Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement

von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

[1]  G. Limongelli,et al.  Von Willebrand Factor and Cardiovascular Disease: From a Biochemical Marker to an Attractive Therapeutic Target. , 2017, Current vascular pharmacology.

[2]  J. Oldenburg,et al.  Transcatheter aortic valve implantation leads to a restoration of von Willebrand factor (VWF) abnormalities in patients with severe aortic stenosis - Incidence and relevance of clinical and subclinical VWF dysfunction in patients undergoing transfemoral TAVI. , 2017, Thrombosis research.

[3]  A. Kappetein,et al.  Von Willebrand factor multimers during transcatheter aortic valve replacement-an additional clue for detecting post-procedural aortic regurgitation? , 2016, Journal of thoracic disease.

[4]  J. Eikenboom,et al.  Von Willebrand's Disease. , 2016, The New England journal of medicine.

[5]  G. Lemesle,et al.  Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement. , 2016, The New England journal of medicine.

[6]  K. Babaoğlu,et al.  Acquired von Willebrand syndrome in children with aorticand pulmonary stenosis , 2016, Cardiovascular journal of Africa.

[7]  Dong Chen,et al.  von Willebrand Factor Abnormalities and Heyde Syndrome in Dysfunctional Heart Valve Prostheses. , 2016, JAMA cardiology.

[8]  A. Federici Current and emerging approaches for assessing von Willebrand disease in 2016 , 2016, International journal of laboratory hematology.

[9]  R. Nicoll,et al.  The effect of statins therapy in aortic stenosis: Meta-analysis comparison data of RCTs and observationals , 2016, Data in brief.

[10]  A. Sahebkar,et al.  The impact of statin therapy on plasma levels of von Willebrand factor antigen , 2015, Thrombosis and Haemostasis.

[11]  M. Leon,et al.  von Willebrand Disease After TAVR: The Missing Link? , 2015, JACC. Cardiovascular interventions.

[12]  O. Morel,et al.  Effects of transcutaneous aortic valve implantation on aortic valve disease-related hemostatic disorders involving von Willebrand factor. , 2015, The Canadian journal of cardiology.

[13]  K. Kuck,et al.  Treatment of acquired von Willebrand syndrome in aortic stenosis with transcatheter aortic valve replacement. , 2015, JACC. Cardiovascular interventions.

[14]  A. Undas,et al.  Bleeding in patients with severe aortic stenosis in the era of transcatheter aortic valve replacement. , 2015, JACC. Cardiovascular interventions.

[15]  F. Mouquet,et al.  Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions. , 2015, Circulation research.

[16]  A. Undas,et al.  Blood coagulation and fibrinolysis in aortic valve stenosis: links with inflammation and calcification , 2015, Thrombosis and Haemostasis.

[17]  B. Jilma,et al.  VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP , 2014, Thrombosis and Haemostasis.

[18]  M. Mack,et al.  Incidence, predictors, and prognostic impact of late bleeding complications after transcatheter aortic valve replacement. , 2014, Journal of the American College of Cardiology.

[19]  M. Stark,et al.  Shear stress‐associated acquired von Willebrand syndrome in patients with mitral regurgitation , 2014, Journal of thrombosis and haemostasis : JTH.

[20]  G. Finet,et al.  Resolution of acquired von Willebrand syndrome after transcatheter aortic valve implantation through a left transcarotid approach. , 2014, International journal of cardiology.

[21]  M. Bryckaert,et al.  Of von Willebrand factor and platelets , 2014, Cellular and Molecular Life Sciences.

[22]  J. Fredi,et al.  Effect of transcutaneous aortic valve implantation on the Heyde's syndrome. , 2014, The American journal of cardiology.

[23]  P. Mannucci,et al.  Gastrointestinal angiodysplasia and bleeding in von Willebrand disease , 2014, Thrombosis and Haemostasis.

[24]  Dong Chen,et al.  Acquired Von Willebrand syndrome secondary to mitral and aortic regurgitation. , 2014, The Canadian journal of cardiology.

[25]  G. Limongelli,et al.  Adipose tissue and vascular inflammation in coronary artery disease. , 2014, World journal of cardiology.

[26]  K. Grande-Allen,et al.  Age-Related Changes in Aortic Valve Hemostatic Protein Regulation , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[27]  A. DeAnda,et al.  Management of blood transfusion in aortic valve surgery: impact of a blood conservation strategy. , 2014, The Annals of thoracic surgery.

[28]  Obi-Wan Kenobi von Willebrand factor , Jedi knight of the bloodstream , 2014 .

[29]  R. De Cristofaro,et al.  Proteolytic Processing of Von Willebrand Factor by Adamts13 and Leukocyte Proteases , 2013, Mediterranean journal of hematology and infectious diseases.

[30]  E. Tuzcu,et al.  Severe aortic stenosis and coronary artery disease--implications for management in the transcatheter aortic valve replacement era: a comprehensive review. , 2013, Journal of the American College of Cardiology.

[31]  C. Weidenmaier,et al.  Ultralarge von Willebrand Factor Fibers Mediate Luminal Staphylococcus aureus Adhesion to an Intact Endothelial Cell Layer Under Shear Stress , 2013, Circulation.

[32]  Antonio Colombo,et al.  Clinical ResearchInterventional CardiologyIncidence, Predictors, and Outcomes of Aortic Regurgitation After Transcatheter Aortic Valve Replacement: Meta-Analysis and Systematic Review of Literature , 2013 .

[33]  A. Undas,et al.  Impaired fibrinolysis is associated with the severity of aortic stenosis in humans , 2013, Journal of thrombosis and haemostasis : JTH.

[34]  O. Alfieri,et al.  Heyde's syndrome incidence and outcome in patients undergoing transcatheter aortic valve implantation. , 2013, Journal of the American College of Cardiology.

[35]  F. Akerström,et al.  Aortic stenosis: a general overview of clinical, pathophysiological and therapeutic aspects , 2013, Expert review of cardiovascular therapy.

[36]  Dong Chen,et al.  Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study). , 2013, The American journal of cardiology.

[37]  C. Casari,et al.  von Willebrand factor: the old, the new and the unknown , 2012, Journal of thrombosis and haemostasis : JTH.

[38]  J. Loscalzo From clinical observation to mechanism--Heyde's syndrome. , 2012, The New England journal of medicine.

[39]  M. Zenker,et al.  Bleeding diathesis in Noonan syndrome: is acquired von Willebrand syndrome the clue? , 2012, Thrombosis research.

[40]  A. Hughes,et al.  Endothelial Von Willebrand factor regulates angiogenesis , 2012 .

[41]  E. Yeh,et al.  Role of C-reactive protein in acute myocardial infarction and stroke: possible therapeutic approaches. , 2012, Current pharmaceutical biotechnology.

[42]  J. Batlle,et al.  Acquired von Willebrand syndrome and mitral valve prosthesis leakage. A pilot study , 2011, European journal of haematology.

[43]  F. Loffredo,et al.  C-reactive protein is released in the coronary circulation and causes endothelial dysfunction in patients with acute coronary syndromes. , 2011, International journal of cardiology.

[44]  D. Lane,et al.  Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. , 2011, Blood.

[45]  S. Susen,et al.  Ambivalent effect of aortic stenosis on von Willebrand factor and thrombin generation. Is transvalvular gradient the guilty party? , 2011, Heart.

[46]  K. Bykowska,et al.  Increased thrombin generation and platelet activation are associated with deficiency in high molecular weight multimers of von Willebrand factor in patients with moderate-to-severe aortic stenosis , 2011, Heart.

[47]  A. Hughes,et al.  Endothelial von Willebrand factor regulates angiogenesis. , 2011, Blood.

[48]  W. D. Merryman Mechano-potential etiologies of aortic valve disease. , 2010 .

[49]  R. Kiss,et al.  Galectins and Gliomas , 2009, Brain pathology.

[50]  Craig A Simmons,et al.  Aortic valve mechanics: an emerging role for the endothelium. , 2009, Journal of the American College of Cardiology.

[51]  E. Stępień,et al.  Heyde’s syndrome without a decrease in large von Willebrand factor multimers: A case of intestinal bleedings reversed by valve replacement in a patient with aortic stenosis , 2009, Thrombosis and Haemostasis.

[52]  J. Fraile,et al.  Endocarditis Caused by Staphylococcus aureus: A Reappraisal of the Epidemiologic, Clinical, and Pathologic Manifestations With Analysis of Factors Determining Outcome , 2009, Medicine.

[53]  R. Pai,et al.  Risk factors for progression of calcific aortic stenosis and potential therapeutic targets , 2008, The International journal of angiology : official publication of the International College of Angiology, Inc.

[54]  A. Federici Acquired von Willebrand syndrome: is it an extremely rare disorder or do we see only the tip of the iceberg? , 2008, Journal of thrombosis and haemostasis : JTH.

[55]  M. Olschewski,et al.  Increased levels of circulating microparticles in patients with severe aortic valve stenosis , 2008, Thrombosis and Haemostasis.

[56]  Chris A Rogers,et al.  Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery , 2007, Circulation.

[57]  G. Grandaliano,et al.  Inflammation may modulate IL-6 and C-reactive protein gene expression in the adipose tissue: the role of IL-6 cell membrane receptor. , 2007, American journal of physiology. Endocrinology and metabolism.

[58]  A Alexander-Katz,et al.  Shear-induced unfolding triggers adhesion of von Willebrand factor fibers , 2007, Proceedings of the National Academy of Sciences.

[59]  S. Ayaz,et al.  Coagulation, Fibrinolytic System Activation and Endothelial Dysfunction in Patients With Mitral Stenosis and Sinus Rhythm , 2007, Angiology.

[60]  C. Gahmberg,et al.  P-selectin glycoprotein ligand 1 and beta2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor. , 2006, Blood.

[61]  Robert M Nerem,et al.  Valvular endothelial cells regulate the phenotype of interstitial cells in co-culture: effects of steady shear stress. , 2006, Tissue engineering.

[62]  J. Moake,et al.  Platelets adhered to endothelial cell‐bound ultra‐large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress , 2005, Journal of thrombosis and haemostasis : JTH.

[63]  J. Webb,et al.  Heyde's syndrome: a review. , 2004, The Journal of heart valve disease.

[64]  Robert M Nerem,et al.  Unique Morphology and Focal Adhesion Development of Valvular Endothelial Cells in Static and Fluid Flow Environments , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[65]  A. Erbay,et al.  Decreased platelet activation and endothelial dysfunction after percutaneous mitral balloon valvuloplasty. , 2003, International journal of cardiology.

[66]  S. Susen,et al.  Acquired von Willebrand syndrome in aortic stenosis. , 2003, The New England journal of medicine.

[67]  Shaji K. Kumar,et al.  Acquired von Willebrand's syndrome: A single institution experience , 2003, American journal of hematology.

[68]  S. Achenbach,et al.  Progression of Aortic Valve Calcification: Association with Coronary Progression of Aortic Valve Calcification Association with Coronary Atherosclerosis and Cardiovascular Risk Factors , 2022 .

[69]  D. Malenka,et al.  Outcome of mild periprosthetic regurgitation detected by intraoperative transesophageal echocardiography. , 2001, Journal of the American College of Cardiology.

[70]  Z. Ruggeri Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation. , 2001, Best practice & research. Clinical haematology.

[71]  E. Mohler Are atherosclerotic processes involved in aortic-valve calcification? , 2000, The Lancet.

[72]  P. V. van Genderen,et al.  Acquired von Willebrand Syndrome: Data from an International Registry , 2000, Thrombosis and Haemostasis.

[73]  G. Lip,et al.  von Willebrand factor, fibrinogen, and soluble P-selectin levels after mitral valve replacement versus mitral valve repair. , 2000, American Journal of Cardiology.

[74]  T. Katogi,et al.  [A case of acquired von Willebrand disease due to pulmonary stenosis after Jatene's operation]. , 1995, [Zasshi] [Journal]. Nihon Kyobu Geka Gakkai.

[75]  E. Salzman,et al.  Changes in von Willebrand factor during cardiac surgery: effect of desmopressin acetate. , 1988, Blood.

[76]  E. Giuliani,et al.  The association of unexplained gastrointestinal bleeding with calcific aortic stenosis. , 1987, The Annals of thoracic surgery.

[77]  I. Nilsson In memory of Erik Jorpes. von Willebrand's disease from 1926-1983. , 2009, Scandinavian journal of haematology. Supplementum.

[78]  M. Barrett,et al.  von Willebrand syndromes and mitral-valve prolapse; linked mesenchymal dysplasias. , 1981, The New England journal of medicine.

[79]  E. C. Heyde Gastrointestinal bleeding in aortic stenosis. , 1958 .