Medical Management Across Different stages of Chronic Venous Diseases

Chronic venous disease is long-standing anatomic or functional changes inside the venous system related to clinical signs or symptoms that expeditious investigation or care (1). It is portrayed by a myriad of symptoms going from lower leg swelling and skin redness to venous leg ulcers (VLUs) (2). It is perhaps the most well-known vascular disorder observed across the world and has a remarkable prevalence, with an expected annual occurrence of 2% (3).

According to the widely used CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification, the clinical picture of CVD can range from C0 (no visible or palpable signs) to C6 (active venous ulcer) (4). Telangiectasias or reticular veins in C1 stage followed by varicose veins (C2), edema(C3), skin changes ascribed to venous disease (C4), and skin changes with healed ulceration (C5) (5).

CVD infers an incredible expense for the health system, especially in occidental societies; consequently, it is important to grow information towards more appropriate management of the disease (3). Moreover, because of the heterogeneous clinical presentation and absence of a unifying terminology or classification system, early epidemiologic studies probably underestimated disease burden (1).

Pathophysiology of Chronic Venous Disease

The pathophysiological changes that underlie CVD include persistent ambulatory venous hypertension and the resulting inflammation (4). The clinical manifestations of chronic venous disease are primarily caused by ambulatory venous hypertension or failure to adequately lower venous pressure with ambulation in the upright position. The severity of the chronic venous disease is closely related to the magnitude of venous hypertension (5). CVD affects lower limbs, producing venous hypertension which is the difficulties of the venous blood return to the heart, having been described as the valvular failure as a key factor of this process (3).

Genetic predisposition, age, female sex, height, obesity, standing for prolonged periods of time, and pregnancy are some of the risk factors involved in CVD (4).

Diagnosis

Diagnostic evaluation in patients with the suspected chronic venous disease begins with clinical findings (6). A thorough history, physical examination, and supportive noninvasive testing will support the diagnosis and correct CEAP classification (1). This is followed by clinical examination of lower limbs using Duplex ultrasonography which will differentiate the potential candidate for CVD intervention.

In all patients presenting with a suspicion of lower limb CVD, based on history and clinical examination, full leg Duplex ultrasonography (DUS) should be performed routinely. If there is any suspicion of supra-inguinal pathology, based on clinical examination or specific DUS findings, additional abdominal and pelvic DUS is the next step. Where intervention is contemplated, it may be appropriate to assess the inflow from the deep femoral vein (DFV) into the common femoral vein (CFV) by DUS.

If the DUS findings only indicate disease below the inguinal ligament, this may be isolated superficial venous reflux or combined superficial and deep venous reflux, for which superficial venous intervention may be planned.

Finally, in patients with isolated deep venous incompetence, descending venography may be indicated.

Suspected supra-inguinal venous obstruction is further evaluated, by abdominal DUS or directly, by means of cross-sectional imaging, most commonly magnetic resonance venography (MRV) or computed tomography venography (CTV). In selected patients, where cross-sectional imaging is inadequate or not available, venography and/or intravascular ultrasound (IVUS) may be planned.

Guidelines on the management of CVD

European Society for Vascular Surgery (ESVS) 2022 laid down clinical guidance for the management of Chronic Venous Disease as follows (6):

Physical Method: Physical methods for treating CVD are studied increasingly as an adjunct or alternative to interventional treatment. Physical exercise, targeting lower limb muscle strength and ankle mobility, and physiotherapy may improve general mobility, promote weight loss, strengthen the calf muscle pump, and increase the range of ankle movements, all these facilitating venous returns. For patients with symptomatic chronic venous disease, exercise should be considered to reduce venous symptoms.

Compression: Compression therapy is a widespread treatment modality in Chronic Venous Disease. It mainly consists of four different compression modalities: elastic compression stockings (ECS), elastic and inelastic bandages, adjustable compression garments (ACG), and intermittent pneumatic compression (IPC) devices.

The guideline recommends compression therapy by graduated ECS exerting an ankle pressure ranging from 15 to 32 mmHg has proven effective in relieving symptoms in patients with C1 to C3 CEAP clinical class by decreasing pain, heaviness, cramps, and oedema related to CVD.

Compression therapy by ECS has also been shown to reduce skin induration in patients with lipodermatosclerosis (CEAP clinical class C4)

For patients with chronic venous disease and lipodermatosclerosis and/or atrophie blanche (CEAP clinical class C4), using below knee elastic compression stockings, exerting a pressure of 20 to 40 mmHg at the ankle, is recommended to reduce skin induration.

For patients with the post-thrombotic syndrome, below knee elastic compression stockings, exerting a pressure of 20 to 40 mmHg at the ankle, should be considered to reduce the severity

For patients with post-thrombotic syndrome, adjuvant intermittent pneumatic compression may be considered to reduce its severity.

Pharmacological treatment: Medical treatments such as Venoactive drugs (VAD) have been used for decades. VADs have beneficial effects on objective measures of leg oedema and on some symptoms and signs related to CVD. VAD enhances sympathetic mediated venous contractility and calcium sensitivity and mitigating venous valve deterioration and reflux. And they also lower the production of inflammatory cytokines in macrophages and neutrophils (7).

Micronized purified flavonoid fraction (MPFF; 90% diosmin and 10% concomitant active flavonoids) is the most widely prescribed VAD. In the recently updated management guidelines for CVD of the lower limbs, MPFF has been given strong recommendations. In clinical trials, MPFF has been shown to prevent the inflammatory consequences and microcirculatory dysfunction precipitated by chronic venous hypertension and to break the vicious cycle of venous inflammation that can lead to patient discomfort, skin changes, and venous ulcers (8). MPFF alone can be used at all stages of CEAP (C0 and C1-C6) or as an adjunct to surgery, sclerotherapy, endovenous thermal ablation, or compression (9).

Other VAD such as Ruscus extracts combined with hesperidin methyl chalcone (HMC) and ascorbic acid, and horse chestnut seed extract is also known to significantly improved several leg symptoms, including pain, heaviness, fatigue, feeling of swelling, cramps, paresthesia, global symptoms, and clinical findings such as ankle circumference and leg/foot volume.

Sclerotherapy: the targeted chemical ablation of varicose veins by intravenous injection of a liquid or foamed sclerosing drug. Liquid sclerotherapy is considered to be the method of choice for the treatment of C1 (clinical, aetiological, anatomical, and pathological elements [CEAP] classification) varicose veins (reticular varicose veins and telangiectasia). Foam sclerotherapy is an additional treatment option for C1 varicose veins (10).

In the treatment of incompetent saphenous veins, thermal ablation or surgery are well-established methods (10).

In CVD patients with superficial venous incompetence, management strategies mainly depend on clinical presentation (history, symptoms, signs) and detailed individual Duplex Ultrasound findings.

Summary and Way Forward

CVD is generally non-life-threatening and the symptoms are relatively nonspecific (1). Having said that, it stays one of the conspicuously misjudged and ignored diseases, consequently, patients and physicians tend to overlook or under-recognized CVD (1).

Knowing CVD's strong problematic nature, its prevalence increases with age and is more common in women than men (4); it is vital to give it genuine thought and to characterize appropriate measures from the internal medicine and cardiovascular communities to recognize the impact of this disease and embrace an understanding of the evaluation and management.

Early recognition and prompt treatment can alleviate and/or prevent the physical, functional, and psychological complications of this chronic vascular disorder (2). Taking cautious clinical chronicles and performing detailed physical and imaging assessments empower the therapy of this disease. As overall experience increases and devoted innovation improves, persistently better treatment and outcomes should result.

References:

1. Teresa L. Carman, Ali Al-Omari. Evaluation and Management of Chronic Venous Disease Using the Foundation of CEAP. 2019. PERIPHERAL VASCULAR DISEASE

2. Teresa J. Kelechi,Jan J. Johnson,and Stephanie Yates. Chronic venous disease and venous leg ulcers: An evidence-based update. 2015. Journal of Vascular Nursing.

3.Miguel A. Ortega,Oscar Fraile-Martínez, Ángel Asúnsolo,Clara Martínez-Vivero,Leonel Pekarek, Santiago Coca et.al. Chronic Venous Disease Patients Showed Altered Expression of IGF-1/PAPP-A/STC-2 Axis in the Vein Wall. 2020

4. Eberhard Rabe, Catherine Regnier , Fabienne Goron, Ghislaine Salmat, Felizitas Pannier. The prevalence, disease characteristics and treatment of chronic venous disease: an international web-based survey. 2020. Journal of Comparative Effectiveness Research

5. Nam. Tran and Mark H. Meissner. The Epidemiology, Pathophysiology, and Natural History of Chronic Venous Disease. 2002

6. Marianne G. De Maeseneer, Stavros K. Kakkos , Thomas Aherne , Niels Baekgaard, Stephen Black, Lena Blomgren. et.al. European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs

7. Mansilha A, Sousa J. Pathophysiological Mechanisms of Chronic Venous Disease and Implications for Venoactive Drug Therapy. Int J Mol Sci. 2018;19(6):1669. Published 2018 Jun 5. doi:10.3390/ijms19061669

8. McArdle M, Hernandez-Vila EA. Management of Chronic Venous Disease. Tex Heart Inst J. 2017;44(5):347-349. Published 2017 Oct 1. doi:10.14503/THIJ-17-6357

9. Jorge H. Ulloa. Micronized Purified Flavonoid Fraction (MPFF) for Patients Suffering from Chronic Venous Disease: A Review of New Evidence. 2019. Adv Ther

10. E Rabe, FX Breu , A Cavezzi , P Coleridge Smith , A Frullini, JL Gillet ,et.al ; for the Guideline Group. European guidelines for sclerotherapy in chronic venous disorders.2013. Phleobology.