Noninvasive diagnosis of upper and lower extremity arterial disease

INTRODUCTION — Accurate diagnostic evaluation, staging, and imaging of the patient with suspected arterial disease is fundamental to successful management. In addition to a thorough history and physical examination, noninvasive vascular studies serve to confirm the clinical diagnosis and define the level and extent of vascular pathology affecting extremity perfusion, which can help determine the likelihood of wound healing and limb salvage after open surgical and endovascular revascularization.

Noninvasive vascular testing is most commonly obtained to evaluate patients suspected of having peripheral artery disease (PAD) based upon patient risk factors (eg, tobacco use, diabetes mellitus, chronic kidney disease), symptomology (eg, intermittent claudication, ischemic rest pain, nonhealing wounds), and physical examination findings (eg, tissue loss, gangrene) [1]. Follow-up evaluation is also important after vascular reconstruction to detect recurrent or progressive disease or complications [2,3].

Vascular laboratory testing can be broadly divided into two main categories: physiological testing and ultrasound-based imaging. A variety of noninvasive examinations are available to assess the presence, extent, and severity of arterial disease and help to inform decisions about revascularization. Physiologic tests include segmental limb pressures and the calculation of pressure index values (eg, ankle-brachial index, toe-brachial index, wrist-brachial index), exercise testing, segmental volume plethysmography, transcutaneous oxygen measurements, and photoplethysmography. Duplex ultrasonography (DUS), as the name implies, provides information on both the anatomic location and extent of the disease as well as information about flow velocity and volume.

DUS is usually the first imaging modality used, and in some settings may be the only imaging mode available. Other studies frequently used to image the vasculature include computed tomographic (CT) angiography, magnetic resonance (MR) angiography, and digital subtraction angiography (DSA). CT angiography provides high-resolution, contrast-enhanced images that can be viewed in multiple planes or as a three-dimensional reconstruction. MR angiography has the potential to produce images comparable to DSA except at the level of the foot and ankle or in patients with heavily calcified tibial vasculature. Both of these are important adjunctive or alternative methods for vascular assessment; however, the cost and the time necessary for these studies limits their use for routine testing, and thus, these are typically limited to planning intervention [4]. DSA remains the gold standard imaging to which all other imaging is compared but is invasive and not without risk. DSA may be selected if concomitant intervention is being considered or when target vessels are being evaluated for infrapopliteal bypass.

Physiologic testing and the use of DUS in the evaluation of extremity arterial disease is reviewed. The optimal choice of imaging for various vascular conditions that affect perfusion to the extremities and role of advanced imaging for the evaluation of arterial disease including CT or MR angiography and DSA are discussed separately.

●Peripheral artery disease (See "Clinical features and diagnosis of lower extremity peripheral artery disease", section on 'Diagnosis of lower extremity PAD' and "Advanced vascular imaging for lower extremity peripheral artery disease" and "Upper extremity atherosclerotic disease", section on 'Physical examination'.)

●Aneurysmal disease (See "Clinical manifestations and diagnosis of thoracic aortic aneurysm", section on 'Imaging diagnosis' and "Overview of aneurysmal disease of the aortic arch branches or upper extremity arteries in adults" and "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Diagnosis' and "Iliac artery aneurysm", section on 'Diagnosis' and "Femoral artery aneurysm", section on 'Diagnosis' and "Popliteal artery aneurysm", section on 'Diagnosis'.)

●Vascular injury (See "Severe upper extremity injury in the adult patient", section on 'Vascular assessment' and "Severe lower extremity injury in the adult patient", section on 'Vascular assessment'.)

●Aortic dissection (See "Clinical features and diagnosis of acute aortic dissection", section on 'Cardiovascular imaging'.)

INDICATIONS FOR TESTING — The need for noninvasive vascular testing to supplement the history and physical examination depends upon patient history, clinical scenario, and urgency of the patient's condition. An exhaustive battery of tests is not required for all patients. In general, only tests that confirm the presence of arterial disease, drive decision-making, or provide evidence-based surveillance data should be performed.

Patients with arterial obstruction or occlusion can be asymptomatic or symptomatic. Symptoms vary depending upon the vascular bed affected, the extent and severity of the disease, and the presence and effectiveness of collateral circulation. The clinical presentations of various vascular disorders are reviewed separately. (See "Clinical features and diagnosis of lower extremity peripheral artery disease" and "Overview of thoracic outlet syndromes" and "Clinical manifestations and diagnosis of Raynaud phenomenon" and "Clinical features and diagnosis of abdominal aortic aneurysm".)

Noninvasive vascular testing may be performed to:

●Evaluate an acute change in physical examination resulting from thromboembolism. (See "Embolism to the upper extremities" and "Embolism to the lower extremities" and "Overview of upper extremity ischemia".)

●Confirm a diagnosis of arterial disease in patients with chronic symptoms or signs. (See "Clinical features and diagnosis of lower extremity peripheral artery disease" and "Upper extremity atherosclerotic disease".)

●Define the ischemia grade for patients presenting with chronic limb-threatening ischemia (CTLI) using the Society for Vascular Surgery Threatened Limb Classification System (WIfI). The ischemia grade correlates with the probability of wound healing and limb salvage after revascularization. (See "Management of chronic limb-threatening ischemia".)

●Screen patients who have risk factors for peripheral artery disease (PAD). Patients with lower extremity PAD have an increased risk of coronary heart disease (CHD), myocardial infarction, stroke, and cardiovascular mortality. Thus, even asymptomatic patients may benefit from identification of vascular disease if the information will be used for future cardiovascular risk factor modification [2,5-9]. (See "Asymptomatic peripheral artery disease".)

●Identify peripheral vascular obstruction in patients with other vascular diseases (eg, aneurysm, dissection). (See "Clinical features and diagnosis of acute aortic dissection" and "Clinical features and diagnosis of abdominal aortic aneurysm".)

●Identify a vascular injury. (See "Severe lower extremity injury in the adult patient" and "Severe upper extremity injury in the adult patient".)

●Evaluate patients prior to or during planned vascular procedures. (See "Patient evaluation prior to placement of hemodialysis arteriovenous access" and "Endovascular techniques for lower extremity revascularization" and "Lower extremity surgical bypass techniques".)

●Provide surveillance after vascular intervention. (See "Carotid endarterectomy", section on 'Duplex surveillance' and "Endovascular techniques for lower extremity revascularization", section on 'Surveillance after endovascular interventions' and "Lower extremity surgical bypass techniques", section on 'Graft surveillance'.)

PHYSIOLOGIC TESTING — Physiologic testing is used to establish the presence of arterial stenosis or obstruction. For patients with suspected peripheral artery disease (PAD), physiologic testing defines the severity and extent of disease and helps determine wound healing potential. While the primary use of physiologic testing is to establish a diagnosis of PAD, any disease process that leads to stenosis or obstruction of the extremity arteries (eg, occlusion of peripheral aneurysm, thromboembolic debris, arterial dissection) can be evaluated using these studies.

Studies include the following: ankle-brachial index (ABI), toe-brachial index (TBI), wrist-brachial index (WBI), segmental limb pressures, pulse volume recordings, exercise testing, digit plethysmography, and transcutaneous oxygen measurements.

Ankle-brachial index — Calculation of the ABI is a relatively simple and inexpensive method to confirm the clinical suspicion of lower extremity arterial stenosis or occlusion [2,10]. The higher resting systolic blood pressure at the ankle is compared with the higher systolic brachial pressure, and the ratio of the two pressures defines the ABI. For patients with PAD, the ABI provides a measure of the severity of disease and is predictive of coronary heart disease and cerebrovascular disease [2,5-9,11]. (See "Overview of lower extremity peripheral artery disease" and "Upper extremity atherosclerotic disease".)

The use of the ABI in the trauma patient is discussed separately. (See "Severe lower extremity injury in the adult patient", section on 'Injured extremity index' and "Overview of upper extremity ischemia", section on 'Diagnosis'.)

To obtain an accurate ABI, the patient should rest for 15 to 30 minutes prior to measuring the ankle pressure. The study starts with measuring the dorsalis pedis and posterior tibial artery pressures at the ankle.

●Place an appropriately sized blood pressure cuff just above the ankle.

●While listening to either the dorsalis pedis or posterior tibial artery signal with a continuous wave Doppler (picture 1), insufflate the cuff to a pressure above which the audible Doppler signal disappears.

●Slowly release the pressure in the cuff until the pedal signal returns.

●Record the systolic pressure at which the signal returns.

●Repeat the measurement in the same manner for the other pedal vessel in the ipsilateral extremity and repeat the process in the contralateral lower extremity.

●Measure the systolic brachial artery pressure bilaterally in a similar fashion with the blood pressure cuff placed around the upper arm and using the continuous wave Doppler (CWD).

The ABI for each lower extremity is calculated by dividing the higher ankle pressure (dorsalis pedis or posterior tibial artery) in each lower extremity by the higher of the two brachial artery systolic pressures. For patients without severely calcified ankle/foot vasculature, the ABI provides a reasonable estimate of foot wound healing potential [12-15]. Conversely, using the highest ankle pressure may fail to identify patients who might benefit from coronary heart disease (CHD) risk factor modification, which is why CHD screening uses the lower rather than the higher of the two ankle pressures (dorsalis pedis or posterior tibial artery) as the numerator in the calculation [12]. (See "Asymptomatic peripheral artery disease".)

Calculation of the ABI at the bedside is usually performed with a CWD probe (picture 1) using two separate ultrasound crystals (one for sending and one for receiving sound waves). CWD is used primarily to aid blood pressure measurement and cannot be used for imaging or to identify Doppler shifts since sound waves are continuously transmitted. The handheld probe provides a signal that is a summation of all the vascular structures through which the sound has passed and is limited in the evaluation of a specific vascular structure when multiple vessels are present. However, the intensity and quality of the CWD signal can give an indication of the severity of vascular disease proximal to the probe (waveform 1A-C). The quality of the arterial signal can be described as triphasic (like the heartbeat), biphasic (bum-bum), or monophasic. Biphasic signals may be normal in patients older than 60 because of decreased peripheral vascular resistance; however, monophasic signals unquestionably indicate significant pathology. Monophasic signals must be distinguished from venous signals, which vary with respiration and increase in intensity when the surrounding musculature is compressed (ie, augmentation of venous flow). It is often quite difficult to obtain ABI values in patients with monophasic CWD signals.

The disadvantage of using CWD is a lack of sensitivity at extremely low pressures where it may be difficult to distinguish arterial from venous flow. A venous signal can be confused with an arterial signal (especially if pulsatile venous flow is present, as can occur with heart failure) [16,17]. Under these conditions, duplex ultrasound can be used to distinguish between arteries and veins by identifying the direction of flow. (See 'Duplex ultrasound' below.)

A low ABI is associated with a higher risk of CHD, stroke, transient ischemic attack, progressive renal insufficiency, and all-cause mortality [18-23]. The ABI is generally, but not absolutely, correlated with clinical measures of lower extremity function such as walking distance, speed of walking, balance, and overall physical activity [24-29]. Further evaluation is dependent upon the ABI value (algorithm 1A-B).

●An ABI >0.9 with an upper limit of 1.3 generally excludes clinically significant arterial occlusive disease. Normally, the pressure is higher in the ankle than in the arm (ie, ABI >1 to 1.3). An ABI of 0.9 to 0.99 is classified as borderline normal.

At rest, mild or diffuse disease, disease of individual tibial arteries, and arterial entrapment syndromes can produce false negative tests. If ABIs are normal at rest but symptoms strongly suggest claudication, exercise testing should be performed [30]. (See 'Exercise testing' below.)

●An ABI >1.3 suggests the presence of noncompressible calcified vessels and the need for additional vascular studies, such as pulse volume recordings, measurement of the toe pressures and TBI, transcutaneous oxygen measurements, or arterial duplex studies. (See 'High ABI' below and 'Toe-brachial index' below and 'Duplex ultrasound' below and 'Transcutaneous oxygen measurements' below.)

●In the setting of artificially elevated ABIs, toe pressures, toe-brachial indices (TBIs) and/or transcutaneous oxygen measurement (ie, TcPO₂) should be used when determining the healing potential of a wound or proposed surgical site. It is important to note that in cases of calcification and partial, but not complete, vessel incompressibility, ABI may also be falsely normal; waveform assessment may circumvent this problem to a degree. (See 'Toe-brachial index' below and 'Transcutaneous oxygen measurements' below.)

●An ABI ≤0.9 is diagnostic of occlusive arterial disease in patients with symptoms of claudication or other signs of ischemia and has 95 percent sensitivity (and 100 percent specificity) for detecting arteriogram-positive occlusive lesions associated with ≥50 percent stenosis in one or more major vessels [24].

●An ABI of 0.4 to 0.9 suggests a degree of arterial obstruction often associated with claudication [26].

●An ABI below 0.4 usually represents multilevel disease (any combination of iliac, femoral, or tibial vessel disease) and may be associated with nonhealing ulcerations, ischemic rest pain, or pedal gangrene.

High ABI — A potential source of error with the ABI is that calcified vessels may not compress normally, thereby resulting in falsely elevated pressure measurements. An ABI above 1.3 is suspicious for calcified vessels that may occur in the setting of underlying diabetes mellitus or end-stage renal disease (ESRD) [29]. ABI may not accurately reflect degree of atherosclerotic disease even when ABI is less than 1 for patients with diabetes mellitus or ESRD, hence the rationale for further testing in this subgroup of patients. (See "Overview of peripheral artery disease in patients with diabetes mellitus".)

The National Health and Nutrition Survey (NHANES) estimated that 1.4 percent of adults age >40 years in the United States have an ABI >1.4; this group accounts for approximately 20 percent of all adults with PAD [31].

As with low ABI, abnormally high ABI (>1.3) is also associated with higher cardiovascular risk [20,32].

●The Multi-Ethnic Study of Atherosclerosis (MESA) study evaluated 4972 patients without clinical cardiovascular disease and found a greater left ventricular mass index in patients with high ABI (>1.4) compared with normal ABI (90 versus 72 g/m²) [32]. Increases in left ventricular mass are predominantly attributable to an increase in afterload.

●The Strong Heart Study followed 4393 Native American patients for a mean of eight years [20]. High ABI (>1.4) was present in 9.2 percent of patients, and low ABI (≤0.9) was found in 4.9 percent of patients. Adjusted hazard ratios for all-cause mortality and cardiovascular mortality rates were 1.8 and 2, respectively, for high ABI 1.7 and 2.5,respectively, for low ABI relative to normal ABI (0.9<ABI≤1.4).

For patients with diabetes mellitus or ESRD, more reliable information is often obtained using toe pressures, TBIs, pulse volume recordings, and transcutaneous oxygen measurements. (See 'Toe-brachial index' below and 'Pulse volume recordings' below and 'Transcutaneous oxygen measurements' below.)

Toe-brachial index — The TBI is a more reliable indicator of limb perfusion in patients with diabetes mellitus and ESRD because the digital vessels are frequently spared from medial calcification.

The TBI is obtained by placing a pneumatic cuff on one of the toes. The great toe is usually chosen, but in the face of amputation, any toe may be used. A photo-electrode is placed on the end of the toe to obtain a photoplethysmographic (PPG) arterial waveform using infrared light (figure 1). The infrared light is transmitted into the superficial layers of the skin, and the reflected portion is received by a photosensor within the photo-electrode. The signal is proportional to the quantity of red blood cells in the cutaneous circulation.

Analogous to the ankle and wrist pressure measurements, the toe cuff is inflated until the PPG waveform flattens, and then the cuff is slowly deflated. The systolic pressure is recorded at the point in which the baseline waveform is reestablished. The ratio of the recorded toe systolic pressure to the higher of the two brachial pressures gives the TBI.

A pressure gradient of 20 to 30 mmHg normally exists between the ankle and the toe, and thus, a normal TBI is 0.7 to 0.8. An absolute toe pressure >30 mmHg is favorable for wound healing [33], although toe pressures >45 to 55 mmHg may be required for healing in patients with diabetes [34-36]. Toe pressures are useful to define perfusion at the level of the foot, especially in patients with incompressible vessels, but they provide no indication of the site of occlusive disease. In addition to measuring toe systolic pressures, the toe Doppler arterial waveforms should also be evaluated. (See 'Pulse volume recordings' below.)

Wrist-brachial index — The WBI is used to identify the level and extent of upper extremity arterial stenosis or occlusion. Upper extremity PAD is far less common than lower extremity PAD, and abnormalities in WBI have not been correlated with adverse cardiovascular risk as seen with ABI. Thus, WBIs are typically measured only when the patient has clinical signs or symptoms consistent with upper extremity arterial stenosis or occlusion. The use of the WBI in the trauma patient is discussed separately. (See "Severe upper extremity injury in the adult patient", section on 'Vascular assessment'.)

The WBI is obtained in a manner analogous to the ABI. (See 'Ankle-brachial index' above.)

Pressure measurements are obtained for the radial and ulnar arteries at the wrist and brachial arteries in each extremity. The WBI for each upper extremity is calculated by dividing the higher wrist pressure (radial artery or ulnar artery) by the higher of the two brachial artery pressures. The normal value for the WBI is 1.

Incompressibility can also occur in upper extremity arteries. The radial or ulnar arteries may have a supranormal WBI. This finding may indicate the presence of medial calcification in the patient with diabetes.

Segmental pressures — Once arterial occlusive disease has been verified using the ABI measurements (resting or postexercise) (see 'Exercise testing' below), the level and extent of disease can be determined noninvasively and relatively inexpensively using segmental limb pressures, which can be performed for the upper or lower extremity. Specialized equipment is used to obtain blood pressures at successive levels of the extremity to localize the level of disease fairly accurately, although duplex ultrasound is more accurate to the extent that many vascular laboratories in the United States infrequently perform segmental pressures. (See 'Duplex ultrasound' below.)

Lower extremity segmental pressures — The patient is placed in a supine position and rested for 15 minutes. Three or four standard-sized blood pressure cuffs are placed at several positions on the extremity. A three-cuff technique uses above-knee, below-knee, and ankle cuffs. A four-cuff technique (picture 2) uses two narrower blood pressure cuffs rather than one large cuff on the thigh and permits the differentiation of aortoiliac and superficial femoral artery disease [37].

The pedal vessel (dorsalis pedis, posterior tibial) with the higher systolic pressure is used, and the pressure that occludes the pedal signal for each cuff level is measured by first inflating the cuff until the signal is no longer heard and then progressively deflating the cuff until the signal resumes. The pressure at each level is divided by the higher systolic arm pressure to obtain an index value for each level (figure 2).

A 20 mmHg or greater reduction in pressure is indicative of a flow-limiting lesion if the pressure difference is present either between segments along the same leg or when compared with the same level in the opposite leg (ie, right thigh/left thigh, right calf/left calf) (figure 2). Well-developed collateral vessels may diminish the observed pressure gradient and obscure a hemodynamically significant lesion. Successive significant (>20 mmHg) decrements in the same extremity indicate multilevel disease.

Pressure gradients may be increased in the hypertensive patient and decreased in patients with low cardiac output. When performing serial examinations over time, changes in index values >0.15 from one study to the next are considered significant and suggest progression of disease.

With a four-cuff technique, the high-thigh pressure should be higher than the brachial pressure, though in the normal individual, these pressures would be nearly equal if measured by invasive means. The four-cuff technique introduces artifact because the high-thigh cuff is often not appropriately 120 percent the diameter of the thigh at the cuff site. A <30 mmHg decrement between the higher systolic brachial pressure and high-thigh pressure is considered abnormal.

A normal high-thigh pressure excludes occlusive disease proximal to the femoral artery bifurcation. If the high-thigh systolic pressure is reduced compared with the brachial pressure, then the patient has a lesion at or proximal to the bifurcation of the common femoral artery. If the high-thigh pressure is normal but the low-thigh pressure is decreased, the lesion is in the superficial femoral artery. The four-cuff technique allows for delineation of level(s) of arterial obstructive disease and has been found to correctly identify the level of the occlusive lesion in 78 percent of extremities [37]. (See 'Duplex ultrasound' below.)

For patients with claudication, the localization of the lesion may have been suspected from their history. The site of pain and site of arterial disease correlate with pressure reductions seen on segmental pressures [2,38]:

●Buttock, hip, or thigh pain – Pressure gradient between the brachial artery and the upper thigh is consistent with arterial occlusive disease at or proximal to the femoral bifurcation.

●Calf pain – Pressure gradient from the high to lower thigh indicates superficial femoral artery disease. Pressure gradient from the lower thigh to calf reflects popliteal disease.

●Low calf pain – Pressure gradient from the calf and ankle is indicative of infrapopliteal disease.

●Foot pain – Pressure gradient from the ankle and toe suggests infra-malleolar occlusive disease.

As with ABI measurements, lower extremity segmental pressure measurements may be artifactually increased or not interpretable in patients with noncompressible vessels [2]. Patients with diabetes (who have medial sclerosis) or patients with chronic kidney disease often have nonocclusive pressures with ABIs >1.3, limiting the utility of segmental pressures in these populations. Pulse volume recordings (which are independent of arterial compression) or arterial duplex are preferentially used to evaluate these patients instead. (See 'Pulse volume recordings' below and 'Duplex ultrasound' below.)

Upper extremity segmental pressures — Segmental pressures may also be performed in the upper extremity. Generally, three cuffs are used with above and below elbow cuffs and a wrist cuff (figure 3). Index values are calculated at each level. In the upper extremity, a difference of ≥10 mmHg between the left and right brachial systolic pressures suggests innominate, subclavian, axillary, or proximal brachial arterial occlusion. Differences of more than 10 to 20 mmHg between successive arm levels suggest intervening occlusive disease.

Pulse volume recordings — Current vascular testing machines can use air plethysmography to measure volume changes within the limb, in conjunction with segmental limb pressure measurements. The same pressure cuffs are used for each test (picture 2). (See 'Segmental pressures' above.)

Cuffs are placed and inflated, one at a time, to a constant standard pressure. Volume changes in the limb segment beneath the cuff are reflected as changes in pressure within the cuff, which is detected by a pressure transducer and converted to an electrical signal to produce an analog pressure pulse contour known as a pulse volume recording (PVR).

A normal PVR waveform is composed of a systolic upstroke with a sharp systolic peak followed by a downstroke that contains a prominent dicrotic notch (picture 3). Alterations in the pulse volume contour and amplitude indicate proximal arterial obstruction. The degree of these changes reflects disease severity [39,40]. Mild disease is characterized by loss of the dicrotic notch and an outward "bowing" of the downstroke of the waveform (picture 3). With severe disease, the amplitude of the waveform is blunted (picture 3). Pulse volume recordings are most useful in detecting disease in calcified vessels, which tend to yield falsely elevated pressure measurements. (See 'High ABI' above.)

Since the absolute amplitude of plethysmographic recordings is influenced by cardiac output and vasomotor tone, interpretation of these measurements should be limited to the comparison of one extremity to the other in the same patient and not between patients. The dicrotic notch may be absent in normal arteries in the presence of low resistance, such as after exercise.

Digit waveforms — Patients with distal small vessel occlusive disease (eg, Buerger disease, secondary [systemic] Raynaud syndrome, end-stage kidney disease, diabetes mellitus) often have normal ankle-brachial index and wrist-brachial index values. Arterial occlusion distal to the ankle or wrist can be detected using digit plethysmography, which is performed by placing small pneumatic cuffs on each of the digits of the hands or feet depending upon the disease being investigated. In a manner analogous to pulse volume recordings described above, volume changes in the digit segment beneath the cuff are detected and converted to produce an analog digit waveform. (See 'Pulse volume recordings' above.)

Exercise testing — Exercise testing is a sensitive method for evaluating patients with symptoms suggestive of arterial obstruction when the resting index values (ABIs, WBIs) are normal. Segmental blood pressure testing, TBI measurements, and PVR waveforms can be obtained before and after exercise to unmask occlusive disease not apparent on resting studies.

Exercise testing (formal, informal) is commonly performed to justify more invasive testing for patients with claudication and normal resting ABIs. Exercise testing will unmask arterial disease that is physiologically significant with exercise but not evident at rest. Exercise testing is generally performed for lower extremity arterial disease. The discussion below focuses on lower extremity exercise testing. The principles of testing are the same for the upper extremity, except that a tabletop arm ergometer (hand crank) is used instead of a treadmill.

The dynamics of blood flow across a stenotic lesion depend upon the severity of the obstruction and whether the individual is at rest or exercising. Exercise normally increases systolic pressure and decreases peripheral vascular resistance. The effects of exercise on the cardiovascular system are discussed elsewhere. (See "Exercise physiology".)

Exercise augments the pressure gradient across a stenotic lesion. An arterial stenosis less than 70 percent may not be sufficient to alter blood flow or produce a systolic pressure gradient at rest; however, following exercise, a moderate stenosis may be unmasked and the augmented gradient reflected as a reduction from the resting ABI following exercise. Repeat ABIs demonstrate a recovery to the resting, baseline ABI value over time.

Protocols — There are many protocols for treadmill testing, including fixed routines, graded routines, and alternative protocols for patients with limited exercise ability [41].

●With a fixed routine, patients are exercised with the treadmill at a constant speed with no change in the incline of the treadmill over the course of the study. A common fixed protocol involves walking on the treadmill at 2 mph at a 12 percent incline for five minutes or less if the patient is forced to stop due to pain (not due to shortness of breath or angina). The walking distance, time to the onset of pain, and nature of any symptoms are recorded. The ABI is recorded at rest, one minute after exercise, and every minute thereafter (up to five minutes) until it returns to the level of the resting ABI. The ABI in patients with severe disease may not return to baseline within the allotted time period.

●Graded routines may increase the speed of the treadmill, but more typically the percent incline of the treadmill is increased during the study. A meta-analysis of eight studies compared continuous versus graded routines in 658 patients in whom testing was repeated several times [42]. The estimated reliability in determining the intermittent claudication distance (initial distance to calf pain) and absolute claudication distance (patient can no longer walk) as assessed by the intraclass correlation coefficient was found to be significantly better for the graded protocol for absolute but not intermittent claudication distance. The reliability of a continuous protocol using a 12 percent grade approached the reliability of the graded protocol.

●For patients with limited exercise ability, alternative forms of exercise can be used. Plantar flexion exercises or "toe ups" involve having the patient stand on a block and raise onto the balls of the feet to exercise the calf muscles. This form of exercise has been verified against treadmill testing as accurate for detecting claudication and PAD [43].

●For patients who cannot exercise, reactive hyperemia testing or the administration of pharmacologic agents such as papaverine or nitroglycerin are alternative testing methods to imitate the physiologic effect of exercise (vasodilation) and unmask a significant stenosis. Reactive hyperemia testing involves placing a pneumatic cuff at the thigh level and inflating it to a supra-systolic pressure for three to five minutes. This produces ischemia and compensatory vasodilation distal to the cuff; however, the test is painful, and thus, it is not commonly used.

Interpretation — A normal response to exercise is a slight increase or no change in the ABI compared with baseline. If the patient develops symptoms with walking on the treadmill and does not have a corresponding decrease in ankle pressure, arterial obstruction as the cause of symptoms is essentially ruled out and the clinician should seek other causes for the leg symptoms.

A fall in ankle systolic pressure by more than 20 percent and/or >30mmHg from its baseline value, or below an absolute pressure of 60 mmHg that requires >3 minutes to recover, is considered abnormal [44]. Severe claudication can be defined as an inability to complete the treadmill exercise due to leg symptoms and postexercise ankle systolic pressures below 50 mmHg. Single-level disease is inferred with a recovery time that is <6 minutes, while a ≥6 minute recovery time is associated with multilevel disease, particularly a combination of suprainguinal and infrainguinal occlusive disease [24].

TRANSCUTANEOUS OXYGEN MEASUREMENTS — Transcutaneous oxygen measurement (TcPO₂) may provide supplemental information regarding local tissue perfusion, and the values have been used to assess the healing potential of lower extremity ulcers or amputation sites. (See "Basic principles of wound management" and "Techniques for lower extremity amputation".)

Platinum oxygen electrodes are placed on the chest wall and extremities and on any digits that are being evaluated. The absolute value of the oxygen tension at the limb, foot or hand, or a ratio of the foot or hand value relative to chest wall value, can be used. A normal value at the foot is 60 mmHg, and a normal chest/foot ratio is 0.9 [45,46]. Local edema, skin temperature, emotional state (sympathetic vasoconstriction), inflammation, and pharmacologic agents limit the accuracy of the test.

The level of TcPO₂ that predicts tissue healing remains controversial. It is generally accepted that in the absence of diabetes and tissue edema, wounds are likely to heal if oxygen tension is greater than 40 mmHg [47]. A higher value is needed for healing a foot ulcer in the patient with diabetes. Patients with values of <20 mmHg are severely ischemic and are likely to need revascularization for wound healing. A meta-analysis of four studies found a more than threefold risk of developing a chronic wound healing complication in patients with a TcPO₂ below a threshold of 20 to 30 mmHg (odds ratio 3.2, 95% CI 1.1-9.7) [47].

DUPLEX ULTRASOUND — Duplex ultrasound (DUS) is the mainstay and initial noninvasive vascular imaging obtained when arterial stenosis or obstruction are suspected and is very useful in identifying aortoiliac/femoral arterial disease. DUS provides information on lesion severity (eg, measurement of peak systolic velocity [PSV], PSV ratios, waveform analysis), morphology, anatomic location, and extent of disease, and information about flow volume and velocity, when needed [11].

Duplex scanning can be used to evaluate the vasculature preoperatively, intraoperatively, or postoperatively, and can be used for stent or graft surveillance. A meta-analysis of 14 studies reported sensitivities and specificities for ≥50 percent stenosis or occlusion at 86 and 97 percent for aortoiliac disease, respectively, and 80 and 98 percent for femoropopliteal disease, respectively [48]. Duplex ultrasonography has gained a prominent role in the noninvasive assessment of the peripheral vasculature, overcoming the main limitation of other noninvasive methods (eg, need for intravenous contrast) and providing precise anatomic localization and accurate grading of lesion severity [49,50].

General principles — Real-time ultrasonography uses reflected sound waves (echoes) to produce images and assess blood velocity. Ultrasound modes routinely used in vascular imaging include the B (brightness) mode and the Doppler mode (B mode imaging + Doppler flow detection = DUS); other modes are also available (eg, power Doppler, three-dimensional ultrasound, contrast-enhanced ultrasound). The B-mode provides a greyscale image useful for evaluating anatomic detail (image 1). The quality of a B-mode image depends upon the strength of the returning sound waves (echoes). Echo strength is attenuated and scattered as the sound wave moves through tissue. Angles of insonation of 90° maximize the potential return of echoes. Higher-frequency sound waves provide better lateral resolution compared with lower-frequency waves. Thus, high-frequency transducers are used for imaging shallow structures at 90° of insonation.

The identification of vascular structures from the B-mode display is enhanced in the color mode, which displays movement (blood flow) within the field (waveform 2). The shift in sound frequency between the transmitted and received sound waves due to movement of red blood cells is analyzed to generate velocity information (Doppler mode). Flow toward the transducer is displayed as red by default, and flow away from the transducer is blue by default; the colors are semiquantitative and do not represent actual arterial or venous flow and can be altered by the operator.

Accurate measurements of Doppler shift and, therefore, velocity measurements require proper positioning of the ultrasound probe relative to the direction of flow. An angle of insonation of 60° is ideal; however, an angle between 30° and 70° is acceptable. The severity of stenosis is best assessed by positioning the Doppler probe directly at or just distal to the site of the stenotic lesion guided by color flow imaging.

The ratio of the velocity of blood at a suspected stenosis to the velocity obtained in a normal portion of the vessel is calculated. Velocity ratios >4 indicate a >75 percent stenosis in peripheral arteries (table 1).

●The normal peripheral arterial Doppler velocity waveform is triphasic (waveform 1A) with a sharp upstroke, forward flow in systole with a sharp systolic peak, sharp downstroke, reversed flow component at the end of systole, and forward flow in late diastole [51,52]. With high peripheral resistance, late diastolic flow may be reduced or absent.

●The biphasic arterial Doppler velocity waveform (waveform 1B) has a rapid upstroke, sharp peak, and fairly rapid downstroke, with a short period of antegrade flow in diastole. Flow is not seen below the baseline. A biphasic arterial Doppler waveform is seen with single-level arterial occlusive disease.

●The monophasic arterial Doppler velocity waveform (waveform 1C) has a slow upstroke, rounded peak, slow downstroke, no flow reversal, and is nonpulsatile. A monophasic arterial Doppler waveform is seen with multilevel obstructive arterial disease.

Different velocity waveforms are obtained depending upon whether the probe is proximal or distal to a stenosis. Progressive obstruction proximal to the Doppler probe results in a decrease in systolic peak, elimination of the reversed flow component, and an increase in the flow seen in late diastole. Decreased peripheral vascular resistance is responsible for the loss of the reversed flow component, and this finding may be normal in older patients or reflect compensatory vasodilation in response to an obstructive vascular lesion.

The pitch of the duplex signal changes in proportion to the velocity of the blood, with high-pitched harsh sounds indicative of stenosis. Proximal to a high-grade stenosis with minimal compensatory collateralization, a thumping sound is heard.

Anatomic sites

●Aortoiliac – Aortoiliac imaging requires the patient to fast for approximately 12 hours to reduce interference by bowel gas. It is therefore most convenient to obtain these studies early in the morning. Satisfactory aortoiliac Doppler signals (waveform 3) can be obtained from approximately 90 percent of individuals who have been properly prepared. Complete examination involves the visceral aorta, iliac bifurcation, and iliac arteries distally.

●Lower extremity – For the lower extremity, examination begins at the common femoral artery and is routinely carried through the popliteal artery. The tibial arteries can also be evaluated. In the upper extremities, the extent of the examination is determined by the clinical indication. Visualization of the subclavian artery is limited by the clavicle. Any areas of stenosis are initially localized with color Doppler and then quantified and assessed by measuring Doppler velocities. In general, the ratio of the peak systolic velocity (PSV) within an area of stenosis is compared with the PSV in the vessel just proximal to it to estimate the degree of stenosis. For the lower extremity, the percent stenosis can be estimated. A PSV ratio <2 indicates a <50 percent arterial stenosis, and a ratio >4 indicates >75 percent stenosis (table 1). The same general principles apply when determining the degree of stenosis within a lower extremity bypass graft.

●Upper extremity – There are no generally agreed upon criteria for determining stenosis in upper extremity arteries, and most vascular laboratories tend to extrapolate criteria from lower extremity arteries to upper extremity arteries.

Surveillance after intervention — Surveillance describes the routine, scheduled use of serial objective testing to evaluate the status of a vascular procedure. The primary goal of surveillance is to detect significant postprocedural problems at an early stage so that they can be managed safely and effectively, before recurrent clinical symptoms and signs manifest and before occlusion of the reconstruction occurs [3,53].

All open surgical and endovascular procedures have modes of failure that must be identified to ensure the best possible long-term results. Postprocedural surveillance is the key to detecting in situ stenotic lesions within a bypass graft or stent or complications that can increase morbidity and mortality. With the understanding that clinical monitoring alone may not accurately identify postprocedural vascular pathology, surveillance is generally performed routinely for patients postintervention even if the patient is asymptomatic postintervention. Performing surveillance assumes that action will be taken for significant problems that are identified on surveillance study.

Open lower extremity arterial revascularization — Revascularization of the lower extremities includes a variety of procedures for aortoiliac and infrainguinal artery reconstruction. Surveillance protocols for lower extremity revascularization include assessment of ABIs and clinical evaluation of the reconstructed segment(s) with duplex ultrasound (DUS) [54]. The optimal frequency and duration of surveillance depends on the intervention performed and vessels that are reconstructed. Generally, surveillance starts immediately after surgery and at 3, 6, and 12 months postoperatively and annually thereafter. This schedule is reapplied with each reintervention of the primary reconstruction.

Lower extremity revascularizations fail because of inadequate inflow or outflow, anastomotic stenoses, or problems within the bypass graft itself. Surveillance ABIs identify any significant variations from the postprocedural ABI, whereas DUS identifies graft-related lesions. Identifying and revising graft-threatening lesions has been demonstrated to prolong bypass graft patency [55-57].

●Aortoiliac revascularization – Aortoiliac reconstruction includes anatomic and extra-anatomic revascularizations. Validated criteria demonstrating an improvement in patency is available only for femoral-femoral bypass grafting.

•Aortobifemoral bypass – Aortobifemoral artery bypasses are performed to treat aortoiliac occlusive or aneurysmal disease. These grafts are associated with high patency rates because of the associated high flow in these large conduits. Patency rates range from 88 to 93 percent at three to five years [58,59]. To date, there are no studies describing validated surveillance protocols for these bypasses.

•Iliofemoral bypass – Iliofemoral bypass can be used, rather than femoral-femoral artery bypass, to treat unilateral iliofemoral occlusive disease. The in-line flow produced from iliofemoral bypass is associated with higher patency rates compared with extra-anatomic bypass (ie, femoral-femoral bypass) [60-62]. In addition, iliofemoral bypass reduces the number of groin incisions. There are no validated surveillance protocols for these bypasses.

•Femoral-femoral bypass – Femoral-femoral bypasses can be performed for unilateral iliac artery occlusive or in conjunction with concomitant axillary to femoral artery bypass for bilateral iliac artery occlusive disease. Patency rates are lower for femoral-femoral bypass compared with aortobifemoral bypass with demonstrated five-year patency rates of 72, 56, and 35 percent for aortobifemoral, iliofemoral, and femoral-femoral bypasses, respectively [63]. DUS criteria have been developed to guide revision of femoral-femoral bypasses. Grafts at risk include those with DUS-derived criteria of peak systolic velocity (PSV) >300 cm/s and PSV ratio >3.5. Intervening for these criteria increases the five-year assisted primary patency from 62 to 88 percent [64].

•Axillobifemoral bypass – Extra-anatomic axillobifemoral bypass is performed for patients in whom the risk for performing aortoiliac or femoral bypass is deemed to be too high, or for those with native aortic or aortic graft infections. Patency rates are lower for axillobifemoral bypass compared with femoral-femoral bypass, with higher rates of thrombosis likely driven by the length of the graft, burden of disease, and presence of infection. Cumulative three- to four-year patency rates are 85 to 87 percent. There are no validated surveillance criteria or protocols for these types of bypass [65,66].

●Infrainguinal revascularization

•Autogenous vein bypass – Autogenous infrainguinal bypass grafts are at risk for early, midterm, and late failure with graft failure and adverse outcomes related to inflow and outflow targets, type and quality of vein graft used, and patient-related factors as well. Graft surveillance is essential for long-term patency. Intrinsic vein graft stenosis is the most common cause of infrainguinal vein bypass graft failure and occurs most commonly within the first 18 months after graft implantation. ABI and DUS can dependably identify graft-threatening lesions, and criteria have been established to identify those grafts at risk for progression to occlusion. Such lesions are readily identified, graded for severity, and monitored for progression by a postoperative surveillance protocol.

The hemodynamic features of a successful infrainguinal autogenous graft include an postprocedure ABI >0.9, increase in ABI postprocedure >0.15, and graft flow velocity of >45 cm/s with low-resistance outflow waveforms [67]. Grafts at risk for thrombosis include those with a focal increase in peak systolic velocity (PSV, 180 cm/s to 300 cm/s) and velocity ratio (Vr). Vr = PSV at the site of the stenosis divided by the PSV in normal vessel proximal to the stenosis. The highest risk for graft thrombosis is identified by focal increase in PSV >300 cm/s, Vr >3.5, graft velocity <45, and drop in ABI >0.15 [67]. Surveillance with DUS may be associated with a small reduction in the rate of amputation [68], but compared with ABI and clinical exam, DUS PSV surveillance does not alter primary, assisted primary, or secondary patency or mortality [68-70]. This may be related to differences in vessel and graft diameters. As such, clinical exam and changes in ABI warrant further investigation.

•Prosthetic bypass – Graft surveillance is not effective for predicting failure of prosthetic lower extremity arterial bypass grafts [71]. Despite this evidence, low graft flow velocities have been used as a predictor for graft thrombosis, and this information has been used to support the use of anticoagulation with coumadin [71-74].

Endovascular lower extremity arterial revascularization — The use of endovascular techniques (eg, balloon angioplasty/stenting, atherectomy, laser-induced shock wave angioplasty, adjunctive drug-eluting therapies), has surpassed open surgical treatment for the management of lower extremity arterial disease. While postintervention surveillance has been suggested, the optimal frequency and method of DUS surveillance after endovascular therapy for lower extremity occlusive disease have not been established.

Some authors report routine DUS for surveillance, while others see no role for it, preferring physical exam alone for following patients. The DUS velocity criteria for detecting stenoses in native vessels or autogenous vein grafts, have been used for surveillance, but these may not be valid after endovascular revascularization. A baseline DUS within the first month after revascularization is recommended to establish a post-treatment baseline. Because the natural history of restenosis after EVT is unclear, surveillance schedules after EVT remain poorly defined.

●Aortoiliac revascularization – Short-term, midterm, and long-term primary patency rates for endovascular repair of aortoiliac occlusive disease are excellent and measured at 93, 83, and 78 percent at one year, three years, and five years, respectively [75-77]. PSV >300 cm/s and a Vr >2.5 have been used to identify hemodynamically significant stenoses [78].

●Femoropopliteal revascularization – The superficial femoral artery is the most commonly treated arterial segment using endovascular techniques. DUS has been used to evaluate this segment before and after intervention. Established criteria for determining a >50 percent stenosis include the combination of PSV >190 cm/s and Vr >1.5, which has a sensitivity of 85 percent, specificity of 95 percent, positive predictive value of 98 percent, and negative predictive value of 85 percent [79]. Criteria for high-grade restenosis include PSV >300 cm/s and Vr >3.5, and criteria correlate with angiographic findings of high-grade stenosis [79].

●Tibial revascularization – Tibial vessel revascularization is almost exclusively performed for chronic limb-threatening ischemia, and is associated with high rates of restenosis and low, intermediate, and long-term patency rates [80-82]. Reports are conflicting on the utility of DUS after endovascular tibial vessel revascularization, with some authors reporting a poor correlation with angiography, and others reporting DUS as reliable for surveillance after intervention [83,84]. Predictors for severe restenosis include a PSV >300 cm/s and Vr >3.5 [85]. These criteria, along with worsening clinical exam, can be used to indicate angiography.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Peripheral artery disease and claudication (The Basics)" and "Patient education: Duplex ultrasound (The Basics)")

●Beyond the Basics topics (see "Patient education: Peripheral artery disease and claudication (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Noninvasive vascular testing – Noninvasive vascular testing is an extension of the vascular history and physical examination and is used to confirm a diagnosis of arterial disease and determine the level, extent, and severity of disease. Available studies include physiologic tests that correlate symptoms with site and severity of arterial occlusive disease, and duplex ultrasonography (DUS) that further delineate vascular anatomy. (See 'Introduction' above.)

●Indications – Noninvasive vascular testing may be indicated to screen patients with risk factors for arterial disease, establish a diagnosis in patients with symptoms or signs consistent with occlusive arterial disease, identify a vascular injury, or evaluate the vasculature preoperatively, intraoperatively, or for surveillance following a vascular procedure (eg, stent, bypass). (See 'Indications for testing' above.)

●Physiologic testing – Physiologic tests include segmental limb pressure measurements and the determination of pressure index values (eg, ankle-brachial index [ABI], wrist-brachial index [WBI], toe-brachial index [TBI]), exercise testing, segmental volume plethysmography, and transcutaneous oxygen measurements. These tests generally correlate to clinical symptoms and are used to stratify the need for further evaluation and treatment. (See 'Physiologic testing' above.)

●Ankle-brachial index – The comparison of the resting systolic blood pressure at the ankle to the systolic brachial pressure is referred to as the ABI. (See 'Ankle-brachial index' above and 'Wrist-brachial index' above.)

•An ABI >0.9 with an upper limit of 1.3 generally excludes clinically significant arterial occlusive disease. Normally, the pressure is higher in the ankle than in the arm (ie, ABI >1 to 1.3). An ABI of 0.9 to 0.99 is classified as borderline normal.

•ABI ≤0.90 is diagnostic of arterial obstruction.

•ABI >1.30 suggests the presence of calcified vessels.

●Wrist-brachial index – The analogous index in the upper extremity is the WBI. The WBI is the comparison of the resting systolic blood pressure at the wrist to the systolic brachial pressure.

•WBIs are typically measured only when the patient has clinical signs or symptoms consistent with upper extremity arterial stenosis or occlusion.

•The normal value for the WBI is 1.

●Further lower extremity evaluation – The need for further lower extremity evaluation depends upon the ABI value (algorithm 1A-B).

•Normal ABI – For patients with a normal ABI and symptoms of claudication, we suggest exercise testing (formal, informal). An ABI that decreases by 20 percent following exercise is diagnostic of arterial obstruction, whereas a normal ABI following exercise eliminates a diagnosis of arterial obstruction and suggests the need to seek other causes for the leg symptoms. (See 'Exercise testing' above.)

•Low ABI – For symptomatic patients with an ABI ≤0.9 who are possible candidates for intervention, we perform additional noninvasive vascular studies to further define the level and extent of disease. Depending upon the clinical scenario and availability of resources, additional testing may include additional physiologic tests or DUS. (See 'Ankle-brachial index' above and 'Physiologic testing' above and 'Duplex ultrasound' above.)

•High ABI – For patients with an ABI >1.3, the TBI and pulse volume recordings (PVRs) should be performed. Normal TBI is 0.7 to 0.8. A normal PVR waveform is composed of a systolic upstroke with a sharp systolic peak followed by a downstroke that contains a prominent dicrotic notch. Progressive arterial stenosis alters the normal waveform and blunts its amplitude. (See 'High ABI' above and 'Toe-brachial index' above and 'Pulse volume recordings' above.)

●Digit waveforms – For patients with a normal ankle- or wrist-brachial index and distal extremity ischemia, individual digit waveforms and digit (toe) systolic pressures can be used to identify small-vessel occlusive arterial disease. (See 'Digit waveforms' above.)

●Transcutaneous oxygen – To assess potential for healing a wound or proposed amputation level, in addition to toe systolic pressure, transcutaneous oxygen measurement (or skin perfusion pressure studies) will provide information regarding local tissue perfusion. A normal value at the foot is 60 mmHg, and a value of 40 mmHg or higher predicts wound healing (a higher value may be required for patients with diabetes). (See 'Transcutaneous oxygen measurements' above.)

●Duplex ultrasound – Duplex ultrasound (DUS) is routinely used for diagnostic vascular imaging and for surveillance following intervention. Areas of stenosis localized with Doppler can be quantified by comparing the peak systolic velocity (PSV) within a narrowed area to the PSV in the vessel just proximal to it (PSV ratio). The percent stenosis in lower extremity native vessels and vascular grafts can be estimated (table 1). A PSV ratio <2 indicates a <50 percent arterial stenosis, and a PSV ratio >4 indicates >75 percent stenosis. These criteria can also be used for the upper extremity. (See 'Duplex ultrasound' above.)

All open surgical and endovascular procedures have modes of failure that can be identified to ensure appropriate management and best possible long-term results. Postprocedural surveillance is important to detect to graft/stent in situ stenoses/complications and recurrent disease that can increase morbidity and mortality. (See 'Surveillance after intervention' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic review.