Hemodynamics-based treatment of varices: A therapeutic concept counteracting the intrinsic tendency of varicose veins to recur

Abstract

Varicose vein disease is characterized by tenacious tendency to recur. Measures recommended to prevent recurrences (flush ligation at the saphenofemoral junction, removal of incompetent great saphenous vein in the thigh, and insertion of mechanical barriers in the fossa ovalis) did not succeed in preventing recurrence. Reflux recurrence is triggered by the hemodynamic phenomenon called hemodynamic paradox. Abolition of saphenous reflux removes the hemodynamic disturbance of any degree of severity but at the same time it releases the pathological process leading to recurrent reflux. This process is induced by drainage of venous blood from incompetent superficial thigh veins into deep lower leg veins during calf pump activity, which evokes the development of ambulatory pressure gradient between the femoral vein and incompetent segments of the saphenous system in the thigh. The pressure gradient sets off biophysical and biochemical events inducing recurrent reflux. The designed therapeutic strategy consists of reliable abolition of saphenous reflux and of hindering the pathological drainage of venous blood at the knee level in order to preclude development of the hemodynamic preconditions for reflux recurrence. In this way, the dividing line of the ambulatory pressure gradient would be kept below the knee, as is the case with healthy people.

Keywords

Recurrent varices varicose veins venous pressure venous reflux

Introduction

Varicose vein recurrence was reported to occur in a wide range up to 80% depending on the length of follow-up, the mode of therapy, and the method used to diagnose recurrence.^1–5 Recurrent reflux in the groin region is the most frequent concomitant phenomenon in these cases.⁶ Inadequate surgery was regarded in the past as being responsible for recurrences in a lot of papers: especially low ligation of the great saphenous vein (GSV) leaving behind incompetent saphenofemoral junction (SFJ) with saphenous stump and venous tributaries, and overlooking additional sources of reflux, for example, the short saphenous vein. Meticulous dissection and flush ligation at the SFJ has been regarded as indispensable part of the surgical treatment of varicose veins to avoid recurrences.^7–15 Similarly, leaving behind incompetent GSV trunk in the thigh was mentioned as another factor that accelerates and facilitates recurrence; higher recurrence rate was reported after pure crossectomy in comparison with crossectomy and stripping.^3,11,14–20 Nevertheless, recurrences occur also after correctly performed crossectomy and stripping, which was documented by ultrasonography and phlebography.^2,5,21–23 Some authors tried to hinder the development of recurrent reflux in the groin by suturing the cribriform fascia, inverting suturing of the femoral vein, and by creating various types of mechanical barriers in the fossa ovalis using synthetic patches.^24–32 These attempts either moderately reduced reflux recurrence in the groin in some studies or were ineffective in others; in any case, they did not preclude the development of recurrent reflux. Turton et al.²² expressed the opinion that recurrent reflux in varicose vein disease was unavoidable, no matter how carefully the primary procedure was carried out, and postulated that the tendency of varicose veins to recur might be related to unspecified hemodynamic factors.

The tenacious tendency of varicose veins to recur

Ambulatory pressure gradient of 37.4 ± 6.4 mm Hg,³³ conceivably 33 ± 11.8 mm Hg³⁴ arises between thigh veins and lower leg veins during calf pump activity. Arnoldi³⁴ measured venous pressure in healthy people during calf pump activity simultaneously in the posterior tibial vein and in the popliteal vein. Venous pressure sank markedly in the posterior tibial vein, whereas in the popliteal vein it displayed pressure variations during calf muscle contractions and relaxations but did not decrease; it kept the original value of the hydrostatic pressure registered in quiet standing. Thus, the dividing line of the ambulatory pressure gradient in healthy people is situated just below the knee where the posterior tibial vein transforms into the popliteal vein.

In patients with primary varicose veins, ambulatory pressure gradient triggers venous reflux, that is, centrifugal streaming through the incompetent saphenous vein into deep lower leg veins. When the reflux is abolished, for example, at the SFJ (high ligation), the venous blood contained in incompetent superficial thigh veins is drained during calf pump activity into deep lower leg veins, and the lower pressure extends from deep lower leg veins into the superficial thigh veins.³³ Because the ambulatory pressure in the femoral vein does not decrease, ambulatory pressure difference arises between the femoral vein and the incompetent superficial thigh veins; its value is 37.4 ± 6.4 mm Hg. Thus, the dividing line of the ambulatory pressure gradient is transferred from below the knee into the thigh, and is situated between the femoral vein and the incompetent superficial thigh veins.^33,35 The process of the relocation of the dividing line of the ambulatory pressure gradient is illustrated in Figure 1. The pressure gradient, once transmitted into the thigh, enhances flow rate through the pre-existing, hitherto inactive communicating channels between deep and superficial thigh veins, which increases fluid shear stress on the endothelium of these tiny vessels. Increased fluid shear stress activates release of nitride oxide and vascular endothelial growth factor,^36–39 which entails ongoing enlargement of the tiny communicating channels between deep and superficial veins in the upper part of the thigh and results in progressively increasing recurrent reflux; the consequence is continuous deterioration of the hemodynamic situation during the follow-up, as shown in Figure 2.

Figure 1.

Illustration of the displacement of the ambulatory pressure gradient from the knee level into the thigh, which triggers the process inducing recurrent reflux. (a) Ambulatory pressure gradient (APG) in healthy people yielding the value of 37.4 ± 6.4 mm Hg arises during calf pump activity. The dividing line of the APG lies at the beginning of the popliteal vein. (b) After elimination of reflux at the saphenofemoral junction the venous blood is drained from the superficial thigh veins into deep lower leg veins during calf pump activity. (c) The consequence: the dividing line of the APG is displaced into the thigh between the femoral vein and superficial thigh veins and triggers the process leading to recurrent reflux. + means higher pressure, − means lower pressure.

Figure 2.

Strain gauge plethysmographic results assessing refill time t-90 and t-50 during the follow-up after crossectomy in 70 patients. w: week; y: years. Clearly pathological values before treatment became entirely physiological one week after abolition of saphenous reflux in the groin. Progressive deterioration of the hemodynamic situation took place during the 4-year follow-up due to progressively increasing intensity of recurrent reflux.

The drainage of venous blood from superficial thigh veins into deep lower leg veins is a characteristic pathological feature of varicose vein disease; it does not exist in healthy people, competent valves preclude it. Therefore, no pressure difference between the femoral vein and the superficial veins in the thigh can arise during calf pump activity in people with healthy veins, and no triggering impulse for neovascularization can occurs after harvesting of GSV for bypass grafts.

The same process triggered by the pressure gradient and based on the same biophysical and biochemical events creates collateral circulation in arterial obliterations and in venous thrombotic occlusions; that may be regarded as a pre-programmed repair mechanism designated for counteracting tissue hypoxia in arterial obliteration, and for relieving the untoward venous hypertension in venous thrombotic occlusions. In varicose vein patients, the flow in the incompetent GSV is predominantly centrifugal, like in the arteries; thus, restoration of the centrifugal flow in the remaining incompetent GSV after high ligation may be considered as a derailment of the physiological repair mechanism. The tendency to restore the centrifugal flow in incompetent GSV is very impressive, as documented in Figure 3. Retrograde phlebography performed a few years after crossectomy depicted a new meandering venous channel arisen between the common femoral vein and the remnant of the GSV. Moreover, the diameter of the GSV diminished after abolition of saphenous reflux and a previously incompetent valve became competent; nevertheless, it was bypassed by a newly created venous channel, which made the whole saphenous trunk incompetent again. The tendency to restore the centrifugal flow in incompetent GSV is indeed very spectacular! A competent valve is not able to resist this tendency and to insure the competence of the otherwise incompetent venous channel.

Figure 3.

Retrograde phlebography performed in a standing position a few years after crossectomy. Contrast dye was applied into the common femoral vein. Refluxing flow was induced by manual squeezing of the calf and enhanced by Valsalva pressing after release of the manual calf compression. SFJ: saphenofemoral junction; C: new venous collateral channel bypassing a competent valve in the great saphenous vein, documenting the extremely pronounced tendency to restore the centrifugal flow in incompetent great saphenous vein.

The hemodynamic paradox

A curious hemodynamic phenomenon arises as a consequence of treatment of varicose veins and explains the adamant tendency to recurrence irrespective of the applied therapeutic procedure. In primary varicose veins, saphenous reflux is the most important pathological phenomenon: it causes ambulatory venous hypertension and is responsible for the severity of the hemodynamic disturbance, clinical symptoms, and chronic venous insufficiency. Abolition of saphenous reflux removes the hemodynamic disturbance and restores physiological hemodynamic conditions even in patients afflicted with the severest form of chronic venous insufficiency, as evidenced by plethysmography and venous pressure measurements and depicted on Figure 4. But curiously enough, abolition of saphenous reflux generates simultaneously preconditions for the development of recurrent reflux and for progressive comeback of the previous pathological situation; this phenomenon has been called hemodynamic paradox. Once the dividing line of the ambulatory pressure gradient is transferred into the thigh, it triggers the process leading to reflux recurrence;³⁵ the mechanism has been explained in the previous chapter.

Figure 4.

Strain gauge plethysmographic parameters refill time t-90, t-50 (a) and refill volume (b) in 37 patients with primary varicose veins and chronic venous insufficiency CEAP 4–6 showed very severe hemodynamic disturbance before surgery. Abolition of reflux in the great saphenous vein by crossectomy without stripping and without interruption of large calf perforators restored normal venous hemodynamics (examined one week after surgery).

Under these circumstances, the question arises whether it would be possible to disrupt this unfavorable chain of events characterizing the hemodynamic paradox in order to counteract the tendency to recurrence. This topic will be dealt with in the following sections.

Is there any possibility to counteract the tendency of varicose veins to recur?

This question can be answered in the affirmative. The rationale is to preclude the drainage from the incompetent thigh saphenous system into deep lower leg veins in order to hinder the displacement of the dividing line of the ambulatory pressure gradient into the thigh and to keep it below the knee level, as it is distinctive of healthy people. The interruption of the drainage ensures that the preconditions for the biophysical and biochemical events inducing reflux recurrence cannot develop. The knee level is the most appropriate site where the interruption of venous drainage should be done. It represents an anatomical strait: all draining superficial veins must pass this narrow space between the skin and the bones. Therefore, interrupting the pathological drainage at this strait is the easiest and most effective measure. It can be done during the original operation from small incisions in local anesthesia. All incompetent venous channels in this location must be detected preoperatively using duplex ultrasonography. Nevertheless, new draining channels may develop during the follow-up; they must be searched for and obliterated by sclerotherapy.

The hemodynamic basis of the proposed therapeutic procedure

This procedure has been called hemodynamics-based treatment of varices. The conception is based on the following hemodynamic evidences:

Activity of the calf pump induces pressure difference between veins in the thigh and the lower leg; it has been called ambulatory pressure gradient. The dividing line of the ambulatory pressure gradient lies in healthy people just below the knee at the beginning of the popliteal artery.

Ambulatory pressure gradient triggers reflux in incompetent saphenous system.

Abolition of saphenous reflux removes the hemodynamic disturbance.

After abolition of saphenous reflux the blood contained in the incompetent saphenous system in the thigh is sucked during calf pump activity into deep lower leg veins. This induces decrease in pressure in the superficial thigh veins and entails the development of pressure difference between the femoral vein and the saphenous system in the thigh, which triggers the process leading to recurrent reflux.

The outward flow within calf perforators occurring during calf muscle contractions is no pathological reflux but a physiological centripetal, that is, toward the heart oriented streaming that does not cause any hemodynamic disturbance. Abolition of saphenous reflux at the SFJ normalizes the hemodynamic condition in spite of the presence of large incompetent calf perforators. Large incompetent calf perforators in primary varicose veins are the consequence of hemodynamically significant saphenous reflux. The more intense is the saphenous reflux, the larger are calf perforators because the more refluxing venous blood streams through them inward into deep lower leg veins. The diameter of calf perforators diminishes after abolition of saphenous reflux. Large incompetent calf perforators neither induce the hemodynamic disturbance nor cause leg ulcers. The ligation of calf perforators is unnecessary; it does not improve the hemodynamic disorder.

Thus, the proposed procedure embodies the following therapeutic steps:

Abolition of the source(s) of saphenous reflux, which removes the hemodynamic disturbance of any degree of severity and restores physiological decrease in ambulatory venous pressure in the veins below the knee during calf pump activity, as documented by plethysmography and venous pressure measurement.

Interruption of drainage of venous blood from superficial thigh veins into deep lower leg veins, which impedes the extension of the lower ambulatory pressure from deep lower leg veins into the superficial thigh veins, and hinders in this way the development of ambulatory pressure difference between the femoral vein and superficial veins in the thigh. The absence of the pressure gradient in the thigh precludes activation of the process setting off vascular remodeling and leading to recurrent reflux. The interruption of the drainage is done at the strait, that is, at the knee level, where it can be performed easiest and most effectively. In this way, hemodynamic conditions characteristic of the healthy people will be established.

Notwithstanding, new draining channels may develop in the course of follow-up. These new channels should be searched at the knee level during the follow-up examinations and obliterated using sclerotherapy.

This procedure, in addition to removing the hemodynamic disorder and counteracting the tendency to recurrence might preserve the GSV in the thigh and in the lower leg, which would be another beneficial effect. When the GSV maintains patency (there is a good case to believe this will happen), it might be used for bypass graft in the future, if needed. The fate of the GSV in the thigh and the lower leg should be assessed during the follow-up examinations.

Fate of the GSV trunk in the thigh

One of the benefit of the designed procedure is the intended preservation the of the GSV for possible bypass graft in the future. As emphasized above, refluxing GSV in the thigh triggers the development of recurrent reflux and constitutes an undesirable condition. Therefore, refluxing flow in the thigh segment of the GSV should be thwarted by interruption of reflux-carrying venous channels at the knee level. It is uncertain whether under these circumstances the thigh segment of the GSV remains patent after high ligation and interruption at the knee level. The following chapter analyses this situation. Another question is if the GSV of varicose vein patients is generally suitable for bypass graft in arterial reconstructions; this continues to be a contentious issue. And last but not least, it is not known how many of operated varicose vein patients will really be in need of a bypass. All these questions will be dealt with in the following chapters.

How high is the probability that the GSV remains patent after high ligation or crossectomy?

The flow in the incompetent GSV is predominantly centrifugal. After high ligation or crossectomy both the centrifugal flow and the physiological centripetal flow is interrupted. Under these conditions, one would presume that the GSV in the thigh will thrombose. Interestingly enough, such assumption did not prove to be true. The incompetent stem of the GSV retained patency and incompetence in most cases after high ligation or crossectomy. Varicograms showed patency of GSV in the thigh in 54% 2–33 years after high ligation.⁴⁰ Other studies documented yet higher patency rate. Duplex ultrasonography showed patency of the GSV trunk in the thigh in 89% 52 months after crossectomy + calf perforator ligation + avulsion of varicose veins; all preserved saphenous veins could have been used as arterial bypasses.⁴¹ In another study, 60 limbs were evaluated 10 months after crossectomy using duplex ultrasonography; the stem of the GSV in the thigh was patent in 78%; in patients where no varicose vein excisions were performed and crossectomy was supplemented by postoperative sclerotherapy the GSV trunk remained patent in 96% of cases.⁴² In a prospective study assessing 70 patients 4 years after crossectomy patency of the GSV stem in the thigh was found in 87.2%.⁴³ A few other studies evaluating lesser number of patients showed similar results.^44,45

Experience has revealed the amazing ability of the GSV to preserve patency. It can be realistically presumed that the GSV will remain patent in most cases even after interruption at the SFJ and the knee level.

Is the stem of the GSV in varicose vein patients suitable for bypass?

There is no agreement whether the GSV of varicose vein patients can be used for bypass in arterial reconstructions. Some authors assessed the suitability of the GSV for arterial grafting during duplex ultrasound examination of patients with primary varicose veins.^46,47 The GSV stems in the thigh were of normal size or slightly dilated; some GSVs had one or more minor areas of localized dilatation. The phlebography showed that the below-knee portion of the GSV did not become varicose, not even in cases with excessive below-knee varicosities. This segment remained patent in most cases even after surgical removal of the main trunk down the knee and radical avulsion of all visible varicose veins in the limb.

The GSV stem in the thigh is not afflicted with varicose vein degeneration; it is just incompetent. It can have some few localized small bulges that can be repaired using atraumatic stitches. When such veins are used as arterial grafts they neither dilate nor tend to form aneurysmatic protrusions; they retain long-term patency similar to normal vein grafts. For fear of potential dilatation, GSVs harvested from patients with varicose veins were wrapped in some studies either locally (around the dilated sites) or totally with mesh grafts or polytetrafluoroethylene prostheses to reinforce the grafts. Such grafts were used for infra-inguinal arterial reconstructions with patency rate of about 80% several years after surgery. Duplex scans failed to demonstrate stenosis of the reinforced venous segments or aneurysmatic dilatation of the non-reinforced segments.^48,49 Reinforced GSV from varicose vein patients were used also for coronary artery bypass grafting reconstructions. Zurbrugg et al.⁵⁰ reported on 200 patients having undergone aortocoronary bypasses with biocompound grafts. These grafts were formed by using an ultraflexible metal mesh tube that was placed outside the vein harvested from varicose patients, and the two pieces were joined together with fibrin glue. The patency rate of the native veins was 68.7% and that one of biocompound grafts 68.3% at 3 years.

The author’s view based on his own satisfactory results with saphenous veins harvested in patients with varicose veins and used for bypass grafts both in peripheral arterial reconstructions and coronary artery bypass surgery (unpublished data) is in accordance with the above-mentioned opinions, as concerns the suitability and the patency rates. There are presumably other surgeons who occasionally used saphenous veins of varicose patients for arterial reconstructions but did not publish their experience. On the top of that, GSVs gained during varicose vein operations and stored in an organ bank were used as homologous bypass grafts in lower extremities and displayed 84% patency 12 months after arterial reconstructions.⁵¹

How high is the probability that the preserved GSV will be used as bypass in the future?

It is difficult to answer this question or to organize a conclusive study. The mean age of varicose vein patients who undergo varicose vein treatment is significantly lower than of those who are treated for arterial obliteration in the lower extremity or for coronary artery stenoses/occlusions. Moreover, varicose vein operations are performed predominantly on females, arterial reconstructions on males. According to an old study published in 1985, only 13 of 580 varicose vein patients would have needed GSV as arterial bypass in the course of 20 years.⁵² Since that time, the situation has changed markedly both as concerns the number of performed arterial reconstructions and other therapeutic possibilities—endovascular procedures. In addition, the mean survival of the population increases, people continue to grow older and older, and the probability that they will need treatment for arterial occlusions rises. Thus, preservation of usable venous segments for arterial grafting without raising the risk of recurrence would be surely advantageous.

Conclusion

Varicose vein disease has an intrinsic tendency to recurrence, which is caused by a curious phenomenon called hemodynamic paradox. Abolition of saphenous reflux removes the hemodynamic disorder and restores physiological hemodynamic conditions but at the same time, in addition to this excellent therapeutic effect, it creates preconditions for reflux recurrence. After abolition of saphenous reflux, the low ambulatory pressure arising in deep lower leg veins induces drainage of blood from the whole incompetent saphenous system into deep lower leg veins. As a consequence, the low pressure extends from deep lower leg veins into the saphenous system in the thigh. Because the ambulatory pressure in the femoral veins does not decrease, a pressure difference develops between the femoral veins and the saphenous system in the thigh; this triggers the biophysical and biochemical process bringing about reflux recurrence.

The designed therapeutic procedure is aimed, in addition to abolition of saphenous reflux, at hindering the drainage from incompetent superficial thigh vein into deep lower leg veins. The interruption of the draining venous channels should be carried out at the knee level, where it can be done very easy and most effectively. In this way, the displacement of the dividing line of the ambulatory pressure gradient into the thigh, and thereby the development of preconditions that trigger the pathological process leading to recurrence would be impeded. Moreover, the trunk of the GSV in the thigh and in the lower leg might be preserved for potential bypass graft.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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