Advertisement

Bicuspid Aortic Valvulopathy and Associated Aortopathy: a Review of Contemporary Studies Relevant to Clinical Decision-Making

  • Michael H. KwonEmail author
  • Thoralf M. Sundt
Valvular Heart Disease (J Dal-Bianco, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Valvular Heart Disease

Opinion statement

The bicuspid aortic valve (BAV) phenotype is becoming increasingly recognized as a complex and heterogeneous clinical entity, with some but not all patients developing accelerated degrees of both aortic insufficiency (AI) and aortic stenosis (AS) in comparison to patients with tricuspid aortic valves (TAV). In addition, there remains a well-established association between the BAV phenotype and aortic enlargement independent of valve function as well as progression among some to ascending aortic aneurysm and the attendant concern over risk of aortic dissection. Because the understanding of the complexity of the BAV phenotype is evolving as quickly as are the options for medical, surgical, and interventional therapy, this review aims to provide an update on the most clinically relevant recent advances in the realm of BAV and associated aortopathy from a genetic, morphologic, and clinical outcomes perspective in order to give the practicing clinician a deeper understanding of how to approach both medical and surgical decision-making in the patient with BAV. The following major principles have emerged in recent years including (1) the importance of cusp anatomy and its implications on the long-term risk of AI, aortic dilation, and aortic dissection, (2) the role of post-valvular flow dynamics in the pathogenesis of aortic dilation in BAV patients, (3) the ability of aortic valve replacement to halt accelerated dilation rates, and (4) the finding that the risk of aortic dissection, while still overall intermediate is much more akin to the baseline risk present in TAV patients rather than the much higher rates observed in patients with Marfan’s disease. Together, these data support the less aggressive approach to aortic replacement in BAV patients as reflected in the most recent ACC/AHA guidelines and provide a stronger basis upon which future studies, including those aimed at medical and transcatheter therapies, stand to make further impact on our ability to optimally treat this epidemiologically important and complex population of patients.

Keywords

Bicuspid aortic valve Aortic insufficiency Aortic stenosis Tricuspid aortic valves 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Siu SC, Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol. 2010;55(25):2789–800.CrossRefPubMedGoogle Scholar
  2. 2.
    Ward C. Clinical significance of the bicuspid aortic valve. Heart. 2000;83(1):81–5.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Longobardo L, Jain R, Carerj S, Zito C, Khandheria BK. Bicuspid aortic valve: unlocking the morphogenetic puzzle. Am J Med. 2016;129(8):796–805.CrossRefPubMedGoogle Scholar
  4. 4.
    Koenig SN, Bosse K, Majumdar U, Bonachea EM, Radtke F, Garg V. Endothelial Notch1 is required for proper development of the semilunar valves and cardiac outflow tract. J Am Heart Assoc. 2016;5(4).Google Scholar
  5. 5.
    Fernandez B, Duran AC, Fernandez-Gallego T, et al. Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities. J Am Coll Cardiol. 2009;54(24):2312–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Prodromo J, D’Ancona G, Amaducci A, Pilato M. Aortic valve repair for aortic insufficiency: a review. J Cardiothorac Vasc Anesth. 2012;26(5):923–32.CrossRefPubMedGoogle Scholar
  7. 7.
    Mathieu P, Bosse Y, Huggins GS, et al. The pathology and pathobiology of bicuspid aortic valve: state of the art and novel research perspectives. J Pathol Clin Res. 2015;1(4):195–206.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Sievers HH, Schmidtke C. A classification system for the bicuspid aortic valve from 304 surgical specimens. J Thorac Cardiovasc Surg. 2007;133(5):1226–33.CrossRefPubMedGoogle Scholar
  9. 9.
    Friedman T, Mani A, Elefteriades JA. Bicuspid aortic valve: clinical approach and scientific review of a common clinical entity. Expert Rev Cardiovasc Ther. 2008;6(2):235–48.CrossRefPubMedGoogle Scholar
  10. 10.
    Sabet HY, Edwards WD, Tazelaar HD, Daly RC. Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2715 additional cases. Mayo Clin Proc. 1999;74(1):14–26.CrossRefPubMedGoogle Scholar
  11. 11.
    Shin HJ, Shin JK, Chee HK, Kim JS, Ko SM. Characteristics of aortic valve dysfunction and ascending aorta dimensions according to bicuspid aortic valve morphology. Eur Radiol. 2015;25(7):2103–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Page M, Mongeon FP, Stevens LM, Souliere V, Khairy P, El-Hamamsy I. Aortic dilation rates in patients with biscuspid aortic valve: correlations with cusp fusion phenotype. J Heart Valve Dis. 2014;23(4):450–7.PubMedGoogle Scholar
  13. 13.
    Kim JS, Ko SM, Chee HK, Shin JK, Song MG, Shin HJ. Relationship between bicuspid aortic valve phenotype, valvular function, and ascending aortic dimensions. J Heart Valve Dis. 2014;23(4):406–13.PubMedGoogle Scholar
  14. 14.
    • Khoo C, Cheung C, Jue J. Patterns of aortic dilatation in bicuspid aortic valve-associated aortopathy. J Am Soc Echocardiogr: Off Publ Am Soc Echocardiogr. 2013;26(6):600–5. This study demonstrates that the RL cusp fusion pattern is associated with faster rates of aortic root and ascending aortic dilation.CrossRefGoogle Scholar
  15. 15.
    Thanassoulis G, Yip JW, Filion K, et al. Retrospective study to identify predictors of the presence and rapid progression of aortic dilatation in patients with bicuspid aortic valves. Nat Clin Pract Cardiovasc Med. 2008;5(12):821–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(22):2438–88.CrossRefPubMedGoogle Scholar
  17. 17.
    Nataatmadja M, West M, West J, et al. Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm. Circulation. 2003;108(Suppl 1):II329–34.PubMedGoogle Scholar
  18. 18.
    Fedak PW, de Sa MP, Verma S, et al. Vascular matrix remodeling in patients with bicuspid aortic valve malformations: implications for aortic dilatation. J Thorac Cardiovasc Surg. 2003;126(3):797–806.CrossRefPubMedGoogle Scholar
  19. 19.
    Schmoker JD, McPartland KJ, Fellinger EK, et al. Matrix metalloproteinase and tissue inhibitor expression in atherosclerotic and nonatherosclerotic thoracic aortic aneurysms. J Thorac Cardiovasc Surg. 2007;133(1):155–61.CrossRefPubMedGoogle Scholar
  20. 20.
    Shiraya S, Miyake T, Aoki M, et al. Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration. Atherosclerosis. 2009;202(1):34–40.CrossRefPubMedGoogle Scholar
  21. 21.
    Taylor AP, Yadlapati A, Andrei AC, et al. Statin use and aneurysm risk in patients with bicuspid aortic valve disease. Clin Cardiol. 2016;39(1):41–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Goel SS, Tuzcu EM, Agarwal S, et al. Comparison of ascending aortic size in patients with severe bicuspid aortic valve stenosis treated with versus without a statin drug. Am J Cardiol. 2011;108(10):1458–62.CrossRefPubMedGoogle Scholar
  23. 23.
    Yuan SM, Jing H, Lavee J. The bicuspid aortic valve and its relation to aortic dilation. Clinics. 2010;65(5):497–505.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116(15):1736–54.CrossRefPubMedGoogle Scholar
  25. 25.
    Duval X, Alla F, Hoen B, et al. Estimated risk of endocarditis in adults with predisposing cardiac conditions undergoing dental procedures with or without antibiotic prophylaxis. Clin Inf Dis: Off Publ Inf Dis Soc Am. Jun 15 2006;42(12):e102–e107.Google Scholar
  26. 26.
    Edwards WD, Leaf DS, Edwards JE. Dissecting aortic aneurysm associated with congenital bicuspid aortic valve. Circulation. 1978;57(5):1022–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Della Corte A, Bancone C, Quarto C, et al. Predictors of ascending aortic dilatation with bicuspid aortic valve: a wide spectrum of disease expression. Eur J Cardiothorac Surg: Off J Eur Assoc Cardiothor Surg. 2007;31(3):397–404. discussion 404–395CrossRefGoogle Scholar
  28. 28.
    •• Verma S, Siu SC. Aortic dilatation in patients with bicuspid aortic valve. The New England Journal of Medicine. 2014;370(20):1920–9. An excellent review of BAV that describes cogently the link between post-valvular flow dynamics and their effect on patterns of aortic dilation as well the associated changes in the microstructural composition of the aortic wall in BAV patients.CrossRefPubMedGoogle Scholar
  29. 29.
    Ferencik M, Pape LA. Changes in size of ascending aorta and aortic valve function with time in patients with congenitally bicuspid aortic valves. Am J Cardiol. 2003;92(1):43–46.Google Scholar
  30. 30.
    Svensson LG, Kim KH, Lytle BW, Cosgrove DM. Relationship of aortic cross-sectional area to height ratio and the risk of aortic dissection in patients with bicuspid aortic valves. J Thorac Cardiovasc Surg. 2003;126(3):892–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010;121(13):e266–369.CrossRefPubMedGoogle Scholar
  32. 32.
    Eleid MF, Forde I, Edwards WD, et al. Type A aortic dissection in patients with bicuspid aortic valves: clinical and pathological comparison with tricuspid aortic valves. Heart. 2013;99(22):1668–74.CrossRefPubMedGoogle Scholar
  33. 33.
    Etz CD, von Aspern K, Hoyer A, et al. Acute type A aortic dissection: characteristics and outcomes comparing patients with bicuspid versus tricuspid aortic valve. Eur J Cardiothorac Surg: Off J Eur Assoc Cardiothorac Surg. 2015;48(1):142–50.CrossRefGoogle Scholar
  34. 34.
    Wasfy JH, Armstrong K, Milford CE, Sundt TM. Bicuspid aortic disease and decision making under uncertainty—the limitations of clinical guidelines. Int J Cardiol. 2015;181:169–71.CrossRefPubMedGoogle Scholar
  35. 35.
    • Sundt TM. Aortic replacement in the setting of bicuspid aortic valve: how big? How much? The Journal of Thoracic and Cardiovascular Surgery. 2015;149(2 Suppl):S6–9. A short editorial that describes the concept of “denominator neglect” and the associated pitfalls inherent in assuming that just because some BAV patients present with aortic dissection at moderate diameters, all patients with moderately dilated aortas should be replaced.CrossRefPubMedGoogle Scholar
  36. 36.
    Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline 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. J Thorac Cardiovasc Surg. 2014;148(1):e1–e132.CrossRefPubMedGoogle Scholar
  37. 37.
    ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the management of patients with thoracic aortic disease representative M, Hiratzka LF, et al. Surgery for aortic dilatation in patients with bicuspid aortic valves: a statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;133(7):680–6.CrossRefGoogle Scholar
  38. 38.
    Girdauskas E, Disha K, Borger MA, 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(1):276–82.CrossRefPubMedGoogle Scholar
  39. 39.
    Charitos EI, Stierle U, Petersen M, et al. The fate of the bicuspid valve aortopathy after aortic valve replacement. Eur J Cardiothorac Surg: Off J Eur Assoc Cardiothorac Surg. May 2014;45(5):e128–35.CrossRefGoogle Scholar
  40. 40.
    • Regeer MV, Versteegh MI, Klautz RJ, et al. Effect of aortic valve replacement on aortic root dilatation rate in patients with bicuspid and tricuspid aortic valves. Ann Thorac Surg. 2016. This study demonstrates the ability of AVR to stabilize the rate of aortic dilation in BAV patients to that seen in the general population, suggesting that the correction of flow dynamics accompanying AVR may be responsible for this effect.Google Scholar
  41. 41.
    Mahadevia R, Barker AJ, Schnell S, et al. Bicuspid aortic cusp fusion morphology alters aortic three-dimensional outflow patterns, wall shear stress, and expression of aortopathy. Circulation. 2014;129(6):673–82.CrossRefPubMedGoogle Scholar
  42. 42.
    Barker AJ, Markl M, Burk J, et al. Bicuspid aortic valve is associated with altered wall shear stress in the ascending aorta. Circ Cardiovasc Imaging. 2012;5(4):457–66.CrossRefPubMedGoogle Scholar
  43. 43.
    Fedak PW, Barker AJ, Verma S. Year in review: bicuspid aortopathy. Curr Opin Cardiol. 2016;31(2):132–8.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Atkins SK, Cao K, Rajamannan NM, Sucosky P. Bicuspid aortic valve hemodynamics induces abnormal medial remodeling in the convexity of porcine ascending aortas. Biomech Model Mechanobiol. 2014;13(6):1209–25.CrossRefPubMedGoogle Scholar
  45. 45.
    Atkins SK, Sucosky P. Etiology of bicuspid aortic valve disease: focus on hemodynamics. World J Cardiol. 2014;6(12):1227–33.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Davies RR, Kaple RK, Mandapati D, et al. Natural history of ascending aortic aneurysms in the setting of an unreplaced bicuspid aortic valve. Ann Thorac Surg. 2007;83(4):1338–44.CrossRefPubMedGoogle Scholar
  47. 47.
    Hardikar AA, Marwick TH. Surgical thresholds for bicuspid aortic valve associated aortopathy. JACC Cardiovasc Imaging. 2013;6(12):1311–20.CrossRefPubMedGoogle Scholar
  48. 48.
    Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic valves. JAMA. 2011;306(10):1104–12.CrossRefPubMedGoogle Scholar
  49. 49.
    Tzemos N, Therrien J, Yip J, et al. Outcomes in adults with bicuspid aortic valves. JAMA. 2008;300(11):1317–25.CrossRefPubMedGoogle Scholar
  50. 50.
    •• Itagaki S, Chikwe JP, Chiang YP, Egorova NN, Adams DH. Long-term risk for aortic complications after aortic valve replacement in patients with bicuspid aortic valve versus Marfan syndrome. J Am Coll Cardiol. 2015;65(22):2363–9. A timely clinical study that examines the post-AVR natural history of aortopathy in patients with BAV, TAV, and Marfan’s syndrome and demonstrates a significantly higher rate of aortic complications in Marfan’s patients compared to both other groups. This argues strongly in favor of an approach to aortic replacement in BAV patients that does not simply extrapolate from Marfan’s disease.CrossRefPubMedGoogle Scholar
  51. 51.
    Hughes GC, Zhao Y, Rankin JS, et al. Effects of institutional volumes on operative outcomes for aortic root replacement in North America. J Thorac Cardiovasc Surg. 2013;145(1):166–70.CrossRefPubMedGoogle Scholar
  52. 52.
    Hiratzka LF, Creager MA, Isselbacher EM, et al. Surgery for aortic dilatation in patients with bicuspid aortic valves: a statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;67(6):724–31.CrossRefPubMedGoogle Scholar
  53. 53.
    Park CB, Greason KL, Suri RM, Michelena HI, Schaff HV, Sundt TM 3rd. Fate of nonreplaced sinuses of Valsalva in bicuspid aortic valve disease. J Thorac Cardiovasc Surg. 2011;142(2):278–84.CrossRefPubMedGoogle Scholar
  54. 54.
    Park CB, Greason KL, Suri RM, Michelena HI, Schaff HV, Sundt TM 3rd. Should the proximal arch be routinely replaced in patients with bicuspid aortic valve disease and ascending aortic aneurysm? J Thorac Cardiovasc Surg. 2011;142(3):602–7.CrossRefPubMedGoogle Scholar
  55. 55.
    Mack MJ, Leon MB, Smith CR, et al. 5-Year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015;385(9986):2477–84.CrossRefPubMedGoogle Scholar
  56. 56.
    Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. The New England Journal of Medicine. 2016;374(17):1609–20.CrossRefPubMedGoogle Scholar
  57. 57.
    Bauer T, Linke A, Sievert H, et al. Comparison of the effectiveness of transcatheter aortic valve implantation in patients with stenotic bicuspid versus tricuspid aortic valves (from the German TAVI Registry). The American Journal of Cardiology. 2014;113(3):518–21.CrossRefPubMedGoogle Scholar
  58. 58.
    Zhao ZG, Jilaihawi H, Feng Y, Chen M. Transcatheter aortic valve implantation in bicuspid anatomy. Nat Rev Cardiol. 2015;12(2):123–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Mylotte D, Lefevre T, Sondergaard L, et al. Transcatheter aortic valve replacement in bicuspid aortic valve disease. Journal of the American College of Cardiology. 2014;64(22):2330–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Perlman GY, Blanke P, Dvir D, et al. Bicuspid aortic valve stenosis: favorable early outcomes with a next-generation transcatheter heart valve in a multicenter study. JACC. Cardiovascular Interventions. 2016;9(8):817–24.CrossRefPubMedGoogle Scholar
  61. 61.
    Yousef A, Simard T, Webb J, et al. Transcatheter aortic valve implantation in patients with bicuspid aortic valve: a patient level multi-center analysis. Int J Cardiol. 2015;189:282–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Division of Cardiac Surgery, Department of SurgeryMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

Personalised recommendations