Surgical treatment of bicuspid aortic valve disease: Knowledge gaps and research perspectives

Abstract

Sempre la pratica deve essere edificata sopra la bona teorica. [Practice must always be founded on sound theory.]—Leonardo Da Vinci (1452-1519; provided the first depiction of a bicuspid aortic valve) Research on bicuspid aortic valves (BAV) and associated conditions is increasing exponentially. A major part of the current knowledge on BAV is derived from investigations carried out in the clinical setting, especially the surgical setting, as a consequence of the epidemiologic and surgical importance of its valvular and vascular complications. For example, most of the stenotic valves explanted at the time of aortic valve replacement are congenitally malformed.1Roberts W.C. Ko J.M. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation.Circulation. 2005; 111: 920-925Crossref PubMed Scopus (669) Google Scholar However, BAV is most frequently a clinically silent condition until those complications occur. Thus, although previous clinical research has contributed to increase the awareness of the problem, it has been most often limited by an inherent referral bias related to clinical and surgical presentation. The current basic knowledge of BAV, particularly its causes, mechanisms, and early interventions, is probably more limited than generally believed.2Fedak P.W. Verma S. The molecular fingerprint of bicuspid aortopathy.J Thorac Cardiovasc Surg. 2013; 145: 1334Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 3Losenno K.L. Goodman R.L. Chu M.W. Bicuspid aortic valve disease and ascending aortic aneurysms: gaps in knowledge.Cardiol Res Pract. 2012; 2012: 145202Crossref PubMed Scopus (68) Google Scholar Surgical treatment of the most common complications of congenital BAV is not believed to be a particular challenge today, at least from a merely technical perspective. Replacement of the valve and/or the aorta can be performed with very low early mortality and morbidity, and in the past 20 years, valve repair has become an additional available option for the regurgitant BAV.4El-Hamamsy I. Yacoub M.H. A measured approach to managing the aortic root in patients with bicuspid aortic valve disease.Curr Cardiol Rep. 2009; 11: 94-100Crossref PubMed Scopus (33) Google Scholar However, it is now increasingly recognized that the scientific basis for surgical management criteria is still rudimentary3Losenno K.L. Goodman R.L. Chu M.W. Bicuspid aortic valve disease and ascending aortic aneurysms: gaps in knowledge.Cardiol Res Pract. 2012; 2012: 145202Crossref PubMed Scopus (68) Google Scholar, 4El-Hamamsy I. Yacoub M.H. A measured approach to managing the aortic root in patients with bicuspid aortic valve disease.Curr Cardiol Rep. 2009; 11: 94-100Crossref PubMed Scopus (33) Google Scholar, 5Sundt III, T.M. Replacement of the ascending aorta in bicuspid aortic valve disease: where do we draw the line?.J Thorac Cardiovasc Surg. 2010; 140: S41-S44Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 6Della Corte A. Phenotypic heterogeneity of bicuspid aortopathy: a potential key to decode the prognosis?.Heart. 2014; 100: 96-97Crossref PubMed Scopus (20) Google Scholar and persistent gaps in knowledge of the genetics, pathophysiology, and clinical history of BAV are responsible for inconsistencies in surgical practice and lack of a rational and patient-tailored approach.6Della Corte A. Phenotypic heterogeneity of bicuspid aortopathy: a potential key to decode the prognosis?.Heart. 2014; 100: 96-97Crossref PubMed Scopus (20) Google Scholar, 7Verma S. Yanagawa B. Kalra S. Ruel M. Peterson M.D. Yamashita M.H. et al.Knowledge, attitudes, and practice patterns in surgical management of bicuspid aortopathy: a survey of 100 cardiac surgeons.J Thorac Cardiovasc Surg. 2013; 146: 1033-1040Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar A recent survey among cardiac surgeons on BAV-associated aortopathy showed that the timing and technique of surgical treatment is most often dictated by surgeon preference or institutional policy rather than being tailored to the individual patient's features and disease characteristics.7Verma S. Yanagawa B. Kalra S. Ruel M. Peterson M.D. Yamashita M.H. et al.Knowledge, attitudes, and practice patterns in surgical management of bicuspid aortopathy: a survey of 100 cardiac surgeons.J Thorac Cardiovasc Surg. 2013; 146: 1033-1040Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar Frequently, the surgeon's decision regarding timing of an intervention is even in disagreement with the current guidelines from professional societies.4El-Hamamsy I. Yacoub M.H. A measured approach to managing the aortic root in patients with bicuspid aortic valve disease.Curr Cardiol Rep. 2009; 11: 94-100Crossref PubMed Scopus (33) Google Scholar, 5Sundt III, T.M. Replacement of the ascending aorta in bicuspid aortic valve disease: where do we draw the line?.J Thorac Cardiovasc Surg. 2010; 140: S41-S44Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 6Della Corte A. Phenotypic heterogeneity of bicuspid aortopathy: a potential key to decode the prognosis?.Heart. 2014; 100: 96-97Crossref PubMed Scopus (20) Google Scholar, 7Verma S. Yanagawa B. Kalra S. Ruel M. Peterson M.D. Yamashita M.H. et al.Knowledge, attitudes, and practice patterns in surgical management of bicuspid aortopathy: a survey of 100 cardiac surgeons.J Thorac Cardiovasc Surg. 2013; 146: 1033-1040Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar The International Bicuspid Aortic Valve Consortium (BAVCon) has been created for the purpose of identifying and addressing current knowledge gaps in BAV, taking advantage of different sources of data, expertise, multiple specialties, and available methodologies from different participating institutions (Appendix E1). The present review focuses on the controversial or unexplored aspects of BAV that are relevant to the surgical management and will be among the research objectives of the Consortium in the coming years. Rather than reiterating the state of the art in surgical management of BAV and its sequelae, this review highlights the gray zones within current knowledge and the questions that remain unanswered, and proposes new research avenues for their resolution. In terms of both postoperative in-hospital/30-day mortality and complications, early outcomes of valve surgery for BAV do not differ from those for tricuspid aortic valve disease.8Girdauskas E. Disha K. Borger M.A. Kuntze T. Long-term prognosis of ascending aortic aneurysm after aortic valve replacement for bicuspid versus tricuspid aortic valve stenosis.J Thorac Cardiovasc Surg. 2014; 147: 276-282Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar, 9Aicher D. Fries R. Rodionycheva S. Schmidt K. Langer F. Schäfers H.J. Aortic valve repair leads to a low incidence of valve-related complications.Eur J Cardiothorac Surg. 2010; 37: 127-132Crossref PubMed Scopus (226) Google Scholar Comparing the 2 largest BAV replacement series, it seems that in-hospital mortality has improved over the decades from an average 2.8% (1960-1995)10McKellar S.H. Michelena H.I. Li Z. Schaff H.V. Sundt III, T.M. Long-term risk of aortic events following aortic valve replacement in patients with bicuspid aortic valves.Am J Cardiol. 2010; 106: 1626-1633Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar to 1.5% (1990-2003).11Borger M.A. David T.E. Management of the valve and ascending aorta in adults with bicuspid aortic valve disease.Semin Thorac Cardiovasc Surg. 2005; 17: 143-147Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Long-term outcomes are satisfactory, in part explained by the relatively young age of the patients undergoing surgery for BAV. Reported 15-year survival ranged between 68% and 78% after isolated aortic valve replacement (AVR),8Girdauskas E. Disha K. Borger M.A. Kuntze T. Long-term prognosis of ascending aortic aneurysm after aortic valve replacement for bicuspid versus tricuspid aortic valve stenosis.J Thorac Cardiovasc Surg. 2014; 147: 276-282Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar, 12Goland S. Czer L.S. De Robertis M.A. Mirocha J. Kass R.M. Fontana G.P. et al.Risk factors associated with reoperation and mortality in 252 patients after aortic valve replacement for congenitally bicuspid aortic valve disease.Ann Thorac Surg. 2007; 83: 931-937Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar whereas survival was lower when concomitant coronary artery bypass surgery was needed10McKellar S.H. Michelena H.I. Li Z. Schaff H.V. Sundt III, T.M. Long-term risk of aortic events following aortic valve replacement in patients with bicuspid aortic valves.Am J Cardiol. 2010; 106: 1626-1633Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 12Goland S. Czer L.S. De Robertis M.A. Mirocha J. Kass R.M. Fontana G.P. et al.Risk factors associated with reoperation and mortality in 252 patients after aortic valve replacement for congenitally bicuspid aortic valve disease.Ann Thorac Surg. 2007; 83: 931-937Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar: these figures are not different from those reported for age-matched patients with a tricuspid aortic valve (TAV).8Girdauskas E. Disha K. Borger M.A. Kuntze T. Long-term prognosis of ascending aortic aneurysm after aortic valve replacement for bicuspid versus tricuspid aortic valve stenosis.J Thorac Cardiovasc Surg. 2014; 147: 276-282Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Despite such satisfactory surgical outcomes, the scientific basis on which the current surgical approach to bicuspid aortic valvulopathy is founded remains defective. Because recent surgical and clinical research on the topic of BAV has mostly focused on the associated aortopathy, important gaps in knowledge remain on the genetic basis, causative mechanisms, and clinical history of bicuspid valvulopathy. Although current guidelines for surgical treatment of aortic valve dysfunction are well supported, they do not distinguish between the TAV and BAV,13Bonow R.O. Carabello B.A. Chatterjee K. de Leon Jr., A.C. Faxon D.P. Freed M.D. et al.2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.Circulation. 2008; 118: e523-e661Crossref PubMed Scopus (1149) Google Scholar, 14Vahanian A. Alfieri O. Andreotti F. Antunes M.J. Barón-Esquivias G. Baumgartner H. et al.Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).Eur Heart J. 2012; 33: 2451-2496Crossref PubMed Scopus (3188) Google Scholar Yet patients with BAV disease are generally younger at the time of surgery: their longer life expectancy compared with patients with TAV disease implies longer exposure to valve-related complications (eg, structural deterioration of tissue prostheses, prosthetic endocarditis, and so forth) and greater concerns about lifestyle (eg, sports, exercise, and so forth), or desire for pregnancy. The situation is further complicated by recent studies suggesting that the functional severity of BAV stenosis, as a consequence of its asymmetric geometry, can be greater than assessed by common imaging methods, and so may be its impact on both ventricular remodeling and flow alterations in the ascending aorta.15Conti C.A. Della Corte A. Votta E. Del Viscovo L. Bancone C. De Santo L.S. et al.Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data.J Thorac Cardiovasc Surg. 2010; 140: 890-896Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 16Richards K.E. Deserranno D. Donal E. Greenberg N.L. Thomas J.D. Garcia M.J. Influence of structural geometry on the severity of bicuspid aortic stenosis.Am J Physiol Heart Circ Physiol. 2004; 287: H1410-H1416Crossref PubMed Scopus (42) Google Scholar, 17Santarpia G. Scognamiglio G. Di Salvo G. D'Alto M. Sarubbi B. Romeo E. et al.Aortic and left ventricular remodeling in patients with bicuspid aortic valve without significant valvular dysfunction: a prospective study.Int J Cardiol. 2012; 158: 347-352Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Even the echocardiographically normally functioning BAV opens asymmetrically thus causing an abnormal postvalvular flow pattern and subclinical stenosis.15Conti C.A. Della Corte A. Votta E. Del Viscovo L. Bancone C. De Santo L.S. et al.Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data.J Thorac Cardiovasc Surg. 2010; 140: 890-896Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 18Bissell M.M. Hess A.T. Biasiolli L. Glaze S.J. Loudon M. Pitcher A. et al.Aortic dilation in bicuspid aortic valve disease: flow pattern is a major contributor and differs with valve fusion type.Circ Cardiovasc Imaging. 2013; 6: 499-507Crossref PubMed Scopus (285) Google Scholar However, it is not yet known whether these notions should influence the timing of surgery. For example, should a mild stenosis be treated at the time of surgery for ascending dilatation if the valve is bicuspid? If not replaced, how fast will it progress to a severe degree or symptomatic stenosis? Can traditional or newer imaging modalities provide reliable predictors of valve stenosis progression in the BAV population? An echocardiography-based valve degeneration score was proposed that proved predictive of aortic valve surgery in the follow-up19Michelena H.I. Desjardins V.A. Avierinos J.F. Russo A. Nkomo V.T. Sundt T.M. et al.Natural history of asymptomatic patients with normally functioning or minimally dysfunctional bicuspid aortic valve in the community.Circulation. 2008; 117: 2776-2784Crossref PubMed Scopus (447) Google Scholar: could computed tomography−based criteria/indexes, with the inherent better definition of calcification patterns, add important information to the current limited capability to predict valvulopathy progression? Will genetic tests help in this prediction of the fate of a borderline valve function (Table 1)?Table 1Gaps in knowledge and research perspectives in surgery for BAV: key pointsCurrent knowledgeKnowledge gapsProposed strategies to improve knowledgeBicuspid valvulopathy Greater flow derangement with BAV stenosis than with TAV stenosis, for each given orifice areaDifferent criteria for indication to AVR according to valve type (BAV/TAV)?Comparing the natural history of BAV versus TAV stenosis. Searching for the predictors of faster stenosis progression in patients with BAV The goal of BAV repair surgery: restoring a coapting and less stressed valveWhich BAV features affect leaflet stress? Which technique for annular reduction?Identifying (bioengineering studies, clinical series) factors affecting long-term durability of BAV repair TAVR in BAV: concerns of noncircular deployment (risk of perivalvular leak)Are BAV calcifications always asymmetric and the orifice always eccentric?Identifying imaging criteria for definition of a subset of patients with BAV for whom TAVR is feasible Different BAV morphotypes, associated with unique clinical features and different valve dysfunction risksDifferential valve surgery approach according to the morphotype (RL, RN, LN)?Natural history studies on large populations of patients with BAV, stratifying according to the valve morphotypeBicuspid aortopathy Diverse BAV morphotypes are associated with different patterns of aortic dilatationDifferent surgical approach to the aorta for different BAV morphotypes (RL, RN, LN)?Investigating the correlation between valve type and aortopathy risk and features A proportion of patients with BAV experience acute aortic dissection at small diametersAny other nondimensional determinant of the risk of dissection?Identifying aortic risk markers (other than diameter): circulating biomarkers, aortic flow patterns, wall load-bearing properties, genetic markers, phenotypic markers Various proposed classification schemes for the aortic phenotypeAny prognostic significance of the aortic phenotype; any relevance to surgical timing? Which classification?Stratifying longitudinal studies according to the aortic phenotype. Assessing the prognostic value of the different classifications in prospective studies Different phenotypes of aortic dilatation. Choice of the procedure often left to the individual surgeon’s discretionSurgical technique tailored to the aortic phenotype?Exploring the risk/benefit of tailoring the procedure to the aortic phenotypeBAV, Bicuspid aortic valve; TAV, tricuspid aortic valve; AVR, aortic valve replacement; TAVR, tricuspid aortic valve replacement; RL, right-left coronary leaflet fusion; RN,right-noncoronary leaflet fusion; LN, left-noncoronary leaflet fusion. Open table in a new tab BAV, Bicuspid aortic valve; TAV, tricuspid aortic valve; AVR, aortic valve replacement; TAVR, tricuspid aortic valve replacement; RL, right-left coronary leaflet fusion; RN,right-noncoronary leaflet fusion; LN, left-noncoronary leaflet fusion. A significant source of clinical heterogeneity in BAV disease lies in the variable morphology of the valve, that is, patterns of congenital cusp fusion (also referred to as morphotypes).20Sabet H.Y. Edwards W.D. Tazelaar H.D. Daly R.C. Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases.Mayo Clin Proc. 1999; 74: 14-26Abstract Full Text Full Text PDF PubMed Scopus (328) Google Scholar Evidence has been presented suggesting that different genetic substrates could underlie the diverse morphotypes.21Fernández B. Durán A.C. Fernández-Gallego T. Fernández M.C. Such M. Arqué J.M. et al.Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities.J Am Coll Cardiol. 2009; 54: 2312-2318Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar Arguing against this, however, it has been recently found that the 2 most frequent morphotypes (fusion of right-left coronary leaflets and fusion of right noncoronary leaflets) can be interchangeably inherited in familiar forms of BAV.22Robeldo-Carmona J. Rodriguez-Bailòn I. Carrasco-Chinchilla F. Fernàndez B. Jimènez-Navarro M. Porras-Marin C. et al.Hereditary patterns of bicuspid aortic valve in a hundred families.Int J Cardiol. 2013; 168: 3443-3449Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Thus, to compellingly determine the clinical and surgical implications of differences in the valvular anatomy, future studies will need to include large numbers of patients for each morphotype. Even within a single morphotype, BAVs can be further distinguished for the degree of leaflet fusion,23Mangini A. Lemma M. Contino M. Pettinari M. Gelpi G. Antona C. Bicuspid aortic valve: differences in the phenotypic continuum affect the repair technique.Eur J Cardiothorac Surg. 2010; 37: 1015-1020Crossref PubMed Scopus (15) Google Scholar the characteristics of the raphe if present, and the respective positions of the 2 true commissures.24Jermihov P.N. Jia L. Sacks M.S. Gorman R.C. Gorman III, J.H. Chandran K.B. Effect of geometry on the leaflet stresses in simulated models of congenital bicuspid aortic valves.Cardiovasc Eng Technol. 2011; 2: 48-56Crossref PubMed Scopus (57) Google Scholar All these features can affect valve biomechanics in terms of stress and strain,24Jermihov P.N. Jia L. Sacks M.S. Gorman R.C. Gorman III, J.H. Chandran K.B. Effect of geometry on the leaflet stresses in simulated models of congenital bicuspid aortic valves.Cardiovasc Eng Technol. 2011; 2: 48-56Crossref PubMed Scopus (57) Google Scholar that is, stimuli that are known to be able to promote valve calcification through the pathways of bone morphogenetic proteins and transforming growth factor β.25Sun L. Chandra S. Sucosky P. Ex vivo evidence for the contribution of hemodynamic shear stress abnormalities to the early pathogenesis of calcific bicuspid aortic valve disease.PLoS One. 2012; 7: e48843Crossref PubMed Scopus (71) Google Scholar Thus, a potentially relevant unknown in BAV surgery is whether gross and subtle anatomic variants have any prognostic significance and should be therefore considered in surgical decision making; for example, whether to spare a normally functioning or mildly dysfunctional BAV at the time of surgery for an aortic aneurysm. To increase knowledge on these aspects, surgical cohorts should be specifically stratified according to the valve morphotype (Table 1), instead of including all variants under the same BAV descriptor. Improved understanding of BAV morphologic diversity is advocated also in the setting of transcatheter aortic valve replacement (TAVR)26Hayashida K. Bouvier E. Lefèvre T. Chevalier B. Hovasse T. Romano M. et al.Transcatheter aortic valve implantation for patients with severe bicuspid aortic valve stenosis.Circ Cardiovasc Interv. 2013; 6: 284-291Crossref PubMed Scopus (136) Google Scholar: although BAV was initially excluded from the indications to TAVR in the PARTNER trial27Leon M.B. Smith C.R. Mack M. Miller D.C. Moses J.W. Svensson L.G. et al.PARTNER Trial InvestigatorsTranscatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.N Engl J Med. 2010; 363: 1597-1607Crossref PubMed Scopus (5420) Google Scholar because of concerns about the risk of noncircular deployment of the prosthesis as a result of eccentricity of the orifice and asymmetry of calcifications, more recent studies have shown that TAVR can be performed in selected subsets of patients with BAV at high surgical risk with similar success as in patients with TAV.26Hayashida K. Bouvier E. Lefèvre T. Chevalier B. Hovasse T. Romano M. et al.Transcatheter aortic valve implantation for patients with severe bicuspid aortic valve stenosis.Circ Cardiovasc Interv. 2013; 6: 284-291Crossref PubMed Scopus (136) Google Scholar, 28Wijesinghe N. Ye J. Rodés-Cabau J. Cheung A. Velianou J.L. Natarajan M.K. et al.Transcatheter aortic valve implantation in patients with bicuspid aortic valve stenosis.JACC Cardiovasc Interv. 2010; 3: 1122-1125Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar Imaging methods are available today for detailed morphologic phenotyping of BAV, and transcatheter prosthesis design is evolving, therefore the application of TAVR in inoperable patients with BAV is fertile research ground. Although aortic stenosis in the adult is only treatable by prosthetic valve replacement, aortic regurgitation can be repaired, avoiding anticoagulation-related risks.29Nash P.J. Vitvitsky E. Li J. Cosgrove III, D.M. Pettersson G. Grimm R.A. Feasibility of valve repair for regurgitant bicuspid aortic valves–an echocardiographic study.Ann Thorac Surg. 2005; 79: 1473-1479Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Several techniques have been proposed, including plication of redundant leaflet tissue, raphe resection and conjoint cusp reconstruction, pericardial patch augmentation, free-margin reinforcement or resuspension, subcommissural stitching, and suture or ring annuloplasty. Several studies have shown the feasibility of BAV repair, however midterm durability has been inconsistent.30Aicher D. Kunihara T. Abou Issa O. Brittner B. Gräber S. Schäfers H.J. Valve configuration determines long-term results after repair of the bicuspid aortic valve.Circulation. 2011; 123: 178-185Crossref PubMed Scopus (267) Google Scholar, 31Kunihara T. Aicher D. Rodionycheva S. Groesdonk H.V. Langer F. Sata F. et al.Preoperative aortic root geometry and postoperative cusp configuration primarily determine long-term outcome after valve-preserving aortic root repair.J Thorac Cardiovasc Surg. 2012; 143: 1389-1395Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar It seems logical that the stability of the repair depends on leaflet tissue quality including the degree of fibrosis and calcification.29Nash P.J. Vitvitsky E. Li J. Cosgrove III, D.M. Pettersson G. Grimm R.A. Feasibility of valve repair for regurgitant bicuspid aortic valves–an echocardiographic study.Ann Thorac Surg. 2005; 79: 1473-1479Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar However, no study has yet tested the risk/benefit of earlier treatment, aimed at performing surgery on a better-preserved cusp structure. Recent evidence indicates that the anatomic features of the BAV may have a strong prognostic impact on the durability of repair.32Navarra E. El Khoury G. Glineur D. Boodhwani M. Van Dyck M. Vanoverschelde J.L. et al.Effect of annulus dimension and annuloplasty on bicuspid aortic valve repair.Eur J Cardiothorac Surg. 2013; 44: 316-322Crossref PubMed Scopus (69) Google Scholar, 33Badiu C.C. Bleiziffer S. Eichinger W.B. Zaimova I. Hutter A. Mazzitelli D. et al.Are bicuspid aortic valves a limitation for aortic valve repair?.Eur J Cardiothorac Surg. 2011; 40: 1097-1104PubMed Google Scholar Advancements in our understanding of BAV geometry and kinematics has led to the notion that late BAV repair failures might be incited by abnormal leaflet stresses, inherent to the morphology of the repaired valve.15Conti C.A. Della Corte A. Votta E. Del Viscovo L. Bancone C. De Santo L.S. et al.Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data.J Thorac Cardiovasc Surg. 2010; 140: 890-896Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 24Jermihov P.N. Jia L. Sacks M.S. Gorman R.C. Gorman III, J.H. Chandran K.B. Effect of geometry on the leaflet stresses in simulated models of congenital bicuspid aortic valves.Cardiovasc Eng Technol. 2011; 2: 48-56Crossref PubMed Scopus (57) Google Scholar In particular, 40% lower rates of 10-year freedom from valve reoperation have been observed in patients with an aorto-ventricular junction diameter exceeding 28 to 30 mm compared with patients with a smaller diameter,30Aicher D. Kunihara T. Abou Issa O. Brittner B. Gräber S. Schäfers H.J. Valve configuration determines long-term results after repair of the bicuspid aortic valve.Circulation. 2011; 123: 178-185Crossref PubMed Scopus (267) Google Scholar, 32Navarra E. El Khoury G. Glineur D. Boodhwani M. Van Dyck M. Vanoverschelde J.L. et al.Effect of annulus dimension and annuloplasty on bicuspid aortic valve repair.Eur J Cardiothorac Surg. 2013; 44: 316-322Crossref PubMed Scopus (69) Google Scholar leading to the recent development of different strategies for annular reduction and support.34Aicher D. Schneider U. Schmied W. Kunihara T. Tochii M. Schäfers H.J. Early results with annular support in reconstruction of the bicuspid aortic valve.J Thorac Cardiovasc Surg. 2013; 145: S30-S34Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 35de Kerchove L. Boodhwani M. Glineur D. Vandyck M. Vanoverschelde J.L. Noirhomme P. et al.Valve sparing-root replacement with the reimplantation technique to increase the durability of bicuspid aortic valve repair.J Thorac Cardiovasc Surg. 2011; 142: 1430-1438Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar However, the ideal correction of annular dilatation still has to be determined (Table 1). The orientation of the 2 true commissures also affects postrepair outcomes; when the commissures are located 160° to 180° apart, leaflet stresses are lower24Jermihov P.N. Jia L. Sacks M.S. Gorman R.C. Gorman III, J.H. Chandran K.B. Effect of geometry on the leaflet stresses in simulated models of congenital bicuspid aortic valves.Cardiovasc Eng Technol. 2011; 2: 48-56Crossref PubMed Scopus (57) Google Scholar and 10-year freedom from reoperation rates can be more than 40% higher than in patients with less than 160° commissural orientation.32Navarra E. El Khoury G. Glineur D. Boodhwani M. Van Dyck M. Vanoverschelde J.L. et al.Effect of annulus dimension and annuloplasty on bicuspid aortic valve repair.Eur J Cardiothorac Surg. 2013; 44: 316-322Crossref PubMed Scopus (69) Google Scholar, 33Badiu C.C. Bleiziffer S. Eichinger W.B. Zaimova I. Hutter A. Mazzitelli D. et al.Are bicuspid aortic valves a limitation for aortic valve repair?.Eur J Cardiothorac Surg. 2011; 40: 1097-1104PubMed Google Scholar It has been pointed out36Etz C.D. Misfeld M. Borger M.A. Luehr M. Strotdrees E. Mohr F.W. Current indications for surgical repair in patients with bicuspid aortic valve and ascending aortic ectasia.Cardiol Res Pract. 2012; 2012: 313879Crossref PubMed Scopus (23) Google Scholar that although repairing a TAV fundamentally means restoring normal native anatomy, BAV repair requires complete rearrangement of valve orifice geometry, aiming at producing a new, more physiologic flow architecture, with consequent lower leaflet stresses.15Conti C.A. Della Corte A. Votta E. Del Viscovo L. Bancone C. De Santo L.S. et al.Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data.J Thorac Cardiovasc Surg. 2010; 140: 890-896Abstract Full Text Full Text PDF PubMed Scopus (96) Google Schol