Upper extremity atherosclerotic disease

INTRODUCTION — Atherosclerotic disease affecting the upper extremity arteries is common and is most often asymptomatic. However, it can cause exertional pain, ischemic pain, gangrene, or ulceration. Exertional pain is a reproducible discomfort of a defined group of muscles induced by exercise, when the demand for oxygenated blood exceeds the supply, and can be relieved with rest.

An overview of the clinical manifestations, diagnosis, and management of atherosclerotic disease of the upper extremity is presented. Surgical and endovascular techniques for upper extremity revascularization, when indicated, are reviewed separately. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization".)

Peripheral artery disease affecting the lower extremities is discussed in detail separately. (See "Overview of lower extremity peripheral artery disease".)

UPPER EXTREMITY ATHEROSCLEROSIS — Atherosclerosis is the most frequent etiology of upper extremity arterial stenosis. It can affect any of the upper extremity arteries, although it has the highest propensity for the proximal arteries (eg, subclavian artery, brachiocephalic artery). Some of the risk factors associated with peripheral atherosclerosis include increased age, hypertension, dyslipidemia, and tobacco use. These are discussed elsewhere. (See "Overview of established risk factors for cardiovascular disease".)

The prevalence of upper extremity atherosclerotic disease is much lower than that of lower extremity arterial disease [1]. Sex-specific data show that males are more likely than females to be affected during their lifetime. However, due to a longer life expectancy, the prevalence of atherosclerotic disease in the population is higher in females [2].

Proximal atherosclerotic disease — In a large study of extracranial arterial disease, the incidence of proximal upper extremity arterial occlusive disease (subclavian and innominate [brachiocephalic] arteries) was 17 percent [3]. Approximately 30 percent of such patients have subclavian artery stenosis [4], Approximately 30 percent of such patients have subclavian artery stenosis [3], which most commonly occurs on the left (>75 percent), possibly due to a more acute origin resulting in accelerated atherosclerosis from an increased turbulence in the blood flow [5-10]. Innominate disease is also not infrequent and can lead to right-sided symptoms.

Distal atherosclerotic disease — While proximal atherosclerotic disease is more commonly diagnosed, atherosclerosis is a systemic process that can also involve the distal upper extremity arteries (eg, brachial, radial, ulnar arteries) as well [11-17]. This is increasingly seen in systemic diseases affecting the medium and small vessels, such as diabetes and chronic kidney disease. These patients are at higher risk for developing calcification within the medial layer of the arterial wall, which can increase the risk for adverse outcomes and is a strong predictor of cardiovascular mortality [18].

In studies evaluating the radial artery as a possible conduit for coronary artery bypass, creation of a forearm flap, or hemodialysis arteriovenous access, atherosclerosis is commonly encountered and should be investigated prior to moving forward with these procedures [14-16]. Severe atherosclerotic disease in the arteries below the elbow is indicative of severe widespread atherosclerotic disease. In a review of 28 patients undergoing intervention for severe hand ischemia, 68 percent had coronary artery disease, 86 percent had peripheral artery disease, and 50 percent had a prior major lower limb amputation [13]. Typical presentations include older, dialysis-dependent patients with complaints of vascular access dysfunction, hand pain, or a nonhealing wound.

Occlusive disease affecting the digital arteries can also be due to atherosclerosis; however, symptomatic disease is more likely due to proximal embolization (eg, atheroembolism, thromboembolism) or autoimmune disease (eg, thromboangiitis obliterans, rheumatoid arthritis, scleroderma) [19]. (See 'Differential diagnosis' below and "Overview of upper extremity ischemia", section on 'Isolated hand symptoms'.)

VASCULAR ANATOMY — The subclavian artery provides blood flow to the upper extremity. The left subclavian artery originates directly from the aorta distal to the left common carotid artery. On the right, the brachiocephalic trunk (ie, innominate artery) arises from the aorta then divides into the right common carotid artery and the right subclavian artery. Anomalies of the aortic arch (figure 1) occur frequently within the population.

The vertebral arteries are most often the first branch of the subclavian artery. However, in approximately 6 percent of patients, the vertebral artery may originate directly from the aortic arch [20]. The subclavian artery lies posterior to the anterior scalene muscle and then passes between the first rib and the clavicle (figure 2) as it becomes the axillary artery at the lateral margin of the first rib.

The axillary artery is divided into three parts based on its relation to the pectoralis minor muscle and becomes the brachial artery (figure 3) at the lower margin of the teres major muscle. The brachial artery passes between the biceps and triceps muscles accompanied by the ulnar and median nerves and adjacent to the humerus. It supplies the soft tissues of the arm. In the antecubital fossa, the brachial artery divides (figure 4) into the radial, interosseous, and ulnar arteries to supply the soft tissues of the forearm. The ulnar artery and radial artery provide blood flow to the hand (figure 5) and terminate as the superficial and deep palmar arch in the hand.

Collateral circulation — An extensive collateral circulation around the shoulder usually compensates for stenosis or occlusion of the innominate, subclavian, or axillary arteries (figure 6). Blood flow is maintained to the arm via connections between the superior and inferior thyroid arteries; vertebral arteries, intercostal arteries, superior epigastric and internal thoracic arteries; profunda cervicis and the descending branch of the occipital artery; scapular branches of the thyrocervical trunk and the branches of the axillary artery; and the thoracic branches of the axillary artery via the aortic intercostals [21].

Collateral circulation around the elbow (figure 7) is often able to compensate for arterial disease at the antecubital fossa. The collateral circulation around the elbow includes contributions from the radial recurrent arteries, the anterior and posterior ulnar recurrent arteries and the inferior and superior ulnar collateral arteries, and the deep brachial and dorsal interosseous arteries.

CLINICAL FEATURES

Presentations — Most patients with upper extremity atherosclerotic disease are asymptomatic and are found incidentally to have asymmetric arm blood pressures or during ultrasound testing in patients with carotid or coronary artery disease. (See 'Physical examination' below.)

When symptoms occur, they can be related to embolism, or to hemodynamic alterations that reduce perfusion to the extremity, the brain, or heart (in patients with coronary artery bypass grafts). A thorough review of the patient's symptoms, their location, and time of onset can provide valuable information to aid in diagnosis.

Chronic upper extremity ischemia — Chronic upper extremity ischemia occurs in association with proximal arterial stenosis or obstruction due to reduced blood flow to the distal extremity. Exercise-induced arm pain/fatigue is relatively common in patients with subclavian stenosis, occurring in approximately one-third of patients. Patients with prior radiotherapy for breast cancer may present with long-segment stenosis or occlusion of the axillary-subclavian arteries, which can be misdiagnosed as brachial plexopathy [22]. More distal arterial occlusions can result in trophic changes or tissue loss, particularly in patients on dialysis using an arteriovenous access. (See "Overview of upper extremity ischemia", section on 'Chronic ischemia'.)

Vascular steal syndromes — Proximal atherosclerotic disease can produce alterations in flow that may produce cerebrovascular symptoms (ie, subclavian steal syndrome) or cardiac ischemia (ie, coronary-subclavian steal syndrome). However, only a minority of patients with proximal stenosis develop such a condition, predominantly because of the extensive collateral network of vessels around the shoulder (figure 6) [1,23-33]. In a study of 7881 patients presenting for ultrasound examination of the extracranial neck vessels, 432 were identified with subclavian stenosis/occlusion, with only 38 (8.8 percent) experiencing symptoms [10]. (See 'Collateral circulation' above and 'Subclavian steal' below and 'Coronary-subclavian steal' below.)

Subclavian steal — Atherosclerotic disease is one of several etiologies that can cause subclavian steal. The stenotic proximal segment decreases the blood pressure in the distal subclavian artery [5,34]. As a result, blood flows from the contralateral vertebral artery to the basilar artery and may flow in a retrograde direction down the ipsilateral vertebral artery away from the brainstem to perfuse the upper extremity, a phenomenon known as subclavian steal (figure 8) [4,35].

Subclavian steal syndrome refers to the occurrence of cerebrovascular symptoms due to the reversal of flow in the vertebral artery as it becomes an important collateral pathway for blood flow to the arm. Patients with documented steal physiology have a low incidence of developing symptoms [3,36]. Left-sided subclavian steal is more prevalent due to the propensity for atherosclerosis on the left, although right-sided steal has also been reported (image 1) [37-39]. The clinical features and diagnostic criteria for subclavian steal syndrome are reviewed separately. (See "Subclavian steal syndrome".)

Coronary-subclavian steal — A coronary-subclavian steal has been described in patients who have undergone prior coronary artery bypass surgery (CABG) using the internal mammary artery (IMA) [40-42]. In the presence of a hemodynamically significant subclavian artery stenosis proximal to the origin of the ipsilateral IMA, flow through the IMA may reverse and "steal" flow from the coronary circulation causing angina during upper extremity exertion (figure 9) .

Patients who have had a prior cardiac bypass presenting with chest pain and a measurable blood pressure difference in the upper extremities should be evaluated for coronary-subclavian steal. Coronary and aortic angiography will demonstrate retrograde flow in the grafted IMA [43].

The prevalence of subclavian artery stenosis is approximately 5 percent in patients referred for coronary artery bypass grafting [44,45]; however, there is little guidance concerning screening. Patients identified with high-grade subclavian artery stenosis should be treated (percutaneously or surgically) prior to CABG [46]. In one review comparing a combined and staged approach with revascularization, complications, mortality, and symptom recurrence were similar for patients with symptomatic subclavian lesions who underwent coronary artery bypass [47].

Thromboembolism — Acute thrombosis or embolism from atherosclerotic plaque can cause distal peripheral occlusion leading to acute ischemia [48]. Physical signs include classic symptoms (ie, pain, pallor, pulselessness, coolness of the extremity [ie, poikilothermia], paresthesia, paralysis) and may involve the entire extremity or be limited to the more distal circulation. When collateral circulation is insufficient to compensate, minor sensory deficits develop as a sign of early nerve dysfunction; major sensory or motor loss indicates advanced ischemia. (See "Overview of upper extremity ischemia", section on 'Acute ischemia' and "Embolism to the upper extremities".)

Atherosclerotic disease of the innominate or subclavian arteries can also be a source of cerebrovascular embolism, causing transient ischemia attack or stroke affecting the anterior or posterior cerebral circulation [49]. (See "Stroke: Etiology, classification, and epidemiology", section on 'Embolism'.)

Physical examination — A thorough examination of the upper extremity and comparison to the nonaffected extremity provides useful information that can help the clinician not only in diagnosis but also localization of the diseased arterial bed.

Blood pressure differential — A difference in resting brachial systolic blood pressure between the affected and normal arm of at least 10 mmHg indicates a significant proximal stenosis. A systematic review identified 20 studies evaluating blood pressure differentials in the upper extremity [50]. In noninvasive studies, a pooled difference of ≥15 mmHg or more was associated with a significant stenosis with high specificity (specificity 96 percent, 95% CI 94-98). A large pressure differential of >40 mmHg between the upper extremities is more commonly associated with symptoms and the need for treatment. (See "Overview of upper extremity ischemia".)

If a blood pressure difference is identified, we repeat the blood pressure measurement in both arms to confirm the finding. In a small cohort study of cardiac surgery patients, approximately 40 percent with a systolic pressure differential in the arm of 15 mmHg or more had a subclavian stenosis [51]. The authors also reported that 10 percent of those without a difference in blood pressure also had subclavian artery stenosis. However, this finding may reflect an inadequate pressure measurement technique.

The blood pressure differential in the upper extremity can be further investigated in the noninvasive vascular laboratory. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Upper extremity segmental pressures'.)

Vascular examination — A complete vascular examination of the upper extremity extends from the neck to the wrist to determine the characteristics of the pulse, the presence of any arterial bruits, the temperature of the skin and capillary refill, gross sensation, and the presence of any scars or open wounds. It is recommended to avoid using the thumb during the evaluation of the pulses to prevent confusion with the clinician’s own digital pulsations [52].

Simultaneous palpation of the bilateral radial arteries at the wrist may disclose a decrease in the intensity or a delay in arrival on the affected side, but this may be difficult to appreciate in the absence of an obvious blood pressure differential (waveform 1).

It is important to examine the subclavian arteries in the supraclavicular fossa using palpation to characterize the pulse or feel for the presence of a thrill and auscultation for bruits. The carotid arteries in the neck should also be carefully examined for evidence of occlusive arterial disease. Auscultation over the suboccipital region for vertebral artery bruits should also be performed.

Approximately 6 percent of patients with asymptomatic neck bruits have a significant lesion on duplex scanning [37,53]. In one prospective study, among 500 patients with asymptomatic neck bruits, 9 percent had subclavian stenosis [53]. None of the patients had exertional upper extremity pain but approximately half had evidence of subclavian steal physiology.

Evaluate the skin of the hands and nail beds for signs of atheroembolism which may cause cyanosis, livedo reticularis, digital ischemia, ulceration, or splinter hemorrhages under the nail beds. (See "Embolism to the upper extremities".)

Patients with an abnormal upper extremity examination may also have clinical findings consistent with lower extremity peripheral artery disease (PAD; eg, claudication symptoms, reduced lower extremity pulses, ankle-brachial index ≤0.9). (See "Noninvasive diagnosis of upper and lower extremity arterial disease".)

An analysis of several large patient cohorts reported subclavian stenosis in 6 percent of men and 9.7 percent of women who had lower extremity PAD. By comparison, less than 2 percent of individuals without lower extremity PAD had subclavian stenosis [6].

DIAGNOSIS — Upper extremity atherosclerotic disease may be suspected based on clinical features (exertional pain, differential blood pressures, distal embolization, steal syndromes), but the diagnosis requires the demonstration of atherosclerotic stenosis or occlusion on vascular imaging (duplex ultrasound, angiography). For symptomatic patients, it is also important to confirm that the location and severity of the lesion is sufficient to be the cause of the patient's symptoms.

Duplex ultrasound — Duplex ultrasound of extracranial cerebrovascular and upper extremity arterial circulation is the first-line imaging modality for the detection of upper extremity atherosclerotic disease. Duplex ultrasound also demonstrates steal physiology when present. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Duplex ultrasound'.)

For patients with suspected upper extremity atherosclerotic disease, duplex ultrasound will often identify the specific site and severity of stenosis or occlusion based on the characteristics of the arterial waveform proximal, distal, and at the site of disease [54]. A normal waveform will display a sharp systolic upstroke with a retrograde wave in early diastole followed by a small antegrade component due to the normal compliance of the artery known as a triphasic waveform. As a stenosis becomes clinically significant, the waveform changes to a monophasic waveform as there is loss of the retrograde wave due to decreased compliance of the vessel wall. At the site of the stenosis, there is an increase in the amplitude of the systolic waveform indicating an increase in the velocity of the blood flow. The waveform distal to a stenosis is blunted and characterized by a delayed and low-amplitude systolic wave. If the vessel is occluded, no blood flow will be seen, and blood flow may be reconstituted distally from collateral vessels [55].

Typically, a peak systolic velocity (PSV) increase of more than 100 percent or velocity ratio >2 in an adjacent artery indicates a 50 to 74 percent stenosis. As there is more severe narrowing in the artery, a fourfold increase in the PSV or velocity ratio >4 indicates a >75 percent stenosis. There is no consensus criteria for the interpretation of subclavian artery velocities. However, a single institution, retrospective review showed a subclavian artery with a PSV >240 cm/second predicted a significant (>70 percent) stenosis [56]. Using these values, the sensitivity and specificity were 90.9 and 82.5 percent, respectively. In a later review, optimal cutoff values were PSV ≥340 cm/second and PSV ratio ≥3 in predicting ≥70 percent stenosis [54]. Duplex ultrasound is also highly accurate for the assessment of significant extracranial carotid artery occlusive disease.

Duplex ultrasound is also highly accurate for the assessment of significant extracranial carotid and vertebral artery occlusive disease. Duplex can demonstrate reversal of flow in the vertebral artery (image 2) ipsilateral to a significant proximal subclavian or innominate artery stenosis. The likelihood of finding retrograde flow in the vertebral artery increases in proportion to the severity of the subclavian artery stenosis. Prior to developing this reversal of flow, duplex will demonstrate a sharp decrease in blood flow velocity following the PSV in the vertebral artery. Recognition of these early changes may identify patients at risk for development of a steal syndrome (see 'Vascular steal syndromes' above) [57,58]. In patients with moderate subclavian artery stenosis (approximately 50 percent stenosis), flow reversal in the vertebral artery is constant in 56 percent and intermittent (alternating "to-and-fro" flow) in 36 percent. When severe stenosis (>80 percent narrowing) of the proximal subclavian artery is present, 65 percent of patients have constant flow reversal in the ipsilateral vertebral artery, and 30 percent have intermittent flow reversal [36,59].

A reactive hyperemia test, while not routinely performed, can demonstrate occult or intermittent subclavian steal [60-62]. This test applies a blood pressure cuff to the ipsilateral extremity that is inflated at least 20 mmHg above the patient's systolic pressure for three to four minutes to induce ischemia and compensatory vasodilation in the distal extremity. Following cuff deflation, as blood flow increases in the upper extremity, reversal of blood flow in the ipsilateral vertebral artery may be observed and symptoms may be provoked [63].

Angiography — In symptomatic patients with upper extremity atherosclerotic disease and abnormal findings on duplex ultrasound, computed tomography (CT) angiography can be performed to confirm and grade any stenotic lesions or is indicated when ultrasound is nondiagnostic but suspicion for atherosclerotic disease remains high. CT angiography can also reveal anatomic abnormalities or pathology such as thrombosis, aneurysm, and vasculitis [10,64,65].

Contrast-enhanced magnetic resonance (MR) angiography combined with phase-contrast MR imaging can characterize the majority of supra-aortic arteries with excellent image quality and diagnostic value comparable to CT angiography or conventional catheter-based arteriography [66,67]. MR angiography is also accurate and reliable for patients with subclavian stenosis [68]. Flow reversal in the vertebral artery ipsilateral to a subclavian stenosis is inferred when there is vertebral artery patency on three-dimensional contrast-enhanced MR but absence of flow on time-of-flight localizer images [69]. In addition to evaluation of the extracranial vessels, MR also provides detailed anatomic information of the intracranial cerebrovascular circulation. Pitfalls in the use of MR as an arterial imaging modality include the possibility of overestimating the severity of stenosis and the inability to discriminate near-complete from complete arterial occlusion.

Digital subtraction arteriography is generally not needed to establish a diagnosis but is typically performed concomitantly and just prior to endovascular intervention. It can also be used to identify intracranial atherosclerotic disease and anomalies of the circle of Willis.

DIFFERENTIAL DIAGNOSIS — Atherosclerosis is the most common cause of ischemic upper extremity disease (table 1), but upper extremity ischemia (acute or chronic) can be caused by other etiologies such as arterial injury, arterial dissection, thrombosed aneurysm, atheroembolism, thromboembolism, thromboangiitis obliterans, fibromuscular dysplasia, arteritis (eg, Takayasu disease, giant cell arteritis), and repetitive arterial injury (thoracic outlet syndrome, crutch injury) [70,71]. (See "Overview of upper extremity ischemia".)

Patients who present with a blood pressure differential and acute chest pain should be evaluated for an acute aortic syndrome (eg, aortic dissection, aortic intramural hematoma). (See "Clinical features and diagnosis of acute aortic dissection".)

MANAGEMENT

Cardiovascular risk reduction — Upper extremity atherosclerotic disease is associated with an increased risk of overall mortality as well as cardiovascular mortality. Upper extremity atherosclerotic disease has also been frequently associated with atherosclerosis of other large vessels, particularly the carotid, coronary, and lower extremity arteries.

●In one systematic review, blood pressure differentials in the upper extremity (≥15 mmHg or more) were associated with increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1.7, 95% CI 1.1-2.5) and all-cause mortality (HR 1.6, 1.1-2.3) [50].

●A study using baseline and longitudinal data for three cohorts (1778 participants recruited from two noninvasive vascular laboratories and one community dwelling) followed patients over a mean of 9.8 years [72]. Subclavian artery stenosis correlated with higher all-cause and cardiovascular mortality independent of the presence of cardiovascular risk factors or peripheral arterial disease.

Conservative and medical management to improve outcomes in patients with peripheral artery disease and for secondary prevention of cardiovascular disease are discussed in detail separately. (See "Overview of lower extremity peripheral artery disease", section on 'Risk factor modification' and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Indications for intervention

Asymptomatic — Revascularization is rarely needed in patients with asymptomatic proximal upper extremity arterial occlusive disease. However, it may be warranted in patients undergoing coronary artery bypass grafting, especially when planning on use of an internal mammary artery graft. Selected hemodialysis patients requiring the creation or preservation of an upper extremity hemodialysis access may also benefit from revascularization to prevent ischemic symptoms as well as improve fistula maturation.

Symptomatic — For symptomatic patients, vascular intervention is required for those with:

●A threatened upper extremity (eg, acute limb ischemia, chronic limb-threatening ischemia) to restore perfusion, alleviate symptoms, and heal any ulcers

●Significant cardiac symptoms related to coronary-subclavian steal syndrome

●Embolization (cerebral, peripheral) from the lesion to exclude it from the circulation and prevent future ischemia

●End-stage kidney disease to allow the creation or preservation of upper extremity hemodialysis access

In patients with neurologic symptoms and subclavian steal physiology, it may be difficult to determine if steal phenomena is the primary etiology of their symptoms. Revascularization remains controversial, and therefore, the approach to these patients is individualized. (See "Subclavian steal syndrome", section on 'Atherosclerotic subclavian steal syndrome'.)

Intervention for proximal disease — Selection of the most appropriate intervention (surgical, endovascular) is individualized based on anatomic factors (eg, lesion severity, location, calcification, proximity to the vertebral artery), the presence of concomitant ipsilateral carotid disease, and the patient's overall medical status.

For symptomatic proximal stenosis or occlusion, options include surgical and percutaneous transluminal angioplasty and stenting [73-75]. Surgical revascularization is more durable compared with endovascular intervention. However, percutaneous angioplasty/stenting may be associated with less perioperative morbidity. Techniques for proximal upper extremity revascularization are reviewed separately. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization".)

●Endovascular intervention – High-quality data are limited and a 2022 systematic review found no randomized trials comparing angioplasty alone with stenting for subclavian artery stenosis [73]. However, retrospective studies suggest that endovascular intervention in the subclavian artery is safe with low morbidity and mortality; one study of 110 patients who had percutaneous transluminal angioplasty reported a 3.6 percent combined stroke and death rate [76]. Immediate technical success was greater than 93 percent, with failures usually related to an inability to cross occluded lesions [77-79]. Five-year primary patency rates are approximately 85 percent [78]. In a single-center retrospective review of 167 patients with left subclavian artery stents who were being evaluated for coronary artery bypass, stent patency rates were 75.2 percent at 10 years [80]. Freedom from reintervention for the target vessel and sustained resolution of ischemic symptoms is observed in most patients (>95 percent) [76,78,79,81-83]. Whether angioplasty alone has inferior outcomes compared with angioplasty and stenting depends on the nature of the lesion being treated [84,85]. Angioplasty alone has inferior outcomes when recanalizing occlusive subclavian lesions. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization", section on 'Angioplasty/stenting'.)

●Surgical revascularization – Extra-anatomic revascularization (eg, carotid-subclavian bypass [86,87], subclavian-carotid transposition [88]) is the most common form of surgical revascularization for proximal stenosis. As with angioplasty and stenting, high-quality data from randomized trials are lacking. Overall patency rates of 95 percent at one year, 86 percent at three years, and 73 percent at five years have been reported [89]. Procedures using the common carotid artery as the donor vessel generally have high patency rates at five years compared with those using the contralateral subclavian or axillary arteries (83 versus 46 percent) [89]. Axillo-axillary bypass is an alternative method of extra-anatomic revascularization that can be used in high-risk surgical patients [90].

Significant (>70 percent) recurrent stenosis or obstruction following subclavian revascularization occurs in approximately 10 percent of patients. In a study of 138 patients, predictors of restenosis were continued tobacco use and chronic obstructive pulmonary disease, younger age, lack of statin use, vessel diameter <7mm, and right-sided intervention [91]. In a review of 114 patients, assisted primary patency and freedom from recurrent symptoms were worse in patients presenting with arm ischemia compared with those presenting with cardiac or posterior circulation symptoms at five years [92]. Recurrent lesions are typically treated with repeat angioplasty; however, surgery may be required in up to 5 percent of patients [76]. Patients with a continuous (compared with intermittent) subclavian and coronary artery steal may have a higher risk of subclavian artery restenosis following endovascular intervention [93].

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".)

SUMMARY AND RECOMMENDATIONS

●Upper extremity atherosclerosis – Although symptoms due to peripheral artery disease (PAD) are more common in the lower extremities, upper extremity exertional pain, pain at rest, and tissue loss may also manifest in the upper extremities due to atherosclerotic disease. Atherosclerosis is predominantly localized to the subclavian artery, but distal vessels can also be affected. (See 'Upper extremity atherosclerosis' above.)

●Arterial anatomy – The subclavian arteries provide blood flow to the upper extremities. On the left, the subclavian artery originates directly from the aorta distal to the left common carotid artery. On the right, blood flows first through the innominate artery, then into the right subclavian artery. The collateral circulation around the shoulder (figure 6) and elbow (figure 7) is usually sufficient to provide flow around a focal proximal stenosis. (See 'Vascular anatomy' above.)

●Clinical features

•No symptoms – Most patients with upper extremity atherosclerotic disease have few to no symptoms because of the robust collateral circulation. Those with proximal atherosclerotic disease may manifest with a significant difference in brachial systolic blood pressure (>15 mmHg differential) between the affected and normal extremity, and for many, the finding is incidental. (See 'Clinical features' above and 'Physical examination' above.)

•Symptoms – When symptoms do occur, exertional arm pain or posterior circulation symptoms (eg, dizziness, vertigo) are most common. However, evidence of distal thromboembolism, acute limb ischemia, or more severe chronic ischemic symptoms (eg, rest pain) can also occur. In some patients, stenosis or occlusion proximal to the origin of the vertebral artery can cause a reversal of flow in the vertebral artery, which in association with cerebrovascular symptoms is referred to as subclavian steal syndrome (figure 8). In patients with an internal mammary artery (IMA) bypass graft to the heart, a coronary steal syndrome can similarly occur (figure 9). (See 'Clinical features' above.)

•Physical examination – On physical examination, in addition to a blood pressure differential, patients may exhibit reduced distal pulses in the affected upper extremity and a thrill or bruit overlying the affected vasculature.

●Diagnosis – For patients with suspected upper extremity atherosclerotic disease, duplex ultrasound is the first-line imaging modality to identify and quantify the severity of any stenoses. Duplex ultrasound can also demonstrate a reversal of flow in the ipsilateral vertebral artery if present. If needed, angiography that includes the aortic arch vessels and intracranial vessels can be accomplished with CT, MR, or occasionally, digital subtraction arteriography. (See 'Diagnosis' above.)

●Differential diagnosis – Atherosclerosis is the most common cause of ischemic upper extremity disease (table 1), but other causes include arterial injury, arterial dissection, thrombosed aneurysm, atheroembolism, thromboembolism, fibromuscular dysplasia, arteritis (eg, giant cell arteritis, Takayasu disease, giant cell arteritis), small artery disease (eg, vasculitis), and repetitive arterial injury. (See 'Differential diagnosis' above.)

●Risk reduction – Upper extremity atherosclerotic disease is a marker for atherosclerotic disease in other arterial beds (eg, carotid, coronary, lower extremity arteries) and is associated with an increased risk of morbidity and mortality. All patients with atherosclerotic disease benefit from secondary prevention measures such as smoking cessation, control of hypertension, lipid modification, and antiplatelet therapy. (See 'Cardiovascular risk reduction' above.)

●When to intervene – (See 'Indications for intervention' above.)

•For most asymptomatic patients, no specific intervention is generally necessary, other than cardiovascular risk reduction. However, intervention may be needed prior to coronary artery bypass grafting that will use an internal mammary (thoracic) artery graft or in selected hemodialysis patients to allow the creation or preservation of an upper extremity hemodialysis access.

•For symptomatic patients, in addition to cardiovascular risk reduction, vascular intervention is required for those with:

-A threatened upper extremity (eg, acute limb ischemia, chronic limb-threatening ischemia) to restore perfusion, alleviate symptoms, and heal any ulcers

-Significant cardiac symptoms related to coronary-subclavian steal syndrome

-Embolization (cerebral, peripheral) related to the lesion to prevent future ischemia

-End-stage kidney disease to allow the creation or preservation of upper extremity hemodialysis access

●Choice of intervention – Selection of the most appropriate intervention (surgical, endovascular) is individualized based upon anatomic factors (eg, lesion severity, location, calcification, proximity to the vertebral artery), the presence of concomitant ipsilateral carotid disease, and the patient's overall medical status. For proximal lesions (subclavian artery, innominate artery), extra-anatomic reconstruction is more durable compared with endovascular intervention. However, percutaneous angioplasty/stenting may be associated with less perioperative morbidity. (See 'Intervention for proximal disease' above.)

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Neal R Barshes, MD, MPH, FACS, who contributed to earlier versions of this topic review.

The UpToDate editorial staff also acknowledges Emile R Mohler, III, MD (deceased), who contributed to earlier versions of this topic review.