The role of iliac vein stent placement in pelvic venous disorder management.

The use of antithrombotic therapy after iliac vein stent placement remains controversial. Stents placed for NIVLs generally have excellent patency, upwards of 95% in reported studies. 47 One retrospective study concluded that perioperative stent thrombosis in this setting is very uncommon. 48 Based on this, we typically do not anticoagulate patients with stents placed for NIVLs even in the short term and caution against prolonged anticoagulation in the absence of data supporting its efficacy. For post-thrombotic etiology iliac vein lesion stents, long-term patency is generally poorer. 47 , 49 Anticoagulation plays an important role in post-thrombotic stent patency, but there are a wide range of anticoagulation protocols employed in practice. Our practice for thrombotic etiology iliac stents is to anticoagulate with a short-term course of low molecular weight heparin, which is selected in part due to its anti-inflammatory effects and has been shown to reduce odds of early reocclusion. 50 , 51 After approximately 4 weeks, the patient is bridged to a direct-acting oral anticoagulant. Because most direct-acting oral anticoagulants do not have a recommended prophylactic dose, we prescribe a full dose. The duration of anticoagulation in post-thrombotic patients is largely guided by whether the thrombosis is provoked or unprovoked, initial or subsequent, and the extent of anatomy involved. For those with recurrent or unprovoked thrombosis, indefinite antithrombotic therapy is generally favored. Antiplatelet therapy is controversial; we usually elect for monotherapy over dual agent therapy given insufficient evidence validating antiplatelet use and increased bleeding risk. 52 Establishing clinical follow-up is important to identify the minority of patients who develop significant in stent stenosis (up to 5% of all patients at 72 months; 10% in post-thrombotic occlusions and 1% NIVL); early reintervention in these cases is more likely to be successful. 53 , 54 Ultrasound or cross-sectional imaging at regular intervals is suggested, particularly for thrombotic lesions. There is no conclusive data to inform a surveillance timeline at present. We suggest ultrasound, or if not visible, CT at 1, 3, 6, and 12 months and subsequently annually for post-thrombotic occlusions. A more infrequent surveillance schedule would be reasonable for patients with NIVL.

Conception and design: KD, RG, NM Analysis and interpretation: Not applicable Data collection: Not applicable Writing the article: KD, RG, NM Critical revision of the article: KD, RG, NM Final approval of the article: KD, RG, NM Statistical analysis: Not applicable Obtained funding: Not applicable Overall responsibility: KD

Imaging should be guided by the patient’s dominant symptoms. For S 1 (left flank pain), an abdominal ultrasound is a cost-effective initial study when performed by experienced sonographers. For S 2 (pelvic), an extended pelvic ultrasound is the initial exam of choice to evaluate for ovarian vein reflux. Ovarian vein diameter of 6 mm or greater is frequently associated with ovarian reflux. 16 The presence of four or more ipsilateral tortuous para-uterine veins measuring 4 mm or more in diameter is another reported sign of ovarian reflux. 17 , 18 Experienced sonographers can also reliably image the iliac vein in most scenarios. For S 3 patients, a lower extremity and pelvic ultrasound are the initial imaging choice to map varicosities and segments of reflux. Ultrasound is the mainstay diagnostic imaging modality in many practices but is heavily dependent on local sonographer expertise. Axial imaging in the form of computed tomography venography or magnetic resonance venography can be obtained when intervention is being considered to delineate anatomy and help with procedural planning. Magnetic resonance venography is particularly helpful in cases of proximal occlusion (such as ilio-caval obstruction) and atypical or extensive collateralization and has the added benefit of evaluating for non-venous etiologies for symptoms.

Patients with chronic iliofemoral venous obstruction (CIVO) may present with pelvic pain, lower extremity symptoms, or both depending on the degree of compensation and the presence of other concurrent venous pathology. CIVO can be thrombotic (eg, P CIV, O, T ) or non-thrombotic (eg, P CIV, O, NT ) in etiology. Only a subset of patients with non-thrombotic iliac vein lesions (NIVLs) will benefit from stent placement, making patient selection critical in this population. This is because anatomic compressions are frequently identified in up to 70% of asymptomatic individuals, which implies that an NIVL can be an incidental noncontributory finding in a symptomatic patient. 21 , 22 , 23 However, NIVLs contribute to symptoms in many patients with PeVD, and failure to treat this subset of patients could result in a suboptimal or failed clinical response. 24 Therefore, the challenge is determining what constitutes a clinically significant NIVL and excluding other causes of pathology. Iliac vein stenoses are typically identified during initial imaging workup of a patient with PeVD, and it is important to recognize the limitations of diagnostic imaging. For example, obesity or dehydration can falsely exaggerate the degree of stenosis on cross-sectional imaging; the false positive rate of magnetic resonance venography has been reported as high as 41.5%. 25 Ultrasound is a useful pre-intervention screening modality for iliac stenoses; recent data has demonstrated that normalized ultrasound diameter measurements combined with velocity measurements of stenoses correlate with intravascular ultrasound (IVUS)-derived area reductions. 26 , 27 However, the reliability of ultrasound measurements depend on sonographer variability and experience. Venography can be helpful when collateral pathways are present to suggest hemodynamic significance; however, it can also miss lesions. IVUS is a more sensitive and precise tool than venography for identifying iliofemoral venous obstruction. 28 We suggest evaluating iliac obstructive lesions by both venography and IVUS routinely before placing a stent. The positioning of the patient during imaging will affect the degree of stenosis on venography and ultrasound. Stenoses found in patients while supine often disappear when the patient is repositioned to left side down or standing. 29 Reverse Trendelenburg is considered the optimal positioning for venography. 30 True venous stenoses will persist despite repositioning and remain fixed despite exam maneuvers such as Valsalva. 29 Determining the severity of an iliac vein stenosis is important when evaluating whether an NIVL is likely to be clinically meaningful. Historically, thresholds ranging from 20% to 50% area stenosis were used as the minimum stenosis warranting treatment. 21 Some continue to advocate for lower thresholds for intervention in NIVLs for patients with quality of life-impairing symptoms who have failed conservative treatment. 31 Validation of such thresholds is necessary in multicenter, bias-limited cohorts. The Venogram vs intravascular ultrasound (IVUS) for Diagnosing Iliac Vein Obstruction (VIDIO) trial prospectively evaluated iliofemoral obstruction in 45 patients with C4-C6 venous disease; their analysis suggested treatment of ≥61% diameter, 86% area stenosis (by IVUS) in patients with NIVL yielded positive results in their patient cohort. 28 The external validity of the results has been questioned, given that the studied patient population was limited to those with C4-C6 disease. 26 Peak vein velocity ratio >2.5 in the area of stenosis is a reported ultrasound criterion for identifying a significant NIVL. 26 Reversal of flow in the internal iliac vein, balloon pullback test, and the presence of collaterals have been anecdotally reported as helpful signs of a significant NIVL. 32 Patients with post-thrombotic iliac vein obstruction generally present with symptoms of post-thrombotic syndrome in addition to pelvic symptoms. Treatment of the specific symptom of pelvic pain in post-thrombotic iliac vein obstruction is not well-studied, as existing literature focuses on lower extremity symptoms. In our experience, patients with chronic pelvic pain and post-thrombotic iliac obstruction can present with an asymmetrically higher burden of lower extremity symptoms in addition to pelvic pain. We tend to have a lower threshold to treat these patients given the favorable risk/benefit ratio of intervention when compared with NIVLs; not only are the etiology of symptoms clearer, the degree of lower extremity symptoms is often more debilitating. In cases of chronic post-thrombotic outflow obstruction, the patient’s anatomy must be individually assessed to ensure that adequate inflow is present to support durable stent patency and symptom improvement. 33 Once an iliac vein obstruction has been determined as significant, the next decision is when to stent if the patient has concurrent ovarian vein reflux, a common clinical scenario. 11 The topic is controversial and without conclusive evidence. Although some advocate for the treatment of ovarian reflux first when present, others support initial treatment of the NIVL. Available data is confounded by lack of control arms, inhomogeneous patient populations, varying criteria for defining an obstructing lesion, and heterogeneous treatment protocols. The treatment decision should also factor in whether the ovarian vein reflux is primary (S 2 V 2 P BGV,R,NT ) or secondary to left renal vein compression (S 2 V 1,2 P LRV,O,NT; LGV,R,NT ). In secondary ovarian vein reflux, where there are clinical features of a pressurized renal reservoir (hematuria, flank pain), treatment of renal vein compression may be necessary. There are two approaches: endovascular stent placement and renal/ovarian transposition. Although large series are not present to suggest the best course of treatment, we favor operative intervention at centers with experience in renal/ovarian transposition. If stent placement is considered, there should be an extensive review of sizing prior to implantation, given the known risk of migration. The patient should be counseled on the risks and potential benefits of all approaches prior to potential treatment. One retrospective study of 227 women compared visual analog pain scores (VAS) after patients were treated with ovarian vein embolization (n = 39), staged embolization and iliac stent (n = 94), simultaneous embolization and stent (n = 30), and stent alone (n = 50). 34 Eleven patients were treated with ovarian vein embolization with venoplasty or venoplasty alone. Within this patient population, 80% of patients had an iliac vein obstruction as defined by >50% area iliac vein stenosis by IVUS. In the staged group, only nine of 94 patients reported significant VAS decrease with embolization alone. After staged stent placement, a significant decrease in VAS from 8.6 to 1.3 was reported. Simultaneous stent and ovarian vein embolization also achieved a VAS reduction, although the post treatment pain scores were slightly higher than the staged approach (VAS of 2.4). There was a short interval of 2 to 4 weeks between embolization and stent placement. Additionally, only the left ovarian vein was treated in all patients. These aspects of the study design may explain why embolization alone did not result in a better clinical response. Another retrospective study by Lakhanpal et al examined patients with iliac vein stenosis and concurrent ovarian vein reflux treated with only iliac vein stent placement. A threshold of >50% area iliac vein stenosis by IVUS was set as the inclusion criteria, with an average area reduction of 74.1% in their patient population. The authors concluded that stent placement alone could achieve symptom resolution in a majority of patients. 35 However, many of these patients (44%) had an untreated pelvic reservoir, and the long-term durability of their reported symptom response is unclear, given that patients were only followed 6 months post treatment. In the absence of conclusive evidence, we typically offer ovarian embolization first for patients with primary ovarian vein reflux and an NIVL presenting with pelvic pain. 36 , 37 , 38 If symptoms resolve, the patient is spared potential risks associated with iliac stent placement. If symptoms persist at 3 to 6 months, an iliac vein stent is then placed in a staged approach. When treating a combination of iliac vein obstruction and ovarian reflux where the presenting complaints are dominant in the lower extremity or back pain secondary to large paravertebral collaterals, we suggest individualized treatment based on what symptoms most impact the patient; initial iliac vein stent placement may be reasonable here. A stent-first approach may also be sensible if the degree of iliac obstruction is severe and ovarian reflux appears very mild; however, there are no validated criteria to grade severity of ovarian reflux.

Pelvic venous disease is common but has historically been challenging to diagnose and treat. The SVP classification can help specify the clinical presentation and serve as a reporting standard for population comparison studies in research. Although non-thrombotic iliac vein lesions are a significant contributive factor in many patient’s PeVD, only a subset of patients with an NIVL will benefit from a venous stent. Many patients will have both ovarian vein reflux and an NIVL; however, data on the optimal treatment approach in this population is limited. There is a need for more robust research in nearly every aspect of PeVD. Randomized controlled trials are needed to better understand the relationship of symptoms and pathophysiology, validate thresholds for reflux and stenoses, and determine clinical response to treatment with minimization of bias. In the absence of conclusive evidence, exercising careful clinical judgement and treating each patient individually is prudent.

K.D. has served as a paid consultant and is on the speaker’s bureau for the following companies: Cook Medical, Boston Scientific, Becton Dickinson/CR Bard, Medtronic, Penumbra, Tactile Medical, and Philips; and has served as a paid consultant for W.L Gore , Shockwave Medical , Asahi Intecc , Veryan , 10.13039/100006479 Cordis , and Surmodics .