Subclavian Artery Stenosis

Etiology

Subclavian artery stenosis causes notable morbidity because it causes symptomatic ischemic problems that affect the upper extremities, brain, and heart. Atherosclerosis is the most common cause.[2] Other etiologies include arteritis, inflammation due to radiation exposure, compression syndromes, fibromuscular dysplasia, Takayasu arteritis, and neurofibromatosis.[3] Congenital abnormalities, including arteria lusoria (aberrant subclavian artery) and right-sided aortic arch, might be etiological risk factors for subclavian artery stenosis.[2][4]

Epidemiology

Peripheral arterial disease (PAD) of the major vessels is associated with the narrowing of the arteries due to atherosclerosis. It is estimated that approximately 2% of the population has subclavian artery PAD. The prevalence of PAD in adults older than 70 years is about 15%. Of these, nearly 25% will require revascularization, and 5% of patients will progress to critical limb ischemia. Subclavian artery stenosis has been reported in up to 1.9% of the community population and 7.1% of the patient population with vascular disease.[4] The majority of the patients are asymptomatic due to slow disease progression. Symptoms usually appear once there is a 50% luminal narrowing of the vessel diameter.[5]

The prevalence of disease in a brachiocephalic artery in patients with known PAD is about 42%. Patients with known peripheral arterial disease can also have stenosis of the left subclavian artery (30%). Half of the patients with subclavian artery disease have coronary artery disease, and one-third have carotid or vertebral disease.[6]

In rare circumstances, bilateral subclavian artery stenosis has been reported.[4]   

Pathophysiology

Atherosclerosis risk factors account for atherogenesis in this category of patients. Vascular risk factors, including diabetes, hyperlipidemia, hypertension, and tobacco abuse, augment cell adhesion molecules, which promote inflammatory cells to adhere to the arterial wall. This process causes remodeling of the arterial wall and lipid deposition with the tunica media. As this process evolves, the narrowing of the arterial lumen eventually follows and, in turn, causes calcification of the arterial wall. [7]In addition, brachiocephalic arteries, including the innominate and subclavian, can be affected by vasculitides like Takayasu arteritis and giant cell arteritis. Brachiocephalic atherosclerosis disease can be unifocal or multifocal. The disease of the brachiocephalic arteries can manifest in several ways, including transient ischemic attack (TIA), upper extremity ischemia or claudication, and vertebrobasilar insufficiency. Aneurysms of the brachiocephalic arteries occur infrequently and can be related to atherosclerotic post-stenotic dilatation, trauma, inflammation, or infection.[8][9][10]

The pathophysiology of atherosclerotic type subclavian artery stenosis has been attributed to a process of cell adhesion: inflammatory cells attachments to the vascular wall, with subsequent remodeling, lipid accumulation, and consequent calcification. However, the process is aggravated in patients with metabolic syndrome. 

History and Physical

The left subclavian artery is more likely to be affected than the right or innominate arteries. If there is isolated stenosis, the likelihood of symptoms is less than in other vascular beds; however, if the obstructive disease affects other aortic arch vessels, such as the carotid or vertebral arteries, the likelihood of steal or ischemic symptoms increases.

Upper extremity symptoms include arm claudication, muscle fatigue, rest pain, and finger necrosis. Neurologic issues include vertebrobasilar hypoperfusion, including visual disturbances, syncope, ataxia, vertigo, dysphasia, dysarthria, and facial sensory deficits.

In patients with internal mammary artery grafts as a result of coronary artery bypass graft surgery, the symptoms of ischemic heart disease, including angina pectoris, due to coronary-subclavian steal, predominate.

While the diagnosis typically rests on imaging, a thorough physical exam is important.[11] On examination, patients can display the following:

• Unequal arm blood pressures
• Refractory hypotension in rare cases of bilateral subclavian artery stenosis[4]
• The presence of a faint pulse in the upper extremities and systolic blood pressure (BP) difference of greater than 15 mmHg between the right and left upper extremities
• Absent or significantly diminished pulses
• Neurologic and cardiac sequelae.
• Bruits
• Ulcers
• Gangrenous skin changes
• Nail bed splinter hemorrhages
• ABI value greater than 1.3 in patients with bilateral subclavian artery stenosis[4]
• vertebrobasilar hypoperfusion evidence with syncope, ataxia, and dysphagia[4]

Evaluation

Initial assessment of patients with subclavian artery disease includes blood pressure measurement in both arms to evaluate for discrepancies in the upper extremities and the presence of bruits (carotid, cervical, or supraclavicular). Less frequent physical findings include finger ulcers, necrosis, splinter hemorrhages, or gangrenous skin changes. Auscultation for bruits in the subclavian or carotid arteries will narrow the search for any occult disease.

Duplex ultrasound with color flow imaging is the noninvasive modality of choice in evaluating subclavian artery disease. Dampened or monophasic waveforms, turbulent color flow imaging, and increased velocities in the region of stenosis are characteristic findings of obstruction. Reversal of ipsilateral vertebral artery flow is seen in subclavian steal syndrome. CT scan angiography offers an excellent anatomic resolution and determines the length of the lesion as well as its location.[1] Its drawback, however, is that it does not provide optimal information on the degree of calcification. Digital subtraction angiography and fluoroscopy also do not quantify the degree of calcification.

MR angiography can be misinterpreted as the reduced flow can be interpreted as an exaggerated disease. The definite test is invasive angiography; non-subtracted images provide anatomical mapping, while digital subtraction further characterizes the stenosis. There is a small risk of stroke (less than 1%) when manipulating the aortic arch and brachiocephalic arteries.

Treatment / Management

Most patients with subclavian artery stenosis due to atherosclerotic occlusive plaques are asymptomatic.[2] Intervention in managing subclavian artery stenosis is indicated in the symptomatic patient. (B2)

Endovascular Approach 

An endovascular approach is recommended in the primary management of the lesions at the proximal site of the subclavian artery. The endovascular approach has the advantage of a minimally-invasive procedure and should be attempted before open subclavian artery revascularizations.[2] Accordingly, angioplasty and stenting are the primary interventions to be attempted with reasonable long-term outcomes for more than ten years.[2][12] Notwithstanding the safety and efficacy of endoluminal treatment in the management of subclavian artery stenosis, the open surgical approaches outcomes are more promising in low-risk patients.[2](B2)

Several open surgical revascularization techniques, including the carotid-subclavian bypass, might be utilized to manage subclavian artery stenosis, including; 1. transposition of subclavian to the carotid artery, 2. carotid–subclavian or subclavian–axillary.[2][13] Surgical intervention is indicated in 1. failure of endovascular management and 2. stent occlusion episodes. The transposition of the subclavian artery on the common carotid artery is the preferred management of proximal subclavian artery lesions.[2] (B2)

Indications for the treatment are as follows;

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.[14]

Surgical treatment is sometimes necessary. In 1951, Shimizu and Sano first reported surgical repair of subclavian artery thrombosis.[15] 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.[16]

Endovascular intervention is the best modality for relieving subclavian artery thrombosis, including percutaneous transluminal angioplasty with stenting or ballooning.[17](B2)

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).[18](B3)

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.[18] It should be noted that the mentioned results were released by a PEripheral Use of AngioJet Rheolytic (PEARL)Thrombectomy with a variety of catheter Lengths. Of note, only 3% of the patients treated in the PEARL registry had upper extremity acute limb ischemia.(B3)

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).[2] 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.(B2)

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.[20][21](B2)

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. A coronary balloon catheter is 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
   • Jailed balloon
   • Blood pressure cuff
   • 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
3. Distal limb embolism.

The protective measures include invasive protection via the filter and jailed balloon and non-invasive measures through reactive hyperemia.[22](B3)

Differential Diagnosis

• Carotid artery disease
• Subclavian steal
• Stroke[23][4]
• Cardiogenic shock in patients with bilateral subclavian artery stenosis[4]

Prognosis

Carotid-subclavian artery bypass with a prosthetic graft is considered a generally safe surgical procedure with mortality rates ranging from 0 to 3% and stroke risk of 0 to 5%.[2][24]

According to one study, endovascular interventions are successful, with studies showing an overall remission of clinical symptom remission of over 95%.[25]

Complications

Stent fracture following an endovascular approach is considered a potential post-procedural complication.[26] Moreover, re-occlusion of the subclavian artery followed by stent fracture is predictable.[27]

Recurrent myocardial ischemia due to the coronary-subclavian steal syndrome is expected in patients with proximal disease in the left subclavian artery.[28]