Nonmalignant superior vena cava syndrome: Pathophysiology and management

Branislav Schifferdecker, MD, James A. Shaw, MBBS, PhD, Thomas C. Piemonte, MD, FACC, Andrew C. Eisenhauer, MD, FACC

Introduction

Superior vena cava (SVC) syndrome results from the obstruction of the blood flow in the superior vena cava [[1]]. Though malignancy with tumor infiltration or compression has historically been the most common etiology [[2]], it can be caused by a variety of other things, including fibrosis and in situ venous thrombosis resulting from pacemaker/defibrillator leads or central venous catheters [[3]]. Given its association with advanced malignancy, previous therapy for SVC syndrome was primarily supportive. However, the widespread use of permanent central venous access catheters coupled with the improved success of chemotherapy and the increasing use of multilead implantable cardiac rhythm management devices has increased the incidence of SVC syndrome not caused by direct tumor infiltration (nonmalignant SVC syndrome). Further, with the increasing acceptance of percutaneous and minimally invasive therapy, the treatment of SVC syndrome with balloon dilatation and stenting has also become more common. In this article, we review our experience with percutaneous therapy of nonmalignant SVC syndrome and then discuss the spectrum of pathophysiology and management of this condition.

Materials and methods

Patients

All patients who underwent intervention for nonmalignant obstruction of the SVC with stenting at Brigham and Women's Hospital and Lahey Clinic between January 1996 and October 2003 were included. Data from all patients were collected prospectively and maintained in secure databases that included all patients undergoing intervention in the interventional cardiovascular medicine program. These records were then retrospectively reviewed and data were collected. In addition, patients were assessed either in person and, when this was not possible, by telephone and were asked about recurrence of symptoms similar to those that occurred prior to the intervention. Contact was made with their additional health care providers to assess the patient's health and vital status.

Technique

SVC lesions are initially approached from below, via femoral vein access. Initially, the lesion is crossed with a wire, usually a 0.035 Glidewire (Boston Scientific/Terumo; Fig. 1) and a venogram is then performed. If the lesion is difficult to cross, a venogram is done as the initial step, then the lesion was crossed and predilatation performed (Fig. 2A). In the case of focal lesions and the use of a balloon-expandable stent, the stent is placed carefully to straddle the residual stenosis (Fig. 2B) and deployed (Figs. 2C, 3A) and a final venogram is made to confirm wide patency (Fig. 3B). A pullback pressure recording is made across the stented segment to confirm abolition of hemodynamic obstruction.

In severely fibrotic and totally occlusive lesions, the first attempt to cross the occlusion is made with a stiffer 0.038 wire. If that fails, access is obtained in the arm, usually percutaneously through a brachial vein using a 4 or 5 Fr Glidecath (Boston Scientific/Terumo) catheter and the 0.035 and/or 0.038 Glidewires to cross the occlusion from above. If all these measures fail, the back end of a 0.025 Glidewire is curved slightly using a hemostat and then advanced to pierce the occlusion. Care is taken to ensure that this very stiff wire is clearly passing from lumen to lumen before additional catheters are passed over it. In this series, two of the seven patients required both the femoral and brachial approach with the occlusions successfully crossed with the reversed 0.025 Glidewire.

Once the wire is across the total occlusion, a 4-5 Fr multipurpose catheter or Glidecath is advanced over it and intraluminal position is confirmed by injecting radiographic contrast. In cases where crossing the occlusion with the Glidecath is difficult, a smaller 0.014 wire is passed through the catheter and the catheter is exchanged for a balloon. Initial balloon dilatation is performed with a 3-4 mm × 4 cm coronary balloon such as the Long Ranger (Boston Scientific) to achieve a lumen sufficient to accept larger shaft equipment. The initial dilatation is followed by dilatations with larger balloons and then stenting, usually with a self-expanding stent.

Results

Seven patients (three male) underwent SVC stenting between 1996 and 2003. Patient demographics, etiology of their SVC syndrome, and procedural information are summarized in Tables I and II. The average age at the time of the intervention was 52.9 years. The cause of the SVC occlusion was related to central venous catheters in four cases, three of which were in place for delivery of chemotherapy. In three cases, pacemaker/defibrillator leads were the cause of the obstruction. Six patients had stents placed during their initial procedure; one of these patients had balloon dilatation previously performed at another institution and represented with recurrent symptoms from restenosis of the SVC and was successfully treated with stent placement. In the patient who had only balloon dilatation, he had pacemaker leads in place, thus making the placement of a stent complicated. Thrombolytic therapy was not used in any of our cases. However, in one case, mechanical thrombectomy with AngioJet (Possis) was performed. There were no procedure-related complications. All patients achieved prompt resolution of symptoms, including a reduction in facial swelling and subjective feelings of head fullness. Stent placement was universally associated with a pleuritic chest discomfort for several days after the procedure, likely related to caval distention.

Table I. Baseline Patient Characteristics

SVC, superior vena cava; ICD, implantable.

Table II. Procedural Characteristics

The average follow-up for our patient cohort was 36 months, with all patients having achieved immediate and long-term symptomatic improvement. All patients were alive at follow-up. Three patients had cancer at the time of their procedure, but their SVC syndrome was caused by indwelling catheters and chemotherapy that led to SVC fibrosis/scarring, rather than malignant SVC infiltration. In two of these patients, it was judged prudent to remove the catheter. In one, however, we chose to preserve the catheter and were able to reposition it within the stented segment (Figs. 4-6) so further chemotherapy could be administered.

Discussion

This series shows that percutaneous revascularization is a safe and effective treatment of nonmalignant SVC syndrome. Stenting provided prolonged symptomatic relief without causing any acute or late complications. Patients with varying causes of SVC syndrome were treated successfully regardless of the underlying cause, and good long-term results were achieved. Given the increasing recognition and improved overall prognosis of patients with SVC syndrome related to indwelling leads, electrodes, catheters, and curative chemotherapy, it is important to review the pathophysiology of SVC syndrome and the therapeutic modalities currently available to treat this condition.

Etiology and Clinical Presentation

SVC syndrome is most frequently associated with malignancy (Table III) leading to compression and/or infiltration of the vena cava by tumor [[1]]. Lung tumors are the most common, followed by lymphoma, teratoma, and others. The development of SVC syndrome in a patient with malignancy is a sign of very poor prognosis. Despite advances in cancer therapy, palliation remains the mainstay of malignant SVC syndrome therapy. Patients with cancer may also develop nonmalignant SVC syndrome due to the indwelling catheters and sclerosing properties of administered chemotherapy. Unlike the patients with SVC syndrome associated with direct tumor infiltration, many of those with nonmalignant SVC obstruction can look forward to decades of survival.

Table III. Historical Etiology of Superior Vena Cava Syndrome

Once an important cause of caval obstruction, infection leading to SVC syndrome has dramatically decreased in frequency in the antibiotic era [[4]]. An exception, however, is SVC syndrome from septic thrombosis or thrombophlebitis associated with intravenous drug abuse.

More than 15,000 patients are diagnosed with SVC syndrome every year in the United States [[3]]. The diagnosis of SVC syndrome is usually made at the bedside and in up to 59% of the patients; SVC syndrome may be the first presentation of another underlying disease [[5]]. Whether patients present acutely or with the gradual onset of symptoms depends on the acuity of the pathological process and the development of collateral circulation. For example, in those with a rapidly invading malignancy, SVC obstruction will occur before the development of any collaterals and thus symptoms will present acutely and will often be severely limiting. Patients usually observe symptoms for 2 to 4 weeks before the diagnosis is made [[2]]. Facial fullness, cough, shortness of breath, hoarseness, nasal congestion, epistaxis, hemoptysis, and dysphagia are common presenting symptoms [[1]]. Venous distention and edema of the upper thorax, neck, face, and upper extremities are the most frequent signs on presentation. Upper body cyanosis, facial plethora, and conjunctival injection may also be present. Severe SVC syndrome may cause life-threatening airway obstruction or a decline in mental status leading to coma due to cerebral venous hypertension [[6]]. Clinical diagnosis is confirmed by an imaging study, usually computed tomography, that also helps to evaluate the underlying disease and severity of thrombosis in the SVC. Magnetic resonance imaging can also be used in diagnosing this condition but not in patients with a pacemaker or defibrillator in place.

SVC Syndrome of Nonmalignant Etiology

In the developed world, SVC syndrome of nonmalignant etiology (benign SVC syndrome) is usually iatrogenic in origin, most frequently due to indwelling intravenous catheters and pacing leads (Table III). Complications of pacemaker lead placement, such as venous thrombosis or stenosis, occur in up to 30% of patients. Only a few patients, however, become symptomatic [[7]]. The presence of multiple leads, retention of severed lead(s), and previous lead infection may increase the risk of SVC syndrome [[8]]. The largest series of percutaneous therapy in benign SVC syndrome included 16 patients. Ten patients had SVC syndrome due to indwelling catheter(s), two due to the pacemaker lead(s), and one each due to goiter, fibrous mediastinitis, heart-lung transplant, and spontaneous thrombosis. The patency rate in 13 patients who were followed for a mean of 17 months was 85% [[9]]. Rosenblum et al. [[10]] reported excellent results in their series of six patients with SVC syndrome due to central lines. All patients were successfully treated and five patients followed for up to 2 years with 100% patency [[10]].

Stenting Technique

Traditionally, access has been obtained through the femoral vein, though internal jugular, subclavian, and basilic vein access have been reported to be a safe alternatives [[29]]. In patients with bilateral innominate vein involvement, femoral access is preferable since bilateral stenting may be necessary. The area of stenosis is traversed with a guidewire that is used in an over-the-wire fashion. Contrast injections into the proximal and distal vein segment in at least two projections using rapid filming are necessary for accurate evaluation of the lesion. Pressure gradient measurements across the stenosis are useful in patients whose symptoms are not fully consistent with SVC syndrome or can be explained by alternative medical conditions [[11]] and to confirm resolution of hemodynamic obstruction after stenting. In patients with apparent ingrowth of the tumor into the lumen of the SVC, the use of a directional atherectomy device has been described to obtain tissue for histological diagnosis of underlying malignancy [[12]].

The presence of extensive thrombus may prompt the use of thrombolytics. After placing the tip of the infusion catheter inside the thrombus, the thrombolytic agent (most frequently, tissue plasminogen activator at a rate of 0.02 mg/kg/hr) is infused and venograms are repeated at 4- to 6-hr intervals. The catheter is then advanced into the remaining thrombus. Pulse-spray injection of thrombolytic agents significantly decreases lysis times [[13]]. Complications of intraprocedural thrombolytic use are identical to those seen with thrombolytic therapy for other indications. Massive intracerebral hemorrhage [[14]], severe gastrointestinal bleeding, and the development of large hematoma have complicated its use in the treatment of SVC syndrome [[9]]. Thrombus removal with devices such as the Amplatz aspiration thrombectomy catheter [[15]] or AngioJet may be an adjunct or alternative to lengthy intralesional thrombolysis.

Predilatation of the stenosis is necessary in most cases since radial force with stent deployment may not be sufficient for lesion dilatation. The stenosis, however, should only be predilated to approximately 80% of the reference segment to prevent stent migration. Currently, the most frequently used stents in SVC stenting are self-expanding Wallstent (Meditech-Boston Scientific) composed of woven stainless steel mesh, Smart Control Stent (Cordis), and other similar self-expanding nitinol stents. A variety of large balloon-expandable stents are available from a number of manufacturers. The Gianturco Z-stent (William Cook), built from stainless steel wire bent in a zigzag pattern, is uncommonly used today, though it was popular as one of the first self-expanding stent designs.

The recommended diameter of self-expanding stents is 1.2-1.5 times the venous diameter. Some self-expanding stents foreshorten by up to 30% of their total length. This process may continue beyond the period immediately after stent deployment, especially when the stent is not sufficiently postdilated. Length oversizing of such self-expanding stents is therefore crucial [[16]]. Due to continuous radial expanding force, self-expanding stents may also migrate if deployed into a tight stenosis. The stent becomes cone-shaped and the terminal prongs across the stenosis may worsen the obstruction and increase the risk of acute SVC thrombosis [[17]]. Two stents placed together forming a double stent may prevent migration. Such a stent segment, however, is more rigid and the low radial expanding force at the junction may result in poor stenosis dilatation or restenosis in the junction area [[18]]. Fixation barbs on the stent have also been employed as a strategy to prevent self-expanding stent migration [[19]]. The tight weave design of the Wallstent may prevent tumor ingrowth even in patients with total encasement of SVC by tumor [[20]]. The open design of the older Gianturco stent, on the other hand, was believed to carry a lower risk of thrombosis and may remain useful in cases where critical side branches are covered by the stent [[21]].

Balloon-expandable stents allow precise positioning and their diameter can be adjusted with postdilatation. These stents can also be placed within self-expanding stents to treat short resistant segments of a longer stenosis. Side branches covered by the original Palmaz stent usually remain patent [[22]]. The Palmaz stent is rigid and was therefore useful only in relatively straight vascular segments. Subsequent generations of balloon-expandable stents are more flexible. The final deployed diameter of the Palmaz stent and other balloon-expandable stents should not be oversized by postdilatation by more than 20% since the associated trauma may engender acute thrombosis or late restenosis secondary to more vigorous intimal hyperplasia [[23]].

Most operators use heparin during the procedure but the use of long-term anticoagulation is controversial. Some of the authors recommend warfarin to prevent abrupt stent closure after cessation of the procedural anticoagulation, while others use warfarin only in patients with a documented high burden of thrombus in SVC obstruction [[18]]. In recent literature, the trend toward use of antiplatelet agents such as aspirin, clopidogrel, or ticlopidine instead of long-term anticoagulation after stenting can be observed. Such a strategy, when associated with stenting, does not seem to increase the risk of SVC syndrome recurrence [[24]].

Complications

The most frequently reported complication of SVC stenting is stent thrombosis (0-21.4%) [[25]]. Despite lack of randomized data or expert consensus, vigorous heparin anticoagulation is used routinely during the procedure. Stent migration has been reported with stents found in the heart [[26]] or pulmonary artery [[7]]. Avoidance of excessive predilation (> 80% of reference diameter) and length oversizing of self-expanding stents may help to prevent this complication. Pulmonary edema may develop after SVC stenting due to increased venous return and can be managed with diuretics, oxygen, and inotropes [[27]]. Infection of the stent has been described but is very rare due to early stent endothelization [[28]]. Antibiotic prophylaxis is considered on a case-by-case basis in high-risk patients. Transient hemidiaphragm elevation has occurred after stent placement, likely secondary to compression of phrenic nerve against tumor [[18]]. As is also true in stenting of the thoracic aorta, patients often report a pleuritic type of chest discomfort likely related to distention of the superior vena cava. This discomfort usually wanes within 48 hr.

Indications for Stenting Therapy

Opinion about the role of stenting in SVC syndrome is evolving. Its efficacy and safety are now established and the procedure represents only a small increase in the overall cost of care of the patient [[14]]. SVC stenting is a low-risk procedure that provides fast and durable symptomatic relief. Debate about which therapy is better is not substantiated. Radiation and/or chemotherapy may be limited by side effects but may prolong a patient's life by also addressing the tumor burden. However, radiation and chemotherapy can be combined with SVC stenting as needed to provide patients with the benefit of life prolongation, together with effective symptom control. Stenting is indicated in SVC syndrome patients with moderate to severe or rapidly worsening symptoms, those who have failed to respond to (or recurred after) radiation and/or chemotherapy, those who have reached a dose limit of radiation or chemotherapy, and those who have a nonmalignant obstruction.

Stenting therapy should not routinely be used in patients with mild symptoms who will undergo further radiation and/or chemotherapy that alone may be sufficient for relief. Patients, however, should be instructed to return if their symptoms do not improve, or continue to worsen, despite such a treatment. In patients with terminal disease with expected survival of only days to weeks, a generalized recommendation cannot be given. Here, benefit of SVC stenting has to be judged on a case-by-case basis considering the burden of symptoms related to SVC syndrome and the overall clinical picture. In patients with SVC syndrome of nonmalignant etiology, based on mid-term follow-up results, stenting should become the treatment of choice. Surgical therapy should be reserved for patients with benign SVC syndrome refractory to percutaneous therapy, and few patients are likely to become truly refractory. The majority of patients with recurrent SVC syndrome can be treated successfully with repeated percutaneous intervention [[29]].

Our series demonstrates the safety and sustained effectiveness of stenting as primary therapy in SVC syndrome of nonmalignant etiology. Stenting provides immediate, pronounced, and durable symptom relief and does not interfere with diagnostic evaluation and therapy of the underlying disease. It is minimally invasive, requires minimal hospital stay, and is well tolerated. Based on current evidence, SVC stenting should be used as the treatment of choice in the majority of patients with SVC syndrome whose symptoms warrant therapy.

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