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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 5
| Issue : 1 | Page : 22-27 |
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Clinical improvement after stenting for chronic iliofemoral venous obstruction: A review of large studies
Arjun Jayaraj, Seshadri Raju
The RANE Center for Venous and Lymphatic Diseases, St. Dominic Hospital, Jackson, MS, USA
| Date of Submission | 08-Dec-2021 |
| Date of Decision | 13-Dec-2021 |
| Date of Acceptance | 16-Dec-2021 |
| Date of Web Publication | 22-Mar-2022 |
Correspondence Address:
Dr. Arjun Jayaraj
The RANE Center, 971 Lakeland Drive, Suite #401, Jackson, MS 39216
USA
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2589-9686.340413
A review of large studies where patients underwent stenting for symptomatic chronic iliofemoral venous obstruction (CIVO) and had validated clinical and/or quality of life metrics with a follow-up of at least 12 months was performed. Such studies were identified through searches of the MEDLINE and Embase databases in addition to a search of the Cochrane Central Register of Controlled Trials using appropriate search terms. These studies demonstrated that venous stenting is a durable intervention that confers clinical and quality of life improvement in patients with symptomatic CIVO who have failed conservative therapy. While significant improvement is common, complete resolution is rare, and in such patients, consideration should be given to treatment of other concomitant diagnoses including deep venous reflux, lymphedema, and chronic compartment syndrome.
Keywords: Venous stenting, May Thurner syndrome, Post thrombotic syndrome
How to cite this article:
Jayaraj A, Raju S. Clinical improvement after stenting for chronic iliofemoral venous obstruction: A review of large studies. Vasc Invest Ther 2022;5:22-7 |
How to cite this URL:
Jayaraj A, Raju S. Clinical improvement after stenting for chronic iliofemoral venous obstruction: A review of large studies. Vasc Invest Ther [serial online] 2022 [cited 2023 Jun 8];5:22-7. Available from: https://www.vitonline.org/text.asp?2022/5/1/22/340413 |
| Introduction | |  |
Venous stenting for chronic iliofemoral venous obstruction (CIVO) has become the standard of care for patients presenting with symptomatic disease not responding to conservative therapy.[1],[2],[3],[4] Such obstruction can be due to postthrombotic syndrome (PTS) or a nonthrombotic iliac vein lesion (NIVL). While the technique of stenting is the same for both types of lesions, the outcomes are different, with better outcomes noted for NIVL.[4],[5],[6] While many metrics exist to evaluate outcomes after stenting, one metric of relevance is clinical/quality of improvement. The relevance of this metric lies in the fact that, unlike arterial disease, intervention for venous disease is not to save limb or life but to improve the quality of life. In this regard, metrics such as stent patency and reintervention rates act as indirect surrogates. They are considered indirect because stent patency or reintervention does not necessarily translate into clinical or quality of improvement. Hence, assessing clinical and quality of life improvement is paramount to determining the success of venous stenting. This represents the focus of this review alongside reflection on other aspects including patient selection and lack of clinical improvement after intervention.
| Methods | | |
Search strategy
Searches of the MEDLINE and Embase databases were conducted in addition to a search of the Cochrane Central Register of Controlled Trials. The search was restricted to studies published in the English language. References of these studies were reviewed for potential additional studies which were then searched for manually.
Eligibility criteria
Studies were included if they had a sample size of at least 100 limbs that underwent stenting for stenotic lesions. Patients also had to have at least 12 months of follow-up. In addition, studies also needed to have at least one metric of objective clinical evaluation – the Venous clinical severity score (VCSS) and/or the Villalta–Prandoni score (VPS). If they had neither but had a quality-of-life measure either disease specific (e.g., chronic venous insufficiency questionnaire [CIVIQ-20), VEINES–quality of life) or generic (e.g., SF-36, Nottingham Health Profile, and EuroQol), they were also included. Studies which did not have either a measure of objective clinical evaluation or a quality-of-life measure were excluded. Also excluded were studies that focused exclusively on stenting for chronic total occlusive lesions or studies that evaluated stenting in the acute setting (deep venous thrombosis).
Outcomes evaluated
Outcomes appraised included improvement or lack of improvement of pain, swelling, heaviness, tiredness, tightness, venous claudication, and skin/soft-tissue changes including hyperpigmentation and lipodermatosclerosis. Improvement in objective scores – VCSS and/or the VPS and/or quality of life measures after stenting when reported were also analyzed.
| Results | | |
A total of nine studies met the eligibility criteria and included 3158 limbs that underwent stenting.[3],[5],[6],[7],[8],[9],[10],[11],[12] All except three studies had a combination of PTS and NIVL limbs. While one[7] had only PTS limbs, two[3],[11] had only NIVL limbs. One study[10] included stenting in the acute setting in addition to stenting of PTS and NIVL limbs. Follow-up varied from 12 to 50 months. The characteristics of the different studies are listed in [Table 1].
Clinical outcomes
Visual analog scale pain score
In the study by Yin et al.,[7] VAS pain score improvement from 7 to 3 (P < 0.01) was noted after stenting. While Ye et al.[3] demonstrated a VAS pain score improvement from 4.3 to 0.4 (P < 0.01) after stenting, Yang et al.[11] found a VAS pain score improvement of 2.3 versus 1.1 (P = 0.01) when endovenous laser ablation (EVLA) was combined with stenting versus EVLA alone. Razavi et al.[9] using a 100 mm VAS pain score, noted a mean VAS pain score improvement of 21.4 mm at 12 months after stenting. While Neglén et al.[5] reported a VAS pain score improvement from 3.7 to 0.8 (P < 0.0001), Jayaraj et al.[6] from the same group found an improvement of the VAS pain score from 5 to 2 (P < 0.0001) after stenting.
Grade of swelling
Fewer studies reported on the impact of stenting on grade of swelling compared with the VAS pain score. Grade of swelling was characterized by Yin et al.[7] and Ye et al.[3] as none (0), evening edema in the ankle only (1), afternoon edema above the ankle (2), or morning edema above the ankle requiring activity change (3). Neglén et al.[5] and Jayaraj et al.[6] assessed swelling as Grade 0 – absent; Grade 1 – pitting, not obvious; Grade 2 – visible ankle edema; and Grade 3 – massive, encompassing the entire leg. After stenting, Yin et al.[7] found an improvement in the grade of swelling from 3 to 1 (P < 0.01), while Ye et al.[3] noted an improvement in grade from 1.7 to 0.6 (P < 0.01). Neglén et al.[5] reported an improvement in grade of swelling from 1.7 to 0.8 (P < 0.0001), while Jayaraj et al.[6] found an improvement in the grade of swelling from 3 to 1 (P < 0.0001).
Venous claudication
Van Vuuren et al.[8] observed improvement in venous claudication in 90% of patients with NIVL over a median follow-up of 17 months, while it improved in 83% of limbs with PTS over a median follow-up of 13 months.
Other clinical features
The impact of stenting on other clinical manifestation of CIVO including heaviness, tiredness, tightness, hyperpigmentation, and lipodermatosclerosis were not considered in the studies.
Prevalence of symptom relief
In the study by Ye et al.,[3] the cumulative relief of edema was 89.1% (156/175 limbs). Yang et al.[11] noted a cumulative pain relief of 71.1% in patients who underwent EVLA with stenting, while only 43.5% had improvement in such relief in the group that underwent EVLA alone. Sebastian et al.[10] noted improvement of clinical symptoms in 69.2% of limbs, while only 15.4% had complete resolution of symptoms in the NIVL cohort. Similar data were not provided for the PTS cohort. Van Vuuren et al.[8] noted clinical improvement after stenting in 63% of limbs with NIVL and 72% in limbs with PTS, while no response was noted in 24% of limbs with NIVL and 23% of limbs with PTS. In this group, there was worsening of symptoms in 14% and 5% of the NIVL and PTS cohorts, respectively. Neglén et al.[5] found that, at 5 years, 62% and 32% remained completely free of pain and swelling, respectively. The prevalence of limbs with severe pain decreased from 41% to 11%, while the prevalence of limbs with severe swelling decreased from 36% to 18%. There was no significant difference in the prevalence of complete relief of pain at 5 years between the PTS and NIVL limbs: 59% versus 65% (P = 0.725). However, PTS limbs appear to be more frequently free from swelling that the NIVL limbs (39% vs. 24% P = 0.004). Jayaraj et al.[6] noted complete relief of pain and/or swelling in 60% of limbs, partial relief of pain and/or swelling in 25%, and no relief in the remaining (15%) limbs. Importantly, no worsening was noted in the study population over the course of the follow-up.
Ulcer healing
While Yin et al.[7] reported a 24-month recurrence-free ulcer healing rate of 86.6%, Ye et al.[3] reported a 48-month recurrence-free ulcer healing rate of 82.3%, and Van Vuuren et al.[8] noted a recurrence-free ulcer healing rate of 80%. Yang et al.[11] found that EVLA with stenting improved the recurrence-free ulcer healing rate to 82.8% from 68.8% with EVLA alone. Sebastian et al.,[10] Neglén et al.,[5] and Jayaraj et al.[6] documented recurrence-free ulcer healing rates 88%, 63%, and 64%, respectively.
Venous clinical severity score
Six studies evaluated and reported VCSS before and after stenting. Van Vuuren et al.[8] noted an improvement in the VCSS in both PTS and NIVL limbs after stenting. Along similar lines, Sebastian et al.[10] also found improvement in the revised VCSS in both PTS (7-3) and NIVL limbs (5-3) after stenting. Yang et al.[11] found that EVLA with addition of stenting resulted in a lower mean VCSS of 8.3 than 11.7 with EVLA alone (P = 0.01). At 12 months after stenting, Razavi et al.[9] noted an improvement in the mean VCSS of 4.2, Dake et al.[12] reported an improvement in the mean VCSS of 1.7, and Jayaraj et al.[6] found a VCSS improvement from 6 to 4 (P < 0001).
Villalta–Prandoni score
Of the three studies that reported on VPS, Yin et al.[7] reported a 14-point improvement in the VPS (14-8; P < 0.01) in PTS limbs after stenting. Similarly, Van Vuuren et al.[8] also noted an improvement in the VPS in PTS after stenting. Sebastian et al.[10] reported an improvement in the median VPS from 8 to 4 after stenting.
Quality of life
Quality of life was assessed in five studies through the use of CIVIQ. While Ye et al.[3] just reported a statistically significant improvement (P < 0.001) in the score poststenting, studies by Razavi et al.[9] and Dake et al.[12] quantified the improvement as being a 13.1 point (P < 0.0001) improvement and a 15.7 point improvement (P < 0.0001) 12 months after stenting. Neglén et al.[5] also reported a statistically significant improvement in the CIVIQ score over a mean follow up of 22 months (P < 0.001). Jayaraj et al.[6] noted a 24-point improvement (P < 0.0001) over a median follow-up of 26 months.
| Discussion | | |
Venous stenting has replaced open surgery as the first line of treatment for patients with symptomatic CIVO. In line with this, the last several years have witnessed the introduction of dedicated venous stents. While an increasing number of studies have evaluated the outcomes of venous stenting, they are more so related to stent patency/reintervention and less so to objective measurements of clinical or quality of life improvement. This review evaluates large studies and attempts to collate and evaluate the improvement in clinical and quality of life parameters after stenting.
Clinical improvement following stenting
The studies that evaluated venous stenting through the use of validated instruments of clinical manifestations are few. Those that have, demonstrate an improvement in poststenting clinical scores. This is applicable to both the venous clinical severity score and the Villalta–Prandoni score. While the latter has been validated only for PTS, the VCSS can be use used for both PTS and NIVL. While the improvement in the VCSS and VPS after stenting for CIVO is important, also noteworthy is the existence of a residual score, indicating a lack of complete resolution of symptoms/signs. This is due to multiple factors. Both the VCSS and VPS instruments are constructed in a manner that there will always be a residual score for advanced disease. For example, a patient with a healed ulcer, given the persistence of skin changes in the medial malleolar area, will receive a score of 1 under skin changes and so will never have a VCSS of 0. The latter is only possible for C 3 disease (presence of swelling) or for C 0–2 (venous claudication or venous hypertension syndrome) in the CIVO domain. This is true for the VPS instrument as well since it too has components that never completely normalize. The other reason is the actual presence of residual pain and/or swelling. This is a more common problem that we would like it to be. Persistence of swelling is likely to be related phlebolymphedema, and such patients will benefit from measures focused to treat the lymphedema including complex decongestive therapy. Axial deep venous reflux is another possibility, and patients with this problem should benefit from correction of such reflux either through open or endovenous means. In patients with combined deep venous obstruction and reflux, the obstruction should be corrected first as only a small percentage of patients have deep reflux that contributes to persistent symptoms following correction of obstruction.[6],[13] Persistence of quality-of-life impairing leg pain could be related to permanent alteration in the venous hemodynamics/vein wall compliance, resulting in chronic compartment syndrome. In the authors' experience, this is seen in about 1% of patients who undergo stenting. It typically involves the posterior superficial compartment of the leg and measurement of compartment pressure in the supine, upright, and postexercise modes as indicated will help confirm the diagnosis. Once such a diagnosis is confirmed, pursuance of compartment fasciotomy and fasciectomy usually provide symptom relief. Correction of the venous outflow obstruction should precede such an intervention given the low incidence of chronic compartment syndrome and the much higher prevalence of iliofemoral venous obstruction. Persistence of ulcers despite the correction of superficial and deep venous pathology merits treatment of periulcer incompetent perforators/varicose veins. In this regard it is imperative that a comprehensive history and physical examination be performed at the first clinic visit. Initial diagnostic testing for venous disease must include comprehensive evaluation of the deep (including iliac veins), superficial and perforator systems (duplex ultrasound and computed tomographic venogram/magnetic resonance venogram) besides the evaluation of the lymphatic system. Patients with clinical presentation clearly suggestive of chronic iliofemoral venous obstructive pathology that has not improved with conservative therapy (including the use of compression and lifestyle changes) warrant intravascular ultrasound (IVUS) interrogation and stenting as indicated. There is neither a role for prophylactic stenting nor is there a role for stenting patients with minimal symptoms either not impairing their quality of life or which has responded to conservative therapy.
Quality of life improvement poststenting
Only a few large studies looked at the impact of venous stenting on quality of life. The CIVIQ questionnaire was utilized in all the studies. Improvement in both the global and individual domain scores was observed after stenting with such improvement noted to be statistically significant. Such a change is an important finding since the main reason for intervention in venous disease is to improve the quality of life. The authors hope that such reporting will become standard part of any study involving venous stenting.
Patient selection for iliofemoral venous stenting
Patient selection for venous stenting is an important aspect in the treatment of patients with CIVO. Only patients with a clinical presentation producing impairment of quality of life that has not responded to conservative measures should be offered IVUS interrogation for confirmation of diagnosis and subsequent stenting. The confirmation of diagnosis of CIVO must be based on IVUS and not venography alone. In addition, IVUS criteria should be through the use of normal minimal luminal areas as opposed to comparative criteria. This latter is often through use of “50% stenosis” either in the “normal vein on the same side” or “normal vein on the contralateral side.” The 50% stenosis concept is extrapolated from the arterial literature and has no basis in venous disease.[14],[15],[16] In veins, venous hypertension arising from CIVO is continuous and nonlinear.[16] A set percentage is not required for the occurrence of venous hypertension. Given the not uncommon occurrence of skip lesions, long segment stenosis and bilateral disease, comparison with either the “normal ipsilateral” or normal contralateral' is fraught with error and should not be used.[15] In the authors practice, normal minimal luminal areas are used. These are 125 mm2, 150 mm2, and 200 m2 in the common femoral, external iliac, and common iliac veins, respectively.[17] Any reduction in the luminal areas below these cutoffs in the symptomatic patient who has not responded to conservative therapy warrants IVUS interrogation and stenting postconfirmation. The principles of stenting call for coverage of all areas of disease and extending from an area of good inflow into an area of good outflow.
Limitations of the review lie in its eligibility criteria of large studies that have used validated measurements for clinical or quality of life improvement and have at least 12 months of follow-up. However, not only are such measurements important, but also they should be an integral part of venous studies as should long-term follow-up be. While the authors have restricted follow up to at least 12 months, multiple studies in the review have longer follow-up.
| Conclusions | | |
Venous stenting is a durable intervention that confers clinical and quality of life improvement in patients with symptomatic CIVO who have failed conservative therapy. While significant improvement is common, complete resolution is rare and, in such patients, consideration should be given to treatment of other concomitant diagnoses including deep venous reflux, lymphedema, and chronic compartment syndrome.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Hartung O, Loundou AD, Barthelemy P, Arnoux D, Boufi M, Alimi YS. Endovascular management of chronic disabling ilio-caval obstructive lesions: Long-term results. Eur J Vasc Endovasc Surg 2009;38:118-24.  |
| 2. | Gutzeit A, Zollikofer Ch L, Dettling-Pizzolato M, Graf N, Largiadèr J, Binkert CA. Endovascular stent treatment for symptomatic benign iliofemoral venous occlusive disease: Long-term results 1987-2009. Cardiovasc Intervent Radiol 2011;34:542-9. |
| 3. | Ye K, Lu X, Li W, Huang Y, Huang X, Lu M, et al. Long-term outcomes of stent placement for symptomatic nonthrombotic iliac vein compression lesions in chronic venous disease. J Vasc Interv Radiol 2012;23:497-502. |
| 4. | Seager MJ, Busuttil A, Dharmarajah B, Davies AH. Editor's choice – A systematic review of endovenous stenting in chronic venous disease secondary to iliac vein obstruction. Eur J Vasc Endovasc Surg 2016;51:100-20. |
| 5. | Neglén P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: Long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 2007;46:979-90. |
| 6. | Jayaraj A, Noel C, Kuykendall R, Raju S. Long-term outcomes following use of a composite Wallstent-Z stent approach to iliofemoral venous stenting. J Vasc Surg Venous Lymphat Disord 2021;9:393-400.e2. |
| 7. | Yin M, Shi H, Ye K, Lu X, Li W, Huang X, et al. Clinical assessment of endovascular stenting compared with compression therapy alone in post-thrombotic patients with iliofemoral obstruction. Eur J Vasc Endovasc Surg 2015;50:101-7. |
| 8. | van Vuuren TM, de Wolf MA, Arnoldussen CW, Kurstjens RL, van Laanen JH, Jalaie H, et al. Editor's choice – Reconstruction of the femoro-ilio-caval outflow by percutaneous and hybrid interventions in symptomatic deep venous obstruction. Eur J Vasc Endovasc Surg 2017;54:495-503. |
| 9. | Razavi MK, Black S, Gagne P, Chiacchierini R, Nicolini P, Marston W, et al. Pivotal study of endovenous stent placement for symptomatic iliofemoral venous obstruction. Circ Cardiovasc Interv 2019;12:e008268. |
| 10. | Sebastian T, Gnanapiragasam S, Spirk D, Engelberger RP, Moeri L, Lodigiani C, et al. Self-expandable nitinol stents for the treatment of nonmalignant deep venous obstruction. Circ Cardiovasc Interv 2020;13:e009673. |
| 11. | Yang X, Wu X, Peng Z, Yin M, Lu X, Ye K. Outcomes of endovenous laser ablation with additional iliac vein stenting of nonthrombotic lesions in patients presenting with active venous ulcers. J Vasc Surg Venous Lymphat Disord 2021;9:1517-25. |
| 12. | Dake MD, O'Sullivan G, Shammas NW, Lichtenberg M, Mwipatayi BP, Settlage RA, et al. Three-year results from the venovo venous stent study for the treatment of iliac and femoral vein obstruction. Cardiovasc Intervent Radiol 2021;44:1918-29. |
| 13. | Raju S, Darcey R, Neglén P. Unexpected major role for venous stenting in deep reflux disease. J Vasc Surg 2010;51:401-8. |
| 14. | Jayaraj A, Powell T, Raju S. Utility of the 50% stenosis criterion for patients undergoing stenting for chronic iliofemoral venous obstruction. J Vasc Surg Venous Lymphat Disord 2021;9:1408-15. |
| 15. | Jayaraj A, Noel C, Raju S. Contralateral limb improvement after unilateral iliac vein stenting argues against simultaneous bilateral stenting. J Vasc Surg Venous Lymphat Disord 2020;8:565-71. |
| 16. | Kassab G, Raju S. Grading venous stenosis is different from arterial lesions. J Vasc Surg Venous Lymphat Disord 2019;7:151-2. |
| 17. | Raju S, Buck WJ, Crim W, Jayaraj A. Optimal sizing of iliac vein stents. Phlebology 2018;33:451-7. |
[Table 1]
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