Continuing Education Activity

Subclavian artery thrombosis is a common condition that is felt to be underdiagnosed. It involves obstruction of blood flow through the subclavian artery and is four times more common in the left subclavian artery than in the right. It can cause significant ischemia of the brain, upper extremities, and, occasionally, the heart. The incidence of subclavian artery thrombosis in patients with peripheral vascular disease is approximately 11 to 18%. Likewise, the patient with subclavian artery thrombosis will have a 50% chance of having coronary artery disease, 27% for lower extremity artery disease, and 29% for carotid artery disease. This activity illustrates the evaluation and treatment of subclavian artery thrombosis and reviews the role of interprofessional team members in managing those with this condition.

Objectives:

• Describe the typical exam findings in a patient with subclavian artery thrombosis.
• Summarize the differential diagnosis of subclavian artery thrombosis.
• Outline considerations that influence the management of subclavian artery thrombosis.
• Review the importance of improving care coordination among the interprofessional team in educating patients about the many consequences of smoking and the benefits of quitting, particularly concerning the likelihood of morbidity and mortality associated with subclavian artery thrombosis.

Introduction

The subclavian arteries (SCAs) may be affected by a wide range of nontraumatic pathologies, such as atherosclerosis, type A aortic dissection, arterial thoracic outlet syndrome, and acute arterial thrombosis.[1] Subclavian artery thrombosis is typically underdiagnosed by physicians. Harrison, in 1829 was the first to uncover stenosis of the initial segment of the subclavian artery.[2] Bachman and Kim 1980 performed the first angioplasty of the subclavian artery.[3] The disease is four times more common in the left subclavian artery than in the right. Subclavian artery stenosis can cause significant ischemic symptoms in the upper extremities, brain, and rarely in the heart. 

Etiology

The most widely recognized etiology for subclavian artery thrombosis is atherosclerosis; other uncommon etiologies are congenital deformities, fibro-muscular dysplasia, neurofibromatosis, autoimmune vasculitis-like Takayasu, radiation exposure, neurofibromatosis, inadvertent puncture and mechanical causes including injury or compression disorders.[4][5]

Epidemiology

The incidence of subclavian artery thrombosis in a patient with peripheral vascular disease is approximately 11 to 18%.[6] Likewise, the patient with subclavian artery thrombosis will have a 50% chance of having coronary artery disease, 27% for lower extremity artery disease, and 29% for carotid artery disease.[7] Because of the common pathogenesis, patients with subclavian artery thrombosis have an elevated risk for coronary artery disease, transient ischemic attack, and cerebrovascular ischemia or infarction. This risk correlates more with the left-sided lesion.[8][9][10]

Pathophysiology

The risk factors for subclavian artery thrombosis are the same as thrombosis in any other body site. The main risk factors are obesity, hypertension, diabetes mellitus, smoking, and metabolic syndrome. Like other artery thromboses, subclavian artery thrombosis also involves an area subjected to increased shear stress leading to endothelial injury and subsequent platelet aggregation and release of platelet-derived growth factor. This sequence triggers the proliferation of smooth muscle cells in the arterial intima and forms the locus of the atherosclerotic plaque. 

History and Physical

The presence of symptoms depends on collateralization. Upper limb symptoms comprise arm claudication or muscle fatigue, rest pain, and finger necrosis from embolic debris. Characteristic neurologic symptoms include vertebrobasilar hypoperfusion, including visual abnormalities (diplopia), drop attacks, syncope, ataxia, vertigo, dysphasia, dysarthria, dizziness, nystagmus, tinnitus, hearing loss, facial sensory deficits. Vertebrobasilar insufficiency develops when subclavian artery thrombosis is distal to the origin of the vertebral artery; thus, during conditions of increased flow distal to the stenosis like exercise, results in retrograde flow in the vertebral artery, followed by decreased flow in the basilar artery.

One of the rare complications of subclavian stenosis that develops in a patient who has had coronary artery bypass surgery with the internal mammary artery (IMA) graft is angina pectoris. The internal mammary artery arises from the subclavian artery and can be affected by stenosis. If there is subclavian artery thrombosis proximal to the IMA graft, flow impairment to the IMA may occur. In severe stenosis, retrograde flow from the grafted coronary artery to the brachial artery may lead to angina, a phenomenon called coronary steal syndrome.

Physical examination, particularly cardiovascular examination, may reveal unequal blood pressure in arms, absent or diminished pulses (axillary, brachial, and radial/ulnar) compared to the contralateral arm, and cervical or supraclavicular bruits. Ischemic findings such as gangrenous skin changes of the fingers or splinter hemorrhages of the nail bed may also be present. The examination should also focus on cerebral circulation, including palpation of carotid pulses and auscultation for vertebral (suboccipital region) and carotid bruits.

The inter-arm systolic blood pressure difference of less than 10mm Hg has a negative predictive value of 99%.[6] 

Evaluation

The goal standard diagnostic modality is imaging. However, diagnosis is possible from clinical findings, which may suggest possible subclavian artery thrombosis, including unequal upper limb blood pressures, absent or diminished axillary, brachial, radial, or ulnar pulses, and digital ulceration or gangrene. 

The difference in systolic blood pressure of over 10 mm Hg between both arms has a positive predictive value of 13%.[6] However, if the systolic cut-off increases to 15 or 20 mm Hg, the positive predictive value increases from 67% to 100%, and the negative predictive value up to 100%.[11][12]

Non-invasive diagnostic imaging for the diagnosis of subclavian artery thrombosis is duplex ultrasound with color flow. Duplex ultrasonography shows waveform dampening or monophasic changes, color aliasing suggestive of turbulent flow, and increased blood flow velocities at the location of the stenosis. Doppler ultrasonography can also diagnose a reversal of ipsilateral vertebral artery flow, as seen in subclavian steal syndrome. 

Duplex ultrasonography of the subclavian arteries enables the detection of stenosis. Detection of high-velocity flows indicates a greater than 50% stenosis.[1] However, it should be noted that differentiating high-grade subclavian artery ostial stenosis from complete obstructive lesions is challenging. The majority of subclavian artery ostial lesions are located proximally. The following findings suggest the high-grade, greater than 70% stenotic lesions in the proximal subclavian arteries; 1. monophasic post-stenotic flow, and 2. altered flow in the ipsilateral vertebral artery.[1] 

Detailed Duplex evaluations are mandatory to identify the severe stenotic or obstructive right brachiocephalic trunk. Reduced flow velocities in the right subclavian and common carotid arteries reflect higher grades of right brachiocephalic trunk stenotic lesions.[1][13] Anatomic imaging, including CT-angiography or magnetic resonance angiography, is indicated in these circumstances. The major advantage of CT angiography is providing comprehensive extravascular information. This potential is specifically important in evaluating patients with the impression of vascular thoracic outlet syndrome. Moreover, supra-aortic lesions have distinguished characteristics on CT-angiography images.[14]

More accurate diagnostic modalities include computed tomography and magnetic resonance angiography (MRA), reserved for when intervention is mandatory. The advantage of MRA in evaluating these lesions is providing not only morphological but also functional characteristics, enabling optimal differentiation and measuring the stenotic severity.  

Multi-detector CT (MDCT) angiography is an excellent measure for diagnosing pathologic conditions of the subclavian arteries.[1] Several factors must be respected to optimize the quality of an MDCT examination to evaluate subclavian artery thrombosis. These factors include 1. arm positioning, 2. contrast material application technique, 3. data acquisition, and 4. reconstruction parameters.[1]The recommendations for screening include when a patient is undergoing coronary artery revascularization using the intermammary artery, such as coronary artery bypass graft (CABG), and the suspicion of subclavian stenosis is high, or if a patient has a history of peripheral artery disease or systolic blood pressure differences in their upper limbs of over 10 mm Hg.[15]

Treatment / Management

Treatment Indications

1. Morbid upper arm ischemia (57%)
2. Upper limb claudication
3. Upper extremity pain at rest
4. Fingers embolization
5. Vertebrobasilar insufficiency from steal syndrome (37%)
6. Anginal symptoms from coronary steal via Intermammary artery graft (21%)
7. Leg claudication in the presence of axillofemoral graft

Medical therapy includes aspirin or clopidogrel, HMG-CoA reductase inhibitors, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. The patient was counseled against smoking, and if diabetes is present, strict glycemic control is advisable, with the target HbA1c of less than 7.[4]

Surgical treatment is sometimes necessary. In 1951, Shimizu and Sano first reported surgical repair of subclavian artery thrombosis.[16] The different options to correct subclavian artery pathology include:

• Axillary–axillary bypass
• Carotid-subclavian bypass
• Transposition of the subclavian artery

The axillary–axillary bypass surgery has a good prognosis regarding morbidity and mortality.[17]

Endovascular intervention is the best modality for relieving subclavian artery thrombosis, including percutaneous transluminal angioplasty with stenting or ballooning.[18]

Rheolytic pharmacomechanical thrombectomy (PMT) with the Angiojet device is well-established for managing acute arterial thrombosis. This technique implies the adjunctive application of thrombolytic therapy via either a thrombectomy catheter or a prolonged infusion. The latter might be delivered through an indwelling catheter and is considered a (catheter-directed thrombolysis, or CDT).[5]

Pharmacomechanical thrombectomy alone in managing subclavian artery thrombosis was used in almost half of the patients, and the remaining half received catheter-directed thrombolysis along with PMT. Interestingly, patients with PMT alone had improved outcomes. The following criteria characterized improved outcomes; a. higher rates of procedural success and b. 12-month amputation-free survival.[5] It should be noted that the results were released by a PEripheral Use of AngioJet Rheolytic (PEARL)Thrombectomy with various catheter lengths. Of note, only 3% of the patients treated in the PEARL registry had upper extremity acute limb ischemia.

Precious risk factor control and best medical therapy (BMT) for cardiovascular risk reduction are recommended in all patients with symptomatic upper extremity artery disease.[19] However, management of subclavian artery pathologies with revascularization is indicated in the following group of symptomatic patients; 1. patients with signs and symptoms indicative of transient ischemic attack/stroke, 2. patients with signs and symptoms suggestive of coronary subclavian steal syndrome, 3. ipsilateral hemodialysis access dysfunction or 4. impaired quality of life (QOL).[20] Moreover, revascularization should be considered in asymptomatic patients in the following circumstances; 1. planned coronary artery bypass grafting (CABG) with the internal mammary artery, 2. patients with ipsilateral hemodialysis vascular access, and 3. significant bilateral subclavian stenosis/occlusion to provide adequate blood pressure surveillance.

For revascularization plans, both endovascular and surgical procedures are recommended. According to recent reviews, the results of the endovascular and open repair and significant complications, including vertebrobasilar and post-procedural stroke, were comparable. Still, no RCTs have evaluated endovascular vs. open repair in managing subclavian artery pathologies. The risk of severe complications, including vertebrobasilar stroke, is low with both approaches.[21][22]

The following step-wise management to address severe thrombotic stenosis of the proximal section of the left subclavian artery has been recommended in a case report. Reversed blood flow in the left vertebral artery on Doppler ultrasound and angiographic confirmation of severe left subclavian artery thrombotic lesion are the primary steps to be undertaken in signs and symptoms suggestive of left subclavian artery thrombotic stenosis.

1. placement of a long guiding sheath, 2. placement of an anti-embolic filter into the left brachial artery; this step was recommended for distal protection, 3. blood pressure cuff inflation over the left brachial artery, the blood pressure cuff should be inflated for pressures above the maximum systolic arterial blood pressure for 10 minutes, 4. coronary balloon catheter was inflated specifically at the first segment of the vertebral artery, at the origin of the left subclavian artery, 5. a peripheral stent was placed and dilated distal to the subclavian stenosis, 6. The consecutive deflation was undertaken as follows; a. Jailed balloon, b. blood pressure cuff, c. post-dilation balloon, 7. control angiography after Jailed balloon catheter retrieval was undertaken.

The three distinct measures were applied for the potential complications; 1. plaque shift to the vertebral artery, 2. cerebral, and 3. distal limb embolism. The protective measures include invasive protection via the filter and jailed balloon and non-invasive measures through reactive hyperemia.[23]

Differential Diagnosis

• Congenital malformations
• Fibromuscular dysplasia
• Neurofibromatosis
• Autoimmune vasculitis like Takayasu
• Radiation exposure
• Mechanical causes like trauma or compression syndromes

Prognosis

The prognosis is good with early intervention before the development of complications. 

Complications

The complications of subclavian artery thrombosis are the following:

1. Morbid upper arm ischemia (57%)
2. Upper limb claudication
3. Upper extremity pain at rest
4. Fingers embolization
5. Vertebrobasilar insufficiency from steal syndrome (37%)
6. Anginal symptoms from coronary steal via Intermammary artery graft (21%)
7. Leg claudication in the presence of axillofemoral graft

Procedural complications are as follows:

• Stroke
• Subclavian artery dissection
• Transient ischemic attack (TIA)
• Distal emboli
• Thrombosis
• Hematoma
• Bleeding
• Access site infection or bleeding[22]

Deterrence and Patient Education

Smoking cessation is paramount in cases of atherosclerosis. The patient should receive counsel and education regarding the dangerous consequences of continued smoking which can literally threaten both life and limb due to the progression of atherosclerosis to other vasculature of the body. 

Enhancing Healthcare Team Outcomes

Subclavian artery thrombosis is a rare presentation, but it is often symptomatic when it occurs. The condition is best managed by an interprofessional team that includes a cardiologist, radiologist, vascular surgeon, nursing staff, and pharmacists. It is essential to treat the condition causing subclavian artery thrombosis, and this will also include reducing risk factors like smoking, hypertension, hyperlipidemia, and diabetes. To that end, the various clinicians from different specialties will drive the overall direction of care, but nursing and pharmacy will make significant contributions.

Nurses will assist in patient evaluation, help coordinate specialist referrals, and assist in surgical procedures. Pharmacists will coordinate medication management, offer patient medication counsel, help with anticoagulant protocols, and perform medication reconciliation. All specialists, nurses, and pharmacists must maintain open communication lines with the rest of the team and maintain accurate and updated records so everyone involved in care has access to the latest accurate patient data. This interprofessional paradigm will result in the best patient outcomes. [Level 5]