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33. Williams L. ATTRACT Trial to investigate image-guided DVT treatment.Available at: www.medwire-news.md/62/84502/Thrombosis_News/ATTRACT_Trial_to_investigate_image-guided_DVT_treatment.html.

34. Pittler MH, Ernst E. Horse chestnut seed extract for chronic venousinsufficiency. Cochrane Database Sys Rev 2006:CD003230.

35. Raju S, Neglén P. Percutaneous recanalization of total occlusions of theiliac vein. J Vasc Surg 2009;50:360-8.

36. Wang SM, Hu ZJ, Li SQ, Huang XL, Ye CS. Effect of externalvalvuloplasty of the deep vein in the treatment of chronic venousinsufficiency of the lower extremity. J Vasc Surg 2006;44:1296-300.

CRITICAL ISSUES IN PREVENTING POST-THROMBOTIC RE-ULCERATION

—Peter Pappas, MD, Newark, NJ

The lack of effective therapies and the recurrent natureof chronic venous insufficiency (CVI) place a heavy burdenon the United States healthcare system. The population-based costs in the United States for treatment of CVI andvenous ulcer care has been estimated at over one billiondollars a year. The high incidence and increasing cost ofCVI care has renewed interest in this disease process andmuch has been learned in the past decade.

Primary valvular incompetence with or without obstruc-tion causes ambulatory venous hypertension in the lowerextremity. Increased pressure is transmitted to the dermalmicrocirculation resulting in extravasation or red blood cells(RBCs) and macromolecules. RBCs and macromoleculescause an injury to the dermal architecture resulting in micro-circulatory activation of adhesion molecules and leukocyterecruitment. Activated leukocytes in conjunction with in-creased extra-cellular matrix tension may be the underlyingcause of venous ulcer formation. Recently published data fromour laboratory indicates that CVI disease progression is asso-ciated with increased fibroblast mediated contractile proper-ties and a potential ability to accelerate venous ulcer healing. Aconsequence of this adaptive wound healing response is in-creased stored kinetic energy and tension in dermis of patientswith CVI. In our experiments, we observed gel contraction inunstipulated gels indicating that fibroblasts surrounded by anextracellular matrix, exert a baseline degree of tension on theirsurrounding environment. This tension is increased whenstimulated with transforming growth factor-�1 and/or extra-cellular signal-regulated kinase inhibition. We believe that aninjury to the CVI dermal architecture releases stored kineticenergy in the dermis and clinically manifests itself initially aswound separation. This clinical situation is analogous to astretched rubber band. When external forces are used tostretch a rubber band, tension is exerted on the elastic fiberswithin the band. When the rubber band is released, the storedkinetic energy within the elastic fibers is released and the bandcontracts. It is clear that increased fibroblast contractility isbeneficial in healing wounds. However, in patients with der-mal fibrosis and increased matrix tension, an injury that causesarchitectural damage may be the underlying stimulus thatreleases kinetic energy and causes initial wound separation.

If the above hypothesis is true, then it is logical toassume that medical or surgical correction of venous hyper-tension should prevent RBC and macromolecule extrava-

sation and stops the underlying inflammatory injury event.

Given the fact that compression therapy is the mainstay ofvenous ulcer healing, there seems to be credence to thishypothesis. Therefore, one must assume that venous re-ulceration is partially if not completely related to the per-sistence of venous hypertension in primary CVI. In patientswith PTS, the effectiveness of clot resolution and anticoag-ulation is another related factor.

PTS is the development of CVI after an episode of deepvenous thrombosis. Patients with PTS can manifest any ofthe signs of the CVI from pain and edema to severelipodermatosclerosis and venous ulceration. Every clinicalvenous study performed has indicated that PTS patientshave worse symptoms and higher venous ulcer recurrencerates. Why the outcomes are poorer is currently unknown.In a recent review by Prandoni in the British Journal ofHematology a proximal venous thrombosis, previous ipsilat-eral DVT, insufficient oral anticoagulation, and poor veinrecanalization after 6 months of anticoagulation were allstrong predictors for the development of PTS. Based uponthese facts, what are the current road blocks to preventingre-ulceration in patients with PTS?

1. Pathophysiology of venous ulcer formation. Althoughgreat progress has been made over the past 2 decades, thepathophysiology of ulcer formation is still poorly under-stood. Effective medical and surgical therapies cannot bedeveloped without a better understanding of how endorgan damage is caused by venous hypertension.

2. Ineffective anticoagulation and poor venous recanalizationstrongly suggest that lytic therapy may play a significantrole in decreasing the incidence of PTS. Presumably thiseffect is secondary to valve function preservation and/orthe prevention of venous outflow obstruction. Random-ized trials are currently being conducted to evaluate therole of venous lysis in the prevention of PTS.

3. We have no objective method or good imaging techniquesfor determining venous obstruction. Current data on sur-gical valve repairs or valve transplants have all dependedheavily on the subjective assessment of vein patency basedon venography. Examination of excised, recanalized veinshave documented high-grade stenoses in damaged veinsdespite their patent appearance on venography. To over-come this road block, I suggest the following:(a) Re-assess valve repair in conjunction with stenting

and/or endophlebectomy.(b) Consider re-evaluating angioscopy as a method to

assess venous obstruction. Perhaps the angioscopecan be modified with a side port that can cutendovenous scar tissue and widen lumen patency.

(c) Consider a natural history study using an intravas-cular ultrasound scan to assess venous anatomy inpatients with PTS.

4. Compression therapy is currently the gold standard forulcer healing and recurrence. Despite this fact, ulcerrecurrence is still seen in compression patients for rea-sons that are currently unknown. I propose the follow-

ing to overcome this roadblock:

JOURNAL OF VASCULAR SURGERYNovember Supplement 201074S Abstracts

(a) We need a different type of stocking. I proposedeveloping smart stockings that can provide clini-cians with clinically relevant data. For example, canstocking fibers that change color when the degreeof compression decreases be developed? Can wedevelop remote pressure sensors or holter typepressure sensors that can be interrogated to deter-mine the effectiveness of compression much likeholter monitors collect heart rhythm data over a1-week to 2-week period.

(b) Can we develop a technology that measures skintension? The greater the dermal fibrosis and scar-ring the higher the skin tension and, therefore,the greater the likelihood of a venous ulcerrecurrence.

5. We need an objective way to assess end organ dam-age. Imaging that identifies high-risk dermal architec-ture may help clinicians determine which patients areat risk for developing ulcer recurrences and who arenot.