Diagnosis and Treatment of Peripheral Arterial Disease

高雄長庚醫院心臟內科傅懋洋教授

Leg Ulcers Differential Diagnosis• Vascular Arterial Atherosclerosis obliterans Thromboangiitis obliterans Hypertensive arteriolar Venous• Vasculitis• Diabetic Mellitus• Infection• Pressure (impaired sensation)• Hematological diseases• Neoplastic diseases

Leg Claudication

Unusual causesAortic dissection Temporal arteritisFibromuscular dysplasia Takayasu arteritisRetroperitoneal fibrosis Popliteal cystic diseaseRadiation fibrosis Popliteal entrapmentAbdominal coarctation Ergot intoxicationAortic neurofibromatosis TraumaPrimary artery tumor Miscellaneous

Peripheral Arterial Disease

• Atherosclerotic occlusion of the arteries to the legs• Important manifestation of systemic atherosclerosis• Prevalence : 12% ( Age adjusted)• Affect man and woman equally• Had the same risk of death as patient with CAD• The severity of PAD is closed associated with MI,

CVA and death from vascular causes

Atherosclerosis Obliterans

• Responsible to etiology in 50-90% of patients• Patients may have multiple risk factors• Two types of involvement• Patients with diffuse involvement have a high incidence of coronary artery disease and death from myocardial infarction

Chronic Occlusive Arterial Diseases

Prevalence of Peripheral Arterial Disease, Claudication and Associated Cardiovascular Diseases

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Risk of Death from All Causes and from Cardiovascular Causes in Patients with Peripheral Arterial Disease

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Atherothrombosis: a Generalized and Progressive ProcessAtherothrombosis: a Generalized and Progressive Process

NormalNormalFattyFattystreakstreak

FibrousFibrousplaqueplaque

Athero-Athero-scleroticscleroticplaqueplaque

PlaquePlaquerupture/rupture/fissure &fissure &

thrombosisthrombosis MIMI

IschemicIschemicstroke/*TIA stroke/*TIA

Critical leg Critical leg ischemiaischemia

Clinically silentClinically silent

CardiovascularCardiovasculardeathdeath

Increasing ageIncreasing age

Intermittent claudicationIntermittent claudication

UnstableUnstableanginaangina

*ACS, acute coronary syndrome; TIA, transient ischemic attack

Stable anginaStable angina

Major Clinical Manifestations of Atherosclerotic Disease

Major Clinical Manifestations of Atherosclerotic Disease

TIA, Ischemic stroke

Unstable angina pectorisQ-wave & none Q-wave MI

Renovascular diseaseRenovascular disease

- Cold sensation, numbness - Intermittent claudication - Rest pain, gangrene, amputation- Critical limb ischemia

- Cold sensation, numbness - Intermittent claudication - Rest pain, gangrene, amputation- Critical limb ischemia

Intestinal IschemiaIntestinal Ischemia

Erectile dysfunctionErectile dysfunction

Peripheral Arterial Occlusive Disease (PAOD)

重松宏 ( 東京大 ), Therapeut. Res., 13, 4099, 1992

HypertensionDM

IHDCVD

22.5%

49.7%

28.2%

23.2%

PAOD 與相關疾病之合併率PAOD 與相關疾病之合併率

PAOD

Associated Cardiovascular Conditions• History of MI/Angina• Recent onset or difficult to control H/T ( renovascular hypertension ) • Postprandial pain, weight loss, change in bowel habits ( mesenteric ischemia )• Impotence in man ( Leriche syndrome )• History of stroke / TIA

Atherosclerosis Obliterans

Peripheral Arterial Occlusive DiseasesPeripheral Arterial Occlusive Diseases

患者背景

糖尿病高血壓高脂血症老年人

血流量低下 機能低下 組織壞死

Fontaine I Fontaine II Fontaine III Fontaine IVFontaine I Fontaine II Fontaine III Fontaine IV

血小板

動脈管壁損傷

於損傷處聚集 形成血塊 管徑 50% 狹窄

面積 75% 狹窄

Resting Pain

IntermittentClaudication

NumbnessCold sensationRaynauld’s syndrome

管徑 60% 狹窄面積 82% 狹窄

Ulcer

Gangrene

Fontaine’sFontaine’s

ClassificationClassification

Weighted mean prevalence of intermittent claudication in large population-based studies

Weighted mean prevalence of intermittent claudication in large population-based studies

0

1

2

3

4

5

6

7

8

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

Age-group

Prev

alen

ce (

%)

* Overall prevalence for men and women aged 55~74: 4.5%

Thromboangiitis Obliterans Buerger Disease• Occurs in young ( 30 - 40 years old )• Man : women = 95 : 5• Heavy smoker• Affects small arteries and vein• Upper and lower extremities involvement• Progresses proximally• More prevalent in oriental population• Cessation of smoking will arrest it

Thromboangiitis ObliteransBuerger Disease

Differential Diagnosis Atherosclerosis Thromboangiitis

Artery large smallCourse slow rapidSymptoms less severe more severeClaudication calf, thigh, hip foot, archArm usually not often Phlebitis not may involveRevascularization possible notAmputation may occur often occurAssociated CAD often notDeath from MI often rare

Chronic Occlusive Arterial Diseases

Atherosclerosis Obliterans Risk Factors• Cigarettes smoking• Diabetic Mellitus• Hyperlipidemia• Hypertension• Family History• Oral contraceptives

Chronic Occlusive Arterial Diseases

PAODPAOD 的臨床診斷的臨床診斷PAODPAOD 的臨床診斷的臨床診斷自覺症狀 :

1. cold sensation ( 冷感 ), numbness( 酸麻 ), pain( 疼痛 )

2. Intermittent claudication ( 間歇性跛行 )

醫師診斷 :

1. 視診：下肢體表溫差、色差及毛髮生長狀況 2. 血管脈搏觸診： Dorsal pedis 、 Posterior tibial artery 、 Popliteal artery 、 Radial artery

3. 間歇性跛行問卷 4. 周邊血管超音波檢查 : ABI index (Ankle-Brachial Index)

5. PVR or PWV

6. Treadmill Exercise Tests

7. Angiography 或 MRI/MRA

Chronic Occlusive Arterial Diseases Manifestations• Claudication• Ischemia Resting pain Ischemic neuropathy Ulcerations Gangrene• Microcirculatory lesions• Impotency

Claudication• Sterotyped distress• Exercise - induced• Reproducible• Relieved by rest

Chronic Occlusive Arterial Diseases

Intermittent Claudication : 患者於步行 100~200 m 後，因下肢肌肉疼痛而無法繼續行走，但於坐下休息一會兒後，疼痛即自行消失

病患自覺症狀 (Subjective symptoms)

病患自覺症狀 (Subjective symptoms)

Pseudoclaudication• Exercise or position induced• Discomfort often dysthetic• Clumsiness may accompany• Specific position may relieve• Reset relief slow

Chronic Occlusive Arterial Diseases

Claudication Variants• ?Vasospastic • Pseudoclaudication Neurologic Myogenic

Chronic Occlusive Arterial Diseases

Arteries of the Pelvis and Lower ExtremityArteries of the Pelvis and Lower Extremity

Aorta or Iliac Artery

Femoral Artery or Branches

Popliteal Artery

Obstruction in:Obstruction in: Ischemia in:Ischemia in:

Buttock Hip Thigh

Thigh Calf

Calf Ankle Foot

Common Sites of ClaudicationCommon Sites of Claudication

Vascular Examination

• Pulses• Bruit• Color Changes• Trophic changes

Posterior tibial arteryPosterior tibial arteryPopliteal arteryPopliteal artery

PAODPAOD 的臨床診斷的臨床診斷 -- 血管脈搏觸診PAODPAOD 的臨床診斷的臨床診斷 -- 血管脈搏觸診

Dorsal pedisDorsal pedis

Grade system of pulses 0 = absent 1 = markedly decreased 2 = moderately decreased 3 = mildly decreased 4 = normal 5 = aneurysm( 0 - 4 : 2 = mildly decreased, 3 = normal, 4 = aneurysm )

The Arterial Examination

Elevation Dependence Test

Elevation: 60 degree for 60 seconds

Dependence: Venous filling time Dependent Rubor

Elevation Pallor 60 degrees elevation for 60 seconds

0 No pallor 60 1 Pallor 60 2 Pallor 30 - 60 3 Pallor under 30 4 Pallor leg level

The Arterial Examination

Venous Filling Time

0-15? Normal

15-30? Mild - good healing

30-45? Moderate - slow healing

>60? Severe - healing rare

The Arterial Examination

Arterial Vascular Laboratory

• Doppler signal• Pulse trace• Segmental systolic pressure• Segmental pressure indices• Exercise • Color flow mapping• Duplex scan• Arteriography

Ankle Brachial Index

Ankle Systolic Blood Pressure

Brachial Systolic Blood Pressure

= ABI

非侵入性動脈硬化篩檢儀 (VP-1000)非侵入性動脈硬化篩檢儀 (VP-1000)

ABI : stenosis of lower limb.

ABI =Ankle Systolic Blood Pressure

Brachial Systolic Blood Pressure

PWV =Distance between two sites

Pulse wave Transmit Time(PTT)

PWV : Arterial Stiffness

< 0.9

>1400cm/s

Segmental Systolic Pressure

Right ABIHigher right-ankle pressure

Higher arm pressure

Left ABIHigher left-ankle pressure

Higher arm pressure

Interpretation of ABI

Noncompressible

Normal

Mild-to-moderate peripheralarterial disease

Severe peripheral arterialdisease

> 1.30

0.91–1.30

0.41–0.90

0.00–0.40

Left-armsystolic pressure

Right-armsystolic pressure

DP

PT

Right-anklesystolic pressure

DP

PT

Left-anklesystolic pressure

Measurement of the Ankle–Brachial Index (ABI)Measurement of the Ankle–Brachial Index (ABI)

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Symptoms SLP, mmHg ABI

Claudication 70 - 100 0.5 - 0.8 Rest pain < 50 0.3 Gangrene 0 - 30 < 0.2SLP = Segmental limb pressureABI = Ankle brachial index

The Arterial Examination

Angiography

Uncomplicated Claudication

Natural History

Authors Cases Unchanged Worse Amputation Followed

Imperato 104 82% 22% 6% 5 - 8 yrs

Richards 106 69% 24% 7% 5 + yrs

Juergens 104 93% 7% 7% 5 + yrs

Framingham 4% 8.3 yrs

Boyd 1440 7% 5 + yrs

Uncomplicated Occlusive Femoral Artery 5 - 9 years Follow Up

Diabetics Non-diabeticsUlceration 12% 5%Gangrene 40% 5%Amputation 27% 7%5 yr survival 54% 75%9 yr survival 38% 59%

Chronic Occlusive Arterial Diseases

Adapted from Weitz Jl. Circulation. 1996;94:3026-49.

Population >55 y

Intermittent claudication40%

PAD outcomes

Cardiovascular

morbidity/mortality

Worsening claudication

16%

Leg bypass surgery

7%

Major amputation

4%

Nonfatal events

(MI/stroke) 20%

Mortality 30%

Critical leg ischemia

10%

Asymptomatic 50%

Stable claudication 73%

(5-year outcomes)

Clinical Outcomes in Patients With PAODClinical Outcomes in Patients With PAOD

Atherosclerosis Obliterans

Conservative Treatment

Definite value Probable value No proven value

General measures Control of Fibrinolytic therapyStop smoking Diabetics Mellitus Anticoagulant RxExercise regimens Hypertension Vasodilators Hyperlipidemia Calcium blocker Antiplatelet Rx ?

No symptoms Symptoms or signs at rest Disabled for occupation

Conservative treatment

Symptoms improved Progression Surgery or stabilize of symptoms Angioplasty

Atherosclerosis Obliterans

Foot CareTrauma causes more than 50% of amputation Avoid trauma: mechanical, thermal, chemical Keep foot warm, clean, dry Nails: trim straight across Callouses: podiatry whetstone Dry skin: simple emollients Socks: comfortable, absorbent Shoes: comfortable, break in Tinea: control Wound: prompt care

Chronic Occlusive Arterial Diseases

Claudication

Role of Exercise 129 patients 30 - 60 min/day, 3x week Results of 3 months % Treadmill Location improvement Aortic-iliac 205 Distal 247 Combined 230

Role of Cigarette Smoking at 5 years

Amputation %

Aortic-iliac Femoral

Continued 5.9 14.8

Ceased 0 0

Claudication

Aggressive Treatments• Percutaneous transluminal angioplasty• Atherectomy: rotational directional• Intraarterial stent• Laser angioplasty• Surgical revascularization• Sympathectomy ( periarterial )• Amputation

Atherosclerosis Obliterans

Percutaneous Transluminal Angioplasty

Peripheral Arterial Stent

Percutaneous Transluminal Angioplasty

Results

Iliac Femo-PoplitealImmediate 85-90% 80-90%1 year 75-80% 60-65%2 year 65-75% 50-55%5 year 50% -

Indications for Surgery• Limiting claudication• Progression of symptoms• Resting pain• Ulcer and gangrane change• Distal microembolization

Atherosclerosis Obliterans

Atherosclerosis Obliterans Drug TreatmentModification of risk factors: Smoking cessation Treatment of Hyperlipidemia Treatment of Diabetic Mellitus Treatment of Hypertension• Antiplatelet drug therapy Aspirin Ticlopidine Clopidogrel• Vasodilator drug• Pentoxifyline• Cilostazol• Naftidrofuryl• Levocarnitine and Propionyl Levocarnitine• Prostagladins

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Drug Therapy for Claudications

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Drug Therapy for Claudications

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Cilostazol• Inhibit phosphodiesterase type 3

• Increase intrcellular concentration of cyclic AMP

• Inhibit platelet aggregation

• Inhibit formation of arterial thrombi

• Inhibit vascular smooth muscle proliferation

• Produce vasodilation

Drugs Therapy for Claudications

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Drugs Therapy for Claudications

Side Effects of Cilostazol

• Headache

• Transient diarrhea

• Palpitation

• Dizziness

Hiatt,W.R.: N Engl J Med, 344(21), 1608, 2001

Evaluation of Patients in Whom PAD is Suspected

Evaluation and Treatment of Patients with Proved Peripheral Arterial Disease

Peripheral arterial diseasePeripheral arterial disease

Assess cardiovascular risk factors

Assess cardiovascular risk factors

Assess severity of claudication Treadmill MWD and PFWD SF-36 and WIQ questionnaires

Assess severity of claudication Treadmill MWD and PFWD SF-36 and WIQ questionnaires

Critical leg ischemiaCritical leg ischemia

Risk-factor modification Smoking cessation LDL cholesterol < 100 mg/dl Glycosylated hemoglobine < 7.0% Blood pressure < 130/85 mmHg Angiotensin-converting- enzyme inhibition Antiplatelet therapy Aspirin or clopidogrel

Risk-factor modification Smoking cessation LDL cholesterol < 100 mg/dl Glycosylated hemoglobine < 7.0% Blood pressure < 130/85 mmHg Angiotensin-converting- enzyme inhibition Antiplatelet therapy Aspirin or clopidogrel

Therapy for claudication Supervised exercise CilostazolCilostazol

Therapy for claudication Supervised exercise CilostazolCilostazol

Symptoms improve

Symptoms improve

Symptoms worsen

Symptoms worsen

ContinueContinue Localize the lesion Hemodynamic localization Duplex ultrasonography Magnetic resonance angiography Conventional angiography

Localize the lesion Hemodynamic localization Duplex ultrasonography Magnetic resonance angiography Conventional angiography

Revascularization

Angioplasty

Bypass surgery

Revascularization

Angioplasty

Bypass surgeryHiatt WR. N Engl J Med, Vol. 344, No. 21, May, 2001

Acute Arterial Occlusion

Acute Arterial Occlusion

Pulseless Pale Pain Paresthesia Paraplegia

Acute Arterial Occlusion

PresentationAsymptomatic loss of pulse

Reduction of claudication distance

Tissue ischemia

Acute Arterial Occlusion

Determinants of PresentationSite of occlusion

Status of collaterals

Status proximal, distal beds

Subsequent clot propagation

Suddenness of occlusion

Duration of ischemia

Physical FiningsAbsent pulse

Distal ischemia: of varying degree

Skin: cool, pale, mottled

Muscle: weakness, tender

Nerve: sensory? motor loss

Acute Arterial Occlusion

Etiology

Trauma

Embolism

Thrombosis in situ

Acute Arterial Occlusion

Acute Arterial OcclusionCommon Causes

Thrombosis Occlusive arterial disease Aneurysmal arterial disease Embolism Atrial fibrillation, Left atrial thrombus ( MS ) Ventricular thrombus ( MI, cardiomyopathy, aneurysm) Arterial aneurysm Arterial occlusive diseases Endocarditis Prosthetic valve

Acute Arterial OcclusionUnusual Embolic Sources

CardiacMyxomaCardioversionCatheter, etcProsthetic materials

Paradoxical venous Miscellaneous:

Air, BulletsTumorParasites

Acute Arterial OcclusionAcute Arterial Occlusion ThrombosisUsual causes:

Atherosclerotic occlusive diseases

Atherosclerotic aneurysmal diseases

Dissection of aorta

Unusual causes:

Degenerative, dysplatic arteriopathy

Fibromuscular dysplasia

Ehler?Danlos syndrome

Cystic diseases of femoral, popliteal artery

Acute Arterial OcclusionAcute Arterial Occlusion ThrombosisUnusual causes:

Inflammatory Thromboangiitis obliteransGiant cell arteritisNecrotizing arteritis

Polyarteritis nodosaSystemic lupus erythematosus

HematologicPolycythemia vera, DysproteinemiaThrombocytosis, DIC

Acute Arterial OcclusionThrombosis

MechanicalLocal traumaInvasive diagnostic, therapeutic procedureUnusual muscular effort ( anterior compartment syndrome )Entrapment by bone, muscle, ligamentThoracic outlet syndrome

MiscellaneousMaligancyInfection, debilityCongestive heart failure, ShockErgotism

Acute Arterial OcclusionDifferential Diagnosis

Acute aortic dissectionChest painBranch vessel deficitsWide mediastinum

Low cardiac outputFour limbs involveHypotension, tachycardiaClinical settings

Ergot intoxication

Always ask

Acute Arterial Occlusion

Differential DiagnosisDeep vein Acute arterialthrombosis occlusion

Temp. Normal, increased Decreased

Color Normal, cyanotic Pallor

Edema Present Absent

Pulses Present Absent

V. pattern Distended Collapse

Acute Arterial OcclusionThrombosis vs Embolism

Thrombosis in situ

History: Antecedent claudication

Examinations: Proximal vessels or other limb show

occlusive disease Embolism

Exclude thrombosis in situ

Examine: test for embolic sourceAneurysmal disease can occlude locally throw emolic distally

Embolism may be superimposed on thrombosis

Acute Arterial Occlusion

Surgical Approach Thrombosis

Occlusive disease or aneurysm: often requireArteriographyReconstructive surgery

EmbolismWith good inflow, runoff, no proximal aneurysm

Arteriography not needLocal anesthesiaFogarty catheter removal feasible

Acute Arterial Occlusion

Initial Therapy Treat underlying disease Protect collaterals Heparinization immediately Thrombolytic therapy? Protect from trauma

mechanialthermalchemical

Therapeutic Decision Risk of underlying diseases Urgency of surgery Risk of surgery

Risk of amputation

Role of forgarty catheter

Acute Arterial OcclusionAcute Arterial Occlusion

Role of Anticoagulants Prevent clot propagation Control embolic source Minimize venous

thromboembolism

Acute Arterial Occlusion

Paradoxical Emolism

Proved:

Venous clot lodged in the intracardiac

defect at autopsy Presumptive:

Venous thrombosis / embolism

Intracardiac shunt allowing R to L shunt

Arterial embolism without evidence of

origin in left side of heart or systemic

circulation

The Arterial Examination

Pulses

Bruits

Aneurysms

ExtensionsAllen testPerfusion test ( Elevation dependance test )Exercise testThoracic outlet maneuvers

The Arterial Examination

Localization Site Symptoms Aorta Buttocks, back, thighs, calves Iliac Buttocks, thigh, calf Int. Iliac Buttocks C. Femoral Thighs S. Femoral 2/3 calf, foot Popliteal 1/3 calf, foot Tibial Foot, ankle

The Arterial Examination

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