Intermittent Claudication 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

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 QoL Limb Loss Premature Mortality Temporal Arteritis is very rare before 45 years. Buerger’s unheard of under 55. Raynaud’s patients or varicose will usually remember symptoms starting before 30.

Risk Factors for PVD: Framingham Heart Study Reduced Increased Smoking Diabetes Hypertension Hypercholesterolemia Hyperhomocysteinemia Fibrinogen C- Reactive Protein Alcohol Relative Risk .5 1 2 3 4 5 6 Data from the Framingham Heart Study of 381 men and women who were followed for 38 years revealed that the odds ratio for developing intermittent claudication was 2.6 for diabetes mellitus, 1.2 for each 40 mg/dL (1 mmol/L) elevation in the serum cholesterol concentration,1.4 for each 10 cigarettes smoked per day, and 1.5 for mild and 2.2 for moderate hypertension [5]. In addition, diabetic patients have worse arterial disease and a poorer outcome than nondiabetics [9]. Mean follow-up 38 years

PAD is Associated with Poor Outcomes Annual Incidence Prevalence Mortality/yr (%) Stroke 0.73 4.6 28 TIA 0.50 4.9 6.3 ACS 2.3 12.6 45 PAD 8-12 4-25% Criqui M, et al. Circulation 1985; 71:510

Outcomes in PVD Patients

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

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

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.

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

Medium and small vessel occlusions 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

Specific to certain anatomical sites 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

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). Pain can be excruciating and is usually located in the dorsal aspect of the toes. The foot may become pale with exercise.

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

Location, 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.

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

Elevation and dependency test 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

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: V303-311

Noninvasive Work-up

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

Limitations Noncompressible vessels Diabetes Renal Failure ABI >1.5 Use toe-brachial index Normal >0.7 Rest pain <0.2 Subclavian/Brachiocephalic Occlusive disease

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

Noninvasive Functional Assessment Targeted towards evaluating the arterial flow dynamics in the affected area, and are invariably supplemented with radiological depiction of anatomic abnormality Pressure measurements (ABI) Plethysmography Continuous wave Doppler

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

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.

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

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

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

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

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

MRA vs. DSA

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

MRI

Limitations of MRI Uncooperative patient Claustrophobia Metal artifact Pacemakers/ICDs Lack of visualization of calcium

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

CTA of PVD

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 3D Volume rendering A 3D model of the study in any projection and from any angle in order to evaluate the patient for the presence of a stenosis or aneurysm.

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

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.

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

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

Medical Treatments for PAD 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

Suggested Algorithm for Work-up

Noninvasive Vascular Lab is first line evaluation in nonacute patients 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

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

CTA indicated for intervention planning 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