peripheral arterial disease: simulation training curriculum

1

Peripheral Arterial Disease:

Simulation TrainingCurriculum

2

Peripheral Arterial DiseasePeripheral Arterial Disease

Etiology Epidemiology Physical examination

Clinical Manifestations Diagnosis

Indications Treatment Options

Prognosis

3

Peripheral Arterial Disease: Etiology

• Atherosclerosis

• Degenerative diseases: Marfan and Ehlers-Danlos syndrome, neurofibromatosis, arteriomegaly

• Dysplastic disorders: Fibromuscular dysplasia

• Vascular inflamation : Takayasu’s disease

• In situ thrombosis

• Thromboembolism

Hirsh et al Circulation 2006; 113(11): e463-654ACC/AHA Guidelines

4

Atherosclerosis: A Progressive and Systemic Process

NormalNormalFattyFatty

StreakStreakFibrousFibrousPlaquePlaque

Occlusive Occlusive AtheroscleroticAtherosclerotic

PlaquePlaque

PlaquePlaqueRupture/Rupture/Fissure &Fissure &

ThrombosisThrombosis

MIMI

StrokeStroke

Critical Critical Leg Leg

IschemiaIschemia

Clinically SilentClinically Silent

Coronary Coronary DeathDeath

Increasing AgeIncreasing Age

Effort AnginaEffort Angina

ClaudicationClaudicationRenovascular DzRenovascular Dz

UnstableUnstableAnginaAngina

5

Peripheral Arterial Disease: Overlap of Atherosclerotic Disease

Patients with one manifestation often have coexisted disease in other vascular beds

38% overlap> 2 Vascular beds

Ness et al Am J Geriatr Soc 1999; 47:1255-6

Peripheral Arterial Disease

Cerebrovascular disease

Coronary artery disease

6

30 34 38 50 55

CHF COPDAverage

Adult

Average Well Adult

Adapted from Ware JE. Ann Rev Pub Health. 1995;16:327-354.

Physical Component Score

SF-36 Physical Function Scores

36

IntermittentClaudication

No. of People

CLI

7

Atherosclerosis Disease in the U.S.

Prevalence

(millions)

Coronary heart disease 13.2

Cerebrovascular disease 4.8

Peripheral arterial disease 8.0 – 12.0

Ness J et al J Am Geriat Soc 1999; 47: 1255-1256

8

Risk of Ischemic Events in Atherosclerotic Clinical Syndromes

*Sudden death defined as death documented within 1 hour and attributed to Coronary Heart Disease (CHD)† Includes only fatal MI and other CHD; does not include nonfatal MI

1. Adult treatment Panel II Circulation 1994; 89: 1333 – 14352. Kannel et al J Cardiovasc Risk 1994;1:333-3393. Witerdink et al Arch Neurol 1992; 49: 857 – 8634. Criqui et al N E J Med 1992; 326: 381-386

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EtiologyEpidemiology Physical examination



Prognosis

10

Prevalence of PAD in 1990s

Projected US

Age Abnormal ABI Prevalence

40-59 3% 2.1 million

60-69 8% 1.6 million

>70 19% 4.7 million

Total 8.4 million

Criqui et al N Engl J Med 1992;326:381-86 Hiatt et al Circulation 1995;91:1472-79

11

Peripheral Arterial Disease Prevalence by age

0

5

10

15

20

25

<60 60-64 65-69 70-74 >75

Men

Women

Criqui et al Circulation 1985; 71: 510-5 (77)

Age Groups

PA

D P

rev

ale

nce

12

Newman et al Circulation 1993;88:837-845. Hiatt WR et al Circulation 1995;92:614-621. Graham et al JAMA 1997;277:1775-1781.TASC Working Group J Vasc Surg 2000;31(1, pt 2):S1-S288. Ridker PM et al Circulation 1998;97:425-428.

.5 1 2 3 4 5 6Relative Risk

Smoking

Diabetes

Hypertension

Hypercholesterolemia

Hyperhomocysteinemia

Fibrinogen

C-Reactive Protein

Alcohol

Reduced Increased

Risk Factors for PAD

13

Nobel Risk Factors as Predictors of PDA

Adjusted for age, smokin, DM, family history, HTN, exercise level, and BMI

Ridker et al JAMA 2001; 285:2481-5

Pradhan et al Circulation 2002; 106: 820-5

14

Lower Extremity PAD: Prevalence

• Affects a large proportion of most adult populations worldwide

• Increases with age and with exposure to atherosclerotic risk factors.

• Defined by– Claudication as a symptomatic marker

– Abnormal ankle-to brachial systolic blood pressure

– Underlying atherosclerosis risk factor profile

– Presence of other concomitant manifestations of atherosclerosis


15

Risk of developing lower extremity PAD


16

Prevalence of intermittent claudication in various studies

Dormandy JA, Rutherford RB J VAsc Surg 2000;31: S1-S296

17

Mean Prevalence of intermittent claudication in large population studies

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74

Age group

Dormandy JA, Rutherfors RB J Vasc Surg 2000; 31: S1-S296

18





Prognosis

19

CVD

CAD

RVD

PAD

20

Peripheral Arterial Disease: Clinical Diagnosis

• Must have a high index of suspicion

• Must perform a thorough physicial examination

• Determine the global atherosclerotic burden

• Utilize the vascular diagnostic laboratory

• Magnetic resonance angiography is rapidly

replacing invasive testing

• Reserve arteriography for cases requiring

intervention

TCT 2005

21

Vascular Review of Systems• Any exertional limitation of the lower extremity muscles or

any history of walking impairment (fatigue, numbness, aching, or pain

• Any poorly healing or non healing of the legs or feet• Any pain at rest localized at the lower leg or foot and its

association with the upright or recumbent positions• Postprandial abdominal pain that reproducibly is provoked

by eating and is associated with weight loss• Family history of a first-degree relative with Abdominal

Aortic Aneurysm

ACC/AHA Guidelines

22

Vascular Physical Examination• Measurement of blood pressure in both arm and notation of any

interarm assymetry• Palpation of the carotid pulses and notation of the carotid upstroke

and amplitude and presence of bruits• Auscultation of the abdomen and flank for bruits• Palpation of the pulses at the brachial, radial ulnar, femoral,

popliteal, dorsalis pedis, and posterior tibial sites. Performance of Allen’s test when knowledge of hand perfusion is needed

• Auscultation of both femoral ateries for the presence of bruits• Pulse intensity should be recorded numerically: 0, absent; 1,

diminished; 2, normal; 3, bounding• Additional findings: distal hair loss, trophic sin changes

hypertrophic nails

ACC/AHA Guidelines

23

Physical Examination

Beard JD. BMJ. 2000;320:854.

Dorsalis Pedis

Posterior Tibial

Popliteal Artery

Femoral Pulse

24

Signs of PAD

• Decreased or absent pulses

• Bruits

• Muscle atrophy

• Pallor of feet with elevation

• Dependent rubor

• Signs of chronic ischemia:

Hair loss, thickened nails, smooth & shiny skin, coolness, pallor or cyanosis

25





Prognosis

26Hirsch AT. Fam Pract Recertification. 2000;15(suppl):6-12.

Clinical Presentation of PAD Patients

Chronic limb ischemia

Acute Limb Ischemia

StableClaudication

AsymptomaticPAD

27

Lower Extremity Arterial Disease in the Population > 55 y

Population >55 y

Asymptomatic ABI <0.9

10%

Intermittentclaudication

5%

Chronic critical leg ischemia

1%

Peripheral vascular outcomes

Other cardiovascular morbidity / total mortality

Worsening claudication

16%

Lowe extremity bypass surgery

7%

Major Amputation

4%

NonfatalCardiovascular event

20%

5-yMortality

30%

Repeat Revascularization

26%

Major Amputation

20%

Cardiovascular Cause

75%

Non-cardiovascular cause 25%

Weitz et al Circulation 1996; 94(11):3026-3049

28

Individuals at Risk for Lower-extremity Peripheral Arterial Disease

• Age less than 50 years, with diabetes and one other atherosclerosis risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia)

• Age 50 to 69 years and history of smoking or diabetes

• Age 70 years and older

• Leg symptoms with exertion (suggestive of claudication) or ischemic rest pain

• Abnormal lower extremity pulse examination

• Known atherosclerotic coronary, carotid, or renal artery disease

ACC/AHA Guidelines

29

Common Sites of Claudication

25-30%

80-90%

Tibial and peroneal arteries

40-50%

Adapted from TCT 2005

Foot

30

Classification of Peripheral Arterial Disease

FONTAINEStage Clinical Grade Category Clinical

I Asymptomatic 0 0 Asymptomatic

IIa Mild claudication I 1 Mild claudication

IIb Moderate–severe claudication I 2 Moderate claudication

I 3 Severe claudication

III Ischemic rest pain II 4 Ischemic rest pain

IV Ulceration or gangrene III 5 Minor tissue loss

IV 6 Ulceration or gangrene

RUTHERFORD

Dormandy JA, Rutherfors RB J Vasc Surg 2000; 31(1): S1-S296

32

Pathophysiology of Intermittent Claudication

Intermittent claudication is associated with:

• Metabolic abnormalities stemming from reduced blood flow and O2 delivery1

• Significant reduction (50%) in muscle fibers compared with controls2

• Smaller type I and II muscle fibers with greater arterial ischemia2

• Hyperplastic mitochondria and demyelination of nerve fibers3

1 Lundgren et al Am J Physiol. 1988;255:H1156-64.2 Hedberg et al. Eur Vasc Surg. 1989;3:315-22.3 Farinon et al. Clin Neuropathol 1984;3:240-52.

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PAD Symptom Severity

• Maximal walking speed

– Normal = 3-4 mph

– PAD = 1-2 mph

• Maximal walking distance

– Normal = unlimited

– PAD, 31% difficulty walking in home

– PAD, 66% difficulty walking 1/2 block

• Peak VO2

– PAD reduced 50% (NYHA class III CHF)

Otsuka data set, J Appl Physiol 1992;73:346

34



Clinical Manifestations Diagnosis Indications

Treatment Options Prognosis

35

Diagnostic Methods

• Ankle-and Toes – Brachial Indices, segmental pressure examination

• Pulse volume recording

• Continuous wave doppler ultrasound

• Treadmill exercise testing with and without ABI assessments and 6 minute walk test

• Duplex ultrasound

• Computed tomographic angiography

• Magnetic resonance angiography

• Contrast angiography


36

Clinical presentation Noninvasive vascular test

Asymptomatic lower extremity PAD ABI

Claudication ABI, PVR, or segmental pressures

Duplex ultrasound

Exercise test with ABI or assess functional status

Possible pseudoclaudication Exercise test with ABI

Postoperative vein graft follow-up Duplex ultrasound

Femoral pseudoaneurysm; iliac or popliteal aneurysm

Duplex ultrasound

Suspected aortic aneurysm; serial AAA follow-up

Abdominal ultrasound, CTA, or MRA

Candidate for revascularization Duplex ultrasound, MRA, or CTA

Typical Noninvasive Vascular Laboratory Tests for Lower Extremity PAD Patients by Clinical Presentation

ACC/AHA GuidelinesAdapted from primary cardiology, 2nd ed., Braunwald E, Goldman L, eds. “Recognition and management of peripheral arterial disease”.

37

Diagnostic Algorithm for PDA

History, Physical examinationSuggestive of PDA? NO

Yes

Search for alternate diagnosis

Ankle-Brachial Index

<0.9 >0.9 >1.30

PAD

Still suspicious?

Vascular Lab Referral •Segmental pressures, PVR•Graded treadmill test

Anatomic Assessment: DUS, MRA, CTA

TCT 2005

38

Diagnosis of asymptomatic PAD and Atypical Leg Pain

Individual at risk of PAD

Perform a resting ankle-brachial index measurement

ABI > 1.30(abnormal)

ABI < 0.90 (abnormal)

ABI 0.91 to 1.30(borderline & normal)

Pulse volume recordingToe-brachial index(Duplex ultrasound)

Normal results:No PAD

Abnormal results

Measure ankle-brachial index after exercise test

Normal:No PAD

Decreased

Evaluate other causes of leg symptoms

Confirmation of PAD diagnosis

ACC/AHA Guidelines

39

Diagnosis of ClaudicationClassic claudication symptoms:

Muscle fatigue, cramping, or pain that reproducibly begins during exercise and that promptly resolves with rest

Chart document the history of walking impairment and specific lifestyle limitations

Document pulse examination

ABI

ABI less than or equal to 0.90

Confirmed PAD diagnosis

ABI >0.90 Exercise ABI

(TBI, segmental pressure, or duplex ultrasound examination)

Abnormal results Normal results

No PAD or consider arterialentrapment syndromes

ACC/AHA Guidelines

40

Diagnosis of Acute Limb Ischemia

Rapid or sudden decrease in limb perfusion threatens tissue viability

History and physical examination; determine time of onset of symptoms

Emergent assessment of severity of ischemia:Loss of pulses

Loss of motor and sensory functionVascular laboratory assessment

ABI, TBI, or duplex ultrasound

Nor or minimal PAD Severe PAD documented:• ABI less than 0.4• Flat PVR waveform• Absent pedal flow

Consider and evaluate source of: atheroembolism, thromboembolism

or phlegmasia cerulea dolens

ACC/AHA Guidelines

41

Diagnosis of Critical Limb IschemiaChronic 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

Assess factor that may contribute to limb risk: diabetes, neuropathy, chronic renal failure, infection

ABI, TBI, or duplex ultrasound

No or minimal atheroscleroticarterial occlusive disease

Severe lower extremity PAD ABI less than 0.4; flat PVR waveform;

absent pedal flow

ACC/AHA Guidelines

42

The Ankle-Brachial Index

• The resting ABI should be used to stablish the lower extremity PAD diagnosis in patients with suspected lower extremity PAD

– Exertional leg symptoms

– Non healing wounds

– 70 years and older or 50 years and older with history of smoking or diabetes

• ABI should be measured in both legs in all new patients with PAD of any severity to confirm the diagnosis and establish a baseline


43

• The toe-brachial index should be used to establish the lower extremity PAD diagnosis in patients in whom lower extremity PAD is clinically suspected but in whom the ABI test is not reliable due to noncompressible vessels (advance age or diabetes)

• Leg segmental pressure measurements are useful to establish the lower extremity PAD diagnosis when anatomic localization of lower extremity PAD is required to create a therapeutic plan



44

Belch JJ et al, Arch Intern Med, 2003;163:8841. Nanda et al Ann Intern Med 2000;132:810-92. Allison et al New Eng J Med 1996;334:155-93. Ferrini et al Ame J Prev Med 1996;12:340-14. Dormandy et al Semin Vasc Surg 1999;12:96 -1085. Fowkes et al Inter J Epid 1991; 20:384-3926. Newman et al Arterioscler Thromb Vasc Biol. 1999;19:538–545

Effectiveness of the ABI vs Other Common Screening Test

Diagnostic Test Sensitivity, % Specificity, %

Pap smear 1 30 - 87 86 – 100

Fecal occult blood test 2 37 - 78 87 – 98

Mammography 3 75 - 90 90 – 95

ABI 4,5,6 95 100

45TCT 2005

46

ABI =

• Ankle and brachial systolic pressures taken using a hand-held Doppler instrument

• Supine, after ~10 minutes rest


Ankle systolic pressureBrachial systolic pressure

Normal ABI 0.90-1.30

PAD ABI <0.90

Rest pain/ulceration ABI <0.40

Non-compressible ABI >1.30

47

Segmental Pressures/ Pulse Volume Recordings

TCT 2005

48

64 yo Male with Right Hip Discomfort with Walking

Treadmill stress test

TCT 2005

49

Peripheral Arterial disease: Duplex Ultrasound

Benefits Limitations

• Can establish the lower extremity PAD diagnosis, establish localization, and define severity of local lower extremity arterial stenoses

• Can be useful to select candidates for endovascular or surgical revascularization

• Accuracy is diminished in proximal aortoiliac arterial segments in some individuals

• Dense arterial calcification can limit diagnostic accuracy

• Sensitivity is diminished for detection of stenoses downstream from a proximal stenosis

• Diminished predictive value in surveillance or prosthetic bypass grafts


50

Peripheral Arterial Disease: Magnetic Resonance

Benefits Limitations• Useful to asses PAD anatomy

and presence of significant stenoses

• Useful to select patients who are candidates for endovascular or surgical revascularization

• Tends to overestimate the degree of stenosis

• May be inaccurate in arteries treated with metal stents

• Can not be used in patients with contraindications to the magnetic resonance technique


51

Peripheral Arterial Disease: MRArterial segment n=226

Sensitivity (%) Specificity (%) Agreement (k ±SE)

Iliac arteries 100 85.7 087± 0.12

Femoropopliteal arteries 95.6 90.3 086 ± 0.06

Calf arteries 96.8 96.1 0.90 ± 0.04

Overall 96.5 94.3 0.90 ± 0.03

Moderate stenosis > 50% lumen reduction

Arterial segment n=226

Sensitivity (%) Specificity (%) Agreement (k ±SE)

Iliac arteries 100 100 100± 0.00

Femoropopliteal arteries 97.0 90.7 087 ± 0.06

Calf arteries 96.4 96.2 0.89 ± 0.05

Overall 97.0 95.0 0.90 ± 0.03

Severe stenosis > 75% lumen reduction

Deutschmann et al Cardiovasc Interv Rad 2006; Apr 19

The following grading scale was used: grade 1, 0–9% (normal, irregularity of vessel wall); grade 2, 10–49% (mild stenosis); grade 3, 50–74% (moderate stenosis); grade 4, 75–99% (severe stenosis); grade 5, 100% (occlusion

52

3D moving-table MR angiogram of a 58-year-old man .The image shows a long stenosis of the left superficial femoral artery (long arrows) and occlusion of the reconstituted popliteal artery (short arrows). Furthermore, occlusion of the right superficial femoral artery (arrowheads) with reconstitution in the middle third can be seen (arrowheads)

Deutschmann et al Cardiovasc Interv Rad 2006; Apr 19

53

Peripheral Arterial Disease: Computed Tomographic Angiography

Benefits Limitations• Useful to asses PAD anatomy and

presence of significant stenoses

• Useful to select patients who are candidates for endovascular or surgical revascularization

• Helpful to provide associated soft tissue diagnostic information that may be associated with PAD presentation

• Metal clips, stents, and metallic prostheses do not cause significant CTA artifacts

• Scan times are significantly faster than for MRA

• Single-detector computed tomography lacks accuracy for detection of stenosis

• Spatial resolution lower than digital subtraction angiography

• Accuracy and effectiveness not as well determined as MRA

• Asymmetrical opacification in legs may obscure arterial phase in some vessels

• Requires iodinated contrast and ionizing radiation

• Venous opacification can obscure arterial filling


54



Clinical Manifestations Diagnosis Indications Treatment Options

Prognosis

55

Automatic Indications for Revascularization

• Gangrene

• Non-healing ulcers

• Ischemic rest pain

• Claudication causing lifestyle deterioration

refractory to pharmacologic intervention and

behavioral modification

56



Clinical Manifestations Diagnosis Indications Treatment Options

Prognosis

57

Peripheral Arterial Disease: Goals of Therapy

• Improvement in quality of life and functional

status

• Identification and treatment of established

systemic atherosclerosis Prolong survival

• Prevention of progression of atherosclerosis Aggressive risk factor intervention

• Limb salvage

58

What are you trying to achieve?

Survival benefit?

End organ function preservation?

Healing?Symptom relief?

59

Treatment of Asymptomatic PAD and Atypical Leg Pain

Risk factor normalization:•Immediate smoking cessation

•Treat hypertension•Treat lipids

•Treat Diabetes mellitus: hbA1c less than 0.7% †

Pharmacological Risk Reduction:Antiplatelet therapy(ACE inhibition) ‡

Confirmation of PAD diagnosis

† It is not yet proven that treatment of diabetes mellitus will significantly reduce PAD – specific (limb ischemic) end points. Treatment of diabetes mellitus should be continued according to established guidelines‡The benefit of ACE inhibition in individuals without claudication has not been specifically documented in prospective clinical trials, but has been extrapolated from other “at risk populations.

ACC/AHA Guidelines

60

Treatment of Symptomatic Lower Extremity Atherosclerotic Occlusive Disease:

Nonoperative Endovascular Surgery

• Risk factor modification

• Exercise• Drugs (including

thrombolytic agents

• Transluminal angioplasty

• Endovascular stents• Intra-arterial

thrombolytic therapy

• Endarterectomy• Bypass grafting • Autogenous

prosthetic• Amputation

Weitz et al Circulation 1996; 94; 3026-49

61

Treatment of ClaudicationConfirmed PAD diagnosis

No significantFunctional disability

Lifestyle-limiting symptoms Lifestyle-limiting symptoms withEvidence of inflow disease

• No claudication treatment• Follow –up visit annually to

monitor for development of ischemic symptoms

Supervised exercise program

Pharmacological therapy:

Cilostazol(Pentoxifyline)

Further anatomic definition by more extensive noninvasive or angiographic diagnostic techniques

Three-month trial

Three-month trial

Endovascular therapyOr surgical bypass per anatomy

Pre/post program exercise testing for

efficacy

Clinical Improvement:Follow-up visits at least annually

Significant disability despite medical therapy and/or endovascular therapy

Evaluation for additional endovascular or surgical revascularization

ACC/AHA Guidelines

62

Claudication Exercise Programs

• Supervised 3 times/week, 2 times unsupervised• Duration: 3 to 6 months • Effective at improving exercise performance, walking

ability and physical functioning• Safe• Cost-effective • Availability of supervised programs is limited• Require discipline and motivation• Benefits dissipate unless exercise regimen is

maintained

63

0

5

10

15

Baseline 6 weeks 12 weeks

Exe

rcis

e T

ime

(min

ute

s)

Duration of Treatment

Control

Exercise training

Effect of Exercise Conditioning on Treadmill Exercise Time

Hiatt et al. Circulation. 1990

64

0

20

40

60

80

100

120

140

160

180

ICD ACD

Ch

ang

e in

Tre

adm

ill

Wal

kin

g D

ista

nce

(%

)

Gardner et al., JAMA, 1995

Exercise TrainingControl

Meta-Analysis of Exercise Training in Claudication

66

Mechanisms of Action of Exercise Therapy in Peripheral Arterial Disease

• Enlarging the radius of the supply vessel

• Enhance collateral growth (unlikely)

• Increase pressure gradient across stenosis

• Increase oxidative capacity of muscle cells

• Increase in Type I muscle fibers

• Higher ‘fluidity’ of arterial blood flow

• Enhanced oxygen affinity of hemoglobin

• Improved endothelial function

67

Cornerstones of Medical Therapies in PAD

Antiplatelet

Smoking cessation

Ace Inhibitors

Cilostazol

Exercise

Statins

68

Efficacy of ACE-I, Stantins and Antiplatelet therapy in PAD

*PAD Subgroup only

APTC Antiplatelet Trialists’ Collaboration BMJ 1994; 308:81-106CAPRIE Steering Committee Lancet 1996; 348: 1329-1339HOPE Study Investigators N Engl J Med 2000; 342:145-153HPS Collaborative group Lancet; 2002; 360:7-22

69

CAPRIE StudyEfficacy of Clopidogrel in Primary Analysis of MI,

Ischemic Stroke, or Vascular Death

ITT Analysis

CAPRIE Steering Committee Lancet 1996; 348: 1329-1339

70

CAPRIE StudyOutcome by Subgroup

CAPRIE Steering Committee Lancet 1996; 348: 1329-1339

71

BaselineFeature

STATIN worse

No prior CHD

CVD 182 215

PAD n = 3748 332 427

Diabetes 279 369

ALL PATIENTS 2042 2606(19.9%) (25.4%)

24% SE 2.6 reduction(2P<.001)

0.4 0.6 0.8 1.0 1.2 1.4

Heart Protection Study:Vascular Event by Prior Disease

Previous MI 1007 1255

Other CHD (not MI) 452 597

Prior MI or Other CHD 568 681(19.9%) (25.4%)

Risk ratio and 95% CI STATIN STATIN Better Worse

STATIN (10269)

PLACEBO (10267)

Heart Protection Study Collaborative Group. Lancet.

2002;360:7-22.

73

The HOPE Study: PAD Subgroup Analysis

0.6 0.8 1.0 1.2

PAD 4046 22.0

No PAD 5251 14.3

No. of Patients

Incidence of Composite Outcome

in Placebo Group

The Heart Outcomes Prevention and Evaluation Study Investigators N. Engl. J. Med. 2000; 342: 145-153

Relative Risk in Ramipril Group

74

Antithrombotic Trialists’ Collaboration: PAD

• 42 clinical trials

• 9,214 patients with PAD

• 23% reduction in serious adverse vascular events (P=.004)

• Benefits similar among PAD subtypes (intermittent claudication, peripheral grafting, and peripheral angioplasty)

Antithrombotic Trialist’s Collaboration. BMJ. 2002;324:71-86.

75

Pharmacotherapy for PADFDA Approved Drugs

• Pentoxifylline• Cilostazol

Drugs Under Investigation

• Atorvastatin• Rosiglitazone• Propionyl- L-Carnitine• L-Arginine• Prostaglandins• Angiogenic Factors: VEGF,bFGF

76

Antithrombotic activity

Antithrombotic activity

VasodilatationVasodilatation

Mildly increases Heart rate

Mildly increases Heart rate

IncreasesBlood flow

IncreasesBlood flow

IncreasesHDL -C

IncreasesHDL -C

Decreasestriglycerides

Decreasestriglycerides

In vitro inhibitionof vascular

smooth musclecells

In vitro inhibitionof vascular

smooth musclecells

Antiplatelet activity

Antiplatelet activity

Cilostazol

Adapted from TCT 2005

Pharmacologic Effects of Cilostazol

77

Effect of Cilostazol on walking distance in patients with intermittent Claudication

Hiatt WR N Engl J Med 2001; 344: 1608 - 1621

78

Effect of Cilostazol vs. Pentoxifylline on Walking Distance in Patients with Claudication

0

10

20

30

40

50

0 4 8 12 16 20 24

Weeks of Treatment

Per

cen

t C

han

ge

fro

m

Bas

elin

e M

WD

(m

ean

)Cilostazol 100 mg bid poPentoxifylline 400 mg tidPlacebo

P <0.05 at all time points

Dawson, et al. Am. J. Med., 2000.

**

**

79

Effect of Simvastatin on Intermittent Claudication in 4S

Pederson et al. Am. J. Cardiol., 1998

4.0

2.0

3.0

1.0

00 54321

Years

%

PlaceboSimvastatin

RR = .62

p< 0.008

80

Effect of Atorvastatin on Pain Free Walking Time in Patients with Intermittent

Claudication

Mohler EM, et al., Circulation, 2003;108:1481-1486

*

*p = 0.025 for 80 mg. dose at 12 months

82

Therapeutic Angiogenesis for PAD

83

Treatment of Acute Limb IschemiaSevere PAD documented

Immediate anticoagulation:Unfractionated heparin or low molecular heparin

Assess etiology:-Embolic -Leg bypass graft thrombosis -Poplietal cyst or entrapment-Progressive PAD and -Arterial trauma -Phlegmasia cerulea dolens in situ thrombosis -Ergotism -Hypercoagulable state

Obtain prompt vascular specialist consultation Diagnostic testing strategy / therapeutic plan

Viable limb salvageable limbThreatened marginally

salvageable limbThreatened immediately

Nonviable limb

AmputationRevascularization: thrombolysis, endovascular, surgical

ACC/AHA Guidelines

84

Treatment of Critical Limb ischemiaSevere lower extremity PAD documented

Systemic antibiotics if skin ulceration and limb infection are present

Obtain prompt vascular specialist consultation Diagnostic testing strategy / therapeutic plan

Patient is a candidate for revascularization

Patient is not a candidate for

revascularization

Medical therapy or amputation

Define limb arterial anatomy and assess clinical severity of ischemia

Imaging of relevant arterial circulation (non invasive and angiographic)

Revascularization possible Revascularization not possible: Medical therapy or amputation

Ongoing vascular surveillance-risk factor normalization

Written instruction for self-surveillance

ACC/AHA Guidelines

85

Endovascular Treatment of Critical Limb Ischemia

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII1. For individuals with combined inflow and

outflow disease with CLI, inflow lesions should be addressed first

2. If it is unclear whether hemodynamically significant inflow disease exists, intra-arterial pressure measurements across suprainguinal lesions should be measured before and after the administration of a vasodilator

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII 1. For individuals with combined inflow and outflow disease, in whom symptoms of CLI or infection persist after inflow revascularization, an outflow revascularization procedure should be performed

ACC/AHA Guidelines

86

Lower Limb Bypass Surgery

• Risk of MI ranges from 1.9 to 3.4%• Death 1.3 to 6%• Wound infection 10-30%• Scar-related neuropathic pain in 23% • 30% of grafts will require revision during their lifetime

Why?

High risk population

Widespread atherosclerotic disease

High incidence of diabetics thus the infection risk

87

Peripheral Arterial Disease: Surgical Treatment of Claudication

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

1. Individuals with claudication symptoms who have significant functional disability that is vocational or lifestyle limiting, who are unresponsive to exercise or pharmacotherapy, and who have a reasonable likelihood of symptomatic improvement

2. A preoperative cardiovascular risk evaluation should be taken

in those patients with lower extremity PAD in whom a major vascular surgical intervention is planned

ACC/AHA Guidelines

88

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII 1. Because the presence of more aggressive atherosclerotic occlusive disease is associated with less durable results in patients < 50 years of age, the effectiveness of surgical intervention in this population for intermittent claudication is unclear

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII 1. Surgical intervention is not indicated to prevent progression to limb-threatening ischemia in patients with intermittent claudication

Peripheral Arterial Disease: Surgical Treatment of Claudication

ACC/AHA Guidelines

89

Peripheral Arterial Disease: Surgical Treatment of Critical Limb ischemia

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII 1. For individuals with combined inflow and outflow

disease with CLI, inflow lesions should be addressed

first

2. For individuals with combined inflow and outflow

disease in whom symptoms of CLI or infection persist

after inflow revascularization, and outflow

revascularization procedure should be performed

ACC/AHA Guidelines

90

Peripheral Arterial Disease: Surgical Treatment of Critical Limb ischemia



1. Patients who have significant necrosis of the weight – bearing portions (in ambulatory patients), an uncorrectable flexion contracture, paresis of the extremity, refractory ischemic rest pain, sepsis, or a limited life time expectancy due to comorbid conditions should be evaluated for primary amputation of the leg

1. Surgical and endovascular intervention is not indicated in patients with severe decrements in limb perfusion in the absence of clinical symptoms of CLI

ACC/AHA Guidelines

91



Clinical Manifestations Diagnosis Indications

Treatment Options Prognosis

92

• Changing technology: PTA vs stent• Evolving medical therapy• Case series• Heterogenous lesions: stenosis vs occlusion• Heterogenous population: symptom status• Outcome measures: • Hemodynamic vs clinical patency

• CFA flow pattern• ABI• Thigh/brachial index

• absence of sxs• improvement of sxs

Endovascular Treatment: Interpreting Outcomes

93

Peripheral Arterial Disease: Prognosis

• The prognosis of patients with PAD is determined by an increased risk for cardiovascular ischemic event due to concomitant coronary artery disease and cerebrovascular artery disease

• The prognosis of the limb is determined by:

– The extend of the arterial disease

– The acuity of limb ischemia

– The feasibility and rapidity of restoring arterial circulation to the foot


94

Patients with chronic arterial occlusive disease and continued progression of the symptoms to CLI

Prognosis is very poor unless revascularization can be established

Patients with acute occlusive events

Prognosis is related to the rapidity and completeness of revascularization before the onset of irreversible ischemic tissue or nerve damage

Peripheral Arterial Disease: Prognosis

96

PAD and Relative Risk of Death

0

1

2

3

4

5

6

7

All Causes CardiovascularDisease

Coronary HeartDisease

Cause of Death

Rel

ativ

e R

isk

(95

% C

l)

3.11.9 – 4.9

5.93.0 – 11.4

6.62.9 –14.9

Adapted from Criqui et al N Engl J Med 1992; 326: 381-386

97

818

2332

39

86

0

20

40

60

80

100

ProstateCancer*

Hodgkin'sDisease

BreastCancer*

PAD ColorectalCancer*

Lung Cancer*

* American Cancer Society. Cancer Facts and Figures, 2000.† Criqui MH, et al. N Engl J Med. 1992;326:381-386.

Relative 5-Year Mortality RatesP

ati

en

ts (

%)

99

Peripheral Arterial Disease: Survival Curve

Criqui et al N Engl J Med 1992; 326: 381-386

100

5 Year Risk of Developing Ischemic Ulceration

0

10

20

30

40

50

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

ABI

Ris

k o

f Is

ch

emic

Ulc

erat

ion

(%

) DM Present DM Absent

Follow up of 1244 Claudicants over 15 years

Aquino, R. J Vasc Surg 2001; 34(6): 962

101

YearYear

McKenna et al Atherosclerosis 1991;87:119-128.

ABI: Predictor of Survival

20

30

40

50

60

70

80

90

100

0 2 4 6 8 10

Su

rviv

al (%

)

ABI >0.85ABI >0.85

ABI 0.4-0.85ABI 0.4-0.85

ABI <0.4ABI <0.4

102

Relative Risk of CV Mortality by ABI and CVD Status

Cardiovascular Health Study

0

5

10

15

Rela

tive R

isk (

95%

CI)

ABI ABI >>0.90.9 ABI <0.9

Relative 6-Year CV MortalityRelative 6-Year CV Mortality

†P<0.01 within groupings, Cox proportional hazards model.

CV Death includes death from CHD, MI, sudden death, or stroke.

CVD Present†

N=5714

ABI <0.9 ABI ABI >>0.90.9No CVD†

Adapted from Newman et al. Arterioscler Thromb Vasc. Biol. 1999;19:538-545

103

Age-Adjusted Mortality rates and number of deaths in men with possible, probable and No Intermittent claudication

Smith et al Circulation 1990;82(6): 1925 - 1931

Rates are for 1,000 person-yearsAll causes mortality include 13 deaths in the gropus without intermitent claudication in which the specific cause of death was unknowPercent, percentage of deaths attributed to each cause or group of causesTests for differences between possible or probable intermittent claudication and non intermittent claudication groups: *p < 0.001; †p <0.05; ‡p <0.01

peripheral arterial disease: simulation training curriculum

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