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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
Harvard Medical School
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
Harvard Medical School
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
Harvard Medical School
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
Harvard Medical School
Outcomes in PVD PatientsOutcomes in PVD PatientsOutcomes in PVD PatientsOutcomes in PVD Patients
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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
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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.
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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..
Harvard Medical School
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
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PVD EtiologyPVD EtiologyPVD EtiologyPVD Etiology
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
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PVD EtiologyPVD EtiologyPVD EtiologyPVD Etiology
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
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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).
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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
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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. .
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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
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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
Harvard Medical School
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
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Noninvasive Work-upNoninvasive Work-up
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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
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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
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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
Harvard Medical School
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
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Doppler Waveform Analysis: Hemodynamic Doppler Waveform Analysis: Hemodynamic InformationInformation
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.
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Doppler Waveform Analysis: Hemodynamic Doppler Waveform Analysis: Hemodynamic InformationInformation
Doppler Waveform Analysis: Hemodynamic Doppler Waveform Analysis: Hemodynamic InformationInformation
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
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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
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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
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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
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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
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MRA vs. DSAMRA vs. DSAMRA vs. DSAMRA vs. DSA
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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
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MRIMRIMRIMRI
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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
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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
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CTA of PVDCTA of PVDCTA of PVDCTA of PVD
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CTA of PVDCTA of PVDCTA of PVDCTA of PVD
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
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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
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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.
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Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)
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
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Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)Digital Subtraction Angiography (DSA)
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
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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
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Suggested Algorithm for Work-upSuggested Algorithm for Work-upSuggested Algorithm for Work-upSuggested Algorithm for Work-up
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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
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Workup-Take-homeWorkup-Take-homeWorkup-Take-homeWorkup-Take-home
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
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Workup-Take-homeWorkup-Take-homeWorkup-Take-homeWorkup-Take-home
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