Successful Iliac Vein and Inferior Vena Cava Stenting Ameliorates Venous Claudication and Improves Venous Outflow, Calf Muscle Pump Function, and Clinical Status in Post-Thrombotic Syndrome

Abstract

Objectives:

Stent therapy has been proposed as an effective treatment of chronic iliofemoral (I-F) and inferior vena cava (IVC) thrombosis. The purpose of this study was to determine the effects of technically successful stenting in consecutive patients with advanced CVD (CEAP_3–6 ± venous claudication) for chronic obliteration of the I-F (±IVC) trunks, on the venous hemodynamics of the limb, the walking capacity, and the clinical status of CVD. These patients had previously failed to improve with conservative treatment entailing compression and/or wound care for at least 12 months.

Methods:

The presence of venous claudication was assessed by ≥3 independent examiners. The CEAP clinical classification was used to determine the severity of CVD. Outflow obstruction [Outflow Fraction at 1- and 4-second (OF₁ and OF₄) in %], venous reflux [Venous Filling Index (VFI) in mL/100 mL/s], calf muscle pump function [Ejection Fraction (EF) in %] and hypertension [Residual Venous Fraction (RVF) in %], were examined before and after successful venous stenting in 16 patients (23 limbs), 6 females, 10 males, median age 42 years; range, 31–77 yearas, left/right limbs 14/9, using strain gauge plethysmography; 7/16 of these had thrombosis extending to the IVC. Contralateral limbs to those stented without prior I-F ± IVC thrombosis, nor infrainguinal clots on duplex, were used as control limbs (n = 9). Excluded were patients with stent occlusion or stenoses, peripheral arterial disease (ABI <1.0), symptomatic cardiac disease, unrelated causes of walking impairment, and malignancy. Preinterventional data (≤30 days) were compared with those after endovascular therapy (8.4 months; interquartile range [IQR], 3–11.8 months). Nonparametric analysis was applied.

Results:

Compared with the control group, limbs with I-F ± IVC thrombosis before stenting had reduced venous outflow (OF₄) and calf muscle pump function (EF), worse CEAP clinical class, and increased RVF (all, P < 0.05). At 8.4 months (IQR, 3–11.8 months) after successful I-F (±IVC) stenting, venous outflow (OF₁, OF₄) and calf muscle pump function (EF) had both improved (P < 0.001) and the RVF had decreased (P < 0.001), at the expense of venous reflux, which had increased further (increase of median VFI by 24%; P = 0.002); the CEAP status had also improved (P < 0.05) from a median class C₃ (range, C3–C6; IQR, C3–C5) [distribution, C6: 6; C4: 4; C3: 13] before intervention to C2 (range, C2–C6; IQR, C2–C4.5) [distribution, C6: 1; C5: 5; C4: 4; C2: 13] after intervention. At this follow up (8.4 months median), venous outflow (OF₁, OF₄), calf muscle pump function (EF), and RVF of the stented limbs did not differ significantly from those of the control; significantly worse (P < 0.025) were the amount of venous reflux (VFI), and the CEAP clinical class, despite the improvement with stenting. Incapacitating venous claudication noted in 62.5% (10 of 16, 95% CI, 35.8%–89.1%) of patients (15 of 23 limbs; 65.2%, 95% CI, 44.2%–86.3%) before stenting was eliminated in all after stenting (P < 0.001).

Conclusions:

Successful I-F (±IVC) stenting in limbs with venous outflow obstruction and complicated CVD (C3–C6) ameliorates venous claudication, normalizes outflow, and enhances calf muscle pump function, compounded by a significant clinical improvement of CVD. The significant increase in the amount of venous reflux of the stented limbs indicates that elastic or inelastic compression support of the successfully stented limbs would be pivotal in preventing disease progression.

We determined the effects of successful stenting for chronic obliteration of the I-F (±IVC) trunks in 23 limbs of 16 consecutive patients, median age 42 years, with chronic venous disease (CVD, CEAP_3–6 ± venous claudication) after failure of conservative treatment (≥12 months), on the walking capacity, the clinical severity of CVD, and the venous hemodynamics with strain gauge plethysmography. Limbs without prior thrombosis (contralateral to those stented) were used as the control (n = 9). Data before (≤30 days) and after (median, 8.4 months) stent therapy were compared. Successful stenting ameliorated venous claudication, normalized outflow, and enhanced the calf muscle pump function, resulting in a distinct clinical improvement of CVD, amid a significant increase in the amount of venous reflux.

Conservative management entailing anticoagulation, bed rest, leg elevation, and elastic compression had been, and in most nonspecialized institutions still is, the likely form of treatment of acute iliofemoral venous thrombosis (I-F_DVT).^1–5 However, it is increasingly appreciated that conservative treatment is associated with disappointing long-term outcomes,^2–5 pertaining to the development of post-thrombotic syndrome caused by venous outflow obstruction,^5–9 valvular incompetence,^1,5,10 and their combined detrimental effect on the calf muscle pump function.^5,11,12 The resulting leg swelling, venous claudication, skin changes, and ulceration^5,13–15 have been linked to a significant deficit in quality of life.⁵ After a median follow-up of 5 years, 44% of patients with I-F_DVT treated conservatively experienced venous claudication, commencing at a distance of 130 m, and 15% were forced to stop at a distance of 240 m due to its intensity.⁵ The affected limbs had reduced venous outflow and abnormally high venous reflux and residual venous volume on calf muscle exertion.⁵ Four in 5 limbs had venous valvular incompetence both in the superficial and the deep veins.⁵ Clinical deterioration in the CEAP¹⁶ and Venous Clinical Severity Scoring systems¹⁷ was compounded by a significant compromise in quality of life, including physical functioning and role, general health, social function, and mental health.

Contrary to the adverse outcomes of chronic occlusive thrombus formation, thrombus elimination in patients with recently sustained I-F_DVT using catheter-directed thrombolysis (urokinase) improves health-related quality of life, courtesy of better physical functioning, less stigma and health distress, and fewer post-thrombotic symptoms;^3,4 outcomes in lytic failures parallel those with conservative treatment. Although the adverse effects of chronic I-F_DVT on venous valvular function are established relatively early in the disease course,^18,19 aggressive recanalization has been advocated in the subset of patients with complicated chronic venous disease (CVD), largely attributable to venous outflow obstruction, particularly if clinically refractory to conservative treatment (Table 1).^20–30 The increasingly practiced iliofemoral (I-F) and inferior vena cava (IVC) balloon venoplasty (dilatation) and stenting, offering minimally invasive recanalization of the occluded venous trunks, is purported to result in marked clinical improvement and acceptable early and midterm patency rates.¹⁵ However, the global hemodynamic changes in the lower limb attached to endovascular therapy in chronic occlusive I-F_DVT remain largely undetermined.^7,8 This study examined the effects of successful endovenous stenting of the I-F veins (±IVC) for complicated (CEAP_3–6 ± venous claudication) chronic occlusive thrombosis on the global venous hemodynamics of the limb, the walking capacity and the clinical status of CVD in consecutive patients on whom conservative treatment with elastic compression (±wound care) for over 12 months previously had failed to heal their ulcers and/or to improve the CVD related symptoms.

TABLE 1. Tabulated Literature Review of Clinical Studies on the Etiology, Associated Interventions, Surveillance Means, and Luminal Patency of Post-Thrombotic or Stenotic Iliofemoral ± Caval Venous Segments After Endovenous Stenting Performed for Disobliteration of Venous Outflow Obstruction Secondary to Thrombosis, Stenoses, and the May-Thurner Syndrome

METHODS

The data of this controlled, Institutional Review Board approved study were accumulated and analyzed retrospectively, based on a standardized protocol of detailed investigations prospectively reported. Included were consecutive patients with complicated CVD largely attributable to chronic I-F_DVT with venous outflow obstruction on ilio-cavography³¹ performed within 30 days of their endovascular therapy, which consisted of balloon dilatation and stenting of the iliac veins, with or without inclusion of the IVC.^15,30 Previously, patients had undergone conservative treatment [elastic compression (±optimal wound care)] for at least a year that had failed to heal the ulcers or to relieve the symptoms related to chronic thrombosis. Excluded were patients with 1) failed endovascular therapy defined as reocclusion of the vein lumen or in-/peri-stent stenosis; 2) peripheral arterial disease manifested clinically by weak or absent peripheral pulses with resting ankle brachial pressure index less than 1.0,³² and 3) those unable to undergo plethysmographic investigation. The study consists of 16 patients (10 men and 6 women; median age, 42 years; interquartile range, 40–56 years; total range, 31–77 years). Unilateral endovenous stent therapy was successfully performed in 9 of these patients (56%) and bilateral stenting in the remaining 7 (44%). Thus, the clinical and hemodynamic impact of endovenous stent therapy was studied in 23 limbs: 9 right ones and 14 left ones. Limbs contralateral to the stented ones in patients with unilateral endovascular therapy (n = 9) were used as the control and were assessed concurrently with the stented limbs, provided that had not sustained I-F_DVT, confirmed venographically,^15,31 nor had venous thrombus infra-inguinally on duplex ultrasound examination or venography at the time of our study.^32,33

Patients included in the study had 1) their clinical notes examined in detail, 2) stratification of CVD in the CEAP clinical classes (C-class)^16,34,35 before surgery (≤30 days), confirmed on the day of surgery, and after endovascular therapy, 3) clinical assessment of the lower limb arteries with determination of the resting ankle-brachial index,³² 4) lower limb venous duplex investigation before and after the intervention to determine the sites and extent of venous reflux,^34,36 and to confirm graft-patency, 5) preoperative and intraoperative (±follow up) multiplanar ilio-cavography with or without descending venography of the lower limb,^15,31 6) global venous hemodynamic assessment of the lower limbs performed before (≤30 days) and after endovascular therapy with strain-gauge plethysmography,^34,37 and 7) femoral mean venous pressure measurement in the horizontal position before and on completion of endovascular therapy on the treated side with a calibrated pressure transducer.¹⁵ Venous reflux exceeding 0.5 seconds was considered as abnormal.^34,36 Outward perforator vein flow exceeding 0.5 seconds upon release of manual limb compression applied distally was also taken as abnormal.³⁶ Limbs were stratified according to the presence of 1) superficial_[S] vein incompetence, with or without perforator_[P] reflux [S ± P] and 2) superficial and deep_[D] vein incompetence, with or without perforator_[P] reflux [S + D ± P].

Venous hemodynamic assessment of the lower limb with strain-gauge plethysmography^34,37 included: 1) the venous filling index (VFI, calculated from the tangential of the refilling venous volume curve [first second], in mL/100 mL/s) reflecting the amount of venous reflux;5–9,11,33,34 2) the ejected volume (EV, calf venous volume ejected with a single calf muscle contraction, in ml/100 mL); 3) the ejection fraction (EF, EV divided by the total calf venous volume ×100, in %) representing the calf muscle pump ejection capacity;5–9,11,33,34 4) the residual volume fraction (RVF, residual calf venous volume after 10 calf muscle contractions divided by the total calf venous volume ×100, in %) mirroring the ambulatory venous pressure;5,11,33,34 and 5) the outflow fraction (OF, percentage of calf venous outflow at 1 and 4 seconds from the release of a thigh cuff inflated at 50 mm Hg on recumbency divided by the total calf venous volume) reflecting the venous outflow.5,33,34,38 Calculation of the venous global hemodynamics was performed as previously described.^5,33,34 The sites and the extent of I-F (±IVC) obstruction or stenosis were defined with transfemoral ascending digital subtraction contrast venography and ilio-cavography.^15,31 This was combined with descending digital subtraction venography or duplex sonography for evaluation of venous valvular incompetence, in addition to venous pressure gradient estimation.^15,31 Transjugular or brachial ilio-cavography and abdominal vena-cavography enabled visualization of the IVC proximal to the occlusion. Iliocaval stenting was performed under conscious sedation and local anesthesia. Angioplasty pain in chronically occluded venous trunks was controlled with stronger analgesia (fentanyl with sedatives such as midazolam). Stenting preceded by open femoral thrombectomy was performed under general anesthesia.³⁹ Venous access was gained at a site remote from the obstruction preferably the right internal jugular or popliteal veins. A 5-Fr glide catheter (Terumo Medical Corporation, Somerset, NJ) and an angled, stiff, hydrophilic glide-wire facilitated access to the occluded iliac vein. Spinning of the guidewire between dry, gloved fingers, combined with angiographic views obtained intermittently, ensured its advancement. Contrast injected past the obstruction confirmed the wire’s location in relation to the inflow tributaries and enabled identification of residual venous occlusion. Anticoagulation (heparin 5000 IU) was administered after venous access had been secured aiming at an activated clotting time of 280 to 300 seconds. Heparin infusion was repeated during the procedure as required.

The occluded segment was predilated to the intended stent diameter, usually 12 mm for the common femoral and external iliac veins, and 14 to 16 mm for the common iliac vein; 16 to 20 mm stents were deployed in the IVC. Predilatation was performed with a large balloon. Occasionally, a 5-mm balloon was used before a larger balloon could be negotiated. If the catheter or the balloon could not be advanced past the occlusion, despite the guidewire being in place, a puncture was made in the common femoral or femoral veins distal to the obstruction and the wire was snared and pulled out through this puncture site. By applying tension at both ends of the guidewire simultaneously, the catheter and balloon were then forcefully pulled through the occluded segment. The diseased venous segments and most often the common and external iliac veins were stented in their entirety, and always in continuity. For stent deployment into the common femoral vein for thromboses extending inferiorly to the inguinal ligament, the preservation of most large venous collaterals was crucial (Fig. 1). In unilateral common iliac vein occlusion extending up to the IVC ostium, stents were deployed with a 10- to 15-mm overhang into the IVC. This ensured prevention of stent stenosis at the IVC–common iliac vein confluence, as the expansive strength of balloon-expanded stents is weakest at the ends. After the introducers from either the internal jugular or popliteal veins were removed on completion of the procedure, compression was applied for 5 to 10 minutes. In jugular vein access, the head of the bed was elevated to 30° for 2 hours. In popliteal vein access, hemostasis was ensured with small gauze rolls compressed against the popliteal fossa using elastic compression leg bandaging. Heparin was not reversed. Ambulation was encouraged as soon as sedation had worn off. Full anticoagulation with low-molecular-weight heparin was used, with transition to oral anticoagulation. The patient was observed overnight. I-F stent patency was confirmed the following day with duplex. In thrombophilia, anticoagulation was advised indefinitely. If reversible factors were the cause of I-F_DVT, 3 to 6 months of anticoagulation was recommended, when patency and venous inflow to the stented segment were uncompromised. Clopidogrel (Plavix, Sanofi-Synthelabo, New York) 75 mg OD was administered for 4 weeks, followed by aspirin, 81 mg OD, for life. The stented vein segments and the stents deployed are demonstrated in Figure 2. In 4 limbs, the critically compromised venous inflow to the iliocaval segments, deemed essential for the prevention of rethrombosis, was improved with limited open femoral thrombectomy and vein patch angioplasty, immediately prior to endovascular therapy.

FIGURE 1. A, Ultrasound guided access to the femoral vein just below its confluence with the profunda femoris vein. Post-thrombotic changes in the common femoral vein (arrow), occlusion of external and common iliac veins (two arrow heads), and large collaterals via the internal iliac vein are noted. B, A stiff angled glide wire (Terumo Medical Corporation, Somerset, NJ) and the introducer are in place. C, Three 14-mm-wide (one ×60 mm, one ×40 mm long) Smart stents (Cordis Corporation, Miami, FL) have been deployed from the bifurcation of the inferior vena cava to the mid common femoral vein. The common and external iliac veins and the common femoral vein have been predilated with a 14 mm × 4 cm high-pressure balloon. Stents also dilated postdeployment with the same balloon. The upper stent-end just enters the IVC but does not override the opposite side (arrow). D, Completion venography performed from the sheath just below the stented area. Pressure measurements revealed no gradient between the inferior vena cava and the common femoral vein. Note the short distance from the distal end of the stent (arrow) to the entry point of the introducer (arrow).

FIGURE 2. Anatomic location and extent of iliofemoral (±inferior vena cava) venous stenting, and type of stents (Gianturco, Smart, Wallstent) used in the recanalization of chronic thrombosis. Stenting extended to the veins listed and included the intervening venous segments. IVC, inferior vena cava; CIV, common iliac vein; EIV, external iliac vein; CFV, common femoral vein

Attributable to well-documented outflow obstruction, venous claudication was defined as the onset of thigh and/or leg pain and tightness on physical exercise challenge, subsiding with rest.^10,40–42 With all other etiologies on the list of differential diagnoses having been eliminated, venous claudication in the study patients, if present, was independently identified by at least 3 expert vascular consultants.

All baseline clinical and hemodynamic assessments, except femoral venous pressure, were obtained within 30 days before the procedure. Clinical status was reassessed on the day of intervention. The period between the procedure and the follow-up clinical and hemodynamic assessments performed together, was a median 8.4 (interquartile range [IQR], 3–11.8) months. Femoral pressure was determined on the day of the procedure before and after stent deployment. Chronic thrombosis was attributable to thrombophilia in 4 (25%) patients, major surgery or trauma in 5 (31.25%), and May-Thurner syndrome in 2 (12.5%).23–25,27–29

Analysis of the study data was performed with nonparametric statistics. Quantitated paired data comparisons between the preprocedural and postprocedural hemodynamics and the CEAP clinical class were conducted with the Wilcoxon sign-ranked test. Comparisons of quantitated nonpaired data on global venous hemodynamics and the clinical status of CVD between the treated and the control limbs, both preprocedurally and postprocedurally, were conducted with the Mann-Whitney U test. The 95% confidence interval (CI) of the estimated median difference (Wilcoxon test), point estimate (Mann-Whitney U test), and select proportions are quoted. Bonferroni correction was applied, if appropriate. Differences in proportion were assessed with the χ² test. The Spearman’s rank correlation coefficient (R) was calculated. A P value of less than 0.05 was considered as significant. Data are expressed as median and IQR.

RESULTS

Anatomic Distribution of Thrombosis

Propensity for total occlusive thrombosis decreased with distance from common iliac vein bifurcation (R = −0.929; P < 0.01), as shown: IVC 12 of 23 limbs (52.2%, 95% CI, 30.1%–74.3%); common iliac, 17 of 23 (73.9%, 95% CI, 54.4%–93.3%); external iliac, 9 of 23 (39.1%); common femoral, 6 of 23 (26.1%); femoral, 3 of 23 (13%), and posterior tibial vein, 1 of 23 (4.3%). On the other hand, venous luminal stenosis increased from the IVC (2 of 23, 8.7%) through the common iliac (3 of 23, 13%) and external iliac vein (6 of 23, 26.1%), peaked at the common femoral vein (9 of 23, or 39.1%, 95% CI, 17.5%–60.7%) and remained attenuated from the femoral vein (6 of 23) through the popliteal (5 of 23, 21.7%) and the axial calf veins (posterior and anterior tibial veins 5 and 4 limbs respectively, peroneal vein 6). Post-thrombotic changes were identified in the external iliac, common femoral, femoral and popliteal veins (2 of 23 limbs each) and the axial calf veins (posterior and anterior tibial and peroneal veins, 3 of 23 limbs each).

Anatomic Distribution of Post-thrombotic Venous Valvular Incompetence

Infrainguinal valvular incompetence occurred significantly more often among limbs with prior I-F_DVT than the control in the common femoral [16 of 23 (69.6%) vs. 2 of 9 (22.2%); P < 0.01], femoral [15 of 23 (65.2%) vs. 2 of 9 (22.2%); P < 0.05] and popliteal [17 of 23 (73.9%) vs. 3 of 9 (33.3%); P < 0.05] veins, but not in the posterior tibial vein [13 of 23 (56.5%) vs. 3 of 9 (33.3%); not significant]. The likelihood of reflux in both the superficial and deep venous systems was higher (P < 0.05) in the stented limbs (18 of 23) (78%, 95% CI, 60%–96.5%) than the control (3 of 9, 33%). This was true for perforator incompetence [19 of 23 (82.6%) vs. 4 of 9 (44.4%); P < 0.01]. Finally, 22% of the stented limbs (5 of 23) and 44% of the control (4 of 9) had superficial (no deep) incompetence.

Global Venous Hemodynamic Performance

Venous Outflow

Endovascular therapy resulted in a significant improvement of the OF₁ (P < 0.001; EMD = 6.38%, 95% CI, 3.1%–9.6%) and the OF₄ (P < 0.001; EMD = 10%, 95% CI, 6.1%–13.5%) in the treated limbs; on the other hand, changes in the control limbs were small [OF₁: P > 0.8, OF₄: P > 0.4] (Fig. 3A, B). The OF₄ was significantly lower in the thrombosed limbs before surgery (P < 0.05; PE = −11.1%, 95% CI, −23% to 0%); however, the difference between the 2 groups was small after surgery (P > 0.3). Before surgery, the OF₁ of the treated limbs was markedly lower than that of the control ones (PE = −4.22%, 95% CI, −14.25% to 3.78), although statistical significance was missed. After successful intervention, differences in the OF₁ between the 2 groups were attenuated (P > 0.6).

FIGURE 3. Venous hemodynamics, including venous outflow (outflow fraction at 1 and 4 seconds; A, B), calf muscle pump function (ejection fraction; C), amount of venous reflux (venous filling index; D) and venous hypertension (residual volume fraction; E), and the CEAP clinical class (F) in 23 limbs with chronic iliofemoral (I-F) ± inferior vena cava (IVC) thrombosis (DVT) and 9 control limbs, before (≤30 days) and after (median, 8.4; interquartile range, 3–11.8 months) successful I-F (±IVC) venous stenting. Data are median and interquartile range.

Venous Pressure

The absolute venous pressure at the common femoral vein of the limbs that underwent stenting on recumbency decreased by an estimated median of 7 mm Hg (95% CI, 5.5–9) or 87.5%, from 8 (7–10.5) mm Hg before intervention to 1 (1–2) mm Hg after successful intervention (P = 0.002).

Calf Muscle Pump Function

Before surgery, differences between the control and treated limbs were significant in the EV (P = 0.0072; PE = 0.6 mL/100 mL, 95% CI, 0.19–1), and the EF (P = 0.0057; PE = 19.8 mL/100 mL; 95% CI, 8.5–33.7; Fig. 3C). Endovascular therapy resulted in an increase both in the EV (P = 0.004; EMD = 0.3 mL/100 mL; 95% CI, 0.1–0.475 mL/100 mL) and EF (P = 0.002; EMD = 13.7%; 95% CI, 6.7%–22.5%) of the treated limbs. On the other hand, the control limbs did not show significant changes in both of these parameters [EV: P > 0.6, EF: P = 0.2]. After successful intervention, differences between the 2 groups were attenuated to the level of statistical insignificance [EV, P = 0.1; EF, P = 0.16].

Venous Reflux

The VFI was the single hemodynamic parameter that deteriorated in the stented limbs, its median increasing from 16.9 (IQR, 11.9–29.8) mL/100 mL before surgery to 21 (IQR, 15.7–32.4) mL/100 mL after surgery (ie, by 24.3%; P = 0.004; EMD = 3.8 mL/100 mL; 95% CI, 1.3–9.1; Fig. 3D). Changes in the control limbs with surgery were small (P > 0.6). Before surgery the VFI was markedly higher in the thrombosed limbs (PE = 11.7 mL/100 mL; 95% CI, −1 to 15.3), yet the discrepancy increased further after surgery (P = 0.022; PE = 9.5 mL/100 mL; 95% CI, 1.5–18.3).

Residual Volume Fraction

RVF was significantly higher among the limbs with I-F (±IVC) thrombosis than the control before stenting (P = 0.018; PE = −26.8%; 95% CI, −4.9 to −47.3; Fig. 3E). Endovascular therapy resulted in a significant decrease in the RVF (P = 0.002; EMD = 17.7%; 95% CI, 9.6%–25.6%) of the treated limbs, but caused no change in the RVF of the control (P > 0.5). Consequently, differences between the 2 groups were small (P = 0.285) after stenting.

CEAP Clinical Class

Venous stenting resulted in a significant (P < 0.01; EMD = 1 level of CEAP clinical class; 95% CI, 0.5–1) improvement in the CVD status of treated limbs from CEAP clinical classes (range, C3–C6; median, C3; IQR, C3–C5 [CVD distribution C6, 6; C4, 4; C3, 13]) before intervention to C2–C6 (median, C2; IQR, C2–C4.5 [CVD distribution C6, 1; C5, 5; C4, 4; C2, 13]) after intervention (Fig. 3f). The status of the control limbs was CEAP clinical classes (range, 0–4; median, 2; IQR, 1–2 at baseline [CVD distribution C4, 2; C2, 3; C1, 3; C0, 1]) and did not change after the patients underwent endovascular therapy. The control limbs had a significantly better CEAP clinical class than the thrombosed limbs before stenting (P = 0.0044, PE = 2 levels of CEAP clinical classes; 95% CI, 1–3), but the difference decreased after successful stent therapy (P < 0.05, PE = 1 level of CEAP clinical class; 95% CI, 0–3).

Intermittent Venous Claudication

Incapacitating venous claudication was experienced at least by 62.5% (10 of 16 patients; 95% CI, 35.8%–89.1%) of the patients (15 of 23 limbs; 65.2%; 95% CI, 44.2%–86.3%) prior to successful stenting but was eliminated in all of them after the procedure (P < 0.001).

Hospital Stay and Perioperative Complications

Intervention time averaged 94 minutes (IQR, 88–159 minutes). The median postoperative hospital stay, including the day of surgery [I-F (±IVC) venous stenting (±limited open femoral thrombectomy)], was 2.5 days (range, 2–8 days; IQR, 2–4.5). Perioperative complications occurred in 4 patients (25%). These included an iatrogenic neck hematoma (right) evacuated with open surgery on postoperative day 2; heparin induced thrombocytopenia compelling the use of Hirudin drips for anticoagulation; an iatrogenic femoral false aneurysm (right), managed effectively with open hematoma evacuation and ligation of a torn small common femoral artery branch; and finally, thrombosis of an iliac stent, which required reintervention within hours of the original procedure, and an additional stent insertion; the latter patient who had also undergone limited open femoral thrombectomy developed lymphatic leak from her thigh wound, which settled with conservative treatment (moderate compression and bed rest) in 2 days. During the study period, 4 patients underwent stent treatment unsuccessfully.

DISCUSSION

Introduced in the 1990s for the treatment of vena cava stenoses,^43,44 endovenous stent therapy has emerged as an effective, minimally invasive discipline for restoring patency in chronic iliofemoral/caval vein obstruction caused by I-F_DVT7,8,20–22,25,26,29,30 or the May-Thurner syndrome.7,23–25,27–29 Performed under local anesthesia and intravenous analgesia^15,39 with a technical success of 90% or greater, and a midterm assisted patency exceeding 80% (Table 1), it facilitates the treatment of related venous complications (C3–C6), and improves the walking capacity of the afflicted individuals.7,8,14,15,20–22,25,26,29,30

There is paucity of published data on the hemodynamic impact of I-F (±IVC) stenting for complicated chronic occlusive thrombosis, except for the reports by Raju and Neglen.^7,8 They examined 38 limbs with iliac (±femoral ±IVC) vein occlusion but did not identify changes in the venous reflux and calf muscle pump function when they reexamined half of these limbs (17 of 38) plethysmographically poststent deployment,⁸ despite the marked clinical improvement; the ambulatory venous pressure, venous filling time (VFT), VFI, EF, RVF, arm-foot pressure differential and obstruction grade Raju test remained unchanged.⁸ A year later (2003), Neglen et al reported that the ambulatory venous pressure, VFT, VFI, and obstruction grade Raju test did not change after stent deployment both in limbs with obstruction and reflux and in limbs with obstruction alone.⁷ They noticed the detrimental hemodynamic effect of reflux in limbs with obstruction but did not register any hemodynamic improvement with reversal of obstruction, except for small but significant changes in the hand-foot pressure differential from 1.4 (±1.7) to 0.8 (±1.4) mm Hg.⁷ In this background, the clinical justification for selecting I-F (±IVC) stenting to treat limbs with complicated CVD refractory to conservative management appears hemodynamically unfounded. The need to relate the marked clinical improvement offered by I-F (±IVC) stenting with the venous hemodynamic milieu of the limb, encompassing the calf muscle pump function, venous hypertension and outflow prompted the current study.11,33,34,45

Venous outflow obstruction in limbs with prior I-F_DVT has been reported independently by different investigators.1,6,9,10,33,38 In our series comprising patients with complicated CVD (C3–C6), and incapacitating claudication in 62.5%, successful recanalization of I-F (±IVC) thrombosis with stent therapy achieved normalization of venous outflow. Estimated dynamically from the calf venous volume outflow curve at 2 different time points, venous outflow was enhanced by 45.7% and 22.46% at 1 (OF_1[median]) and 4 (OF_4[median]) seconds from the release of forced venous occlusion in the thigh with a pneumatic tourniquet (50 mm Hg), respectively.5,33,34,38,46 Normalization of venous outflow facilitated a significant improvement in the calf muscle pump function within a median period of 8.4 (IQR, 3–11.8) months of stent deployment. Treated limbs demonstrated a significant increase in the venous volume expelled with a single calf muscle contraction, and a proportional improvement of the EF. This was associated with an inverse decrease in the residual calf venous volume after repeated calf contractions, mirroring a proportional reduction of ambulatory venous hypertension.^33,34 By causing the fixed outflow resistance to decrease, recanalization of the obliterated and/stenosed iliofemoral conduits facilitated the efficacy of calf muscle pump, whatever its baseline impairment, by way of enabling it to expel the venous volumes against normalized outflow.⁴⁷ It is the combination of venous valvular incompetence, outflow obstruction, and calf muscle pump impairment that generates the hemodynamic milieu leading to the development of post-thrombotic complications.11,33,34,45–48 Five years after its onset, patients with I-F_DVT treated conservatively have impaired venous outflow, venous reflux, and RVF, whereas those with incapacitating claudication also have calf muscle pump function [EF] attenuation by 50% or more.⁵ In keeping with these findings, the amount of venous reflux and the RVF in the limbs with I-F(±IVC)_DVT of the current study before endovenous stenting were higher than those of the control ones by 44% and 127%, respectively, whereas the EF and the venous outflow were lower by 37.5% and 22%, respectively.

The occurrence of ulceration increases incrementally with valvular incompetence from 2% to 30% and 41% in limbs with a VFI of 2 to 5 mL/s, 5 to 10 mL/s, and 10 to 20 mL/s, respectively, but intact calf muscle pump function; however, in calf muscle pump impairment, the likelihood of ulceration increases multifold to 32%, 63%, and 71%, respectively.³³ The less common occurrence of ulceration in limbs with normal calf muscle pump function underscores the protective role of the latter to the hypertensive effects of reflux in limbs with CVD. Using the EF as an estimate of the pumping capacity of the calf muscle, Araki et al⁴⁶ reported that limbs with impaired calf muscle pump function accounted for 60% of those with varicose veins and/or edema (C2–C3), for 76% of limbs with healed ulcers, and for 90.5% of limbs with active ulcers. Calf muscle pump impairment in limbs with I-F_DVT¹ and complicated CVD¹³ has been well correlated with venous hypertension,¹² in keeping with the high RVF and the reduced EV, EF of the limbs with I-F (±IVC) thrombosis of the current study before stent deployment. Tissue hypoxia and inflammatory response to venous hypertension deprive the muscles and extrafascial tissues of their natural properties.^49–51 Sustained episodes of ischemia-reperfusion, triggering leukocyte margination, pavementing, adhesion, infiltration, sequestration and kinin production, compounded by disuse, and denervation cause muscle injury and calf muscle pump dysfunction.⁵¹ Morphologic skeletal muscle injuries comprise: 1) atrophy of type 2 muscle fibers, 2) denervation, and 3) myopathic abnormalities, including fiber degeneration, inflammation, and necrosis with accumulation of lymphocytes perivascularly.⁴⁹ Even if the calf muscle pump is intact at the time of thrombosis, outflow obstruction and valvular incompetence are capable of causing venous hypertension and complicated CVD.^33,34,50 The impaired hemodynamics in limbs with I-F_DVT due to venous outflow obstruction, valvular incompetence, and calf muscle pump impairment lead to a 6-fold likelihood of skin changes and ulceration (34.2%).⁵

The current study has demonstrated a significant deterioration of venous reflux (ie, 24%) after I-F (±IVC) stenting. This was not surprising as 74% of the stented limbs had axial deep reflux extending into the popliteal vein. By reinstituting patency in the large iliofemoral venous conduits stent deployment exposes the damaged infrainguinal valves to the dynamic and kinetic energy of refluxing venous volume reaching the heart. Effectively, recanalization eliminates the buffering role of previously occluded segments and extra-anatomic collaterals on the refluxing blood. A VFI increase (ie, 10%, not significant) poststent deployment has been reported by Neglen et al in limbs with obstruction and reflux.⁷ Differences in the axial deep venous reflux may have prevented a higher VFI increase. Five years after I-F_DVT, valvular incompetence causes a near-critical amount of reflux in more than 50% of the afflicted limbs.⁵ Reflux is an independent determinant of the CEAP clinical class, in post-thrombotic limbs.^52,53

Despite the deterioration of reflux, I-F (±IVC) recanalization in our series resulted in marked clinical improvement by one CEAP clinical class_[median] at a follow up of 8.4 months_[median], attributable to the leg ulcers having healed in all patients (n = 6) but one (83%), and the swelling having subsided in all C3 limbs. Since only successfully recanalized patients were recruited, our findings are not estimates of the clinically efficacy of I-F (±IVC) stenting, but nevertheless are in support of previous reports,7,8,14,15,22,25,29,30 particularly when considering that conservative treatment of over a year had failed to heal the ulcers or to control the edema. Incapacitating venous claudication, noted in 62.5% of our patients, was ameliorated with successful recanalization in all afflicted patients/limbs. Noted by different investigators,10,40–42,48 venous claudication has been a common occurrence in chronic I-F (±IVC) thrombosis, but its likelihood and effect on the walking capacity of afflicted individuals were only recently acknowledged.⁵

The clinical outcomes in our series indicate that the hemodynamic improvements generated by reversing outflow obstruction with recanalization and its beneficial effect on the calf muscle pump outweigh the detrimental impact of venous reflux enhancement. This is mirrored in the highly significant decrease in the RVF, a noninvasive estimate of the ambulatory venous pressure,5,11,33,34 and the aggregate product of venous reflux, calf muscle pump efficacy and venous outflow. Similarly, the significant attenuation in the femoral venous pressure suggests that successful recanalization with stent insertion in chronic I-F (±IVC) thrombosis could be seen as the equivalent to venous decompression of the infrainguinal venous system, particularly during lower limb activation on dependency.

CONCLUSION

Successful I-F (±IVC) stent recanalization in limbs with complicated CVD (C3–C6) ameliorates venous claudication, normalizes venous outflow, and enhances calf muscle pump function, compounded by a significant clinical improvement of CVD. The increase in the amount of venous reflux of the stented limbs indicates that elastic or inelastic compression support of the successfully stented limbs would be pivotal in preventing disease progression.