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Editor's Choice – European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs

  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Marianne G. De Maeseneer
    Correspondence
    Corresponding author.
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Stavros K. Kakkos
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Thomas Aherne
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Niels Baekgaard
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Stephen Black
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Lena Blomgren
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Athanasios Giannoukas
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Manjit Gohel
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Rick de Graaf
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Claudine Hamel-Desnos
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Arkadiusz Jawien
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Aleksandra Jaworucka-Kaczorowska
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Christopher R. Lattimer
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Giovanni Mosti
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Thomas Noppeney
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Marie Josee van Rijn
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    Gerry Stansby
    Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
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    b ESVS Guidelines Committee: Philippe Kolh (Chair, Review Coordinator) (Liège, Belgium), Frederico Bastos Gonçalves (Lisboa, Portugal), Nabil Chakfé (Strasbourg, France), Raphael Coscas (Boulogne-Billancourt, France), Gert J. de Borst (Utrecht, The Netherlands), Nuno V. Dias (Malmö, Sweden), Robert J. Hinchliffe (Bristol, United Kingdom), Igor B. Koncar (Belgrade, Serbia), Jes S. Lindholt (Odense, Denmark), Santi Trimarchi (Milan, Italy), Riikka Tulamo (Helsinki, Finland), Christopher P. Twine (Bristol, United Kingdom), Frank Vermassen (Ghent, Belgium), Anders Wanhainen (Uppsala and Umeå, Sweden).
    ESVS Guidelines Committee
    Footnotes
    b ESVS Guidelines Committee: Philippe Kolh (Chair, Review Coordinator) (Liège, Belgium), Frederico Bastos Gonçalves (Lisboa, Portugal), Nabil Chakfé (Strasbourg, France), Raphael Coscas (Boulogne-Billancourt, France), Gert J. de Borst (Utrecht, The Netherlands), Nuno V. Dias (Malmö, Sweden), Robert J. Hinchliffe (Bristol, United Kingdom), Igor B. Koncar (Belgrade, Serbia), Jes S. Lindholt (Odense, Denmark), Santi Trimarchi (Milan, Italy), Riikka Tulamo (Helsinki, Finland), Christopher P. Twine (Bristol, United Kingdom), Frank Vermassen (Ghent, Belgium), Anders Wanhainen (Uppsala and Umeå, Sweden).
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    c Document Reviewers: Martin Björck (Uppsala, Sweden and Tartu, Estonia), Nicos Labropoulos (Stony Brook, NY, USA), Fedor Lurie (Toledo, OH, USA), Armando Mansilha (Porto, Portugal), Isaac K. Nyamekye (Worcester, United Kingdom), Marta Ramirez Ortega (Madrid, Spain), Jorge Ulloa, (Bogota, Colombia), Tomasz Urbanek (Katowice, Poland), Andre van Rij (Dunedin, New Zealand), Marc Vuylsteke (Tielt, Belgium).
    Document Reviewers
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    c Document Reviewers: Martin Björck (Uppsala, Sweden and Tartu, Estonia), Nicos Labropoulos (Stony Brook, NY, USA), Fedor Lurie (Toledo, OH, USA), Armando Mansilha (Porto, Portugal), Isaac K. Nyamekye (Worcester, United Kingdom), Marta Ramirez Ortega (Madrid, Spain), Jorge Ulloa, (Bogota, Colombia), Tomasz Urbanek (Katowice, Poland), Andre van Rij (Dunedin, New Zealand), Marc Vuylsteke (Tielt, Belgium).
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  • Author Footnotes
    a Writing Committee: Marianne G. De Maeseneer (Chair)* (Rotterdam, The Netherlands), Stavros K. Kakkos (Co-Chair) (Patras, Greece), Thomas Aherne (Galway, Ireland), Niels Baekgaard (Copenhagen, Denmark), Stephen Black (London, United Kingdom), Lena Blomgren (Örebro, Sweden), Athanasios Giannoukas (Larissa, Greece), Manjit Gohel (London, United Kingdom), Rick de Graaf (Friedrichshafen, Germany), Claudine Hamel-Desnos (Caen, France), Arkadiusz Jawien (Torun, Poland), Aleksandra Jaworucka-Kaczorowska (Gorzów, Poland), Christopher R. Lattimer (London, United Kingdom), Giovanni Mosti (Lucca, Italy), Thomas Noppeney (Regensburg, Germany), Marie Josee van Rijn (Rotterdam, The Netherlands), Gerry Stansby (Newcastle upon Tyne, United Kingdom)
    b ESVS Guidelines Committee: Philippe Kolh (Chair, Review Coordinator) (Liège, Belgium), Frederico Bastos Gonçalves (Lisboa, Portugal), Nabil Chakfé (Strasbourg, France), Raphael Coscas (Boulogne-Billancourt, France), Gert J. de Borst (Utrecht, The Netherlands), Nuno V. Dias (Malmö, Sweden), Robert J. Hinchliffe (Bristol, United Kingdom), Igor B. Koncar (Belgrade, Serbia), Jes S. Lindholt (Odense, Denmark), Santi Trimarchi (Milan, Italy), Riikka Tulamo (Helsinki, Finland), Christopher P. Twine (Bristol, United Kingdom), Frank Vermassen (Ghent, Belgium), Anders Wanhainen (Uppsala and Umeå, Sweden).
    c Document Reviewers: Martin Björck (Uppsala, Sweden and Tartu, Estonia), Nicos Labropoulos (Stony Brook, NY, USA), Fedor Lurie (Toledo, OH, USA), Armando Mansilha (Porto, Portugal), Isaac K. Nyamekye (Worcester, United Kingdom), Marta Ramirez Ortega (Madrid, Spain), Jorge Ulloa, (Bogota, Colombia), Tomasz Urbanek (Katowice, Poland), Andre van Rij (Dunedin, New Zealand), Marc Vuylsteke (Tielt, Belgium).
Open AccessPublished:January 11, 2022DOI:https://doi.org/10.1016/j.ejvs.2021.12.024

      ABBREVIATIONS AND ACRONYMS

      AASV
      anterior accessory saphenous vein
      ABI
      ankle brachial index
      ACG
      adjustable compression garments
      AP
      ambulatory phlebectomy
      ASVAL
      Ambulatory Selective Varicose vein Ablation under Local anaesthesia
      AVVQ
      Aberdeen Varicose Vein Questionnaire
      AVF
      arteriovenous fistula
      BMI
      body mass index
      CAC
      cyanoacrylate adhesive closure
      CEAP
      Clinical Etiological Anatomical Pathophysiological (classification)
      CDFS
      catheter directed foam sclerotherapy
      CFV
      common femoral vein
      CHIVA
      ambulatory conservative haemodynamic treatment of venous incompetence in outpatients (= French acronym for ‘Cure Hémodynamique de l’Insuffisance Veineuse en Ambulatoire’)
      CI
      confidence interval
      CIV
      common iliac vein
      CIVIQ
      chronic Venous Insufficiency Questionnaire
      CLaCS
      cryolaser and cryosclerotherapy guided by augmented reality
      CPP
      chronic pelvic pain
      CT
      computed tomography
      CTV
      computed tomography venography
      CVD
      chronic venous disease
      CVI
      chronic venous insufficiency
      DFV
      deep femoral vein
      DOAC
      direct oral anticoagulant
      DUS
      duplex ultrasound
      DVI
      deep vein incompetence
      DVT
      deep vein thrombosis
      eASVAL
      endovenous Ambulatory Selective Varicose vein Ablation under Local anaesthesia
      ECS
      elastic compression stockings
      EHIT
      endothermal heat induced thrombosis
      EIV
      external iliac vein
      EMLA
      eutectic mixture of local anaesthesia
      EMT
      electromagnetic therapy
      ESC
      European Society of Cardiology
      ESVS
      European Society for Vascular Surgery
      ESCHAR (trial)
      Effect of Surgery and Compression on Healing And Recurrence
      EVLA
      endovenous laser ablation
      EVMA
      endovenous microwave ablation
      EVRA (trial)
      Early Venous Reflux Ablation
      EVSA
      endovenous steam ablation
      EVTA
      endovenous thermal ablation
      fEVLA
      flush endovenous laser ablation
      FV
      femoral vein
      GSV
      great saphenous vein
      GWC
      Guideline Writing Committee
      HLS
      high ligation and stripping
      IB
      inelastic bandages
      IU
      international units
      IIV
      internal iliac vein
      IPC
      intermittent pneumatic compression
      IVC
      inferior vena cava
      IVUS
      intravascular ultrasound
      KTP
      potassium titanyl phosphate (laser)
      LMWH
      low molecular weight heparin
      MOCA
      mechanochemical ablation
      MPFF
      micronised purified flavonoid fraction
      MR
      magnetic resonance
      MRV
      magnetic resonance venography
      NIVL
      non-thrombotic iliac vein lesion
      OR
      odds ratio
      PASV
      posterior accessory saphenous vein
      PDL
      pulsed dye laser
      PE
      pulmonary embolism
      PeVD
      pelvic venous disorders
      POL
      polidocanol
      POPV
      popliteal vein
      PREVAIT
      PResence of Varices After Interventional Treatment
      PROMs
      patient reported outcome measures
      PTS
      post-thrombotic syndrome
      PV
      perforating vein
      PVI
      pelvic vein incompetence
      QoL
      quality of life
      RCT
      randomised controlled trial
      REVAS
      recurrent varicose veins after surgery
      RFA
      radiofrequency ablation
      RFITT
      radiofrequency induced thermal therapy
      r-VCSS
      revised venous clinical severity score
      SEPS
      subfascial endoscopic perforator surgery
      SFJ
      saphenofemoral junction
      SF-36
      Short Form 36
      SPJ
      saphenopopliteal junction
      SSI
      static stiffness index
      SSV
      small saphenous vein
      STS
      sodium tetradecyl sulphate
      SVT
      superficial vein thrombosis
      TCL
      transcutaneous laser
      TVUS
      transvaginal ultrasound
      UGFS
      ultrasound guided foam sclerotherapy
      UFH
      unfractionated heparin
      VA
      venous aneurysm
      VAD
      venoactive drug
      VAS
      visual analogue scale
      VCSS
      venous clinical severity score
      VEINES-QOL/Sym
      VEnous INsufficiency Epidemiological and Economic Study Quality of Life/symptoms
      VTE
      venous thromboembolism
      VLU
      venous leg ulcer
      VV
      varicose vein

      WHAT IS NEW IN THE 2022 GUIDELINES, COMPARED WITH THE 2015 GUIDELINES?

      Compared with the 2015 version of the guidelines on the management of chronic venous disease (CVD),
      • Wittens C.
      • Davies A.H.
      • Baekgaard N.
      • Broholm R.
      • Cavezzi A.
      • Chastanet S.
      • et al.
      Editor's Choice - Management of chronic venous disease: clinical practice guidelines of the European Society for Vascular Surgery (ESVS).
      the global structure of the document has been modified considerably in an attempt to make it more practical and user friendly. Special subsections on management strategy with accompanying flowcharts have been added to the different chapters.
      • An extensive chapter has been entirely dedicated to superficial venous incompetence. A new subsection on evidence supporting endovenous non-thermal ablation has been included. A new subsection on incompetence of perforating veins has been added, as well as a subsection on practical strategies for special anatomical presentations. The management of recurrent varicose veins is discussed at the end of this chapter.
      • Deep venous pathology is discussed in a separate chapter, with an emphasis on the increasing evidence in the field of managing iliofemoral and iliocaval obstruction. In addition, new topics in this chapter are the combination of superficial and deep venous problems, aneurysms of the deep veins and popliteal vein entrapment syndrome.
      • An entirely new chapter has been dedicated to the management of patients with venous leg ulcers.
      • A new chapter describes the management of patients with varicose veins, related to underlying pelvic venous disorders.
      • A new chapter considers special patient characteristics and their potential influence on management strategy.
      • Gaps in evidence and future perspectives are briefly discussed in a separate chapter.
      • A lay summary of the guidelines provides useful information for patients.
      In view of the new chapters and subsections, many new recommendations have been added, briefly summarised in Fig. 1. Compared with the 2015 CVD guidelines, five recommendations have also been upgraded, while another three have been downgraded (Fig. 2).
      Figure 1
      Figure 1New recommendations included in the European Society for Vascular Surgery 2022 clinical practice guidelines on the management of chronic venous disease of the lower limbs in comparison to the previous 2015 guidelines. Numbers correspond to the numbers of the recommendations in the guideline document. AASV = anterior accessory saphenous vein; ABI = ankle brachial index; CVD = chronic venous disease; DUS = duplex ultrasound; ECS = elastic compression stockings; EVTA = endovenous thermal ablation; GSV = great saphenous vein; IVUS = intravascular ultrasound; PTS = post-thrombotic syndrome; PV = perforating vein; UGFS = ultrasound-guided foam sclerotherapy; VV = varicose vein; VLU = venous leg ulcer.
      Figure 2
      Figure 2Changes in class of recommendations included in the European Society for Vascular Surgery 2022 clinical practice guidelines on the management of chronic venous disease of the lower limbs in comparison to the previous 2015 guidelines. Numbers correspond to the numbers of the recommendations in the guideline document. ASVAL = Ambulatory Selective Varices Ablation under Local Anaesthesia; EVTA = endovenous thermal ablation; PTS = post-thrombotic syndrome; SSV = small saphenous vein; UGFS = ultrasound-guided foam sclerotherapy.

      Introduction

      Purpose of these guidelines

      The European Society for Vascular Surgery (ESVS) has prepared new guidelines for the treatment of patients with CVD, to update the existing ESVS guidelines on the management of CVD, which were published in 2015.
      • Wittens C.
      • Davies A.H.
      • Baekgaard N.
      • Broholm R.
      • Cavezzi A.
      • Chastanet S.
      • et al.
      Editor's Choice - Management of chronic venous disease: clinical practice guidelines of the European Society for Vascular Surgery (ESVS).
      The focus of the present guidelines is on CVD of the lower limbs, related to pathology of the superficial, perforating and deep veins of the lower limbs as well as to abdominal and pelvic venous pathology. The guidelines report several recommendations on diagnosis and treatment of these pathologies in different chapters, with details on health questions and population described in the related text. These guidelines do not include patients with venous pathologies unrelated to CVD of the lower limbs nor patients suffering from venous or arteriovenous malformations. These guidelines provide guidance for vascular and general surgeons, vascular physicians, interventional radiologists, phlebologists, dermatologists, and emergency medicine physicians. The guidelines promote high standards of care (based on evidence, whenever available), established by specialists in the field.
      We wish to clarify that these guidelines are intended to support clinical decision making and that the recommendations may not be appropriate in all circumstances. The authors have created a clinical guideline and, as such, this reports only on treatment efficacy and clinical outcomes, not on costs, which may be very different from one country to another. In most healthcare systems, the question of management, whether to opt for conservative management or to intervene, as well as when and with which technique to intervene in CVD patients, is heavily influenced by cost (and cost effectiveness). The decision to follow a recommendation from the guidelines must be made by the responsible practitioner on an individual patient basis, taking into account the specific condition of the patient as well as local resources, regulations, laws, and clinical practice recommendations. Deviation from the guidance for specific reasons is perfectly permissible and should not in itself be interpreted as negligence.
      To further underline the supportive character of the guidelines, both European and non-European reviewers were invited to review the document, so that the document also can serve practitioners treating patients outside Europe. This is also the rationale behind the decision that all ESVS guidelines are free to download from the publisher’s website and the ESVS website www.esvs.org. In addition, an ESVS clinical guidelines App is available, where the guidelines can be found in easily readable form for use in everyday practice.

      Methodology

      Guideline Writing Committee

      Members of the Guideline Writing Committee (GWC) were selected by the ESVS to represent clinicians involved in the treatment of CVD and included vascular surgeons, vascular physicians, an interventional radiologist, and a gynaecologist - obstetrician. All members of the GWC were involved in selecting and rating the evidence for each of the different chapters and subsections under their responsibility (see Appendix with Supplementary Table of topics, search terms, and responsible authors), as agreed in the introductory meeting. All GWC members were involved in formulating the final recommendations.
      GWC members have provided disclosure statements regarding all relationships that might be perceived as real or potential sources of conflicts of interest. These are filed and available at the ESVS headquarters. GWC members received no financial support from any pharmaceutical, device, or surgical industry to develop these guidelines.

      Workflow for producing the guidelines

      The GWC held an introductory meeting in November 2019 in Amsterdam, Netherlands, at which the list of topics and author tasks were determined. Contributions from GWC members were compiled into a draft of the guidelines by the chair and co-chair. After the first draft was completed and internally reviewed, the GWC met again in September 2020 in Frankfurt, Germany, to review and approve the wording of each recommendation. The guidelines then underwent three rounds of external reviews, and appropriate revisions were implemented.

      Literature search

      GWC members agreed on a common systematic literature search strategy for each of the chapters. A comprehensive literature search of articles published was performed using MEDLINE (through PubMed), Embase, Cardiosource Clinical Trials Database, and the Cochrane Library databases between 1 January 2013 and 30 June 2020, for relevant papers published in English. The search terms used for the different chapters and subsections are mentioned in the Appendix (Supplementary Table). Reference checking and manual search by the GWC members added other relevant literature. Only peer reviewed, published literature and studies presenting pre-defined outcomes were considered. The selection process followed the “pyramid of evidence”, with aggregated evidence at the top of the pyramid (meta-analyses of several randomised controlled trials [RCTs], other meta-analyses, and systematic reviews), followed by RCTs and finally observational studies. Single case reports, abstracts, and in vitro studies were excluded, leaving expert opinion at the bottom of the pyramid. Articles published after the search date or in another language were included only if they were of paramount importance to this guideline. After the first and second external review, the members of the GWC performed a second and third literature search within their area of responsibility to determine if any important publications had been published between July 2020 and February 2021, and further until the end of June 2021, respectively.

      Evidence and Recommendations criteria

      The European Society of Cardiology (ESC) system was used for grading evidence and recommendations. A, B, or C reflects the level of current evidence (Table 1) and the strength of each recommendation was then determined to be class I, IIa, IIb, or III (Table 2).
      Table 1Levels of evidence according to ESC (European Society of Cardiology)
      Level of evidence AData derived from multiple randomised clinical trials or meta-analyses
      Level of evidence BData derived from a single randomised clinical trial or large non-randomised studies
      Level of evidence CConsensus of experts opinion and/or small studies, retrospective studies, and registries
      Table 2Classes of recommendations according to ESC (European Society of Cardiology)
      Class of recommendationDefinition
      Class IEvidence and/or general agreement that a given treatment or procedure is beneficial, useful and effective
      Class IIConflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure
      Class IIaWeight of evidence/opinion is in favour of usefulness/efficacy
      Class IIbUsefulness/efficacy is less well established by evidence/opinion
      Class IIIEvidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful
      To formulate recommendations, the strengths and limitations of the available evidence were considered, as well as benefit versus harm and applicability to clinical practice context. Details of study methodology limitations, appropriateness of primary and secondary outcomes, and consistency of results across studies were discussed in the main text.

      Tables of Evidence

      The members of the GWC provided summaries of the selected articles, used to support the evidence for the different recommendations, in Tables of Evidence (ToEs). These ToEs are available online, as Supplementary Material.

      The revision process and update of guidelines

      The guidelines document underwent external review for critical evaluation of the content and recommendations by members of the ESVS Guidelines Steering Committee, and by other independent experts in the field. After each review round, the reviewers’ general and detailed comments were compiled into one document. The manuscript was then revised according to the reviewers’ comments and all amendments were discussed and approved by all members of the GWC. In addition, a point to point reply to the reviewers was provided. After three review and subsequent revision rounds, the final document was approved and submitted to the European Journal of Vascular and Endovascular Surgery on 10 November 2021. These guidelines will be updated in 2026, according to the ESVS policy to update all guidelines which are part of the core curriculum of the vascular surgeon every four years.

      The patient perspective

      The importance of patient and public involvement in clinical guideline development is widely recognised and accepted. Patient engagement improves validity, increases quality of decisions, and is encouraged by national and international groups.
      To improve accessibility and interpretability for patients and the public, a plain English summary has been produced for this guideline and subjected to a lay review process. Information for patients was drafted for each subchapter which was read and amended by a vascular nurse specialist and at least one lay person or patient.
      Lay summaries were evaluated by a patient focus group, consisting of eight patients in the United Kingdom National Health Service with a history of CVD (six patients with C2-C5 disease and two patients with C6 disease) and three lay members of the public without CVD. All members of the focus group had been sent the lay summaries prior to the meeting, which was held virtually because of COVID-19 restrictions. At the meeting, the background and rationale for the ESVS CVD guidelines were presented and focus group feedback was obtained for each section of the document, systematically. All members of the focus group welcomed the invitation to contribute to the process and many commented that their personal experiences of care had been very different to the treatments recommended in the guidelines. Specifically, referral for specialist venous assessment had often been very delayed, although this may be a specific reflection of the United Kingdom National Health Service.
      Several patients stated that they had tried compression garments but found them difficult to wear. The group felt it important to express that where compression is recommended to patients, aids to help donning and removal of the stockings should be provided. The section describing superficial venous ablation procedures was found to be complex by the patients and lay members of the focus group and was simplified accordingly. Six of the patients in the focus group had been treated with endovenous ablation procedures. The group emphasised the importance of shared decision making and stated that they would want to discuss potential treatment options even if not locally available. Feedback from the focus group was used to amend the lay summaries.

      Areas not covered by these guidelines

      The general rule for ESVS guidelines is to avoid covering groups of patients in multiple guidelines as that may result in redundancy. Therefore, patients with superficial vein thrombosis (SVT) are mentioned only briefly and patients with deep vein thrombosis (DVT) are not covered in these guidelines, even if both SVT and DVT may occur as acute complications in patients with CVD. As these acute conditions require different management, the reader is referred to the ESVS 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis.
      • Kakkos S.K.
      • Gohel M.
      • Baekgaard N.
      • Bauersachs R.
      • Bellmunt-Montoya S.
      • Black S.A.
      • et al.
      Editor's Choice - European Society for Vascular Surgery (ESVS) 2021 clinical practice guidelines on the management of venous thrombosis.
      It was also decided to leave out congenital venous malformations, which will be part of future ESVS guidelines on vascular malformations, as well as venous tumours.

      1. General considerations

      In the VEIN-TERM transatlantic interdisciplinary consensus document, the term chronic venous disease (CVD) has been defined as “(any) morphological and functional abnormalities of the venous system of long duration manifest either by symptoms and/or signs indicating the need for investigation and/or care”.
      • Eklof B.
      • Perrin M.
      • Delis K.T.
      • Rutherford R.B.
      • Gloviczki P.
      • American Venous Forum
      • et al.
      Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document.
      As not all venous abnormalities can be considered a “disease”, the term “chronic venous disorders” has also been introduced, to encompass the full spectrum of morphological and functional abnormalities of the venous system. In the present guideline document the focus is on patients with symptoms and/or signs of CVD, requiring investigation and/or care. To describe CVD in the lower limbs of these patients, the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification is used, which is the most widely used descriptive tool for chronic venous disorders and disease.
      • Beebe H.G.
      • Bergan J.J.
      • Bergqvist D.
      • Eklof B.
      • Eriksson I.
      • Goldman M.P.
      • et al.
      Classification and grading of chronic venous disease in the lower limbs. A consensus statement.
      ,
      • Eklof B.
      • Rutherford R.B.
      • Bergan J.J.
      • Carpentier P.H.
      • Gloviczki P.
      • Kistner R.L.
      • et al.
      Revision of the CEAP classification for chronic venous disorders: consensus statement.
      CEAP allows detailed documentation of disease status at a specific time point, within four domains: clinical, aetiological, anatomical, and pathophysiological (Table 3). A recent update of the CEAP classification was published in 2020, including new categories for corona phlebectatica (C4c), recurrent varicose veins (C2r), and recurrent leg ulceration (C6r), a subdivision of secondary aetiology into intravenous (Esi) and extravenous (Ese) causes, and new abbreviations for anatomical terms, to replace the previously used numerical description (Table 4).
      • Lurie F.
      • Passman M.
      • Meisner M.
      • Dalsing M.
      • Masuda E.
      • Welch H.
      • et al.
      The 2020 update of the CEAP classification system and reporting standards.
      Table 3The 2020 update of the CEAP (Clinical Etiological Anatomical Pathophysiological) classification
      • Lurie F.
      • Passman M.
      • Meisner M.
      • Dalsing M.
      • Masuda E.
      • Welch H.
      • et al.
      The 2020 update of the CEAP classification system and reporting standards.
      ClassDescription
      Clinical (C) class
       C0No visible or palpable signs of venous disease
       C1Telangiectasia or reticular veins
      C2Varicose veins
      C2rRecurrent varicose veins
       C3Oedema
      C4Changes in skin and subcutaneous tissue secondary to CVD
      C4aPigmentation or eczema
      C4bLipodermatosclerosis or atrophie blanche
      C4cCorona phlebectatica
       C5Healed ulcer
      C6Active venous ulcer
      C6rRecurrent venous ulceration
       Symptomatic or not: subscript ‘S’ or subscript ‘A’S: symptomatic, including ache, pain, tightness, skin irritation, heaviness, and muscle cramps, and other complaints attributable to venous dysfunction

      A: asymptomatic
      Etiological (E) class
       EpPrimary
       EsSecondary
       EsiSecondary – intravenous
       EseSecondary – extravenous
       EcCongenital
       EnNone identified
      Anatomical (A) class
       AsSuperficial
       AdDeep
       ApPerforators
       AnNo identifiable venous location
      Pathophysiological (P) class
      Reporting of pathophysiological class must be accompanied by the relevant anatomical location (see Table 4). CVD = chronic venous disease.
       PrReflux
       PoObstruction
       Pr,oReflux and obstruction
       PnNo pathophysiology identified
      Reporting of pathophysiological class must be accompanied by the relevant anatomical location (see Table 4). CVD = chronic venous disease.
      Table 4The 2020 update of CEAP (Clinical Etiological Anatomical Pathophysiological): Summary of anatomical classification
      • Lurie F.
      • Passman M.
      • Meisner M.
      • Dalsing M.
      • Masuda E.
      • Welch H.
      • et al.
      The 2020 update of the CEAP classification system and reporting standards.
      Anatomical classificationSegment number
      Numbers of anatomical segments used in the 2004 revision5 of the CEAP classification.
      New anatomical site
      New specific anatomical location(s) to be reported under each Pathophysiological (P) class to identify anatomical location(s) corresponding to P class.
      Description
      As (Superficial)1TelTelangiectasia
      1RetReticular veins
      2GSVaGreat saphenous vein, above knee
      3GSVbGreat saphenous vein, below knee
      4SSVSmall saphenous vein
      AASVAnterior accessory saphenous vein
      5NSVNon-saphenous vein
      Ad (Deep)6IVCInferior vena cava
      7CIVCommon iliac vein
      8IIVInternal iliac vein
      9EIVExternal iliac vein
      10PELVPelvic vein
      11CFVCommon femoral vein
      12DFVDeep femoral vein
      13FVFemoral vein
      14POPVPopliteal vein
      15TIBVCrural (Tibial) vein
      15PRVPeroneal vein
      15ATVAnterior tibial vein
      15PTVPosterior tibial vein
      16MUSVMuscular veins
      16GAVGastrocnemius vein
      16SOVSoleal vein
      Ap (Perforator)17TPVThigh perforator vein
      18CPVCalf perforator vein
      An (No venous anatomic location identified)
      Numbers of anatomical segments used in the 2004 revision
      • Eklof B.
      • Rutherford R.B.
      • Bergan J.J.
      • Carpentier P.H.
      • Gloviczki P.
      • Kistner R.L.
      • et al.
      Revision of the CEAP classification for chronic venous disorders: consensus statement.
      of the CEAP classification.
      New specific anatomical location(s) to be reported under each Pathophysiological (P) class to identify anatomical location(s) corresponding to P class.
      The term “chronic venous insufficiency” (CVI) is reserved for advanced CVD, which is applied to functional abnormalities of the venous system, producing oedema, skin changes, or venous ulcers, corresponding with C3 to C6 of the CEAP classification.
      • Eklof B.
      • Perrin M.
      • Delis K.T.
      • Rutherford R.B.
      • Gloviczki P.
      • American Venous Forum
      • et al.
      Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document.

      1.1 Epidemiology

      A recently published comprehensive systematic review on global epidemiology of CVD identified 32 studies from six continents including > 300 000 adults.
      • Salim S.
      • Machin M.
      • Patterson B.O.
      • Onida S.
      • Davies A.H.
      Global epidemiology of chronic venous disease: a systematic review with pooled prevalence analysis.
      Nineteen studies were used for unadjusted, pooled prevalence for each C class of the CEAP classification, from C0S (symptomatic, no clinical signs) to C6 (venous leg ulcer). Pooled estimates were: C0S: 9%, C1: 26%, C2: 19%, C3: 8%, C4: 4%, C5: 1%, C6: 0.4%. The pooled prevalence of C2 disease was highest in Europe (21%) and lowest in Africa (5.5%). The annual incidence of C2 disease ranged from 0.2% to 2.3%. CVD progression was estimated to affect 31.9% of patients at a mean follow up of 13.4 years. C2 disease had a progression rate of 22% developing a venous leg ulcer (VLU) in six years. Commonly reported risk factors for CVD included female gender, age, obesity, prolonged standing, positive family history and parity. The authors of this review conclude that significant heterogeneity exists in epidemiological studies and future research needs to use diagnostic duplex ultrasound (DUS), to provide more complete data. The high prevalence of C0S in the systematic review mentioned above is mainly the result of an important contribution by studies from the Vein Consult Programme, an international survey performed by general practitioners worldwide during 100 000 routine consultations, without DUS, where a prevalence of C0S of 19.7% was found.
      • Rabe E.
      • Guex J.J.
      • Puskas A.
      • Scuderi A.
      • Fernandez Quesada F.
      • VCP Coordinators
      Epidemiology of chronic venous disorders in geographically diverse populations: results from the Vein Consult Program.
      It should be acknowledged that the available evidence on C0S remains very limited.
      Although progression of CVD is important, few epidemiological studies have investigated its natural history. In the Edinburgh Vein Study, a random sample of 1 566 men and women aged 18 – 64 years had been examined at baseline.
      • Evans C.J.
      • Fowkes F.G.
      • Ruckley C.V.
      • Lee A.J.
      Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study.
      Of these, 880 were followed up for 13 years and underwent clinical evaluation and DUS scanning of the deep and superficial venous systems, and 0.9% (CI 0.7 – 1.3%) of this adult population developed reflux each year. Progression occurred more often in overweight subjects and in those with a history of DVT, but there was no association with patient sex or age. In two thirds of all cases reflux was limited to the superficial venous system. The presence of venous reflux at baseline was significantly associated with the development of new varicose veins (VVs) at follow up, especially when combined deep and superficial reflux was present.
      • Robertson L.A.
      • Evans C.J.
      • Lee A.J.
      • Allan P.L.
      • Ruckley C.V.
      • Fowkes F.G.
      Incidence and risk factors for venous reflux in the general population: Edinburgh Vein Study.
      During the 13 years of observation, CVD progression was reported in 57.8%, for an annual rate of 4.3%, and one third of patients with uncomplicated VVs at baseline developed skin changes.
      • Lee A.J.
      • Robertson L.A.
      • Boghossian S.M.
      • Allan P.L.
      • Ruckley C.V.
      • Fowkes F.G.
      • et al.
      Progression of varicose veins and chronic venous insufficiency in the general population in the Edinburgh Vein Study.
      The natural history of CVD was also investigated in a large longitudinal study, the Bochum study I-IV, which included initially 740 pupils of 10 – 12 years (Bochum I), 136 of whom underwent follow up to the age of 30 years (Bochum IV). This study revealed that preclinical venous reflux, identified in a young population, represented a 30% risk (95% CI 13 – 53%) of developing truncal VVs within four years.
      • Schultz-Ehrenburg U.
      • Reich-Schupke S.
      • Robak-Pawelczyk B.
      • Rudolph T.
      • Moll C.
      • Weindorf N.
      • et al.
      Prospective epidemiological study on the beginning of varicose veins. Bochum Study I–IV.

      1.2 Anatomy

      The anatomy of the superficial, perforating, and deep veins of the lower limbs has been described extensively.
      • Caggiati A.
      • Bergan J.J.
      • Gloviczki P.
      • Jantet G.
      • Wendell-Smith C.P.
      • Partsch H.
      • et al.
      Nomenclature of the veins of the lower limbs: an international interdisciplinary consensus statement.
      ,
      • Caggiati A.
      • Bergan J.J.
      • Gloviczki P.
      • Eklof B.
      • Allegra C.
      • Partsch H.
      • et al.
      Nomenclature of the veins of the lower limb: extensions, refinements, and clinical application.
      The anatomical terms and their abbreviations used in the present guidelines correspond with the 2020 update of the CEAP classification (Table 4).
      • Lurie F.
      • Passman M.
      • Meisner M.
      • Dalsing M.
      • Masuda E.
      • Welch H.
      • et al.
      The 2020 update of the CEAP classification system and reporting standards.
      The main veins of the lower limbs are represented in Fig. 3.
      Figure 3
      Figure 3Anatomy of the deep veins and the main superficial veins (great saphenous vein and small saphenous vein) of the lower limbs. ∗Appears usually as paired veins.

      1.2.1 The superficial and perforating veins of the lower limb

      The great saphenous vein (GSV) drains into the common femoral vein (CFV) at the level of the saphenofemoral junction (SFJ). The GSV lies in its saphenous compartment, which is easily recognisable on B mode ultrasound scanning. The most important accessory saphenous vein is the anterior accessory saphenous vein (AASV), which runs almost parallel and slightly lateral to the GSV in the thigh, in its own saphenous compartment (Fig. 4). The small saphenous vein (SSV) ascends upwards on the posterior calf to join the popliteal vein (POPV) in the popliteal fossa in the majority of cases, although the level of the junction with the deep venous system may vary. Veins connecting the GSV and SSV are called “intersaphenous veins”. A particular intersaphenous vein is the Giacomini vein (Fig. 4) connecting the SSV in the popliteal fossa with the cephalad GSV. DUS has revealed the large variability of the superficial veins and therefore it is mandatory to rely on the so called “duplex anatomy” to plan any treatment.
      • Cavezzi A.
      • Labropoulos N.
      • Partsch H.
      • Ricci S.
      • Caggiati A.
      • Myers K.
      • et al.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part II. Anatomy.
      ,
      • De Maeseneer M.
      • Pichot O.
      • Cavezzi A.
      • Earnshaw J.
      • van Rij A.
      • Lurie F.
      • et al.
      Duplex ultrasound investigation of the veins of the lower limbs after treatment for varicose veins - UIP consensus document.
      Tributaries of the saphenous trunks and accessory veins are situated in the subcutaneous tissue with a very variable distribution and present as visible or palpable, usually tortuous VVs. Perforating veins (PVs) are variable in arrangement and distribution, connecting the deep and superficial veins, with unidirectional valves assuring flow from superficial to deep veins, except in the foot. PVs form a complex subfascial network of interconnected veins.
      Figure 4
      Figure 4Anatomy of the main accessory saphenous veins and Giacomini vein (intersaphenous vein connecting the small saphenous vein with the great saphenous vein). In the presence of a Giacomini vein, the saphenopopliteal junction may be present or absent.

      1.2.2 The deep veins of the lower limb

      The paired posterior tibial veins and the peroneal veins in the calf join to form the tibioperoneal trunk, which joins the anterior tibial veins. Large veins of the soleus and gastrocnemius muscles join these to form the POPV. This ascends in the adductor canal becoming the femoral vein (FV), which joins the deep femoral vein (DFV) to form the CFV in the groin. Above the inguinal ligament, the CFV continues as the external iliac vein (EIV) and, after receiving the internal iliac vein (IIV), continues as the common iliac vein (CIV). On the left side the CIV passes between the right common iliac artery and the vertebral column. From the confluence of the right and left CIV, the inferior vena cava (IVC) ascends alongside the right of the aorta.

      1.2.3 Small veins and the microvenous circulation

      Small veins of the subcutaneous and cutaneous venous network have been studied less extensively than large veins and their valves.
      • Ortega-Santana F.
      • Hernández-Morera P.
      • Ruano-Ferrer F.
      • Ortega-Centol A.
      Infrared illumination and subcutaneous venous network: can it be of help for the study of CEAP C1 limbs?.
      Previously, the belief was that venous valves did not exist in veins and venules of < 2 mm. However, detailed studies of small veins in the skin of the lower leg showed that valves do exist even in veins with a diameter from 100 μm – 2 mm, and that these microvenous valves also can be incompetent.
      • Phillips M.N.
      • Jones G.T.
      • van Rij A.M.
      • Zhang M.
      Micro-venous valves in the superficial veins of the human lower limb.
      A study using retrograde resin venography in amputated lower limbs demonstrated that valvular incompetence can exist in these small veins, independently of valvular competence of the GSV. In the third generation of tributaries from the GSV the so called “boundary” valves can be seen, which are able to prevent reflux to the skin. When GSV reflux is present, incompetence of these microvalves may play a critical role in progression of skin changes.

      Vincent JR, Jones GT, Hill GB, van Rij AM. Failure of microvenous valves in small superficial veins is a key to the skin changes of venous insufficiency. J Vasc Surg 2011;54(Suppl. 6):62S–9S.

      1.3 Pathophysiology

      The pathophysiology of CVD is best considered as having two distinct components, namely the events that occur within the larger superficial and deep veins and those that occur subsequently in the microcirculation and surrounding tissues of the skin. In the superficial veins changes occur within the venous wall and valves leading to valve incompetence, changes in vasomotor tone, and reflux. This is followed by vascular remodelling and degenerative loss of elastin and collagen as well as fibrosis with changes in wall thickness and development of VVs. The initial causes of these changes are believed to be inflammatory phenomena.
      • Raffetto J.D.
      Pathophysiology of chronic venous disease and venous ulcers.
      ,
      • Mansilha A.
      • Sousa J.
      Pathophysiological mechanisms of chronic venous disease and implications for venoactive drug therapy.
      Endothelial cells play a key role in this inflammatory cascade, with consequent pathological venous changes and increasing deterioration of CVD.
      • Castro-Ferreira R.
      • Cardoso R.
      • Leite-Moreira A.
      • Mansilha A.
      The role of endothelial dysfunction and inflammation in chronic venous disease.
      These pathophysiological phenomena may progress in an ascending (first in the tributaries, followed by the saphenous trunks, thereafter at the junction) or descending pattern (first at the junction, followed by the saphenous trunks, thereafter in tributaries).
      • Labropoulos N.
      • Giannoukas A.D.
      • Delis K.
      • Mansour M.A.
      • Kang S.S.
      • Nicolaides A.N.
      • et al.
      Where does venous reflux start?.
      The consequence of reflux and changing wall compliance is faster refilling, less efficient venous emptying, and venous hypertension particularly in the erect position and with walking. Perforator flow, which is normally from superficial to deep veins (re-entry), may also increase leading to remodelling, enlargement, and development of PV incompetence.
      In the deep veins, the pathophysiology differs and venous emptying is compromised by either obstruction and/or reflux. This is most often secondary to DVT and is categorised as “Esi” (secondary aetiology, intravenous) in the updated CEAP classification.
      • Lurie F.
      • Passman M.
      • Meisner M.
      • Dalsing M.
      • Masuda E.
      • Welch H.
      • et al.
      The 2020 update of the CEAP classification system and reporting standards.
      If the thrombus lyses or recanalises, the valves may be damaged or destroyed and deep venous reflux occurs. If the thrombus does not lyse or recanalise sufficiently, the vessel lumen remains narrow or occluded and outflow is obstructed. PVs may be similarly affected, lose valvular competence, remodel, and enlarge with outward flow. As a consequence, the deep venous changes may lead to venous hypertension in the superficial veins.
      • Lee B.B.
      • Nicolaides A.N.
      • Myers K.
      • Meissner M.
      • Kalodiki E.
      • Allegra C.
      • et al.
      Venous hemodynamic changes in lower limb venous disease: the UIP consensus according to scientific evidence.
      This pathway and related symptoms/signs has been called post-thrombotic syndrome (PTS).
      • Eklof B.
      • Perrin M.
      • Delis K.T.
      • Rutherford R.B.
      • Gloviczki P.
      • American Venous Forum
      • et al.
      Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document.
      When both obstruction and reflux are present, the clinical course may be more severe.
      • Labropoulos N.
      • Patel P.J.
      • Tiongson J.E.
      • Pryor L.
      • Leon Jr., L.R.
      • Tassiopoulos A.K.
      Patterns of venous reflux and obstruction in patients with skin damage due to chronic venous disease.
      Other causes of impaired venous emptying and venous hypertension with similar outcomes (categorised as “Ese” [secondary aetiology, extravenous] in the updated CEAP classification)
      • Lurie F.
      • Passman M.
      • Meisner M.
      • Dalsing M.
      • Masuda E.
      • Welch H.
      • et al.
      The 2020 update of the CEAP classification system and reporting standards.
      include extrinsic vein compression (e.g., intra-abdominal masses or iliac vein compression), raised venous pressure with right heart failure, impaired muscle pump, and obesity.
      The pathophysiology of CVD in the skin and subcutaneous tissue of the lower leg is distinct from that seen in the larger veins and is primarily a consequence of venous hypertension on the microcirculation. Small veins and venules also have valves which become incompetent and, along with capillaries, elongate, dilate, and become tortuous. The severity of these morphological changes observed with capillaroscopy correlate well with the severity of skin changes of CVD.
      • Bollinger A.
      • Leu A.J.
      • Hoffmann U.
      • Franzeck U.K.
      Microvascular changes in venous disease: an update.
      As these changes occur, the endothelium of the capillary and post-capillary venules becomes progressively dysfunctional with fluid leakage, complex inflammatory mediators, and cell migration. These result in oedema, fibrin cuff formation, inflammatory reaction, and a chronic deteriorating sequence of inflammation, fibrosis, pigmentation, and calcification within the dermis, with paradoxical hyperaemic hypoxia and loss of normal integrity of the skin with VLU formation.
      The clinical significance of venous hypertension has been extensively investigated with direct venous pressure measurements in a dorsal foot vein. When standing the venous pressure is high (80 – 90 mmHg), but with activation of the calf muscle pump as during tip toe exercise or walking, known as ambulatory venous pressure (AVP), it is substantially reduced (20 – 30 mmHg). Failure to adequately lower the standing venous pressure while walking results in a high AVP. A recent large retrospective study including 4 132 limbs with CVD symptoms, confirmed that an increase in AVP is associated with a higher clinical class of CVD, but was mainly associated with reflux and less commonly with proximal obstruction.
      • Raju S.
      • Knight A.
      • Lamanilao L.
      • Pace N.
      • Jones T.
      Peripheral venous hypertension in chronic venous disease.

      1.4 Clinical presentation

      1.4.1 Symptoms

      The symptoms of CVD are extremely variable and may cause significant morbidity to patients, negatively affecting quality of life (QoL). Symptoms increase with age and are more commonly reported in women. Patients may present with heaviness, tired legs, feeling of swelling, itching of the skin, nocturnal cramps, throbbing, burning pain, aching of the legs, which is exacerbated by prolonged standing or sitting, or venous claudication during exercise. It is sometimes difficult to attribute symptoms to a venous aetiology and call them “venous symptoms”. All clinical CEAP classes from C0S to C6 can be associated with the same symptoms, which do not necessarily correlate with the presence or severity of venous hypertension.
      • Perrin M.
      • Eklof B.
      • Van Rij A.
      • Labropoulos N.
      • Vasquez M.
      • Nicolaides A.
      • et al.
      Venous symptoms: the SYM Vein Consensus statement developed under the auspices of the European Venous Forum.
      CVD can be asymptomatic, even in limbs with extensive VVs and even C4 and C5 clinical CEAP class, while venous symptoms can be present without any clinical sign of CVD (C0S). On the other hand, similar symptoms are frequently present in patients with other diseases of the lower limbs.
      • Van der Velden S.K.
      • Shadid N.H.
      • Nelemans P.J.
      • Sommer A.
      How specific are venous symptoms for diagnosis of chronic venous disease?.
      Symptoms of heaviness, sensation of swelling, burning, itching, and pain/aching are associated with higher C of the CEAP clinical class both in intensity and number of symptoms. Symptoms such as fatigue, cramps, and restless legs are less specific for CVD.
      • Wrona M.
      • Jockel K.H.
      • Pannier F.
      • Bock E.
      • Hoffmann B.
      • Rabe E.
      Association of venous disorders with leg symptoms: results from the Bonn Vein Study 1.
      ,
      • Vuylsteke M.E.
      • Thomis S.
      • Guillaume G.
      • Modliszewski M.L.
      • Weides N.
      • Staelens I.
      Epidemiological study on chronic venous disease in Belgium and Luxembourg: prevalence, risk factors, and symptomatology.
      Venous claudication is a symptom presenting as increasing pain on exercise. It is caused by outflow obstruction at the iliofemoral and/or caval level as well as popliteal vein entrapment, leading to limited walking capacity.
      • Perrin M.
      • Eklof B.
      • Van Rij A.
      • Labropoulos N.
      • Vasquez M.
      • Nicolaides A.
      • et al.
      Venous symptoms: the SYM Vein Consensus statement developed under the auspices of the European Venous Forum.
      In a small study in 39 patients, at a median follow up of five years after iliofemoral DVT, a standardised treadmill test (3.5 km/h, slope 10%) elicited venous claudication, necessitating interruption of walking in 15% of patients.
      • Delis K.T.
      • Bountouroglou D.
      • Mansfield A.O.
      Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life.

      1.4.2 Signs

      In CVD, clinical signs are described per limb as the “C” component of the CEAP classification, from C1 to C6 (Table 3).
      • Lurie F.
      • Passman M.
      • Meisner M.
      • Dalsing M.
      • Masuda E.
      • Welch H.
      • et al.
      The 2020 update of the CEAP classification system and reporting standards.
      Other typical clinical signs, not included in the CEAP classification, are the presence of cross pubic collaterals in case of unilateral iliac vein obstruction, abdominal collaterals in case of IVC obstruction (caused by previous DVT, congenital absence/hypoplasia, or extrinsic compression) (see Chapter 5) and vulvar VVs in women with pelvic venous disorders (PeVD) (see Chapter 7).

      1.4.3 Acute complications

      Acute complications are uncommon in patients with CVD. The most common is SVT, which may be limited to a varicose tributary, or affect a saphenous trunk. This can be complicated by extension into the deep venous system as a concomitant DVT and, exceptionally cause pulmonary embolism (PE). In patients with CVD, DVT or a recurrent DVT may occur. In general, VVs are considered a minor risk factor for developing DVT, as discussed in the ESVS guidelines on the management of venous thrombosis.
      • Kakkos S.K.
      • Gohel M.
      • Baekgaard N.
      • Bauersachs R.
      • Bellmunt-Montoya S.
      • Black S.A.
      • et al.
      Editor's Choice - European Society for Vascular Surgery (ESVS) 2021 clinical practice guidelines on the management of venous thrombosis.
      In a population based study it was concluded that it is unclear whether the association between VVs (without SVT) and DVT is causal or a result of common risk factors.
      • Chang S.L.
      • Huang Y.L.
      • Lee M.C.
      • Hu S.
      • Hsiao Y.C.
      • Chang S.W.
      • et al.
      Association of varicose veins with incident venous thromboembolism and peripheral artery disease.
      Another acute complication is haemorrhage, which is commonly associated with a traumatised superficial vein or telangiectasia, but significant bleeding can also arise from an area of ulceration. The resulting blood loss may be extensive and even life threatening.
      • Serra R.
      • Ielapi N.
      • Bevacqua E.
      • Rizzuto A.
      • De Caridi G.
      • Massara M.
      • et al.
      Haemorrhage from varicose veins and varicose ulceration: a systematic review.

      1.5 Scoring systems

      When considering scoring systems for CVD, it is important to realise that the CEAP classification gives a descriptive snapshot of a limb with CVD at a point in time, allowing grouping into CVD subgroups. While changes in CEAP class provide useful information and may guide management, the CEAP classification is categorical and therefore not well suited for monitoring treatment success, assessing disease progression, or rationing interventions. Scoring tools, which provide continuous variables, are more suitable for this purpose.

      1.5.1 Clinical scoring systems

      Clinical scoring systems were developed to provide a more dynamic assessment of patient status over time. The revised Venous Clinical Severity Score (r-VCSS) is the most widely used clinical scoring tool and is designed to measure changes in status after venous intervention (Table 5).
      • Vasquez M.
      • Rabe E.
      • McLafferty R.
      • Shortell C.
      • Marston W.
      • Gillespie D.
      • et al.
      Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group.
      ,
      • Passman M.A.
      • McLafferty R.B.
      • Lentz M.F.
      • Nagre S.B.
      • Iafrati M.D.
      • Bohannon W.T.
      • et al.
      Validation of Venous Clinical Severity Score (VCSS) with other venous severity assessment tools from the American Venous Forum, National Venous Screening Program.
      The Villalta scale is an in part patient rated and in part physician rated tool for diagnosing and evaluating the severity of PTS in the lower extremity (Table 6).
      • Villalta S.B.P.
      • Picolli A.
      • Lensing A.
      • Prins M.
      • Prandoni P.
      Assessment of validity and reproducibility of a clinical scale for the post thrombotic syndrome.
      ,
      • Kahn S.R.
      Measurement properties of the Villalta scale to define and classify the severity of the post-thrombotic syndrome.
      While the Villalta scale is widely used and validated for use in patients with PTS, it should be noted that its specificity has been questioned, as several of the included symptoms and signs are features of CVD in patients without a history of DVT.
      Table 5The revised Venous Clinical Severity Score (r-VCSS)
      • Vasquez M.
      • Rabe E.
      • McLafferty R.
      • Shortell C.
      • Marston W.
      • Gillespie D.
      • et al.
      Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group.
      VariableDescription (score)
      Absent (0)Mild (1)Moderate (2)Severe (3)
      Pain
      Ache, heaviness, fatigue, soreness, and burning presumptive of a venous origin.
      or ulcer discomfort
      NoneOccasionalDaily, interfering with, but not preventing regular activitiesDaily, limiting most regular activities
      Varicose veinsNoneFew, scattered or corona phlebectaticaConfined to calf or thighInvolve calf and thigh
      Venous oedemaNoneLimited to foot or ankleExtends above ankle but below kneeExtends to knee or above
      Skin pigmentationNone or focalLimited to perimalleolar areaDiffuse over lower third of calfWider distribution (above lower third of calf)
      InflammationNoneLimited to perimalleolar areaDiffuse over lower third of calfWider distribution (above lower third of calf)
      IndurationNoneLimited to perimalleolar areaInvolving lower third of calfInvolving more than lower third of calf
      Number of active ulcersNone12> 2
      Active ulcer durationNone< 3 mo> 3 mo but < 1 y> 1 y
      Active ulcer sizeNoneDiameter < 2 cmDiameter 2–6 cmDiameter > 6 cm
      Compression therapyNot usedIntermittent use of stockingStocking use most daysFull compliance with stockings
      Ache, heaviness, fatigue, soreness, and burning presumptive of a venous origin.
      Table 6The Villalta scale and its interpretation for post-thrombotic syndrome (PTS)
      • Villalta S.B.P.
      • Picolli A.
      • Lensing A.
      • Prins M.
      • Prandoni P.
      Assessment of validity and reproducibility of a clinical scale for the post thrombotic syndrome.
      Clinical findings
      Each variable is given a score of between 0 and 3 indicative of a severity of none, mild, moderate, or severe, respectively, with a maximum score of 33.
      NoneMildModerateSevere
      Symptoms
       Pain0123
       Cramping0123
       Heaviness0123
       Pruritis0123
       Paraesthesia0123
      Signs
       Oedema0123
       Induration0123
       Hyperpigmentation0123
       Venous ectasia0123
       Redness0123
       Calf tenderness0123
      Interpretation of severity of post thrombotic syndrome
       Villalta score< 55–910–14> 14 or the presence of venous ulceration
      Each variable is given a score of between 0 and 3 indicative of a severity of none, mild, moderate, or severe, respectively, with a maximum score of 33.

      1.5.2 Patient reported outcome measures

      Tabled 1
      Recommendation 1Unchanged
      For patients with chronic venous disease, the use of the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification is recommended for clinical audit and research.
      ClassLevelReferences
      ICConsensus
      Tabled 1
      Recommendation 2Unchanged
      For patients with chronic venous disease, grading of clinical severity and evaluation of treatment success using the revised Venous Clinical Severity Score (r-VCSS) and the Villalta scale for post-thrombotic syndrome, should be considered for clinical audit and research.
      ClassLevelReferences
      IIaCConsensus

      2. Investigations

      This chapter describes the value of the different investigations used in patients with CVD. It describes physical examination and available additional tests. In the diagnostic work up, the nature of the problem and the severity of the disease should be determined.

      2.1 Clinical examination

      After medical history taking, focusing on venous symptoms (see subsection 1.4.1), thromboembolic history, allergies, and medication, the patient is examined in the standing position, whenever possible. Clinical signs of CVD as described in 1.4.2 are carefully sought, including visible scars in case of recurrence after previous VVs surgery and the presence of cross pubic, anterior, and lateral abdominal wall collaterals, which raises the suspicion of supra-inguinal venous pathology. Other possible causes for complaints and lower extremity clinical signs, such as arterial disease, orthopaedic, rheumatological, or neurological pathology are also evaluated. The circumference of both legs at the ankle and calf may be measured for oedema cases. Photographs may be added to the patient’s file for future comparison, in particular for skin changes.

      2.2 Handheld continuous wave Doppler

      Handheld continuous wave Doppler provides no information on venous morphology, has low reliability in detecting obstruction or reflux in deep veins, and research has shown that pre-operative planning on the basis of continuous wave Doppler alone, instead of DUS, results in inadequate treatment in a significant proportion of patients and therefore has no role in the diagnosis of CVD.
      • Rautio T.
      • Perälä J.
      • Biancari F.
      • Wiik H.
      • Ohtonen P.
      • Haukipuro K.
      • et al.
      Accuracy of hand-held Doppler in planning the operation for primary varicose veins.
      For these reasons, it has been replaced by DUS.
      However, in patients with a suspicion of concomitant lower extremity atherosclerotic disease, handheld Doppler is still used to measure the ankle pressure and the ankle brachial index (ABI) (see subsections 3.2.1.3 and 6.3.3).

      2.3 Duplex ultrasound

      2.3.1 Duplex ultrasound of the lower limbs

      DUS of the lower extremities is the primary diagnostic test of choice in patients with CVD.
      • Cavezzi A.
      • Labropoulos N.
      • Partsch H.
      • Ricci S.
      • Caggiati A.
      • Myers K.
      • et al.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part II. Anatomy.
      ,
      • Blomgren L.
      • Johansson G.
      • Emanuelsson L.
      • Dahlberg-Akerman A.
      • Thermaenius P.
      • Bergqvist D.
      Late follow-up of a randomized trial of routine duplex imaging before varicose vein surgery.
      ,
      • Coleridge-Smith P.
      • Labropoulos N.
      • Partsch H.
      • Myers K.
      • Nicolaides A.
      • Cavezzi A.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles.
      It provides information about venous anatomy, patency, vein wall pathology, and flow. Morphological examination of deep veins and evaluation of normal phasic flow in the CFV may be performed in the supine position. To evaluate the presence or absence of reflux, DUS is preferentially done in the upright position with the knee of the investigated leg slightly bent. Reflux must be provoked, either from above with dependency testing or a Valsalva manoeuvre, or from below, using an automatic pneumatic pressure cuff or manual compression of the thigh, calf, or foot.
      • Cavezzi A.
      • Labropoulos N.
      • Partsch H.
      • Ricci S.
      • Caggiati A.
      • Myers K.
      • et al.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part II. Anatomy.
      ,
      • Coleridge-Smith P.
      • Labropoulos N.
      • Partsch H.
      • Myers K.
      • Nicolaides A.
      • Cavezzi A.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles.
      The Valsalva manoeuvre is typically used to assess the SFJ. The clinical significance of measuring reflux duration is questionable other than to establish its presence beyond a cut off duration. It depends on the provocation manoeuvre used and may be difficult to quantify. The cut off values most used are 1 second for reflux in the CFV, FV and POPV and 0.5 seconds in superficial veins and PVs, although 0.35 seconds has been used as a threshold for PVs as well.
      • De Maeseneer M.
      • Pichot O.
      • Cavezzi A.
      • Earnshaw J.
      • van Rij A.
      • Lurie F.
      • et al.
      Duplex ultrasound investigation of the veins of the lower limbs after treatment for varicose veins - UIP consensus document.
      ,
      • Coleridge-Smith P.
      • Labropoulos N.
      • Partsch H.
      • Myers K.
      • Nicolaides A.
      • Cavezzi A.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles.
      ,
      • Labropoulos N.
      • Tiongson J.
      • Pryor L.
      • Tassiopoulos A.K.
      • Kang S.S.
      • Mansour M.
      • et al.
      Definition of venous reflux in lower-extremity veins.
      Other useful information on ultrasound in CVD includes the course of the reflux, the length of the refluxing trunk, and saphenous trunk diameter, which should be measured in the upright position in a vein segment without focal dilatation (for the GSV at about 15 cm from the SFJ).
      • Mendoza E.
      • Blattler W.
      • Amsler F.
      Great saphenous vein diameter at the saphenofemoral junction and proximal thigh as parameters of venous disease class.
      ,
      • Hamel-Desnos C.M.
      • De Maeseneer M.
      • Josnin M.
      • Gillet J.L.
      • Allaert F.A.
      DIAGRAVES Study Group
      Great saphenous vein diameters in phlebological practice in France: a report of the DIAGRAVES Study by the French Society of Phlebology.
      A detailed methodology for performing DUS of the lower extremities has been described previously.
      • Cavezzi A.
      • Labropoulos N.
      • Partsch H.
      • Ricci S.
      • Caggiati A.
      • Myers K.
      • et al.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part II. Anatomy.
      ,
      • De Maeseneer M.
      • Pichot O.
      • Cavezzi A.
      • Earnshaw J.
      • van Rij A.
      • Lurie F.
      • et al.
      Duplex ultrasound investigation of the veins of the lower limbs after treatment for varicose veins - UIP consensus document.
      In addition to a written DUS report, it is important to make an accurate graphical representation of the DUS findings in the superficial and deep veins of the examined limbs, called “venous mapping”. This is an essential tool to plan and perform venous interventions.

      2.3.1.1 Varicose veins (first presentation)

      The CFV, FV, and POPV are checked for patency, reflux, and any post-thrombotic obstruction. Then, the GSV, AASV, and SSV, including the SFJ and saphenopopliteal junction (SPJ), are examined for reflux, followed by any other relevant incompetent superficial veins. PV incompetence is sought especially in the vicinity of a VLU, severe skin changes, absence of SFJ or SPJ incompetence as a source of reflux, and/or atypically located VVs.
      • Stuart W.P.
      • Adam D.J.
      • Allan P.L.
      • Ruckley C.V.
      • Bradbury A.W.
      The relationship between the number, competence, and diameter of medial calf perforating veins and the clinical status in healthy subjects and patients with lower-limb venous disease.
      The definition of PV incompetence remains controversial. PV incompetence is characterised by having a net outward flow of > 0.35 seconds duration (or > 0.5 seconds, according to others) on DUS and a vessel diameter > 3.5 mm is usually considered “pathological”, in particular in an area with skin changes.
      • Labropoulos N.
      • Tiongson J.
      • Pryor L.
      • Tassiopoulos A.K.
      • Kang S.S.
      • Mansour M.
      • et al.
      Definition of venous reflux in lower-extremity veins.
      ,
      • Sandri J.L.
      • Barros F.S.
      • Pontes S.
      • Jacques C.
      • Salles-Cunha S.X.
      Diameter-reflux relationship in perforating veins of patients with varicose veins.

      2.3.1.2 Recurrent varicose veins

      Recurrent VVs often display recanalisation of a saphenous trunk, previously treated by endovenous ablation, neovascularisation at the location of previous surgery (in particular at the SFJ), or reflux in other veins such as the AASV, the SSV, or PVs, which may have been healthy previously. The aim of the investigation is to identify the nature and source of the recurrence.
      • De Maeseneer M.
      • Pichot O.
      • Cavezzi A.
      • Earnshaw J.
      • van Rij A.
      • Lurie F.
      • et al.
      Duplex ultrasound investigation of the veins of the lower limbs after treatment for varicose veins - UIP consensus document.

      2.3.2 Abdominal ultrasound

      Whenever there is a suspicion of supra-inguinal pathology, based on clinical examination (extensive unilateral oedema, healed or active VLU, abdominal wall collaterals) or on specific DUS findings while examining the lower limbs (absence of phasic flow in the CFV, or post-thrombotic fibrosis in the deep veins), the next step is to perform an additional abdominal DUS. It should be acknowledged that DUS examination of abdominal and pelvic veins (i.e. gonadal veins and IIVs) requires appropriate expertise. If this is not available, cross sectional imaging may be preferred. In certain patients it may be technically difficult to perform abdominal DUS because of abdominal obesity or the presence of bowel gas. Abdominal DUS is preferably performed after the patient has been fasting overnight.
      • Labropoulos N.
      • Jasinski P.T.
      • Adrahtas D.
      • Gasparis A.P.
      • Meissner M.H.
      A standardized ultrasound approach to pelvic congestion syndrome.
      The patient is placed in supine position and the IVC and iliac veins are examined with DUS to detect potential compression or luminal obstruction and to evaluate direction of flow and velocities. The presence of collaterals, absence of phasic flow in the CFV, and flow velocity changes may indicate obstruction.
      • Metzger P.B.
      • Rossi F.H.
      • Kambara A.M.
      • Izukawa N.M.
      • Saleh M.H.
      • Pinto I.M.
      • et al.
      Criteria for detecting significant chronic iliac venous obstructions with duplex ultrasound.
      ,
      • Sloves J.
      • Almeida J.I.
      Venous duplex ultrasound protocol for iliocaval disease.
      When DUS was compared with intravascular ultrasound (IVUS), a velocity ratio (maximum through obstruction velocity/maximum pre-obstruction velocity) ≥ 2.5 was found to be the best criterion for detecting significant venous outflow obstructions in iliac veins.
      • Metzger P.B.
      • Rossi F.H.
      • Kambara A.M.
      • Izukawa N.M.
      • Saleh M.H.
      • Pinto I.M.
      • et al.
      Criteria for detecting significant chronic iliac venous obstructions with duplex ultrasound.
      When PeVD are suspected, the left renal, gonadal, peri-uterine and para-vaginal veins, and the tributaries of the IIVs are examined.
      • Labropoulos N.
      • Jasinski P.T.
      • Adrahtas D.
      • Gasparis A.P.
      • Meissner M.H.
      A standardized ultrasound approach to pelvic congestion syndrome.
      After venous thrombolysis and stenting, DUS is often used for patency surveillance.

      2.4 Cross sectional imaging

      Cross sectional imaging encompasses techniques generating two dimensional images perpendicular to the axis of the body, most commonly magnetic resonance (MR) imaging and computed tomography (CT).
      • Arnoldussen C.W.
      • de Graaf R.
      • Wittens C.H.
      • de Haan M.W.
      Value of magnetic resonance venography and computed tomographic venography in lower extremity chronic venous disease.
      ,
      • Uhl J.F.
      Three-dimensional modelling of the venous system by direct multislice helical computed tomography venography: technique, indications and results.
      Cross sectional imaging may offer an alternative tool in the detection of deep venous pathology when DUS is inadequate or not feasible. Whether to perform MR or CT to investigate the deep veins is mainly dependent on the local expertise in performing and evaluating these images.

      2.4.1 Magnetic resonance venography

      MR venography (MRV) can provide information about the venous system that is enhanced by 3-D reconstruction. Dynamic imaging information can be provided as well with regard to velocity and volume. MRV can visualise deep vein obstruction, fibrotic scarring of the vein wall and in the lumen (post-thrombotic fibrosis), as well as collaterals and VVs.
      • Helyar V.G.
      • Gupta Y.
      • Blakeway L.
      • Charles-Edwards G.
      • Katsanos K.
      • Karunanithy N.
      Depiction of lower limb venous anatomy in patients undergoing interventional deep venous reconstruction-the role of balanced steady state free precession MRI.

      2.4.2 Computed tomography venography

      CT venography (CTV) is generally more available than MRV and its imaging protocols receive wider acknowledgement by the medical community.
      • Coelho A.
      • O'Sullivan G.
      Usefulness of direct computed tomography venography in predicting inflow for venous reconstruction in chronic post-thrombotic syndrome.
      Obviously, CTV necessitates the use of iodinated contrast and ionising radiation, comparing unfavourably with MRV. There are two main techniques for performing lower limb CTV. Indirect CTV is performed as post-intravenous contrast enhanced CT, with imaging results largely dependent on cardiac output, size of the intravenous line, rate of injection, and degree of hydration. Direct CTV generally involves intravenous injection of contrast in the foot or directly into the FV or POPV with ascending acquisition of imaging, providing improved detail. Direct CTV may allow for increased detailed imaging of luminal pathology. However, contrast transit times are hard to predict and therefore adequate imaging of abdominal, pelvic, and peripheral veins may be cumbersome.

      2.5 Endovenous imaging

      Historically, angiography has been established as the “gold standard” to diagnose macroscopic vascular pathology. However, for CVD, venography has not been adequately validated. Ever since endovascular treatment became available for chronic venous obstruction, IVUS has challenged venography for dominance. However, it needs to be emphasised that none of the currently available imaging modalities have been validated for clinically relevant CVD.

      2.5.1 Venography

      Classical ascending venography (also called phlebography) by access and contrast injection from a foot vein has no additional value over DUS to screen for deep venous obstruction and is now considered obsolete. Venography with access gained through the POPV, FV, or CFV, has previously been used to evaluate particular aspects of supra-inguinal venous obstruction. It can indirectly diagnose left CIV obstruction through the identification of a combination of collaterals and a flattened CIV (pancaking).
      • Lau I.
      • Png C.Y.M.
      • Eswarappa M.
      • Miller M.
      • Kumar S.
      • Tadros R.
      • et al.
      Defining the utility of anteroposterior venography in the diagnosis of venous iliofemoral obstruction.
      Although multiplanar venographic imaging in at least two perpendicular projections may improve its diagnostic value, it is impractical and increases radiation exposure and iodinated contrast use. Another challenge relates to the immobile, prone, or supine position of the patient, which may over- or underdiagnose CVD. Intravenous imaging of proximal venous outflow obstruction has primarily been substituted by IVUS. However, the method can still be used if other imaging techniques are inadequate or unavailable. Descending venography may also be applicable in rare cases where deep valve reconstructive surgery is being considered (see subsection 5.4).

      2.5.2 Intravascular ultrasound

      IVUS has become an increasingly useful investigation for deep venous pathology over the last decade. Like CTV and MRV, IVUS accurately determines cross luminal diameter and surface area of the deep veins. However, in addition, IVUS can identify subtle intraluminal changes and vein wall abnormalities that may remain obscure if other imaging techniques are used. It has been shown to be more sensitive than venography in identifying deep venous lesions, as has been shown in the VIDIO trial. In this RCT, 100 patients with C4 to C6 CEAP clinical class and suspected iliofemoral vein obstruction underwent both IVUS and multiplanar venography. IVUS proved to be more sensitive than venography in identification and quantification of iliofemoral vein obstructive lesions. Therefore, IVUS may provide an additional advantage in patient selection for venous stenting.
      • Gagne P.J.
      • Tahara R.W.
      • Fastabend C.P.
      • Dzieciuchowicz L.
      • Marston W.
      • Vedantham S.
      • et al.
      Venography versus intravascular ultrasound for diagnosing and treating iliofemoral vein obstruction.
      However, IVUS is an invasive modality and can be used only if the lesion of interest can be crossed with a guidewire first.

      2.6 Plethysmography

      Air plethysmography measures the global change in volume in mL/s of the part of the calf enclosed by the cuff, in response to gravitational filling on dependency (venous filling index) and drainage on leg elevation (venous drainage index).
      • Lattimer C.R.
      • Mendoza E.
      Reappraisal of the utility of the tilt-table in the investigation of venous disease.
      ,
      • Raju S.
      • Knepper J.
      • May C.
      • Knight A.
      • Pace N.
      • Jayaraj A.
      Ambulatory venous pressure, air plethysmography, and the role of calf venous pump in chronic venous disease.
      Rapid filling and slow elevation drainage are indicative of global venous incompetence and obstruction, respectively.
      • Lattimer C.R.
      • Doucet S.
      • Geroulakos G.
      • Kalodiki E.
      Validation of the novel venous drainage index with stepwise increases in thigh compression pressure in the quantification of venous obstruction.
      This is in contrast to ultrasound flow measurements in selected vein segments induced by a compression/release manoeuvre.
      Tabled 1
      Recommendation 3Unchanged
      For diagnosis and treatment planning in patients with suspected or clinically evident chronic venous disease, full lower limb venous duplex ultrasound is recommended as the primary imaging modality.
      ClassLevelReferencesToE
      IBBlomgren et al. (2011)
      • Blomgren L.
      • Johansson G.
      • Emanuelsson L.
      • Dahlberg-Akerman A.
      • Thermaenius P.
      • Bergqvist D.
      Late follow-up of a randomized trial of routine duplex imaging before varicose vein surgery.
      Tabled 1
      Recommendation 4New
      For patients with suspected supra-inguinal venous obstruction, in addition to full leg duplex assessment, ultrasound of the abdominal and pelvic veins should be considered, as part of the initial assessment.
      ClassLevelReferencesToE
      IIaCMetzger et al. (2016)
      • Metzger P.B.
      • Rossi F.H.
      • Kambara A.M.
      • Izukawa N.M.
      • Saleh M.H.
      • Pinto I.M.
      • et al.
      Criteria for detecting significant chronic iliac venous obstructions with duplex ultrasound.
      Tabled 1
      Recommendation 5Unchanged
      When an intervention is contemplated in patients with suspected supra-inguinal venous obstruction, cross sectional imaging by magnetic resonance venography or computed tomography is recommended in addition to duplex ultrasound assessment.
      ClassLevelReferencesToE
      ICCoelho et al. (2019)
      • Coelho A.
      • O'Sullivan G.
      Usefulness of direct computed tomography venography in predicting inflow for venous reconstruction in chronic post-thrombotic syndrome.
      Tabled 1
      Recommendation 6Unchanged
      For selected patients with suspected supra-inguinal venous obstruction, where cross sectional diagnostic imaging is inadequate or not available, venography and/or intravascular ultrasound may be considered.
      ClassLevelReferencesToE
      IIbBGagne et al. (2017),
      • Gagne P.J.
      • Tahara R.W.
      • Fastabend C.P.
      • Dzieciuchowicz L.
      • Marston W.
      • Vedantham S.
      • et al.
      Venography versus intravascular ultrasound for diagnosing and treating iliofemoral vein obstruction.
      Lau et al. (2019)
      • Lau I.
      • Png C.Y.M.
      • Eswarappa M.
      • Miller M.
      • Kumar S.
      • Tadros R.
      • et al.
      Defining the utility of anteroposterior venography in the diagnosis of venous iliofemoral obstruction.
      Tabled 1
      Recommendation 7Unchanged
      For patients with chronic venous disease, air plethysmography may be considered for quantification of reflux and/or obstruction, in particular when duplex ultrasound results do not reconcile with the clinical findings.
      ClassLevelReferencesToE
      IIbCLattimer et al. (2016),
      • Lattimer C.R.
      • Mendoza E.
      Reappraisal of the utility of the tilt-table in the investigation of venous disease.
      Lattimer et al. (2017),
      • Lattimer C.R.
      • Doucet S.
      • Geroulakos G.
      • Kalodiki E.
      Validation of the novel venous drainage index with stepwise increases in thigh compression pressure in the quantification of venous obstruction.
      Raju et al. (2019),
      • Raju S.
      • Knepper J.
      • May C.
      • Knight A.
      • Pace N.
      • Jayaraj A.
      Ambulatory venous pressure, air plethysmography, and the role of calf venous pump in chronic venous disease.
      Lattimer et al. (2019),
      • Lattimer C.R.
      • Mendoza E.
      Which venous patients need to be investigated with air-plethysmography and why?.
      Kalodiki et al. (2019)
      • Kalodiki E.
      • Azzam M.
      • Schnatterbeck P.
      • Geroulakos G.
      • Lattimer C.R.
      The Discord Outcome Analysis (DOA) as a reporting standard at three months and five years in randomised varicose vein treatment trials.

      2.7 Diagnostic strategy

      Although in this chapter medical history taking, clinical examination and DUS have been described as separate parts of the investigation, in clinical practice, they may be done either sequentially or simultaneously, depending on the local setting.
      DUS can be used to diagnose venous reflux, to plan treatment, for ultrasound guidance during treatment, and is also a useful tool for post-operative assessment and surveillance in CVD. It may be performed by the physician, as an integral part of the examination of the patient, or by a vascular technologist reporting to the physician.
      The main diagnostic pathways are summarised in Fig. 5. In all patients presenting with a suspicion of lower limb CVD, based on history and clinical examination, full leg DUS should be performed routinely. If there is any suspicion of supra-inguinal pathology, based on clinical examination or specific DUS findings (see subsection 2.3.2), additional abdominal and pelvic DUS is the next step. Where intervention is contemplated, it may be appropriate to assess the inflow from the DFV into the CFV by DUS.
      Figure 5
      Figure 5Main diagnostic pathways for patients with suspected chronic venous disease (CVD) of the lower limbs and main treatment pathways. Patients with symptomatic varicose veins and clinical suspicion of pelvic venous disorders are not included in this flowchart (see ). ∗Clinical examination includes inspection of abdomen for potential collaterals, in particular in case of suspected iliac or iliocaval obstruction. DUS = duplex ultrasound; GP = general practitioner; MRV = magnetic resonance venography; CTV = computed tomography venography; IVUS = intravascular ultrasound.
      The anatomical extent of reflux or obstruction in affected veins combined with the patient’s general characteristics, symptoms, and clinical signs can help the clinician to plan and customise treatment.
      • Cavezzi A.
      • Labropoulos N.
      • Partsch H.
      • Ricci S.
      • Caggiati A.
      • Myers K.
      • et al.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part II. Anatomy.
      ,
      • De Maeseneer M.
      • Pichot O.
      • Cavezzi A.
      • Earnshaw J.
      • van Rij A.
      • Lurie F.
      • et al.
      Duplex ultrasound investigation of the veins of the lower limbs after treatment for varicose veins - UIP consensus document.
      ,
      • Coleridge-Smith P.
      • Labropoulos N.
      • Partsch H.
      • Myers K.
      • Nicolaides A.
      • Cavezzi A.
      Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles.
      There is considerable individual variation in the vulnerability to venous hypertension and thus the presence of reflux on DUS is not an indication for treatment per se (see subsection 4.1.1). If it is concluded, after DUS, that the symptoms and signs are not related to CVD, referral to the general practitioner or to another specialist is the logical next step. If the patient is not a candidate for intervention, advice about conservative measures should be provided (see Chapter 3) as well as follow up appointments, as necessary.
      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 (see Chapter 4). In rare cases, superficial veins may contribute significantly to venous outflow by bypassing an obstructed femoropopliteal segment. Intervention on these veins is contraindicated (see subsection 5.5).
      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 MRV or CTV.
      • Metzger P.B.
      • Rossi F.H.
      • Kambara A.M.
      • Izukawa N.M.
      • Saleh M.H.
      • Pinto I.M.
      • et al.
      Criteria for detecting significant chronic iliac venous obstructions with duplex ultrasound.
      ,
      • Arnoldussen C.W.
      • de Graaf R.
      • Wittens C.H.
      • de Haan M.W.
      Value of magnetic resonance venography and computed tomographic venography in lower extremity chronic venous disease.
      ,
      • Coelho A.
      • O'Sullivan G.
      Usefulness of direct computed tomography venography in predicting inflow for venous reconstruction in chronic post-thrombotic syndrome.
      In selected patients, where cross sectional imaging is inadequate or not available, venography and/or IVUS may be planned.
      Air plethysmography, if available, may be of diagnostic value in specific clinical scenarios such as unexplained leg oedema, even after previous treatment, and skin changes, including VLU, persisting after treatment of all sources of reflux. The specialised technique of occlusion plethysmography may be of value also in patients with complex PTS.
      • Lattimer C.R.
      • Mendoza E.
      Which venous patients need to be investigated with air-plethysmography and why?.
      The diagnostic approach for patients with VVs and suspected underlying PeVD is described in Chapter 7.

      3. Conservative management

      This section mainly focuses on conservative measures in CVD patients without active VLU. The conservative management options for patients with VLU are discussed extensively in Chapter 6.

      3.1 Physical methods

      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 return.
      • Araujo D.N.
      • Ribeiro C.T.
      • Maciel A.C.
      • Bruno S.S.
      • Fregonezi G.A.
      • Dias F.A.
      Physical exercise for the treatment of non-ulcerated chronic venous insufficiency.
      • Caggiati A.
      • De Maeseneer M.
      • Cavezzi A.
      • Mosti G.
      • Morrison N.
      Rehabilitation of patients with venous diseases of the lower limbs: state of the art.
      • Gurdal Karakelle S.
      • Ipek Y.
      • Tulin O.
      • Alpagut I.U.
      The efficiency of exercise training in patients with venous insufficiency: a double blinded, randomized controlled trial.
      • Silva K.L.S.
      • Figueiredo E.A.B.
      • Lopes C.P.
      • Vianna M.V.A.
      • Lima V.P.
      • Figueiredo P.H.S.
      • et al.
      The impact of exercise training on calf pump function, muscle strength, ankle range of motion, and health-related quality of life in patients with chronic venous insufficiency at different stages of severity: a systematic review.
      Nevertheless larger studies are still needed.
      Subsequently this may reduce leg oedema and prevent or ameliorate skin changes caused by CVD. It may also alleviate symptoms and signs of PTS, although available evidence is scarce.
      • Kahn S.R.
      • Shrier I.
      • Shapiro S.
      • Houweling A.H.
      • Hirsch A.M.
      • Reid R.D.
      • et al.
      Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial.
      Despite the paucity of studies specifically on CVI, the indirect evidence for the benefit of exercise on venous function is considerable and thus it should be promoted.
      • Caggiati A.
      • De Maeseneer M.
      • Cavezzi A.
      • Mosti G.
      • Morrison N.
      Rehabilitation of patients with venous diseases of the lower limbs: state of the art.
      Leg elevation and the use of insoles to improve the foot muscle pump may be beneficial but most studies are small. Other methods with less evidence for treatment of CVD, but with improvement of health related QoL, include massage, balneotherapy, and cooling therapy.
      • Araujo D.N.
      • Ribeiro C.T.
      • Maciel A.C.
      • Bruno S.S.
      • Fregonezi G.A.
      • Dias F.A.
      Physical exercise for the treatment of non-ulcerated chronic venous insufficiency.
      ,
      • Kelechi T.J.
      • Dooley M.J.
      • Mueller M.
      • Madisetti M.
      • Prentice M.A.
      Symptoms associated with chronic venous disease in response to a cooling treatment compared to placebo: a randomized clinical trial.
      ,
      • de Moraes Silva M.A.
      • Nakano L.C.
      • Cisneros L.L.
      • Miranda F Jr
      Balneotherapy for chronic venous insufficiency.
      Tabled 1
      Recommendation 8New
      For patients with symptomatic chronic venous disease, exercise should be considered to reduce venous symptoms.
      ClassLevelReferencesToE
      IIaBKahn et al. (2011),
      • Kahn S.R.
      • Shrier I.
      • Shapiro S.
      • Houweling A.H.
      • Hirsch A.M.
      • Reid R.D.
      • et al.
      Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial.
      Araujo et al. (2016),
      • Araujo D.N.
      • Ribeiro C.T.
      • Maciel A.C.
      • Bruno S.S.
      • Fregonezi G.A.
      • Dias F.A.
      Physical exercise for the treatment of non-ulcerated chronic venous insufficiency.
      Gurdal Karakelle et al. (2021)
      • Gurdal Karakelle S.
      • Ipek Y.
      • Tulin O.
      • Alpagut I.U.
      The efficiency of exercise training in patients with venous insufficiency: a double blinded, randomized controlled trial.

      3.2 Compression

      Compression therapy is a widespread treatment modality in CVD. 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. ACG are made from stiff material with self adhesive straps, usually applied from the ankle to the knee. The straps can be stretched and adjusted around the leg. The more they are stretched, the higher the compression pressure. This section only addresses compression in limbs with clinical class C0S - C5 whereas compression in case of active VLU (C6) will be discussed in subsection 6.3. In limbs with clinical class C0S - C5 mainly ECS and ACG are used.
      ECS, intended for medical use, exert a graduated compression pressure, which means compression pressure is always higher at ankle level than at calf level. ECS, bandages, and IPC can be knee or thigh high. No evidence is available about the preferred ECS length in different clinical situations. In practice, thigh length compression devices are prescribed mainly for oedema involving the whole leg (mainly caused by secondary lymphoedema in patients with PTS after extensive DVT), for SVT of the GSV above the knee and for post-operative use after high ligation and stripping (HLS) or endovenous GSV ablation. In all other cases, knee length compression devices are used routinely.
      When prescribing a compression device for CVD management, it is necessary to check for potentially concomitant lower extremity atherosclerotic disease by measuring the absolute pressure value at the ankle and the ABI. In diabetics, additional toe pressure measurement is indicated, as ABI may not be reliable due to medial arterial sclerosis. Compression pressure must be reduced in cases of impaired arterial status or severe neuropathy.
      • Rabe E.
      • Partsch H.
      • Morrison N.
      • Meissner M.H.
      • Mosti G.
      • Lattimer C.R.
      • et al.
      Risks and contraindications of medical compression treatment - a critical reappraisal. An international consensus statement.
      This is particularly important in patients with mixed arterial and venous ulcers (see subsection 6.3.3).

      3.2.1 Elastic compression stockings, adjustable compression garments, and inelastic bandages

      3.2.1.1 Evidence

      Compression therapy by graduated ECS exerting an ankle pressure ranging from 15 to 32 mmHg has proven effective in relieving symptoms in patients with C1s – C3s CEAP clinical class by decreasing pain, heaviness, cramps, and oedema related to CVD.
      • Benigni J.P.
      • Sadoun S.
      • Allaert F.A.
      • Vin F.
      Efficacy of Class 1 elastic compression stockings in the early stages of chronic venous disease. A comparative study.
      ,
      • Kakkos S.K.
      • Timpilis M.
      • Patrinos P.
      • Nikolakopoulos K.M.
      • Papageorgopoulou C.P.
      • Kouri A.K.
      • et al.
      Acute effects of graduated elastic compression stockings in patients with symptomatic varicose veins: a randomised double blind placebo controlled trial.
      Compression therapy comprising ECS, inelastic bandages (IB), and ACG is effective in oedema treatment.
      • Mosti G.
      • Picerni P.
      • Partsch H.
      Compression stockings with moderate pressure are able to reduce chronic leg oedema.
      • Mosti G.
      • Partsch H.
      Bandages or double stockings for the initial therapy of venous oedema? A randomized, controlled pilot study.
      • Mosti G.
      • Cavezzi A.
      • Partsch H.
      • Urso S.
      • Campana F.
      Adjustable velcro compression devices are more effective than inelastic bandages in reducing venous edema in the initial treatment phase: a randomized controlled trial.
      ECS exerting 23 – 32 mmHg have been compared with IB exerting about 60 mmHg. IB were significantly more effective in reducing oedema after 48 hours but not anymore after seven days, showing that ECS are almost as effective as IB in reducing venous oedema.
      • Mosti G.
      • Picerni P.
      • Partsch H.
      Compression stockings with moderate pressure are able to reduce chronic leg oedema.
      In two comparable studies by the same group, a combination of two superimposed ECS in one study,
      • Mosti G.
      • Partsch H.
      Bandages or double stockings for the initial therapy of venous oedema? A randomized, controlled pilot study.
      and an ACG in another study,
      • Mosti G.
      • Cavezzi A.
      • Partsch H.
      • Urso S.
      • Campana F.
      Adjustable velcro compression devices are more effective than inelastic bandages in reducing venous edema in the initial treatment phase: a randomized controlled trial.
      both of these compression devices exerting a pressure of about 40 mmHg were again compared with IB, exerting about 60 mmHg immediately after applying the bandages. Superimposed ECS and ACG were, respectively, as effective or more effective in reducing pitting venous oedema, when compared with IB. This equal or greater effectiveness of superimposed ECS or ACG can be explained by both devices being able to maintain their exerted pressure. IB quickly lose their initial high pressure, especially in oedematous legs, thereby becoming less effective.
      In addition to the traditional graduated ECS, which exert a higher pressure at ankle than at calf level, progressive ECS, exerting a higher pressure at calf level than at the ankle level, have been reported to be more effective than graduated ECS in reducing venous symptoms, such as pain and heaviness.
      • Couzan S.
      • Leizorovicz A.
      • Laporte S.
      • Mismetti P.
      • Pouget J.F.
      • Chapelle C.
      • et al.
      A randomized double-blind trial of upward progressive versus degressive compressive stockings in patients with moderate to severe chronic venous insufficiency.
      This higher efficacy could be explained by higher pressure being exerted over the calf, where the muscle and venous reservoir are located, than over the ankle where there are just tendons and bones. Indeed, it has been demonstrated that progressive ECS are more effective than graduated ECS in improving the venous haemodynamics by ameliorating the muscle pumping function.
      • Mosti G.
      • Partsch H.
      Improvement of venous pumping function by double progressive compression stockings: higher pressure over the calf is more important than a graduated pressure profile.
      Occupational oedema was also reduced more effectively by progressive ECS at calf level.
      • Mosti G.
      • Partsch H.
      Occupational leg oedema is more reduced by antigraduated than by graduated stockings.
      These results are partially contradicted by a RCT in which progressive ECS were shown to be effective, but to a lesser extent, when compared with graduated ECS
      • Riebe H.
      • Konschake W.
      • Haase H.
      • Junger M.
      Advantages and disadvantages of graduated and inverse graduated compression hosiery in patients with chronic venous insufficiency and healthy volunteers: a prospective, mono-centric, blinded, open randomised, controlled and cross-over trial.
      .
      Compression therapy by ECS has also been shown to reduce skin induration in patients with lipodermatosclerosis (CEAP clinical class C4b).
      • Vandongen Y.K.
      • Stacey M.C.
      Graduated compression elastic stockings reduce lipodermatosclerosis and ulcer recurrence.
      In patients with PTS there is limited evidence on the effectiveness of ECS, despite their common use in clinical practice. There are just three small studies on ECS with short duration of follow up.
      • Ginsberg J.S.
      • Hirsh J.
      • Julian J.
      • Vander LaandeVries M.
      • Magier D.
      • MacKinnon B.
      • et al.
      Prevention and treatment of postphlebitic syndrome: results of a 3-part study.
      • Frulla M.
      • Marchiori A.
      • Sartor D.
      • Mosena L.
      • Tormene D.
      • Concolato A.
      • et al.
      Elastic stockings, hydroxyethylrutosides or both for the treatment of post-thrombotic syndrome.
      • Lattimer C.R.
      • Azzam M.
      • Kalodiki E.
      • Makris G.C.
      • Geroulakos G.
      Compression stockings significantly improve hemodynamic performance in post-thrombotic syndrome irrespective of class or length.
      Two studies showed no benefit of compression over no compression.
      • Ginsberg J.S.
      • Hirsh J.
      • Julian J.
      • Vander LaandeVries M.
      • Magier D.
      • MacKinnon B.
      • et al.
      Prevention and treatment of postphlebitic syndrome: results of a 3-part study.
      ,
      • Frulla M.
      • Marchiori A.
      • Sartor D.
      • Mosena L.
      • Tormene D.
      • Concolato A.
      • et al.
      Elastic stockings, hydroxyethylrutosides or both for the treatment of post-thrombotic syndrome.
      The other study reported beneficial effects on venous haemodynamics (as evaluated by air plethysmography) and not on clinical outcome.
      • Lattimer C.R.
      • Azzam M.
      • Kalodiki E.
      • Makris G.C.
      • Geroulakos G.
      Compression stockings significantly improve hemodynamic performance in post-thrombotic syndrome irrespective of class or length.
      Finally, wearing compression to slow the progression or prevent the recurrence of VVs is not supported by the current published evidence.
      • Palfreyman S.J.
      • Michaels J.A.
      A systematic review of compression hosiery for uncomplicated varicose veins.
      There is only one study reporting that compression therapy was effective to reduce or prevent disease progression.
      • Kostas T.I.
      • Ioannou C.V.
      • Drygiannakis I.
      • Georgakarakos E.
      • Kounos C.
      • Tsetis D.
      • et al.
      Chronic venous disease progression and modification of predisposing factors.
      Therefore ECS should not be used exclusively for this aim.

      3.2.1.2 Compliance

      Compression therapy is generally well accepted and tolerated by patients with CVD,
      • Kankam H.K.N.
      • Lim C.S.
      • Fiorentino F.
      • Davies A.H.
      • Gohel M.S.
      A summation analysis of compliance and complications of compression hosiery for patients with chronic venous disease or post-thrombotic syndrome.
      although compliance remains an issue for a large number of patients, certainly in hot climate, in particular in tropical countries.
      • Ayala A.
      • Guerra J.D.
      • Ulloa J.H.
      • Kabnick L.
      Compliance with compression therapy in primary chronic venous disease: results from a tropical country.
      Innovative methods to investigate true compliance should be further evaluated.
      • Uhl J.F.
      • Benigni J.P.
      • Chahim M.
      • Frederic D.
      Prospective randomized controlled study of patient compliance in using a compression stocking: importance of recommendations of the practitioner as a factor for better compliance.
      ,
      • Lurie F.
      • Schwartz M.
      Patient-centered outcomes of a dual action pneumatic compression device in comparison to compression stockings for patients with chronic venous disease.
      The main complaints by non-compliant patients are pain, discomfort, sensation of heat, and skin irritation. Difficulties in donning and doffing ECS are also reported, especially by older patients, patients with functional impairments such as hand osteoarthritis, restricted mobility and joint problems in the spine and hip, or morbid obesity, making bending to the feet problematic or even impossible. In these cases, donning and doffing aids are available. In a small RCT, 40 elderly patients, aged > 65 years, suffering from advanced CVD (C4 – C6), tested different donning devices. It was concluded that donning devices improved patient ability to don ECS successfully.
      • Sippel K.
      • Seifert B.
      • Hafner J.
      Donning devices (foot slips and frames) enable elderly people with severe chronic venous insufficiency to put on compression stockings.
      A new type of compression stocking, without compression at the foot and heel, also has been shown to make donning and doffing easier.
      • Buset C.S.
      • Fleischer J.
      • Kluge R.
      • Graf N.T.
      • Mosti G.
      • Partsch H.
      • et al.
      Compression stocking with 100% donning and doffing success: an open label randomised controlled trial.
      However, the problem of donning is not completely solved for all patients.

      3.2.1.3 Contraindications to compression treatment

      Many clinical conditions that were considered a contraindication for compression in the past (arterial disease, skin infection, vasculitis, cellulitis) are no longer considered as such, provided proper precautions are taken. Only a few contraindications for sustained compression treatment remain, which are listed in Table 7.
      • Rabe E.
      • Partsch H.
      • Morrison N.
      • Meissner M.H.
      • Mosti G.
      • Lattimer C.R.
      • et al.
      Risks and contraindications of medical compression treatment - a critical reappraisal. An international consensus statement.
      Table 7Contraindications to compression treatment (modified with permission from Rabe et al., 2020
      • Rabe E.
      • Partsch H.
      • Morrison N.
      • Meissner M.H.
      • Mosti G.
      • Lattimer C.R.
      • et al.
      Risks and contraindications of medical compression treatment - a critical reappraisal. An international consensus statement.
      )
      Severe lower extremity atherosclerotic disease with ABI < 0.6 and/or ankle pressure < 60 mmHg
      Extra-anatomic or superficially tunnelled arterial bypass at the site of intended compression
      Severe heart failure, NYHA Class IV
      Heart failure NYHA Class III and routine application of compression devices without clinical and haemodynamic monitoring
      Confirmed allergy to compression material
      Severe diabetic neuropathy with sensory loss or microangiopathy with the risk of skin necrosis
      May not apply to inelastic compression exerting low levels of sustained compression pressure (modified compression).
      ABI = ankle brachial index; NYHA = New York Heart Association; NYHA Class IV: fatigue, palpitations, dyspnoea and/or angina at rest; NYHA Class III: ordinary physical activity causes undue fatigue, palpitations, dyspnoea and/or angina - comfortable at rest.
      May not apply to inelastic compression exerting low levels of sustained compression pressure (modified compression).

      3.2.2 Other compression methods

      3.2.2.1 Intermittent pneumatic compression

      IPC has a limited role in the conservative treatment of CVD. It can be used for oedema treatment in addition to compression by ECS, bandages, or ACG, or to replace them when sustained compression is not tolerated. There are no consistent data available on the use of IPC in CEAP clinical class C0S – C4. In patients with PTS, IPC has been used to alleviate symptoms. However, most studies are small and of short duration, resulting in a low level of evidence for the use of IPC for this indication.
      • Azirar S.
      • Appelen D.
      • Prins M.H.
      • Neumann M.H.
      • de Feiter A.N.
      • Kolbach D.N.
      Compression therapy for treating post-thrombotic syndrome.
      The use of IPC in VLUs is further discussed in subsection 6.3.2.
      A new device combining sustained static pneumatic compression during ambulation and IPC while at rest has been investigated in a pilot study. This device was more effective than ECS, with better acceptance by the patients, resulting in increased compliance with compression therapy and oedema reduction.
      • Lurie F.
      • Schwartz M.
      Patient-centered outcomes of a dual action pneumatic compression device in comparison to compression stockings for patients with chronic venous disease.
      Further studies will be necessary to confirm these findings.

      3.2.2.2 Neuromuscular electrical stimulation

      Neuromuscular electrical stimulation is an alternative system to increase venous return from the lower limbs. This device stimulates calf muscle contraction through application of an electric current, leading to better emptying of the deep veins. A literature review including 46 studies showed an improvement in venous haemodynamics with stimulation of the calf muscle pump compared with rest.
      • Williams K.J.
      • Ravikumar R.
      • Gaweesh A.S.
      • Moore H.M.
      • Lifsitz A.D.
      • Lane T.R.
      • et al.
      A review of the evidence to support neuromuscular electrical stimulation in the prevention and management of venous disease.
      In particular, calf flow, femoral and popliteal peak velocity increased, as well as ejection volume from the lower leg. More recently, neuromuscular electrical stimulation did not demonstrate any effectiveness in reducing lower leg volume
      • Benigni J.P.
      • Uhl J.F.
      • Balet F.
      • Filori P.
      • Chahim M.
      Evaluation of three different devices to reduce stasis edema in poorly mobile nursing home patients.
      and to date, its use in CVD remains very limited.
      • Williams K.J.
      • Ravikumar R.
      • Gaweesh A.S.
      • Moore H.M.
      • Lifsitz A.D.
      • Lane T.R.
      • et al.
      A review of the evidence to support neuromuscular electrical stimulation in the prevention and management of venous disease.

      3.2.2.3 Tension free compression

      Tabled 1
      Recommendation 9Unchanged
      For patients with symptomatic chronic venous disease, elastic compression stockings, exerting a pressure of at least 15 mmHg at the ankle, are recommended to reduce venous symptoms.
      ClassLevelReferencesToE
      IBBenigni et al. (2003),
      • Benigni J.P.
      • Sadoun S.
      • Allaert F.A.
      • Vin F.
      Efficacy of Class 1 elastic compression stockings in the early stages of chronic venous disease. A comparative study.
      Kakkos et al. (2018)
      • Kakkos S.K.
      • Timpilis M.
      • Patrinos P.
      • Nikolakopoulos K.M.
      • Papageorgopoulou C.P.
      • Kouri A.K.
      • et al.
      Acute effects of graduated elastic compression stockings in patients with symptomatic varicose veins: a randomised double blind placebo controlled trial.
      Tabled 1
      Recommendation 10Unchanged
      For patients with chronic venous disease and oedema (CEAP clinical class C3), compression treatment, using below knee elastic compression stockings, inelastic bandages or adjustable compression garments, exerting a pressure of 20 – 40 mmHg at the ankle, is recommended to reduce oedema.
      ClassLevelReferencesToE
      IBMosti et al. (2012),
      • Mosti G.
      • Picerni P.
      • Partsch H.
      Compression stockings with moderate pressure are able to reduce chronic leg oedema.
      Mosti et al. (2013),
      • Mosti G.
      • Partsch H.
      Occupational leg oedema is more reduced by antigraduated than by graduated stockings.
      Mosti et al. (2015)
      • Mosti G.
      • Cavezzi A.
      • Partsch H.
      • Urso S.
      • Campana F.
      Adjustable velcro compression devices are more effective than inelastic bandages in reducing venous edema in the initial treatment phase: a randomized controlled trial.
      CEAP = Clinical Etiological Anatomical Pathophysiological (classification).
      Tabled 1
      Recommendation 11New
      For patients with chronic venous disease and lipodermatosclerosis and/or atrophie blanche (CEAP clinical class C4b), using below knee elastic compression stockings, exerting a pressure of 20 – 40 mmHg at the ankle, is recommended to reduce skin induration.
      ClassLevelReferencesToE
      IBVandongen et al. (2000)
      • Vandongen Y.K.
      • Stacey M.C.
      Graduated compression elastic stockings reduce lipodermatosclerosis and ulcer recurrence.
      CEAP = Clinical Etiological Anatomical Pathophysiological (classification).
      Tabled 1
      Recommendation 12New
      For patients with post-thrombotic syndrome, below knee elastic compression stockings, exerting a pressure of 20 – 40 mmHg at the ankle, should be considered to reduce severity.
      ClassLevelReferencesToE
      IIaBAzirar et al. (2019)
      • Azirar S.
      • Appelen D.
      • Prins M.H.
      • Neumann M.H.
      • de Feiter A.N.
      • Kolbach D.N.
      Compression therapy for treating post-thrombotic syndrome.
      Tabled 1
      Recommendation 13New
      For patients with post-thrombotic syndrome, adjuvant intermittent pneumatic compression may be considered to reduce its severity.
      ClassLevelReferencesToE
      IIbBAzirar et al. (2019)
      • Azirar S.
      • Appelen D.
      • Prins M.H.
      • Neumann M.H.
      • de Feiter A.N.
      • Kolbach D.N.
      Compression therapy for treating post-thrombotic syndrome.

      3.3 Pharmacological treatment

      Medical treatment has been used for decades, but there is some controversy over its exact place as a treatment modality for CVD. Venoactive drugs (VADs) are widely prescribed in some countries but are not available in others. They can be classified into two groups: natural and synthetic drugs. The main modes of action of VADs are to decrease capillary permeability, reduce release of inflammatory mediators, or improve venous tone.
      A Cochrane review of 53 trials on VADs providing quantifiable data involving 6 013 participants was published in 2016,
      • Martinez-Zapata M.J.
      • Vernooij R.W.
      • Uriona Tuma S.M.
      • Stein A.T.
      • Moreno R.M.
      • Vargas E.
      • et al.
      Phlebotonics for venous insufficiency.
      and updated in 2020.
      • Martinez-Zapata M.J.
      • Vernooij R.W.
      • Simancas-Racines D.
      • Uriona Tuma S.M.
      • Stein A.T.
      • Moreno Carriles R.M.M.
      • et al.
      Phlebotonics for venous insufficiency.
      These reviews concluded that, when compared with placebo, VADs may have beneficial effects on objective measures of leg oedema and on some symptoms and signs related to CVD such as pain, cramps, restless legs, sensation of swelling, paraesthesia, and trophic disorders, but can produce more adverse effects and may not affect QoL based on a pooled analysis of the included VADs.
      • Martinez-Zapata M.J.
      • Vernooij R.W.
      • Simancas-Racines D.
      • Uriona Tuma S.M.
      • Stein A.T.
      • Moreno Carriles R.M.M.
      • et al.
      Phlebotonics for venous insufficiency.
      Another meta-analysis showed that four VADs reduced the objective clinical sign of oedema in patients with CVD.
      • Allaert F.A.
      Meta-analysis of the impact of the principal venoactive drugs agents on malleolar venous edema.
      Table 8 summarises the most important findings on the effect of different VADs on venous symptoms and oedema.
      Table 8Global summary of the effects of the main venoactive drugs on venous symptoms and oedema
      Symptom or signRuscus extracts
      • Kakkos S.K.
      • Allaert F.A.
      Efficacy of Ruscus extract, HMC and vitamin C, constituents of Cyclo 3 fort(R), on improving individual venous symptoms and edema: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials.
      MPFF
      • Kakkos S.K.
      • Nicolaides A.N.
      Efficacy of micronized purified flavonoid fraction (Daflon(R)) on improving individual symptoms, signs and quality of life in patients with chronic venous disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials.
      Calcium dobesilate
      • Ciapponi A.
      • Laffaire E.
      • Roque M.
      Calcium dobesilate for chronic venous insufficiency: a systematic review.
      • Flota-Cervera F.
      • Flota-Ruiz C.
      • Trevino C.
      • Berber A.
      Randomized, double blind, placebo-controlled clinical trial to evaluate the lymphagogue effect and clinical efficacy of calcium dobesilate in chronic venous disease.
      • Martinez-Zapata M.J.
      • Moreno R.M.
      • Gich I.
      • Urrutia G.
      • Bonfill X.
      Chronic Venous Insufficiency Study Group
      A randomized, double-blind multicentre clinical trial comparing the efficacy of calcium dobesilate with placebo in the treatment of chronic venous disease.
      • Rabe E.
      • Ballarini S.
      • Lehr L.
      • Doxium E.D.X.S.G.
      A randomized, double-blind, placebo-controlled, clinical study on the efficacy and safety of calcium dobesilate in the treatment of chronic venous insufficiency.
      • Rabe E.
      • Jaeger K.A.
      • Bulitta M.
      • Pannier F.
      Calcium dobesilate in patients suffering from chronic venous insufficiency: a double-blind, placebo-controlled, clinical trial.
      Horse chestnut extract
      • Pittler M.H.
      • Ernst E.
      Horse chestnut seed extract for chronic venous insufficiency.
      Hydroxyethyl-rutosides
      • Aziz Z.
      • Tang W.L.
      • Chong N.J.
      • Tho L.Y.
      A systematic review of the efficacy and tolerability of hydroxyethylrutosides for improvement of the signs and symptoms of chronic venous insufficiency.
      Red vine leaf extract
      • Kiesewetter H.
      • Koscielny J.
      • Kalus U.
      • Vix J.M.
      • Peil H.
      • Petrini O.
      • et al.
      Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial.
      • Kalus U.
      • Koscielny J.
      • Grigorov A.
      • Schaefer E.
      • Peil H.
      • Kiesewetter H.
      Improvement of cutaneous microcirculation and oxygen supply in patients with chronic venous insufficiency by orally administered extract of red vine leaves AS 195: a randomised, double-blind, placebo-controlled, crossover study.
      • Rabe E.
      • Stucker M.
      • Esperester A.
      • Schafer E.
      • Ottillinger B.
      Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study.
      Sulodexide
      • Bignamini A.A.
      • Matuska J.
      Sulodexide for the symptoms and signs of chronic venous disease: a systematic review and meta-analysis.
      Pain+++++++
      Heaviness+++++
      Fatigue++
      Feeling of swelling+++
      Cramps+++++
      Paresthesia+++
      Pruritus++
      Oedema+++++
      MPFF = micronised purified flavonoid fraction.

      3.3.1 Ruscus extracts

      A systematic review on Ruscus extracts has identified 10 double blind placebo controlled RCTs involving 719 patients with unilateral or bilateral CVD (CEAP clinical class of affected limbs ranging between C2 and C5).
      • Kakkos S.K.
      • Allaert F.A.
      Efficacy of Ruscus extract, HMC and vitamin C, constituents of Cyclo 3 fort(R), on improving individual venous symptoms and edema: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials.
      On quantitative analysis, Ruscus extracts 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.

      3.3.2 Micronised purified flavonoid fraction

      A systematic review on micronised purified flavonoid fraction (MPFF) identified seven double blind placebo controlled RCTs involving 1 692 patients.
      • Kakkos S.K.
      • Nicolaides A.N.
      Efficacy of micronized purified flavonoid fraction (Daflon(R)) on improving individual symptoms, signs and quality of life in patients with chronic venous disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials.
      On quantitative analysis, MPFF improved several leg symptoms (Table 8) functional discomfort, QoL, and ankle circumference.

      3.3.3 Calcium dobesilate

      Calcium dobesilate is a synthetic VAD, which had been evaluated in 10 RCTs up to 2004 involving 778 patients included in a meta-analysis.
      • Ciapponi A.
      • Laffaire E.
      • Roque M.
      Calcium dobesilate for chronic venous insufficiency: a systematic review.
      It significantly reduced a number of leg symptoms (Table 8) and discomfort, while lower limb oedema was improved and the investigators’ opinions of symptom improvement were positive, albeit with some heterogeneity. Subgroup analysis showed greater improvements in pain, heaviness, paresthesia, and leg oedema in the group of patients with severe symptoms and signs than in those with milder ones. Four more recent double blind placebo controlled RCTs involving 1 165 patients with CVD also showed improvement of symptoms and objective measures of oedema, again with some heterogeneity.
      • Flota-Cervera F.
      • Flota-Ruiz C.
      • Trevino C.
      • Berber A.
      Randomized, double blind, placebo-controlled clinical trial to evaluate the lymphagogue effect and clinical efficacy of calcium dobesilate in chronic venous disease.
      • Martinez-Zapata M.J.
      • Moreno R.M.
      • Gich I.
      • Urrutia G.
      • Bonfill X.
      Chronic Venous Insufficiency Study Group
      A randomized, double-blind multicentre clinical trial comparing the efficacy of calcium dobesilate with placebo in the treatment of chronic venous disease.
      • Rabe E.
      • Ballarini S.
      • Lehr L.
      • Doxium E.D.X.S.G.
      A randomized, double-blind, placebo-controlled, clinical study on the efficacy and safety of calcium dobesilate in the treatment of chronic venous insufficiency.
      • Rabe E.
      • Jaeger K.A.
      • Bulitta M.
      • Pannier F.
      Calcium dobesilate in patients suffering from chronic venous insufficiency: a double-blind, placebo-controlled, clinical trial.

      3.3.4 Horse chestnut extract

      A Cochrane review on horse chestnut extract of 17 RCTs involving 1 593 patients showed that this VAD was effective (Table 8).
      • Pittler M.H.
      • Ernst E.
      Horse chestnut seed extract for chronic venous insufficiency.

      3.3.5 Hydroxyethylrutosides

      A systematic review and meta-analysis of the efficacy of hydroxyethylrutosides for treating symptoms and signs of CVD reported on 15 trials involving 1 643 participants.
      • Aziz Z.
      • Tang W.L.
      • Chong N.J.
      • Tho L.Y.
      A systematic review of the efficacy and tolerability of hydroxyethylrutosides for improvement of the signs and symptoms of chronic venous insufficiency.
      It showed that hydroxyethylrutosides significantly reduced venous symptoms (Table 8).

      3.3.6 Red vine leaf extract

      The effect of red vine leaf extract has been evaluated in two RCTs involving 260 and 248 patients, respectively.
      • Kiesewetter H.
      • Koscielny J.
      • Kalus U.
      • Vix J.M.
      • Peil H.
      • Petrini O.
      • et al.
      Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial.
      ,
      • Kalus U.
      • Koscielny J.
      • Grigorov A.
      • Schaefer E.
      • Peil H.
      • Kiesewetter H.
      Improvement of cutaneous microcirculation and oxygen supply in patients with chronic venous insufficiency by orally administered extract of red vine leaves AS 195: a randomised, double-blind, placebo-controlled, crossover study.
      Red vine leaf extract reduced CVD related symptoms and lower limb oedema substantially more than placebo, although only pain was reduced in both RCTs (Table 8). A third cross over double blind RCT assessed objective measures of oedema and patient reported global assessment of efficacy, both in favour of red vine leaf extract.
      • Rabe E.
      • Stucker M.
      • Esperester A.
      • Schafer E.
      • Ottillinger B.
      Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study.

      3.3.7 Sulodexide

      Sulodexide was evaluated by a 2020 meta-analysis, which included 13 studies on 1 901 participants.
      • Bignamini A.A.
      • Matuska J.
      Sulodexide for the symptoms and signs of chronic venous disease: a systematic review and meta-analysis.
      Sulodexide decreased the intensity of pain, cramps, heaviness, feeling of swelling (Table 8), and total symptom score, and also reduced inflammatory mediators in patients with CVD.

      3.3.8 Clinical applicability

      Tabled 1
      Recommendation 14Unchanged
      For patients with symptomatic chronic venous disease, who are not undergoing interventional treatment, are awaiting intervention, or have persisting symptoms and/or oedema after intervention, medical treatment with venoactive drugs should be considered to reduce venous symptoms and oedema, based on the available evidence for each individual drug.
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      • Koscielny J.
      • Grigorov A.
      • Schaefer E.
      • Peil H.
      • Kiesewetter H.
      Improvement of cutaneous microcirculation and oxygen supply in patients with chronic venous insufficiency by orally administered extract of red vine leaves AS 195: a randomised, double-blind, placebo-controlled, crossover study.
      Flota-Cervera et al. (2008),
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      • Flota-Ruiz C.
      • Trevino C.
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      Randomized, double blind, placebo-controlled clinical trial to evaluate the lymphagogue effect and clinical efficacy of calcium dobesilate in chronic venous disease.
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      • Moreno R.M.
      • Gich I.
      • Urrutia G.
      • Bonfill X.
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      A randomized, double-blind multicentre clinical trial comparing the efficacy of calcium dobesilate with placebo in the treatment of chronic venous disease.
      Rabe et al (2011),
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      • Jaeger K.A.
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      Calcium dobesilate in patients suffering from chronic venous insufficiency: a double-blind, placebo-controlled, clinical trial.
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      Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study.
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      Horse chestnut seed extract for chronic venous insufficiency.
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      A systematic review of the efficacy and tolerability of hydroxyethylrutosides for improvement of the signs and symptoms of chronic venous insufficiency.
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      • Ballarini S.
      • Lehr L.
      • Doxium E.D.X.S.G.
      A randomized, double-blind, placebo-controlled, clinical study on the efficacy and safety of calcium dobesilate in the treatment of chronic venous insufficiency.
      Kakkos et al. (2017),
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      Kakkos et al. (2018),
      </