Hemodynamic changes in iliofemoral disease

Abstract

Background

Iliofemoral venous obstruction, caused by post-thrombotic disease, can be treated by percutaneous angioplasty and additional stenting with good results. However, no hemodynamic parameter determining the need for treatment has been defined. This article describes the preliminary results of a study investigating the pressure changes occurring in post-thrombotic deep venous obstruction.

Methodology

Four patients with post-thrombotic deep venous obstruction of the iliofemoral tract were identified. Intravenous pressure was pre-operatively measured in the common femoral vein and in a dorsal foot vein bilaterally. During these pressure measurements patients were asked to walk on a treadmill with a speed of 3.2 km/h and a zero per cent slope, with the slope increasing two per cent every two minutes.

Results

Four patients (two male, two female) with age varying from 23 to 40 were identified. In two patients, disease extended below the femoral confluence. Pressure in the dorsal foot vein was not notably different between the affected and the control side. Pressure in the common femoral vein was markedly higher in post-thrombotic limbs compared to the control limb, with ambulatory pressure increasing more in post-thrombotic limbs.

Conclusions

These preliminary results are highly illustrative for the hemodynamic effect of iliofemoral deep venous obstruction due to post-thrombotic disease, even though sample size is admittedly limited. Furthermore, these results suggest that pressure measurements of the common femoral vein, and not the dorsal foot vein, might be able to identify a significant outflow obstruction due to post-thrombotic disease, though further inclusion of patients is necessary.

Keywords

Deep venous obstruction post-thrombotic syndrome hemodynamic changes intravenous pressure common femoral vein dorsal foot vein venous claudication treadmill stenting

Background

Every year about one per 1000 people in Western European countries develop deep venous thrombosis (DVT).¹ In circa 40% of these DVTs the iliofemoral tract is affected, which leads to a complete outflow obstruction of the affected leg.² After a DVT develops, the human body tries to resolve the blood clot and thus recanalises the blood vessel. In about 70% of the cases where the iliac tract is involved, the recanalisation process is unsuccessful and scarring of the blood vessel occurs.³ This residual obstruction can lead to clinical signs and symptoms of venous disease, and is then classified as post-thrombotic syndrome (PTS).^4,5

One of the most debilitating symptoms associated with PTS is venous claudication, which is described as pain during activity that occurs when venous outflow is diminished in such a way that arterial inflow cannot be properly drained. Venous tension rises, leading to pain.⁶ Unlike arterial claudication, the pain generally does not subside when standing still, meaning patients usually need to sit or lie down and elevate the leg to help drain the excess blood out of the limb.

In the past, PTS was generally treated via a combination of compression stockings and mobilisation. However, during the last decade percutaneous angioplasty (PTA) and stenting have been introduced for the treatment of deep venous obstructions. Today PTA and stenting is generally accepted as the first line of treatment in eligible patients with a significant improvement of quality of life and clinical signs and symptoms as a result.⁷ Technical success can be reached in most cases with follow-up up to 72 months showing a primary patency of 50–80%, an assisted primary patency of 76–82%, and a secondary patency of 82–90%.^7–9 Fortunately, no decreased quality of life has been reported if technical success was not established.

However, no clear indication for stenting has been defined. The decision to stent is now made based on patient history, combined with clinical signs and the extent of disease identified with duplex ultrasonography, magnetic resonance venography (MRV), computed tomography venography (CTV), intravascular ultrasonography (IVUS) and/or venography.^10–12 There is no hemodynamic parameter that can be relied upon to assess the need for treatment, nor can be predicted what patients will benefit from stenting.

The aim of the on-going study is to objectify the pressure changes that occur in post-thrombotic iliofemoral deep venous obstruction; this article describes its preliminary results.

Methodology

This article describes four patients who have undergone pressure measurements in combination with a treadmill stress test. These four patients were identified from the treadmill pilot study, currently running in our centre. The medical ethical committee approved this study and principles according to the declaration of Helsinki were followed.

Subjects

Subjects were recruited from our tertiary, specialised, outpatient clinic. All patients with an iliofemoral deep venous obstruction of post-thrombotic nature and an indication for unilateral stenting were approached. Exclusion criteria were deep venous obstruction of the contralateral limb, post-thrombotic changes or compression of the inferior vena cava, peripheral arterial disease, pregnancy, life expectancy of less than six months, and patients younger than eighteen years of age. Patients requiring an endophlebectomy with concomitant placement of an arteriovenous fistula (AV-fistula), in addition to PTA and stenting, were also included in this study.

Pressure measurements

Before treatment, pressure was bilaterally measured intravenously in a dorsal foot vein and at the level of the common femoral vein. For pressure measurements in the common femoral vein, a 4 French sheath was placed under ultrasound guidance. The primary goal was to place this sheath just above the saphenofemoral junction, though this was not possible in all cases due to extensive post-thrombotic disease at that level. In those subjects, the sheath was placed as close as possible to the obstructed tract that was going to be treated. Sheath placement on the contralateral side was performed for control measurements and done at the same level as in the affected limb. Pressure was also measured in one of the arm veins as a control.

Treadmill test

Following the placement of the cannulas, pressures were measured in supine and erect position. After obtaining these values, a provocation test on a treadmill was performed with pressure measurements still running. The treadmill was set to a speed of 3.2 kilometres per hour with a starting inclination of zero per cent, which was increased every two minutes by two per cent. Subjects were asked to notify the investigator when they started feeling pain in their leg during walking. This time point was noted, after which the subject was asked to continue walking until he or she felt they could no longer continue walking due to the pain. At 26 minutes, the treadmill was running for two minutes at the maximum inclination. If subjects reached that point, the test was stopped. The investigator did not motivate subjects during this test.

Results

Four subjects, two male and two female, have undergone the treadmill test. Patient characteristics are displayed in Table 1. Type of post-thrombotic disease was diverse. In one patient, post-thrombotic disease was relatively confined with a fibrotic left common iliac vein with iliac vein compression syndrome at that level. Disease extended into the external iliac vein and proximal common femoral vein, which were partly recanalised. Another patient only had a focal obstruction of the right common femoral vein, most likely caused by trauma of the vessel wall due to blood transfusion through the common femoral vein when he was a neonate. Both other patients had more extensive disease. One patient had a right iliac tract with little recanalisation and additional trabeculations down until the popliteal vein. The other patient had a fibrotic left iliac tract with a partly recanalised common femoral vein and disease extending until the popliteal vein with partial recanalisation (Figures 1 –4).

Figure 1.

Phlebography patient #1.

Figure 2.

Phlebography patient #2.

Figure 3.

Phlebography patient #3.

Figure 4.

Phlebography patient #4.

Table 1.

Patient characteristics.

	Patient #1	Patient #2	Patient #3	Patient #4
Sex	Female	Female	Male	Male
Age (years)	23	24	40	29
BMI (kg/m²)	19.4	32.7	22.2	27.2
Affected side	Left	Right	Left	Right
Duration of complaints	17 months	18 months	36 months	36 months
Venous claudication	During sports	During walking, action radius variable	During walking, action radius 5000 metres	During walking, action radius 1000 metres
History of venous interventions	None	None	Endovenous treatment of GSV bilaterally, surgical redo GSV bilaterally, SCT bilaterally	None
Villalta score	7	11	8	6
VCSS	5	8	9	9
C of CEAP	0	1, 3	1,2,4a	2,3,4a
VAS pain	1.5	8.2	3.2	7.0

GSV: great saphenous vein; SCT: sclerocompression therapy; VCSS: venous clinical severity score; VAS: visual analog scale.

Pressure results are given in Table 2. Except for the pressures at the dorsal foot vein in erect position, absolute values of the various pressures appear to be variable; in diseased limbs as well as control limbs (Figure 5–6). The pressure differences between the lowest measured ambulatory pressure and the highest measured ambulatory pressure show that pressure difference at the common femoral vein is higher in all four patients, compared to the control limb. This finding was not confirmed by pressure changes in the dorsal foot vein. In patient number two, pressure in the dorsal foot vein actually increased more in the control limb and in patient number four pressures were about the same on both sides. In patient number one pressure measurements in both dorsal foot veins were lost during ambulation due to a technical failure. Pressure of the common femoral vein at the diseased side steadily increased in patient one and three, though fluctuated more in patient two and four with an initial increase in pressure, after which the pressure dropped, followed by a continued fluctuation in increase and decrease (Figure 5).

Figure 5.

Pressure change in the dorsal foor vein (DFV).

Figure 6.

Pressure change in the common femoral vein (CFV).

Table 2.

Intravenous pressure results (mmHg).

	Patient #1		Patient #2		Patient #3		Patient #4
	Diseased	Control	Diseased	Control	Diseased	Control	Diseased	Control
DFV supine	9.5	7.0	19.5	19.5	13.5	7.0	29.0	18.0
DFV standing	–	81.0	89.0	89.0	92.0	87.0	101.0	98.0
Lowest DFV during ambulation	–	0.4	0.2	3.5	28.5	13.7	40.3	38.1
Highest DFV during ambulation	–	55.9	25.0	33.4	58.2	54.6	53.9	51.7
Pressure rise DFV during walking	–	55.5	24.8	29.9	29.7	40.9	13.6	13.6
CFV supine	12.0	10.0	19.0	33.5*	22.0	2.5	27.5	25.0
CFV standing	46.5	8.5	44.0	34.0	71.0	48.0	79.0	19.0
Lowest CFV during ambulation	36.5	4.7	42.4	21.2	75.4	48.6	77.3	14.9
Highest CFV during ambulation	96.1	13.6	69.7	31.3	114.1	56.7	91.7	20.4
Pressure rise CFV during walking	59.6	8.9	27.3	10.1	38.7	8.1	14.4	5.5

DFV = dorsal foot vein, CFV = common femoral vein

difficult to interpret, sheath control side caught against valve or vessel wall

All patients reported pain while walking during the treadmill test. Patient two already developed pain after one and a half minute and patient four developed pain after five minutes, while the other patients developed pain at thirteen and a half and eighteen and a half minutes. Intravenous pressure changes of the common femoral vein at that point were not notably higher in patient two and four though. Patient one stopped at 22 minutes, patient two at fourteen minutes, and patient four at seven minutes, while patient three completed the test without stopping. At that moment, pressure reached a peak for patient one. Pressure in patient two was actually decreasing at the moment and in patient four pressure was relatively steady below the earlier reached maximum pressure.

In supine position, absolute pressure values also varied between patients. Pressure of the common femoral vein in the control limb of patient two was 33.5 mmHg in supine position, though with periods of considerable fluctuation and peaks up to 90 mmHg. A day later, during the intervention, pressure was measured again, and turned out to be 11 mmHg.

Control measurement of an arm vein in erect position showed a pressure of 14 mmHg in patient one, 37 mmHg in patient two, 39 mmHg in patient three and 32 mmHg in patient four. Arm vein pressures remained relatively stable during the treadmill test with no clear trend in increasing pressure.

Discussion

These results exemplify how extensive post-thrombotic disease can become, even though the population size is still limited at the moment. In all patients the pressure at the common femoral vein (CFV) in erect position was considerably higher in the post-thrombotic limb compared to the contralateral side. Even in supine position, when pressures are lower due to less hydrostatic and gravitational effect, pressures between the affected and control limb were notably different. In one patient, supine pressure in the control limb was substantially higher. Because the sheath pushed up against the vein wall or a venous valve during positioning, it had to be pulled back. Due to the length of the sheath, we could only pull it back a little without luxating it. Therefore, it is likely that after mobilisation the sheath was caught against the valve or against the vessel wall again, causing a misleading measurement. Pressure measurements during the intervention the following day showed a lower supine pressure, confirming this hypothesis.

Some studies have measured intravenous pressure in the dorsal foot veins, though generally only while the patient is standing still. Neglen et al. (2007) did perform a test for ambulatory pressure measurements by measuring dorsal foot vein pressure in erect position before and after ten tiptoe movements, but only reported this as a percentage difference between the two and did not report absolute values.⁷ Looking at the different pressure curves obtained from the four patients in this study, one can determine that ten tiptoe movements cannot be directly compared to actual walking. Neglen et al. (2007) showed a drop in pressure after these tiptoe movements,⁷ which could be compared to the initial drop in pressure when starting to walk. However, these preliminary results show that after the initial drop in pressure, an increase in pressure develops. Within the dorsal foot vein, pressure at the start of movement was still not superseded, though pressure in the common femoral vein rapidly surpassed the baseline pressure before walking. This suggests that, in post-thrombotic limbs, one should address pressure changes rather as a rise than a drop.

Nicolaides et al. (1993) showed that a dorsal foot vein pressure of more than 30 millimetres mercury was linearly correlated with the risk of developing a venous ulcer.¹³ Yet, no studies have focussed on the ambulatory pressures at femoral level with reference to post-thrombotic disease. The data this study has yielded, so far, suggests that ambulant venous pressure measurements of the dorsal foot vein may not be the best indicator for venous hypertension in patients with an outflow obstruction due to post-thrombotic disease. Pressure at the dorsal foot vein did not increase consistently, while pressure in the CFV increased in all post-thrombotic limbs.

Some studies did measure pressure at femoral level in supine position during intervention, but neither compared this to a healthy control. Mean pressures were different between studies. Neglen et al. (2000) reported a mean pressure of 12 mmHg [range 5–25 mmHg]¹⁴ and Delis et al. (2007) reported a mean pressure of 8 mmHg [range 7–10.5 mmHg].¹⁵ Hurst et al. (2001) measured a pressure gradient of 5.6 ± 3.6 mmHg,¹⁶ though it was not completely clear over what specific trajectory the pressure gradient was measured and some patients only showed iliac vein compression without post-thrombotic changes. Supine femoral pressures in this study were also different, suggesting that reference values should be based on individual pressure changes rather than absolute pressure values.

In all patients, pressure in the CFV on the control side remained reasonably stable during walking, with two patients showing an initial drop in pressure. Nevertheless, in two patients this stable pressure was notably higher. One of these patients showed signs of iliac vein compression in the control limb on MRV, though this was not confirmed by duplex ultrasonography. Conversely, phlebography showed a collateral vein that ran from the post-thrombotic limb to the contralateral side before stenting, and changed flow direction towards the treated limb after stenting, which is suggestive for iliac vein compression also on the healthy side and could explain the increase in pressure on this side. The other subject who showed an increase in pressure in the control limb had a focal post-thrombotic lesion in the common femoral vein, which was initially missed on MRV. Although this lesion did not have direct clinical consequences, it might be the cause for the relatively high pressure in the contralateral control limb.

Another notable difference between the pressure curves was that two of the four curves in the diseased limb showed a constant increase in pressure, while the other two had a more fluctuating pattern with maximum pressure being reached long before the patient had to stop walking due to the pain. This might be explained due to the fact that, in these two patients, the obstructed tract was partially recanalised, while both other patients had an (near) occluded fibrotic common iliac vein. Pre-operative phlebography showed some amount of blood flowing through the iliac tract towards the inferior vena cava in patient two and some blood flowing through the obstructed tract of the common femoral vein in patient four. Hence, we believe that, due to the post-thrombotic changes, the amount of blood using this route might oscillate, causing a fluctuation in intravenous pressure distal from this obstructed tract.

Pressures, at the moment of the occurrence of pain during the treadmill test and pressures at the moment of stopping the stress test did not show a pattern. Alternatively, it is hard to determine a pattern in such a limited sample size. Conclusions can therefore not be drawn at the moment, and more patients need to be included into this study before we can hypothesise about pressure values during these moments, especially the differences in ambulatory dorsal foot vein pressures, probably also influenced by concomitant other obstructive and incompetent venous problems in the leg.

Conclusion

The preliminary results of this study are highly illustrative and promising due to the vast difference between intravenous pressures at the common femoral vein in patients with outflow obstructions due to post-thrombotic disease and control limbs, even though the sample size is admittedly limited.

Subsequently, these results suggest that pressure measurements at the level of the common femoral vein, and not the dorsal foot vein, might be able to identify a significant outflow obstruction due to post-thrombotic disease, but further inclusion of patients should determine whether this will be of clinical relevance.

Footnotes

Funding

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

Conflict of interest

All the authors have no conflict of interest and nothing to disclose.

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