Superior Vena Cava Syndrome: An Update and Literature Review of Percutaneous Endovascular Treatments

Superior vena cava syndrome (SVCS) is a spectrum of symptoms resulting from the obstruction of the easily compressible SVC, due to either external compression from the mediastinal structures or internal narrowing of the vessel. SVCS was first described in 1757 by famed anatomist Sir William Hunter. ¹ Malignant causes are the main etiology of SVCS, ranging from 70 to 85% of cases, predominantly due to lung cancer. ^{2 3} Historically, infectious conditions such as granulomatous mediastinitis secondary to tuberculosis and syphilitic aortic aneurysm were the predominant causes; however, this has shifted due to antibiotic treatment and increased utility of central venous catheters and endovascular cardiac leads. ⁴ There is a paucity of guidelines and randomized trials to guide the clinical practice, and SVCS is treated on an individual basis, taking into account the etiology, severity of symptoms, and disease prognosis. ⁵ Endovascular therapy is considered the first-line treatment for the emergent and benign cases of SVCS, and can be a well-tolerated treatment for long-term symptomatic relief, in conjunction with other therapies.

Anatomy and Pathophysiology

Normal venous pressure in the SVC ranges from 2 to 8 mm Hg; however, compression can cause it to rise up to 20 to 40 mm Hg. ⁴ In cases of chronic SVC occlusion, collateral vessels form over the course of several weeks and mask symptoms. The most crucial collaterals in SVC occlusion are the azygous-hemiazygos veins and intercostal veins. ⁴ Additional pathways include the internal and external mammary veins, lateral thoracic, and vertebral veins. Less common collaterals include cavoportal and intrahepatic vein systems. ⁶ A classic finding is opacification of the superior vein of Sappey, which communicates with the superior epigastric and internal thoracic veins after draining the area of the falciform ligament and can produce a pathognomonic “hot quadrate sign”—enhancement in hepatic segment IVa ( Fig. 1 ). The formation of collaterals results in less pronounced symptoms. ⁵ Additionally, anatomic variants such as persistent left SVC should be noted by interventional radiologists. The majority of persistent left SVC, which drains into the coronary sinus, coexists with a right-sided SVC draining as expected into the right atrium. ³ The presence of a persistent left SVC would likely dampen the effects of SVC stenosis unless both SVCs are obstructed.

Fig. 1.

A 61-year-old woman with chronic implantable cardioverter defibrillator for hypertrophic obstructive cardiomyopathy and known superior vena cava stenosis. The contrast-enhanced CT of the abdomen shows dense enhancement in hepatic segment IV, also known as the hot quadrate sign (solid arrows). A collateral vessel is visualized within the upper abdominal subcutaneous tissue (dotted arrow).

Clinical Symptoms

Venous congestion from partial or complete occlusion of the SVC results in a range of symptoms including facial edema and plethora, swelling of the neck and larynx causing stridor and dyspnea, nasal epistaxis, swelling of the upper extremities and torso, as well as headache. There are case reports of swelling in the ipsilateral breast. ⁷ The symptoms most likely to respond to treatments include facial and upper extremity swelling, while laryngeal edema and dyspnea are the most likely to be resistant to the treatments and may take longer to improve. ⁸ These symptoms tend to worsen when the patient is supine, and improve when the patient is upright. ¹ Characteristically, the right internal jugular vein (IJV) becomes distended and prominent on the physical exam when the patient is positioned supine or at a 45-degree angle. ⁴ Intercostal collateral vessels may appear prominently on the chest wall depending on the time course of collateralization. ⁴ The presence of more worrisome neurological symptoms including dizziness, confusion, and headache may signal cerebral edema, which may eventually result in coma and death. Additionally, while SVCS itself is unlikely to cause hemodynamic alteration, the extension of the mediastinal mass effect onto the heart hemodynamics may be life-threatening, and can be assessed on physical exam with signs of postural syncope. ⁹ While the symptoms are clinically very dramatic in presentation and provide significant discomfort to patients, it is rarely a true “emergency” as deaths from SVCS are extremely rare. ⁴

Clinical Scoring Systems

Acute SVC obstruction is often due to narrowing of the mediastinum from a tumor with sudden development of SVC thrombosis secondary to venous stasis in the narrowed vessel. ³

Several scoring systems have been introduced to assess the acuity of the obstruction and symptoms. An algorithm proposed by a team from Yale University in 2008 assigns a grade from 0 to 5 associated with symptoms ranging from radiographic signs to neurological signs to help differentiate symptom acuity ( Table 1 ). ⁹ This proposed algorithm is meant to guide treatments when grade 4 symptoms are present which may need urgent treatments including stent placement. These symptoms include cerebral edema, noted by confusion or altered mentation, pronounced laryngeal edema and stridor, hemodynamic compromise, and syncope. Similarly, the Kishi scoring system subdivides symptoms into neurologic signs, thoracic or pharyngeal–laryngeal signs resulting in dysphagia, facial edema, or vessel dilation and assigns a score to determine the acuity of symptoms ( Table 2 ). A score of 4 or higher may be an indication for endovascular stent placement. ⁵ The Stanford classification system was initially used to determine candidates for open surgical repair, based on the extent of SVC stenosis and the likelihood of developing life-threatening symptoms such as laryngeal or cerebral edema ( Table 3 ). Additionally, this classification includes the involvement of the brachiocephalic veins unilaterally or bilaterally and the presence of retrograde of anterograde azygos vein flow. ¹⁰ A recent proposed anatomic classification by Azizi et al is based on the location of the stenosis at either bilateral brachiocephalic veins or distal versus proximal SVC stenosis. ³

Table 1. Yale Grading System for SVC Syndrome.

Grades	Symptoms
Grade 0	Asymptomatic	Radiographic signs of SVC syndrome without symptoms
Grade I	Mild	Facial plethora, lip cyanosis, swelling of the head or neck
Grade II	Moderate	Swelling of the head or neck with dysphagia, ocular edema, or limited jaw or eyelid movements
Grade III	Severe	Headache or dizziness signaling cerebral edema, laryngeal edema, diminished cardiac reserve (heralded by postural syncope)
Grade IV	Life-threatening	Confusion, obtunded patient indicating cerebral edema, profound laryngeal edema denoting stridor, hypotension or syncope denoting hemodynamic collapse or compromise
Grade V	Death

Abbreviation: SVC, superior vena cava.

Notes: Grades I–III symptoms can be treated on a case-by-case basis to determine the appropriateness of chemotherapy or radiotherapy or obtaining a tissue diagnosis prior to initiation of therapy for optimal disease management. Grade IV symptoms necessitate urgent endovascular stent placement.

Source: Adapted with permission from Yu et al. ⁹

Table 2. Kishi Scoring System for Superior Vena Cava Syndrome.

Class of symptoms	Symptoms	Score
Neurologic symptoms	Stupor, coma	4
	Blurry vision, headache, dizziness, vertigo	3
	Altered mental status	2
	Malaise	1
Respiratory symptoms	Laryngeal edema, orthopnea	3
	Stridor, dyspnea, dysphagia	2
	Coughing, chest pain	1
Facial swelling	Lip swelling, epistaxis, nasal swelling	2
	Facial swelling	1
Vasculature	Dilated vessels in the neck, face, arms	1

Note: A score totaling 4 or greater can be an indication for stent placement.

Source: Adapted from with permission from Kishi et al. ³⁵

Table 3. Stanford et al. Classification for SVC Syndrome.

Grade	Findings
Type I	Incomplete SVC obstruction (up to 90%) with patent azygos vein with anterograde flow
Type II	90–100% stenosis of the SVC with patent azygos vein with anterograde flow
Type III	Occluded SVC, retrograde azygos flow, with the collateral flow without involving mammary and epigastric veins 4 10
Type IV	Complete obstruction of the SVC and collateral flow through the mammary and epigastric veins

Abbreviation: SVC, superior vena cava.

Notes: This classification gauges the severity of symptoms specifically airway compromise necessitating surgical treatment but can be adapted in modern practice to guide recommendations for stent placement.

Source: Adapted from with permission from Stanford and Doty. ¹⁰

Benign Causes of Superior Vena Cava Syndrome

The leading benign cause of SVCS is complications from indwelling devices such as central venous catheters and electrode leads causing venous thrombosis, though, in relation to the number of indwelling catheters placed, the percentage of individuals to develop SVCS is low. ⁴ SVCS secondary to implantable cardioverter defibrillator (ICD) leads is usually due to chronic fibrosis from ICD or pacemaker placements with superimposed new venous thrombosis causing sudden or worsening occlusion. ¹¹ Fibrosing mediastinitis is the next most common etiology after catheter- and ICD-based vascular thrombosis. ³ Historically, a more common benign cause of SVCS was infections including mediastinal lymphadenopathy secondary to tuberculosis and tertiary syphilitic aortic aneurysm; however, these entities have become rare with the advent of antibiotic treatments. ^{5 12 13 14} Radiation fibrosis and mediastinal hematoma are less common etiologies.

It is reported that up to 10% of patients with ICD lead insertion had complete SVC occlusion with a higher incidence in those with prior pacemakers, and central venous stenosis of any degree can occur in up to 30% of patients with pacemakers. ^{15 16} Given the time course of the disease, the presence of large collateral veins tends to mitigate the symptoms so that the majority do not present with SVCS. ^{11 16} SVCS associated with pacemaker or ICD leads may be complicated by abandoned leads in the vein. These scenarios are rare but should be considered prior to stent placement in such cases. ¹⁷ The proposed treatments for catheter- or ICD-based SVCS include long-term anticoagulation or thrombolytics, as well as angioplasty or stent placement for symptom relief followed by 1 to 6 months of anticoagulation after the procedure with good long-term outcomes. ^{11 15}

Malignant Causes of Superior Vena Cava Syndrome

Approximately 70% of SVCS cases are due to malignancy. ³ Roughly 75% of malignant SVCS cases are due to non-small cell lung cancer (NSCLC) or small cell lung cancer, and approximately 3 to 5% of patients with lung cancer develop SVCS. NSCLC accounts for 50% of SVCS, while small cell lung cancer leads to 25% of malignant SVCS. ⁴ Approximately 4% of patients with lung cancers have some grade of SVCS at the time of cancer diagnosis. ¹⁸ The remaining cases of malignant SVCS are due to lymphoma, and other malignancies that populate the mediastinum are thymoma, mesothelioma or germ cell neoplasms, or metastatic lymphadenopathy. ^{3 5} A primary consideration in the treatment algorithm for malignant SVCS is whether or not the symptoms necessitate urgent treatment such as stenting to alleviate symptoms within 0 to 72 hours, or whether disease-focused treatment should be pursued. In many cases, if SVCS is the presenting symptom, obtaining a tissue diagnosis to guide treatment is important, and radiation or chemotherapy prior to tissue diagnosis can hamper disease identification. An advantage of stent placement is that it does not preclude later biopsy results due to treatment. ⁹

Percutaneous Endovascular Treatment

Treatment options for malignant SVCS include chemotherapy, radiation, and balloon angioplasty, with or without stent placement. Treatment is specific to etiology, symptoms, and prognosis, though there is a paucity of published societal consensus guidelines. Malignant SVCS signals a poor prognosis in the course of the disease and the mean life expectancy after symptom presentation is reported to be 6 months, but can range from 2 days to 43 months. ⁸

Medical treatments to alleviate the symptoms include elevating the head of the bed, fluid restriction, consideration of diuretics, and supplemental oxygen therapy, though these are not definitive therapies. ⁵ Chemotherapy is used to treat nonemergent cases of malignant SVCS and is expected to produce symptom relief in approximately 2 weeks. ¹⁹ Chemotherapy with or without radiation provides symptom relief in 60% of patients with NSCLC; however, 19% of those patients may have a recurrence. ²⁰ Traditionally, steroids such as oral prednisolone or IV dexamethasone were used as first-line therapy to reduce laryngeal edema, particularly in cases undergoing radiation which may acutely worsen with radiation. ⁵ Additionally, steroids may have a role in treating hematologic malignancies such as Hodgkin lymphoma, but they may complicate the posttreatment biopsy results because of their cytotoxic effects on cells. ²¹ Steroids have been reported as the first line for pediatric cases of SVCS with lymphoma as well as patients with fibrosing mediastinitis. ^{13 22} The benefit of steroids alone in the treatment of SVCS is questionable, and some even reported poor outcomes associated with the steroid use. ²³

Endovascular stent placement has become the first-line treatment in cases that require rapid symptom relief, even though there are no randomized control trials establishing it as superior to radiation or chemotherapy. Retrospective studies showed high rates of technical success, with primary- and assisted-patency rates of 87 and 96% in patients with malignant SVCS, respectively. ^{24 25} Compared with medical treatments, the clinical success rate of self-expanding bare stents to treat SVCS is reported to be 95% with a restenosis rate of 11 to 22%. ¹⁸ Subsequent endovascular intervention may provide clinical relief in 90% of that subset with restenosis. ²⁰ Rates of restenosis after stenting is variable and appears to differ based on the type of stent used. A meta-analysis combining multiple studies with a variety of stents found an overall restenosis rate of 10.5% after endovascular stent placement. ¹⁸ Restenosis can be treated with angioplasty or additional stent placement. ²⁵ Additionally, stent placement does not preclude other therapies such as radiation or chemotherapy because most patients with acute SVCS may need directed cancer treatment as well which can affect life span. ²⁵

Procedural Technique

Preprocedural imaging includes CT venogram and fluoroscopic venography. The benefit of a CT venogram is that it delineates the regional soft-tissue structures to better identify the cause of the SVCS, while fluoroscopic venography can functionally assess anterograde and retrograde collateral flow, which grades the severity of the stenosis. ¹ Though treatment is usually tailored to the etiology of the SVCS, endovascular angioplasty with possible stenting is considered the first-line treatment for emergent cases. Stenting is used to achieve rapid symptom relief within the span of 24 to 72 hours. ^{5 18} Complications include stent thrombosis, which can occur early or late. This can be avoided with anticoagulation, although there have been no studies on the use of long-term anticoagulation, and there are mixed reports on the use of postprocedural anticoagulation. ^{4 19 26} In cases of Stanford type IV occlusion, mechanical thrombectomy may be considered prior to stenting. ²⁷

The endovascular procedures can be performed under moderate sedation or general anesthesia when there is a concern for respiratory compromise. The endovascular treatments offered range from angioplasty alone, angioplasty with stent placement, recanalization with angioplasty and stent placement, and kissing stent placement ( Figs. 2 3 4 ). In some cases, the SVC stenosis may be difficult to traverse from the IJV, and the stent placement may be performed via the femoral vein. Less common additional access sites include the brachial vein. ^{18 28} The most secure way is to pair a femoral venous access with a jugular venous access, or a subclavian or brachial access to establish a through-and-through access, which adds technical options including a “push-pull” technique. ²⁷ If a through-and-through access is not established, the wire should be positioned distal to the point of occlusion so that there is a safe length of anchored wire in case of stent migration ( Fig. 5 ). For a jugular approach, the wire should be anchored in the IVC, and for a femoral approach, the wire should be into the subclavian vein or distally. ¹ Preintervention SVC and gradient pressures can be measured. A combination of straight/angled glide catheter, such as the GLIDECATH Hydrophilic Catheter (Terumo Tokyo, Japan) or Kumpe Access catheter (Cook Medical, Bloomington, IN), and an 0.035-inch hydrophilic guidewire may be used to traverse the severe stenosis or for conventional recanalization. Alternatively, sharp recanalization with a stiff end of a guidewire or 20-gauge Chiba Biopsy Needle (Cook Medical), or using a radiofrequency wire, such as the PowerWire RF Guidewire (Baylis Medical, Mississauga, Ontario, Canada), can be considered if the conventional recanalization is not successful. ²⁹ Serious adverse events have been reported with this technique including transection of the SVC into the pericardium, resulting in cardiac tamponade. ^{1 30 31} Intravascular ultrasound may be utilized and is advised in severe stenoses or cases with thromboses. Intraprocedural cone-beam CT is helpful and may provide additional anatomical information. Once a secure access is achieved, the hydrophilic guidewire should be exchanged for a working stiff guidewire. Intravenous heparin bolus is often administered intraprocedurally. The stenosis can be predilated using balloon angioplasty depending on the severity of the stenosis. Then, the stent, typically a balloon-mounted/expandable stent, is deployed across the stenosis. If feasible, post-stent venoplasty may be considered depending on the stent. As a rule of thumb, the stent should be 10 to 20% larger than the vessel diameter to prevent migration. ⁴ A postprocedure venogram can confirm stent patency and positioning. The goal is an increase in vessel diameter greater than 50%, resolution of the pressure gradient, and preprocedural collaterals on the final venogram. ⁸ Monitoring change in central venous pressure before and after the procedure can also confirm technical success, with a goal of returning to physiologic SVC pressure of 2 to 8 mm Hg or gradient pressure across stenosis less than 3 to 5 mm Hg. ^{4 19} Additional angioplasty can be used to improve stent patency after placement.

Fig. 2.

A 56-year-old woman with end-stage renal disease and chronic right internal jugular tunneled dialysis catheter presented with voice change and arm and facial swelling. Central venography ( a ) shows severe stenosis of the distal superior vena cava (SVC; arrows, a ) with multiple collaterals. The patient underwent balloon angioplasty and stent placement of the SVC (dotted arrows, b and c ). A dialysis catheter was replaced through the new SVC stent (arrows, c ).

Fig. 3.

A 39-year-old woman with known history of mediastinitis fibrosis. Axial ( a ) and coronal ( b ) contrast-enhanced CT images demonstrate severe narrowing of the superior vena cava (SVC; solid arrows). There is complete truncation of the right main pulmonary artery (dotted arrows, a ). Central venography ( c ) demonstrating severe stenosis of the SVC (arrows). The patient underwent balloon angioplasty ( d ) and stent placement (arrows, e ). Follow-up sagittal contrast-enhanced CT shows appropriate positioning and patency of the SVC stent (arrows, f ).

Fig. 4.

A 62-year-old man with a history of prior right internal jugular vein tunneled dialysis catheter. Digital subtracted image of bilateral upper extremity venography ( a ) shows severe stenosis of the right brachiocephalic vein (solid arrow, a ) with multiple collaterals at the neck (dotted arrow, a ). The patient underwent kissing stents placement within the left brachiocephalic and the right brachiocephalic and subclavian veins (solid arrows, b and c ).

Fig. 5.

Superior vena cava stent placement complicated by stent migration to the right atrium (arrows, a, b ). A through-and-through access is critical and prevents further migration of the stent to the right ventricle. The stent is fixed and removed into a large sheath by two forceps from the internal jugular and femoral veins approach.

The level of stenosis can be at the SVC only or may include unilateral or bilateral brachiocephalic veins. Multiple stents can be deployed to reconstruct the SVC confluence or to adequately cover the stenosis length. ²⁷ When there is concurrent stenosis of the brachiocephalic vein and SVC, the so-called kissing stents can be placed in the bilateral brachiocephalic veins, as well as the proximal SVC. However, as expected there are higher rates of stenosis and complications in the bilateral brachiocephalic stent placement. ⁴

There is a wide range of commercially available stents with various diameters, tensile strength, stent coverage, and compressibility ( Table 4 ). Stents in SVC often range from 10 to 14 mm in diameter and 30 to 80 mm in length to cover the entire venous lesion. ²⁷ Using stents greater than 16 mm is predictive of complications such as hemorrhage, pulmonary edema, stent collapse, migration, or infection. ³² Historically, the Gianturco-Z stent was the first stent placed in the SVC in 1986, and the downside was its large introducing sheath. ²⁷ Self-expandable stents including Gianturco-Z stent (Cook Medical) and WALLSTENT (Boston Scientific, Marlborough, MA) reach a predetermined size once they are deployed, which risks vessel injury. Balloon-expanding stents, such as the Palmaz (Cardinal Health, Dublin, OH) and the historic Strecker stents, are deployed over a balloon and have the advantage of high radial force with operator-determined expansion. Over time, however, since these stents are compressible, it can result in restenosis. ²⁶

Table 4. An overview of various types of stents used for treating SVC stenosis.

Stent name	Company	Type	Advantages (A)/Disadvantages (D)
Palmaz-Genesis	Cordis, Miami Lakes, FL	Uncovered Balloon-expandable	A: Larger sizes D: It is not premounted and needs to be mounted manually
Wallstent	Boston Scientific, Marlborough, MA	Uncovered Self-expandable	A: Highly radiopaque D: Early stent shortening
Gianturco Z stent	Cook Medical, Bloomington, IN	Uncovered Self-expandable	A: Available in larger diameter, high radial force D: Primarily a tracheobronchial Stent
Memotherm	Angiomed/Bard, Karlsruhe, Germany	Uncovered Self-expandable	D: Poor radiopacity
Epic	Boston Scientific	Uncovered Self-expandable	A: Flexible
Abre	Medtronic, Minneapolis, MN	Uncovered Self-expandable	A: Wide range of lengths
Venovo	BD, Franklin Lakes, NJ	Uncovered Self-expandable	A: Wide range of lengths
Zilver Vena	Cook Medical	Uncovered Self-expandable	A: Wide range of lengths
Fluency	BD	Covered (bare ends) Self-expandable	D: Limited large diameters
Viabahn/VBX	Gore Medical, Flagstaff, AZ	Covered Balloon-expandable	A: Can be overdilated

Abbreviation: SVC, superior vena cava.

Covered stents have a risk of migration and can occlude branch vessels such as the left brachiocephalic vein if placed at the confluence. ²⁸ In one study, none of the patients with patent contralateral brachiocephalic vein prior to covered stent placement developed left arm venous thrombosis during the 12-month follow-up period. ²⁸ Balloon-expandable uncovered stents do not occlude the branch vessels and are preferred for benign cases with catheter-induced SVCS. On the contrary, the recurrent rate of symptoms in cases with SVCS secondary to fibrosing mediastinitis is reported less after covered stent placement (29%) compared with uncovered stents (60%). ³³

Patients diagnosed with SVCS secondary to thrombus are prescribed anticoagulation, which some advocate continuing indefinitely after treatment. ⁵ If an endovascular treatment is planned, these patients should be started on a heparin drip, which can be more quickly reversed intraprocedurally and can be bridged to a definitive anticoagulation treatment. ³ Anticoagulation is often prescribed for patients with SVCS who are treated with an endovascular stent. The first few weeks after stent placement is known as the “intimasation” period, as the stent is covered with endothelial intima. These patients with malignancy or venous compression are prone to venous thrombosis and therefore have increased risk of stent thrombosis during this period. ⁸ The benefits of post-stent anticoagulation are not well-studied, but most studies recommend continuing anticoagulation in a majority of patients to prevent stent occlusion. ^{33 34} Some authors recommend anticoagulation for at least 1 to 3 months, either using warfarin titrated to an international normalized ratio of 2.0 to 3.0 or single- or dual-antiplatelet therapies, though a specific guideline is lacking. ^{3 25}

Summary

Patients with SVCS may be started on anticoagulation, and chemotherapy or radiation depending on the underlying cause and acuity of symptoms. Endovascular treatments including recanalization, angioplasty, and stent placement can be considered the first-line treatment for selected benign and malignant cases of SVCS with emergent or refractory symptoms. This review highlights the need for large-scale trials in the treatment algorithm for SVCS.