Possible Impact of Hemodynamic Factors on the Development of Recurrent Reflux in Primary Varicose Veins

Summary

Definition of reflux as a centrifugal flow within an incompetent vein connecting both poles of the ambulatory pressure gradient and causing ambulatory venous hypertension is presented. Recurrent reflux occurs also after correctly performed crossectomy and stripping. Growth of new vessels (neo-angiogenesis) or dilatation of pre-existing venous channels (vascular remodelling) has been claimed to be the main cause of recurrences in these instances. Attempts to blockade the development of recurrent reflux in the groin by inserting mechanical barriers over the ligated saphenofemoral junction failed to prevent recurrences.

The synergistic effect of two hemodynamic factors – pressure difference between the femoral vein and the saphenous remnant in the thigh on one side, and the propensity to restore centrifugal flow on the other side – may play a crucial role in the development of recurrent reflux. Pressure gradient apparently triggers the event. Restoration of centrifugal flow might be the pre-programmed phenomenon that improves compromised blood supply in arterial occlusions, but evokes recurrent reflux in incompetent superficial veins. In this way, it can be explained why recurrent reflux can occur after any therapeutic procedure.

Key words:
venous reflux – recurrent reflux – pressure gradient – restoration of centrifugal flow

INTRODUCTION

Recurrence after varicose vein surgery is a common event with a wide range depending on the length of follow-up, the applied therapeutic procedure (type of surgery, sclerotherapy, endovenous ablation), the method used to diagnose recurrence (clinical observation, duplex ultrasonography, phlebography), and the comprehension of the reflux itself. Under the term „venous reflux” different sorts of venous flow have been understood. The outward component of the bidirectional flow in calf perforators continues to be regarded as reflux, eventually interpreted and reported as recurrent reflux [1–5]. On the other way, CHIVA proponents claim that drainage of venous blood from the thigh into the deep lower leg veins via incompetent saphenous remnant after ligation of the saphenofemoral junction (SFJ) is a physiological event, not a recurrent reflux [6–8]. Hence, diverging interpretations of the term venous reflux provide for misunderstanding and affect the reported recurrence rates.

This review study attempts to define the venous reflux, compiles the findings concerning recurrent reflux from the references, and comments on attempts focussed on prevention of recurrences. The possible role of two hemodynamic factors is discussed – the pressure gradient between the femoral vein and the saphenous remnant (or another incompetent vein) in the thigh, and the propensity to restore centrifugal flow in incompetent veins. These hemodynamic factors obviously play a significant part in the process leading to varicose vein and reflux recurrence.

REFLUX DEFINITION

Reflux is the most important hemodynamic factor in primary varicose veins. Physiologically, venous flow is directed toward the heart. Centrifugal flow, i.e. in the opposite direction toward the periphery is a pathological phenomenon. In the clinical praxis, reflux is usually diagnosed in a segment of a superficial or deep vein without bearing in mind that it comprises, being a flow, not only a reflux-carrying channel, but also a source and a mouth, and that a pressure difference exists between both these points. It is a similar situation as in electricity: tension and a conductor are necessary for the current to occur. Reflux was claimed to develop in any vein without an apparent feeding source [9], or in tributaries of the great saphenous vein (GSV) [3, 10]. Putative reflux in incompetent calf perforating veins was supposed to play, among other factors, a substantial role in worsening chronic venous insufficiency [11].

Lack of agreement upon fundamental features of venous reflux promotes confusion; consensus on definition of reflux is necessary to avoid misinterpretations. The definition of reflux may be expressed as follows:

Venous reflux in the lower extremity is a centrifugal flow of blood within an incompetent venous channel connecting both poles of the ambulatory pressure gradient. The higher pole of the ambulatory pressure gradient lies in the thigh vein, the lower pole in the lower leg vein. Reflux takes place during relaxation of the calf musculature and stops as soon as the ambulatory pressure gradient is equalized.

Reflux causes ambulatory venous hypertension, the degree of which depends on the intensity of retrograde flow expressed in ml/s.

Reflux stops as soon as ambulatory pressure gradient is equalised.

The hydrostatic pressure per se does not release fluid flow; therefore, there is no reflux in quiet standing with relaxed calf musculature [12, 13]. The potential for centrifugal flow in the lower extremity arises during calf pump activity: hydrostatic venous pressure drops in the veins of the lower leg and foot, but in contrast with this, it remains uninfluenced in deep veins of the thigh [14, 15]. The pressure difference arising in this way between the veins of the thigh and the lower leg reaches about 37 mm Hg; it has been called ambulatory pressure gradient [16]. It forces the blood to flow in the retrograde direction; competent vein valves impede retrograde flow and ensure lower pressure in lower leg veins. However, if an incompetent venous conduit connects both poles of the pressure gradient, reflux occurs and diminishes the physiological pressure difference, causing ambulatory venous hypertension.

There is no reflux, but a bidirectional flow with a clearly prevalent inward oriented vector in calf perforating veins [17]. The outward oriented component does not cause ambulatory venous hypertension in primary varicose veins, neither in cases with incompetent calf perforators. On the contrary, the pressure in the incompetent calf perforator as well as in the adjacent superficial vein of the lower leg decreases during calf pump activity. In reality, physiological decrease in pressure occurs once the reflux in the incompetent saphenous vein has been abolished [17].

RECURRENT REFLUX

The prevalence of varicose vein recurrence following surgery varies in a wide range right up to 90% [18–21]. The majority of recurrences are associated with further reflux in the groin. Debates still exist as to the mechanism by which this occurs. Apart from disease progression inadequate surgery and technical failure at the time of the original surgery have been blamed to be the main cause of most recurrences, especially low transection of the GSV in the groin leaving behind saphenous stump with venous collaterals and with an incompetent sapheno-femoral junction, as well as failure to remove the great saphenous vein in the thigh [18–25]. Meticulous dissection of the SFJ was considered to be the sound protection from varicose vein and reflux recurrence.

GROIN RECURRENCES DUE TO NEOVASCULARIZATION

Nevertheless, groin recurrences arose after correctly performed crossectomy and stripping as well, which was documented with duplex scanning and phlebography [1, 20, 26–31]. New venous channels emanating from the femoral vein in the groin connected to incompetent superficial veins in the thigh: the theory of neovascularization emerged, and has since been considered to be the most significant cause of recurrent varicose veins.

Allegra et al. [1] reported 25% reflux recurrence in the groin documented by duplex scanning 5 years after crossectomy and stripping. Jones et al. [20] found recurrent veins in 43% after high ligation and in 25% after high ligation and stripping at two years follow-up. Most tributaries were less than 3 mm in diameter. Frings et al. [26] found reflux recurrence in 10,7 % two years after correctly performed crossectomy and stripping; tortuous reflux-carrying venous channels with an average diameter of 3.3 mm (2.5–4.8 mm) originating in femoral vein in the groin were detected by duplex ultrasonography. Fischer et al. [28] presented late results at a mean follow-up 34 years after crossectomy and stripping with a 60% incidence of recurrent reflux in the groin region. Most recurrences were depicted as strand on colour coded duplex ultrasonography; only 36% of them were clinically relevant. All but two of the recurrences that required new treatment presented single-lumen channels refluxing venous blood from the femoral vein into a superficial vein.

Two types of vessels come up in the groin in connection with recurrent varicose veins:

1. Vascular remodelling, i.e. communications arisen through dilatation of pre-existing minor veins; they are apparent as single tortuous channels with a diameter of about 3 mm; they originate from the upper part of the femoral vein and connect with an incompetent superficial vein in the thigh [18, 20, 26, 28]. They are hemodynamically relevant.
2. New veins arisen as a result of neo-angiogenesis; they have the form of a strand or tangle consisting of multiple tiny vessels; they originate at the previous SFJ and connect with the remnant of the saphenous vein or its branches [28, 32]. The hemodynamic significance of these strand-like formed channels is contestable.

IMMUNOHISTOLOGICAL FINDINGS

Geier et al. [19] presented histological criteria that differentiated between neo-angiogenesis and residual stumps or dilated preformed veins. Neo-angiogenesis is characterized by incomplete wall structure, absence of valves and nerve fibres, bizarre form of lumen, and multiple channel recurrence. Residual stump collaterals or dilated preformed veins contain three-layered wall, venous valves, and intramural nerve fibres; they form single tortuous channels. Presence of the neural marker S100 protein in immunohistological findings indicates pre-existing dilated vessels, its absence new grown vessels.

Nyamekye et al. [32] examined immunohistologically tissue blocks from the saphenofemoral region in patients operated for recurrent varicose veins and concluded that neo-angiogenesis was the principal cause of recurrent saphenofemoral incompetence. Nevertheless, he found additional communicating vessels that he described as residual missed veins. In contrast with this, El Wajeh et al. [18] found little evidence of neo-angiogenesis associated with recurrent varicose veins in the saphenofemoral region on the basis of histological and immunohistological findings; the neural marker S100 protein was present in most vessels of examined samples. No statistical difference was found between the venous recurrence group versus control group (first varicose vein operation, or operation for recurrent inguinal hernia) in respect to all histological features. The authors concluded that new veins occurring at the previously ligated SFJ represented adaptive dilatation of pre-existing venous channels, probably in response to abnormal hemodynamic forces; they postulated that development of collateral channels was the result of the pulling force from the persistent GSV, acting as a sump drain.

ATTEMPTS TO PREVENT RECURRENCES ARISING FROM NEOVASCULARIZATION. EFFECTIVENESS OF MECHANICAL BARRIERS

Because of the belief that the ligated SFJ initiated growing of new vessels, attempts were made to counteract new vessel formation and to prevent recurrent reflux in the groin by creating a barrier above the ligated SFJ. Different types of mechanical barriers were used: over-sewing the ligated SFJ in order to hinder the contact of endothelial cells with the neighbouring tissue [27, 33, 34], suture of the cribriform fascia [29, 35], and implantation of various types of patches [36–40].

According to the randomised study by Frings et al. [27] recurrent reflux in the groin was reduced (but not prevented) by over-sewing the ligated SFJ with Prolene. In contrast to this, Heim et al. [33] demonstrated that exposed endothelial cells of the ligated saphenous stump did not promote neovascularization. In a cohort where the common femoral vein venotomy was closed with a running inverting suture recurrent varicose veins in the thigh occurred even more frequently than in the control group with simple stump ligation, assessed 2 years after surgery. Similarly, Winterborn et al. [34] found in a randomised trial no advantage of over-sewing the SFJ with 4/0 polypropylene over standard ligation with an absorbable suture.

Glass [29] found that closure of the cribriform fascia reduced the incidence of recurrent varicose veins, assessed clinically four years after surgery. Sheppard [35] introduced coverage of the foramen ovale with pectinous fascia. Gibbs et al [36] presented a prospective randomised study assessing the benefit of pectinous fascia flap to reduce re-recurrence of varicose veins. The patients were examined a minimum of eighteen months after the procedure both clinically and by duplex ultrasound scanning. The study failed to demonstrate any apparent benefit of this measure. The number of re-recurrences arising from the common femoral vein as well as the size of refluxing venous channels was nearly the same in the patch and no-patch cohort. De Maeseneer et al. [37] found 6.7% recurrence in the groin after closure of the cribriform fascia 1 year postoperatively, which was comparable with silicon patch saphenoplasty and superior to the previously assessed cohort without barrier. Earnshaw et al. [38] used a 2 cm by 1 cm patch of PTFE sutured over the saphenous opening and reported that small serpentine tributaries were visible at the SFJ in 20% on duplex imaging 1 year after patch insertion. The authors stated that there was a disappointingly high incidence of neovascularization despite the PTFE patch. Bhatti et al. [39] reported 23% incidence of visible varicose veins and 37% of re-recurrent reflux after polytetrafluorethylene patch saphenoplasty at a median of 19 months after operation, diagnosed by ultrasound scanning and confirmed by varicography in some. The type of newly formed refluxing channels in the groin matched with those in patients without mechanical barrier. A significant number of recurrent channels originated below the SFJ, suggesting that they were pre-existing collateral veins. Winterborn and Earnshaw found out nearly the same number of recurrences in the groin in a randomised trial comparing patients with and without PTFE patch 2 years postoperatively [40].

Thus, mechanical barriers either moderately reduced reflux recurrence at the groin level in some studies or were ineffective in others, but in all they did not preclude development of recurrent reflux. Some authors expressed the opinion that recurrent reflux in varicose vein disease is unavoidable, no matter how careful and painstaking the primary procedure might be [26, 38]. Turton et al. postulated that neovascularization might be the effect of altered venous hemodynamics in susceptible veins [30]. Similarly, El Wajeh et al. anticipated that a hemodynamic factor might trigger the recurrence process [18].

HEMODYNAMIC FACTORS ASSUMED TO TRIGGER RECURRENT REFLUX

The synergistic effect of two hemodynamic factors may be responsible for the tenacity with which recurrent reflux occurs in varicose vein disease. These factors are:

1. Pressure difference occurring between the femoral vein and an incompetent vein in the thigh during calf pump activity; it might play a part as the trigger of the process, and
2. Prediposition to restore the impeded centrifugal flow.

PRESSURE DIFFERENCE BETWEEN THE FEMORAL VEIN AND THE SAPHENOUS REMNANT AFTER EXCLUSION OF INCOMPETENT SFJ

Venous pressure measurements in the incompetent saphenous vein in the thigh revealed pressure difference of about 37 mm Hg occurring during calf pump activity between the femoral vein and the saphenous segment below the tourniquet that inhibited reflux [16]. Similarly, the same pressure gradient arises between the femoral vein and the saphenous remnant or other incompetent superficial vein in the thigh after ligation of the SFJ. The pressure gradient enhances flow rate through pre-existing collateral channels, which increases fluid shear stress on the endothelium, and obviously evokes biochemical events leading to progressive enlargement of the communicating channel.

Pressure difference arises also in arterial occlusions between the segments above and below the occlusion and stimulates development of arterial collateral circulation; this may be an encoded, pre-programmed recovery mechanism designated for counteracting tissue hypoxia.

Neovascularization occurs only in varicose vein disease where pressure difference emerges between the femoral vein and the incompetent superficial vein in the thigh. It does not occur in healthy people, e.g. after harvesting of the GSV in the groin for bypass graft. In persons with healthy veins no drainage of venous blood from the thigh into the lower leg can take place due to competent valves. Therefore, no decrease in venous pressure arises in superficial veins in the thigh; no pressure difference can occur between the femoral vein and the saphenous vein or its branches, no triggering impulse can emerge.

RESTORATION OF CENTRIFUGAL FLOW

As mentioned above, restoration of centrifugal flow is a well-known phenomenon in arterial occlusions: development of collateral circulation improves the impaired blood supply. In varicose vein disease, calf muscle venous pump is the motive force creating hemodynamic prerequisites for restoration of centrifugal flow in incompetent superficial veins. However, restoration of centrifugal flow in incompetent veins entails recurrent reflux.

Figure 1 shows a broad meandering venous communication that developed after crossectomy outside of the original field of surgery between the femoral vein and the GSV, obviously due to dilatation of pre-existing minor veins, i.e. due to vascular remodelling. The fact that the communicating channel developed outside of the original field of surgery evidenced that the surgical procedure per se had nothing to do with this event. Besides, tiny hair like channels originating at the previous saphenofemoral junction and heading toward the saphenous remnant are imaged, representing neo-angiogenesis; they are hemodynamically insignificant in comparison with the single serpentine communication.

The diameter of the saphenous remnant diminished after crossectomy and a previously incompetent valve became competent. Curiously enough, a newly created venous collateral (black arrow) bypassed the competent valve and rendered the entire saphenous stem again incompetent; the centrifugal flow in the saphenous remnant was re-established, reflux recurred. Evidently, a single surgically repaired valve in the GSV in the thigh would not have been able to avert recurrent reflux, even if it had preserved its competence for years. Pressure gradients between the femoral vein and the saphenous remnant as well as between the segments of the saphenous remnant above and below the competent valve obviously triggered the process leading to restoration of centrifugal flow in the saphenous vein. Both crossectomy and competent valve in the saphenous remnant constituted impediments to centrifugal flow; both obstacles were bypassed, which restored centrifugal flow in a similar manner as it is common in arterial occlusions. The incompetent saphenous vein behaved as an artery.

CONCLUSION

Centrifugal flow within an incompetent venous channel connecting both poles of the ambulatory pressure gradient and causing ambulatory venous hypertension is the characteristic feature of venous reflux.

Recurrent reflux in primary varicose veins occurs after any therapeutic procedure including correctly performed surgery. In that case, neovascularization has been considered to be the most common cause of recurrence. The term neovascularization means formation of new communications between the femoral vein and the incompetent GSV or its branches in the thigh, and encompasses dilated pre-existing minor veins (vascular remodelling) as well as new grown vessels (neo-angiogenesis). Venous channels arising from vascular remodeling mostly form single meandering communications with a diameter large enough to cause hemodynamically significant recurrent reflux.

Insertion of mechanical barriers over the ligated saphenofemoral junction failed to prevent reflux recurrence in the groin.

Two hemodynamic factors – pressure gradient between the femoral vein and the saphenous remnant in the thigh as well as propensity to restore the centrifugal flow – may play a decisive part in reflux recurrence. The pressure gradient obviously triggers the biophysical and biochemical events leading to recurrence; the ability to restore the centrifugal flow might be an encoded, pre-programmed recovery phenomenon ensuring improvement of impaired circulation in arterial occlusions, but causing harm in varicose vein disease, evoking recurrent reflux in incompetent superficial vein.

In this way, it can be explained why recurrent reflux occurs sooner or later after any therapeutic procedure.

Čestmír Reček, MD,

Mantlergasse 24,

A-1130 Vienna

Austria

e-mail: recek@aon.at