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Duane S. Pinto, M. D. Director Peripheral Angiographic Core Laboratory, TIMI Data Coordinating Center Duane S. Pinto, M. D. Director Peripheral Angiographic Core Laboratory, TIMI Data Coordinating Center Director, Cardiology Fellowship Training Program Interventional Cardiologist Beth Israel Deaconess Medical Center Assistant Professor of Medicine, Harvard Medical School Intermittent Claudication Diagnosis and Work-up Harvard Medical School

PAD is a common disorder § Occurs in approximately 1/3 of patients § Over PAD is a common disorder § Occurs in approximately 1/3 of patients § Over age 70 § Over age 50 who smoke or have DM § Strong association with CAD § Obvious associated risk of stroke, MI, cardiovascular death § Progressive disease in 25% with progressive intermittent claudication/limb threatening ischemia § Outcomes § § § Impaired Qo. L Limb Loss Premature Mortality Harvard Medical School

Risk Factors for PVD: Framingham Heart Study Reduced Increased Smoking Diabetes Hypertension Hypercholesterolemia Hyperhomocysteinemia Risk Factors for PVD: Framingham Heart Study Reduced Increased Smoking Diabetes Hypertension Hypercholesterolemia Hyperhomocysteinemia Fibrinogen Mean follow-up 38 years C- Reactive Protein Alcohol Relative Risk . 5 1 2 3 4 5 6 Harvard Medical School

PAD is Associated with Poor Outcomes Stroke Annual Incidence 0. 73 Prevalence Mortality/yr (%) PAD is Associated with Poor Outcomes Stroke Annual Incidence 0. 73 Prevalence Mortality/yr (%) 4. 6 28 TIA 0. 50 4. 9 6. 3 ACS 2. 3 12. 6 45 8 -12 4 -25% PAD Criqui M, et al. Circulation 1985; 71: 510 Harvard Medical School

Outcomes in PVD Patients Harvard Medical School Outcomes in PVD Patients Harvard Medical School

Diagnostic Modalities § History § Physical § Ankle Brachial Index (ABI) § Noninvasive vascular Diagnostic Modalities § History § Physical § Ankle Brachial Index (ABI) § Noninvasive vascular laboratory § Angiography: MRA, CT, DSA Harvard Medical School

Initial Assessment § Identifying risk factors and symptoms § Pulse palpability § Further assessment Initial Assessment § Identifying risk factors and symptoms § Pulse palpability § Further assessment relies on functional noninvasive testing and radiological imaging § Determine not only the anatomic, but also the physiological aberration of peripheral vascular flow. Harvard Medical School

Intermittent Claudication § Intermittent claudication (derived from the Latin word for limp) § A Intermittent Claudication § Intermittent claudication (derived from the Latin word for limp) § A reproducible discomfort of a defined group of muscles that is induced by exercise and relieved with rest. § Supply ≠ Demand § Location depends upon the location of the disease. § Buttock, thigh, calf or foot claudication, either singly or in combination. Harvard Medical School

PVD Etiology § Large arteries § Atherosclerosis § Thromboembolism § Trauma § Arteritis of PVD Etiology § Large arteries § Atherosclerosis § Thromboembolism § Trauma § Arteritis of various types including § Buerger’s disease § Fibromuscular dysplasia § Takayasu’s Harvard Medical School

PVD Etiology § Medium and small vessel occlusions § Diabetes § Chronic recurrent trauma PVD Etiology § Medium and small vessel occlusions § Diabetes § Chronic recurrent trauma § Multiple small emboli § Collagen vascular diseases § Dysproteinemias § Polycythaemia vera § Pseudoxanthoma elasticum § Drug Reaction § Vasospasm Harvard Medical School

PVD Etiology § Specific to certain anatomical sites § Cystic adventitial disease of the PVD Etiology § Specific to certain anatomical sites § Cystic adventitial disease of the popliteal artery § Popliteal artery entrapment § Iliac endofibrosis (cyclists) § Various neurovascular compression syndromes affecting the upper limb § Cervical rib § Costoclavicular syndrome § Scalenus tunnel syndrome § Hyperabduction syndrome § Quadrangular space syndrome Harvard Medical School

PVD Differential Diagnosis § Deep venous thrombosis § Musculoskeletal disorders § OA § Restless PVD Differential Diagnosis § Deep venous thrombosis § Musculoskeletal disorders § OA § Restless leg syndrome § Peripheral neuropathy § Spinal Stenosis (pseudoclaudication) § Worse with erect posture (lordosis) better sitting or lying down. § Can find relief by leaning forward and straightening the spine (pushing a shopping cart or leaning against a wall). Harvard Medical School

Differential Diagnosis of Intermittent Claudication Venous Claudication Neurogenic Claudication Quality of pain Cramping Differential Diagnosis of Intermittent Claudication Venous Claudication Neurogenic Claudication Quality of pain Cramping "Bursting" Electric shock-like Onset Gradual, consistent Gradual, can be immediate Can be immediate, inconsistent Relieved by Standing still Elevation of leg Sitting down, bending forward Location Muscle groups (buttock, thigh, calf) Whole leg Poorly localized, can affect whole leg Legs affected Usually one Often both Harvard Medical School

Location, Location! § Buttock/hip § Usually indicates aortoiliac occlusive disease (Leriche's syndrome) § Some Location, Location! § Buttock/hip § Usually indicates aortoiliac occlusive disease (Leriche's syndrome) § Some cases, thigh claudication too § Question diagnosis of bilateral disease if erectile dysfunction is not present § Thigh § Occlusion of the common femoral artery leads to claudication in the thigh, calf, or both. § Calf § Symptoms in upper 2/3 is usually due to SFA § Lower 1/3 is due to popliteal disease. Harvard Medical School

PVD History § Use of the history alone to detect peripheral arterial disease will PVD History § Use of the history alone to detect peripheral arterial disease will result in missing up to 90 percent of cases. § Asymptomatic patients with abnormal ABI have 50% increased risk of cardiovascular complications Hirsch AT, et al. JAMA 2001; 286: 1317 Hooi JD, et al. J Clin Epidem 2004; 57: 294 Harvard Medical School

Physical Exam § Trophic Signs § Skin atrophy, thickened nails, hair loss, dependent rubor Physical Exam § Trophic Signs § Skin atrophy, thickened nails, hair loss, dependent rubor § Ulceration, gangrene § Pulse exam § May miss more than 50% § Elevation and dependency test Criqui M, et al. Circulation, 1985: 71; 516 -521 Harvard Medical School

Physical Exam: Elevation and Dependency Test Color Return(s) Venous Filling(s) Normal 10 10 -15 Physical Exam: Elevation and Dependency Test Color Return(s) Venous Filling(s) Normal 10 10 -15 Adequate Collaterals 15 -25 15 -30 Severe Ischemia >35 >40 Halperin, Throm Res. 2002; 106: V 303 -311 Harvard Medical School

Harvard Medical School Noninvasive Work-up Harvard Medical School Noninvasive Work-up

Ankle Brachial Index § Cornerstone of lower extremity vascular evaluation § Blood pressure cuffs, Ankle Brachial Index § Cornerstone of lower extremity vascular evaluation § Blood pressure cuffs, Doppler § Ankle (DP or PT) to brachial artery pressure Normal 0. 96 Claudication 0. 50 -0. 95 Rest Pain 0. 21 -0. 49 Tissue loss 0. 20 Significant change 0. 15 or more Harvard Medical School

Limitations § Noncompressible vessels § Diabetes § Renal Failure § ABI >1. 5 § Limitations § Noncompressible vessels § Diabetes § Renal Failure § ABI >1. 5 § Use toe-brachial index § Normal >0. 7 § Rest pain <0. 2 § Subclavian/Brachiocephalic Occlusive disease Harvard Medical School

Segmental Pressures § Pneumatic cuffs at multiple levels § Doppler pressure at pedal artery Segmental Pressures § Pneumatic cuffs at multiple levels § Doppler pressure at pedal artery § Drop >30 mm Hg between levels § Drop >20 mm Hg between limbs § Reflects status of artery above drop in pressure § Inaccurate with calcified vessels Rose SC. J Vasc Interv Radiol. 2000; 11: 1107 -1114 Harvard Medical School

Duplex Doppler § Non-invasive method of evaluating the blood vessels using sound waves, similar Duplex Doppler § Non-invasive method of evaluating the blood vessels using sound waves, similar to ultrasonography and echocardiography. § Can obtain both anatomic and hemodynamic information. § Anatomical detail § vessel wall § intraluminal obstructive lesions § perivascular compressive structures Harvard Medical School

Doppler Waveform Analysis: Hemodynamic Information § Sensitivity of 92. 6% and specificity of 97% Doppler Waveform Analysis: Hemodynamic Information § Sensitivity of 92. 6% and specificity of 97% (angiography gold standard) § Inaccurate at adductor canal and the aorto-iliac regions. § 95% accuracy in the detection of bypass graft stenosis, but can overestimate stenosis. Polack JF. Duplex Doppler in peripheral arterial disease. Radiol Clin N Amer 1995; 33 : 71 -88. Harvard Medical School

Doppler Waveform Analysis: Hemodynamic Information § Qualitative assessment of waveform analysis § Simple Equipment Doppler Waveform Analysis: Hemodynamic Information § Qualitative assessment of waveform analysis § Simple Equipment § Not affected by medial calcinosis § Supplements segmental pressures Harvard Medical School

Pulse Volume Recordings § Pneumatic Cuffs at Multiple Levels § Inflated to 65 mm Pulse Volume Recordings § Pneumatic Cuffs at Multiple Levels § Inflated to 65 mm Hg § Extremity Volume Increases in Systole § Changes pressure in cuff § Waveform Analysis § Not Impacted by Calcification Harvard Medical School

Pulse Volume Recordings § Advantanges § Widely available § Cheap § Reproducible § Disadvantages Pulse Volume Recordings § Advantanges § Widely available § Cheap § Reproducible § Disadvantages § Technician dependent § Time Consuming § Detection of Collaterals is low § Presence of gas and calcification degrade images Harvard Medical School

Is this enough? § Noninvasive lab documents presence and severity of disease § No Is this enough? § Noninvasive lab documents presence and severity of disease § No comprehensive anatomic information § No ability to plan interventions Harvard Medical School

Radiologic Imaging: MRA and CTA § DSA (conventional angiography) remains the gold standard for Radiologic Imaging: MRA and CTA § DSA (conventional angiography) remains the gold standard for evaluation of PVD § Newer modalities that match its accuracy are rapidly evolving § It is a matter of time before imaging replaces DSA, with the invasive angiographic techniques reserved for interventional procedures Harvard Medical School

MRA vs. DSA Harvard Medical School MRA vs. DSA Harvard Medical School

MRA: Current Technique § 3 D gradient echo (fast acquisition) § Gadolinium Enhanced § MRA: Current Technique § 3 D gradient echo (fast acquisition) § Gadolinium Enhanced § 20 -40 cc § Automated Scan delay § Renal arteries to toes § Stepping table or bolus chase § 45 -min exam Harvard Medical School

MRI Harvard Medical School MRI Harvard Medical School

Limitations of MRI § Uncooperative patient § Claustrophobia § Metal artifact § Pacemakers/ICDs § Limitations of MRI § Uncooperative patient § Claustrophobia § Metal artifact § Pacemakers/ICDs § Lack of visualization of calcium Harvard Medical School

CTA of PVD § Multidetector CT scanner necessary (4+) § Many hospitals now have CTA of PVD § Multidetector CT scanner necessary (4+) § Many hospitals now have 64 Slice § Iodinated contrast volume similar to conventional angiography § 80 -150 cc § Automated Scan Delay § Renal arteries to ankles § 20 -minute exam § High powered post processing software crucial Harvard Medical School

CTA of PVD Harvard Medical School CTA of PVD Harvard Medical School

CTA of PVD § Large volumes of data are generated via CTA studies and CTA of PVD § Large volumes of data are generated via CTA studies and displayed in various formats to refine the analysis of study results § Maximum Intensity Projection -MIP (most common) § Shaded surface display § 3 D Volume rendering Harvard Medical School

CT Limitations § With significant and dense calcifications, a false diagnosis of patency can CT Limitations § With significant and dense calcifications, a false diagnosis of patency can result. § Uncooperative patient § Pregnancy § Bad Pump § Inconsistent pedal vessel visualization § Renal failure/contrast allergy Harvard Medical School

Digital Subtraction Angiography (DSA) § Gold standard of arterial imaging § Has almost totally Digital Subtraction Angiography (DSA) § Gold standard of arterial imaging § Has almost totally replaced conventional cut film angiography § Compares a pre contrast image with a post contrast image using a computer, and "subtracts" elements common to both. § Prevents images of objects like bones etc from obscuring vascular details. § Contrast resolution is improved through use of image enhancement software. Harvard Medical School

Digital Subtraction Angiography (DSA) § Radiation exposure and contrast volumes are lower than conventional Digital Subtraction Angiography (DSA) § Radiation exposure and contrast volumes are lower than conventional angiography § Images are immediately available for review. § Images are stored in digital format on computerized data storage media § Interventional procedures can be performed Harvard Medical School

Digital Subtraction Angiography (DSA) §Drawbacks precluding use as a screening modality §Technique is invasive Digital Subtraction Angiography (DSA) §Drawbacks precluding use as a screening modality §Technique is invasive and expensive. §Requires arterial puncture §Longer study than CT §Contrast nephrotoxicity Harvard Medical School

Medical Treatments for PAD Treatment Effect Smoking cessation 10 -year mortality ↓ 54% to Medical Treatments for PAD Treatment Effect Smoking cessation 10 -year mortality ↓ 54% to 18%; at 7 years, rest pain drops from 16% to 0%* Antiplatelet agent 22%↓ in vascular events; possible increase in walking distance Diabetes control RR=0. 94 (0. 8 - 1. 1) for mortality; RR=0. 51 (0. 01 - 19. 64) for amputation BP to <140/85 mm Hg RR=0. 87 (0. 81 - 0. 94) for mortality; effect on PAD not known ACE inhibitors RR=0. 73 (0. 61 - 0. 86) for MI, stroke, or CV death Exercise program 24% ↓ in CV mortality; 150% further walking distance Cholesterol decrease RR=0. 81 (0. 72 - 0. 87) for MI, stroke, or revascularization; no clinical benefit in PAD† Cilostazol significant ↑ in walking distance *Survival Bias †Excepting Stroke Harvard Medical School

Suggested Algorithm for Work-up Harvard Medical School Suggested Algorithm for Work-up Harvard Medical School

Workup-Take-home § Noninvasive Vascular Lab is first line evaluation in nonacute patients § ABI Workup-Take-home § Noninvasive Vascular Lab is first line evaluation in nonacute patients § ABI is easy screening test § Beware noncompressible vessels in renal failure and diabetes § Segmental limb pressures often combined with doppler waveform anlaysis § Not sufficient to plan intervention Harvard Medical School

Workup-Take-home § MRA indicated for intervention planning § MRA (gadolinium enhanced) provides excellent renal Workup-Take-home § MRA indicated for intervention planning § MRA (gadolinium enhanced) provides excellent renal to pedal imaging § Surpasses CT in the foot § Overestimation of stenoses in small vessels § Limited by metal artifact, magnetic field, and length of study Harvard Medical School

Workup-Take-home § CTA indicated for intervention planning § CTA provides excellent renal to ankle Workup-Take-home § CTA indicated for intervention planning § CTA provides excellent renal to ankle imaging § Pedal imaging poor § Soft tissues and bone also imaged § Small vessel calcification is limitation Harvard Medical School