Iliac compression syndrome and recanalization of femoropopliteal and iliac venous thrombosis: A prospective study with magnetic resonance venography☆
Article Outline
Abstract
Objectives
Poor iliac vein recanalization has been associated with compression of the left common iliac vein by the right common iliac artery (RCIA/LCIV compression); however, this finding has been difficult to confirm. In a baseline study, RCIA/LCIV compression was detected with magnetic resonance imaging in patients with deep venous thrombosis. We compared recanalization of left femoropopliteal and iliac thrombosis with and without RCIA/LCIV compression.
Methods
This was a prospective blinded study carried out in a 1355-bed university hospital. Thirty-one patients were recruited from consecutive cohorts of patients with iliofemoral and femoropopliteal DVT who underwent direct thrombus magnetic resonance imaging, venous enhanced peak arterial magnetic resonance venography, and magnetic resonance arteriography as part of the baseline study relating RCIA/LCIV compression to extent of thrombosis. Magnetic resonance venography was performed 6 weeks, 6 months, and 1 year after diagnosis of deep venous thrombosis. Femoropopliteal and iliac venous segments that were occluded at diagnosis were classified as occluded, partially occluded, or patent on follow-up scans.
Results
At 6-week follow-up, recanalization of all segments was incomplete. At both 6-month and 1-year follow-up, recanalization of left iliac segments associated with RCIA/LCIV compression was poorer compared with recanalization of left iliac segments not associated with compression (6 of 6 occluded vs 1 of 6 occluded and 1 of 6 partially occluded at 6 months, P =.015; 6 of 6 occluded vs 5 of 5 patent at 1 year, P = .002). This was due to complete failure of recanalization of left common iliac veins associated with RCIA/LCIV compression in 6 of 6 cases. All other iliac and femoropopliteal segments including left external iliac veins associated with RCIA/LCIV compression had high rates of recanalization at both 6 months and 1 year.
Conclusion
RCIA/LCIV compression is associated with persistent occlusion of the left common iliac vein. The recanalization rate for all other femoropopliteal and iliac segments was high.
Obstruction of the proximal lower limb veins has a significant additive effect with valvular reflux in the development of ambulatory venous hypertension and post-phlebitic disease.1, 2, 3, 4 Serial duplex ultrasound scanning has shown high recanalization rates for femoral and popliteal thrombosis.5, 6, 7 However, recanalization rates for iliac thrombosis are poor. Studies using radionuclide and conventional venography have reported that 65% to 82% of iliac segments remain obstructed and 35% to 59% remain occluded 5 to 10 years after deep venous thrombosis (DVT).8, 9, 10, 11 Cockett and colleagues12, 13 proposed that compression of the left common iliac vein by the right common iliac artery (RCIA/LCIV compression) is a frequent cause of left iliofemoral thrombosis, and causes failure of subsequent recanalization, which leads to persistent iliac vein occlusion. This mechanism has been difficult to confirm. However, defects attributed to RCIA/LCIV compression are commonly detected after thrombus removal via catheter-directed thrombolysis and thrombectomy in acute iliofemoral DVT.10, 14, 17
In a baseline study, 2 MRI sequences were used to detect RCIA/LCIV compression in patients with acute DVT. Venous enhanced peak arterial magnetic resonance venography (VESPA) was used to produce both venographic and arteriographic images (magnetic resonance venography [MRV] and magnetic resonance angiography [MRA] images) and thereby visualize the anatomy of patent iliac veins and the iliac arteries; thrombosed iliac veins were visualized with magnetic resonance direct thrombus imaging (MRDTI).18, 19 These sequences enabled RCIA/LCIV compression to be detected noninvasively in patients with acute iliofemoral thrombosis, and showed that RCIA/LCIV compression is strongly associated with left iliofemoral DVT in which distal thrombosis is either absent (isolated iliofemoral DVT) or not contiguous with the thrombus in the iliac veins (Fig 1).
Fig 1.
Number of thrombosed segments at baseline divided according to pattern of thrombosis in patients with left-sided deep venous thrombosis (DVT) associated compression of the left common iliac vein by the right common iliac artery (RCIA/LCIV compression) and in patients with left-sided or right-sided DVT in the absence of RCIA/LCIV compression. Details of the presence of calf thrombosis and details of whether thrombosis was contiguous from the calf (*) are shown. Patients with left ileofemoral DVT associated with RCIA/LCIV compression had a different pattern of thrombosis than did patients with ileofemoral DVT not associated with such compression.
The purpose of this study was to use MRV to assess the relationship between RCIA/LCIV compression detected in the baseline study and subsequent femoropopliteal and iliac vein recanalization.
Material and methods
The ethical committee at our institution granted approval for the study, and all patients gave written informed consent. Inclusion criteria included treatment with anticoagulation and willingness to undergo repeat magnetic resonance imaging (MRI). Exclusion criteria included previous ipsilateral femoropopliteal or ileofemoral DVT, treatment with thrombolysis or thrombectomy, recurrent ipsilateral DVT during the study period, and advancing cancer.
MRV at diagnosis was used to assess the presence of occluded venous segments. Venous segments with nonocclusive thrombus were not recorded. Recanalization of the occluded segments was assessed with repeat MRV at 6 weeks, 6 months, and 12 months. Once full recanalization occurred, repeat scans were not obtained and continued patency was assumed. Femoropopliteal and iliac venous segments with occlusive thrombus were graded as patent, partially occluded, or occluded on follow-up studies.
Further analysis included separate assessment of recanalization within popliteal, femoral, common femoral, external iliac, and common iliac veins. Recanalization of venous segments in the left leg associated with RCIA/LCIV compression was then compared with recanalization of venous segments in the left or right leg not associated with such compression.
Detection of RCIA/LCIV compression in baseline study
Patent left common iliac veins (LCIVs) were visualized with multiplanar reconstruction of the MRV datasets, and thrombosed LCIVs were visualized with multiplanar reconstruction of the MRDTI datasets. The positions of the right common iliac artery (RCIA) and LCIA were visualized in relation to stenoses of the LCIV by overlaying the corresponding MRA images. RCIA/LCIV compression was defined as greater than 50% reduction in luminal cross-sectional area of the LCIV at the point where the LCIV was crossed by the RCIA. A threshold of 50% luminal narrowing has previously been used for angioplasty of venous spurs thought to be caused by RCIA/LCIV compression after catheter-directed thrombolysis.15 Image interpretation was performed by 2 reviewers at the time of acquisition.
Assessment of femoropopliteal and iliac vein recanalization
Recanalization was determined with MRV. At each study, unblinded image interpretation was performed by reviewer A, and if persistent occlusion was present, repeat scanning was arranged as per protocol. After completion of the study, repeat interpretation of all scans was performed by reviewer B, who was unaware of the time of each study or of other test results. The latter interpretation is reported in this study. Interobserver variability of the interpretations made by reviewers A and B was calculated.
Interpretation of MRV images was performed with standard image reconstruction techniques together with analysis of source data. Venous segments were classified as occluded in the presence of nonfilling of part or the entire segment. Partial occlusion was defined qualitatively as marked narrowing of the lumen visually estimated to be equivalent to a reduction in cross-sectional area of 70% or greater.
MRI sequences
MRDTI is a high-resolution, T1-weighted, magnetization–prepared 3-dimensional gradient-echo sequence.19 Fat and blood signals are suppressed by using a selective water-excitation pulse, and an inversion time is chosen to null blood signal. Acute thrombus is visualized as high signal against a suppressed background.
VESPA is a 3-dimensional contrast material–enhanced gradient-echo sequence. Sequential acquisitions before and after a contrast material bolus produce background images, early arterial phase images, and late venous phase images. MRA images are produced by using post-processing to remove background signal from early arterial phase images. MRV images are produced by using post-processing to remove arterial and background signal from late venous phase images. In this way selective MRV and MRA images are produced.18 In most patients a single field of view was sufficient to visualize the popliteal, femoral, and iliac veins, with 20 mL of contrast (gadopentate dimeglumine; Magnevist, Berlex Laboratories). Cases in which a single field of view did not provide adequate coverage were scanned with 2 imaging blocks, covering the popliteal and femoral veins and the femoral and iliac veins, respectively; 10 mL of contrast material was given with the first (distal) set of measurements, and 30 mL was given with the second (proximal) set of measurements.
Statistical analysis
The following comparisons were made at 6 weeks, 6 months, and 1 year, with the 2-sided Fisher exact test: (1) overall rate of femoropopliteal compared with iliac vein recanalization; (2) recanalization of left iliac veins associated with RCIA/LCIV compression compared with recanalization of left iliac veins not associated with RCIA/LCIV compression; and (3) recanalization of left femoral and popliteal veins associated with RCIA/LCIV compression compared with recanalization of left and right femoral and popliteal veins not associated with RCIA/LCIV compression.
Results
The baseline study included 18 consecutive patients with ileofemoral thrombosis and 28 consecutive patients with femoropopliteal thrombosis. Four patients with femoropopliteal thrombosis in the baseline study were excluded because of either nondiagnostic MRDTI, nondiagnostic MRV, or discordance between these tests and conventional venography. Another 11 patients were excluded from follow-up because of advancing cancer (n = 5), unwillingness to undergo further scanning (n = 4), ipsilateral rethrombosis (n = 1), and treatment with thrombolysis (n = 1). The remaining 19 patients with femoropopliteal DVT (7 left-sided, 12 right-sided) and 12 patients with ileofemoral DVT (all left-sided) underwent serial MRV. The pattern of thrombosis in these patients is shown in Fig 1. All patients received anticoagulation therapy for 3 months.
Follow-up was incomplete in 3 patients. One patient with occluded femoral and popliteal segments at 6 weeks and RCIA/LCIV compression died before imaging at 6 months. One patient with partially occluded femoral and popliteal segments in the absence of RCIA/LCIV compression declined to undergo imaging at 6 months and 1 year. One patient with occluded common iliac and femoral veins and partially occluded external iliac and common femoral veins at 6 months declined to undergo imaging at 1 year.
The overall rates of femoropopliteal and iliac recanalization were not significantly different at 6 weeks (9 of 12 iliac segments occluded and 1 of 12 partially occluded, compared with 17 of 31 femoropopliteal segments occluded and 3 of 31 partially occluded; P = .54). At 6 months, recanalization of the iliac segments was poorer than recanalization of the femoropopliteal segments (7 of 12 iliac segments occluded and 1 of 12 partially occluded, compared with 6 of 29 femoropopliteal segments occluded and 0 of 29 partially occluded; P = .011). This difference was maintained at 1 year (6 of 11 iliac segments occluded and 0 of 11 partially occluded, compared with 3 of 28 femoropopliteal segments occluded and 1 of 28 partially occluded; P = .007).
Recanalization of left iliac segments associated with RCIA/LCIV compression (Fig 2) was poorer compared with recanalization of left iliac segments not associated with such compression at both 6 months (P = .015) and 1 year (P = .002). Iliac occlusions were not observed at 1 year in the absence of RCIA/LCIV compression. Separate analysis of the external iliac and common iliac veins showed that the site of persistent iliac vein occlusion in cases associated with RCIA/LCIV compression was the left common iliac vein in 6 of 6 cases at 6 months and at 1 year (Fig 3; Table). Recanalization of the left external iliac vein in these cases, though poor at 6 weeks, was successful at 6 and 12 months.
Fig 2.
Patency of femoropopliteal and iliac veins during follow-up divided according to the presence of compression of the left common iliac vein by the right common iliac artery (RCIA/LCIV compression). Recanalization of femoropopliteal and iliac segments not associated with RCIA/LCIV compression was high at both 6 and 12 months, whereas left iliac segments associated with RCIA/LCIV compression remained occluded. Failure of femoropopliteal vein recanalization associated with RCIA/LCIV compression at 6 weeks may have been related to more extensive thrombosis at presentation and persistent occlusion of adjacent iliac veins. Fempop, femoropopliteal; NS, nonsignificant.
Fig 3.
Patency of popliteal, superficial femoral, common femoral, external iliac, and common iliac segments divided according to the presence of compression of the left common iliac vein by the right common iliac artery (RCIA/LCIV compression). Follow-up was at 6 weeks, 26 weeks (6 months), and 52 weeks (1 year). Patency of left venous segments associated with RCIA/LCIV compression was compared with recanalization of right and left venous segments not associated with RCIA/LCIV compression. Recanalization rates were high at 6 months and 1 year for all segments except left common iliac veins associated with RCIA/LCIV compression.
Table. Recanalization at 6 weeks, 6 months, and 1 year of individual femoropopliteal and iliac segments, with occlusive thrombus at baseline, according to presence of compression of right common iliac artery by left common iliac vein∗
| 6 Weeks | 6 Months | 1 Year | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Patent | partly occluded | Occluded | Patent | Partly occluded | Occluded | Patent | partly occluded | Occluded | |
| Left or right DVT, no compression | |||||||||
| Popliteal | 13 | 1 | 9 | 21 | 20 | ||||
| Femoral | 11 | 1 | 10 | 16 | 5 | 17 | 3 | ||
| Common femoral | 5 | 1 | 4 | 9 | 1 | 9 | |||
| External iliac | 3 | 3 | 5 | 1 | 5 | ||||
| Common iliac | 1 | 1 | 2 | 2 | 1 | 1 | 3 | ||
| Left DVT with RCIA/LCIV compression | |||||||||
| Popliteal | 2 | 1 | 1 | ||||||
| Femoral | 3 | 2 | 2 | ||||||
| Common femoral | 1 | 4 | 4 | 1 | 4 | 1 | |||
| External iliac | 1 | 4 | 4 | 1 | 4 | 1 | |||
| Common iliac | 6 | 6 | 6 | ||||||
∗ Once full recanalization occurred, repeat imaging was not performed and continued patency was assumed. Follow-up at 6 months and 1 year was not performed in 1 patient with occluded femoral and popliteal veins and 1 patient with partially occluded femoral popliteal veins at 6 weeks. Follow-up at 1 year was not performed in 1 patient with occluded common iliac and femoral veins and partially occluded external iliac and common femoral veins at 6 months. |
Recanalization of left femoropopliteal segments associated with RCIA/LCIV compression was poorer compared with recanalization of left or right femoropopliteal segments not associated with RCIA/LCIV compression at 6 weeks (P = .035, figure 2). However, at 6 and 12 months, recanalization of left femoropopliteal segments associated with RCIA/LCIV compression was similar to recanalization of left or right femoropopliteal thrombi not associated with compression. Separate analysis of popliteal, femoral vein, and common femoral vein recanalization showed that the only occluded segments observed at 12 months were femoral vein occlusions that were well collateralized by either the deep femoral vein (n = 2) or a patent duplicated second branch of the femoral vein that was visible at diagnosis (n = 1).
Interobserver variability between the unblinded and blinded interpretations by reviewers A and B for patent, partially occluded, and occluded segments was 0.84 (weighted κ statistic).
Discussion
Iliac vein recanalization was poorer than femoropopliteal vein recanalization. This was due to complete failure of recanalization of the left common iliac vein in cases associated with RCIA/LCIV compression. Recanalization rates at 6 and 12 months were high for all other iliac and femoropopliteal segments. This study therefore suggests that poor iliac vein recanalization is due to RCIA/LCIV compression, as proposed by Cockett et al.13
Despite the small study size, a strong association between RCIA/LCIV compression and persistent occlusion of the left common iliac vein was found. Patency of the iliac veins has been difficult to study noninvasively with conventional techniques, and thus has not been extensively studied. The multiplanar capabilities of MRI make it ideally suited for visualization of the pelvic veins, and several authors have considered it the standard noninvasive test for this indication.20 Furthermore, the VESPA MRV technique is an improvement on time-of-flight techniques in current use, which suffer from long imaging times and flow artifacts at the origin of the inferior vena cava and common iliac veins.21, 22 In a recent study of 55 patients, femoral and iliac vein thromboses were detected with VESPA MRV, with sensitivity and specificity of 97% to 100% and κ values for interobserver variability of 0.85 and 0.97, respectively.18 Contrast-enhanced MRV has also shown excellent agreement with conventional venography and computed tomography (CT) venography in the setting of venous anomalies and chronic thrombosis.23, 24, 25 Intravascular ultrasound is the most accurate test for assessment of iliac vein anatomy, and shows that single-plane femoral venography may significantly underestimate the severity of eccentric stenoses.26 MRV lacks the resolution of these invasive techniques, but enables cross-sectional areas of stenoses to be measured directly.
MRDTI used in the baseline study directly images thrombus as high signal, and thus differs from conventional CT and MRI techniques that visualize flowing blood, with thrombus detected as filling defects. This sequence is therefore uniquely able to visualize the structure of thrombosed venous segments in 3 dimensions and at high resolution. This enabled RCIA/LCIV compression in the baseline study to be detected in patients with thrombosed iliac veins. In a study of 101 patients with acute thrombosis MRDTI detected femoral and iliac thrombosis with sensitivity and specificity of 97% to 100% and κ values for interobserver variability of 0.96 and 0.98, respectively; accuracy was also maintained below knee.19
To our knowledge, this is the first prospective study to use MRV to assess iliac vein recanalization and to relate recanalization to the presence of RCIA/LCIV compression. Although patients with ileofemoral DVT and femoropopliteal DVT were consecutively recruited, there were no patients with right iliac thrombosis. This was related both to the small study size and the left-sided predominance of iliofemoral DVT in the population studied. Left-sided predominance of ileofemoral DVT has been reported in several other series.13, 16
Cockett and colleagues12, 13 described poor recanalization of the iliac veins in association with RCIA/LCIV compression in patients with severe post-phlebitic disease and a history of ileofemoral DVT. They examined these patients with iliac phlebography, and concluded that RCIA/LCIV compression was not only the cause of the iliac thrombosis but also prevented its recanalization. These findings have been difficult to reproduce with noninvasive techniques, and have therefore remained unconfirmed. However, defects attributed to RCIA/LCIV compression are detected in as many as 60% of cases of ileofemoral DVT after thrombectomy and catheter-directed thrombolysis, and are successfully treated with angioplasty and stenting.10, 14, 15, 16, 17 After such treatment high patency rates are achieved, which persist up to 5 years after presentation.10, 17 Endothelial lesions in the left common iliac vein associated with RCIA/LCIV, such as intraluminal webs and spurs13, 27, were not clearly evident in the baseline study, but may have contributed to the reduction of luminal area recorded.
The definition of partial occlusion was greater than 70% reduction of the luminal cross-sectional area in the absence of occlusion. This definition was chosen because we have observed that MRV with the VESPA technique may show apparent minor stenoses due to underfilling of vessels with contrast material when the patient is supine (Fig 4). Occlusion was defined as complete absence of visible lumen. The interobserver variability for patent, partially occluded, and occluded venous segments with these definitions was satisfactory. The level at which venous stenoses are functionally significant is incompletely understood, and functional testing was not performed.28 However, studies have shown significant clinical improvement if iliac stenoses greater than 50% are treated with stenting, and some authors have considered that stenoses greater than 30% may be significant.29, 30 This study may therefore have underestimated the proportion of patients with significant venous obstruction in the absence of occlusion.
Fig 4.
a, Magnetic resonance venogram at diagnosis shows ileofemoral thrombosis extending from left femoral and iliac veins into the inferior vena cava (arrows) in a patient without compression of the left common iliac vein (LCIV) by the right common iliac artery. b, After 1 year, recanalization of all thrombosed segments has occurred (arrows). c, Magnetic resonance venogram at diagnosis shows disparate thrombosis in the left femoral veins (open arrows) and LCIV (solid arrow) in a patient with compression of the LCIV by the right common iliac artery. d, After 1 year, full recanalization of the femoral segments has occurred (open arrows), whereas the LCIV remains occluded (solid arrow). Incomplete filling of the right common femoral vein in the absence of thrombosis is also seen (double arrow).
The functional significance of iliac vein occlusion in terms of the venous function of the leg was also not assessed in this study. Iliac vein occlusion is frequently well collateralized, and is not likely to cause significant venous hypertension in the absence of valvular reflux. However, in combination with valvular reflux venous obstruction significantly exacerbates venous hypertension and post-phlebitic complications, and the importance of iliocaval chronic venous obstruction is being increasingly recognized.2, 3, 4, 29 Furthermore, interventional treatment for ileofemoral DVT with catheter-directed thrombolysis and angioplasty with stenting maintains long-term iliac vein patency and reduces post-phlebitic symptoms, compared with anticoagulation therapy alone.10 It remains therefore to be tested whether interventional treatment has greater benefit in patients with left ileofemoral DVT associated with RCIA/LCIV compression, in whom this study suggests low spontaneous patency rates can be expected. Conversely, interventional treatment may be less beneficial in patients with ileofemoral DVT not associated with RCIA/LCIV compression, in whom high spontaneous patency rates would be expected.
The study protocol had several limitations. First, the protocol assumed continued patency of the femoropopliteal and iliac segments once full patency had been achieved, and further MRV scans were not performed. This protocol tended to overestimate the patency at 6 months and 1 year when patients with previous occlusion dropped out. However, the dropout rate was low, and did not significantly affect the conclusions of this study. Second, recanalization of femoral and iliac segments was assessed individually, and account was not taken of either the extent of thrombosis within each segment or the occurrence of thrombosis in adjacent segments. Adjacent occlusive iliac vein thrombosis and extensive thrombosis at presentation in 6 of 7 patients with femoropopliteal thrombosis associated with RCIA/LCIV compression may have caused the poor femoropopliteal vein recanalization observed in these patients at 6 weeks (Fig 2). However, at 6 and 12 months these effects are unlikely to have been significant, because recanalization of all segments, except left iliac segments associated with RCIA/LCIV compression, was high, irrespective of the extent of thrombosis within that segment or the occurrence of adjacent occlusion. Furthermore, at 1 year the only segments that remained occluded were LCIVs associated with RCIA/LCIV compression and femoral segments that were well- collateralized. Follow-up was terminated at 1 year, and it is possible that further recanalization occurred subsequently. However, prospective studies with follow-up to 5 years after DVT have shown only minor changes in iliac vein recanalization from 6 months to 5 years.8
In conclusion, this study showed that persistent occlusion of the LCIV occurred in cases of left ileofemoral DVT associated with RCIA/LCIV compression. All other iliac and femoropopliteal segments became recanalized in a high proportion of cases. Persistent iliac vein occlusion in the former patients could have an important influence on the development of subsequent post-phlebitic disease and therefore the potential benefit of acute interventional treatment.
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☆ Supported by the British Heart Foundation.Competition of interest: none.
PII: S0741-5214(04)00770-0
doi:10.1016/j.jvs.2004.05.029
© 2004 The Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
