb-threatening isch-
emia. J Vasc Surg. 2019;69; 3S–125S e140.
Multidisciplinary, global collaborative effort to redefine diagno-
sis, management, and treatment of chronic limb-threatening
ischemia (CLTI). Important new concepts include wound, isch-
emia, and foot infection (WIfI) threatened limb classification,
patient, limb, and anatomy (PLAN), target artery path (TAP) and
Global Limb Anatomic Staging System (GLASS)). While the
concepts need to be validated, these systems will finally allow
comparison of alternative methods of treatments for compara-
bly risk stratified patients, limbs, and anatomic lesions.
Fowkes FG, Rudan D, Rudan I, et al. Comparison of global
estimates of prevalence and risk factors for peripheral artery
disease in 2000 and 2010. A systematic review and analysis.
Lancet. 2013;382:1329–1340.
Important systematic review on prevalence and risk factors
for the development of peripheral artery disease.
Mills JL Sr, Conte MS, Armstrong DG, et al. The Society for
vascular surgery lower extremity threatened limb classifica-
tion system: risk stratification based on wound, ischemia,
and foot infection (WIfI). J Vasc Surg. 2014;59:220–234
e221– e222.
Key change in perspective to classify threatened limb at
baseline based on the combination of three factors (wound,
ischemia, and foot infection) that correlate with likelihood of
healing, risk of amputation, and potential benefit of revascu-
larization.
Prompers L, Schaper N, Apelqvist J, et al. Prediction of out-
come in individuals with diabetic foot ulcers: focus on the
differences between individuals with and without periph-
eral arterial disease. The EURODIALE Study. Diabetologia.
2008;51:747–755.
Important data on frequent association of diabetic foot ul-
cer (DFU) and peripheral artery disease (PAD), and critical
impact of PAD + infection on risk of amputation in patients
with DFU.