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Chronic Venous Insufficiency

2014; Lippincott Williams & Wilkins; Volume: 130; Issue: 4 Linguagem: Inglês

10.1161/circulationaha.113.006898

1524-4539

Robert T. Eberhardt, J.D. Raffetto,

Peripheral Artery Disease Management

HomeCirculationVol. 130, No. 4Chronic Venous Insufficiency Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBChronic Venous Insufficiency Robert T. Eberhardt, MD and Joseph D. Raffetto, MD Robert T. EberhardtRobert T. Eberhardt From the Cardiovascular Medicine Center, Boston Medical Center, Boston, MA (R.T.E.); Boston University School of Medicine, Boston, MA (R.T.E.); Vascular Surgery, Boston VA Health Care System, Boston, MA (J.D.R.); and Harvard Medical School, Boston, MA (J.D.R.). and Joseph D. RaffettoJoseph D. Raffetto From the Cardiovascular Medicine Center, Boston Medical Center, Boston, MA (R.T.E.); Boston University School of Medicine, Boston, MA (R.T.E.); Vascular Surgery, Boston VA Health Care System, Boston, MA (J.D.R.); and Harvard Medical School, Boston, MA (J.D.R.). Originally published22 Jul 2014https://doi.org/10.1161/CIRCULATIONAHA.113.006898Circulation. 2014;130:333–346IntroductionChronic venous disease (CVD) is often overlooked by healthcare providers because of an underappreciation of the magnitude and impact of the problem, as well as incomplete recognition of the various presenting manifestations of primary and secondary venous disorders. The importance of CVD is related to the number of persons afflicted and the socioeconomic impact of its more severe manifestations. CVD is a very common problem, with varicose veins affecting more than 25 million adults in the United States and more than 6 million with more advanced venous disease.1 Because of this high prevalence of venous disease, the National Venous Screening Program was conducted by the American Venous Forum in the United States to increase awareness. The program identified varicose veins in >30% of participants and more advanced venous disease in >10%.2 The most common manifestations of CVD are telangiectases, reticular veins, and varicose veins. Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities, with the sine qua non being persistent ambulatory venous hypertension causing various pathologies, including pain, edema, skin changes, and ulcerations. CVI often indicates the more advanced forms of venous disorders, including manifestations such as hyperpigmentation, venous eczema, lipodermatosclerosis, atrophie blanche, and healed or active ulcers. However, because varicose veins also have incompetent valves and increased venous pressure, we use the term "CVI" to represent the full spectrum of manifestations of CVD.3Varicose veins have an estimated prevalence between 5% and 30% in the adult population, with a female:male predominance of 3:1, although a more recent study supports a higher male prevalence.4 The Edinburgh Vein Study screened 1566 subjects with duplex ultrasound for reflux, finding CVI in 9.4% of men and 6.6% of women after age adjustment, which rose significantly with age (21% in men >50 years, and 12% in women >50 years).5 The San Valentino Vascular Screening Project found among the 30 000 subjects evaluated by clinical assessment and duplex ultrasound a prevalence of 7% for varicose veins but 12% of workers with venous ulcers.15 The financial burden of venous ulcer disease on the healthcare system is readily apparent, with an estimated $1 billion spent annually on treatment of chronic wounds in the United States or ≤2% of the total healthcare budget in Western countries, and estimates placing the cost of venous ulcer care at $3 billion annually.16,17Given the prevalence and socioeconomic impact of CVD, an understanding of the clinical manifestations, diagnostic modalities, and therapeutic options is warranted. This article reviews clinical aspects of CVI, with a focus on the diagnostic and therapeutic options, and places these in context of the Clinical Practice Guidelines (CPG) of the Society for Vascular Surgery and American Venous Forum of 2011, which used best evidence-based practice, and applied a grading system.18Venous PathophysiologyNormal Venous Anatomy and FunctionTo appreciate the pathophysiology of CVI, it is first useful to understand normal venous anatomy and function. The peripheral venous system functions as a reservoir to store blood and as a conduit to return blood to the heart. Proper functioning of the peripheral venous system depends on patency of vessels containing a series of 1-way valves and muscle pumps. In the erect position, blood that enters into the lower extremity venous system must travel against gravity and other pressures to return to the central circulation.The veins of the lower extremity are divided into superficial, deep, and perforator veins.19,20 The superficial venous system is located above the muscular fascial layer. It is composed of an interconnecting network of veins and several truncal superficial veins, including the great saphenous vein (GSV) and small saphenous vein, as well as several accessory veins, which may develop pathology contributing to CVI. The deep venous system is located below the muscular fascia and serves as collecting veins and the outflow from the extremity. The deep veins of the lower extremity consist of axial veins, which follow the course of the major arteries, and intramuscular veins, including venous sinusoids and plexi. The perforating veins traverse the anatomic fascial layer to connect the superficial to the deep venous system.The valves within the veins are essential in assuring that blood flows in the correct direction, particularly while in the upright posture.19 There is a series of 1-way bicuspid valves located throughout the deep and superficial veins that open to allow flow toward the heart but close to prevent the return of blood toward the feet. There are 4 phases of valve function which include opening, equilibrium, closing, and closed. The critical factors to valve function are axial vortical of blood flow opening the valve and vertical velocity in the valve cups that increases mural pressure relative to the luminal pressure leading to valve closure.21 The frequency of these venous valves increases from the proximal to distal leg to prevent an increase pressure within the distal veins because of gravitational effects. In addition, perforating veins also contain valves that only allow blood flow from the superficial to the deep veins.The valves function in concert with venous muscle pumps to allow the return of blood against gravity to the heart.22 Contraction of the muscle pumps, primarily in the calf, force blood out of the venous plexi to ascend up the deep venous system. The valves prevent blood from being forced more distally within the deep system or through perforator veins into the superficial system. Immediately after ambulation, the pressure within the veins of the lower extremity is normally low because the venous system has been emptied by the muscle pump action (Figure 1). Relaxation of the muscle pump then allows blood to refill to the deep venous system. With prolonged standing, the veins become distended as the vein fills via antegrade flow, allowing the valves to open and pressure to increase. Contraction of the muscle pump will again empty the veins and reduce venous pressure.Download figureDownload PowerPointFigure 1. Illustrative ambulatory foot venous pressure measurements during exercise and at rest over time in the standing position. A, Normal venous pressure. The resting standing venous pressure in ≈80 to 90 mm Hg. The pressure drops to ≈20 to 30 mm Hg (or >50% decrease) with calf exercise. The return in pressure is gradual, with refill taking >20 seconds. B, Abnormal venous pressure with venous reflux. The resting standing pressure is usually higher than normal. The drop in pressure with exercise is blunted (<50% decrease). The return in venous pressure to the resting level is rapid because of a short refill time (<20 seconds). C, Abnormal venous pressure with venous obstruction. Resting standing venous pressure is usually higher than normal. There is minimal-to-no drop in pressure with exercise.Venous Pathophysiology and DysfunctionVenous pathology develops when venous pressure is increased and return of blood is impaired through several mechanisms.23 This may result from valvular incompetence of axial deep or superficial veins, perforator veins, venous tributaries, or venous obstruction, or a combination of these mechanisms. These factors are exacerbated by muscle pump dysfunction, most notably of the calf muscles. These mechanisms serve to produce global or regional venous hypertension, particularly with standing or ambulation. Contributing to the macrocirculatory hemodynamic disturbances are alterations within the microcirculation.24,25 Unabated venous hypertension may result in dermal changes with hyperpigmentation; subcutaneous tissue fibrosis, termed "lipodermatosclerosis"; and eventual ulceration.Dysfunction or incompetence of the valves in the superficial venous system also allows retrograde flow of blood, which is called "reflux" and serves to increase hydrostatic pressures. Valve failure of the superficial veins may be primarily because of pre-existing weakness in the vessel wall or valve leaflets or secondary to direct injury, superficial phlebitis, or excessive venous distention resulting from hormonal effects or high pressure.23 Failure of valves located at the junctions of the deep and superficial systems, at the saphenofemoral and saphenopopliteal junctions, can be a source of reflux leading to CVI. Incompetence of the valves of the superficial veins with reflux has been shown in ≤90% of patient presenting the CVD with reflux in the GSV, accounting for 70% to 80%, and in ≈84% of those presenting with venous ulcers.26,27Dysfunction of the valves of the deep system is most often a consequence of damage from previous deep vein thrombosis. The damage to the valves of the deep veins leads to rapid refilling by pathologic retrograde venous flow and may even reduce the blood volume exiting the limb. The venous pressure immediately after ambulation may be slightly elevated or even normal, but the veins refill quickly with the development of high venous pressure without ongoing muscle contraction (Figure 1).28 Dysfunction of the deep vein valves has been shown to increase the rate of progression of venous disease with a higher rate of venous ulceration formation.29,30Failure of the valves in the communicating perforator veins may also allow high pressure to enter into the superficial system.31,32 Perforator valve incompetence allows blood to flow from deep veins backward into the superficial system with force because of the high pressures generated by the muscle pump action. This excessive local pressure can produce dilatation of the superficial veins and their valve cusps with secondary failure of the valves. This may result in a localized cluster of dilated veins that ascends up the leg.33In addition, reflux may also occur in venous tributaries in the absence of any truncal superficial or deep vein or perforator vein reflux.34 The most common tributaries with reflux are in communication with the GSV (≈60%), small saphenous vein (≈20%), or both (≈10%). This process of isolated tributary reflux may contribute to progression of disease within the other superficial or deep venous segments.Obstruction of the deep veins may limit the outflow of blood, causing increased venous pressure with muscle contraction, and lead to secondary muscle pump dysfunction. Venous obstruction may result from an intrinsic venous process, such as chronic deep vein thrombosis or venous stenosis, or because of extrinsic compression. Venous outflow obstruction plays a significant role in the pathogenesis of CVI.35 Postthrombotic venous obstruction, as with deep vein valve dysfunction, has a high rate of venous ulceration development and more rapid progression of disease.29Dysfunction of the muscle pumps may lead to ineffective emptying of venous blood from the distal lower extremity. This rarely occurs as a primary disorder with neuromuscular conditions or muscle-wasting syndromes. However, muscle pump dysfunction often occurs with severe reflux or obstruction. Because of ineffective venous emptying, the immediate postambulatory venous pressure will be nearly as high as the pressure after prolonged standing. Muscle pump dysfunction appears to be a significant mechanism for the development of complications such as venous ulcers.36,37Changes in the hemodynamics of the large veins of the lower extremity are transmitted into the microcirculation and lead to the development of venous microangiopathy.24 In addition, dysfunction of the microvenous valves seems to be play a key role and may occur independent of the macrovenous dysfunction.38 These hemodynamic perturbations contribute to the development of microangiopathic findings, with elongation, dilation, and tortuosity of capillary beds; thickening of basement membranes with increased collagen and elastic fibers; endothelial damage with widening of interendothelial spaces; and increased pericapillary edema with halo formation; however, normal interendothelial junctions have also been found in advance CVI.39 The abnormal capillaries with increased permeability and high venous pressure lead to the accumulation of fluid, macromolecules, and extravasated red blood cells into the interstitial space. There have been several postulated mechanisms for the development of venous microangiopathy, including fibrin cuff formation, growth factor trapping, and white blood cell trapping, but further work in this area is needed to better define this pathophysiology.24Clinical ManifestationsCVD represents a spectrum of conditions ranging from simple telangiectases or reticular veins to more advanced stages, such as skin fibrosis and venous ulceration. It is important to realize that the same clinical manifestations may result from different pathogenic mechanisms, including incompetent valves, venous obstruction, muscle pump dysfunction, or a combination. The major clinical features of CVI are dilated veins, edema, leg pain, and cutaneous changes in the leg. Varicose veins are dilated superficial veins that become progressively more tortuous and enlarged (Figure 2A). They may develop bouts of superficial thrombophlebitis, recognized by painful, indurated, inflamed areas along the varicose vein. Edema begins in the perimalleolar region and ascends up the leg with dependent fluid accumulation. Leg discomfort is often described as heaviness or aching after prolonged standing and is relieved by elevation of the leg. This discomfort is thought to be produced by increased intracompartmental and subcutaneous volume and pressure. There may also be tenderness along varicose veins because of venous distention. Obstruction of the deep venous system may lead to venous claudication (or intense leg discomfort with ambulation). Cutaneous changes include skin hyperpigmentation because of hemosiderin deposition and eczematous dermatitis (Figure 2B). A fibrotic process may occur in the dermis and subcutaneous fat termed "lipodermatosclerosis." There is an increased risk of cellulitis, leg ulceration, and delayed wound healing (Figure 2C). In addition, protracted CVI may also contribute to the development of lymphedema, representing a combined process.Download figureDownload PowerPointFigure 2. Manifestations of chronic venous insufficiency. A, Extensive varicose veins involving the thigh and leg. B, Hyperpigmentation and severe lipodermatosclerosis with leg edema. Notice healed ulcers in the gaiter region of the medial leg. C, Medial malleolar venous ulcers. Notice concomitant eczema and lipodermatosclerotic skin.The manifestations of CVI may be viewed in terms of a well-established clinical classification scheme. The Clinical, Etiology, Anatomic, Pathophysiology (CEAP) classification was developed by an international consensus conference to provide a basis of uniformity in reporting, diagnosing, and treating CVI (Table 1).40 The clinical classification has 7 categories (0–6) and is further categorized by the presence or absence of symptoms. The etiologic classification is basis on congenital, primary, and secondary causes of venous dysfunction. Congenital disorders are those that are present at birth but may be recognized later in life. These include the well-recognized syndromes of Klippel-Trenaunay (varicosities and venous malformations, capillary malformation, and limb hypertrophy) and Parkes-Weber (venous and lymphatic malformations, capillary malformations, and arteriovenous fistulas).41 Primary venous insufficiency is of uncertain etiology, whereas secondary venous insufficiency is attributed to an acquired condition. The anatomic classification describes the superficial, deep, and perforating venous systems, with multiple venous segments that may be involved. The pathophysiologic classification describes the underlying mechanism resulting in CVI, including reflux, venous obstruction, or both. Validation of the CEAP classification system has often focused on the clinical classification.42 The classification is a valuable tool in the objective evaluation of CVI, providing a system to standardize CVI classification with emphasis on the manifestations, cause, and distribution of the venous disease.43 The use of the CEAP classification in the evaluation of CVD has a strong recommendation in the CPG (grade 1A).18Table 1. CEAP Classification of Chronic Venous DiseaseCEAP ClassificationClinical classification (C)*† C0 No visible sign of venous disease C1 Telangiectases or reticular veins C2 Varicose veins C3 Edema C4 Changes in skin and subcutaneous tissue‡ A Pigmentation or eczema B Lipodermatosclerosis or atrophie blanche C5 Healed ulcer C6 Active ulcerEtiologic classification (E) Ec Congenital (eg, Klippel-Trenaunay syndrome) Ep Primary Es Secondary (eg, postthrombotic syndrome, trauma) En No venous cause identifiedAnatomic classification (A) As Superficial Ad Deep Ap Perforator An No venous location identifiedPathophysiologic classification (P) Pr Reflux Po Obstruction, thrombosis Pr,o Reflux and obstruction Pn No venous pathophysiology identified*Telangiectases are 3 mm measured in the upright position; however, in the Venous Clinical Severity Score, varicose veins are considered to be >4 mm. The Revised Venous Clinical Severity Score considers varicose veins to be ≥3 mm in the standing position.†The descriptor A (asymptomatic) or S (symptomatic) is placed after the C clinical class.‡C4 is subdivided into A and B, with B indicating higher severity of disease and having a higher risk for ulcer development.To complement the CEAP classification and further define the severity of CVI, a venous clinical severity score was developed.44,45 The revised venous clinical severity score provides clarification of the terms and better definition of the descriptors and has further clinical applicability (Table 2).46 The venous clinical severity score consists of 10 attributes with 4 grades (absent, mild, moderate, and severe). It has been shown to be useful in evaluation of the response to treatment in CVD and is recommended for routine clinical use in the CPG (grade 1B).18,45 To better evaluate patient-perceived success, severity of disease, and treatment outcome in CVI, the use of validated disease-specific quality-of-life questionnaires is also encouraged by the CPG (grade 1B).18Table 2. Venous Clinical Severity ScoreAttributeVenous Clinical Severity ScoreAbsent = 0Mild = 1Moderate = 2Severe = 3PainNoneOccasional, not restricting daily activityDaily, interfering but not preventing daily activityDaily, limits most daily activityVaricose veinsNoneFew, isolated branch varices, or clusters, includes ankle flareConfined to calf or thighInvolves calf and thighVenous edemaNoneLimited to foot and ankleExtends above the ankle but below kneeExtends to knee and aboveSkin pigmentationNone or focalLimited to perimalleolarDiffuse, over lower third of calfWider distribution above lower third of calfInflammationNoneMild cellulitis, ulcer margin limited to perimalleolarDiffuse over lower third of calfWider distribution above lower third of calfIndurationNoneLimited to perimalleolarDiffuse over lower third of calfWider distribution above lower third of calfUlcer number012≥3Ulcer durationNA 3 mo but 1 yUlcer sizeNADiameter 6 cmCompressive therapyNot usedIntermittentMost daysFull complianceNA indicates not applicable.Diagnosis of CVIA complete history and physical examination are important to establish a proper diagnosis of CVI and may be assisted by noninvasive testing. Invasive testing may also be used to establish the diagnosis but is typically reserved for assessing disease severity or if surgical intervention is being contemplated. The methods used to assess CVI are described below, but comprehensive overviews have been published previously.47Physical ExaminationThe physical examination not only aids in establishing a diagnosis but plays an important role in helping to guide therapy in CVI. Visual inspection and palpation may reveal evidence of venous disorders. The skin is examined for prominent, dilated superficial venous abnormalities, such as telangiectasis, reticular veins, or varicose veins. The surface is inspected for irregularities or bulges to suggest the presence of dilated tortuous veins. The distribution of these varicose veins may follow the course of the affected superficial vein, such as the GSV and small saphenous vein. This evaluation should include positioning in the upright posture to allow for maximal distention of the veins. Additional skin findings may be seen, such as hyperpigmentation, stasis dermatitis, atrophie blanche (or white scarring with a paucity of capillaries), or lipodermatosclerosis. The presence of edema and its severity is assessed. The edema seen in CVI is dependent and usually pitting; however, it may become more resilient to palpation if protracted. There is often relative sparing of the forefoot to help distinguish the etiology of other causes of edema, such as lymphedema. An early finding of venous congestion includes calf fullness or increased limb girth, so the calf muscle consistency should be assessed, and measurement of the limb girth should be performed. There is no universally agreed on scale for grading the severity of edema. The venous clinical severity score graded edema on the basis of the level of the most proximal involvement in the limb (see Table 2). Other scales (typically range from 0 to 4+) use the presence of visual distortion of the limb, the depth of indentation, and the duration for rebound of the pitting. Palpation along the course of dilated veins may reveal tenderness. The presence of active or healed ulcers, typically in a distribution near the medial aspect of the ankle with GSV reflux or lateral aspects of the ankle with small saphenous vein reflux, may be seen with more advanced disease.48A classic tourniquet (eg, the Brodie-Trendelenburg) test may be performed at bedside to help distinguish deep from superficial reflux.49 The test involves applying a tourniquet or manual compression over the superficial veins after the patient lies down to empty the veins. The veins are observed with resumption of an upright posture; in the presence of superficial reflux, the varicose veins will take >20 seconds to dilate; in contrast, in the presence of deep (or combined) venous reflux, the varicose veins will rapidly dilate. Similarly, the use of handheld continuous-wave Doppler may also be used to assist in the bedside evaluation.50 Although these adjunctive bedside techniques are potentially useful to help determine the presence and location of CVI, this is typically performed with noninvasive testing using venous duplex imaging.Differential DiagnosisThere is a broad differential for the most common presenting symptoms of limb swelling and discomfort that are seen in CVI. The initial task is to exclude an acute venous problem, such as deep vein thrombosis. Then, systemic causes of edema need to be considered, such as heart failure, nephrosis, liver disease, or endocrine disorders. Importantly, adverse effects of medication should be considered, such as those with calcium channel blockers, nonsteroidal anti-inflammatory agents, or oral hypoglycemic agents. Critical disorders to consider are lymphedema, lipedema, and the combined disorder of lipolymphedema. Lymphedema because of obstruction of lymphatic drainage leads to fluid accumulation that extends into the foot and toes, in contrast with CVI, which relatively spares the foot. The edema may be pitting early in the course of the disease but as the disease progresses becomes nonpitting. In contrast, lipedema is characterized by fatty tissue accumulation rather than fluid, thus, it is not pitting. It usually spares involvement of the feet, often with a cuff of tissue at the ankle. Finally, other regional considerations should be made, such as ruptured popliteal cyst, soft tissue hematoma or mass, exertional compartment syndrome, or gastrocnemius tear. The use of examination findings and noninvasive testing should allow for the proper diagnosis to be established.Noninvasive TestingVenous Duplex ImagingVenous duplex imaging is currently the most common technique used to confirm the diagnosis of CVI and assess its etiology and anatomy and is highly recommended in the CPG (grade 1A).18,51,52 Venous duplex imaging combines B-mode imaging of the deep and superficial veins with pulsed Doppler assessment of flow direction with provocative maneuvers. The presence of venous obstruction because of chronic deep vein thrombosis or venous stenosis may be directly visualized or inferred from alteration in spontaneous flow characteristics. The direction of flow may also be assessed in the reverse Trendelenburg position during a Valsalva maneuver or after augmenting flow with limb compression. However, the preferred method to assess for reflux involves the use of a cuff inflation-deflation technique with rapid cuff deflation in the standing position.53 This provides information about the anatomic distribution of reflux disease involving the deep and superficial venous systems, as well as perforator veins.The presence of reflux is determined by the direction of flow, because any significant flow toward the feet is suggestive of reflux (Figure 3). The duration of reflux is known as the reflux time. A reflux time of >0.5 seconds for superficial veins and 1.0 second for deep veins is typically used to diagnose the presence of reflux.54 A longer duration of reflux implies more severe disease but does not correlate well with clinical manifestations.55 Venous duplex imaging provides information about local valve function to construct an anatomic map of disease in terms of the systems and levels of involvement. This is often sufficient data to help guide therapy, but if the contribution of the reflux to global hemodynamics is required, then further testing, such as plethysmographic techniques, should be considered.Download figureDownload PowerPointFigure 3. Venous duplex ultrasound demonstrating reflux in the great saphenous vein. Blood flow direction is determined after increasing central venous return with rapid cuff inflation then deflation. Flow in the direction of the feet is because of incompetent valves, as shown in red in the color image and above the baseline in the pulse Doppler. The Doppler spectrum quantifies the duration of reflux, and in the example above it is ≈4 seconds.Air PlethysmographyAir plethysmography (APG) has the ability to measure each potential component of the pathophysiologic mechanisms of CVI, including reflux, obstruction, and muscle pump dysfunction.56,57 Changes in limb volume are measured by air displacement in a cuff surrounding the calf during maneuvers to empty and fill the venous system (Figure 4). Venous outflow is assessed during rapid cuff deflation on an elevated limb that has a proximal venous occlusion cuff applied. The venous outflow at 1 secon