1. Intermittent Claudication
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

2. 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
Temporal Arteritis is very rare before 45 years. Buerger’s unheard of under 55. Raynaud’s patients or varicose will usually remember symptoms starting before 30.

3. Risk Factors for PVD: Framingham Heart Study
Reduced Increased
Smoking
Diabetes
Hypertension
Hypercholesterolemia
Hyperhomocysteinemia
Fibrinogen
C- Reactive Protein
Alcohol
Relative Risk
Data from the Framingham Heart Study of 381 men and women who were followed for 38 years revealed that the odds ratio for developing intermittent claudication was 2.6 for diabetes mellitus, 1.2 for each 40 mg/dL (1 mmol/L) elevation in the serum cholesterol concentration,1.4 for each 10 cigarettes smoked per day, and 1.5 for mild and 2.2 for moderate hypertension [5]. In addition, diabetic patients have worse arterial disease and a poorer outcome than nondiabetics [9].
Mean follow-up 38 years

4. PAD is Associated with Poor Outcomes
Annual Incidence
Prevalence
Mortality/yr (%)
Stroke
0.73
4.6 28
TIA
0.50
4.9
6.3
ACS
2.3
12.6 45
PAD
8-12
4-25%
Criqui M, et al. Circulation 1985; 71:510

5. Outcomes in PVD Patients

6. Diagnostic Modalities
History
Physical
Ankle Brachial Index (ABI)
Noninvasive vascular laboratory
Angiography: MRA, CT, DSA

7. Identifying risk factors and symptoms Pulse palpability
Initial Assessment
Identifying risk factors and symptoms
Pulse palpability
Further assessment relies on functional non-invasive testing and radiological imaging
Determine not only the anatomic, but also the physiological aberration of peripheral vascular flow.

8. 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.

9. PVD Etiology Large arteries Atherosclerosis Thromboembolism Trauma
Arteritis of various types including
Buerger’s disease
Fibromuscular dysplasia
Takayasu’s

10. Medium and small vessel occlusions
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

11. Specific to certain anatomical sites
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

12. 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).
Pain can be excruciating and is usually located in the dorsal aspect of the toes. The foot may become pale with exercise.

13. Differential Diagnosis of 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
Often both

14. 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.

15. 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

16. Elevation and dependency test
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;

17. 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 ; 106: V

18. Noninvasive Work-up

19. 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
Rest Pain
Tissue loss
0.20
Significant change
0.15 or more

20. Limitations Noncompressible vessels
Diabetes
Renal Failure
ABI >1.5
Use toe-brachial index
Normal >0.7
Rest pain <0.2
Subclavian/Brachiocephalic Occlusive disease

21. 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:

22. Noninvasive Functional Assessment
Targeted towards evaluating the arterial flow dynamics in the affected area, and are invariably supplemented with radiological depiction of anatomic abnormality
Pressure measurements (ABI)
Plethysmography
Continuous wave Doppler

23. 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

24. 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 :

25. Doppler Waveform Analysis: Hemodynamic Information
Qualitative assessment of waveform analysis
Simple Equipment
Not affected by medial calcinosis
Supplements segmental pressures

26. 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

27. 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

28. Is this enough?
Noninvasive lab documents presence and severity of disease
No comprehensive anatomic information
No ability to plan interventions

29. 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

30. MRA vs. DSA

31. 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

32. MRI

33. Limitations of MRI
Uncooperative patient
Claustrophobia
Metal artifact
Pacemakers/ICDs
Lack of visualization of calcium

34. CTA of PVD Multidetector CT scanner necessary (4+)
Many hospitals now have 64 Slice
Iodinated contrast volume similar to conventional angiography cc
Automated Scan Delay
Renal arteries to ankles
20-minute exam
High powered post processing software crucial

35. CTA of PVD

36. 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
A 3D model of the study in any projection and from any angle in order to evaluate the patient for the presence of a stenosis or aneurysm.

37. 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

38. 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.

39. 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

40. 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

41. Medical Treatments for PAD
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 ( ) for mortality; RR=0.51 ( ) for amputation
BP to <140/85 mm Hg
RR=0.87 ( ) for mortality; effect on PAD not known
ACE inhibitors
RR=0.73 ( ) for MI, stroke, or CV death
Exercise program
24% ↓ in CV mortality; 150% further walking distance
Cholesterol decrease
RR=0.81 ( ) for MI, stroke, or revascularization; no clinical benefit in PAD†
Cilostazol
significant ↑ in walking distance
*Survival Bias
†Excepting Stroke

42. Suggested Algorithm for Work-up

43. Noninvasive Vascular Lab is first line evaluation in nonacute patients
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

44. 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

45. CTA indicated for intervention planning
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