Abstract
The investigation of patients with severe chronic venous insufficiency (CVI, C3–C6) represents a challenge that requires the understanding of venous pathophysiology and a multidisciplinary approach; it should be aimed to assess valve function, evaluate the haemodynamic significance of obstruction and assess the function of the vein-muscle pump. Combining haemodynamic tests and imaging techniques best accomplish the investigation of these three aspects of the pathophysiology in CVI. The information obtained from ambulatory venous pressure and color duplex ultrasound is accurate when assessing reflux in the different segments of the different venous systems. The valve anatomic location and dynamic picture is supplied by descending phlebography. In case of venous obstruction, the haemodynamic tests lack accuracy and sensitivity. Therefore, imaging catheter techniques have to fill-in to depict vein morphology as well as inflow/outflow characteristics. The participation of several specialties in the investigation of these patients widens the treatment possibilities by identifying those who may benefit from advanced surgical and/or endovascular procedures. This interventional-targeted approach should be a centralized function.
Keywords
Introduction
Patients with chronic venous insufficiency (CVI) and leg ulceration constitute a serious medical and social problem. Generally, the prevalence of venous leg ulcers is reported to be 0.1–1.0%.1–3 The total direct annual cost of treatment of venous leg ulcers in Sweden has been estimated to €73 million, based on a prevalence of 0.3%. 4 In the UK the cost is between 400-£600 million per year. 5
Etiologically patients can suffer from primary venous insufficiency (PCVI) of unknown origin but where familial disposition plays a role. The defective venous valves in this group of patients often are amenable for repair. In secondary insufficiency (SCVI) valve leaflets have often been damaged after an episode of deep venous thrombosis (DVT), making surgical repair impossible. Venous valve destruction and insufficient recanalization occur during both the acute inflammatory phase of thrombosis and during the re-absorption of the thrombi; which in turn may lead to venous reflux and/or outflow obstruction. The serious clinical consequences of this process are leg ulceration and/or venous claudication experienced by at least 15% of patients with SCVI.
The pattern of spontaneous recanalization after DVT varies according to the affected anatomical segment as shown by color duplex ultrasound (CDU) studies. While recanalization occurs in up to 90% of the femoropopliteal veins after one year, this is rarely the case (<5%) after iliofemoral thrombosis. Persistent, chronic venous outflow obstruction in the iliofemoral veins leads to the development of venous claudication in about 43% of these patients.6,7
Patients with chronic venous disease present with a variety of symptoms and signs that range from varicose veins to leg ulcer. The severity of the clinical symptoms, the aetiology, the anatomical affected segment/system and the pathophysiology of chronic venous disease of the lower extremities can be put into the framework of the CEAP (clinical, aetiological, anatomical and pathological elements) classification. 8
The investigation of these patients should be aimed to assess valve function and to evaluate the haemodynamic significance of obstruction and the function of the vein-muscle pump. Combining haemodynamic tests and imaging techniques best accomplish the investigation of these three aspects of the pathophysiology in CVI.
The combination of haemodynamic measurements supplemented by targeted imaging techniques should not only elucidate whether there is reflux, obstruction or both. But it also should provide enough information to generate a therapeutic scheme for the individual patient.
The options of treatment for CVI have expanded in the last decades further than superficial/perforator surgery and compression therapy. Reconstructive deep venous surgical and endovascular techniques have at special centres become a real alternative for selected cases. The selection of patients amenable to venous valve reconstruction and/or recanalization and stenting of chronic deep vein occlusions demands accurate and targeted work-up. A large number of venous functional and haemodynamic measurements can be found in the literature. The topic of contrast imaging modalities is not addressed as much. Each vascular unit dealing with CVI should make the choice of tests to be included in the work-up. The ready availability of a vascular laboratory and the collaboration among specialties like interventional radiology, haematology and vascular surgery seem necessary to achieve the best work-up and treatment modality for CVI patients. Full understanding of venous pathophysiology is necessary to interpret haemodynamic tests and contrast imaging examinations. The aim of this chapter is to present an interventional targeted approach when investigating patients with this condition.
Haemodynamic methods
Ambulatory venous pressure
This measurement is still considered the reference standard in the assessment of global reflux, function of the veno-muscular pump and the severity of venous hypertension. The test is performed by inserting a 21-gauge ‘butterfly’ needle into a vein in the leg and connected to a pressure transducer, a pressure monitor and a recorder (Figure 1). Cannulation of dorsal foot veins should be avoided due to the possibility of falsely normal values caused by functioning valves at the ankle level. At upright position the patient takes support onto a frame. At rest, the distance between the heart level and the cannulation site determines the recorded venous pressure. The patients then perform a standardized ‘walking on the spot’ exercise. The mean venous pressure recorded when the curve flattens at the end of this exercise indicates the ambulatory venous pressure (AVP). Normally, the pressure drops to below 30 mmHg. The measurement is then repeated after selective occlusion of the superficial veins. A 30 cm wide pneumatic tourniquet is placed around the thigh and inflated to 60 mmHg to occlude the long saphenous and other superficial thigh veins. The short saphenous vein may be occluded with a rubber tourniquet. By selectively occluding the superficial segments it is possible to identify the incompetent venous system (i.e. either the long or short superficial saphenous veins or the deep system) (Figure 1).
(a) Vein pressure recording setup, (b) Typical superficial vein pressure curves at rest and during walking in subjects with no venous insufficiency (normal), superficial and deep venous insufficiency, and venous outflow obstruction. Note that dorsal foot vein is not cannulated.
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Pt, pressure transducer; PM, pressure monitor; A/P, ambulatory venous pressure
AVP measurement provides the following information: pressure drop during exercise, ambulatory pressure and recovery time, which is the time taken from cessation of the step test until the resting pressure level is reached.
High levels of AVP are directly associated to the risk of developing a leg ulcer as shown in Figure 2.
The direct relation between high levels of ambulatory venous pressure and the risk of developing ulceration has been well documented for years. Modified from Nicolaides et al.
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Colour duplex ultrasound
Colour duplex ultrasound (CDU) is used to evaluate axial reflux in the different anatomical segments of each venous system. The examination is performed with the patient standing, weight bearing primarily on the contralateral limb. A 12-cm wide pneumatic cuff is placed distally to the segment to be examined, and connected to a venous compression unit, which enables very fast (<0.2 seconds) inflation and deflation. The inflation pressure is adjustable, and set at 150 mmHg. The venous compression unit ensures a standardized repeatable venous reflux procedure (inflation of the cuff, sustained for 3 seconds and then deflated), which in our opinion to a larger degree mimics venous reflux than the commonly used Valsalva manoeuvre. The latter method may miss distal venous incompetence, which is masked by a competent proximal valve, and in some elderly patients the effort applied to the manoeuvre is reduced because of fear of incontinence.
Five and 10 MHz ultrasound probes are used to detect venous reflux. A valve closure time >0.5 seconds is defined as pathological. Although there are recent reports in the literature suggesting that the peak reflux velocity correlates better with the severity of venous insufficiency, valve closure time is more widely used. 9
In addition, CDU can detect obstruction in the different vein segments and give some indication of vein wall thickness and intraluminal fibrosis.
Patients with a history of previous DVT, a coagulation disorder, and clinical symptoms suggesting venous obstruction such as venous claudication, oedema and ulcer should be further investigated.
Venous occlusion plethysmography
Venous occlusion plethysmography is performed to exclude persistent venous outflow obstruction by using an air Plethysmograph. In the recumbent position, venous occlusion and recording cuffs are applied proximally to the patella and at the calf, respectively. An occlusive cuff pressure of 50 mmHg is maintained for one minute. This permits uninhibited arterial flow into the limb, while the venous outflow is compromised, resulting in an increased leg volume. On decompression of the thigh cuff, the leg volume decreases rapidly when the venous outflow is normal. In case of the presence of a functional venous obstruction, the leg volume will decrease slowly.
Venous pressure gradient
Venous pressure gradient obtained by comparing venous pressure measurements before and after a reactive hyperemia test of the lower extremity. An inflatable tourniquet is applied to the thigh, and venous pressure is recorded in a superficial leg vein. With the patient in supine position, a basal measurement is done. The thigh tourniquet is then inflated to 300 mmHg of pressure and sustained for three minutes. After releasing the tourniquet, reactive hyperemia increases arterial flow and thus venous outflow. A venous pressure increase above 8 mmHg may indicate an outflow obstruction. 11
The information obtained from AVP and CDU is accurate when assessing reflux in the different segments of the different venous systems. The valve anatomic location and dynamic picture is supplied by descending phlebography.
In case of venous obstruction the haemodynamic tests lack accuracy and sensitivity. Therefore, imaging catheter techniques have to fill-in to depict vein morphology as well as inflow/outflow characteristics.
Catheter-based imaging techniques
In this chapter, we will describe five phlebograpic techniques: Descending phlebography, ascending (‘classic’) phlebography, phlebography with popliteal, femoral and jugular access. The first and second of these are well represented in the literature; some of the others have gained less attention. Thus, we will describe our experiences with the various techniques, with special emphasis on in which clinical settings we prefer the different methods. If obstruction is suspected, we prefer to perform indirect computed tomography phlebography, to get a ‘map’ before, if necessary, performing catheter phlebography.
Descending phlebography
This is a dynamic imaging method allowing classification of the severity of axial reflux and imaging the venous valve leaflets that may be amenable to repair. Contrast medium is injected through 4-F catheter introduced in the common femoral vein, using the Seldinger technique. First an injection is done to exclude obstruction in the iliocaval segment. The patient is then tilted 60°, head upward, and dye injected during a Valsalva manoeuvre. Under fluoroscopy, the dye column is followed distally until it stops or the Valsalva manoeuvre is completed. It is graded into four categories described by Kistner grade I proximally in the thigh, grade II above the knee, grade III below the knee and grade IV to the ankle. The fluoroscopy scenes are saved with the ‘save fluoroscopy’ button and sent to the picture archiving and communication system (PACS) system. According to some reports, descending phlebography has been shown to underestimate reflux in the lower leg compared with duplex scanning12,13 (Figure 3).
Descending venography: The table is tilted 60° and the patient performs a Valsalva manoeuvre. In sequence I, a primary CVI case showing reflux grade and valves amenable to repair. In sequence II a secondary CVI case. Because many patients are young, we use as little radiation exposure as possible. This is the reason for reduced ‘sharpness’
Ascending ‘classic’ venography
This old technique is preferred method for diagnosing DVT, but during the last decade, has to a large degree been replaced by compression ultrasound in this clinical setting. In the evaluation of CVI, we use the ‘classic’ phlebography when we are in doubt as to the quality of the calf veins or the popliteal vein. Ascending phlebography remains essential to display anatomical abnormalities found in some post-thrombotic limbs that are not associated with reflux. 14
The technique is really not catheter-based, but is described here for the sake of completeness. A large number of different techniques have been described in the literature. A small needle is inserted into a vein on the dorsal side of the foot. A tourniquet is applied in the ankle region to ‘force’ the contrast into the deep venous system. Contrast is injected while the patient is in a semi-upright position. Flow is monitored with fluoroscopy and films obtained at appropriate moments as the veins are filled.
Phlebography with popliteal access
This is performed by using ultrasound and fluoroscopy guidance. In an angiographic suite and with the patient prone, access is obtained in the popliteal vein, using a ‘micro puncture’ set. Over a 0.035 wire, a 5-F sheath is introduced. Contrast medium (150–300 mg I/mL) is injected and images are obtained at one frame per second. In this way, a precise delineation of the popliteal and femoral vein is possible. If major post-thrombotic, obstructive lesions are present in the femoral vein, the contrast (and blood) usually follows either collaterals to the great saphenous vein or to the deep femoral vein (axial transformation of the deep femoral vein).
Optimal visualization of the common femoral vein is crucial for planning optimal endovascular and/or surgical treatment. If major post-thrombotic, obstructive lesions are present in the femoral vein, the common femoral vein is not adequately visualized when injecting contrast in the popliteal vein. Inflow of blood not containing contrast makes the interpretation of images even more difficult. In post-DVT cases, we catheterize the diseased femoral vein and inject contrast with the tip of the catheter in the groin region. We find it useful to ‘zoom’ in this area and take series in various medial/lateral angles. In this way ‘sharp’ films of this region are obtained, visualizing the common femoral vein, the upper part of the femoral vein, the deep femoral vein and great saphenous vein. This is crucial in order to decide where to place stents (Figure 4).
Phlebography with popliteal access, showing a duplicated popliteal and femoral vein with post-thrombotic changes distally Only with the tip of the catheter in the groin region, it is shown that the left external iliac vein is not occluded
Phlebography with tibial access
Is quite similar to the popliteal access, using ultrasound and fluoroscopy to access the posterior tibial vein in the ankle region. We use this access if color/Doppler ultrasound and ‘classic’ ascending phlebography does not give adequate information as to the quality of the popliteal vein. If adequate filling of the popliteal vein is not obtained, the tip of the catheter is placed in the popliteal vein and contrast injected.
Phlebography with femoral access
This access requires normally not ultrasound guidance and access is gained using ‘standard’ 0.035-inch equipment, similar to the technique used for descending phlebography. As the common femoral vein often is affected in post-DVT cases, this access is not often used.
If the pelvic veins are not occluded, both the ipsi- and contralateral common femoral vein can be visualized, using ‘crossover’ technique.
Phlebography with jugular access
This is performed by using ultrasound and fluoroscopy. This access is not often used in the preoperative evaluation, as the common femoral vein cannot be visualized if the iliac vein and/or the inferior vena cava are occluded. However, this access is very useful when recanalizing occluded pelvic veins and/or the inferior vena cava, especially if the common femoral vein is diseased and the distal stent has to be ‘landed’ in the deep femoral vein. Before deciding precisely where to place the stent in the common or deep femoral vein, a forceful injection through a long 7-F sheath, introduced in the right internal jugular vein, is performed. In this way, both the calibre and quality of the veins draining the extremity can be adequately assessed, helping to decide where to place the distal part of the stent.
Discussion
It is now well documented in the literature that between 40% and 50% of the venous leg ulcers is caused by superficial insufficiency alone. In our opinion, AVP and CDU findings are sufficient before these patients can be treated accordingly. The other part of patients with venous leg ulcer has a combined insufficiency involving the deep venous system. Distinguishing between PCVI and SCVI is done with the CDU examination. The majority of patients with severe symptoms such as venous claudication, skin changes and ulcer (C3–C4) belong to the SCVI group.
In patients with only reflux, the haemodynamic investigations are rather sensitive and need only to be supplemented by descending phlebography before venous valve reconstruction is considered. Patients with venous obstruction experience symptoms of venous claudication. Leg ulcer may develop in patients with obstruction only in patients with femoropopliteal reflux and high levels of AVP. There is an obvious need for more accurate haemodynamic tests to assess obstruction. Catheter-based imaging techniques seem to provide the best morphological and haemodynamic information needed before endovascular treatment for venous outflow obstruction is carried out. In cases of both obstruction and reflux, it is important to treat obstruction first to avoid exposing the venous valve reconstruction to high-pressure reflux.
We claim that the presence of supra-pubic varicosities, visible enlarged veins on the abdomen, large network of pelvic and paravertebral collaterals are signs of central obstruction and high pressure, contrasting the common attitude that the presence of collaterals represents a state of compensation. The axial transformation of the deep femoral vein and the long saphenous vein become the main venous outflow routes in the lower extremities when the femoral vein is occluded. These may provide good enough inflow for an iliac-cava recanalization. Post-thrombotic obstruction at the popliteal level is poorly demonstrated by CDU. The operative findings under endophlebectomy diverge often from the findings in the preoperative investigations.
CDU and AVP are the examinations of choice to determine outcome.
When performing catheter phlebography it is important to bear in mind several technical aspects. Combined or crossover approach may be necessary to determine inflow and outflow conditions before recanalization/stenting. The collateral network drains most of the dye. The more diseased a venous segment is, the less it will fill with contrast, precluding a complete image-based evaluation.
In order to obtain optimal visualization of the deep veins, and especially the common femoral vein, we most often prefer phlebography with popliteal access. If major post-thrombotic, obstructive lesions are present in the femoral vein, the contrast (and blood) usually follows either collaterals to the great saphenous vein or to the deep femoral vein (axial transformation of the deep femoral vein). In these cases, the common femoral vein most often is not adequately visualized when injecting contrast in the popliteal vein. Inflow of blood not containing contrast makes the interpretation of images even more difficult. Thus, in post DVT cases, we catheterize the diseased femoral vein and inject contrast with the tip of the catheter in the groin. In this way, we get ‘sharp’ films of this region, visualizing both the common femoral vein and the upper part of the femoral vein, the deep femoral vein and great saphenous vein.
In regularly scheduled multidisciplinary vein meetings the clinical findings in the patient and the result of the work-up are discussed. In this way, the treatment is chosen for the individual patient. By having this multidisciplinary approach to the diagnostics of venous disease, we have developed skills to treat deep venous reflux and obstruction with advanced techniques of reconstructive venous surgical and endovascular techniques.