title: Rationale and design of GISSI OUTLIERS VAR Study in bicuspid aortic valve patients: prospective longitudinal, multicenter study to investigate correlation between surgical, echo distinctive features, histologic and genetic findings in phenotypically homogeneous outlier cases.
abstract: OBJECTIVE
  Bicuspid aortic valve (BAV) is the most common congenital heart disorder, affecting up to 2% of the population. Involvement of aortic root and ascending aorta (aneurysm or, eventually, dissection) is frequent in patients with pathologic or normal functioning BAV. Unfortunately, there are no well-known correlations between valvular and vascular diseases. In VAR protocol, with a new strategy of research, we analysemultiple aspects of BAV disease through correlation between surgical, echo, histologic and genetic findings in phenotypically homogeneous outlier cases.
  
  
  METHODS
  VAR protocol is a prospective, longitudinal, multicenter study. It observes 4 homogeneous small groups of BAV surgical patients (15 patients each): isolated aortic regurgitation, isolated ascending aortic aneurysm, aortic regurgitation associated with aortic aneurysm, isolated aortic stenosis in older patients (>60years). Echo analysis is extended to first-degree relatives and, in case of BAV, genetic test is performed. Patients and relatives are enrolled in 10 cardiac surgery/cardiologic centers throughout Italy.
  
  
  CONCLUSIONS
  The aim of the study is to identify predictors of favorable or unfavorable evolution of BAV in terms of valvular dysfunction and/or aortic aneurysm. Correlations between different features could help in identification of various BAV risk groups, rationalizing follow-up and treatment.
authors.affiliation: S.C. Cardiochirurgia, Department of Cardiology and Cardiovascular Surgery, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Merlanti
authors.affiliation: S.C. Cardiologia IV, Department of Cardiology and Cardiovascular Surgery, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: De Chiara
authors.affiliation: ANMCO Research Center, Florence, Italy. Electronic address: centrostudi@anmco.it.
authors.forename: Aldo Pietro
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: S.C. Cardiologia IV, Department of Cardiology and Cardiovascular Surgery, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Moreo
authors.affiliation: Department of Cardiovascular Research, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Pileggi
authors.affiliation: Department of Cardiac, Vascular and Thoracic Sciences, University of Padua, Padua, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Romeo
authors.affiliation: S.C. Cardiochirurgia, Department of Cardiology and Cardiovascular Surgery, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Claudio Francesco
authors.initials: CF
authors.lastname: Russo
authors.affiliation: Cardiovascular Pathology, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: Cardiothoracic Surgery, ICLAS-Istituto Clinico Ligure Alta Specialità, Rapallo, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Martinelli
authors.affiliation: Heart Care Foundation, Florence, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Maseri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000473:pathology*; D001014:Aortic Aneurysm / Q000150:complications / Q000209:etiology; D001021:Aortic Valve / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D001022:Aortic Valve Insufficiency / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000601:surgery; D000082882:Bicuspid Aortic Valve Disease; D006348:Cardiac Surgical Procedures; D004108:Dilatation, Pathologic / Q000150:complications / Q000209:etiology / Q000601:surgery; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery; D006349:Heart Valve Diseases / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology* / Q000601:surgery*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D016311:Outliers, DRG / Q000706:statistics & numerical data*; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014463:Ultrasonography
keywords: Aortic aneurysm; BAV; BAV genetic; Bicuspid aortic valve; Outliers