harvard medical school duane s. pinto, m.d. director peripheral angiographic core laboratory, timi...

Harvard Medical School

Duane S. Pinto, M.D.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 ClaudicationIntermittent ClaudicationDiagnosis and Work-upDiagnosis and Work-up


PAD is a common disorderPAD is a common disorderPAD is a common disorderPAD is a common disorder

Occurs in approximately 1/3 of patientsOccurs in approximately 1/3 of patients Over age 70Over age 70 Over age 50 who smoke or have DMOver age 50 who smoke or have DM

Strong association with CADStrong association with CAD Obvious associated risk of stroke, MI, cardiovascular deathObvious associated risk of stroke, MI, cardiovascular death

Progressive disease in 25% with progressive intermittent Progressive disease in 25% with progressive intermittent claudication/limb threatening ischemiaclaudication/limb threatening ischemia

OutcomesOutcomes Impaired QoLImpaired QoL Limb Loss Limb Loss Premature MortalityPremature Mortality


Risk Factors for PVD: Framingham Heart StudyRisk Factors for PVD: Framingham Heart StudyRisk Factors for PVD: Framingham Heart StudyRisk Factors for PVD: Framingham Heart Study

Reduced IncreasedReduced Increased

SmokingSmoking

DiabetesDiabetes

HypertensionHypertension

HypercholesterolemiaHypercholesterolemia

HyperhomocysteinemiaHyperhomocysteinemia

FibrinogenFibrinogen

C- Reactive ProteinC- Reactive Protein

AlcoholAlcohol

Relative Risk .5 1 2 3 4 5 6Relative Risk .5 1 2 3 4 5 6

Mean follow-up 38 yearsMean follow-up 38 years


PAD is Associated with Poor Outcomes PAD is Associated with Poor Outcomes PAD is Associated with Poor Outcomes PAD is Associated with Poor Outcomes

Annual Annual IncidenceIncidence

PrevalencePrevalence Mortality/yr Mortality/yr (%)(%)

StrokeStroke 0.730.73 4.64.6 2828

TIATIA 0.500.50 4.94.9 6.36.3

ACSACS 2.32.3 12.612.6 4545

PADPAD 8-128-12 4-25%4-25%

Criqui M, et al. Circulation 1985; 71:510Criqui M, et al. Circulation 1985; 71:510


Outcomes in PVD PatientsOutcomes in PVD PatientsOutcomes in PVD PatientsOutcomes in PVD Patients


Diagnostic ModalitiesDiagnostic ModalitiesDiagnostic ModalitiesDiagnostic Modalities

HistoryHistory PhysicalPhysical Ankle Brachial Index (ABI)Ankle Brachial Index (ABI) Noninvasive vascular laboratoryNoninvasive vascular laboratory Angiography: MRA, CT, DSAAngiography: MRA, CT, DSA


Initial AssessmentInitial AssessmentInitial AssessmentInitial Assessment

Identifying risk factors and symptomsIdentifying risk factors and symptoms Pulse palpability Pulse palpability Further assessment relies on functional non-Further assessment relies on functional non-

invasive testing and radiological imaging invasive testing and radiological imaging Determine not only the anatomic, but also the Determine not only the anatomic, but also the

physiological aberration of peripheral vascular physiological aberration of peripheral vascular flow. flow.


Intermittent ClaudicationIntermittent ClaudicationIntermittent ClaudicationIntermittent Claudication

Intermittent claudication Intermittent claudication (derived from the Latin word for (derived from the Latin word for limp) limp)

A reproducible discomfort of a defined group of A reproducible discomfort of a defined group of muscles that is induced by exercise and relieved with muscles that is induced by exercise and relieved with rest.rest.

Supply Supply ≠ ≠ DemandDemand

Location depends upon the location of the disease.Location depends upon the location of the disease. Buttock, thigh, calf or foot claudication, either Buttock, thigh, calf or foot claudication, either

singly or in combinationsingly or in combination..


PVD EtiologyPVD EtiologyPVD EtiologyPVD Etiology

Large arteriesLarge arteries Atherosclerosis Atherosclerosis ThromboembolismThromboembolism TraumaTrauma Arteritis of various types including Arteritis of various types including

Buerger’s diseaseBuerger’s disease Fibromuscular dysplasiaFibromuscular dysplasia Takayasu’sTakayasu’s



Medium and small Medium and small vessel occlusionsvessel occlusions

DiabetesDiabetes Chronic recurrent Chronic recurrent

trauma trauma Multiple small Multiple small

emboliemboli Collagen vascular Collagen vascular

diseasesdiseases

Dysproteinemias Dysproteinemias Polycythaemia Polycythaemia

veravera Pseudoxanthoma Pseudoxanthoma

elasticumelasticum Drug Reaction Drug Reaction VasospasmVasospasm



Specific to certain Specific to certain anatomical sitesanatomical sites

Cystic adventitial Cystic adventitial disease of the disease of the popliteal artery popliteal artery

Popliteal artery Popliteal artery entrapmententrapment

Iliac endofibrosis Iliac endofibrosis (cyclists)(cyclists)

Various neurovascular Various neurovascular compression syndromes compression syndromes affecting the upper limbaffecting the upper limb

Cervical ribCervical rib Costoclavicular syndromeCostoclavicular syndrome Scalenus tunnel Scalenus tunnel

syndromesyndrome Hyperabduction syndromeHyperabduction syndrome Quadrangular space Quadrangular space

syndrome syndrome


PVD Differential DiagnosisPVD Differential DiagnosisPVD Differential DiagnosisPVD Differential Diagnosis

Deep venous thrombosisDeep venous thrombosis Musculoskeletal disorders Musculoskeletal disorders

OAOA Restless leg syndromeRestless leg syndrome

Peripheral neuropathyPeripheral neuropathy Spinal Stenosis (pseudoclaudication)Spinal Stenosis (pseudoclaudication)

Worse with erect posture (lordosis) better sitting or Worse with erect posture (lordosis) better sitting or lying down. lying down.

Can find relief by leaning forward and straightening Can find relief by leaning forward and straightening the spine (pushing a shopping cart or leaning against the spine (pushing a shopping cart or leaning against a wall).a wall).


Differential Diagnosis of Intermittent ClaudicationDifferential Diagnosis of Intermittent ClaudicationDifferential Diagnosis of Intermittent ClaudicationDifferential Diagnosis of Intermittent Claudication

Intermittent Intermittent ClaudicationClaudication

Venous Venous ClaudicationClaudication

Neurogenic Neurogenic ClaudicationClaudication

Quality of painQuality of pain CrampingCramping "Bursting""Bursting" Electric shock-likeElectric shock-like

OnsetOnset Gradual, consistentGradual, consistent Gradual, can be Gradual, can be immediateimmediate

Can be immediate, Can be immediate, inconsistentinconsistent

Relieved byRelieved by Standing stillStanding still Elevation of legElevation of leg Sitting down,Sitting down,bending forwardbending forward

LocationLocation Muscle groups Muscle groups (buttock, thigh, calf)(buttock, thigh, calf)

Whole legWhole leg Poorly localized,Poorly localized,can affect whole legcan affect whole leg

Legs affectedLegs affected Usually oneUsually one Usually oneUsually one Often bothOften both


Location, Location, Location!Location, Location, Location!Location, Location, Location!Location, Location, Location!

Buttock/hipButtock/hip Usually indicates aortoiliac occlusive disease (Leriche's Usually indicates aortoiliac occlusive disease (Leriche's

syndrome)syndrome) Some cases, thigh claudication too Some cases, thigh claudication too Question diagnosis of bilateral disease if erectile dysfunction Question diagnosis of bilateral disease if erectile dysfunction

is not presentis not present

ThighThigh Occlusion of the common femoral artery leads to Occlusion of the common femoral artery leads to

claudication in the thigh, calf, or both.claudication in the thigh, calf, or both.

CalfCalf Symptoms in upper 2/3 is usually due to SFASymptoms in upper 2/3 is usually due to SFA Lower 1/3 is due to popliteal diseaseLower 1/3 is due to popliteal disease. .


PVD HistoryPVD HistoryPVD HistoryPVD History

Use of the history alone to detect peripheral Use of the history alone to detect peripheral arterial disease will result in missing up to arterial disease will result in missing up to 90 90 percentpercent of cases. of cases.

Asymptomatic patients with abnormal ABI Asymptomatic patients with abnormal ABI have 50% increased risk of cardiovascular have 50% increased risk of cardiovascular complicationscomplications

Hirsch AT, et al. JAMA 2001; 286: 1317Hooi JD, et al. J Clin Epidem 2004; 57:294


Physical ExamPhysical ExamPhysical ExamPhysical Exam

Trophic SignsTrophic Signs Skin atrophy, thickened nails, hair loss, Skin atrophy, thickened nails, hair loss,

dependent rubordependent rubor Ulceration, gangreneUlceration, gangrene

Pulse examPulse exam May miss more than 50%May miss more than 50%

Elevation and dependency testElevation and dependency test

Criqui M, et al. Circulation, 1985: 71; 516-521


Physical Exam: Elevation and Dependency TestPhysical Exam: Elevation and Dependency TestPhysical Exam: Elevation and Dependency TestPhysical Exam: Elevation and Dependency Test

Halperin, Throm Res. 2002; 106: V303-311

Color Return(s)Color Return(s) Venous Filling(s)Venous Filling(s)

NormalNormal 1010 10-1510-15

Adequate Adequate CollateralsCollaterals

15-2515-25 15-3015-30

Severe IschemiaSevere Ischemia >35>35 >40>40


Noninvasive Work-upNoninvasive Work-up


Ankle Brachial IndexAnkle Brachial IndexAnkle Brachial IndexAnkle Brachial Index

Cornerstone of lower extremity vascular evaluationCornerstone of lower extremity vascular evaluation Blood pressure cuffs, DopplerBlood pressure cuffs, Doppler Ankle (DP or PT) to brachial artery pressureAnkle (DP or PT) to brachial artery pressure

NormalNormal 0.960.96

ClaudicationClaudication 0.50-0.950.50-0.95

Rest PainRest Pain 0.21-0.490.21-0.49

Tissue lossTissue loss 0.200.20

Significant changeSignificant change 0.15 or more0.15 or more


LimitationsLimitationsLimitationsLimitations

Noncompressible vesselsNoncompressible vessels DiabetesDiabetes Renal FailureRenal Failure ABI >1.5ABI >1.5 Use toe-brachial indexUse toe-brachial index

Normal >0.7Normal >0.7 Rest pain <0.2Rest pain <0.2

Subclavian/Brachiocephalic Occlusive diseaseSubclavian/Brachiocephalic Occlusive disease


Segmental PressuresSegmental PressuresSegmental PressuresSegmental Pressures

Pneumatic cuffs at multiple Pneumatic cuffs at multiple levelslevels

Doppler pressure at pedal Doppler pressure at pedal arteryartery

Drop >30 mm Hg between Drop >30 mm Hg between levelslevels

Drop >20 mm Hg between Drop >20 mm Hg between limbslimbs

Reflects status of artery Reflects status of artery above drop in pressureabove drop in pressure

Inaccurate with calcified Inaccurate with calcified vesselsvessels

Rose SC. J Vasc Interv Radiol. 2000; 11:1107-1114


Duplex DopplerDuplex DopplerDuplex DopplerDuplex Doppler

Non-invasive method of evaluating the blood Non-invasive method of evaluating the blood vessels using sound waves, similar to vessels using sound waves, similar to ultrasonography and echocardiography.ultrasonography and echocardiography.

Can obtain both anatomic and hemodynamic Can obtain both anatomic and hemodynamic information. information.

Anatomical detail Anatomical detail vessel wallvessel wall intraluminal obstructive lesionsintraluminal obstructive lesions perivascular compressive structuresperivascular compressive structures


Doppler Waveform Analysis: Hemodynamic Doppler Waveform Analysis: Hemodynamic InformationInformation


Sensitivity of 92.6% and Sensitivity of 92.6% and specificity of 97% specificity of 97% (angiography gold (angiography gold standard) standard)

Inaccurate at adductor Inaccurate at adductor canal and the aorto-iliac canal and the aorto-iliac regions. regions.

95% accuracy in the 95% accuracy in the detection of bypass graft detection of bypass graft stenosis, but can stenosis, but can overestimate stenosis.overestimate stenosis. Polack JF. Duplex Doppler in peripheral arterial disease. Radiol

Clin N Amer 1995; 33 : 71-88.




Qualitative Qualitative assessment of assessment of waveform analysiswaveform analysis

Simple EquipmentSimple Equipment Not affected by Not affected by

medial calcinosismedial calcinosis Supplements Supplements

segmental pressuressegmental pressures


Pulse Volume RecordingsPulse Volume RecordingsPulse Volume RecordingsPulse Volume Recordings

Pneumatic Cuffs at Pneumatic Cuffs at Multiple LevelsMultiple Levels

Inflated to 65 mm HgInflated to 65 mm Hg Extremity Volume Extremity Volume

Increases in SystoleIncreases in Systole Changes pressure Changes pressure

in cuffin cuff

Waveform AnalysisWaveform Analysis Not Impacted by Not Impacted by

CalcificationCalcification


Pulse Volume RecordingsPulse Volume RecordingsPulse Volume RecordingsPulse Volume Recordings

AdvantangesAdvantanges Widely availableWidely available CheapCheap ReproducibleReproducible

DisadvantagesDisadvantages Technician dependentTechnician dependent Time ConsumingTime Consuming Detection of Detection of

Collaterals is lowCollaterals is low Presence of gas and Presence of gas and

calcification degrade calcification degrade imagesimages


Is this enough?Is this enough?Is this enough?Is this enough?

Noninvasive lab documents presence and Noninvasive lab documents presence and severity of diseaseseverity of disease

No comprehensive anatomic informationNo comprehensive anatomic information No ability to plan interventionsNo ability to plan interventions


Radiologic Imaging: MRA and CTARadiologic Imaging: MRA and CTARadiologic Imaging: MRA and CTARadiologic Imaging: MRA and CTA

DSA (conventional angiography) remains the DSA (conventional angiography) remains the gold standard for evaluation of PVDgold standard for evaluation of PVD

Newer modalities that match its accuracy are Newer modalities that match its accuracy are rapidly evolvingrapidly evolving

It is a matter of time before imaging replaces It is a matter of time before imaging replaces DSA, with the invasive angiographic DSA, with the invasive angiographic techniques reserved for interventional techniques reserved for interventional procedures procedures


MRA vs. DSAMRA vs. DSAMRA vs. DSAMRA vs. DSA


MRA: Current TechniqueMRA: Current TechniqueMRA: Current TechniqueMRA: Current Technique

3D gradient echo (fast 3D gradient echo (fast acquisition)acquisition)

Gadolinium EnhancedGadolinium Enhanced 20-40 cc 20-40 cc Automated Scan delayAutomated Scan delay

Renal arteries to toesRenal arteries to toes Stepping table or bolus chaseStepping table or bolus chase 45-min exam45-min exam


MRIMRIMRIMRI


Limitations of MRILimitations of MRILimitations of MRILimitations of MRI

Uncooperative patientUncooperative patient ClaustrophobiaClaustrophobia Metal artifactMetal artifact Pacemakers/ICDsPacemakers/ICDs Lack of visualization of Lack of visualization of

calciumcalcium


CTA of PVDCTA of PVDCTA of PVDCTA of PVD

Multidetector CT scanner Multidetector CT scanner necessary (4+) necessary (4+)

Many hospitals now have 64 SliceMany hospitals now have 64 Slice Iodinated contrast volume similar to Iodinated contrast volume similar to

conventional angiography conventional angiography 80-150 cc80-150 cc Automated Scan DelayAutomated Scan Delay

Renal arteries to anklesRenal arteries to ankles 20-minute exam20-minute exam High powered post processing High powered post processing

software crucialsoftware crucial



Large volumes of data are Large volumes of data are generated via CTA studies generated via CTA studies and displayed in various and displayed in various formats to refine the formats to refine the analysis of study resultsanalysis of study results

Maximum Intensity Maximum Intensity Projection -MIP (most Projection -MIP (most common)common)

Shaded surface displayShaded surface display 3D Volume rendering 3D Volume rendering


CT LimitationsCT LimitationsCT LimitationsCT Limitations

With significant and dense With significant and dense calcifications, a false diagnosis calcifications, a false diagnosis of patency can result. of patency can result.

Uncooperative patientUncooperative patient PregnancyPregnancy Bad PumpBad Pump Inconsistent pedal vessel Inconsistent pedal vessel

visualizationvisualization Renal failure/contrast allergyRenal failure/contrast allergy


Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)

Gold standard of arterial imagingGold standard of arterial imaging Has almost totally replaced conventional cut film Has almost totally replaced conventional cut film

angiographyangiography

Compares a pre contrast image with a post contrast Compares a pre contrast image with a post contrast image using a computer, and "subtracts" elements image using a computer, and "subtracts" elements common to both. common to both.

Prevents images of objects like bones etc from Prevents images of objects like bones etc from obscuring vascular details. obscuring vascular details.

Contrast resolution is improved through use of image Contrast resolution is improved through use of image enhancement software.enhancement software.



Radiation exposure and contrast volumes are Radiation exposure and contrast volumes are lower than conventional angiographylower than conventional angiography

Images are immediately available for review.Images are immediately available for review. Images are stored in digital format on Images are stored in digital format on

computerized data storage media computerized data storage media Interventional procedures can be performedInterventional procedures can be performed



Drawbacks precluding use as a Drawbacks precluding use as a screening modalityscreening modalityTechnique is invasive and expensive. Technique is invasive and expensive. Requires arterial punctureRequires arterial punctureLonger study than CTLonger study than CTContrast nephrotoxicity Contrast nephrotoxicity


Medical Treatments for PADMedical Treatments for PADMedical Treatments for PADMedical Treatments for PAD

TreatmentTreatment EffectEffect

Smoking cessationSmoking cessation 10-year mortality ↓ 54% to 18%;10-year mortality ↓ 54% to 18%;at 7 years, rest pain drops from 16% to 0%* at 7 years, rest pain drops from 16% to 0%*

Antiplatelet agentAntiplatelet agent 22%↓ in vascular events;22%↓ in vascular events;possible increase in walking distancepossible increase in walking distance

Diabetes control Diabetes control RR=0.94 (0.8 - 1.1) for mortality;RR=0.94 (0.8 - 1.1) for mortality;RR=0.51 (0.01 - 19.64) for amputationRR=0.51 (0.01 - 19.64) for amputation

BP to <140/85 mm HgBP to <140/85 mm Hg RR=0.87 (0.81 - 0.94) for mortality; effect on PAD not RR=0.87 (0.81 - 0.94) for mortality; effect on PAD not knownknown

ACE inhibitors ACE inhibitors RR=0.73 (0.61 - 0.86) for MI, stroke, or CV deathRR=0.73 (0.61 - 0.86) for MI, stroke, or CV death

Exercise programExercise program 24% ↓ in CV mortality;24% ↓ in CV mortality;150% further walking distance150% further walking distance

Cholesterol decreaseCholesterol decrease RR=0.81 (0.72 - 0.87) for MI, stroke, or revascularization; RR=0.81 (0.72 - 0.87) for MI, stroke, or revascularization; no clinical benefit in PADno clinical benefit in PAD††

Cilostazol Cilostazol significant ↑ in walking distancesignificant ↑ in walking distance

*Survival Bias*Survival Bias††Excepting StrokeExcepting Stroke


Suggested Algorithm for Work-upSuggested Algorithm for Work-upSuggested Algorithm for Work-upSuggested Algorithm for Work-up


Workup-Take-homeWorkup-Take-homeWorkup-Take-homeWorkup-Take-home

Noninvasive Vascular Lab is first line Noninvasive Vascular Lab is first line evaluation in nonacute patientsevaluation in nonacute patients

ABI is easy screening testABI is easy screening test Beware noncompressible vessels in renal failure Beware noncompressible vessels in renal failure

and diabetesand diabetes Segmental limb pressures often combined Segmental limb pressures often combined

with doppler waveform anlaysiswith doppler waveform anlaysis Not sufficient to plan interventionNot sufficient to plan intervention



MRA indicated for intervention planningMRA indicated for intervention planning MRA (gadolinium enhanced) provides MRA (gadolinium enhanced) provides

excellent renal to pedal imagingexcellent renal to pedal imaging Surpasses CT in the footSurpasses CT in the foot Overestimation of stenoses in small vesselsOverestimation of stenoses in small vessels Limited by metal artifact, magnetic field, and Limited by metal artifact, magnetic field, and

length of studylength of study



CTA indicated for intervention planningCTA indicated for intervention planning CTA provides excellent renal to ankle CTA provides excellent renal to ankle

imagingimaging Pedal imaging poorPedal imaging poor

Soft tissues and bone also imagedSoft tissues and bone also imaged Small vessel calcification is limitationSmall vessel calcification is limitation

harvard medical school duane s. pinto, m.d. director peripheral angiographic core laboratory, timi...

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dsa slide

ischemia progressive

limp intermittent claudication

pvd patients

foot claudication

small vessel occlusions