Original Article

Hemodynamic significance of collateral blood flow in chronic venous obstruction

Phlebology 2015, Vol. 30(1S) 27–34 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355515569433 phl.sagepub.com

RLM Kurstjens1,2, MAF de Wolf1,2, JHH van Laanen1, MW de Haan3, CHA Wittens1,2,4 and R de Graaf3

Abstract Introduction: Complaints related to the post-thrombotic syndrome do not always correlate well with the extent of post-thrombotic changes on diagnostic imaging. One explanation might be a difference in development of collateral blood flow. The aim of this study is to investigate the hemodynamic effect of collateralisation in deep venous obstruction. Methodology: Resting intravenous pressure of the common femoral vein was measured bilaterally in the supine position of patients with unilateral iliofemoral post-thrombotic obstruction. In addition, pressure in control limbs was also measured in the common femoral vein after sudden balloon occlusion in the external iliac vein. Results: Fourteen patients (median age 42 years, 12 female) were tested. In eleven limbs post-thrombotic disease extended below the femoral confluence. Median common femoral vein pressure was 17.0 mmHg in diseased limbs compared to 12.8 mmHg in controls (p ¼ 0.001) and 23.5 mmHg in controls after sudden balloon occlusion (p ¼ 0.009). Results remained significant after correcting for non-occlusive post-thrombotic disease. Conclusion: This study shows that common femoral vein pressure is increased in post-thrombotic iliofemoral deep venous obstruction, though not as much as after sudden balloon occlusion. The latter difference could explain the importance of collateralisation in deep venous obstructive disease and the discrepancy between complaints and anatomical changes; notwithstanding, the presence of collaterals does not eliminate the need for treatment.

Keywords Collateral blood flow, deep venous obstruction, pressure, post-thrombotic syndrome, common femoral vein, hemodynamic effect

Introduction Post-thrombotic syndrome (PTS) can be a debilitating condition with extensive effects on quality of life.1 Annually 1–2 per 1000 adults will develop a deep venous thrombosis (DVT),2 25–56% of whom will develop PTS.1,3–6 The extent of complaints caused by PTS greatly varies; some patients show minor evidence of post-thrombotic disease on diagnostic imaging techniques, though present with severe complaints, while other patients with extensive disease visible on imaging show very little to no complaints.7–10 Spontaneous recanalisation of the affected tract can probably partly explain this difference. However, a discrepancy between complaints and evidence of postthrombotic changes detected by imaging techniques such as duplex ultrasonography (DUS), magnetic resonance venography (MRV), and phlebography still persists.

Another possible explanation for this discrepancy may be the development of a network of collaterals, diverting blood flow, in patients with prolonged central venous outflow obstruction. Several studies have reported on the occurrence of such patterns and its clinical presentation in patients with pelvic deep 1 Department of Vascular Surgery, Maastricht University Medical Centreþ, Maastricht, The Netherlands 2 CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands 3 Department of Radiology, Maastricht University Medical Centreþ, Maastricht, The Netherlands 4 Department of Vascular Surgery, University Hospital Aachen, Aachen, Germany

Corresponding author: Ralph LM Kurstjens, Maastricht University Medical Centreþ, Department of Surgery, attn. C. Wittens/R. Kurstjens, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Email: [email protected]

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venous obstruction.11–15 Nevertheless, little is known about the hemodynamic implications of these collateral blood flow patterns. The aim of this study was to investigate the hemodynamic effect of collateralisation in iliofemoral deep venous obstruction.

Methodology Patient selection Patients with unilateral post-thrombotic iliofemoral obstruction who were planned to undergo percutaneous angioplasty (PTA) and stenting were approached to participate in this study. Patients who were also to receive concomitant endophlebectomy and creation of an arteriovenous fistula were eligible for inclusion as well. Exclusion criteria were venous obstructive disease in the contralateral limb, peripheral arterial disease, pregnancy, and age under 18 years. This was a medical ethical review board approved study and principles according to the 2013 revised declaration of Helsinki were followed. Extent of postthrombotic disease was assessed using DUS and MRV as described in literature.14 Intra-operative phlebography was used to confirm whether, at some point of the obstructed tract, an occlusion was present. Patients were examined pre-operatively, during which Villalta score, Clinical-Etiology-Anatomy-Pathophysiology classification (CEAP), medical history, general complaints, and presence of collaterals on the abdomen or in the groin were assessed.

Model With the patient in the supine position and under general anaesthesia, both femoral veins (FVs) were cannulated under ultrasound guidance using a 5 French sheath, and placing the tips of the sheaths in the common femoral vein (CFV). Subsequently, pressures in both CFVs were measured using a pressure monitoring set (Edwards Lifesciences LLC, Irvine, CA, USA) attached to either an IntelliVue MX800 or an IntelliVue MP30 patient monitoring system (Philips Medical Systems, Best, The Netherlands). Next, a catheter was placed in the inferior vena cava (IVC), just proximal from the iliac confluence, to also measure pressure proximal from the obstruction. Following pressure measurements, the obstructed tract was recanalised as described before.16 When the postthrombotic tract was passed, a balloon catheter was placed over the iliac confluence into the contralateral external iliac vein, and a 16 mm40 mm non-compliant balloon (Maxi LD, Cordis/Johnson & Johnson, Warren, NJ USA) was inflated. A small amount of contrast was injected through the sheath in the control limb to assess whether the vein was fully occluded by the

Figure 1. Sudden balloon occlusion test. A 16 mm40 mm non-compliant balloon is inflated in the external iliac vein of the control limb and a small amount of contrast is injected to check for complete obstruction.

balloon (Figure 1). While the balloon was inflated, pressure was continuously measured in the CFV, distal from the balloon. The balloon occlusion test was ended when pressure remained stable for at least ten seconds.

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Figure 2. Occlusive and non-occlusive post-thrombotic disease. (a) Example of occlusive post-thrombotic disease. (b) Example of what we defined as occlusive disease, though minute flow is seen in the occluded tract. (c) Example of non-occlusive post-thrombotic disease with flow in a recanalised iliac tract.

Statistical analysis and definitions IBM SPSS statistics version 21.0.0.0 (IBM Corporation, Armonk, NY, USA) was used for statistical analysis and graphs were created using GraphPad Prism version 5.04 (GraphdPad Software, San Diego, CA, USA). Since most parameters are not normally distributed, continuous variables are described as median values with concomitant range and Wilcoxon signed rank test was used to test for statistical differences. A sub-analysis was performed for diseased limbs with only occlusive postthrombotic changes and control limbs that showed no collateral flow on phlebography during the sudden balloon occlusion test. Post-thrombotic tracts that showed either no or minute flow of contrast, passing the obstruction far slower than the diverted collateral flow, were defined as occlusive (Figure 2). PTS according to the Villalta scale is presented as follows: no PTS (score 0– 4), mild PTS (score 5–9), moderate PTS (score 10–14), severe PTS (score  15 or presence of an ulcer).1

Results Fourteen patients were included for analysis. Median age was 42 years (23–65) and 12 patients were female.

Median duration of complaints was 5.3 years (1.3– 42.9). Seven of the fourteen patients had a history of previous venous interventions, five of whom were treated for superficial incompetence, one had occluded bypasses from the left profunda femoral vein (PFV) to the left common iliac vein and the left PFV to the IVC, and the last had a patent DePalma bypass from left to right. In eleven cases post-thrombotic disease extended below the femoral confluence, five of which involved both the PFV and FV. Severity of PTS according to the Villalta scale was mild, moderate, and severe in seven, four, and three diseased limbs, respectively. Two control limbs were classified with mild PTS according to Villalta. Six diseased limbs showed a C-classification, according to CEAP, of 3, five a C-class of 4–6, and three a C-class lower than 3, though all suffered from significant venous claudication, which is not reflected in CEAP or Villalta. Control limbs all showed a C-class of lower than 3. Eleven out of fourteen patients presented with abdominal wall collaterals (Table 1). Median pressure in the CFV of diseased limbs was 17.0 mmHg (4.0–31.0 mmHg) compared to 12.8 mmHg (2.0–24.0 mmHg) in controls (p ¼ 0.001) (Figure 3). Median difference in pressure between the IVC and

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Table 1. Patient characteristics. Patient characteristics (n ¼ 14) Median age (years, range) Sex (M/F) Median BMI (kg/m2, range) Median duration of complaints (years, range) Venous claudication History of previous venous interventionsa Superficial collateral abdomen/groin Post-thrombotic segments in diseased limb CIV–CFV PFV FV PFV and FV

42 2/12 26.7 5.3 14 7 11

(23–65) (14.3%/85.7%) (19.4–37.6) (1.3–42.9) (100%) (50.0%) (78.6%)

14 (100%) 5 (35.7%) 11 (78.6%) 5 (35.7%) Diseased limb

Highest C of CEAP C0 C1 C2 C3 C4a C4b C5 C6 Villalta scale No PTS Mild PTS Moderate PTS Severe PTS

1 (7.1%) 2 (14.3%) 6 (42.9%) 2 (14.3%) 1 (7.1%) 1 (7.1%) 1 (7.1%) 7 (50.0%) 4 (28.6%) 3 (21.4%)

Control limb 2 5 3 4

(14.3%) (35.7%) (21.4%) (28.6%) -

12 (85.7%) 2 (14.3%) -

CFV: common femoral vein; CIV: common iliac vein; FV: femoral vein; PFV: profunda femoral vein; PTS: post-thrombotic syndrome. a Only two of these patients had a history of previous deep venous interventions: one had a bypass from the left PFV to the left CIV and from the left PFV to the IVC, which were both occluded, and the other had a still patent DePalma bypass from left to right.

CFV was 3.8 mmHg (–2.0–19.0 mmHg) in diseased and 1.0 mmHg (–6.0–2.0 mmHg) in control limbs (p ¼ 0.001). After balloon occlusion of the EIV in the control limb, CFV pressure significantly rose to a median pressure of 23.5 mmHg (7.0–66.0 mmHg) (p ¼ 0.001) (Figure 4). Compared to diseased limbs, control limbs with sudden balloon occlusion showed a significantly higher pressure (p ¼ 0.009) (Figure 5, Table 2). After contrast injection to check for complete balloon occlusion, phlebography in one patient revealed a collateral vein bypassing the balloon occlusion in the control limb (Figure 6). Intravenous pressure in this patient changed from 1.0 mmHg at the moment right before occlusion to 7.0 mmHg after balloon occlusion. Based on phlebography, two of the postthrombotic limbs did not have an occlusion at any

point of the obstructed tract. Results did not significantly change after performing a sub-analysis without the aforementioned limbs.

Discussion This study shows that supine CFV pressure is significantly increased in limbs with chronic deep venous iliofemoral obstruction, compared to healthy control limbs. Although pressure measurements have been extensively performed in the past, little has been reported on CFV pressure in relation to PTS. Recent insights, however, suggest that dorsal foot vein pressures, as have been measured in the past, do not reflect the severity of iliofemoral deep venous obstruction as well as CFV pressures.17

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Figure 3. Common femoral vein pressure in post-thrombotic and control limbs.

Figure 4. Common femoral vein pressure before and after sudden balloon occlusion in control limbs.

Neglen et al.12 did measure CFV pressures and reported a mean pressure of 12 mmHg (5–25 mmHg), which is comparable to what we found in control limbs. Comparison with their control limbs is not possible though, since they did not report on those pressures. Furthermore, our study included a large number of patients with occlusive disease, which was not the case in the aforementioned study. Neglen et al. reported on a broad range of obstruction, varying from 0 to 99% stenosis, which may explain the higher pressures in our study. Another study that already reported on CFV pressures in these types of patients was that of Delis et al.18 They reported a median pressure of 8 mmHg (7–10.5 mmHg) in post-thrombotic limbs, which was lower than both diseased and control limbs in our

study. However, comparison between pressures in control limbs is not possible, since they did not report on this. Additionally, more than half of the measurements were obtained by testing patients undergoing bilateral recanalisation, which could have confounded results, and occlusive disease was again more prevalent in our study, potentially explaining why our study yielded higher pressures in both control and diseased limbs. Hemodynamic changes can also be expressed by measuring pressure gradients over the obstructed tract, which has been previously done by Hurst et al.19 They described a mean pressure gradient of 5.6  3.6 mmHg in a similar population size, though only seven patients showed post-thrombotic changes. Six patients had an acute DVT and five patients

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Figure 5. Common femoral vein pressure: post-thrombotic limbs versus sudden balloon occlusion in control limbs.

Table 2. Pressure measurements.

Diseased limbs (n ¼ 14) Control limbs (n ¼ 14)

Pressure CFV

Pressure gradient IVC–CFV

After balloon occlusion

17.0 (4.0–31.0) 12.8 (2.0–24.0)

3.8 (–2.0–19.0) 1.0 (–6.0–2.0)

– 23.5 (7.0–66.0)

All values are presented as median with range in mmHg. CFV: common femoral vein; IVC: inferior vena cava.

suffered from iliocaval compression without acute or chronic thrombotic changes. Pressure gradient was measured over the obstructed tract, though exact locations were not given and do not seem to be consistent. Despite these differences, though, ranges of measured pressure gradients were similar in our study. To our knowledge, sudden occlusion tests akin to ours have not been performed in the past. Notwithstanding, the importance of collateral blood flow has been suggested in several studies. Neglen et al.12,13 published two papers in which they stated that up to 78% of post-thrombotic limbs showed collateralisation on venography. After PTA and stenting, 72% of those limbs did not show collateral veins on phlebography anymore. In 17% of the limbs collateralisation was less evident and in only 11% collateralisation patterns remained unchanged. This vast reduction clearly illustrates the importance of collateral blood flow in deep venous obstruction. The significantly lower pressure in chronic obstructions compared to the acute balloon occlusion test, as seen in our study, shows that collateral blood flow limits the pressure increase caused by the obstruction and can therefore assist in lower limb venous outflow, which is further illustrated by the high number of patients with abdominal wall collateralisation in this study. These results were obtained from patients in

the supine position under general anaesthesia though. Differences in pressure between control and diseased limbs are likely to be even more profound during ambulation, and the effect of collaterals may be even more significant. The patient in whom a collateral vein spontaneously appeared on phlebography after balloon occlusion further exemplifies the importance of collateral flow. Contrast was washed away with an almost normal speed via a direct bypass around the vein segment where the balloon was inflated. At first we suspected that the balloon was not fully inflated or that the preexistent collateral system resulting from the chronic obstruction in the contralateral limb was used as an alternative pathway. Phlebography in a lateral plane, however, showed that blood flow was diverted via a collateral vein on the ipsilateral side. The minor pressure increase of 6 mmHg during the occlusion test corroborates the hypothesis that development of adequate collateral flow can reduce the hemodynamic effects of deep venous obstruction. Interestingly, the results of the balloon occlusion test might help explain the more striking acute clinical signs of a DVT, compared to PTS. In PTS, collaterals develop over time and the extent of the collateral network may relate to the clinical presentation and could thus explain the discrepancy often noticed between

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Figure 6. Spontaneous collateral vein after sudden balloon occlusion in a control limb. (a) Anterior plane, (b) lateral plane.

complaints and the degree of iliac vein obstruction. This appealing theory should however be substantiated by assessing the quantitative effect of collateral blood flow on complaints in PTS patients. Conversely, it should not be concluded that the presence of collateralisation implies that these patients should not be treated. Intravenous pressure in limbs with chronic obstruction was still significantly higher than in control limbs, and treatment of such patients has shown positive results in the past. In this study we only tested patients with sufficient complaints, warranting an intervention, though future research should include patients with post-thrombotic deep venous obstruction and little to no complaints. Following these results, it might be postulated that collateral flow patterns already in place due to the postthrombotic obstruction on the contralateral side can exhibit reversed flow due to the sudden occlusion in the control limb, influencing results of the sudden

balloon occlusion test, yet no evidence of this was present during phlebography. Furthermore, two control limbs suffered from mild PTS according to the Villalta scale, though on DUS, MRV, and phlebography no evidence of venous obstruction was found in the control limbs of these patients. It is known, though, that in patients with PTS the Villalta scale can suggest PTS in healthy contralateral limbs.20 In conclusion, this study shows that pressure in the CFV is significantly increased in clinically significant post-thrombotic iliofemoral obstruction, but that a sudden occlusion in a healthy CFV leads to an even higher pressure. The latter difference explains the importance of collateralisation in deep venous obstruction and substantiates the theory that adequate collateral blood flow can prevent severe complaints in patients with extensive post-thrombotic disease; notwithstanding, the presence of collaterals does not eliminate the need for treatment.

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Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest None declared.

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Hemodynamic significance of collateral blood flow in chronic venous obstruction.

Complaints related to the post-thrombotic syndrome do not always correlate well with the extent of post-thrombotic changes on diagnostic imaging. One ...
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