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Persistent symptoms after endovenous thermal ablation may suggest proximal venous outflow obstruction
From the American Venous Forum
Persistent symptoms after endovenous thermal ablation may suggest proximal venous outflow obstruction Jesse Chait, BS, Emily K. Chapman, BA, Sneha Subramaniam, BA, Kevin Chun, BA, Ageliki G. Vouyouka, MD, Rami Tadros, MD, Michael Marin, MD, Peter Faries, MD, and Windsor Ting, MD, New York, NY
ABSTRACT Objective: Proximal venous outflow obstruction (PVOO) in the iliac veins and superficial venous disease are inter-related in ways not fully understood. We observed among our patients undergoing vein stent placement for PVOO a significant number having had prior endovenous thermal ablations (EVTA) in their history. This study was undertaken to better characterize these patients and develop an algorithm in their management. Methods: In a combined retrospective and prospective data registry of 682 patients who underwent vein stent placement for chronic PVOO at a single institution from March 2013 to November 2017, 100 limbs of 99 patients (14.5% of all patients) had a history of EVTA or other superficial venous procedures before their vein stenting. Limbs with dilated truncal veins on ultrasound examination or limbs that underwent poststent EVTA or superficial venous procedures were excluded. The mean age of these 99 patients was 60.2 years (range, 28-88 years; standard deviation, 13.855). Fifty-one percent of the patients were male. The most common presenting symptom of the patient cohort was edema (n ¼ 59), followed by venous-related skin changes (n ¼ 22). Results: Bilateral stents were performed in 58%, with a mean number of 2.06 stents per patient. EVTA was the primary superficial vein procedure in 97%. Bilateral EVTA were performed in 53% and unilateral EVTA in 47%. The mean time between the first EVTA to vein stenting was 1202.7 days. Patients were followed at 30 days, 90 days, 6 months, 1 year, and >1 year. The outcome for each patient at each postoperative visit was compared with preoperative parameters (subject’s assessment, physical examination, and provider assessment) and was scored as follows: -1 (worse than preoperative), 0 (no change), þ1 (mildly improved), þ2 (significantly improved), or þ3 (completely recovered). The mean outcome score at 30 days was 1.63 (84 patients), 2.05 at 90 days (62 patients), 2.09 at 6 months (74 patients), 1.93 at 1 year (54 patients), and 1.97 at >1 year (39 patients). Conclusions: Approximately 15% of patients undergoing vein stent placement for chronic PVOO have an antecedent history of superficial venous disease and EVTA. PVOO should be considered and the patient evaluated accordingly if symptoms persisted or recurred after EVTA. Vein stent placement among these patients with PVOO will result in further symptomatic relief, but complete symptomatic relief is not observed in everyone. The algorithm for the management of these patients warrants further investigation. (J Vasc Surg: Venous and Lym Dis 2019;-:1-6.) Keywords: Venous insufficiency; Saphenous vein; Iliac vein stenting; May-Thurner syndrome; Post-thrombotic syndrome; Endovenous thermal ablation; Vascular surgery
Chronic venous insufficiency (CVI) is the most common vascular disorder in the United States and places a significant financial burden on the current health care system.1-3 Historically, the etiology of CVI has been attributed to the presence of superficial venous reflux (SVR); however, over the past few decades, proximal venous outflow obstruction (PVOO) has also been found to From the Division of Vascular Surgery, Icahn School of Medicine at Mount Sinai. Author conflict of interest: W.T. is on the speaker’s bureau for Jansen pharmaceuticals. Presented at the Thirty-first Annual Meeting of the American Venous Forum, Rancho Mirage, Calif, February 19-22, 2019. Correspondence: Jesse Chait, BS, Division of Vascular Surgery, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029 (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 2213-333X Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvsv.2019.04.015
play a major role.4-7 Although these two distinct pathophysiologic processes are well-defined, and a relationship between increased deep venous hypertension and superficial disease exists,8,9 their relationship in terms of modern treatment modalities is unknown, and the current therapy options aimed at treating CVI reflects this lack of understanding. The ever-growing armamentarium of percutaneous techniques used to treat CVI is split into correcting either SVR or PVOO, and although guidelines that address the treatment of venous disease exist, there is no modern, evidence-based algorithm for the management of patients with combined superficial and deep disease.9-11 In our experience of treating PVOO with iliac vein stenting, it was noted that a significant percentage of patients had previously received endovenous thermal ablation (EVTA). This study aimed to better characterize these patients and develop a framework for diagnosis and treatment of PVOO when EVTA fails to alleviate the signs and symptoms of CVI. 1
2
Chait et al
Journal of Vascular Surgery: Venous and Lymphatic Disorders ---
METHODS Study design. A combined retrospective and prospective database of 682 patients who underwent venous stent placement for chronic PVOO at the Mount Sinai Hospital in New York City from 2013 to 2017 was reviewed. Institutional review board approval was obtained following the principles outlined in the Declaration of Helsinki, and informed consent was waived owing to the low-risk and retrospective nature of the study. The principal investigator (W.T.) and the Icahn School of Medicine at Mount Sinai have an investigational device exemption certificate from the Food and Drug Administration to establish a venous stent registry and to evaluate the outcomes of Wallstents (Boston Scientific, Marlborough, Mass).
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ARTICLE HIGHLIGHTS d
d
d
Type of Research: Single-center retrospective cohort study Key Findings: Of 99 patients who underwent iliac vein stenting, 14.5% had prior endovenous thermal ablation. Patients who underwent vein stenting had significant resolution of symptoms. Take Home Message: Patients with persistent or recurrent symptoms after successful endovenous thermal ablation should be evaluated for iliofemoral vein obstruction. Stenting of the iliofemoral veins is safe and effective in patients with persistent symptoms after the elimination of saphenous reflux.
Patient selection. Patients who presented at our institution with signs and symptoms of CVI were evaluated with a history, physical, and duplex ultrasonography (DUS) of the bilateral lower extremities to identify any venous reflux or deep venous thrombosis. Magnetic resonance (MR) venography of the abdomen and pelvis was performed to evaluate the iliocaval and femoral veins. For patients who could not undergo MR evaluation, computed tomography (CT) venogram was used instead. Patients with significant symptoms suggestive of CVI who lacked SVR on DUS, or had evidence of PVOO on MR venogram, were recommended to undergo bilateral venogram and intravascular ultrasound (IVUS) examination (Visions PV 035, Philips Volcano, San Diego, Calif) of the iliocaval and lower extremity venous systems. During endovascular intervention, vein stent placement is performed when the luminal area reduction of the iliac or common femoral vein is 50% or greater when compared with a neighboring vein segment free of disease. Wallstents in 16-mm and 18-mm diameters and 60-mm and 90-mm lengths were used, guided by the diameter of a nearby reference vessel, the length of the stenosis, and location of the stenosis. All patients were discharged on the day of the procedure. Every patient was given a regiment of postoperative antithrombotic therapy that included 10 mg of rivaroxaban daily followed by long-term, 81 mg of daily aspirin, except in those patients already on anticoagulation, a sensitivity to one of these medications, or if declined by the patient. All patients were followed at 1 month, 3 months, and then every 6 months thereafter with a physical examination and DUS.
and þ3 symptoms completely resolved with a normal physical examination. A full breakdown of our clinical assessment guidelines can be found in Table I. Numeric scores were documented at follow-up visits at 30 days, 90 days, 6 months, 1 year, and >1 year. Data were collected in a single-center registry using Microsoft Excel 2014 (Microsoft, Redmond, Wash). Variables included patient age, gender, date of prior EVTA procedure, date of iliac vein stent placement, location and number of vein stents, clinical-etiology-anatomypathophysiology classification, and the aforementioned numerical follow-up score. Patients were included in analysis who met the following criteria: (1) presentation with venous symptoms such as edema, (2) history of one or more prior EVTA procedure(s) of a superficial truncal vein in a symptomatic limb that received a vein stent, (3) confirmed closure of the superficial truncal vein(s) and varicosities on ultrasound examination, and (4) evidence of PVOO in the iliac or common femoral veins as suggested on MR or CT venogram. Limbs with dilated truncal veins on ultrasound examination or limbs that underwent poststent EVTA or superficial venous procedures were excluded. Wilcoxon Mann-Whitney tests were run for categorical variables such as active ulceration and whether unilateral or bilateral stents were placed. Kruskal-Wallis tests were run for ordinal variables such as total number of stents placed. Finally, ordered logistic regressions were run for outcomes at 30 days, 90 days, 6 months, and 1-year follow-up visits.
Data collection and statistical analysis. Each patient was given a numeric score at each follow-up visit reflective of outcome as follows: 1 symptoms or physical examination worse than preoperative visit; 0 symptoms or physical examination unchanged from preoperative baseline, þ1 symptoms or physical examination mildly improved compared with preoperative status; þ2 symptoms or physical examination significantly improved;
In a combined retrospective and prospective data registry of 682 patients who underwent vein stent placement for chronic PVOO at a single institution from March 2013 to November 2017, 100 limbs of 99 patients (14.5% of all patients) were found to have a history of EVTA or other superficial venous procedures before vein stenting. The mean age of these 99 patients was 60.2 years (range, 28-88 years; standard deviation, 13.86).
RESULTS
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Table I. Clinical assessment guidelines
Table II. Patient characteristics
Clinical assessment score
Characteristics
1
0
1
2
3
3
-
Description Patient noted worsened symptoms with or without physical examination demonstrated increased edema or other symptoms. Patient noted no change in symptoms or physical examination showed no change in edema or other symptoms. Patient noted minor improvement in symptoms or physical examination showed minor decrease in edema or other symptoms.
Cohort size Stent cohort, N Prior history of EVTA, n (%)
682 99 (14.5%)
Demographics Age, mean 6 SD Male patients, %
60.20 6 13.86 51
Prestent CEAP classification C1
1
C2
3
Patient noted significant improvement in symptoms or physical examination showed major decrease in edema or other symptoms.
C3
59
C4
22
C5
8
Patient noted complete resolution of symptoms or physical examination revealed no findings of edema or stigmata of CVI.
C6
7
CEAP, Clinical-etiology-anatomy-pathophysiology; EVTA, endovenous thermal ablation; SD, standard deviation.
CVI, Chronic venous insufficiency.
Fifty-one percent of the patients were male. The most common presenting symptom was edema (C3 disease) and venous-related skin changes (C4 disease) in 59% and 22% of the patient cohort, respectively. A full distribution of prestent clinical-etiology-anatomypathophysiology class can be found in Table II. The sole patient with C1 disease had reported persistence of bilateral leg pain and heaviness, despite technically successful bilateral EVTA procedures, both of which were performed 8 years before stenting. Bilateral stents were placed in 58% of patients, with a mean number of 2.06 stents per patient. EVTA was the primary superficial vein procedure in 97%. Bilateral EVTA procedures were performed in 53%. The mean time between first EVTA to vein stenting was 1202.7 days. The outcome of each patient at each postoperative visit was compared with preoperative parameters (subject’s assessment, physical examination, and provider assessment) and was scored as follows: 1 (worse than preoperative), 0 (no change), þ1 (mildly improved), þ2 (significantly improved), or þ3 (completely recovered). Ninety-six patients reported for at least one follow-up visit. A full distribution of poststent symptom scoring can be found in the Fig.
DISCUSSION The operative and nonoperative management of CVI is complex and multifaceted, with a lack of consensus regarding an algorithmic standard of care. This lack of uniformity is likely owing to the varying etiologies of venous disease combined with a substantial increase in the availability of percutaneous interventions used to treat CVI that lack high-quality evidence regarding safety and efficacy.12 Many of the techniques and devices aimed at treating CVI available in the United States
either focus on correcting SVR or PVOO; however, a large percentage of patients have combined disease of both the superficial and deep systems.13 Although SVR has historically been associated as the major pathophysiologic mechanism of venous disease, PVOO, in the form of postthrombotic syndrome and nonthrombotic iliac vein lesions, has now been established as a prominent etiology of CVI.7,14 Various retrospective and prospective trials showing symptom reduction and increased quality of life after stenting of the vena cava and iliofemoral veins have confirmed the major role of PVOO in the pathophysiology of CVI.15,16 The presence of pathologic SVR is a well-documented cause of CVI,4-6 and EVTA has established itself as the gold standard in the elimination of SVR owing to a high technical success rate, low incidence of complications, and significant decrease in symptoms.17-19 Furthermore, EVTA has been found to increase the rate of active ulcer healing and decrease the incidence of ulcer recurrence.20-22 Although the benefits of EVTA are well-documented, the management of persistent CVI-related symptoms after the successful elimination of SVR has not been defined. A prior investigation by Neglén et al23 suggests that combined superficial and deep venous insufficiency should be treated concomitantly in those with severe disease to most effectively reduce symptomology and a recent study by Chait et al24 demonstrated a decrease in great and small saphenous reflux with bilateral iliac vein stenting. These investigations support a combined or deep first treatment approach, whereas others support initial treatment of the superficial venous system.9 This lack of consensus is likely tied to the fact that PVOO is difficult to definitively diagnose without initial invasive measures, such as venography or IVUS
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Fig. Distribution of follow-up scores, with a peak number of patients reporting symptom resolution at 6 months after stent placement.
examination,25 whereas the presence of SVR can be ascertained with routine transcutaneous DUS examination. The majority of our patients who presented with CVIrelated symptoms after successful EVTA procedure(s) experienced persistent or recurrent lower extremity edema and heaviness. A recent study by Wallace et al26 identified a 5-year symptom recurrence rate of 20.9% after EVTA, despite a technical success rate, as observed on DUS, of 93.2%.26 This finding suggests that, even with successful vein closure, persistent CVI-related symptoms may be due to a variety of etiologies including neovascularization, development of new SVR in a patent saphenous vein or perforator vein, or the presence of underlying PVOO.27 Our long-term results suggest significant symptom improvement in patients with persistent and recurrent CVI symptoms after successful EVTA with the placement of subsequent iliac vein stents. The laterality of prior EVTA and subsequent vein stenting was similar, with 53% and 58% receiving bilateral vein closures and ilia vein stents, respectively. This finding suggests that the majority of patients presenting with CVI symptoms after EVTA likely have underlying PVOO, often in the same limb distribution as their initially treated SVR. An interesting finding that warrants further investigation is the timing of maximum symptom relief after iliac vein stenting. At 30-days after stent placement, only
14.2% of patients (12/84) reported complete symptom resolution, whereas at 6 months, 34% (25/74) had complete resolution (P ¼ .003; Fig). Current evidence-based guidelines for the care of venous disease lacks recommendations for iliac vein stenting,10,11 including indications and recommended follow-up protocol. However, a 6-month reassessment interval for both symptom relief and monitoring of technical success has been used in many high-quality studies,15 including a recent doubleblinded randomized controlled trial demonstrating the efficacy of vein stenting.16 The limitations of this investigation are consistent with its single-center and partially retrospective methodology. The retrospective nature of this study prevented our group from successfully obtaining preoperative and postoperative Venous Clinical Severity Score, which would have strengthened the subjective nature of our results; however, we believe our scoring system and strong follow-up adds validity to our findings. The initial approach to the patient with CVI should be comprehensive and evaluate both the superficial and deep venous systems. Although the diagnosis of SVR is easily obtained via DUS, a proper diagnosis of deep venous disease attributed to PVOO is more difficult through noninvasive means. Transcutaneous DUS can readily identify the presence of deep venous thrombosis and deep venous reflux; however, proper identification of iliac vein compression is typically limited.28 The accuracy
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of cross-sectional imaging, such as CT or MR venography, to diagnose iliofemoral lesions has not been validated in large-scale studies, and therefore a lack of compression on preoperative imaging should not preclude patients from more accurate interrogation with IVUS examination.29-31 Patients with persistent or recurrent CVI symptoms after technically successful EVTA should be evaluated for PVOO via IVUS interrogation of the vena cava and iliofemoral veins. When signs and symptoms of PVOO are present at initial examination, such as edema above the ankle,32 EVTA monotherapy should not be expected to successfully decrease the symptoms of CVI. A decrease in PVOO via iliac vein stenting is safe and effective in patients with persistent symptoms after EVTA.
CONCLUSIONS Persistent symptoms after successful obliteration of incompetent saphenous veins may suggest underlying chronic PVOO. Furthermore, our data demonstrated peak symptom relief was achieved in the highest percentage of patients at 6 months. Our data suggest that patients with persistence or recurrence of CVI symptoms after successful EVTA should be evaluated for PVOO, because correction of venous obstruction by stenting of the vena cava and iliofemoral veins is effective in the reduction of venous-related signs and symptoms.
AUTHOR CONTRIBUTIONS Conception and design: SS, AV, RT, MM, PF, WT Analysis and interpretation: JC, EC, SS, KC, AV, RT, MM, WT Data collection: JC, EC, SS, KC Writing the article: JC, SS, KC Critical revision of the article: JC, EC, KC, AV, RT, MM, PF, WT Final approval of the article: JC, EC, SS, KC, AV, RT, MM, PF, WT Statistical analysis: Not applicable Obtained funding: Not applicable Overall responsibility: WT
REFERENCES 1. Eberhardt R, Raffetto J. Chronic venous insufficiency. Circulation 2014;130:333-46. 2. Criqui MH. Chronic venous disease in an ethnically diverse population: the San Diego Population Study. Am J Epidemiol 2003;158:448-56. 3. Chi Y, Schul M, Gibson K, Rosenblatt M, Kabnick L, Jaff M. Chronic venous disorder registry: a new perspective. Phlebology 2013;29:415-27. 4. Labropoulos N, Leon M, Nicolaides AN, Giannoukas AD, Volteas N, Chan P. Superficial venous insufficiency: correlation of anatomic extent of reflux with clinical symptoms and signs. J Vasc Surg 1994;20:953-8. 5. Vasdekis SN, Clarke GH, Nicolaides AN. Quantification of venous reflux by means of duplex scanning. J Vasc Surg 1989;10:670-7. 6. Labropoulos N, Leon M, Geroulakos G, Volteas N, Chan P, Nicolaides AN. Venous hemodynamic abnormalities in patients with leg ulceration. Am J Surg 1995;169:572-4.
7. Labropoulos N, Volteas N, Leon M, Sowade O, Rulo A, Giannoukas AD, et al. The role of venous outflow obstruction in patients with chronic venous dysfunction. Arch Surg 1997;132:46-51. 8. Jacobs BN, Andraska EA, Obi AT, Wakefield TW. Pathophysiology of varicose veins. J Vasc Surg Venous Lymphat Disord 2017;5:460-7. 9. Sottiurai V. Current surgical approaches to venous hypertension and valvular reflux. Int J Angiol 1996;5:49-54. 10. Gloviczki P, Comerota AJ, Dalsing MC, Eklof BG, Gillespie DL, Gloviczki ML, et al. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg 2011;53(Suppl):2S-48S. 11. O’Donnell TF, Passman MA, Marston WA, Ennis WJ, Dalsing M, Kistner RL, et al. Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular SurgeryÒ and the American Venous Forum. J Vasc Surg 2014;60(2 Suppl):1S-2S. 12. Alsheekh A, Hingorani A, Marks N, Ascher E. The next frontier of office-based inferior vena cava filter placement. J Vasc Surg Venous Lymphat Disord 2016;4:283-5. 13. Danielsson G, Eklof B, Grandinetti A, Lurie F, Kistner RL. Deep axial reflux, an important contributor to skin changes or ulcer in chronic venous disease. J Vasc Surg 2003;38:1336-41. 14. Raju S, Neglen P. High prevalence of nonthrombotic iliac vein lesions in chronic venous disease: a permissive role in pathogenicity. J Vasc Surg 2006;44:136-44. 15. Raju S. Best management options for chronic iliac vein stenosis and occlusion. J Vasc Surg 2013;57:1163-9. 16. Rossi FH, Kambara AM, Izukawa NM, Rodrigues TO, Rossi CB, Sousa AG, et al. Randomized double-blinded study comparing medical treatment versus iliac vein stenting in chronic venous disease. J Vasc Surg Venous Lymphat Disord 2018;6:183-91. 17. Bos RV, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg 2009;49:230-9. 18. Puggioni A, Kalra M, Carmo M, Mozes G, Gloviczki P. Endovenous laser therapy and radiofrequency ablation of the great saphenous vein: analysis of early efficacy and complications. J Vasc Surg 2005;42:488-93. 19. Puggioni A, Marks N, Hingorani A, Shiferson A, Alhalbouni S, Ascher E. The safety of radiofrequency ablation of the great saphenous vein in patients with previous venous thrombosis. J Vasc Surg 2009;49:1248-55. 20. Brittenden J, Cotton SC, Elders A, Ramsay CR, Norrie J, Burr J, et al. A randomized trial comparing treatments for varicose veins. N Engl J Med 2014;371:1218-27. 21. Harlander-Locke M, Lawrence PF, Alktaifi A, Jimenez JC, Rigberg D, Derubertis B. The impact of ablation of incompetent superficial and perforator veins on ulcer healing rates. J Vasc Surg 2012;55:458-64. 22. Harlander-Locke M, Lawrence P, Jimenez JC, Rigberg D, Derubertis B, Gelabert H. Combined treatment with compression therapy and ablation of incompetent superficial and perforating veins reduces ulcer recurrence in patients with CEAP 5 venous disease. J Vasc Surg 2012;55:446-50. 23. Neglén P, Hollis KC, Raju S. Combined saphenous ablation and iliac stent placement for complex severe chronic venous disease. J Vasc Surg 2006;44:828-33. 24. Chait J, Kibrik P, Kenney K, Alsheekh A, Ostrozhynskyy Y, Marks N, et al. Bilateral iliac vein stenting reduces great and small saphenous venous reflux [published online ahead of print June 6, 2019]. Vascular doi: 10.1177/1708538119854614. 25. Gagne PJ, Tahara RW, Fastabend CP, Dzieciuchowicz L, Marston W, Vedantham, et al. Venography versus
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intravascular ultrasound for diagnosing and treating iliofemoral vein obstruction. J Vasc Surg Venous Lymphat Disord 2017;5:678-87. 26. Wallace T, El-Sheikha J, Nandhra S, Leung C, Mohamed A, Harwood A, et al. Long-term outcomes of endovenous laser ablation and conventional surgery for great saphenous varicose veins. Br J Surg 2018;105:1759-67. 27. O’Donnell TF, Balk EM, Dermody M, Tangney E, Iafrati MD. Recurrence of varicose veins after endovenous ablation of the great saphenous vein in randomized trials. J Vasc Surg Venous Lymphat Disord 2016;4:97-105. 28. Lamba R, Tanner DT, Sekhon S, Mcgahan JP, Corwin MT, Lall CG. Multidetector CT of vascular compression syndromes in the abdomen and pelvis. Radiographics 2014;34: 93-115.
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29. McDermott S, Oliveira G, Ergul E, Brazeau N, Wicky S, Oklu R. May-Thurner syndrome: can it be diagnosed on a single magnetic resonance venography study? Diagn Interv Radiol 2012;9:44-8. 30. Massenburg BB, Himel HN, Blue RC, Marin ML, Faries PL, Ting W. Magnetic resonance imaging in proximal venous outflow obstruction. Ann Vasc Surg 2015;29:1619-24. 31. Kuo Y, Chen C, Chen J, Lin C, Ku J, Hsu H, et al. MayeThurner syndrome: correlation between digital subtraction and computed tomography venography. J Formos Med Assoc 2015;114:363-8. 32. Raju S, Neglén P. Chronic venous insufficiency and varicose veins. N Engl J Med 2009;360:2319-27. Submitted Jan 17, 2019; accepted Apr 20, 2019.
Persistent symptoms after endovenous thermal ablation may suggest proximal venous outflow obstruction Jesse Chait, BS, Emily K. Chapman, BA, Sneha Subramaniam, BA, Kevin Chun, BA, Ageliki G. Vouyouka, MD, Rami Tadros, MD, Michael Marin, MD, Peter Faries, MD, and Windsor Ting, MD, New York, NY
ABSTRACT Objective: Proximal venous outflow obstruction (PVOO) in the iliac veins and superficial venous disease are inter-related in ways not fully understood. We observed among our patients undergoing vein stent placement for PVOO a significant number having had prior endovenous thermal ablations (EVTA) in their history. This study was undertaken to better characterize these patients and develop an algorithm in their management. Methods: In a combined retrospective and prospective data registry of 682 patients who underwent vein stent placement for chronic PVOO at a single institution from March 2013 to November 2017, 100 limbs of 99 patients (14.5% of all patients) had a history of EVTA or other superficial venous procedures before their vein stenting. Limbs with dilated truncal veins on ultrasound examination or limbs that underwent poststent EVTA or superficial venous procedures were excluded. The mean age of these 99 patients was 60.2 years (range, 28-88 years; standard deviation, 13.855). Fifty-one percent of the patients were male. The most common presenting symptom of the patient cohort was edema (n ¼ 59), followed by venous-related skin changes (n ¼ 22). Results: Bilateral stents were performed in 58%, with a mean number of 2.06 stents per patient. EVTA was the primary superficial vein procedure in 97%. Bilateral EVTA were performed in 53% and unilateral EVTA in 47%. The mean time between the first EVTA to vein stenting was 1202.7 days. Patients were followed at 30 days, 90 days, 6 months, 1 year, and >1 year. The outcome for each patient at each postoperative visit was compared with preoperative parameters (subject’s assessment, physical examination, and provider assessment) and was scored as follows: -1 (worse than preoperative), 0 (no change), þ1 (mildly improved), þ2 (significantly improved), or þ3 (completely recovered). The mean outcome score at 30 days was 1.63 (84 patients), 2.05 at 90 days (62 patients), 2.09 at 6 months (74 patients), 1.93 at 1 year (54 patients), and 1.97 at >1 year (39 patients). Conclusions: Approximately 15% of patients undergoing vein stent placement for chronic PVOO have an antecedent history of superficial venous disease and EVTA. PVOO should be considered and the patient evaluated accordingly if symptoms persisted or recurred after EVTA. Vein stent placement among these patients with PVOO will result in further symptomatic relief, but complete symptomatic relief is not observed in everyone. The algorithm for the management of these patients warrants further investigation. (J Vasc Surg: Venous and Lym Dis 2019;-:1-6.) Keywords: Venous insufficiency; Saphenous vein; Iliac vein stenting; May-Thurner syndrome; Post-thrombotic syndrome; Endovenous thermal ablation; Vascular surgery
Chronic venous insufficiency (CVI) is the most common vascular disorder in the United States and places a significant financial burden on the current health care system.1-3 Historically, the etiology of CVI has been attributed to the presence of superficial venous reflux (SVR); however, over the past few decades, proximal venous outflow obstruction (PVOO) has also been found to From the Division of Vascular Surgery, Icahn School of Medicine at Mount Sinai. Author conflict of interest: W.T. is on the speaker’s bureau for Jansen pharmaceuticals. Presented at the Thirty-first Annual Meeting of the American Venous Forum, Rancho Mirage, Calif, February 19-22, 2019. Correspondence: Jesse Chait, BS, Division of Vascular Surgery, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029 (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 2213-333X Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvsv.2019.04.015
play a major role.4-7 Although these two distinct pathophysiologic processes are well-defined, and a relationship between increased deep venous hypertension and superficial disease exists,8,9 their relationship in terms of modern treatment modalities is unknown, and the current therapy options aimed at treating CVI reflects this lack of understanding. The ever-growing armamentarium of percutaneous techniques used to treat CVI is split into correcting either SVR or PVOO, and although guidelines that address the treatment of venous disease exist, there is no modern, evidence-based algorithm for the management of patients with combined superficial and deep disease.9-11 In our experience of treating PVOO with iliac vein stenting, it was noted that a significant percentage of patients had previously received endovenous thermal ablation (EVTA). This study aimed to better characterize these patients and develop a framework for diagnosis and treatment of PVOO when EVTA fails to alleviate the signs and symptoms of CVI. 1
2
Chait et al
Journal of Vascular Surgery: Venous and Lymphatic Disorders ---
METHODS Study design. A combined retrospective and prospective database of 682 patients who underwent venous stent placement for chronic PVOO at the Mount Sinai Hospital in New York City from 2013 to 2017 was reviewed. Institutional review board approval was obtained following the principles outlined in the Declaration of Helsinki, and informed consent was waived owing to the low-risk and retrospective nature of the study. The principal investigator (W.T.) and the Icahn School of Medicine at Mount Sinai have an investigational device exemption certificate from the Food and Drug Administration to establish a venous stent registry and to evaluate the outcomes of Wallstents (Boston Scientific, Marlborough, Mass).
2019
ARTICLE HIGHLIGHTS d
d
d
Type of Research: Single-center retrospective cohort study Key Findings: Of 99 patients who underwent iliac vein stenting, 14.5% had prior endovenous thermal ablation. Patients who underwent vein stenting had significant resolution of symptoms. Take Home Message: Patients with persistent or recurrent symptoms after successful endovenous thermal ablation should be evaluated for iliofemoral vein obstruction. Stenting of the iliofemoral veins is safe and effective in patients with persistent symptoms after the elimination of saphenous reflux.
Patient selection. Patients who presented at our institution with signs and symptoms of CVI were evaluated with a history, physical, and duplex ultrasonography (DUS) of the bilateral lower extremities to identify any venous reflux or deep venous thrombosis. Magnetic resonance (MR) venography of the abdomen and pelvis was performed to evaluate the iliocaval and femoral veins. For patients who could not undergo MR evaluation, computed tomography (CT) venogram was used instead. Patients with significant symptoms suggestive of CVI who lacked SVR on DUS, or had evidence of PVOO on MR venogram, were recommended to undergo bilateral venogram and intravascular ultrasound (IVUS) examination (Visions PV 035, Philips Volcano, San Diego, Calif) of the iliocaval and lower extremity venous systems. During endovascular intervention, vein stent placement is performed when the luminal area reduction of the iliac or common femoral vein is 50% or greater when compared with a neighboring vein segment free of disease. Wallstents in 16-mm and 18-mm diameters and 60-mm and 90-mm lengths were used, guided by the diameter of a nearby reference vessel, the length of the stenosis, and location of the stenosis. All patients were discharged on the day of the procedure. Every patient was given a regiment of postoperative antithrombotic therapy that included 10 mg of rivaroxaban daily followed by long-term, 81 mg of daily aspirin, except in those patients already on anticoagulation, a sensitivity to one of these medications, or if declined by the patient. All patients were followed at 1 month, 3 months, and then every 6 months thereafter with a physical examination and DUS.
and þ3 symptoms completely resolved with a normal physical examination. A full breakdown of our clinical assessment guidelines can be found in Table I. Numeric scores were documented at follow-up visits at 30 days, 90 days, 6 months, 1 year, and >1 year. Data were collected in a single-center registry using Microsoft Excel 2014 (Microsoft, Redmond, Wash). Variables included patient age, gender, date of prior EVTA procedure, date of iliac vein stent placement, location and number of vein stents, clinical-etiology-anatomypathophysiology classification, and the aforementioned numerical follow-up score. Patients were included in analysis who met the following criteria: (1) presentation with venous symptoms such as edema, (2) history of one or more prior EVTA procedure(s) of a superficial truncal vein in a symptomatic limb that received a vein stent, (3) confirmed closure of the superficial truncal vein(s) and varicosities on ultrasound examination, and (4) evidence of PVOO in the iliac or common femoral veins as suggested on MR or CT venogram. Limbs with dilated truncal veins on ultrasound examination or limbs that underwent poststent EVTA or superficial venous procedures were excluded. Wilcoxon Mann-Whitney tests were run for categorical variables such as active ulceration and whether unilateral or bilateral stents were placed. Kruskal-Wallis tests were run for ordinal variables such as total number of stents placed. Finally, ordered logistic regressions were run for outcomes at 30 days, 90 days, 6 months, and 1-year follow-up visits.
Data collection and statistical analysis. Each patient was given a numeric score at each follow-up visit reflective of outcome as follows: 1 symptoms or physical examination worse than preoperative visit; 0 symptoms or physical examination unchanged from preoperative baseline, þ1 symptoms or physical examination mildly improved compared with preoperative status; þ2 symptoms or physical examination significantly improved;
In a combined retrospective and prospective data registry of 682 patients who underwent vein stent placement for chronic PVOO at a single institution from March 2013 to November 2017, 100 limbs of 99 patients (14.5% of all patients) were found to have a history of EVTA or other superficial venous procedures before vein stenting. The mean age of these 99 patients was 60.2 years (range, 28-88 years; standard deviation, 13.86).
RESULTS
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Table I. Clinical assessment guidelines
Table II. Patient characteristics
Clinical assessment score
Characteristics
1
0
1
2
3
3
-
Description Patient noted worsened symptoms with or without physical examination demonstrated increased edema or other symptoms. Patient noted no change in symptoms or physical examination showed no change in edema or other symptoms. Patient noted minor improvement in symptoms or physical examination showed minor decrease in edema or other symptoms.
Cohort size Stent cohort, N Prior history of EVTA, n (%)
682 99 (14.5%)
Demographics Age, mean 6 SD Male patients, %
60.20 6 13.86 51
Prestent CEAP classification C1
1
C2
3
Patient noted significant improvement in symptoms or physical examination showed major decrease in edema or other symptoms.
C3
59
C4
22
C5
8
Patient noted complete resolution of symptoms or physical examination revealed no findings of edema or stigmata of CVI.
C6
7
CEAP, Clinical-etiology-anatomy-pathophysiology; EVTA, endovenous thermal ablation; SD, standard deviation.
CVI, Chronic venous insufficiency.
Fifty-one percent of the patients were male. The most common presenting symptom was edema (C3 disease) and venous-related skin changes (C4 disease) in 59% and 22% of the patient cohort, respectively. A full distribution of prestent clinical-etiology-anatomypathophysiology class can be found in Table II. The sole patient with C1 disease had reported persistence of bilateral leg pain and heaviness, despite technically successful bilateral EVTA procedures, both of which were performed 8 years before stenting. Bilateral stents were placed in 58% of patients, with a mean number of 2.06 stents per patient. EVTA was the primary superficial vein procedure in 97%. Bilateral EVTA procedures were performed in 53%. The mean time between first EVTA to vein stenting was 1202.7 days. The outcome of each patient at each postoperative visit was compared with preoperative parameters (subject’s assessment, physical examination, and provider assessment) and was scored as follows: 1 (worse than preoperative), 0 (no change), þ1 (mildly improved), þ2 (significantly improved), or þ3 (completely recovered). Ninety-six patients reported for at least one follow-up visit. A full distribution of poststent symptom scoring can be found in the Fig.
DISCUSSION The operative and nonoperative management of CVI is complex and multifaceted, with a lack of consensus regarding an algorithmic standard of care. This lack of uniformity is likely owing to the varying etiologies of venous disease combined with a substantial increase in the availability of percutaneous interventions used to treat CVI that lack high-quality evidence regarding safety and efficacy.12 Many of the techniques and devices aimed at treating CVI available in the United States
either focus on correcting SVR or PVOO; however, a large percentage of patients have combined disease of both the superficial and deep systems.13 Although SVR has historically been associated as the major pathophysiologic mechanism of venous disease, PVOO, in the form of postthrombotic syndrome and nonthrombotic iliac vein lesions, has now been established as a prominent etiology of CVI.7,14 Various retrospective and prospective trials showing symptom reduction and increased quality of life after stenting of the vena cava and iliofemoral veins have confirmed the major role of PVOO in the pathophysiology of CVI.15,16 The presence of pathologic SVR is a well-documented cause of CVI,4-6 and EVTA has established itself as the gold standard in the elimination of SVR owing to a high technical success rate, low incidence of complications, and significant decrease in symptoms.17-19 Furthermore, EVTA has been found to increase the rate of active ulcer healing and decrease the incidence of ulcer recurrence.20-22 Although the benefits of EVTA are well-documented, the management of persistent CVI-related symptoms after the successful elimination of SVR has not been defined. A prior investigation by Neglén et al23 suggests that combined superficial and deep venous insufficiency should be treated concomitantly in those with severe disease to most effectively reduce symptomology and a recent study by Chait et al24 demonstrated a decrease in great and small saphenous reflux with bilateral iliac vein stenting. These investigations support a combined or deep first treatment approach, whereas others support initial treatment of the superficial venous system.9 This lack of consensus is likely tied to the fact that PVOO is difficult to definitively diagnose without initial invasive measures, such as venography or IVUS
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Fig. Distribution of follow-up scores, with a peak number of patients reporting symptom resolution at 6 months after stent placement.
examination,25 whereas the presence of SVR can be ascertained with routine transcutaneous DUS examination. The majority of our patients who presented with CVIrelated symptoms after successful EVTA procedure(s) experienced persistent or recurrent lower extremity edema and heaviness. A recent study by Wallace et al26 identified a 5-year symptom recurrence rate of 20.9% after EVTA, despite a technical success rate, as observed on DUS, of 93.2%.26 This finding suggests that, even with successful vein closure, persistent CVI-related symptoms may be due to a variety of etiologies including neovascularization, development of new SVR in a patent saphenous vein or perforator vein, or the presence of underlying PVOO.27 Our long-term results suggest significant symptom improvement in patients with persistent and recurrent CVI symptoms after successful EVTA with the placement of subsequent iliac vein stents. The laterality of prior EVTA and subsequent vein stenting was similar, with 53% and 58% receiving bilateral vein closures and ilia vein stents, respectively. This finding suggests that the majority of patients presenting with CVI symptoms after EVTA likely have underlying PVOO, often in the same limb distribution as their initially treated SVR. An interesting finding that warrants further investigation is the timing of maximum symptom relief after iliac vein stenting. At 30-days after stent placement, only
14.2% of patients (12/84) reported complete symptom resolution, whereas at 6 months, 34% (25/74) had complete resolution (P ¼ .003; Fig). Current evidence-based guidelines for the care of venous disease lacks recommendations for iliac vein stenting,10,11 including indications and recommended follow-up protocol. However, a 6-month reassessment interval for both symptom relief and monitoring of technical success has been used in many high-quality studies,15 including a recent doubleblinded randomized controlled trial demonstrating the efficacy of vein stenting.16 The limitations of this investigation are consistent with its single-center and partially retrospective methodology. The retrospective nature of this study prevented our group from successfully obtaining preoperative and postoperative Venous Clinical Severity Score, which would have strengthened the subjective nature of our results; however, we believe our scoring system and strong follow-up adds validity to our findings. The initial approach to the patient with CVI should be comprehensive and evaluate both the superficial and deep venous systems. Although the diagnosis of SVR is easily obtained via DUS, a proper diagnosis of deep venous disease attributed to PVOO is more difficult through noninvasive means. Transcutaneous DUS can readily identify the presence of deep venous thrombosis and deep venous reflux; however, proper identification of iliac vein compression is typically limited.28 The accuracy
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of cross-sectional imaging, such as CT or MR venography, to diagnose iliofemoral lesions has not been validated in large-scale studies, and therefore a lack of compression on preoperative imaging should not preclude patients from more accurate interrogation with IVUS examination.29-31 Patients with persistent or recurrent CVI symptoms after technically successful EVTA should be evaluated for PVOO via IVUS interrogation of the vena cava and iliofemoral veins. When signs and symptoms of PVOO are present at initial examination, such as edema above the ankle,32 EVTA monotherapy should not be expected to successfully decrease the symptoms of CVI. A decrease in PVOO via iliac vein stenting is safe and effective in patients with persistent symptoms after EVTA.
CONCLUSIONS Persistent symptoms after successful obliteration of incompetent saphenous veins may suggest underlying chronic PVOO. Furthermore, our data demonstrated peak symptom relief was achieved in the highest percentage of patients at 6 months. Our data suggest that patients with persistence or recurrence of CVI symptoms after successful EVTA should be evaluated for PVOO, because correction of venous obstruction by stenting of the vena cava and iliofemoral veins is effective in the reduction of venous-related signs and symptoms.
AUTHOR CONTRIBUTIONS Conception and design: SS, AV, RT, MM, PF, WT Analysis and interpretation: JC, EC, SS, KC, AV, RT, MM, WT Data collection: JC, EC, SS, KC Writing the article: JC, SS, KC Critical revision of the article: JC, EC, KC, AV, RT, MM, PF, WT Final approval of the article: JC, EC, SS, KC, AV, RT, MM, PF, WT Statistical analysis: Not applicable Obtained funding: Not applicable Overall responsibility: WT
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