Peripheral%20arterial%20disease Diagnosis

• Individuals at risk for lower extremity peripheral arterial disease (PAD) should undergo review of vascular symptoms and comprehensive vascular examination to assess walking impairment, claudication, ischemic rest pain and/or the presence of nonhealing wounds

Review of Vascular Symptoms

• Location of exertional pain or discomfort
  • Primarily in the buttock, thigh, calf, or foot described as fatigue, aching, numbness, or pain
• Onset and duration of symptoms
• Improving or worsening as time passes
• Distance the patient can walk when pain starts and distance it takes for pain to be so intense that the patient must stop walking
• Necessary position patient must take to relieve pain (eg standing at rest, sitting, lying)
• Inquire if pain occurs consistently with same time and distance traveled
• Determine any background pertaining to origin, differential diagnosis and concurrent disease
• Poorly healing or nonhealing wounds of the legs or feet
• Postprandial abdominal pain that is reproducibly provoked by eating and is associated with weight loss
• Family history of a first-degree relative with abdominal aortic aneurysm (AAA)

Vascular Physical Examination

• Assessment of circulatory system as a whole to establish the presence of risk factors or target organ damage
• Blood pressure measurement in both arms and notation of any arm asymmetry/widened pulse pressure
• Palpation of the carotid pulses and determination of the carotid upstroke, amplitude, and presence of carotid bruits
• Check for heart murmurs, arrhythmias, and palpation of maximal impulse
• Look for signs of respiratory problems such as diaphragmatic excursion, poor inspiratory effort, and adventitious breath sounds
• Auscultation and palpation of the abdomen and flanks to note the presence of aortic pulsation, its diameter, and bruits
• Palpation of pulses at the brachial, radial, ulnar, femoral, popliteal, dorsalis pedis and posterior tibial sites
  • 1-2 of pedal pulses may be absent even in normal patients
  • Sometimes normal pulses can be found in PAD patients with intermittent thigh or calf claudication
  • Exceptionally strong pulse should raise suspicion of aneurysm
  • Pulse palpation should be correlated with claudication distance and location of pain for this can indicate the location and severity of the responsible arterial lesions
  • Check ankle-brachial index (PAD if ≤ 0.9) and if necessary, post-exercise test, hyperemia test, toe-brachial index
  • Perform Allen’s test to evaluate hand perfusion when necessary

• Auscultation of both femoral arteries for the presence of bruits
• Pulse intensity should be assessed and recorded numerically:
  • 0 = absent
  • 1 = diminished
  • 2 = normal
  • 3 = bounding

• Examine skin of the legs especially feet, nails and intertriginous areas
  • Check for color, temperature, skin integrity, swelling, ulcers, and scars of previous ulcerations, ie elevation pallor/dependent rubor, gangrene, nonhealing wound
  • Muscle atrophy from inability to exercise
  • Decreased hair growth or distal hair loss
  • Hypertrophied, slow-growing nails

• Examine for severe chronic ischemia
  • Presence of trophic changes associated with severe chronic ischemia (eg thin, dry skin, hair loss or loss of subcutaneous fat, thickened nails)
  • These changes are usually absent or mild in claudicant patient

• The following should be performed in all patients presenting with intermittent claudication for the first time in order to detect treatable risk factors or to diagnose associated diseases or target organ damage

Hematologic and Biochemical Tests

• Complete blood count (CBC) and platelet count
  • To detect anemia or polycythemia which may aggravate claudication symptoms
  • Reveal associated hematologic diseases (eg chronic myelogenous leukemia)

• Fasting blood glucose and/or glycosylated hemoglobin (HbA_1c)
  • Assess for diabetes mellitus (DM) which is a significant risk factor for peripheral arterial disease (PAD)

• Creatinine, blood urea nitrogen (BUN), urinalysis for glycosuria and proteinuria/albuminuria
  • Reduced renal function may be present and associated with hypertension or DM

• Fasting lipid profile
  • Assess presence of hyperlipidemia

• Resting electrocardiogram (ECG)
• Other tests that may be performed based on results of the above:
  • Tests for thrombophilias if hypercoagulable state is suspected
  • Plasma homocysteine levels if claudicant patient does not have any of the usual risk factors for PAD
  • C-reactive protein (CRP) levels for monitoring anti-inflammatory effects of statins in cardiovascular (CV) risk reduction

Lower Extremity Peripheral Arterial Disease Clinical Staging¹

Fontaine Classification

• Stage I - No symptoms present
• Stage IIa - Presence of non-disabling intermittent claudication
• Stage IIb - Presence of disabling intermittent claudication
• Stage III - Presence of ischemic rest pain
• Stage IV - Presence of ulceration or gangrene

Rutherford Classification

• Grade 0
  • Category 0 - No symptoms present
• Grade I
  • Category 1 - Presence of mild claudication
  • Category 2 - Presence of moderate claudication
  • Category 3 - Presence of severe claudication
• Grade II
  • Category 4 - Presence of ischemic rest pain
•  Grade III
  • Category 5 - Presence of minor tissue loss 
  • Category 6 - Presence of major tissue loss

• Ratio of systolic blood pressure (SBP) in the dorsalis pedis or posterior tibial arteries to that of the brachial arteries 
• Standard 1st-line test for the screening and diagnosis of lower extremity PAD
• Quick and cost-effective way to confirm or rule out the diagnosis of lower extremity PAD
• Monitors the efficacy of therapeutic interventions
• Useful to predict limb survival, wound healing, and patient survival
• Detects lower extremity PAD at all stages of the disease process
  Must be measured in all patients who present with claudication
  • ABI should be measured in both legs of all new patients with PAD of any severity to confirm the diagnosis of lower extremity PAD and establish a baseline
  • May be falsely normal or high in individuals with poorly compressible vessels eg diabetic patients, elderly
• ABI measurement is reasonable in patients at increased risk of PAD but have no history or PE findings suggestive of PAD  
• Periodic ABI measurement is also done in follow-up of patients with PAD who underwent lower extremity revascularization

 Advantages to Obtaining ABI on Initial Visit

• Confirms or rules out hemodynamically significant occlusive disease between the heart and the ankle
• Provides a rough guide to the severity of the occlusive disease in relation to the patient’s symptoms
• ABI can aid in differential diagnosis:
  • If patient has exercise-related leg pain from other causes, the patient should have a normal ankle pressure or a reduction in ankle pressure to a degree that does not correspond with the severity of disability
• Can be used to detect asymptomatic disease in the contralateral extremity

ABI >1.4 (Noncompressible)

• More common in the elderly, mostly in diabetic and chronic kidney disease patients, it indicates stiffened arteries and is associated with a higher risk of cardiovascular events and mortality 
• A falsely high ABI can be present in DM patients and further tests are necessary to determine if PAD is present
  • Patients with history of DM may have calcified noncompressible vessels that cause a falsely exaggerated ankle pressure
  • Alternative tests may include toe-brachial index, toe pressure or Doppler waveform analysis of the ankle arteries

 ABI is between 0.91-1.40

• ABI 1.00-1.40 (Normal)
• ABI 0.91-0.99 (Borderline)
• In patients experiencing intermittent claudication (IC) with ABI between 0.9-1.3, consider performing treadmill exercise test
  • ABI value >0.9 at rest but decreases by 20% after exercise is diagnostic of PAD

ABI < 0.9

• ABI 0.41 - 0.90 (Mild-moderate PAD)
• ABI 0.00 - 0.40 (Severe PAD)
  • Patients with chronic limb-threatening ischemia usually have ABI < 0.4
• Resting ABI <0.9 is up to 95% sensitive in detecting angiogram-positive PAD and is usually considered diagnostic
  • This may not be true for DM patients
• Correlated with a 2- to 3-fold increase in risk of total and CV death

• Severity of claudication can be assessed with a treadmill exercise test and a 6-minute walk test
• Patient walks a standard speed and grade on a treadmill (3.2 km/hr, 10-12% grade) until claudication pain occurs or until a time limit has been reached (max 5 minutes) after which ankle pressure is measured again normally 1 minute after exercise
  • There will be a significant decrease in the ABI from resting to the post-exercise level, eg >20% 
• Establishes the diagnosis of lower extremity peripheral arterial disease (PAD) when resting measurements of the ABI are normal or borderline
• May be used to objectively assess functional status of patients with PAD and ABI ≤0.9
• Useful in patients who are at risk for lower extremity PAD but have no classic symptoms of claudication and no other clinical evidence of atherosclerosis
• Documents the severity of symptom limitation in patients with lower extremity PAD and claudication
• Measures the functional improvement achieved with therapeutic interventions
• Used to assess the safety of exercise and individualize exercise prescriptions in patients with claudication before initiation of an exercise program
• Used to assess the hemodynamic significance of arterial occlusive disease in the lower extremities
• Differentiates claudication from pseudoclaudication
  • Claudication is likely when there is a decrease in post-exercise ABI
  • Pseudoclaudication is suggested by a normal post-exercise ABI
• Use a standardized exercise protocol (either fixed or graded) with a motorized treadmill to ensure reproducibility of pain-free walking distance and maximal walking distance

6-Minute Walk Test

• May provide an objective assessment of the functional limitation of claudication and response to therapy in elderly patients or those patients not amenable to treadmill testing
• May be performed before and after any risk factor management or clinical events and in periodic follow-ups as a measure of functional status 
• Walking exercise may be done by climbing stairs or in the hallway if a treadmill is not available

 Duplex Ultrasound

• 1st-line imaging study for the diagnosis of lower extremity artery disease lesions
  • Alternative diagnostic modality in patients suspected with ALI
• Useful in diagnosing anatomic location and degree of stenosis of PAD
  • Peak systolic velocity ratio >2 correlates with a stenosis >50% diameter
  • Subclinical artery disease such as a carotid plaque can be detected
  • Provides morphological view of vascular walls, perivascular tissue or details of early atherosclerotic change
• Used together with ABI measurement, it is an alternative diagnostic test in patients with normal or high ABI but with symptoms that strongly suggest lower extremity PAD
• Helpful in patients who are candidates for endovascular or surgical revascularization
• Allows for safe planning of necessary treatment steps whether conservative treatment, catheter intervention or bypass surgery
• Recommended for routine surveillance after femoral-popliteal or femoral-tibial-pedal bypass with a venous conduit and after endovascular procedures in patients with PAD

Magnetic Resonance Angiography (MRA)

• Useful in diagnosing anatomic location and degree of stenosis of PAD
  • Alternative diagnostic modality in patients suspected with ALI
• Useful in selecting patients with lower extremity PAD who are candidates for endovascular intervention
• Considered in selecting patients for surgical bypass and in determining the sites of surgical anastomosis, though limited by the inability to show arterial calcifications
• Used for surveillance after revascularization in patients with lower extremity PAD
• An alternative diagnostic procedure in patients with mild to moderate chronic kidney disease
• Cannot be used in patients with contraindications to magnetic resonance technique (eg pacemakers, defibrillators, intracranial metallic stents, clips, and coils)

Computed Tomographic Angiography (CTA)

• Considered for the diagnosis of anatomic location and presence of significant stenosis in patients with lower extremity PAD
  • Recommended 1st-line diagnostic modality for anatomical imaging in patients suspected with ALI
• Used to select patients who are candidates for endovascular or surgical revascularization
• Provides soft tissue diagnostic information that may be associated with PAD presentation
• Substitute for MRA for those patients with contraindications to MRA
• Scan times are faster than MRA but accuracy and effectiveness are not well-determined as MRA
• Limited use in patients with renal dysfunction because CTA requires iodinated contrast administration

Contrast Angiography

• Gold standard in providing detailed information about arterial anatomy
• Recommended for evaluation of patients with CLTI when revascularization is contemplated
• Useful in guiding percutaneous peripheral interventional procedures

• Considered as the gold-standard in vascular imaging in terms of accuracy and clarity
• Recommended as additional diagnostic modality if Duplex sonography fails to show underlying pathology and elective surgical revascularization is contemplated
• Considered as the standard diagnostic modality to diagnose ALI
• More accurate in evaluating in-stent stenoses

• Alternative to digital subtraction angiography (DSA) and may be used for patients with renal failure
• Imaging of the popliteal artery and proximal calf arteries is feasible

Continuous Wave Doppler Ultrasound Blood Flow Measurement

• Permits initial estimation of lower extremity PAD location and severity, monitors lower extremity PAD progression, and provides quantitative follow-up after revascularization procedures
• Measures velocity wave forms and SBP at sequential segments of the upper and lower extremities
• Provides useful information to localize abnormality in patients with poorly compressible arteries and normal resting ABI values

Leg Segmental Pressure Measurement

• Establishes lower extremity PAD especially when anatomic localization and magnitude of arterial stenoses are needed for therapeutic plan
• Focal stenosis is suggested by a gradient of >20 mmHg between adjacent segments
• Performed by measuring arterial pressures with plethysmographic cuffs placed sequentially along the limb at various levels
• Can predict limb survival, wound healing, and patient survival
• Helps monitor the efficacy of treatment interventions

• Non-invasive procedures which may be used to evaluate PAD in patients with medial calcific sclerosis and acral circulatory disorders
• Oscillography is quick and simple to perform and is able to identify the approximate level of stenosis or occlusion
• LRR is helpful in acral perfusion examination and for bilateral comparison
  • Facilitates rapid diagnosis of the presence of peripheral blood flow disorders and assessment of the severity of the perfusion disorder

Pulse Volume Recording

• Establishes the initial lower extremity PAD diagnosis and assesses its localization and severity
• Alternative diagnostic test in patients with normal or high ABI but with symptoms that strongly suggest lower extremity PAD
• Useful in assessing the adequacy of limb perfusion after revascularization and in predicting the outcome in CLI and risk of amputation
• Can provide a tool for the evaluation of small-vessel disease when applied to the feet

Toe Brachial Index

• Establishes diagnosis of lower extremity PAD for patients with noncompressible ankle arteries suggested by ABI values >1.40 or when there is abnormal augmentation in a measured lower extremity systolic pressure beyond the normal physiological amplification of systolic pressure from the heart to the limb arterial segment
• Recommended for detection of PAD in patients with trophic disorders, DM and those with ABI >1.3
  • Toe pressure measurement remains a diagnostic test in these patients because digital arteries have no calcinosis that alters compressibility of more proximal arteries
• Can be used to diagnose CLTI in patients with normal or borderline ABI with nonhealing wounds or gangrene or to evaluate local perfusion in patients with PAD and abnormal ABI or noncompressible arteries, with nonhealing wound or gangrene
• Can measure digital perfusion when there is small-vessel arterial occlusive disease
• Useful to predict wound healing and limb survival, and to monitor efficacy of therapeutic intervention
• Lower extremity PAD diagnosis is made with toe-brachial index of < 0.7
• Systolic perfusion pressure of the toe is represented by toe pulsatility using a plethysmographic detection device

• Can be used to diagnose CLTI in patients with normal or borderline ABI with nonhealing wounds or gangrene or to evaluate local perfusion in patients with PAD and abnormal ABI or noncompressible arteries, with nonhealing wound or gangrene
• May be used to estimate risk and/or level of amputation in CLTI
• TcPO2 <40 mmHg is associated with high complication rate after amputations
• TcPO2 <30 mmHg is an independent risk factor for disorders in wound healing
• Measurements should be done on the involved extremity over ≥3 different positions to increase validity
• Can predict wound healing and is useful in monitoring the efficacy of revascularization