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Reviews and Commentary

Endovascular Interventions
for Acute and Chronic Lower
Extremity Deep Venous Disease:
n State of the Art

State of the Art1
Akhilesh K. Sista, MD
The societal and individual burden caused by acute and
Suresh Vedantham, MD
chronic lower extremity venous disease is considerable. In
John A. Kaufman, MD
the past several decades, minimally invasive endovascular
David C. Madoff, MD interventions have been developed to reduce thrombus
burden in the setting of acute deep venous thrombosis to
prevent both short- and long-term morbidity and to recan-
alize chronically occluded or stenosed postthrombotic or
nonthrombotic veins in symptomatic patients. This state-
of-the-art review provides an overview of the techniques
and challenges, rationale, patient selection criteria, com-
plications, postinterventional care, and outcomes data for
Online SA-CME endovascular intervention in the setting of acute and
See www.rsna.org/education/search/ry chronic lower extremity deep venous disease.
Online supplemental material is available for this article.

Learning Objectives:
After reading the article and taking the test, the reader will
be able to: RSNA, 2015
n Identify risk factors for the development of the
postthrombotic syndrome
n Discuss the current state of endovascular intervention
to treat acute deep vein thrombosis
n Explain the endovascular options for the treatment of
established postthrombotic syndrome
n Discuss the endovascular options and imaging
evaluation of nonthrombotic deep venous disease
Accreditation and Designation Statement
The RSNA is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing
medical education for physicians. The RSNA designates this
journal-based SA-CME activity for a maximum of 1.0 AMA
PRA Category 1 Credit. Physicians should claim only the
credit commensurate with the extent of their participation in
the activity.
Disclosure Statement
The ACCME requires that the RSNA, as an accredited
provider of CME, obtain signed disclosure statements from
the authors, editors, and reviewers for this activity. For this
journal-based CME activity, author disclosures are listed at
the end of this article.
1
From the Department of Radiology, Weill Cornell Medical
College, 525 E 68th St, P-518, New York, NY 10065 (A.K.S.,
D.C.M.); Mallinckrodt Institute of Radiology, Washington
University School of Medicine, St Louis, Mo (S.V.); and
Dotter Interventional Institute, Oregon Health and Science
Center, Portland, Ore (J.A.K.). Received November 17,
2013; revision requested December 20; revision received
February 4, 2014; accepted February 17; final version
accepted March 21. Address correspondence to D.C.M.
(e-mail: dcm9006@med.cornell.edu).
q
RSNA, 2015
Radiology: Volume 276: Number 1July 2015 n radiology.rsna.org 31

STATE OF THE ART: Endovascular Intervention for Lower Extremity Deep Venous Disease Sista et al
L
ower extremity deep venous dis art in the endovascular management of Administration for the treatment of ve-
ease is highly prevalent, econom- lower extremity deep venous disease. nous thromboembolism (VTE) and has
ically burdensome, morbid, and The first section discusses acute gained traction due to its convenience
debil
itating. In selected situations, deep venous thrombosisits epidemi- and paucity of drug-drug interactions
when associated with acute pulmonary ology, consequences beyond pulmonary compared with warfarin. Its pharma-
embolus or limb-threatening venous is- embolus (ie, postthrombotic syndrome cokinetics are also unaffected by diet.
chemia, it can be fatal. This article re- [PTS]), patient selection for catheter- However, no validated antidote exists at
views the interventional management of directed intervention, and outcomes present in the event of serious bleeding.
acute and chronic lower extremity deep of prior and modern techniques. The This agent and others have shown com-
venous disease. While many questions second section describes both throm- parable efficacy to warfarin in the pre-
remain to be answered, substantial pro- botic and nonthrombotic chronic lower vention of recurrent VTE (5,6). Post-
gress has been made in our understand- extremity venous disease, including marketing surveillance will be essential
ing of the disease and how and when imaging and clinical assessment, non- to determine if these newer agents are
to intervene. Techniques have evolved interventional management, endovas- as effective and safe as prior regimens.
to reduce bleeding and more efficiently cular techniques, postprocedure man-
remove acute thrombus. Endovascular agement, and outcomes data. Upper Beyond Pulmonary Embolism:
recanalization in the setting of chronic extremity deep venous disease and pul- Postthrombotic Syndrome
venous disease has compared well monary embolus will not be addressed Contemporary prospective studies sug-
against open surgery with much lower in this review. gest that the above concept of pulmonary
morbidity. Thus, this article seeks to embolism prevention alone needs to be
comprehensively review the state of the modernized substantially. Despite the
Part 1: Acute Lower Extremity Deep use of anticoagulant therapy, these stud-
Vein Thrombosis ies indicate that PTS develops in approx-
Essentials
imately 40% of patients who experience
nn Lower extremity deep venous Epidemiology a first episode of symptomatic lower ex-
disease is the third most common In 2008, echoing what has long been tremity DVT (7). PTS is a chronic con-
cardiovascular disease and is asso- recognized by health care professionals, dition defined as a set of symptoms and
ciated with significant individual the U.S. Surgeon General issued a na- signs that develop in a limb months to
morbidity and high societal cost. tional Call to Action that recognized years after an acute DVT. These include
nn Postthrombotic syndrome (PTS) is deep vein thrombosis (DVT) as a clear daily limb pain and/or aching, fatigue,
a long-term complication of acute and present danger to public health (1). heaviness, and/or swelling that worsens
deep venous thrombosis that By numbers, DVT represents the third with upright position and activity. In se-
occurs in a large number of indi- most common cardiovascular disease. verely affected patients, limiting venous
viduals despite optimal The most feared consequence of claudication, stasis dermatitis, subcu-
anticoagulation. DVT is pulmonary embolism, given taneous fibrosis, and/or skin ulceration
nn Endovascular interventions such as its significant case fatality rate. There- may develop. Studies have consistently
pharmacomechanical catheter- fore, treatment recommendations for shown that PTS impairs DVT patients
directed therapy (PCDT) have DVT have historically been rooted in quality of life, and a large prospective
been developed to prevent PTS; preventing pulmonary embolism by
prior studies have shown promise, means of anticoagulant drugs (2). For
most patient groups, initial therapy Published online
and the ongoing ATTRACT trial 10.1148/radiol.2015132603 Content codes:
will better define the role of PCDT consists of a parenteral anticoagu-
in the prevention of this lant drug (unfractionated heparin, a Radiology 2015; 276:3153
syndrome. low-molecular-weight heparin, or fon-
Abbreviations:
adaparinux) with subsequent transition
nn Established PTS should be man- CDT = catheter-directed thrombolysis
to long-term oral vitamin K antagonist DVT = deep vein thrombosis
aged with optimal noninvasive
therapy for at least 3 months, with the IVC = inferior vena cava
methods; select patients may ben-
duration of therapy dependent on the PCDT = pharmacomechanical CDT
efit from endovascular
presence or absence of ongoing risk PMT = percutaneous mechanical thrombectomy
recanalization. PTS = postthrombotic syndrome
factors for recurrence. The preferred
nn Stent placement in the setting of VTE = venous thromboembolism
anticoagulant for patients with active
chronic thrombotic and non- cancer is low-molecular-weight heparin Funding:
thrombotic deep venous disease monotherapy for at least 36 months S.V. supported by the National Institutes of Health National
has shown good long-term clinical (3,4). In November 2012, rivaroxaban, Heart, Lung, and Blood Institute (grants U01-HL-088476 and
outcomes, with secondary patency U01-HL-112321).
an oral direct thrombin inhibitor, was
greater than 85% in most studies. approved by the U.S. Food and Drug Conflicts of interest are listed at the end of this article.
32 radiology.rsna.org n Radiology: Volume 276: Number 1July 2015

cohort study (the VETO [Venous Throm- 2.5-fold increase in PTS was observed the incidence of PTS (31,32). However,
bosis Outcomes] study) found the pres- in patients whose international nor- a subsequent much larger, placebo-con-
ence and severity of PTS to be the lead- malized ratio was nontherapeutic more trolled, double-blind, multicenter ran-
ing predictors of patients health-related than 50% of the time (26). Therefore, domized controlled trial (the SOX trial)
quality of life 2 years after a DVT epi- anticoagulation should be viewed as a found no difference in PTS in patients
sode (8,9). PTS has also been shown to key PTS prevention measure, but it is using elastic compression stockings ver-
lead to venous leg ulcers that are difficult clear that despite anticoagulation many sus a sham stocking (33,34). Hence,
to treat and that often recur. The direct DVT patients will still develop PTS. while elastic compression stockings may
medical costs of treating PTS and the in- Studies have identified relatively minor help some patients with symptom con-
direct costs of the related work disability PTS risk increases in patients of ad- trol and are a low-risk intervention, it is
have been shown to result in substan- vanced age, increased body mass index, most likely that they do not prevent the
tial economic burden to the health care and female sex. development of PTS.
systems of several North American and The anatomic extent of DVT is an
European countries (1013). important predictor of a patients sub- Beyond Anticoagulation: The Open Vein
The pathogenesis of PTS is complex sequent risk of developing PTS. Patients Hypothesis and Lessons Learned from
and poorly understood. Studies have with proximal DVT have a higher inci- Systemic Thrombolysis for DVT
demonstrated that an initial inflamma- dence of PTS compared with patients It has been hypothesized for many years
tory response to thrombosis strongly with isolated calf DVT (7). More impor- that rapid thrombus elimination and
influences thrombus resolution, organi- tantly, patients with iliofemoral DVT restoration of unobstructed deep ve-
zation, and subsequent vein wall injury (defined as DVT involving the common nous flow in patients with acute DVT
(1416). The ultimate result of this femoral vein and/or iliac vein, with or may prevent late valvular reflux, venous
process on the composition of the adja- without involvement of other veins as obstruction, and PTS. Proof-of-concept
cent vein wall appears to be an increase well), experience recurrent VTE twice support for this open vein hypothesis
in thickness and reduced compliance, as frequently as patients with less ex- exists. In a secondary analysis of data
impaired valvular function, and other ab- tensive proximal DVT, and have 2-year from a randomized trial evaluating the
normalities. At a macroscopic level, the PTS rates that exceed 50% despite use of compression therapy, Prandoni
continued presence of thrombus within the use of anticoagulation therapy et al (21) found that 2-year PTS de-
the deep venous system during the ini- (7,27,28). These patients are also more veloped more frequently in proximal
tial weeks after an acute DVT leads to likely to develop severe PTS manifesta- DVT patients who had residual venous
PTS by at least two pathways. First, even tions such as disabling venous claudi- thrombus or popliteal valvular reflux at
with anticoagulant therapy, incomplete cation and venous ulcers (29,30). The 6-month follow-up. In 2005, Hull et al
clearance of thrombus physically blocks common femoral vein is frequently in- (35) performed a meta-analysis of 11
venous blood flow (obstruction). Sec- volved in cases of iliofemoral DVT, and randomized DVT treatment trials and
ond, the inflammatory response to acute many of these patients can be identified found a strong correlation between
thrombosis directly damages the venous from the initial ultrasonography (US) the amount of residual thrombus after
valves and alters the adjacent vein wall, that was performed to diagnose the a course of anticoagulant therapy and
leading to valvular reflux (1721). Un- DVT, although isolated iliac vein throm- the subsequent incidence of recurrent
involved distal deep veins and superfi- bus, which is unusual in the authors VTE. As discussed above, recurrent
cial collaterals may dilate and become experience and in the literature, can VTE is associated with the development
incompetent as well. When reflux and/ potentially be missed with US. Hence, of PTS. Finally, small randomized trials
or obstruction is present, ambulatory clinicians should consider iliofemoral have observed the use of contempo-
venous hypertension develops and ulti- DVT a high-risk condition for which rary surgical venous thrombectomy and
mately leads to edema, tissue hypoxia particular attention to secondary VTE systemic thrombolysis to be associated
and injury, progressive calf pump dys- prevention and PTS prevention should with reduced PTS rates compared with
function, subcutaneous fibrosis, and skin be paid. anticoagulation alone, but at the price of
ulceration (2225). greater invasiveness and more complica-
Noninterventional Methods to Prevent tions, including major bleeding (3642).
Risk Factors for Developing PTS after DVT PTS An important observation from
The predictors for the development of The study of adjunctive measures to systemic thrombolysis studies was the
PTS are also poorly understood. The prevent PTS has been very limited to finding that significant clot lysis oc-
occurrence of recurrent ipsilateral DVT our knowledge. In two open-label, sin- curred much more frequently in pa-
is associated with a two- to sixfold in- gle-center, randomized trials that did tients with nonocclusive thrombi rather
creased risk of PTS (7). Additionally, not utilize a placebo control, the daily than occlusive thrombi, suggesting that
the quality of anticoagulant therapy use of 3040 mm Hg, knee-high elastic the systemic administration route af-
delivered probably influences the later compression stockings in patients with forded inadequate access of the throm-
development of PTS. In one registry, a proximal DVT was observed to decrease bolytic drug to its target sites within the

Table 1
Endovascular Techniques for Thrombus Removal
Technique Description Examples Advantages Disadvantages
CDT Multi-sidehole catheter directed Conventional infusion catheter; Ease and rapidity of Increased bleeding risk with
lytic infusion US-assisted infusion catheter placement longer infusions
Patient discomfort
PMT Maceration/aspiration of thrombus Aspiration catheter; trerotola Increased surface area for Potential for embolization
without infusion of lytic device endogenous thrombus clearance Limited efficacy
Lower bleeding risk
First-generation PCDT* 1) CDT followed by PMT (infusion-first) Potentially shorter infusion Longer procedure duration
2) PMT followed by CDT (buzz-lyse) Greater degree of active thrombus
removal
Second-generation Employment of devices that AngioJet; Trellis Potential single-session completion Longer procedure duration
PCDT* simultaneously macerate thrombus
and infuse a lytic drug
Note.PCDT 5 pharmacomechanical catheter directed thrombolysis, PMT 5 percutaneous mechanical thrombectomy.

*PCDT is a combination of CDT and PMT.
thrombus (43). The use of intermittent excellent target if patent, owing to its itored for bleeding. A complete blood
injections of a plasminogen activator size and the ability to compress it after count, partial thromboplastin time, and
into nearby veins in the affected leg, sheath removal. The situation is more fibrinogen level can be drawn every 6
with or without a tourniquet system challenging if the popliteal vein is oc- hours, although absolute values should
to direct the drug into the deep veins cluded. In such instances, access can not be solely relied on to cease or con-
(flow-directed thrombolysis), did not be gained into the caudal aspect of the tinue the lytic infusion. Minor sentinel
prove more effective (44,45). In con- thrombosed popliteal vein, into a calf bleeds, pericatheter oozing, and epi-
trast, the imaging-guided intrathrombus vein, or into the posterior tibial vein, staxis should prompt closer monitoring
infusion of thrombolytic drugs into DVT although these latter two may be more and, in conjunction with laboratory
has shown greater efficacy and safety, technically challenging. Internal jugular values, may require adjustment of the
and this principle underlies the use of venous access can also be utilized, al- infusion (47). At the end of the infu-
catheter-directed thrombolytic DVT though going against the direction of sion, repeat venography is performed,
therapy in current practice (46,47). valves in the femoropopliteal veins can the catheter is repositioned to span the
be problematic. Internal jugular access remaining thrombus, and the infusion
Image-guided Endovascular Thrombus also requires long catheters and wires. is continued. Clot maceration with an
Removal: Description and Evolution of A venogram is then obtained to define angioplasty balloon is sometimes used
Techniques the extent of thrombus. The multi-side- to facilitate thrombolysis by increasing
Catheter-directed thrombolysis.Cath- hole catheter is embedded within the the surface area for thrombolysis. Af-
eter-directed thrombolysis (CDT) re- thrombus and attached to an infusion ter thrombus removal, venography is
fers to the infusion of a fibrinolytic drug of a dilute solution of a thrombolytic used to evaluate for obstructive lesions.
directly into thrombus by means of a drug. Although no lytic drug is cur- Once identified, these are treated with
multi-sidehole catheter embedded in rently approved by the U.S. Food and balloon angioplasty and/or stent place-
the thrombus (Table 1). This practice Drug Administration, those used in ment (46,47). Stents are typically re-
aims to deliver a higher local intrath- clinical practice include recombinant served for iliac obstructions, although
rombus drug concentration (enhancing tissue plasminogen activator (0.01 mg/ extension into the com mon femoral
efficacy) with a reduced drug dose kg/h up to a maximum of 1.0 mg/h), vein is necessary if the obstruction
(enhancing safety). It was the first en- reteplase (0.250.50 units/h), and te- includes it or the peripheral external
dovascular thrombolytic method ap- necteplase (0.25 mg/h). No specific iliac vein. While no stent has U.S. Food
plied to DVT patients (46,47). With comparison has been made among and Drug Administration approval for
this technique, US guidance is used these agents to suggest superiority or venous obstructions, longitudinally flex-
to obtain access into the deep venous safety of one over the other, and lytic ible, self-expandable bare stents are
system of the affected limb; whenever choice is based on operator and institu- generally favored (Fig 1) because (a)
possible, it is ideal to access an open tional preference. The infusion is typi- they conform to tortuous veins, (b)
flowing vein below the thrombosed ve- cally continued for 624 hours, during they have sufficient hoop strength for
nous segment. The popliteal vein is an which time the patient is carefully mon- most venous obstructions, and (c) they

Figure 1
Figure 1: CDT and stent placement in a patient with progressive bilateral DVTs in spite of anticoagulation. (a) Left femoral venogram (patient prone) demonstrates
extensive acute thrombus along the length of the vein. (b) Right iliac venogram demonstrates no filling of the iliac vein. (c) Fluoroscopic image depicts infusion cathe-
ters along the length of the left and right iliac thrombi. (d) Postinfusion left femoral venogram demonstrates excellent patency. (e) After stent placement, venogram of
both iliacs demonstrates rapid flow through the stents (see also Figs E1a and E1b in this patient [online]).
allow inflow from nonthrombosed trib- only 2%4% of patients (4850). Rea- drug dose), (b) valvular preservation
utaries. The routine use of inferior vena sons for this apparent difference may because of better lysis of perivalvular
cava (IVC) filters during CDT is unnec- be improved patient selection, use of thrombus, and (c) reduced venous wall
essary; in a large prospective registry, subtherapeutic heparin dosing dur- and valvular trauma compared with me-
symptomatic pulmonary embolism oc- ing thrombolysis, and the routine use chanical thrombectomy devices. How-
curred in only 1.3% of individuals un- of US-guided venipuncture, which has ever, these potential advantages should
dergoing CDT (45). limited access site bleeding due to inad- be considered unproven until clinical
Limitations of the original CDT vertent arterial puncture. studies verify improved outcomes (52).
technique include the long infusion After successful lysis, patients PMT without thrombolysis.PMT
times required to obtain complete lysis should receive optimal medical man- devices macerate thrombus and/or re-
of extensive DVT (typically 13 days) agement for their DVT, including full move thrombus fragments from the ve-
and the health care resources used. anticoagulation, if safe, to prevent re- nous lumen. The use of PMT increases
In an early multicenter registry, ma- current thrombosis. As mentioned the surface area of residual thrombus
jor bleeding occurred in 11% of DVT previously, routine use of compression and can create a central flow channel
patients treated with urokinase CDT stockings is controversial but can be within an occluded vein, which together
infusions (45). In this registry, which used for symptomatic relief. may improve the efficiency of endoge-
included a relatively unselected patient Subsequent CDT technologies have nous thrombolysis. However, potential
population, intracranial bleeding was evolved to address the above limitations. disadvantages of PMT methods include
observed in 0.4% of patients. Symp- One approach is the use of low-power the increased on-table procedure time,
tomatic pulmonary embolism and fatal ultrasound energyequipped catheter to the potential for embolizing thrombus
pulmonary embolism occurred in 1.3% disperse the thrombolytic drug within with mechanical manipulation, and the
and 0.2% of patients, respectively. In the thrombus (EKOS, Bothell, Wash) theoretical potential for causing venous
more recent experiences using infu- (51) (Fig 2). Proponents cite theoretical valve injury. Published experience with
sions of recombinant tissue plasmin- advantages to this approach: (a) fast in- stand-alone PMT (ie, without concom-
ogen activator at low doses (0.51.0 trathrombus drug dispersion (and there- itant infusion of a fibrinolytic drug)
mg/h), major bleeding has occurred in fore faster thrombolysis using a lower for DVT has been disappointingwith

Figure 2 knowledge. Two general categories of nutes, after which the AngioJet cath-
PCDT techniques may be considered: eter is used to aspirate the residual
First-generation PCDT methods in- thrombus. With isolated thromboly-
volve the use of thrombectomy devices sis, inflation of catheter-mounted bal-
with traditional infusion CDT, to speed loons on the Trellis Peripheral Infusion
thrombolytic progress and reduce the System (Bacchus Vascular, Santa Clara,
needed drug dose. Single-session Calif) is used to isolate a clot-contain-
PCDT methods enable rapid intrath- ing segment and deliver a bolus dose
rombus dispersion of a thrombolytic of a thrombolytic drug directly into the
drug bolus to enable complete on-table thrombus (57,58) (Fig 4). Activation of
removal of thrombus in a single 13- an oscillating wire is then used to me-
hour procedure. chanically disperse the drug within the
It should be noted that retrievable thrombus, after which the drug may be
IVC filter insertion prior to PCDT has aspirated through a port on the device.
not been fully evaluated to our knowl- Initial reported experiences with these
edge, so it is frequently at the discretion techniques suggest that effective DVT
of the operator as to whether a filter is therapy can be accomplished in 80%
indicated. It is reasonable to insert a 90% of patients, of whom perhaps 50%
filter during PCDT if IVC thrombus is may be treated in a single procedure
present, although every effort should be session. It should be noted that the im-
made to retrieve the filter when appro- pact of these techniques on the develop-
priate. ment of PTS has not been established,
First-generation PCDT.Two forms to our knowledge. If PTS prevention is
of first-generation PCDT have been achieved with reasonable safety, the
Figure 2: Spot fluoroscopic image of US-assisted used. Infusion-first PCDT refers to efficiency with which these treatments
catheter infusion in a patient with common femoral the use of an initial CDT infusion, with can be delivered seems likely to hasten
and femoral deep venous thrombosis. Note the subsequent use of PMT (with either an their widespread adoption.
caudal aspect of an external iliac stent. aspirating or nonaspirating device) at
follow-up sessions to macerate and/or Patient Selection for Catheter-directed
currently available devices, it does not remove residual thrombus. The other Therapy: Anatomic and Clinical
appear to remove sufficient thrombus method, termed by some buzz-lyse, Considerations
volumes to be clinically useful (53). A involves use of as aspirating device to DVT patients require careful evaluation
recently introduced device (AngioVac; first debulk the thrombus, followed by prior to the initiation of CDT therapy
Angiodynamics, Latham, NY) employs CDT infusion. In limited studies, first- (Table 2). Important factors that must
a recirculation circuit and a large bore generation PCDT has resulted in (a) ini- be assessed include the following:
(22-F) suction catheter to remove tial treatment safety and clot removal Projected risk of bleeding.All
thrombus from large vessels such as the efficacy at least comparable to tradi- patients in whom CDT is considered
IVC (Fig 3). tional stand-alone CDT; (b) 40%50% must undergo careful evaluation for
PCDT.PCDT, which is the com- reductions in drug dose and treatment factors that may increase the risk of
bined use of CDT and PMT, has en- time compared with traditional stand- major bleeding, including the presence
hanced physicians ability to efficiently alone CDT; and (c) reduced hospital of active bleeding, recent gastrointes-
remove large thrombus volumes in stays, intensive care unit utilization, tinal bleed ing (,3 months); recent
patients with DVT. This combination and hospital costs (54). major surgery, trauma, pregnancy,
therapy is predicated on the ideas that Single-session PCDT.Two PCDT cardiopulmonary resuscitation, or
(a) PMT can increase the surface area techniques can enable single-session other invasive procedure; thrombo-
of thrombus, accelerate pharmacologic endovascular DVT therapy to be com- cytopenia or other bleeding diathesis
thrombolysis, reduce the required drug pleted without the need for further or severe liver dysfunction; the pres-
dose and infusion duration, and thereby drug infusions or monitoring in the ence of bleeding-prone lesions in crit-
reduce bleeding complications, and (b) intensive care unit. With the power- ical areas such as the central nervous
CDT can dissolve PMT-created throm- pulse technique, a rheolytic throm- system; a history of internal eye sur-
bus fragments that might otherwise bectomy catheter (AngioJet; Bayer gery or hemorrhagic retinopathy
cause pulmonary embolism. Healthcare) is first used to forcefully within the last 3 months; or a history
Physicians have used many different pulse-spray a bolus dose of the throm- of stroke or intracranial and/or intra-
combinations of drugs and devices for bolytic drug directly into the thrombus spinal bleeding (47).
DVT treatment, but no single technique (55,56). The drug is allowed to dwell Clinical severity of DVT.The pri-
has been established as superior, to our within the thrombus for 1530 mi- mary intent of aggressive therapy in any

Figure 3
Figure 3: Caval thrombus treated with large-bore aspiration device. (a) IVC venogram demonstrates
extensive caval thrombus and a malpositioned suprarenal IVC filter. (b) Fluoroscopic image depicts the
suction/aspiration device (AngioVac; Angiodynamics) in the IVC. The arrow points to the balloon at the tip,
which when inflated flares the tip. (c) Photograph of the recirculation filter shows bulky extracted throm-
bus. (d) Fluoroscopic image during filter retrieval shows a tip deflecting wire grasping the malpositioned
filter. The tip of the wire has been snared, and the filter is subsequently pulled through the sheath. (e) IVC
venogram obtained the next day after IVC filter removal demonstrates marked reduction in thrombus
burden and free flow through the cava. No lytic drug was used during this case owing to a hemorrhagic
stroke in this patient 3 weeks earlier.
tors for bleeding. Group 3 includes pa-

tients with symptomatic DVT for whom
thrombolysis is being pursued with
the primary purpose being to prevent
late PTS. Overall, aggressive therapy
for group 1 above should clearly be
patient should be clearly understood 2 includes patients for whom throm- pursued even when the patient is clin-
and can be grouped into three cate- bolysis is believed to be reasonable due ically ill, owing to the absence of other
gories (29,59): Group 1, patients for to a failure of initial anticoagulation to good treatment options, whereas a low
whom urgent thrombolysis is indicated achieve early therapeutic objectives. threshold for exclusion should be ap-
to prevent life-, limb-, or organ-threat- Such patients are those who have major plied to groups 2 and 3 when risk fac-
ening complications of acute DVT. This anatomic DVT progression, a substan- tors for complications exist.
would include situations in which limb tial increase in clinical severity, and/or Anatomic extent of DVT.It is rea-
perfusion is acutely compromised (eg, inability to tolerate ongoing major DVT sonable to provide patients who have
phlegmasia cerulea dolens) (Fig 5) symptoms (ie, pain and swelling that acute iliofemoral DVT and low pro-
or when progressive IVC thrombosis are not relieved or that preclude phys- jected bleeding risk with a balanced
(Fig 6b and 6c) despite anticoagulation ical activity) despite the use of initial discussion of the risks and possible
is believed to increase the risk of fatal anticoagulant therapy. In these situa- benefits of elective endovascular throm-
pulmonary embolism or acute renal fail- tions, a low threshold should be applied bolysis for the purpose of PTS preven-
ure to unacceptably high levels. Group to exclude patients if there are risk fac- tion (29,59). On the contrary, patients

Figure 4
Figure 4: Second-generation PCDT using the Trellis (Bacchus Vascular) device. (a, b) Acute thrombus involving the femoral and iliofemoral deep veins. (c) Fluoro-
scopic image of the Trellis device deployed along the length of the thrombus. Arrow 5 the proximal balloon, arrowhead 5 the macerating wire. Alteplase is being
infused along the length of the wire. The distal balloon is not shown. (d, e) Post-PCDT venograms demonstrate successful thrombus removal.
Table 2 Patients personal values and prefer

ences.For aggressive therapies like
Decision Model to Perform CDT Based on Clinical Presentation and Risk of Bleeding
DVT thrombolysis for which the ben-
Bleeding Risk efits have not been conclusively estab-
Clinical Scenario Low Moderate High lished, it is important for the patient to
receive a balanced discussion regarding
Acute limb threat Yes Yes Surgical
the rationale, the intended benefits
Extensive IVC thrombosis Yes Yes No
(and possible lack of benefits), the at-
Progression of symptoms or anatomic Yes Usually no No
tendant risks and inconveniences, and
extent despite anticoagulation
treatment alternatives. Patients may ar-
Iliofemoral DVT to prevent PTS Yes Usually no No
Femoropopliteal DVT to prevent PTS Usually no No No
rive at different conclusions regarding
their own amenability to aggressive
Note.Adapted, with permission, from reference 109. therapy (29).
The Role of Imaging in Stratifying Patients

and Planning for Potential Intervention
with asymptomatic DVT or isolated Life expectancy, baseline ambulatory Any patient suspected of having a DVT
calf DVT should not be offered CDT capacity, and comorbidities.Patients should be evaluated with duplex US,
since the risk of developing PTS is low who are chronically unable to walk or which has excellent sensitivity and spec-
(60). For patients with femoropopliteal who have very short life expectancy are ificity for the detection of infrainguinal
DVT that does not extend to the level less likely to benefit meaningfully from DVT (61). Many patients can be evalu-
of the common femoral vein, there is aggressive therapy to prevent PTS, given ated up to the peripheral external iliac
little published literature, to our knowl- that PTS affects mobility and function- vein by using this technique. In patients
edge, to support the added efficacy of ality and is only truly established 2 years in whom imaging is difficult, either be-
thrombolytic therapy, and we suggest after the acute thrombotic event (7). In cause of obesity or severe pain with
therefore that the use of CDT should be addition, patients with substantial re- compression US, cross-sectional imaging
limited only to motivated, very symp- spiratory compromise or other acute with computed tomographic (CT) venog-
tomatic patients with very low pro- illness may not be able to tolerate the raphy or magnetic resonance (MR) ve-
jected risk for bleeding. procedure. nography should be considered. If there

Figure 5
Figure 5: Catheter-directed treatment of phlegmasia. (a) Acutely swollen, mottled, cyanotic leg in the setting of an extensive occlusive DVT. (b, c) Preintervention
venograms demonstrate extensive thrombus along the length of the (b) femoral and (c) iliofemoral deep veins. (d, e) After thrombolysis, angioplasty, and stent
deployment, the flow through these segments is markedly improved. (f) Appearance of the leg 10 days after treatment. (Case courtesy of Brooke Spencer, MD.)
is clinical suspicion for IVC involvement ifying patients. Furthermore, it informs al (62) analyzed data from 68 CDT-treat-
(eg, bilateral leg swelling, acute renal fail- the interventionalist of the extent of clot ed acute iliofemoral DVT patients from a
ure), cross-sectional imaging can be used burden and may influence the strategy multicenter prospective CDT registry and
to confirm the diagnosis. In the setting for endovascular thrombus removal. found that they had fewer PTS symptoms
of renal failure, noncontrast-enhanced (P 5 .006), better physical functioning
MR venography may be useful (Fig 6b Outcomes of Interventional DVT Therapy (P 5 .046), less stigma of chronic venous
and 6c). If the US examination is nega- The ability of CDT or PCDT to rapidly insufficiency (P 5 .033), and less health
tive but there is strong clinical suspicion remove venous thrombus and prevent distress (P 5 .022) at a mean follow-up
of a proximal DVT, CT or MR venogra- PTS in proximal DVT patients is support- of 16 months than did 30 retrospectively
phy can be used to identify a central iliac ed by a number of comparative studies, matched patients who were treated
thrombus. As discussed above, anatomic although each had substantial methodo- with anticoagulation alone. However,
involvement plays a major role in strat- logical limitations. In 2000, Comerota et this comparison was limited by marked

Figure 6
Figure 6: CT and MR appearance of acute iliocaval thrombosis. (a) CT image in a patient with a retrievable infrarenal filter with acute thrombus expanding
the IVC and iliac veins (arrowhead). Above the filter, the IVC is patent (arrow). (b, c) Ultrafast T2-weighted coronal MR images in a different patient with acute
iliocaval thrombus depict (b) low signal intensity within the IVC (arrow) consistent with thrombus, and (c) a patent intrahepatic IVC (arrow).
age differences in the two cohorts. In 2012. In this study, outcomes were re- coagulant therapy and elastic compres-
2001, AbuRahma et al (63) described a ported in 189 patients with femoral and/ sion stockings) or standard DVT therapy
prospective study in which 51 acute ilio- or iliac vein DVT in southern Norway alone. PTS is assessed at follow-up visits
femoral DVT patients were permitted to who had been randomized to receive ei- every 6 months during the 2-year fol-
choose to receive adjunctive CDT (with ther CDT plus anticoagulation or antico- low-up period by using the Villalta PTS
urokinase or recombinant tissue plas- agulation alone (65). At 2-year follow-up, scale, a validated measure of PTS that is
minogen activator) plus anticoagulation the relative risk of PTS was reduced by endorsed by the International Society of
or anticoagulation alone. The patients 26% with use of CDT (41.1% versus Thrombosis and Haemostasis (67,68).
treated with CDT had more frequent ve- 55.6%, P 5 .04). A total of 3.3% of CDT- Secondary outcomes being assessed in-
nous patency at 6 months (83% versus treated patients had major bleed ing, of clude venous disease-specific and generic
24%, P , .0001) and absence of symp- whom one required a blood transfusion quality of life; resolution of acute DVT
toms at 5 years (78% versus 30%, P 5 and one required surgery to address. symptoms (pain and swelling); rates of
.0015). However, this study was limited There were no CDT-related deaths or major bleeding, symptomatic pulmonary
by nonrandomized design, performance intracranial bleeds, and the authors con- embolism, recurrent VTE, and death;
in a single center, and small sample size. cluded that the bleeding did not affect the and cost-effectiveness. ATTRACT, which
In 2002, Elsharawy et al (64) described patients ultimate outcome. This studys has enrolled 500 patients and is expected
a single-center Egyptian randomized trial applicability to clinical practice is limited to complete enrollment in 2014, should
comparing adjunctive CDT (with strep- by its modest size and by the fact that an provide a definitive answer to the ques-
tokinase) versus anticoagulation alone in older drug-only infusion CDT technique tion of whether PCDT should be used as
35 patients with acute iliofemoral DVT. was used relative to current U.S. prac- first-line therapy for proximal DVT.
At 6 months, patients treated with CDT tice, which features widespread use of
had a higher rate of normal venous func- thrombectomy devices (Table 3).
tion (72% versus 12%, P , .001) and The ATTRACT trial (Acute Venous Part 2: Interventional Management of
less valvular reflux (11% versus 41%, P Thrombosis: Thrombus Removal with Chronic Lower Extremity Deep Venous
5 .04). However, this study was limited Adjunctive Catheter-Directed Throm- Disease
by small sample size and performance in bolysis), is an ongoing, multicenter ran-
a single center, and it did not evaluate domized trial sponsored by the National Background
clinically meaningful outcomes such as Heart, Lung, and Blood Institute (www. As discussed above, chronic lower ex-
PTS and quality of life. clinicaltrials.gov, NCT00790335) (66). tremity venous disease is morbid and
The most rigorous currently available For this study, patients with symptomatic expensive. Venous ulcers in the United
data, to our knowledge, on the efficacy proximal DVT are being randomized in States alone are estimated to cost up-
of CDT is derived from the multicenter 5060 clinical centers to receive either ward of $3 billion annually and con-
randomized CaVenT Trial, published in PCDT plus standard DVT therapy (anti- tribute to the loss of 2 million working

Table 3
Data from CDT Trials and Registries
Study and Reference No. Design Result Shortcomings
Comerota et al, 2000 (62) Multicenter registry Statistically significant: No randomization

Reduction in PTS Cohort differences
Better physical functioning
Less health distress
AbuRahma et al, 2001 (63) Prospective, nonrandomized 83% vs 24% 6-month venous patency, and 78% vs 30% Nonrandomized
symptom-free at 5 years Single center
Small sample size
Elsharawy et al, 2002 (64) Randomized trial 72% vs 12% normal venous function Small sample size
Single center
PTS not assessed
CaVenT, 2012 (65) Prospective, multicenter randomized trial Statistically significant reduction in PTS at 2 years in patients Infusion only technique
treated with CDT Modest-size
days, and quality of life is substantially valve leaflets to coapt. Collaterals sub- Patient Assessment
worsened (69). Chronic venous disease sequently develop to decompress the A thorough clinical history should be
can result from prior thrombosis, non- affected limb. Although poorly under-
obtained for any patient presenting
thrombotic obstruction, and/or super- stood or characterized, the degree of
with signs and symptoms of chronic ve-
ficial venous disease. This discussion collateral formation plays a major role
nous disease. Contributory data include
will focus on the chronic sequelae of in whether and to what extent an in-
a history of VTE, any past surgeries,
thrombotic and nonthrombotic deep dividual develops PTS. The majority of
trauma, a history of lower extremity
venous disease; it is important to note patients who develop the PTS will have
fistula creation or dialysis catheter in-
that a significant number of individuals mild or moderate forms of the disease.
sertion, remote central catheter place-
with chronic venous disease have both A minority will go on to develop severe
ment, IVC filter placement, and cathe-
deep and superficial venous disease, PTS and/or venous ulcers (7).
terization in the right side of the heart.
and treating both may be necessary to Nonthrombotic causes of chronic
If the patient has a known malignancy,
alleviate symptoms (70). lower extremity venous disease in-
cross-sectional imaging may reveal ob-
Greater than 12% of chronic lower clude extrinsic compression, trauma,
extremity venous disease is attribut- structing abdominopelvic masses or
surgery, and congenital abnormalities
able to PTS (71), with the rest made (49). Lower extremity central venous lymphadenopathy.
up by nonthrombotic obstructive deep access, either in the setting of dialysis Important factors include the dura-
venous disease, venous reflux, superfi- or acute hospitalization, can result in tion and severity of symptoms. If the
cial venous disease, or a combination a deep venous stenosis or occlusion. patient describes an acute exacerbation,
of these. The presence of thrombus Extrinsic compression may be second- acute deep venous thrombosis needs to
in the deep venous system results in ary to nonneoplastic anatomic factors, be either diagnosed or excluded, most
a significant inflammatory response such as May-Thurner syndrome and commonly with lower extremity duplex
(72), mediated by cellular components its variants, in which the common iliac US evaluation. Other symptoms that are
in the venous wall and circulating leu- vein is compressed between a pulsat- consistent with chronic venous disease
kocytes. The sequence of events is not ing adjacent artery, most commonly include heaviness, pain, paresthesia,
completely understood, but incom- the right common iliac artery, and a and fatigue, especially later in the day.
plete fibrinolysis and thrombus frag- vertebral body (discussed further be- Pertinent physical examination docu-
mentation from this response result low). Pelvic or abdominal neoplasms, mentation includes the degree of swell-
in incomplete recanalization of the oc- lymphadenopathy, or lymphoceles may ing, the presence of dermatitis, and ac-
cluded venous segment with intralumi- compress or obstruct the deep pelvic tive or healed ulceration. Calf and thigh
nal endothelial-lined pockets and webs veins. Penetrating trauma may cause circumferences, and if possible, a photo-
(73,74). While the channels within laceration or complete avulsion of the graph of the affected limb(s), establish a
these webs permit some blood flow, IVC or pelvic veins (discussed further preintervention baseline. Involvement of
the segment has a higher resistance, below). Congenital abnormalities, such the calf alone implies femoral or femoro-
leading to venous hypertension, which as IVC atresia, may manifest in early popliteal disease, whereas thigh and calf
also affects valvular function if the in- adolescence or adulthood as chronic symptoms together suggest iliofemoral
creased capacitance does not allow venous disease. obstruction. Bilateral lower extremity

Table 4 Table 5 presenting with an acute exacerbation

of swelling or pain, lower extremity du-
Clinical Portion of CEAP Classification of Villalta Scale for PTS plex US can be used to identify whether
Chronic Venous Disease Type Finding an acute DVT is the reason. If the du-
Scale Description plex study is negative, cross-sectional
Symptoms Cramps imaging, either with CT or MR, can be
C0 No visible signs of venous disease Itching
used to uncover acute iliocaval throm-
C1 Telangiectasias or reticular veins Pins and needles
bosis (Fig 6).
C2 Varicose veins Leg heaviness
If the presenting symptoms are
C3 Edema Pain
more chronic, imaging can often be
C4a Hyperpigmentation or venous eczema Signs Pretibial edema
C4b Lipodermatosclerosis Skin induration
used to determine the cause. Duplex
C5 Healed venous ulceration Hyperpigmentation US can frequently be used to evaluate
C6 Active venous ulceration Venous ectasia up to the external iliac vein, especially
Redness in thin patients. It can be used to iden-
Pain during calf compression tify areas of chronic thrombosis, nar-
Ulcer present? rowing, or wall thickening, and can be
symptoms could indicate a caval lesion, used to assess which venous segments
Note.Each symptom or sign is assigned a grade of
especially with a history of IVC filter are patent. More central obstructions
none/minimal, mild, moderate, or severe, with 03
placement. Chronicling chronic venous points assigned for each. The presence of an ulcer can be inferred from waveform analysis.
disease with standardized scales, in- automatically confers severe PTS. A score greater than 5 Deep and superficial venous reflux can
cluding the C or clinical class of the is considered diagnostic of PTS. also be documented (80). Cross-sec-
CEAP classification (Table 4) or the Vil- tional imaging, either with CT or MR
lalta scale (Table 5), adds to the baseline venography, can be used to detect ex-
data and quantifies disease severity. The may provide symptomatic relief. Auto- trinsic (masses/lymphadenopathy) or
clinical class of the CEAP assessment is mated pneumatic compression devices intrinsic lesions (81,82). CT is usually
based on the physical examination find- can be considered for symptomatic re- more diagnostic than MR if an IVC fil-
ings ranging from swelling to ulceration lief in some patients (75,76), although ter is present, as some filters contain
to categorize the severity of venous in- their consistent ability to reduce PTS metallic elements that result in consid-
sufficiency, while the Villalta scale takes scores has not been documented. erable MR signal loss. CT assessment in
into account both signs and symptoms Lifestyle modification, including the setting of an IVC filter can be used
to determine the presence of mild, mod- weight loss, smoking cessation, and to confirm the presence or absence of
erate, or severe disease. exercise, should be encouraged for all caval narrowing or chronic thrombosis
patients with chronic venous disease, (Fig 7). The caliber of the deep pelvic
Noninterventional Management given that the former two are risk fac- veins and IVC can also be used to as-
Conservative management should be tors for venous thrombosis and can ex- sess noninvasively with MR or CT ve-
optimized for all patients with chronic acerbate existing disease and the last nography, although the diameter needs
venous disease. If the patient has had a may have some symptomatic benefit to be interpreted with caution, since
DVT within the past 3 months, ensur- (77). respiratory variability, position, and hy-
ing that she or he has not improperly While a full discussion on optimal dration status affect this measurement.
terminated or been subtherapeutic on wound care is beyond the scope of this However, if there is an abrupt caliber
anticoagulation is essential, given that article, venous ulcers should be aggres- change, real stenosis should be enter-
rethrombosis is a major risk factor for sively and actively treated through a tained (Fig 8). Quality CT venography
PTS. Moreover, many patients with combination of compression, analgesics or high spatial and contrast resolution
PTS have an ongoing thrombotic risk, and anti-inflammatories, targeted lymph- MR imaging, particularly with venous
either from an obstruction or identi- edema therapy, and minor surgical pro- blood pool agents, may be used to de-
fied or occult thrombophilia, and re- cedures and antibiotics if necessary. In tect intraluminal webs that form from
quire prolonged anticoagulation. Close addition to these measures, pentoxifylline repeated trauma from arterial pulsa-
partnership and consultation with he- and micronized purified flavinoid fraction tions and compression.
matologists ensures optimal medical have demonstrated benefit (78,79). Imaging can also aid in treatment
management for these patients. planning. In the setting of an IVC fil-
Compression stockings may be con- Imaging Assessment ter, either contrast-enhanced or unen-
sidered for limbs in those with chronic There are several indications for imag- hanced CT can be used to identify the
venous disease and may reduce symp- ing the deep venous system in chronic type of filter, its position in the cava,
toms and swelling in certain individuals venous disease: (a) worsening symp- the direction of the hook (if present),
(2). As mentioned above, they play an toms, (b) determining etiology, and (c) and leg penetration. Such information
equivocal role in preventing PTS, but treatment planning. If the patient is can be valuable if a complex retrieval

Figure 7 Figure 8
Figure 7: Chronic venous disease from filter-induced caval narrowing. (a) Coronal contrast-enhanced CT
reformation demonstrates a chronically indwelling Greenfield infrarenal IVC filter with caval narrowing (arrow)
and markedly atretic left common iliac vein (white arrowhead) with intraabdominal and body-wall collaterals
(yellow arrowheads). (b) Patients leg demonstrates characteristic changes, including redness, swelling,
hyperpigmentation, and ulceration treated with a medicated dressing. (c) Right iliac venogram illustrates an
atretic common iliac vein and caudal IVC with marked collateralization. Figure 8: MR appearance of May-Thurner variant.
(a) On the high-spatial-resolution blood-pool steady-
is planned (83). US, CT, and MR can pass (84). Now, surgery is considered in state axial MR image, the left common iliac vein is
all be useful in determining the extent specialized centers for those patients in compressed (arrowhead) between the left internal
of venous involvement, which in turn whom endovascular techniques fail or iliac artery and vertebral body. (b) The patients left
informs the interventionalist about the for whom endovascular techniques are leg has altered pigmentation, swelling, and an ulcer
best potential site of entry into the ve- not possible. A full discussion of surgical overlying the anterior tibia.
nous system (eg, the internal jugular options for these patients is beyond the
vein, common femoral vein, or popliteal scope of this article. Patients should be
vein). The level of obstruction can also selected for interventional procedures attention paid to renal function, platelet
be inferred by the presence of body by balancing the likelihood of improving count, and the international normalized
wall, cross-pelvic, or thigh collaterals. their symptoms with the risk of proce- ratio. Many interventionalists will per-
dural complications. Additionally, since form these procedures while there is
Patient Selection and Preparation many PTS patients require angioplasty full anticoagulation in the patient, given
After conservative management has and/or stent placement, they should be the propensity toward intraprocedure
been optimized with the strategies de- candidates for anticoagulation to pre- thrombosis. Procedures can be lengthy,
scribed above, many patients may be vent early rethrombosis (70). Patient so a patient needs to be able to tolerate
candidates for endovascular interven- work-up should include a complete moderate sedation. Additionally, prone
tion. Before the advent of these tech- blood count, basic metabolic panel, and positioning is required if the popliteal
niques, patients underwent surgical by- coagulation parameters, with particular vein is to be accessed. For individuals

unable to tolerate a lengthy or position- Figure 9

ally challenging procedure, general an-
esthesia may be required.
Interventional Treatment of Iliocaval

Stenoses and Occlusions
Chronic iliocaval obstructions may
be postthrombotic, compressive, or a
combination. Depending on the sever-
ity and duration of the obstruction, the
vein may appear markedly diminished
or even nonvisible on cross-sectional
images (Fig 9). This finding does not
necessarily mean that the lesion cannot
undergo recanalization, as frequently
there is an infundibulum that leads into
the atretic lumen that can be traversed
with a wire. Specific scenarios are dis-
cussed below. Figure 9: MR appearance of postthrombotic iliac veins. Contrast-enhanced blood pool axial
IVC obstruction or stenosis caused image demonstrates no visible left common iliac vein (yellow arrowhead) and an atretic right
by a chronically embedded IVC filter. common iliac vein (white arrowhead), with body wall collaterals (arrow).
More scrutiny has been placed on IVC
filters in recent years, due to increased
awareness of complications including Figure 10
migration, penetration, and fracture.
Another known complication is caval
stenosis (85). Whether this stenosis
is secondary to thrombus formation
in the filter that propagates caudally
or a primary venous response is un-
clear. Regardless, a certain number
of patients develop symptoms from
this stenosis, which can extend into
the iliac veins and result in recurrent
thrombotic episodes. The PREPIC trial
from the late 1990s demonstrated that
patients with IVC filters were found to
have a higher rate of DVT than those
without, although the overall rate of
VTE was found to be similar because
of a lower incidence of pulmonary em-
bolism (86). To our knowledge, the
relationship of IVC filters to the devel-
opment of PTS is unclear. In a non- Figure 10: Examples of chronic recanalization techniques. (a) Combination of a stiff-tipped hydrophilic
randomized retrospective study from catheter guided by an angled stiff hydrophilic wire. This combination is useful in traversing most chronic
2007, patients without DVTs who had venous occlusions. (b) Fluoroscopic image obtained during recanalization of an occluded stent demonstrates
prophylactic filters placed developed the back end of a stiff wire within a metal cannula contained within a sheath. The combination is advanced
PTS at a similar rate to patients with along the length of the occluded stent until the other side is reached.
proximal DVTs without filters. Patients
with DVTs that required caval filtration confirmed an association, to our knowl- monary embolism and contraindication
had a higher rate of PTS, with approx- edge. to anticoagulation), the integrity of the
imately 50% developing the syndrome Patients with IVC filters who have device, and IVC patency. When IVC
and approximately 14% developing symptomatic PTS or penetration-asso- recanalization is planned, the identity
severe PTS (87). Hence, while there ciated morbidity (bowel perforation, of the filter should be determined with
may be a relationship between IVC fil- pain) should be evaluated for need for certainty, as retrieval may be consid-
ters and PTS, no randomized trial has the filter (ie, continued high risk of pul- ered prior to IVC angioplasty and/or

stent placement. CT scans in the venous filter integrity and the brand of device contact are more difficult to retrieve af-
phase provide excellent information implanted. If necessary, the high spatial ter extended indwell times (88).
about filter position, penetration, and resolution of abdominal radiographs Well-centered and positioned filters
caval patency. Thin CT reformations can aid in these assessments (83). In can often be retrieved by using stan-
and scout images can be used to assess general, filters with extensive IVC wall dard snares and sheaths. Devices that
Figure 11
Figure 11: Creation of a neo-IVC 17 years after traumatic laceration. (a) Transjugular IVC contrast material injection demonstrates no detectable infrarenal IVC.
(b) Right iliac venogram shows numerous collaterals and diminutive native vein. (c) Spot fluoroscopic image demonstrates a snare within a sheath that has been
advanced through sharp recanalization (arrow) and two wires via bilateral common femoral veins (arrowheads). The right iliac wire has entered a lumbar collateral
(based on subsequent imaging) and is not in the native IVC. (d) Spot fluoroscopic image of the snare cinching the back end of a stiff wire within the retroperitoneal
fat. (e) Fluoroscopic image of undilated self-expanding stainless steel stent spanning the length of the absent IVC. (f, g) Digital subtraction venograms demonstrate
brisk flow through the iliac and IVC stents into the suprarenal IVC and right atrium. See also Figs E2aE2d in this patient (online). (Case courtesy of Thomas Sos, MD,
and Akhilesh Sista, MD, Weill Cornell Medical College.)

are tilted such that the hook is covered obstructions or connect discontinuous Figure 12
by neo-endothelium may be removed caval segments (Fig 10) (94). If conven-
by using more advanced techniques tional wire manipulation is not possible
such as rigid bronchoscopy forceps due to a recalcitrant obstruction or a
(89). When the device elements are completely discontinuous cava, sharp
firmly adherent to the wall of the IVC, recanalization by means of the back
removal can be accomplished using an end of a stiff wire, a thin-gauge needle,
excimer laser sheath (90). Open-design or powered wires (ie, radiofrequency/
filters with deeply penetrated legs or laser-assisted) may be used (95). While
arms, including those that penetrated these latter wires have the ability to pen-
adjacent structures, can be removed etrate through nearly any obstruction,
safely provided that the filter hook can they are no more directable than other
be engaged (91). Advanced removal sharp tools and, given the three-dimen-
techniques should be performed by sional limitations of fluoroscopy, may
experienced individuals and after fully not offer much more benefit except in
considering all of the management op- very specific circumstances. Moreover,
tions. Major complications are rare but these techniques are new and unproven
have occurred, including IVC disruption and require substantial expertise and
and fragmentation of filters with central experience to be used safely. If sharp
embolization to the heart and pulmo- recanalization is necessary, access is
nary circulation (92). Kuo et al (90) most commonly gained from above and
cited a 3% major complication rate below. Sharp techniques are used on Figure 12: May-Thurner syndrome. Inferior vena
and a 7% minor complication rate in one or both ends until the recanaliza- cavagram of procedure performed from an internal
their series of 100 consecutive patients tion instruments are near one another. jugular venous approach demonstrates flattening/
undergoing complex filter removal with A snare catheter is used to grasp the effacement of the left common iliac vein with a
excimer laser assistance. wire coming from the other access site. well-formed lumbar collateral. Also seen is an infra-
Filters associated with IVC stenosis The snared wire is then pulled through renal IVC filter.
or occlusion that cannot be removed the first access site, and through and
can be managed by placement of stents through access is achieved. After bal- thought to lead to endothelial damage,
through the filter followed by angioplasty loon dilatation, a stent is placed that and a fibrotic response can lead to
to collapse and displace the filter ele- bridges the discontinuous or obstructed webs within the venous lumen. Vari-
ments (93). A stent with sufficient radial segment. The stent is most commonly ants can occur anywhere along the
force or postangioplasty rigidity should 2024 mm in size and can be uncovered length of the iliac vein, including at the
be used. Stents may extend to a supra- and self-expanding. Even in the setting bifurcation of the common iliac artery.
renal location; noncovered stents should of complete caval discontinuity, the ret- There are several lines of evidence that
be deployed to avoid blocking renal veins roperitoneal fat provides a sufficient indicate that May-Thurner syndrome
inflow. This approach increases the lu- wall for an uncovered stent. Internal is significant for some individuals. In
minal diameter of the IVC and traps balloon angioplasty then expands the nonthrombotic patients with left lower
the filter between the stent and the stent to its desired diameter, and the extremity swelling and no other iden-
IVC wall. Subsequent filter removal, if gap between IVC segments is effectively tifiable cause, correcting the obstruc-
necessary, would require surgical access bridged (Fig 11). tion leads to symptomatic relief (97).
to the IVC. The long-term patency rates Interventional treatment of May- Moreover, it is considered a risk factor
of stents placed through IVC filters is not Thurner syndrome and its variants. for DVT. In a case-control series, the
known, to our knowledge. The May-Thurner compression is a degree of compression correlated
Endovascular treatment of caval controversial topic for radiologists, with the likelihood of DVT develop-
stenosis, occlusion, or absence.Ei- since most individuals with this ana- ment (98). Furthermore, when com-
ther because of prior surgical ligation, tomic finding are asymptomatic. In one bined with another risk factor, such
trauma, atresia, or long-standing throm- study, the mean compression of the as oral contraceptive use, the odds
botic disease, the IVC may be markedly left common iliac vein by the crossing of developing a DVT are multiplica-
narrowed, stenotic, or completely ab- artery in individuals scanned for other tive (99). It is important to recognize
sent for a portion of its length. Surgical reasons was greater than 30% (96). that nonthrombotic compression is a
reconstruction can be a morbid and dif- Classic May-Thurner syndrome repre- risk factor for thrombosis. While the
ficult procedure. For this reason, endo- sents a compression of the left common mechanism is not clearly understood,
vascular techniques ranging from wire iliac vein between the crossing right any stenotic lesion can result in stasis,
manipulation to sharp recanalization common iliac artery and the verte- endothelial disruption, and turbulent
have been used with success to traverse bral body. The chronic compression is flow, promoting thrombus formation.

Figure 13
Figure 13: Intravascular US before and after stent

placement. (a) Left iliac venogram demonstrates an
occlusive lesion in the peripheral external iliac vein
(arrow). (b) Intravascular US image at the level of com-
pression. The arrows delineate the estimated borders
of the narrowed venous segment. (c) Intravascular US
image of the common iliac vein just central to the ste-
nosis in image b. (d) Venogram obtained after stent
placement demonstrates markedly improved flow and
caliber of the left pelvic deep veins. (e) Intravascular
US image obtained after stent placement at the level of
the stenosis in image b reveals the improved caliber
and the hyperechoic stent in cross section.
cross-sectional diameter. Intravascular

US is more sensitive than venography
for the detection of luminal narrowing
(100); however, it is unclear whether
or to what degree this increased sensi-
tivity should be acted on. If the classic
venographic findings are present and
the patient is symptomatic, most prac-
Many of these individuals develop sig- Nonthrombotic May-Thurner syn titioners will place a stent in the lesion.
nificant chronic venous disease. drome can usually be treated in the su- Self-expanding nitinol or stainless steel
It is important to distinguish throm- pine position. Access is gained via the stents are most commonly used and are
botic from nonthrombotic May-Thurner ipsilateral common femoral vein, and typically 1416 mm in size (101103).
syndrome, as treatment of nonthrom- a vascular sheath is placed. After the They are extended either to the iliac bi-
botic disease is usually a simpler proce- lesion is traversed with a wire, venog- furcation or into the IVC. Appropriate
dure and arguably requires less antico- raphy will classically show a flattened stent sizing is important to prevent mi-
agulation after stent placement. On the common iliac vein just peripheral to the gration and edge stenoses. Venography
other hand, May-Thurner syndrome caval bifurcation, with cross-pelvic and after stent placement typically demon-
complicated by thrombosis will likely lumbar collaterals (Fig 12). Intravascu- strates resolution of collateral vessels
require more extensive stent proce- lar US can be used to assess the lumen and brisk flow into the cava.
dures, possibly a lower access point if of the iliac vein at an area of stenosis Thrombotic May-Thurner syndrome
the disease extends infrainguinally, and (Fig 13). It can reveal intraluminal webs is a more difficult disease to treat, as
longer anticoagulation after treatment. and be used to measure a comparative the postthrombotic vein peripheral to

the lesion is frequently scarred and Figure 14

diminutive. Moreover, disease may
extend below the inguinal ligament,
requiring access from a lower venous
segment. While some practitioners will
access the femoral vein, most select the
popliteal vein for initial access. While
the former offers the convenience of
keeping the patient supine, it is difficult
to compress the femoral vein, which
runs deep within the thigh, and a post-
procedural hematoma may develop.
Popliteal access requires the patient to
be positioned prone. Once the obstruc-
tion is reached, venography typically
shows abrupt tapering of the native
channel with marked collateralization
around the obstruction. Recanalization
of the atretic postthrombotic veins can
be challenging, especially in long-stand-
ing obstructions (.1 year). Hydrophilic
wires and catheters can usually trav-
erse such obstructions; however, occa-
sionally sharp recanalization techniques
are needed. Once the thrombotic lesion
is crossed, angioplasty is sometimes Figure 14: May-Thurner syndrome complicated by chronic thrombosis. (a) Venogram of the
required before stent placement to al- left common iliac vein (patient is prone) demonstrates chronic effacement and thrombosis of
low passage of larger catheters and the proximal left common iliac vein and an atretic and postthrombotic left iliac venous system.
sheaths. Stents are deployed along the (b) Venogram obtained after stent placement demonstrates brisk flow from the left common
entire length of the obstruction and femoral vein into the IVC. See also Figs E3a and E3b in this patient (online).
are frequently extended below the in-
guinal ligament into the common fem-
oral vein. Doing so has not adversely venous disease in the setting of femo- Complications
affected stent patency and, while there ropopliteal thrombosis, endovascular The procedures described above are
is mobility across the inguinal ligament, recanalization is controversial. Treating generally safe given that most work
self-expanding stents in this location such patients requires a careful risk-ben- is being done in the venous system
perform well (70,101). Extending stents efit analysis. If the patient is motivated (101103). The most common com-
into the femoral vein is not routinely because of lifestyle limitations and is at plication is access site bleeding, es-
recommended, as stent patency in the very low risk of complications, he or she pecially in the setting of anticoagula-
femoral vein has been historically poor may be suitable for such a procedure. It tion during the procedure. Typically
(45). Some also argue that stents com- should be noted that data are lacking in this minor complication is easily con-
promise valvular function in the femoral the treatment of femoropopliteal chronic trolled with manual compression, and
vein and could lead to reflux. However, disease, and that, at this time, much of rarely does anticoagulation need to be
it should be noted that inflow into the the experience is anecdotal. The recan- stopped for access site bleeding. As
pelvic stents is absolutely essential to alization procedure often involves access part of either blunt or sharp recana-
maintain patency, which in some cases of a calf vein or the posterior tibial vein lization, wires and catheters may exit
can only be achieved by stent place- at the ankle, such that an open vein is the venous system. However, given
ment into the femoral or deep femoral accessed. Next, wire access through the the low to zero flow through occluded
vein. Venography performed after stent native deep venous system is typically segments, significant bleeding from
placement typically demonstrates brisk achieved with a combination of a stiff such transgressions is rare, and the
flow through the treated lesion with hydrophilic wire and a stiff hydrophilic case continues after the intervention-
resolution of collaterals (Fig 14). catheter. The recanalization is often alist withdraws to the point of exit
Femoropopliteal disease.Most indi- performed with angioplasty (Fig 15). and reattempts recanalization through
viduals who have isolated femoropopliteal The treatment of chronic femoropopli- the native channel. Patients may ex-
disease are not affected with severe PTS teal thrombotic disease is actively being perience considerable pain during
(7). For those who do develop chronic researched. angioplasty and stent treatment of

Figure 15
Figure 15: Recanalization of chronically occluded left femoropopliteal veins. (a) Spot fluoroscopic image of wire access into the left posterior tibial vein at the level
of the ankle. (b) Popliteal venogram demonstrates heavily diseased popliteal vein, expanded by chronic thrombus, with partially recanalized channels. (c) Femoral
venogram shows atretic femoral vein with collateralization. (d) Prolonged balloon angioplasty of the central femoral vein, with a representative waist at areas of ste-
nosis. (eg) Venograms obtained after angioplasty show improved flow and resolution of collaterals through the (e) popliteal, (f) peripheral femoral, and (g) central
femoral veins. Three months later, the patient had no objective PTS per Villalta assessment, and (h) duplex US demonstrated a patent femoral vein. See also Figs E4a
and E4b in this patient (online).
chronic occlusions. The pain may last the procedure might not be technically Postprocedural Management
for several days after the procedure, successful and that there is a reason- Anticoagulation.The duration and
so adequate outpatient pain manage- ably high chance of reintervention at type of anticoagulation after chronic re-
ment is essential. Stent migration oc- a later date; between 15% and 40% of canalization procedures is not well stud-
curs rarely, and is usually secondary patients who undergo stent placement ied. A general rule of thumb is that
to undersizing or misplacement (104). require reintervention within 4 years thrombotic venous disease needs to be
Patients should also be cautioned that (70,102). medically managed more aggressively af-

Table 6
Clinical Outcomes for Endovascular Treatment of Established Chronic Venous Disease
Study and Reference No. Population No. of Limbs Clinical Outcome
Nayak et al (70) Thrombotic 45 80% complete or partial improvement

Raju et al (102) Thrombotic and nonthrombotic 528 78% and 55% substantial improvement in pain and swelling, respectively
Ye et al (97) Nonthrombotic 224 89.1% and 82.3% relief of edema and ulcer healing, respectively
Neglen et al (103) Thrombotic and nonthrombotic 982 68% and 32% complete relief of pain and swelling, respectively; 58% ulcer healing rate
Sarici et al(108) Thrombotic 59 Significant decrease in Villalta and VCSS 6 months after stent placement
Rosales et al (107) Thrombotic 34 Reduction in VCSS in both C3 and C6 patients
Note.VCSS 5 venous clinical severity score.
ter a procedure than nonthrombotic (103). Unsurprisingly, primary patency emerging to treat its deleterious acute
disease owing to higher rethrombosis was found to be higher in nonthrombotic and chronic manifestations. Advances
rates in the former group (discussed fur- limbs. The next largest series in 2012, in- in knowledge, endovascular techniques,
ther below). A typical regimen will involving 224 limbs, showed excellent pri- and medical devices have made ve-
clude an enoxaparin bridge to warfarin. mary and primary-assisted patencies of nous interventions safer and more ef-
Some advocate 1 month of enoxaparin 98.7% and 100% at 4 years (97). Impor- fective. It is therefore likely that these
before switching to warfarin. More prac- tantly, these data were derived from non- minimally invasive and often effective
titioners are considering rivaroxaban as thrombotic limbs. Early stent thrombosis techniques will continue to play an im-
a warfarin alternative; however, data are is relatively rare, between 1% and 7% portant role in the treatment of lower
lacking regarding its efficacy after recan- in published reports (105). Clinical out- extremity deep venous disease; their
alization and in the setting of stent pro- comes are promising as well. In a series exact role will be determined by their
cedures. The duration of anticoagulation of 504 patients, stent treatment in the continued evolution and the results of
is also variable. For postthrombotic le- setting of deep venous reflux significantly prospective clinical trials.
sions, most recommend long-term decreased pain and swelling and had a
Disclosures of Conflicts of Interest: A.K.S. dis-
therapy, while nonthrombotic disease is positive impact on patients with the closed no relevant relationships. S.V. Activities
typically managed with 13 months of worst CEAP classi fications. In patients related to the present article: none to disclose.
anticoagulation. Antiplatelet agents such with a classification of C4 prior to inter- Activities not related to the present article:
grants from Covidien, Bayer Healthcare, Genen-
as aspirin and clopidogrel are used by vention, venous dermatitis was resolved tech; nonfinancial support from Genentech and
many after venous stent placement, but in 80%. Preintervention C5 patients BSN Medical. Other relationships: none to dis-
this practice is based on arterial data (healed ulcers) had an 88% likelihood of close. J.A.K. Activities related to the present
and physiology (105). being ulcer-free after stent placement. In article: none to disclose. Activities not related to
the present article: grant from Cook Group for
Adjunctive supportive care.Com- 50% of C6 patients (active ulcers), there IVC filter registry; personal fees from Crux Med-
pression stockings, pneumatic compres- was complete resolution of their ulcers ical, for work on DSMB for clinical trial of IVC
sion, and wound care should continue following stent procedures (106). In the filter; Other, stock ownership in Veniti, a start-
up company focused on venous diseases (no
as before the procedure, based on each 2012 study mentioned above, treated
commercial activity at this time), and stock op-
treatments relative efficacy. Patients patients demonstrated a statistically tions in Bio2 Medical, a start-up company with
should be seen at set follow-up points significant decrease in pain, edema, fa- venous filter in early clinical trial. Other rela-
to mark progress and adjust anticoagu- tigue, and sleep disturbance. In the same tionships: none to disclose. D.C.M. disclosed no
relevant relationships.
lation and other supportive measures study, 78% of patients had edema prior
as necessary. to treatment, while only 10% had edema
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Note.PCDT 5 pharmacomechanical catheter directed thrombolysis, PMT 5 percutaneous mechanical thrombectomy.

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tors for bleeding. Group 3 includes pa-

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Table 2 Patients personal values and prefer

The Role of Imaging in Stratifying Patients

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Comerota et al, 2000 (62) Multicenter registry Statistically significant: No randomization

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Table 4 Table 5 presenting with an acute exacerbation

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unable to tolerate a lengthy or position- Figure 9

Interventional Treatment of Iliocaval

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Figure 13: Intravascular US before and after stent

cross-sectional diameter. Intravascular

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the lesion is frequently scarred and Figure 14

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Nayak et al (70) Thrombotic 45 80% complete or partial improvement

Note.VCSS 5 venous clinical severity score.

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