Author: Rei Mitsuyama, MS3, Brown University

Introduction

Benign superior vena cava (SVC) syndrome is caused by nonmalignant obstruction of the SVC. The most common causes are long-term central lines, long-term cardiac devices, and fibrosing mediastinitis. Symptoms may include headache, facial swelling, and upper limb edema which may present acutely or chronically. Currently, endovascular stent placement is the first-line treatment for both acute and chronic SVC syndrome [1]. 

Long-term anticoagulation is used in the management of many medical conditions including deep vein thrombosis, hypercoagulable conditions, and mechanical valve prostheses. Though anticoagulation is also commonly used to prevent stent thrombosis, few studies have evaluated whether anticoagulation improves stent patency in the context of benign SVC syndrome. This retrospective study aimed to evaluate the effect of long-term anticoagulation on stent patency and symptom relief after endovascular stent placement for benign SVC syndrome [2].

Study Population and Treatment Protocol 

This study defined benign SVC syndrome as nonmalignant obstruction of the SVC that caused signs and symptoms as described by Kishi et al [4]. A retrospective review of an institutional database identified 81 patients who underwent stent placement for benign SVC syndrome from January 1999 and July 2017. Of the 81 identified patients 58 met inclusion and exclusion criteria and were included in the study. Signs of SVC syndrome seen in these patients included dilation of neck veins and swelling of the face, neck, eyes, periorbital region, or upper extremities. Symptoms of SVC syndrome within these patients included headache, chest pain, shortness of breath, dizziness, weakness, and changes in voice or vision. The most common sign was neck swelling (n = 26, 45%) and the most common symptom was headache (n = 18, 31%). The study population included 34 women (58%) and 24 men (42%). The mean age at the time of stent placement was 49 years (range, 24-80 y). Etiology of the benign SVC syndrome included long term central line/pacemaker wire (64%) and fibrosing mediastinitis (36%)

The mean follow-up time was 2.4 years (range, 2 mo – 11 y).

All patients received chest computed tomography (CT) with iodinated contrast prior to the procedure in order to demonstrate nonmalignant obstruction. Digital subtraction venography was obtained during the procedure and, along with preoperative CT, was used to classify the obstructions by the Society of Interventional Radiology Reporting Standards for Thoracic Central Vein Obstruction [3]. 91% of the patients had type 4 occlusions, defined as any SVC obstruction that prevents or impedes direct thoracic venous flow to the right atrium. The remaining cases (9%) were type 3 obstructions, which consist of SVC and bilateral brachiocephalic vein obstructions. The severity of the obstructions were also classified based on Stanford and Doty criteria (type I – <90% stenosis of SVC with patent azygous-right atrial pathway; type II – 90-100% stenosis with antegrade azygous-RA flow; type III – 90-100% stenosis with reversal of azygous-RA flow; type IV –  complete obstruction of the SVC and one of the major caval tributaries) [4].

The right internal jugular, brachial, or common femoral vein was used for access. Angioplasty with an 8- or 10-mm balloon was performed before stent placement in all cases. Stent length was chosen to ensure full coverage of the obstruction (range 10-100 mm, median 40 mm). The type of stent used was based on provider preference with a median diameter of 14 mm (range 10-20 mm). Stent patency without collateral flow was the endpoint for technical success. Symptom relief or a Kishi score of <4 were endpoints for clinical success [5]. 

Following stent placement, 36 patients (62%) received indefinite anticoagulation while 22 patients (38%) did not receive anticoagulation. The decision to anticoagulate following stent placement was multifactorial, including pre-existing conditions that required anticoagulation (19 patients), patient preference, willingness to follow up for monitoring, and concern for stent thrombosis.  Anticoagulation medications used for therapy included warfarin, enoxaparin, rivaroxaban, or apixaban, with the specific medication based on provider and patient preference, and with warfarin being the most common (n = 26). For those patients on warfarin, the target international normalized ratio (INR) was 2.0-3.0 for all patients except one patient with a cardiac valve prosthesis whose target INR was 2.5-3.5. Within the anticoagulation group 14 patients (39%) had covered stents placed, while the remaining 22 patients (61%) had uncovered stents, while in the non-anticoagulated group 11 patients (50%) had covered stents placed and the 11 patients (50%) had uncovered stents.

Data Collection

Patients had follow-up appointments at 3 months, 6 months, and yearly thereafter as per clinical practice. More urgent evaluation was done at the request of patients reporting signs or symptoms of SVC syndrome. 

Stent patency was measured on post-stenting imaging by percent in-stent stenosis, which was calculated as smallest stent diameter divided by normal non-stenotic diameter of the stent, multiplied by 100%. This information was collected via image review at 3 months, 6 months, and yearly thereafter, by a resident and verified by an attending interventional radiologist with 26 years of experience.

Baseline patient characteristics and outcomes were compared using Chi-square or Fisher exact test for categorical variables and t test for continuous variables. A Kaplan-Meier curve was used to demonstrate time to loss of primary patency following initial intervention, where primary patency was defined as uninterrupted patency following initial stent placement. 

Outcomes

Technical success was achieved in all cases and there were no procedure-related deaths. There was no significant difference in percent stenosis between the anticoagulated (40.4% ± 34.7) and nonanticoagulated (32.1% ± 29.2%) groups (P = 0.361). There was also no significant difference in the number of patients reporting return of signs or symptoms (anticoagulated, 44.4%; nonanticoagulated, 50%; P = 0.681), nor in the number of days from procedure to return of signs or symptoms (anticoagulated, 735.9 ± 1,003.1; nonanticoagulated, 478 ± 826.6; P = 0.488). Reintervention was required in 24 patients (50%) with angioplasty required in all cases, additional stent placement in 5 cases, and/or thrombolysis in 1 patient. The rate of reintervention did not differ between groups (anticoagulated, 36.3%; nonanticoagulated, 44.4%; P = 0.591).

Conclusions

Benign SVC syndrome is an uncommon disease for which the first-line intervention is stent placement [1]. Maintaining patency of these stents is tantamount to long-term prognosis, and anticoagulation is commonly used in the setting of stent placement for other medical conditions [6]. However, there is a lack of data regarding the potential benefit of anticoagulation following stent placement for benign SVC syndrome, and post procedural recommendations are unclear. 

The currently reviewed study results demonstrate no significant improvement in stent patency or return of SVC symptoms with the use of anticoagulation following stent placement for benign SVC syndrome. Additionally, there was no significant difference in the need for re-intervention with the use of anticoagulation.

The lack of significant improvement of outcomes with anticoagulation following stenting of benign SVC syndrome within this study is helpful in managing patient care. The use of anticoagulation following stenting of benign SVC syndrome results in increased patient costs, need for follow-up, and potential for complications, most commonly related to hemorrhage [6,7]. Roughly half (53%) of the patients in the anticoagulated group were already on anticoagulation medications due to preexisting conditions and would have required continued anticoagulation regardless of intervention. However, it is conceivable that the other 17 patients in the group would have had the same outcome even if they were never placed on anticoagulation. 

There are several limitations to this study. The inconsistent criteria for anticoagulation and retrospective nature of this study in particular are problematic. For example, one of the factors when considering anticoagulation was noted to be “concern for stent thrombosis.” It is possible that those who were not anticoagulated were at lower risk of thrombosis from the beginning and anticoagulation improved outcomes for those who were at higher risk. Similarly, it is impossible to know whether the patients who were anticoagulated and did not have return of symptoms would have fared just as well without anticoagulation. Furthermore, using return of symptoms as an endpoint is difficult as symptoms vary among patients and may be acknowledged at different degrees of severity depending on patient tolerance. Lastly, there was notable variability in the procedures themselves. Angioplasty balloons were either 8 or 10 mm in diameter; stents types were chosen based on operator preference; stent length ranged from 10 to 100 mm with the only requirement being that the underlying obstruction was covered by the stent.

References

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