Duane S. Pinto, M.D.
Director Peripheral Angiographic Core Laboratory,
TIMI Data Coordinating Center
Director, Cardiology Fellowship Training Program
Interventional Cardiologist Beth Israel Deaconess Medical Center
Assistant Professor of Medicine, Harvard
Medical School
Intermittent Claudication
Diagnosis and Work-up
Harvard
Medical
School
PAD is a common disorder
 Occurs in approximately 1/3 of patients
 Over age 70
 Over age 50 who smoke or have DM
 Strong association with CAD
 Obvious associated risk of stroke, MI, cardiovascular death
 Progressive disease in 25% with progressive intermittent
claudication/limb threatening ischemia
 Outcomes
 Impaired QoL
 Limb Loss
 Premature Mortality
Harvard
Medical
School
Risk Factors for PVD: Framingham Heart Study
Reduced
Increased
Smoking
Diabetes
Hypertension
Hypercholesterolemia
Hyperhomocysteinemia
Fibrinogen
Mean follow-up 38 years
C- Reactive Protein
Alcohol
Relative Risk
.5
1
2
3
4
5
6
Harvard
Medical
School
PAD is Associated with Poor Outcomes
Stroke
Annual
Incidence
0.73
Prevalence Mortality/yr
(%)
4.6
28
TIA
0.50
4.9
6.3
ACS
2.3
12.6
45
8-12
4-25%
PAD
Criqui M, et al. Circulation 1985; 71:510
Harvard
Medical
School
Outcomes in PVD Patients
Harvard
Medical
School
Diagnostic Modalities
 History
 Physical
 Ankle Brachial Index (ABI)
 Noninvasive vascular laboratory
 Angiography: MRA, CT, DSA
Harvard
Medical
School
Initial Assessment
 Identifying risk factors and symptoms
 Pulse palpability
 Further assessment relies on functional noninvasive testing and radiological imaging
 Determine not only the anatomic, but also the
physiological aberration of peripheral vascular
flow.
Harvard
Medical
School
Intermittent Claudication
 Intermittent claudication (derived from the Latin
word for limp)
 A reproducible discomfort of a defined group of
muscles that is induced by exercise and
relieved with rest.
 Supply ≠ Demand
 Location depends upon the location of the
disease.
 Buttock, thigh, calf or foot claudication,
either singly or in combination.
Harvard
Medical
School
PVD Etiology
 Large arteries
 Atherosclerosis
 Thromboembolism
 Trauma
 Arteritis of various types including
 Buerger’s disease
 Fibromuscular dysplasia
 Takayasu’s
Harvard
Medical
School
PVD Etiology
 Medium and small
vessel occlusions
 Diabetes
 Chronic recurrent
trauma
 Multiple small
emboli
 Collagen vascular
diseases
 Dysproteinemias
 Polycythaemia
vera
 Pseudoxanthoma
elasticum
 Drug Reaction
 Vasospasm
Harvard
Medical
School
PVD Etiology
 Specific to certain
anatomical sites
 Cystic adventitial
disease of the
popliteal artery
 Popliteal artery
entrapment
 Iliac endofibrosis
(cyclists)
 Various neurovascular
compression syndromes
affecting the upper limb
 Cervical rib
 Costoclavicular
syndrome
 Scalenus tunnel
syndrome
 Hyperabduction
syndrome
 Quadrangular space
syndrome
Harvard
Medical
School
PVD Differential Diagnosis
 Deep venous thrombosis
 Musculoskeletal disorders
 OA
 Restless leg syndrome
 Peripheral neuropathy
 Spinal Stenosis (pseudoclaudication)
 Worse with erect posture (lordosis) better sitting or
lying down.
 Can find relief by leaning forward and straightening
the spine (pushing a shopping cart or leaning against
a wall).
Harvard
Medical
School
Differential Diagnosis of Intermittent Claudication
Intermittent
Claudication
Venous
Claudication
Neurogenic
Claudication
Quality of pain Cramping
"Bursting"
Electric shock-like
Onset
Gradual, consistent
Gradual, can be
immediate
Can be immediate,
inconsistent
Relieved by
Standing still
Elevation of leg
Sitting down,
bending forward
Location
Muscle groups
(buttock, thigh, calf)
Whole leg
Poorly localized,
can affect whole leg
Legs affected
Usually one
Usually one
Often both
Harvard
Medical
School
Location, Location, Location!
 Buttock/hip
 Usually indicates aortoiliac occlusive disease (Leriche's
syndrome)
 Some cases, thigh claudication too
 Question diagnosis of bilateral disease if erectile dysfunction
is not present
 Thigh
 Occlusion of the common femoral artery leads to
claudication in the thigh, calf, or both.
 Calf
 Symptoms in upper 2/3 is usually due to SFA
 Lower 1/3 is due to popliteal disease.
Harvard
Medical
School
PVD History
 Use of the history alone to detect peripheral
arterial disease will result in missing up to 90
percent of cases.
 Asymptomatic patients with abnormal ABI
have 50% increased risk of cardiovascular
complications
Hirsch AT, et al. JAMA 2001; 286: 1317
Hooi JD, et al. J Clin Epidem 2004; 57:294
Harvard
Medical
School
Physical Exam
 Trophic Signs
 Skin atrophy, thickened nails, hair loss,
dependent rubor
 Ulceration, gangrene
 Pulse exam
 May miss more than 50%
 Elevation and dependency test
Criqui M, et al. Circulation, 1985: 71; 516-521
Harvard
Medical
School
Physical Exam: Elevation and Dependency Test
Color Return(s)
Venous Filling(s)
Normal
10
10-15
Adequate
Collaterals
15-25
15-30
Severe Ischemia >35
>40
Halperin, Throm Res. 2002; 106: V303-311
Harvard
Medical
School
Harvard
Medical
School
Noninvasive Work-up
Ankle Brachial Index
 Cornerstone of lower extremity vascular evaluation
 Blood pressure cuffs, Doppler
 Ankle (DP or PT) to brachial artery pressure
Normal
0.96
Claudication
0.50-0.95
Rest Pain
0.21-0.49
Tissue loss
0.20
Significant change
0.15 or more
Harvard
Medical
School
Limitations
 Noncompressible vessels
 Diabetes
 Renal Failure
 ABI >1.5
 Use toe-brachial index
 Normal >0.7
 Rest pain <0.2
 Subclavian/Brachiocephalic Occlusive disease
Harvard
Medical
School
Segmental Pressures
 Pneumatic cuffs at multiple
levels
 Doppler pressure at pedal
artery
 Drop >30 mm Hg between
levels
 Drop >20 mm Hg between
limbs
 Reflects status of artery
above drop in pressure
 Inaccurate with calcified
vessels
Rose SC. J Vasc Interv Radiol. 2000; 11:1107-1114
Harvard
Medical
School
Duplex Doppler
 Non-invasive method of evaluating the blood
vessels using sound waves, similar to
ultrasonography and echocardiography.
 Can obtain both anatomic and hemodynamic
information.
 Anatomical detail
 vessel wall
 intraluminal obstructive lesions
 perivascular compressive structures
Harvard
Medical
School
Doppler Waveform Analysis: Hemodynamic
Information
 Sensitivity of 92.6% and
specificity of 97%
(angiography gold
standard)
 Inaccurate at adductor
canal and the aorto-iliac
regions.
 95% accuracy in the
detection of bypass
graft stenosis, but can
overestimate stenosis.
Polack JF. Duplex Doppler in peripheral arterial disease. Radiol
Clin N Amer 1995; 33 : 71-88.
Harvard
Medical
School
Doppler Waveform Analysis: Hemodynamic
Information
 Qualitative
assessment of
waveform analysis
 Simple Equipment
 Not affected by
medial calcinosis
 Supplements
segmental pressures
Harvard
Medical
School
Pulse Volume Recordings
 Pneumatic Cuffs at
Multiple Levels
 Inflated to 65 mm Hg
 Extremity Volume
Increases in Systole
 Changes pressure
in cuff
 Waveform Analysis
 Not Impacted by
Calcification
Harvard
Medical
School
Pulse Volume Recordings
 Advantanges
 Widely available
 Cheap
 Reproducible
 Disadvantages
 Technician
dependent
 Time Consuming
 Detection of
Collaterals is low
 Presence of gas
and calcification
degrade images
Harvard
Medical
School
Is this enough?
 Noninvasive lab documents presence and
severity of disease
 No comprehensive anatomic information
 No ability to plan interventions
Harvard
Medical
School
Radiologic Imaging: MRA and CTA
 DSA (conventional angiography) remains the
gold standard for evaluation of PVD
 Newer modalities that match its accuracy are
rapidly evolving
 It is a matter of time before imaging replaces
DSA, with the invasive angiographic
techniques reserved for interventional
procedures
Harvard
Medical
School
MRA vs. DSA
Harvard
Medical
School
MRA: Current Technique
 3D gradient echo (fast
acquisition)
 Gadolinium Enhanced
 20-40 cc
 Automated Scan delay
 Renal arteries to toes
 Stepping table or bolus chase
 45-min exam
Harvard
Medical
School
MRI
Harvard
Medical
School
Limitations of MRI
 Uncooperative patient
 Claustrophobia
 Metal artifact
 Pacemakers/ICDs
 Lack of visualization of
calcium
Harvard
Medical
School
CTA of PVD
 Multidetector CT scanner
necessary (4+)
 Many hospitals now have 64 Slice
 Iodinated contrast volume similar
to conventional angiography
 80-150 cc
 Automated Scan Delay
 Renal arteries to ankles
 20-minute exam
 High powered post processing
software crucial
Harvard
Medical
School
CTA of PVD
Harvard
Medical
School
CTA of PVD
 Large volumes of data are
generated via CTA studies
and displayed in various
formats to refine the
analysis of study results
 Maximum Intensity
Projection -MIP (most
common)
 Shaded surface display
 3D Volume rendering
Harvard
Medical
School
CT Limitations
 With significant and dense
calcifications, a false diagnosis
of patency can result.
 Uncooperative patient
 Pregnancy
 Bad Pump
 Inconsistent pedal vessel
visualization
 Renal failure/contrast allergy
Harvard
Medical
School
Digital Subtraction Angiography (DSA)
 Gold standard of arterial imaging
 Has almost totally replaced conventional cut film
angiography
 Compares a pre contrast image with a post contrast
image using a computer, and "subtracts" elements
common to both.
 Prevents images of objects like bones etc from
obscuring vascular details.
 Contrast resolution is improved through use of image
enhancement software.
Harvard
Medical
School
Digital Subtraction Angiography (DSA)
 Radiation exposure and contrast volumes are
lower than conventional angiography
 Images are immediately available for review.
 Images are stored in digital format on
computerized data storage media
 Interventional procedures can be performed
Harvard
Medical
School
Digital Subtraction Angiography (DSA)
Drawbacks precluding use as a
screening modality
Technique is invasive and expensive.
Requires arterial puncture
Longer study than CT
Contrast nephrotoxicity
Harvard
Medical
School
Medical Treatments for PAD
Treatment
Effect
Smoking cessation
10-year mortality ↓ 54% to 18%;
at 7 years, rest pain drops from 16% to 0%*
Antiplatelet agent
22%↓ in vascular events;
possible increase in walking distance
Diabetes control
RR=0.94 (0.8 - 1.1) for mortality;
RR=0.51 (0.01 - 19.64) for amputation
BP to <140/85 mm Hg
RR=0.87 (0.81 - 0.94) for mortality; effect on PAD not
known
ACE inhibitors
RR=0.73 (0.61 - 0.86) for MI, stroke, or CV death
Exercise program
24% ↓ in CV mortality;
150% further walking distance
Cholesterol decrease
RR=0.81 (0.72 - 0.87) for MI, stroke, or revascularization;
no clinical benefit in PAD†
Cilostazol
significant ↑ in walking distance
*Survival Bias
†Excepting Stroke
Harvard
Medical
School
Suggested Algorithm for Work-up
Harvard
Medical
School
Workup-Take-home
 Noninvasive Vascular Lab is first line
evaluation in nonacute patients
 ABI is easy screening test
 Beware noncompressible vessels in renal
failure and diabetes
 Segmental limb pressures often combined
with doppler waveform anlaysis
 Not sufficient to plan intervention
Harvard
Medical
School
Workup-Take-home
 MRA indicated for intervention planning
 MRA (gadolinium enhanced) provides
excellent renal to pedal imaging
 Surpasses CT in the foot
 Overestimation of stenoses in small vessels
 Limited by metal artifact, magnetic field, and
length of study
Harvard
Medical
School
Workup-Take-home
 CTA indicated for intervention planning
 CTA provides excellent renal to ankle
imaging
 Pedal imaging poor
 Soft tissues and bone also imaged
 Small vessel calcification is limitation
Harvard
Medical
School