Peripheral arterial disease

 Atherosclerosis affects up to 10% of the Western
population older than 65 years.
 It is estimated that 2% of the population aged 40-60 years
and 6% of the population older than 70 years are affected
with PAD (claudication).
 Most commonly manifests in men older than 50 years.
 PAD has no racial predilection.

Asymptomatic: Without obvious symptomatic complaint
(but usually with a functional impairment).
Classic claudication: Lower extremity symptoms confined
to the muscles with a consistent (reproducible) onset with
exercise and relief with rest.
“Atypical” leg pain: Lower extremity discomfort that is
exertional but that does not consistently resolve with rest,
consistently limit exercise at a reproducible distance, or
meet all “Rose questionnaire” criteria.

Critical limb lschemia: Ischemic rest pain, nonhealing
wound, or gangrene/
Acute limb ischemia: The five “P”s, defined by the clinical
symptoms and signs that suggest potential limb jeopardy:
 Pain
 Pulselessness
 Pallor
 Paresthesias
 Paralysis

 Intermittent claudication typically causes pain that occurs
with physical activity.
 Determining how much physical activity is needed before
the onset of pain is crucial.
 Walking distance helps quantify patients’ condition before
and after therapy.

 Pain is reproducible within the same muscle groups.
 It ceases with a resting period of 2-5 minutes.
 PAD is most common in the distal superficial femoral
artery.
 This corresponds to claudication in the calf muscle area.
 When atherosclerosis is distributed throughout the aorto
iliac area, thigh and buttock muscle claudication
predominates.

~15%
Classic (Typical)
Claudication
~33%
Atypical
Leg Pain
(functionally limited)
50%
Asymptomatic
1%-2%
Critical
Limb Ischemia

Claudication Pseudoclaudication
Characteristic of
discomfort
Cramping, tightness,
aching, fatigue
Same as claudication
plus tingling, burning,
numbness
Location of
discomfort
Buttock, hip, thigh,
calf, foot
Same as
claudication
Exercise-induced Yes Variable
Distance Consistent Variable
Occurs with standing No Yes
Action for relief Stand Sit, change position
Time to relief <5 minutes 30 minutes
Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.

Factors that reduce blood flow to the microvascular
bed
 Diabetes
 Severe renal failure
 Severely decreased cardiac output (severe heart failure or shock)
 Vasospastic diseases or concomitant conditions (e.g., Raynaud’s
phenomenon, prolonged cold exposure)
 Smoking and tobacco use
Factors that increase demand for blood flow to the
microvascular bed
 Infection (e.g., cellulitis, osteomyelitis)
 Skin breakdown or traumatic injury

 50-90% of patients with definite intermittent claudication
do not report their symptom to clinician.
 Most patients appear to accept a decrease in walking
distance as a part of aging.
 The risk factors for PAD are the same as those for CAD or
cerebro vascular disease and include the following:

 Diabetes
 Hypertension
 Hyperlipidemia
 Family history
 Sedentary lifestyle
 Tobacco use

 Smoking is the greatest of all the cardiovascular risk
factors.
 The mechanism is unknown.
 Degree of damage is directly related to the amount of
tobacco used.

 Complete lower-extremity evaluation and pulse
examination.
 Pulses should be examined from the abdominal aorta to
the foot.
 The absence of a pulse signifies arterial obstruction
proximal to the area.

Pulse intensity should be assessed and should be recorded
numerically as follows:
 0, absent
 1, diminished
 2, normal
 3, bounding
Use of a standard
examination should
facilitate clinical
communication
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Patients at risk of CLI (ABI less than 0.4 in a
nondiabetic individual, or any diabetic
individual with known lower extremity PAD)
should undergo regular inspection of the feet
to detect objective signs of CLI.
The feet should be examined directly, with
shoes and socks removed, at regular intervals
after successful treatment of CLI.

 Auscultation for bruits in the abdominal and pelvic
regions.
 Atrophy of calf muscles,
 Loss of extremity hair, and
 Thickened toe nails are clues to underlying PAD.

 When palpable pulses are not present, further assessment
with handheld Doppler device.
 An audible Doppler signal assures the clinician that some
blood flow is perfusing the extremity.
 If no Doppler signals can be heard, a vascular surgeon
should be consulted immediately.

Lower extremity systolic pressure
Brachial artery systolic pressureABI =
• The ankle-brachial index is 95% sensitive and 99% specific for PAD
• Establishes the PAD diagnosis
• Identifies a population at high risk of CV ischemic events
• “Population at risk” can be clinically & epidemiologically defined:
 Exertional leg symptoms, non-
healing wounds, age > 70, age > 50
years with a history of smoking or
diabetes.

 An accurate pressure reading is obtained as follows:
 Place the pneumatic cuff around the ankle
 Position the Doppler probe over the dorsalis pedis or the
posterior tibial artery
 Inflate the cuff to a reading above the systolic pressure and
deflate; the systolic tone at the ankle vessel is the pressure
recorded

http://www.nhlbi.nih.gov/health/dci/Diseases/pad/pad_diagnosis.html

 A healthy person the pressure at the ankle may be 10-20 mm
Hg higher.
 In a patient with claudication, the measured pressure at the
ankle will be diminished, depending on the severity of PAD.
 A useful tool in assessing a patient with claudication is the
ankle-brachial index .
 Ratio of systolic blood pressure at the ankle to systolic blood
pressure in the arm.
 A normal ABI is 0.9-1.1.
 ABI < 0.9 =PAD.
 As PAD worsens, the ABI decreases further.

Adapted from Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192. Figure 6.
ABI Interpretation
1.00–1.29 Normal
0.91–0.99 Borderline
0.41–0.90 Mild-to-moderate disease
≤0.40 Severe disease
≥1.30 Noncompressible

 Indicated when the ABI is
normal or borderline but
symptoms are consistent
with claudication;
 An ABI fall post-exercise
supports a PAD diagnosis;
 Assesses functional capacity
(patient symptoms may be
discordant with objective
exercise capacity).
.

 The ABI may be a less accurate assessment tool in
patients with diabetes.
 Peripheral vessels in patients with diabetes may have
extensive medial-layer calcinosis, which renders the
vessel resistant to compression by the pneumatic cuff.

 Incompressible arteries (elderly patients,
patients with diabetes, renal failure, etc.)
 Resting ABI may be insensitive for detecting
mild aorto-iliac occlusive disease
 Not designed to define degree of functional
limitation
 Normal resting values in symptomatic patients
may become abnormal after exercise
 Note: “Non-compressible” pedal arteries is a
physiologic term and such arteries need not be
“calcified”

 The toe-brachial index
(TBI) is calculated by
dividing the toe pressure
by the higher of the two
brachial pressures.
 TBI values remain
accurate when ABI
values are not possible
due to non-compressible
pedal pulses.
 TBI values ≤ 0.7 are
usually considered
diagnostic for lower
extremity PAD.

1. Chronic Venous Insufficiency
2. Compartment Syndrome, Lower Extremity
3. Degenerative Disk Disease
4. Osteoarthritis
5. Spinal Stenosis
6. Thromboangiitis Obliterans
7. Varicose Veins

Neuropathic Ulcer Neuroischemic Ulcer
Painless Painful
Normal pulses Absent pulses
Typically punches-out appearance Irregular margins
Often located on sole or edge of foot or
metatarsal head
Commonly located on toes
Presence of calluses Calluses absent or infrequent
Loss of sensation, reflexes, and vibration
sense
Variable sensory findings
Increase in blood flow
(arteriovenous shunting)
Decrease in blood flow
Dilated veins Collapsed veins
Dry, warm foot Cold foot
Bone deformities No bony deformities
Red appearance Pale, cyanotic
Reprinted with permission from Dormandy JA, Rutherford RB. J Vasc Surg. 2000;31:S1-S296.

 Laboratory studies
 Renal function
 Elevated lipid profiles.
 Angiography
 Computed tomography angiography (CTA)
 Magnetic resonance angiography (MRA)
 Duplex ultrasonography.

Perform a resting ankle-brachial index measurement
Recognizing the “at risk” groups leads to recognition of the five
main PAD clinical syndromes:
No leg pain Classic
claudication
Chronic
critical limb
ischemia
(CLI)
Acute
limb
ischemia
(ALI)
“Atypical”
leg pain
Obtain history of walking impairment and/or limb ischemic
symptoms:
Obtain a vascular review of symptoms:
• Leg discomfort with exertion
• Leg pain at rest; non-healing wound; gangrene

 Angiography is the criterion standard arterial imaging
study for the diagnosis of PAD.
 Usually reserved for when an intervention is planned.

1. MRA is useful for imaging large and small vessels.
MRA also to help plan the type of intervention.
2. CTA is another modality used to image arterial disease.
Requires a large amount of contrast media.
3. Duplex ultrasonography is performed to evaluate the
status of a patient’s vascular disease.
 Noninvasive
 Requiring no contrast media.
 Unfortunately, it is highly technician-dependent.

• Duplex ultrasound of the extremities
is useful to diagnose anatomic
location and degree of stenosis of
peripheral arterial disease.
• Duplex ultrasound is useful to
provide surveillance following
femoral-popliteal bypass using
venous conduit (but not prosthetic
grafts).
• Duplex ultrasound of the extremities
can be used to select candidates for:
(a) endovascular intervention;
(b) surgical bypass, and
(c) to select the sites of surgical
anastomosis.
However, the data that
might support use of
duplex ultrasound to
assess long-term
patency of PTA is not
robust.

MRA of the extremities is useful to diagnose
anatomic location and degree of stenosis of
PAD.
MRA of the extremities should be performed
with a gadolinium enhancement.
MRA of the extremities is useful in selecting
patients with lower extremity PAD as candidates
for endovascular intervention.
Magnetic Resonance Angiography (MRA)

CTA of the extremities may be considered
to diagnose anatomic location and
presence of significant stenosis in
patients with lower extremity PAD.
CTA of the extremities may be considered
as a substitute for MRA for those patients
with contraindications to MRA.
Computed Tomographic Angiography (CTA)

 Treatment of claudication is medical, except in severe
cases.
 Goal - is to impede the progression of the disease.
1. Pharmacologic
2. Nonpharmacologic measures.

 The most expedient way of impeding the progression of
PAD is to stop tobacco use.

 Aspirin is recommended for overall cardiovascular care.
 Standard dosages range from 81 to 325 mg/day, but no
consensus has been reached on the most effective dose.
 Pentoxifylline shows promise.
 Numerous RCT have documented modest improvements in
walking distance in pentoxifylline treatment groups as
compared with placebo treatment groups.
 Treatment may take as long as 2-3 months to produce
noticeable results.

 Clopidogrel bisulfate
 Enoxaparin sodium
 Cilostazol
 ↑walking distance
 Lipid profiles- also improved
 Statins - seemed to be the best at improving maximal
walking distance.

Antiplatelet Therapy
Antiplatelet therapy is indicated to reduce the risk of
myocardial infarction, stroke, or vascular death in
individuals with atherosclerotic lower extremity PAD.
Aspirin, in daily doses of 75 to 325 mg, is recommended as
safe and effective antiplatelet therapy to reduce the risk
of myocardial infarction, stroke, or vascular death in
individuals with atherosclerotic lower extremity PAD.
Clopidogrel (75 mg per day) is recommended as an
effective alternative antiplatelet therapy to aspirin to
reduce the risk of myocardial infarction, stroke, or
vascular death in individuals with atherosclerotic lower
extremity PAD.

Pharmacotherapy of Claudication
Cilostazol (100 mg orally two times per
day) is indicated as an effective therapy to
improve symptoms and increase walking
distance in patients with lower extremity
PAD and intermittent claudication (in
the absence of heart failure).

 In July 2014, the SCAI issued a consensus statement on the treatment of
infrapopliteal arterial disease.
1. Endovascular intervention is not appropriate for most single-vessel,
mildly symptomatic, or asymptomatic blockages of infrapopliteal vessels.
2. It is not appropriate to treat most cases of moderate-to-severe claudication
or major tissue loss in one-vessel disease and mild claudication in one-,
two-, or three-vessel disease.
3. Primary amputation should be the preferred intervention in non
ambulatory patients with a limited life expectancy and extensive necrosis
or gangrene.
4. Consider surgical bypass and evaluate its associated risks for ambulatory
patients with a patent infrapopliteal artery that has direct flow to the foot
and an adequate autologous venous conduit.
5. Use balloon angioplasty for clinically significant infra popliteal arterial
disease; consider bailout bare-metal and drug-eluting stents for tibial
arterial disease that is refractory to treatment with balloon angioplasty.

 The SCAI indicated that intervention for infrapopliteal
disease is appropriate in
1. Patients with two- or three-vessel disease and moderate-
to-severe claudication with a focal arterial lesion.
2. ischemic foot pain during rest (Rutherford classification
4)
3. Minor and major (skin necrosis, gangrene) tissue loss.

 Diabetes- Control
 BARI 2D trial- those treated with insulin-sensitizing
therapy (16.9%) (ie, metformin or a glitazone) were less
likely to develop any type of new PAD during 4.6 years of
follow-up than were patients treated with insulin-
providing therapy (24.1%).

 Surgical treatment options
1. Patients with more severe disease or
2. Nonsurgical management fails
A. Open bypass surgery
B. Endovascular therapy (eg, stents, balloons, or
atherectomy devices).

Endovascular intervention is not indicated if
there is no significant pressure gradient
across a stenosis despite flow augmentation
with vasodilators.
Primary stent placement is not
recommended in the femoral, popliteal, or
tibial arteries.
Endovascular intervention is not indicated
as prophylactic therapy in an asymptomatic
patient with lower extremity PAD.
Endovascular Treatment for Claudication

Patients who have significant necrosis of the
weight-bearing portions of the foot, an
uncorrectable flexion contracture, paresis of the
extremity, refractory ischemic rest pain, sepsis, or
a very limited life expectancy due to co-morbid
conditions should be evaluated for primary
amputation.
Surgery is not indicated in patients with severe
decrements in limb perfusion in the absence of
clinical symptoms of critical limb ischemia.

For individuals with combined inflow and
outflow disease with critical limb ischemia,
inflow lesions should be addressed first.
When surgery is to be undertaken, an aorto-
bifemoral bypass is recommended for patients
with symptomatic, hemodynamically
significant, aorto-bi-iliac disease requiring
intervention.

Bypasses to the above-knee popliteal
artery should be constructed with autogenous
saphenous vein when possible.
Bypasses to the below-knee popliteal artery
should be constructed with autogenous vein
when possible.
Prosthetic material can be used effectively
for bypasses to the below knee popliteal
artery when no autogenous vein from ipsilateral
or contralateral leg or arm is available.

Femoral-tibial artery bypasses should be
constructed with autogenous vein, including
ipsilateral greater saphenous vein, or if
unavailable, other sources of vein from the leg
or arm.
Composite sequential femoropopliteal-tibial
bypass, or bypass to an isolated popliteal
arterial segment that has collateral outflow to
the foot, are acceptable methods of
revascularization and should be considered
when no other form of bypass with adequate
autogenous conduit is possible.

Patients with ALI and a salvageable
extremity should undergo an emergent
evaluation that defines the anatomic level of
occlusion, and that leads to prompt
endovascular or surgical intervention.
Patients with ALI and a non-viable extremity
should not undergo an evaluation to define
vascular anatomy or efforts to attempt
revascularization.

Obtain history of walking impairment and/or limb ischemic symptoms:
Obtain a vascular review of symptoms:
• Leg discomfort with exertion
• Leg pain at rest; nonhealing wound; gangrene
No leg pain Classic
claudication
Chronic critical
limb ischemia
(CLI)
“Atypical”
leg pain
Diagnosis and Treatment
of Asymptomatic PAD
and Atypical Leg Pain
Diagnosis and
Treatment of
Claudication
Diagnosis and
Treatment of
Critical Limb
Ischemia
Diagnosis and
Treatment of Acute Limb
Ischemia
Diagnosis and
Treatment of
Asymptomatic
PAD and Atypical
Leg Pain
Individuals
“at risk”
for PAD
Age 50 to 69 years and history of smoking or diabetes
Age ≥ 70 years
Abnormal lower extremity pulse examination
Known atherosclerotic coronary, carotid, or renal arterial disease
Acute limb
ischemia
(ALI)

Individual at PAD risk: No leg symptoms or atypical leg symptoms
Consider use of the San Diego Walking Impairment Questionnaire
Confirmation of
PAD diagnosis
ABI ≥ 1.30
(abnormal)
ABI ≤ 0.90
(abnormal)
Pulse volume recording
Toe-brachial index
(Duplex ultrasonography)
Abnormal
results
Evaluate other causes of
leg symptoms
Decreased post-exercise
ABI
Normal post-exercise
ABI:
No PAD
Measure ABI after
exercise test
ABI 0.91 to 1.30
(borderline & normal)
Normal results:
No PAD
ACC/AHA Guideline for the Management of PAD:
Diagnosis and Treatment of Asymptomatic PAD

Diagnosis and Treatment of Asymptomatic PAD
Risk factor normalization:
Immediate smoking cessation
Treat hypertension: JNC-7 guidelines
Treat lipids: NCEP ATP III guidelines
Treat diabetes mellitus: HbA1c less than 7%
Pharmacological Risk Reduction:
Antiplatelet therapy (ACE inhibition; Class IIb, LOE
C)
Confirmation of PAD
diagnosis
ACE=angiotensin-converting enzyme; JNC-7=Joint National Committee on Prevention ;
NCEP=National Cholesterol Education Program – Adult Treatment Panel III.

Diagnosis of Claudication and Systemic Risk Treatment
Classic Claudication Symptoms:
Muscle fatigue, cramping, or pain that reproducibly
begins during exercise and that promptly resolves with
rest
Document pulse
examination
ABI
Exercise ABI
(TBI, segmental pressure, or
Duplex ultrasound examination)
Chart document the history of walking impairment
(pain-free and total walking distance) and specific
lifestyle limitations
Confirmed PAD diagnosis
ABI greater
than 0.90
ABI less than or equal to 0.90
No PAD or consider arterial
entrapment syndromes
Normal
results
Abnormal
results
Cont’d
Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.ABI=ankle-brachial index; TBI=toe-brachial index.

Diagnosis of Claudication and Systemic Risk Treatment
Risk factor normalization:
Immediate smoking cessation
Treat hypertension: JNC-7 guidelines
Treat lipids: NCEP ATP III guidelines
Treat diabetes mellitus: HbA1c less than
7%
Pharmacological risk reduction:
Antiplatelet therapy
(ACE inhibition; Class IIa)
Confirmed PAD
diagnosis
Treatment of Claudication
ACE=angiotensin-converting enzyme; JNC-7=Joint National Committee on Prevention ;
NCEP=National Cholesterol Education Program – Adult Treatment Panel III.

Significant disability despite medical
therapy and/or inflow endovascular
therapy, with documentation of outflow
PAD, with favorable procedural
anatomy and procedural risk-benefit
ratio
No significant
functional disability
Lifestyle-limiting symptoms
Supervised
exercise
program
Three-month trial
Preprogram and
postprogram
exercise testing for
efficacy
Lifestyle-limiting symptoms
with evidence of inflow disease
Further anatomic
definition by more
extensive noninvasive or
angiographic diagnostic
techniques
Clinical improvement:
Follow-up visits
at least annually
Endovascular
therapy or surgical
bypass per anatomy
Pharmacological
therapy:
Cilostazol
(Pentoxifylline)
Three-month trial
Evaluation for additional endovascular or surgical revascularization
Confirmed PAD Diagnosis
• No claudication treatment
required.
• Follow-up visits at least
annually to monitor for
development of leg,
coronary, or
cerebrovascular ischemic
symptoms.
Treatment of Claudication

Diagnosis and Treatment of Critical Limb Ischemia
Chronic CLI symptoms: Ischemic rest pain, gangrene, nonhealing wound
Ischemic etiology must be established promptly by examination and objective vascular studies
Implication: Impending limb loss
History and physical examination:
Document lower extremity pulses;
Document presence of ulcers or infection
ABI, TBI, or Duplex
US Evaluation of source
(ECG or Holter monitor; TEE;
and/or abdominal US, MRA,
or CTA);
or venous Duplex
Consider atheroembolism,
thromboembolism, or
phlegmasia cerulea
dolens
No or minimal
atherosclerotic arterial
occlusive disease
Assess factors that may contribute to limb risk:
diabetes, neuropathy, chronic renal failure,
infection
Severe lower extremity PAD
documented:
ABI less than 0.4; flat PVR waveform; absent pedal
flow
Cont’d
ABI=ankle-brachial index; CLI=critical limb ischemia; CTA=computed tomographic angiography;
ECG=electrocardiogram; MRA=magnetic resonance angiography; PVR=pulse volume recording;
TEE=transesophageal echocardiogram; TBI=toe-brachial index; US= ultrasound.

Obtain prompt vascular specialist consultation:
• Diagnostic testing strategy
• Creation of therapeutic intervention plan
Ongoing vascular surveillance
Written instructions for
self-surveillance
Patient is not a candidate for
revascularization
Medical therapy
or amputation (when
necessary)
Severe lower extremity PAD documented:
ABI less than 0.4; flat PVR waveform; absent pedal flow
Systemic antibiotics if skin ulceration
and limb infection are present
ABI=ankle-brachial index; PVR=pulse volume recording.
Diagnosis and Treatment of Critical Limb Ischemia (1)
Cont’d
Patient is a candidate for
revascularization

• Define limb arterial anatomy
• Assess clinical and objective severity of ischemia
Revascularization possible
(see treatment text, with application of
thrombolytic, endovascular, and surgical
therapies)
Revascularization not possible:
medical therapy;
amputation (when necessary)
Ongoing vascular surveillance
Written instructions for self-surveillance
Patient is a candidate for
revascularization
Diagnosis and Treatment of Critical Limb Ischemia (2)
Imaging of relevant arterial circulation
(noninvasive and angiographic)

 Regular walking programs result in substantial
improvement (80-234% in controlled studies).
 A daily walking program of 45-60 minutes is
recommended.
 The patient walks until claudication pain occurs, rests
until the pain subsides, and then repeats the cycle.
 Exact mechanism -unknown,
 Condition muscles, work more efficiently (ie, extract more
blood)
 Increase collateral vessel formation.

Supervised Exercise Rehabilitation
A program of supervised exercise training is
recommended as an initial treatment
modality for patients with intermittent
claudication.
Supervised exercise training should be
performed for a minimum of 30 to 45
minutes, in sessions performed at least three
times per week for a minimum of 12 weeks.

 Every 4-6 months to assess the effects of therapy.
 Hypertension and diabetes should be controlled.
 A repeat pulse examination should be performed and the
ABI measured.
 If the patient’s symptoms are worsening, intervention and
referral to a vascular surgeon.

 Limb-threatening ischemia leading to amputation.
 In the Framingham study, only 1.6% of patients with
claudication reached the amputation stage after 8.3 years
of follow-up.

 Predicted mortality for patients with claudication is
approximately
 30% at 5 years of follow-up.
 50% at 10 years.
 70% at 15 years.

 The US FDA has approved the first drug-coated balloon
(DCB) for the treatment of peripheral arterial vascular
disease, the Lutonix 035 Drug Coated Balloon.
 Percutaneous Transluminal Angioplasty Catheter (Lutonix
DCB).
 The device is coated with paclitaxel and intended for use
to treat stenotic or obstructive lesions in the femoro
popliteal arteries to improve limb perfusion.

Peripheral arterial disease

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