Benign superior vena cava syndrome: Stenting is now the first line of treatment
Article Outline
Background
Endovascular repair (EVR) is emerging as first-line treatment for patients with superior vena cava (SVC) syndrome of benign etiology, but data on its durability remain scarce. The aims of this study were to assess the efficacy and durability of EVR and compare results of EVR with open surgical reconstruction (OSR).
Methods
Data from 70 consecutive patients undergoing treatment for benign SVC syndrome between November 1983 and November 2006 were retrospectively reviewed.
Results
There were 30 males and 40 females (mean age, 41 years; range, 5-75 years). Etiology included indwelling catheters or pacemaker wires in 35 patients, mediastinal fibrosis in 31, idiopathic thrombosis in 2, hypercoagulable disorder in 1, and postsurgical thrombosis in 1. In 42 patients, OSR was done through a median sternotomy: repair was with spiral saphenous vein in 22, expanded polytetrafluoroethylene (ePTFE) in 13, femoral vein grafts in 6, and human allograft in 1. Fifteen OSRs followed failed EVR interventions. EVR was attempted in 32 patients and was successful in 28 (88%): 19 had stenting, 14 had percutaneous transluminal balloon angioplasty (PTA), 2 had thrombolytic therapy with PTA, and 3 had stenting. All four technical failures subsequently underwent OSR. There were no early deaths in either group. Periprocedural morbidity was 19% after OSR and 4% in the EVR group. Six early surgical graft failures were successfully treated with surgical revision; one restenosis after EVR was restented. During a mean follow-up of 4.1 years (range, 0.1-17.5 years) after OSR, 11 patients underwent 18 secondary interventions. Mean follow-up after EVR was 2.2 years (range, 0.2-6.4 years), and nine patients underwent 21 secondary EVR interventions. Primary, assisted primary, and secondary patency rates of surgical bypass grafts were, respectively, 45%, 68%, and 75% at 3 and 5 years. Primary, assisted primary and secondary patency rates after EVR were 44%, 96%, and 96% at 3 years. Assisted primary patency was significantly higher in vein grafts than in ePTFE grafts (P = .05). Assisted primary and secondary patency was significantly higher in patients undergoing stenting compared with PTA (P = .02). At last follow-up, 93% of patients in both OSR and EVR groups had significant relief from symptoms.
Conclusions
OSR of benign SVC syndrome is effective, with durable long-term relief from symptoms. EVR is less invasive but equally effective in the mid-term, albeit at the cost of multiple secondary interventions, and is an appropriate primary treatment for benign SVC syndrome. OSR remains an excellent choice for patients who are not suitable for EVR or in whom the EVR fails.
Benign etiologies historically have accounted for up to 22% of cases of superior vena cava (SVC) syndrome, with half of these resulting from mediastinal fibrosis.1, 2, 3 A recent report suggests that benign etiologies may now comprise up to 40% of cases.4 This increase is primarily due to a rise in the use of indwelling central venous catheters and cardiac pacemakers during the past 2 decades, resulting in a higher incidence of SVC thrombosis.
We have had a longstanding interest in this condition at the Mayo Clinic. We have treated these patients with bypass grafting from the innominate or jugular vein to the SVC or right atrial appendage for >2 decades and have previously reported our results after open surgical reconstruction (OSR) and our preliminary results with endovascular repair (EVR).5
During the last 5 years our practice has shifted significantly towards EVR as primary therapy, and patients treated by EVR have far outnumbered those undergoing OSR (Fig 1). Several authors have reported initial success with EVR; however, the durability of this approach remains largely unknown, with few reports including long-term follow-up.6, 7, 8, 9, 10, 11 The aims of this study were to assess the feasibility, efficacy, and durability of endovascular treatment of benign SVC syndrome and to compare the results of EVR with those after OSR.
Fig 1.
Treatment modalities in 70 consecutive patients with benign superior vena cava syndrome over 23 years.
Methods
Patients
Clinical data of 70 consecutive patients with SVC syndrome of benign etiology treated at the Mayo Clinic from November 1983 to November 2006 were retrospectively analyzed. Data were collected under a protocol approved by the Institutional Review Board in compliance with Health Insurance Portability and Accountability Act (HIPAA) standards. Data collected included preoperative patient demographics, clinical status, noninvasive and invasive imaging, operative and endovascular procedural details, postprocedural imaging surveillance, early and late adjunctive procedures, and clinical outcome during follow-up. Patients with no clinical follow-up >1 year were categorized as “lost to follow-up.”
All patients underwent venography before intervention, and the patterns of SVC stenosis/occlusion were classified into four groups as described by Stanford and Doty.12 In the earlier phase of this study, which spans >2 decades, venography was the gold standard to define anatomy preoperatively and confirm patency postoperatively. At present, computed tomography (CT) venography is the first imaging study performed and conventional venography is performed at the time of attempted endovascular intervention. Patients were divided into two groups according to the intervention performed at our institution: 42 had open surgical reconstruction and 28 had endovascular repair (EVR).
Open surgical bypass
OSR was performed through a median sternotomy. The choice of conduit was determined by the surgeon. Autologous vein, either spiral saphenous or femoral vein, was the conduit of choice if available. Externally supported expanded polytetrafluoroethylene (ePTFE) was used if a suitable autologous vein was unavailable. The technique of autologous spiral saphenous vein bypass grafting has been described previously.5, 13 The proximal anastomosis was performed to the internal jugular or innominate vein, and the distal anastomosis was to the SVC or right atrial appendage.
Endovascular intervention
EVR was performed through percutaneous venous access of the common femoral vein, through which 6F to 10F sheaths were placed and hydrophilic guidewires and 5F catheters were used to cross the stenotic/occlusive lesion. If the lesion could not be crossed from this approach, the right internal jugular vein was accessed. Once wire access across the lesion was obtained, primary percutaneous transluminal balloon angioplasty (PTA) using standard 10- to 16-mm angioplasty balloons was performed, followed by stenting. If thrombolysis was determined to be appropriate before PTA or stenting, a catheter of suitable length with side-holes was placed across the lesion and recombinant tissue plasminogen activator (r-TPA) was infused. Serial imaging before PTA or stenting was obtained before discontinuation of thrombolysis. Technical success was defined as <30% residual stenosis after intervention.
All surgical bypass grafts were imaged with venography before the patient was discharged from the hospital. Postprocedural anticoagulation was at the discretion of the surgeon or interventionalist. Most patients were discharged with warfarin therapy for oral anticoagulation and remained on it for 3 months to indefinitely. All patients with a known thrombophilia risk factor, as well as OSR and EVR patients with early (<30 days) reconstruction failure, remained on warfarin anticoagulation indefinitely, the remainder remained on antiplatelet therapy with aspirin/clopidogrel.
During follow-up after OSR or EVR, patients underwent surveillance imaging by duplex ultrasonography (DUS), magnetic resonance imaging (MRI), CT, or venography. In the early phase of the study, all surgical patients were reviewed at 3 to 6 months and at 12 months with a venogram at each visit. Patients were reviewed annually thereafter, and grafts were imaged noninvasively with CT or MRI, with venography being performed only in patients with recurrent symptoms. With experience, it became evident that stenoses requiring intervention were associated with recurrence of symptoms, and in the later stages of the study, most patients returned for follow-up only if symptoms recurred. The EVR patients were followed up with the latter protocol.
Post-treatment clinical outcome was graded according to the Subcommittee on Reporting Standards in Venous disease14: complete relief of symptoms, +3; moderate clinical improvement, +2; mild clinical improvement, +1; and no clinical change, 0.
Statistical analysis
Kaplan-Meier survival curves were used to estimate bypass graft and endovascular patency with respect to primary patency, assisted primary patency, and secondary patency. The date of the initial bypass graft or endovascular procedure was the starting point, and the dates where an endovascular or surgical intervention was performed to maintain assisted primary or secondary patency were counted as events. The 95% confidence intervals (CI) are reported for 1, 3, and 5 years. Risk factors were assessed univariately for bypass graft or endovascular patency using a log-rank test. A value of P < .05 was considered statistically significant. Data analysis was performed using SAS 9 software (SAS Institute, Cary, NC).
Results
Patients
The study included 30 males and 40 females (mean age, 41 years; range, 5-75 years) who were treated for SVC syndrome of benign etiology. Of these, 42 patients (18 male, 24 female; mean age, 40 years; range, 5-69 years) underwent OSR and 28 (12 male, 16 female; mean age, 47 years; range, 11-75 years) underwent EVR. All patients had significant morbidity from SVC syndrome despite maximal medical measures. The most common symptoms were head and neck fullness and dyspnea on exertion, and the most common signs were head and neck swelling and distended collateral veins. Mean duration of symptoms before treatment was 21.4 months (range, 1-72 months) in the OSR group and 11.9 months (range, 0.25-96 months) in the EVR group.
The predominant etiology of SVC syndrome was mediastinal fibrosis in the OSR patients (n = 22, 52%) and indwelling catheter or pacemaker wire related thrombosis in the EVR group (n = 19, 68%). In one OSR patient, antithrombin III deficiency was the sole cause of SVC syndrome (Table I). Additional thrombophilic risk factors in the OSR patients included a history of deep venous thrombosis (DVT) in 8 (25%), protein C/S deficiency in 2 (4%), and one patient (2%) each with factor V Leiden heterozygous state, lupus antiphospholipid antibody, and Behçet disease. Additional risk factors amongst the EVR group included previous history of DVT in two (7%), history of neck irradiation in one (3%), and Behçet disease in one (3%).
Table I. Primary causes of benign superior vena cava syndrome in 70 patients
| Causes | Total (n=70), No. (%) | Surgical (n=42), No. (%) | Endovascular (n = 28), No. (%) | P⁎ |
|---|---|---|---|---|
| Mediastinal fibrosis | 31 (44) | 22(52) | 9(32) | .14 |
| Sclerosing mediastinal fibrosis | 16(23) | 13(31) | 3(11) | .08 |
| Histoplasmosis | 12(17) | 6(14) | 6(21) | .52 |
| Mediastinal granulomatous disease | 2(3) | 2(5) | 0(0) | .51 |
| Postradiation | 1(1) | 1(2) | 0(0) | >.99 |
| Venous thrombosis | 38(54) | 19(45) | 19(68) | .09 |
| Indwelling catheter/pacemaker wire | 33(47) | 14(33) | 19(68) | .007 |
| Ventriculoatrial shunt | 2(3) | 2(5) | 0(0) | .51 |
| Hypercoagulable state | 1(1) | 1(2) | 0(0) | >.99 |
| Idiopathic | 2(3) | 2(5) | 0(0) | .51 |
| Surgical excision | 1(1) | 1(2) | 0(0) | >.99 |
⁎Fisher’s exact test, two-tail P comparing surgical and endovascular intervention. |
In the OSR group, 17 patients had undergone prior attempts at repair elsewhere. Two patients had undergone OSR through a sternotomy. Of attempted EVR in 15 patients, 10 were initially successful but eventually failed. Failed EVR included thrombolysis in 1, thrombolysis with PTA or stent in 3, PTA or stent in 6, and failed attempt at recanalization in 5. Of these, 14 were occluded and one had a >70% stenosis at the time of presentation to our institution. We attempted a further endovascular recanalization for four of these occlusive lesions, but these were unsuccessful, and they eventually underwent OSR. No patient successfully treated in the EVR group had undergone a previous attempt at repair.
Preoperative imaging evaluation
All patients underwent preprocedural venography, and the SVC lesion was classified according to the extent of stenosis/occlusion. Additional imaging included CT (86%), DUS (68%), and MRI (11%). OSR patients had 15 type III lesions (36%) and 20 type IV (47%), whereas 12 EVR patients (43%) had type II lesions and 13 had type III (46%; Table II). No patient in the EVR group had a type IV SVC occlusion (P < .001).
Table II. Classification⁎ and underlying etiology of 70 patients based on venographic pattern of superior vena cava stenosis/occlusion
| Type | Definition | Total (n = 70), No. (%) | Surgical (n = 42), No. (%) | Endovascular (n = 28), No. (%) | P† |
|---|---|---|---|---|---|
| I | ≤90% stenosis of the SVC with patency and antegrade flow of the azygos–right atrial pathway | 6(9) | 3 (7) (mediastinal fibrosis, 3) | 3 (11) (mediastinal fibrosis, 1; venous thrombosis, 2) | .67 |
| II | >90% stenosis or occlusion of the SVC with patency and antegrade flow in the azygos–right atrial pathway | 16(23) | 4 (10) (mediastinal fibrosis, 3; idiopathic, 1) | 12 (43) (mediastinal fibrosis, 3; venous thrombosis, 9) | .003 |
| III | >90% stenosis or occlusion of the SVC with reversal of azygos blood flow | 28(40) | 15 (36) (mediastinal fibrosis, 7; venous thrombosis, 8) | 13 (46) (mediastinal fibrosis, 5; venous thrombosis, 8) | .46 |
| IV | Occlusion of the SVC and one or more of the major caval tributaries including the azygos systems | 20(28) | 20 (47) (mediastinal fibrosis, 9; venous thrombosis, 8; hypercoagulable state, 1; prior surgery, 1; idiopathic, 1) | 0 (0) | <.0001 |
†Fisher exact test, two-tail P. |
Open surgical reconstruction
Forty-two bypass grafts were performed in 42 patients. Spiral saphenous vein graft (SSVG) was used in 22 patients (52%), ePTFE in 13 (31%), and femoral vein in 6 (14%). Cadaveric iliocaval vein was used in 1 (2%) patient undergoing concomitant orthotopic liver transplantation for sclerosing cholangitis (Table III). There were 40 straight grafts and two bifurcated SSVGs. In one instance, the contralateral left innominate vein was implanted into the straight vein graft. Two pediatric patients, age 5 and 8, underwent OSR with a SSVG and PTFE graft, respectively. The etiology in these two patients was a prior SVC resection and antithrombin III deficiency.
Table III. Procedural details of 42 patients with open surgical reconstruction and 28 patients with endovascular repair
| Type of repair | Patients, No. | (%) |
|---|---|---|
| Open surgical reconstruction | ||
| Autologous vein | 28 | 67 |
| Spiral saphenous vein | 22 | 52 |
| Straight grafts | (19) | (43) |
| Bifurcated grafts | (2) | (5) |
| Straight graft + reimplantation opposite innominate vein | (1) | (2) |
| Femoral vein | 6 | 14 |
| Iliocaval allograft | 1 | 2 |
| Expanded polytetrafluoroethylene | 13 | 31 |
| Total | 42 | 100 |
| Endovascular repair | ||
| Catheter-directed thrombolysis with PTA | 2 | 7 |
| Catheter-directed thrombolysis with stenting | 3 | 11 |
| PTA | 4 | 14 |
| Stenting | 19 | 68 |
| Total | 28 | 100 |
| Location of PTA or stenting | ||
| SVC | 19 | 68 |
| SVC and innominate vein | 5 | 18 |
| Innominate vein | 3 | 11 |
| SVC and internal jugular vein | 1 | 3 |
| Type of stent | ||
| Wallstent (Boston Scientific, Natick, Mass) | 6 | 21 |
| S.M.A.R.T (Cordis, Piscataway, NJ) | 6 | 21 |
| Palmaz (Cordis, Piscataway, NJ) | 5 | 18 |
| Viabahn (W.L. Gore, Newark, Del) | 3 | 11 |
| Lumminexx (C.R. Bard, Covington, Ga) | 1 | 3 |
| Protégé (eV3 Inc, Plymouth, Minn) | 1 | 3 |
The mean pressure gradient across the SVC occlusion recorded in 24 patients was 21 mm Hg (range, 9-43 mm Hg) before reconstruction and 6 mm Hg (range, 0-13 mm Hg) after the reconstruction. All bypass grafts were imaged before discharge, and 35 of 42 patients (83%) were prescribed oral anticoagulation therapy at discharge. The median length of stay was 9 days (range, 4-48 days).
Endovascular repair
Primary EVR was performed in 28 patients and attempted in an additional four. Technical success was achieved 28 of 32 patients (88%). Four patients underwent primary PTA (14%), and 19 patients (68%) underwent stenting after PTA. Details of type and location of intervention are in Table III. One pediatric patient (age 11) underwent stenting for catheter-related thrombosis. Five patients presented with subacute SVC syndrome (duration of symptoms, 1-4 weeks) and were initially treated with catheter-directed thrombolysis, followed by PTA (n = 2) or stenting (n = 3). The duration of thrombolytic therapy did not exceed 48 hours.
The mean pressure gradient across the SVC stenosis or occlusion recorded in 11 patients was 12 mm Hg (range, 5-22 mm Hg) preintervention and 2 mm Hg (range, 0-6 mm Hg) postintervention. Warfarin therapy was prescribed to 22 patients (78%) at discharge, and therapy for the rest was aspirin or clopidogrel. The median length of stay was 2 days (range, 1-14 days).
Early results (within 30 days)
Morbidity and mortalityThere were no in-hospital or early postoperative deaths. Eight patients (19%) who underwent OSR had 11complications. In one patient in the EVR group (4%), an arm hematoma developed at a peripheral intravenous access site while receiving thrombolysis, which was treated non-surgically (Table IV).
Table IV. Thirty-day complication rate after open surgical reconstruction or endovascular repair for superior vena cava syndrome
| Complication | Patients, No. |
|---|---|
| Surgical | 8 |
| Mediastinal hematoma requiring evacuation | 1 |
| Deep venous thrombosis | 2 |
| Pulmonary embolus | 1 |
| Prolonged mechanical ventilation | 2 |
| Pericardial effusion requiring drainage | 1 |
| Tracheostomy, prolonged mechanical ventilation, pleural effusion requiring drainage, pneumonia | 1 |
| Endovascular | 1 |
| Arm hematoma | 1 |
In six patients (14%) in the OSR group, early graft thrombosis developed within the first 2 postoperative days, all of which were successfully treated with surgical revision. Three occluded ePTFE grafts underwent surgical thrombectomy. One ePTFE graft occluded on the first postoperative day owing to inflow compromise and was replaced with a new ePTFE graft with inflow from the contralateral internal jugular vein. Two SSV bifurcated grafts had occlusion of the side limb and were thrombectomized and revised; however, one side limb rethrombosed early. All bypass grafts, except one limb of a bifurcated graft, were patent at the time of discharge. None of these six patients sustained a complication due to the early repeat surgical intervention to maintain secondary patency, and their length of stay was not significantly prolonged (median, 10 days; range, 9-22 days). The 30-day primary, assisted primary, and secondary patencies were 93%, 98%, and 100%, respectively.
Patency of reconstruction for endovascular repairIn the EVR group, one patient (4%) required early reintervention for a nonocclusive residual thrombus proximal to an innominate vein stent on postoperative day 1. This was successfully treated with proximal placement of a new stent. In another patient with thrombosis related to a pacemaker lead, rethrombosis of the SVC developed 18 days after catheter-directed thrombolysis and stenting. No further intervention was performed in this patient. The 30-day primary, assisted primary, and secondary patencies were 93%, 96%, and 96%, respectively.
Late results
MortalityMean follow-up in the entire patient cohort was 3.2 years (range, 0.1-17 years). In the OSR group, 14 patients were lost to follow-up and five late deaths occurred during a mean follow-up of 4.1 years (range, 0.1-17.5 years). The first patient, with longstanding Crohn disease, died of new bronchogenic carcinoma after remaining asymptomatic for 8 years after SSVG. One patient died of septic complications of longstanding tuberculous peritonitis 17 months after an ePTFE graft for central catheter–related thrombosis. Three patients died of unknown causes at 8 months, and 3 and 8 years after OSR.
The mean follow-up in the EVR group was 2.2 years (range, 0.2-6.4 years). Seven patients were lost to follow-up. Cardiac failure resulted in one late death at 4.5 years. This patient was awaiting heart transplantation after undergoing thrombolysis and stent placement for SVC syndrome from central vein thrombosis due to a pacemaker wire lead.
PatencyIn the OSR group, postoperative graft surveillance was performed with venography at 3, 6, and 12 months and DUS, MRI, or CT scan yearly thereafter, or earlier if symptoms recurred. Mean duration of follow-up determined from the date of the last imaging study was 3.4 years (range, 1 day-17.4 years). To maintain patency during follow-up, 11 patients required 18 reinterventions (PTA, 10; stenting, 7, thrombolysis, 1); and seven of these were within the first year (Fig 2).
Fig 2.
Secondary interventions required to maintain patency in (A) the open surgical group (n = 42) and (B) the endovascular group (n = 28). The bars represent the percentage of patients in each group, and the line graphs represent the total number of interventions. Secondary interventions in the surgical group include new superior vena cava bypass grafts in two patients after occlusion of the primary grafts.
Seven grafts eventually occluded during follow-up, of which three underwent an intervention. One SSVG graft was successfully treated with recanalization and stenting, one occluded ePTFE graft was replaced with a new SSVG, and one occluded SSVG was replaced with a femoral vein graft. The remaining four occluded grafts did not undergo intervention; two of these were re-do grafts in patients with prior OSR bypasses. No complications or deaths were elated to the secondary EVR or OSR interventions.
The 1, 3, and 5-year cumulative primary patency rates of OSR were 58% (95% CI, 43%-77%), 45% (95% CI, 30%-68%), and 45% (95% CI, 29%-68%); assisted primary patency rates were 81% (95% CI, 69%-95%), 68% (95% CI, 52%-88%), and 68% (95% CI, 49%-88%); and secondary patency rates were 85% (95% CI, 74%-98%), 75% (95% CI, 61%-94%), and 75% (95% CI, 57%-94%; Fig 3, A). After excluding PTFE grafts and analyzing only the 28 vein grafts and the cadaveric allograft, the 5-year rates were cumulative primary patency, 49% (95% CI, 31%-75%); assisted primary patency, 78% (95% CI, 59%-98%); and the secondary patency, 81% (95% CI, 63%-100%).
Fig 3.
A, Cumulative primary, assisted primary, and secondary patency rates at 1, 3, and 5 years of open surgical reconstruction (n = 42). Range bars represent the standard error of the mean <10%. B, Cumulative primary, assisted primary, and secondary patency rates at 1 and 3 years of endovascular repair (n = 28). Range bars represent the standard error of the mean <10%.
In the EVR group, the mean length of follow-up based on the last imaging was 1.8 years (range, 0 days-6.3 years). Nine patients required 21 secondary interventions to maintain patency, four of which were within the first year (Fig 2). These included 19 PTAs, one stent, and one thrombolysis, followed by stenting. Secondary interventions were performed in 55% (5 of 9) of patients with mediastinal fibrosis and 26% (5 of 19) of patients with indwelling catheter/pacemaker wire-related thrombosis; this trend did not reach statistical significance (P = .2). One patient with mediastinal fibrosis underwent 10 additional PTAs during a 6.5-year period to treat symptomatic in-stent restenoses. These episodes of restenosis were immediately treated with PTA, and his symptoms would promptly resolve. The restenotic lesion was amenable to an endovascular intervention each time, and the patient had a strong preference for this treatment modality vs surgical repair. His stent was still patent at the last follow-up. One patient chose to undergo SSVG at another institution after the third restenosis after EVR. One patient was found to have asymptomatic stent occlusion on follow-up imaging, and no further intervention was performed.
There were two complications (cardiac tamponade) and no deaths related to secondary endovascular interventions. The episodes of cardiac tamponade occurred at the time of second and sixth PTA, were confirmed with echocardiography, and were successfully managed with immediate pericardiocentesis, with no further sequelae.
The cumulative 1- and 3-year rates of EVR were primary patency, 70% (95% CI, 51%-94%) and 44% (95% CI, 22%-82%); assisted primary patency, 96% (95% CI, 87%-100%) and 96% (95% CI, 82%-100%); and secondary patency, 96% (95% CI, 87%-100%) and 96% (95% CI, 82%-100%). One additional EVR failed at 3.9 years, but the life-table analysis was only reported out to 3 years because of diminishing numbers beyond this point adversely affecting accuracy (Fig 3, B).
No significant difference was found in primary patency (P = .91), assisted primary patency (P = .29), or secondary patency (P = .36) when OSR was compared with EVR.
OutcomeAt the last clinical assessment, 39 of 42 patients (93%) in the OSR group had mild or no symptoms compared with 26 of 28 patients (93%) in the EVR group (P > .99; Fig 4). Only one OSR patient and two EVR patients in the combined cohort had no clinical improvement after treatment. Graft or endovascular occlusion developed in six patients (4 OSR, 2 EVR) for which no further intervention was performed. One EVR patient remained symptomatic after early stent rethrombosis; the remaining 5 patients maintained some clinical improvement despite reocclusion.
Fig 4.
Grading of symptom relief at last clinical follow-up in patients undergoing open surgical reconstruction (n = 42) or endovascular repair (n = 28).
Univariate analysis was performed to assess the impact of sex, age (<40 years vs >40 years), type of SVC occlusion (type I/II vs type III/IV), etiology (mediastinal fibrosis vs venous thrombosis), history of an EVR (PTA or stenting), type of bypass conduit (autologous vs PTFE), and type of intervention (PTA vs stenting) on patency (Table V). At 3 years, the ePTFE grafts demonstrated worse assisted primary patency than autologous grafts (P = .05), with rates of 26% (95% CI, 5%-100%) vs 78% (95% CI, 62%-98%), respectively. At 3 years, stenting compared with PTA had improved assisted primary and secondary patency (P = .02), with rates of 100% vs 88% (95% CI, 57-100), respectively.
Table V. Univariate analysis⁎ of clinical and procedural risk factors on patency in patients undergoing open surgical reconstruction or endovascular repair
| Risk factor | Surgical patency | Endovascular patency | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Patients, No | Primary | Secondary | Patients, No. | Primary | Secondary | |||||
| % | P | % | P | % | P | % | P | |||
| Sex | ||||||||||
| Female | 24 | 51 | .70 | 70 | .30 | 16 | 57 | .78 | 92 | 0.69 |
| Male | 18 | 40 | 83 | 12 | 27 | 100 | ||||
| Age | ||||||||||
| <40 | 23 | 28 | .06 | 74 | .78 | 10 | 56§ | .03 | 100 | 0.17 |
| >40 | 19 | 68 | 78 | 18 | 78 | 94 | ||||
| SVC obstruction type | ||||||||||
| Type I/II | 7 | 57 | .15 | 100 | .16 | 15 | 45 | .88 | 92 | 0.27 |
| Type III/IV | 35 | 40 | 69 | 13 | 32∥ | 100 | ||||
| Etiology | ||||||||||
| Mediastinal fibrosis | 22 | 43 | .83 | 74 | .84 | 9 | 29∥ | .90 | 100 | 0.17 |
| Central line/wire | 16 | 50 | 81 | 19 | 63 | 94 | ||||
| Prior endovascular intervention | ||||||||||
| Yes | 10 | 54§ | .75 | 86 | .94 | … | … | … | … | … |
| No | 27 | 49 | 75 | … | … | … | ||||
| Type of bypass graft | ||||||||||
| PTFE | 13 | 23 | .58 | 42 | .35 | … | … | … | … | … |
| Vein† | 28 | 49 | 81 | … | … | … | ||||
| Endovascular intervention‡ | ||||||||||
| PTA | … | … | … | … | … | 4 | 42 | 0.31 | 88 | 0.02 |
| Stenting | … | … | … | 19 | 40 | 100 | ||||
⁎Log-rank test. |
†Includes 28 vein grafts and 1 iliocaval allograft. |
‡Includes 23 primary endovascular interventions and excludes 5 patients who underwent thrombolysis. |
§Kaplan-Meier estimates of patency at only 1 year. |
∥Kaplan-Meier estimates of patency at only 2 years. |
Discussion
Although SVC syndrome of benign etiology remains an uncommon disease, increasing use of indwelling central catheters and pacemaker wires in the past 20 years has led to a marked increase in its incidence. More than 5 million central venous catheters and 170,000 pacemakers are now implanted annually in the United States and are associated with upper extremity or central vein DVT in 7% to 33% of patients.15, 16, 17, 18 SVC syndrome reportedly occurs in 1% to 3% of patients with central venous catheters and in 0.2% to 3.3% of patients with implanted pacemakers.4, 19 Catheter-related thrombosis has overtaken mediastinal fibrosis as the leading cause of this syndrome. In the past, mediastinal fibrosis comprised up to 80% of cases of benign SVC syndrome,1, 2, 3 but recent data attribute up to 74% of new cases to indwelling catheters or wires.4, 6 In our present series, 57% of cases were SVC thromboses related to catheters or wires.
Until recently, OSR has been the mainstay of treatment of these patients in contrast to SVC syndrome secondary to malignancy, where EVR has long been the accepted mode of treatment. Patients with benign SVC syndrome are younger, with a longer life expectancy, and therefore need a good, durable reconstruction. OSR for benign SVC syndrome has been performed with low morbidity and mortality and excellent long-term results. Doty et al20 reported no perioperative deaths and 87.5% graft patency at 10.9 years associated with complete resolution of symptoms in 93% of patients after 16 SSVGs. Similar results have been reported from our institution, with no operative mortality, 80% graft patency at 5 years (90% in vein grafts), and 79% symptom relief.5
EVR is rapidly becoming the preferred primary method of treatment of benign SVC syndrome, along with the widespread increase in EVR for all vascular problems. Commensurate with this global change, our practice has also shifted significantly towards EVR as primary therapy, with most patients undergoing an attempt at EVR. In eight of 13 patients operated on in the last 5 years, an endovascular intervention had failed or was unsuccessful.
Our patency rates of EVR are comparable with other small series that demonstrate 57% to 79% primary patency and 85% to 100% primary-assisted primary or secondary patency.6, 7, 8 Graft patency was maintained during longer follow-up in the OSR group, with most secondary interventions being performed within the first few years after the operative procedure. In the EVR group, however, the need for secondary interventions continued over the mid-term, although the small numbers of patients make it difficult to predict a difference (Fig 2). Symptom relief was excellent and comparable in both groups during the study period (Fig 4).
The major advantage of endovascular therapy over open reconstruction is decreased procedure-related morbidity and shorter recovery period in these young patients in the prime of their working lives. OSR, however, was associated with excellent long-term outcome without the continuing need for reinterventions over time. Although EVR was associated with very little initial morbidity, two patients presented with cardiac tamponade from intrapericardial rupture during repeat EVR in the follow-up period. Of interest, both cases of pericardial tamponade occurred in patients who underwent subsequent repeat PTA for restenosis (second and sixth reinterventions, respectively). Pericardial tamponade after EVR for both benign and malignant SVC syndrome is uncommon, and whether it is attributable to stenting or PTA is unknown.21 Both cases of pericardial tamponade were immediately recognized, confirmed with echocardiography, and promptly treated with ultrasound-guided pericardiocentesis.
Overall, EVR has become the primary mode of treatment of SVC syndrome of benign etiology for the aforementioned reasons, despite the greater need for reintervention possibly extending out to the long-term. Although not statistically significant, a trend was noted toward more reinterventions after EVR in patients with mediastinal fibrosis (55%) than in those with catheter-related thrombosis (26%). Further follow-up is needed to clarify this fact, and this may ultimately guide the choice of initial treatment.
Whether thrombolysis before PTA/stenting in the acute-on-chronic occlusions related to indwelling catheters affects long-term patency is not clear. In a small series by Gray et al,22 initiation of thrombolysis ≤5 days of onset of symptoms was associated with relief of symptoms. Other studies have described the use of thrombolysis before stenting for benign SVC syndrome, but outcomes in this subset were not reported separately.6, 10 Five patients in our study with acute-on-chronic catheter-related SVC occlusion with symptoms ranging from 1 to 4 weeks underwent catheter-directed thrombolysis before PTA or stenting. All five were technically successful, but rethrombosis of the EVR occurred in two patients, one at 18 days and the other at 3.6 years. Our practice for patients with catheter-related thrombosis is to proceed initially with thrombolysis if the duration of symptoms is <4 weeks. If the venous thrombosis is due to an indwelling central catheter, the catheter should be removed if feasible and replaced after successful PTA or stenting. Thrombosis related to a pacemaker lead may require a laser-sheath to temporarily extract the lead and replace it after completion of thrombolysis and PTA or stenting.23
As with endovascular interventions in general, the shorter the length of the occlusion the more amenable it is to a successful EVR. No patient in our series with a type IV SVC occlusion was treated by endovascular means. We attempted primary EVR in two patients with type IV lesions but were unsuccessful. This would suggest that this subgroup of patients might be unsuitable anatomically for an EVR. However, Qanadli et al11 reported successful stenting in six patients with type IV SVC occlusions from benign causes, with rapid resolution of symptoms. Bornak et al10 reported similar success in two patients, but neither commented on maintenance of patency in this subgroup of patients.
Although we were unsuccessful in treating a type IV occlusion in our study patients, making this subgroup possibly unsuitable for EVR, we believe it is not unreasonable to attempt recanalization of this type of occlusion. Of 15 patients undergoing OSR after failed EVR, the SVC occlusions were type IV in eight (53%) and type III in six (40%). The question arises whether all these were long occlusions at the outset or became so after EVR, with likelihood of repeat interventions and further extension of stents, and does this adversely affect the outcome of eventual OSR? Although this certainly remains a consideration, we were not able to make a definite determination because the original venous imaging and intervention was performed elsewhere in all patients. We have not yet had to perform OSR on any patients successfully treated with EVR at our institution, although one patient chose to have an SVC bypass at another institution for restenosis of a type II lesion. In our current experience, long-term graft patency was not adversely affected in these patients undergoing long bypasses after occlusion of their EVRs.
Despite the shift towards primary EVR for patients with benign SVC syndrome, OSR remains an excellent option in selected patients. Spiral saphenous vein is our preferred conduit; however, femoral vein provides comparable patency when saphenous vein is unavailable, albeit at the risk of developing sequelae of lower extremity venous hypertension.24 After occlusion of side branches occurred in two patients early in our experience, we have shied away from bilateral reconstructions and have found that collateralization across the midline is usually adequate to decompress both sides with a single graft. Since analysis and report of our experience 5 years ago, which revealed poorer patency with ePTFE compared with vein grafts, we have avoided long reconstructions with ePTFE.5 Data from treatment of malignant SVC syndrome suggest that short, predominately intrathoracic ePTFE grafts have improved patency vs longer ePTFE grafts originating from the internal jugular vein.25, 26 Since our last report, we have performed five short ePTFE bypass grafts originating from the innominate vein, and only one has required subsequent stenting for an anastomotic stenosis to maintain assisted primary patency.
Our practice paradigm has shifted dramatically in the past 7 years. Our present philosophy for the management of patients who present with benign SVC syndrome unresponsive to medical therapy, regardless of etiology, is to initially attempt an EVR if possible. Patients with acute or subacute venous thrombosis may benefit from catheter-directed thrombolysis before PTA or stenting. Only patients who have a failed EVR or whose occlusion cannot be recanalized are considered for OSR.
Conclusion
Endovascular treatment is an appropriate primary intervention in patients with superior vena cava syndrome of benign etiology. It is less invasive with lower morbidity compared with open surgical reconstruction with equal efficacy and patency in the mid-term, albeit at the cost of multiple secondary interventions. It does not adversely affect the feasibility or patency of subsequent open surgical reconstruction. Surgical bypass is associated with durable long-term relief from symptoms of superior vena cava syndrome and remains an excellent option in patients not suitable for or who fail endovascular treatment
Author contributions
References
- . Diagnosis and treatment of superior-vena-cava obstruction. AMA Arch Surg. 1951;63:311–325
- . Superior vena cava obstruction: clinical syndrome, etiology, and treatment. Curr Probl Cancer. 1986;10:441–484
- . Etiologic considerations in superior vena cava syndrome. Mayo Clin Proc. 1981;56:407–413
- . The superior vena cava syndrome: clinical characteristics and evolving etiology. Medicine (Baltimore). 2006;85:37–42
- Open surgical and endovascular treatment of superior vena cava syndrome caused by nonmalignant disease. J Vasc Surg. 2003;38:215–223
- . Endovascular stenting of nonmalignant superior vena cava syndrome. Catheter Cardiovasc Interv. 2005;65:405–411
- Percutaneous treatment of superior vena cava syndrome using metallic stents. Eur Radiol. 2003;13:853–862
- . Superior vena cava syndrome: treatment with catheter-directed thrombolysis and endovascular stent placement. Radiology. 1998;206:187–193
- . Nonmalignant superior vena cava syndrome: pathophysiology and management. Catheter Cardiovasc Interv. 2005;65:416–423
- . Endovascular treatment of stenoses in the superior vena cava syndrome caused by non-tumoral lesions. Eur Radiol. 2003;13:950–956
- Subacute and chronic benign superior vena cava obstructions: endovascular treatment with self-expanding metallic stents. AJR Am J Roentgenol. 1999;173:159–164
- . The role of venography and surgery in the management of patients with superior vena cava obstruction. Ann Thorac Surg. 1986;41:158–163
- . Reconstruction of the vena cava and of its primary tributaries: a preliminary report. J Vasc Surg. 1990;11:373–381
- . Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg. 1995;21:635–645
- Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115:e69–e171
- . Intravascular-catheter-related infections. Lancet. 1998;351:893–898
- Venous obstruction after pacemaker implantation. Pacing Clin Electrophysiol. 2007;30:199–206
- . Prevalence of upper extremity deep venous thrombosis diagnosed by color Doppler duplex sonography in cancer patients with central venous catheters. J Ultrasound Med. 2006;25:1297–1303
- . Transvenous pacing lead-induced thrombosis: a series of cases with a review of the literature. Cardiology. 2000;93:142–148
- . Superior vena cava obstruction: bypass using spiral vein graft. Ann Thorac Surg. 1999;67:1111–1116
- . Balloon dilation of the superior vena cava (SVC) resulting in SVC rupture and pericardial tamponade: a case report and brief review. Cardiovasc Intervent Radiol. 2005;28:372–376
- . Safety and efficacy of thrombolytic therapy for superior vena cava syndrome. Chest. 1991;99:54–59
- . Exchange of pacing or defibrillator leads following laser sheath extraction of non-functional leads in patients with ipsilateral obstructed venous access. Heart. 2000;83:E12
- Venous morbidity after superficial femoral-popliteal vein harvest. J Vasc Surg. 1999;29:282–289discussion 289-91
- Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors. J Thorac Cardiovasc Surg. 1991;102:259–265
- . Surgical reconstruction of the superior vena cava. Cardiovasc Surg. 1994;2:598–604
Competition of interest: none.CME article
PII: S0741-5214(07)01598-4
doi:10.1016/j.jvs.2007.09.071
© 2008 The Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.